Cushing's and Addison's disease Flashcards
1
Q
What are the causes of Cushing’s syndrome?
A
Causes can be divided into 2 groups:
- ACTH-dependent:
- excessive ACTH from the pituitary (Cushing’s disease → pituitary adenoma, ~80% of ATCH dependent disease)
- ectopic ACTH-producing tumour (such as small-cell carcinoma of the lung or bronchial carcinoid tumours)
- excess ACTH administration - Non-ACTH-dependent:
- adrenal adenomas
- adrenal carcinomas
- excess glucocorticoid administration
- most often due to a unilateral tumours (adrenal adenoma in 60% and adrenal carcinoma in 40% of cases)
- rare causes of Cushing’s syndrome: corticotropin-dependent macronodular adrenal hyperplasia, primary pigmented nodular adrenal disease and McCune-Albright syndrome
2
Q
Distinguish between primary and secondary adrenal insufficiency.
A
- Primary insufficiency (Addison’s disease): inability of the adrenal glands to produce enough steroid hormones
- Secondary insufficiency: inadequate pituitaru or hypothalamic stimulation of the adrenal glands
3
Q
What are the potential causes of primary adrenal insufficiency?
A
- Anatomic destruction of the gland (acute or chronic)
- Addison’s disease (autoimmune)
- Surgical removal
- Trauma + more - Metabolic failure in hormone production
- Congenital adrenal hyperplasia
- Enzyme inhibition (ketoconazole, fluconazole, etomidate, metapyrone)
- Accelerated hepatic metabolism of cortisol (phenytoin, barbiturates, rifampicin) - Other causes
- ACTH-blocking antibodies
- Mutation in ACTH receptor gene
- Adrenal hypoplasia congenita
4
Q
What are the potential causes of secondary adrenal insufficiency?
A
- Hypothalamic-related
- Congenital
- CRH deficiency
- Trauma (fracture of the skull base) - Suppression of hypothalamic-pituitary axis
- Exogenous steroid administration
- Antipsychotic medication (chlorpromazone)
- Steroid production from tumours - Pituitary
- Congenital → aplasia
- Tumours → cysts, adenoma, meningiomas, craniopharyngiomas
- Panhypopituitarism → Sheehan’s syndrome
5
Q
Describe the acute presentation of adrenal insufficiency.
A
- Presentation may be a crisis (Addisonian) precipitated by infection, surgery or trauma
- Features include: hypotension, hypovolaemic shock, acute abdo pain, low-grade pyrexia, vomiting
- Sudden onset of insufficiency, such as Waterhouse-Friderischen syndrome (infarction of adrenals 2° to septicaemia) presents as collapse and shock
6
Q
List the non-specific symptoms in which you shoulder consider a diagnosis of adrenal insufficiency.
A
- fatigue + weakness
- anorexia
- N+V
- weight loss
- abdo pain
- diarrhoea
- constipation
- cravings for salt and salty foods (primary insufficiency)
- muscle cramps and joint pains
- syncope or dizziness (due to hypotension)
- confusion
- personality change
- irritability
- loss of pubic or axillary hair in women, delayed puberty in children
7
Q
What are the signs of adrenal insufficiency?
A
- hyperpigmentation (not present in secondary adrenal insufficiency)
- hypotension
- postural hypotension
8
Q
What investigations are carried out to diagnose adrenal insufficiency and Addison’s disease?
A
- Serum sodium: reduced in 90% of new cases of 1° adrenal insufficiency
- Serum potassium: raised in 50% of new cases of 1° adrenal insufficiency
- Serum calcium: raised in 10-20% of new cases of primary adrenal insufficiency
- FBC: may be anaemia, mild eosinophilia and lymphcytosis
- Glucose: often low in children
- LFTs: may be raised liver transaminase
- Cortisol: usually reduced
- levels of <100 nmol/L should prompt urgent investigation or admission
- levels of 100-500 nmol/L require referral to an endocrinologist for further investigation - ACTH: allows differentiation between 1° and 2° (raised in 1°, reduced in 2°)
- Plasma renin and aldosterone levels: high renin, low aldosterone in Addison’s; usually unaffected in 2°
- Other:
- short synacthen test
- insulin tolerance test
- adrenal autoantibodies
- CXR (exclude lung neoplasm)
- AXR
- CT scan (adrenal glands)
- MRI (hypothalamus + pituitary)
- other HPA hormones
9
Q
Describe the management for adrenal insufficiency.
