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

Abstract

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 mg 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, 14.1G4.3 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, 3.8G1.1 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.

From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network

“…AHO is a clinical entity initially described together with PHP in 1942, which encompasses heterogeneous clinical findings such as brachydactyly, rounded face, short stature, stocky build and subcutaneous ossifications (4,21,22). Additional features that may not directly relate to AHO, yet extensively associated with PHP1A individuals, include obesity, varying degrees of intellectual disability and resistance to several hormones, including TSH, GHRH and calcitonin (23,24,25,26,27,28). The subcategory of PHP1C has all the characteristics of PHP1A, except that Gsa activity in erythrocytes was found comparable to controls (29,30).…”

Case Report: An Unusual Cause for Hypocalcemia

“…Patients with PHP type 1a may have disturbances in taste, smell, vision, and hearing, and they may be hyporesponsive to the biologic effects of other peptide hormones that use the alpha subunit of the Gsa protein to enhance cAMP production. The hormones under this class include thyrotropin, antidiuretic hormone, the gonadotropins, glucagon, adrenocorticotropin, and growth hormonereleasing hormone h. Primary hypothyroidism occurs in most patients with PHP type 1a [7,8].…”

Alteration of Hypothalamic–Pituitary–Thyroid Axis Function in Non-Small-Cell Lung Cancer Patients

“…The response is exquisitely sensitive to minor changes in the level of circulating thyroid hormones, and a direct correlation between basal serum TSH values and the maximal response to TRH has been observed even in the absence of thyroid hormone abnormalities, suggesting that there may be a fine modulation of pituitary sensitivity to TRH in the euthyroid state. [34][35][36] Figure 2. x-y Plots showing linear regression lines with 95% confidence limits between all original 4-hourly values of TRH versus TSH and TRH versus FT4 serum levels in 11 healthy participants and 9 small-cell lung cancer patients. No significant correlation was found for TSH versus TRH in either group (top panels), whereas FT4 versus TRH showed a positive correlation in controls (r = 0.36; slope = +0.46; P = .003) and a negative correlation in cancer patients (r = 0.49; slope = −0.38; P < .001)-bottom panels Abbreviations: TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone; FT4, free thyroxine; IL-2, interleukin 2.…”