ACTA ENDOCRINOLOGICA (BUC)

Background. Hirsutism is part of current criteria of polycystic ovary syndrome (PCOS), as a clinical expression\r\nof hyperandrogenism.\r\nObjective. To evaluate the significant factors for hirsutism severity in PCOS.\r\nPatients. A total of 235 PCOS patients, consecutively coming for medical advice, aged 18-35 yrs, all of Romanian origin, were diagnosed according to Rotterdam criteria.\r\nMethods. Hirsutism, quantified using the modified Ferriman-Gallwey (mFG) procedure, was defined by values equal or\r\nmore than 6. Other parameters evaluated were: body mass index (BMI), fasting insulinemia, insulin resistance quantified by QUICKI, total testosterone (TT), free androgen index (FAI), dehydroepiandrosterone sulfate (DHEAs), 17OH progesterone, fasting glycemia. In a subset of 106 patients, androgen receptor (AR) was explored by CAG repeat\r\ngenotyping and X-chromosome inactivation analysis.\r\nResults. The total PCOS population (235) was divided in group A (n=139, 59.14%) with hirsutism and group B (n=96, 40.85%) without hirsutism. In univariate correlations, serum\r\ninsulin levels (p<0.05) and insulin resistance quantified by QUICKI (p<0.05), but not FAI, TT, DHEAs, 17OH progesterone or BMI were associated significantly with mFG score, in group A of hirsute PCOS patients and also in group B\r\nof nonhirsute PCOS. In a stepwise regression mFG model,\r\nincluding TT, insulin and BMI, only insulin remained independently associated with mFG score (p<0.05) in the group A of hirsute PCOS patients, whereas in group B\r\nof the nonhirsute PCOS, there were not significant associations. Androgen receptor parameters explored in 106 cases, i.e. by the biallelic means and X-weighted biallelic means of CAGn, did not show significant associations with mFG score in univariate correlations. Only insulin was significantly associated (p<0.05) in another stepwise\r\nregression model of mFG including as parameters insulin, TT, biallelic means of CAGn and BMI.\r\nConclusions. Our results support that insulin is significantly associated with the\r\nseverity of mFG score in PCOS patients, independent of serum androgens or androgen receptor sensitivity expressed by\r\nCAGn polymorphism. This suggests a possible pathogenic role of high insulin level for the development and progression\r\nof hirsutism, at least in PCOS.

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Pituitary radiotherapy (RT) has undergone important progress in the last decades due to the development of new stereotactic techniques which provide more precise tumour targeting with less overall radiation received by the adjacent brain structures. Pituitary surgery is usually firstline therapy in most patients with nonfunctioning (NFPA) and functioning adenomas (except for prolactinomas and large growth hormone (GH) secreting adenomas), while RT is used as second or third-line therapy. The benefits of RT (tumour volume control and, in functional tumours, decreased hormonal secretion) are hampered by the long latency of the effect and the potential side effects. This review presents the updates in the efficacy and safety of the new stereotactic radiation techniques in patients with NFPA, GH-, ACTH- or PRL-secreting pituitary adenomas. Methods. A systematic review was performed using PubMed and articles/abstracts and reviews detailing RT in pituitary adenomas from 2000 to 2017 were included. Results. Stereotactic radiosurgery (SRS) and fractionated stereotactic RT (FSRT) provide high rates of tumour control i.e. stable or decrease in tumour size, in all types of pituitary adenomas (median 92 - 98%) at 5 years. Endocrinological remission is however significantly lower: 44-52% in acromegaly, 54-64% in Cushing’s disease and around 30% in prolactinomas at 5 years. The rate of new hypopituitarism varies from 10% to 50% at 5 years in all tumour types and as expected increases with the duration of follow-up (FU). The risk for other radiation-induced complications is usually low (0-5% for new visual deficits, cranial nerves damage or brain radionecrosis and extremely low for secondary brain tumours), however longer FU is needed to determine rates of secondary tumours. Notably, in acromegaly, there may be a higher risk for stroke with FSRT. Conclusion. Stereotactic radiotherapy can be an effective treatment option for patients with persistent or recurrent pituitary adenomas after unsuccessful surgery (especially if residual tumour is enlarging) and/or resistance or unavailability of medical therapy. Comparison with conventional radiation therapy (CRT) is rather difficult, due to the substantial heterogeneity of the studies. In order to evaluate the potential brain-sparing effect of the new stereotactic techniques, suggested by the current data, longterm studies evaluating secondary morbidity and mortality are needed.

