Parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentration in elderly patients

Summary In 50 patients of a geriatric hospital (33 women, aged 65–96 years, mean age 80 years, and 17 men, aged 68–91, mean age 78.3 years) calcium, albumin, phosphate, urea, creatinine, parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were determined. Forty patients with serum creatinine levels up to 1.4 mg/dl (124 mol/l) and 10 patients with creatinine concentrations 1.5 mg/dl (132mol/l) were evaluated. In patients with normal creatinine, a positive correlation was found between parathyroid hormone and age (r=0.41;P<0.01). In patients with elevated creatinine, negative correlations were found in 1,25-dihydroxyvitamin D and calcium (r=–0.724;P<0.05), 1,25dihydroxyvitamin D and creatinine (r=–0.79;P<0.01) and 1,25-dihydroxyvitamin D and phosphate (r=–0.87;P< 0.002). The best correlation was observed in patients with elevated serum creatinine for 1,25-dihydroxyvitamin D and phosphate (r=–0.91;P< 0.001). The results suggest that low levels of calcium and phosphate stimulate the 1-hydroxylation of 25-hydroxyvitamin D even in advanced age and that the calcium metabolism of these patients is frequently disturbed. Nineteen patients had low levels of 25-hydroxyvitamin D, indicating an insufficient supply of vitamin D or rare exposure to sunlight. In 49 of 50 patients, one ore more of the parameters of calcium metabolism were outside the normal range.Abbreviations 25-OH-D 25-hydroxyvitamin D - 1,25(OH)₂D 1,25-dihydroxyvitamin D - PTH parathyroid hormone Supported by the Deutsche Forschungsgemeinschaft (Schm 405–407)     

Long-term therapy with cyclosporin A does not influence serum concentrations of vitamin D metabolites in patients with multiple sclerosis

Summary Animal studies have shown that cyclosporin A (CyA) stimulates renal 25-hydroxyvitamin D₃ [25(OH)D₃]-1-hydroxylase activity; in contrast, studies in renal transplant recipients indirectly suggest that CyA reduces 1,25-dihydroxyvitamin D₃ [1,25 (OH)₂D₃] production. To clarify the effect of CyA on vitamin D metabolite concentrations, we measured parameters of calcium metabolism in 37 CyA-treated patients (median trough whole blood levels 171–222 ng/ml) with multiple sclerosis and initially normal kidney function. The patients participated in a randomized double-blind study to assess the efficacy of CyA in multiple sclerosis. An age- and sex-matched control group (n = 39) received azathioprine (Aza). Measurements were made at the end of a 2-year treatment period. The 1,25(OH)₂D₃ serum concentrations were not significantly different between the two groups, although they were numerically lower in CyA-treated patients [median (range), 28.4 pg/ml (7.8–85.9) vs 41.0 pg/ml (9.2–105.1) in Aza-treated patients]. The 25(OH)D₃ levels were comparable in both groups. There was no correlation between the 25(OH)D₃ and 1,25(OH)₂D₃ concentrations. The renal function in both groups was stable in the last 6 months of the study. At the end of the study period, the endogenous creatinine clearance was significantly lower in the CyA-treated group (85 ± 17 ml/min versus 99 ± 22 in the Aza-treated group, P < 0.05). The carboxyterminal parathyroid hormone (C-PTH) was within the normal range in both groups, although CyA-treated patients had significantly higher concentrations (P<0.01). The urinary excretion of mineral ions, cations and protein was similar in both groups. Our data suggest that long-term treatment with CyA does not cause clinically important alterations of vitamin D metabolism in humans. Subtle differences in the concentrations of 1,25(OH)₂D₃ and C-PTH between CyA- and Aza-treated patients result presumably from a slight impairment of renal function through CyA.Abbreviations CyA cyclosporin A - Aza azathioprine - 25(OH)D₃ 25-hydroxyvitamin D₃ - 1,25(OH)₂D₃ 1,25-dihydroxyvitamin D₃ - PTH parathyroid hormone - C-PTH carboxyterminal-PTH - AP alkaline phosphatase - Ccr endogenous creatinine clearance - gamma-GT gamma-glutamyltransferase     

Hypomagnesaemia-induced hypocalcaemia: concentrations of parathyroid hormone, prolactin and 1,25-dihydroxyvitamin D during magnesium replenishment.

