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Bone densitometry, regardless of the specific technique, is not perfectly reproducible even when consistently performed in exact accordance with the manufacturer's recommendations. Precision must be quantified at each densitometry facility in precision studies of the various skeletal sites used for monitoring. The precision, as the root-mean-square standard deviation or root-mean-square coefficient of variation, is then used to determine the change in bone density that constitutes the least significant change and the minimum interval between follow-up measurements. Until precision studies are performed, the least significant change cannot be determined for any level of statistical confidence, making the interpretation of serial studies impossible.

The secondary hyperparathyroidism of chronic renal failure is a result of many factors which result in chronic stimulation of parathyroid hormone secretion and secondary hyperplasia of the parathyroid glands. The secretion and metabolism of parathyroid hormone and its fragments in chronic renal failure are complex and only partially understood. Constant elevated levels of PTH contribute to bone disease and other clinical features of chronic renal failure. Calcium supplementation, high calcium dialysis, control of plasma phosphate and judicious use of the vitamin D metabolites can, to a large extent, prevent or control the development of secondary hyperparathyroidism. Subtotal parathyroidectomy or total parathyroidectomy with autotransplantation is indicated in certain cases, sometimes on an emergency basis. Prevention of postoperative hypocalcemia requires careful management. Successful renal transplantation is usually associated with gradual healing of the bone disease and slow, but sometimes incomplete involution of the parathyroid hyperplasia.

The results of parathyroid arteriography, venography and venous hormone assay were evaluated in 50 patients with proved hyperparathyroidism. Complete selective venous sampling representative of drainage sites in both upper and lower poles of the thyroid lobes was obtained in 94 per cent of the patients and was found to be an innocuous technic. Venous sampling alone provided correct localization and differentiation of parathyroid lesions in all patients without prior exploration. Venous sampling followed by limited arteriography provided specific identification of abnormal solitary parathyroid glands in 17 of 20 patients with unsuccessful prior explorations. Selective-magnification thyroid arteriography was positive in all patients retrospectively, but only a 77 per cent prospective accuracy could be achieved because of difficulty in differentiating thyroid lesions from parathyroid lesions. Venography without hormone assay was only occasionally helpful. These technics provided a significant contribution to the management of the previously explored patients. Furthermore, selective venous hormone assay should be considered in the routine preoperative evaluation of patients with primary hyperparathyroidism.

“Big” human placental lactogen has been purified by affinity chromatography. On SDS 1 -polyacrylamide disc gel electrophoresis, “big” hPL had a molecular weight of about 45,000. Following reduction with mercaptoethanol, a single band with a molecular weight of 23,000 was noted. These observations suggest that “big” hPL consists of two peptide chains linked by a disulfide bond.

The maintenance of a normal serum calcium concentration requires a stable equilibrium between mineral in the skeleton and the extracellular fluid and the carefully integrated and balanced actions of parathyroid hormone (PTH), vitamin D, and, to a much lesser extent, calcitonin. The amino acid sequences of bovine, porcine, and part of human PTH have recently been determined. It has been recognized that some of the difficulties encountered in measuring PTH by radioimmunoassay in serum are due to the conversion of the hormone into fragments, to the variable specificity and sensitivity of the antisera used in these determinations, and to the presence of a previously unrecognized precursor in the synthesis of the hormone. Parathyroid hormone appears to stimulate its target tissues (bone and kidney) through the adenyl cyclase mechanism, and it has now been appreciated that factors other than calcium have regulatory control over the secretion of hormone. The metabolism of vitamin D has been elucidated, and the active metabolite, 1,25-dihydroxy-cholecalciferol, has been identified. Production of this compound in the kidneys is under feedback control so that vitamin D takes on the characteristics of a hormone. Future developments involve the synthesis of more active and shorter-acting metabolites of vitamin D, drugs that will be of considerable usefulness to the clinician. Despite many years of research and a number of interesting biochemical, physiologic, and clinical studies, the importance of calcitonin in human physiology has not yet been determined. Nevertheless, its measurement in blood is a useful diagnostic aid in medullary carcinoma of the thyroid. Multiphasic screening programs have disclosed a surprisingly high prevalence of hypercalcemia in a random population. In most instances, the differential diagnosis can be made by carefully collecting a data base and using conventional laboratory procedures. Nevertheless, the assay for PTH has proven useful for diagnosis in some patients, particularly in the preoperative localization of parathyroid adenomas. The path is cleared for the development of more meaningful hormone assays and additional prospective studies on the management of asymptomatic patients with hyperparathyroidism. This review is written at an exciting time when major advances are being made in our understanding of calcium homeostasis, and rapid changes are occurring in the spectrum of hypercalcemic disorders being presented to the physician. Many of these research developments are summarized in relation to the clinical problem.

