Transport, Metabolism &Excretion

Adrenocortical hormones are bound to

plasma CHONs

Cortisol-binding globulin (transcortin),

albumin
Slows down elimination long half-life
60% of aldosterone binds to pCHONs
40% free: short half-life
ECF: combined and free
Stress/ACTH secretion
 Adrenocortical hormones are
metabolized in the liver
Glucuronic acid
Bile feces
Circulax -> soluble in plasma -> kidneys
Aldosterone: 6ng/100ml
150 g/day
Cortisol: 12g/100ml
15-20mg/day
Functions of the Glucocorticoids

Effect on Carbohydrates
Stimulation of Gluconeogenesis
cortisol increases enzymes required to
convert AA to glucose in hepatocytes
causes mobilization of AA from
extrahepatic tissues from muscle
inc. gluconeogenesis inc. glycongen
stores
 decreased glucose utilization by cells
depressed oxidation of NADH to NAD+

elevated blood glucose concentration

& adrenal diabetes
secretion of insulin
decreased sensitivity
high levels of fatty acids
50% above normal
Management
saline infusion (1L/hour)
glucocorticoid replacement (100mg
hydrocortisone)
100-200 mg over 24hours (IV or IM)
mineralocorticoid replacement
100-150 g fludrocortisone
adrenal androgen replacement
 electrolytes, glucose, ACTH, cortisol,
aldosterone, and plasma renin activity
ACTH stimulation test
IV soln D5NSS
IV hydrocortisone

~10mg/m2/24hr of cortisone
Acute Adrenal Insufficiency: Adrenal
Crisis
reversal of hypotension & electrolyte
abnormalities
rapid IV infusion of D%NSS
repletion of circulating glucocorticoids
dexamethasone NaPo4 (4mg)
use supportive measures as needed
once stable
dx and tx of precipitating cause
confirm dx
tapering of glucocorticoid therapy
begin mineralo corticoid replacement
Morphology
pituitary gland
Crooke hyaline change
N granular basophilic paler and
homogeneous
accumulation of keratin filaments
adrenal gland
cortical atrophy, diffuse hyperplasia,
macro/micronodular hyperplasia and an
adenoma or carcinoma
bilateral cortical atrophy
diffuse hyperplasia
 hyperplastic cortex: lipid-poor zona reticularis, compact
eosinophilic cells, outer zone of lipid-rich cells
nodules: lipid-rich cells yellow coloring
macronodular hyperplasia: almost entirely replaced by
prominent nodules, mixed, 3cm
micronodular hyperplasia: 1-3mm, darkly pigmented
brown to black micronodules, with atrophic intervening areas
PRIMARY ADRENOCORTICAL NEOPLASMS
malignant/benign
functional/nonfunctional
women aged 30-50
adenomas: yellow tumors, thin or well-developed capsules,
weigh <30g
mx: composed of cells similar to those encountered in the
normal zona fasciculata
 carcinomas: larger than adenomas, unencapsulated,
freq. exceeding 200-300g in wt, anaplastic characteristics
of cancer
functional tumors: adjacent & contralateral adrenal
cortex are atrophic
suppression of endogenous ACTH by high cortisol levels
Management
FINE-CUT CT scanning of adrenal region
excellent visualization of morphology
larger tumors
selective adrenal vein sampling
no obvious lesion on CT scan or unilateral lesion in px older
than 40
comparison of aldosterone levels in IVC and between right
and left adrenal veins
lateralization
Laparoscopic adrenalectomy
mineralocorticoid receptor antagonist spironolactone
12.5-50mg bid (max 400mg/day)
control BP and normalize K
menstrual irregularity, decreased libido, gynecomastia
 eplerenone
more selective MR antagonist
25mg bid (max: 200mg/day)
amiloride
Na channel blocker (5-10mg/day)
dexamethasone
lowest dose possible to control BP
addtl MR antagonist tx
 nonaldosterone-related mineralocorticoid excess
suppressed renin & aldosterone w/ hypokalemic
hypertension
GC/MS profiling of urinary steroid metabolite
inc free cortisol over free cortisone
dexamethasone
CYP11B1, 17A1 def or irreg steroid secretion (DOC-producing
carcinoma)
if normal: consider Liddles syndrome
sensitive to amiloride, but unresponsive to MR antagonist tx
defect due to a constitutively active ENaC
 treatment
surgical excision of adenoma (laparoscopic
adrenalectomy)
dietary Na restriction
administeration of aldosterone antagonist (25-100mg
spirolactone/8hrs)
idiopathic bilateral hyperplasia: surgery is indicated only
when significant symptomatic hypokalemia cannot be
controlledby medical therapy