Evidence for the existence of a
hormone that is stimulable by
adrenocorticotropic hormone (
ACTH) and capable of causing
hypertension has been collected in several patients. This
hormone is not a known
mineralocorticoid or
glucocorticoid. The hypothesis that a
steroid can produce
hypertension was tested in an 18-year-old man with
dexamethasone-suppressible
hypertension. During
dexamethasone treatment, when
aldosterone secretion was suppressed, less than normal and the patient was normotensive,
steroids were given by constant infusion in an attempt to reproduce the
hypertension of the
dexamethasone-free state.
Hypertension was not caused by 5 days of administration of
aldosterone,
18-hydroxydeoxycorticosterone (18-OH-DOC) at 1 mg/day, or
deoxycorticosterone (DOC) at 30 mg/day. However,
sodium retention and
potassium loss were observed during infusion of
aldosterone and DOC.
Hypertension was produced within 5 days during infusion of
ACTH or oral
metyrapone. The hypertensive effect of the
metyrapone was eliminated by the additional treatment with
aminoglutethimide. These studies suggest that an
ACTH-dependent
steroid rather than
aldosterone, 18-OH-DOC, or DOC may be the cause of the
hypertension in this patient. Study of a 3-year-old child who presented with short stature,
hypertension, hypokalemic
alkalosis, suppressed
renin and
ACTH, and decreased excretion of all known
steroids suggested excessive secretion of a pressor
hormone. Reversal of the
hypertension and hypokalemic
alkalosis occurred when
spironolactone was administered.
ACTH exacerbated the clinical and biochemical abnormalities, suggesting that the secretion of the unknown factor was dependent on
ACTH. A study of the urinary
steroids revealed remarkably low excretion of
aldosterone and
cortisol. Plasma levels of
ACTH were low. The low production of
aldosterone was not associated with the increased excretion of precursor metabolites. These finding suggest the secretion of an unknown
hypertensive factor of remarkably high potency, with the ability to suppress the secretion of both
renin and
ACTH.