Primary Adrenal insufficiency

• Addison’s disease refers specifically to when the adrenal glands have been damaged, resulting in reduced cortisol and aldosterone secretion. This is called primary adrenal insufficiency. The most common cause is autoimmune.
• Addison's disease (primary adrenal insufficiency) is caused by destruction of the adrenal cortex.
• • This causes reduced production of glucocorticoids (such as cortisol), mineralocorticoids (such as aldosterone), and adrenal androgens (such as dehydroepiandrosterone).
• • The absence of cortisol leads to increased production of adrenocorticotrophic hormone (ACTH) because negative feedback to the pituitary gland is reduced.
• Causes of Primary adrenal insufficiency:

  Autoimmunity

  Congenital adrenal hyperplasia

  Adrenoleukodystrophy

  infections such as tuberculosis, meningococcus, Haemopholus influenzae, HIV, cryptococcosis, CMV

  Adrenal metastases

  Amyloidosis

  Haemochromatosis

  Bilateral adrenalectomy

  Adrenal haemorrhage

  Cancer treatment
• The most common age of onset is between 30–50 years in addison's
• More women than men are affected in addison's
• • Conditions associated with Addison’s disease include autoimmune thyroid disease, pernicious anaemia, vitiligo, and type 1 diabetes mellitus.
• Of people with autoimmune Addison's disease, about two-thirds have an autoimmune polyendocrine syndrome.

  Type 1 - Triad of Addison's disease, hypoparathyroidism, and chronic candidiasis

  Type 2 - Usually involves Addison's disease and autoimmune thyroid disease or type 1 diabetes mellitus
• Symptoms:

  Fatigue, weight loss, loss of appetite, premature satiety, nausea, vomiting, abdominal pain, salt cravings, muscle weakness, muscle cramps, joint pain, postural dizziness, headache, low-grade fever, polydipsia, polyuria, anxiety, depression
• Clinical signs of Addison's disease:

  Hyperpigmentation in palmar creases and mucous membranes, loss of axillary and/or pubic hair in women
• Conditions which may present alongside addison's disease:

  Hypothyroidism where symptoms worsen when levothyroxine started

  Type 1 diabetes mellitus and recurrent hypoglycaemic episodes

  Hyponatraemia and Hyperkalaemia
• Signs of Addison's disease in children:

  Prolonged neonatal jaundice, failure to thrive, delayed puberty
• Initial investigations for suspected Addison's disease:

  Serum cortisol

  U&Es (low sodium, high potassium usually but normal levels don't exclude diagnosis)

  Blood glucose (may be borderline or low)

  FBC (anaemia, mild eosinophilia, lymphocytosis)

  LFTs (increased liver enzymes)

  TFTs (high TSH - hypothyroid picture)

  Calcium (mild to moderate hypercalcaemia)
• Things to bear in mind when looking at serum cortisol:

  People may work shifts

  Long term cortricosteroid treatment

  Oestrogen treatment (HRT, OCP)

  Pregnancy

  These factors may require the patient to undergo a Synacthen test
• Serum cortisol:

  If <100nmol/L admit patient to hospital as adrenal insufficiency is highly likely.

  If 100-500nmol/L refer to endocrinology for ACTH Synacthen test - urgency of referral depends on severity of symptoms and serum cortisol levels. Postural hypotension +/- electrolyte disturbance are indications for an urgent referral or admission to hospital.

  If >400nmol/L then addison's is less likely but cannot be excluded if the person is acutely unwell at the time.
• Diagnosis for Addison's disease is always made in secondary care
• To confirm a diagnosis of Addison's disease a ACTH stimulation (Synacthen) test has to be carried out
• To confirm diagnosis of Addison's disease:

  • Synacthen - Serum cortisol does not increase
  • ACTH levels - High
  • Plasma renin - High
  • Plasma aldosterone - Low
  • Serum DHEAS - Low
  • TFTs - may show hypothyroidism picture
  • Autoantibodies - Adrenal cortex autoantibodies or antibodies against 21-hydroxylase are present in more than 80% of people with recent onset autoimmune adrenalitis
  • CT/MRI - may be requested if TB or another infection, haemorrhage, infiltration or neoplastic disease is suspected
• ACTH stimulation Synacthen test:

  • Check serum cortisol levels
  • Before and 30 minutes after administering 250 micrograms of tetracosactide (synthetic ACTH) IV/IM
  • Can be performed at any time of day
  • Normal person - serum cortisol increases to more than 500-550nmol/L after 30 or 60 minutes
  • Adrenal insufficiency - Serum cortisol does not increase adequately in response
• Management of Addison's disease:

  • Glucocorticoid replacement - 15-25mg Hydrocortisone (10mg morning, 5mg noon, 5mg early evening)
  • Mineralocorticoid replacement - Fludrocortisone 50-200mcg, may need to be increased if in high temparutes/humidity, children have a higher requirement also
  • Androgen replacement - DHEA replacement may be required in specific circumstances such as persistent fatigue
• Advice for those with Addison's disease

  Need to carry emergency information:

  • MedicAlert ID - HCPs can access 24 hour helpline
  • NHS steroid emergency card - states the person is on steroids and should not be stopped, also emergency treatment for adrenal crisis
  • Emergency crisis letter
• Follow up of Addison's disease:

  • Screen for other endocrine or autoimmune disorders such as pernicious anaemia, Type 1 diabetes mellitus and thyroid dysfunction
  • Ask about menstrual cycle to check for premature ovarian insufficiency and pregnancy
• Sick day rules:

  • Moderate intercurrent illness = double dose of Hydrocortisone
  • Severe nausea = 20mg Hydrocortisone orally and sip rehydration solution
  • Severe intercurrent illness = Emergency injection of 100mg Hydrocortisone and seek medical advice
  • Injury = 20mg Hydrocortisone orally to avoid shock
  • Serious trauma = emergency injection
  • Strenuous exercise = double dose