Nonautonomy of parathyroid hormone and urinary cyclic AMP in primary hyperparathyroidism

1977 ◽  
Vol 133 (4) ◽  
pp. 498-505 ◽  
Author(s):  
J.M. Monchik ◽  
H.L. Wray ◽  
M. Schaaf ◽  
J.M. Earll
1977 ◽  
Vol 53 (5) ◽  
pp. 431-438
Author(s):  
D. A. Walker ◽  
S. Joyce Davies ◽  
K. Siddle ◽  
J. S. Woodhead

1. The maximum tubular reabsorption capacity for phosphate relative to glomerular filtration rate (Tm,P/GFR) was found to range from 0·8 to 1·5 mmol/l in 32 normal fasting subjects. In 14 patients with primary hyperparathyroidism and five patients with hyperparathyroidism secondary to vitamin D deficiency or malabsorption values ranged from 0·2 to 0·8 mmol/l. 2. Plasma parathyroid hormone concentrations measured by an immunoradiometric technique ranged from <0·15 to 0·9 ng/ml in the normal subjects and from 0·5 to 10 ng/ml in the patients with hyperparathyroidism. There was no correlation, however, between plasma parathyroid hormone and Tm,P/GFR in either normal or abnormal groups. 3. Plasma parathyroid hormone was lower in 11 out of 13 patients with primary hyperparathyroidism 3 or 4 weeks after tumour removal than immediately before the operation. In all cases there was a rise in Tm,P/GFR, though not all values were normalized. 4. Changes in plasma parathyroid hormone, Tm,P/GFR and plasma and urinary cyclic AMP concentrations were measured during infusion of bovine parathyroid hormone into normal fasting subjects. Phosphate reabsorption fell markedly in response to low doses of parathyroid hormone (0·5 i.u. h−1 kg−1), higher doses (4 i.u. h−1 kg−1) producing little additional change in Tm,P/GFR despite large changes in cyclic AMP excretion. At the highest doses used (8 i.u. h−1 kg−1) apparent saturation of the renal adenylate cyclase occurred. During an infusion of hormone, 0·25 i.u. h−1 kg−1 over 3 h, a fall in Tm,P/GFR was recorded at concentrations of immunoreactive parathyroid hormone within the normal range for endogeneous hormone. At such concentrations it was not possible to detect significant changes in either plasma or urine cyclic AMP. 5. It is concluded that parathyroid hormone is an important regulator of renal phosphate handling under normal physiological conditions. Such a regulatory process has been implicated in the control of vitamin D metabolism.


1975 ◽  
Vol 228 (1) ◽  
pp. 179-183 ◽  
Author(s):  
N Beck ◽  
BB Davis

In potassium depletion, a possible alteration of the proximal tubular response to parathyroid hormone (PTH) was evaluated in rat kidney. 1) There were impairments of both phosphaturic and urinary cyclic AMP responses to PTH. The site of the impairment was further investigated by studying the PTH-dependent cycle AMP system in renal cortex. 2) There was a lesser increase of cyclic AMP concentration by PTH in potassium-depleted slices, indicating the lesser urinary cyclic AMP was due to the specific impairment of PTH-dependent cyclic AMP in the kidney. 3). The activation of adenylate cyclase by PTH was impaired , but phosphodiesterase activity was not affected by potassium depletion, indicating the impairment of cyclic AMP generation was due to inhibition of adenylate cyclase. 4) The phosphaturic response to dibutyryl cyclic AMP infusion was also significantly less in the potassium-depleted animals, indicating the step subsquent to the cyclic AMP generation is also impaired. All above results indicate that, in potassium depletion, the renal response to PTH is impaired, and the impairment is both within the step of cyclic AMP generation and after the cyclic AMP generation.


1984 ◽  
Vol 106 (2) ◽  
pp. 219-226
Author(s):  
S. Khoury ◽  
J. R. Tucci

Abstract. Studies were performed in 60 patients with proven primary hyperparathyroidism pre-operatively and in 54 of these patients post-operatively, 22 patients with permanent hypoparathyroidism and 34 normal subjects. Urinary and nephrogenous cyclic AMP excretion were increased in the hyperparathyroid patients with an overlap of values with the normal group of 10 and 9%, respectively. Values fell in all patients post-operatively, and were decreased in those with permanent hypoparathyroidism. TmPO4/GFR was decreased in the preoperative hyperparathyroid patients and rose postoperatively while it was increased in the hypoparathyroid patients with an overlap of values with the normal group of 9%. Post-operative hypocalcaemia due to bone hunger was associated with continuing normo- or hypophosphataemia and urinary cyclic AMP that exceeded 4.5 nm/dl GF while those who developed permanent hypoparathyroidism had hyperphosphataemia, increased TmPO4/GFR and urinary cyclic AMP that was less than 3.5 nM/dl G.F. Urinary and nephrogenous cyclic AMP were equally effective in characterizing patients with primary hyperparathyroidism and less effective in distinguishing patients with hypoparathyroidism from normal while TmPO4/GFR estimates were more effective in delineating the hypoparathyroid state.


