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Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), or polyglandular autoimmune syndrome type 1 (PAS-1/APS-1), is a rare autosomal recessive disorder linked to mutations in the autoimmune regulator (AIRE) gene. This review provides a detailed analysis of cutaneous manifestations in APECED, focusing on chronic mucocutaneous candidiasis (CMC), alopecia areata (AA), and vitiligo. The classic triad of hypoparathyroidism, adrenal insufficiency, and CMC serves as a diagnostic cornerstone. However, the varied clinical spectrum of APECED, particularly its cutaneous presentations, poses a diagnostic challenge. CMC, often an early sign, varies in prevalence across populations, including Finnish (100%), Irish (100%), Saudi Arabian (80%), Italian (60–74.7%), North American (51–86%), and Croatian (57.1%) populations. Similarly, AA prevalence varies in different populations. Vitiligo also exhibits variable prevalence across regions. The review synthesizes the current knowledge arising from a narrative analysis of 14 significant human studies published in English up to October 2023. Moreover, this paper underscores the importance of early detection and monitoring, emphasizing cutaneous manifestations as key diagnostic indicators. Ongoing research and clinical vigilance are crucial for unraveling the complexities of this rare autoimmune syndrome and enhancing patient care.

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.

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.

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.

Primary thyroid lymphoma represents a challenging, multi-disciplinary condition that it may be found in addition to positive antibodies against thyroid. Early recognition is essential for an adequate management. A thyroid nodule but usually the entire goiter may rapidly progress to a voluminous mass causing local compressive symptoms. Most of the patients with primary thyroid lymphoma had a history of Hashimoto thyroiditis. Epidemiologically, primary thyroid lymphoma represents an exceptional entities opposite to papillary or follicular cancer. The first tool of evaluation is ultrasound; in order to appreciate the local and distance invasion, computed tomography is useful. Fine needle aspiration and cell block analysis or biopsy and immunohistochemistry report are essential for adequate diagnostic in order to avoid unnecessary surgery. Diffuse large B-cell lymphoma is the most frequent histological type. Chemotherapy and local radiation represents the elective management. Considering this unusual condition, awareness is the key operative word for different practitioners.

Poorly differentiated/undifferentiated thyroid carcinoma represents a very severe type of malignancy with limited therapeutically resources. Fortunately, the diagnosis is very rare in general population; however, delayed presentation to a health care system might aggravate the evolution and during COVID-19 pandemic it was suggested an exacerbation of this phenomenon. This is a case report of a 56-year old lady diagnosed with poorly differentiated undifferentiated thyroid carcinoma according to fine needle aspiration – based cytological exam. Despite having progressive large, neck mass with bone pain, asthenia, weight loss, and dysphagia since last months, she delayed the medical examination because of social anxiety amid COVID-19 pandemics. Poorly differentiated carcinoma still represents a sector of endocrinology with poor survival. Controversies around endocrine practice amid pandemic are still ongoing topics.

Premenstrual syndrome (PMS), including the severe subtype premenstrual dysphoric disorder (PMDD), DSM-5 category, represents a challenging combination of hormonal, environmental and neuroendocrine dysfunctions with menstrual cycle-related pattern. Controversies around the role of daily stress and associated anomalies of hypothalamic-pituitary-adrenal axis are related to the fact that stress is all the time, not just a fluctuating element. This is a narrative review on PMS/PMDD and cortisol profile. 46 articles are cited (between 2009 and 2020). PMD/PMDD underlines multiple imbalances and anomalies of the cortisol levels or its secretory pattern may be a few of them, despite the fact that multiple controversies are still present and most of studies are of limited statistical power. Women with PMS may have higher levels of cortisol in relationship to stress independently of the cycle phase, also a delay of CAR (cortisol awakening response) peak and a delayed cortisol slope during day time. It does not seem that CAR pattern is related to the phases of menstrual cycle. CAR anomalies may be associated with pain perception disturbances in PMS females. The most modern area of interest is related to allopregnanolone, a progesterone metabolite with neuroactive profile. The diurnal serum baseline cortisol and the values of cortisol after dexamethasone suppression test may be similar between patients with PMS and without, but the females with PMS that have higher allopregnanolone associate blunted values of cortisol during the night versus control (without PMS) and versus women with low allopregnanolone levels, thus proving a suboptimal response to stress. Allopregnanolone modules GABA receptors on a paradoxical manner inducing anxiety and irritability during luteal phase on women with a specific predisposal configuration of GABA receptor as those confirmed with PMDD. Overall, PMS/PMDD impairs the quality of life, thus the more we understand about its pathogeny, the easier it gets to control it.

