0021 -972X/78/4703-0537$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society
Vol. 47, No. 3 Printed in U.S.A.
Urinary cAMP Excretion during Surgery: An Index of Successful Parathyroidectomy in Patients with Primary Hyperparathyroidism* ALLEN M. SPIEGEL, STEPHEN J. MARX, MURRAY F. BRENNAN, EDWARD M. BROWN, JAN 0. KOEHLER, AND G. D. AURBACH ^ Metabolic Diseases Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases (A.M.S., S.J.M., E.M.B., J.O.K., G.D.A.), and the Surgery Branch, National Cancer Institute (M.F.B.), . National Institutes of Health, Bethesda, Maryland 20014 ABSTRACT. Urinary phosphate (Up) and urinary cAMP (UCAMP) excretion were determined in patients undergoing neck exploration for primary hyperparathyroidism in order to evaluate these parameters as indices of successful surgery. UCAMP fell below 1.5 jumol/g creatinine in all 12 patients in whom single gland removal corrected hypercalcemia and in 0 of 3 patients in whom no parathyroid tissue was found. The mean time to drop below 1.5 was 2.0 ± 0.8 h (mean ± SD) from the time of parathyroidectomy. UCAMP fell below 1.5 in only 1 of 6 patients who had multiple enlarged parathyroid glands removed, irrespective of the outcome of surgery.
Changes in U,, excretion lagged behind UCAMI- changes, so that within the time period studied U,, fell to varying degrees in only 10 of 15 patients in whom hypercalcemia was corrected. A spurt in U,AMI> excretion, possibly reflecting parathyroid hormone release due to manipulation of a parathyroid gland, occurred in 3 patients. The results suggest that an intraoperative fall in U, AMI' below 1.5 predicts successful parathyroidectomy and that an intraoperative spurt in U.AMI- may provide a clue to the location of abnormal parathyroid tissue. (J Clin Endocrinol Metab Al: 537, 1978)
T
HE CURRENT definitive treatment for primary hyperparathyroidism is surgical resection of abnormal parathyroid tissue, but there is considerable uncertainty as to the appropriate amount of tissue to be resected. A variable that could be monitored intraoperatively to determine adequacy of parathyroid resection would be useful. Serum calcium, the ultimate criterion for successful treatment, changes too slowly to be useful in this regard. Studies suggesting that urinary phosphate (Up) (2) and urinary cAMP (UCAMP) (3-6) decline significantly after parathyroidectomy prompted us to evaluate these variables as intraoperative indices in patients undergoing neck exploration for primary hyperparathyroidism.
tients undergoing other major surgical procedures (four radical neck dissection, three laparotomy, one groin dissection, and one hemipelvectomy) who served as controls were studied. A catheter was placed in the bladder after anesthesia had been induced. As bladder catheterization is not our routine practice during neck exploration, informed consent was obtained. Patients in whom there was a contraindication to bladder catheterization {e.g. renal stones or diabetes mellitus) were excluded from study unless catheterization was indicated for other reasons. Urine present upon initial catheterization was discarded. Urine was collected at halfhourly intervals throughout the procedure and for 2-3 h in the recovery room. Samples were stored frozen until the time of assay. The surgeon noted the time of removal of parathyroid tissue whenever possible. Each urine sample was analyzed for cAMP, phosphorus, and creatinine. cAMP was measured by Patients and Methods RIA (7) and all samples from an individual patient Twenty-one patients undergoing neck explorawere measured in the same assay. The detection tion for primary hyperparathyroidism and nine pa- limit for cAMP in urine in this assay was 0.1 nmol/ml. As all UCAMP data were expressed as miReceived November 28, 1977. Address requests for reprints to: Dr. A. M. Spiegel, cromoles per g creatinine, the detection limit varied Building 10, Room 9D-20, National Institutes of Health, with the creatinine concentration of each sample Bethesda, Maryland 20014. and ranged between 0.1-1.0 jumol/g creatinine. The * This work was presented in part at the National normal range for UCAMP in 20 normal volunteers Meeting of the AFCR, May 1977 (see Ref. 1). 537
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 20 November 2015. at 03:30 For personal use only. No other uses without permission. . All rights reserved.
SPIEGEL ET AL.
538
was 1.49-3.60 /zmol/g creatinine (4). Phosphorus was measured by the method of Fiske and Subbarow (8) and creatinine was measured by the method of Folin and Wu (9), as modified for the autoanalyzer. The 21 patients with primary hyperparathyroidism were divided into four groups based upon the results of surgery. Group I consisted of 12 patients in whom single gland removal resulted in cure of hypercalcemia. Four of these 12 developed persistent hypocalcemia postoperatively, requiring vitamin D therapy. (All 4 had undergone prior surgery with removal of several normal parathyroid glands.) Group II consisted of 3 patients in whom no parathyroid tissue could be found and who remained hypercalcemic postoperatively. All 3 had undergone at least one prior neck exploration and were presumed to have persistent primary hyperparathyroidism based on elevated peripheral parathyroid hormone (PTH) and no evidence of malignancy as well as a step-up of PTH in one or more small neck vein samples compared with the peripheral PTH concentration. In group III, there were 3 patients from whom 2 (2 cases) or 3.5 (1 case) enlarged parathyroid glands were removed and who were rendered normocalcemic. Two of these 3 had a family history of hyperparathyroidism. Group IV consisted of 3 patients from whom one or more enlarged parathyroid glands were removed and in whom serum calcium declined postoperatively but returned within 1 week to elevated values. All 3 had a family history of hyperparathyroidism.
Results
JCE&M Vo!47
1978 No 3
the thymic specimen on subsequent histological examination. Patient 11 showed significant renal impairment (creatinine clearance,
Vol. 47, No. 3 Printed in U.S.A.
