Evaluate PAI Patients Annually for Symptoms and Signs of Over- and Under-Replacement

STEP 1 — Gather Information

Collect weight, supine and standing blood pressure, presence of peripheral edema, and symptoms: glucocorticoid excess (weight gain, insomnia, hyperglycemia, peripheral edema), glucocorticoid deficiency (fatigue, weight loss, nausea, hyperpigmentation), mineralocorticoid excess (hypertension, hypokalemia), mineralocorticoid deficiency (salt craving, postural hypotension, hyperkalemia, hyponatremia). Review current glucocorticoid and mineralocorticoid doses.

STEP 2 — Rule In / Rule Out

Determine if any symptoms or signs suggestive of over- or under-replacement are present. If none are identified, consider replacement adequate and proceed to routine annual care; if any are present, proceed to classification.

STEP 3 — Classify or Stratify

Classify findings into: glucocorticoid over-replacement (e.g., weight gain, insomnia, edema), glucocorticoid under-replacement (fatigue, weight loss, hypotension, hyperpigmentation), mineralocorticoid over-replacement (hypertension, hypokalemia), mineralocorticoid under-replacement (salt craving, postural hypotension, hyperkalemia, hyponatremia), or mixed patterns based on clinical assessment.

STEP 4 — Decide

For glucocorticoid over-replacement, consider reducing the glucocorticoid dose; for under-replacement, consider increasing the glucocorticoid dose. For mineralocorticoid over-replacement, consider reducing fludrocortisone; for under-replacement, consider increasing fludrocortisone or advising adequate salt intake. If replacement appears adequate, maintain current regimen and reassess at next annual visit.

Clinical Guardrails / Mimics / Pitfalls

Do not attribute symptoms solely to PAI without excluding concurrent illness, other endocrine disorders, or medication side effects. Avoid dose adjustments based on isolated abnormal labs without clinical correlation. Do not rely on ACTH levels to guide dosing in adequately replaced patients. Refrain from making dose changes during acute illness without addressing stress‑dosing needs first.

Concrete Clinical Example

A 48‑year‑old man with PAI on hydrocortisone 25 mg daily and fludrocortisone 100 µg daily reports 4 kg weight gain, difficulty sleeping, and mild leg edema over the past year; blood pressure is 142/88 mmHg, no salt craving or postural dizziness. Assessment indicates glucocorticoid over‑replacement; hydrocortisone is reduced to 20 mg daily with re‑evaluation in 3 months.

Source: Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2016, DOI:10.1210/jc.2015-1710