A
Glucocorticoid + mineralocorticoid replacement are required
- Glucocorticoid
- hydrocortisone is mainstay treatment (15-30mg in 3 divided doses with the highest dose in the morning
- increase dose during illness/surgery to avoid adrenal crisis - Mineralcorticoid
- usually required in primary adrenal insufficiency
- fludrocortisone is used and the usual dose is 50-300 micrograms per day
10
Q
What are signs of steroid hormone over-replacement in adrenal insufficiency?
A
- raised BP
- thin skin
- striae
- easy bruising
- glucose intolerance
- hyperglycaemia
- electrolyte abnormalities
11
Q
What are signs of steroid hormone under-replacement in adrenal insufficiency?
A
- persisting symptoms of Addison’s disease (fatigue, postural hypotension, nausea, weight loss and salt craving)
12
Q
Describe the emergency management of acute adrenal insufficiency.
A
- requires urgent admission to hospital
- administration of glucocorticoids is the only definitive therapy
- immediate administration of hydrocortisone IV or IM:
- 100mg for an adult
- at high doses hydrocortisone has mineralocorticoid action so fludrocortisone is not required - rehydration with normal saline infusion
- continuous cardiac and electrolyte monitoring
- following rehydration, administration of 100-200mg hydrocortisone in 5% glucose over 24h by IV infusion
- treatment of the underlying precipitating disorder (e.g. infection with abx)
- once stabilised, gradual reduction of IV steroid dose and re-institution of oral therapy
13
Q
Describe the clinical presentation of Cushing’s syndrome.
A
- Truncal obesity, supraclavicular fat pads, buffalo hump, weight gain
- Facial fullness, moon face, facial plethora
- Proximal muscle wasting and weakness
- Diabetes or impaired glucose tolerance
- Gonadal dysfunction, reduced libido
- Hypertension
- Nephrolithiasis
- Skin; skin atrophy, purple striae, hirsutism, acne
- Psychological problems: depression, cognitive dysfunction, emotional lability
- Osteopenia or osteoporosis
- Oedema
- Irregular menstruation
- Polyphagia, polydipsia, polyuria
- Impaired immune system
14
Q
What investigations should be carried out to confirm the presence of Cushing’s syndrome?
A
- 24h urinary free cortisol:
- can diagnose Cushing’s syndrome if 2+ collections measure cortisol excretino as 3x ULN - 1mg overnight dexamethasone suppression test:
- useful if unable to reliably collect a 24h urine sample
- 1mg of dexamethasone is ingested at 11pm and serum cortisol emasured at 8am the next morning
- cortisol not suppressed, ACTH undetectable or low - Late-night salivary cortisol
- FBC: raised WBC
- U&Es, ABG: hypokalaemia (common in ectopic ATCH), metabolic alkalosis
15
Q
What investigations should be carried out to determine the cause of Cushing’s syndrome?
A
- Plasma ACTH:
- measure at 8am (when it should be highest)
- if levels are undetectable with an elevated cortisol this is diagnostic of ACTH-independent Cushing’s syndrome
- an elevated ACTH level is consistent with ACTH-dependent disease
If plasma ACTH is detectable, the following tests are indicated: - High-dose dexamethasone suppression test:
- 8mg overnight dexamethasone suppression
- >90% reduction in basal urinary free cortisol levels supports diagnosis of pituitary adenoma
- ecoptic ACTH causes lesser degrees of suppression - Inferior petrosal sinus sampling:
- performed with CRH stimulation to aid in determining the source of excess ACTH
- baseline and stimulated ratio of IPS:peripheral ACTH <1.8 is suggestive of ectopic ACTH
- IPS:peripheral ACTH >2 consistent with pituitary adenoma - MRI of the pituitary
- Chest and abdo CT scan
- for suspected adrenal tumours or ectopic ACTH - Plasma CRH
