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Non-functioning (NF) accidentally detected PitNETs (PIs) are common findings of CT/MRI scans currently. Data concerning their behavior vary, and some PIs will potentially experience a size change over time that might become clinically relevant., Objective: We aimed to evaluate CT-related PIs diameters following 3 aspects: a cross-sectional analysis based on the age' groups at first PI diagnosis and on the gender distribution and a longitudinal analysis in PIs with <0.5 cm versus ≥0.5 cm as the largest diameter at baseline., Methods: A retrospective, real-life, multi-centric study in adults with NF micro-PIs was performed., Results: 208 subjects (92.79% females) were included (average age 43.18 ± 12.58 y). The mean largest diameter (between transversal and longitudinal diameters) was 0.55 ± 0.16cm, and 44.71% of the PIs were located on the right part of the pituitary gland. The patients were divided into 10 age-groups (21 to 70 y), and no difference was observed between the mean largest diameters of these groups ( p = 0.693). Females and males had a similar age at PIs diagnosis ( p = 0.353), transverse diameter ( p = 0.910), longitudinal diameter ( p = 0.229), and PI location ( p = 0.368). Serial CT scans (2 to 4 per patient) included a median (Q1-Q3) of 20 (12-36) months for the second CT scan, 58 (36-84) for the third CT scan, 78 (53-118) for the fourth CT scan, and a total follow-up between baseline and last CT scan of 40 (13-72) months. The initial largest diameter correlated with the diameter change between the baseline and the last CT (r = -0.575, p = 0.000). The largest PI diameter was similar between each serial CT scan ( p = 0.840). According to the cut-off value of 0.5 cm diameter (for initial largest tumor diameter), group A (N = 78, 37.50%, <0.5 cm) and group B (N = 130, 62. 50%; ≥0.5 cm) had similar age at baseline (43.83 ± 12.72 versus 42.79 ± 12.54 y, p = 0.565) and PIs locations (right, left, median). The largest PI diameter remained smaller in group A versus B amid the second CT scan ( p = 0.000) and the last CT scan ( p = 0.009). The largest diameter change from the first to the last CT scan showed an increase in group A (median of +0.10 cm, p = 0.000) and a decrease in group B (median of -0.01 cm, p = 0.002); this diameter change was different in group A versus B ( p = 0.000). The cumulative probability of tumor-growth-free survival showed different survival functions (log rank p = 0.000): group A exhibited a more gradual decrease versus B; at 60 months, the cumulative probability was 0.32 ± 0.08 for group A versus 0.75 ± 0.07 for B. During follow-up, all PIs remained NF, and no hypopituitarism was noted (as limits, we mention that dynamic hypopituitarism testing was selectively performed)., Conclusions: NF micro-PIs in adults showed a similar age and sex distribution. During follow-up, PIs with a largest diameter < 0.5 cm increased after a median of 40 months but remained <1 cm, while in PIs with ≥0.5 cm, the largest diameter decreased. This highlights a lower predictability in tumor behavior than expected, particularly in larger micro-PIs that, overall, remained without relevant clinical implications after surveillance.

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

Chronic kidney disease (CKD) causes specific hormonal disturbances, such as variations in leptin and testosterone levels and function. These disturbances can promote errors in signaling interaction and cellular information processing and can be implicated in the pathogenesis of atherosclerosis. This study investigates the factors that affect leptin in CKD patients and examines how leptin is related to markers of vascular disease. We conducted a cross-sectional study of 162 patients with CKD in pre-dialysis and dialysis stages. We recorded clinical and laboratory data, including leptin, testosterone, and subclinical atherosclerosis markers like brachial-ankle pulse wave velocity (ba PWV) in pre-dialysis CKD patients and flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) in hemodialysis (HD) patients. Leptin was significantly correlated with testosterone in CKD pre-dialysis stages ( p < 0.001) and also in HD ( p = 0.026), with adipose tissue mass in pre-dialysis stages ( p < 0.001), and also in HD ( p < 0.001). In women HD patients, leptin correlated with NMD ( p = 0.039; r = -0.379); in all HD patients, leptin correlated with C reactive protein ( p = 0.007; r = 0.28) and parathormone ( p = 0.039; r = -0.220). Our research emphasizes the connection between leptin, adipose tissue, and testosterone in all stages of CKD. Leptin was associated with NMD in HD women and correlated with inflammatory syndrome and parathyroid hormone in all HD patients.

Brown tumors, an exceptional bone complication of severe primary (PHP) or renal (secondary) hyperparathyroidism (RHP), are caused by long-standing, elevated parathormone (PTH)-induced osteoclast activation causing multinucleated giant cell conglomerates with hemosiderin deposits in addition to the local production of cytokines and growth factors. We aim to present an adult case series including two females displaying this complication as part of a multidisciplinary complex panel in high PTH-related ailments. The approach was different since they had distinct medical backgrounds and posed a wide area of challenges amid real-life settings, namely, a 38-year-old lady with PHP and long-term uncontrolled hypercalcemia (with a history of pregnancy-associated PHP, the removal of a cystic jaw tumor, as well as a family and personal positive diagnosis of polycystic kidney disease, probably a PHP-jaw tumor syndrome), as well as, a 26-year-old woman with congenital single kidney and chronic renal disease-associated RHP who was poorly controlled under dialysis and developed severe anemia and episodes of metabolic acidosis (including one presentation that required emergency hemodialysis and was complicated with convulsive seizures, followed by resuscitated respiratory arrest). Both subjects displayed a severe picture of PHP/RHP with PTH levels of >1000 pg/mL and >2000 pg/mL and elevated serum bone turnover markers. Additionally, they had multiple brown tumors at the level of the ribs and pelvis (asymptomatically) and the spine, skull, and pelvis (complicated with a spontaneous cervical fracture). As an endocrine approach, the control of the underlying parathyroid disease was provided via surgery in PHP (for the postparathyroidectomy hungry bone syndrome) via medical intervention (with vitamin D analogs) in RHP. Additionally, in this case, since the diagnosis was not clear, a multidisciplinary decision to perform a biopsy was taken (which proved inconclusive), and the resection of the skull tumor to confirm the histological traits. This series highlights the importance of addressing the entire multidisciplinary panel of co-morbidities for a better outcome in patients with PHP/RHP-related brown tumors. However, in the instance of real-life medicine, poor compliance and reduced adherence to recommendations might impair the overall health status. Thus, sometimes, a direct approach at the level of cystic lesion is taken into consideration; this stands for a narrow frame of decision, and it is a matter of personalized decision. As seen here, brown tumors represent the hidden face of PHP/RHP, primarily the complex and severe forms, and awareness is essential even in the modern era.

