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Background: Medullary thyroid carcinoma (MTC), the third most frequent histological type of thyroid malignancy, may be found isolated or as part of multiple endocrine neoplasia type 2 (MEN2). One particular subtype of this autosomal dominant-transmitted syndrome includes an association with cutaneous lichen amyloidosis, although, generally, a tide genotype–phenotype correlation is described in patients who carry RET proto-oncogene pathogenic variants. Methods: Our objective was to provide an endocrine perspective of a case series diagnosed with RET-positive familial MTC associated with cutaneous primary lichen amyloidosis amid the confirmation of MEN2. Six members of the same family had cutaneous lesion with different features (from hyperpigmented, velvety to red/pink appearance) and four of them harbored a RET pathogenic variant at 634 codon (exon 11): c.1900T>G, p.634G (TGC634CGC). Results: All six patients were females with the lesion at the interscapular region. Except for two women, four of these subjects were investigated and had MTC (three of them with postoperatory confirmation). The youngest affected individual was 6 years old. The three adult females were confirmed with RET pathogenic variant during their 30s, while the girl underwent the familial screening as a newborn. None of them had primary hyperparathyroidism until the present time, except for one subject, and two out of the three adults also had bilateral pheochromocytoma. Notably, all patients were rather asymptomatic from the endocrine perspective at the moment when endocrine tumor/cancer was confirmed, and the skin was progressively affected a few years before the actual MEN2 confirmation. Conclusions: This case series highlights the following key message: awareness of the dermatologic findings in MTC/MEN2 patients is essential since lesions such as cutaneous lichen amyloidosis might represent the skin signature of the endocrine condition even before the actual endocrine manifestations. These data add to the limited published reports with respect to this particular presentation, noting the fact that RET-C634 is the most frequent pathogenic variant in MEN2-associated lichen amyloidosis; females are more often affected; the interscapular region is the preferred site; the age of diagnosis might be within the third decade of life, while we reported one of the youngest patients with the lesion. The same RET pathogenic variant is not associated with the same dermatologic features as shown in the vignette. The same RET mutation does not mean that all family members will present the same skin anomaly.

Background: Ectopic organ-associated conditions belong to the larger panel of developmental ailments, and among this challenging medical and surgical chapter, ectopic endocrine glands-related picture is mostly focused on the presence of the ectopic parathyroid and thyroid. Ectopic thyroid tissue within mediastinum (ETTM) stands for a less common ETT site; while, globally, less than 1% of the mediastinum masses are ETTM. Objective: We aim to introduce a rare case of ETTM in a senior lady to whom one-time synchronous thyroidectomy with ETT removal was successfully performed via a minimally invasive modern procedure upon cervicotomy and intra-operatory use of the Cooper thymectomy retractor. Results: The panel of pros and cons with respect to providing endocrine thoracic surgery for ETTM resection in a 73-year-old subject is discussed amid a PubMed search of original English-language original reports from January 2000 until 15 August 2024 in order to identify similar distinct cases (individuals of 70 years or older who underwent surgery for ETTM). Conclusions: 1. We propose the term “three-leaf-clover thyroid” to capture the imaging essence of having an enlargement of both (eutopic) thyroid lobes and ETTM. 2. The modern surgical approach under these circumstances provided a rapid patient recovery with a low rate of complications and a minimum hospital stay. Hence, the procedure may be expanded to older patients after a careful consideration of their co-morbidities and of the need to releasing connected complaints (e.g., a 7-month history of intermittent dyspneea was found in this case with post-operatory remission). 3. The management remains a matter of individualised decision, and age may not be a limiting factor. 4. At the present time, this case adds to the very limited number of similar published cases in the mentioned age group that we could identify (seven patients, aged between 72 and 84; male-to-female ratio of 5 to 2; the rate of malignant ETTM was 3/7); of these cases, not all were reported to have a trans-cervical approach, and none reported the use of the Cooper thymectomy retractor to help the overall surgical procedure. This innovative surgical procedure offers the advantage of avoiding a sternotomy incision which has clear functional and aesthetic implications, while the video-assisted approach allows optimal visualization of the mediastinal anatomy and safe vascular sealing under visual control, without the risk of a major hemorrhage.

Magnesium (Mg), an essential nutrient with a wide area of physiological roles, stands as a cofactor in over 600 enzymatic reactions involved in the synthesis of proteins and nucleic acids, DNA repair, neuromuscular functions, neuronal transmission, cardiac rhythm regulation, and the modulation of metabolic pathways, as well as acting as a natural blocker for the calcium channels. Our objective was to highlight the most recent clinical data with respect to daily Mg intake (DMI) and metabolic traits, particularly type 2 diabetes mellitus (DM). This was a PubMed-based review of the English-language medical papers across different key terms of search; the time frame was from January 2019 until April 2024. We included (clinically relevant) original studies and excluded cases reports, series, reviews, editorials, opinion, experimental studies, and non-human data as well as studies that did not specifically assessed DMI and only provided assays of serum Mg, studies on patients diagnosed with type 1 or secondary DM. A total of 30 studies were included and we organized the key findings into several sections as follows. Studies investigating DMI in relationship with the adherence to local recommendations in diabetic subjects (n = 2, one transversal and another retrospective cohort; N = 2823) found that most of them had lower DMI. Deficient DMI was correlated with the risk of developing/having DM across five studies (n = 5, one prospective and four of cross-sectional design; N = 47,166). An inverse correlation between DMI and DM prevalence was identified, but these data are presented amid a rather heterogeneous spectrum. Four novel studies (N = 7279) analysed the relationship between DMI and DM control according to various methods (HbA1c, fasting and postprandial glycaemia, and insulin); the association may be linear in diabetic subjects only at certain levels of DMI; additionally, the multifactorial influence on HBA1c should take into consideration this dietary determinant, as well, but there are no homogenous results. Three studies concerning DMI and diabetic complications (one cross-sectional, one prospective, and another case–control study) in terms of retinopathy (n = 1, N = 3794) and nephropathy (n = 2, N = 4805) suggested a lower DMI was associated with a higher risk of such complications. Additionally, two other studies (one prospective and one retrospective cohort) focused on mortality (N = 6744), which, taking only certain mortality indicators into consideration, might be decreased in the subgroups with a higher DMI. Seven studies (N = 30,610) analysed the perspective of DMI in the general population with the endpoint of different features amid glucose profile, particularly, insulin resistance. Concerning HOMA-IR, there were three confirmatory studies and one non-confirmatory, while fasting plasma glucose was highlighted as inversely correlated with a DMI (n = 1). The highest level of evidence regarding Mg supplementation effects on glucose metabolism stands on seven randomised controlled trials (N = 350). However, the sample size was reduced (from 14 to 86 individuals per study, either diabetic or pre-diabetic) and outcomes were rather discordant. These clinical aspects are essential from a multidisciplinary perspective and further trials are mandatory to address the current areas of discordant results.

Background: Amid the large panel of autoimmune thyroid diseases, Hashimoto’s thyroiditis (HT) represents a major point across multidisciplinary daily practice. When it comes to the clinical picture, particularly in regard to asthenia (also described as “fatigue” or “decreased energy”), the differential diagnosis is challenging, and a meticulous anamnesis should be backed up by focused lab investigations. Our objective was to analyze the thyroid panel in newly diagnosed patients with HT in relationship with the presence of asthenia as an admission complaint. Methods: This was a retrospective, multi-centric, real-life study conducted in secondary endocrine units (university hospitals) from July 2022 to July 2023. The exclusion criteria were COVID-19 infection; an active malignancy, etc. Results: The cohort (N = 120) included an asthenia group (AS, 49.2%) and a non-AS group of a similar age (49.3 ± 14.7 vs. 47.1 ± 14.8 y, p = 0.426). Headache was more frequent in the AS group (35.6% vs. 18%, p = 0.03). Thyroid function and HT-related antibodies assays were similar between the groups and show no correlation with serum total cholesterol and triglycerides, respectively. TSH levels did not vary among the age sub-groups (p = 0.701). One third of the studied population was affected by hypothyroidism (TSH > 4.5 μIU/mL), being seen at a higher rate in the AS (39%) vs. non-AS group (23%). Total cholesterol positively correlated with the patients’ age (r = 0.180, p = 0.049) and triglycerides (N = 120; r = 0.324, p < 0.001), as found only in the non-AS group (r = 0.246, p = 0.006, respectively, r = 0.319, p < 0.001). Conclusions: The analysis of the AS vs. non-AS group pinpointed the fact that, in regard to daily practice, asthenia as an admission complaint seems less of an indicator of an underlying thyroid dysfunction or a higher level of serum antibodies against thyroid in patients without a full clinical picture of thyrotoxicosis or myxoedema.

An ectopic thyroid (ET) involves numerous scenarios of detection and outcomes, while its current management is not standardised. A mediastinal ET (MET) represents a low index of suspicion. In this paper, we introduce a 47-year-old female who was accidentally identified with an MET, and a modern surgical approach was provided. An anterior mediastinal mass of 3.2 cm was found at CT upon a prior COVID-19 infection. Previous to the infection, she experienced non-specific complaints for a few months (intermittent night sweats, facial erythema, chest pressure, and dyspnoea). Also, CT identified a thymus-like mass and a left adrenal incidentaloma of 3 cm. The endocrine panel was normal, and the subject declined further investigations. She was re-admitted 12 months later: the MET had increased +1 cm (+45% volume) and was confirmed at a 99mTc pertechnetate scintigraphy. Noting the symptoms, mediastinal anatomy, and size change, the MET was removed via a minimally invasive trans-cervical approach (eutopic gland preservation) with the help of a Cooper thymectomy retractor (which also allowed for a synchronous thymus mass resection). No post-operatory complications were registered, the thyroid function remained normal, and the mentioned symptoms were remitted. A histological exam confirmed a benign MET and thymus hyperplasia, respectively. To conclude, this case pinpoints important aspects, such as the clinical picture became clear only upon thoracic surgery due to the complete remission of the complaints that initially seemed widely non-specific. The incidental MET finding was associated with a second (adrenal) incidentaloma, a scenario that might not be so rare, following multiple imaging scans amid the COVID-19 era (no common pathogenic traits have been identified so far). The co-presence of a thymus mass represented one more argument for surgery. Minimally invasive cervicotomy associated with eutopic gland conservation and the use of a Cooper thymectomy retractor highlight modern aspects in video-assisted thoracic surgery, which provided an excellent outcome, involving one of the lowest mediastinal thyroids to be removed by this specific procedure. Awareness of such unusual entities helps inform individualised, multidisciplinary decisions for optimum prognoses.

