An Evaluation of the Thyrotrophin-Releasing Hormone Stimulation Test in Paediatric Clinical Practice

Abstract

Aim: The aim of this retrospective study was to evaluate the clinical usefulness of the thyrotropin-releasing hormone (TRH) test in children with suspected hypothalamic or pituitary dysfunction. Methods: We reviewed the case notes of all patients in whom a TRH test had been performed over a 6-year period. Group 1 (n = 85, 34 males, aged 0.9–18.8 years) was the reference group with no evidence of hypothalamic, pituitary or thyroid dysfunction. Group 2 (n = 42, 24 males, 0.1–18.0 years) were being investigated for possible pituitary or hypothalamic insufficiency. Results: In Group 1, thyrotropin (TSH) responses were higher in females than males (p < 0.01). In Group 2, TSH responses were normal for gender in 26 patients, subnormal in 5, and exaggerated/delayed in 11. Four patients with normal TSH responses and 4 with exaggerated/delayed responses had persistently low free thyroxine (FT₄) or later developed low FT₄ and were treated with thyroxine. All those with subnormal TSH responses had normal FT₄ and were not treated. The TRH test did not reliably discriminate between hypothalamic and pituitary disorders. Conclusions: The TRH test did not give useful clinical information. Clinical decisions regarding thyroxine treatment were based on FT₄, not the TRH test. The TRH test should be abandoned in paediatric practice.

Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement

“…A similar range was observed in previous reports on congenital central hypothyroidism 2,3 , and is lower than observed in age-matched controls (14-37 mU/L) 3 . At later ages (7.3-63 years), TSH peaks were between 4.3-8.5 mU/L, which is in the lower half of the reported reference ranges for males (3.7-12.5 mU/L 4 or 4.1-13.9 mU/L 5 ). In eight patients, the increment of serum FT4 [mean (SD) 14.2 (7.9)%] was lower than that reported for controls [mean (SEM) 23.9 (2.7)%], but the FT3 response to TRH was normal (36.3% vs. 41.8% in controls 6, 7 (Supplementary Table 3).…”

Abnormal Responses to TRH in Children Born Small for Gestational Age That Failed to Catch Up

“…While normalization of TSH shows responsiveness of the hypothalamic pituitary axis to T4 and excludes the diagnosis of resistance to thyroid hormones, the lack of change of FT4 and the absent clinical impact suggest that the observed abnormalities of TSH may be related to a different underlying mechanism of TSH modulation. This mild abnormality does not per se explain the lack of catch-up underscoring the practice, suggesting that SGA patients with abnormal TSH response to TRH but normal FT4 do not require treatment with thyroxine [24]. …”