Three patients with hypomagnesaemia-induced hypocalcaemia were investigated during the phase of magnesium replenishment. Before treatment, serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were at the lower limit of normal. In spite of a rapid rise of parathyroid hormone (PTH) after intravenous administration of magnesium, a reactive increase in 1,25-dihydroxyvitamin D in serum was absent or delayed. The increase of serum calcium into the normal range occurred before any consistent change in the concentrations of this vitamin D metabolite. The rise of serum prolactin in response to the increase in PTH was blunted or absent, and is a further example of a transient PTH resistance during the phase of magnesium replenishment.     

Vitamin D deficiency and low osteocalcin concentrations in anorexia nervosa.

The calcium, vitamin D, and osteocalcin concentrations were investigated in 17 patients with anorexia nervosa. Serum 25-hydroxyvitamin D (25 OHD) concentrations below normal were observed in 15 (88%); only two patients has serum 1,25 dihydroxycholecalciferol (1,25(OH)2D) concentrations below normal. Serum parathyroid hormone (PTH) concentration was also normal in all except these two patients. Serum osteocalcin concentration was below normal in seven of 14 patients. Although a low concentration of serum 25 OHD is common in patients with anorexia nervosa in the United Kingdom, 1,25(OH)2D concentrations are usually normal. Hypovitaminosis D with secondary hyperparathyroidism is relatively uncommon. The subnormal osteocalcin concentrations observed in these patients probably reflect diminished osteoblastic activity, which may contribute to their osteopenia.     

Effect of sunlight exposure on circulating 1,25-dihydroxyvitamin D in hemodialyzed patients and of exogenous parathyroid hormone in anephric patients

Sunshine exposure increased the serum concentration of 25-hydroxyvitamin D (25-OHD) in 9 hemodialyzed patients. Mean 1,25-dihydroxyvitamin D (1,25-(OH)2D) was unchanged, but in two patients with low initial 25-OHD values this increase was accompanied by a rise in circulating 1,25-(OH)2D, although not to normal levels. One hemodialyzed patient developed liver insufficiency with a resultant reduction of serum 25-OHD concentration accompanied by a decrease in serum 1,25-(OH)2D concentration. The results indicate that the circulating levels of 1,25-(OH)2D in patients with end-stage renal failure are to some extent regulated by the serum 25-OHD concentrations. Injection of parathyroid hormone (PTH) induced minor increases in serum concentrations of 1,25-(OH)2D in patients with end-stage renal failure and even in anephric patients, suggesting the existence of an extrarenal PTH-sensitive 1-alpha-hydroxylase. However, the enzyme was stimulated by supraphysiological concentrations of PTH, and therefore not necessarily of importance in the normal regulation of calcium metabolism.     

Blockade of the renal tubular effects of vitamin D by cycloheximide in the rat

To further characterize the mechanisms by which 25(OH)vitamin D₃ (25(OH)D₃) and 1.25(OH)₂ vitamin D₃ (1,25(OH)₂D₃) suppress the phosphaturic action of parathyroid hormone (PTH) we have studied the effects of cycloheximide (cyclohex), a protein synthesis inhibitor, on the interaction between PTH and vitamin D metabolites in parathyroidectomized (PTX) rats, both in vivo and in vitro experiments. In clearance studies PTX PTH-infused rats were pretreated with cyclohex 2 h before the administration of vitamin D. In control, PTX PTH-infused rats not pretreated with cyclohex, the administration of 25(OH)D₃ and 1,25(OH)₂D₃ was associated with a fall in fractional excretion of phosphate (CP/CIN) from 0.30±0.05 to 0.16±0.02 and from 0.31±0.05 to 0.13±0.01 (P<0.005) respectively. Cyclohex-pretreated PTX PTH-infused rats failed to respond to both 25(OH)D₃ and 1,25(OH)₂D₃, and CP/CIN, which rose after PTH, remained 0.32±0.05 and 0.29±0.03 respectively. In vitro, both 25(OH)D₃ and 1,25(OH)₂D₃ inhibited the PTH-induced activation of adenylate cyclase in the renal isolated membrane fractions. Pretreatment with cyclohex abolished this effect of vitamin D metabolites. These results show that cyclohex blocks the antiphosphaturic effects of both 25(OH)D₃ and 1,25(OH)₂D₃ but does not alter the response to PTH. These findings are consistent with the possibility that the acute renal action of vitamin D depends on de novo synthesis of protein.An abstract of this work appeared in Clinical Research, 28 (2) A 387, 1980.     