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

Pro-B amino-terminal natriuretic peptide (NT-proBNP) is a diagnostic marker for heart failure (HF), a severe complication of chronic kidney disease (CKD). However, its significance in CKD is not clear, as other factors, such as renal function, may also have an impact. Recent studies have shown that ghrelin treatment is effective in HF in the general population, but the impact of ghrelin on cardiac function in CKD patients is still unknown. Our study aimed to investigate the factors associated with NT-proBNP in pre-dialysis CKD patients and to evaluate the correlation between NT-proBNP and ghrelin and acyl-ghrelin, molecules determined using ELISA methods. In a cross-sectional observational study, we included 80 patients with pre-dialysis CKD, with a mean age of 68 years and 50% men. The median values for NT-proBNP were 351.8 pg/mL, for acyl ghrelin 16.39 pg/mL, and for ghrelin 543.32 pg/mL. NT-proBNP was correlated with ghrelin ( p = 0.034, r = 0.24), acyl-ghrelin ( p = 0.033, r = -0.24), estimated glomerular filtration rate ( p = 0.027, r = -0.25), serum urea ( p = 0.006, r = 0.31), and ferritin ( p = 0.041, r = 0.28). In multivariate analysis, ghrelin ( p = 0.040) and blood urea ( p = 0.040) remained significant predictors for NT-proBNP levels. NT-proBNP was a significant predictor for acyl-ghrelin ( p = 0.036). In conclusion, in pre-dialysis CKD patients, a high value of NT-proBNP was associated with a high value of total ghrelin and a low value of acyl-ghrelin.

Cardiovascular diseases (CVD) are the first cause of chronic kidney disease (CKD) mortality. For personalized improved medicine, detecting correctable markers of CVD can be considered a priority. The aim of this study was the evaluation of the impact of nutritional, hormonal and inflammatory markers on brachial-ankle Pulse Wave Velocity (PWV) in pre-dialysis CKD patients. A cross-sectional observational study was conducted on 68 pre-dialysis CKD patients (median age of 69 years, 41.2% with diabetes mellitus, 52.9% male). Laboratory data were collected, including levels of prolactin, triiodothyronine, TGF α, IL-6, and IL-1β. The high values of brachial-ankle PWV were associated with reduced muscle mass ( p = 0.001, r = -0.44), low levels of total cholesterol ( p = 0.04, r = -0.26), triglycerides ( p = 0.03, r = -0.31), triiodothyronine ( p = 0.04, r = -0.24), and prolactin ( p = 0.02, r = -0.27). High PWV was associated with advanced age ( p < 0.001, r = 0.19). In the multivariate analysis, reduced muscle mass ( p = 0.018), low levels of triiodothyronine ( p = 0.002), and triglycerides ( p = 0.049) were significant predictors of PWV, but age ( p < 0.001) remained an important factor. In conclusion, reduced triiodothyronine together with markers of malnutrition and age were associated with PWV in pre-dialysis CKD patients.

DNA damage repair pathways, including mismatch repair (MMR) genes, are prone to carcinoma development in certain patients. The assessment of the MMR system is widely recognized as part of strategies concerning solid tumors (defective MMR cancers), especially MMR proteins (through immunohistochemistry), and molecular assays for microsatellite instability (MSI). We aim to highlight the status of MMR genes-proteins (including MSI) in the relationship with ACC (adrenocortical carcinoma) according to current knowledge. This is a narrative review. We included PubMed-accessed, full-length English papers published between January 2012 and March 2023. We searched studies on ACC patients for whom MMR status was assessed, respectively subjects harboring MMR germline mutations, namely Lynch syndrome (LS), who were diagnosed with ACC. MMR system assessments in ACCs involve a low level of statistical evidence. Generally, there are two main types of endocrine insights: 1. the role of MMR status as a prognostic marker in different endocrine malignancies (including ACC)-which is the topic of the present work, and 2. establishing the indication of immune checkpoint inhibitors (ICPIs) in selective, mostly highly aggressive, non-responsive to standard care forms upon MMR evaluation (which belongs to the larger chapter of immunotherapy in ACCs). Our one-decade, sample-case study (which, to our knowledge, it is the most comprehensive of its kind) identified 11 original articles (from 1 patient to 634 subjects per study diagnosed with either ACC or LS). We identified four studies published in 2013 and 2020 and two in 2021, three cohorts and two retrospective studies (the publication from 2013 includes a retrospective and a cohort distinct section). Among these four studies, patients already confirmed to have LS (N = 643, respective 135) were found to be associated with ACC (N = 3, respective 2), resulting in a prevalence of 0.0046%, with a respective of 1.4% being confirmed (despite not having a large amount of similar data outside these two studies). Studies on ACC patients (N = 364, respective 36 pediatric individuals, and 94 subjects with ACC) showed that 13.7% had different MMR gene anomalies, with a respective of 8.57% (non-germline mutations), while 3.2% had MMR germline mutations (N = 3/94 cases). Two case series included one family, with a respective four persons with LS, and each article introduced one case with LS-ACC. Another five case reports (between 2018 and 2021) revealed an additional five subjects (one case per paper) diagnosed with LS and ACC (female to male ratio of 4 to 1; aged between 44 and 68). Interesting genetic testing involved children with TP53 -positive ACC and further MMR anomalies or an MSH2 gene-positive subject with LS with a concurrent germline RET mutation. The first report of LS-ACC referred for PD-1 blockade was published in 2018. Nevertheless, the use of ICPI in ACCs (as similarly seen in metastatic pheochromocytoma) is still limited. Pan-cancer and multi-omics analysis in adults with ACC, in order to classify the candidates for immunotherapy, had heterogeneous results, and integrating an MMR system in this larger and challenging picture is still an open issue. Whether individuals diagnosed with LS should undergo surveillance for ACC has not yet been proven. An assessment of tumor-related MMR/MSI status in ACC might be helpful. Further algorithms for diagnostics and therapy, also taking into consideration innovative biomarkers as MMR-MSI, are necessary.

