Disease of adrenal gland

DR. UMALKHAYR OMAR

Adrenal gland

 Adrenal gland is divided into two areas ,the cortex

and the medulla
 The cortex subdivided into three areas
 Outer zone (glomerulosa)-is site of aldosterone
synthesis –angiotensin 2
 Central zone (fasciculata) –is site of cortisol
synthesis-ACTH
 Inner zone (reticularis)-is site of androgen synthesis
-ACTH
 Medulla –release epinephrine under control of
autonomic nervous system
Cont.

 The disorder of hyper functioning of the gland is associated with the following specific
hormones :
1. Increase cortisol –Cushing syndrome
2. Increased aldosterone – hyperaldestronism
3. Increase adrenal androgen –virilization of women
Hyper functioning of the gland
 CUSHING SYNDROME

 Def. A group of clinical abnormalities caused by prolonged exposure to increased

amounts of cortisol or related corticosteroids .
 Causes:
1. ACTH dependent
 Pituitary adenoma secreting ACTH( Cushing disease)
 ectopic ACTH syndrome (bronchial carcinoid ,small cell lung carcinoma, other neuro-
endocrine tumor)
 Iatrogenic (ACTH therapy)
Cont.

2.Non-ACTH dependent
 Iatrogenic (chronic glucocorticoid therapy)
 Adrenal adenoma
 Adrenal carcinoma
Signs and symptoms
Pathophysiology of Cushing syndrome
Diagnosis

 Several tests are usually combined to establish the diagnoses

 Whether the patient has Cushing syndrome and
 to define the cause
 To establish the diagnoses is use 1mg overnight dexamethasone suppression test and/or
24hr urine free cortisol
 To establish precise etiology of cortisol excess are ACTH level, high dose
dexamethasone test ,CT and MRI scanning
Cont.
Cont.
Management

 Depends on the etiology ;can be treated surgical or medical. unrespectable adrenal tumor
are treated with ketoconazole or metyrapone.
Hyperaldosteronism

 Def.is syndrome associated with hyper secretion of the major adrenal mineral corticoid
,aldosterone.
 The normal function of aldosterone is to reabsorb the sodium and excrete potassium and
acid (H+)
 Hyperaldosteronism can be divided
1. Primary aldosteronism
2. Secondary aldosteronism
Cont.

 Causes of primary aldosteronism :

1. Unilateral adrenal adenoma (70%)
2. Bilateral hyperplasia (25%-30%)
 Causes of secondary aldosteronism
1. Inadequate renal perfusion ; e.g. diuretics ,heart failure , etc.
2. Renin secreting renal tumor (very rare )
Secondary aldosteronism

Decrease intravascular
volume
Secondary
aldestorenism

Increase renin

Increase sodium
retention
Increase aldosterone
production
Primary aldosteronism

Increase aldosterone
production
Primary
aldosteronism

Increase sodium
retention

Decrease renin

Increase
intravascular volume
Difference between primary and secondary
aldosteronism

Primary aldosteronism Secondary aldosteronism

 Hypertension  Hypotension
 Low renin level  High renin level
 No edema  +edema
Clinical features

 Hypertension/hypotension
 Hypokalemia
 Polyuria ,polydipsia ,muscle weakness
 Metabolic alkalosis (tetany )
Diagnosis

 The preliminary screen for hyperaldosteronism is plasma aldosterone concentration and

plasma renin activity .
 Positive screen is PAC/PRA>20:1 and a PAC>15
 Low potassium and high sodium level
Management

Primary aldosteronism
 Adrenal adenoma are removed surgically
 Bilateral hyperplasia is treated spiroloctone which blocks aldosterone
Syndrome of adrenal androgen excess

 Def. excess androgen result from excess production of dehydroepiandrosterone

(DHEA) ,and androstenedione which are converted to testosterone in extra glandular
tissues .
 The elevated testosterone accounts for most androgen effect
 Clinical symptoms and signs: hirsutism, oligomenorrhea , acne, and virilization .
 Causes by congenital adrenal hyperplasia ,adrenal adenoma ,adrenal carcinoma
Congenital adrenal hyperplasia

 Def. CAH is syndrome associated with increased adrenal androgen production because of enzymatic
defiance
 Commonest enzymatic defiance associated CAH is 21-OH defiance
 Relative decrease in aldosterone
 Relatively decrease cortisol
 Adrenal androgen excess
 Female :ambiguous genitalia
 Male :normal ,later hypotension
 Diagnosis :elevated progesterone
 Treatment :hydrocortisone replacement
Cont.
CLINICAL MANIFESTATIONS

 The clinical spectrum of disease ranges from the most severe to mild forms, depending
on the degree of 21-hydroxylase deficiency (21OHD).
 Females with the classic form (salt-losing and non-salt-losing) present with genital atypia
 Males with the salt-losing form who are not identified by neonatal screening present with
failure to thrive, dehydration, hyponatremia, and hyperkalemia typically at 7 to 14 days
of life.
 Males with the classic non-salt-losing form who are not identified by neonatal screening
typically present at two to four years of age with early virilization (pubic hair, growth
spurt, adult body odor).
Treatment

 The goals of therapy for adults with classic 21-hydroxylase deficiency (21OHD) include
providing glucocorticoids in sufficient doses to replace the cortisol deficiency
plus mineralocorticoids to restore blood pressure, serum electrolyte concentrations, and
extracellular fluid volume to normal.
Hypo function of the gland

Adrenal insufficiency
 Def. Adrenal insufiency can be divided into primary adrenocorticoid insufficiency
(Addison disease )and secondary failure in elaboration of ACTH
 Etiology :
1. Secondary (dec.ACTH).
 Withdrawal of suppressive glucocorticoid therapy
 Hypothalamic or pituitary disease
Cont.