Background. Incidentalomas have an increasing incidence all over the world due to a larger access to imaging assessments, and endocrine incidentalomas make no exception in this matter, including pituitary incidentalomas (PIs). Objective. Our objective was to analyse the dynamic changes amid a second computed tomography (CT) scan after adult patients were initially confirmed with a PI (non-functioning micro-adenoma). Methods. This was a multi-centric, longitudinal, retrospective study in adults (aged between 20 and 70 y) amid real-world data collection. We excluded patients who experienced baseline pituitary hormonal excess or deficiency or those with tumours larger than 1 cm. Results. A total of 117 adults were included (94.02% females) with a mean age of 43.86 ± 11.99 years, followed between 6 and 156 months with a median (M) of 40 months (Q1 Q3: 13.50, 72.00). At the time of PI diagnosis, the transverse diameter had a mean value of 0.53 ± 0.16 cm, the longitudinal mean diameter was 0.41 ± 0.13 cm, and the largest diameter was 0.55 ± 0.16 cm. No PI became functioning during follow-up, neither associated hypopituitarism nor increased >1 cm diameter. A total of 46/117 (39.32%) patients had a larger diameter during follow-up (increase group = IG) versus a non-increase group (non-IG; N = 71, 60.68%) that included the subjects with stationary or decreased diameters. IG had lower initial transverse, longitudinal, and largest diameter versus non-IG: 0.45 ± 0.12 versus 0.57 ± 0.17 (p < 0.0001), 0.36 ± 0.11 versus 0.43 ± 0.13 (p = 0.004), respectively, 0.46 ± 0.12 versus 0.6 ± 0.16 (p < 0.0001). IG versus non-IG had a larger period of surveillance: M (Q1, Q3) of 48 (24, 84) versus 32.5 (12, 72) months (p = 0.045) and showed similar age, pituitary hormone profile, and tumour lateralisation at baseline and displayed a median diameter change of +0.14 cm versus −0.03 cm (p < 0.0001). To conclude, a rather high percent of patients might experience PI diameter increase during a longer period of follow-up, including those with a smaller initial size, while the age at diagnosis does not predict the tumour growth. This might help practitioners with further long-term surveillance protocols.

Many causes of secondary osteoporosis have been identified; endocrine types (such as those linked to male hypogonadism, Cushing’s syndrome, acromegaly, thyrotoxicosis, primary hyperparathyroidism, etc.) represent one of the most challenging ailments since a personalized approach of the endocrine disease is simultaneous required. We aimed to introduce the case of a senior lady who was diagnosed with secondary osteoporosis that was associated with primary hyperparathyroidism and a conservative approach was decided, from anti-osteoporosis drug and calcium lowering agents to the physical rehabilitation and lifestyle recommendations. She also presented double unilateral adrenal incidentaloma and a pituitary incidentaloma as well as a suspected ovarian cyst that she further declined to investigate. Mitigating the non-surgical management in primary hyperparathyroidism showcase (in addition to the zoledronic acid for both osteoporosis and hypercalcemia) a complex program of rehabilitation that included a diet intervention in terms of an adequate hydration and a personalized nutrition for kidney stones primary and secondary prevention, mild physical exercise, avoidance of calcium supplements and keeping a daily chole-calciferol replacement.

Cholangiocarcinomas (CCAs), a heterogeneous group of challenging malignant tumours which originate from the biliary epithelium, are associated with an alarming increasing incidence during recent decades that varies between different regions of the globe. Thus, awareness represents the key operating factor. Our purpose was to overview the field of CCAs following a double perspective: the constellation of the risk factors, and the presence of the paraneoplastic syndromes, emphasizing the endocrine features amid the entire multidisciplinary panel. This is a narrative review. A PubMed-based search of English-language original articles offered the basis of this comprehensive approach. Multiple risk factors underlying different levels of statistical evidence have been listed such as chronic biliary diseases and liver conditions, inflammatory bowel disease, parasitic infections (e.g., Opisthorchis viverrini, Clonorchis sinensis), lifestyle influence (e.g., alcohol, smoking), environmental exposure (e.g., thorotrast, asbestos), and certain genetic and epigenetic interplays. With regard to the endocrine panel, a heterogeneous spectrum should be taken into consideration: non-alcoholic fatty liver disease, obesity, type 2 diabetes mellitus, and potential connections with vitamin D status, glucagon-like peptide 1 receptor, or the galanin system, respectively, with exposure to sex hormone therapy. Amid the numerous dermatologic, hematologic, renal, and neurologic paraneoplastic manifestations in CCAs, the endocrine panel is less described. Humoral hypercalcaemia of malignancy stands as the most frequent humoral paraneoplastic syndrome in CCAs, despite being exceptional when compared to other paraneoplastic (non-endocrine) manifestations and to its reported frequency in other (non-CCAs) cancers (it accompanies 20–30% of all cancers). It represents a poor prognosis marker in CCA; it may be episodic once the tumour relapses. In addition to the therapy that targets the originating malignancy, hypercalcaemia requires the administration of bisphosphonates (e.g., intravenous zoledronic acid) or denosumab. Early detection firstly helps the general wellbeing of a patient due to a prompt medical control of high serum calcium and it also provides a fine biomarker of disease status in selected cases that harbour the capacity of PTHrP secretion. The exact molecular biology and genetic configuration of CCAs that display such endocrine traits is still an open matter, but humoral hypercalcaemia adds to the overall disease burden.

The COVID-19 pandemic brought into prominence several emergent medical and surgical entities, but, also, it served as trigger and contributor for numerous apparently unrelated ailments such as arterial and venous thromboembolic complications. Additional risk factors for these thrombotic traits may be concurrent (known or unknown) malignancies, including at hepatic level. Among these, cholangiocarcinoma (CCA), a rare cancer of intra- and extra-hepatic biliary ducts, represents a very aggressive condition that typically associates local and distant advanced stages on first presentation requiring a prompt diagnosis and a stratified management. This neoplasia has been reported to present a large spectrum of paraneoplastic syndromes in terms of dermatologic, renal, systemic, neurologic, endocrine, and cardiovascular settings, that, overall, are exceptional in their epidemiologic impact when compared to other cancers. Our aim was to introduce a most unusual case of CCA-associated distant thrombosis in a male adult who initially was considered to experience COVID-19-related thrombotic features while having a history of obesity and bariatric surgery. This is a hybrid type of paper: this clinical vignette is accompanied by two distinct sample-focused analyses as a basis for discussion; they each had different methods depending on their current level of statistical evidence. We only included English-published articles in PubMed, as follows: Firstly, we conducted a search of reports similar to the present case, regarding distant vein thrombosis in CCA, from inception until the present time. We performed a literature search using the keywords “cholangiocarcinoma”, “thrombosis”, and “Trousseau’s syndrome” and identified 20 cases across 19 original papers; hence, the current level of evidence remains very low Secondly, we searched for the highest level of statistical evidence concerning the diagnosis of venous thrombosis/thromboembolism in patients who underwent COVID-19 infection (key search terms were “COVID-19”, alternatively, “coronavirus”, and “SARS-CoV-2”, and “thrombosis”, alternatively, “thromboembolism”) and included the most recent systematic reviews and meta-analyses that were published in 2024 (from 1 January 2024 until 8 July 2024). After excluding data on vaccination against coronavirus or long COVID-19 syndrome, we identified six such articles. To conclude, we presented a probably unique case of malignancy with an initial manifestation consisting of recurrent superficial vein thrombosis under anticoagulation therapy, with no gastrointestinal manifestations, in a patient with a notable history for multiple episodes of SARS-CoV-2 infection and a prior endocrine (gastric) surgery. To our knowledge, this is the first identification of a CCA under these specific circumstances.

Non-functioning adrenal incidentalomas (NFAIs) have been placed in relationship with a higher risk of glucose profile anomalies, while the full-blown typical picture of Cushing’s syndrome (CS) and associated secondary (glucocorticoid-induced) diabetes mellitus is not explicitly confirmed in this instance. Our objective was to highlight the most recent data concerning the glucose profile, particularly, type 2 diabetes mellitus (T2DM) in NFAIs with/without mild autonomous cortisol secretion (MACS). This was a comprehensive review of the literature; the search was conducted according to various combinations of key terms. We included English-published, original studies across a 5-year window of publication time (from January 2020 until 1 April 2024) on PubMed. We excluded case reports, reviews, studies on T1DM or secondary diabetes, and experimental data. We identified 37 studies of various designs (14 retrospective studies as well 13 cross-sectional, 4 cohorts, 3 prospective, and 2 case–control studies) that analysed 17,391 individuals, with a female-to-male ratio of 1.47 (aged between 14 and 96 years). T2DM prevalence in MACS (affecting 10 to 30% of NFAIs) ranged from 12% to 44%. The highest T2DM prevalence in NFAI was 45.2% in one study. MACS versus (non-MACS) NFAIs (n = 16) showed an increased risk of T2DM and even of prediabetes or higher fasting plasma glucose or HbA1c (no unanimous results). T2DM prevalence was analysed in NFAI (N = 1243, female-to-male ratio of 1.11, mean age of 60.42) versus (non-tumour) controls (N = 1548, female-to-male ratio of 0.91, average age of 60.22) amid four studies, and two of them were confirmatory with respect to a higher rate in NFAIs. Four studies included a sub-group of CS compared to NFAI/MACS, and two of them did not confirm an increased rate of glucose profile anomalies in CS versus NFAIs/ACS. The longest period of follow-up with concern to the glycaemic profile was 10.5 years, and one cohort showed a significant increase in the T2DM rate at 17.9% compared to the baseline value of 0.03%. Additionally, inconsistent data from six studies enrolling 1039 individuals that underwent adrenalectomy (N = 674) and conservative management (N = 365) pinpointed the impact of the surgery in NFAIs. The regulation of the glucose metabolism after adrenalectomy versus baseline versus conservative management (n = 3) was improved. To our knowledge, this comprehensive review included one of the largest recent analyses in the field of glucose profile amid the confirmation of MACS/NFAI. In light of the rising incidence of NFAI/AIs due to easier access to imagery scans and endocrine evaluation across the spectrum of modern medicine, it is critical to assess if these patients have an increased frequency of cardio-metabolic disorders that worsen their overall comorbidity and mortality profile, including via the confirmation of T2DM.

