HYDROCORTISONE REPLACEMENT THERAPY IN CHILDREN AND ADOLESCENTS WITH HYPOPITUITARISM

OBJECTIVE Appropriate replacement doses of glucocorticoid are importan t to determine in primary and secondary adrenal deficiency in children , both to avoid the risks of hypoglycaemia and adrenal crisis associat ed with undertreatment, and to avoid growth suppression and reduced fi nal height potential associated with steroid excess. The aim of this s tudy was to assess how closely conventional twice daily hydrocortisone administration mimics physiological cortisol secretion in a group of ACTH-deficient children and adolescents. PATIENTS Fifty children and a dolescents (aged 3-20 years) were studied who had had surgery +/- radi otherapy to the hypothalamopituitary region for removal of a craniopha ryngioma. The patients were subdivided into two groups: group I compri sed 44 patients known to be ACTH deficient (as determined by glucagon or insulin provocation tests of anterior pituitary function performed after surgery) and maintained on twice daily oral hydrocortisone repla cement; group II comprised six patients known to be ACTH sufficient at their last assessment of pituitary function and not on hydrocortisone replacement. A third group of 10 boys (aged 7-13 years) who had no kn own endocrinopathy were used as controls (group III). MEASUREMENTS Aft er intravenous cannula insertion, blood samples were taken every 2 h f or measurement of plasma cortisol and glucose over a period of 24 h. P atients in group I continued on their usual doses of hydrocortisone, p rescribed at 0800 and 1800 h. RESULTS The mean total daily replacement dose of hydrocortisone for patients in group I was 12.3 mg/m(2)/day ( range, 5.5-18.5). On the conventional twice daily dose regimen, there was a supraphysiological medium plasma cortisol level (629 nmol/l, ran ge 185-1600; z = -3.76, P = 0.0002) 2 h after the morning dose relativ e to the control group, and a prolonged and unphysiological nadir from 1400-1800 h (median at 1600 h 42 nmol/l, range 13-1170; z = -3.13, P < 0.002) before the second dose of hydrocortisone was administered. Co rtisol values were low, and often negligible, during the early hours o f the morning (median at 0600 h 15 nmol/l, range 13-277, z = -4.87, P < 0.00001) and spontaneous hypoglycaemia was documented in one patient on a single 0800 h sample. One patient in group II was shown to be un equivocally cortisol deficient and median cortisol values for the rema ining five suggested a suboptimal rise in plasma cortisol during the e arly hours of the morning. CONCLUSION Our cohort of patients provides an excellent model for the study of glucocorticoid replacement in cort isol-deficient children and adolescents and shows, as in adults, that the aim of mimicking the physiological nyctohemeral secretion of corti sol is difficult to achieve in practice and raises a number of importa nt considerations unique to steroid substitution therapy in this age g roup.