Early diagnosis of pregnancy- and lactation-associated osteoporosis (PLO) is mandatory for a good outcome. Standard care is not a matter of conventional guidelines, rather it requires an individualized strategy while true overall incidence and pathogeny remain open issues. This is a narrative review based on full-length English articles, published between January 2021 and March 2023 and accessed via PubMed (no traumatic fractures or secondary osteoporosis are included). Our case-sample-based analysis included 836 females with PLO (the largest cohort based on published cases so far) through 12 studies and 24 single case reports. Except for one survey, these involved retrospective cohorts of small size (6-10 females/study) to medium size (23-47 women/study), and large cohorts with >50 subjects per study (a maximum of 379). Age of diagnosis: from 24 to 40 years for case reports (most subjects being over 30 and primigravida), while original studies indicated an average age between 31 and 34.18 years. Type of fractures underlined a most frequent vertebral phenotype (a mean of 2 to 5.8 vertebral fractures per patient) versus a most severe non-vertebral phenotype (hip and femoral neck fractures mostly requiring surgery). Potential contributors varied: smoking (1/3-1/2 of subjects), family history of osteoporosis (1/3), heparin and glucocorticoid use in pregnancy, low body mass index (majority of cases), hypovitaminosis D; and (with a low level of statistical significance) anti-psychotic medication, gestational diabetes, lupus, thrombophilia, anemia, in vitro fertilization (1/3 in one study), twin pregnancy, tocolysis with MgSO4, and postpartum thyroiditis. Most remarkably, up to 50% of PLO patients harbor mutations of LRP5, WNT1 , and COL1A1/A2 (more damaged form with potential benefits from osteoanabolic drugs); gene testing might become the new norm in PLO. The low index of clinical suspicion should be supported by performing magnetic resonance imaging (gold standard in pregnancy) with DXA (in lactation). Low bone mineral density is expected (Z-score varying from -2.2 SD to -4 SD, unless normal which does not exclude PLO). Bone turnover markers might be useful in individuals with normal DXA, in pregnancy when DXA cannot be performed, and in following the response to anti-osteoporosis drugs. Alternatively, microarchitecture damage might be reflected by DXA-trabecular bone score and high-resolution peripheral quantitative computed tomography. Specific medical interventions are currently focused on teriparatide (TPT) use (3 studies; n = 99 females treated with TPT and an additional subgroup of 18 patients from the gene-analysis-based study, thus a total of 117 females) which seems to be the therapy of choice as reflected by these new data: 6-24 months, 20 µg/day, no sequential therapy needed; case selection based on high fracture risk is necessary). The first case using romosozumab was reported in 2022. PAO/LAO remains a challenging condition which is a battle for the wellbeing of two individuals, on one hand, considering maternal-fetal outcomes and taking care of the offspring, but it is a battle for a multidisciplinary team, on the other hand, since a standardized approach is lacking.

Acromegaly-related sub/infertility, tidily related to suboptimal disease control (1/2 of cases), correlates with hyperprolactinemia (1/3 of patients), hypogonadotropic hypogonadism—mostly affecting the pituitary axis in hypopituitarism (10−80%), and negative effects of glucose profile (GP) anomalies (10−70%); thus, pregnancy is an exceptional event. Placental GH (Growth Hormone) increases from weeks 5−15 with a peak at week 37, stimulating liver IGF1 and inhibiting pituitary GH secreted by normal hypophysis, not by somatotropinoma. However, estrogens induce a GH resistance status, protecting the fetus form GH excess; thus a full-term, healthy pregnancy may be possible. This is a narrative review of acromegaly that approaches cardio-metabolic features (CMFs), somatotropinoma expansion (STE), management adjustment (MNA) and maternal-fetal outcomes (MFOs) during pregnancy. Based on our method (original, in extenso, English—published articles on PubMed, between January 2012 and September 2022), we identified 24 original papers—13 studies (3 to 141 acromegalic pregnancies per study), and 11 single cases reports (a total of 344 pregnancies and an additional prior unpublished report). With respect to maternal acromegaly, pregnancies are spontaneous or due to therapy for infertility (clomiphene, gonadotropins or GnRH) and, lately, assisted reproduction techniques (ARTs); there are no consistent data on pregnancies with paternal acromegaly. CMFs are the most important complications (7.7−50%), especially concerning worsening of HBP (including pre/eclampsia) and GP anomalies, including gestational diabetes mellitus (DM); the best predictor is the level of disease control at conception (IGF1), and, probably, family history of 2DM, and body mass index. STE occurs rarely (a rate of 0 to 9%); some of it symptoms are headache and visual field anomalies; it is treated with somatostatin analogues (SSAs) or alternatively dopamine agonists (DAs); lately, second trimester selective hypophysectomy has been used less, since pharmaco-therapy (PT) has proven safe. MNA: PT that, theoretically, needs to be stopped before conception—continued if there was STE or an inoperable tumor (no clear period of exposure, preferably, only first trimester). Most data are on octreotide > lanreotide, followed by DAs and pegvisomant, and there are none on pasireotide. Further follow-up is required: a prompt postpartum re-assessment of the mother’s disease; we only have a few data confirming the safety of SSAs during lactation and long-term normal growth and developmental of the newborn (a maximum of 15 years). MFO seem similar between PT + ve and PT − ve, regardless of PT duration; the additional risk is actually due to CMF. One study showed a 2-year median between hypophysectomy and pregnancy. Conclusion: Close surveillance of disease burden is required, particularly, concerning CMF; a personalized approach is useful; the level of statistical evidence is expected to expand due to recent progress in MNA and ART.