Camelia Stanciu Gavan, Adelina Birceanu, and Cezar Betianu were not included as authors in the original publication [...]

Petrified ear (PE), an exceptional entity, stands for the calcification ± ossification of auricular cartilage (CAC/OAC); its pathogenic traits are still an open matter. Endocrine panel represents one of the most important; yet, no standard protocol of assessments is available. Our objective was to highlight most recent PE data and associated endocrine (versus non-endocrine) ailments in terms of presentation, imagery tools, hormonal assessments, biopsy, outcome, pathogenic features. This was a comprehensive review via PubMed search (January 2000–March 2024). A total of 75 PE subjects included: 46 case reports/series (N = 49) and two imagery-based retrospective studies (N = 26) with CAC/OAC prevalence of 7–23% (N = 251) amid routine head/temporal bone CT scans. Endocrine PE (EPE): N = 23, male/female ratio = 10.5; average age = 56.78, ranges: 22–79; non-EPE cohort: N = 26; male/female ratio = 1.88, mean age = 49.44; ranges: 18–75 (+a single pediatric case).The longest post-diagnosis follow-up was of 6–7 years. The diagnosis of PE and endocrine anomalies was synchronous or not (time gap of 10–20 years). A novel case in point (calcified EPE amid autoimmune poly-endocrine syndrome type 2 with a 10-year post-diagnosis documented follow-up) was introduced. We re-analyzed EPE and re-classified another five subjects as such. Hence, the final EPE cohort (N = 50) showed: adrenal insufficiency was the most frequent endocrine condition (36%) followed by hypopituitarism (22%) and hypothyroidism (18%); 39% of the patients with adrenal failure had Addison’s disease; primary type represented 72% of all cases with hypothyroidism; an endocrine autoimmune (any type) component was diagnosed in 18%. We propose the term of “endocrine petrified ear” and a workflow algorithm to assess the potential hormonal/metabolic background in PE.

Adrenal incidentalomas (AIs) are clinically silent adrenal masses that are unintentionally found during various abdominal imaging procedures. Our objective was to evaluate the bone profile in menopausal females diagnosed with AI versus a non-AI control group. This was an observational, retrospective, multi-centric, case-control study, a sub-analysis of PRECES study (“Parameters of Romanian Patients with Endocrine Conditions with or without Endocrine Surgery: real-world-evidence and retrospective study”), a multi-centric, Romanian collaborative in the field of endocrinology and connected specialities (real-world community setting). Inclusion criteria: women in menopause between 40 and 85 years. Ex-clusion criteria: active endocrine tumours or cancers, prior or current medication against osteoporosis. Assessments included bone turnover markers, central DXA, FRAX-based os-teoporotic fracture risk evaluation. AIs were defined as having a value of second day plas-ma morning cortisol after 1-mg dexamethasone suppression test of < 1.8 µg/dL [without mild autonomous cortisol secretion (MACS free), as seen in control group that did not dis-play the imaging evidence of an adrenal tumour] or between 1.8 and 5 µg/dL (MACS sub-group). Results: Demographic features of both groups (N=39 versus 95 patients) were simi-lar in terms of age (60.95±10.46 versus 61.55±7.2 years), years since menopause (14.92±10.32 versus 14.52±8.85 years), body mass index (28.03 versus 27 kg/sqcm); (p>0.1 for each). Osteopenia was the most prevalent DXA category in each group (43.6% versus 53.7%), followed by osteoporosis (20.5% versus 22.1%), while lumbar, total hip, femoral neck BMD were similar between AIs and controls. A statistically significant lower osteocal-cin in subjects with AIs, with a median (Q1, Q3) of 16.5 (11.96-20.09) ng/mL compared with the value in control groups of 23.17 (15.9-31.46) ng/mL (p=0.003) was found. In AIs group, serum baseline morning cortisol positively correlated with lumbar Z-score, and correlation coefficient reached a statistical significance (p = 0.035). Of note, a tendency for correlation with total hip BMD was found, too. To conclude, decreased osteocalcin might be the signa-ture of mild cortisol anomalies in AIs, but DXA-BMD and FRAX algorithm revealed similar parameters in AI group versus controls, as found between MACS and MACS free sub-groups.

Primary osteoporosis, a geriatric bone metabolic condition affecting both the mineral density and the microarchitecture, comes with a complex burden. Bone turnover markers tidily reflect the changes of skeleton status that are part of the physiological process or theyhighlight the abnormal status including in osteoporosis in addition to other biomolecules evaluation such as hormones, inflammatory markers, myokines and adipokines. In this narrative review, we aimed to highlight several aspects regarding osteoporosis-related rehabilitation amid mitigating the role of physical exercise as bone formation booster. Bone turnover markers assays, by capturing the essence of the bone remodelling, registered a great progress during latest years, thus show-ing an enhanced index of applicability in daily practice (despite being known and studied for more than three decades). Irisin, a novel player in the muscle-bone-metabolism cross-talk, represents a muscle-derivate hormone that is expected to highlight the interplay between physical exercise and bone formation. Other concurrent signal transduction pathways include recently described biomarkers such as preptin or the spectrum associated with serotonin-LRP5-Wnt/beta catenin canonical and non-canonical loops. Current pitfalls of the topic include the personalized recommendation of physical activity due to severe co-morbidities, the lack of homogenous studies to measure the intervention and the consecutive bone health and great variations of using the bone turnover markers amid daily practice in different centers. To conclude, part of the monitoring protocol in osteoporotic patients under specific medication against osteoporosis or during bisphosphonates drug holiday, bone turnover markers assays stands for a practical insight in every day practice. The contributing role of physical exercise to boost bone formation as reflected by these biomolecules is well understood across a multitude of signal transduction pathways. However, a current gap in practical use and surveillance of the prescription of physical activity, mechanical load and rehabilitation programs in these patients is confirmed so far.

Zoledronate (or zoledronic acid) represents a standard (guideline-based) approach in the area of anti-resorptive medication (namely, an annual 15-minute perfusion of 5 mg for os-teoporosis treatment), while the same drug (with doses/regimes variations) is used for other bone metabolic conditions such as Paget’s disease of the bone or skeleton metastasis originating from different cancers. The objective of this narrative review was to highlight the most recent published data with respect to zoledronic acid use as part of the complex clinical management amid primary osteoporosis in addition to other osteo-metabolic clin-ical entities. This was a research based on exploring PubMed database with respect to the search words “zoledronic acid” and “primary osteoporosis”. We included highly relevant (from the clinical perspective), English-published, full-length articles that have been re-cently published (between January 2023 and March 2024). From 249 results, 31 articles met the inclusion timeline criteria across the 15-month analysis and the final results were based on data provided from 16 articles. Important insights concern not only the zoledronic acid administration, the efficacy and the safety profile, but, also, an extension on daily indications with concern to diabetic bone disease, liver osteodystrophy, osteogen-esis imperfecta or Paget’s disease of the bone.

Neuroendocrine neoplasia (NEN) represents a sensational field of modern medicine; immense progress in emerging biochemical, molecular, endocrine, immunohistochemical, and serum tumour markers of disease, respectively, which are part of early diagnosis, genetic testing, and multidisciplinary approaches [...]

Primary cardiac tumours are relatively uncommon (75% are benign). Across the other 25%, representing malignant neoplasia, sarcomas account for 75–95%, and primary cardiac intimal sarcoma (PCIS) is one of the rarest findings. We aimed to present a comprehensive review and practical considerations from a multidisciplinary perspective with regard to the most recent published data in the specific domain of PCIS. We covered the issues of awareness amid daily practice clinical presentation to ultra-qualified management in order to achieve an adequate diagnosis and prompt intervention, also emphasizing the core role of MDM2 immunostaining and MDM2 genetic analysis. An additional base for practical points was provided by a novel on-point clinical vignette with MDM2-positive status. According to our methods (PubMed database search of full-length, English publications from January 2021 to March 2023), we identified three studies and 23 single case reports represented by 22 adults (male-to-female ratio of 1.2; male population with an average age of 53.75 years, range: 35–81; woman mean age of 55.5 years, range: 34–70) and a 4-year-old child. The tumour-related clinical picture was recognized in a matter of one day to ten months on first admission. These non-specific data (with a very low index of suspicion) included heart failure at least NYHA class II, mitral regurgitation and pulmonary hypertension, acute myocardial infarction, ischemic stroke, obstructive shock, and paroxysmal atrial fibrillation. Awareness might come from other complaints such as (most common) dyspnoea, palpitation, chest pressure, cough, asthenia, sudden fatigue, weakness, malaise, anorexia, weight loss, headache, hyperhidrosis, night sweats, and epigastric pain. Two individuals were initially misdiagnosed as having endocarditis. A history of prior treated non-cardiac malignancy was registered in 3/23 subjects. Distant metastasis as the first step of detection (n = 2/23; specifically, brain and intestinal) or during follow-up (n = 6/23; namely, intestinal, brain and bone, in two cases for each, and adrenal) required additional imagery tools (26% of the patients had distant metastasis). Transoesophageal echocardiography, computed tomography (CT), magnetic resonance imagery, and even 18F-FDG positronic emission tomography-CT (which shows hypermetabolic lesions in PCIS) represent the basis of multimodal tools of investigation. Tumour size varied from 3 cm to ≥9 cm (average largest diameter of 5.5 cm). The most frequent sites were the left atrium followed by the right ventricle and the right atrium. Post-operatory histological confirmation was provided in 20/23 cases and, upon tumour biopsy, in 3/23 of them. The post-surgery maximum free-disease interval was 8 years, the fatal outcome was at the earliest two weeks since initial admission. MDM2 analysis was provided in 7/23 subjects in terms of MDM2-positive status (two out of three subjects) at immunohistochemistry and MDM2 amplification (four out of five subjects) at genetic analysis. Additionally, another three studies addressed PCISs, and two of them offered specific MDM2/MDM2 assays (n = 35 patients with PCISs); among the provided data, we mention that one cohort (n = 20) identified a rate of 55% with regard to MDM2 amplification in intimal sarcomas, and this correlated with a myxoid pattern; another cohort (n = 15) showed that MDM2-positive had a better prognostic than MDM2-negative immunostaining. To summarize, MDM2 amplification and co-amplification, for example, with MDM4, CDK4, HMGA3, CCND3, PDGFRA, TERT, KIT, CCND3, and HDAC9, might improve the diagnosis of PCIS in addition to MDM2 immunostaining since 10–20% of these tumours are MDM2-negative. Further studies are necessary to highlight MDM2 applicability as a prognostic factor and as an element to be taken into account amid multi-layered management in an otherwise very aggressive malignancy.

