Rahaf Jereisat DISEASES OF THE ADRENAL GLAND - PowerPoint Presentation

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Rahaf Jereisat

DISEASES OF THE ADRENAL GLAND

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Pyramidal in shape. 3- 5 cm in height , 3 cm in width , less than 1 cm

thicK

, Mass

3.5 - 5 g

The

adrenal gland is divided into 2 areas, the cortex and medulla.

The cortex is divided into 3 areas: GFR

the outer zone (

glomerulosa

):

aldosterone synthesis

the central zone (

fasciculata

):

cortisol synthesis

the inner zone (

reticularis

):

androgen biosynthesis.

The adrenal medulla is an extension of the sympathetic nervous system that secretes

catecholamines

into capillaries rather than synapses.

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Glucocorticoids:

Cortisol is the major glucocorticoid in humans.

Levels are highest in the morning on waking and lowest in the middle of the night.

Cortisol levels rises dramatically during stress.

95% protein bound (cortisol-binding globulin/

transcortin

) which is increased by estrogens, free fraction is biologically active

Adrenal Hormones

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Mineralocorticoids:

Aldosterone is the most important one.

Stimulated by angiotensin 2.

Water and Na retention, K and H excretion

Adrenal Androgens:

Secreted in response to ACTH

Probably important in initiation of puberty

Catecholamines

:

Small proportion of NA from medulla, remaining from sympathetic nerve endings

Major source of Adrenaline

Conversion of NA to Adrenaline by Catechol-O-

MethylTransferase

(COMT), which is induced by glucocorticoids.

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A group of clinical abnormalities caused by prolonged exposure to increased amounts of cortisol or related corticosteroids.

Causes:

1.Exogenous:

iatrogenic causes are the

most common

overall causes of Cushing syndrome

2.Endogenous

-uncommon

About 15% of Cushing cases are from ACTH from a source that cannot be located.

Cushing syndrome

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Striae

:

Purple, >1cm

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1.

deposition of adipose tissue in characteristic sites

:

moon

facies

;

interscapular buffalo hump; and mesenteric bed, truncal obesity. 2. hypertension, muscle weakness, and fatigability related to

mobilization of peripheral supportive tissue

; osteoporosis caused by

increased bone catabolism

; cutaneous striae; and easy bruisability

. 3. Women may have acne, hirsutism, and oligomenorrhea

/

amenorrhea

(increased adrenal androgen secretion.)

4.

Emotional changes

range from irritability or emotional lability to severe depression or confusion; even psychosis can occur as well.

5. Glucose intolerance is common, with 20% of patients having diabetes.6. hypokalemia (mineralocorticoid effect) and leukocytosis. Clinically significant hypokalemia is uncommon.

7. delayed wound healing, renal calculi from

increased calcium levels

, and glaucoma. Polyuria is from hyperglycemia.

8. There

is increased susceptibility to infections

because neutrophils exhibit diminished function because of high glucocorticoid levels.

Clinical Findings

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Diagnosis

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The 1-mg overnight dexamethasone suppression test is used to rule out the diagnosis of Cushing syndrome or glucocorticoid

excess: If

you give a milligram of dexamethasone at 11 p.m., the cortisol level at 8 a.m. should come to normal if there is the normal ability to suppress ACTH production over several hours.

The problem with this test is that there can be falsely abnormal or positive tests. Any drug that increases the metabolic breakdown of dexamethasone will prevent its ability to suppress cortisol

levels, like phenytoin

, carbamazepine, and rifampin.

Stress increases glucocorticoid levels. The 1-mg overnight dexamethasone suppression test can be falsely positive in stressful conditions such as starvation, anorexia, bulimia, alcohol withdrawal, or depression.

An abnormality on the 1-mg overnight test should be confirmed with a 24-hour urine-free cortisol. The 24-hour urine-free cortisol is more accurate and is the

gold standard

for confirming or excluding Cushing’s syndrome

.

