The combined pituitary function test in children: an evaluation of the clinical usefulness of TRH and LHRH stimulation tests through a retrospective analysis of one hundred and twenty six cases.

Abstract

The combined pituitary function test is routinely used in the endocrine investigation of short children. The TRH and luteinising hormone-releasing hormone (LHRH) response tests have been shown to be of minimal value in adults. We have evaluated the clinical utility of these tests in the context of combined pituitary function testing in children. A retrospective analysis of basal hormone measurements and pituitary stimulation tests in relation to clinical assessment of pituitary function. One hundred and twenty-six children, 82 boys and 44 girls, aged 2-17 years, who had undergone pituitary function testing were studied. The TSH response to TRH stimulation correlated directly with basal plasma TSH but not basal plasma total T4. In patients with an impaired response to stimulation, basal TSH concentrations were <2.0 mIU/l and significantly lower than in patients with a normal response (P < 0.0001). An impaired response to TRH stimulation had a positive predictive value of 0.43 and a negative predictive value of 0.90 for the diagnosis of hypopituitarism. A basal TSH concentration of <2.0 mIU/l had a positive predictive value of 0.22 and a negative predictive value of 0.92. A low basal T4 (normal range 60-140 nmol/l) in combination with an inappropriately low or normal basal TSH was always associated with a diagnosis of hypopituitarism. The responses of plasma LH and FSH to LHRH stimulation correlated directly with basal plasma LH and FSH concentrations. Basal gonadotrophin concentrations, basal sex hormone concentrations or response to LHRH stimulation could not distinguish patients with constitutional delay of growth and puberty from those with hypopituitarism. There was no apparent relationship between either basal gonadotrophin concentrations or response to LHRH stimulation and clinical assessment of pituitary function. In patients ≥13 years with constitutional delay of growth and puberty the median and interquartile ranges of basal LH and FSH were 1.4 IU/l (0.7-3.6) and 2.6 IU/l (2.2-5.2) respectively. The three hypopituitary patients in this study with chronological age ≥13 years had undetectable concentrations of both gonadotrophins. The response of LH and FSH to LHRH stimulation was significantly lower in patients ≥13 years with clinical hypopituitarism than in those with intact pituitary function (P <0.02). TRH and LHRH tests in children with short stature appear to have little value over and above the baseline hormone measurements. An abnormal response to hormone stimulation is not diagnostic of hypothalamic-pituitary disease. We have demonstrated that neither TRH nor LHRH stimulation tests should be routinely used in the investigation of children with short stature.