Disorders of the human adrenal gland Flashcards
What is adrenal insufficiency?
Inadequate adrenocortical function
What causes primary adrenal insufficiency?
o Addison’s disease
o Adrenal TB/malignancy
o Congenital Adrenal Hyperplasia (CAH) = neonatal form
What can cause secondary adrenal insufficiency?
Due to lack of ACTH stimulation of the adrenal glands
- Iatrogenic (excess administration of exogenous steroid)
- Pituitary/hypothalamic disorders
What causes congenital adrenal hyperplasia?
genetic disease:
- autosomal recessive
= lack of 21-hydroxylase activity
= deficiency of cortisol and aldosterone
= increased adrenal androgens
What is the significance of lack of 21-hydroxylase activity?
most important enzyme in aldosterone and cortisol production
How do boys present with CAH?
adrenal insufficiency
How do girls present with CAH?
masculinisation of female genitalia due to
excess exposure to androgens in utero
What is Addison’s disease?
Autoimmune destruction of adrenal cortex
o >90% destroyed before symptomatic
o Autoantibodies positive in 70%
What are the clinical features of Addison’s disease?
Non-specific symptoms o Anorexia, weight loss o Fatigue/lethargy o Dizziness and low BP o Abdominal pain, vomiting, diarrhoea o Skin pigmentation (should not be missed!) on palmar creases and buccal mucosa
Symptoms are often precipitated by an intercurrent illness
What tests are used to diagnose adrenal insufficiency?
- electrolyte derrangement
- Short synacthen test
- High ACTH levels
- high renin
- low aldosterone
- adrenal autoantibodies
Describe biochemistry results in adrenal insufficiency
marked electrolyte derangement
- Low Na
- High K
- hypoglycaemia
Describe the short synacthen test
SYNACTHEN = synthetic ACTH
- Stimulate cortisol
- Measure plasma cortisol before and 30 minutes
after IV ACTH injection
Normal: baseline >250nmol/L, post ACTH >;480
Describe the ACTH levels in adrenal insufficiency
Increased
- Pituitary attempts to stimulate cortisol production
- This is what causes skin pigmentation
Describe the renin levels in adrenal insufficiency
Raised renin because of stimulation by RAAS
Describe the aldosterone levels in adrenal insufficiency
low
- causes hyperkalaemia and hyponatraemia
How is adrenal insufficency treated?
- Hydrocortisone as cortisol replacement
- Fludrocortisone as aldosterone replacement
Why is hydrocortisone used in adrenal insufficency?
Metabolised to cortisol. Most physiological way of replacing cortisol
Describe treatment pattern of hydrocortisone in adrenal insufficiency
If unwell, give intravenously first
o Then 15-30mg oral tablets daily in divided doses (for long-term maintenance)
o Try to mimic diurnal rhythm
Highest levels in the morning, therefore give higher dose in the morning
What is the significance of adrenal insufficiency
- untreated = fatal
(Do not delay treatment to confirm diagnosis)
‘sick day rules’ – double oral hydrocortisone for 3 days when unwell
o Cannot stop suddenly, as this will cause adrenal crisis
o Need to wear identification
What are the main causes of secondary adrenal insufficiency?
(LACK OF CRH/ACTH)
- pituitary/hypothalamic disease (tumour, surgery, radiotherapy)
- exogenous steroid use
How does exogenous steroid use cause secondary adrenal insufficiency?
Commonest cause
o Risk for patients on exogenous steroids for
> 6 weeks (possibly even >3 weeks)
o Negative feedback of endogenous steroids
on CRH/ACTH
What are the clinical features of secondary adrenal insufficiency?
similar to Addison’s EXCEPT:
o Skin pale (no ACTH, therefore no pigmentation)
o No electrolyte abnormalities as aldosterone production is intact (regulated by RAAS)
How is secondary adrenal insufficiency treated?
hydrocortisone replacement
What is Cushing’s syndrome?
Excess cortisol secretion
What are the clinical features of Cushing’s syndrome?
cortisol excess:
- Centripetal obesity
- Thin bones
- Prone to HTN/hyperglycaemia
What are non-specific symptoms of cushing’s?
