Cushings Syndrome Flashcards
What is Cushings syndrome?
Cushing syndrome is the clinical manifestation of pathological hypercortisolism from any cause.
Epidemiology of Cushings
- Cushing’s syndrome is uncommon, with an estimated 1-10 cases per million in the population
- It most commonly affects people aged 20 to 50 years
- Occurs 3 times more commonly in women than in men
What is Cushings disease?
a pituitary adenoma secreting excess ACTH
Aetiology of Cushings other than Cushings disease
- Iatrogenic - due to exogenous steroid use
- Primary disease - e.g. adrenal adenoma or adrenal hyperplasia - secreting excess cortisol
- Paraneoplastic Cushing’s- cancer producing ectopic ACTH e.g. from small cell lung cancer or neuroendocrine tumours
- Carney complex - a genetic disorder with multiple benign tumours, e.g. cardiac myxoma
- Micronodular adrenal dysplasia - rare cause
RFs for Cushing’s
- Long term steroid use
- Pituitary adenoma
- Adrenal adenoma
- Small cell lung cancer
- Neuroendocrine tumours
Signs of Cushings
- Hypertension
- Moon face
- Buffalo hump
- Central adiposity
- Violaceous striae
- Muscle wasting and proximal myopathy
- Ecchymoses and fragile skin
- Acne
Symptoms of Cushings
- Bloating and weight gain
- Mood change
- Tiredness
- Easy bruising
- Increase susceptibility
- Menstrual irregularity
- Reduced libido
1st line investigation for Cushings
- 24-hour urinary free cortisol
- Overnight dexamethasone suppression test:most sensitive; shows failure of cortisol suppression
- Low dose dexamethasone suppression test:shows failure of cortisol suppression
- Late-night salivary cortisol - helps to demonstrate a loss of the normal circadian pattern.
Any of these is fine
Gold standard investigation for Cushings
- 24-hour urinary free cortisol
- Overnight dexamethasone suppression test
What will a 9am ACTH test show?
- Ifelevated: suggests anACTH-dependentcause and warrants ahigh dose dexamethasone suppression test
- Iflow: suggests anACTH-independentcause and warrants aCT adrenalsto look for adrenal pathology
What will a High dose dexamethasone suppression test show
suppression of cortisol occurs in Cushing’s disease (pituitary adenoma), butnotin an ectopic ACTH source
Differential Diagnosis for Cushings syndrome
- Obesity
- Metabolic syndrome
Management of ACTH - dependent cause
- Cushing’s disease (pituitary adenoma):first-line treatment is withtrans-sphenoidal resectionof the pituitary. There is a role for medical therapy (e.g. glucocorticoid antagonists) or radiotherapy if surgery fails
- Ectopic ACTH source:treatment of underlying cancer
Management of ACTH-independent causes
- Iatrogenic:review the need for medication and try weaning if possible
- Adrenal tumour:tumour resection or adrenalectomy - Unilateral adrenal adenoma, Bilateral adrenal hyperplasiam adrenal carcinoma
Treatment for unilateral adrenal adenoma
Unilateral adrenalectomy offers curative therapy
Following surgery patients will need a tapering course of exogenous steroids for a period of time as their endogenous CRH and ACTH will be suppressed.
Treatment for bilateral adrenal hyperplasia
In patients with overt Cushing’s bilateral adrenalectomy may be offered. Following this patients require replacement of glucocorticoids and mineralocorticoids.
Treatment for adrenal carcinoma
Following appropriate staging resection is the mainstay of management. Adjuvant chemotherapy, radiotherapy or mitotane may be given.
Monitoring of Cushings
Recurrence of adrenocorticotrophic hormone-dependent Cushing syndrome is common, with at least a 5% to 26% risk of recurrence at 5 years.
Patients who have achieved remission should be screened periodically (every 6-12 months) for recurrence of disease.
Complications associated with action of cortisol
- Osteoporosis
- Increased susceptibility to infection
- Diabetes mellitus
- Hypertension
Treatment-related complications
- Hypopituitarism
- Adrenal insufficiency
- Nelson syndrome after bilateral adrenalectomy - enlarged pituitary, development of adenomas.
- Hypothyroidism
- Growth hormone deficiency
- Hypogonadism
Features of Pseudo Cushings
- Cushingoid features and abnormal cortisol levels butnotassociated with HPA pathology
- Common causes include alcohol excess, severe depression, obesity, pregnancy
- Results in afalse positivedexamethasone suppression test and 24h urinary free cortisol
- Differentiated using an insulin stress test
