Endo Case Challenge: Amenorrhea for Months, Mood Swings, Weight Gain in a 38-Year-Old Woman

Benjamin Scott Harris, MD, MPH; Thomas Michael Price, MD


September 13, 2022

Adrenal insufficiency was also unlikely in this patient. A morning cortisol level < 3 µg/dL is highly suggestive of adrenal insufficiency. Her morning cortisol levels were normal.

Cushing syndrome is rare, with an incidence of 6-8 per million per year.[1] Approximately 60%-70% of cases are due to an ACTH-producing pituitary adenoma (Cushing disease), 10%-15% to ectopic ACTH production, and 20% to adrenal tumors.[2] Symptomatology is nonspecific. The most common symptoms are decreased libido, obesity/weight gain, plethora, round facies, cycle irregularity, increased body hair, high blood pressure, ecchymoses, fatigue, depression, and glucose intolerance.

Adrenal adenomas are benign tumors of the adrenal cortex that are often found incidentally on imaging, particularly if they are hormonally inactive and are not causing symptoms. About 15% of adrenal adenomas are hormonally active and present with hypercortisolism (1%-29%), hyperaldosteronism (1.5%-3.3%), and/or adrenergic symptoms due to pheochromocytoma (1.5%-11%).[3,4]

Hypercortisolism that causes Cushing syndrome can be difficult to diagnose, given that it can present with a wide range of symptoms, including hypertension; hyperglycemia; obesity; muscle weakness and fatigue; depression; osteopenia; and dermatologic changes, such as striae and acne. Figure 1 shows an example of striae in Cushing syndrome.

Figure 1.

The prevalence of striae in patients with Cushing syndrome is less than 50%; however, when present, striae are specific for the syndrome.[5] Menstrual cycle changes, including oligomenorrhea and amenorrhea, are present in nearly 80% of women with Cushing syndrome, owing to low concentrations of luteinizing hormone and FSH resulting from gonadotropin-releasing hormone suppression by excess cortisol.[6,7]

CT is recommended if an adrenal tumor is suspected. Features that are more consistent with a benign adenoma than with cancer include[8]:

  • Round tumors that are < 4 cm and have sharp margins and homogenous density

  • Low attenuation (< 10 Hounsfield units) on unenhanced CT

If an adenoma is found, the Endocrine Society guidelines recommend testing patients for Cushing syndrome.[9] The diagnosis is confirmed when two different screening tests are abnormal. Discordant testing requires further evaluation. Recommended screening tests include measurement of 24-hour urinary free cortisol, late-night salivary cortisol (sample collected 11 PM to midnight), late-night serum cortisol (> 7.5 µg/dL is an abnormal result), and/or a low-dose dexamethasone suppression test (AM cortisol level >1.8 µg/dL is an abnormal result). When Cushing syndrome is suspected in patients with hyperandrogenism, the low-dose dexamethasone suppression test is an appropriate first step. It is performed by administering 1.0 mg of dexamethasone by mouth between 11 PM and midnight, followed by measurement of the serum cortisol at 8:00 AM the following morning.[10,11] Loss of diurnal variation in blood cortisol, as seen in this patient, is also commonly found in Cushing syndrome.[12]


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