Search

Patients with adrenal incidentalomas (AI) may experience detrimental consequences due to a minimal cortisol excess sustained by adrenal adenoma. SNPs of the glucocorticoid receptor gene (NR3C1) modulate individual sensitivity to glucocorticoids and may interfere with the clinical presentation.To compare the frequency of N363S, ER22/23EK and BclI SNPs in patients with AI with the general population and to evaluate whether these SNPs are linked to consequences of cortisol excess.Multicentric, retrospective analysis of patients referred from 2010 to 2014 to 4 centers (Orbassano, Milano, Messina [Italy] and Zagreb [Croatia]).411 patients with AI; 153 males and 258 females and 186 from blood donors.All patients and controls were genotyped for BclI, N363S and ER22/23EK and SNPs frequency was associated with clinical and hormonal features.SNP frequency was: SNP frequency was: N363S 5.4% (MAF 0.027), BclI 54.7% (MAF 0.328), ER22/23EK 4.4% (MAF 0.022), without any significant difference between patients and controls. N363S was more frequent in hypertensive patients (p = 0.03) and was associated with hypertension (p = 0.015) in patients with suppressed cortisol after the 1-mg DST.Our results demonstrate that SNPs of the glucocorticoid receptor gene do not play a pathogenetic role for AI. The impact of any single SNP on the phenotypic expression of minimal cortisol excess is limited and their analysis does not provide additional data that may be exploited for patient management.

Abstract Background X-linked acrogigantism (X-LAG; MIM: 300942) is a severe form of pituitary gigantism caused by chromosome Xq26.3 duplications involving GPR101. X-LAG-associated duplications disrupt the integrity of the topologically associating domain (TAD) containing GPR101 and lead to the formation of a neo-TAD that drives pituitary GPR101 misexpression and gigantism. As X-LAG is fully penetrant and heritable, duplications involving GPR101 identified on prenatal screening studies, like amniocentesis, can pose an interpretation challenge for medical geneticists and raise important concerns for patients and families. Therefore, providing robust information on the functional genomic impact of such duplications has important research and clinical value with respect to gene regulation and triplosensitivity traits. Methods We employed 4C/HiC-seq as a clinical tool to determine the functional impact of incidentally discovered GPR101 duplications on TAD integrity in three families. After defining duplications and breakpoints around GPR101 by clinical-grade and high-density aCGH, we constructed 4C/HiC chromatin contact maps for our study population and compared them with normal and active (X-LAG) controls. Results We showed that duplications involving GPR101 that preserved the centromeric invariant TAD boundary did not generate a pathogenic neo-TAD and that ectopic enhancers were not adopted. This allowed us to discount presumptive/suspected X-LAG diagnoses and GPR101 misexpression, obviating the need for intensive clinical follow-up. Conclusions This study highlights the importance of TAD boundaries and chromatin interactions in determining the functional impact of copy number variants and provides proof-of-concept for using 4C/HiC-seq as a clinical tool to acquire crucial information for genetic counseling and to support clinical decision-making in cases of suspected TADopathies.

