ACTA ENDOCRINOLOGICA (BUC)

IGF-I (Insulin like growth factor-I) plays a definitive role in the central nervous system (CNS) by modulating neuronal regeneration and survival. The local production of IGF-I in CNS has been demonstrated, but the contribution of circulating IGF-I transported through blood-brain barrier (BBB) has been just suggested in animals. There is currently no data available concerning IGF-I transport in CNS in humans. In order to investigate the passage of IGF-I over BBB in humans we have simultaneously measured the IGF-I and GH levels in serum and CSF in 25 patients with active acromegaly. IGF-I and GH levels in CSF were lower than in serum (2.2 ? 0.24 ng/mL vs 686.6 ? 46.83 ng/mL for IGF-I and 2.13 ? 0.627 mU/l vs 58.8 ? 15.86 mU/L for GH). However, both IGF-I and GH serum levels correlated with their CSF levels (r= 0.4, p<0.05 for IGF-I and r= 0.651, p= 0.006 for GH), suggesting that BBB is permeable for both hormones. In conclusion, we demonstrate the correlation of the IGF-I levels in serum and CSF, providing indirect evidence for IGF-I passage through BBB.

Background. Hidradenitis suppurativa (HS) is a chronic, debilitating disease with a profound impact on the quality of life of patients. Objectives. To describe a rare case of HS with postmenopausal onset, to review the literature data regarding late onset HS and to discuss the current knowledge on the role of endocrine abnormalities in the development of HS. Case report. We report the case of a 68-year-old patient in whom HS occurred 10 years after menopause. She was referred to our clinic for the presence of an open fistula on the left groin, fibrotic scars and visible alteration of the vulvar anatomy due to numerous surgical interventions. The patient shared features of the metabolic syndrome (obesity, arterial hypertension, dyslipidemia, aortic atherosclerosis), but showed no signs of virilism and no hormonal abnormality. HS was controlled using antiseptics, topical retinoids and antibiotics. Conclusions. This case is of particular interest given the late onset of HS, long time after menopause. The development of HS requires a complex interaction between genetic predisposing factors, endocrine dysregulation, metabolic alterations, bacterial overgrowth and an aberrant inflammatory response. Evidence points to an important role of sex-hormones in the emergence and progression of the disease, but the underlying mechanisms are still unclear. A better understanding of HS pathogenesis is needed to elucidate the precise way in which endocrine factors influence the disease onset and course. This would guide the way to novel therapies and a better control of this challenging disease.

Many women with polycystic ovary syndrome (PCOS) also present with nonalcoholic fatty liver disease (NAFLD) secondary to obesity and/or insulin resistance. Assuming that fatty liver, by inducing impairments in steroid metabolism might contribute to characteristic hyperandrogenemia in women with PCOS, we studied a group of 44 women with PCOS and a control group of 20 women matched according to age, waist circumference and body mass index. In PCOS group, serum testosterone was significantly higher when the degree of lipid infiltration of the liver (ultrasonographically assessed) was higher (1.34?0.14 ng/mL in steatotic PCOS group vs. 0.72+0.1 ng/ml in non-steatotic PCOS group, p=0.001). Our study offers an additional explanation for high testosterone levels in women with PCOS, implying liver in the pathogenic chain that leads to excess androgen.

