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