Cushing's syndrome Flashcards
What is the aetiology of Cushing’s syndrome
Exogenous exposure (most common)
- Long-term steroid treatment e.g. nephrotic syndrome, asthma, cancers, auto-immune
- Steroid use
Endogenous
ACTH dependent (80%)
- Cushing’s disease (pituitary)
- Ectopic ACTH (lung cancer)
ACTH independent
- Adrenal adenoma or carcinoma
- Mutation in cAMP/PKA pathway
- Adrenocortical hyperplasia e.g. McCune Albright syndrome
What are the symptoms and signs of Cushing’s syndrome
Reduced growth rate/short stature
Face and trunk obesity (centripetal)
Moon face (facial plethora) and red cheeks
Hirsutism ± amenorrhoea/menstrual irregularities
Striae
Bruising
Insulin resistance (diabetes)
Muscle weakness and wasting (Proximal myopathy)
Osteopenia
Emotional lability/depression
Acne
Buffalo hump
Thin Skin
Hypertension, hypokalaemia
Pre-pubertal virilisation
(Pigmentation in ACTH dependent causes)
What investigations should be done for Cushing’s syndrome
Bedside:
- 11pm Salivary cortisol (elevated)
- Urinary free cortisol 24h (>50)
Bloods:
-U&Es: mild hypokalaemia
- Serum glucose: elevated
- Overnight dexamethasone suppression test: >50 in the morning
- Low dose dexamethasone suppression test: >50 in the morning (measure before 9am)
- Plasma ACTH: reduced (independent) or raised (dependent)
Other
- Inferior petrosal sinus sampling: Elevated central/peripheral ACTH ratio (pituitary dependent)
- CT/MRI adrenals: ?adenoma, hyperplasia
- CXR/CT chest: ?ectopic tumour
- MRI: ?Pituitary adenoma
What is the management for Cushing’s syndrome due to exogenous exposure
Discontinue administration, lower steroid dose, use alternative steroid-sparing agent
this side effect of corticosteroid medication can be reduced by taking it in the morning on alternate days
What is the management for Cushing’s disease
- Pre-operative medical therapy with mifepristone (300mg OD) or metyrapone (250mg OD)
- Transsphenoidal pituitary adenomectomy
- Post-operative corticosteroid replacement with hydrocortisone 10-25mg per m2 body surface area/day OD in 2-3 divided doses with larger dose in the morning
- Replacement
- Levothyroxine 1.8 micrograms/day OD
- Testosterone transdermal 2/5-7.5mg/day transdermal OR estradiol 2mg/day OD
- Somatropin (recombinant)
- Desmopressin 0.1mg OD 1-3x/day
What is the management for Cushing’s syndrome due to ectopic ACTH
- Pre-operative medical therapy with mifepristone (300mg OD) or metyrapone (250mg OD) or ketoconazole
- Surgical resection or ablation of tumour and metastases
- Adjunct - Chemotherapy or radiotherapy for primary tumour
What is the management for Cushing’s syndrome caused by an adrenal carcinoma or adenoma
- Pre-operative medical therapy with mifepristone (300mg OD) or metyrapone (250mg OD)
- Unilateral/bilateral adrenalectomy or tumour resection
If bilateral: Permanent post-surgical corticosteroid replacement therapy i.e.
- Hydrocortisone 10-25mg per m2 body surface area/day OD with larger morning dose
- Fludrocortisone 0.05-0.1mg OD once daily
What are the complications of Cushing’s syndrome
Diabetes Mellitus
Osteoporosis
Adrenal insufficiency secondary to adrenal suppression
Cardiovascular disease
Hypertension
Nephrolithiasis
Nelson’s syndrome after bilateral adrenalectomy (pituitary enlargement → hypopituitarism + hyperpigmentation)
Hypothyroidism, GH deficiency, Adrenal insufficiency, Hypopituitarism, Hypogonadism
Hyponatraemia
Diabetes insipidus
What is the prognosis for Cushing’s syndrome
Without treatment, the hypercortisolism persists
Untreated there is a survival rate of 50% at 5 years
Worsening of the Cushing phenotype and increased mortality, mainly from cardiovascular disease
With treatment - mortality rate similar to the general population and any of the characteristic features (moon face, striae and supraclavicular fat pads) will resolve
Cardiovascular risk, hypertension, obesity, and decreased quality of life may persist in some patients even after biochemical cure
