Effect of Altered Thyroid Function on Calcium and Phosphorus Circadian Rhythms

Abstract

The circadian rhythms in the concentration of calcium, phosphorus and creatinine in the serum and urine of control, hyperthyroid and hypothyroid subjects were compared during standard or around the clock liquid metabolic diets. No significant differences were noted in the urinary calcium rhythms between control and hyperthyroid subjects on either feeding regimen. In contrast to standard feedings, in which a higher rate of calcium excretion was present during the day, metabolic feedings reversed the timing of the excretory cycle so that nocturnal calcium excretion exceeded diurnal calcium excretion. The concentration of serum or urinary calcium, however, did not correlate with urinary phosphate excretion in control or hyperthyroid subjects on either feeding regimen. During standard feedings, hyperthyroidism exaggerated the circadian rhythms of urinary phosphorus excretion. In contrast, when individual hypothyroid patients were compared, no reproducible rhythm of serum or urinary phosphorus excretion emerged. Around the clock liquid metabolic feedings of hyperthyroid subjects blunted the amplitude of the cycle in serum phosphorus and urinary phosphorus excretion so that their circadian variations were indistinguishable from similarly fed control subjects. In hypothyroid patients fed standard diets, the temporal variations in urinary phosphorus excretion were more highly correlated with serum phosphorus concentration and glomerular filtered phosphorus than in similarly fed hyperthyroid subjects. These data suggested that changes in the glomerular filtered load of phosphorus are sufficient to account for urinary phosphate variations in hypothyroid subjects; whereas an additional, more dominant renal tubular factor is necessary to account for urinary phosphate variations in hyperthyroid subjects fed standard diets. The phosphodiuretic effects of iv T₃ were demonstrated to be temporally dependent, cyclic in nature, and apparently independent of parathyroid hormone. Therapy directed at establishing a euthyroid state was associated with a return to a normal circadian rhythm of phosphorus excretion in hypothyroid patients, and an elevation to the normal range in the decreased forenoon phosphate clearance in hyperthyroid patients. The data were interpreted to indicate that: 1) Thyroid hormone is permissively necessary for the expression of a normal phosphaturic rhythm; 2) circulating levels of thyroid hormone influence the amplitude of the phosphaturic rhythm; and 3) the phosphodiuretic actions of iv T₃ depend upon the intrinsic circadian responsiveness of the renal tubule.