Biomedical subjects
Publications and source records attributed to S Posen.
With the advent of serum parathyroid hormone assays the diagnosis of hyperparathyroidism has become relatively straightforward. Current unresolved problems comprise the selection of patients for surgery, the pre-operative localization of lesions and the medical management of patients who, for one reason or another, are unsuitable for surgery.
Iliac crest biopsies and serum specimens were obtained from 36 non-dialyzed uraemic patients. The mean serum 25-hydroxycalciferol concentration of the patients was lower than that of normal subjects and a significant correlation was found between 25-hydroxycalciferol values and the severity of osteomalacia. Parathyroid osteopathy was significantly correlated with serum immunoreactive parathyroid hormone but not with serum 25-hydroxycalciferol values. While normal serum 25-hydroxycalciferol concentrations in uraemic patients do not exclude the presence of osteomalacia, a low concentration is virtually diagnostic of this disorder.
A woman with metastatic carcinoma of the breast developed hypercalcemia 39 months after mastectomy. The hypercalcemia remitted after treatment but recurred 12 months later, accompanied by elevated levels of serum immunoreactive parathyroid hormone (PTH). A urea/HC1 extract of hepatic metastases contained immunoreactive PTH, material which stimulated the resorption of fetal rat bone in tissue culture, and material which stimulated chick renal adenylate cyclase activity. These findings strongly suggest that this breast cancer produced a PTH-like substance.
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We studied 173 patients with Paget's disease and 105 patients with hyperparathyroidism. Nine patients were found to have both disorders.
Two families with "new" types of spondyloepiphyseal dysplasias are reported. The disease(s) are characterised by spinal changes, capital femoral epiphyseal involvement and minor changes in the first family and shortening of the hands and feet in the second.
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A virilizing, gonadotrophin-responsive adrenal cortical adenoma was removed from a 54-year-old woman. Following removal of the tumour, which contained and secreted androgens and estradiol, serum gonadotrophins rose to menopausal levels and the patient experienced menopausal symptoms. Pre-operative attempts to localize the source of androgens were unsuccessful.
Thirty-two patients with osteitis deformans were treated with porcine calcitonin for 240 patient-months. Relief of pain occurred in 10 patients, while a fall in the serum alkaline phosphatase level was observed in 22 out of 24 patients whose treatment lasted for more than two weeks. Pain relief occurred predominantly in patients with pain in the lower limbs, although not all patients with lower limb pain showed improvement. Side effects, usually mild in nature, were reported by half the patients. Antiporcine calcitonin antibodies were detected in sera of six out of 14 patients. The presence of circulating antibodies seemed unrelated to the effect of therapy or to the occurrence of side effects.
Spectacular transient increases in serum alkaline phosphatase were observed in five infants in the absence of demonstrable pathology.
Methods available for the assay of 25-hydroxycalciferol in human serum are evaluated and compared to one another. Ethanol was chosen for use in the initial extraction procedure and rat-kidney cytosol as the binding protein, although good alternative methods are also available. We used silicic acid for chromatography and found this an essential step. Reproducibility was increased when, after "bound" and "free" material were separated, an aliquot of the supernate was pipetted into the counting vial instead of the entire supernatant fluid being decanted. Beta-lipo-protein added to the assay system was of no advantage; added bovine serum albumin interfered with the assay by giving rise to high blank values. With ethanol extraction, silicic acid chromatography, rat kidney cytosol and separation on dextran-coated charcoal, sera from normal subjects showed a mean 25-hydroxycalciferol concentration of 28.5 microng/liter (range, 13.1 to 43.9) during the fall season. Coefficients of variation for a control serum were 4.9% (intra-assay) and 10.9% (interassay).
Twenty-four karotypically proven patients with Klinefelter's syndrome were studied. The majority suffered from disorders of personality and social adjustment. All were poorly educated. Two-thirds showed gynaecomastia and all had small testes. Eunuchoid body proportions were seen in the majority of patients. Half the patients had plasma androgen levels in the low normal range; in the rest the levels were subnormal. The serum LH level was elevated in 80% and could not be adequately suppressed by exogenous androgens in seven out of nine patients. Abnormalities of carbohydrate metabolism were demonstrated in seven patients. Bilateral mastectomy was a valuable form of therapy, but androgens were withheld for phychosocial reasons.
Four patients had symptomless osteomalacia at the time of starting regular haemodialysis. After 21-40 months they became hypophosphataemic and developed disabling skeletal symptoms. In each case an exacerbation of histological osteomalacia was shown. Symptoms improved after measures designed to raise serum inorganic phosphate concentrations or vitamin D administration, or both. Patients undergoing maintenance haemodialysis should have their serum phosphate and alkaline phosphatase levels monitored every month. Predialysis phosphate levels below 1 mmol/1 (3 mg/100 ml) and rising serum alkaline phosphatase concentrations are danger signals. If the diagnosis is confirmed early aggressive treatment should be started.
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Renal transplantation reduced circulating parathyroid hormone in recipients of renal allografts. Nevertheless, biochemical and histological evidence of mild hyperparathyroidism persisted up to eight years after renal transplantation despite good graft function.
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