Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical evidence of resistance to TSH and TRH.

OBJECTIVE: Hypothyroidism is a manifestation of multi-hormonal resistance in pseudohypoparathyroidism type Ia (PHP Ia). The objective of the study was to determine the mechanisms of hypothyroidism in PHP Ia.

DESIGN: A prospective study.

PATIENTS: Ten patients with PHP Ia.

MEASUREMENTS: The serum concentrations of TSH, free triiodothyronine (FT(3)), free thyroxine (FT(4)), and prolactin (PRL) were measured at baseline and after stimulation with TRH (200 microg i.v).

RESULTS: The median basal serum TSH concentration was 4.92 mU/l. Basal serum TSH concentration was slightly elevated in eight patients (4.22-7.0 mU/l; normal range, 0.4-3.6 mU/l), normal in one patient (2.5 mU/l), and high in one patient (13.1 mU/l). After the TRH test, TSH concentrations increased to 13.4-36.0 mU/l (normal range, 4.0-20.0 mU/l). The absolute values after the test were normal in three patients and high in seven patients. However, TSH responses relative to the baseline value (stimulated/basal TSH and expressed as a fold increase), which reflect the relative increases after TRH stimulation, were low in seven patients (2.3- to 4.3-fold TSH) and normal in three patients. Basal FT(4) concentration was normal in seven patients and low in three patients (range, 8.4-20.0 pmol/l; mean, 14.1+/-4.3 pmol/l; normal range, 10.5-23.0 pmol/l). Basal FT(3) concentration was normal in nine patients and low in one patient (range, 0.9-5.0 pmol/l; mean, 3.8+/-1.1 pmol/l; normal range, 3.3-6.1 pmol/l). FT(4) and FT(3) were not significantly increased after the TRH test. PRL concentration was normal at baseline and increased from 7 to 96 ng/ml after TRH.

CONCLUSION: Our results support the hypothesis that patients with PHP Ia have impaired sensitivity to both TSH and TRH.