Parathyroid function in chronic vitamin D deficiency in man: A model for comparison with chronic renal failure

Summary It has become obvious, from the elegantin vitro studies of Cohnet al. (3) and of others, that calcium may act at various steps in the biosynthesis, storage, degradation and secretory release of parathyroid hormone. It would be premature to attempt to interpret our simple clinical observations in terms of these still incompletely defined mechanisms. These clinical studies have, however, identified several different components in the overall pattern of parathyroid response in chronic vitamin D deficiency. In significantly hypocalcaemic patients there was an inverse proportional relationship between serum calcium and serum iPTH, both in the steady-state (9) and during calcium infusion (Fig. 2A); a similar pattern was seen in primary hyperparathyroidism (Fig. 2B). One is tempted to regard this relationship as reflecting an action of calcium on hormonal biosynthesis. There is the further suggestion that profound hypocalcaemia in vitamin D deficiency might limit the capacity of the parathyroid gland to release its hormone (Figs. 3, 4). In the majority of cases of chronic vitamin D deficiency, the serum calcium is maintained close to normal but varying between 8.1 and 11.1 mg/dl in different individual patients of the present series; and in all these cases there is very obvious evidence of increased parathyroid activity. In such patients, it appears that the serum iPTH represents the maximum rate of secretion that the parathyroid gland can currently produce; and the level of serum calcium reflects the extent to which that parathyroid secretion compensates for lack of vitamin D action on gut, bone and kidney. If this equilibrium state is disturbed by an induced, barely detectable, increment in serum calcium there appears to be an immediate inhibition of parathyroid secretion (Fig. 5). There is nothing in the data to suggest that a direct action of vitamin D on the parathyroid glands is required for any of these patterns of parathyroid response, since all were observed in patients with clinical vitamin D deficiency. Only the very slow decay in the steady-state concentration of serum iPTH after correction of vitamin D deficiency in the two hypercalcaemic patients (Fig. 6) suggests a possible direct action of vitamin D on the parathyroid glands. The very slowness of this decay must imply a process of structural involution. Is it possible that vitamin D is involved in some way in coupling the calcium dependent processes of hormonal synthesis and secretion with a calcium dependent mechanism controlling cell division? At present one can do little more than ask the question and wonder it it is a disturbance of such coupling that permits the development of hypercalcaemic secondary hyperparathyroidism.