Introduction: Despite successful therapy, acromegalic patients have reduced health-related quality of life (HRQoL) compared to healthy controls. Finding predictors of poor HRQoL can be crucial to improving these patients’ global health state. Aim: The primary objective of the study was to find out predictors of HRQoL. Secondary objectives were: (I) to determine correlations with AcroQoL subscales, and (II) to identify predictors for subscales.Materials and methods: In this cross-sectional study conducted in 2019 at the Messina Policlinic Hospital, 45 acromegalic patients were assessed at the Physical and Rehabilitative Medicine Ambulatory. During routine outpatient clinic attendances, the following questionnaires were administered: Acromegaly Quality of Life Questionnaire (AcroQoL), Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and Western Ontario and McMaster Universities Arthritis Index (WOMAC). We furthermore included the following variables obtained by medical record review: age, BMI, disease duration, previous surgery (Yes/No), previous radiotherapy (Yes/No), use of GH lowering medications (Yes/No), hypertension (Yes/No), diabetes mellitus (Yes/No), and biochemical control of the disease (Yes/No): immunoradiometric assays were employed to serum GH and IGF-1 measurements to identify biochemical control of the disease. Correlation between outcome measures and AcroQoL has been performed. Pearson’s r was calculated for continuous data following normal distribution (AcroQoL, PASQ, AcroQoL-B, AcroQoL-R, WOMAC-P), while Spearman’s rank order correlation was calculated for non-normally distributed data (WOMAC, WOMAC-F, WOMAC-S, AcroQoL-P) and point-biserial correlation for binary variables (biochemically controlled disease, use of GH lowering medications, radiotherapy, surgery). The same correlation analysis was performed for the AcroQoL subscales.Multiple linear regression with backwards, stepwise analysis was used to assess the influence on AcroQoL of correlated variables.Results: AcroQoL was strongly negatively correlated with PASQ (r=−0.700, p

Sellar region hosts a wide range of different types of lesions. Most of these lesions present with mass effect symptoms and, often, with symptoms related to hormonal disturbances, mimicking a pituitary neuroendocrine tumour (PitNET). We report two cases of sellar lesions with clinical and radiological features suggestive for PitNET. Histological and immunohistochemical analysis led to a diagnosis respectively for lymphocytic hypophysitis (LH) and meningioma.

ObjectiveDifferentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and meta-analysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0–19 years.MethodsThe systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC.ResultsAfter the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies (n = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33–0.59) and 0.07 (95% CI: 0.02–0.12) per 100,000 person-years, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities.ConclusionOur data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC.

IntroductionHypophosphatasia (HPP) is a rare genetic disease caused by inactivating variants of the ALPL gene. Few data are available on the clinical presentation in Italy and/or on Italian HPP surveys.MethodsThere were 30 suspected HPP patients recruited from different Italian tertiary cares. Biological samples and related clinical, biochemical, and anamnestic data were collected and the ALPL gene sequenced. Search for large genomic deletions at the ALPL locus (1p36) was done. Phylogenetic conservation and modeling were applied to infer the effect of the variants on the protein structure.ResultsThere were 21 ALPL variants and one large genomic deletion found in 20 out of 30 patients. Unexpectedly, NGS-driven differential diagnosis allowed uncovering three hidden additional HPP cases, for a total of 33 HPP subjects. Eight out of 24 coding variants were novel and classified as “pathogenic”, “likely pathogenic”, and “variants of uncertain significance”. Bioinformatic analysis confirmed that all the variants strongly destabilize the homodimer structure. There were 10 cases with low ALP and high VitB6 that resulted negative to genetic testing, whereas two positive cases have an unexpected normal ALP value. No association was evident with other biochemical/clinical parameters.DiscussionWe present the survey of HPP Italian patients with the highest ALPL mutation rate so far reported and confirm the complexity of a prompt recognition of the syndrome, mostly for HPP in adults. Low ALP and high VitB6 values are mandatory for the genetic screening, this latter remaining the gold standard not only to confirm the clinical diagnosis but also to make differential diagnosis, to identify carriers, to avoid likely dangerous therapy in unrecognized cases.