Introduction. Glucocorticoids (GC) are largely used for their anti-inflammatory and immunosuppressive effects. Until recently “local” administration (inhalation, topical, intra-articular, ocular and nasal) was considered devoid of important systemic side effects, but there is no administration form, dosing or treatment duration for which the risk of iatrogenic Cushing’s syndrome (CS) and consequent adrenal insufficiency (AI) can be excluded with certainty. Patients and methods. We present the case of a pregnant woman who developed overt CS with secondary AI in the second trimester of pregnancy. She had low morning plasma cortisol 6.95 nmol/L (normal non-pregnant range 166 – 507) and low ACTH level 1.54 pg/mL (normal range 7.2 – 63.3), suggestive for iatrogenic CS. A thorough anamnesis revealed chronic sinusitis long-term treated with high doses of intranasal betamethasone spray (6 - 10 applications/day, approximately 10 mg betamethasone/week, for 5 months). After decreasing the dose and switching to an alpha-1 adrenergic agonist spray, the adrenal function recovered in a few weeks without manifestations of AI. The patient underwent an uneventful delivery of a normal baby. A review of the literature showed that only a few cases with exogenous CS and consequent AI caused by intranasal GC administration were described, mostly in children, but none during pregnancy. Conclusion. Long-term high doses of intranasal GC may induce iatrogenic CS and should be avoided. Low levels of ACTH and cortisol should prompt a detailed anamnesis looking for various types of glucocorticoid administration.

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In the latest decade, translational medicine has played an important role. In neuroendocrine tumor field, genetic results are associated with clinical and paraclinical disease implications. This translational knowledge allows a faster action in some mutation types with aggressive outcome. In the following pages we will make a review about actualities in translational approach from genetics to clinical neuroendocrinology.

for non-functioning pituitary macroadenomas (NFMAs) is still under debate. Aim. To appreciate the best timing for postoperative high voltage radiotherapy (hRT) in different type of NFMAs (classified using immunohistochemistry (IHC)). Subjects and Methods. Of 97 patients with a remnant (>1 cm) and IHC for anterior pituitary hormones, 41 patients (groups A & B) were submitted to hRT and followed up at least 5 years. RT was performed in 20/41 patients (Group A) within the first year after surgery, 21/41 patients (Group B) afterwards while in control group C, 56 patients were followed up without hRT. The progression of postoperative remnant was defined as a change of minimum of 25% of any diameter (transversal or vertical) by serial imaging studies. Results. The IHC of NFMAs revealed the following: 38 (39%) null cell, 29 (30%) gonadotropinomas, 12 (12%) silent plurihormonal, 11 (11%) silent corticotroph and 7 (7%) silent GH/PRL adenomas. Immunoreactive adenomas have relapse rate higher than null cell adenomas (ACTH> GH/ PRL> FSH/ LH> null cell) with a significant rate for silent ACTH 6/8 (75%). The null cell adenoma relapse rate was 6/23 (26%), p<0.009 in group without hRT. The relapse rate was significantly lower in group AB with hRT than in group without RT (p=0.025), at five years. Immediate hRT (applied within in first years) improved the control of the tumour growth in 90% (18/20) cases. In the group A, 10 % (2/20) patients relapsed than 24% (5/21) patients in group B and 39% (22/56) patients, Group C. Conclusion. An optimal time for radiotherapy is within the first year after the partial surgical removal of NFMAs, particularly if a large amount of residual tumour remains. Patients with silent corticotroph adenoma require special attention.