ACTA ENDOCRINOLOGICA (BUC)

We report the case of a 6.6 years old boy, born to healthy unrelated parents, from a normal pregnancy, admitted for severe growth retardation. His height was 71 cm\r\n(-9.3 SD), with a weight of 6.6 kg and he presented a triunghiular face, mycrognatia, proeminent nose and hypertelorism resulting in a ?bird headed? profile. He associated clinodactyly of the 5th finger and a slightly longer left leg. Tanner stages were P1 G1. The\r\nbiochemical panel was normal, but he presented mild hypocromic anemia. The thyroid function was normal, and the IGF1 low. The karyotype was 46 XY and the bone age 4.5\r\nyears. The pituitary computed tomography revealed empty sella. Based on the clinical picture, the possible diagnosis of Seckel syndrome was suspected. A short course of treatment with Metandienonum 0.04 mg/kg/day for 3 months was recommended, without success (growth speed of 6 cm/year - -0.14 SD)

Smith-Lemli-Opitz syndrome is an autosomal recessive disorder caused by mutations of 3-hydroxysterol –7reductase gene (DHCR7) which maps to 11q12-13 and was the first discovered defect in cholesterol biosynthesis resulting in a congenital dysmorphology syndrome. We present the case of a 46,XY newborn with ambiguous genitalia and multiple congenital anomalies (atrial septal defect, ventricular septal defect, syndactyly of the second and third toe, cleft palate, webbed neck, small fontanels, mesomelia, simian palmar crease, micrognathia, wide nasal bridge with anteverted nostrils, low set ears). Hormonal assessment performed at twelve days revealed a decreased testosterone level (0.03 ng/mL), a high estradiol level (448.8 pg/mL), normal LH (2.8UI/mL), DHEAS (86.61?g/dL), progesterone (1.34ng/mL) and 17 hydroxyprogesterone (1.08ng/mL) levels. Cholesterol was low (44mg/dL) confirming the diagnostic of Smith-Lemli-Opitz syndrome.

Context. Gender identity, psychosexual function, psychiatric adjustment and quality of life have been investigated in congenital adrenal hyperplasia(CAH) patients. Objective. We aimed to investigate gender identity problems and the psychiatric disorders and associated factors in children and adolescents with CAH patients. Subjects and methods. Forty-five children and adolescents with CAH were included in the study. Psychiatric comorbidity was assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children – Present and Lifetime Version. Gender identity problems were investigated using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Results. The mean age of the sample was 11.02 years (SD: 3.25, range: 6–18). 51.1% of the patients had at least one lifetime comorbid psychiatric disorder. The most common diagnoses were anxiety disorders, attention deficit hyperactivity disorder(ADHD), tic disorders and enuresis nocturna. Tic disorders and ADHD were higher in males but they were not statistically significant. Two female patients were diagnosed with gender dysphoria and 18.5% of females showed variably masculinized behaviors. The girls with gender identity problems expressed lower satisfaction with their sex than other girls and boys. Conclusions. Children and adolescents with CAH had many psychiatric disorders, especially neurodevelopmental disorders. ADHD and tic disorders should be kept in mind during assessment especially in male patients. Gender dysphoria and masculine behaviors seem to be common in female patients with CAH so they should be carefully investigated.

Vitamin D is essential in efficient absorption of calcium and normal mineralization of bone. Severe vitamin D deficiency produces impairment of bone mineralization and osteomalacia. Less severe vitamin D deficiency, called vitamin D insufficiency or inadequacy, causes secondary hyperparathyroidism, increased bone turnover and bone loss. The aims of our study were: the evaluation of vitamin D status and its seasonal variation in postmenopausal women with osteoporosis, from Romania; we studied also the relationship between vitamin D and parathyroid hormone serum concentrations in order to establish the threshold level of vitamin D which determines secondary hyperparathyroidism. The study was performed on 834 postmenopausal (natural or surgical) women who attended the National Osteoporosis Center and were diagnosed with osteoporosis using dual absorptiometry with X ray (DEXA). None was receiving vitamin D supplementation and they were not taking drugs affecting bone and mineral metabolism and were not suffering from such diseases. Estimation of vitamin D and parathyroid hormone status was made by determining 25-hydroxyvitamin D (25OHD) and PTH-intact (PTH) serum concentrations from a single blood sample using immuno-enzyme methods. The results were compared using Student? t test for unpaired values and linear regression to establish the correlation. All data were expressed as mean value ? standard deviation and a value of p<0.05 was considered as statistically significant. In a previous study we reported for premenopausal normal women the mean value for 25OHD at 26.58?10ng/ml. At the same time, we defined the vitamin D deficiency as the levels below 12 ng/mL, and the insufficiency of vitamin D (vitamin D inadequacy) as the values between 12 and 26.58 ng/mL. The mean serum 25OHD concentration for our study group was 20.04?144.22 mg/mL. We defined arbitrary values (using data from international studies) for 25OHD serum levels to estimate the prevalence of vitamin D deficiency and vitamin D inadequacy in our study group. In 834 postmenopausal women with osteoporosis, living in Romania, without vitamin D supplementation or pharmacological therapy to treat or prevent osteoporosis, the prevalence of vitamin D deficiency was 32.2% and the prevalence of vitamin D inadequacy was 42.3%. Seasonal variation of 25OHD was found statistically significant (p<0.05), with lower values at the end of winter. Statistical tests applied to results have shown a significant negative correlation between PTH and 25OHD serum levels (p<0.001) and established the cut-off concentration for 25OHD which determine secondary hyperparathyroidism at 20 ng/mL. Our data underscore the need for adequate vitamin D supplementation in women with osteoporosis.

