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

¹ , Clinique Endocrinologique Marc Linquette² Laboratoire de Médecine Nucléaire, CHU, 59037 Lille-Cedex, France

(Correspondence should be addressed to A-S Balavoine who is now at Service d'Endocrinologie et Maladies Métaboliques, Clinique Endocrinologique Marc Linquette, CHRU, 59037 Lille Cedex, France; Email: asbalavoine{at}yahoo.fr)

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 (FT₃), free thyroxine (FT₄), and prolactin (PRL) were measured at baseline and after stimulation with TRH (200 µg 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 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.

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