Measuring Late-Night Salivary or Serum Cortisol in Patients with Eucortisolism After TSS

STEP 1 — Gather Information

Collect postoperative morning serum cortisol and/or UFC, medication list (especially glucocorticoids), timing of transsphenoidal surgery, and any symptoms suggestive of recurrence (e.g., weight gain, hypertension, hyperglycemia). Confirm eucortisolism (normal morning cortisol and UFC) and absence of exogenous glucocorticoids.

STEP 2 — Rule In / Rule Out

If morning cortisol or UFC is elevated (not eucortisolemic) → manage persistent hypercortisolism per guideline; if morning cortisol and UFC are normal (eucortisolemic) → proceed to measure late-night cortisol.

STEP 3 — Classify or Stratify

If late-night salivary or serum cortisol is within the laboratory’s reference range → classify as likely remission; if late-night cortisol is above the reference range → classify as suspicious for recurrence.

STEP 4 — Decide

For likely remission → continue routine surveillance with clinical assessment and periodic morning cortisol/UFC every 6–12 months; for suspicious recurrence → repeat late-night cortisol, obtain UFC, and perform pituitary MRI; consider referral for re-intervention (repeat TSS, medical therapy, or radiation).

Clinical Guardrails / Mimics / Pitfalls

Do not rely solely on morning cortisol/UFC to exclude recurrence; do not measure late-night cortisol while patient is on exogenous glucocorticoids; avoid interpreting a single borderline result without repeat testing under standardized conditions; do not use late-night cortisol in patients with irregular sleep schedules or shift work without adjusting sample timing; do not base treatment decisions on late-night cortisol alone without correlating with clinical symptoms and other biochemical tests.

Concrete Clinical Example

A 48‑year‑old woman had TSS for Cushing disease. At 5‑month postoperative visit, morning serum cortisol and UFC were normal, she was asymptomatic, and not on glucocorticoids. A late‑night salivary cortisol drawn at 11 PM was within normal limits, supporting remission; she continued routine follow‑up. In another case, a similar patient had an elevated late‑night salivary cortisol, prompting repeat UFC and MRI, which revealed a residual adenoma requiring repeat TSS.

Source: Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline, Nieman et al., Endocrine Society, 2015, DOI:10.1210/jc.2015-1818