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Addisonian Crisis is an acute exacerbation ofsymptoms in someone with Addisons disease(namely adrenal insufficiency)

Addisons disease is seen in someone with adeficiency in corticosteroids.

Whereas Cushings syndrome is seen inpatients with excess corticosteroids,

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Addison disease is adrenocortical insufficiency

due to the destruction or dysfunction of the entireadrenal cortex.

affects both glucocorticoid and mineralocorticoidfunction.

The onset of disease usually occurs 90% of bothadrenal cortices are dysfunctional or destroyed.

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Much like Thyroid disease, Addisons diseaseis failure of some aspect the complex system ofhormones and feedback loops

Also, like Thyroid disease, there may bedysfunction as these hormones and messengers

interact with the hypothalamus, pituitary andthe site of hormone release (in this case theadrenal glands)

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Adrenal Cortex1)Mineralocortioids

Aldosterone

Function Regulates electrolyte & fluid homeostasis

2)Glucocorticoids Cortisol Hydrocortisone

Function Stim. gluconeogenesis & K blood glucose Anti-inflammatory Anti-immunity Anti- allergy

3)Androgen Sex hormones

Function Female

Stim. Sex drive

Men Negligible

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SALT,

SUGAR &

SEX

Aldosterone = promotes salt retention Cortisol= sugar Androgens = sex hormones

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Race: no association.

Gender: Idiopathic autoimmune Addison

disease tends to be more common in andchildren.

Age: The most common 30-50 years, but may

present earlier in patients with:

polyglandular autoimmune syndromes,

congenital adrenal hyperplasia (CAH)

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Usually are due to

failure or delay in making the diagnosis or

failure to institute adequate glucocorticoid andmineralocorticoid replacement.

If not treated promptly, acute addisonian crisismay result in death.

May be either de novo, such as by adrenal

hemorrhage, or In the setting of an acute event superimposed on

chronic or

Inadequately treated adrenocortical insufficiency

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y Idiopathic autoimmune adrenocorticalinsufficiency:

- The most common cause.

- Accounts for more than 80% of cases.

Due to -y autoimmune atrophy,

y

fibrosis, andy lymphocytic infiltration of the adrenal cortex, usually

with sparing of the adrenal medulla.

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y Idiopathic autoimmune Addison disease may occur in isolation orin association with other autoimmune phenomena such as:

Schmidt syndrome:The association of Addison disease and Hashimoto thyroiditis.

Polyglandular autoimmune syndrome type 1:The association of Addison disease with hypoparathyroidism andmucocutaneous candidiasis.

Polyglandular autoimmune syndrome type2:

The association of Addison disease with type 1 diabetes mellitusand Hashimoto thyroiditis or Graves disease. It may be associatedwith HLA-B8 and DR-3.

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Chronicgranulomatous diseases:

TB, sarcoidosis, histoplasmosis, blastomycosis,and cryptococcosis could involve the adrenalglands.

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Malignancies:

Malignant infiltration of the adrenal cortices, as with Hodgkinand non-Hodgkin lymphoma and leukemia, may causeAddison disease.

Metastatic malignant disease: Bilateral involvement of theadrenal glands could occur in the setting of metastaticcancer of the lung, breast, or colon or renal cell carcinoma.

Infiltrative metabolic disorders :

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

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y Acquired immunodeficiency syndrome:

as a result of invasion of CMV, Mycobacterium aviumintracellulare, cryptococci, or Kaposi sarcoma.

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Drug-related causes:

-Ketoconazole inhibits the adrenal cytochrome P450steroidogenic enzymes.

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

-Busulphan, etomidate, and trilostane inhibit orinterfere with adrenal steroid biosynthesis.

AbdominalIrradiation.

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Infection

Myocardial infarction

Trauma

Parturition

Septicemia

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The onset of symptoms most often is insidiousand nonspecific.

- Hyperpigmentation of the skin and mucousmembranes often precedes all other symptoms

by months to years. Due to stimulant effect of excess (ACTH) on the

melanocytes to produce melanin. Seen on the sun-exposed areas of the skin,

extensor surfaces, knuckles, elbows and knees inaddition to mucous membranes; dentogingival

margins and buccal areas.- Vitiligo:

common in autoimmune Addison disease as aresult of melanocytes destruction.

