ENDOCRINOLOGICAL STUDIES ON PATHOGENESIS OF UROLITHIASIS

II. Cyclic AMP as an Index of Parathyroid Function in Primary Hyperparathyroidism

Abstract

The urinary excretion of adenosine 3'.5'-monophosphate (cyclic AMP) was investigated in 13 subjects with hyperparathyroidism.
1. The average cyclic AMP excretion in the hyperparathyroid patients was 9.51±7.51μ mole/g. creatinine (mean±S.D.). This value was significantly greater than that in healthy control subjects. However, when an upper normal limit of 4.76μ moles/g. creatinine (mean±S.D.) obtained for the cyclic AMP excretion in the control group was applied to the patient with hyperparathyroidism, some materials were found to have normal excretion. Such an overlap hasbeen observed in several previous studies.
2. The urinary excretion of cyclic AMP appeared to be somewhat lower in women than in men (8.58 and 11.08μ moles/g. creatinine, respectively) although this difference was not statistically significant.
3. Whereas control persons exhibited only small daily variations in cyclic AMP excretion, a marked fluctuation was observed in patients with hyperparathyroidism. This maximum value was about twenty. There was a circadian rhythem in cyclic AMP excretion in 2 of 4 patients, but not in the other 2 patients. It is supposed that these daily and diurnal variations cause an overlap of the cyclic AMP excretion value between control subjects and hyperparathyroid patients.
4. Plasma cyclic AMP was 26.95±8.50p mole/ml in the patients with hyperparathyroidism. In comparison with healthy control subjects, the plasma cyclic AMP was not raised.
5. There was a significant positive correlation of urinary cyclic AMP excretion with serum calcium and ionized calcium p<0.01 and p<0.05, respectively). In addition urinary cyclic AMP was correlated positively with urinary excretion of calcium and phosphate (p<0.01 and p<0.05, respectively). However, no correlation was obtained between the urinary cyclic AMP and serum phosphate and magnesium.
6. A positive correlation could be demonstrated between urinary cyclic AMP and the serum parathyroid hormone (p<0.01). There was no strong negative correlation between %TRP and urinary cyclic AMP.
7. Renal cyclic AMP (Urinary cyclic AMP-Plasma cyclic AMP x C.Cr) was not superior to total urinary cyclic AMP excretion in distinguishing patients with hyperparathyroidism from controls, because the value of renal cyclic AMP was negative in some patients with hyperparathyroidism.
8. Every surgically sucessful cases showed a significant fall in excretion of urinary cyclic AMP. The mean time to drop significantly was about 4 hours from the time of parathyroidectomy. A significant postopertive rise in urinary cyclic AMP was observed in 2 patients. This rise was closely associated temporally with manipulation. The decline in serum Ca and Ca⁺⁺ in six patients was slightly slower than the decline in urinary cyclic AMP. Changes in urinary phosphate excretion lagged behind urinary cyclic AMP and serum Ca changes. The mean time to the drop was 8 hours.