Nephrogenous Cyclic Adenosine Monophosphate as a Parathyroid Function Test

Broadus, Arthur E.; Mahaffey, J E; Bartter, Frederic C.; Neer, Robert M.

doi:10.1172/jci108831

Cited by 295 publications

(135 citation statements)

References 45 publications

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“…An increase in adenylate cyclase activity and accumulation of intracellular cAMP after PTH administration have been demonstrated (16,26). The intracellular accumulation of cAMP and subsequent leakage from the renal tubular cells is considered to be an explanation for the increase in urinary excretion of CAMP, and thus, the latter change has been used as an indicator of the renal responsiveness to PTH (3,8,22,32). Our study confirms the earlier reports of a phosphaturic response to CT in both humans (1, 2, 7, 19) and rats (24).…”

Section: Resultssupporting

confidence: 88%

“…Studies have shown increased renal formation and urinary excretion of cAMP in response to PTH (1 I, 12). This change in the urinary excretion of cAMP is considered a qualitative indicator of the effect of PTH on the kidney (8,22,32). Some studies also have shown an increase in the formation of cAMP in the kidney after CT administration (20,27).…”

Section: Speculationmentioning

confidence: 99%

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Urinary Excretion of Cyclic Nucleotides and Phosphate in Response to Parathyroid Hormone and Calcitonin in Man

et al. 1981

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SummaryThe response to parathyroid hormone (PTH) and calcitonin (CT) was studied in eight children with various bone diseases by determining the serum calcium (Ca) and phosphate (P) concentration, urinary phosphate excretion rate, renal phosphate clearance, the percentage of filtered phosphate reabsorbed by the renal tubule (%TRP), creatinine clearance (Ccr), urinary cyclic adenosine 3',5' monophosphate excretion rate (UcA~pV), and urinary cyclic guanosine 3',5' monophosphate excretion rate (Ucc~pV). Administration of PTH caused no significant change in serum Ca and P values, whereas CT produced a decrease ih Ca (A Ca, -1.4 + 0.1 mg/100 ml) and P (AP; -1.1 + 0.1 mg/100 ml). There was an increase in U c~~p V ( A U r~~p V ; 437 74 nmoles/min/100 ml Ccr) without any significant change in UcCMpV after administration of PTH. Phosphaturia was produced by both PTH (A TRP, -18 k 3%) and CT (ATRP, -13 -t 2%). However, CT did not elicit any increase in either U c~~p V or U c~~p V . SpeculationParathyroid hormone (PTH) and calcitonin (CT) induce phosphaturia of a similar magnitude whereas PTH alone increased the urinary excretion of cyclic adenosine 3',5' monosphosphate (CAMP). The phosphaturia induced by CT may not be mediated by a similar mechanism involving the adenylate cyclase-CAMP system as demonstrated for PTH.Parathyroid hormone (PTH) and calcitonin (CT) have opposing effects on bone resorption; PTH induces hypercalcemia by stimulating bone resorption whereas CT induces hypocalcemia by inhibiting bone resorption. Despite their opposing effects on bone, they both act on the kidney to produce phosphaturia. The actions of PTH and CT on both bone and kidney are presumably mediated through the adenylate cyclase cyclic adenosine 3',5'-monophosphate (CAMP) system. Studies have shown increased renal formation and urinary excretion of cAMP in response to PTH (1 I, 12). This change in the urinary excretion of cAMP is considered a qualitative indicator of the effect of PTH on the kidney (8,22,32). Some studies also have shown an increase in the formation of cAMP in the kidney after CT administration (20,27). However, few studies have investigated urinary excretion of cAMP after CT administration, and those that are available, report conflicting results. No increase in urinary excretion of cAMP was reported after CT administration in parathyroiaectomized rats, dogs (I I), and in one patient with hypoparathyroidism (28), whereas an increase in cAMP was reported in hamsters (23) and parathyroidectomized rats (24). Some studies in man (1, 2, 28) have shown an increase in urinary cAMP in response to salmon or porcine CT, but the magnitude of rise was insignificant when compared to the rise after PTH. Therefore, to assess the relationship of urinary cAMP excretion and the phosphaturic response to CT in man, we have studied the effect of synthetic human CT on patients with various bone diseases, all of whom had normal phosphaturic and cAMPuric responses to PTH. In view of the possible role of cyclic guanosine 3',Sf-monophosphate (c...

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Section: Resultssupporting

confidence: 88%

Section: Speculationmentioning

confidence: 99%

Urinary Excretion of Cyclic Nucleotides and Phosphate in Response to Parathyroid Hormone and Calcitonin in Man

et al. 1981

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“…We determined NcAMP as an index ofthe biological activity of PTH on the kidney (21,22). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Acute metabolic acidosis enhances circulating parathyroid hormone, which contributes to the renal response against acidosis in the rat.