Various plasticizers and nanomaterials have been linked to endocrine disruptors or endocrine-disrupting chemicals (EDCs) which represent a large, heterogeneous, yet incompletely understood group of structures acting on normal and pathological body pathways such as hormonal production, secretion, transport and receptor binding. By contrast, various applications of nanoparticles are currently under investigation since the delivery of useful drugs, particularly insulin in diabetes mellitus, is essential in case of insulin deficiency. The aim of the present review was to introduce and examine different plasticizers and nanomaterials with potential applications for diabetic patients (such as selenium or gold-based nanoparticles that help the oral delivery of insulin) or plasticizers/nanomaterials acting similarly to EDCs in relation to the human and animal body, particularly glucose metabolism impairment such as diabetes mellitus (DM). Bisphenol A is a chemical used worldwide; however, the effect of exposure varies with regard to the source, environment, time of exposure and the age of the organism. Daily exposure is mostly related to food and drinks stored in polycarbonate plastics. However, exposure may also be through the skin or through the maternal placenta or breast milk which are risk factors for the fetus and for the newborn. It exerts an estrogen-like profile, but it also induces insulin resistance by impairing peripheral insulin receptors or it decreases insulin secretion by acting at the level of insulin-secreting pancreatic β-cells. Phthalates, compounds of flexible plastics, act as EDCs via their human metabolites such as diethyl phthalate and derivative monoethyl phthalate. Their role in inducing gestational DM and weight gain/obesity during pregnancy has been showcased. The vast field of plasticizers and nanomolecules acting as endocrine disruptors is widely linked to clinical aspects of DM, a serious condition with a major population impact. The importance of understanding and using these agents and applications is reflected in saving numerous human lives., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Primary hyperparathyroidism (PHPT), an endocrine condition caused by a parathyroid adenoma (PTA) in 80-85% of the cases, has shifted in the modern era to a mildly symptomatic phenotype due to the prompt recognition of hypercalcemia and to a minimally invasive surgical approach which has a curative potential. Clinical complications of PHTH are either related to high calcium or parathyroid hormone [also parathormone (PTH)] or both, while the originating tumor typically is small, without local mass effects. A distinct entity is represented by giant PTA (GPTA) which is considered at a weight of more than 3 (3.5) grams. The present article is a review of the literature involving practical points of non-syndromic PHPT-related GPTA. Most authors agree that pre-operatory calcium and PTH are higher in GPTA vs. non-GPTA. However, the clinical presentation of PHPT may be less severe, probably due to local mass effects that bring the patient to an early medical evaluation. Age distribution, sex ratio, rate of successful pre-operatory location do not differ from non-giant PTA. Hypovitaminosis D is more frequent in PTA of higher dimensions. Post-operative hypocalcemia, but not recurrent/persistent PHPT, is expected, even hungry bone disease. A higher rate of atypia is described although the tumor is mostly benign. Unusual presentations such as cystic transformation, initial diagnosis during pregnancy or auto-infarction have been reported. The ectopic localization of PTA presented in almost 15% of all cases may also be found in GPTA. What are the exact cutoffs for defining GPTA is still an open issue., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Aggressive prolactinoma (APRL) is a subgroup of aggressive pituitary tumors (accounting for 10% of all hypophyseal neoplasia) which are defined by: invasion based on radiological and/or histological features, a higher proliferation profile when compared to typical adenomas and rapidly developing resistance to standard medication/protocols in addition to an increased risk of early recurrence. This is a narrative review focusing on APRL in terms of both presentation and management. Upon admission, the suggestive features may include increased serum prolactin with a large tumor diameter (mainly >4 cm), male sex, early age at diagnosis (<20 years), and genetic predisposition [multiple endocrine neoplasia type 1 ( MEN1) , aryl hydrocarbon receptor interacting protein (AIP) , succinate dehydrogenase ( SDHx) gene mutations]. Potential prognostic factors are indicated by assessment of E-cadherin, matrix metalloproteinase (MMP)-9, and vascular endothelial growth factor (VEGF) status. Furthermore, during management, APRL may be associated with dopamine agonist (DA) resistance (described in 10-20% of all prolactinomas), post-hypophysectomy relapse, mitotic count >2, Ki-67 proliferation index ≥3%, the need for radiotherapy, lack of response in terms of controlling prolactin levels and tumor growth despite multimodal therapy. However, none of these as an isolated element serves as a surrogate of APRL diagnosis. A fourth-line therapy is necessary with temozolomide, an oral alkylating chemotherapeutic agent, that may induce tumor reduction and serum prolactin reduction in 75% of cases but only 8% have a normalization of prolactin levels. Controversies surrounding the duration of therapy still exist; also regarding the fifth-line therapy, post-temozolomide intervention. Recent data suggest alternatives such as somatostatin analogues (pasireotide), checkpoint inhibitors (ipilimumab, nivolumab), tyrosine kinase inhibitors (TKIs) (lapatinib), and mTOR inhibitors (everolimus). APRL represents a complex condition that is still challenging, and multimodal therapy is essential., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

This is a narrative review focusing on neuroendocrine neoplasia (NEN) and bone status, in terms of metastases and osteoporosis/fractures. One fifth of NEN have skeletal dissemination, this affinity being regulated by intrinsic tumor factors such as the C-X-C chemokine receptor 4 (CXCR4). Bone colonization impairs the patient quality of life, representing a surrogate of reduced survival. Patients with NEN without bone metastases may exhibit low bone mineral density, perhaps carcinoid-related osteoporosis, yet not a standardized cause of osteoporosis. Case-finding strategies to address bone health in NEN with a good prognosis are lacking. Contributors to fractures in NEN subjects may include: menopausal status and advanced age, different drugs, induced hypogonadism, malnutrition, malabsorption (due to intestinal resection, carcinoid syndrome), hypovitaminosis D, impaired glucose profile (due to excessive hormones such as glucagon, somatostatinoma or use of somatostatin analogues), various corticoid regimes, and high risk of fall due to sarcopenia. Pheocromocytoma/paraganglioma involve bone through malignant forms (bone is an elective site) and potential secondary osteoporosis due to excessive hormonal content and increased sympathetic activity which is a key player of bone microarchitecture/quality as reflected by low Trabecular Bone Score. Glucocorticoid osteoporosis is related to NEN-associated ectopic Cushing syndrome. Currently, there are a lack of studies to emphasis that excessive gut-derivate serotonin in NENs with carcinoid syndrome is a specific activator of bone loss thus a contributor to carcinoid-related osteoporosis., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Anorexia nervosa is an eating disorder characterized by restrictive eating and an intense fear of gaining weight. It is a disease with an increasing incidence during the last few decades, and represents a complex psychiatric condition which includes secondary amenorrhea, nutritional and metabolic damage, and impaired endocrine panel up to bone loss as well as cardiac, gastrointestinal and hematological complications. This is a narrative review which includes an update on this eating disorder from the perspective of an endocrine panel of anomalies, especially of the skeleton, considering the pressure of the recent global COVID-19 pandemic changes. Practically affecting every organ, anorexia nervosa needs to be taken into consideration during the pandemic period because of the higher risk of relapse due to new living conditions, social distancing, self-isolation, changes in food access, more intense use of social media platforms, disruption of daily habits, and more difficult access to healthcare practitioners. The lack of physical activity in addition to vitamin D deficiency related to low sun exposure or to the use of facial masks may also be connected to further bone damage related to this disease., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

