Multicenter retro-prospective observational study on chronic hypoparathyroidism and rhPTH (1-84) treatment.

PURPOSE: The main purpose of this study was to investigate the effects of 12 months of rhPTH (1-84) (Natpar®) treatment in a cohort of patients selected according to the indications of hypoparathyroidism guidelines. The use of recombinant human PTH (1-84) [rhPTH (1-84)] is approved as hormonal replacement therapy in patients with hypoparathyroidism not adequately controlled with conventional therapy. METHODS: It is a multicenter, observational, retro-prospective, open label study. Eleven Italian Endocrinological centers, members of Hypoparathyroidism Working Group of the Italian Society of Endocrinology (HypoparaNET) were involved. Main outcome measures were serum and urinary calcium and phosphate concentration, calcium-phosphate product, renal function, oral calcium and vitamin D doses, and clinical manifestations. RESULTS: Fourteen adult subjects, affected by chronic hypoparathyroidism, were treated with rhPTH (1-84) for 12 months. At 12 months of rhPTH (1-84) treatment, 61.5% of patients discontinued calcium supplement and 69.2% calcitriol. Mean albumin-adjusted total serum calcium levels quickly normalized after initiation of rhPTH (1-84) treatment compared to baseline (p = 0.009), remaining in the normal range until 12 months. Rare hypo-hypercalcemia episodes were reported. Renal function was maintained normal and no renal complications were reported. Serum and urinary phosphate and urinary calcium were maintained in the normal range. Mean phosphatemia levels linearly decreased from 3 months up to 12 months compared to baseline (p = 0.014). No severe adverse events were described. CONCLUSIONS: Biochemical and clinical results confirm the efficacy and safety of rhPTH (1-84) therapy, which represents an important option for hypoparathyroid patients unresponsive to conventional therapy.

Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement: Clinical Management of Vitamin D Deficiency in Adults

Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice.

Effectiveness and safety of calcium and vitamin D treatment for postmenopausal osteoporosis.

Imbalance of bone resorption and bone formation is responsible for osteoporosis that is characterized by decreased bone mass and mineral density. The aim of this study was to evaluate the available data that could clarify the effectiveness and safety of supplementations with calcium and vitamin D, alone or in combination, to slow down bone loss in postmenopausal and elderly women. Using search key words, we performed a research both in the PubMed and Cochrane Library in order to find all meta-analysis, prospective and randomized clinical studies published from 2000 to 2014 that had investigated the effectiveness of calcium and vitamin D in the treatment of osteoporosis. At the moment it is not possible either to provide reassurance that calcium supplements given with vitamin D do not cause adverse cardiovascular events or to link them with certainty to increased cardiovascular risk. According to the data now available, vitamin D, at dosage of at least 800 IU/day, alone or in combination with antiresorptive drugs, should be administered in osteoporotic and osteopenic patients for a primary and secondary prevention. Further studies are needed and the debate remains ongoing. However, every administration needs the calculation of the absolute fracture risk of the patient. Especially considering the high cost of osteoporosis prevention, more studies are mandatory to clarify indications and contraindications.

Acquired cystic kidney disease: the hormonal hypothesis.

Based on the reported sex difference in the incidence of acquired cystic kidney disease (ACKD) in patients with chronic renal failure, it is hypothesized that the hormonal derangement, well documented in male and female uremic patients on long-term dialysis, could be responsible for the pathogenesis of ACKD. The decreased androgen/estrogen ratio, and the increased estrogen value could be responsible for an estrogen receptor mediated effect on the tubular epithelial cell proliferation, an event further potentiated by the action of regulatory peptides like epidermal growth factor (EGF). The epithelial stimulation is more pronounced in men because male tissues are less adapted than female tissues to high estrogen values. Furthermore the androgen reduction, more remarkable in male than female patients, is responsible for an up-regulation of EGF-R. Therefore hormones and growth factors, by means of their own receptor in renal tissue (homologous to the two oncogenes c-erb A and c-erb B), may be responsible for the development of ACKD, and may play an important role in the pathogenesis of multiple adenomas and renal carcinomas reported with high incidence among uremic patients with ACKD.

Epidermal growth factor binding and steroid receptor content in human benign prostatic hyperplasia.

The receptor for epidermal growth factor (EGF-R) was characterized on membrane fractions from human benign prostatic hyperplasia (BPH). Specific binding of [125I]EGF reached equilibrium after 40 min at 25 degrees C and was stable for up to 120 min. Saturation analysis of EGF-R, performed by incubating the membranes with 0.0156-15 nM [125I]EGF in the presence and in the absence of 100-fold excess of cold EGF for 60 min, revealed the presence of two classes of binding sites with high and low affinities (Kd = 0.35 +/- 0.23 and 9.60 +/- 2.87 nM respectively). Competition experiments revealed that FSH, insulin and calcitonin did not compete with [125I]EGF. The simultaneous determination of EGF-R and that of estradiol (ER), progesterone (PR) and androgen receptors (AR) was performed using the same buffer to homogenate the tissues and to obtain cellular membranes. The steroid receptors (SR) were determined by means of the dextran-coated charcoal method. There was a significant negative correlation between nuclear SR and binding capacity of EGF-R. The presence of specific and high affinity binding sites for EGF and the modulation of the level of these sites by steroid receptors suggest a possible role of EGF in prostatic hyperplasia.