Addison’s disease, also known as primary adrenal insufficiency, is a rare endocrine disorder in which the adrenal glands do not produce enough cortisol and aldosterone. It often goes undiagnosed for a long time because its symptoms are similar to those of several other conditions. Some diseases that can mimic Addison’s disease include:
Secondary Adrenal Insufficiency
Secondary adrenal insufficiency occurs when the pituitary gland does not signal the adrenal glands to produce cortisol properly. The adrenal glands themselves are healthy, but they do not receive the right signals from the pituitary to make enough cortisol. This can happen due to pituitary tumors, radiation treatment affecting the pituitary, or other damage to the pituitary gland. Symptoms of secondary adrenal insufficiency are very similar to primary adrenal insufficiency and the two may be confused.
Chronic Fatigue Syndrome
Chronic fatigue syndrome (CFS) involves extreme fatigue that lasts 6 months or longer and is not improved by rest. The fatigue worsens with physical or mental activity but does not improve with rest. CFS can mimic some of the key symptoms of Addison’s like fatigue, body aches, low blood pressure, dizziness, and more. However, CFS does not cause low blood sodium or high blood potassium like Addison’s does.
Hypothyroidism
An underactive thyroid gland, known as hypothyroidism, can cause symptoms like fatigue, weakness, cold intolerance, dry skin, hair loss, and weight gain. This is due to low levels of thyroid hormones. These symptoms overlap with those of Addison’s, making hypothyroidism one of the conditions that should be ruled out when diagnosing adrenal insufficiency.
Diabetes
Diabetic ketoacidosis is a serious complication of diabetes that occurs when insulin levels are very low and the body starts to use fat for fuel, creating acidic ketones as a byproduct. Symptoms include nausea, vomiting, stomach pain, fatigue, and difficulty breathing. These are also common symptoms in Addisonian crisis, an adrenal crisis in someone with Addison’s disease. Distinguishing between the two conditions requires blood tests for glucose, ketones, sodium, and potassium.
Cushing’s Syndrome
Cushing’s syndrome is the opposite hormonal problem from Addison’s disease – the adrenal glands produce too much cortisol. However, in some cases, as Cushing’s syndrome starts to resolve, the adrenal glands can suddenly be unable to keep up with cortisol production, resulting in adrenal insufficiency. Thisoverlap in symptoms can make promptly diagnosing Addison’s challenging in some patients.
Lyme Disease
Lyme disease is caused by a bacterial infection transmitted through tick bites. In some cases, Lyme disease can damage the adrenal glands and lead to adrenal insufficiency. Symptoms like fatigue, muscle aches, abdominal pain, and low blood pressure may occur in both Lyme and Addison’s. Tick exposure history and Lyme disease blood tests help distinguish between them.
Tuberculosis
Tuberculosis is an infection that most commonly affects the lungs but can spread to other organs like the adrenals. Tuberculosis adrenalitis impairs adrenal function, causing symptoms of adrenal insufficiency. Other clues are a cough, fever, and testing positive for TB exposure. However, adrenal insufficiency can persist even after TB treatment, requiring ongoing cortisol replacement.
HIV/AIDS
HIV can sometimes directly infect the adrenal glands and decrease cortisol production over time. Adrenal insufficiency occurs in up to 10% of AIDS patients. Fatigue, weight loss, low blood pressure, and hyperpigmentation of both Addison’s disease and advanced AIDS make differentiating between them difficult, especially in at-risk populations.
Cancers
Cancers that metastasize to the adrenals (like lung, breast, kidney, and melanoma) can impair cortisol production and mimic Addison’s disease. Carcinoma can also develop directly from the adrenal cortex. Symptoms like fatigue, nausea, low blood pressure, and unintentional weight loss may be present in both cancer and Addison’s patients. Imaging and biopsy confirm cancer diagnoses.
