Subclinical Cushing’s syndrome involves a mild, sustained overproduction of the hormone cortisol, without the overt signs of full-blown Cushing’s syndrome. This disorder often remains “silent” because its symptoms are subtle or can be attributed to other common health issues. Understanding this subtle hormonal imbalance is important for its potential long-term health implications.
Understanding Subclinical Cushing’s Syndrome
Subclinical Cushing’s syndrome is defined by autonomous cortisol production that is not sufficient to cause the pronounced symptoms of classic Cushing’s syndrome, such as significant muscle wasting, thin skin, or purple stretch marks. This condition is much more common than classic Cushing’s syndrome, with an estimated prevalence of 79 cases per 100,000 persons.
The primary cause is typically a benign tumor, an adenoma, on one of the adrenal glands. These glands produce cortisol autonomously, meaning they function independently of the usual regulatory signals from the pituitary gland in the brain. Cortisol is a steroid hormone that regulates metabolism, blood sugar, blood pressure, inflammation, and stress response. Even a mild excess over time can significantly affect glucose and lipid metabolism, blood pressure, and bone health.
Recognizing the Subtle Signs and Diagnosis
Subclinical Cushing’s syndrome is often discovered incidentally during imaging tests performed for unrelated conditions. For example, a computed tomography (CT) scan might reveal an “adrenal incidentaloma”—an adrenal mass. Up to 7% of adults undergoing abdominal imaging may have an adrenal incidentaloma, and between 5% and 30% of these can be hormonally active.
Individuals with the subclinical form may present with non-specific health issues that prompt further investigation. These subtle signs can include new or worsening hypertension, type 2 diabetes or impaired glucose tolerance, obesity, and bone density loss (osteoporosis). Other symptoms might involve dyslipidemia, mood changes, and poor wound healing. These symptoms are common in the general population, making diagnosis challenging as they can easily be attributed to other conditions.
The diagnostic process involves specific hormonal tests to confirm mild cortisol excess. A common screening test is the overnight 1-mg dexamethasone suppression test (DST). In this test, a patient takes dexamethasone, a synthetic steroid, and blood cortisol levels are measured the following morning. In healthy individuals, dexamethasone suppresses cortisol production, but in those with subclinical Cushing’s syndrome, cortisol levels are not adequately suppressed.
Other diagnostic tests include 24-hour urinary free cortisol (UFC) measurement and late-night salivary cortisol tests. A diagnosis is typically considered when at least two standard hormonal tests show abnormal results.
Health Implications and Management Approaches
Untreated subclinical cortisol excess carries long-term health risks. Chronic cortisol elevation can contribute to various metabolic and vascular diseases. Complications include cardiovascular disease, such as hypertension and dyslipidemia, which can increase the risk of heart attack and stroke. Diabetes mellitus or impaired glucose tolerance is also frequently observed.
Bone density loss, leading to osteoporosis and an increased risk of fractures, is another concern. Vertebral fractures may even be an initial symptom in otherwise asymptomatic individuals. Subclinical hypercortisolism has been associated with a higher incidence of cardiovascular events and mortality compared to non-secreting adrenal incidentalomas.
Management approaches typically involve either watchful waiting with regular monitoring or surgical removal of the adrenal tumor, known as adrenalectomy.
Watchful Waiting
Watchful waiting involves closely observing the patient’s associated health conditions, such as hypertension, diabetes, and bone health. This approach is often considered for patients with very mild cortisol excess or those without significant associated health problems.
Adrenalectomy
Surgical removal of the adrenal tumor is often recommended when the patient has associated health conditions like uncontrolled hypertension, type 2 diabetes, or progressive bone loss. Adrenalectomy can lead to improvements in hypertension, obesity, diabetes, and cholesterol levels. The decision to pursue surgery is influenced by factors such as tumor size, severity of associated health conditions, and overall patient health. While surgery can offer a cure, it may lead to temporary adrenal insufficiency in the remaining adrenal gland, requiring temporary glucocorticoid replacement therapy.