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

Abstract

ObjectiveHypothyroidism 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.DesignA prospective study.PatientsTen patients with PHP Ia.MeasurementsThe serum concentrations of TSH, free triiodothyronine (FT3), free thyroxine (FT4), and prolactin (PRL) were measured at baseline and after stimulation with TRH (200 μg i.v).ResultsThe 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 FT4 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 FT3 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). FT4 and FT3 were not significantly increased after the TRH test. PRL concentration was normal at baseline and increased from 7 to 96 ng/ml after TRH.ConclusionOur results support the hypothesis that patients with PHP Ia have impaired sensitivity to both TSH and TRH.