Cushing's Syndrome – GCC Nurse Clinical Guide

Overview

Clinical Features

Diagnosis

Treatment

GCC Context

MCQ Practice

🧬 Cushing's Syndrome — Overview

Cushing's syndrome results from chronic exposure to excess cortisol (glucocorticoids). It can be ACTH-dependent or ACTH-independent.

Cushing's SYNDROME vs Cushing's DISEASE:
Cushing's SYNDROME = any cause of excess cortisol (including exogenous steroids)
Cushing's DISEASE = specifically pituitary ACTH-secreting adenoma (most common cause of endogenous Cushing's)

Causes

Category	Cause	Frequency
Exogenous (iatrogenic)	Long-term corticosteroid use (most common cause overall)	Most common
ACTH-dependent: Pituitary (Cushing's Disease)	ACTH-secreting pituitary adenoma → bilateral adrenal hyperplasia	~70% of endogenous
ACTH-dependent: Ectopic ACTH	Small cell lung cancer (most common); carcinoid; pancreatic tumour	~15% of endogenous
ACTH-independent: Adrenal adenoma	Cortisol-secreting adrenal adenoma; ACTH suppressed	~15% of endogenous
ACTH-independent: Adrenal carcinoma	Virilisation features often present	Rare

👤 Clinical Features of Cushing's Syndrome

Classic Physical Signs

Moon face (round, plethoric face)
Central (truncal) obesity
Buffalo hump (dorsocervical fat pad)
Supraclavicular fat pads
Purple/violaceous striae (stretch marks) — wide, purple (>1 cm)
Skin thinning and easy bruising
Proximal muscle weakness (difficulty rising from chair)

Metabolic Complications

Hypertension (mineralocorticoid effect)
Diabetes mellitus / hyperglycaemia
Hypokalaemia (especially ectopic ACTH — very high cortisol)
Osteoporosis (most significant long-term complication)
Dyslipidaemia
Increased infection risk (immunosuppression)

Other Features

Amenorrhoea / irregular periods (women)
Hirsutism (androgen effect, especially adrenal carcinoma)
Acne
Depression, anxiety, psychosis
Poor wound healing
Growth retardation in children
Oedema (sodium retention)

Ectopic ACTH — Additional Features

Very rapid onset of features
Profound hypokalaemia
Pigmentation (high ACTH → MSH activity)
Severe muscle wasting
Features of underlying malignancy (weight loss, cough)

🔬 Biochemical Diagnosis

Step 1: Confirm Hypercortisolism (Screening Tests)

24-hour urinary free cortisol (UFC): >3× upper limit of normal × 2 collections = Cushing's confirmed
Late-night salivary cortisol: Cortisol should be lowest at midnight (normal diurnal variation). Elevated midnight salivary cortisol = abnormal
Overnight low-dose dexamethasone suppression test (LDDST): 1 mg dexamethasone at 11pm → cortisol measured at 8am. Normal: cortisol <50 nmol/L (suppressed). Cushing's: cortisol >50 nmol/L (NOT suppressed)

Step 2: Determine ACTH-Dependency

Measure plasma ACTH:
- ACTH suppressed (<5 pmol/L) = ACTH-INDEPENDENT → adrenal cause (CT adrenals)
- ACTH normal or elevated = ACTH-DEPENDENT → pituitary or ectopic

Step 3: Localise the Source (if ACTH-dependent)

MRI pituitary — if adenoma visible and >6mm = likely Cushing's disease
High-dose dexamethasone suppression test (HDDST): 8 mg dexamethasone → pituitary tumour suppresses (cortisol falls >50%) but ectopic ACTH does NOT suppress
Inferior petrosal sinus sampling (IPSS): gold standard to confirm pituitary source — invasive procedure
CT thorax/abdomen if ectopic ACTH suspected (small cell lung cancer, carcinoid)

Pseudo-Cushing's: Alcoholism, obesity, major depression, and poorly-controlled diabetes can produce mildly elevated cortisol and some cushingoid features without true Cushing's — requires careful biochemical differentiation.

💊 Treatment of Cushing's Syndrome

Cause	Treatment
Exogenous steroids (iatrogenic)	Gradual steroid tapering — NEVER stop abruptly (adrenal crisis risk)
Cushing's disease (pituitary)	Trans-sphenoidal surgery (TSS) — first-line; bilateral adrenalectomy if surgery fails; radiotherapy
Adrenal adenoma	Unilateral adrenalectomy (laparoscopic) — curative
Adrenal carcinoma	Surgery + mitotane (adrenolytic) ± chemotherapy
Ectopic ACTH (benign carcinoid)	Remove primary tumour; bilateral adrenalectomy if tumour not found
Ectopic ACTH (malignant, e.g., SCLC)	Medical adrenal blockade (ketoconazole, metyrapone, mifepristone) while treating malignancy

