medwireNews: About one in five children with isolated growth hormone deficiency (IGHD) of organic causes will go on to develop multiple pituitary hormone deficiency (MPHD), research shows.

This “may have far-reaching clinical consequences”, say Christopher Child (Lilly Research Laboratories, Windlesham, UK) and study co-authors.

They stress that 13% of children who developed additional hormone deficiencies became deficient in adrenocorticotropic hormone (ACTH), which, if undetected, can lead to life-threatening adrenal crisis.
And they warn: “Although many patients exhibited characteristics that predict MPHD development, other patients developed MPHD without obvious prognostic factors.”

Using data from the multinational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS), the team identified 716 patients with organic IGHD. Most (71%) patients had congenital causes, primarily abnormal pituitary development, and the most common acquired cause was intracranial tumour and/or irradiation.

During an average 3.3 years of follow-up, 9.9% of these patients developed additional hormone deficiencies. But because duration of follow-up played a big part in determining the likelihood of developing MPHD, Child et al limited their analysis to 290 patients with about 4 years of follow-up, and found a MPHD rate of 20.7%.

The rate was markedly higher than the researchers previously reported for children with idiopathic IGHD, of 5.5% over 4 years. Nevertheless, they describe the continued absence of MPHD in four out of five children with organic causes as “somewhat surprising”, and suggest that “monitoring for additional pituitary deficiencies should continue for an extended period, perhaps indefinitely.”

Of the 71 children from the full cohort who developed MPHD, 58 had a new deficiency in just one hormone, 12 in two hormones and one became deficient in three additional hormones. The most common new deficiency was in thyroid stimulating hormone (66%), followed by gonadotropin (32%), ACTH (13%) and antidiuretic hormone (8%). No patient developed prolactin deficiency.

Factors predicting MPHD in the full cohort after accounting for confounders, besides duration of follow-up, were older age, female gender and lower peak stimulated GH.

“Except for gender, these are the same predictors as in GeNeSIS patients with idiopathic GHD”, the team observes in the European Journal of Endocrinology.
They say that the effect of female gender in organic IGHD patients seemed to be driven by a high rate of MPHD among girls with acquired GHD, particularly as a result of intracranial tumour.

“As the hypothalamic-pituitary-gonadal axis functions somewhat differently in girls than in boys, it may be more susceptible to irradiation in girls and potentially, at least in part, driving the higher rate of MPHD development in girls”, the team suggests.

By Eleanor McDermid, Senior medwireNews Reporter

Eur J Endocrinol 2016; Advance online publication

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