1980 ◽  
Vol 239 (2) ◽  
pp. E119-E124 ◽  
Author(s):  
U. Trechsel ◽  
J. A. Eisman ◽  
J. A. Fischer ◽  
J. P. Bonjour ◽  
H. Fleisch

The increase of plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) in response to Ca restriction has been suggested to be essentially mediated by parathyroid hormone (PTH). In this study, we have assessed the influence of variations in calcium intake on plasma 1,25(OH)2D in pair-fed sham-operated (sham) and in hypocalcemic hypoparathyroid rats after thyroparathyroidectomy (TPTX). In sham rats, plasma 1,25(OH)2D increased from 189 +/- 16 to 486 +/- 41 pM when dietary calcium was inreased from 1.2% Ca to 0.2% Ca. This increase was associated with an increase in plasma PTH level. In TPTX rats, plasma 1,25(OH)2D increased from 112 +/- 9 to 332 +/- 36 pM when dietary calcium was decreased. In this case, the increase was not associated with a rise in plasma PTH level nor with an increase in urinary cyclic AMP. When TPTX rats were infused chronically with PTH (60 U/day), plasma 1,25(OH)2D was 62 +/- 9 pM when the 1.2% Ca diet was given and 281 +/- 45 pM with the 0.2% Ca diet. These reults confirm that the thyroparathyroid glands influence plasma 1,25(OH)2D but they also provide evidence for a PTH-independent response of plasma 1,25(OH)2D to Ca restriction.


1984 ◽  
Vol 66 (5) ◽  
pp. 557-559 ◽  
Author(s):  
D. G. Waller ◽  
J. D. M. Albano ◽  
J. G. B. Millar ◽  
A. Polak

1. Inhibition of adenylate cyclase has been proposed as a mechanism for hypothyroidism and nephrogenic diabetes insipidus occurring during lithium treatment, but these disorders are rarely found in the same patients. 2. We have measured plasma levels of adenosine 3′:5′-cyclic monophosphate (cyclic AMP) after an intravenous injection of glucagon in eight patients receiving long term lithium treatment and in six control subjects. Urinary cyclic AMP levels after an intravenous injection of bovine parathyroid hormone (PTH) were also measured in the patients. 3. The plasma cyclic AMP response to glucagon in the patient group was significantly lower than that of the controls. No correlation was demonstrated between the plasma cyclic AMP response after glucagon and the urinary cyclic AMP response after PTH. 4. We have previously shown that impairment of the response to PTH correlates with reduced urine concentrating ability during lithium treatment. In contrast, there was no correlation between the responses to PTH and glucagon in individual patients. These results are consistent with the hypothesis that inhibition of adenylate cyclase is an important factor in lithium-induced endocrine dysfunction.


PEDIATRICS ◽  
1972 ◽  
Vol 50 (1) ◽  
pp. 14-23 ◽  
Author(s):  
Louie G. Linarelli ◽  
John Bobik ◽  
Caroline Bobik

Since the renal action of parathyroid hormone is known to be mediated via 3',5'-adenosine monophosphate (cyclic AMP), urinary cyclic AMP studies were used to determine proximal tubular maturation. Ten formula fed full-term male infants showed a thirty- to sixtyfold increase in phosphate clearance and excretion with a three- to fourfold increase in urinary cyclic AMP comparing their first and third day 24-hour urines (2.37 ± 0.41 to 6.93 ± 0.96 Nm/mg creatinine M. ± S.E.M. first and third days respectively). Seven breast-fed infants showed cyclic AMP excretion of 3.6 ± 0.3 S.E.M. and 6.5 ± 0.3 S.E.M. on Day 1 and Day 3 respectively, showing an insignificant difference to the formula-fed infants. An additional 10 formula-fed infants 5 to 10 days of age excreted 7.0 ± 0.9 S.E.M. Nm/mg of creatinine which is comparable to the 3 to 4 days of age group. The threefold increase in cyclic AMP after the first day of life may possibly reflect increasing parathyroid renal responsiveness. One- and 3-day-old infants and adults were given a 1-hour parathyroid (PTH) infusion (5 U/kg/hr) with measurement of urinary cyclic AMP in time periods before and after the infusions. Peak increases in responses from baseline of cyclic AMP were 1.64 ± 0.34, 7.1 ± 1.5, and 36.0 ± 0.73 Nm/mg of creatinine M. ± range on first day, third day, and in adults respectively with similar relationships of increasing phosphate excretion. Thus, there is most likely a maturational renal proximal tubular responsiveness to PTH on the cellular cyclic AMP level.


1974 ◽  
Vol 77 (1_Suppl) ◽  
pp. S174 ◽  
Author(s):  
H. Schmidt-Gayk ◽  
H. Seitz ◽  
E Ritz ◽  
E. Böhme

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