Membranous glomerulonephritis associated with Graves' disease.

Renal involvement in thyroid diseases is an unusual event. Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis has been reported in propylthiouracil-treated patients. Membranous glomerulonephritis has been reported in association with both antithyroglobulin and thyroid antimicrosomal antibodies. The development of membranous glomerulonephritis may be associated with administration of 131I. We present a patient who developed membranous glomerulonephritis after administration of 131I. The clinical and pathological features of renal involvement in thyroid diseases are reviewed.

Physiological effects of slow release potassium phosphate for absorptive hypercalciuria: a randomized double-blind trial.

PURPOSE: We examined the physiological effects and tolerance of UroPhos-K, a slow release neutral form of potassium phosphate (155 mg. phosphate and 8 mEq. potassium per tablet) in patients with absorptive hypercalciuria. MATERIALS AND METHODS: A total of 31 patients with absorptive hypercalciuria were studied at baseline and after 3 months of treatment with 4 tablets twice daily of UroPhos-K or placebo (identical in appearance) in a prospective randomized, placebo controlled, double-blind trial during a 4-day inpatient study with a daily constant metabolic diet containing 400 mg. calcium, 100 mEq. sodium and 800 mg. phosphate. RESULTS: Treatment with UroPhos-K did not cause significant gastrointestinal side effects, increase fasting serum potassium or phosphorus, or reduce hemoglobin or creatinine clearance. It reduced urinary calcium excretion from 277 +/- 72 to 166 +/- 43 mg. per day (p < 0.001), associated with a reduction in serum 1,25-dihydroxyvitamin D concentration from 50 +/- 11 to 42 +/- 9 pg./ml. (p < 0.001). Indexes of intestinal calcium absorption and markers of bone turnover also decreased modestly. None of these changes was seen in the placebo group. CONCLUSIONS: In patients with absorptive hypercalciuria UroPhos-K seems to correct hypercalciuria by a combination of reduced intestinal absorption, bone resorption and improved renal calcium reabsorption. The drug is well tolerated compared to placebo.

Sustained reduction in urinary calcium during long-term treatment with slow release neutral potassium phosphate in absorptive hypercalciuria.

PURPOSE: We tested whether UroPhos-K, a new slow release neutral form of potassium phosphate (155 mg. phosphate, 8 mEq. potassium per tablet) in a dose of 4 tablets twice daily would produce a sustained hypocalciuric response and maintain bone mass in patients with absorptive hypercalciuria, a major cause of nephrolithiasis characterized by excessive intestinal calcium absorption accompanied in some patients by excessive bone loss. MATERIALS AND METHODS: A total of 25 patients with absorptive hypercalciuria were studied in a 4-year, prospective, open trial with UroPhos-K at yearly intervals during a 4-day inpatient physiological study with a constant metabolic diet containing 400 mg. calcium, 100 mEq. sodium and 800 mg. phosphate daily. RESULTS: Treatment with UroPhos-K caused a sustained, marked reduction in urinary calcium (264 to 181 mg. daily). Fractional 47calcium absorption decreased modestly (74.0 to 64.6%) commensurate with a reduction in serum 1,25-dihydroxyvitamin D (42 to 34 pg./ml.). Intact parathyroid hormone increased within the normal range (30 to 42 pg./ml.). Bone mineral density was stable at the lumbar spine, femoral neck and distal third of the radius. CONCLUSIONS: UroPhos-K may provide a long-term alternative for hypercalciuric patients in whom thiazide therapy fails.

Evidence for normal vitamin D receptor messenger ribonucleic acid and genotype in absorptive hypercalciuria.

