Evaluation of Pituitary Function in the Fatigued Patient: a Review of 59 Cases

Objective: The aim of this study was to review the results of dynamic pituitary testing in patients presenting with fatigue.

Methods: We reviewed clinical histories and insulin tolerance test (ITT) results of 59 patients who presented with fatigue and other symptoms of glucocorticoid insufficiency over a 4-year period. All patients referred for ITT had an early-morning cortisol level of <400 nM and a low or normal ACTH level.

Results: Peak cortisol and GH responses following insulin-induced hypoglycaemia were normal in only seven patients (12%). Median age of the remaining 52 patients was 47 years (range, 17-67 years); all but five were female. Common presenting symptoms were neuroglycopaenia (n = 47), depression (n = 37), arthralgia and myalgia (n = 28), weight gain (n = 25), weight loss (n = 9), postural dizziness (n = 15) and headaches (n = 13). Other medical history included autoimmune disease (n = 20; particularly Hashimoto's thyroiditis, Graves' disease and coeliac disease), postpartum (n = 8) and gastrointestinal (n = 2) haemorrhage and hyperprolactinaemia (n = 13). 31 subjects had peak cortisol levels of <500 nM (suggestive of ACTH deficiency; 18 of whom had levels < 400 nM) and a further six had indeterminate results (500-550 nM). The remaining 15 subjects had normal cortisol responses (median 654 nM; range, 553-1062 nM) but had low GH levels following hypoglycaemic stimulation (5.9 mU/l; 3-11.6 mU/l).

Conclusion: Our results suggest that patients presenting with fatigue and symptoms suggestive of hypocortisolism should be considered for screening for secondary adrenal insufficiency, particularly in the presence of autoimmune disease or a history of postpartum or gastrointestinal haemorrhage. Whether physiological glucocorticoid replacement improves symptoms in this patient group is yet to be established.