Dr.P.Layegh
Department of Endocrinology
Imam Reza,s Medical center
.
Common Adrenal
Disorders
Blood supply of adrenals
Adrenal anatomy
ADRENAL GLAND
MINERALOCORTICOIDS :
regulate sodium retention and potassium loss and body fluid
GLUCOCORTICOIDS :
act as anti-inflammatory agents; affect metabolism.
ANDROGENS : regulates growth and development of genetalia and
puberty
Adrenal Medulla, Function :
ADRENALINE (EPINEPHRINE) : increases heart rate and blood
pressure.
NORADRENALINE (NOREPINEPHRINE) : constricts arterioles
Regulation of adrenal gland secretion
ACTH
Cortisol Cortisol
Adrenal Dysfunction
Decrease function
• Adrenal insufficiency
Increase function
• Cushing syndrome
• High Cortisol
• Hyperaldosteronism
• High aldestrone
• Pheochromocytoma
• High
catecholamines
• Androgen- producing
tumors
.
Causes of Adrenal insufficiency
• Addison disease( Autoimmune Adrenalitis)
• Infections (TB, meningococcemia)
• Congenital adrenal hyperplasia(CAH)
• Adrenoleukodystrophy
• Adrenal metastases
.
Primary Adrenal Insufficiency
Hyperpigmentation
Dehydration
Hypotension
Hyperkalemia
Hyponatremia
Hypoglycemia
Addison disease
• Autoimmune
• Isolated or associated with other autoimmune disease
• Low Aldestrone & low cortisol , high ACTH and high
renin
• Low sodium , high potasium
• Dx with : ACTH stimulation test Etiology: confirme
with adrenal autoantibodies against 21-hydroxylase
• Treatment : glucocorticoids and mineralocorticoid
.
Addisonian crisis
• Life threatening complication
• Severe vomiting and diarrhoea followed by dehydration
• Low blood pressure and shock
• Hypoglycemia
• Loss of consciousness
• Treatment: IV fliuds+IV hydrocortisone
Congenital Adrenal Hyperplasia(CAH)
• There is cortisol insufficiency and elevated ACTH in all classic forms of CAH( salt wasting & simple virilizing)
• Each disorder results from a deficiency of one of several enzymes necessary for steroid synthesis in adrenals
• Autosomal Recessive (M=F)
• 21-hydroxylase deficiency is the most common form( 1: 16000 newborn)
Steroid biosynthetic enzymes
Cholesterol side chain cleavage(SCC) or (20,22 desmolase)
3-Hydoxysteroid dehydrogenase(3βHSD)
3) 17 hydroxylase and 17,20 –lyase
4) 21-Hydroxylase
5) 11-Hydroxylase
6) Aldosterone synthetase (11,18 hydroxylase & 18 oxidase
CAH due to 21-Hydroxylase Deficiency
90–95% of CAH cases are caused by
21- OHD
CAH (21- hydroxylase deficiency)
Presentations of 21 Hydroxylase CAH
• Ambiguous genitalia in girls and with early pubic hair, precocious puberty and accelerated growth in boys
• Dehydration
• Shock
• Salt-loss presentations with electrolytes imbalance
– Hyponatremia
– Hyperkalaemia
• Hypoglycemia
• Hyperpigementations
Ambiguous genitalia in newborn girls
.
Precocious puberty in boys .
Nonclassical CAH
There is some residual enzyme activity
Non salt losing CAH
present late in childhood with precocious pubic hair and/or clitoromegaly and accelerated growth
Present in adolescence or adulthood with varying virilizing symptoms ranging from oligomenorrhea to hirsutism and infertility
Diagnosis of 21 hydroxylase CAH
Serum electrolytes & glucose Low Na & high K
hypoglycemia
Elevated serum urea due to associated dehydration
Elevated plasma Renin & ACTH levels
Low Cortisol
High 17 – OHP
High androgens especially testosterone level
Low Aldosterone
Chromosome study and pelvic US is needed
Management of 21-hydroxylase deficiency CAH
• Hydrocortisone
• Fludrocortisone 0.05 - 0.2 mg/day
• Triple hydrocortisone duiring stress.
• During adrenal crisis intravenous hydrocortisone and IV fliud
• Surgey for female external genetalia
Cushing’s syndrome
• Cushing’s Syndrome causes
Exogenous cushing
ACTH-secreting tumor of the pituitary
(Cushing’s disease)
Neoplasm of adrenal cortex
Ectopic secretion of ACTH
Frequency of signs and symptoms in Cushing’s syndrome
Sign
or
symptom
Occurrence
% Sign
or
symptom
Occurrence
%
Central obesity 94 Easy bruisability 60
Hypertension 82 Osteoporosis 60
Glucose intolerance 80 Personality
changes
55
Hirsutism 75 Acne 50
Amenorrhea or impotency 75 Edema 50
Purple striae 65 Headache 40
Plethoric faces 60 Poor wound
healing
40
Treatment of Cushing’s syndrome
• Treatment is based on Etiology
• Surgery for neoplasia
.