treatment of postmenopausal osteoporosis. It has estrogen agonist effects on bone and on surrogate markers of cardiovascular risk, but estrogen antagonist effects on breast and endometrium. It inhibits bone resorption and decreases bone turnover, increases bone mineral density and reduces the risk of vertebral fractures in postmenopausal women.\r\nObjectives: The main endpoint of our study was to evaluate the effect of raloxifene therapy (60 mg/day) on biochemical markers of bone turnover in romanian osteoporotic postmenopausal women. Secondary endpoints were the effect on bone mineral density (BMD), body mass composition and lipid profile.\r\nMaterials and methods: We performed a longitudinal, prospective, open study, investigating 29 postmenopausal white women with osteoporosis (Group 1) aged 56.9?7.8 years (mean ? SD) and in addition a control group of 29 premenopausal healthy white women (Group 2) with a mean age of 35.10 ? 7.8 years. The diagnosis of osteoporosis was established by dual-energy x-ray absorptiometry. We appreciated in both groups the bone turnover, measuring a marker of bone resorption: serum beta CrossLaps and a marker of bone formation: serum osteocalcin. We determined also the lipid profile: plasma cholesterol (mg/dL), HDL cholesterol (mg/dL), LDL cholesterol (mg/dL) and triglycerides (mg/dL) in all patients. Osteoporotic women received raloxifene 60 mg/day for one year. Biochemical bone markers, lipid profile and body composition have been evaluated at 3, 6 and 12 months of treatment and BMD was performed at 6 and 12 months of therapy.\r\nResults: Postmenopausal osteoporotic women showed an increased bone turnover in comparison with premenopausal women, with statistically significant increased serum values of both resorption and formation biochemical bone markers: respectively 0.48?0.2 vs 0.23?0.1 ng/mL for beta CrossLaps and 27.94?12.1 vs 17.30?8.9 ng/mL for osteocalcin, p<0.001. Raloxifene therapy for three months reduced significantly both bone resorption and formation: 0.36 ? 0.2 vs 0.48 ? 0.2 ng/mL, p< 0.005 for beta CrossLaps and 22.03 ? 10.1 vs 27.94 ?12.1 ng/mL, p< 0.001 for osteocalcin. After 3, 6 and 12 months of therapy with raloxifene the bone markers were statistically significant reduced: -21.2%, -20.4% and respectively -31.6% for osteocalcin and -25%, -39.6% and respectively -50% for beta CrossLaps (p< 0.01). After six months of therapy, serum levels of beta CrossLaps were reduced to premenopausal range (0.29 ? 0.1 vs. 0.23 ? 0.1 ng/mL, p=ns). Total cholesterol and LDL-C were reduced after 12 months (p< 0.03), with no increase in triglycerides and at the same time body mass composition was unchanged.\r\nConclusions: Our results suggest that raloxifene reduces as early as three months the bone turnover in postmenopausal osteoporosis. It reduces bone turnover in premenopausal range after only six months of therapy, for the bone resorption (beta CrossLaps) and after 12 months for bone formation (osteocalcin). In addition raloxifene treatment has favorable effects on BMD and lipid profile, proving safety and a stable body mass composition.

Introduction: There is a large agreement about the positive effect of GH therapy in patients with panhypopituitarism. Objective: We investigated the potential psychological effect of GH replacement in hypopituitary patients secondary to surgery + radiotherapy for pituitary tumors. The study design was prospective, non-placebo controlled.\r\nPatients and methods: after informed consent, we enrolled 14 subjects with pituitary tumor, submitted to transfrontal (FS) or transsphenoidal (SS) surgery and with GH < 1 ng/mL after insulin-induced hypoglycemia. Our subjects were aged 50.2 + 14 years, 11 men, 3 women, with craniopharyngioma (n=3, all postfrontal surgery=post FS), nonfunctioning pituitary adenoma (n=10, 6 post FS, 4 post SS) and 1 macroprolactinoma (post FS). Seven subjects were submitted to radiotherapy. GH (Norditropin) was provided by Novonordisk, in 5 mg vials, self-administered by a specific device (pen) provided by manufacturer in a dose of 0.01 mg/kg/day. GH and IGF 1 were assayed monthly, using a commercial kit. Quality of Life (QoL) was assessed monthly by a 22 item questionnaire provided by Novonordisk, which measures a total QoL score, as well as subscores for depression, anxiety, personal well being and self perceived sense of energy. A statistically significant improvement of QoL score is indicative of positive effect of therapy. Fasting glucose and tumoral dimensions were monitorised every 3 months; 2 patients were excluded from study after diabetes mellitus occurrence; one additional patient discontinued therapy for fears of tumoral outgrowth.\r\nResults: a positive effect could be noticed concerning QoL total score and subscores, concerning auto-perceived level of energy and personal well being. Prior radiotherapy tends to blunt this beneficial effect. IGF 1 increased first 2 months, then we noticed a significant and sustained increase of IGF 1 with frequent upper normal values, especially in more obese and in men rather than in women. Adiposity and BMI decreased during therapy, which favorably influence QoL.\r\nConclusions: patients benefit psychologically from GH therapy. We found an unexpected high rate of metabolic complication (2 out of 14 subjects drop out study because of diabetes mellitus). Prior radiotherapy might blunt the psychological effect of GH.

