Cushing's Syndrome

Question 1

Definition

Answer 1

Excess Cortisol

Question 2

Epidemiology

Answer 2

Age 20 - 50 years
Women > Men

Question 3

Risk Factors

Answer 3

Exogenous steroid use - LT
Pituitary adenoma
Adrenal adenoma
Adrenal carcinoma
Neuroendocrine tumours
Small cell lung cancer

Question 4

Aetiology

Answer 4

ACTH independent causes:
- Iatrogenic = Oral steroid use (most common) e.g., PREDNISOLONE
- Adrenal adenoma/carcinoma -
ACTH dependant causes
- Cushing’s disease = pituitary adenoma ->
- Ectopic Cushing’s = coming from elsewhere, e.g., paraneoplastic syndrome, small cell lung cancer
MOST COMMON CAUSE OVERALL: Iatrogenic

Question 5

Pathophysiology

Answer 5

CRH -> ACTH -> Cortisol
CRH typically released with circadian rhythm (high in morning, low at night)
Here the rhythm is lost; excessive unregulated CRH, ACTH, + Cortisol
Cushing’s Disease: pituitary adenoma -> bilateral adrenal hyperplasia due to ACTH hypersecretion

Question 6

Signs

Answer 6

Moon face
Buffalo hump
Central obesity
Hirsutism
Purple Abdo striae
Muscle wasting & proximal myopathy
Osteoporosis
Thin easily bruising skin
Plethoric complexion

Question 7

Symptoms

Answer 7

Bloating + weight gain
Mood change
Tiredness
Easily bruising
Menstrual irregularities
Reduced libido

Question 8

Diagnosis

Answer 8

Drug History - exclude steroid use
FIRST LINE: Random serum cortisol if higher then test at 12am (cortisol is normally at its LOWEST here, if high then v. abnormal)
GOLD STANDARD: Dexamethasone suppression test (overnight) = dexamethasone = essentially cortisol therefore in healthy patient should -ve feedback HPA and decrease cortisol
1. Give dex and measure cortisol before giving dex at 00.00
2. measure cortisol 8 hrs later
- non-Cushing’s = suppression > 50nmol/L
- Cushing’s = little/no suppression
If +ve - then measure PLASMA ACTH
High ACTH = ACTH dependant cause -> Cushing’s disese (PA)
Low ACTH = ACTH independent cause = Adrenal adenoma

Question 9

Treatment

Answer 9

Cushing’s Disease = Transsphenoidal pituitary resection or bilateral adrenalectomy
Adrenal Adenoma = Unilateral Adrenalectomy
Ectopic ACTH = surgical removal e.g., SCLC
Cortisol inhibitors: METYRAPONE, KETOCONAZOLE

Question 10

Complication of bilateral adrenalectomy

Answer 10

NELSONS SYNDROME = Pituitary tumour will continue to enlarge with no -ve feedback from adrenals = HIGHHH ACTH + skin hyper pigmenting

Question 11

Complication

Answer 11

Osteoporosis
HTN
CVD
DM