Role of the Thyrotropin-Releasing Hormone Stimulation Test in Diagnosis of Congenital Central Hypothyroidism in Infants

Abstract

lp;&-8qContext:A shortage of thyroid hormone during prenatal life and the first years after birth results in a spectrum of neuropsychological disorders, depending on the duration and severity of the deficiency. In the case of congenital hypothyroidism of central origin (CH-C), the majority of patients have multiple pituitary hormone deficiencies (MPHD). This condition poses an additional threat to postnatal central nervous system development, primarily on account of neuroglycopenia due to ACTH/cortisol deficiency with or without additional GH deficiency. Therefore, in CH-C, rapid diagnosis is even more urgent than in congenital hypothyroidism of thyroidal origin. Objective:In the assessment of hypothalamic-pituitary-thyroid function, we considered the pituitary response to iv administration of TRH (TRH test) pivotal. We evaluated the usefulness of the TRH test in a cohort of infants with neonatal congenital hypothyroidism screening results indicative of CH-C by analyzing the results within the framework of investigations of the anatomical and functional integrity of the hypothalamo-hypophyseal system. Design and Setting:The study was a Dutch nationwide prospective study (1994 -1996). Patients were included if neonatal congenital hypothyroidism screening results were indicative of CH-C and patients could be tested within 3 months of birth. Patients:Ten male and five female infants with CH-C, detected by neonatal screening, and six infants with false-positive screening results, nonthyroidal illness, or transient hypothyroidism, were included in the study. Main Outcome Measures:Results of TRH tests, within the framework of extensive endocrinological examinations and cerebral magnetic resonance imaging, were measured.Results: All patients with type 3 TSH responses to TRH had MPHD, and the majority (67%) of patients with type 2 responses had isolated TSH deficiency. Conclusions:The TRH test has a pivotal role in the diagnosis of TSH deficiency in young infants. Abnormal TRH test results, especially a type 3 response, urge immediate assessment of integral hypothalamic-pituitary function because the majority of patients have MPHD. T hyroid hormone is extremely important for normal brain development. A shortage of thyroid hormone during prenatal life and the first years after birth results in a spectrum of neuropsychological disorders, depending on the duration and severity of the deficiency (1, 2). In the case of congenital hypothyroidism (CH), the damage appears to be especially related to postnatal T 4 deficiency (3). Apparently, central nervous system development can at least be partly preserved by

Hypogonadotropic Hypogonadism in Infants with Congenital Hypopituitarism: A Challenge to Diagnose at an Early Stage

“…In the present study and in line with a previous report [27], CPHD appears to be more frequent in boys, even though in most patients, genital anomalies were undetected by pediatricians before their referral to us. Thus, the different prevalence between genders is apparently not related to the presence of genital anomalies.…”

Central hypothyroidism

“…8 These studies have also shown that low baseline TSH, as seen in our case, are more likely with pituitary cause for TSH deficiency. In this background and as TRH is not readily available for clinical use in India, we considered isolated TSH deficiency and proceeded with mutation analysis of TSHB gene.…”

Central Hypothyroidism

“…In the neonates, CeH can be identifi ed only by screening programs based on concomitant TSH and total T4 measurements in the dry blood spot [ 4 -8 ]. CeH confi rmation by serum FT4 and abnormal TSH response to TRH testing may reveal the risk of CPHDs and impending adrenal crisis [ 8 ]. CPHDs represent the more frequent forms of neonatal CeH.…”