What is the Difference Between Primary and Secondary Adrenal Insufficiency

Primary and secondary adrenal insufficiency are two types of adrenal insufficiency. Adrenal insufficiency starts when the adrenal glands don’t make enough of the hormone cortisol. There are two adrenal glands located just above the kidneys. Adrenal glands work with the hypothalamus and pituitary glands to make cortisol hormone. Cortisol helps break down fats, proteins, and carbohydrates in the body.

The key difference between primary and secondary adrenal insufficiency is their cause. Primary adrenal insufficiency occurs when adrenal glands do not make enough cortisol due to damage in the adrenal glands, while secondary adrenal insufficiency occurs when adrenal glands do not make enough cortisol as the pituitary gland doesn’t make enough of the hormone ACTH.

CONTENTS

1. Overview and Key Difference
2. What is Primary Adrenal Insufficiency
3. What is Secondary Adrenal Insufficiency  
4. Similarities – Primary and Secondary Adrenal Insufficiency
5. Primary vs Secondary Adrenal Insufficiency in Tabular Form
6. Summary – Primary vs Secondary Adrenal Insufficiency
7. FAQ – Primary and Secondary Adrenal Insufficiency

What is Primary Adrenal Insufficiency?

Primary adrenal insufficiency, or Addison’s disease, occurs when the adrenal glands produce too little cortisol and aldosterone due to damage to the adrenal glands. This is usually an autoimmune condition. The other causes include tuberculosis, other infections of adrenal glands, bleeding into adrenal glands, spread of cancer to the adrenal glands, and medicines such as ketoconazole and etomidate that block the body’s ability to make glucocorticoid.

The typical symptoms of this condition are extreme fatigue, weight loss or loss of appetite, darkened skin, salt craving, low blood sugar, nausea, diarrhea or vomiting, abdominal pain, muscle or joint pain, muscle and joint pain, irritability, depression, body hair loss, sexual issues in some people and Addisonian crisis.

Primary adrenal insufficiency can be diagnosed through medical history, physical symptoms evaluation, blood test, ACTH stimulation test, insulin induced hypoglycemia test, and imaging tests such as CT scan and MRI. Furthermore, treatments for primary adrenal insufficiency are medicines such as hydrocortisone, prednisone or methylprednisolone, fludrocortisone acetate, glucocorticoid injection, and giving sugar.

Figure 01: Types of Adrenal Insufficiency

What is Secondary Adrenal Insufficiency?

Secondary adrenal insufficiency occurs when the adrenal glands produce too little cortisol and aldosterone, which is due to the pituitary glands making too little ACTH. This can happen because of pituitary cancer, inflammation, and surgery. Too little ACTH can cause adrenal glands to make too little glucocorticoids and androgens, which leads to secondary adrenal insufficiency. The symptoms of secondary adrenal insufficiency include severe fatigue, vomiting, nausea, diarrhea, loss of appetite, weight loss, muscle weakness, irritability, and depression.

Secondary adrenal insufficiency can be diagnosed through medical history, physical examination, low dose ACTH stimulation test, blood levels of ACTH, and cortisol. Furthermore, treatments for secondary adrenal insufficiency are replacement oral glucocorticoid medication such as hydrocortisone and prednisone.

Similarities Between Primary and Secondary Adrenal Insufficiency

1. Primary and secondary adrenal insufficiency are two different types of adrenal insufficiency.
2. Both types lead to cortisol deficiency.
3. These may have similar symptoms.
4. Both types can be diagnosed through medical history, physical examination, and blood tests.
5. They can be treated by replacing oral glucocorticoid medication such as hydrocortisone and prednisone.

Difference Between Primary and Secondary Adrenal Insufficiency

Definition

1. Primary adrenal insufficiency is the condition in which the adrenal glands do not make enough of the hormones cortisol and aldosterone due to damage to the adrenal glands.
2. Secondary adrenal insufficiency is a type of adrenal insufficiency that occurs when the pituitary gland doesn’t make enough of the hormone ACTH.

