Vitamin D supplementation in primary hyperparathyroidism: effects on 1,25(OH)2 vitamin D and FGF23 levels.

PURPOSE: In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with and without PHPT. METHODS: Individuals with and without PHPT (CTRL) received 14,000 IU/week of oral vitamin D3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH)2vitamin D (1,25(OH)2D), intact Fibroblast Growth Factor 23 (FGF23), 25OHD, Parathormone, and other biochemical markers. The 1,25(OH)2D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS). RESULTS: 70 PHPT patients and 75 CTRL were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. After the intervention, there were significant increases in the FGF23 levels (PHPT: 47.9 ± 27.1 to 76.3 ± 33.3; CTRL: 40.5 ± 13.9 to 59.8 ± 19.8 pg/mL, p < 0.001), and significant decreases in 1,25(OH)2D levels (PHPT: 94.8 ± 34.6 to 68.9 ± 25.3; CTRL: 68.7 ± 23.5 to 56.4 ± 20.7 pg/mL, p < 0.001). The reduction of 1,25(OH)2D was inversely associated with the increase of FGF23 in both the PHPT (r = -0.302, p = 0.028) and CTRL (r = -0.278, p = 0.027). No changes in plasmatic or uninary calcium concentrations were observed in both groups. CONCLUSION: The weekly administration of 14,000 IU of Vitamin D3 was safe and efficient to increase in 25OHD levels in both groups. However, a paradoxical decrease in 1,25(OH)2D levels measured by LC-MS/MS was associated with a significant increase in FGF23 levels in both groups. This phenomenon might represent a defense against hypercalcemia after vitamin D supplementation and paves the way for new studies in this regard.

Big data-based parathyroid hormone (PTH) values emphasize need for age correction.

PURPOSE: We aimed to study the relationship between aging and increased parathyroid hormone (PTH) values. METHODS: We performed a retrospective cross-sectional study with data from patients who underwent outpatient PTH measurements performed by a second-generation electrochemiluminescence immunoassay. We included patients over 18 years of age with simultaneous PTH, calcium, and creatinine measurements and 25-OHD measured within 30 days. Patients with glomerular filtration rate < 60 mL/min/1.73 m2, altered calcemia, 25-OHD level < 20 ng/mL, PTH values > 100 pg/mL or using lithium, furosemide or antiresorptive therapy were excluded. Statistical analyses were performed using the RefineR method. RESULTS: Our sample comprised 263,242 patients for the group with 25-OHD ≥ 20 ng/mL, that included 160,660 with 25-OHD ≥ 30 ng/mL. The difference in PTH values among age groups divided by decades was statistically significant (p < 0.0001), regardless of 25-OHD values, ≥ 20 or ≥ 30 ng/mL. In the group with 25-OHD ≥ 20 ng/mL and more than 60 years, the PTH values were 22.1-84.0 pg/mL, a different upper reference limit from the reference value recommended by the kit manufacturer. CONCLUSION: We observed a correlation between aging and PTH increase, when measured by a second-generation immunoassay, regardless of vitamin D levels, if greater than 20 ng/mL, in normocalcemic individuals without renal dysfunction.

COPD as an independent risk factor for osteoporosis and fractures.

Fractures are common in individuals with COPD and occur at higher bone mass values than expected. COPD appears to be an important risk factor for bone fragility. INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of osteoporosis and fractures, but screening and prophylactic measures to prevent both disorders are often neglected in this population. This case-control study assessed the prevalence of osteopenia, osteoporosis, and fractures in patients with COPD, and identified potential risk factors for fractures in this population. METHODS: Overall, 91 patients with COPD (COPD group; COPDG) and 81 age- and sex-matched controls (control group; CG) were assessed with bone mineral density (BMD), thoracic/lumbar spine radiographs, and serum PTH and 25-hydroxyvitamin D (25[OH]D) levels. The occurrence of prior fractures was retrieved from clinical history. RESULTS: The prevalence of total fractures in the COPDG was 57.1% (odds of fracture 4.7 times greater compared with the CG), and the femoral neck T-score emerged as the best predictor of fractures. Compared with the CG, the COPDG had lower spine and femoral BMD (p ≤ 0.01) and 25(OH)D levels (p = 0.01) and 2.6 times greater odds of osteoporosis. Among men, vertebral fractures were more prevalent in the COPDG versus CG (25.9% vs. 6.5%, respectively, p = 0.01). The odds of fracture increased with femoral neck T-scores ≤ - 2.7 in the CG and ≤ - 0.6 in the COPDG. CONCLUSION: These results add robust evidence to an increased odds of osteoporosis and fractures in COPD. Fractures in the COPDG occurred at higher BMD values than expected, suggesting that COPD may be an independent marker of fracture risk, reinforcing a need for regular osteoporosis screening with BMD measurement and prophylaxis of fractures in patients with this disorder.