Urinary cAMP Excretion during Surgery: An Index of Successful Parathyroidectomy in Patients with Primary Hyperparathyroidism* ALLEN M. SPIEGEL, STEPHEN J. MARX, MURRAY F. BRENNAN, EDWARD M. BROWN, JAN 0. KOEHLER, AND G. D. AURBACH ^ Metabolic Diseases Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases (A.M.S., S.J.M., E.M.B., J.O.K., G.D.A.), and the Surgery Branch, National Cancer Institute (M.F.B.), . National Institutes of Health, Bethesda, Maryland 20014 ABSTRACT. Urinary phosphate (Up) and urinary cAMP (UCAMP) excretion were determined in patients undergoing neck exploration for primary hyperparathyroidism in order to evaluate these parameters as indices of successful surgery. UCAMP fell below 1.5 jumol/g creatinine in all 12 patients in whom single gland removal corrected hypercalcemia and in 0 of 3 patients in whom no parathyroid tissue was found. The mean time to drop below 1.5 was 2.0 ± 0.8 h (mean ± SD) from the time of parathyroidectomy. UCAMP fell below 1.5 in only 1 of 6 patients who had multiple enlarged parathyroid glands removed, irrespective of the outcome of surgery.
Changes in U,, excretion lagged behind UCAMI- changes, so that within the time period studied U,, fell to varying degrees in only 10 of 15 patients in whom hypercalcemia was corrected. A spurt in U,AMI> excretion, possibly reflecting parathyroid hormone release due to manipulation of a parathyroid gland, occurred in 3 patients. The results suggest that an intraoperative fall in U, AMI' below 1.5 predicts successful parathyroidectomy and that an intraoperative spurt in U.AMI- may provide a clue to the location of abnormal parathyroid tissue. (J Clin Endocrinol Metab Al: 537, 1978)
T
HE CURRENT definitive treatment for primary hyperparathyroidism is surgical resection of abnormal parathyroid tissue, but there is considerable uncertainty as to the appropriate amount of tissue to be resected. A variable that could be monitored intraoperatively to determine adequacy of parathyroid resection would be useful. Serum calcium, the ultimate criterion for successful treatment, changes too slowly to be useful in this regard. Studies suggesting that urinary phosphate (Up) (2) and urinary cAMP (UCAMP) (3-6) decline significantly after parathyroidectomy prompted us to evaluate these variables as intraoperative indices in patients undergoing neck exploration for primary hyperparathyroidism.
tients undergoing other major surgical procedures (four radical neck dissection, three laparotomy, one groin dissection, and one hemipelvectomy) who served as controls were studied. A catheter was placed in the bladder after anesthesia had been induced. As bladder catheterization is not our routine practice during neck exploration, informed consent was obtained. Patients in whom there was a contraindication to bladder catheterization {e.g. renal stones or diabetes mellitus) were excluded from study unless catheterization was indicated for other reasons. Urine present upon initial catheterization was discarded. Urine was collected at halfhourly intervals throughout the procedure and for 2-3 h in the recovery room. Samples were stored frozen until the time of assay. The surgeon noted the time of removal of parathyroid tissue whenever possible. Each urine sample was analyzed for cAMP, phosphorus, and creatinine. cAMP was measured by Patients and Methods RIA (7) and all samples from an individual patient Twenty-one patients undergoing neck explorawere measured in the same assay. The detection tion for primary hyperparathyroidism and nine pa- limit for cAMP in urine in this assay was 0.1 nmol/ml. As all UCAMP data were expressed as miReceived November 28, 1977. Address requests for reprints to: Dr. A. M. Spiegel, cromoles per g creatinine, the detection limit varied Building 10, Room 9D-20, National Institutes of Health, with the creatinine concentration of each sample Bethesda, Maryland 20014. and ranged between 0.1-1.0 jumol/g creatinine. The * This work was presented in part at the National normal range for UCAMP in 20 normal volunteers Meeting of the AFCR, May 1977 (see Ref. 1). 537
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 20 November 2015. at 03:30 For personal use only. No other uses without permission. . All rights reserved.
SPIEGEL ET AL.
538
was 1.49-3.60 /zmol/g creatinine (4). Phosphorus was measured by the method of Fiske and Subbarow (8) and creatinine was measured by the method of Folin and Wu (9), as modified for the autoanalyzer. The 21 patients with primary hyperparathyroidism were divided into four groups based upon the results of surgery. Group I consisted of 12 patients in whom single gland removal resulted in cure of hypercalcemia. Four of these 12 developed persistent hypocalcemia postoperatively, requiring vitamin D therapy. (All 4 had undergone prior surgery with removal of several normal parathyroid glands.) Group II consisted of 3 patients in whom no parathyroid tissue could be found and who remained hypercalcemic postoperatively. All 3 had undergone at least one prior neck exploration and were presumed to have persistent primary hyperparathyroidism based on elevated peripheral parathyroid hormone (PTH) and no evidence of malignancy as well as a step-up of PTH in one or more small neck vein samples compared with the peripheral PTH concentration. In group III, there were 3 patients from whom 2 (2 cases) or 3.5 (1 case) enlarged parathyroid glands were removed and who were rendered normocalcemic. Two of these 3 had a family history of hyperparathyroidism. Group IV consisted of 3 patients from whom one or more enlarged parathyroid glands were removed and in whom serum calcium declined postoperatively but returned within 1 week to elevated values. All 3 had a family history of hyperparathyroidism.
Results
JCE&M Vo!47
1978 No 3
the thymic specimen on subsequent histological examination. Patient 11 showed significant renal impairment (creatinine clearance,
