Complex treatments, diabetes insipidus predicted complications in childhood-onset craniopharyngioma

Yuen KC. J Clin Endocrinol Metab. 2014;doi:10.1210/jc.2013-3631.

  • February 7, 2014

In patients with craniopharyngiomas, complex treatments were predictive of postoperative visual dysfunction while diabetes insipidus was associated with greater rates of anterior pituitary hormone dysfunction and an increased weakness for gender-independent weight gain, according to data published in the Journal of Clinical Endocrinology and Metabolism.

Craniopharyngiomas are usually related to significant morbidity due to their location and treatment effects, according to Kevin C. J. Yuen, MD, of the division of endocrinology, diabetes and clinical nutrition in the department of medicine at the Oregon Health and Science University, and colleagues.

“The higher BMIs and fat mass observed in patients with [diabetes insipidus] further reinforces the role of hypothalamic damage as an important causal factor in inducing subsequent obesity in these patients and implies that the presence of [diabetes insipidus] can be used as a clinical surrogate marker for hypothalamic obesity,” researchers wrote.

Their retrospective analysis included 180 adults with childhood-onset craniopharyngioma (COCP) studied according to the primary treatment regimen (ie, one surgery vs. complex treatment regimen of more than one surgery and/or radiotherapy) and the presence of diabetes insipidus.

Many of the patients with COCP underwent transcranial surgery (77%) without receiving radiotherapy (84%), according to data.

More patients who underwent complex treatment regimens developed visual field defects and ophthalmoplegia compared with the primary treatment regimen group (P<.01), researchers wrote. 

In addition, those with diabetes insipidus demonstrated greater rates of anterior pituitary hormone deficits, BMI and fat mass (P<.01) compared with patients without diabetes insipidus.

Fasting glucose, HbA1c, lipids and quality of life were comparable among patients in the primary treatment regimen vs. complex treatment regimen, and patients without diabetes insipidus.

However, diabetes insipidus in both groups was associated with a greater rate of anterior pituitary hormone deficits and obesity, despite the type of primary treatment they underwent, according to researchers.

Disclosure: Yuen has received research grants from Eli Lilly, Novo Nordisk, Pfizer and Versartis; served on the advisory boards for Corcept Therapeutics, Novo Nordisk and Pfizer. See the study for a full list of all other researchers’ relevant financial disclosures.

Perspective
Tamara L. Wexler, MD, PhD

Tamara L. Wexler

  • Yuen and colleagues use the KIMS database to look for correlations between health outcomes of adults with childhood-onset craniopharyngioma (COCP) and A. whether primary treatment was limited to a single surgery or consisted of >1 surgery and/or radiotherapy, and B. the presence of DI. KIMS is an often-used database; of note, as KIMS includes only patients with growth hormone deficiency, this study evaluated a subset of patients with COCP.

    The authors noted an association between complex treatment regimen (CTrR) as the primary treatment and visual field defects and opthalmoplegia, relating the aggressiveness of the treatment to the visual dysfunction. Diabetes insipidus was found to correlate with anterior pituitary dysfunction and with weight gain (higher BMI and fat mass). 

    As with any correlations, it is difficult to assess causality. For example, it may be that both the type of primary treatment and the higher rate of visual field defect reflect the complexity of the initial tumor itself (ie, tumors judged at a time requiring more aggressive treatment). Also of note, patients were enrolled from 1994 to 2011.

    Hypothalamic obesity is a topic of concern in patients with COCP; almost half (40-50%) of patients with COCP have obesity or an issue with eating (Bereket et al, 2012). It is often very difficult to treat, proving resistant to replacement of anterior pituitary hormones, and to medical treatment.  There is no consistently demonstrated standard medical therapy, though different treatments have been tested, and there are case reports of use of bariatric surgery (Inge et al, 2007)  

    Hypothalamic obesity, as Yuen and colleagues note, is a major factor in quality of life (QOL) following COCP. The QOL in the KIMS database is measured by the validated Assessment of Growth Hormone Deficiency in Adults questionnaire. The authors use diabetes insipidus as a surrogate for hypothalamic damage. Despite the impact of hypothalamic obesity on QOL, which they note, and the putative association between diabetes insipidus and hypothalamic damage, this study did not find a difference in QOL between subjects with diabetes insipidus and those without diabetes insipidus. 

    The authors note the limitations of this type of study. Additional patient level information would provide additional insights. For example, the analysis by Bereket and colleagues found that hypothalamic obesity is predicted by BMI at time of CP diagnosis. Does that hold true in this population?  It would be interesting to further explore why there was no difference in QOL despite a difference in weight in these patients. For example, could, perhaps, the patients’ growth hormone replacement play a role?

    • Tamara L. Wexler, MD, PhD
    • Neuroendocrinologist
      Clinical Associate, Massachusetts General Hospital
  • Disclosures: Wexler reports no relevant financial disclosures.

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