Abstract Background Pituitary metastases are rare, often deriving from lung or breast cancer owing to the upper vena cava proximity. Pituitary metastases can manifest with signs and symptoms of pituitary tumors, consequent to mass effect (headache, visual impairment) and/or hormonal alterations (hyperprolactinemia, hypopituitarism, and diabetes insipidus). Immune checkpoint inhibitors burst immunity against tumors, significantly increasing patients’ survival, but their autoimmune side effects frequently involve the skin, the gastrointestinal tract, and the endocrine glands (pituitary, thyroid, pancreas). Case presentation A 77-year-old Caucasian man had undergone trans-nasal sphenoidal surgery for a nonsecreting pituitary macroadenoma in 2001, without remnant or endocrine deficits. In 2016, he was operated for a shoulder melanoma. In February 2018, imaging evaluation demonstrated metastases in lung, liver, and femur. Therefore, treatment with pembrolizumab (anti-programmed death 1) was scheduled in May 2018, but, before starting this therapy, a brain computed tomography performed for a sudden loss of consciousness detected a sellar mass of 17 × 12 mm, which extended to the pituitary stalk and compressed the optic chiasma. Focused magnetic resonance imaging confirmed the size and characteristics of the lesion, while emergency evaluation of the hormonal profile demonstrated an impairment of adrenal and thyroid function. The pituitary lesion demonstrated a remarkable shrinkage (8 × 6 mm), which was confirmed by subsequent imaging evaluations. Conclusions This is the first case reporting on effectiveness of immune checkpoint inhibitors in a patient with pituitary metastasis from a melanoma.

Factitious Cushing’s syndrome (CS) is a very rare form of Münchausen syndrome. Its presentation and course are extremely heterogeneous, and diagnosis is generally challenging. We report the case of a 52-year-old woman who was initially investigated because of the occurrence of cushingoid features. Nevertheless, endocrine work-up showed very low morning plasma ACTH and serum cortisol levels. In addition, it also demonstrated central hypopituitarism and hypogonadotropic hypogonadism. Head MRI showed a small pituitary mass. Based on these results, and probably overlooking the initial clinical suspicion, general practitioner (GP) referred the patient to our Endocrine Unit for hypopituitarism. At inspection, moon face, central obesity, and bruising were evident. Multiple ulcerative skin lesions were also concentrated in the right arm and leg. Dermatology evaluation suggested that the lesions were self-provoked. For several days, the patient denied the assumption of corticosteroids, but we finally discovered that the GP’ nurse had prescribed betamethasone without the GP’s knowledge for about 2 years. In conclusion, the surreptitious assumption of corticosteroids is very rare, but the physicians should be aware that pituitary function could be impaired by high doses of corticosteroids, mimicking hypopituitarism. In these patients, a multidisciplinary approach and environmental investigation can be useful to diagnose factitious CS.

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant inherited disorder due to inactivating mutations in the calcium-sensing receptor (CaSR), less commonly in the G-protein subunit α11 (GNA11) or the adaptor-related protein complex 2, sigma 1 subunit (AP2S1) genes. It is characterized by mild to moderate hypercalcemia, hypocalciuria, and inappropriately normal or high PTH levels. The disorder is usually asymptomatic, and bone or renal involvement is rare. Adequate differential diagnosis between primary hyperparathyroidism and FHH is important to avoid unnecessary surgery. We report the case of a male patient with FHH showing biochemical heterogeneity to highlight the difficulties of differential diagnosis

Pituitary adenomas (PAs), usually benign lesions, can sometimes present with “aggressive” features (rapid growth, local invasiveness, scarce response to conventional treatments). Despite the fact that a few genetic alterations have been associated to this clinical behavior, the role of epigenetic modifications, mainly methylation and miRNAs activity, is now opening new frontiers in this field. We evaluated the methylation profile of 21 PA (11 GH-omas, 10 nonfunctioning tumors—NFPAs) samples from TNS surgery and 5 normal pituitaries, collected at our neurosurgery between 2015 and 2017. DNA was extracted and sequenced, selecting 184,841 target regions. Moreover, methylation profiles were correlated with demographic, radiological, and clinicopathological features. NFPAs showed higher methylation levels vs. GH-omas, with 178 differentially methylated regions (DMRs) mainly consisting of noncoding and intronic sequences, and mostly localized in the open sea regions. We also found three hypermethylated genes (C7orf50, GNG7, and BAHCC1) involved in tumorigenesis processes and potentially influencing pituitary tumor pathophysiology. Among the clinicopathological features, only the maximum diameter resulted significantly higher in NFPAs. Our data provide further evidence of the complex epigenetic background of pituitary tumors. In line with the current literature, we confirmed a significant prevalence of hypermethylation in NFPAs vs. GH-omas, whose pathophysiological consequence is yet to be defined.

