Growth Hormone Testing for the Diagnosis of Growth Hormone Deficiency in Childhood: A Population Register-Based Study

Abstract

Evaluation of GH secretion using pharmacological GH stimulation tests (GHST) remains a current practice, although the reliability of GHST has been questioned, and many pitfalls have been pointed out. We have analyzed all of the 6373 GH stimulation tests that led to the initiation of GH therapy in 3233 children treated in France from [1973][1974][1975][1976][1977][1978][1979][1980][1981][1982][1983][1984][1985][1986][1987][1988][1989]. Tests and GH measurements were performed by individual centers and collected by the Association France-Hypophyse. GH deficiency (GHD) was due to craniospinal irradiation (11%), was due to organic causes or associated with multiple deficiencies (22%), or was considered idiopathic (65%); 2% of the patients were considered non-GHD. Eleven different pharmacological tests were used, and 62 of the 66 theoretical pairs of tests were used at least once. The most frequent combination of tests (ornithine in one instance and insulin in another) was used in 12.7% of patients. The reliability of the GH peak measured by comparing the results of 2 tests in the same patient was poor, as measured by intraclass correlation coefficients below 0.8. Multivariate analysis identified several parameters positively or negatively associated with peak plasma GH: calendar year of initiation of treatment, etiology of GHD, height SD score, bone age SD score, puberty, weight SD score, genetic target height SD score, and the nature of the pharmacological agent used. We believe that several of these factors (weight SD score, genetic target height SD score, and nature of the agent) identify biases in the diagnosis of GHD. We conclude that GHST should be performed with a very limited number of agents, interpreted after the establishment of reference values in age-matched normal children, and associated with other clinical and biochemical parameters for establishing the diagnosis of GHD. (J Clin Endocrinol Metab 82: [2117][2118][2119][2120][2121] 1997) T HE RELIABILITY of pharmacological tests used for evaluating GH secretion have repeatedly been questioned (1-4) for the lack of normal age-related reference values, the use of variable cut-off values with time, the use of different pharmacological stimuli, the dependence on physiological parameters (age, puberty, and body weight), poorly reproducible results, and the use of different laboratory methods and standards for the measurement of plasma GH. Although the diagnosis of GH deficiency (GHD) involves the analyses of height, growth velocity, GH secretion, and GH-dependent plasma proteins and the search for an etiology (4 -7), GH stimulation tests (GHST) are still one of the essential elements of diagnosis. GHST are used to regulate the use of GH in most countries, with the exception of Australia (8). How several potentially confounding factors can influence the results of GHST, the diagnosis, the decision to initiate GH substitutive therapy, and ultimately the results of treatment have not, to our knowledge, been analyzed in a populationbased cohort of tr...

Retesting the childhood-onset GH-deficient patient

“…These studies have generally been performed in different cohorts of GHD patients with classical provocative tests that are known for their poor reproducibility (30)(31)(32)(38)(39)(40). This evidence clearly led to the statement that there is no justification for the view that patients diagnosed in childhood to be GHD should continue on therapy into adult life without their GH status being reinvestigated and shown to be persistently abnormal.…”

“…The inability to confirm GHD in adulthood could reflect transient GHD in childhood (34) or, alternatively, could merely reflect the lack of reproducibility of classical provocative tests (30)(31)(32)(38)(39)(40). It also has to be considered that even patients with normal GH response to provocative tests but showing impairment of spontaneous GH secretion are presently considered as GH insufficient (the so-called GH neurosecretory dysfunction) and treated with rhGH for replacement (41).…”

Condução do tratamento com hormônio de crescimento (GH) nos pacientes com diagnóstico de deficiência GH (DGH) durante o período de transição da criança para o adulto

“…Em adultos mais idosos o teste do GHRH + arginina tem mostrado sensibilidade e especificidade semelhantes ao ITT (6,32,33). Vários fatores influenciam o padrão de resposta do GH aos testes de estímulo, entre eles: estímulo empregado, idade, percentual de gordura corporal, presença de esteróides sexuais em quantidade adequada para a faixa etária, deficiências hipofisárias associadas e o tratamento adequado destas (34,35).…”

Clinical, Anthropometric and Dynamic Clonidine Stimulated Growth Hormone Study in Short Stature Children

“…Children with growth hormone deficiency usually present with severe short stature and a low growth velocity of less than4 cm/ year. [2,3] Alternative causes of poor growth need to be considered and excluded. One of the normal variants is idiopathic short stature, a group of short children with no definitely recognizable underlying disease.…”