Easy bruising (thin skin)
Facial plethora
Striae
Proximal myopathy
What are the types of cushing’s?
- ACTH dependent
- ACTH independent
What are the causes of ACTH dependent Cushing’s?
o Pituitary adenoma (68%) Cushing’s Disease (cushing’s
syndrome caused by a pituitary adenoma)
(most common cause of endogenous)
o Ectopic ACTH 12% (carcinoid/carcinoma)
o Ectopic CRH <1%
What are the causes of ACTH independent cushing’s?
o Adrenal adenoma (benign) 10%
o Adrenal carcinoma (malignant) 8%
o Nodular hyperplasia 1%
What steps do you need to take to diagnose Cushing’s?
- establish cortisol excess
- determine underlying cause
How can you determine cortisol excess?
- Dexamethasone suppression testing
(V. good screening test) - 24-hour urinary free cortisol
(more accurate due to diurnal rhythm) - Late night salivary cortisol
(Should be almost undetectable)
How do you determine the underlying cause of Cushing’s?
- ACTH dependent or independent?
- If ACTH is low, it must be a problem with the adrenal gland (ACTH-independent)
- If ACTH is high, it must be ACTH dependent
Cushing’s
How is Cushing’s managed?
Surgical
o Transphenoidal pituitary surgery
o Laparoscopic adrenalectomy
o Removal of ACTH source
Medical o Metyrapone/ketoconazole o Inhibit cortisol production, but not very well tolerated o Short term measure
What is IATROGENIC CUSHING’S SYNDROME?
Cushingoid appearance but low plasma cortisol
What causes iatrogenic Cushing’s syndrome?
prolonged high dose steroid therapy
(e. g. asthma, rheumatoid arthritis, inflammatory bowel disease, transplants)
- Steroid therapy for these conditions is usually higher than physiological levels of cortisol
- Usually oral therapy
- Can occur with high dose inhaled steroids or steroid injections
Chronic suppression of pituitary ACTH production and adrenal atrophy
What is the pathophysiology of adrenal suppression?
Long term steroid treatment suppresses ACTH production (negative feedback to anterior pituitary)
Atrophy of adrenal cortex
What are the implications of steroid dependent patients?
Patients become steroid dependent. Implications:
o Unable to respond to stress (illness/surgery)
o Need extra doses of steroid when ill/surgical procedure
o Cannot stop suddenly
o Gradual withdrawal of steroid therapy if >;4-6 weeks
What is PRIMARY ALDOSTERONISM (CONN’S SYNDROME)?
Autonomous production of aldosterone independent of its regulators (angiotensin II/potassium)
What causes primary aldosteronism?
single adrenal adenoma or bilateral adrenal nodules
What are the clinical features of primary aldosteronism?
o Significant hypertension
o Hypokalaemia (in up to 50%)
o Alkalosis
How is Primary Aldosteronism diagnosed?
- Biochemistry
o Plasma aldosterone elevated
o Plasma renin concentration suppressed - Suppression testing
o Intravenous saline load => should switch off RAAS - Adrenal CT scan to identify single lump/bilateral nodules
What are the treatment options of primary aldosteronism
Surgical o Unilateral laparoscopic adrenalectomy o Only if adrenal adenoma o Cure of hypokalaemia o Cures hypertension in 30-70% cases
Medical
o In bilateral adrenal hyperplasia
o Use MR antagonists (spironolactone or eplerenone)
o Or amiloride (blocks Na reabsorption by kidney – blocks ENaC, therefore blocks effect of
aldosterone)
What is PHAEOCHROMOCYTOMA?
Catecholamine secreting tumours of the adrenal medulla
What are the symptoms of phaeochromocytoma?
Hypertension (intermittent in 50%)
Hallmark symptoms: episodes of headache, palpitations, pallor and sweating
How is phaeochromocytoma diagnosed?
Measure 24 hour urinary catecholamines and metabolites (metanephrin and normetanephrin)
CT scan of adrenals
How is phaeochromocytoma treated?
Adrenalectomy is treatment of choice
o Need pre-operative treatment with α1 +/- β1 antagonists to block effects of catecholamine surge
o Can become haemodynamically unstable in surgery if this is not done
