ACTA ENDOCRINOLOGICA (BUC)

Obesity is an increasing public health problem, the fifth leading risk for global deaths according to WHO. It is associated with major comorbidities, such as type 2 diabetes mellitus, ischemic heart disease, hypertension, dyslipidemia, sleep apnea, osteoarthritis, nonalcoholic fatty liver disease and depression. The obesity pathogenesis increasingly became clearer. It is thought to be the result of a neuroendocrine dysregulation of energy intake and energy expenditure. One of the most studied cytokines involved in obesity, leptin is secreted from adipose tissue, proportional to fat mass. It inhibits neuropeptide Y/Agouti-related peptide neurons and activates pro-opiomelanocortin (POMC)/ cocaine amphetamine-related transcript neurons in the hypothalamus, resulting in an anorectic effect.

Introduction: Prolactinomas may grow during pregnancy. Dopamine agonists (DA) prevent tumor growth, but usually suppress prolactin (PRL) both in mother and fetus. Possible long-term consequences on fetal development remain unknown.\r\nAim: to assess whether DA treatment throughout pregnancy in a dosage able to maintain physiological gestational serum levels of prolactin (PRL) still prevents prolactinoma growth.\r\nPatients and methods: We evaluated 68 pregnancies in 49 women with prolactinoma (PRM) and 46 pregnancies in healthy women as controls. Thirty-three pregnancies were recorded in 27 women treated throughout pregnancy with bromocriptine (BRC) (n = 25) or cabergoline (CAB) (n = 2) divided in 2 groups: group A (22 pregnancies in 18 patients) had suppressed serum PRL (below the 5th percentile of the control group Z during the last trimester); group B (11 pregnancies in 10 patients) had physiological serum PRL levels. Other 26 pregnancies in 21 patients were incompletely evaluated and included only in the pregnancy outcome and cure rate analysis. Treated patients were compared with the control group Y 8 women with PRM who discontinued DA after pregnancy induction (9 pregnancies) and a control group Z of 46 healthy pregnant women, randomly selected from two departments of Obstetrics. Patients with multiple pregnancies were recorded in each corresponding study group.\r\nResults: In the control group Y, tumor size showed an increase in 2 (intrasellar macroPRM) out of 8 cases (25%). DA treatment throughout gestation in 27 women with PRM prevented the growth in all cases and induced a shrinkage of more than 30% of tumor mass in 8/14 macroPRM (57.1%), i.e., in 4/7 (57.1%) of macroPRM with physiological serum PRL levels during pregnancy, and in 5/8 (62.5%) of macroPRM with suppressed PRL levels (p = NS) (1 patient had pregnancies in both groups). Low dose DA (BRC 2.5 ? 5 mg/day or CAB 0.5 mg/week) maintains physiological PRL levels in 6/12 (50%) macroPRM, but suppressed PRL in 80% of microPRM. Cure was recorded in 6/49 (12.2%) of patients. Two patients with PRM-induced neuroophthalmic syndrome were successfully treated with DA throughout 1 and respectively 3 pregnancies.\r\nConclusions: Some women with prolactinomas showed a tumour size increase if they were not treated with dopamine agonists throughout pregnancy. Maintaining physiological serum PRL levels during pregnancy (frequently with low doses of DA) prevented tumor growth, avoiding a PRL suppression that may have subtle influence on long-term foetal development.

We present the case of a 29 years young man with acromegaly caused by a plurihormonal pituitary adenoma expressing GH, PRL, FSH and TSH within the tumoral cells. Immunoassays showed a high serum level of GH and PRL, and a serum level within normal ranges for FSH, TSH and LH. Tumoral immunohistochemistry (avidin biotin technique) was positive for GH, PRL and TSH. The presence and colocalisation of GH and FSH was shown by immunelectronmicroscopy with double immunogold techniques. The gold particles (sizes 10 nm for GH and 15 nm for FSH) were colocalised within the same translucent secretory granules of some tumor cells, ultrastructurally similar to gonadotroph cells, aside from other tumor somatotroph cells with dense secretory granules and only 10 nm antiserum GH gold particles. High cerebrospinal fluid (CSF) levels of FSH and a high ratio of CSF/serum FSH concentrations, above 1, were the first indicators that revealed, before pituitary surgery, that FSH is secreted from the pituitary tumor. TSH was a “mute” hormone, without biochemical or clinical expression outside the tumor. This pituitary adenoma showed a good response to surgery and to conventional high voltage conformational radiotherapy with the usual dose of 50 Gy. Bromocriptine and Octreotide, but not the gonadotropin releasing hormone agonist (Triptorelin), produced additional beneficial effects. It is tempting to suggest a somatogonadotroph cell as precursor of this pituitary tumor.

Hypoparathyroidism is a disease characterized by low serum calcium and inappropriate low parathyroid hormone (PTH) levels. Common therapy for chronic hypoparathyroidism usually includes oral calcium and activated vitamin D supplementation (calcitriol), hypoparathyroidism being the one of few endocrine disorders not replaced by the missing hormone. In January 2015, FDA approved PTH (1-84) for the treatment of hypoparathyroidism in patients who cannot be well-controlled on calcium and active forms of vitamin D alone and for whom the potential benefits are considered to outweigh this potential risk. Until now, there are 4 phase 3 clinical trials investigating the role of human recombinant PTH (1-84) for the treatment of hyopoparathyroidism: Replace, Race, Relay, and Repeat. These studies demonstrated a more than 50% reduction in calcium and active vitamin D requirements. Future strategies for the treatment of hypoparathyroidism could be stem cell therapy recombinant with PTH and viral or nonviral factors or parathyroid gland transplantation.

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Introduction. Acromegaly is a chronic disease associated with high mortality rate if untreated. The aim of the study is to evaluate mortality ratio in Romanian patients with acromegaly in latest years, with new therapeutic options. Patients and Methods. This retrospective study analyzed 336 (111M/225F, mean age 48.13±12.40 years) consecutive patients with acromegaly between 1st January 2001 and 31 December 2014, median follow-up 7.36 years (0.48-13.99 years). PAMCOMP computation program assessed standardized mortality ratio (SMR). Kaplan Meier curve was used for comparison between of different cut-off levels of the last GH level on survival. Serum GH levels were measured by IRMA (sensitivity 0.1 ng/mL). Results. During follow-up 2596.34 person-years, 41 patients died, with a SMR of 1.34 (CI 0.96-1.82). Mean age at death was 63.19±11.66 years. Females with acromegaly died 83% more frequently than women in general population: SMR-1.83 (CI 1.21-2.67). Females were older at diagnosis (p=0.006), and were less probable to receive substitution of gonadotrophic failure than males (p<0.001). Independent factors correlated with mortality were age at baseline (p<0.001, HR=1.07), last GH level (p=0.003, HR=1.01) and systolic blood pressure (p=0.029, HR=1.02). Patients with last GH level ≤ 1 ng/mL had a better survival than patients with GH>1 ng/mL (p Log Rank=0.002). SMR of patients with last GH >1 ng/mL was 1.59 (CI 1.08-2.26) for the entire group, 2.2 (CI 1.32-3.44) for females and 1.3 (CI 0.67-2.29) for males. Conclusion. Patients with acromegaly have a high mortality ratio compared to general population, especially in women and those with post-therapeutic serum GH levels over 1 ng/mL. Longer follow-up is needed for the evaluation of the effect of new therapies on mortality.

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