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. 1977 Oct;60(4):771–783. doi: 10.1172/JCI108831

Nephrogenous Cyclic Adenosine Monophosphate as a Parathyroid Function Test

Arthur E Broadus 1,2, Jane E Mahaffey 1,2, Frederic C Bartter 1,2, Robert M Neer 1,2
PMCID: PMC372425  PMID: 197123

Abstract

Nephrogenous cyclic AMP (NcAMP), total cyclic AMP excretion (UcAMP), and plasma immunoreactive parathyroid hormone (iPTH), determined with a multivalent antiserum, were prospectively measured in 55 control subjects, 57 patients with primary hyperparathyroidism (1°HPT), and 10 patients with chronic hypoparathyroidism.

In the group with 1° HPT, NcAMP was elevated in 52 patients (91%), and similar elevations were noted in subgroups of 26 patients with mild (serum calcium ≤10.7 mg/dl) or intermittent hypercalcemia, 19 patients with mild renal insufficiency (mean glomerular filtration rate, 64 ml/min), and 10 patients with moderate renal insufficiency (mean glomerular filtration rate, 43 ml/min). Plasma iPTH was increased in 41 patients (73%).

The development of a parametric expression for UcAMP was found to be critically important in the clinical interpretation of results for total cAMP excretion. Because of renal impairment in a large number of patients, the absolute excretion rate of cAMP correlated poorly with the hyperparathyroid state. Expressed as a function of creatinine excretion, UcAMP was elevated in 81% of patients with 1° HPT, but the nonparametric nature of the expression led to a number of interpretive difficulties. The expression of cAMP excretion as a function of glomerular filtration rate was developed on the basis of the unique features of cAMP clearance in man, and this expression, which provided elevated values in 51 (89%) of the patients with 1° HPT, avoided entirely the inadequacies of alternative expressions.