Effects of Extrinsic, Intraspecific Competition and Host Deprivation on the Biology of Trichopria anastrephae (Hymenoptera: Diapriidae) Reared on Drosophila suzukii (Diptera: Drosophilidae).

The pupal parasitoid Trichopria anastrephae Lima (Hymenoptera: Diapriidae) shows potential to control Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), and understanding the behavior of this parasitoid in challenging environments is important to obtain a higher efficiency in mass rearing and in biological control programs. This study aimed to verify the effects of extrinsic intraspecific competition and the absence of host on the parasitism of T. anastrephae in D. suzukii pupae. Therefore, to evaluate the parasitism of T. anastrephae under intraspecific competition, groups of 20 pupae (24 h old) of D. suzukii were offered for different densities of parasitoids (1, 3, 5, or 10 couples) during a 7-day period. Whereas to evaluate the effects of host deprivation on parasitism of T. anastrephae, we tested different treatments: T1-no deprivation, T2-complete deprivation, T3-deprivation every other day, T4-deprivation for 3 days, and T5-deprivation for 7 days. The increase of density of parasitoids resulted in an increase of oviposition scars on pupae and a longer biological cycle, suggesting the occurrence of superparasitism. Increased density also resulted in a higher percentage of attacked pupae, but did not affect parasitoids emergence nor sex ratio. Host deprivation affected number of parasitized pupae, number and sex ratio of offspring, and the longevity of females. Based on our findings, competition among females do not impair offspring viability, and host deprivation for a period up to 7 days do not influence parasitism capacity, indicating that it can be used as a pre-release strategy.

Comparison of methods for estimates of molecular genetic diversity in genus Croton: influence of coefficients, clustering strategies and data projection.

We investigated 10 similarity (and disimilarity) coefficients in a set of 40 wild genotypes of Croton linearifolius subjected to analyses using hierarchical grouping methods, grouping methods by optimization and data projection in two-dimensional space. Genotypes were characterized by analyzing DNA polymorphism with the use of 15 ISSR and 12 RAPD markers. The distance measurements were compared by the Spearman correlation test, projection in two-dimensional space and grouping efficiency evaluation. The Spearman correlation coefficients between the 10 coefficients evaluated were significant (P < 0.001) and indicated significant changes in genotype ranking due to type of coefficient used (0.76 ≤ rs ≤ 1). Wide variation was also observed in the efficiency of clustering methods, where the unweighted pair group method with arithmetic mean was the most suitable (0.3 ≤ D ≤ 1.5 ; 0.41 ≤ rc ≤ 0.77; 5.99 ≤ S ≤ 12.61). Projection efficiencies in two-dimensional space showed high-stress values (65 < S < 89%). Similar to the results observed for hierarchical clustering methods and for projection in two-dimensional space, the formation of groups with grouping methods by optimization showed variations when using different coefficients. We believe that the results confirm the influence of coefficients in studies of genetic diversity, showing the need to use criteria and standards for selecting appropriate methods for genetic studies of the genus Croton.

Total parathyroidectomy with presternal intramuscular autotransplantation in renal patients: a prospective study of 66 patients.

