ACTA ENDOCRINOLOGICA (BUC)

Introduction. Primary osteoporosis during childhood and adolescence represents an uncommon condition, and secondary forms are more likely to manifest at this age due to chronic disease and adverse effects of medical treatment. Case report. The authors report the case of a young male patient with a history of multiple idiopathic nonvertebral fragility fractures in addition to a family history of maternal osteoporosis and fracture, in whom osteoporosis was confirmed according to 2013 International Society for Clinical Densitometry (ISCD) criteria. Bone markers indicated low bone formation marker osteocalcin. Genetic testing revealed homozygosity for Sp1 COL1A1 gene polymorphism in combination to Fok-I vitamin D receptor (VDR) heterozygous polymorphism, to contribute to low bone mass and increased fracture risk. Severe premenopausal osteoporosis was present in the patient’s mother, who was also tested positive for both gene polymorphisms. Conclusion. This case report highlights the association between COL1A1 and VDR candidate gene polymorphisms and fragility fractures in a family. Individual genetic testing might be of clinical value in idiopathic osteoporosis in young patients, identifying subjects at increased fracture risk.

Introduction. Retrosternal goitre enlargement can cause compression of several mediastinal structures, especially the trachea and the superior vena cava. Retrosternal goitre as a cause of superior vena cava syndrome is a rare occurrence. We report the case of a middle aged man that underwent surgery for retrosternal goitre with compression of both innominate veins presenting as superior vena cava syndrome. Case Presentation. A 50 year old man presented with a 2 year history of cyanosis of the upper limbs, head and neck, marked facial edema, plethora, dyspnea on exertion and choking sensation. Pemberton’s sign was present. Computer tomography diagnosed retrosternal goitre at the level of the aortic arch, tracheal compression and important collateral circulation. Endocrine evaluation showed normal thyroid function (fT4 15.8 pmol/L) with low-normal TSH (0.5mU/L), normal calcitonin (<2 pg/mL). The patient underwent successful total thyroidectomy with cervical approach and his symptoms dramatically improved. The facial oedema persisted for the next 3 weeks. Discussion. Less than 3% of superior vena cava syndromes are secondary to a variety of benign causes. Superior vena cava syndrome caused by slow growing retrosternal goitres is very rare and can be asymptomatic for a long period due to venous collateral development. Conclusion. Superior vena cava syndrome secondary to retrosternal goitres, a very rare occurrence, is an indication for total thyroidectomy, with low postoperative morbidity and dramatic resolution of symptoms.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for various types of hereditary hematologic disease, hematological malignancy, primary immunodeficiency and metabolic disease. Thyroid dysfunction is a common complication of HSCT, which situation is mainly manifested as hypothyroidism and rarely as hyperthyroidism. This report presents a 28-yearold man who developed hyperthyroidism 9 years after sibling allogeneic HSCT, which was most likely caused by chronic GVHD. In the meantime, the patient also suffered from liver dysfunction and pancytopenia, for which he was inappropriate to take antithyroid drugs (ATD) for treatment of hyperthyroidism. The patient was orally administered 259 MBq 131I, an individualized dose. The symptoms of hyperthyroidism were mitigated by 131I treatment.

Turner syndrome is the most common sex chromosomal abnormality in about 1:2000-2500 live female births. While short stature and delayed puberty are the most common presentations of patients, atypical findings can also be seen. In this article, we present the Turner twins, who were diagnosed during inguinal hernia surgery when bilateral uterus and ovaries were found within the hernia sac. To the best of our knowledge, our cases were the first defined heterokaryotic monozygotic twins with isochromosome Xq 46,X,i(X)(q10) and Xq mosacism (46,X,i(X)(q10;q10) [42]/47,X,i(X)(q10;q10)x2[8]).

Diabetes is one of the most prevalent chronic disorders, associating numerous somatic and behavioral modifications. Oxytocin has been widely studied for its involvement in social behavior and psychiatric disorders. This pilot study presents a series of 3 patients with type 1 diabetes and diabetic neuropathy in which the values of plasma oxytocin, neurotensin, β-endorphins, α-MSH, substance P and orexin A were measured in comparison to 3 healthy controls with matching ages. In the diabetic patients group, there was a strong negative correlation between the value of plasma glucose and oxytocin (r=-0.99, p=0.04), respectively neurotensin (r=- 0.99, p=0.03). These values did not correlate in the control group. The results suggest that oxytocin, in conjunction with neurotensin, could be investigated as a potential early detection marker of diabetic neuropathy and, to our knowledge, this is the first report focusing on plasma oxytocin levels in patients with diabetic neuropathy.

