A simplified diagnostic test in hypoparathyroidism and pseudohypoparathyroidism type I with synthetic 1-38 fragment of human parathyroid hormone

Abstract

Bovine parathyroid extract of E. Lilly (Indianapolis), which has been used to differentiate pseudohypoparathyroidism (PHP) and hypoparathyroidism (HP) is no longer available. We therefore evaluated the usefulness of the synthetic 1-38 fragment of human parathyroid hormone (1-38 hPTH), the biologically active part of the intact hormone, in a simplified modification of the traditional Ellsworth-Howard test. 1-38 hPTH was slowly injected over 2 min at a dose of 0.5 micrograms/kg body weight in healthy children and adults (n = 7), as well as in children with HP (n = 4) and PHP (n = 4). In the controls PTH administration induced a significant rise of plasma cAMP (at least 146 nmol/l), urine cAMP and serum prolactin, as well as a decrease of the tubular phosphate reabsorption. The respective responses were similar in the children with HP but markedly impaired in the patients with PHP. In four healthy adults a second PTH administration at an interval of 3 h induced a comparable response of cAMP and prolactin, indicating that these PTH effects are reproducible and not impaired by the first injection. The two PTH administrations caused a significant but variable rise of serum 1,25-dihydroxy-vitamin D in all four adults. In conclusion 1-38 hPTH has effects on the kidney and anterior pituitary similar to purified parathyroid extracts but has the advantage of being chemically and biologically defined and well tolerated. Since timed urine collections may be unreliable in young children, the plasma cAMP measurement at 5 and 10 min after the PTH injection is a good substitute for the traditional Ellsworth-Howard test, peak values over 100 nmol/l being regarded as a normal response.