Hypercalcemia due to constitutive activity of the parathyroid hormone (PTH)/PTH-related peptide receptor

Comparison with primary hyperparathyroidism

A. M. Parfitt, E. Schipani, D. Sudhaker Rao, Warren Kupin, Z. H. Han, H. Jüppner

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

In Jansen's disease (JD), the hypercalcemia found in about half the cases is the result of a mutant, constitutively overactive, form of the PTH/PTHrP receptor, which in these cases also causes the skeletal dysplasia. The subject of the present report was first seen in 1956 and is still under treatment at the same medical center. We report the clinical course and a detailed study of calcium and bone metabolism carried out in 1976 and compare the results with those of six typical patients with mild primary hyperparathyroidism in whom exactly the same studies were carried out. In the patient with JD, the hypercalcemia was of early onset; chronic and nonprogressive; refractory to the administration of phosphate, glucocorticoid, and calcitonin; and accompanied by suppressed PTH levels as determined by two different immunoassays, an undetectable PTHrP level, increased excretion of nephrogenous cAMP (an in vivo bioassay of endogenous PTH production), decreased tubular reabsorption of phosphate, increased tubular reabsorption of calcium, increased biochemical indexes of bone turnover, and increased histological indexes of bone turnover on iliac bone histomorphometry after double tetracycline labeling. There was exaggerated loss of cortical bone and preservation of cancellous bone. All the results in JD relating to renal or skeletal effects of PTH excess were within or close to the ranges found in the hyperparathyroid patients, except that tubular reabsorption of phosphate was more depressed. Because PTH secretion was suppressed, any effects mediated by putative alternative receptors would have been diminished. We conclude that 1) the hypercalcemia due to constitutive overactivity of the PTH/PTHrP receptor is indistinguishable from that of mild primary hyperparathyroidism in clinical characteristics and renal tubular and skeletal features; and 2) the classic laboratory manifestations of primary hyperparathyroidism, with the possible exception of osteitis fibrosa cystica, can all be accounted for by overactivity of a single receptor.

Original languageEnglish
Pages (from-to)3584-3588
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume81
Issue number10
DOIs
StatePublished - Oct 21 1996
Externally publishedYes

Fingerprint

Parathyroid Hormone Receptor Type 1
Primary Hyperparathyroidism
Hypercalcemia
Parathyroid Hormone
Parathyroid Hormone-Related Protein
Bone
Bone Remodeling
Phosphates
Osteitis Fibrosa Cystica
Calcium
Kidney
Bone and Bones
Calcitonin
Tetracycline
Immunoassay
Biological Assay
Glucocorticoids
Bioassay
Metabolism
Refractory materials

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Hypercalcemia due to constitutive activity of the parathyroid hormone (PTH)/PTH-related peptide receptor : Comparison with primary hyperparathyroidism. / Parfitt, A. M.; Schipani, E.; Rao, D. Sudhaker; Kupin, Warren; Han, Z. H.; Jüppner, H.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 81, No. 10, 21.10.1996, p. 3584-3588.

Research output: Contribution to journalArticle

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