The use of the hypoglycaemic clamp in the assessment of pituitary function

The standard dynamic test used to diagnose hypopituitarism is the insulin tolerance test (ITT), in which insulin-induced secretion of ACTH, GH and cortisol is measured. However, because of differences in insulin sensitivity some patients fail achieve sufficient hypoglycaemia to assess pituitary function and colleagues experience severe hypoglycaemia and are at risk for cardiac dysrhythmia, seizure or coma. This risk may be particularly pertinent in the evaluation of older adults. We hypothesized that the hypoglycaemic clamp may be useful in assessing pituitary function in some patients.

Twenty-one normal subjects (14 old [50-76 years] and 7 young [18-36 years]) and 7 hypopituitary subjects were studied. A clamp study was performed in which insulin infusion was given at 2 mU/kg/min and increased to 4 mU/kg/min if the target glucose concentration was not reached after 40 min. Dextrose was infused as needed to clamp the plasma glucose concentration at 2.2 mmol/l for 30 min. On a separate day, 7 young controls also underwent an ITT in which 0.15 U/kg insulin was administered as a bolus intravenous injection at time 0. In both studies, baseline values were taken at - 10, - 5 and 0 min. Samples were then collected every 5 min for plasma glucose and every 10 min for insulin, ACTH, cortisol and GH.

ACTH and GH secretion during each test were similar in younger controls (P = NS) but cortisol secretion was lower during ITT (P < 0.01 vs. clamp). Hypopituitary subjects had significantly less ACTH, cortisol and GH secretion than controls of all ages (P < 0.001 for all). Peak GH secretion was significantly lower in the old controls than in young controls (22 +/- 12 vs. 48 +/- 26 mU/l, respectively; P < 0.01) but significantly higher than the hypopituitary subjects (2 +/- 2 mu/l; P < 0.001).

These data demonstrate that the hypoglycaemic clamp can be used in the assessment of pituitary function and suggest that this technique may be particularly beneficial in the evaluation of GH deficiency in older adults who may not tolerate the ITT.