Medical Treatment for Hypercortisolism

Metyrapone: Blocks cortisol synthesis (11β-hydroxylase inhibitor) — used pre-operatively and in ectopic Cushing's
Ketoconazole: Adrenal steroidogenesis inhibitor — monitor LFTs (hepatotoxic)
Cabergoline: Dopamine agonist for pituitary Cushing's — modest effect
Osilodrostat / Levoketoconazole: Newer agents approved for endogenous Cushing's

⚠️ Adrenal Crisis — Critical Complication

Adrenal insufficiency after treatment of Cushing's syndrome:
After bilateral adrenalectomy or successful TSS, the HPA axis is suppressed. The remaining adrenal gland(s) are atrophied and cannot produce cortisol in response to stress.
Result: ADRENAL CRISIS under stress (surgery, illness, vomiting)

Steroid Sick Day Rules (essential patient education)

Unwell/fever: Double or triple oral steroid dose until recovered
Unable to tolerate oral medications (vomiting): Give IM hydrocortisone 100 mg → attend hospital immediately
Emergency card / MedicAlert bracelet: All patients on long-term steroids should carry emergency steroid card
Hospital emergency cortisol: Hydrocortisone 100 mg IV/IM immediately + 50 mg every 6 hours + IV saline

Nelson's Syndrome

After bilateral adrenalectomy for Cushing's disease — the pituitary adenoma may grow aggressively (loss of cortisol feedback). Presents with marked skin pigmentation and visual field defects. Requires pituitary radiotherapy.

🌍 GCC-Specific Context

Steroid Use and Iatrogenic Cushing's in GCC ▼

Iatrogenic Cushing's (from corticosteroid medications) is the most common form in clinical practice in GCC as globally
Long-term steroid use for asthma, IBD, rheumatological conditions, transplant immunosuppression, brain tumours
Ramadan fasting and corticosteroid use: sick day rules apply — discuss with patient before Ramadan about illness management; steroid coverage during fasting may need adjustment
Steroid-induced diabetes is common — all patients on long-term steroids should have regular HbA1c monitoring

SCFHS / DHA / QCHP Exam Focus ▼

Cushing's SYNDROME = any excess cortisol; Cushing's DISEASE = pituitary ACTH adenoma
Most common cause overall: exogenous (iatrogenic) steroid use
Most common endogenous cause: pituitary Cushing's disease (70%)
Classic features: moon face, central obesity, buffalo hump, purple striae, proximal weakness
Biochemical screening: 24h UFC, late-night salivary cortisol, overnight 1mg LDDST
LDDST: normal = cortisol suppressed to <50 nmol/L; Cushing's = NOT suppressed
ACTH suppressed = adrenal cause (ACTH-independent); ACTH elevated = pituitary/ectopic
Ectopic ACTH: most common cause = small cell lung cancer; profound hypokalaemia
Adrenal crisis prevention: sick day rules, never abruptly stop steroids, carry steroid card
Nelson's syndrome: after bilateral adrenalectomy → pituitary adenoma grows → pigmentation + visual loss

📝 MCQ Practice

1. A patient with rheumatoid arthritis has been on prednisolone 15 mg daily for 3 years. She develops moon face, central obesity, and significant skin thinning. Her morning cortisol is elevated. What is the MOST likely diagnosis?

✅ B — Iatrogenic Cushing's syndrome from long-term exogenous glucocorticoids is the most common cause of Cushing's syndrome overall. The cushingoid features and history of long-term prednisolone use make this the clear diagnosis. Note: plasma ACTH will be suppressed (exogenous steroid suppresses HPA axis).

2. A patient has confirmed Cushing's syndrome. Plasma ACTH is 8 pmol/L (elevated). High-dose dexamethasone (8 mg) suppresses cortisol by 60%. What is the MOST likely source?

✅ C — ACTH elevated = ACTH-dependent (rules out adrenal). High-dose dexamethasone SUPPRESSES cortisol by >50% = pituitary source (pituitary tumours retain some feedback sensitivity). Ectopic ACTH tumours do NOT suppress with high-dose dexamethasone. MRI pituitary is next investigation.

3. A patient on long-term prednisolone for asthma develops severe vomiting and cannot take oral medications. She has known adrenal suppression. What should she do IMMEDIATELY?

✅ C — This is a potential adrenal crisis scenario. When a patient on long-term steroids cannot tolerate oral medication due to vomiting, IM hydrocortisone 100 mg should be administered (patient/family self-injection kit) and they must attend hospital immediately. Without parenteral steroid coverage, adrenal crisis (hypotension, circulatory collapse) can develop rapidly.

4. Which investigation is the GOLD STANDARD screening test for Cushing's syndrome?

✅ C — Screening for Cushing's uses: 24-hour UFC (×2 collections), late-night salivary cortisol, or overnight 1mg LDDST. A random 9am cortisol is non-specific (stress elevates cortisol; diurnal variation makes single measurement unreliable). MRI is used after biochemical confirmation. Plasma ACTH differentiates pituitary vs adrenal AFTER hypercortisolism is confirmed.