- Cushing's syndrome results from cortisol excess
- Commonest cause is iatrogenic from the use of exogenous steroid
medication
- Cushing's disease has an incidence of 1 per 100.000 / year
- Female : male is 5:1
- Peak incidence is 30-50 years
Aetiology
- Primary adrenal disease (20%)
- Adrenal adenoma
- Adrenal carcinoma
- Adrenal cortical hyperplasia
- Secondary adrenal disease
- Cushing's disease = Due to ACTH secreting pituitary microadenoma
(70%)
- Ectopic ACTH production from a malignancy (10%)
- Small cell carcinoma of the lung
- Carcinoid tumours
- Medullary carcinoma of the thyroid
- Pseudo-Cushing's syndrome
- Major depressive illness
- Alcohol excess
Clinical features
| Symptoms |
Signs |
| Weight gain |
Truncal obesity |
| Menstrual irregularity |
Plethora |
| Hirsuitism in women |
'Moon' face |
| Headache |
Hypertension |
| Thirst |
Bruising |
| Back pain |
Striae |
| Muscle weakness |
Buffalo hump |
| Abdominal pain |
Acne |
| Lethargy / depression |
Osteoporosis |
Investigation
- The clinical picture often does not allow identification of the
cause of Cushing's syndrome
- Investigations are aimed at:
- A biochemical confirmation of the diagnosis of Cushing's syndrome
- Identifying the site of the pathological lesion - adrenal,
pituitary, ectopic production
- Identifying the nature of the pathology
Diagnosis can be confirmed by:
- Increased 24 hour urinary free cortisol
- Loss of diurnal rhythm of serum cortisol
- Failure of suppression of serum cortisol with low dose (0.5 mg)
dexamethasone
- Increased salivary cortisol
Anatomical site of lesion identified by:
- Serum ACTH
- Low in adrenal disease, high in pituitary and ectopic production
- CRH test
- Increased ACTH following CRH in pituitary disease
- No increase in ACTH following CRH in ectopic production
- High-dose dexamethasone suppression test (2 mg qds for 2 days)
- Serum cortisol reduced by high-dose in pituitary disease
- Suppression of urinary free cortisol to less than 10% of baseline
Identifying the pathological lesion
- Pituitary CT has a sensitivity of about 50% for identifying
microadenomas
- MRI has increased sensitivity but is not 100% predictive
- If diagnostic doubt need bilateral inferior petrosal sinus sampling
for ACTH
- Abdominal CT will allow identification of adrenal pathology
- Somatostatin scintigraphy to identify sites of ectopic hormone
production
Management
- Cushing's disease is best managed by transphenoidal microadenectomy
- Success rate approximately 90%
- Large tumours occasional require open surgery via the anterior fossa
- Post-operative radiotherapy occasionally required
- If pituitary surgery fails need to consider bilateral adrenalectomy
- Requires postoperative glucocorticoid and mineralocorticoid
replacement
- 25% patients develop Nelson's syndrome after bilateral adrenalectomy
- Adrenal adenomas require adrenalectomy
- Performed either laparoscopically or via open surgery
- Open surgery can be performed via a transabdominal or
retroperitoneal approach
Bibliography
Boscaro M, Barzon L, Fallo F, Sonino N.
Cushing's syndrome. Lancet 2001; 357: 783-791.
Lucarotti M, Farndon J R. Cushing's Syndrome. Curr Pract Surg
1993; 5: 172 -177.
Newell-Price J, Bertagna X, Grossman A B et al.
Cushing's syndrome. Lancet 2006; 367:
1605-1617.
Orth D N. Cushing's
Syndrome. N Engl J Med 1995; 332: 791-803 |