Darryl Telting

Cholecalciferol loading dose guideline for vitamin D-deficient adults.

INTRODUCTION Severe vitamin D deficiency is very common. Evidence-based guidelines for rapid correction with high-dose oral cholecalciferol are not yet available. OBJECTIVE To develop a practical cholecalciferol loading dose regimen. MATERIALS AND METHODS A total of 208 vitamin D-deficient subjects (serum 25-hydroxyvitamin D(3) (25-OHD(3)) level <50 nmol/l), aged 18-88 years, were treated with solubilized cholecalciferol, 50,000 IU/ml. They received either 25,000 IU every fortnight for 8 weeks (total dose 100,000 IU), 25,000 IU every week for 6 weeks (total dose 150,000 IU), or 25 000 IU every week for 8 weeks (total dose 200,000 IU). Blood samples were collected at baseline and 10 days after the final dose of cholecalciferol. Results Most patients were severely vitamin D deficient: 76% had a serum 25-OHD(3) level <30 nmol/l at baseline. Cholecalciferol in a cumulative dose of 100,000, 150,000, and 200,000 IU increased mean serum 25-OHD(3) level by 29 nmol/l (95% confidence interval (CI): 23-35 nmol/l), 43 nmol/l (95% CI: 36-50 nmol/l), and 69 nmol/l (95% CI: 64-75 nmol/l) respectively. The change in 25-OHD(3) (Delta25-OHD(3)) was related to the dose per kilogram body weight (R(2)=0.38, P<0.0001), and is described by the equation: Delta25-OHD(3)=0.025x(dose per kg body weight). CONCLUSION The cholecalciferol loading dose required to reach the serum 25-OHD(3) target level of 75 nmol/l can be calculated as follows: dose (IU)=40x(75-serum 25-OHD(3))xbody weight.

Cinacalcet for hyperparathyroidism in pregnancy and puerperium.

The efficacy and safety of various modes of medical treatment for primary hyperparathyroidism (PHPT) in pregnancy is largely unknown. This report describes two cases of PHPT in pregnancy that were temporarily treated with the calcimimetic cinacalcet. The first case was diagnosed in the 31st week of pregnancy. The patient was asymptomatic and had an albumin-corrected total calcium level (Ca(corr)) of 3.24 mmol/l. As serum calcium was only mildly elevated it was decided to postpone surgery to the postpartum period. Cinacalcet was started immediately after delivery to prevent a postpartum surge in serum calcium. The second patient presented with hypertension and symptomatic hypercalcemia (Ca(corr) 3.96 mmol/l) in the 32nd week of pregnancy. Surgery was postponed because of suspected pheochromocytoma. Treatment with a combination of cinacalcet and calcitonin reduced serum Ca(corr) to 3.0 mmol/l. This report describes the monitoring of mother and child, and explores the pros and cons of the use of calcimimetics during pregnancy and puerperium.

Vitamin D absorption: consequences of gastric bypass surgery.

BACKGROUND Severe vitamin D deficiency is a common finding in morbid obesity, and the incidence increases markedly after RYGB. Normalization of vitamin D levels after RYGB is difficult to achieve because the degree of surgery-induced malabsorption is not known. OBJECTIVE To develop a test that quantifies the changes in intestinal cholecalciferol absorption induced by Roux-en-Y gastric bypass (RYGB) surgery. METHODS Absorption characteristics of cholecalciferol were studied in 14 morbidly obese, premenopausal women before and 4 weeks after laparoscopic RYGB. Serum cholecalciferol levels were measured at baseline and 1, 2, 3, and 14 days after a single oral dose of 50 000 IU solubilized cholecalciferol. RESULTS Peak serum cholecalciferol levels were observed on day 1 in all patients. They were 26.6±3.7% lower after RYGB (P=0.02). Inter-individual variability was high. CONCLUSION Peak cholecalciferol levels are reduced by about 25% after RYGB. Further analysis suggested that the timing of sampling in the current study was not optimal. This might have caused an underestimation of the true decrease in cholecalciferol absorption induced by RYGB.

