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Hirsutism induced by hyperandrogenism can be associated with polycystic ovary syndrome, 21-hydroxylase (OH) deficiency or androgen-secreting tumors, including ovarian and adrenal tumors. Adrenal androgen-secreting tumors are frequently malignant. Adrenal oncocytomas represent rare causes of hyperandrogenism. The aim of the study was to investigate steroidogenic enzyme expression and steroid secretion in an androgen-secreting adrenal oncocytoma in a young woman presenting with hirsutism. Hyperandrogenism was diagnosed on the basis of elevated plasma Δ4-androstenedione and testosterone levels. Pelvic ultrasound was normal, CT scanning revealed a right adrenal mass. Androgens were assessed in adrenal and ovarian vein samples and proved a right adrenal origin. Adrenalectomy normalized androgen levels and the adrenal tumor was diagnosed as an oncocytoma. Real time-PCR, immunohistochemistry and cell culture studies were performed on tumor explants to investigate the steroid secretion profile. Among enzymes required for cortisol synthesis, 17α-OH and 3β-hydroxysteroid dehydrogenase 2 (3β-HSD2) were highly expressed whereas 21-OH and 11β-OH were weakly produced at the mRNA and/or protein levels. Enzymes involved in testosterone production, 17β-HSD5 and 17β-HSD3, were also detected. ACTH receptor was present in the tissue. Cortisol, Δ4-androstenedione and testosterone secretions by cultured cells were increased by ACTH. These results provide the first demonstration, to our knowledge, of abnormal expression profile of steroidogenic enzymes in an adrenocortical oncocytoma. Our results also indicate that Δ4-androstenedione hypersecretion resulted from high 17α-OH and 3β-HSD2 expression in combination with low expression of 21-OH and 11β-OH. Testosterone production was ascribed to occurrence of 17β-HSD5 and 17β-HSD3. Finally, our results indicate that androgen secretion was stimulated by ACTH.

In type 1 diabetes mellitus (T1DM), low concentrations of IGF1 and high concentrations of IGF-binding protein 1 (IGFBP1) have been reported. It has been suggested that these abnormalities in the GH–IGF1 axis are due to low insulin concentrations in the portal vein. We hypothesized that the i.p. route of insulin administration increases IGF1 concentrations when compared with the s.c. route of insulin administration. IGF1 and IGFBP1 concentrations in samples derived from an open-label, randomized cross-over trial comparing the effects of s.c. and i.p. insulin delivery on glycaemia were determined. T1DM patients were randomized to receive either 6 months of continuous i.p. insulin infusion (CIPII) through an implantable pump (MIP 2007C, Medtronic) followed by 6 months of s.c. insulin infusion or vice versa with a washout phase in between. Data from 16 patients who had complete measurements during both treatment phases were analysed. The change in IGF1 concentrations during CIPII treatment was 10.4 μg/l (95% CI −0.94, 21.7 μg/l; P=0.06) and during s.c. insulin treatment was −2.2 μg/l (95% CI −13.5, 9.2 μg/l; P=0.69). When taking the effect of treatment order into account, the estimated change in IGF1 concentrations was found to be 12.6 μg/l (95% CI −3.1, 28.5 μg/l; P=0.11) with CIPII treatment compared with that with s.c. insulin treatment. IGFBP1 concentrations decreased to −100.7 μg/l (95% CI −143.0, −58.3 μg/l; P<0.01) with CIPII treatment. During CIPII treatment, parts of the GH–IGF1 axis changed compared with that observed during s.c. insulin treatment. This supports the hypothesis that the i.p. route of insulin administration is of importance in the IGF1 system.