Surgical treatment of secondary (SHPT) and tertiary hyperparathyroidism (THPT) may involve various surgical approaches. The aim of this paper was to evaluate presternal intramuscular autotransplantation of parathyroid tissue as a surgical option in SHPT and THPT treatment. 66 patients with renal chronic disease underwent surgery from April 2000 to April 2005 at Universidade Federal São Paulo, Brazil. There were 38 SHPT patients (24 women/14 men), mean age of 39.yrs (range: 14-58), and 28 THPT patients (14 women/14 men), mean age of 43.4 yrs (range: 24-62). Postoperative average followup was 42.9 months (range: 12-96). Postoperative intact PTH increased throughout followup from 73.5 pg/mL to 133 pg/mL on average from 1st to the 5th year, respectively, in SHPT and from 54.9 pg/mL to 94.7 pg/mL on average from 1st to 5th year, respectively, in THPT group. Definitive hypoparathyroidism was observed in 4 (6.06%) patients and graft-dependent recurrence in 6 (9.09%). Presternal intramuscular autotransplantation of parathyroid tissue is a feasible and safe surgical option in SHPT and THPT treatment.

A 10-year experience in intraoperative parathyroid hormone measurements for primary hyperparathyroidism: a prospective study of 91 previous unexplored patients.

Introduction. Primary hyperparathyroidism (PHP) is characteristically determined by high levels of calcium and high or inappropriate levels of parathyroid hormone (PTH). Technological advances have dramatically changed the surgical technique over the years once intraoperative parathyroid hormone (IOPTH) assay had allowed for focused approaches. Objective. To evaluate our 10-year experience in employing a rapid intraoperative PTH assay for PHP. Methods. A prospective cohort of 91 PHP-operated patients in a tertiary institution in São Paulo, Brazil, from June 2000 to April 2011. Results. We had 85 (93.4%) successful parathyroidectomies, 6 (6.6%) failed parathyroidectomies in 91 previous unexplored patients, and 5 (100%) successful remedial surgeries. The IOPTH was true-positive in 88.5%, true-negative in 7.3%, false-positive in 2.1%, and false-negative in 2.1% of the procedures. IOPTH was able to obviate additional exploration or to ask for additional exploration in 92 (95.8%) procedures. Conclusion. The IOPTH revealed to be an important technological adjunct in the current parathyroid surgery for PHP.

Zona fasciculata 21-hydroxysteroids and precursor-to-product ratios in 21-hydroxylase deficiency: further characterization of classic and non-classic patients and heterozygote carriers.

INTRODUCTION: Although much is known about the increased levels of the 21-hydroxylase substrates 17-hydroxyprogesterone (17OHP) and 21-deoxycortisol (21DF) - the biochemical markers of all forms of 21-hydroxylase deficiency (21OHD), only limited information is available on the zona fasciculata (ZF) products distal to the enzymatic block: 11-deoxycortisol (S), 11-deoxycorticosterone (DOC), and corticosterone (B). OBJECTIVE: To investigate whether basal and post-ACTH levels of S, DOC, and B and the 21-hydroxylase precursor-to-product ratios determined by tandem mass spectrometry preceded by high-performance liquid chromatography separation (liquid chromatography-tandem mass spectrometry) could disclose distinct profiles in genotypically confirmed classic (no.=14) and non-classic (NC) (no.=18) patients, heterozygote carriers (no.=61) and wildtypes (WT) (no.=27) for 21OHD. RESULTS: Salt wasting (SW) and simple virilizing (SV) had higher basal levels of DOC with no further increase in response to ACTH. Stimulated DOC was similar in 21OHD patients and carriers but was reduced as compared to WT. ACTH-stimulated B increased gradually from SW and SV through WT. The post-ACTH 21DF/B ratio was able to detect 92% of the carriers among WT. All NC patients could be detected by post-ACTH 17OHP/DOC and 21DF/B, with no overlap with 21OHD carriers. CONCLUSION: Although 21-hydroxylase is a key enzymatic step in both 17-hydroxy and 17-deoxy pathways of ZF, the reaction is mostly affected in the latter pathway, leading to a significant impairment of B production, which may further characterize the 21OHD subtypes. Also, the precursor-to-product ratios, particularly 21DF/B, can demonstrate the distinctive outline of 21OHD subtypes, including carriers and normal subjects.

Vitamin D deficiency in patients with active systemic lupus erythematosus.