Absorptive hypercalciuria (a stone-forming condition) is characterized by gut hyperabsorption of calcium, hypercalciuria, and reduced bone density. Inasmuch as these features implicate enhanced calcitriol action in gut and bone, we analyzed the vitamin D receptor (VDR) gene to ascertain whether an abnormality of this gene marks patients with intestinal hyperabsorption of calcium. We have compared the frequency of a restriction fragment length polymorphism (Bsm I) associated with different alleles of the VDR gene in a group of 33 well characterized absorptive hypercalciuric patients and a group of 36 normal race- and age-matched control subjects. There was no difference between the distribution of the VDR alleles in the patient population when compared with the normal population. The coding region of VDR messenger RNA was also normal, as determined by both DNA sequence analysis and chemical mismatch cleavage analysis of copy DNA from 11 index absorptive hypercalciuric patients. On the basis of these results, we propose that the enhanced intestinal calcium absorption invariably seen in absorptive hypercalciuria and attendant symptoms of this disorder are not attributable to mutations of the VDR and are not linked to a common VDR genotype.

Serum IGF 1 is low and correlated with osteoblastic surface in idiopathic osteoporosis.

We have previously reported that bone formation is impaired on histomorphometric analysis of bone in patients with idiopathic osteoporosis. In the present study, 30 patients with idiopathic osteoporosis (18 men and 12 women mean age 44 +/- 12 years) and spinal and/or appendicular fractures were studied. Compared with control values, bone biopsy analysis demonstrated reduced bone volume (13.0 +/- 4.4 vs. 23.2 +/- 4.4, p < 0.0001), osteoid volume (0.13 +/- 0.13 vs. 0.32 +/- 0.19, p = 0.001), osteoid surface (5.9 +/- 4.3 vs. 12.1 +/- 4.6, p = 0.0004), and diminished double-labeled mineralizing surface (MS/BS 2.0 +/- 2.1 vs. 5.1 +/- 2.7%, p = 0.0001) in the patients. Since insulin-like growth factor 1 (IGF-1) is one of the major determinants of bone growth and remodeling, we measured the circulating level of this growth factor in these patients. The mean serum IGF-1 concentration was lower in patients as compared with 33 healthy age-matched controls (193 +/- 59 SD ng/ml vs. 232 +/- 79). A significant difference was noted between the two groups only in subjects younger than 36 years. In patients with idiopathic osteoporosis, regression analysis of serum IGF-1 against the various histological parameters measured from the bone biopsy disclosed significant correlation's between serum IGF-1 and osteoblastic surface (r = 0.429, p = 0.032), mineralizing bone surface with a double label (r = 0.480, p = 0.015), and the bone formation rate (r = 0.457, p = 0.021). These findings suggest that in young eugonadal individuals with idiopathic osteoporosis, reduced IGF-1 concentrations may have an etiological role in the development of this disease.

Oral contraceptive pills, gonadotropin-releasing hormone agonists, or use in combination for treatment of hirsutism: a clinical research center study.

The effectiveness of oral contraceptive pills (OCPs), GnRH agonist (GnRH-a), and a combination of OCPs and GnRH-a in the treatment of hirsute women was compared and the impact of these treatments on hormonal and Ca metabolism was investigated. Thirty-three women were prospectively enrolled and randomized into three treatment groups (11 in each group). The serum levels of LH, estradiol, testosterone, free testosterone, androstenedione, and 17-hydroxyprogesterone declined in all 3 treatment groups, whereas the inclusion of GnRH-a treatment tended to promote a more rapid decrease in these hormone levels. Total cholesterol, low density lipoprotein, and high density lipoprotein levels remained unchanged. The assessment of hirsutism by the Ferriman-Gallwey score revealed a similar 25% reduction in score by all three treatment groups by 6 months. In addition, no difference was detected between groups with respect to hair diameters and the vellus index. Clinical assessment of hirsutism at 3 months by the patients revealed that the GnRH-a and the OCPs-plus-GnRH-a groups had better responses than the group on OCPs alone, but by 6 months all three groups were similar. The symptoms of hot flashes and vaginal dryness were greatest in subjects treated with GnRH-a alone. Serum Ca, phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion levels all increased significantly in subjects treated with the GnRH-a alone, whereas a decrement or no changes occurred for these measurement in the other two groups. The estimated Ca balance was unchanged in the OCPs and the OCPs-plus-GnRH-a groups but declined by 90 mg/day from baseline in the GnRH-a-treated women (p < or = 0.001). Bone density significantly decreased in the lumber spine in women treated with GnRH-a alone, with a less marked decline in the femoral neck. In contrast, women receiving OCPs plus GnRH had increased bone density in the lumbar spine. It is concluded that: 1) clinical measures of hirsutism are not different after 6 months of treatment with OCPs alone, GnRH-a alone, or a combination of the two; 2) the decline in gonadotropins and steroid hormones and improvement in clinical response were more rapid and pronounced when GnRH-a treatment was added to OCP administration; and 3) the negative impact of GnRH-a alone on Ca balance and bone loss limits its usefulness as a single agent for long-term therapy of hirsutism.

