Parathyroid hormone and the kidney in pseudohypoparathyroidism.

Although a relationship between parathyroid hormone, urinary cyclic AMP and phosphate excretion has been established, the exact molecular sequence which characterizes this cascade is still ambiguous. Consequently, the pathogenesis of inherited forms of hypocalcemia with defective renal responsivity to parathyroid hormone is still conjectural.

The control of phosphate uptake by the isolated renal tubule.

An in vitro isolated tubular model is presented which appears to have many characteristics of an active transport system in that Pi accumulation by the preparation is sodium- and temperature-dependent, stimulated by PTH and cAMP and is also conditioned by the metabolic integrity of the tissue. The relationship between the observations made in the dispersed convolutal tubule preparation in the present study and the mechanisms by which PTH affects phosphate transport in isolated perfused tubules and in vivo has not yet been ascertained.

Idiopathic hypothalamic hypogonadotropic hypogonadism with polyostotic fibrous dysplasia.

A 22-year-old woman had polyostotic fibrous dysplasia (POFD) and idiopathic hypothalamic hypogonadotropic hypogonadism (isolated gonadotropin deficiency). Recurrent fracture of dysplastic bone during childhood was associated with primary amenorrhea, clinical and laboratory evidence of estrogen deficiency, and subnormal circulating and urinary gonadotropin levels during adolescence. Gonadorelin (luteinizing hormone-releasing hormone) stimulation initially showed a luteinizing hormone (LH) response but absent follicle-stimulating hormone (FSH) response.

Vitamin D-dependent calcium-binding protein of rat intestine: changes during postnatal development and sensitivity to 1,25-dihydroxycholecalciferol.

To study the role of the vitamin D-endocrine system during the perinatal period, we monitored vitamin D-dependent calcium-binding protein (CaBP) in rat intestine by radial immunodiffusion and polyacrylamide disc gel electrophoresis. Small amounts of CaBp were present 2 days before birth; these levels increased 74-fold by day 38 after birth. Approximately 80% of the increase in CaBP concentration occurred in a 5-day period at the time of weaning (days 17--22 after birth).

Phenobarbital-induced alterations in the metabolism of [3H]vitamin D3 by the perfused rachitic rat liver in vitro.

Anticonvulsant therapy of seizure disorders in man is associated with the development of complications involving bone and mineral metabolism including hypocalcemia, elevated serum immunoreactive parathyroid hormone levels, and increased amounts of unmineralized bone or osteoid. The latter has been attributed to a reduction in serum-25-hydroxycholecalciferol levels resulting from increased hepatic metabolism of vitamin D. Using an in vitro recycling hepatic perfusion system, we have demonstrated that 5 d of phenobarbital treatment increases the hepatic production of [(3)H]25-hydroxyvitamin D(3) (4.

Adult hypophosphatasia. Clinical, laboratory, and genetic investigation of a large kindred with review of the literature.

Investigation of the kindred of a 58-year-old woman with all of the features of "adult" hypophosphatasia revealed 12 individuals in 3 generations with subnormal circulating total alkaline phosphatase (AP) activity. The pattern of inheritance suggested autosomal dominant transmission, with incomplete penetrance of the trait particularly in the young males. Hypophosphatasic individuals other than the proposita were clinically well but had loss of permanent teeth, showing that dental abnormalities could be the only clinical manifestation of the disorder.

Intestinal calcium binding protein in uremia.

In order to assess the usefulness of intestinal biopsies as indicators of end-organ responsiveness to vitamin D in uremic patients, calcium binding activity and calcium binding protein (CaBP) content were measured in intestinal biopsies from 12 uremic patients (glomerular filtration rate less than 5.0 ml/min) and 12 adult controls. Values for both were found to vary with the site of biopsy, highest values being obtained in the duodenal bulb, with lower values distally.

The relationship of biochemical and histometric determinants of uremic bone.

Simultaneous histometric and biochemical analyses were performed on 16 bone biopsy specimens taken from eight patients with chronic renal failure. The bone calcium and phosphorus contents are inversely related to the relative volume of microscopically measured, nonmineralized bone matrix (osteoid) and to the percentage of trabecular surface covered by this tissue. The magnesium content of uremic bone is positively correlated with the quantity of osteoid.

Effect of lithium on parathyroid hormone-induced calcium release from bone rudiments.

Lithium treatment of humans and animals has been associated with adverse effects on bone and mineral metabolism. In order to determine whether lithium was altering the skeletal response to parathyroid hormone, we incubated bone rudiments for 5 days in the presence or absence of the drugs. Lithium had no effect on either parathyroid hormone-induced cyclic AMP generation or 45Ca release from the bone rudiments.

Tuberculous pericarditis.

Tuberculous pericarditis is a rare but dangerous disease with a mortality of 20% to 40%. Early diagnosis and institution of appropriate therapy are critical, and open pericardial biopsy appears to be the most reliable diagnostic tool. Corticosteroids, in conjunction with antituberculous medication, are effective in suppressing the early granulomatous inflammatory response.

Effect of testosterone therapy on bone formation in an osteoporotic hypogonadal male.

Osteoporosis has been reported to complicate androgen deficiency in males. Accordingly, we have evaluated an osteoporotic hypogonadal male with bone histomorphometry before and after 6 months of testosterone replacement. Androgen therapy resulted in increases in relative osteoid volum, total osteoid surface, linear extent of bone formation, and bone mineralization.

Childhood renal osteodystrophy.

The processes of growth and remodeling that characterize growing bone are vulnerable to the biochemical effects of uremia. These processes are affected by the alterations in vitamin D metabolism and hyperparathyroidism that commonly occur with chronic renal insufficiency. Uremia interferes with cartilaginous developments as well.

Assessment of acute and chronic changes in parathyroid hormone secretion by a radioimmunoassay with predominant specificity for the carboxy-terminal region of the molecule.

A sensitive RIA for parathyroid hormone (PTH) with specificity for the carboxy-terminal region of the hormone was developed and applied to clinical studies. The assay was useful in identifying patients with chronic hyperparathyroid states, such as primary and secondary hyperparathyroidism. In addition, the assay could detect acute changes in PTH seen during calcium, pentagastrin, and EDTA infusions and after parathyroidectomy.

Effect of oral glucose ingestion on renal phosphate reabsorption and clearance in vitamin D-resistant rickets.

The effect or oral glucose ingestion on renal phosphate reabsorption was studied in 13 patients with the inherited form of vitamin D-resistant rickets (VDRR) and 5 normal subjects. In contrast to the normal subjects, glycosuria developed in six VDRR patients after glucose ingestion and resulted in a further 43% decrease in renal phosphate reabsorption. This was accompanied by a 33% increase in phosphate clearance.