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.

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.

Alteraçöes neurológicas nas cardiopatias congênitas: um estudo neuropatológico / Neurologic changes in congenital heart diseases: a neuropathologic study

Estudo neuropatológico foi realizado em 190 autópsias consecutivas de pacientes com cardiopatias congênitas: 116 casos foram operados (grupo cirúrgico, GCg e os 74 restantes formam o grupo clínico (GCI). Alteraçöes neuropatológicas foram observadas em 71 casos (41 no GCg e 30 no GCI). Entretanto, a maior parte dos 129 casos com exame normal morreu nas primeiras 72 horas após a cirurgia ou os eventos clínicos responsáveis pela morte. Quase todas as alteraçöes foram hipóxico-isquêmicas. Infartos, únicos ou múltiplos, foram encontrados em 41 casos (23 no GCg e 18 no GCI). Mecanismo embólico foi detectado em 12 casos. Alteraçöes hipóxicas difusas estavam presentes em 17 casos (10 no GCg e 7 no GCI). Hemorragias foram encontradas em 11 (6 no GCg e 5 no GCI). Em 17 casos (5 no GCI e 12 no GCg), o quadro foi o de uma leucomalacia periventricular. Todos os casos eram concernentes a crianças abaixo de 6 meses de idade. Em 7 casos, alteraçöes inflamatórias foram detectadas (micro-abscessos difusos em 6 d abscesso de lobo frontal em 1). Quase todos os casos em ambos os grupos apresentaram complicaçöes clínicas, isoladas ou associadas, potencialmente danosas para o cérebro, como parada cardíaca, baixo débito cardíaco, hipoxemia e insuficiencia respiratória. Foi impossível determinar, em cada caso, a magnitude do fator ou fatores responsáveis pelo padräo neuropatológico corrspondente. Näo houve diferenças do padräo neuropatológico entre as cardiopatias com hiper ou hipofluxo pulmonar

Parathyroid hormone secretory reserve in patients submitted to 131-iodine therapy for hyperthyroidism

Twelve euthyroid patients who had treated with I for hyperthyroidism due to Fraves' disease and six normal controls were submitted to an EDTA infusion test. Ionized calcium and parthyroid hormone were measured in serum samples collected every 10 min during the 2-h-test. Basal values for calcium (1.22 ñ 0.03 vs 1.23 ñ 0.03 pmol/l, mean ñ SD, controls vs patients) and parathyroid hormone (3.3 ñ 0.65 vs 5.5 ñ 2.32 pmol/l_ as well as maximum response during infusion (1.01 ñ 0.04 vs 1.01 ñ 0.05 for calcium and 12.0 ñ 2.2 vs 13.1 ñ 3.7 for parathyroid hormone) were not significantly different. We conclude that I treatment for hyperthyroidism due to Graves' disease had no effect on the parathyroid gland secretory reserve of the patients studied

Circulating molecular forms of parathyroid hormone in primary and secondary hyperparathyroidism

To study the circulating forms of parathyroid hormone (PTH), sera from 5 patients with primary hyperparathyroidism (PHP) and 12 patients with secondary hyperparthyroidism due the chronic renal failure (SHP) were submitted to gel filtration chromatography. The eluent samples were analyzed using two sequence-specific radioimmunoassays (RIA), one amino-terminal (NH2), the other carboxyl-terminal (COOH). The results obtained with the NH2RIA showed a single molecular form in both groups co-eluting with the intact hormone. The COOH assay identified several molecular forms with a broader distribution in the SHP patients. These results confirm the diagnostic superiority of the NH2 assay under both conditions