Factors influencing the urinary excretion of 3',5'-adenosine monophosphate in humans.
01 Mar 1970-The Journal of Clinical Endocrinology and Metabolism (The Endocrine Society)-Vol. 30, Iss: 3, pp 316-324
TL;DR: An effect of steroid and/or pituitary or placental hormones on the urinary excretion of cyclic AMP was suggested from observing a midcycle peak in nucleotide excretion during ovulatory menstrual cycles, and a progressive increase in urinaryexcretion of the nucleotide during pregnan...
Abstract: The 24-hr urinary excretion of cyclic 3′5′-adenosine monophosphate (cyclic AMP) in 21 control subjects (3544 ± 175 nmoles, mean ±sem) was contrasted with the cyclic AMP excretion in patients with hyperparathyroidism (5719 ± 1200 nmoles, p <.01), hypoparathyroidism (1943 ±312 nmoles, p <.001), renal disease (596 ±208 nmoles, p <.001), and women during the menstrual cycle and pregnancy. An effect of parathyroid hormone on the urinary excretion of cyclic AMP was implied from: 1) the increased urinary excretion of the nucleotide in patients with hyperparathyroidism and the low excretion in patients with hypoparathyroidism, and 2) the acute reduction to normal in urine cyclic AMP following removal of a parathyroid adenoma. An effect of steroid and/or pituitary or placental hormones on the urinary excretion of cyclic AMP was suggested from observing a midcycle peak in nucleotide excretion during ovulatory menstrual cycles, and a progressive increase in urinary excretion of the nucleotide during pregnan...
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TL;DR: The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hyperCalciuria.
Abstract: The causes for the hypercalciuria and diagnostic criteria for the various forms of hypercalciuria were sought in 56 patients with hypercalcemia or nephrolithiasis (Ca stones), by a careful assessment of parathyroid function and calcium metabolism. A study protocol for the evaluation of hypercalciuria, based on a constant liquid synthetic diet, was developed. In 26 cases of primary hyperparathyroidism, characteristic features were: hypercalcemia, high urinary cyclic AMP (cAMP, 8.58+/-3.63 SD mumol/g creatinine; normal, 4.02+/-0.70 mumol/g creatinine), high immunoreactive serum parathyroid hormone (PTH), hypercalciuria, the urinary Ca exceeding absorbed Ca from intestinal tract (Ca(A)), high fasting urinary Ca (0.2 mg/mg creatinine or greater), and low bone density by (125)I photon absorption. The results suggest that hypercalciuria is partly secondary to an excessive skeletal resorption (resorptive hypercalciuria). The 22 cases with renal stones had normocalcemia, hypercalciuria, intestinal hyperabsorption of calcium, normal or low serum PTH and urinary cAMP, normal fasting urinary Ca, and normal bone density. Since their Ca(A) exceeded urinary Ca, the hypercalciuria probably resulted from an intestinal hyperabsorption of Ca (absorptive hypercalciuria). The primacy of intestinal Ca hyperabsorption was confirmed by responses to Ca load and deprivation under a metabolic dietary regimen. During a Ca load of 1,700 mg/day, there was an exaggerated increase in the renal excretion of Ca and a suppression of cAMP excretion. The urinary Ca of 453+/-154 SD mg/day was significantly higher than the control group's 211+/-42 mg/day. The urinary cAMP of 2.26+/-0.56 mumol/g creatinine was significantly lower than in the control group. In contrast, when the intestinal absorption of calcium was limited by cellulose phosphate, the hypercalciuria was corrected and the suppressed renal excretion of cAMP returned towards normal. Two cases with renal stones had normocalcemia, hypercalciuria, and high urinary cAMP or serum PTH. Since Ca(A) was less than urinary Ca, the hypercalciuria may have been secondary to an impaired renal tubular reabsorption of Ca (renal hypercalciuria). Six cases with renal stones had normal values of serum Ca, urinary Ca, urinary cAMP, and serum PTH (normocalciuric nephrolithiasis). Their Ca(A) exceeded urinary Ca, and fasting urinary Ca and bone density were normal. The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hypercalciuria.
465 citations
TL;DR: The development of a parametric expression for UcAMP was found to be critically important in the clinical interpretation of results for total cAMP excretion, and this expression provided elevated values in 51 (89%) of the patients with 1 degrees HPT, avoided entirely the inadequacies of alternative expressions.
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 degrees HPT), and 10 patients with chronic hypoparathyroidism. In the group with 1 degrees HPT, NcAMP was elevated in 52 patients (91%), and similar elevations were noted in subgroups of 26 patients with mild (serum calcium
278 citations
TL;DR: The findings in this study support the thesis that magnesium depletion causes impaired synthesis or secretion of parathyroid hormone and account for the hypocalcemia observed in the hypomagnesemic state.