BackgroundHypercortisolism accounts for relevant morbidity and mortality and is often a diagnostic challenge for clinicians. A prompt diagnosis is necessary to treat Cushing’s syndrome as early as possible.ObjectiveThe aim of this study was to develop and validate a clinical model for the estimation of pre-test probability of hypercortisolism in an at-risk population.DesignWe conducted a retrospective multicenter case-control study, involving five Italian referral centers for Endocrinology (Turin, Messina, Naples, Padua and Rome). One hundred and fifty patients affected by Cushing’s syndrome and 300 patients in which hypercortisolism was excluded were enrolled. All patients were evaluated, according to current guidelines, for the suspicion of hypercortisolism.ResultsThe Cushing score was built by multivariable logistic regression, considering all main features associated with a clinical suspicion of hypercortisolism as possible predictors. A stepwise backward selection algorithm was used (final model AUC=0.873), then an internal validation was performed through ten-fold cross-validation. Final estimation of the model performance showed an average AUC=0.841, thus reassuring about a small overfitting effect. The retrieved score was structured on a 17.5-point scale: low-risk class (score value: ≤5.5, probability of disease=0.8%); intermediate-low-risk class (score value: 6-8.5, probability of disease=2.7%); intermediate-high-risk class (score value: 9-11.5, probability of disease=18.5%) and finally, high-risk class (score value: ≥12, probability of disease=72.5%).ConclusionsWe developed and internally validated a simple tool to determine pre-test probability of hypercortisolism, the Cushing score, that showed a remarkable predictive power for the discrimination between subjects with and without a final diagnosis of Cushing’s syndrome.

Background and Aim. Parathyroidectomy is the standard treatment for primary hyperparathyroidism (PHPT). Cinacalcet, an allosteric modulator of the calcium sensing receptor, has been shown to be effective in reducing serum calcium levels and it has gained prominence as a non-invasive treatment in PHTH. Aim of the study was to compare the efficacy and tolerability of medical therapy vs surgery in a cohort of PHPT patients. Patients and Methods. The study included 63 consecutive subjects (14 men and 49 women, median age 62.4 ± 12 yr) with PHPT: 50 subjects (40 F and 10 M, ratio F/M 4:1; median age 59.6 ± 16.6 years, range 37-82) underwent parathyroidectomy, while 13 (9 F and 4 M, ratio F/M 2.5:1, median age 76.5 ± 6.2 years, range 64-83), who were ineligible for surgery, were treated with cinacalcet. Cinacalcet was administered at increasing dosages until normal serum calcium was reached or side effects occurred. Serum calcium and PTH was measured and adverse events were monitored during a 12 month-duration follow-up. Results. All patients who had undergone parathyroidectomy normalized both serum calcium and PTH levels after surgery (P=0.001 vs baseline) and none of them experienced persistent and/or recurrent PHPT during follow-up. In the group under cinacalcet therapy, serum calcium significantly decreased in all patients within 4 weeks (P = 0.01 vs baseline) and normalized in all patients at prolonged follow-up (P=0.001 vs baseline), while PTH slightly decreased during follow-up (P=0.878 vs baseline) and never reached a normal value. Conclusion. Surgical treatment is curative and safe in most cases of PHPT. Cinacalcet represents an effective therapeutic option, from the perspective of hypercalcemia improvement, in PHPT patients who have contraindications to surgery or persistent PHPT after surgery.