Obesity is a rapidly emerging health problem and an established risk factor for cardiovascular diseases. Bariatric surgery profoundly reduces body weight and mitigates sequelae of obesity. The open, randomized controlled Würzburg Adipositas Studie (WAS) trial compares the effects of Roux-en-Y gastric bypass (RYGB) vs psychotherapy-supported lifestyle modification in morbidly obese patients. The co-primary endpoint addresses 1-year changes in cardiovascular function (peak VO₂ during cardiopulmonary exercise testing) and the quality of life (QoL) (Short-Form-36 physical functioning scale). Prior to randomization, all included patients underwent a multimodal anti-obesity treatment for 6–12 months. Thereafter, the patients were randomized and followed through month 12 to collect the primary endpoints. Afterwards, patients in the lifestyle group could opt for surgery, and final visit was scheduled for all patients 24 months after randomization. Sample size calculation suggested to enroll 90 patients in order to arrive at minimally 22 patients per group evaluable for the primary endpoint. Secondary objectives were to quantify changes in body weight, left ventricular hypertrophy, systolic and diastolic function (by echocardiography and cardiac MRI), functional brain MRI, psychometric scales, and endothelial and metabolic function. WAS enrolled 93 patients (72 women, median age 38 years, BMI 47.5 kg/m²) exhibiting a relevantly compromised exercise capacity (median peakVO₂ 18.3 mL/min/kg) and the QoL (median physical functioning scale 50). WAS is the first randomized controlled trial focusing on the effects of RYGB on cardiovascular function beyond hypertension. In addition, it will provide a wealth of high-quality data on the cerebral, psychiatric, hepatic, and metabolic function in obese patients after RYGB.

Low plasma levels of vitamin D causes bone mineral change that can precipitate osteopenia and osteoporosis and could aggravate autoimmune diseases, hypertension and diabetes. The demand for vitamin D supplementation becomes necessary; however, the consumption of vitamin D is not without risks, which its toxicity could have potentially serious consequences related to hypervitaminosis D, such as hypercalcemia and cerebral alterations. Thus, the present study describes the electroencephalographic changes caused by supraphysiological doses of vitamin D in the brain electrical dynamics and the electrocardiographic changes. After 4 days of treatment with vitamin D at a dose of 25,000 IU/kg, the serum calcium levels found were increased in comparison with the control group. The electrocorticogram analysis found a reduction in wave activity in the delta, theta, alpha and beta frequency bands. For ECG was observed changes with shortened QT follow-up, which could be related to serum calcium concentration. This study presented important evidence about the cerebral and cardiac alterations caused by high doses of vitamin D, indicating valuable parameters in the screening and decision-making process for diagnosing patients with symptoms suggestive of intoxication.

Until quite recently, the management of children with growth hormone deficiency (GHD) had focussed on the use of recombinant human GH (rhGH) therapy to normalise final adult height. However, research over the past two decades that has demonstrated deficits in bone health and cardiac function, as well as impaired quality of life in adults with childhood-onset GHD (CO-GHD), has questioned this practice. Some of these studies suggested that there may be short-term benefits of rhGH in certain group of adolescents with GHD during transition, although the impact of GHD and replacement during the transition period has not been adequately investigated and its long-term benefits remain unclear. GH therapy remains expensive and well-designed long-term studies are needed to determine the cost effectiveness and clinical benefit of ongoing rhGH during transition and further into adulthood. In the absence of compelling data to justify widespread continuation of rhGH into adult life, there are several questions related to its use that remain unanswered. This paper reviews the effects of growth hormone deficiency on bone health, cardiovascular function, metabolic profile and quality of life during transition and young adulthood.

Insulin-like growth factor 1 receptor (IGF1R), mapping on the 15q26.3 chromosome, is required for normal embryonic and postnatal growth. The aim of the present study was to evaluate the IGF1R gene expression and function in three unrelated patients with chromosome 15 structural abnormalities. We report two male patients with the smallest 15q26.3 chromosome duplication described so far, and a female patient with ring chromosome 15 syndrome. Patient one, with a 568 kb pure duplication, had overgrowth, developmental delay, mental and psychomotor retardation, obesity, cryptorchidism, borderline low testis volume, severe oligoasthenoteratozoospermia and gynecomastia. We found a 1.8-fold increase in the IGF1R mRNA and a 1.3-fold increase in the IGF1R protein expression (P < 0.05). Patient two, with a 650 kb impure duplication, showed overgrowth, developmental delay, mild mental retardation, precocious puberty, low testicular volume and severe oligoasthenoteratozoospermia. The IGF1R mRNA and protein expression was similar to that of the control. Patient three, with a 46,XX r(15) (p10q26.2) karyotype, displayed intrauterine growth retardation, developmental delay, mental and psychomotor retardation. We found a <0.5-fold decrease in the IGF1R mRNA expression and an undetectable IGF1R activity. After reviewing the previously 96 published cases of chromosome 15q duplication, we found that neurological disorders, congenital cardiac defects, typical facial traits and gonadal abnormalities are the prominent features in patients with chromosome 15q duplication. Interestingly, patients with 15q deletion syndrome display similar features. We speculate that both the increased and decreased IGF1R gene expression may play a role in the etiology of neurological and gonadal disorders.