Cushing’s Syndrome

Cushing’s syndrome is a hormonal disorder caused by prolonged exposure to high levels of cortisol, commonly known as the stress hormone. This condition disrupts normal bodily functions and affects multiple systems, leading to a distinctive set of physical and metabolic changes. Patients with Cushing’s syndrome experience a variety of symptoms that develop gradually, often resulting in significant alterations to appearance and internal health.

Dr Ben Ng

Senior Consultant Endocrinologist

Dr Donovan Tay

Senior Consultant Endocrinologist

Symptoms of Cushing’s Syndrome

Patients with Cushing’s syndrome typically develop a characteristic cluster of signs that may appear gradually over time.

Weight Gain and Fat Distribution

Patients experience increased fat deposits in the face, between the shoulders (buffalo hump), and in the abdomen while limbs remain thin. This redistribution of fat creates a distinctive body shape that differs from typical obesity patterns.
Skin Changes

The skin becomes thin and fragile, bruising easily and healing poorly. Stretch marks (striae) with a purple or pink appearance may develop on the abdomen, thighs, breasts, and arms.
Muscle and Bone Weakness

Cortisol excess leads to muscle wasting and weakness, particularly in the legs and arms. Bone density decreases, leading to osteoporosis and heightened risk of fractures, even with minimal trauma.
Mood and Cognitive Changes

Patients may experience depression, anxiety, irritability, and difficulty concentrating. Sleep disturbances are common, which further exacerbate cognitive difficulties and mood alterations.
Menstrual Irregularities

Women may experience menstrual cycle changes, including irregular periods or complete cessation of menstruation. Excess hair growth (hirsutism) and acne may develop due to androgen excess.
Metabolic Disturbances

High blood pressure, elevated blood glucose levels, and insulin resistance frequently occur. These metabolic changes increase the risk of developing diabetes and cardiovascular disease.

Causes and Risk Factors

Cushing’s syndrome develops when the body is exposed to elevated cortisol levels for extended periods, stemming from several possible sources.

Pituitary Adenoma

A benign tumour in the pituitary gland can produce excess adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce cortisol. This specific cause is referred to as Cushing’s disease and represents the most common form of endogenous Cushing’s syndrome.

Adrenal Tumours

Benign or malignant tumours in the adrenal glands may produce excess cortisol directly. These tumours bypass the normal regulatory mechanisms that control cortisol production.

Ectopic ACTH Production

Certain cancers outside the pituitary gland, such as small cell lung cancer or carcinoid tumours, can produce ACTH. This leads to increased cortisol production by the adrenal glands.

Glucocorticoid Medications

Long-term use of corticosteroid medications, such as prednisone, prednisolone, or dexamethasone, is the most common cause of Cushing’s syndrome. These medications are used to treat inflammatory conditions, autoimmune disorders, and after organ transplantation.

Familial Cushing’s Syndrome

Rare genetic conditions can predispose individuals to tumours that cause Cushing’s syndrome. Multiple Endocrine Neoplasia Type 1 (MEN1) and familial isolated pituitary adenoma (FIPA) are examples of hereditary conditions associated with increased risk.

Diagnostic Methods

Urine Free Cortisol Test

A 24-hour urine collection measures cortisol excretion, providing a comprehensive view of overall cortisol production. As levels can fluctuate daily, multiple collections may be needed for accuracy.

Late-Night Salivary Cortisol Test

This test measures cortisol levels in saliva collected late at night, when cortisol should be at its lowest. In Cushing’s syndrome, this natural rhythm is disrupted. This non-invasive test is useful for screening.

Dexamethasone Suppression Test

This test involves taking a low dose of dexamethasone (a synthetic glucocorticoid) and measuring cortisol levels. In healthy individuals, dexamethasone suppresses cortisol production, whereas in Cushing’s syndrome, suppression does not occur. Higher doses may help differentiate between causes.

Treatment Options

Management of Cushing’s syndrome focuses on lowering cortisol levels while reducing the risk of complications.

Surgical management

Following identification of the source of production of either ACTH or cortisol, the lesion is removed resulting in often a curative solution.

Cortisol-Lowering Medications

Drugs such as ketoconazole, metyrapone, and mitotane suppress cortisol production in the adrenal glands. These medications require regular monitoring to assess liver function, hormone levels, and overall treatment response.

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Prevention and Management

While primary prevention of Cushing’s syndrome is not always possible, certain practices can reduce risks and improve outcomes. Patients prescribed long-term corticosteroid therapy should take the lowest effective dose for the shortest duration necessary. Regular medical monitoring allows early detection of Cushing’s features. After treatment, ongoing follow-up is needed as recurrence can occur, particularly with certain tumour types. Lifestyle modifications, including regular physical activity, calcium and vitamin D supplementation for bone health, and a balanced diet, help manage complications and improve quality of life. Psychological support addresses mood disturbances and adjustment difficulties that commonly accompany this condition.

Frequently Asked Questions

How long does recovery from Cushing’s syndrome take?

Recovery depends on the cause, treatment, and individual factors. Most symptoms improve gradually over 6 to 12 months, though bone density and other effects may take longer.

Can Cushing’s syndrome recur after treatment?

Yes, particularly with certain tumour types. Around 1 in 10 patients with Cushing’s disease experience recurrence within a decade after successful treatment. Long-term follow-up with cortisol testing helps detect recurrence early, and alternative treatments may be needed.

Dr Ben Ng

Senior Consultant Endocrinologist

As a senior consultant endocrinologist with over 20 years of clinical experience, Dr Ben Ng provides comprehensive care for patients managing various endocrine conditions. His expertise includes the diagnosis and treatment of diabetes, thyroid disorders, obesity, and a range of other metabolic and endocrine conditions.

Adj Asst Professor Dr Ben Ng Jen Min graduated from the Queens University of Belfast Northern Ireland, United Kingdom (UK).
He completed his postgraduate training with the certificate of completion of training (CCT) from the Royal College of Physicians (UK) with dual accreditation in diabetes and endocrinology and in general internal medicine.
In 2010, he was awarded an MD with honours by the University of Hull, UK, in recognition for his research in diabetes mellitus

Dr Donovan Tay

Senior Consultant Endocrinologist

As a senior consultant endocrinologist with over 20 years of clinical experience, Dr. Donovan Tay provides comprehensive care for patients managing various endocrine conditions. His expertise includes the diagnosis and treatment of diabetes, thyroid disorders, osteoporosis, and a range of other metabolic and endocrine conditions.

Dr. Donovan Tay graduated from the National University of Singapore (NUS) and obtained his membership in the Royal College of Physicians (UK), Master of Medicine (NUS), and Master of Clinical Investigation (NUS).
After completing training in endocrinology, he was conferred as a Fellow of the Academy of Medicine, Singapore (FAMS).
He further specialised in endocrinology with a fellowship at the prestigious Columbia University Medical Centre in New York City.

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