Background: Stereotactic irradiation is proposed for treatment of pituitary adenomas (PAs) in patients with tumor progression/recurrence after surgery and in cases not eligible for other therapies. In the literature several papers have been published on the role of the Gamma-Knife stereotactic irradiation for management of PAs, but data on the role of stereotactic Cyberknife (CK) are still limited. We describe a single-center experience using CK stereotactic radiosurgery (CK-SRS) and hypofractionated radiotherapy (CK-SRT) for PAs treatment, analyzing its efficacy/safety in the light of current literature. Methods: We retrospectively collected clinical data from PAs patients treated using CK system at the University Hospital of Messina, Italy, between 2008 and 2018. The efficacy was evaluated by analyzing the tumor growth/biochemical disease control rates, and the safety by evaluating post-treatment pituitary and/or visual deficits. Results: Twenty-four PAs patients were included in the study. The mean follow-up was 42.21 ± 32.67 months. The overall tumor growth control rate was 91.6%, but it was higher using the single-session scheme (100%) than using hypofractionated sessions (80%). The biochemical disease control rate was 60%, but increased to 80% in GH-secreting PAs. Post-treatment hypopituitarism occurred in 41.66% of cases, being 35.71% using a hypofractionated scheme, and 50% using a single-session treatment. No cases of post-treatment visual deterioration were observed. Overall and progression-free survival were respectively 84.6% and 83.6% at three years. Conclusions: Cyberknife irradiation is an effective and safe option for PAs treatment, being associated to an excellent tumor growth/biochemical control of the disease, and to a low rate of post-treatment complications. The efficacy seems to be higher when using a single-session scheme even if this could be associated to a higher incidence of post-treatment hypopituitarism. Keywords: Cyberknife, Pituitary adenomas, Radiosurgery

Objective/PurposeThe aryl hydrocarbon receptor (AHR) pathway plays a critical role in the biology of Growth Hormone (GH)-secreting pituitary tumor (somatotropinoma). Germline rs2066853 AHR variant was found to be more frequent among acromegaly patients and associated with a more severe disease with larger invasive somatropinoma, and with resistance to somatostatin analogs treatment in patients living in polluted areas. However, no somatic changes in AHR gene have been reported so far in acromegaly patients. On that basis, the aim of the study was to assess at the somatic level the AHR gene status encompassing exon 10 region, also because of the high rate of variants found in this genomic region.MethodsA cohort of 13 patients aged 20–76 years with biochemical, clinical and histological diagnosis of somatotropinoma was studied. DNA and RNA from pituitary tumor histological samples have been extracted and analyzed by PCR and direct sequencing for AHR gene variants, and compared with corresponding patients’ germline DNA as well as normal pituitary tissue as reference control.ResultsA degenerated letter codes in the region corresponding to AHR exon 10 (c.1239-c.2056) was detected in somatotropinomas-derived DNA but not in that of matched germline and pituitary normal tissue. By multiple PCR and sequencing analysis, we observed amplification only before codon 1246 and after codon 1254, confirming the presence of a tumor-restricted somatic deletion in the 5’ upstream region of AHR exon 10. Analysis of PCR-amplified cDNA revealed a wildtype sequence of exon 9 and 10 in normal pituitary tissue, and a wildtype sequence of exon 9 and 10 up to codon 1246 and no sequence after the deletion region (c.1246-c.1254) in 6 out of 9 tumor samples. Patients carrying the germline rs2066853 AHR variant showed no somatic LOH at the corresponding genetic locus.ConclusionThis is the first demonstration of a recurrent somatic deletion in the exon 10 of the AHR gene in somatotropinomas. The functional impact of this genetic finding needs to be clarified.

Acromegaly is a disease due to chronic GH excess and a consequent rise in IGF-1 levels. This rare endocrine condition is associated with metabolic alterations such as hyperglycaemia, dyslipidaemia, and systemic arterial hypertension, which, in addition to GH excess-related cardiovascular changes, play critical roles in increasing cardiovascular risk and mortality rates. Biochemical control of acromegaly, achieved by means of surgical, and/or medical treatment, positively impacts on cardiovascular risk factors and metabolic alterations, reducing overall patient mortality. However, treatment modalities of acromegaly and disease control differently impact on glucose homeostasis and lipid changes, and consequently on cardiometabolic risk. In this regard, pasireotide was shown to significantly influence glucose metabolism. This review summarizes the cardiometabolic consequences of acromegaly and its treatment, focusing on available data around the effects of medical therapy with pasireotide on factors that influence cardiometabolic risk.

