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The endocrinology of hypothalamic hamartoma surgery for intractable epilepsy

Epileptic Disorders. Volume 5, Number 4, 239-47, December 2003, Original article

Summary

Author(s) : Jeremy L. Freeman, Margaret Zacharin, Jeffrey V. Rosenfeld, A. Simon Harvey , Children‘s Epilepsy Program, Departments of Neurology and Endocrinology and Murdoch Childrens Research Institute, Royal Children‘s Hospital, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Victoria, Australia; Departments of Neurosurgery and Surgery, The Alfred Hospital and Monash University, Prahran, Victoria, Australia; and Epilepsy Research Institute, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia .

Summary : Intractable epilepsy has replaced central precocious puberty (CPP) as the main indication for surgery in patients with hypothalamic hamartoma (HH). However, concern about endocrine complications and the paucity of published endocrine data may dissuade clinicians from recommending HH surgery. We report the preoperative endocrine status and postoperative endocrine findings of patients undergoing HH surgery at our centre. Twenty‐nine patients aged 4‐23 years (mean 10 years) underwent detailed clinical assessment and biochemical testing of the hypothalamic‐pituitary axis before and after transcallosal resection of their HH. The perioperative evaluation included comprehensive evaluation of pubertal status, growth, weight, thyroid and adrenal function, and osmoregulation. Forty‐five percent of patients had CPP at presentation and this was not altered by HH surgery. Asymptomatic deficiencies in thyroid hormone, growth hormone and cortisol response were identified in several patients prior to surgery, and biochemical CPP was present in four, clinically prepubertal children. Free thyroxine fell after surgery in the majority, and to clinically significant levels prompting treatment in 5 patients. Low growth hormone was present in 5\\8 patients who had had previous HH surgery and in 6\\29 following transcallosal surgery at our centre\; short stature did not result during the period of follow‐up. Hypernatraemia developed in most patients postoperatively with sodium > 150 mmol\\L seen in 16 (55%) patients\; however, this was asymptomatic, not often associated with polyuria, and transient\; no patient required ongoing antidiuretic hormone replacement. Appetite stimulation and early postoperative weight gain occurred in 45% patients, but resolved in half. Disturbance of endocrine function may be clinically silent and should be routinely evaluated prior to HH surgery for intractable epilepsy. Following surgery, hypernatraemia, low thyroxine, low growth hormone, and weight gain are the main endocrine problems encountered. Prior, unsuccessful surgery may be a risk factor for endocrinopathy. Except for weight gain in some patients, these postoperative endocrine disturbances appear to be transient, mild or asymptomatic, and easily treated where necessary. Long term follow‐up of growth and sexual development in a large series of patients is required.

Keywords : hypothalamic hamartoma, central precocious puberty, epilepsy surgery, hypothalamic‐pituitary axis

Pictures

Figure 1. Preoperative and postoperative assessment of anterior pituitary function. (A) Results of glucagon stimulation testing of cortisol production, with basal and peak (stimulated) cortisol shown for each patient (points connected by a straight line). Normal peak cortisol levels are twice basal, or greater than 450 mmol/L (horizontal rule). Five patients had an inadequate cortisol rise above basal level before surgery, but no patient developed any new cortisol deficiency. (B) Results of luteinising hormone-releasing hormone (LHRH) stimulation testing of luteinising hormone (LH) production, with basal and peak (stimulated) LH shown for each patient (points connected by a straight line). Any increase from basal levels is consistent with pubertal pituitary function. Two children below 6 years of age with precocious pubertal LH responses before surgery, showed normalization of this test after surgery, but overall, pubertal status was not affected by surgery. (C) Free thyroxine (T4) levels fell to subnormal levels (less than 10 pmol/L) in eight patients following surgery, four to within a range consistent with a sick euthyroid’ state of convalescence from surgery (double-headed arrow between horizontal rules). Four patients with levels below this range, plus one with a normal initial postoperative free T4 required thyroxine sodium supplementation. (D) Peak growth hormone levels in response to glucagon stimulation shown before and after surgery (points connected by a straight line). Prior to surgery, five patients fell within the partially deficient range (double-headed arrow between horizontal rules) and four were severely deficient. Postoperatively, six patients developed deficient peak GH levels. Short stature was not observed in this cohort prior to surgery and growth hormone supplementation has not been required since. (E) Prolactin levels rose above preoperative levels in a few patients, but significant hyperprolactinaemia did not occur.

Figure 2. Modified scatterplot of plasma sodium against time, preoperatively (0 days) and following resection of hypothalamic hamartoma in 29 patients. One sodium measurement per time category was included for each patient, and points for patients with the same value overlap. The last sodium measurements were performed between 8 and 60 (mean 23) days after surgery in 23 patients. The curved line shows the mean sodium for the group at each time interval.

Figure 3. Weight-for-age in children undergoing hypothalamic hamartoma resection. Preoperative (first point) and postoperative (subsequent points) weights are shown as connected points (open circles for girls, solid circles for boys). The curved lines are the 5th (bottom), 50th (middle) and 95th (top) percentiles of weight-for-age for both girls (dashed lines) and boys (solid lines), according to the National Center for Health Statistics 2000 CDC clinical growth charts: USA (http://www.cdc.gov/nchs/about/major/nhanes/growthcharts/clinical_charts.htm). Thirteen patients were overweight at the time of preoperative assessment. Ten patients experienced clinically significant early weight gain following surgery; five showed subsequent return towards preoperative percentiles and five have ongoing overweight concerns.