Subacute effects of thiazide administration on renal hemodynamics and calcium metabolism

Summary To elucidate the renal effects of thiazides as a function of sodium intake, 8 healthy volunteers without renal disease were studied at baseline and 1 day as well as 4 days after the administration of 100 mg hydrochlorothiazide/day. The subjects were compared on two different dietary sodium intakes (120 mmol/day and 220 mmol/day). Measurements comprised inulin clearance (Cin) and paraaminohippurate clearance (Cpah) by infusion clearance technique, total and ionised calcium, immunoreactive parathyroid hormone (1,84 iPTH), 1.25 (OH)₂ vitamin D₃, and indices of hemoconcentration. Acute administration of hydrochlorothiazide (HCTZ) caused no change in Cin (before 111 ± 3 ml/min 1.73 m² ; 24 h after, 107 ± 2 ml/min 1.73 m²) or Cpah (before, 579 ± 9 ml/min 1.73 M²; after, 584 ± 12 ml/min 1.73 m²), while a significant (P < 0.01) decrease was noted on the 4th day after 100 mg HCTZ/day and normal sodium intake. No significant change of creatinine clearance (Ccr) was seen with either manouever. Renal hemodynamic changes after HCTZ administration were marginal when hemoconcentration was prevented by a high salt intake. Acute administration (1 h) of HCTZ caused suppression of 1,84 iPTH (before, 2.3 ±0.5 pmol/l; after, 1.9 ± 0.2 pmol/l; P < 0.01), but after 4 days a lower ionised calcium (baseline, 1.25 ± 0.01 mmol/l; day 5, 1.20 ± 0.02 mmol/l; P < 0.01) was noticed in parallel with hemoconcentration, metabolic alkalosis, and reduced 1,25 (OH)₂ vitamin D₃ concentrations. The level of 1,84 iPTH was elevated. We conclude that (i) hydrochlorothiazide does not affect the renal hemodynamics if hemoconcentration is avoided and (ii) hydrochlorothiazide acutely lowers PTH, while subacutely metabolic alkalosis and decreased ionised calcium may occur with concomitant increase in 1,84 iPTH and decrease in 1,25 (OH)₂ vitamin D₃ concentrations unless hemoconcentration is prevented.Abbreviations GFR glomerular filtration rate - PTH parathyroid hormone - iPTH immunoreactive PTH - PAH paraaminohippurate - HCTZ hydrochlorothiazide - FF filtration fraction - cAMP cyclic adenosine monophosphate - Cin inulin clearance - Cpah PAH clearance - Ccr creatinine clearance - CV coefficient of variation - HPLC high performance liquid chromatography - PRA plasma renia activity     

Substrate-product relation of 1-hydroxylase activity in primary hyperparathyroidism

The synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)2D), is thought to be relatively insensitive to the serum concentration of its precursor, 25-hydroxyvitamin D (25-OH-D). We compared the effect of oral administration of 25-OH-D3 (50 micrograms per day for one month) on serum concentrations of calcium, phosphate, parathyroid hormone, 25-OH-D, and 1,25-(OH)2D in five healthy adults and in six patients with primary hyperparathyroidism. In normal adults the mean (+/- S.D.) serum level of 25-OH-D rose from 18 +/- 9 to 136 +/- 47 ng per milliliter; no significant changes were observed in the other serum levels. In contrast, comparable increases in the levels of circulating 25-OH-D in patients with primary hyperparathyroidism caused a consistent slight rise in serum calcium and phosphate levels, a partial suppression of parathyroid hormone, and a sharp increase in the level of 1,25-(OH)2D. During this period a significant positive correlation was found between serum concentrations of 25-OH-D and 1,25-(OH)2D (P less than 0.001). These results provide evidence that in patients with primary hyperparathyroidism, levels of circulating 1,25-(OH)2D may be more dependent on the prevailing serum concentrations of 25-OH-D than they are in normal adults.     

