Urinary excretion of 3',5'-AMP in syndromes considered refractory to parathyroid hormone.

Abstract Earlier studies showed that parathyroid hormone increases the urinary excretion of cyclic 3′,5′-AMP in normal subjects; patients with pseudohypoparathyroidism showed little or no response. In the current investigation this response to parathyroid hormone was examined in several apparently unrelated syndromes previously characterized as resistant to the hormone in tests for phosphaturia. The disorders studied included the basal cell nevus syndrome (BCN), Gardner's syndrome (GS), vitamin D-resistant osteomalacia (DRO), and the syndrome of basal ganglia calcification (BGC). Urine was collected on two successive mornings and 180 USP units of purified bovine parathyroid hormone were infused between 9 and 9:15 a.m. on day 2. During the control day (Day 1) normal volunteers showed average excretion of 3′,5′-AMP of 3.90 nmoles/mg. creatinine (range 2.4–5.4). Baseline excretion for patients averaged 2.90 (BCN), 5.19 (GS), 5.30 (DRO), and 5.27 (BGC) nmoles of 3′,5′-AMP/mg. creatinine. Base-line excretion rates for patients with GS, DRO, and BGC were significantly greater than normal. This finding possibly reflects secondary hyperparathyroidism in DRO but remains unexplained in GS and BGC. Infusion of hormone into normal subjects caused an increase to 23.7 nmoles of 3′,5′-AMP/mg. creatinine (range 13–42). The responses to the hormone for the patient groups were 32 (BCN), 48 (GS), 56.1 (DRO), and 47.4 (BGC) nmoles of 3′,5′-AMP/mg. creatinine. These results were within the limits of normal. There were wide fluctuations in phosphate excretion from day-to-day as well as hour-to-hour in all groups. These variations obscured the phosphaturic response in the normal subjects and in patients with Gardner's syndrome, vitamin D-resistant osteomalacia and the family with calcification of the basal ganglia. The basal cell nevus syndrome showed a significant phosphaturic response to the hormone. These results confirm previous conclusions that the phosphaturic response is not sufficiently reliable to categorize a syndrome as refractory to PTH. On the other hand, the rate of excretion of 3′,5′-AMP shows less variation and the response provides more valid discrimination between normal subjects and those refractory to the hormone. Thus, the current studies show that several syndromes previously described as resistant to parathyroid hormone indeed respond normally.