Monitor HPA axis before and after GH replacement
STEP 1 — Gather Information
Confirm GH deficiency diagnosis, absence of glucocorticoid replacement, and collect baseline adrenal assessment: morning cortisol drawn at 8–9 AM, ACTH stimulation test if cortisol 3–15 µg/dL, symptoms of adrenal insufficiency, current medications (especially estrogen), and IGF-1 target range. Proceed to evaluate adrenal function.
STEP 2 — Rule In / Rule Out
Is the patient currently receiving glucocorticoid replacement? If yes, this skill does not apply (patient already on GC). If no, proceed to assess HPA axis.
STEP 3 — Classify or Stratify
Interpret morning cortisol: <3 µg/dL suggests adrenal insufficiency (AI); 3–15 µg/dL indeterminate; >15 µg/dL makes AI unlikely. If indeterminate, perform low‑dose (1 mg) or standard‑dose (250 µg) ACTH stimulation test; peak cortisol <18.1 µg/dL indicates AI. If AI confirmed, treat with glucocorticoids before GH; if normal, consider GH initiation.
STEP 4 — Decide
If HPA axis is normal, start GH replacement at 0.2–0.4 mg/d for patients <60 years or 0.1–0.2 mg/d for patients ≥60 years, and schedule reassessment of HPA axis 6–12 weeks after initiation. If HPA axis is abnormal, initiate glucocorticoid replacement first (e.g., hydrocortisone 15–20 mg/day divided), then reassess adrenal adequacy before considering GH.
Clinical Guardrails / Mimics / Pitfalls
Do not rely on random cortisol to rule out AI; do not start GH without confirming adrenal adequacy in patients not on glucocorticoids; be aware that oral estrogen increases corticosteroid‑binding globulin, raising total cortisol and masking insufficiency; do not forget to retest HPA axis after GH initiation as GH may unmask adrenal insufficiency.
Concrete Clinical Example
A 50‑year‑old man with GHD not on glucocorticoids presents for GH initiation. Morning cortisol is 12 µg/dL (indeterminate). Low‑dose ACTH stim shows peak cortisol 16 µg/dL (<18.1), consistent with AI. He is started on hydrocortisone 10 mg morning, 5 mg evening. After 4 weeks, morning cortisol is 18 µg/dL and ACTH stim peak 20 µg/dL. GH replacement is then begun at 0.2 mg/d nightly, with repeat HPA axis testing planned at 6 weeks.
Source: Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2016, DOI:10.1210/jc.2016-2118