Prof. Tariq Waseem

ADRENAL DISORDERS - 1

Dr. Tariq Waseem

Professor of Medicine

King Edward Medical University

Mayo Hospital Lahore.

Prof. Tariq WaseemMunich 2011

Prof. Tariq Waseem

ADRENAL GLANDS Adrenal Cortex Adrenal Medulla

Prof. Tariq Waseem

ADRENAL CORTEX Salt Sugar Sex

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SALT

Mineralocorticoids Fluid & Electrolytes balance

Aldosterone (renin from kidneys controls adrenal cortex production of aldosterone)Na retention Water retentionK excretion

Prof. Tariq Waseem

SUGAR GLUCOCORTICOIDS Regulate metabolism & are critical in stress response

CORTISOL responsible for control and & metabolism of:

a. CHO (carbohydrates)

amount of glucose formed amount of glucose released

Prof. Tariq Waseem

CORTISOLb. FATS-control of fat metabolism

stimulates fatty acid mobilization from adipose tissue

c. PROTEINS-control of protein metabolismstimulates protein synthesis in liverprotein breakdown in tissues

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OTHER FUNCTIONS OF CORTISOL

Inflammatory and allergic response

Immune system therefore Prone to infection

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SEX ANDROGENS

hormones which male characteristicsrelease of testosterone

Seen more in women than men

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CASE 1. A 40 years old man presents to his primary

care physician with a month long history of FATIGUE, LIGHT HEADEDNESS, and MUSCLE WEAKNESS. He noticed 5 kg WEIGHT LOSS, over this time, as well as darkening of skin over his knees. The light headedness is particularly severe when he gets out of bed in morning or rises from seated position. During the entire interview, patient appears irritable and agitated.

Prof. Tariq Waseem

CASE SCENARIO CONTINUED…

O/E blood pressure in supine is 115/75, and standing is 90/60 mmHg.

Other positive physical signs : cachexia, pigmentation in palmar creases, elbows, knees, gums and buccal mucosa.

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DIFFERENTIALS

Adrenal insufficiency Chronic fatigue syndrome Depression Eating disorders

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LABORATORY FINDINGS

Eosinophilia, Na – 125, K – 5.9, BSF – 64mg/dl

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Addison’s Disease

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INTRODUCTION

Addison disease is adrenocortical insufficiency due to the destruction or dysfunction of the entire adrenal cortex. It affects both glucocorticoid and mineralocorticoid function. The onset of disease usually occurs when 90% or more of both adrenal cortices are dysfunctional or destroyed.

Prof. Tariq Waseem

Disease tends to be more common in females and children.

Age at onset: Mostly in adults at 30-50 years

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CAUSES:

Idiopathic Autoimmune. The most common cause, accounts for more than 80% of reported cases.

Associations. Schmidt syndrome: AD + Hashimoto thyroiditis. Polyglandular Autoimmune Syndrome Type 1: AD + hypoparathyroidism + mucocutaneous candidiasis.

Polyglandular Autoimmune Syndrome Type2: AD + type 1 DM + Hashimoto thyroiditis or Graves disease.

Prof. Tariq Waseem

CAUSES Chronic Granulomatous Diseases: Tuberculosis Sarcoidosis, Histoplasmosis, Blastomycosis, and Cryptococcosis

Could involve the adrenal glands.

Prof. Tariq Waseem

CAUSES

Malignancies Metastasis: Infiltrative metabolic disorders :

Amyloidosis and hemochromatosis could involve the adrenal glands and lead to primary adrenocortical insufficiency.

HIV

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SIGNS & SYMPTOMS Onset of symptoms often is insidious. Hyperpigmentation of the skin and

mucous membranes often precedes all other symptoms by months to years.

Excess of (ACTH) stimulates the melanocytes to produce melanin.

Appears on the sun-exposed areas of the skin, extensor surfaces, knuckles, elbows and knees in addition to mucous membranes; dentogingival margins and buccal areas.

