Introduction
Cushing’s Disease and Addison’s Disease are both serious disorders of the adrenal glands, each with distinct causes, symptoms, and treatment approaches. These conditions affect the body’s ability to regulate vital hormones, such as cortisol and aldosterone, that play a crucial role in metabolism, immune function, and the stress response. This post aims to briefly clarify the differences between Cushing’s Disease and Addison’s Disease by examining their aetiology, symptoms, and treatment options.
What is Cushing’s Disease?
Cushing’s Disease is a specific type of Cushing’s Syndrome, which is characterised by excess cortisol levels in the body. The primary cause of Cushing’s Disease is the presence of a pituitary adenoma, a benign tumour that causes the anterior pituitary gland to overproduce adrenocorticotropic hormone (ACTH). This excess ACTH leads to overstimulation of the adrenal glands and the subsequent overproduction of cortisol.
Aetiology
Cushing’s Disease can be caused by:
- Pituitary Adenomas: Benign tumours in the pituitary gland that lead to overproduction of ACTH.
- Ectopic ACTH Secretion: Tumours located outside the pituitary gland (such as in the lungs) that produce ACTH.
- Adrenal Tumours: These directly increase cortisol levels without the involvement of ACTH.
Symptoms
The signs and symptoms of Cushing’s Disease primarily result from prolonged exposure to high levels of cortisol. Common symptoms include:
- Physical Changes: Weight gain, particularly around the abdomen, face (moon face), and upper back (buffalo hump), alongside muscle weakness and thinning skin.
- Metabolic Changes: High blood pressure, high blood sugar levels, and osteoporosis are commonly associated with excess cortisol.
- Psychological Symptoms: Depression, anxiety, irritability, and cognitive impairments may also develop due to the hormone imbalance.
Diagnosis
Diagnosis of Cushing’s Disease typically involves:
- Laboratory Tests: Measuring cortisol levels using tests like the 24-hour urinary cortisol test, low-dose dexamethasone suppression test, or late-night salivary cortisol.
- Imaging Studies: MRI scans of the pituitary gland and sometimes CT scans of the adrenal glands to detect tumours.
Treatment
Treatment options focus on normalising cortisol levels and addressing the underlying cause:
- Surgical Removal of Pituitary Tumour: This is the primary treatment for Cushing’s Disease, typically performed through transsphenoidal surgery.
- Medication: Drugs such as ketoconazole, mitotane, and mifepristone may be prescribed to manage cortisol levels when surgery is not feasible or as a supplemental treatment.
- Radiation Therapy: This may be necessary in cases where surgical treatment is incomplete or ineffective.
What is Addison’s Disease?
In contrast to Cushing’s Disease, Addison’s Disease is characterised by insufficient production of cortisol and, in some cases, aldosterone. Addison’s Disease is also known as primary adrenal insufficiency, and it occurs when the adrenal glands are damaged, often due to an autoimmune process where the body attacks its own adrenal tissues.
Aetiology
The most common cause of Addison’s Disease is autoimmune destruction of the adrenal cortex, but other causes include:
- Infections: Tuberculosis and other infections that affect the adrenal glands.
- Genetic Factors: Certain inherited disorders can contribute to adrenal insufficiency.
- Other Causes: Haemorrhage, medications, and tumours can also lead to Addison’s Disease.
Symptoms
The symptoms of Addison’s Disease are typically more subtle and develop gradually over time, but they become severe during adrenal crises:
- Fatigue and Muscle Weakness: The lack of cortisol and aldosterone leads to extreme fatigue, weight loss, and muscle pain.
- Hypotension: Low blood pressure is a hallmark of Addison’s Disease, which can lead to dizziness and fainting.
- Skin Hyperpigmentation: Due to elevated ACTH levels, the skin, particularly in sun-exposed areas, may become darker, a feature absent in secondary adrenal insufficiency.
Diagnosis
- ACTH Stimulation Test: This is the gold standard for diagnosing Addison’s Disease, assessing adrenal function after administration of synthetic ACTH.
- Blood Tests: Low levels of cortisol, sodium (hyponatremia), and high levels of potassium (hyperkalaemia) are indicative of adrenal insufficiency.
- Imaging: Abdominal CT scans are used to assess adrenal structure, while MRI is reserved for cases with suspected secondary causes.
Treatment
The treatment for Addison’s Disease focuses on lifelong hormone replacement therapy to maintain normal cortisol and aldosterone levels:
- Glucocorticoid Replacement: Hydrocortisone or prednisone are prescribed to replace deficient cortisol.
- Mineralocorticoid Replacement: Fludrocortisone is used to replace aldosterone.
- Emergency Treatment for Adrenal Crisis: During stress or illness, higher doses of glucocorticoids or emergency hydrocortisone injections may be required.