UNLABELLED: We investigated the effects of disease activity on bone metabolism in 36 patients with systemic lupus erythematosus (SLE). Changes in bone remodeling were not explained by corticosteroid use. A high prevalence of 25OHD deficiency in SLE patients indicates the need for vitamin D replacement, mainly during high disease activity periods. INTRODUCTION: We investigated the effects of SLE disease activity on bone metabolism, their relation to inflammatory cytokines and vitamin D levels. METHODS: We performed a cross-sectional analysis of 36 SLE patients classified according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in high activity (group I: 12 patients, mean age 29.6 years) or in minimal activity (group II: 24 patients, mean age 30.0 years), and compared them to normal controls (group III: 26 women, 32.8 years). Serum calcium, phosphorus, parathyroid and sex hormones, bone remodeling markers, interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), IL-1, tumor necrosis factor-alpha (TNF), 25-hydroxivitamin D (25OHD), and 1,25-dihydroxyvitamin D3 were measured, plus bone mineral density. RESULTS: All cytokines were significantly higher in SLE groups; IL-6 could differentiate SLE patients from controls. In group I, 25OHD levels were lower (P < 0.05), which was related to the SLEDAI (R = -0.65, P < 0.001). In multiple regression analysis, the 25OHD level was associated with SLEDAI, osteocalcin and bone-specific alkaline phosphatase. The SLEDAI score was positively correlated with all measured cytokines and especially TNF (R = 0.75, P < 0.001). CONCLUSIONS: SLE patients demonstrated changes in bone remodeling strongly related to disease activity. A high prevalence of 25OHD deficiency was observed in SLE patients, indicating the need for vitamin D replacement.

Analysis of the diagnostic presentation profile, parathyroidectomy indication and bone mineral density follow-up of Brazilian patients with primary hyperparathyroidism.

Primary hyperparathyroidism is an endocrine disorder with variable clinical expression, frequently presenting as asymptomatic hypercalcemia in Western countries but still predominantly as a symptomatic disease in developing countries. The objective of this retrospective study was to describe the diagnostic presentation profile, parathyroidectomy indication and post-surgical bone mineral density follow-up of patients with primary hyperparathyroidism seen at a university hospital. We found 115 patients (92 women, median age 56 years) with primary hyperparathyroidism diagnosed during the last 20 years. We defined symptomatic patients based on the presence of any classical symptom affecting bone, kidney or the neuromuscular system. Surgical criteria followed the guidelines of the National Institutes of Health regarding asymptomatic primary hyperparathyroidism. Symptomatic patients and patients meeting surgical criteria for parathyroidectomy were 66 and 93% of the sample, respectively. Median calcium and parathyroid hormone values were 11.9 mg/dL and 189 pg/mL, respectively. After surgical treatment, 97% of patients were cured, with increases in bone mineral density of 19.4% in the lumbar spine and 15.7% in the femoral neck 3 years after surgery. Greater bone mass increases were detected in pre-menopausal women, men, and in symptomatic and younger patients, both in the lumbar spine and femoral neck. Our results support the previous findings of a predominantly symptomatic disease with a presentation profile that could be mainly related to a delayed diagnosis. Nevertheless, genetic and racial backgrounds, and nutritional factors such as calcium and vitamin D deficiency may play a role in the clinical presentation of primary hyperparathyroidism of Brazilian patients.

Analysis of the diagnostic presentation profile, parathyroidectomy indication and bone mineral density follow-up of Brazilian patients with primary hyperparathyroidism

Primary hyperparathyroidism is an endocrine disorder with variable clinical expression, frequently presenting as asymptomatic hypercalcemia in Western countries but still predominantly as a symptomatic disease in developing countries. The objective of this retrospective study was to describe the diagnostic presentation profile, parathyroidectomy indication and post-surgical bone mineral density follow-up of patients with primary hyperparathyroidism seen at a university hospital. We found 115 patients (92 women, median age 56 years) with primary hyperparathyroidism diagnosed during the last 20 years. We defined symptomatic patients based on the presence of any classical symptom affecting bone, kidney or the neuromuscular system. Surgical criteria followed the guidelines of the National Institutes of Health regarding asymptomatic primary hyperparathyroidism. Symptomatic patients and patients meeting surgical criteria for parathyroidectomy were 66 and 93 percent of the sample, respectively. Median calcium and parathyroid hormone values were 11.9 mg/dL and 189 pg/mL, respectively. After surgical treatment, 97 percent of patients were cured, with increases in bone mineral density of 19.4 percent in the lumbar spine and 15.7 percent in the femoral neck 3 years after surgery. Greater bone mass increases were detected in pre-menopausal women, men, and in symptomatic and younger patients, both in the lumbar spine and femoral neck. Our results support the previous findings of a predominantly symptomatic disease with a presentation profile that could be mainly related to a delayed diagnosis. Nevertheless, genetic and racial backgrounds, and nutritional factors such as calcium and vitamin D deficiency may play a role in the clinical presentation of primary hyperparathyroidism of Brazilian patients.

