Primary vs. Secondary Adrenal Insufficiency. What’s the Difference?

Dr. Tashko explains primary adrenal insufficiency stems from adrenal gland damage, while secondary adrenal insufficiency results from inadequate ACTH production by the pituitary gland.

Adrenal Insufficiency Support in Montgomery County, Maryland

As an adrenal specialist, I provide detailed care for adrenal insufficiency in my community. I utilize personalized treatments to enhance well-being and prevent complications in patients with adrenal disorders.

Conveniently located in Rockville, my practice offers virtual and in-person services, extending support to nearby areas such as Chevy Chase, Bethesda, North Bethesda, Potomac, North Potomac, Gaithersburg, Germantown, Frederick, Silver Spring, Northern Virginia, Howard County, Anne Arundel, and the Eastern Shore of Maryland, ensuring comprehensive care. 

Without delay, let us explore the differences in symptoms, causes, diagnosis, and treatment between primary and secondary adrenal insufficiency.

Introduction to Adrenal Insufficiency

Adrenal insufficiency is a condition where the adrenal glands do not produce sufficient amounts of certain hormones. The adrenal glands, located atop the kidneys, produce hormones like cortisol and aldosterone, which are vital for various bodily functions. Adrenal insufficiency can be classified into two types: primary and secondary. Understanding the differences between these two forms is key for effective diagnosis and treatment. 

1. Differences in Symptoms

Primary Adrenal Insufficiency (Addison’s Disease)

Primary adrenal insufficiency, also known as Addison’s disease, occurs when the adrenal glands themselves are damaged and cannot produce adequate hormones. The symptoms of Addison’s disease are often more severe due to the direct impact on hormone production. Individuals with Addison’s disease frequently experience persistent fatigue and muscle weakness, which can significantly affect their daily activities and overall quality of life. Unintentional weight loss and a decreased appetite are also common, leading to noticeable physical changes and potential nutritional deficiencies.

One of the hallmark signs of Addison’s disease is hyperpigmentation, a condition where the skin darkens, particularly in areas exposed to friction, such as elbows, knees, and knuckles. This symptom can often be one of the first noticeable signs of the disease. Additionally, low blood pressure is a frequent issue, often causing dizziness and fainting spells. People with Addison’s disease may also crave salt due to low levels of aldosterone affecting sodium balance in the body. Digestive issues such as nausea, vomiting, and diarrhea are common, along with joint and muscle pain that may not be linked to physical activity. Changes in mood and mental health, including irritability and depression, are also reported by many patients.

Secondary Adrenal Insufficiency

Secondary adrenal insufficiency occurs when the pituitary gland fails to produce enough adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce cortisol. The symptoms of secondary adrenal insufficiency can be similar to those of Addison’s disease but are generally less severe and may develop more gradually. Fatigue and muscle weakness are common but often less intense than in primary adrenal insufficiency. Weight loss may occur, but it is typically less pronounced. While low blood pressure can happen, it is less likely to cause severe dizziness or fainting.

People with secondary adrenal insufficiency may experience low blood sugar levels, known as hypoglycemia, which can lead to symptoms such as sweating, shakiness, and confusion. This occurs due to a co-deficiency of growth hormone from the pituitary gland. Digestive issues like nausea and vomiting may also occur, though typically less severe. Joint and muscle pain is less common and generally milder compared to primary adrenal insufficiency. Mental symptoms such as mood swings, depression, and irritability can also be present but are usually less pronounced.

2. Differences in Causes

Primary Adrenal Insufficiency

The most common cause of Addison’s disease is an autoimmune response where the immune system mistakenly attacks the adrenal glands. This autoimmune destruction is responsible for the majority of cases. Other causes include infections such as tuberculosis, HIV, and certain fungal infections that can damage the adrenal glands. Hemorrhage, or bleeding into the adrenal glands, can occur due to trauma or surgery, leading to adrenal insufficiency. Metastatic cancer, where cancer spreads to the adrenal glands, is another potential cause. Additionally, genetic disorders such as adrenoleukodystrophy (ALD) can affect adrenal gland function and lead to primary adrenal insufficiency.

Secondary Adrenal Insufficiency

Secondary adrenal insufficiency is primarily caused by problems with the pituitary gland or its ability to produce ACTH. Pituitary tumors, both benign and malignant, can interfere with the production of ACTH, leading to insufficient stimulation of the adrenal glands. Treatments for pituitary tumors, including surgery or radiation, can also damage the pituitary and result in secondary adrenal insufficiency. Sheehan’s syndrome, a rare condition caused by severe blood loss during childbirth, can damage the pituitary gland and disrupt hormone production. Chronic use of corticosteroids, such as those prescribed for inflammatory conditions, can suppress ACTH production and lead to secondary adrenal insufficiency. Additionally, head injuries that affect the pituitary gland can also be a cause.

3. Differences in Diagnosis

Primary Adrenal Insufficiency

Diagnosing Addison’s disease typically involves a combination of medical history, physical examination, and laboratory tests. Blood tests are crucial for measuring levels of cortisol and ACTH. In primary adrenal insufficiency, cortisol levels are low while ACTH levels are elevated due to the pituitary gland’s reaction to stimulate the underperforming adrenal glands. An ACTH stimulation test is often performed, where synthetic ACTH is administered to assess the adrenal glands’ response. Imaging studies such as CT scans or MRI may be used to check for adrenal gland abnormalities or damage.

Secondary Adrenal Insufficiency

The diagnosis of secondary adrenal insufficiency also involves blood tests to measure cortisol and ACTH levels. In this condition, cortisol levels are low while ACTH levels are not elevated (ACTH levels could be low or normal, but certainly not high), indicating a problem with the pituitary gland. An insulin tolerance test may be conducted, where insulin is administered to induce hypoglycemia and stimulate ACTH and cortisol production, allowing doctors to assess the pituitary-adrenal axis. MRI of the pituitary gland can help identify any structural abnormalities or tumors affecting hormone production.

4. Differences in Treatment

Primary Adrenal Insufficiency

The treatment of Addison’s disease involves hormone replacement therapy to compensate for the deficient hormones. Patients are typically prescribed oral corticosteroids such as hydrocortisone, prednisone, or dexamethasone to replace cortisol. Mineralocorticoid replacement with fludrocortisone is also necessary to maintain sodium and potassium balance. Patients must learn to manage their condition during times of stress, illness, or injury, as they may require increased doses of medication. Regular follow-up with an endocrinologist is essential to monitor hormone levels and adjust treatment as needed.

Secondary Adrenal Insufficiency

Treatment for secondary adrenal insufficiency focuses on replacing the deficient cortisol. Oral corticosteroids like hydrocortisone, prednisone, or dexamethasone are prescribed to restore normal cortisol levels. Unlike primary adrenal insufficiency, mineralocorticoid replacement is usually not required because aldosterone production is typically unaffected. Managing underlying conditions affecting the pituitary gland, such as tumors, is also crucial. This may involve surgery, radiation, or other treatments to address the root cause of the insufficiency.


Dr. Tashko, in a tablet format, explains that primary adrenal insufficiency arises from adrenal gland failure. In contrast, secondary adrenal insufficiency results from inadequate ACTH production, leading to impaired cortisol production.

In both types of adrenal insufficiency, patients need to be educated about their condition and how to manage it effectively. They should carry medical alert identification and have an emergency injection of hydrocortisone available in case of severe stress or adrenal crisis. Regular monitoring and follow-up with an endocrinologist is essential to ensure optimal management and to make any necessary adjustments to treatment plans.

Dr. Tashko