Reversible Resistance to the Renal Action of Parathyroid Hormone in Human Vitamin D Deficiency

Lewin, I. G.; Papapoulos, Socrates E.; Hendy, Geoffrey N.; Tomlinson, Stephen; O’Riordan, J. L. H.

doi:10.1042/cs0620381

Cited by 39 publications

(18 citation statements)

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“…Taken these together, it is possible that urinary cAMP response to exogenous PTH could diminish to the extent of PHP type I in some patients with severe vitamin D deficiency with markedly elevated endogenous PTH levels, as in our case 1. As suggested by others, chronic elevation in plasma PTH might induce desensitization of PTH receptors and lead to the development of hormone resistance [19,[31][32][33]. tions were higher in strict vegetarians compared with controls [36].…”

Section: Discussionmentioning

confidence: 80%

“…He speculated that low fish normalities seen in patients with vitamin D deficiency are reversible. Lewin et al reported that the incremental responses of urinary cAMP to exogenous PTH were subnormal in most patients with vitamin D deficiency and the magnitude of responses became much greater after vitamin D repletion [19]. Kruse et al by measuring baseline urinary cAMP also suggested that the renal cAMP production in response to endogenous PTH was decreased in vitamin D deficient states [30].…”

Section: Discussionmentioning

confidence: 98%

“…It is generally accepted that patients with vitamin D deficiency occasionally show biochemical findings resembling PHP type II [12][13][14][15][16][17][18][19]. We conducted extensive literature survey and found several case studies written in English and reporting both the data of serum 25(OH)D levels and the results of PTH infusion test (Table 1) [12-15, 18, 19].…”

Section: Discussionmentioning

confidence: 99%

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Vitamin D deficiency in two young adults with biochemical findings resembling pseudohypoparathyroidism type I and type II

et al. 2010

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abstract.We report two patients with vitamin D deficiency due to unbalanced diet. The patients initially presented with severe hypocalcemia, normophosphatemia and markedly elevated serum PTH levels. Although nutritional vitamin D deficiency was suspected from their history of gastrointestinal problems and dietary restriction, we conducted EllsworthHoward test to exclude the possibility of pseudohypoparathyroidism (PHP). Both patients showed no incremental response of urinary phosphate excretion. However, the urinary cAMP response to exogenous PTH was different between the two. Case 1 showed a blunted response (5-fold and 1.54 µmol/h increase) and case 2 showed a normal response (39-fold and 3.04 µmol/h increase). According to the criteria of Ellsworth-Howard test, the data of case 1 was compatible with PHP type I, and of case 2 with PHP type II. The final diagnosis of vitamin D deficiency was established in both patients based on very low serum 25-hydroxyvitamin D levels (less than 5 ng/mL) and the effect of treatment. After calcium supplementation with or without vitamin D, their biochemical abnormalities disappeared. They maintained normocalcemia without medication after correction of their unbalanced diet. The present study indicated that patients with vitamin D deficiency occasionally showed biochemical findings suggestive of PHP and that such patients could exhibit not only PHP type II pattern of response to exogenous PTH but also of type I pattern. Thus our clinical observation suggests the complexity of PTH resistance in vitamin D deficiency and underscores the importance of diet to prevent the disorder.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Vitamin D deficiency in two young adults with biochemical findings resembling pseudohypoparathyroidism type I and type II

et al. 2010

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“…The majority of these reports (5,6,9,10,(31)(32)(33) Resistance to PTH has been provoked in rats by hypercalcemia (36), hypermagnesemia (37), and hypokalemia (38), and in both rats and chicks by hypocalcemia associated with either vitamin D deficiency or a calcium-deficient diet (27,39). Humans with chronic renal failure (5, 9), vitamin D deficiency (32), and some patients with primary hyperparathyroidism (6)(7)(8)(9) are also refractory to stimulation by exogenous PTH.…”

Section: Resultsmentioning

confidence: 99%

Rapid development of renal resistance to low doses of synthetic bovine parathyroid hormone fragment 1-34. Dissociation of urinary cyclic adenosine monophosphate, phosphaturic, and calciuric responses.