Somatic and psychological effects of low-dose aromatase inhibition in men with obesity-related hypogonadotropic hypotestosteronemia

INTRODUCTION Reduced testosterone levels are frequently observed in obese men. Increased aromatase activity may be an etiological factor. OBJECTIVE In this study, we evaluate the clinical effects of aromatase inhibition in obesity-related hypogonadotropic hypotestosteronemia (OrHH). METHODS Double-blind, placebo-controlled, 6-month trial in 42 obese men with a BMI >35 kg/m(2), and a serum total testosterone <10 nmol/l. All patients started on one tablet of 2.5 mg/week, with subsequent dose escalation every month until a serum total testosterone of 20 nmol/l was reached. ENDPOINTS Psychological function, body composition, exercise capacity, and glucose, lipid, and bone metabolism. RESULTS Thirty-nine patients completed the study according to protocol. Letrozole decreased serum estradiol from 119.1±10.1 to 59.2±6.1 pmol/l (P<0.001), and increased serum LH from 3.3±0.3 to 8.8±0.9 U/l (P<0.0001) and serum total testosterone from 8.6±0.7 to 21.5±1.3 nmol/l (P<0.0001). Significant effects on the predefined endpoints were not observed. CONCLUSION Despite a marked rise in serum testosterone, low-dose aromatase inhibition had no somatic or psychological effects in men with OrHH.

Hypophosphatemia on the intensive care unit: individualized phosphate replacement based on serum levels and distribution volume.

BACKGROUND Hypophosphatemia occurs in about 25% of patients admitted to the intensive care unit. To date, a safe and validated phosphate replacement protocol is not available. OBJECTIVE To evaluate an individualized phosphate replacement regimen. DESIGN Fifty consecutive intensive care unit patients with a serum phosphate level<0.6 mmol/L were treated with sodium-potassium-phosphate intravenously at a rate of 10 mmol/h. The dose was calculated according to the following equation: Phosphate dose in mmol=0.5×Body Weight×(1.25-[serum Phosphate]). Phosphate levels were measured immediately upon completion of the infusion, as well as the next morning at 8 am. RESULTS Post-infusion phosphate levels were >0.6 mmol/L in 98% of the patients. Hyperphosphatemia, hyperkalemia or a decrease in serum calcium were not observed. In about a third of patients serum phosphate decreased to <0.6 mmol/L within the next 24 hours after infusion. The phosphate distribution volume calculated from the results of infusion and corrected for renal phosphate loss during the infusion period was 0.51 L/kg (95% CI 0.42-0.61 L/kg). CONCLUSION This study shows that phosphate replacement with dose calculation based on serum phosphate levels and a Vd of 0.5 L/kg is effective and safe.

Treatment of calcium and vitamin D deficiency in HIV-positive men on tenofovir-containing antiretroviral therapy

Abstract Background: Hypophosphatemia and bone disease are common in HIV-positive (HIV+) patients on tenofovir disoproxil fumarate–containing antiretroviral therapy (TDF-containing ART). The underlying etiology is not completely understood. Objective: To examine the effects of treatment of calcium and vitamin D deficiency on phosphate metabolism and bone disease in HIV+ patients on tenofovir. Methods: This was an open-label, pilot study of calcium and phosphate metabolism, bone turnover, and bone density in 24 HIV+ patients on TDF, who were receiving a 1-year treatment for vitamin D and/or calcium deficiency according to a predefined protocol. Eight patients without calcium or vitamin D deficiency served as controls. Results: One-year treatment improved vitamin D levels, decreased serum parathyroid hormone (PTH), and improved calcium balance and bone mineral density. It did not affect the serum levels of PTH-related peptide (PTH-rp) or fibroblast growth factor 23 (FGF-23) nor did it raise serum phosphate levels or decrease renal phosphate loss. Conclusion: Treatment of calcium or vitamin D deficiency in HIV+ patients on ART including TDF has favorable effects on bone density, but it does not improve serum phosphate levels. Renal phosphate wasting in these patients is not caused by excess PTH, PTH-rp, or FGF-23 nor by vitamin D or calcium deficiency.

Cinacalcet for Hypercalcemia Caused by Pulmonary Squamous Cell Carcinoma Producing Parathyroid Hormone-Related Peptide

Background: Current treatments for hypercalcemia caused by lung cell carcinomas producing parathyroid hormone-related peptide (PTH-rp) have limited efficacy, probably because of their lack of effect on PTH-rp secretion. In this case study we explored the efficacy of the calcimimetic cinacalcet as suppressor of PTH-rp production. Patient: A 57-year-old male with severe and recurrent hypercalcemia induced by a PTH-rp-producing squamous cell lung carcinoma, stage cT4N3M1b, poorly responding to standard treatments. Results: Serum PTH-rp levels were not affected by saline, calcitonin or zoledronate. PTH-rp decreased during chemotherapy and cinacalcet monotherapy. The combination of chemotherapy plus cinacalcet was most effective in rapidly reducing serum calcium and PTH-rp. Conclusion: This case study is the first to suggest that cinacalcet may be of value in some cases of PTH-rp-dependent hypercalcemia. Corroborative evidence is needed.

