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Background. Idiopathic hypercalciuria is a risk factor for nephrolithiasis. Both renal stones and hypercalciuria are associated with lower bone mineral density (BMD), but the relationship between these modifications is not completely understood. Aims. To evaluate some metabolic particularities possibly related to relapsing nephrolithiasis (RN) in young male patients. Methods. We performed a crosssectional study including a group of 30 young male patients with RN and a group of 30 healthy, age and BMI (body mass index) matched controls (CTR). We evaluated calcium and phosphate metabolism, bone remodeling markers alkaline phosphatase (AP) and osteocalcin in serum and 24-hour urine samples, and lumbar and hip BMD. Results. We observed higher values of serum calcium (P<0.05) and 24 hour urinary calcium (P<0.001) in the RN group. Parathyroid hormone (PTH) and AP were also higher in the RN group (P<0.01), whereas serum 25OH-D3 was lower (P<0.01). BMD, T and Z scores were lower in the RN group in both the lumbar (P<0.01) and hip (P<0.05) regions. Conclusions. Young male patients with hypercalciuric RN have lower BMD and higher bone turnover. Higher PTH levels related to vitamin D deficiency may contribute to bone demineralization in certain cases. [ABSTRACT FROM AUTHOR]

Emilia Solomon,1,2 Dumitru Brănișteanu,1,3 Andrei Dumbravă,4 Radu Gheorghe Solomon,5 Lorànt Kiss,5 Mihai Glod,1 Cristina Preda1,3 1Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iaşi, Romania; 2Department of Endocrinology, CF University Hospital, Iaşi, Romania; 3Department of Endocrinology, “Sf. Spiridon” Hospital, Iaşi, Romania; 4Faculty of Psychology, Alexandru Ioan Cuza University, Iaşi, Romania; 5ISUD, Faculty of Medicine, University Lucian Blaga, Sibiu, Romania Introduction: Active acromegaly is a rare chronic endocrine disorder caused by excessive growth hormone (GH). Clinical studies suggest that cognitive performance is impaired in acromegaly – particularly executive function as well as short- and long-term memory. This study compared the quality of life (QoL) and executive functioning in acromegaly patients vs healthy controls.Materials and methods: This was an observational case–control study on 38 subjects divided into 19 acromegaly patients and 19 matched controls. The groups were evaluated for QoL, attention, and executive function. All subjects completed Acromegaly Quality of Life Questionnaire (AcroQoL), Trail Making Test (parts A and B), Stroop, and phonemic fluency tests.Results: Acromegaly patients had an AcroQoL global score that was significantly lower than controls. There were significant differences between the acromegaly group and the control group in terms of the physical effects (P=0.001) and appearance (P

Aims: we wanted to check the importance of sunlight exposure and vitamin D supplementation in reverting secondary hyperparathyroidism at IIIrd age institutionalized patients. Design: cross-sectional study of calcium and bone metabolism in a group of 123 institutionalized IIIrd age volunteers after winter period, followed by a prospective double blind placebo-controlled study of effects upon calcium and bone metabolism, serum 25OH-D3, 1,25(OH)2D3 and PTH levels of daily sunlight exposure during the summer months, with or without vitamin D supplementation (2000 IU 25OH-D3 po, daily). The study was performed on volunteers from the Elderly Resting House of Copou, Iasi, Romania. 25OH-D3 was measured by an inhouse RIA technique. 1,25(OH)2D3 was measured by HPLC, serum calcium by photocolorimetry, bone alkaline phosphatase by immunoenzymatic technique, whereas serum PTH and urinary deoxypyridinoline (DPD) were measured by IRMA. Data was compared using Student's t test and correlation analysis (R²). Almost all volunteers (93.5%) had low 25OH-D3 values, but normal or even increased levels of the active hormone, 1,25(OH)2D3. High PTH was found in 41 cases (33.3%), of which three were primary hyperparathyroidism, whereas the others had low or low-normal calcium levels (secondary hyperparathyroidism). More than half of the cases had high DPD levels, suggesting high bone turnover. Bone turnover parameters were higher in females than in males (p<0.05). A positive correlation between PTH and urinary DPD was noticed (R²=0.351). We further supplemented the vitamin D intake in 42 volunteers with a daily dose of 2000 IU of 25-OHD3 for three months in the summer period, whereas other 42 volunteers received placebo (vitamin B). Normalization of 25-OHD3 levels was seen in both vitamin D and placebo-treated sun-exposed groups. A more significant increase in 25OH-D3, and also of 1,25(OH)2D3 at the upper limit of normal was however observed in the vitamin D-treated group. Normalization of serum PTH, but not of turnover parameters was observed in both groups. Mild hypercalcemia and increase in serum creatinine were noticed in the vitamin D-treated group. Conclusions: Secondary hyperparathyroidism might be of importance in high turnover bone loss at institutionalized IIIrd age patients. Women seem to be more at risk, possibly due to sex hormone depletion. PTH-induced 1α hydroxylation in the elderly with undamaged kidney function partially compensates the paucity of vitamin D substrate, by normalizing active hormone levels. Mild sun exposure at institutionalized patients increases skin resources of vitamin D, normalizing 25OH-D3 levels and reverting secondary hyperparathyroidism. Oral vitamin D supplementation added to sunlight exposure should be done with caution, since it might be accompanied in certain patients by hypercalcemic or nephrotoxic effects at doses higher than 2000 IU/day. [ABSTRACT FROM AUTHOR]

