medwireNews: The Endocrine Society has released a guideline for the diagnosis and treatment of hypothalamic–pituitary and growth disorders in survivors of childhood cancer.

Charles Sklar (Memorial Sloan-Kettering Cancer Center, New York, USA) and guideline co-authors note that 40–50% of childhood cancer survivors “will develop at least one endocrinopathy over the course of their lifetime” and that the risk increases over time, making lifelong screening essential.

As such, they advise annual screening of all patients who had hypothalamic–pituitary axis tumours or surgery, or radiation of at least 30 Gy to the area. These patients should be screened for central hypothyroidism/thyroid-stimulating hormone deficiency, luteinising hormone/follicle-stimulating hormone deficiency and adrenocorticotropic hormone deficiency.

The latter condition should also be screened for in patients starting from 10 years after receipt of 24–30 Gy or if they develop clinical symptoms suggestive of the deficiency. There are no special diagnosis or treatment considerations; Sklar and team advise that these should be in line with routine practice in noncancer patients.

Central precocious puberty should also be assessed for regularly if patients have had hydrocephalus, or tumours or radiation affecting the hypothalamic–pituitary region. In this case, the guideline warns against relying overly on testicular volume in boys previously given gonadotoxic agents and advises measurement of testosterone levels and early morning luteinising hormone levels in addition to clinical examination.

Precocious puberty also has implications for the assessment of growth, the guideline notes, as the stimulatory effects of sex hormones may obscure reduced growth velocity caused by growth hormone deficiency (GHD).

“[T]he treating endocrinologist might miss a diagnosis of GHD unless he/she is knowledgeable in this regard”, warn Sklar and co-authors.

The guideline’s recommendations for growth disorders are based on two specially commissioned meta-analyses, looking at the diagnosis and treatment of GHD in childhood cancer survivors, which are published alongside the guideline in The Journal of Clinical Endocrinology & Metabolism.

The guideline authors advise monitoring of growth – every 6 to 12 months – in patients who were exposed to cranial, craniospinal or total body irradiation, or who have a history of inadequate weight gain or prolonged steroid requirement. Those who had tumours or radiation exposure of at least 18 Gy in the hypothalamic–pituitary region should additionally have lifelong assessment for GHD.

For GHD diagnosis, the guideline writers caution against relying solely on serum insulin-like growth factor-1 levels, which the meta-analysis showed to be less accurate in cancer survivors than in the general population. Provocative testing is advised, but tests involving growth hormone-releasing hormone should be avoided because of the risk of false-negative results in patients with hypothalamic damage.

The team advises against GH treatment in patients without GHD and for delaying GH treatment in deficient patients until they have been free of cancer for 1 year. This is simply because clinicians traditionally wait this long, they say, and “thus, the safety of GH [treatment] prior to that time is not clear.”

Eleanor McDermid

J Clin Endocrinol Metab 2018; Advance online publication

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GHD meta-analysis
GH therapy meta-analysis