ACTA ENDOCRINOLOGICA (BUC)

Background. Ovarian Leydig cell tumour is a very rare steroid hormones producing mass, causing clinical and biochemical hyperandrogenism. Even if the level of evidence is based on case studies, many authors (but not all) agree that raised androgens increase the cardio-metabolic risk thus early diagnosis and treatment are necessary On the other hand, the endocrine features pointing an ovarian tumour source of testosterone do not indicate the specific histological finding which needs a post-operative conformation. Case presentation. We report a case of a 60-yearold woman with a 4-year history of progressive virilisation in association with hypertension, high number of red blood cells, impaired glucose tolerance and dyslipidemia. Total testosterone was 20 times above normal with suppressed gonadotropins, inadequate for menopause. Trans-vaginal ultrasound and pelvic and abdominal computerized axial tomography imaging revealed a right ovarian solid nodule, and no evidence of alteration in the adrenal glands. Total hysterectomy and bilateral salpingo-oophorectomy were performed. Histopathology and immunohistochemistry confirmed the diagnosis of Leydig cell tumour. After surgery, androgen levels returned to normal and the doses of anti-hypertensive drugs were reduced. Conclusions. The hyperandrogenic state with elevated plasma testosterone and progressive signs of virilization raises suspicion of an ovarian androgen-secreting tumor. For a postmenopausal patient with hyperandrogenism the diagnosis of Leydig cell tumour should be considered. However, the exact diagnosis is provided by post-operative histological exam. Prolonged exposure to hyperandrogenism may generate cardiovascular abnormalities and metabolic syndrome which after tumor excision and removal of the source of androgen hormones are expected to significantly improve.

Context. Epilepsy and osteoporosis are closely related. The detrimental effect on bone by older generation of antiepileptic drugs (AEDs) is well known, but newer AEDs can also cause a decline in bone health. Objective. To provide a review on the impact of AEDs on bone mineral density, fractures and bone turnover markers and to analyze the effect of bone active treatments in epileptic patients. Methods. Medline (PubMed) and EMBASE were searched for studies about AEDs and bone health. The PRISMA statement was used. Results. Chronic use of AEDs is associated with alterations in bone metabolism, low bone mineral density values, and increased risk of fractures. These effects appear to be more associated to the use of enzyme-inducing AEDs. Supplements with vitamin D and bone active treatments may have benefits in terms of bone mineral density gain and of mortality risk. More studies are required to determine the impact of non-enzyme-inducing AEDs on bone health and to gather useful information about the management of osteoporosis therapy in epileptic patients. Conclusion. Chronic AED use has a significant impact on bone health; it is therefore necessary to evaluate in such individuals the claim to vitamin D and calcium supplements and bone active treatments.

Context. Mutations in the androgen receptor (AR) gene result in androgen insensitivity syndrome (AIS). In milder forms of AIS, male infertility appears as primary or even sole symptom. Identification of such mutations is fundamental for accurate diagnosis and for appropriate genetic counseling.\r\nObjectives. To determine the prevalence of known point mutations in the AR gene causing male infertility in Syrian\r\nazoospermic men.\r\nDesign. 15 known point mutations in the AR gene were screened in a cohort of 110 Syrian infertile men.\r\nSubjects and methods. The study involved 173 Syrian infertile men suffering from non-obstructive azoospermia.\r\nChromosome aberrations and Y microdeletions were excluded in 110 patients, which were further tested for point mutations in the AR gene by real time PCR or DNA sequencing.\r\nResults. The prevalence of AR mutations in our cohort was 3.6% (4/110). We found two patients with the Ala474Val\r\nmutation and one patient bearing the Pro390Ser mutation. Furthermore, one patient had a new mutation, del 57Leu,\r\ndescribed for the first time in an infertile man. None of the 50 fertile Syrian men had this mutation, indicating that it is not a sequence polymorphism in the Syrian population.\r\nConclusion. The del 57Leu mutation in the AR gene is a possible cause of idiopathic male infertility. Furthermore, the Ala474Val and Pro390Ser mutations (previously found in several infertile men in Italy) might be significant markers for male infertility in Mediterranean populations.

Background. Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of the luteal\r\nphase or early pregnancy after ovulation induction or ovarian stimulation. The late OHSS form presents an onset more than 10 days after ovulation triggering and is\r\ninfluenced by pregnancy-related HCG secretion.\r\nReport. This paper presents three cases of pregnancy-related OHSS after IVF/ICSI cycles discussing risk factors and management according to European Guidelines.\r\nResults. Individual risk factors are identified such as low BMI, high antral follicle count at the beginning of the ovarian stimulation, high estradiol over 3000 pg/ml.\r\nPatients had moderate OHSS (case 2) and severe OHSS (case 1 and 3). In-patient treatment was 3-14 days. OHSS resolved in\r\nall cases, without manifestations of the critical form.\r\nConclusion. The duration of OHSS is longer in the late form, is pregnancy-related and should be monitored for adverse\r\npregnancy outcomes. However the incidence of fatal risks is low and the treatment is successful.

