Adrenal 1 - The Clinical Context Flashcards
3 layers of the adrenal cortex
- Zona glomerulosa (“salt”)
- Zona fasciculata (“sugar”)
- Zona reticularis (“sex”)
What regulates mineralocorticoid?
Renin-angiotensin-aldosterone system (RAAS)
Basic order of RAAS
- Renin released to stimulate angiotensin 1 from angiotensinogen
- Angiotensin 1 –> angiotensin 2 by angiotensin converting enzyme (ACE)
- Angiotensin 2 receptor activated
- Aldosterone release and secreted into blood
Signs of cortisol deficiency
- Weight loss
- Hyperpigmentation
- Hyponatraemia
- Hypercalcaemia
- Hypoglycaemia
- Anaemia
Signs of aldosterone deficiency
- Hypotension
- Hyponatraemia
- Hyperkalaemia
- Uraemia (toxins in blood)
Signs of DHEA/androgen deficiency
Loss of pubic hair (women)
Symptoms of cortisol deficiency
- Weakness, fatigue
- Anorexia
- Muscle/joint paints
Symptoms of aldosterone deficiency
- Nausea, vomiting, abdominal pain
- Salt craving
- Postural dizziness
Symptoms of DHEA/androgen deficiency
Loss of libido (women)
What are the 2 types of ACTH?
- ACTH 1-39 (normal)
- ACTH 1-24 (synacthen)
What does the Short Synacthen Test (SST) diagnose?
Adrenal insufficiency
Method of SST
- 250µg synacthen given i.v. or i.m.
- Blood cortisol levels rise if adrenal glands not insufficient
Order of diagnosing primary adrenal insufficiency
- Measure adrenal auto-antibodies (autoimmune adrenalitis)
- Measure very long chain fatty acids (adrenoleukodystrophy/adrenomyeloneuropathy)
- CT adrenals (tuberculosis)
What is Addison’s disease?
Primary adrenal insufficiency
What is the most frequent causes of primary and secondary adrenal insufficiency?
- P = autoimmune adrenalitis
- S = pituitary tumours
Long-term treatment of adrenal insufficiency
- Replace glucocorticoid with 15mg am and 10mg pm hydrocortisone
- Replace mineralocorticoid with 100-200µg/day fludrocortisone
- DHEA for women
When would an adrenal insufficient patient double their daily glucocorticoid dose?
- Fever
- Infection requiring antibiotics
- Minor surgery under local anaesthesia
What can cause severe stress for an adrenal insufficient patient?
- Trauma
- Major surgery
- Persistent vomiting
- Colonoscopy
- Active labour
What dosage of what corticosteroids are needed when severe stress?
- 100mg hydrocortisone i.v.
- 200mg/day hydrocortisone continuous infusion
Clinical features of Cushing’s syndrome
- Purplish stretch marks (>1cm)
- Thin skin, easy bruising
- Proximal myopathy
- Facial fullness and plethora
- “Buffalo hump”
- Osteoporosis
- Decreased linear growth in children
Types and percentage prevalence of Cushing’s syndrome
- Pituitary dependent Cushing’s syndrome (= Cushing’s disease) (75%)
- Ectopic Cushing’s syndrome (15%)
- ACTH-independent (10%)
What causes pituitary dependent Cushing’s syndrome?
ACTH-producing pituitary tumour
What causes ectopic Cushing’s syndrome?
Ectopic ACTH source (eg. benign lung tumour producing ACTH)
What causes ACTH-independent Cushing’s syndrome?
Cortisol-producing adrenal tumour
3 tests for Cushing’s syndrome
- Dexamethasone overnight suppression test
- 24h urinary free cortisol
- Midnight cortisol (serum or saliva)
Method of dexamethasone overnight suppression test
- 1mg dexamethasone tablet given 11pm
- Blood for serum cortisol 8-9am
- If cortisol levels remain high –> Cushing’s
How does dexamethasone work?
- Mimics cortisol by binding to glucocorticoid receptors but with longer half life
- ACTH downregulated so cortisol levels should drop
What urinary free cortisol levels diagnose Cushing’s?
> 130µg/24h
How do you determine if a patient has ACTH-dependent or -independent Cushing’s syndrome?
- 9am plasma ACTH
- Suppressed = independent
- Normal/high = dependent
How do you determine if a patient has pituitary dependent or ectopic ACTH-dependent Cushing’s syndrome?
- High dose dexamethasone test (2mg 6-hourly for 48h, if >50% decrease in serum cortisol/UFC from start then pituitary dependent)
- CRH test (100µg i.v.)
- Inferior petrosal sinus sampling (IPSS)
What can be done if biochemistry doesn’t show what version of Cushing’s a patient has?
Imaging (CT adrenals or MRI pituitary)
How can Cushing’s be treated?
- Surgery
- Drugs
What mechanisms can drugs use to treat Cushing’s?
- Block cortisol-producing adrenal enzymes
- Block glucocorticoid receptors
- Disrupt adrenal redox so steroidogenesis and cell proliferation
What surgery options are there for Cushing’s?
- Pituitary - transsphenoidal surgery
- Bilateral adrenalectomy
- Laparascopic adrenalectomy (adrenal adenoma)
- Open adrenalectomy (adrenocortical carcinoma)
