OVERNIGHT METABOLIC FUEL DEFICIENCY IN PATIENTS TREATED CONVENTIONALLY FOR HYPOPITUITARISM

BACKGROUND Hormone replacement in hypopituitary adults attempts to rep roduce normal physiology. Conventional regimens fail to mimic normal h ormone profiles over 24 hours. OBJECTIVE To investigate the metabolic consequences of conventional hormone replacement in hypopituitary adul ts by measuring circulating levels of the major fuels, glucose, non-es terified fatty acids (NEFA), glycerol and 3-hydroxybutyrate (3-OHB) ov er 24 hours in hypopituitary subjects and controls. SUBJECTS Ten GH an d adrenocorticotrophin deficient hypopituitary adults on conventional replacement and 13 controls matched for age, sex and body mass index w ere studied. The patients received replacement with hydrocortisone twi ce daily (at 0730 and 1730 h; mean (range) daily dose 22 (10-30) mg/24 h) but not with GH. Other hormones were replaced as clinically necess ary. MEASUREMENTS Circulating glucose, NEFA, glycerol and 3-OHB levels were measured over 24 hours together with concentrations of cortisol (total and free), GH and insulin, and urinary free cortisol. RESULTS L evels of glucose, NEFA and 3-OHB were lower in patients than controls (mean +/- SEM) (4.3 +/- 0.1 vs 5.3 +/- 0.1 mmol/l, P = 0.0001; 291 +/- 46 vs 448 +/- 48 mu mol/l, P = 0.015; 78 +/- 8 vs 136 +/- 24 mu mol/l , P = 0.035, respectively) before breakfast. This decrease in glucose, NEFA and 3-OHB was observed in the patient group throughout the night , from midnight to breakfast. For NEFA, the decrease persisted through out the 24 hours. Glycerol did not differ significantly in patients an d controls. Integrated levels of total and free plasma cortisol, and 2 4-hour urine cortisol excretion, were normal in patients but total and free plasma cortisol concentrations overnight were markedly decreased (overnight area under the curve (AUC) of total cortisol: 440 +/- 154 vs 1593 +/- 267 nmol/l h, P = 0.0024; overnight AUC of free cortisol: 24 +/- 8 vs 161 +/- 26 nmol/l h, P = 0.0001). GH levels were low throu ghout the whole 24 hours in the patient group (24-hour AUC: 10.6 +/- 5 .1 vs 74.6 +/- 19.6 mU/l h, P = 0.008). CONCLUSIONS Hypopituitary adul ts on conventional hormone replacement regimens have low concentration s of metabolic fuels, glucose, non-esterified fatty acids and 3-hydrox ybutyrate throughout the night, possibly related to GH deficiency or t o decreased overnight circulating cortisol levels. This overnight fuel deficiency may underlie the mechanism for the non-specific symptoms, such as fatigue and headache in the early morning, which are frequent in this group of patients.