PIP: The effectiveness of oral contraceptive pills (OCPs), GnRH agonist (GnRH-a), and a combination of OCPs and GnRH-a in the treatment of hirsute women (modified Ferriman-Gallwey score 10), 20-39 years old, was compared and the impact of these treatments on hormonal and Ca metabolism was investigated. 33 women were prospectively enrolled and randomized into 3 treatment groups (11 in each group): 1) OCPs [35 mcg ethinyl estradiol plus 1 mg norethindrone administered cyclically]; 2) GnRH-a, 3.75 mg im, every 4 weeks for 24 weeks; or 3) a combination of both OCPs and GnRH-a at the above doses taken concurrently. All medications were administered for 6 months. The serum levels of LH, estradiol, testosterone, free testosterone, androstenedione, and 17-hydroxyprogesterone declined in all 3 treatment groups. The assessment of hirsutism by the Ferriman-Gallwey score revealed a similar 25% reduction in score by all 3 treatment groups by 6 months. The symptoms of hot flashes and vaginal dryness were greatest in subjects treated with GnRH-a alone. Serum Ca, phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion levels all increased significantly in subjects treated with the GnRH-a alone. In the OCP groups there was significant decline in serum Ca from baseline to 24 weeks (p or = 0.01). There was significant urinary loss of Ca in the GnRH-a group with respect to 24-hour excretion (p or = 0.001). The estimated Ca balance was unchanged in the OCPs and the OCPs-plus-GnRH-a groups, however, it declined by 90 mg/day from baseline in the GnRH-a-treated women from 111 +or- 43 to 21 +or- 58 mg/day (p or = 0.001). Bone density significantly decreased (by 2.7%) in the lumber spine in women treated with GnRH-a alone (p or = 0.02), with a less marked decline in the femoral neck. The negative impact of GnRH-a alone on Ca balance and bone loss limits its usefulness as a single agent for long-term therapy of hirsutism.

Physicochemical effects of a new slow-release potassium phosphate preparation (UroPhos-K) in absorptive hypercalciuria.

A new slow-release, neutral potassium phosphate salt (UroPhos-K) has been formulated in order to minimize gastrointestinal side effects and avoid sodium-induced calciuria. It was tested in a prospective randomized, double-blind trial in a group of 21 kidney stone patients with absorptive hypercalciuria type I (AH). Twelve patients allocated to the UroPhos-K group received four tablets twice daily with breakfast and an evening snack providing 1240 mg of phosphorus and 63.5 mEq of potassium daily. Nine patients assigned to the placebo group received placebo tablets of the same appearance containing excipient only. Subjects were studied during a 3-day period in the hospital while consuming a constant metabolic diet containing 400 mg Ca, 100 mEq Na, and 800 mg P per day before and after 3 months of treatment. Treatment with UroPhos-K did not cause any significant gastrointestinal side effects; nor did it raise fasting serum K or phosphorus, or reduce hemoglobin or creatinine clearance. It was associated with a rise in urinary K from 46 +/- 7 to 98 +/- 9 mEq per day and phosphorus from 744 +/- 185 to 1535 +/- 112 mg per day (p < 0.001 each). UroPhos-K treatment reduced urinary Ca from 288 +/- 63 to 171 +/- 49 mg/day (p < 0.001), without altering oxalate excretion. It reduced the urinary saturation of calcium oxalate without altering that of brushite. Moreover, by increasing urinary excretion of inhibitors (citrate and pyrophosphate), it reduced the propensity for spontaneous nucleation of brushite (increased formation product of brushite) and inhibited crystal agglomeration of calcium oxalate.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiographic ablation of mediastinal parathyroid adenomas: local experience and review of the literature.