In patients who were not previously diagnosed with any thyroid conditions, the scenario of COVID-19-related anomalies of the hypothalamus-pituitary-thyroid axes may include either: A process of central thyroid stimulating hormone (TSH) disturbances via virus-related hypophysitis; an atypical type of subacute thyroiditis which is connected to the virus spread or to excessive cytokine production including a destructive process with irreversible damage of the gland or low T3 (triiodothyronine) syndrome (so called non-thyroid illness syndrome) which is not specifically related to the COVID-19 infection, but which is associated with a very severe illness status. Our objective here was to briefly review thyroid changes due to the COVID-19 infection. Ongoing assessment of the effects of the COVID-19 pandemic will reveal more information on coronavirus-induced thyroid conditions. Routine thyroid assays performed in patients with severe infection/at acute phase of COVID-19 are encouraged in order to detect thyrotoxicosis. After recovery, thyroid function should be assessed to identify potential hypothyroidism. There remain unanswered questions related to the prognostic value of interleukin-6 in infected patients, especially in cases with cytokine storm, and the necessity of thyroid hormone replacement in subjects with hypophysitis-related central hypothyroidism., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Vitiligo, the discoloration of the skin, has different autoimmune mechanisms reflected by many biomarkers as shown by skin histology, staining for CD4 and CD8 T lymphocytes, chemokine ligand 9 or circulating cytokines such as interleukin (IL)-1 beta, interferon (IFN)-gamma, transforming growth factor (TGF)-beta, antibodies, markers of oxidative stress, chemokines, and others. In this narrative review, we aim to overview vitiligo in relationship with chronic autoimmune thyroiditis. Regarding vitiligo, more than 50 different genetic loci have been associated with this disease, and the heritability is high. There is a 20% risk of an environmental connection which may also act as a trigger; moreover, the association with human leukocyte antigen (HLA) expression is well recognized. The specific lesions display CD8+ tissue-resident memory T cells as continuous key activators of melanocytes. The association with chronic thyroiditis is based on common autoimmune background and excessive reactive oxygen species that destroy melanocytes and thyrocytes (oxidative stress hypothesis) with thyroxine and melanin as target molecules, thus sharing a common origin: tyrosine. Moreover, common epigenetic anomalies or mutations of the Forkhead transcription factor D3 (FOXD3) have been described. Since vitiligo affects up to 1-2% of the population worldwide and 34% of patients have positive thyroid antibodies, apart from common autoimmunity background and oxidative stress toxicity, the association is clinically relevant for different practitioners., (©2021 JOURNAL of MEDICINE and LIFE.)

Objectives : The mechanisms of obesity-associated thyroid dysfunction in children are incompletely deciphered. We aimed to evaluate whether visceral adipose tissue (VAT), insulin resistance (IR), inflammation, oxidative stress (OS) are involved in thyroid morpho-functional changes in pubertal obese children. Methods : We recruited 43 obese pubertal children without history of thyroid pathology. Metabolic and thyroid parameters (visceral fat thickness [VFT], waist/hip ratio [WHR], waist/height ratio [WHtR], insulin, glucose, liver parameters, thyroid stimulation hormone [TSH], free thyroxine [FT4], free triiodothyronine [FT3], thyroid and abdominal ultrasonography) were evaluated. Serum monocyte chemoattractant protein-1 (MCP-1) and malondialdehyde (MDA) levels were quantified as markers of inflammation and OS. Results : VFT correlated positively both with WHR (p= 0.034) and the presence of thyroid nodules (p= 0.036). WHR associated with TSH (p= 0.005), FT3/FT4 (p= 0.033) and was independently associated with FT3/FT4 increase (p< 0.001). HOMA-IR increased with visceral obesity (waist circumference, p= 0.001; WHR, p= 0.018; WHtR: p< 0.001), hepatic impairment (alanine aminotransferase, p= 0.019) and hepatic steatosis (HS; p= 0.013) and correlated positively with FT3/FT4 (p= 0.036). TSH was significantly higher in subjects with HS versus those without HS (p= 0.007) and logistic regression analysis identified TSH as a risk factor for HS (p= 0.014). MDA correlated positively with MCP-1 (p= 0.021). Conclusion : VAT and IR may be responsible for changes in thyroid parameters associated with obesity: elevated TSH, FT3/FT4 levels and increased prevalence of thyroid nodules. WHR was predictive of increased FT3/FT4. In obese children, there is an interdependent relationship between HS and thyroid function.

Glucagonoma is a hormonally active rare pancreatic neuroendocrine tumour causing an excess of glucagon. This is a narrative review based on a multidisciplinary approach of the tumour. Typically associated dermatosis is necrolytic migratory erythema (NME) which is most frequently seen at disease onset. Insulin-dependent diabetes mellitus, depression, diarrhoea, deep vein thrombosis are also identified, as parts of so-called 'D' syndrome. Early diagnosis is life saving due to potential aggressive profile and high risk of liver metastasis. NME as paraneoplastic syndrome may be present for months and even years until adequate recognition and therapy; it is remitted after successful pancreatic surgery. Thus the level of practitioners' awareness is essential. If surgery is not curative, debulking techniques may improve the clinical aspects and even the outcome in association with other procedures such as embolization of hepatic metastasis; ablation of radiofrequency type; medical therapy including chemotherapy, targeted therapy with mTOR inhibitors such as everolimus, PRRT (peptide receptor radiotherapy), and somatostatin analogues (including combinations of medical treatments). Increased awareness of the condition involves multidisciplinary practitioners., (Copyright © 2020, Spandidos Publications.)

