Cushing’s syndrome is a rare endocrine disorder resulting from prolonged exposure to excessively high levels of the hormone cortisol. While pregnancy does not cause this condition, it induces a state of physiological hypercortisolism, dramatically increasing the body’s natural cortisol production. This hormonal surge creates immense diagnostic challenges, as the symptoms of a healthy pregnancy can closely mirror those of the disease state. The difficulty in distinguishing between the two makes Cushing’s syndrome during gestation a significant concern for both mother and fetus.
Understanding Cushing’s Syndrome
Cortisol, the “stress hormone,” is a glucocorticoid produced by the adrenal glands. It regulates metabolism, manages the stress response, controls blood pressure, and reduces inflammation. Chronic excess of this hormone, known as hypercortisolism, leads to Cushing’s syndrome.
Cortisol excess is categorized as exogenous or endogenous. Exogenous causes involve taking high doses of corticosteroid medications like prednisone. Endogenous causes, where the body produces too much cortisol internally, are usually due to tumors.
Internal causes often involve a non-cancerous growth (adenoma) in the pituitary gland, termed Cushing’s disease. Less frequently, a tumor on an adrenal gland can directly overproduce cortisol. Consequences of chronic hypercortisolism include:
- Central obesity with slender limbs
- A rounded “moon” face
- Easy bruising
- Pink or purple stretch marks
High blood pressure, muscle weakness, and new-onset diabetes are common features. Untreated, the condition can lead to severe health issues, including heart attack, stroke, and bone loss.
Hormonal Overlap: Why Pregnancy Symptoms Mimic Cushing’s
Normal pregnancy involves significant changes to the hypothalamic-pituitary-adrenal (HPA) axis, leading to “physiological hypercortisolism.” Cortisol levels are naturally elevated throughout gestation. The placenta contributes by producing Corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to increase cortisol output.
The liver also produces more Cortisol-Binding Globulin (CBG), which binds to cortisol and raises the total amount circulating in the blood. This normal hormonal state creates a perfect mimicry of the disease state.
Many common pregnancy symptoms overlap with Cushing’s presentation. Weight gain, fluid retention, and edema can be mistaken for the central obesity and facial roundness seen in Cushing’s. Stretch marks (striae) commonly appear during pregnancy, making the violaceous striae characteristic of Cushing’s less specific as a symptom.
Elevated blood pressure and glucose intolerance, signs of preeclampsia or gestational diabetes, are associated with both a healthy pregnancy and active Cushing’s syndrome. This extensive clinical overlap means a definitive diagnosis cannot be made based on physical examination alone.
Diagnostic Challenges During Pregnancy
Standard biochemical tests used to diagnose Cushing’s syndrome become unreliable during gestation. The 24-hour urine free cortisol (UFC) test is impacted because normal pregnancy causes UFC levels to rise significantly above the non-pregnant limit. This makes establishing a clear cut-off value challenging.
The Dexamethasone Suppression Test (DST) is also compromised. Increased levels of CBG and placental hormones interfere with the expected suppression of cortisol, often producing false-positive results.
A more useful screening tool is the late-night salivary cortisol (LNSC) test. The normal circadian rhythm, where cortisol levels are low late at night, is preserved in a healthy pregnancy. A high LNSC level, indicating a loss of this rhythm, is a stronger indicator of true Cushing’s syndrome.
Once hypercortisolism is confirmed, imaging is necessary to locate the source while ensuring fetal safety. Magnetic Resonance Imaging (MRI) without contrast is the preferred method for viewing the pituitary and adrenal glands, as it avoids radiation exposure associated with CT scans. This specialized diagnostic pathway requires collaboration between endocrinologists and high-risk obstetricians.
Managing Cushing’s Syndrome While Pregnant
Management focuses on controlling hypercortisolism to reduce maternal and fetal risks. Untreated Cushing’s syndrome is associated with high rates of maternal complications, including severe preeclampsia, gestational diabetes, and heart failure. Fetal risks include intrauterine growth restriction, preterm birth, and increased risk of fetal loss.
Surgical intervention is often the definitive treatment, typically recommended during the second trimester if the tumor is localized and accessible. Adrenalectomy or pituitary surgery can be performed during this window to minimize complications. The mother will require steroid replacement therapy following the surgery.
If surgery is not feasible, medical management is an alternative. Metyrapone has been used to block cortisol production, showing a relatively safe profile for the fetus. The decision between medical control and surgery is highly individualized, based on disease severity and stage of gestation.
Conservative management, involving close monitoring and treating complications like hypertension and diabetes, may be considered for mild cases diagnosed late in the third trimester. A multidisciplinary team is necessary to balance treating the mother’s condition with ensuring the best outcome for the baby.