Cushing’s syndrome is a condition arising from prolonged exposure to elevated levels of cortisol, a hormone naturally produced by the adrenal glands. This article focuses on endogenous Cushing’s syndrome, a form where the body itself produces an excess of this hormone. This internal overproduction distinguishes it from exogenous Cushing’s syndrome, which typically results from external sources like long-term use of corticosteroid medications. Understanding the internal mechanisms of this condition is a significant step toward managing its effects.
Internal Causes of High Cortisol
The body’s internal overproduction of cortisol can stem from various sources, each involving different glands in the endocrine system. The most common internal cause originates from the pituitary gland.
Pituitary Gland Tumors (Cushing’s Disease)
The most frequent cause of endogenous Cushing’s syndrome is the presence of a non-cancerous tumor on the pituitary gland, a small gland located at the base of the brain. These benign growths secrete excessive amounts of adrenocorticotropic hormone (ACTH). This surplus ACTH then travels through the bloodstream to the adrenal glands, signaling them to produce and release an abnormally large quantity of cortisol.
Adrenal Gland Tumors
In some instances, the source of excess cortisol lies directly within the adrenal glands themselves. Here, a tumor can independently produce cortisol without receiving signals from the pituitary gland. This direct overproduction of cortisol by an adrenal tumor leads to high cortisol levels in the body, independent of ACTH.
Ectopic ACTH-Producing Tumors
A less common cause involves tumors located outside the pituitary or adrenal glands. These “ectopic” tumors can develop in various parts of the body, including the lungs, pancreas, or thyroid gland. These growths aberrantly produce ACTH, mimicking the pituitary gland’s function and subsequently stimulating the adrenal glands to generate excessive cortisol.
Recognizable Signs and Symptoms
High cortisol levels over an extended period lead to a range of noticeable physical and psychological changes. These manifestations often progress gradually, making early recognition challenging.
Physical Appearance Changes
Individuals with high cortisol often experience progressive weight gain, particularly concentrated around the trunk and abdomen, while the arms and legs may remain slender. A distinctive rounded facial appearance, a “moon face,” and a fatty deposit between the shoulders, known as a “buffalo hump,” are also common. The skin frequently shows changes, including wide, purplish stretch marks, which typically appear on the abdomen, thighs, and breasts. The skin may also become unusually thin and fragile, bruising easily, and cuts or infections can heal at a slower rate.
Systemic Health Effects
High cortisol profoundly impacts internal bodily functions. Many individuals develop high blood pressure, which can increase the risk of cardiovascular complications. Elevated blood sugar levels are also common, potentially progressing to type 2 diabetes due to cortisol’s interference with insulin sensitivity. Prolonged exposure to excess cortisol can also lead to a loss of bone density, which increases the susceptibility to fractures. Muscle weakness, particularly affecting the arms and legs, can make daily activities challenging.
Psychological and Cognitive Effects
Individuals frequently report experiencing heightened anxiety, depression, and increased irritability. Emotional instability and rapid mood swings are common. Cognitive difficulties can arise, affecting memory and the ability to concentrate on tasks. These psychological and cognitive changes can significantly impact an individual’s quality of life and daily functioning.
The Diagnostic Pathway
Confirming a diagnosis of endogenous Cushing’s syndrome involves a methodical series of tests designed to first verify excess cortisol and then identify its specific source. This pathway ensures an accurate and targeted approach.
Step 1: Confirming High Cortisol Levels
The initial phase of diagnosis focuses on demonstrating that the body is indeed producing too much cortisol. A 24-hour urinary free cortisol test collects urine over a day to assess total cortisol. Late-night salivary cortisol measurements can reveal abnormal cortisol patterns, as levels are usually lowest at night. The low-dose dexamethasone suppression test involves administering a small dose of dexamethasone, a synthetic steroid, and then measuring cortisol levels to see if they suppress as expected in a healthy individual.
Step 2: Determining the Cause
Once elevated cortisol levels are confirmed, the next step is to pinpoint the underlying reason for the overproduction. This involves measuring adrenocorticotropic hormone (ACTH) levels in the blood. High ACTH levels usually indicate a pituitary tumor or an ectopic ACTH-producing tumor, as both depend on ACTH to stimulate cortisol production. Conversely, very low or undetectable ACTH levels suggest that the problem lies directly within the adrenal glands, which are overproducing cortisol independently of ACTH signals.
Step 3: Locating the Tumor
After determining whether the cortisol excess is ACTH-dependent or ACTH-independent, imaging studies are used to locate the tumor. If ACTH levels are high, an MRI of the pituitary gland is performed to identify a pituitary adenoma. If ACTH levels are low, a CT scan of the adrenal glands is conducted to look for an adrenal tumor. In cases of suspected ectopic ACTH production, scans of the chest and abdomen may be necessary to find tumors in areas like the lungs or pancreas.
Medical and Surgical Interventions
Managing endogenous Cushing’s syndrome primarily focuses on reducing cortisol levels and addressing the underlying cause. Treatment approaches vary depending on the specific origin of the cortisol excess.
Surgery
Surgery is the primary treatment for endogenous Cushing’s syndrome. For pituitary tumors, a procedure called transsphenoidal surgery is commonly performed, where the tumor is removed through the nasal cavity. When an adrenal tumor is the cause, an adrenalectomy, the surgical removal of the affected adrenal gland, is performed. The primary objective of these surgical interventions is to eliminate the source of excessive hormone production, thereby normalizing cortisol levels.
Radiation Therapy
Radiation therapy serves as a secondary treatment option, particularly for pituitary tumors, when surgical removal is not entirely successful or if surgery is not a suitable option for the patient. This treatment uses high-energy rays to shrink the tumor and reduce its production of ACTH. The effects of radiation therapy are gradual, taking months or even years to achieve full cortisol control.
Medications
Cortisol-inhibiting medications are used to manage endogenous Cushing’s syndrome, especially when surgery or radiation therapy are not immediately viable or while waiting for their full effects. These drugs work by blocking cortisol production at various steps or by inhibiting its action at the tissue level. Medications can also normalize cortisol levels before surgery to improve patient outcomes or serve as a long-term management strategy for individuals who cannot undergo other treatments.