Adrenal insufficiency overview

# Overview
Adrenal insufficiency is a clinical state where there is reduced production of adrenocortical hormones. The adrenal cortex is divided into three zones- zona glomerulosa, zona fasciculata and zona reticularis producing mineralocorticoids, glucocorticoids and androgens respectively. Adrenal insufficiency causes glucocorticoid and mineralocorticoid deficiency. Its classified as primary, secondary and tertiary. Its presentation depends on the rapidity and degree of hormone depletion. It can present acutely as adrenal crisis, especially when the body is under stress due infections, trauma etc. If it presents chronically it is called Addisons disease. Treatment consists of lifelong glucocorticoid and mineralocorticoid replacement.

# Historical Perspective
Adrenal insufficiency was first discovered by Thomas Addison in 1849.  

# Classification
Adrenal insufficiency may be classified according to location of pathology into three subtypes primary adrenal insufficiency, secondary adrenal insufficiency, and tertiary adrenal insufficiency. 

# Pathophysiology
It is thought that adrenal insufficiency is the result of multiple etiologies like autoimmune adrenalitis, X-linked adrenoleukodystrophy, chronic glucocorticoid use, adrenal hemoorage etc. The pathophysiology depends on each etiological subtype.     

# Causes
Common causes of adrenal insufficiency include autoimmune adrenalitis and chronic glucocorticoid use.  

# Differentiating adrenal insufficiency from Other Diseases
Addison's disease must be differentiated from other diseases that cause hypotension, skin pigmentation, and abdominal pain such as myopathies, celiac disease, Peutz-Jeghers syndrome, anorexia nervosa, syndrome of inappropriate antidiuretic hormone (SIADH), neurofibromatosis, porphyria cutanea tarda, salt-depletion nephritis and bronchogenic carcinoma.

# Epidemiology and Demographics
Adrenal insufficiency is a rare disorder. It may present in patients of all age groups. The incidence of autoimmune adrenalitis is more common in females in the age groups of 30 to 50 compared to males. Whereas, adrenal crisis does not show any female to male predilection. The most common cause of primary adrenal insufficiency in the developed world is autoimmune adrenalitis. Whereas, in the developing world it is Tuberculosis. The most common cause of central adrenal insufficiency is chronic glucocorticoid use.  

# Risk Factors
Common risk factors in the development of adrenal insufficiency include chronic glucocorticoid use, tuberculosis, anticoagulant use, etc. .

# Screening
There is insufficient evidence to recommend routine screening for adrenal insufficiency. 

# Natural History, Complications, and Prognosis
Common complications of adrenal insufficiency include cardiovascular complications, disturbed sleep, reduced bone mineral density. Prognosis is generally excellent with replacement therapy. 

# Diagnosis

## Diagnostic Study of Choice
The ACTH stimulation test is considered the diagnostic test of choice.

## History and Symptoms
The hallmark of adrenal insufficiency is fatigue. Most patients with adrenal insufficiency present with non specific symptoms. A positive history of fatigue,nausea and abdominal pain is suggestive of adrenal insufficiency. The most common symptoms of adrenal insufficiency include fatigue, anorexia, and weight loss. Common symptoms of adrenal insufficiency include abdominal pain, nausea, and vomiting. Less common symptoms of adrenal insufficiency include diarrhea, arthralgia, and myalgia. 

## Physical Examination
Patients with adrenal insufficiency usually appear dehydrated and weak. Physical examination of patients with primary adrenal insufficiency is usually remarkable for hyperpigmentation of skin. 

## Laboratory Findings
Laboratory findings consistent with the diagnosis of primary adrenal insufficiency include hyponatremia, hyperkalemia, and hypercalcemia, normocytic normochromic anemia, eosinophilia.

## Electrocardiogram
ECG findings seen in adrenal insufficiency are due to hyperkalemia. These changes include peaked T waves, short QT interval, prolonged PR interval, loss of P wave, widened QRS complex. 

## X-ray
X-ray may be helpful in the diagnosis of etiology of adrenal insufficiency, which include tuberculosis, sarcoidosis. 

## Echocardiography and Ultrasound
There are no echocardiography findings associated with adrenal insufficiency. However, an echocardiography may be helpful in the diagnosis of cardiovascular complications of adrenal insufficiency, which include ischemic heart disease, heart failure, and dilated cardiomyopathy. 

## CT scan
CT scan may be helpful in the diagnosis of etiology of adrenal insufficiency, which include adrenal hemorrhage, tuberculous adrenalitis, and adrenal metastasis.

## MRI
An MRI may be helpful in the diagnosis of etiology of adrenal insufficiency, which include tuberculous adrenalitis, autoimmune adrenalitis.  

# Treatment

## Medical Therapy
Pharmacologic medical therapy is recommended among patients with adrenal insufficiency
Pharmacologic medical therapies for adrenal insufficiency include lifelong glucocorticoid and mineralocorticoid replacement therapy. Mineralocorticoid replacement therapy is only used in patients with primary adrenal insufficiency.  

## Surgery
Surgical intervention is not recommended for the management of adrenal insufficiency. 

## Primary Prevention
There are no established measures for the primary prevention of adrenal insufficiency. 

## Secondary Prevention
There are no established measures for the secondary prevention of adrenal insufficiency.