Metastatic tumors account for 5-10% of all ovarian malignancies. They are usually bilateral tumors with a multinodular surface and extensive extra ovarian spread. Lung cancer is a rare source (0.3% of metastatic ovarian tumors). Among synchronous primary cancers, ovarian cancer is most frequently associated with endometrial cancer. The differential diagnosis between a primary ovarian carcinoma, synchronous primary cancers, and metastatic ovarian carcinoma is very important, as the treatment and prognosis are markedly different. We report the case of a 25-year-old woman who had been diagnosed and treated for stage IIIB small cell lung carcinoma (SCLC). Imaging undertaken for abdominal pain revealed a unilateral 8.5 cm ovarian tumor for which adnexectomy was performed. Histology and immunohistochemistry led to the diagnosis of ovarian metastasis from SCLC, a high-grade neuroendocrine lung tumor. This patient’s particular features, all infrequent in a metastatic tumor, are the lesion’s unilaterality (atypical for ovarian metastases in other cancers, but often observed in SCLC), the smooth ovarian surface with intact capsule, and the absence of intra-abdominal dissemination. The patient developed liver and vertebral metastases. This report focuses on the differential diagnosis between primary and metastatic ovarian neoplasms. We performed an extensive search of the literature on SCLC and ovarian metastases. Immunohistochemistry is essential for diagnosis when imaging and the pathological evaluation of the ovarian tumor cannot make the differential diagnosis.

Context. Memory deficits, anxiety and depression are often associated with diabetes, worsening diabetic patients’ prognosis. Caffeine, a worldwide used psychoactive substance, is a candidate for improving these conditions. Objective. The aim of this study was to assess the behaviour in streptozotocin-induced diabetic Wistar rats and to evaluate the behavioural effects of caffeine administration. Materials and methods. Diabetes was induced by a single intraperitoneal injection of 50 mg/kg BW streptozotocin (n=10), while control rats received the vehicle (n=9). After six weeks, behavioural tests for anxiety, memory and depression were performed: elevated plus maze (EPM) test, novel object recognition (NOR) test and forced swimming test (FST), respectively. The tests were repeated after further 2 weeks of continuous caffeine administration (20 mg/kg BW/day in drinking water). Results. Diabetic rats manifested a high anxiety level, showed by a reduced exploratory activity compared to control rats (p<0.05) and long-term memory impairment, spending more time near the old object in NOR test. Caffeine administered for 2 weeks did not modify glycemic values in either group, and attenuated the behavioural changes observed in the EPM test. Also, in NOR test for long-term memory, caffeine administration induced an increased time spent with the novel object than with the old one in both groups. Conclusions. Our data suggest that chronic caffeine administration has an anxiolytic effect in diabetic rats and improves long-term memory in both diabetic and control rats.

Introduction: Leptin, which is known to regulate appetite and energy expenditures, may also contribute to mediate the effects of fat mass on the bone.\r\nObjective: The aim of this study was to analyse to what extent leptin and total body composition influence the maintenance of bone mass.\r\nSubjects and methods: We evaluated 34 women divided into two BMI-matched groups based on the ovarian function: 12 premenopausal women, aged 34.08?7.18 years and 22 postmenopausal women aged 61.31?4.51 years, respectively. Total body composition (total fat mass, trunk fat mass and lean mass) and bone mineral density were measured by means of dual-energy X-ray absorptiometry (DXA). Serum leptin concentrations were assessed by ELISA.\r\nResults: The bone mineral content was influenced by both the fat mass (women with normal menstrual cycles r=0.62, p=0.03; postmenopausal women r=0.625, p=0.002) and the trunk fat mass (r=0.597, p=0.004 premenopausal women; r=0.675, p=0.001 postmenopausal women), independently of the ovarian function. Only for the postmenopausal group we could identify a significant correlation between leptin levels and the total body bone mineral density (r=0.479, p=0.024) and the total body bone mineral content (r=0.605, p=0.003), respectively. The serum leptin levels were highly significantly correlated with the total fat mass and the trunk fat mass for both groups. No difference was obtained with regard to the serum leptin levels between pre- and postmenopausal women.\r\nConclusions: Our results suggest the role played by leptin and the fat mass in the maintenance of bone mass.

Objective. ARMC5 mutations are responsible for the development of primary bilateral macronodular adrenal hyperplasia (PBMAH). In this study, we aimed to report a novel ARMC5 germline variant in a PBMAH patient family. Method. CT examination and dexamethasone suppression test (DST) were used in the diagnosis of PBMAH. Sanger sequencing was used to validate the familial heredity. For the novel variant, protein predictive analysis was performed to study the changes of secondary and tertiary structures and hydrophobicity. Results. A 45 years old male (proband, III-1) was diagnosed as PBMAH. Whole-exome sequencing (WES) was performed, finding one mutation: c.719_ 724dup, p Arg240_ Pro241dup. Sanger sequencing showed the II-2, III-1, IV-1 with heterozygous gene, confirming the familial heredity. For protein predictive analysis, the predicted secondary structure of variants has one alpha–helix structure incomplete compared with normal ARMC5. The tertiary structure could draw the same conclusion, that hydrophobicity decreases after mutation. Conclusion. We reported a new-found ARMC5 germline variant in PBMAH using WES and protein predictive analysis. With the help of WES, early diagnosis of PBMAH could help variant carriers to prevent the occurrence of cancer by lifetime follow-up.