Background: The evolving association of neurological disorders such as Parkinson's disease (PD) and stroke may aggravate postmenopausal osteoporosis. In this situation, inactivity and lack of movement are the main factors that contribute contribute to exacerbate osteoporosis and the occurrence of osteoporotic fractures. Material and Methods: We present the case of a 62-year-old female patient diagnosed with diffuse postmenopausal osteoporosis, Parkinson's disease, and left frontal ischemic lacuna. 6 months before admission to our rehabilitation clinic, she suffered a trauma by falling that resulted in an L3 vertebral fracture and a right forearm fracture. L2-L4 posterior segmental spinal fusion and right forearm osteosynthesis were per-formed. Postoperatively, a motor deficit was found in the lower limbs. She was diagnosed clin-ically and following neurophysiological investigations with bilateral external popliteal sciatic nerve paresis. In these circumstances, the patient suffered a new trauma, resulting in an open fracture at the same level of the right forearm which also required surgical treatment. Results and discussion: Following the rehabilitation program, the evolution was favorable with im-proved functioning and partial restoration of walking. Conclusion: The association of degener-ative neurological and bone metabolic diseases in this case led to significant disability, making the rehabilitation process more challenging.

Our objective was to overview recent data on metabolic/endocrine disorders with respect to e-cigarette (e-cig) use. This is a narrative review; we researched English, full-length, original articles on PubMed (between January 2020 and August 2023) by using different keywords in the area of metabolic/endocrine issues. We only included original clinical studies (n = 22) and excluded case reports and experimental studies. 3 studies (N1 = 22,385; N2 = 600,046; N3 = 5101) addressed prediabetes risk; N1 showed a 1.57-fold increased risk of dual vs. never smokers, a higher risk that was not confirmed in N2 (based on self-reported assessments). Current non-smokers (N1) who were dual smokers still have an increased odd of prediabetes (a 1.27-fold risk increase). N3 and another 2 studies addressed type 2 diabetes mellitus (DM): a lower prevalence of DM among dual users (3.3%) vs. cigarette smoking (5.9%) was identified. 6 studies investigated obesity profile (4 of them found positive correlations with e-cig use). One study (N4 = 373,781) showed that e-cig use was associated with obesity in the general population (OR = 1.6, 95%CI: 1.3–2.1, p < 0.05); another (N5 = 7505, 0.82% were e-cig-only) showed that obesity had a higher prevalence in dual smokers (51%) vs. cig-only (41.2%, p < 0.05), while another (N6 = 3055) found that female (not male) e-cig smokers had higher body mass index vs. non-smokers. Data on metabolic syndrome (MS) are provided for dual smokers (n = 2): one case–control study found that female dual smokers had higher odds of MS than non-smokers. The need for awareness with respect to potential e-cig-–associated medical issues should be part of modern medicine, including daily anamnesis. Whether the metabolic/endocrine frame is part of the general picture is yet to be determined. Surveillance protocols should help clinicians to easily access the medical background of one subject, including this specific matter of e-cig with/without conventional cigarettes smoking and other habits/lifestyle elements, especially when taking into consideration metabolism anomalies.

Our purpose was to introduce a case on point of a menopausal woman who suffered a domestic fall with consecutive persistent back pain and reduced mobility, and delayed the presentation amid late COVID-19 pandemic. On admission, she was confirmed with osteoporosis according to DXA (lowest T-score of -5.5) and started zoledronate. She refused further orthopedic intervention and remained on non-invasive long term rehabilitation plan while surveillance of anti-osteoporotic medication was offered to her. Fragility vertebral fractures represent increasingly common issues that require prompt intervention to overall a better prognosis. Late presentation and a first diagnosis of 10 vertebral fractures is a part of real life medicine with consequences amid potential lack of compliance to medication and adherence to a rehabilitation plan with short term and long term effects. Transition to post-pandemic reality still represents a concurrent pitfall to delayed hospitalization.

We aim was to present a case of severe osteoporosis with concern to an adult female who was under specific medication against the condition while she experienced inexplicable weight loss in association with an incidental fracture inconsistent with DXA changes. Challenges of the case management and decision making are further on explained. Real-life-medicine poses multiple issues that require an individual decision while respecting the standard protocols. That is why a generalized decision is rather impractical. Here we introduce the clinical case of a lady in her late 60s with a known 6-year history of osteoporosis that required several difficult decisions along surveillance: at first, zoledronic acid represented an available solution, yet after one year, BMD decreased and adjustment was done by initiating a second sequence according to the teri-paratide protocol. DXA-BMD, as well as the spectrum of bone turnover markers, qualified the patient as responsive and she further continued with oral bisphosphonates while being moni-tored via telemedicine amid COVID-19 pandemic. After 24 more months, a second decision of zoledronic acid was done, despite prior partial response, but digestive complains restricted the oral administration of anti-osteoporotic drugs. After one more year, denosumab was initiated and consecutive follow-up is essential. At this point, another challenging aspect was revealed: the discordance between DXA – based scores increase and the presence of an incidental fracture. A supplementary investigation was considered useful (Tc- whole body scintigraphy) noting the clinical presentation with local pain, dysfunctionality, and mild weight loss that also required rehabilitation management.

Diagnosis of primary hyperparathyroidism (PHP) is based on blood assessments in terms of synchronous high calcium and PTH (parathormone), but further management, particularly parathyroid surgery that provides the disease cure in 95–99% of cases, requires an adequate localisation of the parathyroid tumour/tumours as the originating source, with ultrasound and 99m-Technetium (99m-Tc) sestamibi scintigraphy being the most widely used. We aimed to introduce an adult female case diagnosed with PHP displaying unexpected intra-operatory findings (ectopic thyroid tissue) in relation to concordant pre-operatory imaging modalities (ultrasound + dual-phase 99m-Tc pertechnetate and sestamibi scintigraphy + computed tomography) that indicated bilateral inferior parathyroid tumours. A sudden drop in PTH following the removal of the first tumour was the clue for performing an extemporaneous exam for the second mass that turned out to be non-malignant ectopic thyroid tissue. We overviewed some major aspects starting from this case in point: the potential pitfalls of pre-operatory imaging in PHP; the concordance/discordance of pre-parathyroidectomy localisation modalities; the need of using an additional intra-operatory procedure; and the clues of providing a distinction between pathological parathyroids and thyroid tissue. This was a case of adult PHP, whereas triple localisation methods were used before parathyroidectomy, showing concordant results; however, the second parathyroid adenoma was a false positive image and an ectopic thyroid tissue was confirmed. The pre-operatory index of suspicion was non-existent in this patient. Hybrid imaging modalities are most probably required if both thyroid and parathyroid anomalies are suspected, but, essentially, awareness of the potential pitfalls is mandatory from the endocrine and surgical perspectives. Current gaps in imaging knowledge to guide us in this area are expected to be solved by the significant progress in functional imaging modalities. However, the act of surgery, including the decision of a PTH assay or extemporaneous exam (as seen in our case), represents the key to a successful removal procedure. Moreover, many parathyroid surgeons may currently perform 4-gland exploration routinely, precisely to avoid the shortcomings of preoperative localisation.