Context. The prevalence of both heart failure and vitamin D deficiency increases with age and is associated with poor outcome in the elderly. Objectives. We aimed to investigate the relationship between all-cause mortality and vitamin D deficiency in elderly patients with chronic heart failure. Design. It is a retrospective, observational crosssectional study. Median follow-up time was 497 days. Subjects and Methods. 302 patients aged ≥65 years heart failure patients was categorized into tertiles based on the 25-hydroxy-vitamin D levels. Clinical and laboratory parameters were evaluated according to tertiles. Hospitalization rates and overall survival were compared between tertiles. Independent predictors of all cause mortality were defined. Results. Patients with low vitamin D tertile were mostly women (p=0.001), and had a worse NYHA functional class (p=0.005). During follow-up, deaths were more frequent in the first tertile (p = 0.001). All-cause mortality increased significantly with decreasing vitamin D tertiles (from third tertile 7.9%, to 11.9%, to 26%; log rank test p=0.003). No significant difference was observed at the composite endpoint of mortality or HF hospitalizations (P=0.451). Multivariate analysis supported that low vitamin D concentration was an independent predictor of all causes of mortality (HR 0.93; 95% CI 0.89-0.97; p=0.004). Conclusions. Low vitamin D levels were independent predictors of all-cause mortality in the elderly population with chronic heart failure.

Aim: to evaluate the type of surgery performed in pulmonary carcinoids.\r\nMethods. Retrospective study on database of 2282 cases of surgical patients operated\r\nin the Clinic of Thoracic Surgery between 1994 and 2004, in which 92 cases of bronchopulmonary\r\ncarcinoid tumors were included, representing 4% of lung cancers. From these 92\r\ncases, 32 were typical and 60 were atypical carcinoids, 29 women and 63 men.\r\nResults. The mean age was 39.2?18 for typical carcinoid and 51.9?13 for atypical\r\ncarcinoid. More than half of the carcinoid tumors were in 1B stage - 48 cases; the rest of the\r\ntumors were staged as: stage 3A - 20 cases, stage 2B - 12 cases, stage 4 - 5 cases, stage 3B\r\n- 4 cases and stage 1A - 3 cases.\r\nAs surgical interventions, there were performed: 63 classical lung resections, 23\r\nbronchoplastic lung resections, 5 bronchial resections without lung parenchyma and 2\r\nbiopsies: 1 lung biopsy by video-assisted thoracoscopic surgery and 1 pleural biopsy by\r\nthoracoscopy. In 9 cases of atypical carcinoids, associated surgical procedures were\r\nimposed by the tumoral extension or by the associated disorders.\r\nConclusions. The bronchoplastic and bronchoanastomotic procedures have the major\r\nrole of preserving the most of the functional pulmonary parenchyma in case of low-grade\r\nmalignancies, such as carcinoid tumors. Along the pulmonary resection, the authors consider\r\nthat mediastinal lymphadenectomy is mandatory, even in case of typical carcinoid tumors.

Adrenoleukodystrophy (ALD) is a hereditary metabolic disease X-linked (Xq28) with autosomal recessive traits, secondary to a mutation in the ABCD1 gene. The case of a boy aged 7 years and 10 months admitted for vision disturbances, muscle weakness, balance disturbances and spastic paraparesis is presented. Seventeen months prior to this admission, the child was diagnosed with acute adrenal insufficiency and was still on replacement therapy with dexamethasone and fludrocortisone. While on therapy the child presented several relapses that required treatment correction. MRI revealed cerebral atrophy lesions, which, together with the laboratory findings and clinical symptoms, conducted the diagnosis of ALD. This diagnosis was also supported by the pathogenic mutation detected in the ACBD1 gene identified in the pacient and patient?s mother and sister. The child died 8 months after the onset of neurological signs. Childhood ALD is classified as classical ALD form, the most frequent, affecting only boys aged 4 to 10 years. Family screening obliged by the identification of the homozygotes is helpful for the early therapy of heterozygotes, genetic counseling and disease prevention. The prognosis is still poor, the available treatment being hormone substitution therapy and psychological support.

Amiodarone-induced thyroid dysfunction is common but the development of hyperthyroidism following treatment for amiodarone-induced hypothyroidism is very unusual. We recently saw an elderly man who developed severe thyrotoxicosis four years after diagnosis of and initiation of treatment for amiodarone-induced hypothyroidism. The thyrotoxicosis was treated first with methimazole and discontinuation of L-thyroxine replacement and then with methimazole and prednisone. After successful treatment and withdrawal of therapy, he subsequently re-developed hypothyroidism and required resumption of L-thyroxine replacement. This case highlights that amiodarone-induced hyperthyroidism can occur in patients who previously became hypothyroid on the drug.

Reninoma (juxtaglomerular cell tumor) is a rare cause of renin-mediated hypertension. We reported a 18 year old woman with history of hypertension for 3 years. Laboratory findings showed severe hypokalemia and markedly increased levels of renin and aldosterone. Kidney ultrasonography, abdominal computed tomography and magnetic resonance imaging revealed a small mass in the middle region of the right kidney. The patient underwent nephron-sparing surgery; immunohistochemical results demonstrated typical features of reninoma. Postoperatively, blood pressure and potassium levels were normal at 1 month follow-up.