Marcus Schaaf

Phosphate clearance in the diagnosis of parathyroid dysfunction

Abstract Measurement of the ratio of filtered to reabsorbed phosphorus (per cent TRP), while of diagnostic value in hyperparathyroidism, is less satisfactory as a diagnostic test in parathyroid deficiency, and requires measurement of the glomerular filtration rate. A study was therefore made of the applicability of the simpler measurement of phosphate clearance (Cp) in the diagnosis of parathyroid dysfunction. In twenty-five normal subjects the mean Cp, measured during the forenoon under fasting conditions, was 10.8 ± 2.7 ml./min. Except in one patient with associated severe renal disease, Cp was substantially elevated in hyperparathyroidism. In ten patients with parathyroid deficiency Cp was significantly depressed even when the hypocalcemia was corrected by vitamin D 2 therapy. These studies indicate that measurement of phosphate clearance is a valuable screening test for hyperparathyroidism and of diagnostic aid in parathyroid deficiency.

Skeletal responsiveness in pseudohypoparathyroidism: A spectrum of clinical disease

Three cases of pseudohypoparathyroidism with roentgenographic evidence of hyperparathyroid bone disease are described. Renal resistance to exogenous parathyroid hormone (PTH), the hallmark of pseudohypoparathyroidism, was documented by markedly blunted or absent urinary phosphate and cyclic AMP responses to parathyroid extract. At the time of diagnosis all patients were hypocalcemic and hyperphosphatemic with elevated serum alkaline phosphatase levels and subperiosteal resorption noted on skeletal films. Bone biopsy in one patient revealed a histologic appearance consistent with hyperparathyroidism. Serum PTH levels, measured in two patients while they were hypocalcemic, were elevated. None of the patients had short stature, brachydactyly, subcutaneous calcification or mental deficiency. These cases are compared to the 15 well-documented cases previously reported. The presently available information on pseudohypoparathyroidism indicates a variable skeletal response to PTH mediated by several factors extrinsic to bone and suggests that pseudohypoparathyroidism with hyperparathyroid bone disease is one extreme of a clinical spectrum of skeletal responsiveness to PTH. This disorder is part of an expanding clinical picture which makes pseudohypoparathyroidism a diagnostic consideration in any patient with unexplained hypocalcemia, hyperphosphatemia, elevated alkaline phosphatase levels or metabolic bone disease.

Hypocalcemia with osteoblastic metastases in a patient with prostate carcinoma: A cause of secondary hyperparathyroidism

A 68 year old man with prostatic carcinoma and extensive painful osteoblastic metastases was discovered to have hypocalcemia (serum calcium 7.1 mg/dl) without evidence of hypoalbuminemia, renal failure or malabsorption. Baseline studies revealed hypocalciuria (24 hour urine calcium less than 5 mg/day), normal serum phosphate (3.4 mg/dl), low tubular reabsorption of phosphate (68 percent), undetectable serum calcitonin, normal serum 25-hydroxyvitamin D, slightly elevated serum parathyroid hormone level and increased urinary cyclic AMP (8.87 mumol/g creatinine). These studies were compatible with secondary hyperparathyroidism. The intravenous administration of parathyroid extract produced no further change in urinary phosphate but a 25-fold increase in nephrogenous cyclic AMP. Three days administration of intramuscular parathyroid extract slowly and temporarily restored serum calcium to normal levels while increasing urinary cyclic AMP and phosphate. Chemotherapy with cyclophosphamide and 5-fluorouracil rendered the patient free of pain while reducing serum acid and alkaline phosphatase levels and restoring serum total and ionized calcium and urinary cyclic AMP excretion to normal.