Hot flashes (HF), transitory episodes of erythema, heat sensation, anxiety followed by chills, are described in carcinoid syndrome, mastocytosis, medullary thyroid cancer, hyperthyroidism, pheochromocytoma, alcohol consumption, side effects of drugs, and infections. They are pivotal among menopause-related vasomotor symptoms beside genitourinary syndrome in addition to sleep disturbances (40-60% of females), and metabolic changes. HF affect 70% of women (20% of them have a severe impairment of life quality); they last for 4-7 years, starting 4-6 years before last menstruation. The main HF cause is ovarian-derivate estrogen deprivation which activates complex endocrine and neuroendocrine mechanisms involving noradrenaline, 5-hydroxytriptamine (5-HT), calcitonin gen-related peptide, orexin, kisspeptin, neurokinin B, and epigenetic elements like modulation of tachykinin receptor 3, accelerated epigenetic aging (as found in Women's Health Initiative Observational Study), expression of central serotonin transporters. Estrogen deficiency uncouples the negative feedback with preoptic area of hypothalamus, responsible for thermoregulation by inducing an exacerbated vasodilatory response to a small increase of body temperature. TRPV1 (transient receptor potential vanilloid 1) in preoptic hypothalamic area may play a role by NE-α2ADR (norepinephrine-activated α2-adrenergic receptors) activation. Higher expression of serotonin transporter SLC6A4 causes a lack of 5-HT at synapsis which is a trigger for presynaptic 5-HT receptor feedback, thus a release of serotonin amount prevents hot flashes. Kisspeptin and neurokinin B which are co-expressed in infundibular nucleus of hypothalamus are involved in central thermoregulation and gonadotropin releasing hormone anomalies. The NKR3 (neurokinin 3 receptor) antagonist receptor improves HF. Understanding the pivotal role of central neurotransmitters in hot flashes is the basis of new therapeutically researches because otherwise estrogen replacement has a long list of side effects, and it is contraindicated in breast cancer-related hypogonadism.

Diagnosis, tratament and follow-up of patients with melanoma during COVID-19 pandemic is quite challenging. These patients are often immunocompromised, but, on the other hand, management of this malignant skin cancer should not be delayed. It is necessary to diagnose and stage the melanoma as soon as possible, in an attempt to provide a better prognosis. There are few data regarding the treatament of melanoma during COVID-19 pandemia. However, the general recommandations suggest testing all cancer patients prior administration of the therapy. The European Society for Medical Oncology (ESMO) provided guidelines regarding therapy of this skin cancer during COVID-19 pandemic. Every patient is different, and it is always important to evaluate the risks and benefits.

Hypoparathyroidism is a rare condition associating autoimmune, genetic, post-operatory (most frequent) or idiopathic causes. Low calcium causes neuromuscular irritability of chronic or acute type like muscle crample, paresthesia, tingling, cardiac rhythm anomalies, seizures, etc. Despite calcium and active vitamin D replacement, acute complications are frequently seen and generally a reduced quality of life is registered since pathogenic medication like parathormone drug substitution is not currently available in daily practice. Other complications are due to overtreatment with calcium and vitamin D like kidney stones and associated urinary infections and hypercalciuria while increased calcium-phosphor product causes calcifilaxia of different locations causing complications like skin necrosis, brain calcifications with seizures, etc. We introduce a case of hypoparathyoidism in association with other co- morbiditis and a brief discussion around the case related to bone mineral density anomalies or usefulness in general panel of investigations in this particular topic. This is a 43-year old non-smoking male coming from non-endemic area that had a small lesion of skin necrosis at left hand. He has autoimmune thyroiditis and on admission low values of calcium and PTH 2 pg/ml (normal 15-65 pg/ml) are consistent for the diagnosis of hypoparathyroidsm, probably of autoimmune cause. Central DXA shows high BMD at each site. He was offered calcium and vitamin D replacements with a mild clinical improvement. This case of autoimmune hypoparathyroidism associated with Hashimoto’s thyroiditis highlights the idea of high DXA-BMD due to cortical and trabecular effects of PTH deficiency.