The Ala45Thr polymorphism of NEUROD1 is associated with type 1 diabetes in Brazilian women.

BACKGROUND: NEUROD1 encodes a transcription factor expressed in the endocrine pancreas, and involved in beta-cell development, function and mechanisms of apoptosis. In this study, we investigated the association of a frequent polymorphism in exon 2 of NEUROD1 (G > A; Ala45Thr) with Type 1 diabetes in Brazilian subjects. METHODS: A population/association study comprising 246 unrelated Type 1 diabetic and 275 nondiabetic white Brazilian subjects. The Ala45Thr variant was genotyped by a PCR-RFLP method. RESULTS: The frequency of the Thr allele was significantly higher in patients with Type 1 diabetes than in controls (42.3% vs 35.3%, P=0.02). Stratification by gender showed that homozygosity for the Thr allele was associated with Type 1 diabetes in women with odds ratio of 3.66 (95% C.I. 1.43-10.11, P=0.009) as compared to homozygosity for the Ala allele. This effect was not observed in men. CONCLUSIONS: We found a gender-specific association of the Ala45Thr variant of NEUROD1 with Type 1 diabetes in Brazilian women. Our results suggest that gender as well as ethnicity might modulate the association of NEUROD1 with Type 1 diabetes.

Changes in clinical and laboratory findings at the time of diagnosis of primary hyperparathyroidism in a University Hospital in São Paulo from 1985 to 2002.

In contrast to most developed countries, most patients with primary hyperparathyroidism in Brazil are still symptomatic at diagnosis. However, we have been observing a change in this pattern, especially in the last few years. We evaluated 104 patients, 77 females and 27 males aged 11-79 years (mean: 54.4 years), diagnosed between 1985 and 2002 at a University Hospital. Diagnosis was made on the basis of clinical findings and of high total and/or ionized calcium levels, high or inappropriate levels of intact parathyroid hormone and of surgical findings in 80 patients. Patients were divided into three groups, i.e., patients diagnosed from 1985 to 1989, patients diagnosed from 1990 to 1994, and patients diagnosed from 1995 to 2002. The number of new cases diagnosed/year increased from 1.8/year in the first group to 6.0/year in the second group and 8.1/year in the third group. The first group comprised 9 patients (mean serum calcium +/- SD, 13.6 +/- 1.6 mg/dl), 8 of them (88.8%) defined as symptomatic. The second group comprised 30 patients (mean calcium +/- SD, 12.2 +/- 1.63 mg/dl), 22 of them defined as symptomatic (73.3%). The third group contained 65 patients (mean calcium 11.7 +/- 1.1 mg/dl), 34 of them symptomatic (52.3%). Patients from the first group tended to be younger (mean +/- SD, 43.0 +/- 15 vs 55.1 +/- 14.4 and 55.7 +/- 17.3 years, respectively) and their mean serum calcium was significantly higher (P < 0.05). All of symptomatic patients independent of group had higher serum calcium levels (12.4 +/- 1.53 mg/dl, N = 64) than asymptomatic patients (11.4 +/- 1.0 mg/dl, N = 40). Our data showed an increase in the percentage of asymptomatic patients over the years in the number of primary hyperparathyroidism cases diagnosed. This finding may be due to an increased availability of diagnostic methods and/or to an increased awareness about the disease.