Bone involvement in primary hyperparathyroidism (PHPT) is characterized by decreased bone mineral density, bone resorption at both trabecular and cortical sites and bone erosions, up to brown tumors (BT) and cysts, the so-called osteitis fibrosa cystica (OFC). Signs and symptoms of OFC include bone pain, muscle weakness, skeletal deformities and pathological fractures. In recent years, PHPT has greatly changed its clinical expression, especially in Western countries. For these reason BT, a typical expression of OFC, are always less observed and often mistaken for malignancy. An integrated diagnostic approach, considering first a complete biochemical panel and a confirmation by functional imaging, is crucial for a correct diagnosis, mostly considering that such skeletal manifestations may be reversible after surgical cure of PHPT.

Knee osteoarthritis (OA) is a chronic, degenerative, and progressive disease of articular cartilage, producing discomfort and physical disability in older adults. Thirteen percent of elderly people complain of knee OA. Management options for knee OA could be divided into the following categories: conservative, pharmacological, procedural, and surgical. Joint replacement is the gold standard, reserved for severe grades of knee OA, due to its complications rate and increased risk of joint revision. A nonsurgical approach is the first choice in the adult population with cartilage damage and knee OA. Yearly, more than 10% of knee OA-affected patients undergo intra-articular injections of different drugs, especially within three months after OA diagnosis. Several molecules, such as corticosteroids injection, hyaluronic acid (HA), and platelet-rich plasma (PRP), are managed to reduce the symptoms of patients with knee OA. The aim of this review was to offer an overview of intra-articular injections used for the treatment of OA and report the conventional pharmacological products used.

Recently, Basic and Clinical Neuroscience published an article by Lim et al. (2016.entitled Co-occurence of Pituitary Adenoma with Suprasellar and Olfactory Groove Meningiomas. They claimed it as the first case of co-occurence of these two malignancies. However, to our knowledge, this is not the first case reported in this regard. We reported the same case scenario in a 61-year-old woman referred to our outpatient clinic in 2007. In this commentary, we are going to discuss our reported case and present a brief. review over co-occurence of intracranial meningioma with pituitary adenoma.

Acromegaly is a rare disease due to chronic GH excess and to the consequent increase in IGF-1 levels. Both GH and IGF-1 play a role in intermediate metabolism affecting glucose homeostasis. Indeed, chronic GH excess impairs insulin sensitivity, increases gluconeogenesis, reduces the glucose uptake in adipose tissue and muscle and alters pancreatic β cells function. As a consequence, glucose metabolism alterations are a very frequent complication in acromegaly patients, further contributing to the increased cardiovascular risk and mortality. Treatment modalities of acromegaly differently impact on glucose tolerance. Successful surgical treatment of acromegaly ameliorates glucose metabolism abnormalities. Drugs used to treat acromegaly patients may per se affect glucose homeostasis, therefore influencing patients' management. Indeed pegvisomant has been shown to positively impact on glucose metabolism, while somatostatin analogs, especially pasireotide, can cause hyperglycaemia. On the other hand, robust data on the effect of dopamine agonists on glycaemic profile are still lacking. This review summarizes the available data on diabetes mellitus in acromegaly patients, with a focus on the potential effects of the medical treatment of the disease on glucose homeostasis, providing an overview of the current state of the art.