Cause

1. Primary adrenal insufficiency can be caused by autoimmune, tuberculosis, other infections of the adrenal glands, the spread of cancer to the adrenal glands, bleeding into adrenal glands, and medicines such as ketoconazole and etomidate.
2. Secondary adrenal insufficiency can be caused by tumor, infection or diseases like tuberculosis, injury to the pituitary gland and are genetic problems that change how much ACTH is made.

Symptoms

1. Symptoms of primary adrenal insufficiency include weakness, fatigue, dizziness, darkened skin, low blood pressure, muscle spasms, bluish-black color around the nipples, mouth, rectum, scrotum, or vagina, weight loss, fluid loss, loss of appetite, muscle aches, upset stomachs, vomiting, diarrhea, low sugar levels and irregular or no menstrual periods.
2. Symptoms of secondary adrenal insufficiency include tiredness, weakness, weight loss, nausea, vomiting, and diarrhea.

Diagnosis

1. Primary adrenal insufficiency can be diagnosed by medical history, physical examination, blood test, urine test, imaging tests, X-ray, ultrasound and MRI.
2. Secondary adrenal insufficiency can be diagnosed by medical history, physical examination, blood test, CT scan and MRI.

Treatment

1. Primary adrenal insufficiency can be treated with medicines such as hydrocortisone, prednisone or methylprednisolone, fludrocortisone acetate, glucocorticoid injection, giving sugar, increasing the salt intake, especially in hot and humid weather and after strenuous exercise.
2. Secondary adrenal insufficiency can be treated with hydrocortisone or prednisone/prednisolone and dose increase during intercurrent illness.

The following table summarizes the difference between primary and secondary adrenal insufficiency.

Summary – Primary vs Secondary Adrenal Insufficiency

Adrenal insufficiency occurs when the adrenal glands do not work properly and do not make enough of the hormone cortisol. There are 3 types of adrenal insufficiency: primary, secondary and tertiary insufficiency. Primary adrenal insufficiency is adrenal glands do not make enough of the hormones cortisol and aldosterone due to damages to adrenal glands while secondary adrenal insufficiency is adrenal glands do not make enough cortisol because he pituitary gland doesn’t make enough of the hormone ACTH. This is the basic difference between primary and secondary adrenal insufficiency.

FAQ: Primary and Secondary Adrenal Insufficiency

1. What is the most common cause of primary adrenal insufficiency or Addison’s disease?

• Primary adrenal insufficiency is caused by damage to the adrenal glands, which is usually due to an autoimmune condition. In developed countries, autoimmune disease causes 8 or 9 of every 10 cases of Addison’s disease. The other causes are tuberculosis, other infections of the adrenal glands, the spread of cancer to the adrenal glands, bleeding into adrenal glands, and medicines (ketoconazole and etomidate).

2. What are the symptoms of primary adrenal insufficiency?

• The symptoms of primary adrenal insufficiency are fatigue, lethargy, muscle weakness, low mood, loss of appetite, the need to urinate frequently, increased thirst, unintentional weight loss, craving for salty foods, skin hyperpigmentation and neuropsychiatric manifestations such as irritability, apathy, cognitive impairment, depressive symptoms, sleep disorders, and delusions.

3. What are the symptoms of secondary adrenal insufficiency?

• The symptoms of secondary adrenal insufficiency may include severe nausea, vomiting, diarrhea, loss of appetite, weight loss, muscle weakness, irritability, and depression.

4. How to fix secondary adrenal insufficiency?

• Secondary adrenal insufficiency is treated by prescribing hormone medicines to replace hormones that the adrenal glands aren’t making, such as hydrocortisone or prednisone/prednisolone. People will need higher doses during times of physical stress.

Reference:

1. “Addison’s Disease: What It Is, Causes, Symptoms & Treatment.” Cleveland Clinic.
2. “Secondary Adrenal Insufficiency.” National Adrenal Diseases Foundation.

Image Courtesy:

1. “HPA axis combined” By Oddcomb – Own work (CC BY-SA 4.0) via Commons Wikimedia

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