A 52-year-old man from Mumbai presents with progressive hypertension (160/95 mmHg), central obesity, easy bruising, and proximal muscle weakness. He has been on long-term oral prednisolone 20 mg daily for rheumatoid arthritis for 5 years. Laboratory studies show: fasting glucose 185 mg/dL, potassium 3.2 mEq/L, morning cortisol 18 μg/dL, ACTH 8 pg/mL (normal 10–50). A low-dose dexamethasone suppression test (1 mg overnight) shows cortisol of 16 μg/dL (normal <1.8). What is the most appropriate interpretation of these findings?

Explanation

## Clinical Diagnosis: Iatrogenic Cushing's Syndrome ### Key Clinical Features **Key Point:** The patient is receiving exogenous glucocorticoid (prednisolone 20 mg daily), which suppresses the hypothalamic-pituitary-adrenal (HPA) axis. The clinical features of Cushing's syndrome (hypertension, central obesity, proximal weakness, easy bruising, hyperglycaemia, hypokalaemia) are due to the exogenous steroid, not endogenous cortisol overproduction. ### Interpretation of Biochemical Findings | Finding | Interpretation | |---------|----------------| | **Elevated cortisol (18 μg/dL)** | From exogenous prednisolone; total cortisol includes prednisolone metabolites | | **Suppressed ACTH (8 pg/mL)** | Exogenous glucocorticoid suppresses CRH and ACTH via negative feedback | | **No suppression on low-dose dexamethasone** | Expected — endogenous cortisol production is already suppressed; dexamethasone cannot suppress further | | **Clinical Cushing's features** | Iatrogenic — from exogenous steroid dose, not endogenous disease | ### Pathophysiology: HPA Axis Suppression **High-Yield:** Exogenous glucocorticoids suppress the HPA axis at three levels: 1. **Hypothalamus** — inhibit CRH release 2. **Anterior pituitary** — inhibit ACTH secretion 3. **Adrenal cortex** — suppress endogenous cortisol synthesis The low ACTH (8 pg/mL) is the key finding that distinguishes iatrogenic Cushing's from endogenous disease (where ACTH is elevated in secondary/tertiary forms or normal/high in primary forms). ### Why Dexamethasone Suppression Test Shows No Suppression **Clinical Pearl:** In iatrogenic Cushing's syndrome, the dexamethasone suppression test is unhelpful because endogenous ACTH and cortisol are already maximally suppressed by the exogenous steroid. Adding dexamethasone cannot suppress what is already suppressed. The test would be normal (suppression) only if endogenous HPA function were intact. ### Mnemonic: ACTH Patterns in Cushing's **Mnemonic:** **ACTH UP = Ectopic or Cushing's disease; ACTH DOWN = Iatrogenic or adrenal tumour; ACTH NORMAL = Mild Cushing's disease or early adrenal carcinoma** **Key Point:** The suppressed ACTH in the presence of clinical Cushing's features is the diagnostic clue to iatrogenic disease. ### Management Implications **Warning:** Abrupt withdrawal of prednisolone can precipitate acute adrenal insufficiency because the HPA axis is suppressed. The patient requires slow tapering with monitoring of clinical response and, if necessary, glucocorticoid replacement during the taper.