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Adrenocortical Insufficiency - Causes, Clinical Manifestations, Diagnosis, and Treatment

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Adrenocortical Insufficiency - Causes, Clinical Manifestations, Diagnosis, and Treatment

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Adrenocortical insufficiency manifests when the adrenal glands do not produce the required amount of hormones like cortisol, androgens, and aldosterone.

Written by

Dr. Prerana G

Medically reviewed by

Dr. Muhammad Zubayer Alam

Published At August 8, 2022
Reviewed AtFebruary 21, 2023


The adrenal glands are an essential part of the endocrine system (network of organs and glands that release hormones directly into the bloodstream). The hormones secreted by the adrenal glands perform some of the vital functions in the body. Located right above the kidneys, its primary function is to secrete hormones responsible for flight or fight response. The adrenal gland has an outer cortex (which produces cortisol, aldosterone, androgens) and an inner medulla (which produces adrenaline and noradrenaline). Like any other organ in the body, the adrenal glands are prone to conditions that interfere with their function. These glands increase or decrease their hormone production depending on the underlying pathology. Of these, a group of diseases causes insufficient hormone production from the adrenal cortex.

What Is Adrenocortical Insufficiency?

The adrenocortical insufficiency or hypofunction occurs when the body does not produce enough adrenal hormones. To know the effects of their deficiency, it is necessary to understand the function of these hormones. The primary function of cortisol is to respond to stress, glucose metabolism, and anti-inflammatory actions. Aldosterone helps in long-term blood pressure modulation, and androgens help in reproductive development. The deficiency of these hormones disturbs several metabolic and reproductive functions. The patterns of adrenocortical insufficiency can be due to problems inside the gland or through an external influence from the pituitary and hypothalamus glands.

What Causes Adrenocortical Insufficiency?

As discussed above, adrenocortical insufficiency can be broadly classified as primary and secondary.

A. Primary Insufficiency -

1. Due to Loss of Cortex -

The loss of the adrenal cortex can be due to a congenital condition (disease or abnormality present at birth). Congenital adrenal hypoplasia is characterized by a malformation or underdevelopment of the adrenal cortex. Other self-destructive conditions like autoimmune diseases destroy the adrenal cortex's functioning cells, mistaking them as foreign invaders. The cortical cells fail to produce hormones in sufficient quantities in both situations.

2. Infections -

Infections, particularly tuberculosis, accounts for 90 % of the cases of adrenocortical insufficiency. The condition known as tuberculous adrenalitis is associated with active disease. But with the development of antituberculous drugs, the situation has become less common. Amongst the fungi, Histoplasma infection may result in adrenocortical insufficiency. Additionally, patients with AIDS (acquired immunodeficiency syndrome) are at risk for developing this condition due to infection from other opportunistic pathogens.

3. Cancer and Other Disorders - The adrenal glands are a common site for the dissemination of cancer from other sites (metastasis). These tumor cells destroy the adrenal cortex to produce adrenal insufficiency. Metastasis of cancer of the lungs, breast, and skin can lead to adrenal crisis. Other conditions include iron overload, sarcoidosis (autoimmune disease), amyloidosis (build-up amyloid, a type of protein in organs), etc.

4. Metabolic Failure in Hormone Production - Rarely, adrenal hyperplasia (overgrowth of the glands), drug and steroid-induced cell function can lead to adrenocortical insufficiency.

Types of Primary Adrenocortical Insufficiency:

The primary adrenocortical insufficiency can be further divided into acute and chronic based on the course of the disease.

1. Primary Acute Adrenocortical Insufficiency -

It is a sudden reaction of the body due to an extreme lack of cortisol levels. It manifests when the body cannot meet immediate steroid requirements. This condition occurs in a variety of clinical scenarios. It is common in patients who are on external steroid therapy; a rapid withdrawal or failure to increase the dose may precipitate this condition. Also, massive adrenal hemorrhage (bleeding) that destroys the cells causes the adrenocortical crisis. An uncommon syndrome known as Waterhouse-Friderichsen Syndrome leads to adrenal hemorrhage and other fatal changes.