Primary aldosteronism
causes of primary aldosteronism
• aldosterone-producing adenomas (APAs) and
bilateral adrenal hyperplasia( the most common)
• in rare cases, familial hyperaldosteronism type I
(glucocorticoid-remediable aldosteronism [GRA]),
type II, or type III
• Pure aldosterone-producing adrenocortical
carcinomas
• Ectopic aldosterone-producing tumors
Endocrine Society guidelines 2008
test for primary aldosteronism in the following patients :
● Hypertension and spontaneous or low dose diuretic-
induced hypokalemia
● Severe hypertension (>160 mmHg systolic or >100
mmHg diastolic) or drug-resistant hypertension (defined as
suboptimally-controlled hypertension on a three-drug
program that includes an adrenergic inhibitor, vasodilator,
and diuretic)
● Hypertension with adrenal incidentaloma
● Hypertension and a family history of early-onset
hypertension or cerebrovascular accident at a young
age (<40 years)
● All hypertensive first-degree relatives of patients with
primary aldosteronism
Other Causes of Hypertension and Hypokalemia
• Renovascular Disease
• Diuretic therapy
• Cushing’s Syndrome
• Licorice ingestion
• CAH
• Rarely renin-secreting tumors
• Malignant HTN
Initial Approach to Patient with HTN and
Hypokalemia
• Plasma renin activity
• Plasma aldosterone concentration
Plasma Renin Activity in Hypokalemia and HTN
• Low
Primary mineralocorticoid excess
• High
Diuretic therapy
Reno-vascular HTN
Malignant HTN
Rare – renin-secreting tumor
Plasma Aldosteronism/Plasma Renin Activity
• Test in 8 AM after 2 hr ambulation,
• most antihypertensive medications can be
continued and posture stimulation is not required
• Spironolactone or Eplerenone should be stop at
for 6 weeks
• spironolactone and eplerenone should not be
initiated until the evaluation is completed and the
final decisions about treatment are made.
• Usually do not interfere with test in amiloride
and triamteren user unless the patient is on high
doses.
• ACEI and ARB’s may falsely elevate PRA
• a strong predictor for primary
aldosteronism is an undetectable PRA or
PRC in a patient taking one of these
drugs.
Newborn Screening
Plasma Aldosterone concentration/Plasma
Renin Activity Ratio(PAC/PRA)
In normal persons : 4-10
In Primary aldosteronism : 30-50
PRA low in many with essential HTN but high PAC (>15 ng/dl) and abnormal ratio are uncommon
An elevated plasma aldosterone to renin ratio (PAC/PRA) and an increased plasma aldosterone concentration (PAC) are both required for the diagnosis of primary aldosteronism
Confirmation of Primary Aldosteronism
• Elevated PAC/PRA ratio
• Salt load (after control of HTN and correction of K+)
Dietary for 3 days:
5000mg Na diet or NaCl tablets 1g (2 tid)
Watch out for worsening HTN and hypokalemia
Confirmation of Primary Aldosteronism – Cont’d
In the third day of high salt diet :
• collect 24 hr urine for aldosterone, sodium and creatinine
• 24 hr urine Na+ should be > 200meq to show adequate Na+ loading
• Urine aldosterone > 14 mcg/24 hrs consistent with primary hyperaldosteronism
Confirmation of Primary Aldosteronism – Cont’d
• IV sodium chloride
• 2 liters NS IV over 4 hour
• The PAC will fall below 5 ng/dL in normal subjects,
whereas values above 10 ng/dL are consistent with
primary aldosteronism
Familial Hyperaldosteronism
Type 1 :
glucocorticoid-remediable aldosteronism(GRA)
Secondary to ACTH stimulation of aldosterone secretion
Type 2 :
not ACTH dependent and not suppressible with dexamethasone
They can have APA or IHA or both
Type III: there is a point mutation in and near the selectivity filter of the potassium channel KCNJ5
Differentiating Adrenal Adenoma from
Hyperplasia is important because of
different treatments
Differentiating Adrenal Adenoma from Hyperplasia
• Patients with APA:
More severe HTN
More profound hypokalemia < 3.0 mEq/lit
Higher plasma (>25 ng/dl) and urinary (>30
mcg/24 hrs) levels of aldosterone
Younger age < 50 year
Differentiating Adrenal Adenoma from Hyperplasia
Radiographic Tests
• Hypo-dense unilateral macroadenoma (>1 cm)
likely APA
• Abnormality in both glands likely hyperplasia
although both glands my appear normal on CT or
MRI
Differentiating Adrenal Adenoma from Hyperplasia
Radiographic Tests
• Some investigators suggest low K+, non-suppressible hyperaldosteronism, PAC/PRA ratio > 50 and a unilateral mass can go directly to surgery
• But – in 3 studies of 32 pts. – 11 patients (1/3) had bilateral hyperplasia
• Absence of mass does not exclude APA
• Bilateral lesions do not exclude APA
• CT may be accurate only 50% of time
Differentiating Adrenal Adenoma from Hyperplasia
Adrenal Vein Sampling
• Is Gold standard
• Unilateral disease : is associated with a marked (usually fourfold greater than contralateral adrenal) increase in PAC on the side of the tumor, whereas there is little difference between the two sides in patients with bilateral hyperplasia
• Best performed with continuous infusion of ACTH (50 mcg per hour)
• Measure cortisol in same sample to be sure samples from adrenal veins
• Cortisol from right adrenal 25% higher and 10 times higher than peripheral vein
we recommend AVS when:
• CT scan is normal
• shows bilateral abnormalities
• shows a unilateral abnormality, but the patient is
over age 40
• APA is more likely in patients who have
spontaneous hypokalemia and marked elevations
in aldosterone in blood (eg, >30 ng/dL) or 24-hour
urine collection (eg, >30 mcg).