Bone Abstracts

Background: Pseudohypoparathyroidism (PHP) is a group of heterogeneous endocrine disorders characterised by hormone resistance, primarily to parathyroid hormone (PTH). The resistance is caused by defects in the GNAS gene, which encodes the G_sα protein that activates the cAMP pathway. PHP patients demonstrate elevated plasma PTH, hypocalcaemia, hyperphosphataemia with normal renal function. PTH resistance can be confirmed by Ellsworth-Howard test (PTH stimulation test); affected individuals show diminished urinary cAMP and phosphate (PO₄) excretion in response to exogenous administration of biologically active PTH. Availability of suitable PTH for the test has been a problem but preparations licensed for treatment of osteoporosis are now available.

Aim: To compare the plasma PTH (1–34)/cAMP and urine cAMP/PO₄ responses in healthy individuals and PHP patients after 20 μg subcutaneous PTH (1–34; Forsteo).

Method: Plasma cAMP was analysed on EDTA plasma obtained from healthy subjects in a clinical trial and a patient with suspected PHP. A single s.c. injection of 20 μg PTH (1–34) was given immediately after the baseline samples were taken. Post dose blood samples were collected every 15 min for 2 h then hourly for 3 h. Urine cAMP and PO₄ were analysed on samples voided every 30 min for 3 h post PTH (1–34).

Results: Plasma cAMP in healthy subjects increased sharply from baseline of 7.6 (0.8) (mean±S.D) to a peak of 13.1 (1.7) nmol/l within 15 min of injection. The urine cAMP and phosphate levels from the patient suspected of PHP did not change significantly. The PTH (1–34) concentration increased significantly by 88.2 (18.5) pg/ml in all individuals studied.

Conclusion: An Ellsworth-Howard test can be performed using readily available PTH (1–34) when PHP is suspected. This format of the test allows confirmation that a suitable concentration of PTH (1–34) has been achieved that stimulates a diagnostic plasma/urine cAMP and urine PO₄ response.