Vitiligo:In autoimmune Addison due to melanocytes destruction.

Prof. Tariq Waseem

Prof. Tariq Waseem

Prof. Tariq Waseem

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Prof. Tariq Waseem

SIGNS & SYMPTOMS

Dizziness & SyncopeDue to postural hypotensionDue to the combined effects of volume depletion, loss of the mineralocorticoid effect of aldosterone, and loss of the permissive effect of cortisol in enhancing the vasopressor effect of the catecholamines. Myalgias and flaccid muscle paralysis

may occur due to hyperkalemia. Progressive weakness, fatigue, poor

appetite, and weight loss. Gastrointestinal symptoms may include

nausea, vomiting, and occasional diarrhea.

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SECONDARY adrenal insufficiency: Many of the signs and symptoms seen

in primary adrenal insufficiency are also present here

EXCEPT:NO HYPERPIGMENTATIONGI: less common NO salt craving

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DIAGNOSIS

Serum Cortisol

ACTH

PRIMARY ADDISONS

A random plasma cortisol value of 25 mcg/dL or greater effectively excludes adrenal insufficiency of

any kind.

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DIAGNOSIS

Rapid ACTH stimulation test: 1-Blood is drawn in 2 separate tubes for baseline

cortisol and aldosterone values. 2. Synthetic ACTH (1-24 amino acid sequence) in a

dose of 250 mcg (0.25 mg) is given IM or IV. Thirty or 60 minutes after the ACTH injection, 2

more blood samples are drawn; one for cortisol and one for aldosterone.

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Interpreting rapid ACTH stimulation test:

-Two criteria are necessary for diagnosis:

1. An increase in the baseline cortisol value of 7 mcg/dL or more and

2. The value must rise to 20 mcg/dL or more in 30 or 60 minutes, establishing normal adrenal glucocorticoid function.

In patients with Addison disease, both cortisol and aldosterone show minimal or no change in response to ACTH.

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LABS

CHRONIC ADDISON’S

Hyponatremia,Hyperkalemia, HypercalcemiaAzotemiaEosinophiliaAnemiaLow CortisolUnresponsive to

Exogenous ACTH

SECONDARY ADRENAL INSUFFICIENCY

NO hyperkalemia

Hyponatremia often present

Low cortisol LOW ACTHHypoglycemia is

more common

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INVESTIGATIONS OF ADDISON’S

CBC ( eosinophilia, anemia) S/E ( hyponatremia, hyperkalemia, hypercalcemia, Hypoglycemia Low cortisol unresponsive to synthetic ACTH( ACTH STIMULATION TEST – cortisol level fail to

increase in response to exogenous ACTH) ACTH LEVEL TO differentiate primary and

secodnary If autoimmune suspected – adrenal antibodies Tuberculosis causes adrenal calcification X-ray or CT scan abdomen.

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MANAGEMENT

Patients with adrenocortical insufficiency always need glucocorticoid replacement therapy and usually, but not always, mineralocorticoid. Other treatments on the underlying cause.

Prof. Tariq Waseem

MANAGEMENT

Cortisol ( hydrocortisone 15-20 mg PO every am and 5-10 mg every pm)

orPrednisolone 5 mg am and 2.5 mg pm

Fludrocortisone 0.05-0.2 mg PO daily if mineralocorticoid deficient

Increase dose of steroid 2 to 3 fold for a few days during illness or for surgery

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MANAGEMENT: OUTPATIENT

Closely monitor patients for any signs of inadequate replacement (e.g., morning headaches, weakness, and dizziness) and any signs of over-replacement (e.g., cushingoid features).

A periodic bone dual-energy x-ray absorptiometry (DEXA) detecting early osteoporosis in patients who are over-replaced with maintenance steroids.

Patients should be instructed to double or triple their steroid replacement doses in stressful situations such as a common cold or tooth extraction.

