Clues Pointing TO This Diagnosis

Central (truncal) weight gain around the middle with facial and neck fullness — excess fat deposition in the face, back of the neck, and visceral organs is characteristic of hypercortisolism
Wide, deep purple abdominal striae — purple/violaceous striae are a specific skin manifestation of Cushing syndrome
Dorsocervical fat pad ("buffalo hump") — dorsocervical fat pads reflect the abnormal fat redistribution of cortisol excess
Rounded "moon" face with plethora — round facies is a classic feature
Easy bruising with light touch and thin, paper-like skin — easy bruising and thin skin are highly associated skin findings
New hypertension — hypertension is a common metabolic manifestation of hypercortisolism
New hyperglycemia — glucocorticoid excess causes hyperglycemia through insulin resistance
Menstrual irregularity — cortisol excess disrupts the reproductive axis, causing irregular menses
Proximal muscle weakness (difficulty climbing stairs) — proximal myopathy from protein catabolism is typical
Relatively young woman (age 38) with a cluster of these features — clinical features strongly associated with Cushing syndrome in a patient younger than 50 warrant testing

Why It's NOT the Similar Diseases

NOT simple obesity/metabolic syndrome — obesity and metabolic syndrome can cause mild cortisol elevations (pseudo-Cushing), but they do not produce wide purple striae, a dorsocervical fat pad, easy bruising with thin skin, and proximal myopathy together, and biochemical testing confirms true hypercortisolism
NOT polycystic ovary syndrome — PCOS causes menstrual irregularity and can cause mild hypercortisolism, but it does not cause purple striae, thin fragile skin, or proximal muscle wasting, and Loretta's screening tests confirm cortisol excess
NOT exogenous (iatrogenic) Cushing syndrome — the most common overall cause of Cushing syndrome is steroid use, but Loretta has no history of glucocorticoid intake, and her ACTH-dependent pituitary source is confirmed on workup
NOT primary hyperaldosteronism — hyperaldosteronism causes hypertension (often with hypokalemia) but not moon face, purple striae, fat redistribution, or hypercortisolism
NOT an adrenal (ACTH-independent) tumor — an adrenal cause would show suppressed ACTH, whereas Loretta has an ACTH-secreting pituitary adenoma on MRI (Cushing disease)

Differential Diagnosis List

Simple obesity/pseudo-Cushing — ruled out by biochemical confirmation of hypercortisolism and specific findings (purple striae, thin skin, myopathy)
Polycystic ovary syndrome — ruled out by presence of purple striae, fragile skin, and confirmed cortisol excess
Exogenous glucocorticoid use — ruled out by absence of steroid intake and demonstration of an endogenous ACTH-dependent source
Primary hyperaldosteronism — ruled out by cortisol-specific clinical features and confirmed hypercortisolism
Adrenal (ACTH-independent) Cushing syndrome — ruled out by the pituitary adenoma with an ACTH-dependent pattern

Key Distinguishing Test

Diagnosis is a two-step process: first confirm hypercortisolism with first-line screening tests—24-hour urinary free cortisol, late-night salivary cortisol, and/or the 1-mg overnight dexamethasone suppression test (2–3 abnormal results establish the diagnosis)—after excluding exogenous steroid use.
Then measure plasma ACTH to determine the cause: a midnormal-to-elevated ACTH indicates an ACTH-dependent process, and a corticotropin-dependent picture with a sellar mass greater than 6 mm on pituitary MRI confirms Cushing disease with nearly 100% specificity.

Board Note

No single symptom is pathognomonic; test in patients with a cluster of specific features (purple striae, easy bruising, proximal myopathy, fat redistribution), especially those under 50, after excluding exogenous steroids
Screen with 24-hour urinary free cortisol, late-night salivary cortisol, or the 1-mg dexamethasone suppression test; because of variability, obtain 2–3 measurements, and confirm with two abnormal tests
After biochemical confirmation, use plasma ACTH to separate ACTH-dependent (pituitary or ectopic) from ACTH-independent (adrenal) causes; Cushing disease (pituitary adenoma) accounts for roughly 60–70% of endogenous cases
First-line treatment is surgery to remove the source—transsphenoidal resection for Cushing disease—with remission rates around 80% at specialized centers
Expect central adrenal insufficiency after successful pituitary surgery: essentially all patients in remission require glucocorticoid replacement (hydrocortisone) with slow tapering over 6–12+ months until the HPA axis recovers
Refer to endocrinology for the diagnostic workup and to an experienced pituitary center for surgery; second-line options for persistent/recurrent disease include medical therapy, radiation, or bilateral adrenalectomy
The following diagnostic algorithm from the JAMA review maps the sequence—exclude steroids, screen for hypercortisolism, then use ACTH and imaging to localize the source—that underlies Loretta's workup:
Figure 2. Algorithm for the Diagnosis of Cushing Syndrome
Cushing Syndrome: A Review. JAMA. July 10, 2023.
Content used under license from the JAMA Network®
© American Medical Association

“Loretta’s Story”