ACTA ENDOCRINOLOGICA (BUC)

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Aim. The purpose of this study was to examine various hormonal, biochemical and environmental factors (i.e., smoking and alcohol intake) and to investigate their possible correlation to the development of polycystic ovary syndrome (PCOS). The main objective was to evaluate the associations between hormonal profile and the antimüllerian hormone (AMH) levels in PCOS patients and their relation to environmental factors. Patients and Methods. In two gynecological clinics, 38 women with PCOS (defined according to the Rotterdam criteria) were enrolled and observed in relation to AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), Δ4-androstendione (Δ4- A), dehydroepiandrosterone sulfate (DHEA-S) and glucose plasma concentrations. Obesity, smoking and alcohol exposure were also studied. Results. AMH, T, Δ4-Α, DHEA-S, LH and FSH were increased in 76.3%, 50%, 31.8%, 23.7%, 21% and 18.4% of the patients, respectively. The LH/FSH ratio and glucose concentrations increased abnormally in 18.4% and 15.8% of the patients, respectively. AMH and T levels were both increased in 47.4% of the patients whereas both AMH and LH levels increased in 21% of the patients. Smoking, alcohol intake, obesity and glucose concentrations were not associated with AMH concentrations. On the contrary, high levels of T and LH were linked to higher levels of AMH. FSH concentrations were not increased in these patients. Conclusion. AMH is an important hormonal parameter for the diagnosis of PCOS. Larger clinical controlled studies are necessary in an effort to further investigate the inclusion of AMH measurement in the diagnostic criteria of PCOS.

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.

Context. Osteonecrosis (ON) is bone death caused by inadequate blood supply and its optimal management remains uncertain. Objective. We describe the outcomes of BP (pamidronate) treatment in our patients. Design. Data regarding clinical, laboratory, magnetic resonance imaging (MRI) studies, and bone mineral density measurements (BMD) were recorded before and one year after treatment (reevaluation). The severity of the clinical picture was assessed using the criteria of the common terminology criteria for adverse events (CTCAE). Subjects and Methods. There were four female patients (patient 1, acute lymphoblastic leukemia; patient 2, immune thrombocytopenic purpura; patients 3 and 4, systemic lupus erythematosus) .All of them had been treated with high-dose prednisolone. Clinical picture of all patients were consistent with grade 3 according to CTCAE(: severe symptoms, limiting self-care ). Results. ON lesions were multifocal in the lower limbs in all of them and none of them had any fractures. All of them had been treated with high-dose glucocorticoid. Patients were treated with pamidronate (1 mg/kg/day, with maximum dose of 60 mg/day, for two days, quarterly). At the time of re-evaluation(one year after treatment), the lesions were stable on MRI, and their clinical condition was consistent with grade 1 according to CTCAE(asymptomatic). No side effects related to the use of bisphosphonates were observed except for increased BMD (SD score of 2.9) in one of the patients. Conclusions. Pamidronate may be an effective treatment for the improvement of functional impairment and pain among patients with severe osteonecrosis (ON) lesions.

Objective. To examine the prevalence of laryngopharyngeal reflux disease (LPRD) in patients with hypothyroidism.\r\nMaterials and Methods. A total of 85 patients with hypothyroidism vs 31 matched controls were recruited. Demographic data was collected and an RSI questionnaire\r\nfilled. A score > 10 was considered diagnostic of LPRD. The average score of every question was computed for all patients and compared to the corresponding average score in controls.\r\nResults. Mean age of hypothyroidism patients was 44.92 ? 13.77 years (83% females). One third of subjects were smokers and 10% had allergy. In 78.8% of the cases Hashimoto?s disease was the etiological factor and 22.4% patients had history of thyroidectomy. At the time of examination, only 30% had a TSH > 4.2 mU/L. There was\r\na borderline significance where more patients than controls had a RSI > 10 (24.7% patients vs. 9.1% controls), but with non-significant difference (p = 0.077). Similarly, closer\r\nexamination of those with TSH > 4.2mU/L compared to those with controls revealed a higher prevalence in the former group, but statistically non-significant (p = 0.275). A\r\ncomparison between those with TSH > 4.2 mU/L and cases diagnosed with hypothyroidism and normal TSH revealed no\r\nsignificant difference in the prevalence of LPRD. All laryngopharyngeal questions had a score higher in the hypothyroid group than controls.\r\nConclusion. LPRD is more prevalent in hypothyroidism patients compared to normal individuals, but with nonstatistically significant difference. The prevalence of symptoms should alert physicians to the possibility of LPRD and prompt further diagnostic tests and therapeutic intervention.