Serum 25-hydroxyvitamin D levels in early and advanced breast cancer

BACKGROUND: Laboratory and epidemiological studies have implicated vitamin D deficiency in the pathogenesis of breast cancer. 1,25-Dihydroxyvitamin D (1,25(OH)(2)D) promotes differentiation and apoptosis, and potently inhibits proliferation of malignant breast epithelial cells in culture. Serum levels of 1,25(OH)(2)D are higher in normal women than in patients with primary breast cancer. AIM: To clarify the role of vitamin D in breast cancer progression by comparing the levels of serum vitamin D in patients with early and in those with advanced breast cancer. METHODS: Circulating levels of 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and calcium were measured prospectively in 279 Caucasian women with invasive breast cancer, 204 women with early-stage disease and 75 women with locally advanced or metastatic disease. RESULTS: Patients with early-stage breast cancer had significantly higher circulating levels of 25(OH)D (p<0.005) and significantly lower PTH (p<0.001) levels than those with advanced disease. Calcium levels did not differ significantly (p = 0.74). CONCLUSION: Serum levels of 25(OH)D are significantly higher in patients with early-stage breast cancer than in those with locally advanced or metastatic disease.     

Genetic models show that parathyroid hormone and 1,25-dihydroxyvitamin D3 play distinct and synergistic roles in postnatal mineral ion homeostasis and skeletal development

In humans, loss-of-function mutations in parathyroid hormone (PTH) and 25-hydroxyvitamin D3-1alpha-hydroxylase [1alpha(OH)ase] genes lead to isolated hypoparathyroidism and vitamin D-dependent rickets type I, respectively. To better understand the relative contributions of PTH and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] to skeletal and calcium homeostasis, we compared mice with targeted disruption of the PTH or 1alpha(OH)ase genes to the double null mutants. Although PTH-/- and 1alpha(OH)ase-/- mice displayed only moderate hypocalcemia, PTH-/-1alpha(OH)ase-/- mice died of tetany with severe hypocalcemia by 3 weeks of age. At 2 weeks, PTH-/- mice exhibited only minimal dysmorphic changes, whereas 1alpha(OH)ase-/- mice displayed epiphyseal dysgenesis which was most severe in the double mutants. Although reduced osteoblastic bone formation was seen in both mutants, PTH deficiency caused only a slight reduction in long bone length but a marked reduction in trabecular bone volume, whereas 1alpha(OH)ase ablation caused a smaller reduction in trabecular bone volume but a significant decrease in bone length. The results therefore show that PTH plays a predominant role in appositional bone growth, whereas 1,25(OH)2D3 acts predominantly on endochondral bone formation. Although PTH and 1,25(OH)2D3 independently, but not additively, regulate osteoclastic bone resorption, they do affect the renal calcium transport pathway cooperatively. Consequently, PTH and 1,25(OH)2D3 exhibit discrete and collaborative roles in modulating skeletal and calcium homeostasis and loss of the renal component of calcium conservation might be the major factor contributing to the lethal hypocalcemia in double mutants.     

Effects of acute hypercalcaemia on blood pressure in subjects with and without parathyroid hormone secretion

AIM: Acute hypercalcaemia increases the blood pressure, but the mechanism is uncertain. It may partly be the result of the concomitant fall in parathyroid hormone (PTH) secretion as PTH has been reported to have a vasodilator effect. To elucidate this, we infused calcium intravenously in subjects with and without PTH secretion. METHODS: Seven thyroparathyroidectomized subjects with undetectable PTH levels and 10 controls were studied twice, once with a calcium clamp technique that increased plasma ionized calcium in two steps of 0.1 mmol L(-1), each step lasting 60 min, and once with a placebo infusion. RESULTS: On the placebo day, blood pressure and all other variables were unaffected in both groups. On the calcium day, systolic blood pressure increased gradually and significantly from end of baseline till end of the calcium infusion in the controls (123.5 +/- 19.8 and 134.2 +/- 17.6 mmHg, P < 0.004) but not in the thyroparathyroidectomized subjects (124.9 +/- 15.7 and 126.0 +/- 20.6 mmHg, P = ns). Serum PTH levels fell promptly in the controls, and in both groups there was a significant increase in serum phosphate. The diastolic blood pressure and pulse rate, and the plasma adrenaline and noradrenaline, plasma renin activity, and serum aldosterone levels were unaffected by the calcium infusion. CONCLUSION: During acute hypercalcaemia the blood pressure increase appears unrelated to catecholamine secretion and the renin-aldosterone system, whereas the fall in PTH secretion may play a contributory role.     

