Supplemental Readings and References
767
effects of a lowered I:G ratio are similar to those of NE
and E on glycogenolysis, gluconeogenesis, lipolysis, and
ketogenesis, the outcome is a great enhancement of the
metabolic response to adrenergic discharge.
In the neonate, neural NE promotes “nonshivering ther-
mogenesis,” i.e., heat production via stimulation of lipol-
ysis and fatty acid oxidation in brown adipose tissue (/J3)
with the support of thyroid hormone. Brown adipose tissue
contains a high density of mitochondria with an “uncou-
pling protein” that allows the cells to oxidize fatty acids
and generate heat as a major product; NE released at nerve
endings stimulates cAMP-mediated lipolysis in these
cells and promotes thermogenesis by this /i3-mechanism
(Chapter 14).
In the adult, nonshivering thermogenesis is probably a
minor source of body heat production because brown adi-
pose tissue is sparse and limited to only a few regions of the
body. Adults depend on neurogenically induced shivering
thermogenesis, which does not depend on adipose lipol-
ysis. However, even in the resting state, catecholamines
stimulate thermogenesis by promoting the thermogenic
effect of thyroid hormone. Thus, when administered to
adults, E increases resting body temperature and oxygen
consumption (/1), in part due to stimulation by E of skeletal
muscle Na+,K+-ATPase activity (/t2).
Disturbances in Adrenal Medullary Function
Because there is considerable overlap in the functions of
the sympathetic nervous system and the adrenal medulla,
elimination of the adrenal medulla would be tolerated as
long as the autonomic nervous system remains function-
ally intact. However, overproduction of adrenal medullary
hormones would be disruptive. Such catecholamine ex-
cesses are seen in patients with tumors of the adrenal
medullary chromaffin cells and/or tumors of chromaf-
fin tissue located outside of the adrenal gland. These tu-
mors are called
pheochromocytomas,
and, although their
incidence is rare, the pathophysiology should be under-
stood for full appreciation of adrenergic catecholamine
functions under normal conditions. One site at which
pheochromocytomas often develop is the organ of Zuck-
erkandl, a collection of pheochromocytes at the bifurca-
tion of the aorta. Familial predisposition to pheochromo-
cytoma can occur due to activating mutations of the
RET
proto-oncogene that cause multiple endocrine neoplasia
type II (Chapter 37) and mutations in the von Hippel-
Lindau tumor suppressor gene. Pheochromocytoma is usu-
ally characterized by intermittent to permanent hyperten-
sion with potentially life-threatening consequences. The
biochemical diagnosis in patients suspected of pheochro-
mocytoma consists
of measuring epinephrine,
nore-
pinephrine, and their metabolites—namely, metanephrine,
normetanephrine, dihydroxyphenylglycol, and vanillyl-
mandelic acid—in a 24-hour urine specimen. Measure-
ment of plasma levels of total free metanephrine has a very
high sensitivity for detecting pheochromocytoma. Tumors
of the pheochromocytoma can be surgically removed.
Supplemental Readings and References
E.-E. Baulieu: Déhydroépiandrostérone (DHEA): a fountain of youth?
J o u r-
n a l o f C lin ica l E n d o c rin o lo g y a n d M e ta b o lism
81, 3147 (1996).
S. R. Bornstein, C. A. Stratakis, and G. R Chrousos: Adrenocortical tumors:
recent advances in basic concepts and clinical management.
A n n a ls o f
In te rn a l M ed icin e
130,759 (1999).
P. R. Casson, S. A. Carson, and St. J. E. Buster: Replacement déhy-
droépiandrostérone in the elderly: rationale and prospects for the future.
E n d o crin o lo g ist
8, 187 (1998).
K. Clément, C. Vaisse, B. S. J. Manning, et al.: genetic variations in the
f33-
adrenergic receptor and an increased capacity to gain weight in patients
with morbid obesity.
N ew E n g la n d J o u rn a l o f M e d ic in e
333, 352 (1995).
A. Ganguly: Primary aldosteronism.
N ew E n g la n d J o u rn a l o f M ed icin e
339,
1828(1998).
T. L. Goodfriend, M. E. Elliott, and K. J. Catt: Drug therapy: angiotensin
receptors and their antagonists.
N ew E n g la n d J o u rn a l o f M ed ic in e
334,
1649(1996).
P. A. Insel: Adrenergic receptors—evolving concepts and clinical implica-
tions.
N ew E n g la n d J o u rn a l o f M ed ic in e
334,580 (1996).
M. New: The prismatic case of apparent mineralocorticoid excess.
Jo u rn a l
o f C lin ica l E n d o c rin o lo g y a n d M e ta b o lism
79, 1
(1994).
W. Oelkers: Current concepts: adrenal insufficiency.
N ew E n g la n d J o u rn a l
o f M ed ic in e
335, 1206 (1996).
D. N. Orth: Cushing’s syndrome.
N ew E n g la n d J o u rn a l o f M ed ic in e
332,
791 (1995).
T. M. Penning: Molecular endocrinology of hydroxysteroid dehydrogenases.
E n d o crin e R eview s
18, 281(1997).
K. Pacak, W. M. Linehan, G. Eisenhofer, etal.: Recent Advances in Genetics,
Diagnosis, localization, and Treatment of Pheochromocytoma.
A n n a ls o f
In te rn a l M ed icin e
134, 315 (2000).
P. M. Stewart: Mineralocorticoid hypertension.
L a n c e t
353, 1341 (1999).
P. C. White: Disorders of aldosterone biosynthesis and action.
N ew E n g la n d
J o u rn a l o f M ed icin e
331, 250 (1994).
P. C. White and P. W. Speiser: Congenital adrenal hyperlpasia due to 21-
hydroxylase deficiency.
E n d o crin e R eview s
21, 245 (2000).