PURPOSE: To evaluate local experience with a modified technique for angiographic ablation of mediastinal parathyroid adenomas. PATIENTS AND METHODS: Three patients with likely mediastinal parathyroid adenomas that had single feeding arteries underwent attempted arteriographic ablation with a slow continuous infusion of contrast medium. Patients were closely monitored for symptoms and calcium dynamics immediately postprocedure and then on a long-term outpatient basis. RESULTS: All three patients were cured (follow-up 22 to 68 months) with no long-term complications. CONCLUSION: Percutaneous angiographic ablation with contrast medium is a reasonable alternative for patients with hyperparathyroidism due to a mediastinal adenoma who can be treated in centers with well-trained interventional radiologists.

Calcium, estrogen, and progestin in the treatment of osteoporosis.

An adequate calcium intake is important to attain peak bone mass and to oppose that component of age-related bone loss due to insufficient intestinal calcium absorption. Calcium and appropriate vitamin D supplements are particularly important for preventing cortical bone loss and associated hip fractures in the elderly (Type II osteoporosis). Within the initial 5 years following menopause, there is an accelerated loss of trabecular bone from the spine and distal radius (Type I osteoporosis). At that time, estrogen replacement is most effective for preventing the rapid trabecular bone loss that could otherwise result in vertebral or Colles' fractures. During this early period of estrogen deficiency when excessive bone turnover is releasing large amounts of calcium into the circulation, supplemental calcium is ineffective. Progesterone, often given with estrogen to prevent endometrial carcinoma, may itself have a trophic influence on bone.

Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A randomized controlled trial.

OBJECTIVE: To test whether intermittent treatment with slow-release sodium fluoride and continuous calcium citrate supplementation inhibits vertebral fractures without causing fluoride complications. DESIGN: A placebo-controlled, randomized trial. SETTING: Outpatient setting of specialty clinics in Dallas and Temple, Texas. INTERVENTIONS: Slow-release sodium fluoride (25 mg twice daily) in repeated 14-month cycles (12 months on treatment followed by 2 months off treatment) compared with placebo. Both groups took calcium citrate (400 mg calcium twice daily) continuously. PATIENTS: 110 patients with postmenopausal osteoporosis were randomly assigned to two groups. In the slow-release sodium fluoride group, 48 of 54 patients completed more than 1 cycle of treatment (mean, 2.44 cycles/patient), whereas 51 of 56 patients in the placebo group completed at least 1 cycle (mean, 2.14 cycles/patient) in this interim analysis. MEASUREMENTS: Vertebral fracture rate and lumbar bone mineral content. Vertebral fractures were quantified from yearly radiographs. Bone mass was determined annually by densitometry. RESULTS: In the sodium fluoride group, the mean L2 to L4 bone mineral content increased by 4% to 6% in each cycle and the mean femoral neck bone density increased by 4.1% and 2.1% during the first two cycles, but the radial bone density did not change. The placebo group showed no statistical change in bone mass at any site. Compared with the placebo group, the sodium fluoride group had a lower individual new vertebral fracture rate (0.057/patient cycle compared with 0.204/patient cycle, P = 0.017), a higher fracture-free rate (83.3% compared with 64.7%, P = 0.042), and a lower group fracture rate (0.085/patient cycle compared with 0.239/patient cycle, P = 0.006). The side-effect profile was similar for the two groups; no patient developed microfractures, hip fractures, or blood loss anemia. CONCLUSIONS: Intermittent slow-release sodium fluoride plus continuous calcium citrate, administered for about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone mass without decreasing the radial shaft bone density, and is safe to use.

Pathogenesis and management of hypercalciuric nephrolithiasis.