Law¹,

Heath²

1983

J. Clin. Invest.

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A B S T R A C T The designing of parathyroid hormone (PTH)-renal dose-response studies in human beings is complicated by the possibility of rapid homologous receptor down-regulation, a phenomenon that is clearly shown to occur in vitro. Large amounts of PTH given to human subjects as serial injections or prolonged infusions cause decreased urinary 3',5'-cyclic adenosine monophosphate (cAMP) responses to subsequent PTH doses, but it is uncertain whether lower doses given over shorter periods similarly cause renal tachyphylaxis to PTH action. Thus, in seven water-loaded adults, we infused in ascending order 10, 30, 75, 150, and 300 U of synthetic bovine PTH fragment (bPTH 1-34) per 70 kg body wt over 15 min on widely separated days ("separate day administration"). On another day, each subject received all five 15-min doses in ascending order at 75-min intervals ("single day administration"). Urine collection intervals were control, 0-30 min (including the PTH infusion), and 30-60 min. Peak nephrogenous cAMP (NcAMP, nmol/100 ml glomerular filtrate) response was linearly related to the dose of PTH (separate day study, r = 0.94, P < 0.001; single day study, r = 0.88, P < 0.001). However, the slope of NcAMP responses plotted against PTH dose for the single day study was only 36% of that derived from separate day administration of the same PTH doses (P < 0.001). After only 40 U (10 + 30) of bPTH 1-34/70 kg, the NcAMP response to 75 U was reduced 44%, and the effect of 300 U/70 kg, when given as the last of the sequential single day infusions, was 64% less than the response to 300 U of bPTH 1-34 given alone (P < 0.001). The phosphaturic response (fractional excretion of phosphorus, FEP [percent]) was also linearly related to bPTH 1-34 dose, but combined administration of the PTH infusions on one day increased FEP at each dose identically with the effects of separate day administration. A transient, dose-related, early hypercalciuric response to bPTH 1-34 also occurred, and was of equal magnitude in both protocols. These studies demonstrate that significant blunting of the NcAMP response to bPTH 1-34 occurs rapidly and follows brief exposure to relatively low doses of hormone. In contrast, there is no effect of recent PTH administration on the phosphaturic and early hypercalciuric actions of bPTH 1-34. This seeming dissociation of PTH effects makes unclear the physiologic importance of PTH-induced cAMP tachyphylaxis in the regulation of final PTH actions. In any case, studies of NcAMP responses in which the occurrence of tachyphylaxis would be undesirable should be designed to avoid prolonged or closely spaced administrations of the hormone. INTRODUCTION The acute administration of exogenous parathyroid hormone (PTH)' causes increased urinary excretion of

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“…Unlike PHP type 1, the clinical mechanisms of abnormal PTH signaling in PHP type 2 remain obscure. Furthermore, it is questionable if PHP type 2 should stand as a disease entity because the results of the Ellsworth-Howard test in some patients with vitamin D deficiency and/or renal tubular damage resemble those of PHP type 2 19,[22][23][24][25] . In our patient, the clinical findings and initial laboratory results suggested PHP type 2 or PHP type 1b.…”

Section: Adult Onset Pseudohypoparathyroidismmentioning

confidence: 99%

A case of Adult onset Pseudohypoparathyroidism yet to be resolved: “No money no genetics”

Koutroumpi¹,

Stratigou²,

Skodra³

et al. 2017

JRPMS

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Reversible Resistance to the Renal Action of Parathyroid Hormone in Human Vitamin D Deficiency

Cited by 39 publications

References 0 publications

Vitamin D deficiency in two young adults with biochemical findings resembling pseudohypoparathyroidism type I and type II

Vitamin D deficiency in two young adults with biochemical findings resembling pseudohypoparathyroidism type I and type II

Rapid development of renal resistance to low doses of synthetic bovine parathyroid hormone fragment 1-34. Dissociation of urinary cyclic adenosine monophosphate, phosphaturic, and calciuric responses.

A case of Adult onset Pseudohypoparathyroidism yet to be resolved: “No money no genetics”

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