[49.2] A patient suffering from weakness, fatigue, nausea, and vomiting was
found to have low blood concentrations of Na+ and Cl- and high levels
of serum K+. Physical examination revealed a deep tanning of both
exposed and unexposed parts of the body and dark pigmentation inside
the mouth. The hyperpigmentation in this patient most likely resulted
from which of the following?
A. Increased secretion of ACTH
B. Prolonged exposure of the patient to ultraviolet radiation
C. Excessive ingestion of P-carotene-containing foods
D. Activation of melanocytes caused by medication side effects
E. Inhibition of plasma membrane Na+, K+-ATPase
[49.3] Metyrapone is used to block the mitochondrial 1ip-hydroxylase in the
corticosteroid synthetic pathway and is administered to evaluate
hypothalamic-pituitary-adrenal axis function. Which of the following
results is most likely from this overnight diagnostic test in a healthy
A. Feedback inhibition of cortisol biosynthesis
B. Increase in the levels of cortisol precursors
C. Decrease in ACTH levels
D. Inhibition of adenylate cyclase activity in adrenal cortical cells
E. Inhibition of pituitary function
A nsw ers
D. Prednisone acts as a glucocorticoid hormone analog, giving rise to
Cushing syndrome symptoms after prolonged administration.
A. Hyperpigmentation is a feature of Addison disease, the diagnosis
in this case. Decreased plasma cortisol because of adrenal insuffi-
ciency releases feedback inhibition of ACTH secretion by the pitu-
itary, resulting in elevation of ACTH biosynthesis. The ACTH
precursor peptide is cleaved to also yield melanocyte-stimulating hor-
mone, the factor responsible for hyperpigmentation even in areas not
exposed to sunlight.
B. Inhibition of this step in cortisol biosynthesis relieves feedback
inhibition of its biosynthetic enzymes, leading to accumulation of
cortisol precursors, particularly 11-deoxycortisol. Normal patients
will also have a compensatory increase in the secretion of ACTH.
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