25-hydroxyvitamin D, 24, 25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D in human cerebrospinal fluid

Summary Samples of CSF and plasma were obtained simultaneously from 46 adult patients who had no endocrine disorders and were undergoing routine diagnostic lumbar puncture because of suspected or proved prolapse of a disc. Concentrations of 25-OHD, 24,25(OH)₂D and 1,25(OH)₂D were measured. The samples were purified by column chromatography and fractionated by HPLC. In the appropriate fractions the vitamin D metabolites were measured by PBA, and cytoreceptor assay. The results were as follows (median, range in brackets): 25-OHD in CSF 8.3 ng/ml (2.0–24.8), in plasma 14.5 ng/ml (7.0–36.0). 24,25(OH)₂D in CSF 1.8 ng/ml (0.3–4.6) and 2.5 ng/ml (0.4–4.7) in plasma. 1.25(OH)₂ D in CSF 25.0 pg/ml (2.2–39.0) and 31.0 pg/ml (10.1–55.0) in plasma. The correlations between plasma and CSF concentrations were as follows: 25-OHDr=0.479 (P<0.001); 24,25(OH)₂Dr=0.815 (P<0.001) and for 1.25(OH)₂Dr=0.497 (P<0.001).Our findings showed vitamin D metabolites to be present in human CSF.Abbreviations Ca Calcium - CSF Cerebrospinal fluid - Vitamin D₃ Cholecalciferol - CPM Counts per min - 24, 25 (OH)₂D 24, 25-dihydroxyvitamin D₃ - 1,25(OH)₂D 1,25-dihydroxyvitamin D₃ - Vitamin D₂ Ergocalciferol - HPLC High-pressure liquid chromatography - 25OHD 25-hydroxyvitamin D₃ - PTH Parathyroid hormone - PBA Protein binding assay - RIA Radioimmunoassay - D-CaBP Vitamin D dependent calcium-binding protein     

Acute hypothyroidism has no effect on pulmonary vascular resistance

Summary The effect of acute hypothyroidism on the pulmonary circulation was studied in 9 nonobese athyreotic patients by right heart catheterization at rest and during exercise. The patients were studied while they were hypothyroid 2 weeks after ceasing triiodothyronine treatment and while they were euthyroid on replacement therapy. At rest, pulmonary blood flow [4.0±0.6 l/min vs 5.8±1.0 l/min,p<0.01] and systolic pulmonary artery pressure [18±3 mmHg vs 23±2 mmHg,p<0.01] were lower when the patients were hypothyroid than when they were euthyroid. The mean and diastolic pressures in the pulmonary artery and the pulmonary capillary pressures were not different among the groups. Likewise, thyroid hormone levels had no significant effect on pulmonary vascular resistance [100±25 dyn-s-cm^–5 vs 90±23 dyn-s-cm^–5]. With supine exercise, pulmonary blood flow [10.1±1.6 l/min vs. 13.2±2.0 l/min,p<0.01], mean pulmonary artery pressure [25±6 mmHg vs 30±6 mmHg,p<0.02], and systolic pulmonary artery pressure [36±6 mmHg vs 44±8 mmHg,p<0.01] were lower when the patients were hypothyroid. The diastolic pulmonary artery pressure and the pulmonary capillary pressure were similar in both thyroid states. Again, thyroid deficiency had no effect on pulmonary vascular resistance [81±23 dyn-s-cm^–5 vs 76±24 dyn-s-cm^–5]. The lower systolic pressures in the pulmonary artery seen in hypothyroidism are probably due to the decreased systolic volume load of the pulmonary circulation. The data do not suggest that thyroid hormones play a role in the regulation of pulmonary vascular resistance.Abbreviations PVR pulmonary vascular resistance - PAP_M mean pulmonary artery pressure - PCP_M mean pulmonary capillary pressure - PBF pulmonary blood flow     

A multiresponse parathyroid hormone assay: an inhibitor has agonist properties in vivo

