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.

Our aim was to explore the interactions of intercellular adhesion molecule (sICAM-1), TNF-&#945; (tumor necrosis factor-&#945;), interleukin-1&#945; (IL-1&#945;) and interleukin-6 (IL-6) with\r\ndopamine agonists in a culture of adenomatous cells from an nonfunctional macroadenoma.\r\nMaterials and methods. Tissue specimen from pituitary macroadenoma removed in transsphenoidal surgery was prepared for primary culture. Cells were counted and plated at 105/well into 24-well plates in a final volume of 1ml. Cabergoline in molar doses of 10-6, 10-7, 10-8, 10-9 was added and the cells were incubated for 4 days. sICAM-1, TNF-&#945;, IL-1&#945;, IL-6 were measured from cell-culture supernatants by ELISA kits.\r\nResults. sICAM-1, TNF-&#945;, IL-1&#945; and IL-6 were detected in the untreated control cultures after a 4d period. There was a negative correlation between TNF&#945; and IL-1&#945; (p=0.007).\r\nThe levels of PRL and hGH had measurable values above those found in culture medium without tumor cells. PRL positively correlated with IL-1&#945; ( p=0.05). hGH positively correlated with cell proliferation (p=0.049). Cabergoline treatment showed that IL-6 progressively decreased with the dose, ranging from -27.41% to -76.44%. TNF-&#945; significantly decreased (-65.90%; p<0.03)at the cabergoline 10-7 M dose. IL-1&#945; progressively increased with cabergoline dose, ranging\r\nfrom -2.53% to 345 %. sICAM-1 was significantly reduced by cabergoline at 10-9 (-47.12 %; p=0.045) and 10-6 M (-59.16%; p=0.01) doses. TNF-&#945; positively correlated with PRL (p=0.025); IL-6 positively correlated with hGH (p=0.044); sICAM-1 negatively correlated with hGH\r\n(p=0.009), TNF&#945; (p=0.025) and IL-1&#945; (p=0.044).\r\nConclusions. These data support the existence of an immunoendocrine network in pituitary tumorigenesis; TNF-&#945;, IL-6, IL-1&#945;, sICAM-1 significantly interfered by cabergoline\r\ntreatment in a dose-dependent way. However, future studies on different types of pituitary tumours are needed to confirm these findings.

Background. Patients with acromegaly (caused by growth-hormone-secreting pituitary adenomas) are at increased risk of hypopituitarism, in particular hypogonadotropic hypogonadism, before and after multimodal therapy. In affected women of reproductive age, fertility is impaired and complex fertility treatments are needed to achieve conception. C ase presentation. We present the case of a young woman with acromegaly caused by a GH-secreting macroadenoma with suprasellar and bilateral cavernous sinus extension; hypogonadotropic hypogonadism and secondary hypothyroidism were present from the initial evaluation. Neurosurgical intervention was repeatedly recommended but the patient refused it initially; also she was non-compliant to the medical treatment of acromegaly. Transsphenoidal tumor debulking with adjuvant gamma-knife radiotherapy was eventually performed. Following treatment persistent active acromegaly and hypogonadotropic hypogonadism were diagnosed. Under chronic estroprogestative replacement therapy, the patient conceived and delivered a full-term healthy newborn without any complications. Possible mechanisms are discussed. Conclusions. Secondary hypogonadotropic hypogonadism in pituitary patients, even when considered permanent (after surgery and radiotherapy), can exceptionally allow spontaneous conception and normal course of pregnancy.