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).