ACTA ENDOCRINOLOGICA (BUC)

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.

Paget's disease of bone is a metabolic skeleton disorder with different epidemiological patterns: increased incidence up to 3% of the Northern Caucasian population over the age of 55 or a very rare occurrence as in Asia. We present a case of a 69 years old female patient with diffuse bone pain, suspected of osteoporosis after a DXA investigation of bones. She has developed progressive skull deformation over the last 17 years and bilateral sensoneural deafness. On admission in our hospital, she had alkaline phosphatase serum levels five times higher than the upper normal value and low values of 25 hydroxy vitamin D. Parathormone and calcium levels were in normal range. Radiologic findings confirmed the monostotic type of Paget's disease. Other biomarkers of bone remodeling: serum osteocalcin for bone formation and serum beta Cross Laps for bone resorption, showed moderately increased levels. High dose therapy with alendronate and alphacalcidol were given with the normalization of bone markers after 9 months of sustained treatment. The vitamin D deficiency of this patient is an independent, associated disease, producing a decrease of bone mineral density as shown by DXA measurement. The case presentation and the review of the medical literature on this subject are intended to remind clinicians of the importance of appropriate diagnosis and therapy in this disease, as well as the importance of establishing the prevalence of Paget's disease of bone in Romania.

Background. Usually, silver stain is needed to differentiate between normal or hyperplastic hypophysis and pituitary adenomas. Many papers reported the lack of reticular fibers network as mandatory for pituitary adenoma diagnosis. \r\nAim. Differences between the architecture of reticular fibers in normal pituitary and pituitary adenomas \r\nMethods. Gordon- Sweet silver staining of pituitary specimens, prelevated during pituitary surgery performed in 138 patients with the endocrine and imagistic diagnosis of pituitary macro-adenomas. \r\nResults.Pituitary specimens of pituitary adenomas was confirmed in 133 cases; 3 specimens were with normal pituitary tissue, 1 with pituitary hyperplasia, 1 with pituitary apoplexy.Twelve of 133 pituitary adenomas specimens were associated also with normal pituitary tissue.There was a loss of acinar network of reticular fibres in 115 cases, but the present study describes the persistence of reticular fibers networks in 18 (13,53%) of 133 pituitary adenomas. We identified five distribution patterns of remanent reticular fibers network in pituitary adenomas using silver staining. \r\nIn conclusion, persistence of reticular fibers in a small number of pituitary adenomas could be a possible pitfall in the discrimination between the normal hypophysis and pituitary adenoma.

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 &#8220;mute&#8221; 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.

Gangliocytomas are extremely rare tumors, accounting for 0.1-0.5% of all brain tumors. We present a 25 years old woman with several characteristics of restrictive anorexia nervosa in association with a gangliocytoma of pineal region. The patient has been diagnosed with hydrocephalus shortly after birth. A ventriculoperitoneal shunt was initially inserted. At the age of 19 she underwent 2 consecutive occipital craniotomies for a well-defined large mass in the pineal region. Histopathological examination of this tumor revealed a gangliocytoma. Our patient began to reduce her food intake due to the concept that &#8221;the tumor must not be fed&#8221;. After an almost 30 kg weight loss over 5 years, the patient weighs 39 kg at 165 cm height (BMI 14.3 kg/sqm), associated with a 1 year history of secondary amenorrhea and a tumor remnant of 4 cm. The weight loss, amenorrhea and some other psychosocial traits are common for anorexia nervosa. We discuss the difficulty of the differential diagnosis between anorexia nervosa and a hypothalamic eating disorder induced by the pineal gangliocytoma.