A third screening test for Cushing is the midnight salivary cortisol. Cushing patients, cortisol is abnormally elevated at midnight.

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The

precise etiology of the Cushing syndrome is established by using ACTH levels, sometimes in combination with high-dose dexamethasone suppression testing. ACTH levels are elevated with either a pituitary source of ACTH such as an adenoma or with an ectopic source.

High dose dexamethasone

suppression testing can distinguish the difference.

The

output of a pituitary adenoma will suppress with high-dose dexamethasone. The output of an ectopic source will not suppress with high-dose dexamethasone.

If the ACTH level is low, then the etiology is most likely from an adrenal

tumor.

When the adrenal gland is the source of increased cortisol production, there is feedback inhibition on the pituitary and the ACTH level is suppressed.

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When there is a low ACTH level, the precise etiology is confirmed with a CT scan of the adrenals.

When there is a high ACTH level, the precise etiology is confirmed with an MRI of the pituitary looking for an adenoma or a CT scan of the chest looking for an ectopic focus.

If neither of these show a lesion or the MRI of the brain is equivocal, then inferior

petrosal

sinus sampling should be done to see if there is increased ACTH coming out of the brain.

Single random cortisol levels are not reliable.

• High plasma ACTH levels = pituitary or ectopic source

• Low plasma ACTH levels = adrenal tumors or

hyperplasia

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Management

Nelson

syndrome

: abnormal

hormone secretion, enlargement of the pituitary

gland,

and the development of large and invasive growths known as adenomas. It occurs in

people

who undergo surgical removal of the adrenal glands for Cushing 

disease

.

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Hypersecretion

of the major adrenal mineralocorticoid, aldosterone.

Hyperaldosteronism

can be divided into the following:

• Primary

aldosteronism

, in which the stimulus for the excessive aldosterone production is within the adrenal gland

• Secondary

aldosteronism

, in which the stimulus is

extraadrenal

The most common cause of primary

hyperaldosteronism

is a unilateral adrenal adenoma (70%).

Bilateral hyperplasia accounts for 25–30%.

Excessive black licorice ingestion can mimic this effect. Licorice has aldosterone-like qualities.

Hyperaldosteronism

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Primary

hyperaldosteronism

is characterized by hypertension and low potassium levels. Most of the other symptoms, such as muscle weakness, polyuria, and polydipsia, are from the hypokalemia.

Metabolic alkalosis occurs because aldosterone increases hydrogen ion (H+) excretion.

Edema

is uncommon with primary hyperaldosteronism because of sodium release into the

urine (Aldosterone escape mechanism).

Clinical Findings

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Adrenal

adenomas are removed surgically.

Bilateral hyperplasia is treated with spironolactone.

Persistent HTN after surgery may occur due to primary HTN or due to vascular changes caused by HTN .

Management.

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PRIMARY (Addison’s Disease)

Endogenous Failure of adrenal gland to secret hormones, slow progressive

Presence of hyperpigmentation due to stimulation of melanocytes by high ACTH .

SECONDARY

most common cause

and its due to

ACTH

deficiency usually due to inappropriate steroids withdrawal

, or pituitary

tumor,

sheehan

, sarcoidosis, histocytosis

TERTIARY

Hypothalamic

causes

ADRENAL CRISIS

Potentially

fatal and

variable in its presentation , usually precipitated by acute illness or replacement of thyroid hormone in un recognized chronic adrenal insufficiency

Adrenal insufficiency

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Primary adrenal insufficiency (High ACTH

)

1-Addison’s disease

Autoimmune ( most common in west)

destruction of all 3 layers , most

pt

have positive 21 – hydroxylase antibodies . 50 % of these pt

may develop autoimmune endocrine disorder (primary

hypothyrodism

, celiac disease type 1 DM ,

hypoparathyrodism )

