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

OBJECTIVE 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 sen sitivity some patients fail achieve sufficient hypoglycaemia to assess pitu itary function and colleagues experience severe hypoglycaemia and are at ri sk for cardiac dysrhythmia, seizure or coma. This risk may be particularly pertinent in the evaluation of older adults. We hypothesized that the hypog lycaemic clamp may be useful in assessing pituitary function in some patien ts. PATIENTS AND MEASUREMENTS Twenty-one normal subjects (14 old [50-76 years] and 7 young [18-36 years]) and 7 hypopituitary subjects were studied. A cla mp study was performed in which insulin infusion was given at 2 mU/kg/min a nd increased to 4 mU/kg/min if the target glucose concentration was not rea ched after 40 in, Dextrose was infused as needed to clamp the plasma glucos e concentration at 2.2 mol/I for 30 in, On a separate day, 7 young controls also underwent an ITT in which 0.15 U/kg insulin was administered as a bol us intravenous injection at time 0. In both studies, baseline values were t aken at -10, -5 and 0 in, Samples were then collected every 5 in for plasma glucose and every 10min for insulin, ACTH, cortisol and GH. RESULTS ACTH and GH secretion during each test were similar in younger cont rols (P=NS) but cortisol secretion was lower during ITT (P <0.01 vs. clamp) , Hypopituitary subjects had significantly less ACTH, cortisol and GH secre tion than controls of all ages (P <0.001 for all), Peak GH secretion was si gnificantly lower in the old controls than in young controls (22 +/- 12 vs. 48 +/- 26 mU/I, respectively; P <0.01) but significantly higher than the h ypopituitary subjects (2 + 2 mu/l; P <0.001). CONCLUSION 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 adu lts who may not tolerate the ITT.