Which paraneoplastic endocrine syndrome results from ectopic production of adrenocorticotropic hormone (ACTH) and is most commonly associated with small cell lung cancer?

Question

Accepted Answer

B. Ectopic ACTH syndrome (Cushing syndrome). ## Ectopic ACTH Syndrome (Cushing Syndrome) as a Paraneoplastic Syndrome

**Key Point:** Ectopic ACTH syndrome is a paraneoplastic endocrine syndrome caused by tumor production of ACTH, leading to secondary adrenocorticotropic stimulation and cortisol excess (Cushing syndrome).

**High-Yield:** Small cell lung cancer (SCLC) accounts for 50–60% of all ectopic ACTH cases. Other common sources include carcinoid tumors (thymic, bronchial, gastroenteropancreatic) and medullary thyroid carcinoma.

### Pathophysiology

```mermaid
flowchart TD
  A[Tumor produces ACTH] --> B[Stimulates adrenal cortex]
  B --> C[Increased cortisol production]
  C --> D[Cushing syndrome manifestations]
  D --> E[Hypokalemia, hyperglycemia, hypertension]
  D --> F[Proximal muscle weakness, mood changes]
```

### Clinical Features of Ectopic ACTH Syndrome

| Feature | Characteristic |
| --- | --- |
| **Onset** | Rapid (weeks to months) |
| **Hypokalemia** | Severe, often symptomatic (muscle weakness, arrhythmias) |
| **Metabolic alkalosis** | From renal potassium loss |
| **Hyperglycemia** | Often severe, may require insulin |
| **Hypertension** | Due to mineralocorticoid effects of excess cortisol |
| **Proximal myopathy** | Weakness of hip and shoulder girdles |
| **Mood disturbances** | Depression, anxiety, psychosis |
| **Skin manifestations** | Hyperpigmentation (from elevated ACTH), absence of typical striae and obesity (rapid onset) |

### Diagnostic Approach

1. **24-hour urinary free cortisol:** elevated
2. **Plasma ACTH:** elevated (>200 pg/mL suggests ectopic source)
3. **Low-dose dexamethasone suppression test (LDDST):** no suppression of cortisol (unlike pituitary Cushing)
4. **High-dose dexamethasone suppression test (HDDST):** no suppression (ectopic ACTH is autonomous)
5. **Imaging:** CT/MRI to localize tumor source

**Clinical Pearl:** The rapid onset of severe hypokalemia and metabolic alkalosis in a patient with Cushing syndrome should raise suspicion for ectopic ACTH production, particularly in the context of SCLC.

**Mnemonic:** **SCLC + ACTH** = **S**mall **C**ell **L**ung **C**ancer produces **ACTH** → rapid, severe Cushing syndrome with prominent hypokalemia.

Answer

A. Hypoglycemia from insulin-like growth factor II (IGF-II)

Answer

C. Hypercalcemia of malignancy

Answer

D. Syndrome of inappropriate antidiuretic hormone (SIADH)

Which paraneoplastic endocrine syndrome results from ectopic production of adrenocorticotropic hormone (ACTH) and is most commonly associated with small cell lung cancer?

Explanation

Ectopic ACTH Syndrome (Cushing Syndrome) as a Paraneoplastic Syndrome

Pathophysiology

Clinical Features of Ectopic ACTH Syndrome

Diagnostic Approach

Practice similar questions

Join our NEET PG community

Feature	Characteristic
Onset	Rapid (weeks to months)
Hypokalemia	Severe, often symptomatic (muscle weakness, arrhythmias)
Metabolic alkalosis	From renal potassium loss
Hyperglycemia	Often severe, may require insulin
Hypertension	Due to mineralocorticoid effects of excess cortisol
Proximal myopathy	Weakness of hip and shoulder girdles
Mood disturbances	Depression, anxiety, psychosis
Skin manifestations	Hyperpigmentation (from elevated ACTH), absence of typical striae and obesity (rapid onset)