Hypercalciuria has long been recognized as an important metabolic derangement associated with the formation of calcareous renal stones. Hypercalciuria increases the saturation of the urine with respect to stone-forming salts and reduces inhibitor activity. There is now ample evidence that 'idiopathic hypercalciuria' is a heterogeneous disorder, comprising several entities including absorptive, renal and resorptive forms of hypercalciuria. Absorptive hypercalciuria is the most common variety, and recent studies suggest that in a large subset of these patients, increased intestinal calcium absorption is caused by increased production of calcitriol or greater sensitivity to calcitriol (e.g. upregulation of vitamin D receptors). Reduced spinal bone density found in these patients may relate to increased action of calcitriol on bone or to other factors. Since patients with vitamin D-dependent absorptive hypercalciuria may develop negative calcium balance when placed on diets restricted in calcium, therapy is shifting from severe dietary calcium restriction and sodium cellulose phosphate (calcium-binding resin) to thiazides and orthophosphates, which promote calcium retention. For each form of hypercalciuria, selective therapy should provide the best results.

Vitamin D receptor quantitation in human blood mononuclear cells in health and disease.

Vitamin D receptor (VDR) concentration was quantitated in human peripheral blood mononuclear cells (PBMC) from patients with absorptive hypercalciuria (AH) and patients with high 1,25(OH)2D3 due to acquired or transient disease states and the results compared to those in normal subjects. VDR concentration in resting cells was not different between the three groups and represented constitutive receptor expression of monocytes. Following activation with phytohemagglutinin, patients with hypercalcitriolemia demonstrated significantly greater VDR concentrations. Patients with AH demonstrated a normal value for the group, but 6 patients had significantly greater concentrations of VDR despite normal plasma 1,25(OH)2D3 in four of the patients. Proliferation, as assessed from [3H]thymidine incorporation was inversely correlated with serum 1,25(OH)2D3 and was significant (R = -0.299, p = 0.048). Taken together, the results suggest that PBMC provide a useful system for studying VDR status in transient or acquired states of hypercalcitriolemia. Furthermore, the studies in patients with absorptive hypercalciuria disclosed it to be a heterogeneous disorder, characterized by both vitamin D-dependent and D-independent forms of receptor up-regulation.

An evaluation of the effect of gonadotropin-releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebo-controlled, crossover trial.

The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/day) in either the first (protocol A) or last (protocol B) 12-week period along with a 6-month course of the GnRH analog (GnRH-a; leuprolide acetate; 1 mg/day, sc) on uterine and leiomyomata volumes and hormone (estradiol, LH, and FSH) and serum lipid (total cholesterol, triglycerides, and high and low density lipoprotein) levels. Sixteen women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, respectively, and were then crossed over at 12 weeks to placebo or MPA, respectively, for the final 12-week interval of GnRH-a therapy. Total, myoma, and nonmyoma uterine volumes were determined by magnetic resonance imaging, and serum studies were performed at the beginning of the study and at 12 and 24 weeks. In both protocols, LH and estradiol levels declined by 80-90% (P < 0.03) and 55-72% (P < 0.02) of the baseline, respectively, at 12 weeks and remained at this level at 24 weeks. There were no significant changes in the other laboratory tests between protocols or longitudinally over time. Total uterine volume decreased to 73% of the baseline at 12 weeks in protocol B (P < 0.04), but did not change in protocol A. After crossover at 12 weeks, the total uterine volume of women in protocol A decreased to 74% of the baseline (P < 0.02) at 24 weeks. Between-protocol comparisons demonstrated a greater decline in total uterine volume in protocol B than A at 12 weeks, but after cross-over, MPA addition was associated with a significant increase in total uterine volume (protocol B) compared to a decrease in protocol A at 24 weeks (P < 0.005). In contrast, although myoma volume declined in both protocols, no significant changes in myoma volume were detected within or between groups over the treatment period. Nonmyoma volume changes in protocols A and B roughly paralleled total uterine volume changes, with MPA coadministration showing a correlation with a reversal in the GnRH-a-associated decrease in nonmyomatous tissue volume.(ABSTRACT TRUNCATED AT 400 WORDS)

Reduced vertebral bone density in hypercalciuric nephrolithiasis.