Neuroendocrine neoplasia (NEN), priory known as neuroendocrine tumours represent the modern approach of traditionally named “carcinoid” tumours. We shortly introduce benign and malign dermatological aspects that are linked to NEN field. This is a multidisciplinary perspective. The paper is a mini-review. 30 articles are included as references. NEN represents 2% of all cancers, being considered orphan disease. Skin and soft tissue are exceptional sites of NEN, the majority are actually secondary spreading of NEN of other locations. Little data have been published related to the topic. Some cases reports showed invasion of dermis and subcutis, probably more frequent in older adults. The entity has been named low-grade neuroendocrine carcinoma of the skin, also named primary cutaneous carcinoid tumour. As seen in NEN diagnosis, the immunohistochemistry is essential like chromogranin A, synaptophysin, neuron specific enolase which are classical neuroendocrine markers and non-neuroendocrine parameters are useful for differential diagnosis like estrogens, androgens and progesterone receptors, GATA3, carcinoembryonic antigen. Merkel cell carcinoma represents the high grade NEN. It has a poor prognosis, with a 30% risk of local metastasis. The risk factors are either viral infection like Merkel cell polyomavirus, either long time exposure to ultraviolet light. The prognostic is similar between the two factors. Surgical removal is the first line therapy and adjuvant treatment is radiotherapy and chemotherapy. Skin NEN represents an exceptional finding of aggressive profile. Their prompt recognition may help the prognosis.

Skin metastases are not typical. Malignancies like mammary cancer (most frequent in females) and pulmonary neoplasia (most frequent in males) represent the majority and exceptional findings are in those originating from thyroid, prostate, ovaries and oesophagus, usually in advanced, generally disseminated stages, with a poor prognosis. It may be found more often in elderly patients. We aim to present some practical aspects of skin metastases in thyroid cancer that originates from follicular thyroid epithelium. This is a brief literature review. The level of evidence is poor since most data is provided from cases reports. Cutaneous malignant lumps are rarely the first sign of disease, mostly associating a cancer relapse. The location varies from neck and head (majority) to exceptional sites as chest wall and of variable rate for scalp. Underling neck muscle or Meckel’s cave metastasis may be associated. The lesion is usually a lump of medium to small size, sometimes of papular appearance, without local pain (but depends on the site); it may associate erythema. The diagnosis is difficult unless an index of suspicion is positive (in which case whole body radioiodine scintigram may be useful). Biopsy and histological report are essential for diagnosis especially in cases without an evident connection to a prior/synchronous thyroid malignancy. Knowing the exceptional prevalence, the need for awareness in this particular topic is connected with a multidisciplinary daily practice.

MEN (multiple endocrine neoplasia) type 2A syndrome, a rare autosomal dominant condition of RET proto-oncogene gain-of-function mutations mostly involves medullar thyroid cancer and pheocromocytoma (40-50%) while primary hyperparathyroidism has a less frequent incidence (based on genotype-phenotype correlations). We introduce a female case of MEN 2A syndrome with a particular evolution. This is a case report. A 38-old year female with family history of MEN2A syndrome, is currently experiencing transitory flush associated with mild palpitations (maximum 135/80 mmHg, respective 100-100 beats/minute). 6 years ago she had total thyroidectomy for medullar thyroid cancer (normal plasma metanephrines/normetanephrines and adrenal aspects at computed tomography). 2 years later she was detected with a unilateral pheocromocytoma. Laparoscopic left adrenalectomy was done. Currently, only an increase of plasma metanephrines is postive (twice normal upper limits), not plasma normetanephrines, nor urinary 24-hour metanephrines and normetanephrines. Computed tomography showed a right adrenal tumor of 1.3/2.3 cm and a left adrenal tumor of 1.12/0.76 cm. Whole body MIBG (meta-iodo-benzyl guanidine) scintigram was done and confirmed bilateral activity. Bilateral adrenalectomy is necessary. Flush after partial adrenalectomy in patient with prior thyroidectomy for MEN2A syndrome - associated medullar thyroid cancer underlines pheocromocytoma. The newly detected bilateral adrenal masses require an adequate differential diagnosis of post-operatory aspect thus the usefulness of MIBG scintigram.