2. Primary Chronic Adrenocortical Insufficiency: Addison’s Disease

Addison’s disease is a relatively uncommon condition caused by progressive destruction of the adrenal cortex. This condition manifests over time and is characterized by a pattern of symptoms. Diseases that attack the adrenal glands are described above. But more than 90 % of the underlying conditions can be attributed to autoimmunity, tuberculosis, AIDS, and cancer metastasis. The disease does not show any signs or symptoms until 90 % of the cells are destroyed.

B. Secondary Insufficiency -

The master gland of the human body, the pituitary gland, is responsible for the functioning of other endocrine glands. The hypothalamus, pituitary, and adrenal glands have a coordinated function. ACTH (adrenocorticotropic hormone) is released from the pituitary gland with instructions from the hypothalamus gland. It controls the release of cortisol from the adrenal glands. Any disorders of the hypothalamus and pituitary that influence the adrenal glands can lead to its hypofunction. These disorders may be in the form of cancer, infection, irradiation, etc.

What Are the Manifestations of Adrenocortical Insufficiency?

A. Symptoms of Addison’s Disease -

The symptoms appear over time and have systemic and oral manifestations. It affects both males and females equally. Addison’s disease can be life-threatening because of the insidious onset of symptoms.

Symptoms include:


1. General - Progressive weakness, fatigue, loss of appetite, muscle and joint pain, and weight loss.

2. Gastrointestinal - Nausea, vomiting, diarrhea, anorexia, difficulty in swallowing, salt cravings.

3. Dermatologic - Hyperpigmentation is a classical sign of Addison’s disease. It is described as bronzing of the skin, particularly in the sun-exposed areas and pressure points. This is due to increased ACTH levels that stimulate pigment-producing cells or melanocytes. Vitiligo (loss of skin pigmentation) can be seen in a few patients due to autoimmune destruction of melanocytes. Thinning of hair and brittle nails are other symptoms.

4. Psychiatric - Includes mood changes, lack of motivation, and behavioral changes.

5. Sexual - Amenorrhea, loss of libido, loss of pubic hair, and sexual dysfunction.

6. Other - Low blood pressure, hypoglycemia, loss of sodium and potassium, etc.

Oral Manifestations:

Sometimes pigmentation in the oral cavity can be the first presenting signs of the disease. In the oral cavity, signs of hyperpigmentation are evident. Brown patches on the gums, mucosa, palate, and tongue are seen.

B. Symptoms of Acute Adrenocortical Insufficiency

The acute adrenocortical crisis is a life-threatening condition. If not treated on time, death occurs rapidly.

Symptoms include:

1. Abdominal pain, loss of appetite, nausea, vomiting.

2. Confusions, dizziness, loss of consciousness, coma.

3. Vascular collapse, low blood pressure, low blood sugar.

4. Rapid heart rate, rapid respiratory rate.

How Is Adrenocortical Insufficiency Diagnosed?

The diagnosis can be made by clinical and laboratory examinations.

A. Clinical Examination - Studying clinical signs and thorough history of symptoms.

B. Lab Tests - ACTH stimulation test, cortisol levels, blood sugar levels, sodium and potassium levels.

C. Imaging - MRI (magnetic resonance imaging) and CT (computed tomography) scan to rule out cancer metastasis.

What Is the Treatment for Adrenocortical Insufficiency?

Treatment depends on identifying the underlying condition. Patients may require permanent hormonal replacement therapy even after treating the underlying condition. In chronic adrenocortical insufficiency, hydrocortisone, prednisone, methylprednisolone is prescribed. Fludrocortisone is a drug prescribed for replacing aldosterone in Addison’s disease. Sodium-rich diets can be beneficial for some people. In the case of acute adrenocortical insufficiency, an emergency intravenous (IV) or intramuscular (IM) hydrocortisone is given immediately. Intravenous fluids and hospital monitoring are required.


Adrenocortical insufficiency occurs when the hormones produced by the adrenal cortex are at low levels. This condition is caused due to autoimmunity, infections, cancer metastasis of other organs, and metabolic failures. Diseases of the hypothalamus and pituitary glands can also lead to this crisis. Addison’s disease is a common presentation of adrenocortical insufficiency. Chronic cases require hormone replacement therapy. Acute adrenocortical insufficiency can be fatal if steroids are not given right away. However, the condition is uncommon and can be managed if intervened early.

Dr. Muhammad Zubayer Alam
Dr. Muhammad Zubayer Alam

Pulmonology (Asthma Doctors)


adrenal glandadrenal insufficiency
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