Vitamin D-deficient rats subjected to thyroparathyroidectomy (TPTX) were used to evaluate in vivo the biological properties of native bovine parathyroid hormone (bPTH) and chemically synthesized fragments and analogues of the hormone on several parameters of hormone action: calcium and phosphorus fluxes, generation of cyclic adenosine 3',5'-monophosphate (cAMP), and the metabolism of 25-hydroxyvitamin D3 [25(OH)D3]. Vitamin D-deficient rats, after TPTX or sham operation, were intravenously infused with a nutrient containing 7.5 mM CaCl2 for 30 h. During the last 7 h, PTH or one of its analogues was infused intravenously at rates between 0.04 and 20 nmol/h. One hour after the start of the peptide infusion, tritiated 25(OH)D3 was injected. Urine was collected hourly for phosphate and cAMP determinations and, at the end of the experiment, blood was obtained to determine the relative accumulation of tritiated 1,25-dihydroxyvitamin D3 ([3H]1,25(OH)2D3). Infusion of bPTH-(1--84), bPTH-(1--34), human (h)PTH-(1--34), or [Nle8, Nle18, Tyr34]bPTH-(1--34) amide was accompanied by a comparable dose-dependent decrease in plasma phosphate and a dose-dependent increase in plasma calcium and [3H]-1,25(OH)2D3, and urinary excretion of phosphate and cAMP. An evaluation of [Nle8, Nle18, Tyr34]bPTH-(3--34) amide, a potent inhibitor of PTH action in vitro in the renal adenylate cyclase assay, revealed that the analogue possessed weak agonist properties in vivo. The analogue increased excretion of both cAMP and phosphate in the urine, decreased plasma phosphate levels, and increased the accumulation of [3H]-1,25(OH)2D3 in the plasma. This multiparameter model system should aid in the elucidation of the in vivo biological effects of PTH and its analogues.     

Renal refractoriness to PTH in experimental Fanconi syndrome: Evidence for intact adenylate cyclase activation

Previous studies demonstrated renal refractoriness to parathyroid hormone (PTH) in maleate-induced Fanconi syndrome (FS) in rats.In membrane fraction of renal cortex of parathyroidectomized (PTX) rats with FS, PTH increased adenylate cyclase (AC) activity from a basal value of 7.4±0.6 (x±SE) to 16.8±3.5 pmoles cAMP/mg prot/min (P<0.01), similar stimulation by PTH was observed in control incubation with normal kidneys. In membrane fraction of renal cortex of PTX rats incubated with maleate, PTH increased AC from 5.7±0.42 to 10.7±1.08 (P<0.01) similar to control incubation without maleate.In cortical slices from PTX rates with FS incubated in vitro, PTH increased cAMP content only from 4.0±0.21 to 5.27±0.27 pmole cAMP/mg prot (P<0.005), while in slices from the control group the increment by PTH was from 3.9±0.43 to 10.7±0.93 pmoles cAMP/mg prot (P<0.001). For the difference in the increment between the control and FS group,P<0.001.In cortical tissue of PTX rats with FS, PTH injection failed to increase cAMP content: basal value 7.4±0.8 and with PTH 9.2±0.8 pmole cAMP/mg prot (P NS), as compared with controls: basal value 9.5±0.5 and with PTH 23.8±1.6 (P<0.001). ATP content of cortical slices fell from a control value of 2.3±0.18 in PTX rats to 1.0±0.14 nmol/mg prot in PTX rats with FS.These results show, (1) normal response to PTH stimulation of cortical AC from rats with FS, and (2) failure of PTH to enhance formation of cAMP in renal cortical tissue from rats with FS. These findings are consistent with an intact PTH receptor/AC system in maleate induced FS, but inability to increase cAMP production probably because of comprized cellular metabolism causing reduced ATP content.     

Vitamin-D nutrition and bone mass in adolescent black girls

OBJECTIVE: To examine the relationship between bone mass and serum levels of 25-hydroxyvitamin D and parathyroid hormone in African-American adolescent girls. STUDY DESIGN: A cross-sectional sample at a suburban research center. METHODS: Twenty-one adolescent black girls 12-14 years of age, were studied during winter with biochemical measurements of serum 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH). Bone mass assessment was done with dual energy x-ray absorbsiometry (DXA) and peripheral quantitative computed tomography of the radius (p-QCT). Anthropometric, physical activity and nutritional data were collected. RESULTS: All participants were vitamin-D deficient (serum 25-OHD level <50 nmol/L), of whom nine (43%) were severely vitamin-D deficient (serum 25-OHD level <20 nmol/L). Mean daily intake of dietary calcium was 540 mg/d and vitamin D was 195 IU/d. There was a positive correlation, although statistically not significant, between serum 25-OHD and various bone mass measurements. Serum PTH was inversely correlated to total body BMD (r = -0.51, p = 0.02) and other bone mineral density at the lumbar spine, total femur and mid-radius. CONCLUSION: Vitamin-D insufficiency is a widely prevalent problem among adolescent African-American girls. Our data implies that enhancing vitamin-D nutrition resulting in lower serum PTH levels could potentially influence their peak bone mass.     