Scar is part of wound healing and hypertrophic aspects as well as keloids are pathological formation of a scar. Their appearance is seen post-operatory, post-trauma and the consequences are more than cosmetic depending on location, for instance at joins functional impotence is associated. A scar formation involves activation of matrix enzymes, matrix response, local inflammation and fibroblast intervention as well as local cytokines and growth factors action. Our purpose is to introduce to cases of females who developed hypertrophic scars after thyroidectomy in addition to local swelling as revealed by neck ultrasound. The paper is two cases series report. The hormonal assays and ultrasound aspects are provided. A 30-year female with Basedow disease had one month after thyroidectmy TRAb of 2.4 U/l while TSH was 1 of under daily 100 µg of levothyroxine. The subject presented a post-operatory hypertrophic scar in addition to the following ultrasound aspect: right area with an inhomogeneous structure of 1/1.2/4 cm, left area of 1.4/1.7/4 cm, with multiple images with posterior echo and intense local edema. This is a 44–year female referred for total thyroidectomy (for large goiter). The subject did not develop any peri-operatory complication. The histological report showed chronic autoimmune thyoiditis background of focal type in addition to nodules of colloidal and cystic adenomatosis with hyperplasic epithelium. One month later TSH was normal under levothyroxine. The subject presented a post-operatory hypertrophic scar in addition to ultrasound aspect of edema in association with inflammatory lymph nodes at lateral cervical level of 0.6/0.2 cm maximum diameter. It is still a matter of debate to classify the high risk patients for developing post-thyroidectomy scars.

Introduction. High prolactin may cause central hypogonadism including osteoporosis and breast secretion but also rare manifestations like increased androgens in females or galactocele. A part from high prolactin – related large cystic incidental mammary findings, the breast cysts may be associated with infections, local trauma and hemorrhage of priory benign cystic disease or solid tumors. Method. We introduce different clinical aspects of breast nodules with benign appearance, either symptomatic like painful large cyst with local inflammation elements or asymptomatic as an incidental finding. This is a cases series from a multidisciplinary perspective. Cases data. The patients’ age is between 43 and 62 years. The youngest female presented a large left cyst after a potential local trauma with local inflammation signs which were released after liquid evacuation. The oldest patient had bilateral mammary micro-cysts with a good prognostic as incidental finding. Conclusion. Benign breast lesions of adult females may associate local skin changes as redness and increased temperature or they may be completely asymptomatic, being detected as incidental findings. Regardless the scenario, the index of malignancy suspicion is always necessary because of heterogeneous presentation and increased incidence of mammary cancer.

Telangiectasia represents a sign on the skin underlining multiple conditions, characterised by red/purple/blue thin lines caused by dilatation of capillaries/arterioles/venules. Similar lesions may be detected during a surgical procedure at the surface of a solid organ. Pathological conditions associating the lesion are: dermatomyositis, scleroderma, lupus and the syndromes of ataxia-telangiectasia, respective hereditary hemorrhagic telangiectasia. We introduce a male case with anterior and lateral cervical enlargement with local skin changes of telangiectasia type. We introduce a male case with anterior and lateral cervical enlargement with local skin changes of telangiectasia type. The twist of the case is that, despite neck tegument red thin lines, the subject actually had a severe form of thyroid cancer. This is a case presentation. This is an 82-year old non-smoker male from non-endemic area admitted for rapidly enlargement of a tumor mass at neck in addition with local skin changes like telangiectasia and erythema as well as speech, eating and breathing intermittent disturbances. Thyroid function was normal. Thyroid ultrasound showed an enlargement of right lobe, of 3.7 by 4 by 7 cm (centimeter), mostly displayed by a macronodule with mix structure, of oval shape, with extension to isthmus, which is well shaped, of 5.7 by 4 by 5.2 cm. The data are highly suggestive for a thyroid cancer, thus the patient was further referred for total thyroidectomy. The changes of neck skin like telangiectasia and redness may exceptionally be caused by an aggressive thyroid cancer.

Introduction. Skin is deeply affected by aging as all the organs do, including endocrine glands and neuroendocrine circuits. The anomalies of aging are connected to the internal aspects including hormonal panel mostly vitamin D status and glucocorticoid axes integrity, melatonin networking, thyroid function, and catecholamines/serotonin release), state of health/illness, genetic background and bio-neuroendocrine/neurotransmitters pathways as well as immune defence. Moreover, external environment elements like sun exposure, radiations, pollution, physical, chemical and biological agents are consistent with internal mentioned aspects. Our purpose is to provide a mini-review regarding neuroendocrine and endocrine perspective of skin aging. Particular aspects on glucocorticoids, vitamin D and 5-hydroxytryptamine are pointed out. This is a narrative type of review. Skin is situated at the crossroad between intrinsic and extrinsic aging and the neuroendocrine approach is essential for understanding its time dependent changes.

