Journal of Clinical Endocrinology & Metabolism, Vol 55, 56-60, Copyright © 1982 by Endocrine Society
The use of theophylline as an in vivo probe of adrenocortical function
ME Geffner, BM Lippe, SA Kaplan and RM Itami
The first step in the stimulatory action of most polypeptide hormones,
including ACTH, is interaction with a specific target organ plasma membrane
receptor. Theophylline, a nonspecific stimulus of several endocrine
processes, does so presumably by circumventing the receptor step and
directly increasing cAMP by inhibiting phosphodiesterase- mediated
hydrolysis. Five patients with adrenal insufficiency, documented by a lack
of cortisol secretion in response to exogenous ACTH, underwent a 4-h iv
infusion of theophylline. In three of the five individuals, a significant
concentration of cortisol was measured in serum for the first time. The
patients who responded included one patient with the syndrome of ACTH
insensitivity, one with ACTH deficiency, and one with idiopathic primary
adrenal failure. Two patients with autoimmune adrenalitis failed to respond
to theophylline, although one was tested very early in the course of her
disease. We also noted that theophylline stimulated renin secretion and, in
one patient with an intact zona glomerulosa, evoked a secondary rise in
aldosterone equal to that produced by diuresis and upright posture. These
studies suggest that the preservation of cortisol responsiveness to
theophylline, after the loss of sensitivity to ACTH, may be relate to
either the duration of the adrenal insufficiency or to the etiological
mechanism. Patients with autoimmune adrenalitis may undergo more rapid and
complete adrenocortical destruction, therapy losing sensitivity to both
ACTH and theophylline, whereas patients with insufficient or ineffective
ACTH stimulation may have receptor failure before the loss of intracellular
function. Thus, responsiveness to iv theophylline may serve not only as a
probe of potential adrenocortical reserve, but also as an indicator of
pathogenesis.