Different effects of eicosapentaenoic acid and olive oil on blood pressure,intracellular free platelet calcium,and plasma lipids in patients with essential hypertension

Summary In a randomized, double-blind, crossover study our specific aim was to examine the effects of a dietary fish oil or olive oil supplementation on blood pressure, intracellular free platelet calcium, plasma lipoproteins, and circulating vasoactive substances such as norepinephrine, epinephrine, and renin in patients with essential hypertension. Ten hypertensive patients (WHO classes I, II) were randomly assigned to receive 9 g fish oil or 9 g olive oil daily for 6 weeks after a 4-week baseline period. The 6-week treatment periods were separated by a 4-week wash-out. During treatment with fish oil diastolic blood pressure decreased from 103±1 to 98±2 mmHg (P<0.05) but did not change significantly during olive oil intake. Systolic blood pressure was not affected by either treatment. Intracellular free platelet calcium decreased in patients receiving fish oil (from 102±8 nM to 86±6 nM, P < 0.05) but was not significantly altered by olive oil treatment. In contrast, the dose-response curve for thrombin-induced intracellular free platelet calcium was not altered by the fish oil enriched diet. Plasma triglycerides decreased by approximately 40% in the fish oil group while low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and total cholesterol were not altered. Renin activity, norepinphrine, and epinephrine in plasma were not influenced by fish oil supplementation. We conclude that a moderate increase in dietary fish oil reduces diastolic blood pressure, intracellular free platelet calcium, and plasma triglycerides in patients with essential hypertension. The decrease in basal intracellular free platelet calcium concentration does not seem to be due to a diminished responsiveness of the calcium messenger system to thrombin.This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG) Ha-1388/2-3     

Selective deficiency of 1,25-dihydroxycholecalciferol. A cause of isolated skeletal resistance to parathyroid hormone.

To investigate the role of vitamin D metabolites in the pathogenesis of pseudohypoparathyroidism, we studied an elderly man with a unique variant of the disease, which was characterized by hypocalcemia, elevated serum parathyroid hormone (513 +/- 13 pg per milliliter, mean +/- S.E.M., normal, less than 450) but normal renal responses (phosphate and cyclic AMP) to exogenous parathyroid extract. Treatment with parathyroid extract did not produce a calcemic effect, suggesting an isolated skeletal hyporesponsiveness to parathyroid hormone. Although 25-hydroxyvitamin D levels were not reduced, levels of 1,25-dihydroxycholecalciferol were extremely low (0.52 ng per deciliter; normal 3.3 +/- 0.06, S.D.). Treatment with 1,25-dihydroxycholecalciferol (1 microgram by mouth per day for four days) increased circulating levels to normal (4.60 ng per deciliter) and restored to normal the calcemic response to parathyroid (change in calcium 3.0 mg per deciliter). These data suggest that 1,25-dihydroxycholecalciferol deficiency may explain the skeletal resistance, but not the renal resistance, often present in classic pseudohypoparathyroidism.     

Calcium and vitamin D status of pregnant teenagers in Maiduguri, Nigeria.

This study investigates parameters related to calcium and bone metabolism by determining the concentrations of total calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, and phosphorous in young pregnant women. The patient population was 30 pregnant Nigerian teenage women grouped by trimester (10 per group), 10 women immediately following delivery, and 21 healthy age-matched controls. On the basis of serum prealbumin levels, the general nutrition of the pregnant women was found to be significantly below that of the more privileged and better-educated nonpregnant controls. The mean total calcium concentration in sera of the third-trimester women was 8.83 mg/dL, which was significantly below that of the controls (9.77 mg/dL) and the first-trimester group (9.30 mg/dL). Despite the 10% to 15% decline in the serum level of total calcium during pregnancy, the parathyroid hormone level decreased markedly from 0.60 to 0.61 ng/mL in the first and second trimesters to 0.41 ng/mL in the third trimester. Serum vitamin D and 1,25-dihydroxyvitamin D levels in the second and third trimesters were within the normal range. These data indicate that toward the end of gestation, pregnant teenagers in northern Nigeria appear to become calcium deficient and do not exhibit the expected increase in serum parathyroid hormone levels normally seen in pregnant women.