Luteinizing hormone-releasing hormone receptor antagonist may reduce postmenopausal flushing

ObjectiveHormone therapy (HT) is the most effective treatment of postmenopausal (PMP) flushing; however, its use is often contraindicated. As an alternative option, we explored the efficacy of the luteinizing hormone–releasing hormone (LHRH) receptor antagonist cetrorelix in women with severe PMP flushing. MethodsWe conducted an open-label treatment with cetrorelix 250 &mgr;g twice a day on 10 women with a baseline daily flush score of 15 or higher for a period of 4 to 6 weeks. The response to treatment was evaluated through monitoring serum gonadotropin levels, flush scores, and quality of life. ResultsAt baseline, the mean (SEM) daily flush score was 36.1 ± 1.8 (mean ± SEM range, 29-44). All women demonstrated a decrease in serum luteinizing hormone and follicle-stimulating hormone during treatment, but the premenopausal levels of both gonadotropins were reached in only two women. The mean daily flush score decreased by 42.0% ± 7.7% (P < 0.001). This was caused by a decrease in flush frequency of 26.2% ± 6.0% (P < 0.01) and by a decrease in flush severity of 21.2% ± 7.7% (P < 0.05). ConclusionsIn an open-label setting, luteinizing hormone–releasing hormone receptor blockade reduced PMP flushing by at least 25% in 8 of 10 women with severe flushing. A placebo-controlled study will be needed to demonstrate the true benefit of this approach. The present data suggest that the treatment period must be longer than 6 weeks to capture the maximal effect.

Assessment of calcium balance in patients on hemodialysis, based on ionized calcium and parathyroid hormone responses.

BACKGROUND Identification of the underlying causes of secondary hyperparathyroidism (SHPT) in individual patients on hemodialysis (HD) is hampered by the lack of clinically reliable information on calcium balance. The aim of this study was to assess calcium balance during HD sessions with a method that is applicable in day-to-day practice. METHODS Plasma ionized calcium (pCa2+) and parathyroid hormone (PTH) were measured at the beginning and end of HD to evaluate calcium fluxes in 23 patients on a dialysate calcium (DCa) concentration of 1.25 mmol/L. RESULTS HD with a DCa of 1.25 mmol/L caused a decrease in pCa2+ from 1.15 ± 0.01 mmol/L to 1.09 ± 0.01 mmol/L (p<0.0001) and increased plasma PTH from 26.7 ± 1.8 pmol/L to 37.0 ± 2.9 pmol/L (p<0.0001). The changes in pCa2+ were inversely related to the predialysis pCa2+ levels (R2 = 0.86, p<0.001). Patients with a predialysis pCa2+ >1.06 mmol/L had a calcium efflux, whereas those with a predialysis pCa2+ <1.06 mmol/L had a calcium influx during HD. CONCLUSION The results suggest that measurement of pCa2+ and PTH at the beginning and the end of HD provides useful information about calcium fluxes in individual patients. Further validation of this approach 
is warranted.

Elevated Fibroblast Growth Factor 23 Levels in a Newborn With Secondary Hypoparathyroidism

Fibroblast growth factor 23 (FGF-23) is a recently identified hormone that is of prime importance for phosphate homeostasis in humans. FGF-23 is secreted by osteocytes in response to phosphate-loading. It stimulates renal phosphate excretion and suppresses the formation of 1.25-dihydroxy-vitamin D by inhibiting renal 1α-hydroxylase activity. Knowledge about FGF-23 in early infancy is limited. We report here the case of a newborn with transient secondary hypoparathyroidism caused by maternal primary hyperparathyroidism during pregnancy. FGF-23 levels at birth were extremely high in the child (15.850 kilo-Relative Units per liter, kRU/L) (ie, ∼45 times higher than in the mother) and ∼7 times higher than in healthy newborns. The childs FGF-23 levels declined gradually and reached the normal adult range after ∼7 months. We discuss the potential physiologic significance of FGF-23 in newborns.