TBS (Trabecular Bone Score) is the latest tool for clinicians to evaluate bone micro-architecture based on a pixel greyscale, which is provided by lumbar dual-energy X-ray absorptiometry (DXA). Its use enhances fracture prediction in addition to DXA-BMD (Bone Mineral Density). This is independent of fracture risk assessment (FRAX) and DXA results. We present a narrative review regarding the connection between TBS and Glucocorticoids (GC), either as a drug used for different conditions or as a tumor-produced endogenous excess. TBS is a better discriminator for GC-induced vertebral fractures compared to DXA-BMD. This aspect is similarly available for patients with osteoporosis diagnosed by DXA. TBS is inversely correlated with the cumulative dose of GC (systemic or inhaled), with disease duration, and positively correlated with respiratory function in patients with asthma. Low TBS values are found in females with a T-score at the hip within the osteoporosis range, with diabetes mellitus, or who use GC. Lumbar TBS is a screening tool in menopausal women with type 2 diabetes mellitus. TBS is an independent parameter that provides information regarding skeleton deterioration in diabetic patients receiving GC therapy in a manner complementary to DXA-BMD. TBS might become an essential step regarding the adrenalectomy decision in patients with adrenal incidentaloma in whom autonomous cortisol secretion might damage bone micro-architecture. TBS currently represents a standard tool of fracture risk evaluation in patients receiving GC therapy or with endogenous Cushing's syndrome, a tool easy to be applied by different practitioners since GCs are largely used., (©Carol Davila University Press.)

Somatostatinoma is a tumour mainly originating from pancreas or duodenum; overall with an incidence of 1/40 million persons. We introduce a narrative review of literature of somatostatinoma including the relationship with neurofibromatosis type 1. Clinical presentation includes: Diabetes mellitus, cholelithiasis, steatorrhea, abdominal pain, and obstructive jaundice while papillary tumour may cause acute pancreatitis. The neoplasia may develop completely asymptomatic or it is detected as an incidental finding during an imaging or a surgical procedure. It may be sporadic or associated to genetic backgrounds especially for duodenal localisation as neurofibromatosis type 1 ( NF1 gene with malfunction of RAS/MAPK pathway) or Pacak-Zhuang syndrome ( EPAS1 gene encoding HIF). Surgery represents the central approach if feasible but the prognostic depends on location, and grading as indicated by WHO 2017 classification of neuroendocrine tumours. Previously known as Von Recklinghausen disease, neurofibromatosis type 1, the most frequent neurocutaneous syndrome, is an autosomal dominant disorder including: Café-au-lait spot, skin fold freckling on flexural zones, and neurofibromas as well as tumours such as gliomas of optic nerve, gastrointestinal stromal tumours (GISTs), iris hamartomas and brain tumours. Duodenal somatostatinoma is associated with the syndrome which actually involves more often a duodenal tumour of GIST type than a somatostatin secreting neoplasia. Other neuroendocrine tumours are reported: Gastrointestinal NENs at the level of rectum or jejunum and pheocromocytoma. Overall, one quarter of subjects have gastrointestinal tumours of different types. Somatostatinoma, when not located on pancreas but in duodenoum, may be registered in subjects with neurofibromatosis type 1 most probably in addition to other tumours. Overall, this type of neuroendocrine tumour with a challenging presentation has a poor prognosis unless adequate radical surgery is promptly offered to the patient., (Copyright © 2020, Spandidos Publications.)

One of the rarest forms of endometriosis is abdominal wall endometriosis (AWE), which includes caesarean scar endometriosis. AWE remains a challenging condition because some issues related to this topic are still under debate. The increasing number of caesarean sections and laparotomies will expect to increase the rate of AWE. The current incidence in obstetrical and gynaecological procedures is still unknown. The disease is probably underestimated. The pathogenic mechanism involves local environment at the implant site including local inflammation and metalloproteinases activation due to local growth factors, estrogen stimulation through estrogen receptors and potential epigenetic changes. However, the underlying mechanisms are not fully explained, and we need more experimental models to understand them. The clinical presentation is heterogeneous; the patient may be seen by a gynaecologist, an endocrinologist, a general surgeon, an imaging specialist, or even an oncologist. No particular constellation of clinical risk factors has been identified, and the histological report is the major diagnostic tool for confirmation. Surgery is the first line of therapy. Further on we need protocols for multidisciplinary investigations and approaches., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Rarity of Sertoli cell tumours contributes to a low index of suspicion and therefore a thorough knowledge of the clinicopathological and immunological characteristics of such tumours is essential to diagnosis and proper management of the treatment and follow-up. The current narrative review of literature was planned to focus on ovarian Sertoli cell tumours that arise from the sex cords cells, which are typically benign unilateral neoplasia incidentally detected, or associated with hormonal hyperactivity, in women of reproductive age. A priory unpublished case of a 35-year old female is also introduced as the base of discussion Abdominal massrelated syndrome and vaginal bleeding anomalies have been reported. Genetic background, if presented, is mostly related to Peutz-Jeghers syndrome caused by STK11/LKB1 mutation. The tumour displays a microscopic tubular pattern and rarely displays cords or trabecular, retiform, spindles, diffuse or areolar structures. Although immunohistochemistry can be helpful in establishing the diagnosis, the results are sometimes inconclusive and the current results require new research to establish a specific immunological panel.

The aim of this article is to study the possible relation of serum vitamin D concentrations to body mass index (BMI), visceral fat thickness (VFT), insulin resistance (IR), inflammation (serum monocyte chemoattractant protein-1 - MCP-1) and thyroid parameters in obese patients. A total of 158 non-diabetic, obese patients aged 19-68 without a history of thyroid pathology were recruited. Biochemical markers, insulin, 25-OH vitamin D, thyroid parameters (TSH, FT3, FT4, TPO antibodies, TG antibodies) and VFT were measured. Serum MCP-1 evaluated the inflammation. A HOMA-IR cut-off value of 2.5 defined IR. Most patients had severe (70.3%) or moderate (25.3%) vitamin D deficiency. Vitamin D level was negatively associated with BMI (p = .043) and during the cold season with VFT (p = .009). Vitamin D deficiency correlated with Hashimoto's thyroiditis prevalence during the warm season (p = .047) and was a risk factor for its occurrence (p = .021). At 15 ng/mL cut-off value, vitamin D was negatively correlated with MCP-1 (p = .0006). Also, MCP-1 was positive correlated with HOMA- IR (p = .042), TPO-Ab levels (p = .011) and with Hashimoto's thyroiditis (p = .027). MCP-1 was a risk factor for vitamin D deficiency (p < .0001). Our study supports a bidirectional interaction between vitamin D and systemic inflammation in obese patients. Moreover, systemic inflammation is related to the severity and frequency of Hashimoto's thyroiditis. Vitamin D deficiency is the single independent factor associated with Hashimoto's thyroiditis in obese patients.

