A state of hyperfunction of adrenal cortex and it i
s caused by:
1. Exogenous cortisol or ACTH. (iatrogenic or
exogenous Cushing's Syndrome)
2. ACTH producing pituitary microadenoma (C
ushing disease) - 70%
3. Primary adrenal tumors. -20%
4. Ectopic ACTH secretion (bronchial, thymic,
pancreatic tumor, medullary thyroid carcino
ma, & pheochromocytoma ) -10%
• Iatrogenic Cushing syndrome is the most com
• Cushing disease caused by microadenoma of t
he pituitary with bilateral adrenal hyperplasia.
Both Cushing’s disease and cortisol-secreting a
drenal tumours are four times more common in
women than men, usually in the young age.
• Primary adrenal tumors account for 20% cases,
usually unilateral and about 50% are malignan
Hypercortisolism due to other causes (als
o referred to as pseudo-Cushing’s syndro
1- Alcohol excess (biochemical and clinical featu
2- Major depressive illness (biochemical features
only, some clinical overlap)
3- Primary obesity (mild biochemical features, s
ome clinical overlap).
1. Truncal obesity with moon face and buffalo hump i
n the interscapular area..
2. Plethoric face with acne and hirsutism.
3. Easy bruising of skin and violaceous striae in the ab
domen and thigh.
4. Proximal myopathy and osteoporosis.
5. Hypertension and DM.
7. Emotional upset and psychosis.
1. Urine free cortisol(> 2 tests): 24-hr timed collectio
n. Normal range depends on assay
2. Overnight dexamethasone suppression test: the pati
ent given dexamethasone 1mg at 2300 hrs then mea
sure plasma cortisol at 0900 hrs. Plasma cortisol > 5
0 nmol/L (> 1.81 μg/dL) suggest Cushing'syndrome
3. Low dose dex. suppression test: the patient given de
x. 0.5 mg qid for two days. Plasma cortisol > 50 nm
ol/L (> 1.81 μg/dL) suggest Cushing'syndrome.
Establishing the presence of Cush
Cushing’s syndrome is confirmed by using two o
f three main tests:
1. Failure to suppress serum cortisol with low do
ses of oral dexamethasone
2. Loss of the normal circadian rhythm of cortiso
l, with inappropriately elevated late-night seru
m or salivary cortisol
3. Increased 24-hour urine free cortisol
Determining the cause of confirm
ed Cushing’s syndrome.
4. High dose dex. suppression test:
used for differentiation between pituitary ad
enoma and other causes, the patient given 2
mg 6-hourly for 48 hrs; sample 24-hr urine c
ortisol at baseline and during second day. Uri
ne cortisol < 50% of basal suggests pituitary-
dependent disease; > 50% of basal suggests e
ctopic ACTH syndrome.
5. Other tests: ACTH level and imaging study of
the pituitary and adrenals.
• Pituitary microadenoma with adrenal hype
rplasia treated by:
1. Surgical removal of the tumor or whole th
2. Bilateral adrenalectomy→ Nelson syndro
me with an invasive pituitary macroadeno
ma and very high ACTH levels causing pi
gmentation. The risk of Nelson’s syndrom
e may be reduced by pituitary irradiation.
• Medical blocking of steroidogenesis by keton
azole or metyrapone. Typical starting doses a
re 500 mg/tid for metyrapone (maximum dos
e, 6 g) and 200 mg/tid for ketoconazole (max
imum dose, 1200 mg).
• Adrenal tumors are treated by:
total adrenalectomy ± chemotherapy.
1. Primary (Addison's disease):
it is rare condition, occurs at any age an
d caused by: autoimmune atrophy, HIV,
CMV, tuberculosis, bilateral hemorrhag
e and secondaries. adrenal failure may b
e part of PAS I (adrenal and parathyroid
failure and mucocutanous candidiasis) o
r PAS II.
2. Secondary adrenal failure: due to pituita
ry insufficiency or after long use of ster
oids that suppress the pituitary.
Gradual adrenal destruction is cha
racterized by an insidious onset
of fatigability, malaise, anorexia,
nausea and vomiting, weight los
s, cutaneous and mucosal pigme
ntation, hypotension, and hypogl
• Acute adrenal insufficiency cause
d by adrenal hemorrhage or by su
dden withdrawal of prolong steroi
• The patient presents with severe h
ypotension and hypoglycemia and
may leads to shock.
