Addison's disease Flashcards
What is the cause of Addison’s disease (primary adrenal insufficiency)?
caused by destruction or dysfunction of the adrenal cortex.
What is Adrenal insufficiency?
reduction of glucocorticoid +/- mineralocorticoid production such that normal physiology is interrupted
Describe the 3 main types of adrenal insufficiency
Primary adrenal insufficiency (Addison’s disease): caused by destruction or dysfunction of the adrenal cortex
Secondary adrenal insufficiency: caused by a reduction in adrenocorticotropic hormone release. May be seen as part of panhypopituitarism, an isolated deficiency, following brain injury
Tertiary adrenal insufficiency: caused by a reduction in corticotropin-releasing hormone, most commonly seen following chronic glucocorticoid steroid used.
Describe the causes of adrenal glad destruction leading to adrenal insufficiency
Autoimmune adrenalitis
- autoimmune destruction of the adrenal cortex
- more common in women
- autoantibodies target enzymes involved in the biosynthesis of steroids
- One of the main targets 21-hydroxylase enzyme
Infective adrenalitis
- tuberculosis
- Meningitis (water hous fredrickson)
- HIV
- disseminated fungal infection
- syphilis.
Waterhouse-Friderichsen syndrome adrenal haemorrhage occurs secondary to Meningococcal septicaemia
Infiltrative disease as a result of malignant metastasis or amyloid deposits may cause adrenal insufficiency.
How does Addison’s disease most commonly manifest?
acute Addisonian crisis or with chronic disease.
What are the clinical features of chronic Addison’s disease?
Vague and non specific
- fatigue, anorexia and abdominal pain
- Dehydration
- Nausea vomiting
- Depression
- muscle wasting, postural hypotension,
- hyperpigmentation (mucous membranes and palmer creases)
- In women features of androgen deficiency may be seen
Loss of libido
Loss of hair in axillary/pubic regions
Vitiligo
What are the 4 main causes of Addisonian crisis?
- It is most commonly seen in tertiary adrenal insufficiency (termed an ‘adrenal crisis’) as a result of the sudden withdrawal of steroids.
May occur following an acute decompensation where an additional stress (e.g. infection, surgery, illness) results in an exacerbation of a pre-existing deficiency
Bilateral adrenal gland haemorrhage
Acute hypoglycaemia in people with diabetes
What are the clinical features/symptoms of Addisonian crisis?
presents with symptoms of profound glucocorticoid and mineralocorticoid deficiency
Dehydration Hypotension/ shocked Confusion Fever Abdominal pain nausea Vomiting Hyperpigmentation
What are the signs of critical deterioration in someone with Addisonian crisis
Shock (low BP, tachycardia), high T°, coma.
What are the blood test abnormalities see in Addisonian crisis?
Electrolyte abnormalities
hyponatraemia, (deficiency in mineralocorticoids (aldosterone))
hyperkalaemia (deficiency in mineralocorticoids (aldosterone))
Mild hypercalcaemia
Elevated urea/creat – salt and water loss
FBC abnormalities
Normochromic/cytic anaemia
Eosinophilia
Lymphocytosis
Other
hypoglycaemia - esp in children
Raised LFT’s
Reduced cortisol
How is Addison’s disease diagnosed?
Blood tests
Screening tool- does not distinguish types
- Serum cortisol, measured at 8-9 am - when it should be at its highest
-
< 100 nmol/L: adrenal insufficiency very likely
100–500 nmol/L: adrenal insufficiency possible
> 500 nmol/L: adrenal insufficiency unlikely
plasma ACTH - distinguish between primary and secondary/tertiary
High with low or low-normal cortisol: indicative of Addison’s disease (primary adrenal insufficiency)
Normal: inconclusive
Low: indicative of secondary/tertiary adrenal insufficiency
Synacthen test
- IV administration of 250 mcg of tetracosactide, a synthetic analogue of ACTH.
- Cortisol is measured at three time points: immediately before, 30 and 60 minutes following administration
A serum cortisol > 500–550 nanomol/L either before or following the ACTH is considered normal.
long synacthen test- baseline, give synacthen 1mg IM, measure at 1,4,6,24 hours, should rise gradually and peak at 4-6 hours
Plasma renin activity is high due to low serum aldosterone
Hypercalcaemia and anaemia (after rehydration) are sometimes seen
How is Addison’s disease treated?
replacement of deficient hormones.
