Pitfalls in diagnosing impaired growth hormone (GH) secretion: retesting after replacement therapy of 63 patients defined as GH deficient.

Abstract

Possible causes of error in the diagnosis of isolated GH deficiency are the variability of GH response to repeated tests, the existence of transient GH deficiencies, and the low GH levels found in short statured children with delayed puberty. Sixty-three patients with variously expressed GH deficiency were retested (1 sleep test and 2 pharmacological tests) after 1-3.9 yr of GH therapy (dose, 15 U/m2.week). Forty-eight subjects had arginine, L-dopa, and sleep tests (mean serum GH concentration) twice, while 15 had only arginine and L-dopa tests. All patients were retested 1 month after withdrawal from therapy. The criteria used to subdivide the patients were pubertal development and response to pharmacological and sleep tests at first diagnosis and on retesting. The initial diagnosis in 33 subjects (52.4%) was not confirmed, and 13 (20.6%) were no longer deficient on retesting. The percentage of normalization was high for the sleep test (43.9%), lower for the pharmacological test (24.5%), and lower still (12.9%) for pharmacological and sleep tests considered together. While none of the 28 subjects who remained prepubertal at retesting normalized in any of the tests, 13 of the 35 subjects retested during puberty did. When normalization was observed in pubertal subjects, it occurred predominantly in the sleep test. Growth velocity and height age/bone age increment ratio after the first year of therapy were no different for the groups of subjects classified according to GH secretion on retesting. Our study demonstrates that a number of children diagnosed as GH deficient do not have a true deficiency. However, such a diagnostic error seems to have little effect, at least in the first year of therapy, on the effectiveness of GH treatment.

Cut-off limits of the peak GH response to stimulation tests for the diagnosis of GH deficiency in children and adolescents: study in patients with organic GHD

“…Although biochemical tests for GH secretion clearly distinguish children with severe GHD of pituitary origin, recognition of more subtle forms of GH insufficiency still presents a diagnostic dilemma. Furthermore, more than 70% (up to 100% in some studies) of isolated idiopathic GHD patients diagnosed in childhood have normal GH responses to stimulation when retested at the end of statural growth or even a few months apart (21,22,23). Spontaneous resolution of transient GHD in adolescence has been proposed.…”

Final height of patients treated for isolated GH deficiency: examination of 83 patients

“…However, insufficient numbers of patients, different therapy durations, and changes in the time of the dosage prescribed, due, in particular, to a greater availability of the hormone, have led to different results (10,11). In addition, the modifications recently made in the therapy schedule and administration route, as well as the uncertainties of the diagnostic criteria indicating the subjects to be treated (13)(14)(15)(16)(17)(18)(19)(20)(21), will probably further change the final results of the treatment. It is certain, however, that the experience acquired to date has not enabled us to adopt an optimal therapeutic approach, either for the single patient or for the whole group, casting doubt on the auxological outcome of the patients treated.…”

O Papel dos Testes de Estimulação Farmacológica no Diagnóstico da Deficiência de Hormona do Crescimento em Crianças e Adolescentes

“…Os testes farmacológicas de estimulação, apesar das limitações conhecidas (estímulo não fisiológico, limites de cut-off arbitrários, variabilidade intra-individual na resposta ao fármaco), 20,21 continuam a respresentar o método mais consensual para avaliação da secreção da HC.…”