Multiple endocrine neoplasia (MEN)-1 syndrome is a rare disorder, due to the loss of function of the tumor suppressor menin. It consists of the association of two or more endocrine tumors, often presenting in a familial setting, being inherited in an autosomal dominant fashion. The most frequent manifestations of MEN-1 syndrome are primary hyperparathyroidism, followed by pituitary adenomas (mainly prolactinomas) and gastrointestinal neuroendocrine tumors, but several other associated conditions have been reported. Herein we describe the case of a male patient, affected by sporadic MEN-1, diagnosed with primary hyperparathyroidism, TSH-secreting pituitary adenoma and bilateral adrenal hyperplasia causing Cushing’s syndrome, due to a de novo MEN-1 gene mutation. The patient has been successfully treated with first generation somatostatin analog Octreotide LAR (30 mg every 28 days) -with stabilization of the known neuroendocrine lesions and shrinkage of the pituitary adenoma- and with bilateral adrenalectomy. The patient is still regularly followed-up at our Endocrine Unit, and his clinical conditions are stable.

Background: Primary aldosteronism (PA) is a rare condition characterized by inappropriately high secretion of aldosterone, independently of the renin-angiotensin system, not suppressed by sodium loading test. PA represents the most common cause of secondary hypertension and its early detection and treatment can help reduce the cardiovascular (CV) risk. Case presentation: We report on a 42-year-old man who was referred to an outpatients’ clinic reporting headache and vomiting associated with hypertension and was discharged with oral antihypertensive medication (irbesartan) and low-sodium diet. Three years later, he underwent further hospitalization for muscle pain in lower limb associated with severe hypokalemia (1.7 mmol/L) and elevated creatine phosphokinase (CPK) levels (2634 U/L). Abdominal CT scan excluded the presence of adrenal lesions. Acute intravenous potassium chloride (KCL) supplementation normalized serum potassium level and the patient was discharged with diagnosis of rhabdomyolysis and hypokalemia and with antihypertensive medication (spironalactone: 100 mg/day and amlodipine: 5 mg/day) and oral KCL supplementation (600 mg/day). After pharmacological washout, an inappropriately high aldosterone concentration (75.10 pg/ml) and very low renin level (1.10 pg/ml) were detected. PA diagnosis was confirmed by oral saline infusion test (SIT). Aldosterone levels did not normalize after dexamethasone suppression testing. Abdominal MRI showed a nodule measuring 6 mm in the right adrenal. A subsequent adrenal venous sampling (AVS) confirmed the unilateral (right) lateralization of the aldosterone hypersecretion. Conclusion: Although invasive, AVS is the gold standard test to differentiate PA subtypes in patients who can be considered ideal candidates for unilateral adrenalectomy.

PurposeSomatropin [recombinant growth hormone (rGH)] is approved in children and adults for several conditions involving growth disturbances and the corresponding biosimilar is available in Italy since 2006. No population-based data are available on the pattern of rGH use in Italian clinical practice. This study aimed at exploring the pattern of biosimilar and originator rGH use in six Italian centers, where different policy interventions promoted biosimilar use.MethodsThis population-based, drug-utilization study was conducted in the years 2009–2014, using administrative databases of Umbria, Tuscany, and Lazio Regions and Local Health Units of Caserta, Treviso, and Palermo. Naïve rGH users were characterized, and prevalence of use and discontinuation were assessed over time.ResultsAmong 6,785 patients treated with rGH during the study years, 4,493 (66.2%) were naïve users (males/females = 1.3), mostly affected by GH deficiency. The prevalence of rGH use increased from 2009 to 2010, remaining stable thereafter, but it was heterogeneous across centers (twofold higher prevalence of use in center n.2 than centers n.4 and 1 in 2014). Biosimilar rGH uptake increased over time but was low (7.8% in 2014) and heterogeneous as well. Discontinuation of rGH therapy occurred in 54.0% of naïve users, more frequently in females than males (58.1 vs. 50.9%). During the first year of treatment, discontinuation was frequent (39.9%), but no statistically significant differences were observed in treatment persistence for biosimilar vs. originator rGH (p > 0.05).ConclusionGeographical heterogeneity in the prevalence of rGH use was observed. Similarly, the biosimilar rGH uptake was low and variable across centers. Post-marketing monitoring is required to continuously monitor the benefit-risk profile of rGH, thus guaranteeing greater savings than only promoting lowest cost rGH.