Vitamin D is one of the key factors in calcium and bone metabolism. Presently more than 30 natural vitamin D metabolites are known, but only la,25- dihydroxyvitamin D3 [1,25(OH)2D3], synthesized under the action of kidney Ia hydroxylase, is considered as being the final active hormonal product (1). The "classical" targets of 1,25(OH)2D3 are the gut, the bone and the kidney, all these organs possessing vitamin D receptors (VDR). l,25(OH)2D3 controls active intestinal absorption of calcium and phosphate, kidney calcium reabsorption, as well as bone metabolism, by acting directly on osteoblasts that possess VDR, and favoring osteoclast differentiation from monocytic precursors (2). In pharmacological doses, 1,25(OH)2D3 becomes toxic, increasing osteoclast formation and bone turnover, and thus leading to toxic effects (rapid bone loss, hypercalcemia, soft tissue calcifications). These toxic effects seem to be cytokine (IL-il) and prostaglandin-mediated (1). 1 ,25(OH) D3 acts through specific intracellular (nuclear) receptors from the same superfaniily as the retinoic acid, steroid and thyroid hormone receptors. Although there is only one vitamin D receptor (VDR) gene located on chromosome 12q13-14, alternate splicing leads to VDR isoforms, of which two most widespread are the f and F isoforms. The longer isoform, f (Mi), has 427 aminoacids, whereas the shorter VDR isoform, F (M4), has 424 aminoacids, lacking 3 aminoacids at the aminoterminal region (3). The VDR binds as a homodimer or as a heterodimer with the retinoid X receptor (RXR), to specific DNA sequences called vitamin D responsive elements (VDRE), situated in the promoter region of various vitamin D responsive genes (4). Coupling of 1,25(OH)2D3 to the VDR increases the affinity of the dimeric receptor complex to the VDRE. As a consequence of this binding, transcriptional activity is modulated through influencing RNA polymerase activity, a process called transactivation (4). Gene transcription is thus up- or down regulated, producing a specific cellular response. Rapid, "non-genomic" actions of l,25(OH)2D3 have also been described in various cell types (5). VDRs are found not only in the classical tissue targets for vitamin D, but also in other cells or tissues that are not involved in the calcium and bone metabolism, such as the brain and brain stem, muscles, thyroid follicular and parafollicular C cells, gonads, pituitary, endocrine pancreas, adrenal gland, prostate, uterus, hair follicle, tumor cells and cells of the immune system (6-9). The presence of the VDR in these tissues suggests that 1,25(OH)2D3 might play other roles than a mere calcium regulator. Indeed, 1 ,25(OH)2D3 has several non-classical or non-calcemic effects, such as inhibition of proliferation and differentiating effects in normal cells (keratinocytes), as well as tumoral cells (colon, prostate, thyroid and breast cancer, or leukemia cells) (9), or modulation of the immune response (9-11). [ABSTRACT FROM AUTHOR]

The hormone lα, 25 dihydroxyvitamin D3 (l,25(OH)2D3) has potent immunosuppressive effects in vitro. Recent publications also described a protective effect of the hormone in various animal models of immune-mediated diseases. To test its in vivo activity we induced active Heymann nephritis in Lewis rats that were either untreated or treated with l.25(OH) 2D3 or its synthetic 20-epi analogue, KH1060. Treatment with cyclosporine A (CsA) was used as an immunosuppressive control. In this nephrotic model the administration of l,25(OH) 2D3 (0.5μg,/kg body weight) given on alternate days during the first 13 days after active immunization significantly reduced the proteinuria as measured by weeks 7-9. This reduction was comparable to the reduction observed in rats treated with CsA (20 mg/kg) on alternate days. A second series of experiments with 1,25(OH) 2D3 confirmed these findings. The level of autoantibodies was found to be significantly suppressed during the treatment time in the CsA (20 mg/kg) group, whereas the limit of significance (P=0.06) was reached in the 1,25(OH) 2D3(0.5 μg/kg) group. The size of the immune deposits also was found to be substantially smaller in the groups that developed less proteinuria. The administration of 1,25(OH) 2D3 transiently increased the mean serum calcium concentration with 2.5 mg/dl above the pretreatment values, and the urinary calcium excretion by a factor of 3-5 during the short treatment time. Treatment with the analogue KH1060 did not reduce the proteinuria significantly. Our experiments add evidence to the hypothesis that 1,25(OH) 2D3 in pharmacological doses has immunosuppressive potency. [ABSTRACT FROM AUTHOR]