Abstract: Hypocalcemia is a frequent feature of hypomagnesemia in man and several other species. To elucidate the cause of this hypocalcemia, we have studied a child with primary hypomagnesemia and secondary hypocalcemia during magnesium supplementation when he was normomagnesemic and normocalcemic and after magnesium restriction for 16 days when he quickly became hypomagnesemic (0.5 meq/liter) and hypocalcemic (3.4 meq/liter) and had positive Chvostek's and Trousseau's signs. Whether in the normomagnesemic or hypomagnesemic state, intravenous bovine parathyroid extract (PTE) 8 U. S. P. U/kg promptly caused transient increases in the urinary phosphate excretion, renal phosphate clearance and cyclic AMP excretion. The magnitudes of these responses were similar in the two states, and similar to those observed in a hypoparathyroid patient. When the patient was hypomagnesemic and hypocalcemic, intramuscular PTE, 8 U/kg at 8-h intervals for four doses promptly caused hypercalcemia. The findings indicate that the end-organs were responsive to parathyroid hormone. The concentrations of serum parathyroid hormone (PTH) were normal in the normomagnesemic state ranging from 0.15 ng/ml to 0.40 ng/ml. Serum PTH did not increase in the hypomagnesemic state in spite of hypocalcemia. Indeed, PTH became unmeasurable in four consecutive samples at the end of the period of magnesium restriction. The concentrations of serum calcitonin remained unmeasurable (< 0.10 ng/ml) throughout the study, implying that excess calcitonin was not the cause of hypocalcemia in magnesium depletion. The findings in this study support our thesis that magnesium depletion causes impaired synthesis or secretion of parathyroid hormone. This impairment would account for the hypocalcemia observed in the hypomagnesemic state.
202 citations
TL;DR: The diurnal pattern of excretion of both nucleotides was not altered by either exercise or altered parathyroid function, and whereas calcitonin increased cyclic AMP excretion in a patient with Paget's disease, no effects on either nucleotide were observed in a parathyroectomized patient.
Abstract: The urinary excretion of cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) was examined in normal controls, 16 patients with hyperparathyroidism and six with hypoparathyroidism. The diurnal pattern of excretion of both nucleotides was not altered by either exercise or altered parathyroid function. Whereas calcitonin increased cyclic AMP excretion in a patient with Paget's disease, no effects on either nucleotide were observed in a parathyroidectomized patient. Calcium infusions produced variable effects on cyclic AMP and cyclic GMP excretion. Cyclic AMP excretion was elevated in 14 of 15 patients with hyperparathyroidism, and normal renal function; it decreased in all patients after removal of hyperplastic or adenomatous parathyroid glands. Three patients with carcinoma and hypercalcemia excreted normal amounts of cyclic AMP, those with hyperparathyroidism excreted increased amounts, and low levels were excreted by six hypoparathyroid patients and by one with hypercalc...
111 citations
TL;DR: The second messenger function of cyclic AMP is discussed in detail elsewhere in this volume, and appears to serve as an extracellular messenger or chemotactic agent in one or more species of cellular slime mold, mediating cell aggregation and perhaps aiding in food seeking.
Abstract: The actions of a wide variety of hormones are mediated by alterations in the intracellular levels of cyclic AMP in the target tissues responding to the hormones.?\" The second messenger function of cyclic AMP is discussed in detail elsewhere in this volume. The biological role of cyclic GMP, the other naturally occurring cyclic nucleotide, has not yet been determined. In recent years, considerable interest has developed in studying the levels of cyclic AMP and cyclic GMP in extracellular fluids. The increasing interest in this field has been largely for the following reasons: 1. Occurrence. Cyclic AMP was first identified extracellularly in human urine in 1962.20 Cyclic GMP was found in urine a year later, representing the initial discovery of this compound in nature.4 As discussed later, the presence of one or both nucleotides has now been observed in a large number of extracellular fluids (biologic fluids and secretions, incubation and perfusion media, culture broths, et cetera) . 2. Relation to intracellular levels. Changes in extracellular levels of the cyclic nucleotides have been shown to reflect alterations in intracellular levels of the compounds in response to a variety of endocrinologic and other manipulations (see below), and this finding has been found useful in in vitro as well as in in vivo studies. 3 . Regulation of intracellular concentration. The translocation of cyclic AMP into the extracellular space might serve as a means of terminating its metabolic activity. It is probable that the extrusion of cyclic AMP by several strains of E. coli functions in this regard; 5 5 . 64 evidence on this point in other systems is lacking. 4. Extracellular function. Cyclic AMP appears to serve as an extracellular messenger or chemotactic agent in one or more species of cellular slime mold, mediating cell aggregation and perhaps aiding in food seeking.6, 48. 4*--1O However in no other system studied has a physiological role for extracellular cyclic nucleotides been identified, and the very large quantities of extracellular cyclic AMP required to produce physiological responses in intact mammalian tissues would make such a role appear unlikely in higher organisms.
107 citations