Context. Cardiovascular risk is increased in women with polycystic ovary syndrome (PCOS). Do insulin sensitizing agents such as metformin (MET) and myoinositol (MI) ameliorate biomarkers of cardiovascular risk? Objective. To compare the effects of MET and MI on blood pressure, lipid profile and high sensitive C-reactive protein (hs-CRP) in women with PCOS in respect to their body mass index (BMI). Design. Open label, parallel randomized, single center study. Subjects and Methods. Sixty six women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of hormones, lipid profile, oxidized LDL (ox-LDL), hs-CRP, blood pressure measurement and clinical assessment of BMI, waist circumference (WC) and Ferriman Gallwey score (FG score) were performed before and after treatment. Results. Thirty patients in each group completed the trial. Compared with MET, MI significantly decreased diastolic blood pressure (DBP) (p=0.036) and significantly increased serum hs-CRP (p=0.043). No differences between groups in total cholesterol (TC), HDL-cholesterol, LDLcholesterol, ox-LDL and triglycerides were reported after 6 months. Treatment with MI reduced BMI (p=0.037), WC (p=0.005), DBP (p=0.021) and TC (p=0.008). During MET treatment a significant decrease in BMI (p=0.005), WC (p=0.004), FG score (p=0.001), testosterone (p=0.013) and free androgen index (FAI) (p=0.006) was observed. Conclusions. Our study showed an advantage of MI in reduction of DBP and TC thus predicting favorable metabolic and cardiovascular outcomes in PCOS women. MET more effectively decrease indices of hyperandrogenism.

Background. Isolated methylmalonic acidemia refers to a group of inborn errors of metabolism characterized by elevated methylmalonic acid concentrations in the blood and urine. It occurs in approximately one to three out of every 100 thousand Chinese newborns. Mutations in the MMAA gene cause isolated methylmalonic acidemia. Case presentation. A 13-month-old boy was diagnosed with isolated methylmalonic acidemia. We identified two mutations in the MMAA gene in this case: c.491G>A and c.650T>A. The c.491G>A is a novel mutation in the MMAA gene. The boy is a heterozygous carrier of both mutations. The boy was treated with intravenous sodium benzoate and fluids. His sensorium gradually improved and he recovered from the acute illness. Other family members are heterozygous carriers of either mutations but with no symptoms. Conclusions. We identified a novel c.491G>A mutation in the MMAA gene. Heterozygous carriers of both c.491G>A and c.650T>A mutations are associated with isolated methylmalonic acidemia.

Isolated sarcoidosis of the hypothalamic-pituitary system is a very rare form of neurosarcoidosis. A high index of suspicion is required for diagnosis and the choice of therapy embodies another challenge due to lack of standardized protocols. Glucocorticoids are the mainstay of initial treatment, whereas the second and third-line therapy include immunomodulators and cytotoxic drugs, in addition to monoclonal antibodies. This report presents an unusual case of panhypopituitarism in a 32-year-old previously healthy male patient due to isolated hypothalamo-pituitary sarcoidosis confirmed histologically, refractory to pulsedose glucocorticoids and then successfully treated by methotrexate. Based on our report, in patients requiring additional therapy usage of the methotrexate as the second line agent should be considered, however the time frame and the dosing schedule of methotrexate are still unknown and deserve further investigation.

Xanthogranulomas are inflammatory lesions exceptionally rarely occurring in the sellar region. Sellar xanthogranulomas (SXG) result from secondary hemorrhage, infarction, inflammation or necrosis upon existing craniopharyngioma (CP), Rathke`s cleft cyst (RCC) or pituitary adenoma (PA), or represent a stage in xanthomatous hypophysitis evolution. “Pure SXG” are independent of a preexisting lesion. A 70 year old male patient, laryngeal cancer survivor, presented with central diabetes insipidus (CDI). MRI revealed an intra-suprasellar mass of uncertain origin. Transsphenoidal surgery resulted in an efficient lesion resection with maximal pituitary sparing. Pathological report has confirmed SXG without conclusive identification of preexisting sellar lesion. Age at presentation and gender were atypical for SXG. The most frequent presenting signs of SXG were absent. Most SXG are initially misdiagnosed as CP, RCC or PA. Preoperative clinical and radiological uncertainty may impact operative planning. Differentiating from CP is crucial, due to divergent operative target goals and prognosis. Intraoperative frozen section analysis could guide surgical extensiveness. Close collaboration must include endocrinologist, neuroradiologist, neurosurgeon and pathologist. Quantity and quality of provided tissue are essential for avoiding bias in pathohistological analysis of cystic or heterogenous lesions. Awareness is needed of new pathological entities in the sellar-parasellar region. SXG should be considered in differential diagnosis of CDIcausing sellar lesions.