Background. Advances in imaging techniques have led to increasing discovery of\r\nadrenal and pituitary &#8220;incidentalomas&#8221;, tumors with normal endocrine function and no\r\ncompression mass effects. We evaluated the age at diagnosis (AD) in patients with benign\r\nnon-functioning adrenal incidentalomas, as compared to pituitary non-functioning tumors,\r\nin a series of patients from a national center of endocrinology. Methods. From 2,123\r\nconsecutive patients with adrenal and pituitary tumors hospitalized between 1977 - 2009,\r\n2,069 patients were analysed. The study groups included: group A - 137 patients with\r\nadrenal incidentalomas (AI), group B - 534 patients with pituitary incidentalomas (PI).\r\nControl groups included 1,398 patients: group C1 147 patients with adrenal carcinomas or\r\nbenign hormone-secreting adrenal tumors, and group C2, 1,251 patients with pituitary\r\nsecreting adenomas or large non-functioning pituitary macroadenomas (NFA). Imaging was\r\ndone by computed tomography and/or magnetic resonance after 1981 and by skull X-ray or\r\npneumoencephalography before 1981. Results. Mean age AD is more advanced in patients\r\nwith AI (53 ? 11.9 years, range 21 - 78 yr) than in patients with PI (36.8 ? 13.1 years, range\r\n10 - 81 yr), p < 0.01. AD was higher in AI than in patients with secreting adrenal tumors,\r\nbut similar in patients with adrenal malignancy. There is an age-related increase in the\r\nproportion of AI among patients with adrenal tumors, and of NFA, but not of PI, among\r\npatients with pituitary tumors. In patients aged over 65 years, 74% of patients with adrenal\r\ntumors have AI, while only 18% of patients with pituitary tumors have PI and 42% have\r\nNFA. AD in NFA (49.3 ? 13.1 yr, range 12 - 79 yr) was more advanced than in PI (p < 0.01).\r\nAD does not correlate with tumor size. Tumor growth occurred in 24% of AI (follow-up 3.0\r\n? 2.8 yr) and only in 0.7% of PI, p<0.01 (follow-up 3.1 ? 2.5 yr).\r\nConclusions. Adrenal non-functioning benign tumors show a clear association with ageing,\r\nin contrast with pituitary incidentalomas. It seems unlikely that most pituitary incidentalomas in\r\nyoung patients become large NFA, whose development seems to be also age-related. It is tempting\r\nto suggest that pituitary tumorigenesis starts earlier than adrenal tumorigenesis.

Obesity is an important risk factor for obstructive sleep apnea syndrome (OSAS). One would expect that effective treatment by continuous positive airway pressure (CPAP) would lead to weight loss due to decreased daytime sleepiness and improved physical activity. However, many papers suggest that shortage of sleep is a risk factor for obesity.\r\nAim. To assess the weight change after 1 year of effective CPAP treatment for OSAS.\r\nMethods. In this retrospective study OSAS was diagnosed in 109 subjects (50 women, 59 men; age 58?13 years). Eighty subjects used CPAP > 5 h per night in > 70% of nights and were considered treatment subjects. Twenty-nine subjects used CPAP < 5 hours per night or < 70% of nights and were considered control subjects. Patients were diagnosed using complete full-night or split-night polysomnography (70 and 39 patients respectively). Mean effective titrated CPAP pressure was 9.8 cm H2O. CPAP compliance was assessed through downloadable data from CPAP machine (19 patients) or clinical exam (90 patients). Body mass\r\nindex (BMI) was determined at the time of diagnosis and 1 year later (range 10-15 months).\r\nResults. Treatment and control subjects were similar regarding age, sex, BMI and apnea hypopnea index (AHI) at baseline. Weight increased in CPAP users (n=80) by 1.3 kg (CI 95% 0.4, 2.25; p<0.01) but not in control subjects (n=29) (mean difference in controls 0.37 kg, CI 95% -1.8, 2.5; p>0.05). BMI significantly increased in men (p<0.005), in subjects with severe OSAS (AHI>30 events/hour) (p<0.009) and in those younger than 65 years (p<0.01). Sleep architecture was investigated by full-night polysomnography in 50 regular CPAP users and 20 controls. In the subgroup of 18 treatment patients with lack of slow wave sleep (SWS) the increase in body weight was 2.6 kg (CI 95% 0.4, 4.9, p=0.02), more than double as compared with patients with SWS at baseline (n=32).\r\nConclusion. Effective CPAP treatment leads to a modest, but significant weight gain after 1 year in OSAS patients, especially in men with severe sleep apnea. This seems to be in relation to lack of SWS at baseline. An independent medical intervention for weight loss should be associated with CPAP treatment in sleep apnea syndrome.