Results for NcAMP and UcAMP in nonazotemic and azotemic patients with hypoparathyroidism confirmed the validity of the measurements and the expressions employed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnaud C. D., Goldsmith R. S., Bordier P. J., Sizemore G. W. Influence of immunoheterogeneity of circulating parathyroid hormone on results of radioimmunoassays of serum in man. Am J Med. 1974 Jun;56(6):785–793. doi: 10.1016/0002-9343(74)90806-7. [DOI] [PubMed] [Google Scholar]
  2. Arnaud C. D., Tsao H. S., Littledike T. Radioimmunoassay of human parathyroid hormone in serum. J Clin Invest. 1971 Jan;50(1):21–34. doi: 10.1172/JCI106476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Babka J. C., Bower R. H., Sode J. Nephrogenous cyclic AMP levels in primary hyperparathyroidism. Arch Intern Med. 1976 Oct;136(10):1140–1144. [PubMed] [Google Scholar]
  4. Ball J. H., Kaminsky N. I., Hardman J. G., Broadus A. E., Sutherland E. W., Liddle G. W. Effects of catecholamines and adrenergic-blocking agents on plasma and urinary cyclic nucleotides in man. J Clin Invest. 1972 Aug;51(8):2124–2129. doi: 10.1172/JCI107019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beck N., Singh H., Reed S. W., Davis B. B. Direct inhibitory effect of hypercalcemia on renal actions of parathyroid hormone. J Clin Invest. 1974 Mar;53(3):717–725. doi: 10.1172/JCI107610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bell N. H., Clark C. M., Jr, Avery S., Sinha T., Trygstad C. W., Allen D. O. Demonstration of a defect in the formation of adenosine 3',5'-monophosphate in vasopressin-resistant diabetes insipidus. Pediatr Res. 1974 Apr;8(4):223–230. doi: 10.1203/00006450-197404000-00002. [DOI] [PubMed] [Google Scholar]
  7. Berson S. A., Yalow R. S., Aurbach G. D., Potts J. T. IMMUNOASSAY OF BOVINE AND HUMAN PARATHYROID HORMONE. Proc Natl Acad Sci U S A. 1963 May;49(5):613–617. doi: 10.1073/pnas.49.5.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Berson S. A., Yalow R. S. Parathyroid hormone in plasma in adenomatous hyperparathyroidism, uremia, and bronchogenic carcinoma. Science. 1966 Nov 18;154(3751):907–909. doi: 10.1126/science.154.3751.907. [DOI] [PubMed] [Google Scholar]
  9. Bilezikian J. P., Doppman J. L., Powell D., Wells S. A., Heath D. A., Ketcham A. S., Monchik J., Mallette L. E., Potts J. T., Jr, Aurbach G. D. Preoperative localization of abnormal parathyroid tissue. Cumulative experience with venous sampling and arteriography. Am J Med. 1973 Oct;55(3):505–514. doi: 10.1016/0002-9343(73)90208-8. [DOI] [PubMed] [Google Scholar]
  10. Broadus A. E., Kaminsky N. I., Hardman J. G., Sutherland E. W., Liddle G. W. Kinetic parameters and renal clearances of plasma adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in man. J Clin Invest. 1970 Dec;49(12):2222–2236. doi: 10.1172/JCI106441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Broadus A. E., Kaminsky N. I., Northcutt R. C., Hardman J. G., Sutherland E. W., Liddle G. W. Effects of glucagon on adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in human plasma and urine. J Clin Invest. 1970 Dec;49(12):2237–2245. doi: 10.1172/JCI106442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Butlen D., Jard S. Renal handling of 3'-5'-cyclic AMP in the rat. The possible role of luminal 3'-5'-cyclic AMP in the tubular reabsorption of phosphate. Pflugers Arch. 1972;331(2):172–190. doi: 10.1007/BF00587260. [DOI] [PubMed] [Google Scholar]
  13. Carter D. J., Heath D. A. Proceedings. Urinary cyclic AMP excretion in thyroid disease. Clin Sci Mol Med. 1974 Nov;47(5):19P–20P. doi: 10.1042/cs047019pa. [DOI] [PubMed] [Google Scholar]
  14. Chase L. R., Aurbach G. D. Parathyroid function and the renal excretion of 3'5'-adenylic acid. Proc Natl Acad Sci U S A. 1967 Aug;58(2):518–525. doi: 10.1073/pnas.58.2.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chase L. R., Aurbach G. D. Renal adenyl cyclase: anatomically separate sites for parathyroid hormone and vasopressin. Science. 1968 Feb 2;159(3814):545–547. doi: 10.1126/science.159.3814.545. [DOI] [PubMed] [Google Scholar]