Sepsis
Severe infections and sepsis can lead to dysfunction of multiple organs, including the adrenals. Impaired adrenal function during severe illness is known as critical illness-related corticosteroid insufficiency (CIRCI). CIRCI shares features of mineralocorticoid and glucocorticoid deficiency with Addison’s disease. Diagnosis of sepsis-induced adrenal dysfunction relies on clinical judgment, as tests have limitations in critically ill patients.
Panhypopituitarism
Panhypopituitarism refers to underactive production of all pituitary hormones, including ACTH which stimulates the adrenal glands. This leads to secondary adrenal insufficiency along with other hormone deficiency symptoms like hypothyroidism and hypogonadism. Panhypopituitarism can be mistaken for primary adrenal failure like Addison’s, emphasizing the importance of testing ACTH levels to distinguish between the two.
Adrenal Hemorrhage
Bleeding into the adrenal glands, known as adrenal hemorrhage, can rapidly lead to adrenal crisis and adrenal insufficiency. Causes include trauma, blood clots, bleeding disorders, adrenal vein thrombosis, sepsis, and anticoagulant medications. Adrenal hemorrhage requires swift diagnosis and treatment with IV corticosteroids to prevent circulatory collapse, mimicking an Addisonian crisis.
Drug-induced Adrenal Suppression
Certain medications like high-dose steroids, when stopped abruptly, can cause temporary hypocortisolism and mimic Addison’s disease. Critical illness and pituitary disorders treated with steroids can also lead to adrenal suppression. Withdrawal symptoms like hypotension, fatigue, anorexia, and electrolyte disturbances may resemble unmasked primary adrenal failure after steroid tapering or discontinuation.
Familial Glucocorticoid Deficiency
Familial glucocorticoid deficiency is a rare genetic disorder causing cortisol deficiency from childhood. It results from mutations in genes involved in cortisol synthesis and ACTH signaling. Symptoms are similar to Addison’s disease but typically start earlier in life. Making the right diagnosis lets genetic counseling be provided to families affected by this hereditary adrenal condition.
Isolated Aldosterone Deficiency
Isolated hypoaldosteronism is uncommon, accounting for around 6% of primary adrenal insufficiency cases. Aldosterone alone is deficient, while cortisol levels remain normal. Symptoms are mostly related to mineralocorticoid deficiency (salt craving, dehydration, hypotension) without glucocorticoid deficiency symptoms seen in Addison’s disease. Testing aldosterone and renin levels distinguishes between isolated and complete adrenal insufficiency.
Key Differences Between Mimicking Disorders and Addison’s Disease:
| Disease | Key Differentiating Features from Addison’s Disease |
|---|---|
| Secondary Adrenal Insufficiency | ACTH levels are elevated |
| Chronic Fatigue Syndrome | No electrolyte abnormalities |
| Hypothyroidism | TSH and free T4 abnormalities |
| Diabetes | High blood glucose, ketones |
| Cushing’s Syndrome | Cortisol levels are elevated |
| Lyme Disease | Positive Lyme antibodies and exposure history |
| Tuberculosis | Chest imaging findings and positive TB skin/blood test |
| HIV/AIDS | Positive HIV test, low CD4 count |
| Cancers | Tumor visible on CT/MRI/PET scan |
| Sepsis | Positive blood cultures, imaging to rule out adrenal hemorrhage |
| Panhypopituitarism | Multiple pituitary hormone deficiencies |
| Adrenal Hemorrhage | History of trauma/sepsis, imaging confirming hemorrhage |
| Drug-induced | History of recent high-dose steroid use |
| Familial Glucocorticoid Deficiency | Family history, onset in infancy/childhood |
| Isolated Aldosterone Deficiency | Low aldosterone with normal cortisol |
Conclusion
Addison’s disease can be mistaken for many other conditions given its nonspecific symptoms. However, clues from the history, physical exam, and diagnostic tests help distinguish it from other mimicking disorders. Primary adrenal insufficiency warrants prompt diagnosis and treatment with lifelong hormone replacement to prevent an adrenal crisis. Considering Addison’s disease as a possible cause, even if unlikely, facilitates timely identification and management of this rare but serious endocrine disorder.