pituitrin and Pseudohypoparathyroidism

Many hormones initiate their biologic actions by augmenting the intracellular concentrations of 3',5'-adenosine monophosphate (cyclic AMP). The nucleotide has been found in body fluids; its determination in plasma and urine can be performed by a rapid, simple and specific method: the cyclic AMP assay kit of the Radiochemical Centre (Amersham, England). The assay is based on the competition between unlabelled cAMP and a fixed quantity of the tritium labelled compound for binding to a bovine muscle protein which has a high specificity and affinity for cAMP. Different factors must be considered in evaluating the 24 h urinary content of the nucleotide: the renal or extrarenal origin of cAMP and the functional status of the kidneys. In basal conditions the urinary cAMP excretion is significantly correlated with creatinine excretion (n = 67; r = 0.47; p less than 0.001) thus confirming that the most part of cAMP excreted is derived from the plasma by glomerular filtration. Parathyroid hormone (PTH) stimulates adenylate cyclase predominantly in the renal cortex, whereas vasopressin (ADH) stimulated the enzyme in the medulla; thus PTH and ADH could increase the amount of cAMP in the urine from the renal source. In a case of diabetes insipidus and infusion of ADH caused a prompt rise in cAMP urinary excretion. In 5 normals an infusion of bovine synthetic parathyroid hormone caused an increased excretion of cAMP that preceded the phosphaturic response. An infusion of salmon synthetic calcitonin caused a rise in phosphate excretion and no increase in cAMP urinary content. As it concerns the two calciotopic hormones, PTH and CT, it is reasonable to assume that renal receptors are distinct. The 24 h urinary excretion of cAMP in 55 control subjects (3613 +/- 1460 D.S. n moles) was contrasted with the lower excretion in 25 elderly subjects (70-93 years: 1804 +/- 699 n moles), with the high cAMP excretion in a patient with hyperparathyroidism (that fell to normal values following removal of the parathyroid adenoma) and with the low cAMP excretion in patients with primary or surgical hypoparathyroidism. The mean 24 h cAMP excretion in patients with renal insufficiency was significantly decreased when compared to control subjects. These findings and recent reports confirm that the 24 h urinary output of cAMP may be considered an useful index of pharathyroid function in man.

Topics: Adult; Aged; Calcitonin; Circadian Rhythm; Cyclic AMP; Humans; Kidney Failure, Chronic; Parathyroid Diseases; Parathyroid Hormone; Parathyroid Neoplasms; Pseudohypoparathyroidism; Vasopressins

Topics: Animals; Cyclic AMP; Diabetes Insipidus; Glucagon; Humans; Kidney; Parathyroid Hormone; Pseudohypoparathyroidism; Rabbits; Rats; Vasopressins

Topics: Animals; Biological Transport; Creatinine; Cyclic AMP; Cyclic GMP; Escherichia coli; Extracellular Space; Glucagon; Humans; Hyperparathyroidism; Hypoparathyroidism; Kinetics; Parathyroid Hormone; Perfusion; Pseudohypoparathyroidism; Vasopressins

In six patients with pseudohypoparathyroidism (PHP) who were deficient in guanine nucleotide-binding stimulatory protein (Ns) activity, the response to endogenous arginine vasopressin (AVP) was tested during water deprivation. Hourly plasma osmolality (Posm), urinary osmolality (Uosm), and urinary AVP (UAVP) values were compared to those in normal subjects. The Uosm vs. Posm and the UAVP vs. Uosm relationships of the patients were all within the normal range. Four patients with Ns-deficient PHP were subjected to maintained water loads and infused with AVP at three different rates for 1 h each to assess their responses to exogenous AVP. Urinary volume and osmolality values from the final 30 min of each infusion rate were measured. All volume values except 1 were within 1.6 SD of normal, and all osmolality values except 1 were within 1.1 SD of normal. In conclusion, these studies indicate that these six patients with Ns-deficient PHP are not resistant to the antidiuretic (cAMP-mediated) action of endogenous or exogenous AVP, in contrast to the previously documented resistance of patients with Ns-deficient PHP to the actions of PTH, TSH, glucagon, and gonadotropins.

Topics: Adolescent; Arginine Vasopressin; Cyclic AMP; GTP-Binding Proteins; Humans; Kidney; Parathyroid Hormone; Pseudohypoparathyroidism; Thyrotropin; Thyrotropin-Releasing Hormone; Vasopressins

A case of pseudohypoparathyroidism (PHP) associated with several hormonal abnormalities in addition to parathyroid hormone (PTH) was reported. Several endocrinological examinations before and after treatment with 1 alpha-OH-D3 revealed abnormal thyroid stimulating hormone and prolactin responses to thyrotropin releasing hormone, abnormal plasma renin activity responses to renin stimulation test, and abnormal calcitonin responses to calcium infusion test. These abnormalities were not corrected when serum calcium levels returned to normal after therapy. From these results, it was suggested that in PHP resistance to multiple hormones that worked by stimulating adenylate cyclase might be the cause of these hormonal abnormalities, irrespective of serum calcium levels.

Topics: Adult; Calcium; Cyclic AMP; Hormones; Humans; Hydroxycholecalciferols; Male; Prolactin; Pseudohypoparathyroidism; Renin; Thyrotropin; Vasopressins

Topics: Adult; Chromatography, Ion Exchange; Cyclic AMP; Diabetes Insipidus; Diuresis; Female; Glucagon; Humans; Male; Middle Aged; Osmolar Concentration; Parathyroid Hormone; Pseudohypoparathyroidism; Tolbutamide; Vasopressins