Changes in clinical and laboratory findings at the time of diagnosis of primary hyperparathyroidism in a University Hospital in São Paulo from 1985 to 2002

In contrast to most developed countries, most patients with primary hyperparathyroidism in Brazil are still symptomatic at diagnosis. However, we have been observing a change in this pattern, especially in the last few years. We evaluated 104 patients, 77 females and 27 males aged 11-79 years (mean: 54.4 years), diagnosed between 1985 and 2002 at a University Hospital. Diagnosis was made on the basis of clinical findings and of high total and/or ionized calcium levels, high or inappropriate levels of intact parathyroid hormone and of surgical findings in 80 patients. Patients were divided into three groups, i.e., patients diagnosed from 1985 to 1989, patients diagnosed from 1990 to 1994, and patients diagnosed from 1995 to 2002. The number of new cases diagnosed/year increased from 1.8/year in the first group to 6.0/year in the second group and 8.1/year in the third group. The first group comprised 9 patients (mean serum calcium ± SD, 13.6 ± 1.6 mg/dl), 8 of them (88.8 percent) defined as symptomatic. The second group comprised 30 patients (mean calcium ± SD, 12.2 ± 1.63 mg/dl), 22 of them defined as symptomatic (73.3 percent). The third group contained 65 patients (mean calcium 11.7 ± 1.1 mg/dl), 34 of them symptomatic (52.3 percent). Patients from the first group tended to be younger (mean ± SD, 43.0 ± 15 vs 55.1 ± 14.4 and 55.7 ± 17.3 years, respectively) and their mean serum calcium was significantly higher (P < 0.05). All of symptomatic patients independent of group had higher serum calcium levels (12.4 ± 1.53 mg/dl, N = 64) than asymptomatic patients (11.4 ± 1.0 mg/dl, N = 40). Our data showed an increase in the percentage of asymptomatic patients over the years in the number of primary hyperparathyroidism cases diagnosed. This finding may be due to an increased availability of diagnostic methods and/or to an increased awareness about the disease.

Response to an oral calcium load in nephrolithiasis patients with fluctuating parathyroid hormone and ionized calcium levels

The response to an oral calcium load test was assessed in 17 hypercalciuric nephrolithiasis patients who presented elevated parathyroid hormone (PTH) irrespective of the ionized calcium (sCa2+) levels. Blood samples were collected at baseline (0 min) and at 60 and 180 min after 1 g calcium load for serum PTH, total calcium, sCa2+, and 1.25(OH)2D3 determinations. According to the sCa2+ level at baseline, patients were classified as normocalcemic (N = 9) or hypercalcemic (N = 8). Six healthy subjects were also evaluated as controls. Bone mineral density was reduced in 14/17 patients. In the normocalcemic group, mean PTH levels at 0, 60 and 180 min (95 ± 76, 56 ± 40, 57 ± 45 pg/ml, respectively) did not differ from the hypercalcemic group (130 ± 75, 68 ± 35, 80 ± 33 pg/ml) but were significantly higher compared to healthy subjects despite a similar elevation in sCa2+ after 60 and 180 min vs baseline in all 3 groups. Mean total calcium and 1.25(OH)2D3 were similar in the 3 groups. Additionally, we observed that 5 of 9 normocalcemic patients presented a significantly higher concentration-time curve for serum PTH (AUC0',60',180') than the other 4 patients and the healthy subjects, suggesting a primary parathyroid dysfunction. These data suggest that the individual response to an oral calcium load test may be a valuable dynamic tool to disclose a subtle primary hyperparathyroidism in patients with high PTH and fluctuating sCa2+ levels, avoiding repeated measurements of both parameters.

Response to an oral calcium load in nephrolithiasis patients with fluctuating parathyroid hormone and ionized calcium levels.

The response to an oral calcium load test was assessed in 17 hypercalciuric nephrolithiasis patients who presented elevated parathyroid hormone (PTH) irrespective of the ionized calcium (sCa2+) levels. Blood samples were collected at baseline (0 min) and at 60 and 180 min after 1 g calcium load for serum PTH, total calcium, sCa2+, and 1.25(OH)2D3 determinations. According to the sCa2+ level at baseline, patients were classified as normocalcemic (N = 9) or hypercalcemic (N = 8). Six healthy subjects were also evaluated as controls. Bone mineral density was reduced in 14/17 patients. In the normocalcemic group, mean PTH levels at 0, 60 and 180 min (95 +/- 76, 56 +/- 40, 57 +/- 45 pg/ml, respectively) did not differ from the hypercalcemic group (130 +/- 75, 68 +/- 35, 80 +/- 33 pg/ml) but were significantly higher compared to healthy subjects despite a similar elevation in sCa2+ after 60 and 180 min vs baseline in all 3 groups. Mean total calcium and 1.25(OH)2D3 were similar in the 3 groups. Additionally, we observed that 5 of 9 normocalcemic patients presented a significantly higher concentration-time curve for serum PTH (AUC0',60',180') than the other 4 patients and the healthy subjects, suggesting a primary parathyroid dysfunction. These data suggest that the individual response to an oral calcium load test may be a valuable dynamic tool to disclose a subtle primary hyperparathyroidism in patients with high PTH and fluctuating sCa2+ levels, avoiding repeated measurements of both parameters.