Glucocorticoid replacement
- hydrocortisone, 15-30 mg/day given in divided doses
- Regimes should follow the pattern of work in shift workers (i.e 10 mg dose on waking regardless of time of day).
alt - prednisolone
Mineralocorticoid replacement
- fludrocortisone, typically around 50-300 mcg per day.
Androgen replacement
- DHEA replacement in certain settings improves mood and quality of life in women
- Only used by specialists
Patient education
- must understand that treatment for Addison’s disease is (for the majority) lifelong
- Patients should be able to promptly identify an Addisonian crisis as well as carry a steroid card and MediAlert identification.
How is Addisonian crisis treated?
IV hydrocortisone (100mg) - preferred or IM
IV fluid rehydration - with normal saline
Cardiac, electrolyte and blood sugar monitoring
Following initial resuscitation (rehydration), a hydrocortisone/dextrose (hydrocortisone in 5% glucose) infusion may be given with a target of 400mg of hydrocortisone over a 24 hour period.
This will need to be reduced over the coming days, specialist input should be sought.
Treatment of the underlying precipitating disorder - eg, infection with antibiotics.
Which imagining tests are used in Addison’s disease and why?
Chest x ray - exclude lung neoplasms
Abdominal X ray - any adrenal calcification which may indicate previous TB infection.
CT scan - Done if if autoantibodies are negative.
MRI - scan of hypothalamus and pituitary where central causes of adrenal insufficiency are suspected.
Which drugs can cause hypoadrenalism? Describe how the drugs cause the condition
Enzyme inhibition:
ketoconazole, fluconazole, etomidate and metapyrone
Accelerated hepatic metabolism of cortisol:
phenytoin, barbiturates, rifampicin
long term steroids suppressing adrenal function
ketoconazole
Describe the different causes of secondary adrenal insufficiency
Hypothalamic-related
- Corticotropin-releasing hormone (CRH) deficiency.
- Radiotherapy.
- Surgery
- Neoplasm, primary or metastatic.
- Infiltration or infection - eg, sarcoidosis, haemochromatosis, lymphocytic hypophysitis, TB, meningitis.
Suppression of hypothalamic-pituitary axis
- Exogenous steroid administration
- Antipsychotic medication - eg, chlorpromazine.
- Steroid production from tumours.
Pituitary:
- Tumours - eg, cysts, adenomas, meningiomas, craniopharyngiomas.
- Panhypopituitarism of any cause - eg, Sheehan’s syndrome.
- Infection or infiltration (same as above)
- Radiotherapy.
- Trauma.
- Surgery.
- Isolated ACTH deficiency.
Describe the meaning of the term critical illness-related corticosteroid insufficiency. Which conditions can cause this and when should it be suspected in a patient?
Critically ill are increasingly recognised to be at risk of adrenal dysfunction
Conditions where adrenal insufficiency may occur include:
- Sepsis.
- Severe pneumonia.
- Adult respiratory stress syndrome (ARDS).
- Trauma.
- HIV infection.
- After treatment with etomidate.
Diagnosis should be suspected in critically ill people who do not respond to measures to treat hypotension, particularly where sepsis is present.
Which additional situations should provoke the consideration of addisons?
- People with hypothyroidism in whom symptoms get worse when thyroxine treatment is commenced.
- Unexplained recurrent episodes of hypoglycaemia in people with type 1 diabetes. (Hypoglycaemia can be the presenting symptom in children.)
- Presence of other autoimmune diseases.
- Low sodium and high potassium levels - common on those with Addison’s
Which other autoimmune diseases are closely associated with Addison’s?
Type 1 diabetes mellitus.
Pernicious anaemia.
Thyroid disorders.
premature ovarian failure.
Vitiligo.
Chronic atopic dermatitis.
If a patient presents with Addison’s plus other autoimmune conditions, which genetic syndrome should be considered and what is its inheritance patter?
polyglandular autoimmune syndrome
Type 1
Autosomal recessive.
Type 2
Complex genetic factors. Links to HLA DR3 and DR4.
Type 2 specifically has coeliac disease, and Premature ovarian deficiency.
Describe the patient advice which should be given to those diagnosed with addisons?
- Information about the condition.
- Medical emergency identification bracelet or similar.
- Steroid card.
- Importance of not missing steroids and not stopping them abruptly.
- If ill increase medication - seek medical help