  16. Debacker M., Manderlier T., Nijs-Dewolf N., Six R., Corvilain J. Urinary cyclic AMP as an aid in the differential diagnosis of hypercalcemia. Biomedicine. 1974 Aug 10;21(8):338–341. [PubMed] [Google Scholar]
  17. Dohan P. H., Yamashita K., Larsen P. R., Davis B., Deftos L., Field J. B. Evaluation of urinary cyclic 3'5'-adenosine monophosphate excretion in the differential diagnosis of hypercalcemia. J Clin Endocrinol Metab. 1972 Dec;35(6):775–784. doi: 10.1210/jcem-35-6-775. [DOI] [PubMed] [Google Scholar]
  18. Drezner M. K., Neelon F. A., Curtis H. B., Lebovitz H. E. Renal cyclic adenosine monophosphate: an accurate index of parathyroid function. Metabolism. 1976 Oct;25(10):1103–1112. doi: 10.1016/0026-0495(76)90018-4. [DOI] [PubMed] [Google Scholar]
  19. Fichman M. P., Brooker G. Deficient renal cyclic adenosine 3'-5' monophosphate production in nephrogenic diabetes insipidus. J Clin Endocrinol Metab. 1972 Jul;35(1):35–47. doi: 10.1210/jcem-35-1-35. [DOI] [PubMed] [Google Scholar]
  20. Foley T. P., Jr, Harrison H. C., Arnaud C. D., Harrison H. E. Familial benign hypercalcemia. J Pediatr. 1972 Dec;81(6):1060–1067. doi: 10.1016/s0022-3476(72)80232-4. [DOI] [PubMed] [Google Scholar]
  21. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Guttler R. B., Shaw J. W., Otis C. L., Nicologg J. T. Epinephrine-induced alterations in urinary cyclic AMP in hyper- and hypothyroidism. J Clin Endocrinol Metab. 1975 Oct;41(4):707–711. doi: 10.1210/jcem-41-4-707. [DOI] [PubMed] [Google Scholar]
  23. Hamet P., Kuchel O., Fraysse J., Genest J. Plasma adenosine 3',5'-cyclic monophosphate in human hypertension. Can Med Assoc J. 1974 Aug 17;111(4):323–328. [PMC free article] [PubMed] [Google Scholar]
  24. Hamet P., Stouder D. A., Ginn H. E., Hardman J. G., Liddle G. W. Studies of the elevated extracellular concentration of cyclic AMP in uremic man. J Clin Invest. 1975 Aug;56(2):339–345. doi: 10.1172/JCI108098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hardman J. G., Davis J. W., Sutherland E. W. Effects of some hormonal and other factors on the excretion of guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate in rat urine. J Biol Chem. 1969 Dec 10;244(23):6354–6362. [PubMed] [Google Scholar]
  26. Kaminsky N. I., Broadus A. E., Hardman J. G., Jones D. J., Jr, Ball J. H., Sutherland E. W., Liddle G. W. Effects of parathyroid hormone on plasma and urinary adenosine 3',5'-monophosphate in man. J Clin Invest. 1970 Dec;49(12):2387–2395. doi: 10.1172/JCI106458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lin T., Kopp L. E., Tucci J. R. Urinary excretion of cyclic-3',5'-adenosine monophosphate in hyperthyroidism. J Clin Endocrinol Metab. 1973 May;36(5):1033–1036. doi: 10.1210/jcem-36-5-1033. [DOI] [PubMed] [Google Scholar]
  28. Llach F., Massry S. G., Singer F. R., Kurokawa K., Kaye J. H., Coburn J. W. Skeletal resistance to endogenous parathyroid hormone in pateints with early renal failure. A possible cause for secondary hyperparathyroidism. J Clin Endocrinol Metab. 1975 Aug;41(2):339–345. doi: 10.1210/jcem-41-2-339. [DOI] [PubMed] [Google Scholar]
  29. Mallette L. E., Bilezikian J. P., Heath D. A., Aurbach G. D. Primary hyperparathyroidism: clinical and biochemical features. Medicine (Baltimore) 1974 Mar;53(2):127–146. [PubMed] [Google Scholar]
  30. Marx S. J., Spiegel A. M., Brown E. M., Aurbach G. D. Family studies in patients with primary parathyroid hyperplasia. Am J Med. 1977 May;62(5):698–706. doi: 10.1016/0002-9343(77)90873-7. [DOI] [PubMed] [Google Scholar]
  31. Murad F. Clinical studies and applications of cyclic nucleotides. Adv Cyclic Nucleotide Res. 1973;3:355–383. [PubMed] [Google Scholar]
  32. Murad F., Pak C. Y. Urinary excretion of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate. N Engl J Med. 1972 Jun 29;286(26):1382–1387. doi: 10.1056/NEJM197206292862604. [DOI] [PubMed] [Google Scholar]