We introduce dermatological aspects from an endocrine point of view related to pituitary tumours that display active secretor activity. This is a short literature review. 40 papers are cited including narrative reviews and original studies. Acromegaly: GH overproduction causes the thickening of the skin and swelling of the soft tissues in addition to the enlargement of extremities (like nose, hands, feet, jaw), coarsening of facial features (as front head and naso-labial folds), excessive sweating, exaggerate skin wrinkles, oily skin, and acrochordons. Cushing’s disease: cortisol overproduction has a severe protein catabolic effect at skin with collagen network disruption while immune effect of hypercortisolemia induces chronic skin infections and difficulties in wound healing. In females, consecutive androgens excess induces acne, hirsutism, and androgens-related alopecia. The classical phenotype includes: fragile skin or skin atrophy, red/purple striae, easy bruising, facial plethora. Skin changes represent the window to pituitary tumours for clinicians of different specialities, therefore contributing to final diagnosis of endocrinopathies.

Breast fibroadenoma is a benign tumour that is mostly asymptomatic thus it may be detected as an incidentaloma. Typically they are diagnosed in women of reproductive age and they reduce the dimensions during menopause because of estrogens deficiency that is why in menopause are rare. The mass is elastic, mobile and it contains an epithelial part and a stromal component (so called fibroepithelial tumours). Here is the case of a 70-year old female who had done a mammogram for the first time and she was found with such a lesion of 1.5 cm. She also is confirmed with osteopenia, most probable unrelated to the breast tumour. Menopausal fibroadenoma, even at low risk of malignancy requires a good multidisciplinary team of decision. Because of the differential diagnosis with breast cancer the positive diagnostic is based on ultrasound, mammogram and even biopsy. Menopausal fibroadenoma, even at low risk of malignancy requires a good multidisciplinary team of decision. Because of the differential diagnosis with breast cancer the positive diagnostic is based on ultrasound, mammogram and even biopsy. Due to low aggressive profile, the follow-up is, however, the most rational approach

Non-endocrine findings in patients with MEN1 (multiple endocrine neoplasia) syndrome also include skin lesions, especially tumor-type lesions. This is a narrative review of the English-language medical literature including original studies concerning MEN1 and dermatological issues (apart from dermatologic features of each endocrine tumor/neuroendocrine neoplasia), identified through a PubMed-based search (based on clinical relevance, with no timeline restriction or concern regarding the level of statistical significance). We identified 27 original studies involving clinical presentation of patients with MEN1 and cutaneous tumors; eight other original studies that also included the genetic background; and four additional original studies were included. The largest cohorts were from studies in Italy (N = 145 individuals), Spain (N = 90), the United States (N = 48 and N = 32), and Japan (N = 28). The age of patients varied from 18 to 76 years, with the majority of individuals in their forties. The most common cutaneous tumors are angiofibromas (AF), collagenomas (CG), and lipomas (L). Other lesions are atypical nevi, basocellular carcinoma, squamous cell carcinoma, acrochordons, papillomatosis confluens et reticularis, gingival papules, and cutaneous T-cell lymphoma of the eyelid. Non-tumor aspects are confetti-like hypopigmentation, café-au-lait macules, and gingival papules. MEN1 gene, respective menin involvement has also been found in melanomas, but the association with MEN1 remains debatable. Typically, cutaneous tumors (AF, CG, and L) are benign and are surgically treated only for cosmetic reasons. Some of them are reported as first presentation. Even though skin lesions are not pathognomonic, recognizing them plays an important role in early identification of MEN1 patients. Whether a subgroup of MEN1 subjects is prone to developing these types of cutaneous lesions and how they influence MEN1 evolution is still an open issue.

Metastatic cutaneous lesions are seen more commonly in breast cancer than in any other malignancy in women. Secondary breast cancer happens when cancer cells spread from the breast to other parts of the body. Sometimes breast cancer cells can spread to the skin. This can happen through the blood or lymphatic system. The presence of skin metastases signifies widespread systemic disease and a poor prognosis. The chest wall, the abdomen, the back, and the upper extremities are common sites.We present the case of a 69-year-old woman presented to our Surgery Department in June 2019, after appearing in the Dermatology Department a week ago, for the appearance of multiple subcutaneous painless, hardened, skin-colored nodules spread to the cervical region, anterior chest walls and upper limbs. Anatomopathological examination of the skin biopsy, performed on the anterior face of the left arm, showed dermal fragment with neoplastic, suggestive for lobular breast carcinoma (stage IV). The patient was referred to the oncological surgery department where our patient underwent a left total mastectomy and sentinel lymph node biopsy. The technique of mastectomy was the Madden technique. The surgery has no healing character, being more a necessity intervention that seeks to avoid the complications of the local evolution of the disease, such as ulceration, hemorrhage or suppuration, the possibility of applying the other forms of treatment (radiotherapy and / or polychemotherapy), elimination of a source of permanent metastatic sowing thus leading to more efficient treatment.