Key Differences Between Cushing’s Disease and Addison’s Disease
| Feature | Cushing’s Disease | Addison’s Disease |
|---|---|---|
| Cortisol Levels | Excessive cortisol production | Insufficient cortisol production |
| Cause | Pituitary adenoma (Cushing’s Disease), long-term corticosteroid use, ectopic ACTH-producing tumours | Autoimmune destruction of adrenal glands, infections, or genetic disorders |
| Key Symptoms | Weight gain (moon face, buffalo hump), high blood sugar, muscle weakness, high blood pressure | Fatigue, weight loss, low blood pressure, hyperpigmentation |
| Diagnosis | 24-hour urinary cortisol, low-dose dexamethasone suppression test | ACTH stimulation test, low cortisol and aldosterone levels |
| Treatment | Surgery, radiation, medications (e.g., ketoconazole, mitotane) | Lifelong hormone replacement therapy (hydrocortisone, fludrocortisone) |
Memory Aids and Key Study Tips for Addison’s and Cushing’s Diseases
When learning about Addison’s Disease and Cushing’s Disease, it’s essential to not only understand their causes and treatments but also to memorise key symptoms and pathophysiology for exams. Here are some mnemonic aids, symptom groupings, and critical insights to help students recall important information and prioritise their learning.
Mnemonic Memory Aids
- Addison’s Disease:
- Think A for “Added tan” and “Added potassium”. The hallmark signs are hyperpigmentation (due to increased ACTH) and hyperkalaemia (low aldosterone leading to potassium retention).
- Cushing’s Disease:
- Think Cushion of fat—patients present with a large, round body, moon face, and buffalo hump due to fat redistribution caused by excessive cortisol.
Symptom Groupings
- Addison’s Disease:
- Low everything—patients with Addison’s typically have low blood pressure, low sodium, low energy, low weight, and low mood (often presenting with depression). Alopecia (hair loss) is also seen due to hormonal imbalances.
- Cushing’s Disease:
- Big everything—this condition causes high blood pressure, truncal obesity (weight gain), high blood sugar (hyperglycemia), and high sodium levels, contributing to water retention and edema.
Prioritise Critical Symptoms for Exams
- Addison’s Disease:
- Low blood pressure is a critical symptom to focus on. If untreated, this can lead to an Addisonian crisis, which is a life-threatening condition marked by severe hypotension, dehydration, and shock.
- Cushing’s Disease:
- Focus on high blood pressure, hyperglycemia, and slow wound healing—these are key features driven by excess cortisol. Students should remember that cortisol plays a significant role in glucose metabolism, which is why patients often develop diabetes-like symptoms.
Pathophysiology of the Stress Response
- Cortisol’s Role in Stress:
- Cortisol is essential for managing stress by increasing blood sugar and sodium. It helps the body prepare for a “fight or flight” response.
- In Addison’s Disease, there’s too little cortisol, leaving the body in a constant state of “drought” or low steroids, making it difficult to handle stress.
- In Cushing’s Disease, there is an overabundance of cortisol, which leads to excess glucose and sodium, contributing to symptoms like high blood sugar and hypertension.
Treatment Strategies
- Addison’s Disease:
- Think “Add steroids” to manage this condition. Patients need lifelong glucocorticoid (e.g., hydrocortisone or prednisone) replacement, and in times of stress (illness or surgery), steroid doses must be increased to prevent an Addisonian crisis.
- Cushing’s Disease:
- Treatment aims to reduce cortisol levels. If Cushing’s is caused by exogenous steroids, tapering or discontinuing the steroid is necessary. If it’s due to a tumor (adrenal or pituitary), surgery is often required to remove the source of cortisol overproduction.
Conclusion
Both Cushing’s Disease and Addison’s Disease involve the adrenal glands but affect hormone levels in opposite ways. Cushing’s Disease results in an excess of cortisol, while Addison’s Disease leads to insufficient production of both cortisol and aldosterone. These differences in hormone levels cause drastically different symptoms and require tailored treatment approaches. Accurate diagnosis and management are critical to ensure patients maintain a balanced hormonal state, improving their quality of life.
References
- Mayo Clinic. (n.d.). Cushing Syndrome: Symptoms and Causes. Retrieved from https://www.mayoclinic.org/diseases-conditions/cushing-syndrome/symptoms-causes/syc-20351310
- Johns Hopkins Medicine. (n.d.). Cushing Syndrome. Retrieved from https://www.hopkinsmedicine.org/health/conditions-and-diseases/cushing-syndrome
- Bancos, I., Hahner, S., Tomlinson, J., & Arlt, W. (2020). Addison’s Disease. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK441994/
- Endocrine Society. (n.d.). Cushing’s Syndrome and Cushing Disease. Retrieved from https://www.endocrine.org/patient-engagement/endocrine-library/cushings-syndrome-and-cushing-disease
- Healthline. (n.d.). Addison’s Disease vs. Cushing’s Syndrome: What’s the Difference?. Retrieved from https://www.healthline.com/health/addisons-disease-vs-cushings
