1. Hypoglycaemia induces glucose intolerance in normal subjects—the ‘Somogyi effect’–and may be responsible for some instances of ‘brittle diabetes’. This effect may be mediated through the growth hormone response to hypoglycaemia, but other possible hormonal mechanisms have not been excluded.
2. Paired 2-h oral glucose tolerance tests have been carried out 2 h after both (a) i.v. saline (control day) and (b) i.v. insulin (test day) in four normal subjects and twenty-seven patients with pituitary and adrenal under- and over-activity. Plasma glucose, insulin, Cortisol and growth hormone have been estimated at half-hourly intervals during the 4 h of each study.
3. A significant Somogyi effect is usually seen only when there is a growth hormone response to insulin-induced hypoglycaemia; hypopituitary subjects do not show the effect.
4. There is a correlation between the extent of the Somogyi effect and the growth hormone response to insulin, using a simple derived index to represent each function (P < 0·05).
5. Insulin secretion in normal subjects tends to be higher on the test than the control day, making inhibition of insulin release an unlikely primary mechanism.
6. The presence or absence of a Somogyi effect could not be related to insulin-induced changes in plasma Cortisol values.
7. Examination of individual cases supports the view that, while growth hormone may be mainly reponsible for the Somogyi effect, yet it is sometimes difficult to explain the effect without invoking other endocrine mechanisms.