Ovarian hyperthecosis is the most common cause of hyperandrogenism in women during postmenopausal age. However, its diagnosis is frequently challenging, since several causes must be ruled out, involving both adrenal glands and ovaries. Herein we describe the case of a 62 years old woman addressed to our Unit after the casual detection of an adrenal mass, compatible with an adenoma. Biochemical evaluation revealed gonadotropins in menopausal range, high testosterone and androstenedione, while the patient had been complaining of androgenetic alopecia and hirsutism for some years. Ultrasound imaging revealed only a small increase in ovarian volume, in relationship to the patient’s age. A GnRHa test was performed, demonstrating gonadotropins suppression and testosterone normalization, thus confirming the suspect of ovarian hyperthecosis. The administration of these agonists, together with the slow progression of symptoms over years, play a fundamental role into excluding an androgen-secreting neoplasia, also limiting the use of ovarian veins catheterization as second line test. Besides, they represent a valid therapeutical option, especially when surgery is contraindicated (or cannot be performed).

Temozolomide (TMZ) is an alkylating chemotherapeutic agent that has recently been used in some cases as a new therapeutic tool for pituitary carcinomas and aggressive pituitary adenomas. In this report, we present the case of effective TMZ treatment in a 42-year-old man with ACTH-secreting carcinoma. The tumor grew progressively over 4 years, from 2.2 to 31.1 cm3, despite three surgical approaches and gamma-knife treatment. Ki-67 increased from 2 to 18%. An intradural metastasis at the foramen magnum was detected by MRI after the third operation. Thereafter, four cycles of 5-day TMZ administration (200 mg/m2/day during the first, and 150 mg/m2/day during the following cycles) induced dramatic tumor size reduction (>90%). Clinical conditions improved progressively and, after 17 months from the beginning of TMZ administration, the patient is still alive. The treatment was well tolerated except for a transient thrombocytopenia (grade 4 WHO).

We report on a man with a progressively increasing pituitary mass, as demonstrated by MRI. It produced neurological and ophthalmological symptoms, and, ultimately, hypopituitarism. MRI also showed enlargement of the pituitary stalk and a dural tail phenomenon. An increased titer of antipituitary antibodies (1:16) was detected in the serum. Pituitary biopsy showed autoimmune hypophysitis (AH). Neither methylprednisolone pulse therapy nor a subsequent treatment with azathioprine were successful in recovering pituitary function, or in inducing a significant reduction of the pituitary mass after an initial, transient clinical and neuroradiological improvement. Anterior pituitary function evaluation revealed persistent hypopituitarism. AH is a relatively rare condition, particularly in males, but it represents an emerging entity in the diagnostic management of pituitary masses. This case shows that response to appropriate therapy for hypophysitis may not be very favorable and confirms that diagnostic management of nonsecreting pituitary masses can be a challenge. Clinical, imaging, and laboratory findings are useful for suggesting the diagnosis, but pituitary biopsy may be necessary to confirm it.

Pituitary apoplexy is a rare clinical syndrome due to ischemic or haemorrhagic necrosis of the pituitary gland which complicates 2–12% of pituitary tumours, especially nonfunctioning adenomas. In many cases, it results in severe neurological, ophthalmological, and endocrinological consequences and may require prompt surgical decompression. Pituitary apoplexy represents a rare medical emergency that necessitates a multidisciplinary approach. Modalities of treatment and times of intervention are still largely debated. Therefore, the management of patients with pituitary apoplexy is often empirically individualized and clinical outcome is inevitably related to the multidisciplinary team’s skills and experience. This review aims to highlight the importance of a multidisciplinary approach in the management of pituitary apoplexy and to discuss modalities of presentation, treatment, and times of intervention.