Dual-energy x-ray absorptiometry and single-photon absorptiometry were used to determine bone density at the lumbar spine and radial shaft in 62 patients with absorptive hypercalciuria, 27 patients with fasting hypercalciuria, and 31 nonhypercalciuric stone formers. Lumbar bone density was significantly lower in patients with absorptive (-10%) as well as in those with fasting hypercalciuria (-12%), with 74 and 92% of patients displaying values below the normal mean, whereas only 48% of the nonhypercalciuric stone formers had bone density values below the normal mean. In contrast, radial bone density was similar in all three groups of renal stone formers investigated. The comparison of urinary chemistry in patients with absorptive hypercalciuria and low normal bone density compared to those with high normal bone density showed a significantly increased 24 h urinary calcium excretion on random diet and a trend toward a higher 24 h urinary uric acid excretion and a higher body mass index in patients with low normal bone density. Moreover, among the patients with absorptive hypercalciuria we found a statistically significant correlation between the spinal bone density and the 24 h sodium and sulfate excretion and the urinary pH. These results gave evidence for an additional role of environmental factors (sodium and animal proteins) in the pathogenesis of bone loss in absorptive hypercalciuria. In conclusion, our data suggest an osteopenia of trabecular-rich bone tissues in patients with fasting and absorptive hypercalciurias.

Use of ketoconazole to probe the pathogenetic importance of 1,25-dihydroxyvitamin D in absorptive hypercalciuria.

Ketoconazole was used to probe the pathogenetic importance of the serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentration in 19 patients with well characterized absorptive hypercalciuria (AH). Patients were studied while receiving a constant metabolic diet before and after 2 weeks of ketoconazole administration (600 mg daily). Twelve of the patients were classified as ketoconazole responders, because in conjunction with a reduction of serum 1,25-(OH)2D from 113 +/- 36 to 70 +/- 26 pmol/L, intestinal 47Ca absorption decreased from 76.3 +/- 8.1% to 61.9 +/- 7.7%, and 24-h urinary Ca excretion declined from 7.6 +/- 1.4 to 5.7 +/- 1.1 mmol (P < 0.001 each). In these patients, intestinal 47Ca absorption was directly correlated with serum 1,25-(OH)2D levels and 24-h Ca excretion. In another group of 7 patients, termed ketoconazole nonresponders, despite reduction of 1,25-(OH)2D from 122 +/- 36 to 84 +/- 17 pmol/L (P = 0.015), there was no significant change in intestinal Ca absorption (76.0 +/- 8.2% to 72.1 +/- 10.6%) or 24-h urinary Ca excretion (7.3 +/- 1.3 to 7.2 +/- 1.0 mmol). In these patients, neither intestinal Ca absorption nor urinary Ca excretion was correlated with serum 1,25-(OH)2D levels. It, thus, appears that AH is a heterogeneous disorder comprised of both vitamin D-dependent and vitamin D-independent subsets. Although useful to probe the pathogenesis of AH, chronic treatment with ketoconazole is not recommended because of its generalized effects in inhibiting steroid synthesis.

Impaired bone formation in male idiopathic osteoporosis: further reduction in the presence of concomitant hypercalciuria.