Bichara¹,

Mercier²,

Borensztein³

et al. 1990

J. Clin. Invest.

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Acute PTH administration enhances final urine acidification in the rat. HCl was infused during 3 h in rats to determine the parathyroid and renal responses to acute metabolic acidosis. Serum immunoreactive PTH (iPTH) concentration significantly increased and nephrogenous adenosine 3',5'-cyclic monophosphate tended to increase during HCO loading in intact and adrenalectomized (ADX) rats despite significant increments in plasma ionized calcium. Strong linear relationships existed between serum iPTH concentration and arterial bicarbonate or proton concentration (P < 0.0001). Serum iPTH concentration and NcAMP remained stable in intact time-control rats and decreased in CaCl2-infused, nonacidotic animals. Urinary acidification was markedly reduced in parathyroidectomized (PTX) as compared with intact rats during both basal and acidosis states; human PTH-(1-34) infusion in PTX rats restored in a dose-dependent manner the ability of the kidney to acidify the urine and excrete net acid. Acidosis-induced increase in urinary net acid excretion was observed in intact, PTX, and ADX, but not in ADX-thyroparathyroidectomized rats.We conclude that (a) acute metabolic acidosis enhances circulating PTH activity, and (b) PTH markedly contributes to the renal response against acute metabolic acidosis by enhancing urinary acidification. (J. Clin. Invest. 1990. 86:430-443.)

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“…Calcium, phosphorus, magnesium, and electrolytes in serum and PTH in plasma were determined in samples obtained after overnight fast. cAMP was analyzed by radioimmunoassay in at least four sequential 12-h urine collections and adjusted for glomerular filtration rate as follows (17): (UCAMP X SCr)/U,r, where UC,AMP is the urinary concentration of cAMP, and Scr and U,. are serum and urine concentrations of creatinine, respectively.…”

Section: Study Protocolmentioning

confidence: 99%

Urinary calcium excretion in familial hypocalciuric hypercalcemia. Persistence of relative hypocalciuria after induction of hypoparathyroidism

et al. 1983

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A B S T R A C T Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant trait comprising hypercalcemia, hypophosphatemia, parathyroid hyperplasia, and unusually low renal clearance of calcium. We evaluated the role of parathyroid hormone in the relative hypocalciuria of FHH and characterized the renal transport of calcium in this disorder using three previously hypercalcemic FHH patients with surgical hypoparathyroidism and three controls with surgical hypoparathyroidism. Intravenous infusion of calcium chloride in two patients with FHH and in three controls increased serum calcium from a mean basal of 5.0 to a mean peak of 6.8 meq/liter in two FHH patients and from 4.2 to 5.7 in three control subjects. Urinary calcium in a third FHH patient was studied without calcium infusion during recovery from hypercalcemia of vitamin D intoxication. At all serum concentrations of calcium, calcium clearance was lower in FHH than in controls; at base-line serum calcium, the ratio of calcium clearance to inulin clearance (CCa/CIN) in FHH subjects was 32% of that in controls and decreased to 19% during hypercalcemia. Calcium infusion increased the ratio of sodium clearance to inulin clearance in controls from a base line of 0.020 to 0.053 at peak concentrations of calcium in serum, but did not affect this parameter in FHH (0.017 at baseline serum calcium vs. 0.019 at peak). When calcium infusion studies were performed (in two patients with FHH and one control) during administration of acetazolamide, a drug whose principal renal action causes inhibition of proximal transport of solute, CCa/CIN in the patients with FHH was 29 and 7% of that of the control at base-line and peak serum calcium, respectively. In contrast, ethacrynic acid, a diuretic that acts in the ascending limb of the loop of Henle, increased CCa/CIN more in the FHH patients than in the control subject; CCa/CIN was 65% at baseline and 47% at peak serum calcium, compared with that of the control subject. The greater calciuric response to ethacrynic acid than to acetazolamide or calcium infusion alone in FHH indicates that a major renal locus of abnormal calcium transport in this disorder may be the ascending limb of the loop of Henle.Decreased clearance of calcium in patients with FHH and hypoparathyroidism when compared with hypoparathyroid controls indicates that relative hypocalciuria in FHH is not dependent on hyperparathyroidism. Since the parathyroid glands in FHH are not appropriately suppressed by calcium, this implies that FHH represents a disorder of abnormal transport of, and/or response to, extracellular calcium in at least two organs, parathyroid gland and kidney.

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Nephrogenous Cyclic Adenosine Monophosphate as a Parathyroid Function Test

Cited by 295 publications

References 45 publications

Urinary Excretion of Cyclic Nucleotides and Phosphate in Response to Parathyroid Hormone and Calcitonin in Man

Urinary Excretion of Cyclic Nucleotides and Phosphate in Response to Parathyroid Hormone and Calcitonin in Man

Acute metabolic acidosis enhances circulating parathyroid hormone, which contributes to the renal response against acidosis in the rat.

Urinary calcium excretion in familial hypocalciuric hypercalcemia. Persistence of relative hypocalciuria after induction of hypoparathyroidism

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