Navigating Hypercortisolism: A Guide to Understanding Cushing’s Syndrome

The Rare360 Editorial Team

Feb 74 min read

What is Cushing’s Syndrome?

Cushing’s syndrome, also known as hypercortisolism, is a rare hormonal disorder caused by prolonged exposure to high levels of cortisol. This condition can occur due to the body producing excessive cortisol or as a side effect of medications called glucocorticoids, which mimic cortisol’s effects.

Often referred to as the "stress hormone," cortisol is a vital steroid hormone that plays a central role in maintaining blood pressure, supporting the immune system, ensuring cardiovascular health, and managing the body’s response to stress. While cortisol is essential for these functions, persistently elevated levels can disrupt the body’s equilibrium and lead to significant health complications.

Cushing’s syndrome can arise from causes that are endogenous (internal) or exogenous (external). Endogenous Cushing’s syndrome, stemming from internal factors like overactive adrenal glands, is particularly rare, affecting an estimated 40 to 70 people per million. The condition most commonly impacts adults aged 30 to 50 and occurs about three times more often in women than in men. Children and individuals with type 2 diabetes, high blood pressure, and persistent high blood glucose levels may also be at risk.

Cushing's Syndrome vs. Cushing's Disease

It is important to distinguish between Cushing’s syndrome and Cushing’s disease:

Cushing’s syndrome is a broad term that refers to any condition where excess cortisol is present in the body, regardless of the cause.
Cushing’s disease is a specific form of Cushing’s syndrome caused by a pituitary adenoma, a benign tumour in the pituitary gland, which overproduces adrenocorticotropic hormone (ACTH). This excess ACTH overstimulates the adrenal glands, leading to excessive cortisol production.

Cushing’s disease accounts for a significant portion of endogenous Cushing’s syndrome cases but is not the only cause.

Causes of Cushing’s Syndrome

Cushing’s syndrome can stem from various internal and external factors. By identifying the root causes, patients and caregivers can better understand the condition and its wide-ranging implications.

Exogenous Cushing’s Syndrome: The Role of Glucocorticoid Medications

A common cause of Cushing’s syndrome is the prolonged use of glucocorticoid medications, often prescribed to manage inflammatory conditions such as rheumatoid arthritis, lupus, asthma, or autoimmune diseases. These medications, which mimic the effects of cortisol, are also used to treat joint pain, skin rashes, and prevent organ rejection after transplants.

Glucocorticoids can be administered in various forms—oral tablets, injections, creams, or inhalers. However, when taken in high doses over extended periods, they can disrupt the body’s hormonal balance, leading to exogenous Cushing’s syndrome.

Endogenous Cushing’s Syndrome: When the Body Produces Too Much Cortisol

Endogenous Cushing’s syndrome occurs due to internal factors that cause excessive cortisol production. The causes include:

Cushing’s Disease (Pituitary Adenomas): The most common endogenous cause is a benign tumour in the pituitary gland. This tumour overproduces ACTH, leading to excessive cortisol production.
Ectopic ACTH-Producing Tumors: Rarely, tumours outside the pituitary gland, such as those in the lungs or pancreas, produce ACTH, leading to elevated cortisol levels. These tumours may be benign or malignant.
Adrenal Cortical Tumors: A tumour on the adrenal gland itself can independently secrete excessive cortisol. Most of these tumours are benign, though in rare cases, they may develop into adrenal cortical carcinoma, a type of adrenal cancer.

Rare Genetic or Familial Factors

Although most cases of Cushing’s syndrome occur sporadically, some are linked to genetic disorders, such as:

Multiple Endocrine Neoplasia Type 1 (MEN1): A hereditary condition that predisposes individuals to endocrine gland tumours, including the pituitary.
Carney Complex: Another genetic disorder associated with hormone-producing tumours, including those influencing cortisol levels.

Recognizing the Symptoms of Cushing’s Syndrome

Cushing’s syndrome is a complex condition caused by prolonged exposure to elevated cortisol levels, which can lead to a diverse range of symptoms. These symptoms often vary widely between individuals, making early diagnosis challenging.

Distinctive Physical Symptoms

Weight Gain in Specific Areas: Fat accumulation is often concentrated in the face (moon face), upper back (buffalo hump), and abdomen, while the limbs may remain relatively slender.
Thinning, Fragile Skin: Increased skin fragility leads to easy bruising, slow wound healing, and reddish-purple stretch marks (striae).
Muscle Weakness and Fatigue: Cortisol-induced muscle wasting, particularly in the arms and legs, can cause significant weakness.
Excessive Hair Growth and Hair Loss: Women may experience excessive hair growth (hirsutism), while both men and women may experience balding.

Emotional and Psychological Symptoms

Depression and Anxiety: Hormonal imbalances contribute to sadness, worry, or hopelessness.
Mood Swings and Irritability: Sudden emotional outbursts are common.

Systemic Health Complications

High Blood Pressure: Persistent hypertension increases cardiovascular risk.
Osteoporosis: Cortisol weakens bones, raising the likelihood of fractures.
Diabetes: Impaired insulin regulation can cause elevated blood sugar levels.
Libido and Fertility Changes: Women may experience irregular menstrual cycles, while men may encounter erectile dysfunction.

Diagnosing Cushing's Syndrome

Diagnosing Cushing’s syndrome involves:

24-Hour Urinary Free Cortisol Test to measure cortisol excretion.
Late-Night Salivary Cortisol Test since cortisol should naturally drop at night.
Dexamethasone Suppression Test (DST) to assess the body's response to synthetic steroids.
Imaging (MRI or CT Scans) to detect pituitary or adrenal tumours.

Treatment Options for Cushing’s Syndrome

Managing Glucocorticoid Use: For exogenous Cushing’s syndrome, a gradual tapering of steroid medications under medical supervision is crucial.
Surgery
- Transsphenoidal Surgery: The primary treatment for Cushing’s disease involves pituitary tumour removal.
- Adrenalectomy: If an adrenal tumour is the cause, removal of the affected adrenal gland may be necessary.
Radiation Therapy and Medications
- Radiation Therapy: Used if surgery does not fully remove the tumour.
- Medications: Pasireotide, ketoconazole, and mifepristone help manage cortisol levels.

Conclusion

Cushing’s syndrome presents a complex challenge due to its varied symptoms, difficulty in diagnosis, and potential long-term health impacts. However, advancements in diagnostic tools, surgical techniques, and medical therapies have significantly improved the outlook for patients. Early recognition and treatment are essential in mitigating the effects of the disease, and the development of new therapies continues to provide hope for those affected by this rare condition.