Cushing's disease

Cushing's disease
Synonyms	Cushing disease, tertiary or secondary hypercortisolism, tertiary or secondary hypercorticism, Itsenko-Cushing disease
Pronounce	/ˈkʊʃɪŋz/
Field	Endocrinology, Neurosurgery
Symptoms	Weight gain (central obesity, moon face, buffalo hump), purple striae, muscle weakness, hypertension, hirsutism, acne, irregular menstruation, depression, osteoporosis, hyperglycemia
Complications	Diabetes mellitus, osteoporosis, cardiovascular disease, infections, psychiatric disorders, infertility
Onset	Typically 20–50 years of age
Duration	Chronic if untreated
Types	Pituitary ACTH-secreting adenoma (Cushing’s disease); other forms fall under Cushing's syndrome
Causes	Pituitary adenoma secreting excessive adrenocorticotropic hormone (ACTH)
Risks	Female sex, age 20–40 years, genetic predisposition
Diagnosis	Blood test (serum cortisol, ACTH), 24-hour urinary free cortisol, dexamethasone suppression test, salivary cortisol, MRI of the pituitary gland
Differential diagnosis	Cushing's syndrome, adrenal tumor, ectopic ACTH syndrome, Polycystic ovary syndrome, Metabolic syndrome
Prevention	No known prevention; early detection and treatment of pituitary tumors can reduce complications
Treatment	Transsphenoidal surgery, radiation therapy, pituitary tumor resection, adrenalectomy
Medication	Ketoconazole, Metyrapone, Mitotane, Pasireotide, Cabergoline, Mifepristone
Prognosis	Good with early diagnosis and complete tumor resection; risk of recurrence exists
Frequency	~2–3 per million annually
Deaths	Rare with treatment; mortality increases with comorbidities if untreated

Cushings disease - Targeted drugs to Cushing’s disease and their mechanistic scheme. TMZ, temozolomide; RTK, receptor of tyrosine kinase

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Management algorithm of Cushing's disease

Cushing's disease refers to a condition characterized by an overproduction of the hormone cortisol by the adrenal glands, usually caused by a pituitary gland tumor. This hormonal imbalance can result in a variety of health issues, from physical changes to psychological disturbances.

Overview

Cushing's disease is a subtype of Cushing's syndrome, a condition characterized by an excess of cortisol, a hormone that plays a crucial role in numerous bodily functions. The term "Cushing's disease" is specifically used when the excess cortisol is caused by a pituitary adenoma, a tumor in the pituitary gland that stimulates the overproduction of adrenocorticotropic hormone (ACTH). The primary difference between Cushing's disease and other forms of Cushing's syndrome is the source of the excess cortisol production.

Symptoms and Clinical Presentation

Common symptoms of Cushing's disease include:

• Weight gain – especially around the abdomen and face (commonly referred to as a "moon face").
• Skin changes – such as purple stretch marks (striae) and easy bruising.
• Muscle weakness, particularly in the upper arms and thighs.
• Mood changes – such as irritability, depression, and anxiety.
• Irregular menstruation – often in women, due to hormonal imbalances.
• Osteoporosis – a weakening of the bones due to long-term high cortisol levels.
• Hypertension – high blood pressure resulting from fluid retention and increased vascular resistance.
• Hyperglycemia – elevated blood sugar levels due to cortisol’s effects on glucose metabolism.
• Fatigue – due to the body's inability to manage energy efficiently with excess cortisol.

Pathophysiology

In most cases of Cushing's disease, a pituitary adenoma (a benign tumor in the pituitary gland) secretes an excess of adrenocorticotropic hormone (ACTH). ACTH stimulates the adrenal glands to produce more cortisol than the body needs. Cortisol is a hormone that regulates various bodily functions, including metabolism, immune response, and stress adaptation. Overproduction of cortisol leads to the clinical features of Cushing's disease. In some cases, excess cortisol production can also be caused by adrenal tumors or ectopic ACTH production from tumors elsewhere in the body, but Cushing's disease specifically refers to the pituitary origin.

Diagnosis

Diagnosing Cushing's disease can be challenging due to the variability of symptoms and their overlap with other conditions. Diagnosis typically involves the following:

• Blood tests – to measure cortisol levels and ACTH concentrations, including a late-night salivary cortisol test and the dexamethasone suppression test.
• Urine tests – a 24-hour urinary cortisol test is often used to assess cortisol secretion levels.
• Imaging tests – such as MRI or CT scan to visualize the pituitary gland and identify potential adenomas.
• Inferior petrosal sinus sampling (IPSS) – a specialized test to confirm the source of excess ACTH production.

A definitive diagnosis requires a combination of clinical findings, laboratory testing, and imaging studies to confirm the presence of a pituitary tumor.

Treatment

The primary treatment for Cushing's disease is surgical removal of the pituitary tumor (pituitary adenectomy). This is often the first-line treatment and can be highly effective if the tumor is small and localized. Other treatment options include:

• Radiation therapy – used if surgery is not possible or if the tumor is not fully removed.
• Medications – such as ketoconazole or mitotane to inhibit cortisol production, or pasireotide to reduce ACTH secretion. These are typically used when surgery is not an option or as adjuncts to surgery.
• Adrenalectomy – removal of the adrenal glands may be necessary in cases where the condition is caused by an adrenal tumor or when other treatments fail.

In some cases, if the tumor cannot be fully removed or recurs, patients may require long-term medication and monitoring.

Prognosis

The prognosis for individuals with Cushing's disease varies depending on the severity of the disease and the success of treatment. If the tumor is successfully removed, most individuals recover normal cortisol production, although it can take several months to years for the body to return to normal after long-term exposure to excess cortisol. In cases where the tumor cannot be fully removed or recurs, further treatment may be required. Long-term management may involve medications to control cortisol levels.

Complications of untreated Cushing's disease, such as osteoporosis, hypertension, diabetes, and psychological issues, can lead to significant morbidity. However, with appropriate treatment, many individuals can achieve a full recovery and lead normal lives.

Epidemiology

Cushing's disease is relatively rare, with an estimated prevalence of 2 to 3 cases per million people per year. It most commonly affects adults between the ages of 20 and 50 and is more common in women than men. The condition is often associated with other pituitary disorders and can occasionally occur alongside other endocrine conditions such as hypothyroidism or diabetes.

See Also

• Cushing's syndrome
• Pituitary adenoma
• Adrenal glands
• Cortisol
• Pituitary gland
• Osteoporosis
• Hyperglycemia
• Hypertension

External Links

• Cushing's Help - Cushing's Disease Resource
• Cushing's Disease - NIH
• Cushing’s Disease Information and Support

References

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