Prof. Tariq Waseem

DRUGS AND ADRENAL Ketoconazole inhibits the adrenal cytochrome P450

steroidogenic enzymes.

Aminoglutethimide blocks the early conversion of cholesterol to pregnenolone by inhibiting the 20,22-desmolase enzyme.

Mitotane (O,P'-DDD) blocks adrenal mitochondrial steroid biosynthesis.

Busulphan, etomidate, and trilostane inhibit or interfere with adrenal steroid biosynthesis.

Methadone, perhaps by depleting pituitary ACTH, may cause secondary adrenocortical insufficiency in some patients.

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Which famous American President had Addison’s Disease???

Prof. Tariq Waseem

Prof. Tariq Waseem

Prof. Tariq Waseem

CASE SCENARIO A 15 year old boy presented with 3 days

H/O fever, headache and altered consciousness. On 5th day purpuric rash developed over legs, he had repeated vomiting, oliguria and became agitated. BP recorded at that time was 80/50 mmHg. Two liters of 0.9% saline infusion failed to improve the blood pressure.

What’s the diagnosis? What Complication has occurred?

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ADRENAL CRISIS Adrenal Crisis is not to be confused with

Addison’s disease which results from long-term adrenal insufficiency that develops over months to years, with weakness, fatigue, anorexia, weight loss, and hyperpigmentation as the primary symptoms.

In contrast, an acute adrenal crisis can manifest with vomiting, abdominal pain, and hypovolemic shock.

Prof. Tariq Waseem

Adrenal crisis and severe acute adrenocortical insufficiency are often elusive diagnoses that may result in severe morbidity and mortality when undiagnosed or ineffectively treated.

Prof. Tariq Waseem

In every patient presenting with hypotension and hypovolemic shock and not responding to IV fluid replacement alone Acute Adrenal crisis should be considered especially in those on long term steroid therapy for various indications.

Prof. Tariq Waseem

ANTI-INFLAMMATORY EFFECTS OF CORTISOL Maintain normal vascular response to

vasoconstrictors Resist increases in capillary permeability Inhibit interleukin-2 (IL-2) production by

macrophages Stimulate of neutrophil (PMN) leukocytosis Reduce adherence of macrophages to

endothelium Deplete circulating eosinophils and

lymphocytes Reduce circulating lymphocytes (primarily T

cells)

Prof. Tariq Waseem

Suppression of the hypothalamic-pituitary axis from chronic exogenous steroid use is the most common cause of secondary adrenal insufficiency.

Steroid Withdrawl. Sepsis Surgical stress

Acute Adrenal hemorrhage Waterhouse Fredrickson’s Syndrome

Acute Pituitary Necrosis Sheehan’s Syndrome

Prof. Tariq Waseem

Left untreated, a patient with acute adrenal insufficiency has a dismal prognosis for survival. Therefore, treatment upon clinical suspicion is mandatory. Any delay in management while waiting for diagnostic confirmation cannot be justified.

Prof. Tariq Waseem

TREATMENT Maintain ABC Coma protocol (ie, glucose, thiamine,

naloxone). Aggressive volume replacement therapy

(dextrose 5% in normal saline solution [D5NS]). Correct electrolyte abnormalities : Hypoglycemia (67%) Hyponatremia (88%) Hyperkalemia (64%) Hypercalcemia (6-33%) Use dextrose 50% as needed for

hypoglycemia.

Prof. Tariq Waseem

TREATMENT Administer hydrocortisone 100 mg

intravenously (IV) every 6 hours. During adrenocorticotropic hormone (ACTH) stimulation testing, dexamethasone (4 mg IV) can be used instead of hydrocortisone to avoid interference with testing of cortisol levels.

Administer fludrocortisone acetate (mineralocorticoid) 0.1 mg every day.

Always treat the underlying problem that precipitated the crisis.

Prof. Tariq Waseem

Nymphemberg Palace Munich 2011