2-Other causes : TB (mc in developing world), fungal infection HIV/AIDS

Sarcoidosis

, hemochromatosis

Metastatic

carcinoma ( lung cancer , renal cell

cancer ) lymphoma Bilateral adrenal hemorrhage

, sepsis and DIC , anticoagulation protein C deficiency . (e.g. Water-friderichen syndrome)

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Weight

loss

Anorexia

Fatigue

Nausea

and

vomitingDiarrhoea or constipation Hypoglycemia

Skin pigmentation

(

diffuse brown, tan, or bronze darkening of both exposed and unexposed body parts

)

(GLUCOCORTICOID INSUFFICIENCY)

CLINICAL FEATURES in primary disease

(MINERALOCORTICOID INSUFFICIENCY)

Hypotension .

Shock .

Hyponatremia

.

Hyperkalemia.

Chronic: small heart

(ADRENAL ANDROGEN INSUFFICIENCY)

Decreased body hair

Loss of libido especially in female

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All symptoms mentioned above .

Pt

don’t develop hyperpigmentation

.

no hyperkalemia .

SECONDARY DISEASE

ADRENAL CRISIS

-Primary

acute

hypoadrenalism

.

severe fatal symptoms

-Causes: stress, rapid withdrawal of steroids, adrenal hemorrhage, surgery and infection.

-

Circulatory shock with severe hypotension,

hyponatremia

, hyperkalemia.

In some instances hypoglycemia .

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Laboratory

findings

include white blood cell count with moderate neutropenia, lymphocytosis, and eosinophilia; elevated serum potassium and urea nitrogen; low sodium; low blood glucose; and morning low plasma cortisol.

The definitive diagnosis is the

cosyntropin

or ACTH stimulation test.

A cortisol level is obtained before and after administering ACTH. A normal person should show a brisk rise in cortisol level after ACTH administration

.

Differences between primary and secondary adrenal insufficiency:

• Hyperpigmentation (occurs only with primary insufficiency)

• Electrolyte abnormalities

• HypotensionDiagnosis

Adrenal

CT

scan in case of primary disease

Brain MRI in case of secondary disease in absence of steroids intake

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Treatment should not be delayed to wait for results in patients with suspected acute adrenal crisis.

If the patient’s condition permits, it may be appropriate to perform a short ACTH stimulation test before administering hydrocortisone.

Investigations should be performed before treatment is given if the patient’s symptoms suggest chronic adrenal insufficiency

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-

Glucocorticoid replacement (always

):

oral

hydrocortisone 15-20 mg daily in divided doses

.

-Mineralocorticoid replacement (usually): Fludrocortisone 0.05-0.15 mg daily. -Androgen replacement (beneficial in women): DHEA (DeHydro

EpiAndrosterone

) 50mg/day

During stress or illness corticosteroids should be in increase 2 to 3

times. (STRESS DOSE)MANAGEMENT

•

Pateints

with primary adrenal insufficiency require glucocorticoid and mineralocorticoid replacement , but those with central disease require glucocorticoid replacement only

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CAH is

a syndrome associated with increased adrenal androgen production because of enzymatic defects.

CAH is the most common adrenal disorder of infancy and childhood.

CAH arises from autosomal recessive mutations, which produce deficiencies of enzymes necessary for the synthesis of cortisol.

Congenital adrenal hyperplasia (CAH)

Pediatric subject

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C-21 hydroxylase deficiency in 95% of all cases.

C-21

hydroxylase deficiency is associated with reduction in aldosterone secretion in one-third of patients.

Adrenal

virilization

occurs with or without an associated salt-losing tendency, owing to aldosterone deficiency, which leads to

hyponatremia, hyperkalemia, dehydration, and hypotension.

Patients are female at birth with ambiguous external genitalia (female

pseudohermaphrodism

), enlarged clitoris, and partial or complete fusion of the labia.

Postnatally CAH is associated with virilization

. Patients may be male at birth with macrogenitosomia; postnatally this is associated with precocious puberty.