High prevalence of low bone mineral density in pre-dialysis chronic kidney disease patients: bone histomorphometric analysis.

UNLABELLED: Chronic kidney disease (CKD) leads to reduced bone mineral density (BMD) in pre-dialysis and dialysis patients. A few studies have used dual-energy x-ray absorptiometry (DEXA) to assess BMD in pre-dialysis CKD patients and have shown low BMD to be highly prevalent. Until now there have been no studies reporting the histological features of low BMD in pre-dialysis CKD patients. AIM: To determine the prevalence and histological features of low BMD in pre-dialysis CKD patients. METHOD: Pre-dialysis CKD patients (n = 103, 46 females/57 males), median creatinine clearance of 29 (10 - 78) ml/min/ 1.73 m2, were evaluated using biochemical analysis and DEXA. Bone biopsies were obtained from those with low BMD. RESULTS: Fifty (48.5%) out of the 103 patients had low BMD (LBD group) and 53 (51.5%) had normal BMD (NBD group). The risk for low BMD was increased in those patients with alkaline phosphatase levels above 190 U/l and intact-PTH (iPTH) below 70 pg/ml (p < 0.05). Demographic and biochemical parameters from both groups were comparable, except for lower body mass index (BMI) in LBD subjects (p = 0.04). Women who had been post-menopausal for at least 1 year comprised 65% (13/20) and 50% (13/26) of the LBD and NBD groups, respectively (p = NS). In 40 LBD patients, bone histomorphometry revealed adynamic bone disease (ABD, 52.5%), osteomalacia (OM, 42.5%) and mixed bone disease (MBD, 5%). Trabecular bone volume (BV/TV) was lower in ABD and OM patients. A nearly significant association was found between ABD and iPTH < or = 150 pg/ml (p = 0.056), whereas higher values of iPTH were associated with OM. Total alkaline phosphatase < or = 190 U/l was significantly associated with ABD, whereas higher values were associated with OM. No correlation was observed between BV/TV and BMD. CONCLUSION: Low BMD is frequent in pre-dialysis CKD patients, and low turnover bone disease, manifesting as ABD and OM, was the hallmark of this bone loss.

Serum leptin concentration during puberty in healthy nonobese adolescents

Data obtained during the past five years have indicated that there are important age- and gender-based differences in the regulation and action of leptin in humans. To study the physiological changes of leptin during puberty in both sexes, and its relationship with body composition and sexual maturation, we measured leptin concentrations in 175 healthy adolescents (80 girls, 95 boys, 10-18 years of age), representing all pubertal stages. We excluded individuals with a body mass index (BMI) below the 5thor above the 95th percentile relative to age. Serum concentrations of leptin were determined by a monoclonal antibody-based immunofluorimetric assay, developed in our laboratory. Body composition was determined by dual-energy X-ray absorptiometry. Pubertal stage was assigned by physical examination, according to Tanner criteria for breast development in females and genital development in males. Leptin concentration in girls (N = 80) presented a positive linear correlation with age (r = 0.35, P = 0.0012), BMI (r = 0.65, P < 0.0001) and percentfat mass (r = 0.76, P < 0.0001). In boys (N = 95) there was a positive correlation with BMI (r = 0.49, P < 0.0001) and percentfat mass (r = 0.85, P < 0.0001), but a significant negative linear correlation with Tanner stage (r = -0.45, P < 0.0001) and age (r = -0.40, P < 0.0001). The regression equation revealed that percentfat mass and BMI are the best parameters to be used to estimate leptin levels in both sexes. Thus, the normal reference ranges for circulating leptin during adolescence should be constructed according to BMI or percentfat mass to assure a correct evaluation

Serum leptin concentration during puberty in healthy nonobese adolescents.