In this narrative review, we aimed to overview the interplay between lichen planus (LP) and thyroid conditions (TCs) from a dual perspective (dermatologic and endocrine), since a current gap in understanding LP-TC connections is found so far and the topic is still a matter of debate. We searched PubMed from Inception to October 2023 by using the key terms “lichen planus” and “thyroid”, (alternatively, “endocrine” or “hormone”). We included original clinical studies in humans according to three sections: LP and TC in terms of dysfunction, autoimmunity, and neoplasia. Six studies confirmed an association between the thyroid dysfunction (exclusively hypothyroidism) and LP/OL (oral LP); of note, only one study addressed cutaneous LP. The sample size of LP/OLP groups varied from 12–14 to 1500 individuals. Hypothyroidism prevalence in OLP was of 30–50%. A higher rate of levothyroxine replacement was identified among OLP patients, at 10% versus 2.5% in controls. The highest OR (odd ratio) of treated hypothyroidism amid OLP was of 2.99 (p < 0.005). Hypothyroidism was confirmed to be associated with a milder OLP phenotype in two studies. A single cohort revealed a similar prevalence of hypothyroidism in LP versus non-LP. Non-confirmatory studies (only on OLP, not cutaneous LP) included five cohorts: a similar prevalence of hypothyroidism among OLP versus controls, and a single cohort showed that the subjects with OLP actually had a lower prevalence of hypothyroidism versus controls (1% versus 4%). Positive autoimmunity in LP/OLP was confirmed in eight studies; the size of the cohorts varied, for instance, with 619 persons with LP and with 76, 92, 105, 108, 192, 247, and 585 patients (a total of 1405) with OLP, respectively; notably, the largest control group was of 10,441 individuals. Four clusters of approaches with respect to the autoimmunity in LP/OLP were found: an analysis of HT/ATD (Hashimoto’s thyroiditis/autoimmune thyroid diseases) prevalence; considerations over the specific antibody levels; sex-related features since females are more prone to autoimmunity; and associations (if any) with the clinical aspects of LP/OLP. HT prevalence in OLP versus controls was statistically significantly higher, as follows: 19% versus 5%; 12% versus 6%; and 20% versus 9.8%. A single study addressing LP found a 12% rate of ATDs. One study did not confirm a correlation between OLP-associated clinical elements (and OLP severity) and antibody values against the thyroid, and another showed that positive TPOAb (anti-thyroperoxidase antibodies) was more often found in erosive than non-erosive OLP (68% versus 33%). Just the reverse, one cohort found that OLP subjects had a statistically significantly lower rate of positive TPOAb versus controls (9% versus 15%). Five case-control studies addressed the issue of levothyroxine replacement for prior hypothyroidism in patients that were diagnosed with OLP (no study on LP was identified); three of them confirmed a higher rate of this treatment in OLP (at 8.9%, 9.7%, and 10.6%) versus controls. In conclusion, with regard to LP/OLP-TC, we note several main aspects as practical points for multidisciplinary practitioners: OLP rather than LP requires thyroid awareness; when it comes to the type of thyroid dysfunction, mostly, hypothyroidism should be expected; female patients are more prone to be associated with ATDs; a potential higher ratio of OLP subjects taking levothyroxine was found, thus a good collaboration with an endocrinology team is mandatory; and so far, OLP individuals have not been confirmed to be associated with a higher risk of thyroid nodules/cancer.

Our aim is to update the topic of adrenal tumours (ATs) in congenital adrenal hyperplasia (CAH) based on a multidisciplinary, clinical perspective via an endocrine approach. This narrative review is based on a PubMed search of full-length, English articles between January 2014 and July 2023. We included 52 original papers: 9 studies, 8 case series, and 35 single case reports. Firstly, we introduce a case-based analysis of 59 CAH-ATs cases with four types of enzymatic defects (CYP21A2, CYP17A1, CYP17B1, and HSD3B2). Secondarily, we analysed prevalence studies; their sample size varied from 53 to 26,000 individuals. AT prevalence among CAH was of 13.3–20%. CAH prevalence among individuals with previous imaging diagnosis of AT was of 0.3–3.6%. Overall, this 10-year, sample-based analysis represents one of the most complex studies in the area of CAH-ATs so far. These masses should be taken into consideration. They may reach impressive sizes of up to 30–40 cm, with compressive effects. Adrenalectomy was chosen based on an individual multidisciplinary decision. Many tumours are detected in subjects with a poor disease control, or they represent the first step toward CAH identification. We noted a left lateralization with a less clear pathogenic explanation. The most frequent tumour remains myelolipoma. The risk of adrenocortical carcinoma should not be overlooked. Noting the increasing prevalence of adrenal incidentalomas, CAH testing might be indicated to identify non-classical forms of CAH.

Acromegaly, a GH (Growth Hormone) excess – related condition, has co-morbidities varying from cardio-metabolic events, sleep apnea, osteoporotic fractures, and oncologic risk especially of colonic cancer up to oral, facial and dental anomalies. We aim to briefly revise oro-dental status in acromegalic patients through a multidisciplinary perspective. This is a review of literature. Because of GH and IGF1 (Insulin-like Growth Factor) actions, a wide area of anomalies are registered, for example, mandibular protrusion, widening of maxillary, increased spaces between teeth, malocclusion, thick lips, all of them causing functional impairment and facial appearance changes. Oro-facial manifestations are among earliest signs; however, the acromegaly phenotype is recognizable after more than a decade of biochemical exposure to GH excess (unrecognized, untreated and/or uncontrolled acromegaly). The mentioned anomalies require a specialized team of medical dentists, and orthodontists, as well as otorhinolaryngology practitioners in addition to endocrinologists. Mandibular ramus has a larger height in acromegaly, main characteristic being increased L1/MP (labial inclination of mandibular central incisors) which might function as a discriminator parameter from non-acromegalic malocclusion. Some individuals might experience gingivitis, moderate chronic periodontitis or bulky oral bony outgrowths according to AcroDent study. Another consistent chapter of dental and periodontal complications is provided by the presence of secondary diabetes mellitus in acromegalic patients, a “sweet” complication that is controlled at the point when GH excess is controlled, due to hyperglycemic effect of GH and associated insulin resistance. An additional perspective on facial bones is related to GH excess – induced bone remodeling pattern that delays some dental procedures since acromegaly stabilization is mandatory first. Incrementally, the delay of dental intervention limits the dental management, finally requiring prosthetic approach. In the meantime, increased bone turnover associates anomalies of skeleton micro-architecture and increased osteoporotic fracture risk. High bone turnover should be taken into consideration when planning implant surgery. Awareness among dentists and orthodontists is essential to early recognition of acromegaly and its complications in order to improve the outcome. A close collaboration with endocrinologists is required.

The term of “incidentaloma” involves multiple disciplines of the medicine, especially on the era of modern medicine with massive progress of investigations tools that increased the epidemiological implications of this entity. “Endocrine incidentaloma” represents a term mostly used for adrenals and pituitary glands (and less used for thyroid where it is replaced by the term of “thyroid nodule”). Adult adrenal incidentaloma (AAI) is expected to be found up to 5-20% of population depending on age group, co-morbidities, radiological/imaging method (the incidence increases with age), and not in children. We aim to overview the spectrum of pediatric AI (PAI) as an umbrella term for various histological and endocrine conditions. This is a brief narrative review of literature. Inclusion criteria are: PubMed published papers, in extenso articles (English language), the year of publication between 2016 and 2021; the selection is based on clinical relevance. A number of 70 references is included. PAI may be related to various tumors of the cortex and medulla, while AAI mostly means an adrenocortical adenoma with a very good prognostic. AAI diagnostic (based not only on radiological, but also an endocrine assessment) exceptionally underlines an adrenocortical carcinoma or evolves to a malignancy while in pediatric population the eventuality of an incidental adrenocortical carcinoma is not so rare (the non-functional pattern is more frequent in children than in adults). Neural crest-derived tumors may be located at adrenal levels; while ganglioneuroma is a benign tumor which typically respects the incidental detection, neuroblastoma is mostly aggressive and the clinical presentation suggestive for a malignancy is more frequent rather than a completely asymptomatic picture. 10-14% of pheochromocytomas are incidentally detected; however, the adrenalectomy is imperative, regardless the phenotype. PAI represents a large multidisciplinary field which is still a matter of debate in certain areas. The key message is the fact that accidental detection of an adrenal mass on an apparently healthy child needs careful examination; serial follow-up is less likely the elective approach (opposite to adult population) since adrenalectomy provides adequate histological report in order to sustain the endocrine and imaging workup.

Acromegaly embraces typical complications of a pituitary tumor as well as GH (growth hormone) and IGF1 (insulin-like growth factor) excess-related cardio-metabolic and oncologic conditions; and associated medical, surgical treatment or even radiotherapy issues. We point out a few particular aspects concerning acromegaly issues amid COVID-19 pandemic. The review includes only full length, English published papers. One of the most important complications of long standing, untreated or un-responsive to therapy acromegaly is related to respiratory and otorhinolaryngology issues like sleep apnea; this becomes an important aspect causing pulmonary complications in patients with active coronavirus infection. In subjects who are not going through a COVID-19 infection, but they had a prior diagnostic of acromegaly, two main aspects of medical and surgical practice were noted: a massive reduction of surgical volume during the first year of pandemic, mostly during peak months of high infection rate in general population and the introduction of tele (digital) health care systems, of different protocols and various platforms mostly depending of medical center, rather than country or even continent related protocols. Associated central adrenal insufficiency requires a particular attention if COVID-19 positive. The data directly targeting the endocrinologists amid pandemic are very limited. ACROCOVID is a 2021 study that was internationally conducted based on a questionnaire that was applied to 84 endocrinologists (67% of them in Europe); 33% of acromegalic individuals had a delay on procedure because of insufficient COVID-19 assays and 54% of them due to inefficient provision for neurosurgery. Secondary diabetes mellitus (with a potential worsening in some patients due to pasireotide LAR) is at high risk for COVID-19 infection; the level of glycated hemoglobin A1c seems a good predictor at onset of infectious disease. Acromegaly might associate osteoporosis; coronavirus infection aggravates bone loss due to oxidative stress, inflammatory status, cytokine release, immobilization, glucocorticoid use. Acromegaly field concerning pandemic changes represents a complex, still ongoing matter involving both patients and multidisciplinary practitioners.

We aim to update the pandemic literature concerning thyroidectomies for benign and malign conditions. The inclusion criteria: PubMed published papers, the key words of research are “thyroidectomy” or “thyroid surgery” or “endocrine surgery” and “coronavirus”, “pandemic” or “COVID-19”. The reduction of thyroid ultrasound and fine needle aspiration is reflected in a lower volume of indications for surgery depending on the phases of pandemic and the rate of infections in general population. Imperative surgical approach is needed in cases with poor prognostic like poorly differentiated, undifferentiated, anaplastic and medullary carcinoma, while cases with well differentiated carcinoma originating from follicular cells associate a less aggressive behavior, thus the overall prognostic might not be affected if surgery is postponed. During the period of times with severe restrictions and high infection rates in general population, the delay of surgical procedures was unavoidable, thus scores of assigning the moment of operation were introduced as PAPS (Physician Assigned Priority Scoring) and MeNTS (Medically Necessary Time Sensitive). The need of assessing post-thyroidectomy complications is essential in situations when telemedicine is not a solution as severe cases of hypocalcemia, vocal folds damage, local liquid collections, etc. In conclusion, scores validation is still needed. Critical preoperatory decision takes into consideration the pandemic circumstances (COVID-19 status of the patient and of the health workers involved in the procedure). Use of digital health care systems might reduce the pre- and post-operatory burden. Overall, a reduction of thyroid surgery volume was registered during the first year of pandemic all over the world, while the procedure itself seems safe for the patient from a point of view related to the risk of coronavirus cross-infection.