Our aim is to describe a case of a menopausal woman who started with dermatomyositis and then became a patient at endocrinology because of complicated glucocorticoid osteoporosis. This is a 63-year old female who suddenly started to accuse intense muscle pain associated with redness of the skin. She was confirmed with dermatomyositis and offered high doses of oral metilprednisolone. The thyroid ultrasound showed micronodular background and a small nodule of 0.7 cm without clinical relevance with an increase of antibodies thyroperoxidase antibody and normal thyroid function. Bone turnover markers were within normal in addition to decrease of serum 25-hydroxyvitamin D of 20 ng/ml. DXA (Dual-Energy X-Ray Absorptiometry) showed ostepenia based on a minimum T-score of -2.4 SD. The patient was offered high doses of cholecalciferol 2,000 UI per day and 500 mg of calcium daily in addition to weekly alendronate due to the high risk of fracture because of the glucocorticoid doses. 6 months later she suffered and accidental fall and a hip fracture was confirmed and required surgery. Further on the therapy was switched to zolendronic acid one injection per year. The dermatological and muscle progressively improved thus the doses of corticoids were reduced. As particular observation the presence of autoimmune thyroid condition may increase the risk of a second autoimmune disease like dermatomyositis, also the specific antibodies panel was negative. A multidisciplinary team needs to be involved in associated therapy for dermatomyositis and complications of glucocorticoids use.

Adrenal carcinoma is a complex orphan disease with a very poor prognosis. The evolution is rapid and in cases with suggestive symptoms the diagnosis may be established earlier in order to improve the outcome. One third of the patients are negative for a clear hormonal expression or they have an atypical presentation. We introduce an adult patient diagnosed with adrenal carcinoma and a rapid lethal outcome who initially presented with pale skin and non-specific abdominal pain. A multidisciplinary team is essential for adequate diagnosis and prompt intervention. Severe bleeding at the level of the adrenal carcinoma causing symptomatic anaemia is a rare event. The prognosis in adrenocortical carcinoma is severe and the presence of humoral hypercalcemia represents a sign of short survival time.

Acne vulgaris represent a frequent cutaneous disease manifested by chronic or recurrent development of papules, pustules, or nodules at the level of the face, neck, proximal upper extremities or trunk. The pathogenesis of acne vulgaris includes the interaction of multiple factors that lead to the development of comedones and inflammation. Although acne vulgaris dosen’t represent a disease that is physically disabling, its psychologic impact can be striking, contributing to anxiety, low self-esteem and depression. As a result of all these, is a big demand for effective therapies for ane vulgaris. The pathogenesis and the treatment for each pathogenic cause of acne vulgaris will be reviewed here. Topical retinoids have a good influence for both comedonal (non-inflammatory) and inflammatory acne and should be included in the initial management of most of the patients. The efficacy of topical retinoids for inflammatory acne may be due to a combination of the intrinsic anti-inflammatory properties of the topical retinoids and their ability in the prevention of the formation of microcomedones.

Striae rubrae or red striae are found in different circumstances like pregnancy, weight gain and Cushing’s syndrome regardless of endogenous or exogenous type. This type of skin lesion is commonly found in general population and usually does not underline a severe condition. The histological aspect that involves the stretch marks is the destruction of the dermal fibbers and their local network. The fibbers have receptors for glucocorticoids. A secondary epidermal anomaly is also seen. In benign scenarios the prevention with topic applications is still a matter of debate while therapy lasers of different types might help. In cases with pathological glucocorticoids excess the removal of the source improves the skin lesions yet not completely, they become white. We aim to introduce two cases of Cushing’s disease of different origins to whom impressive red striae were positive from the presentation. Red striae may be the hallmark of Cushing’s syndrome in association with different cardio-metabolic and/or bone complications. Despite the remission of the glucocorticoid excess the skin lesions are not completely reversible.

