Interpretative Difficulties with Growth Hormone Provocative Retesting in Childhood-Onset Growth Hormone Deficiency

Abstract

A review of literature demonstrates that there are many ill-understood factors that determine the results of GH provocative (re)testing, so that these results should be interpreted with extreme caution when used for diagnosis or confirmation of diagnosis of GHD. GH provocation tests are probably of no value at all for what has been called ‘partial GHD’. The phenomenon of ‘normalization’ of test results after long-term treatment with GH needs no ‘transient GHD’ hypothesis as it can be largely explained by the very low reproducibility of the tests and by a regression to the mean effect. Moreover, it is possible that ‘normal values’ increase with age. Other determinants of normal peak values may also change from childhood to adulthood and contribute to ‘normalization’.

Growth Response to Recombinant Human Growth Hormone (GH) in Children with Idiopathic Growth Retardation by Level of Maximum GH Peak during GH Stimulation Tests

“…Hereby, a GH peak of 10–20 mU/l is usually labeled ‘partial’ GHD. However, taking into account the poor reproducibility, it is very unlikely that a maximum GH peak between 10 and 20 mU/l provides reliable information with regard to partial impairment of stimulated GH secretion [1, 2, 3, 4, 5, 6, 13, 14, 15, 16, 17, 27]. Rather is it likely that children with a maximum GH peak of 10–20 mU/l are for the most part a selected subgroup of children with normal GH secretion, but who had two low peaks just by chance.…”

“…One of the remaining challenges in endocrinology is how to correctly identify in this group those with minor or partial disturbances of GH secretion because that subgroup would be an obvious candidate for GH replacement therapy [1]. Unequivocal diagnosis of partial GH deficiency (GHD) is not possible today [2, 3, 4, 5], but many pediatricians consider it of importance not to withhold GH treatment from these patients. A tacit consensus has developed that it is allowed to practice some degree of overdiagnosis of ‘partial GHD’.…”

“…Hereby, a maximum rise to 10–20 mU/l during two GH stimulation tests is usually considered indicative of ‘partial GHD’. This is remarkable because stimulated GH values in that range are seen in approximately 20% of the normally growing children [2, 6]. Additional examinations such as medical imaging of the pituitary gland or determination of insulinlike growth factor I (IGF-I) are frequently done in an attempt to corroborate the diagnosis.…”

“…The aim of this study was to address this issue. Based on the poor reproducibility of GH stimulation tests [2, 15, 16, 17], we hypothesized that the classical distinction between ‘partial GHD’ and ISS is artificial and that for this reason no different growth responses between these two groups are to be expected.…”

The Prognostic Value of The Growth Hormone Secretion Stimulating Tests withl-dopa and clonidine in Children with Growth Hormone Deficiency Treated with Recombinant Human Growth Hormone in Western Pomeranian Region

“…Większe wydzielanie hormonu wzrostu w retestingu może wiązać się z fizjologicznym zwiększeniem wydzielania tego hormonu w okresie pokwitania jak również z lepszą kontrolą podwzgórza, którą dziecko uzyskuje po osiągnięciu dojrzałości płciowej [18,32,33]. Niektórzy autorzy uważają jednak, że stwierdzana w retestingu normalizacja wydzielania hormonu wzrostu może świadczyć o niedoskonałości testów diagnostycznych [34].…”