Objective The study's objective was to evaluate the thyroid parameters in obese insulin-resistant patients with euthyroid diffuse or nodular goiter, following Metformin treatment. Patients and methods The study was experimental, open, and prospective. Fifty-three patients aged 18-68 were enrolled for two years. Obese insulin-resistant patients (cut-off Homeostasis-Model-Assessment of Insulin Resistance-HOMA-IR ≥ 2.5) with euthyroid nodular/diffuse goiter were included. Subjects with diabetes, hypo-/hyper-thyroidism, autoimmune thyroiditis, psychiatric disorders, liver or heart failure were excluded. Patients were randomly assigned to one of the following treatment: Metformin 1000 mg/day + Levothyroxine 25 μg/day (M + LT4 group) and only Levothyroxine 25 μg/day (LT4 group). Thyroid and metabolic parameters' evolution was investigated over six months. Results The two groups were comparable at baseline (p ≥ 0.10). TSH, waist/hip ratio (WHR), visceral fat thickness (VFT), insulin, and HOMA-IR decreased significantly more in M + LT4 group compared to LT4 group. TSH decrease correlated with WHR reduction (p = 0.002) only in M + LT4 group. Moreover, the multivariate regression analysis revealed that insulin's and HOMA-IR levels' decrease was an independent factor associated with FT4's increase (p = 0.031, p = 0.033) just in M + LT4 group. No other independent association between the evolution (Δ) of TSH, thyroid volume (TTV), thyroid nodules-maximum diameter (TN-MD), and metabolic parameters was found. In addition, no significant threshold between groups was reached when ΔFT4, ΔTTV, ΔTN-MD were compared (p > 0.07), although their significant improvement was recorded between the baseline and the follow-up moment in each group (p < 0.003). Conclusion Metformin added to obese insulin-resistant patients treated with Levothyroxine for diffuse/nodular goiter determined a significant decrease in TSH and metabolic parameters, compared to those treated with Levothyroxine alone, but no significant difference regarding thyroid morphology after 6 months.

Selenium (Se) has a multilevel, complex and dynamic effect on the human body as a major component of selenocysteine, incorporated into selenoproteins, which include the selenocysteine-containing enzymes iodothyronine deiodinases. At the thyroid level, these proteins play an essential role in antioxidant protection and hormone metabolism. This is a narrative review based on PubMed/Medline database research regarding thyroid physiology and conditions with Se and Se-protein interferences. In humans, Se-dependent enzyme functions are best expressed through optimal Se intake, although there is gap in our knowledge concerning the precise mechanisms underlying the interrelation. There is a good level of evidence linking low serum Se to autoimmune thyroid diseases and, to a lesser extent, differentiated thyroid cancer. However, when it comes to routine supplementation, the results are heterogeneous, except in the case of mild Graves' orbitopathy. Autoimmune hypothyroidism is associated with a state of higher oxidative stress, but not all studies found an improvement of thyroid function after Se was introduced as antioxidant support. Meanwhile, no routine supplementation is recommended. Low Se intake is correlated with an increased risk of developing antithyroid antibodies, its supplementation decreasing their titres; there is also a potential reduction in levothyroxine replacement dose required for hypothyroidism and/or the possibility that it prevents progression of subclinical hypothyroidism, although not all studies agree. In thyroid-associated orbitopathy, euthyroidism is more rapidly achieved if the micronutrient is added to traditional drugs, while controls appear to benefit from the microelement only if they are deficient; thus, a basal assay of Se appears advisable to better select patients who need substitution. Clearly, further Se status biomarkers are required. Future introduction of individual supplementation algorithms based on baseline micronutrient levels, underlying or at-risk clinical conditions, and perhaps selenoprotein gene polymorphisms is envisaged.

Objective: The aim of this study was to evaluate the association between insulin resistance and thyroid pathology in obese patients, and compare the results between insulin-resistant and noninsulin-resistant patients., Subjects and Methods: Obese/nondiabetic patients, aged 18-70 years, attending the outpatient endocrinology service for 2 years were consecutively included. We evaluated the patients' fasting plasma glucose, insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), thyroid-stimulating hormone (TSH), free thyroxine (FT4), antithyroperoxidase antibodies (TPO-Ab), antithyroglobulin antibodies (Tg-Ab), and thyroid ultrasound., Results: We included 82 patients with a mean age 44.21 ± 12.67 years. The thyroid disorders encountered and their prevalences were: hypothyroidism (14.6%, 95% confidence interval [CI] 8.6-23.8%), hyperthyroidism (1.2%, 95% CI 2.0-6.6%), goiter (28.0%, 95% CI 19.5-3.6%), thyroid nodules (35.4%, 95% CI 25.9-46.2%), and Hashimoto's thyroiditis (32.9%, 95% CI 23.7-43.7%). HOMA-IR correlated positively with TSH levels (r = 0.24, p = 0.028), and this correlation remained after adjustment for body mass index (BMI), waist/hip ratio (WHR), serum cortisol, subcutaneous fat thickness (SFT), visceral fat thickness (VFT), triglycerides, γ-glutamyl transpeptidase (GGT), and alanine aminotransferase (ALT) in multivariate regression analysis (b = 0.207, 95% CI, 0.09-0.385, p = 0.023). TSH levels were significantly higher in patients with HOMA-IR ≥ 2.5 than in those with HOMA-IR < 2.5 (2.03 μIU/mL, interquartile range [IQR] 1.59-2.69 μIU/mL) versus 1.59 μIU/mL, IQR 0.94-2.26 μIU/mL, p = 0.023)., Conclusions: The most prevalent thyroid disorder in patients attending our endocrinology clinic for investigation of obesity was thyroid nodules. One in seven patients had hypothyroidism. Our findings suggest that TSH levels correlate with insulin resistance in obese patients.