Sarcoidosis is a multisystemic granulomatous disease, with unknown etiology, characterized histopathologically by the development in the affected organs of some „empty” (non-caseous) granulomas. Cutaneous lesions can sometimes be the first localization of the disease. We present the case of a patient with known sarcoidosis and autoimmune thyroiditis, who developed a rash spread on the trunk and limbs, for which she was treated with dermatocorticoids and antihistamines, but without significant improvement. A skin biopsy was performed with histopathological examination, which revealed: at the dermal level, lympho-histiocytic infiltrates with nodular distribution, forming several granulomas, without areas of necrosis of caseification, including frequent cells with epithelioid appearance, suggestive for the diagnosis of cutaneous sarcoidosis. The patient underwent systemic cortisone therapy and hydroxychloroquine, with favorable outcome. The challenge of diagnosing this pathology is to differentiate it from a number of conditions, including: ring granuloma, cutaneous Crohn’s disease, lipoid necrosis, lupus vulgaris. To establish the diagnosis of certainty, it is necessary to correlate the clinical data with the result of the histopathological examination.

Introduction. Adrenal incidentaloma is a more frequent diagnosis during the last decades since the relative access to abdominal ultrasound, computed tomography or magnetic resonance imagery is higher. Aim. Our aim is to focus on the relationship between bone status (BS) in patients diagnosed and confirmed with adrenal incidentaloma. Method. This is a mini-review of the literature. Most of the included papers were published during the last 5 years. The main research tool is PubMed database. General data. BS is affected in adrenal incidentaloma mainly through persistent autonomous cortisol production which is called (even lately the term is not encouraged) “subclinical Cushing’s syndrome” with a prevalence of 0.2 up to 2% in unselected series of adult people. TBS (Trabecular Bone Score) in both men and women is negatively correlated with plasma cortisol after 1 mg dexamethasone suppression test. There is 2.2% decrease of TBS if subclinical Cushing’s syndrome is confirmed opposite to clear non-functioning pattern of the adrenal incidenaloma. Bone mineral density based on DXA at central sites (lumbar spine and femoral neck) was similar between the subject with unilateral and bilateral incidentaloma. The presence of subliclinical hypercortisolism is positively correlated with a higher risk of osteoporosis and fragility fractures Recently the term of “high risk” patients with adrenal incidentaloma has been introduced in order to describe the subgroup with autonomous cortisol secretion that has an increased risk of cardiovascular morbidities, infections and fractures (even independently of DXA - bone mineral density. Conclusion. The main contributor to BS, as well as to the cardiometabolic damage, remains the autonomous cortisol secretion in adrenal incidentaloma with a potential improvement after adrenalectomy and without a specific anti-osteoporotic medication in this particular situation.

Melanoma is the most serious form of skin cancer, its incidence increases with age. Melanomas are malignant tumors that are derived from melanocytes. The most common site of involvement is represented by the skin. Melanomas are considered a major cause of premature death from cancer. Melanomas produce pigment in varying amounts and may elicit an immune response that will be reflected in the clinical appearance. Some melanomas may lack pigment. A small but significant number of melanomas are undiagnosable clinically. A history of change may be the only clue to the correct diagnosis. We present the case of a 45-year-old woman, presented to our Dermatology Department with a rapidly changing nevus that bled with minimal trauma, located on her back.

We introduce a case of a menopausal woman newly diagnosed with primary osteoporosis who has been detected with a forearm lump. A 57-year old female is confirmed with osteoporosis at DXA. The patient developed within 10 days a painful lump with local redness at dorso-medial part of left forearm. Apparently no local trauma was identified. Neither had she a general infection or any other condition in the mean time. The ultrasound identified a hypoechoic area of 4 by 1.3 by 4 cm, with positive Doppler signal. A local infection was considered and she was offered antibiotics for 10 days. However, since the patient also accused bone pain, she was re-referred for an endocrine assessment. The hormonal panel was consistent with the first assays. Also a mild inflammatory syndrome was detected based on erythrocytes sedimentation rate of 31 mm/1-hour (normal: < 25 mm/1-h) and C reactive protein of 1.4 mg/dl (normal: < 1 ng/ml). An X - Ray of the region was done and showed no anomaly. The bone whole body scintigram was negative at forearm but a fracture rib at the level of 9th left rib was identified and considered osteoporotic. A computed tomography showed the subcutaneous localisation of the lump with small calcifications and no bone involvement. Paget’s disease of the bone was excluded based on normal bone turnover markers and negative bone scintigram. The proximity with a bone disease diagnosis needs to differentiate a subcutaneous lesion from a potential bone deformity caused by a metabolic bone condition.