Common Enzymatic Defects Associated with CAH.

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C-11 hydroxylase

deficiency

The

mineralocorticoid manifestations in C-11 deficiency can be ‘biphasic.’ In early infancy, despite having excessive mineralocorticoid hormones, patients sometimes present with relative ‘salt wasting’ (aldosterone deficiency).

This is because some infants have inefficient salt conservation as well as immature aldosterone production. During this phase, infants can present with hypotension and hyperkalemia (very similar to 21 hydroxylase deficiency). Later in life (childhood and adulthood), there is better ability to hold onto salt, so the patient develops the typical C-11 deficiency syndrome: hypertension and hypokalemia.

C-17 hydroxylase

deficiency

characterized

by

hypogonadism

, hypokalemia, and hypertension resulting from increased production of 11-deoxycorticosterone.

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Diagnosis.

CAH should be considered in all infants exhibiting failure to thrive, especially those with episodes of acute adrenal insufficiency, salt wasting, or hypertension.

The most useful measurements are of

serum testosterone

,

androstenedione

, dehydroepiandrosterone,

17-hydroxyprogesterone

,

urinary 17-ketosteroid

, and pregnanetriol.

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A rare, usually benign, tumor that arises from the

chromaffin

cells of the sympathetic nervous system.

The

rule of 10

%:

10% being

extraadrenal

,

10

% malignant, 10% in children,

10% bilateral or multiple (>right side). 10% are not associated with hypertension.

Pheochromocytoma

Surgical subject

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Familial

pheochromocytoma

occurs in 5% of cases

, and is transmitted as an autosomal dominant trait alone or in combination with

MEN type II or III

,

von Recklinghausen neurofibromatosis, or von Hippel-Lindau retinal cerebellar

hemangioblastomatosis

.

In

adults, 80% of pheochromocytomas

occur as a unilateral solitary lesion with 10% being bilateral and 10% extraadrenal. Solitary

lesions favor the right side.

Extraadrenal

pheochromocytomas

are mostly located within the

abdomen and near the celiac, superior mesenteric, and inferior mesenteric ganglia.

Catecholamine Secretion. Secretion of dopamine occurs more in familial syndromes and is not associated with hypertension.

Epinephrine

secretion causes tachycardia, sweating, flushing, and hypertension.

Norepinephrine

is secreted by all

extraadrenal

tumors.

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P

aroxysms

or

crisis:

The

attack has a sudden onset, lasting from a few minutes to several hours or longer.

Headache, profuse sweating, palpitations, and apprehension are common in this setting. Pain

in the chest or abdomen may be associated with nausea and vomiting.

Blood

pressure is elevated with tachycardia in crisis.

40% have elevated blood pressure elevation only during the attack.

Anxiety, tremor, and weight loss are also found. >33% of pheochromocytomas

cause death prior to diagnosis; death is often due to cardiac arrhythmia and stroke.

Other clinical features include orthostatic hypotension and glucose intolerance.

Clinical Findings.

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I

ncreased

amounts of

catecholamines

or catecholamine metabolites in a

24-hour urine

collection.Recently, plasma

metanephrine

levels have been used in conjunction with urinary tests.

Overall, metanephrines are the most sensitive and specific individual test.

Smoking can increase plasma-free metanephrines. The patient must not smoke at least 4 hours before the test.Clonidine should suppress epinephrine levels. Failure of epinephrine levels to fall after clonidine administration is highly suggestive of

pheochromocytoma

. A

clonidine-suppression test

is used when the above screening tests are equivocal.

When the catecholamine or

metanephrine levels are abnormal, the tumor is confirmed with

CT or MRI scan.

Diagnosis

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Note:

Beta

blockers are used if significant tachycardia occurs

after

alpha blockade; beta blockers are not administered until adequate alpha blockade has been established, since unopposed alpha-adrenergic receptor stimulation can precipitate a hypertensive crisis.

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