[Pseudohypoparathyroidism: investigations of the serum parathyroid hormone level, pte resistance and urinary camp excretion before and during vitamin d treatment (author's transl)]

Abstract

Pseudohypoparathyroidism (PHP) is a hereditary disorder with typical dysmorphic signs, oligophrenia and clinical and laboratory signs of hypoparathyroidism, which is resistant to parathyroid extract (PTE). Pseudopseudohypoparathyroidism (PPHP) is a genetically identical, partial form of PHP without hypoparathyroidism. Many hypotheses exist to explain the pathogenesis of these disorders: Albright and coworkers first demonstrated the PHP is caused by an inability of the renal tubules to respond to parathyroid hormone (PTH). Later hypotheses proposed a general defect in phosphorus transport, defects in the synthesis of PTH, the existence of antibodies to this hormone or hyperthyrocalcitonism. The possibility of measuring PTH in the peripheral serum by radioimmunoassay and improved knowledge of the role of cyclic adenosine monophosphate (cAMP) as a mediator of the action of PTH were necessary to explain the pathogenesis of PHP and PPHP. Three children suffering from PHP and two adults with PPHP were investigated as follows: measurements of PTH in the peripheral serum; assays of PTH levels during artificial hypercalcaemia; serial assays of calcium, phosphorus and PTH levels during vitamin D treatment; changes in the Ellsworth-Howard tests indicative of PTE resistance during vitamin D treatment and measurements of urinary cAMP excretion before and during vitamin D therapy. The following results were obtained: Secondary hyperparathyroidism in PHP, which could be suppressed by hypercalcaemia; normal levels of PTH in PPHP; normalization of serum calcium, phosphorus and PTE during treatment with vitamin D; abnormally low basal levels of cAMP in PHP, which could not be stimulated by PTE either before or during vitamin D treatment. The results of these investigations confirm Albright's hypothesis of endorgan resistance to PTH in PHP. This is caused by the inability of the PTH-sensitive adenylcyclase-system to mediate the action of PTH on its target cells. This is responsible for the distrubances in calcium and phosphorus metabolism and for secondary hyperparathyroidism. While this mediatorial defect seems to be total or almost total in PHP, a partial defect has to be assumed in PPHP.