This is a case report of a female with transitory erythema who was found with thrombocytosis caused by a pheocromocytoma. The skin changes were not accompanied by typical manifestations of an adrenergic crisis although she had high blood pressure episodes without skin colour changes. Both the erythema and the arterial hypertension controlled after the adrenal tumour was removed. Pheocromocytoma associates not only the excessive production of metanephrines and normetanephrines but also other factors like interleukins (for instance, IL-6, causing a general inflammatory syndrome including reactive thrombocytosis) eritropoietin or parathormone related peptide. Thrombocytosis is extremely rare associated with cathecolamines producing tumour and it may become a supplementary contributor to cardiovascular risk.

Introduction. ACTH (adrenocorticotropic hormone) is a key regulator of adrenal production involving cortisol as an essential hormone for life. The melanin is a pigment which is produced by melanocytes at the level of melanosomes (the melanogenesis). Both MSH and ACTH are generated by the cleavage of POMC (proopiomelanocortin) after CRF (corticotropin-releasing factor) stimulation and then MSH acts on the skin causing hyperpigmentation. Aim. To introduce clinical data of literature that link hyperpigmentation with ACTH excess. Three main topics are introduced: Addison’s disease, ectopic Cushing’s syndrome, and Nelson’s syndrome. Method. This is a short overview of literature including papers that have been mostly published within last 5 years. General data. Hyperpigmentation in relationship to ACTH includes its high levels in addition to low cortisol in Addison’s disease and Nelson’s syndrome and high non-suppressible cortisol in ectopic Cushing’s disease. ACTH has a pituitary origin in first two situations and malignancy in the third one. A pituitary tumour is found in cases with Nelson’s syndrome. An autoimmune background may be associated with Addison’s disease. An iatrogenic component is brought by Nelson’s syndrome. All three situations are severe and life threatening of different scenarios. Conclusion. Hyperpigmentation may be the clue to connect dermatology to endocrine pathologies and ACTH massive release by a pituitary or a non-pituitary origin involves a complex panel of conditions.

Renal failure is associated with numerous complications including cardiovascular, dermatological, neurological, surgical and endocrine. Hypovitaminosis D induces secondary hyperparathyroidism and long term effects are represented by autonomous stimulation of the parathyroid glands (tertiary hyperparathyroidism). Fail of PTH (parathyroid hormone) levels control through vitamin D replacement makes necessary a surgical intervention because of the risk of chronic complications in addition to the general morbidities caused by chronic kidney disease including osteoporosis. Our aim is to present a case of an adult woman with a very long history of renal failure complicated with tertiary hyperparathyroidism and osteoporosis. The clue of the case is the difficult localisation of PTH source after total parathyroidectomy was previously done in order to remove it and timing of re-intervention. There is a challenge to adequately locate the parathyroid remnants after a prior glands removal and a skilled surgeon is still the best “tool”. However, the risk of surgery in a cases with multiple complications is very high so it is preferable a pre-operatory localisation. The neck ultrasound is the most accessible tool offering a good accuracy if there is no mediastinal localisation and also the combination with parathyroid scintigram increases the rate of detection.

Obesity is associated with multiple complications like cardiovascular, oncologic, including skin infections potentially with a more severe evolution than in subjects with normal weight. We aim is to introduce two cases of females who initially presented with skin infections associating obesity and two different types of endocrine tumours; both of them underwent bariatric surgery. One case of a young female who had acne and menses anomalies was confirmed with macroprolactinoma and treated with cabergoline with menses control. For obesity she had bariatric surgery with weight and acne control but associating long term hypovitaminosis D. The second case is a menopausal woman with metabolic syndrome and different persistent skin infections in association with features of cardio-metabolic anomalies which were confirmed as adrenal Cushing’s syndrome and referred for unilateral adrenalectomy. The improvement of mentioned parameters was not associated with obesity control so bariatric surgery was done. She suffered a shoulder fracture and she was confirmed with osteoporosis (a lumbar T-score of -3.3 SD). The values of 25-hydroxyvitamin D remained normal only under oral replacement with vitamin D supplements and zolendronic acid was added. Obesity underlines heterogeneous aspects including dermatological, metabolic, cardiovascular and endocrine conditions; some of them are dramatically improved after bariatric surgery, yet not hipovitaminosis D and osteoporosis especially in menopausal women. The prolactin excess, Cushing’s disease or just obesity itself may cause repeated skin infections or acne.