medwireNews: Survivors of paediatric central nervous system (CNS) tumours frequently develop central precocious puberty (CPP) and endocrine disturbances, report researchers.
In particular, these patients had incomplete recovery of growth and a high prevalence of gonadotropin deficiency, and were often obese, but the team found that “these complications seem more related to the primary diagnosis than to CPP itself.”
Overall, 15.2% of 500 patients studied had CPP, with the highest rate of 29.2% seen in those with hypothalamus/pituitary axis (HPA) tumours, making it “among childhood’s most common hypothalamic pituitary dysfunctions following HPA insults and radiotherapy, second only to GHD [growth hormone deficiency].”
The 80 patients who later developed CPP were diagnosed with CNS tumours at around 4 years of age, and between then and their most recent follow-up as young adults they developed a range of endocrine disturbances including thyroid-stimulating hormone deficiency (35.0%), gonadotropin deficiency (32.6%) and adrenocorticotropic hormone deficiency (19.0%).
Obesity was also common, found in 37.7% of patients at most recent follow-up, and became more prevalent over time, having occurred in just 20.8% at puberty onset and 22.6% at completion of gonadotropin-releasing hormone antagonist (GnRHa) therapy.
GHD occurred in 66% of patients, but the researchers found that this was not necessarily directly linked to CPP. In the 23 patients with non-HPA tumours, GHD was diagnosed an average of 1.7 years before CPP, but in the 57 with HPA tumours, it did not appear until an average of 2.3 years after.
“Thus, for this large subset of [HPA tumour] patients […], late onset GHD likely develops as a result of tumour growth, subsequent surgery and/or subsequent treatment with radiotherapy years after presenting with CPP”, write Wassim Chemaitilly (St Jude Children’s Research Hospital, Memphis, Tennessee, USA) and study co-authors in Clinical Endocrinology.
Of the patients with GHD, 34% received growth hormone treatment for less than a year or not at all.
At onset of precocious puberty, 2.4% of patients had a height standard deviation score (SDS) that was at least 2.0 below the norm for their age, increasing over time, to 21.4% at the most recent follow-up. This pattern remained after excluding patients who received inadequate growth hormone treatment.
After accounting for confounders, each additional year of GnRHa therapy was associated with an 11% increased likelihood of a final height SDS at least 2.0 below normal.
“Early diagnosis and treatment of patients with CPP may limit further deterioration of final height prospects”, the researchers suggest.
By Eleanor McDermid, Senior medwireNews Reporter
Clin Endocrinol 2015; Advance online publication
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