Data obtained during the past five years have indicated that there are important age- and gender-based differences in the regulation and action of leptin in humans. To study the physiological changes of leptin during puberty in both sexes, and its relationship with body composition and sexual maturation, we measured leptin concentrations in 175 healthy adolescents (80 girls, 95 boys, 10-18 years of age), representing all pubertal stages. We excluded individuals with a body mass index (BMI) below the 5th or above the 95th percentile relative to age. Serum concentrations of leptin were determined by a monoclonal antibody-based immunofluorimetric assay, developed in our laboratory. Body composition was determined by dual-energy X-ray absorptiometry. Pubertal stage was assigned by physical examination, according to Tanner criteria for breast development in females and genital development in males. Leptin concentration in girls (N = 80) presented a positive linear correlation with age (r = 0.35, P = 0.0012), BMI (r = 0.65, P < 0.0001) and %fat mass (r = 0.76, P < 0.0001). In boys (N = 95) there was a positive correlation with BMI (r = 0.49, P < 0.0001) and %fat mass (r = 0.85, P < 0.0001), but a significant negative linear correlation with Tanner stage (r = -0.45, P < 0.0001) and age (r = -0.40, P < 0.0001). The regression equation revealed that %fat mass and BMI are the best parameters to be used to estimate leptin levels in both sexes. Thus, the normal reference ranges for circulating leptin during adolescence should be constructed according to BMI or %fat mass to assure a correct evaluation.

GHRP-6 is able to stimulate cortisol and ACTH release in patients with Cushing's disease: comparison with DDAVP.

It has been shown that hexarelin stimulates ACTH and cortisol secretion in patients with Cushing's disease. The ACTH release induced by this peptide is 7-fold greater than that obtained by hCRH. The mechanism of action of hexarelin on the hypothalamic-pituitary-adrenal axis has not been fully elucidated. Although controversial, there is evidence that it might be mediated by arginine vasopressin (AVP). The aim of this study was to evaluate the ACTH and cortisol releasing effects of GHRP-6 in patients with Cushing's disease and to compare them with those obtained with DDAVP administration. We studied 10 patients with Cushing's disease (8 female, 2 male; age: 36.7 +/- 4.2 yr), 9 with microadenomas, who were submitted to both GHRP-6 (2 microg/kg iv) and DDAVP (10 micro g i.v.) in bolus administration on 2 separate occasions. ACTH was measured by immunochemiluminometric assay and cortisol by radioimmunoassay. The sensitivities of the assays are 0.2 pmol/l for ACTH, and 11 nmol/l for cortisol. GHRP-6 was able to increase significantly both ACTH (pmol/l, mean +/- SE; basal: 15.5 +/- 1.7 vs peak: 45.1 +/- 9.3) and cortisol values (nmol/l, basal: 583.0 +/- 90.8 vs peak: 1013.4 +/- 194.6). ACTH AUC (pmol/l min(-1)) and cortisol AUC (nmol/l min(-1)) values were 1235.4 and 20577.2, respectively. After DDAVP administration there was a significant increase in ACTH (basal: 13.0 +/- 1.4 vs peak: 50.5 +/- 16.2) and cortisol levels (basal: 572.5 +/- 112.7 vs peak: 860.5 +/- 102.8. AUC values for ACTH and cortisol were 1627.6 +/- 639.8 and 18364.7 +/- 5661.4, respectively. ACTH and cortisol responses to GHRP-6 and DDAVP did not differ significantly (peak: 45.1 +/- 9.3 vs 50.5 +/- 16.2; AUC: 1235.4 +/- 424.8 vs 1627.6 +/- 639.8). There was a significant positive correlation between peak cortisol values after GHRP-6 and DDAVP administration (r = 0.87, p = 0.001). Our results show that GHRP-6 is able to stimulate ACTH and cortisol release in patients with Cushing's disease. These responses are similar to those obtained after DDAVP injection. These findings could suggest the hypothesis that both peptides act by similar mechanisms, either at hypothalamic or pituitary level.