2.Primary (increase ACTH) Addison's disease:

 Autoimmune
 TB
 HIV/AIDS
 Metastatic carcinoma
 B/L adrenalectomy
 Lymphoma
 Intra adrenal hemorrhage
 Amyloidosis
 Hemochromatosis
Cont.

3.Corticosteroid biosynthetic enzyme defect

 Congenital adrenal hyperplasia
 Drugs (metyrapone,ketacanazole )
Cont.;

 Hypotension
 Hyponatremia
 Fatigue
Clinical features
Clinical Cortisol Mineral ACTH-excess Adrenal
features defiance corticoid androgen
insuffiency insuffiency
Weight loss Hypotension Pigmentation
Of sun exposed
areas

Weakness Shock
Nausea/ Hyponatremia
vomiting

Postural Hypokalemia
hypotension
Hypoglycemia

Hyponatremia
Cont.

 If there is adrenal crisis ,the patient may present(exacerbation of adrenal insufiency );

 Circulatory shock with severe hypotension
 Hyponatremia
 Hyperkalemia
 Hypoglycemia
 Hypercalcemia
 Nausea/vomiting
 Abdominal crams
 Un explained fever
Diagnosis

 ACTH administration and measurement of cortisol

 Low sodium and high potassium level
 Morning low serum cortisol
Treatment
 Hydrocortisone +/-fludrocortisone
 Iv fluid saline
 Identified and treat underlying cause
Pheochromocaytoma

 Def. a rare usually benign tumor that arises from the chromaffin cells of sympathetic
nervous system.
 The rule of 10% applies in pheochromocytoma
 10% extra adrenal ,10%malignant ,10%in children ,10%B/L or multiple (right sided )and
10% are not associated with hypertension .
Etiology and clinical features

 Most of the cases are sporadic(80%)

 Familial :associated MEN 2
 Tumors
Clinical features :
 50%suffer from paroxysmal HTN ;the rest have sustained HTN
 Classic triad :episodic pounding headache ,palpitation/tachycardia ,diaphoresis
 Tremor ,anxiety ,chest or abdominal pain ,N/V ,blurred vision ,weight loss
Cont.;

 Other signs :orthostatic hypotension ,papilledema ,dilated cardiomyopathy

 Symptoms may trigger by stress ,exertion ,anesthesia
Investigations
 Urine cathocolamines
 CT scan abdomen
Treatment

 Surgical removal of tumor with ICU care pre and post operative
 Adequate pre-op preparation
 Alpha –blockers for BP control like phenoxybenzamine
 Beta blockers for HR control
 Catecholamine synthesis inhibitors like metyrosine
 Volume restoration with vigorous salt loading and fluids
 Rescreen urine 1-3moths post-op
Quiz

The following statement about adrenal gland physiology are true

A. ACTH normally controls the adrenal secretion of aldosterone
B. ACTH increases adrenal androgen and cortisol secretion
C. The plasma cortisol concentration normally peaks in the evening
D. Hyperglycemia increases the rate of cortisol secretion
E. Cortisol enhances gluconeogenesis and lipogenesis from amino acid
Cont.

A cushingoid appearance would be in expected finding in

A. Chronic alcoholic abuse
B. Pituitary macro adenoma
C. ACTH-secreting bronchial carcinoma
D. Adrenocortical adenoma
E. Fludrocortisone therapy
Cont.

Adverse effects of oral corticosteroids therapy including

A. Peptic ulcer
B. Hypertension
C. Avascular bone necrosis
D. Pseudo goat
E. Insomnia
Cont.

Conns syndrome (primary hyperaldesteronism )

A. Peripheral edema usually present
B. Proximal myopathy is due to hypokalemia
C. Polyuria and polydipsia are characteristics
D. Diabetic mellitus often present
E. Hypertension is associated with hypernatremia
Cont.

In treatment of primary adrenocortical insufficiency

A. Oral hydrocortisone is glucocorticoid of choice
B. Fludrocortisone is usually unnecessary unless there is hyperkalemia
C. The dose of cortisol shouldn't be increased without medical advise
D. Adrenal crisis require intravenous crystalloids and hydrocortisone
E. Typical maintenance compromise at least 50mg cortisol daily
Cont.

Features of congenital adrenal hyperplasia include

A. 21-hydroxylase enzyme deficiency
B. Decreased plasma cortisol and aldosterone concentration
C. Increased mortality in male infants
D. Growth acceleration and precocious puberty
E. Increased plasma 17-alpha-hydroxyprogestrone
Cont.

 A 40y/o alcoholic male is being treated for tuberculosis, but he has not complaint with
his medication. He complains of increasing weakness and fatigue .he appears to have lost
weight and his blood pressure is 80/50mmHg.there is increase pigmentation over the
elbows. Cardiac exam is normal. The next step of the evaluation
Cont.

A. CBC with iron and iron binding capacity

B. Erythrocyte sedimentation rate
C. Early morning serum cortisol and cosyntropin stimulation
D. Blood culture
Cont.

In the advanced stage of this disease, the most likely electrolyte abnormality will be
A. Low serum sodium
B. Low serum potassium
C. Low serum sodium and high serum potassium
D. Low serum potassium
Cont.

 The treatment of choice for this patient is

A. Hydrocortisone once per day
B. Hydrocortisone twice per day plus fludrocortisone
C. Hydrocortisone only during periods of stress
D. Daily ACTH