This study evaluates the differences of radiotherapy in patients with pituitary tumors, in relation to gonadotropin immunoreactivit.\r\nDesign. It is a longitudinal, retrospective study of 117 patients submitted to pituitary surgery and high voltage radiotherapy. The excised tumors were 70 non-functioning adenomas (NFA) and 47 GH-secreting adenomas producing active acromegaly (ACM). They were evaluated before and after pituitary surgery, before radiotherapy as baseline, then at 3 different intervals at 0 - 2, 2 - 5 and > 5 years after baseline.\r\nMethods and patients. Computer tomography was used for measuring the tumor size and specific immunoassays were used for FSH, LH and nadir GH during 75 g oral glucose load. Immunohistochemistry (IHC) was performed with avidin-biotine method. High voltage conformational radiotherapy used a linear accelerator of 10 meV, with a 50 Gy on target tumor. For statistics, student&#8217; t test was used. Data before surgery (tumor volume and hormonal sexretion) were available in 70 unselected patients (31 NFA and 39 ACM from the above group). Postsurgery we defined following groups: NFA-A1 exposed to radiotherapy (n=21) and NFA-C1 unexposed to radiotherapy (n=22); ACM-A2 exposed to radiotherapy (n=20) and ACM-C2 unexposed to radiotherapy (n=10).\r\nResults. Immunohistochemistry for NFA showed 27 immunopositive for FSH or/and LH (GD+) and 40 immunonegative for FSH and LH (GD-), 3 undetermined, while for ACM were 12 GD+, 33 GD-, 2 undetermined. Immunohistochemistry data on defined groups was as follows: NFA-A1 (n=21: 12 GD+, 9 GD-) and NFA-C1 (n=22: 6 GD+, 16 GD-); ACM-A2 (n=20: 4 GD+, 16 GD-) and ACM-C2 (n=10: 3 GD+, 7 GD-). In patients with NFA presented before therapy, there are not significant differences of tumor sizes or of the levels of FSH/LH between GD+ and GD- adenomas. In ACM, before any therapy, the GD+ patients showed a significantly higher FSH levels (20.7+11.4 U/L, n=6) than GD- patients (FSH 6.6+1.6 U/L, n=22, p< 0.05) and a nonsignificant lower serum GH levels (15.1+3.5 ng/mL, n=8 versus 33.5+8.9 ng/mL, n=30 p=0.06), although the tumor size was similar between the two groups. Radiotherapy upon NFA: GD+ adenomas did not decrease their volume after radiotherapy (cranio-caudal diameter 1.63+0.79 cm, before and 1.54+0.68 cm at 2 - 5 years post-radiotherapy n=6, p= NS), in contrast with GD- tumors in which a slightly, but significant decrement in volume could be demonstrated (from 2.79+0.53 cm to 2.43+0.31 cm at 2 - 5 years, n=5, p= 0.01). Radiotherapy in ACM resulted in a decrement of serum GH level and tumor size, as compared with the control group without radiotherapy. The effect was maximal at the interval of 2-5 years. The ACM, GD- tend to respond better to radiotherapy, (i.e. GH levels decreased from 15.1+5.4 to 6.6+2.4 ng/ml at 2-5 years, p=0.05), while in patients with ACM, GD+ the GH level did not show a significant decrease (serum GH was 7.3+3.3 ng/ml before and 5.1+4 ng/mL at 2-5 years post-radiotherapy, p = NS). The CC diameter of GD- decreased from 1.1+0.3 to 0.7+0.2 at 2-5 years, p=.059, while in GD+: from 1.64+0.4 to 1.2+0.3 ng/mL at 2-5 years, p = NS.\r\nConclusion. Pituitary adenomas, both NFA and ACM that contain gonadotropin immunoreactive cells tend to be more radioresistant than those without gonadotroph cells.