Twenty-six patients with chronic renal failure treated by long-term hemodialysis were studied. Radiologic parathyroid bone disease was observed in 15 patients, and in these, serum parathyroid hormone (PTH) levels were significantly higher ( p

Hypocalcemia frequently presents as an acute medical emergency or a chronic disorder which is difficult to control. Occasionally, it is found in routine blood screening tests when it is not anticipated. Recent developments in basic endocrine science have contributed greatly to our understanding and treatment of hypocalcemic disorders. The maintanance of a normal serum calcium concentration depends on the balanced actions of parathyroid hormone (PTH), vitamin D, and, to a lesser extent, calcitonin, Recent work on PTH secretion has defined the factors controlling its secretion in normal and abnormal states. In primary hypoparathyroidism, hormone secretion is decreased or absent, while in most other forms of hypocalcemia, secretion is stimulated secondarily by the hypocalcemia. However, acute or chronci disorders associated with hypomagnesemia may also decrease effective PTH secretion. Patients with the rare disorder, pseudohypoparathyroidism, have defects of hormone action and usually have elevated levels of PTH prior to therapy. Several forms of pseudohypoparathyroidism have been recognized, each representing a defect as a different site of PTH action. Calcitonin excess, as noted in medullary carcinoma of the thyroid, could theorectically cause hypocalcemia, but rarely does so. Vitamin D undergoes a series of two carefully controlled hydroxylation reactions leading to the final active metabolite, 1,25-hihyroxycholecalciferol. Chronic ingestion of certain drugs can lead to osteomalacia and hypocalcemia by potentiating the metabolism of vitamin D to inactive compounds. At least one form of rickets has been shown to result from a specific enzyme defect in the vitamin D pathway. Severe renal damage limits the conversion of vitamin D to its active form and contributes to vitamin D resistance. Current progress in the area depends on the development of procedures for the measurement of the metabolites in plasma and assessing the role of the vitamin (hormone) in normal and abnormal physiology. Although the therapy of acute hypocalcemia is usually readily accomplished, chronic hypocalcemia remains a very difficult therapeutic problem. Vitamin D, the hallmark of therapy, is a long-acting drug with a narrow therapeutic range. The complications of the disease and therapy are sometimes irreversible. The unraveling of vitamin D metabolism has led to the development of new therapeutic agents which might provide better relief of chronic hypocalcemic states. This review related new information about calcium homeostasis to the clinical situation encountered in the patient with hypocalcemia.

The results of studies performed in nine patients who had undergone successful parathyroidectomy and gland transplantation are presented. Transplantation of parathyroid tissue to the forearm, performed for therapeutic reasons, provided a unique opportunity to sample parathyroid gland effluent and to assess secretory function in vivo. The relationship of calcium to immunoreactive parathyroid hormone (iPTH) release was studied during calcium and ethylenediamine tetraacetic acid (EDTA) infusions as well as dialysis against a low calcium bath (low calcium dialysis) in patients with chronic renal failure. Calcium infusions caused an abrupt decrease in hormone release down to a persistent base line within 30 minutes, whereas EDTA infusion caused a sharp increase which peaked between 30 to 60 minutes and returned towards base line despite continuation of the hypocalcemic stimulus. Low calcium dialysis caused an irregular release of hormone which appeared to deplete gland reserves during the period of the stimulus. Ready access to the venous effluent of the transplanted tissue makes this an excellent model for studying parathyroid physiology in man.

Summary In a well-studied physiologically functioning in vitro system for the study of parathyroid hormone (PTH) secretion, both theophylline and dibutyryl cyclic adenosine monophate (dAMP) caused significant stimulation of PTH secretion. The quantity of PTH in the medium paralleled the release of cyclic 3′, 5′-AMP (CAMP) from incubated tissues. These studies suggest strongly that adenyl cyclase is the mediator of the known effects of calcium ion on PTH secretion.

In the first few weeks after the initiation of maintenance hemodialysis in nine patients with chronic renal failure, there was a progressive rise in both total and ionized serum calcium associated with a reciprocal and significant fall in the concentration of plasma parathyroid hormone. Studies in 36 additional patients with chronic renal failure already on hemodialysis indicated that this favorable trend did not continue; a progressive rise in parathyroid hormone concentration was associated with increasing duration of hemodialysis against the calcium concentration generally used by most centers. These observations are consistent with the increase in bone disease often associated with hemodialysis. Experimental increases in dialysate calcium concentration from 2.6 to 3.5 meq/liter for a 2-mo period failed to decrease parathyroid hormone secretion or cause a significant increase in predialysis calcium concentration in 36 uremic patients. Use of high calcium dialysis earlier in the course of the disease, alternate means of parathyroid suppression, and even subtotal parathyroidectomy may be necessary for the management of hyperparathyroidism in uremic patients undergoing hemodialysis.

Physiologic function of normal bovine parathyroid glands and of glands from patients with a variety of disorders of calcium metabolism was studied in an in vitro organ culture system. Calcium (Ca) concentration regulated both the synthesis and the secretion of parathyroid hormone (PTH) by normal tissue; magnesium (Mg) had an equivalent effect on hormone release. The relationship between cation concentration (Ca plus Mg) and hormone secretion was first-order. Evidence was obtained that PTH is synthesized in the glands as a protein that is altered to a smaller, immunologically related peptide before being released into the culture medium or plasma. The latter observation may help to explain some of the difficulties encountered in the radioimmunoassay of PTH in human blood. Most adenomas from patients with primary hyperparathyroidism were autonomous in organ culture, whereas most glands from patients with renal disease still remained responsive. Autonomous or "tertiary hyperparathyroidism" was documented in two patients.