Bilateral adrenal hemorrhage represents a challenging condition which requires multi-modal intervention. Our aim to systematically review the published cased diagnosed with this condition. The method we used is based on PubMed database research. The papers are published between 2005 and 2020. We included articles that follow the subsections: idiopathic type, hemorrhage in patients with adrenal tumors, in subjects with hematologic diseases, with autoimmune/systemic conditions, in COVID-19 positive patients, in subjects using anticoagulants, respective in pregnant females.

Coronavirus disease-2019 (COVID-19) heavily hits the human body through various and dramatic ways, and endocrine system is not an exception. Our purpose is to update the concepts around subjects diagnosed with Basedow disease (BD) before, after or during experiencing COVID-19 infection. This is a literature review based on full-length, English papers that are available through PubMed (published between 2020 and 2021). Angiotensinconverting enzyme 2 and transmembrane protease serine 2 receptors are expressed at thyroid level and this might explain why an active coronavirus infection activates the BD especially in patients with a potential predisposition. Also, the new diagnostic of BD might follow a COVID-19 infection (within weeks). Simultaneously dealing with both conditions requires a more challenging multidisciplinary management, while the diagnostic of thyroid condition after recovery from infection is more likely to follow the general pattern of evolution (as seen in non-COVID-19 cases). A previous diagnostic of autoimmune hyperthyroidism means mostly either: BD is remitted after prior medication treatment with anti-thyroid drugs and/or radioiodine therapy (normal thyroid function), the patient has iatrogenic hypothyroidism that was induced after thyroidectomy or after radioiodine therapy (requiring daily oral levothyroxine substitution) or the subject is under thiamazol (or similar drugs) with either controlled or uncontrolled thyroid function. Most of the clinical studies agree (but not all) that people with treated hypothyroidism and hyperthyroidism are not susceptible to a higher morbidity or mortality concerning coronavirus infection. One exception is concurrent medication with anti-thyroid drugs with a higher risk of agranulocytosis which is a prone condition to any kind of infection. Graves’ ophalmopathy may be synchronous or not with an active thyroid disease. Except for mild forms, typically the condition requires glucocorticoid therapy, preferably a short course of intravenous metiprednisolone which exposes the patient to a higher risk of an infection, including COVID-19. Recently, BD was suspected to be induced or aggravated by COVID-19 vaccination which is still a matter of discussion.

Scleroderma (systemic sclerosis) represents a challenging condition, usually requiring a multi-disciplinary team due to multi-organ involvement; it is mostly considered an autoimmune disease; the signature of the malady is the extensive fibrosis at the level of skin and multiple organs, associating endothelial/vessel damage and anomalies of immune response. We point out a few aspects concerning scleroderma-related osteoporosis. This is a literature review. Patients might associate low bone mineral density (the underling mechanisms are not entirely understood), thus an increased risk of fractures; so early recognition and treatment is mandatory for a better outcome. Some data showed that particularly vertebral fractures are prone to the condition. Almost half of individuals with the malady have osteoporosis (female prevalence, especially post-menopausal) and one third of them have an osteoporotic fracture. Older age and associated vitamin D deficiency increases the risk of fracture. Vitamin D has pleomorphic distribution, also targeting the immune modulation, cytokines puzzle, and the muscle-bone crosstalk in scleroderma. Hypovitaminosis D might be expected in these patients, while general D-supplementation has controversial benefits effects. Chronic inflammatory rheumatic conditions might benefit from the TBS use as fracture risk indicator through micro-architecture evaluation. It seems that patients with systemic sclerosis and malnutrition have lower TBS; high Dkk-1 serum levels (Dickkopf-1) is correlated with reduced TBS and advanced disease; TBS is correlated to the extent of microvascular complications; exposure to glucocorticoids (certain high-dose regimes) supplementary lowers TBS. Gastrointestinal complications are presented in 90% of patients with systemic sclerosis, involving fibrosis at any level which is a poor prognostic factor; malabsorption of nutrients and weight loss correlates with reduced bone formation while esophageal and gastric anomalies contraindicate the use of oral bisphosphonates for osteoporosis. Other abnormal elements of skeleton frame include: premature ovarian failure, serotonin system anomalies, chronic inflammation, potential side effects of immunosuppressant drugs. In patients with systemic sclerosis, the choices of medication targeting osteoporosis are limited; the use of intravenous bisphosphonates remains first line option (if renal function is adequate); the consideration of skin and esophageal anomalies is mandatory in the management of osteoporosis. Overall, the landscape of bone domain in systemic sclerosis is multi-leveled and some areas are still waiting for clear answers.

We aim to address incomplete procedures of adrenalectomy for pheochromocytoma (PHEO) on a bases of a mini-review. Dopamine, adrenaline and noradrenaline – secretor tumors are rare in general population, representing a neuroendocrine neoplasia with a strong genetic driving force and uncertain profile concerning a malignant behavior which may be less or more predicted based on initial post-operative report. There is no linear correlation with the post-operative recurrence in terms of clinical presentation, timing and prognostic. The first laparoscopic – based PHEO removal was done in 1992; and since then, the open procedure was replaced in majority of cases by the new gold standard – laparoscopic adrenalectomy; a current conversion rate is of 5%; alpha and beta - blockade is mandatory for preoperative management since an adrenergic crisis might be triggered by higher intraabdominal pressure during laparoscopy; bilateral PHEO may be addressed through one time procedure; minimally invasive technique is done trans-peritoneal or retroperitoneal; robotic – assisted laparoscopic procedure is the next logical step from traditional laparoscopy; in children, minimally invasive procedure is less likely to be used as in adults. Partial adrenalectomy (in terms of cortical - sparing technique) should be rarely performed for unilateral PHEO; its potential utility is for cases with non-feasible total removal due to tumor anatomy (like advanced local disease) or bilateral adrenal involvement in hereditary syndromes (like MEN 2A, VHL), especially in children and young adults to overcome the need of life long glucocorticoid replacement due to chronic adrenal insufficiency. A meta-analysis focusing on recurrence after total adrenalectomy revealed a 3% ratio after 2 years in PHEO. The percent for partial procedure is more than 10% depending on study. In conclusion, a particular aspect in PHEO management is the recurrence after an adrenalectomy, typically after a partial procedure. Unless bilateral involvement or a clear diagnostic of a hereditary syndrome involving bilateral PHEO, partial adrenalectomy should be limited.

This is a narrative review of literature. We focus on the issue of identifying a parathyroid adenoma without anomalies of function (non-functioning parathyroid adenoma) which is incidentally detected or not, via routine neck ultrasound or through advanced imaging techniques which are mostly performed for other conditions (like assessment of a non-parathyroid oncological condition or emergencies – related neck exploration). The traditional diagnostic of primary hyperparathyroidism is exclusively a biological one based on high calcium and parathormone (PTH), and only a second step of assessment actually involves the localization procedures. However, the detection of a parathyroid tumor does not necessarily mean that it is associated with an over-secretion of PTH. Ultrasound is usually followed by Tc Sestamibi scintigram and/or computed tomography is order to refer the patient to parathyroidectomy in cases with biological confirmation of primary or renal hyperparathyroidism; yet, in cases with non-functioning profile, there is no clear indication of further imaging exploration. In conclusion, the identification of a parathyroid adenoma is rarely associated with a normal parathyroid function and this entity, which most probably is an incidentaloma, is not a subject of particular guidelines yet. Whether it is necessary to continue with other imaging techniques as typically seen in primary hyperparathyroidism is still an open issue, and so is the panel of indications to perform its surgical removal instead of serial follow-up.

COVID-19 pandemic affected every aspect of medical life, including the field of adrenal glands (AG). Our purpose is to overview the literature concerning AG domain, especially adrenal surgery amid COVID-19 pandemic. The approach of adrenal tumors (AT) is reflected by two aspects: what happens to a patient known with an adrenal mass if COVID-19 infection is positive and the other is related to restrictions amid pandemic daily practice that involve AT surgery. Patients with AT underling active hormonal over-production are at higher risk of COVID-19 infection or at increased risk of developing a more severe form of coronavirus infection, for instance, via diabetes mellitus, high blood pressure, and obesity. During the first year of pandemic, especially if considering the periods with severe restrictions and lockdown, there was a massive reduction of adrenalectomies, when compare to the same months of the previous year. Several systems of deciding the timing of intervention were used; they is still an insufficient statistical validation of these scores until now. The reduction of surgery volume was less expressive during the second year of pandemic. The rate of peri-operatory infections is relatively low, but it depends on center. Post-operative adrenal insufficiency exposes the patient to a higher risk of infections, including coronavirus infection. Peri-operative management can be handle via telemedicine in most of cases.

Thyroid domain amid COVID-19 era has been involved in many ways, either in terms of patients with prior thyroid conditions who become COVID-19 positives, or coronavirus-induced de novo thyroid anomalies. This article represents a literature update on thyroid cancer (TC). The PubMed-based research includes a publication timeline regarding the first two years of pandemic (2020-2021). The general scientific interest on TC according to online research decreased during the first half of 2020 and got to the pre-pandemic level by the end of 2020. At the beginning of the pandemic, there was a delay in approaching the thyroid conditions, while telemedicine became a most useful tool, as seen in others areas of medicine. Post - 2020 lockdown medical presentation was associated with a more aggressive behavior of TC when compare to pre-pandemic data. Ongoing debates surround the topic of higher risk of COVID-19 infection in patients with a prior diagnostic of a thyroid malignancy in terms of having a higher risk of contracting the infection or an increased risk of developing a more severe form. There is not clear answer up to this point. Recent assets concerning TC field (non-COVID-19 data) that are released for the last two years concern the understanding of thyroid cancer genetics, the approach of shift from differentiated to anaplastic carcinoma, as well as evidence regarding new players in the oncological endocrinology like tyrosine kinase inhibitors for advanced forms of radioiodine refractory TC. For what we know so far, by the end of the second pandemic year, the patients with TC do not represent a fragile population when facing COVID-19 infection itself. However, the delay of adequate therapy amid restrictions is reflected in more severe malignancy behavior, while general concerns about the virus and pandemics increase the level of psychological and social stress. Case finding strategies to detect high risk patients as those on tyrosine kinase inhibitors with potential lung complications are needed.