Hyperpigmentation of mucous membran
e in Addison's disease
Hyperpigmentation of skin in Add
1. General: hyponatremia, hyperkalemia.
2. ACTH (Synacthen) stimulation test: it is
the best screening test in which plasma
cortisol measured 30 min after im inject
ion of 250 ug ACTH; normally cortisol l
evels should exceed 500 nmol/L (18 ug/
3. ACTH and aldosterone level help in diff
erentiation between primary and second
ary adrenal failure.
1. Corticosteroid replacement in
form of cortisol 15-20 mg/d
or prednisolone 5 -7.5 mg/d (
2/3 on waking and 1/3 at 1500
hrs). The dose should be dou
bled in acute stressful conditi
ons like infection and surgery.
2.Mineralcorticoid replacement in f
orm of fludrocortisone 0.05-0.15
mg/d with adequate salt intake a
nd monitoring the dose by measu
ring electrolytes and blood press
3.Acute adrenal failure (addisonian
crisis) is treated by parenteral ste
roid and normal saline replacem
Secondary adrenal insufficiency
• Hyperpigmentation is absent, other endoc
rine disorders may be present.
• Aldosterone is near normal.
• Iatrogenic type associated with low cortis
ol and ACTH due to prolonged suppressi
on of the pituitary.
• Pituitary insufficiency is treated with cort
isol replacement, iatrogenic type treated b
y gradual tapering of steroid therapy and
some times with ACTH to stimulate the p
ituitary and this may take days to months.
Are tumors that produce, store, and secre
te catecholamines. They are usually deriv
ed from the adrenal medulla (80%) but m
ay develop from chromaffin cells in or ab
out sympathetic ganglia (20%)
It has been estimated that phaeochromocyto
ma accounts for less than 0.1% of cases o
, but is, nevertheless, an important correcta
ble cause of high blood pressure.
Pathology of Pheochromocytoma
• In adults, approximately 80% of pheochr
omocytomas are unilateral and solitary, 1
0% are bilateral, 10% are extraadrenal an
d about 10% are malignant.
• Most of the extraadrenal tumors are locat
ed within the abdomen in association wit
h the celiac, superior mesenteric, and infe
rior mesenteric ganglia. Approximately 1
0% are in the thorax.
• Pheochromocytoma may be part of MEN
type 2a (Sipple's syndrome).
Biochemistry of pheochromocyto
• Most pheochromocytomas contain an
d secrete both norepinephrine and epi
nephrine, and the percentage of norep
inephrine is usually greater than in th
e normal adrenal.
• pheochromocytoma may secrets othe
r hormones like PTH hormone and er
1. Hypertension is the most common
• In about 60% of cases the hyperten
sion is sustained, other 40% have pa
• The hypertension is often severe, an
d may be resistant to treatment with
standard antihypertensive drugs.
2. Panic paroxysms (crisis) occur in 50% of
• The paroxysms may be frequent or sporadi
c occurring at intervals as long as weeks or
• The paroxysm may be precipitated by any a
ctivity that displaces the abdominal contents
or occurs spontaneously.
• The attack may last from a few minutes to s
• The attack characterized by headache, profu
se sweating, palpitations, and apprehension
associated with pallor or flushing. Chest pai
n and abdominal pain may occur. The blood
pressure is elevated.
3. Orthostatic hypotension may occur
as result of diminished plasma volu
me and blunted sympathetic reflex
4. Other features are weight loss, glu
cose intolerance, polycythemia and
• The diagnosis is confirmed by me
asurement of 24 hr urinary excreti
on of vanillylmandelic acid (VM
A), the metanephrines, or free cat
• Localization of the tumor is done
by CT scan or MRI.
• Preoperative control of blood pressure by
alpha blockers like phenoxybenzamine an
d prazocine. Other drugs are calcium cha
nnel blockers and ACE inhibitors.
• Beta-blockers can be used for control of t
achycardia after blocking of alpha recept
• After control of blood pressure the tumor
is removed by surgery.