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Female patients may show an

absence of axillary and pubic hair

decreased body hair.

Due to loss of the adrenal androgens, a major source ofandrogens in women.

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Diagnosis:

Review of patientss history + skin tanning

Biochemical tests (insufficient cortisol) X-ray (calcium deposit: TB)

Synthetic ACTH ( 250 mg i.v.)

30-60 min

Blood/Urine Cortisol (T0, 30,60)

I. Rapid ACTH test

ACTH stimulation test: most specific

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In acute adrenal crisis,

a blood sample for a random plasma cortisol levelshould be drawn prior to starting hydrocortisonereplacement.

A random plasma cortisol value of 25 mcg/dLeffectively excludes adrenal insufficiency of any

kind.

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II. Long ACTH stimulation test:

synthetic ACTH (i.v or i.m)

48-72 hr

Blood / urine cortisol (T 0, 48, 72)

Interpretation: - primary adrenal insufficiency: no response

- secondary adrenal insufficiency: adequate response

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Urea and electrolyte:- Na, K, and a mild nonanion-gap metabolic

acidosis due to the loss of the Na-retaining & K + H ion-secreting action of

aldosterone.

- BUN and creatinine due to hypovolemia, GFR, and renal plasma flow.

- Hypoglycemia may be present in fasted patients, or itmay occur spontaneously

caused by the peripheral utilization of glucose and insulin

sensitivity. more prominent in children and in patients with secondaryadrenocortical insufficiency.

- Urinary and sweat Na also may be .

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y CBC:- may reveal a normocytic normochromic anemia.

Calcium:- hypercalcemia sometimes seen- resolve on treatment

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Chest x-ray:- normal

except in evidence of TB or fungal infection thatinitially cause Addison disease.

CT scan:- Abdominal CT scan may be normal but- May show bilateral enlargementof the Adrenal

glands in patients with Addison disease TB, fungal infections, adrenal hemorrhage, orinfiltrating diseases involving the adrenal glands.

- In idiopathic autoimmune Addison disease, theadrenal glands usually are atrophic.

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y In case of adrenal crisis:

- IV access should be established urgently.

- IV NS to restore volume deficit & correct hypotension.

(1-2L NS/2hrs )- Some patients may require glucose supplementation.

- Find and Correct precipitating cause

- Hydrocort 100 mg IV bolus stat, and 6hrly for 1 day

- 50mg 6hrly for second day, then tapered down accordingclinical status

- Switch to oral hydrocort when can take orally, eg 20mg8hrly

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As long as the patient is receiving 100 mgHydrocort in 24 hours, no mineralocorticoid replacement is necessary. The mineralocorticoid activity of hydrocortisone in

this dosage is sufficient.

Thereafter, as the hydrocort dose is weaned, mineralocorticoid replacement should be instituted

in doses equivalent to the daily adrenal glandaldosterone output of 0.05-0.20 mg every 24hours.

The usual mineralocorticoid used for thispurpose is 9-alpha-fludrocortisone, usually indoses of 0.05-0.20 mg per day.

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Closely monitor Pts on steroid replacementtherapy for any signs of inadequate replacement (e.g.,

morning headaches, weakness, and dizziness) and

any signs of over-replacement (e.g., cushingoidfeatures). A periodic bone dual-energy x-ray absorptiometry

(DEXA) detecting early osteoporosis in patientswho are over-replaced with maintenance steroids.

Patients should be instructed to 2x / 3x tripletheir steroid replacement doses in stressfulsituations such as a common cold or toothextraction.

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Hypofunction Hyperfunction

Disorder Addisonsdisease

Cushing syndrome

S&S Na+ & H20 loss

Hypotension

Hypoglycemia

Fatigue

Hyperkalemia

Na+ & H20 retention

Wt. gain

Hyperglycemia

Buffalo hump

Moon face

Hypokalemia

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Hypofunction Hyperfunction

Usual tx Glucocorticoids

Meneralocorticoid

Restore fluid

Alter steroid Rx

Surgery

Nrs Dx Fluid volume deficit Fluid volumeexcess

Glucose intolerance

Diet K Na+L K+

L Na+

K K+

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