This is a mini-review concerning hypercalcemia of malignancy that represents a challenging condition requiring rapid management, not only in relationship with short term complications, but also with long term mortality concerning the originating tumor approach (if feasible). Hypercalcemia on a patient with previously known or unknown cancer may be caused by dehydration, concurrent medication causing increased serum calcium levels, concomitant primary or renal hyperparathyroidism, over production of vitamin D (which may be tumor-related) or by specific circumstances that induce suppression of parathormone (PTH), so called PTH-independent mechanisms. Specific circumstances related to an active cancer means an ectopic production of parathormone, metastasis causing osteolytic lesions, tumors that produce PTHrP (parathormone related peptide) and abnormal production of 1,25-dihydroxyvitamin D by a hematologic malignancy. Parathyroid carcinoma induces an excess of PTH which is caused by a malignancy but it is not a PTH independent entity. Once a malignancy-related hypercalcemia is identified based on biological panel (mostly blood assays), the investigations are essentially continued with different imaging techniques depending on signs (if any), accessibility, etc. The approach is based on a multidisciplinary panel, on one hand, in order to restore normal levels of calcium, on the other hand, to rapidly address the underlying cause. This is essential to contribute to the outcome which typically is poor.

Parathyroid glands-related issues (also involving calcium-phosphorus metabolism) amid pandemic are represented by: complicated recovery after COVID-19 infection in cases with severe vitamin D (VD) deficiency or uncorrected hypocalcemia (hCa); the cases with primary hyperparathyroidism-related hypercalcemia who are postponed for parathyroid adenoma removal might be complicated with arrhythmia if the patient becomes COVID-19 positive; lockdown restrictions limited the physical activity, a situation which might aggravate sarcopenia and bone mineral density loss; subjects with renal hyperparathyroidism who do not have controlled values of serum calcium are at higher risk of severe COVID-19 infection due to a wide area of chronic renal failure-associated complications, including Ca, VD and PTH disturbances. This is an update concerning parathyroid glands in relationship to two-year pandemic experience. The mini-review of literature is based on PubMed navigation using a combination of key words like “parathyroid glands”, “parathyroid”, “parathormone”, “vitamin D”, “calcium” and “COVID-19” or “coronavirus” or “pandemic”. During the first months of COVID-19 pandemic there was a massive reduction of parathyroidectomies volume which was elective for severe forms associating life threatening values of serum calcium. The number of parathyroidectomies increased during the second year of pandemic Hypocalcemia remains a poor prognostic factor in severe COVID-19 infections while underling mechanisms are complex and might not be exclusively related to vitamin D deficiency which is a topic still on trends. Direct hypoparathyroidism is a new entity amid coronavirus-induced puzzle. E-health is mandatory to follow calcium correcting medication and associated life style intervention in cases with anomalies of calcium/PTH/VD levels.

Bilateral adrenal tumors (BAT) represent a vast domain of endocrinology and connected medical and surgical fields. Our purpose is to introduce several key points in relationship with long time management on a 56-year old female case who is currently admitted for reassessment of a left adrenal tumor with potential autonomous cortisol secretion. She is also known with pituitary incidentaloma since 2014, cerebral meningioma which was partially removed in 2015, uncontrolled diabetes mellitus under metformin and insulin therapy since 2017, and high blood pressure since 2021. Her medical history includes right adrenalectomy for Cushing syndrome in 2014. At that moment, she was first admitted for BAT, a tumor of 2 centimeters (cm) on the left gland according to computed tomography, respective of 3.5 cm maximum diameter on the right adrenal. The hormonal panel confirmed adrenal Cushing syndrome. After 6 months of non-interventional follow-up, the right tumor increased to 4 cm, also associating small areas of necrosis, thus a decision of unilateral laparoscopic adrenalectomy was done with good clinical post-operatory outcome. She did not develop adrenal insufficiency at any point in time, moreover, a low-normal ACTH (Adrenocorticotrop Hormone) with intermittent elevation of morning plasma cortisol levels after Dexamethasone suppression test showed a possible autonomous cortisol secretion of the left adrenal tumor during a 7-year follow-up. In 2014, the female patient received the confirmation of an adrenocortical adenoma which was consistent with cortisol over-secretion. Particular gene contributions are attributed to protein kinase A (PKA) defects (or B) that usually induce bilateral adrenocortical hyperplasia; however, they are not routinely tested in daily endocrine practice, neither had we performed it. Interestingly, the patient was detected with a cerebral meningioma after years of intermittent, mild headache. The diagnostic was established during initial endocrine evaluations. The headache was not associated with uncontrolled high blood pressure, as first expected due to excessive cortisol amount. Recently, it was identified that mutations of ARMC5 (armadillo repeat containing 5) gene are responsible for macronodular adrenal hyperplasia, but also meningioma. They may be also responsible for severe diabetes mellitus as seen here. The key points of following a patient with bilateral adrenal tumors include the timing of uni/bilateral adrenalectomy, the multidisciplinary management of associated complications, as well as the need of understanding the genetic rational behind it.

Early recognition of a pituitary secretor tumor offers a better prognostic; thus acromegaly might be recognized before the actual clinical picture of acromegaly is detectable. This is a 59-year old, non-smoking female admitted for: post-operatory evaluation of acromegaly. The clinical evaluation is non-specific. One year prior she was diagnosed with acromegaly based on cerebral imaging assessment due to intermittent headache. She was treated with cabergoline a few months before neurosurgery was done; post-operatory panel showed complete remission of acromegaly. Prompt detection of the disease allowed the early intervention with a very good outcome. The remission of GH excess after neurosurgery depends on tumor size and practical experience of the surgeon. The longer time of high growth hormone levels exposure the higher is the risk of cardio-metabolic and oncologic complications.

Renal cancer (RC) – associated increased calcium is rather frequent among cases of kidney neoplasia; it may be the first sign of presentation that allows the detection of the malignancy; typically representing a poor prognostic factor. Weight loss is part of the panel underling hypercalcemia - related signs, but also of the malignancy – associated phenotype. We aim to introduce a male case who was admitted for a clinical picture (including weight loss) correlated with alarming high calcium levels; the biochemistry anomaly was actually a paraneoplasic syndrome due to RC. When admitted as emergency, the assays revealed hypercalcemia of 16.9 mg/dl (normal levels between 8.4 and 10.2 mg/dl) with low PTH (Parathormone) and high CrossLaps as bone turnover marker of resorption. Intravenous contrast computed tomography showed a large left retroperitoneal tumor (involving the kidney and adrenal gland) with iodophil pattern, and post-contrast heterogeneous structure of 8.06/11.09 cm (axial), 10.58/12.16 cm (coronal - reconstruction), 9.12/10.59 cm (sagittal - reconstruction), also associating a mixt structure and micro-calcifications as well as hypodense areas. Whole body bone scintigrame did not show metastasis. The calcium levels were controlled under subcutaneous denosumab 60 mg in addition to IV fluids replacement; then the patient was referred to nephrectomy; post operatory confirmation confirmed a clear cell renal cell carcinoma (T4N1Mx). A normalization of calcium and PTH levels was found immediately after surgery. Unintentional weight loss might become a valuable tool in order to assess a routine biochemistry panel that will detect hypercalcemia. Low PTH represents the next step in order to further look for a tumor. Symptomatic control of hypercalcemia in addition to targeted approach of originating tumor are essential to improve the outcome.

There is an alarming increasing incidence of PBC (premenopausal breast cancer) in countries with high income due to, on one hand, more accessible screening tools and, on the other hand, potential implications of daily lifestyle habits and endocrine disruptors of modern society on terms of facilitating tumor growth. A more severe prognostic is found in females younger than 40 years old at first detection, with advanced disease at diagnostic, and those with tumors displaying specific immunohistochemistry configuration (and associated gene profile) like ER (estrogen receptor) positive or HEGFR2 (human epidermal growth factor receptor) negative. Recently, particular aspects are reported in terms of PBC therapy: the switch from offering aromatase inhibitors/tamoxifen only in post-menopausal females was done to premenopausal subjects in addition to medication that offers ovarian function suppression (OFS) – as an alternative to classical oophorectomy - for 5 years up to 10 years extension depending on protocol and patient’ age at first diagnostic. The main endocrine considerations concerning PBC are: OFS and/or chemotherapy or oophorectomy causing prompt hypogonadism, bone status anomalies due to estrogens deficiency, potential endocrine tumors that are prone to be linked (for instance, a higher risk of cancer in acromegalic patients etc.), cardio-metabolic elements as facilitators of early tumorigenesis, fertility issues on PBC survivals etc. The purpose of the present paper is to introduce several key messages that relate to endocrine implications of PBC starting from a case.

