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

in someone with a deficiency in corticosteroids. Whereas Cushings syndrome is seen in patients with excess corticosteroids,

Addison disease is adrenocortical insufficiency

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

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

Also, like Thyroid disease, there may be dysfunction as these hormones and messengers interact with the hypothalamus, pituitary and the site of hormone release (in this case the adrenal glands)

Adrenal Cortex
1)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

SALT, SUGAR & SEX

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

Race: no association. Gender: Idiopathic autoimmune Addison disease tends to be more common in and children. Age: The most common 30-50 years, but may present earlier in patients with:
polyglandular autoimmune syndromes, congenital adrenal hyperplasia (CAH)

Usually are due to

failure or delay in making the diagnosis or failure to institute adequate glucocorticoid and mineralocorticoid replacement.

If not treated promptly, acute addisonian crisis may 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

Idiopathic autoimmune adrenocortical insufficiency:

- The most common cause. - Accounts for more than 80% of cases.

Due to autoimmune atrophy, y fibrosis, and y lymphocytic infiltration of the adrenal cortex, usually with sparing of the adrenal medulla.
y

Idiopathic autoimmune Addison disease may occur in isolation or in 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 and mucocutaneous candidiasis. Polyglandular autoimmune syndrome type2: The association of Addison disease with type 1 diabetes mellitus and Hashimoto thyroiditis or Graves disease. It may be associated with HLA-B8 and DR-3.

 Chronic granulomatous diseases: TB, sarcoidosis, histoplasmosis, blastomycosis, and cryptococcosis could involve the adrenal glands.

 Malignancies: Malignant infiltration of the adrenal cortices, as with Hodgkin and non-Hodgkin lymphoma and leukemia, may cause Addison disease. Metastatic malignant disease: Bilateral involvement of the adrenal glands could occur in the setting of metastatic cancer of the lung, breast, or colon or renal cell carcinoma. Infiltrative metabolic disorders : Amyloidosis and hemochromatosis could involve the adrenal glands and lead to primary adrenocortical insufficiency.

Acquired immunodeficiency syndrome: as a result of invasion of CMV, Mycobacterium avium intracellulare, cryptococci, or Kaposi sarcoma.

Drug-related causes: -Ketoconazole inhibits the adrenal cytochrome P450 steroidogenic enzymes. -Aminoglutethimide blocks the early conversion of cholesterol to pregnenolone by inhibiting the 20,22desmolase enzyme. -Busulphan, etomidate, and trilostane inhibit or interfere with adrenal steroid biosynthesis.

Abdominal Irradiation.

Infection Myocardial infarction Trauma Parturition Septicemia

The onset of symptoms most often is insidious and nonspecific.

- Hyperpigmentation of the skin and mucous membranes 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 in addition to mucous membranes; dentogingival margins and buccal areas.

- Vitiligo:

common in autoimmune Addison disease as a result of melanocytes destruction.

Female patients may show an

absence of axillary and pubic hair decreased body hair.

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

Diagnosis:

Review of patientss history + skin tanning Biochemical tests (insufficient cortisol) X-ray (calcium deposit: TB) ACTH stimulation test: most specific I. Rapid ACTH test Synthetic ACTH ( 250 mg i.v.)
30-60 min

Blood/Urine Cortisol (T0, 30,60)

In acute adrenal crisis,

a blood sample for a random plasma cortisol level should be drawn prior to starting hydrocortisone replacement.

A random plasma cortisol value of 25 mcg/dL effectively excludes adrenal insufficiency of any kind.

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

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 it may occur spontaneously

caused by the peripheral utilization of glucose and insulin sensitivity. more prominent in children and in patients with secondary adrenocortical insufficiency.

- Urinary and sweat Na also may be .

CBC: - may reveal a normocytic normochromic anemia.

Calcium: - hypercalcemia sometimes seen - resolve on treatment

Chest x-ray:
- normal

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

CT scan:
- Abdominal CT scan may be normal but - May show bilateral enlargement of the Adrenal glands in patients with Addison disease

TB, fungal infections, adrenal hemorrhage, or infiltrating diseases involving the adrenal glands.

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

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 according clinical status - Switch to oral hydrocort when can take orally, eg 20mg 8hrly

As long as the patient is receiving 100 mg Hydrocort in 24 hours,

no mineralocorticoid replacement is necessary. The mineralocorticoid activity of hydrocortisone in this dosage is sufficient. mineralocorticoid replacement should be instituted in doses equivalent to the daily adrenal gland aldosterone output of 0.05-0.20 mg every 24 hours.

Thereafter, as the hydrocort dose is weaned,

The usual mineralocorticoid used for this purpose is 9-alpha-fludrocortisone, usually in doses of 0.05-0.20 mg per day.

Closely monitor Pts on steroid replacement therapy 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 2x / 3x triple their steroid replacement doses in stressful situations such as a common cold or tooth extraction.

Hypofunction

Hyperfunction Cushing syndrome

Disorder

Addisons disease

S&S

Na+ & H20 loss Hypotension Hypoglycemia Fatigue Hyperkalemia

Na+ & H20 retention Wt. gain Hyperglycemia Buffalo hump Moon face Hypokalemia

Hypofunction Usual tx
Glucocorticoids Meneralocorticoid Restore fluid Fluid volume deficit

Hyperfunction
Alter steroid Rx Surgery Fluid volume excess Glucose intolerance L Na+ K K+

Nrs Dx

Diet

K Na+ L K+