Background. Advances in imaging techniques have led to increasing discovery of\r\nadrenal and pituitary &#8220;incidentalomas&#8221;, tumors with normal endocrine function and no\r\ncompression mass effects. We evaluated the age at diagnosis (AD) in patients with benign\r\nnon-functioning adrenal incidentalomas, as compared to pituitary non-functioning tumors,\r\nin a series of patients from a national center of endocrinology. Methods. From 2,123\r\nconsecutive patients with adrenal and pituitary tumors hospitalized between 1977 - 2009,\r\n2,069 patients were analysed. The study groups included: group A - 137 patients with\r\nadrenal incidentalomas (AI), group B - 534 patients with pituitary incidentalomas (PI).\r\nControl groups included 1,398 patients: group C1 147 patients with adrenal carcinomas or\r\nbenign hormone-secreting adrenal tumors, and group C2, 1,251 patients with pituitary\r\nsecreting adenomas or large non-functioning pituitary macroadenomas (NFA). Imaging was\r\ndone by computed tomography and/or magnetic resonance after 1981 and by skull X-ray or\r\npneumoencephalography before 1981. Results. Mean age AD is more advanced in patients\r\nwith AI (53 ? 11.9 years, range 21 - 78 yr) than in patients with PI (36.8 ? 13.1 years, range\r\n10 - 81 yr), p < 0.01. AD was higher in AI than in patients with secreting adrenal tumors,\r\nbut similar in patients with adrenal malignancy. There is an age-related increase in the\r\nproportion of AI among patients with adrenal tumors, and of NFA, but not of PI, among\r\npatients with pituitary tumors. In patients aged over 65 years, 74% of patients with adrenal\r\ntumors have AI, while only 18% of patients with pituitary tumors have PI and 42% have\r\nNFA. AD in NFA (49.3 ? 13.1 yr, range 12 - 79 yr) was more advanced than in PI (p < 0.01).\r\nAD does not correlate with tumor size. Tumor growth occurred in 24% of AI (follow-up 3.0\r\n? 2.8 yr) and only in 0.7% of PI, p<0.01 (follow-up 3.1 ? 2.5 yr).\r\nConclusions. Adrenal non-functioning benign tumors show a clear association with ageing,\r\nin contrast with pituitary incidentalomas. It seems unlikely that most pituitary incidentalomas in\r\nyoung patients become large NFA, whose development seems to be also age-related. It is tempting\r\nto suggest that pituitary tumorigenesis starts earlier than adrenal tumorigenesis.

Lingual thyroid is a rare developmental disorder, and it is the result of failure of the thyroid gland to descend from the tongue root to its normal site. The ectopic thyroid with a functioning gland is even rarer. In this case, we present a 44-year-old female patient with a complaint of foreign body sensation, progressive dysphagia and dyspnea due to ectopic thyroid tissue. Her complaints were totally resolved after L-thyroxine treatment. Here we report a patient with functioning ectopic thyroid tissue who had had bilateral subtotal thyroidectomy 10 years ago due to multinodular goiter. In conclusion, if progressive\r\ndysphagia, dyspnea, and foreign body sensation occurs in a patient who had thyroidectomy and living in an endemic goiter region, lingual thyroid may be underlying disorder.

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5% of all cases of primary hyperparathyroidism and it is an exceedingly rare endocrine malignancy first described in 1933. Most experts recommend en bloc excision at initial surgery as the only chance for its cure. Both chemotherapy and radiotherapy have not been demonstrated to be beneficial in parathyroid carcinoma. Some patients have multiple recurrences or metastases. Therefore, new therapies are urgently needed. Inhibition of the interaction between Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) enhances T-cell responses in vitro and mediates clinical antitumour activity. Aim. We analysed the expression of PD-L1 in parathyroid cancer to evaluate its potential as target for immunotherapeutic strategy. Subjects and methods. A cohort of 18 patients were diagnosed with primary or metastatic parathyroid cancer. Immunohistochemistry was performed in 18 formalin-fixed paraffin-embedded specimens using a rabbit monoclonal antibody. A 5% cut-off value was applied for PD-L1 positivity. Results. The anti PD-L1 antibody showed a predominantly membranous staining pattern in parathyroid cancer cells. Programmed Death Receptor Ligand-1 expression was found in 22.2% of all parathyroid carcinoma cases. There was no correlation between the expression of PD-L1 with lymph node metastasis, gender and age (P> 0.05). Conclusion. This expression of PD-L1 in human parathyroid cancer suggests that patients with parathyroid cancer could profit from immunotherapeutic strategies using anti-PDL1 antibodies.

Context. Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. Objective. The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. Subjects and methods. The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. Results. Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. Conclusions. Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%