GH Neurosecretory Dysfunction and Cranial Irradiation

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The group of Shalet in Manchester, UK has made fundamental contributions to the understanding of the broad range of endocrinopathies which may follow cancer therapy in children. In terms of clinical practice, deficiency of growth hormone (GH) following cranial irradiation constitutes an important entity of which all pediatric endocrinologists need to be aware. Prophylactic cranial irradiation for leukemia has been largely replaced by use of intrathecal cytotoxic agents. However, targeted high-dose radiotherapy (RT) for brain tumors outside the hypothalamic pituitary region, such as medulloblastomas, remains an essential and potentially life-saving therapy.

The relationship between the dose of RT and the frequency of subsequent GH deficiency has been clearly established. This article critically considers whether patients who have normal GH responses to pharmacological testing may have a more subtle defect of physiological pulsatile GH release, ie, so-called GH neurosecretory dysfunction. The presence of this ‘defect’ of probable hypothalamic origin was assumed when subnormal pulsatile secretion was reported during adolescence, particularly after low-dose RT in several studies.

Darzy KH, Pezzoli SS, Thorner M, Shalet SM. Cranial irradiation and growth hormone neurosecretory dysfunction: A critical appraisal. J Clin Endocrinol Metab. 2007;92:1666-72.

Editor’s Comment

The combined groups of Shalet and Thorner have performed extremely detailed assessments of physiological GH secretion (cluster analysis) in adult patients, most of whom received RT during childhood, and in normal controls. Such a study would have been impossible in pediatric subjects. The hallmarks of neurosecretory dysfunction, ie normal GH secretion, after provocation compared with decreased spontaneous secretion were not seen. This helpful finding effectively dismisses this abnormality from potential sequelae of cranial RT in childhood. The peak GH concentration after a pharmacological provocation test can be taken as a realistic index of somatotrope secretory capacity. Performing physiological studies is unlikely to add further clinically relevant information.

Martin O. Savage, MD

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Last Updated: 04/30/2008