Effect of growth hormone therapy on thyroid function in isolated growth hormone deficient and short small for gestational age children: a two-year study, including on assessment of the usefulness of the thyrotropin-releasing hormone (TRH) stimulation test

Abstract

BackgroundThe relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy.MethodsWe retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3).ResultsIn groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy.ConclusionsGH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.

International Consensus Guideline on Small for Gestational Age: Etiology and Management From Infancy to Early Adulthood

“…GH treatment leads to lower serum free thyroxine (T4) levels in 14% of children born SGA in the presence of normal TSH levels, which is due an increased conversion of free T4 to biologically active free triiodothyronine (T3) ( 210 ). GH treatment does not result in thyroid dysfunction ( 210 , 211 ).…”

One-year follow-up of thyroid function in 23 infants with Prader-Willi syndrome at a single center in China

“…A few studies have reported the effects of GH treatment on thyroid function in patients with a GH deficiency and hypopituitarism (17)(18)(19). GH may increase the serum FT3 level and decrease the serum FT4 level by up-regulating type 2 iodothyronine deiodinase expression (20).…”

Thyroid Hormone Changes Related to Growth Hormone Therapy in Growth Hormone Deficient Patients

“…On the other hand, low baseline fT4 levels in children with congenital GHD are proposed as a predictor of structural pituitary lesions and diagnosis of MPHD [27]. An interesting idea was postulated recently by Ebuchi et al [29], who reported that a thyrotropin-releasing hormone (TRH) stimulation test, conducted before the initiation of growth promoting treatment, could help to identify individuals who are at risk of central hypothyroidism due to rhGH therapy and could require L-thyroxine replacement therapy. Nevertheless, this method of prediction seems to be relatively expensive and not widely available.…”