Incidentaloma, a modern concept connected to technology progress, represents an accidentally discovered tumour, usually used for hypophysis and adrenals, and rarely for thyroid, parathyroids, and ovaries. This is a narrative review based on PubMed research, between 2012 and 2016 focusing on general and endocrine approach and current controversies. Main dilemma is the terminology itself: randomly imagery finding is enough or non-functioning profile and low-growth rate (not requiring surgery) should be mandatory? The controversies refers to best time framing of re-scanning pituitary and adrenal incidentaloma and setting of clear criteria for subclinical Cushing's syndrome. The need for general practical guidelines is imperative so clinicians from different areas of medicine touse the same definition and protocols. Currently, the widely accepted part is represented by incidental finding. For restricted defined incidentaloma the best intervention is no intervention, while some cases may require surgery depending on tumours features, patient's age and preference.

Adrenal gland ultrasonography is one of the corner stones of the abdominal ultrasonography examination for many medical specialties. The adrenal areas can be easily overlooked though adrenal gland pathology is diverse. We present the normal aspects and various transabdominal ultrasonography findings of the adrenal glands, both common and rare. Even though ultrasound examination is operator and patient dependent, we consider the examination of the adrenal glands very important, due to relatively frequent incidental detection of an adrenal mass.

Background and Aim: The cysts may potentially affect any organ; adrenals cysts are rare. This is a review of the literature regarding adrenal cysts, focusing on children and young adults., General Data: Three major types have been described: pure cysts (endothelial, epithelial, and hemorrhagic or pseudocyst), parasitic (as hydatid) cysts and cystic part of a tumour (most frequent are neuroblastoma, ganglioneuroma, pheocromocytoma, and teratoma). The complications are: bleeding, local pressure effects; infection; rupture (including post-traumatic); arterial hypertension due to renal vessels compression. Adrenal hemorrhage represents a particular condition associating precipitating factors such as: coagulation defects as Factor IX or X deficiency, von Willebrand disease, thrombocytopenia; antiphospholipid syndrome; previous therapy with clopidogrel or corticosteroids; the rupture of a prior tumour. At birth, the most suggestive features are abdominal palpable mass, anemia, and persistent jaundice. Adrenal insufficiency may be found especially in premature delivery. The hemorrhage is mostly self-limiting. Antenatal ultrasound diagnosis of a cyst does not always predict the exact pathology result. The most important differential diagnosis of adrenal hemorrhage/hemorrhagic cyst is cystic neuroblastoma which is highly suggestive in the presence of distant metastases and abnormal catecholamine profile. The major clue to differentiate the two conditions is the fact that the tumor is stable or increases over time while the adrenal hemorrhage is expected to remit within one to two weeks., Conclusion: Pediatric adrenal cysts vary from simple cysts with a benign behavior to neoplasia- related lesions displaying severe prognosis as seen in cystic neuroblastoma. A multidisciplinary team is required for their management which is conservative as close follow-up or it makes necessary different surgical procedures in cases with large masses or if a malignancy suspicion is presented. Recently, laparoscopic approach is regarded as a safe procedure by some authors but generally, open surgery is more frequent used compare to adults; in most cases the preservation of normal gland is advisable.

The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

Background and Aims: Acromegaly is a complex endocrine disorder caused by excessive secretion of GH, secondary to a GH secreting pituitary adenoma or a mixed pituitary adenoma secreting GH and PRL., Methods: The aim of this study was to evaluate the effects of combination therapy: dopamine agonist and somatostatin analogue on GH and IGF1 levels in a group of 30 patients with acromegaly. Cabergoline in a dose of 2 mg/week and 4 mg/week respectively was associated with Sandostatin LAR in a dose of 20 mg/month and 30 mg/months respectively. Eight patients were treated with Lanreotide 30 mg/week and Cabergoline 2 mg/week and 3 patients were treated with Bromocriptine 10 mg/day and Sandostatin LAR 30 mg/month., Results: Combination therapy: Cabergoline and Sandostatin achieved normal levels of IGF1 in 32% of the patients, better results being obtained after 12 months of treatment in the group treated with 4 mg Cabergoline/week. In 37% of cases the levels of IGF1 decreased by 50% after 12 months of treatment. In the group treated with Cabergoline and Somatuline a normal level of IGF1 was achieved in 25% of patients after 12 months of treatment. The outcome for the group treated with Sandostatin and Bromocriptine was similar to that obtained under Cabergoline 2 mg/week. There was no significant correlation between the level of GH and the type or dose of dopamine agonist used., Conclusions: In conclusion, combination therapy consisting of dopamine agonist and somatostatin analogue achieves a significant reduction of IGF1 levels in patients with mixed adenomas secreting GH and PRL. A decrease in IGF1 levels is directly correlated with the dose of Cabergoline used.

Intrathyroid parathyroid adenoma is a rare lesion. Its location is usually achieved by cervical ultrasound and scintigraphy. We present the case of a 48-years old woman admitted for malaise, weight loss, generalized bone pain, and important limitation of hip and scapular-humeral joints mobility. Cervical ultrasound identified a 4 cm nodular mass in the right thyroid lobe. Computed tomography revealed multiple osteolytic lesions in the pelvis, femur, ribs, phalanx, and humerus. Imagery and elevated serum levels of calcium and parathormone led to primary hyperparathyroidism, right parathyroid adenoma and bone "brown tumors". Intraoperatively, the adenoma was found in intrathyroid location. Total right lobectomy was performed. Postoperatively, the patient developed "hungry bone" syndrome requiring prolonged calcium and vitamin D treatment.

Introduction: Epicardial adipose tissue is an ectopic fat storage at the heart surface in direct contact with the coronary arteries. It is considered a metabolically active tissue, being a local source of pro-inflammatory factors that contribute to the pathogenesis of coronary artery disease. The AIM of our study was to establish correlations between echocardiographic assessment of epicardial adipose tissue and anthropometric and ultrasound measurements of the central and peripheral fat depots., Method: The study was conducted on 22 patients with or without coronaropathy. Epicardial adipose tissue was measured using Aloka Prosound α 10 machine with a 3.5-7.5 MHz variable-frequency transducer and subcutaneous and visceral fat with Esaote Megas GPX machine and 3.5-7.5 MHz variable frequency transducer., Results: Epicardial adipose tissue measured by echocardiography is correlated with waist circumference (p < 0.05), visceral adipose tissue thickness measured by ultrasonography (US) and is not correlated with body mass index (p = 0.315), hip and thigh circumference or subcutaneous fat thickness measured by US., Conclusions: Our study confirms that US assessment of epicardial fat correlates with anthropometric and US measurements of the central fat, representing an indirect but reliable marker of the visceral fat.