We present iliac bone histomorphometric data and related biochemical data from 16 nonalcoholic men (50 +/- 11 (SD) years) referred for evaluation of spontaneous skeletal and/or appendicular fractures and reduced spinal bone density. All men were eugonadal and had no known underlying disorder associated with osteopenia. For the group, mean serum chemistry values were within normal limits including immunoreactive parathyroid hormone, osteocalcin and serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. Nine men demonstrated hypercalciuria (greater than or equal to 0.1 mmol/kg per day) while on a constant metabolic diet of 20 mmol/day Ca. Their 24-hour urinary calcium was significantly greater than that for the remaining 7 men (7.4 +/- 1.6 vs. 5.0 +/- 0.8 mmol/day, p = 0.003), as was their calciuric response to a 1 g oral calcium load (0.23 +/- 0.06 vs. 0.15 +/- 0.05 Ca/creatinine, p = 0.042). Serum parameters (including parathyroid hormone and 1,25(OH)2D) of hypercalciuric and normocalciuric men were not significantly different. Histomorphometric indices for cancellous bone demonstrated significant differences between the entire group of osteoporotic men and age-adjusted normal values for bone volume (11.4 +/- 4.0% vs. 23.2 +/- 4.4%), osteoid surface (5.6 +/- 3.9% vs. 12.1 +/- 4.6%), osteoblastic surface (2.0 +/- 2.3% vs. 3.9 +/- 1.9%), and mineralizing surface (1.9 +/- 2.4% vs. 5.1 +/- 2.7%); there were also significant differences in bone formation rate (total surface referent) (0.004 +/- 0.001 vs. 0.011 +/- 0.006 mm3/mm2 per year). Compared with the normocalciuric group the 9 hypercalciuric men had significantly lower osteoblastic surfaces (1.6 +/- 1.9% vs. 2.5 +/- 2.6%) and mineralizing surfaces (1.4 +/- 1.5% vs. 2.7 +/- 3.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary carbohydrates on metabolism of calcium and other minerals in normal subjects and patients with noninsulin-dependent diabetes mellitus.

Transient hypercalciuria has been noted after high carbohydrate meals which is independent of dietary calcium and is probably due to impaired renal calcium reabsorption mediated by an increase in plasma insulin levels. Based on these observations, some investigators believe that long term intake of high carbohydrate diets may increase the risk of nephrolithiasis and possibly osteoporosis. Using a randomized cross-over design, we compared high carbohydrate diets (60% carbohydrate and 25% fat) with high fat diets (50% fat and 35% carbohydrate) for effects on metabolism of calcium and other minerals in eight normal subjects and eight euglycemic patients with noninsulin-dependent diabetes mellitus. All other dietary constituents, such as protein, fiber, fluid, minerals (including Ca, Mg, Na, K, and P), and caffeine intake, were kept constant. Despite higher daylong levels of plasma insulin on the high carbohydrate diets compared to the high fat diet in both normal and noninsulin-dependent diabetic subjects, no changes in daily urinary excretion of calcium or other constituents, associated with renal stone risk, were observed. Furthermore, there was no change in fractional intestinal 47Ca absorption. Although hypercalciuria may ensue transiently after high carbohydrate meals, we conclude that substitution of simple or complex carbohydrates for fats in an isocaloric manner for a longer duration does not result in significant urinary calcium loss, and therefore, high intakes of digestible carbohydrates may not increase the risk of nephrolithiasis or osteoporosis via this mechanism.

New form of pseudohypoparathyroidism with abnormal catalytic adenylate cyclase.

Patients with pseudohypoparathyroidism type Ia have resistance to multiple hormones because of deficient activity of the stimulatory guanine nucleotide-binding protein (Gs) that couples membrane receptors to activation of adenylate cyclase. However, in a subset of patients with pseudohypoparathyroidism who have resistance to multiple hormones yet possess normal erythrocyte membrane Gs activity, the biochemical abnormality responsible for hormone resistance has remained undefined. Cultured skin fibroblasts were derived from a patient with this atypical form of pseudohypoparathyroidism. In the patient's fibroblast membranes, adenylate cyclase stimulation mediated by Gs after fluoride ion treatment produced only 52% of normal activity, yet fibroblast membrane Gs activity measured by cyc- complementation was normal. Activation of the catalytic unit of adenylate cyclase with manganese produced 49% of normal activity; manganese plus forskolin produced 54% of normal adenylate cyclase activity. beta-Adrenergic receptor coupling to Gs and phosphodiesterase activity were normal. A defect in the catalytic unit of adenylate cyclase can account for these results and may be a mechanism for clinical resistance to multiple hormones that act through adenylate cyclase.