  33. Neelon F. A., Birch B. M., Drezner M., Lebovitz H. E. Urinary cyclic adenosine monophosphate as an aid in the diagnosis of hyperparathyroidism. Lancet. 1973 Mar 24;1(7804):631–633. doi: 10.1016/s0140-6736(73)92199-5. [DOI] [PubMed] [Google Scholar]
  34. ORLOFF J., HANDLER J. S. THE CELLULAR MODE OF ACTION OF ANTIDIURETIC HORMONE. Am J Med. 1964 May;36:686–697. doi: 10.1016/0002-9343(64)90180-9. [DOI] [PubMed] [Google Scholar]
  35. Pak C. Y., Kaplan R., Bone H., Townsend J., Waters O. A simple test for the diagnosis of absorptive, resorptive and renal hypercalciurias. N Engl J Med. 1975 Mar 6;292(10):497–500. doi: 10.1056/NEJM197503062921002. [DOI] [PubMed] [Google Scholar]
  36. Popovtzer M. M., Robinette J. B., McDonald K. M., Kuruvila C. K. Effect of Ca++ on renal handling of PO4 identical to: evidence for two reabsorptive mechanisms. Am J Physiol. 1975 Oct;229(4):901–906. doi: 10.1152/ajplegacy.1975.229.4.901. [DOI] [PubMed] [Google Scholar]
  37. Potts J. T., Jr, Murray T. M., Peacock M., Niall H. D., Tregear G. W., Keutmann H. T., Powell D., Deftos L. J. Parathyroid hormone: sequence, synthesis, immunoassay studies. Am J Med. 1971 May;50(5):639–649. doi: 10.1016/0002-9343(71)90119-7. [DOI] [PubMed] [Google Scholar]
  38. Reiss E., Canterbury J. M. Emerging concepts of the nature of circulating parathyroid hormones: implications for clinical research. Recent Prog Horm Res. 1974;30(0):391–429. doi: 10.1016/b978-0-12-571130-2.50014-6. [DOI] [PubMed] [Google Scholar]
  39. Schmidt-Gayk H., Röher H. D. Urinary excretion of cyclic adenosine monophosphate in the detection and diagnosis of primary hyperparathyroidism. Surg Gynecol Obstet. 1973 Sep;137(3):439–444. [PubMed] [Google Scholar]
  40. Scurry M. T., Pauk G. L. Renal tubular localization of parathyroid hormone induced urinary cyclic adenosine 3',5'-monophosphate. Acta Endocrinol (Copenh) 1974 Oct;77(2):282–286. doi: 10.1530/acta.0.0770282. [DOI] [PubMed] [Google Scholar]
  41. Segre G. V., Habener J. F., Powell D., Tregear G. W., Potts J. T. Parathyroid Hormone in Human Plasma: IMMUNOCHEMICAL CHARACTERIZATION AND BIOLOGICAL IMPLICATIONS. J Clin Invest. 1972 Dec;51(12):3163–3172. doi: 10.1172/JCI107143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Shaw J. W., Oldham S. B., Rosoff L., Bethune J. E., Fichman M. P. Urinary cyclic AMP analyzed as a function of the serum calcium and parathyroid hormone in the idfferential diagnosis of hypercalcemia. J Clin Invest. 1977 Jan;59(1):14–21. doi: 10.1172/JCI108611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Silverman R., Yalow R. S. Heterogeneity of parathyroid hormone. Clinical and physiologic implications. J Clin Invest. 1973 Aug;52(8):1958–1971. doi: 10.1172/JCI107380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sinha T. K., Miller S., Feming J., Khairi R., Edmondson J., Johnston C. C., Jr, Bell N. H. Demonstration of a diurnal variation in serum parathyroid hormone in primary and secondary hyperparathyroidism. J Clin Endocrinol Metab. 1975 Dec;41(06):1009–1013. doi: 10.1210/jcem-41-6-1009. [DOI] [PubMed] [Google Scholar]
  45. Streeto J. M. Renal cortical adenyl cyclase: effect of parathyroid hormone and calcium. Metabolism. 1969 Nov;18(11):968–973. doi: 10.1016/0026-0495(69)90037-7. [DOI] [PubMed] [Google Scholar]
  46. Taylor A. L., Davis B. B., Pawlson L. G., Josimovich J. B., Mintz D. H. Factors influencing the urinary excretion of 3',5'-adenosine monophosphate in humans. J Clin Endocrinol Metab. 1970 Mar;30(3):316–324. doi: 10.1210/jcem-30-3-316. [DOI] [PubMed] [Google Scholar]
  47. von Lilienfeld-Toal H., Hesch R. D., Hüfner M., McIntosh C. Excretion of cyclic 3',5'-adenosine monophosphate in renal insufficiency and primary hyperparathyroidism after stimulation with parathyroid hormone. Horm Metab Res. 1974 Jul;6(4):314–318. doi: 10.1055/s-0028-1093837. [DOI] [PubMed] [Google Scholar]

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