Is the patient's condition due to an adrenal or pituitary disorder?

This is Neither Primary Adrenal Nor Primary Pituitary Disease—This Patient Has Normal HPA Axis Function

The dexamethasone suppression test results definitively rule out both adrenal and pituitary pathology: morning cortisol suppressed appropriately to 3.9 µg/dL and ACTH suppressed to 8 pg/mL after dexamethasone administration, confirming an intact and normally functioning hypothalamic-pituitary-adrenal axis. 1

Key Diagnostic Findings That Exclude Adrenal/Pituitary Disease

Normal HPA Axis Suppression

• The patient's cortisol suppressed to 3.9 µg/dL (approximately 108 nmol/L) after dexamethasone, which is well below the threshold for Cushing's syndrome and demonstrates normal negative feedback. 1, 2
• ACTH appropriately suppressed to 8 pg/mL, confirming the pituitary is responding normally to glucocorticoid feedback. 1, 2
• A normal dexamethasone suppression test excludes both ACTH-dependent (pituitary) and ACTH-independent (adrenal) Cushing's syndrome. 3

Normal Imaging Studies

• MRI of the pituitary is normal with no adenoma, excluding pituitary-dependent Cushing's disease. 4
• CT of adrenal glands with adrenal protocol is normal without adenoma, excluding adrenal Cushing's syndrome or other adrenal pathology. 1, 2

24-Hour Urine Free Cortisol is Normal

• The 24-hour urine free cortisol of 63.9 µg/24h is within normal limits (normal range typically <50-100 µg/24h depending on laboratory), further excluding hypercortisolism. 1

What This Patient Actually Has

Likely Diagnosis: Non-Classic Congenital Adrenal Hyperplasia (NC-CAH)

• The 17-hydroxyprogesterone level of 243 ng/dL is moderately elevated and suggests non-classic 21-hydroxylase deficiency CAH, which can present with weight gain, fatigue, and metabolic dysfunction in adult women. 5
• NC-CAH is the most common autosomal recessive disorder in humans, with disease frequency of 1/27 in Ashkenazi Jews. 5
• Women with NC-CAH present with symptoms of androgen excess including hirsutism, acne, oligomenorrhea/amenorrhea, and infertility. 5
• The androstenedione level of 152 ng/dL is mildly elevated, supporting androgen excess from NC-CAH. 5

Concurrent Hypothyroidism

• TSH of 5.2 mIU/L is elevated, indicating primary hypothyroidism, which contributes to weight gain and fatigue. 1
• Hypothyroidism must be treated, but corticosteroids should NOT be started before thyroid hormone in this patient because she does NOT have adrenal insufficiency. 2

Metabolic Syndrome/Insulin Resistance

• The patient has uncontrolled diabetes with continued weight gain, suggesting insulin resistance and metabolic syndrome as the primary driver of her symptoms. 1
• Central obesity and weight gain in the setting of uncontrolled diabetes point to metabolic dysfunction rather than true Cushing's syndrome. 3

Critical Pitfalls to Avoid

Do Not Misdiagnose as Cushing's Syndrome

• A cushingoid appearance (central obesity, weight gain) does NOT equal Cushing's syndrome—the dexamethasone suppression test is the definitive test and it is normal here. 6, 3
• Some patients with NC-CAH can have cushingoid features due to metabolic dysfunction and obesity, but they do not have true hypercortisolism. 6

Do Not Confuse NC-CAH with Adrenal Insufficiency

• NC-CAH is NOT adrenal insufficiency—these patients have normal or near-normal cortisol production but shunting of steroid precursors toward androgen pathways. 5
• The normal dexamethasone suppression test confirms adequate cortisol production. 1, 2

Confirm NC-CAH Diagnosis

• An ACTH stimulation test measuring 17-hydroxyprogesterone at baseline and 60 minutes post-cosyntropin is the gold standard confirmatory test for NC-CAH. 5
• A stimulated 17-OHP level >1000 ng/dL is diagnostic of NC-CAH. 5
• Molecular genetic analysis of CYP21A2 gene mutations can provide definitive confirmation. 5, 6

Recommended Management Algorithm

Step 1: Confirm NC-CAH Diagnosis

• Perform ACTH stimulation test with 17-hydroxyprogesterone measurements at 0 and 60 minutes. 5
• Consider genetic testing for CYP21A2 mutations if biochemical testing is confirmatory. 5, 6

Step 2: Treat Hypothyroidism

• Initiate levothyroxine replacement for TSH 5.2 mIU/L. 1
• In this patient WITHOUT adrenal insufficiency, thyroid hormone can be started without concern for precipitating adrenal crisis. 2

Step 3: Optimize Diabetes Management

• Intensify diabetes management to address uncontrolled hyperglycemia and insulin resistance. 1
• Weight loss and metabolic optimization will improve fatigue and overall symptoms. 1

Step 4: Consider Glucocorticoid Treatment for NC-CAH

• If NC-CAH is confirmed and the patient has significant symptoms of androgen excess, low-dose glucocorticoid therapy (hydrocortisone 15-20 mg daily or prednisone 5-7.5 mg at bedtime) can suppress ACTH-driven androgen production. 5
• Glucocorticoid treatment has been shown to reverse symptoms of hyperandrogenemia within 3 months in NC-CAH patients. 5