Hemoptysis as first sign of a thyroid differentiated cancer represents an atypical behavior of a cervical mass, usually associating lung metastasis or direct tracheal invasion. Late presentation (for instance, due to COVID-19 pandemic circumstances) associates a poor prognosis. This is a case report. We aim to introduce a 70-year old female case who was admitted for an atypical cervical mass associating hemoptysis as onset; the diagnostic of metastatic papillary thyroid cancer was established; the delay of hospital admission did not allow a radical intervention with curative purpose. The lady was admitted as an emergency for an endocrine checkup of a progressively growing cervical mass in addition to hemoptysis that developed a few weeks before. Specific blood endocrine panel confirmed the normal thyroid function with negative thyroid autoimmunity. Anterior cervical ultrasound showed intensely hypoechoic, inhomogeneous, large structure, with macro-calcifications (TIRADS 5). Fine needle aspiration cytology exam revealed a papillary carcinoma of thyroid, consistent with Bethesda 6 score. Computed tomography detected a voluminous thyroid tumor process of 92 by 58 by 89 mm. The superior, middle and inferior left later-cervical lymph nodes which are located posterior to the later-cervical vascular package, have maximum diameters of approximately 30/34 mm (axial) and 54 mm (vertical). Multiple micro-nodules of oval form in both lungs have diameters up to 29 mm (probably secondary lesions). Osteolytic tumor lesion at the level of the lateral arch of the vertebral body thoracic T 1 and the head of the left first rib extends to the level of the left foramen from the spaces cervical C7 to thoracic T1, respective between thoracic T1 and T2, with maximum diameters of 23/32 mm. CT also showed brain metastasis, as a iodophil, inhomogeneous, well-contoured tumor that is located on the right frontal precentral gyrus, with maximum diameters of 10/13 mm (axially) and 13 mm (vertically) and small areas of perilesional edema. Further adjuvant therapy was refused by the patient; palliative tracheostomy is needed. Atypically aggressive presentation of well differentiated thyroid cancer of papillary type might be associated with delayed presentation; whether this comes as direct consequence of pandemic era is still a matter of debate.

In 2021, the scientific community was marked by the introduction of vaccine against COVID-19. This is major step in overcoming the pandemic, but it does not mean that several side effects or precautions are not related to the immunization; however, the current level of statistical evidence concerning potential negative effects is low, as logically expected at this point. We aim to introduce a female case who was confirmed with subacute thyroiditis after COVID-19 vaccination. Prompt recognition of subacute thyroiditis avoids unnecessary investigations, hospitalizations or even exposure to antibiotics as seen in this case. Early intervention with anti-inflammatory medication releases the symptoms. The association with vaccine against COVID-19 might be incidental or not; more evidence is needed but as far as we might think nowadays, the connection is possible, thus the importance of specific awareness.

Our objective was to overview the most recent data on primary hyperparathyroidism (PHP) in children and teenagers from a multidisciplinary perspective. Methods: narrative review based on full-length, English-language papers (from PubMed, between January 2020 and July 2023). Results: 48 papers (14 studies of ≥10 subjects/study, and 34 case reports/series of MEN1, followed by CDC73, CASR, RET, and CDKN1B, as well as one case of VHL. Symptomatic PHP: 70–100% of all cases. Asymptomatic PHP: 60% of genetic PHP cases. Renal involvement: 10.5% of a cohort with genetic PHP, 71% of sporadic PHP cases; 50% (in a cohort with a mean age of 16.7), 29% (in a cohort with a mean age of 15.2); 0% (in infancy) to 50–62% (in teenagers). Bone anomalies: 83% of the children in one study and 62% of those in two other studies. Gastrointestinal issues: 40% of one cohort, but the data are heterogeneous. Cure rate through parathyroidectomy: 97–98%. Recurrent PHP: 2% of sporadic PHP cases and 38% of familial PHP cases. Hungry bone syndrome: maximum rate of 34–40%. Case reports identified another 7/41 subjects with the same post-parathyroidectomy condition; a potential connection with ectopic presentation or brown tumors is suggested, but there are limited data. Minimally invasive thoracoscopic approaches for ectopic tumors seemed safe. The current level of statistical evidence on pediatric PHP qualifies our study- and case-sample-based analysis (n = 48, N = 534) as one of the largest of its kind. Awareness of PHP is the key factor to benefit our young patients.

We aimed to overview the most recent data on sternal metastases from a multidisciplinary approach (diagnosis strategies, outcome, and histological reports). This narrative review based on a PubMed search (between January 2020 and 22 July 2023) using key words such as “sternal”, “manubrium”, and “metastasis” within the title and/or abstract only included original papers that specifically addressed secondary sternal spreading of cancer in adults, for a total of 48 original articles (14 studies and 34 single case reports). A prior unpublished case in point is also introduced (percutaneous incisional biopsy was used to address a 10 cm sternal tumour upon first admission on an apparently healthy male). The studies (n = 14) may be classified into one of three groups: studies addressing the incidence of bone metastases (including sternum) amid different primary cancers, such as prostate cancer (N = 122 with bone metastases, 83% of them with chest wall metastases), head and neck cancers (N = 3620, 0.8% with bone metastases, and 10.34% of this subgroup with sternum involvement); and glioblastoma (N = 92 with bone metastases, 37% of them with non-vertebral metastases, including the sternum); assessment cohorts, including breast cancer (N = 410; accuracy and sensitivity of PET/CT vs. bone scintigraphy is superior with concern to sternum spreading) and bone metastases of unknown origin (N = 83, including a subgroup with sternum metastases; some features of PET/CT help the differentiation with multiple myeloma); and cohorts with various therapeutic approaches, such as palliative arterial embolization (N = 10), thymic neuroendocrine neoplasia (1/5 detected with sternum metastases), survival rates for sternum metastases vs. non-sternum chest wall involvement (N = 87), oligo-metastatic (sternal) breast cancer (3 studies, N = 16 for all of them), oligo-metastatic head and neck cancer (N = 81), conformal radiotherapy (N = 24,215, including an analysis on sternum spreading), and EBRT followed by MR-HIFU (N = 6). Core data coming from the isolated case reports (N = 34) showed a female to male ratio of 1.6; the females’ ages were between 34 and 80 (mean of 57.28) and the males’ ages varied between 33 and 79 (average of 58.78) years. The originating tumour profile revealed that the most frequent types were mammary (N = 8, all females) and thyroid (N = 9, both women and men), followed by bladder (N = 3), lung (N = 2), and kidney (N = 2). There was also one case for each of the following: adenoid cystic carcinoma of the jaw, malignant melanoma, caecum MiNEN, a brain and an extracranial meningioma, tongue carcinoma, cholangiocarcinoma, osteosarcoma, and hepatocellular carcinoma. To our knowledge, this is the most complex and the largest analysis of prior published data within the time frame of our methods. These data open up new perspectives of this intricate, dynamic, and challenging domain of sternum metastases. Awareness is a mandatory factor since the patients may have a complex multidisciplinary medical and/or surgical background or they are admitted for the first time with this condition; thus, the convolute puzzle will start from this newly detected sternal lump. Abbreviations: N = number of patients; n = number of studies; PET/CT = positron emission tomography/computed tomography; EVRT = external beam radiotherapy; MR-HIFU = magnetic resonance-guided high-intensity focused ultrasound; MiNEN = mixed neuroendocrine-non-neuroendocrine tumour.

We introduce a case report of an adult male diagnosed with non-syndromic pheochromocytoma with a first pathological post-operatory report of malignant type with further re-considerations during follow-up for a 6-year period of time. This is 46 - year old male admitted for: post-adrenalectomy status reassessment. In 2013 he was diagnosed with high blood pressure requiring a complex regime of anti-hypertensive drugs to control it. In 2015 he was referred for an endocrine check-up which revealed a pheochromocytoma (noradrenaline type). Computed tomography imaging of the abdomen showed a right adrenal tumor of 28/38 mm, a mass that was clearly contoured, with heterogeneous pattern, and with moderate caption of intravenous contrast. Laparoscopic right adrenalectomy is performed with normalization of high pre-operatory normetanephrines and a dose reduction of anti-hypertensive medication which was still necessary. Pathological report suggested a malignant pheochromocytoma; the initial PASS score of 8 was later re-calculated, and a GAPP score of 5 was achieved showing a moderately differentiated tumor. No genetic backup was identified. Within the first year after tumor removal, the patient suffered a stroke, proving the higher cardiovascular risk than general population even after hormonal imbalance is restored. Lifelong surveillance is the rule.

We introduce an adult male case report with a history of osteogenesis imperfecta related fractures without specific medication against osteoporosis until the age of 50 years; however, within the first year he was offered anti-osteoporotic medication, he suffered a fall and a consecutive fracture was registered despite improved of bone mineral density parameters at DXA (dual-energy x-ray absorptiometry), proving the importance of life style intervention to minimize the dramatic impact on bone fragility due to a genetic condition. Despite the fact that the risk of fracture on a subject with a genetic condition that directly impacts the bone status represents a game changer, the everyday circumstantial situations that cause an increased risk of fall represent strong players that need to be taken into consideration as part of patients’ education.

Introduction. The link between the action of thyroid hormones and neurological, cognitive and affective function is well known. The aim of the study is to evaluate the changes of hormone’s value and symptoms at hyperthyroid patients after 6 months and 1 year of treatment. Materials and methods. In our study, we enrolled 80 patients with hyperthyroidism (new cases) and we asked them to fill out a questionnaire three times: first time was when they were into a thyrotoxic state (before the antithyroid drug therapy – ATD) and after that during ATD treatment (when they were into an euthyroid state after 6-12 months of treatment, average 7 months). Results. There is no statistically significant difference between the ages of the study and control groups (p Student’s t -test = 0.207 > 0.005), nor between the distributions according to gender (p Chi square test = 0.827) or area of residence (p Chi square test = 0.820). For HAMD score, there is highly significant differences (p < 0.001) before treatment, a statistically significant difference after 6 months (p Student’s t-test = 0.015 < 0.05), and no statistically significant difference after 1 year. Conclusion. Depression and anxiety were improved following thyroid function normalization in hyperthyroidism.

Introduction. Depression is a persistent mental state of sadness that can affect an individual`s thoughts, behavior, emotion and well-being. The electroencephalogram (EEG) is of great importance both for experimental neurophysiology and for clinical diagnosis. The purpose of our study was to establish if there is a connection between the values of serotonine, histamine and EEG in patients with depression and endocrine pathology based on the collected data. Materials and methods. We included 50 individuals diagnosed with depression from Endocrinology Clinic of Craiova, over a period of 2 years (2018-2020). Serotonine and histamine were measured in blood and urine/24 hours in all the sample. Electroencephalography was performed to this patients. Outcomes. In our study, 27 patients had mild depression, 17 had moderate depression and 6 had a severe disorder. Also, the serotonine values were low (normal value 80-400 μg/L) in patients with depression and endocrine pathology. Conclusion. In patients with EEG abnormalities occure significant changes in the values of serotonine and histamine (increased urinary histamine and decreased serotonine levels).