The hormone lα, 25 dihydroxyvitamin D3 (l,25(OH)2D3) has potent immunosuppressive effects in vitro. Recent publications also described a protective effect of the hormone in various animal models of immune-mediated diseases. To test its in vivo activity we induced active Heymann nephritis in Lewis rats that were either untreated or treated with l.25(OH) 2D3 or its synthetic 20-epi analogue, KH1060. Treatment with cyclosporine A (CsA) was used as an immunosuppressive control. In this nephrotic model the administration of l,25(OH) 2D3 (0.5μg,/kg body weight) given on alternate days during the first 13 days after active immunization significantly reduced the proteinuria as measured by weeks 7-9. This reduction was comparable to the reduction observed in rats treated with CsA (20 mg/kg) on alternate days. A second series of experiments with 1,25(OH) 2D3 confirmed these findings. The level of autoantibodies was found to be significantly suppressed during the treatment time in the CsA (20 mg/kg) group, whereas the limit of significance (P=0.06) was reached in the 1,25(OH) 2D3(0.5 μg/kg) group. The size of the immune deposits also was found to be substantially smaller in the groups that developed less proteinuria. The administration of 1,25(OH) 2D3 transiently increased the mean serum calcium concentration with 2.5 mg/dl above the pretreatment values, and the urinary calcium excretion by a factor of 3-5 during the short treatment time. Treatment with the analogue KH1060 did not reduce the proteinuria significantly. Our experiments add evidence to the hypothesis that 1,25(OH) 2D3 in pharmacological doses has immunosuppressive potency. [ABSTRACT FROM AUTHOR]

Calcitonin (CT) is a polypeptidic hormone specifically secreted by the thyroid parafollicular cells (C cells) and tangentially involved in human phosphocalcic and bone metabolism. CT from other species (e.g. salmon) is more potent than human CT and has limited therapeutic applications. The neoplastic proliferation of C cells leads to medullary thyroid carcinoma (MTC) generally characterized by an increase of CT secretion. Serum CT is therefore the ideal marker for MTC and can confirm its presence at an early stage, as well as the follow up of its remission or progression/relapse/survival after surgery. There are, however, controversies such as the necessity of CT screening in patients with thyroid nodules, or particular situations causing false positive or false negative results. Our minireview also deals with an up-to-date of surgical procedures for MTC, as well as with non-surgical therapy. [ABSTRACT FROM AUTHOR]

We present the case of a 28 year old pregnant primiparous woman, suspected of primary hyperparathyroidism due to hypercalcemia discovered by routine calcium assessment at 30 weeks of gestation. Diagnosis was strongly suggested by elevated serum calcium (15.2 mg/dL, normal range: 8.4-10.3 mg/dL), low serum phosphorus (0.55 mg/dL, normal range: 2.5-5 mg/dL) and increased urinary hydroxyproline excretion (118 mg/24h, normal range: 10-40 mg/24h), suggesting high bone turnover and confirmed by coexistence of high levels of parathyroid hormone (PTH, 145 pg/mL, normal range 10-65 pg/mL). Neck ultrasound identified a solid nodule of 33x58x20.5 mm situated behind the inferior pole of a normal thyroid left lobe, suggestive for a solid parathyroid tumour located within the left inferior parathyroid gland. Medical treatment with furosemide and hydration decreased serum calcium level but failed to normalize it. After a 3 day preparation for lung maturation with dexamethasone (16 mg per day), successful adenomectomy was performed under local anaesthesia, without major intraoperative or postoperative events. The few uterine contractions were easily managed with papaverine and progesterone. Calcium levels immediately returned to normal after surgery. Our patient delivered a healthy newborn at 40 weeks by caesarean section. A DXA BMD assay performed after one year showed significant bone loss of the mother at radius level (T score of - 2.6). [ABSTRACT FROM AUTHOR]

Context. State of art imaging techniques might be a useful tool to early detect the retinal vessels lesions in diabetes. Objective and design. This analytical observational study investigates the retinal microcirculation changes in type I and II diabetic patients without retinopathy using adaptive optics ophthalmoscopy (AOO) and optical coherence ophthalmoscopy angiography (OCTA). Subjects and methods. Fifty-five subjects were included in this study and were divided in three groups: type I diabetic group (n=16), type II diabetic group (n=19) and control group (n=20). An adaptive optics retinal camera was used to assess the parameters of the temporal superior retinal arterioles. Moreover, vessel density of the superficial capillary plexus across the parafoveal area was measured with OCT-A. All cases were investigated once, in a cross-sectional design. Results. Diabetic patients from both groups had a higher wall-to-lumen-ratio compared to the controls (p=0.01 and 0.01, respectively). Interestingly, no significant differences were found between the two diabetic groups (p=0.69). Moreover, the vessel density was smaller in the type I diabetic group than in the control group (p=0.001) Conclusion. AOO might be a useful tool to detect early retinal vascular changes in diabetes before any clinical signs and together with OCTA it might bring important information on the prognostic and pathophysiology of the disease. [ABSTRACT FROM AUTHOR]