Adrenal Insufficiency

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Overview

Adrenal insufficiency is characterised by insufficient steroid hormone production from the adrenal glands. There are usually reduced amounts of glucocorticoids (cortisol) and/or mineralocorticoids (aldosterone), which are both types of steroid hormones. This section will focus on primary adrenal insufficiency (Addison’s disease).

There are 3 types of adrenal insufficiency:

  • Primary adrenal insufficiency (Addison’s disease):
    • The problem is within the adrenal cortex itself leading to impaired steroid hormone synthesis and secretion
  • Secondary adrenal insufficiency:
    • The problem is with the pituitary gland and there is inadequate adrenocorticotropic hormone (ACTH) release, leading to impaired steroid hormone synthesis and secretion
  • Tertiary adrenal insufficiency:
    • The problem is with the hypothalamus and there is inadequate corticotropin-releasing hormone (CRH) release, leading to impaired steroid hormone synthesis and secretion

To help make sense of this chapter, it may be helpful to refer to Endocrine and Metabolic Physiology.

Epidemiology

  • Addison’s disease is the most common cause of primary adrenal insufficiency in the UK
  • Addison’s disease has an incidence of 4 in 1,000,000 per year in Western populations
  • Most common ages of onset are 30-50 years
  • Women are affected more than men

Causes

Causes of primary adrenal insufficiency

  • Addison’s disease – around 80% of cases:
    • This describes the autoimmune destruction of the adrenal glands
  • Trauma
  • Tuberculosis
  • HIV
  • Congenital adrenal hyperplasia
  • Haemorrhage – Waterhouse-Friderichsen syndrome:

Causes of secondary adrenal insufficiency

Risk Factors

  • Female sex
  • Autoimmune disease
  • Family history
  • Any of the above causes

Presentation

Symptoms can be mild and non-specific. Features may be:

  • Fatigue
  • Weight loss
  • Loss of appetite
  • Hyperpigmentation:
    • Due to excess ACTH stimulating melanocytes
    • Usually in palmar creases and buccal mucosa
  • Craving salt
  • Vague abdominal pain:
  • Nausea and vomiting
  • Loss of pubic hair:
    • Due to decreased androgen synthesis
  • Orthostatic hypotension:
    • Due to mineralocorticoid deficiency leading to fluid and electrolyte imbalances
  • Presenting in an Adrenal crisis

Differential Diagnoses

Congenital adrenal hyperplasia

  • Generally seen in children and adolescents
  • Excess androgen production can lead to ambiguous genitalia, precocious puberty, excess facial hair, menstrual irregularities etc. 

Diabetic ketoacidosis (DKA)

  • Blood sugars and ketones are raised in DKA, whereas in primary adrenal insufficiency, blood sugars may be low

Investigations

  • Morning serum cortisol (usually between 8-9 pm where cortisol levels peak):
    • A value of 100-500nmol/L warrants an ACTH stimulation test
  • ACTH stimulation test (also known as the short Synacthen test) – diagnostic test:
    • Synthetic ACTH is given and plasma cortisol is measured before and 30 minutes after.
    • Serum cortisol is usually <500 nmol/L and fails to rise
  • FBC:
  • Glucose:
    • May be low
  • U&Es:
    • Sodium – usually reduced
    • Potassium – usually raised
    • Calcium – may be raised

Other investigations

Management

Addison’s disease

  • 1st-line: replacement hydrocortisone + fludrocortisone
    • Hydrocortisone is usually divided into 3 doses, with the highest dose in the morning

Monitoring and Patient Advice

Monitoring

  • Patients are followed-up at least annually to assess their response to treatment. They should have an examination, blood pressure and weight measurements, and blood tests for electrolytes

Patient advice

  • Patients should be thoroughly informed about the condition
  • It should be stressed that patients do not miss their replacement steroid doses as this can precipitate an adrenal crisis
  • Patients should be offered steroid cards and medical emergency identification bracelets
  • Patients should be offered a hydrocortisone injection for adrenal crises
  • If patients have an intercurrent illness, they should double the glucocorticoid dose throughout the illness, but keep the fludrocortisone dose the same
  • Patients with Addison’s disease do not need to pay for prescriptions in the UK

Complications

  • Adrenal crises:
    • Usually precipitated by severe stress – the adrenal glands cannot supply the extra cortisol needed to cope with the stress leading to life-threatening symptoms such as hypovolaemic shock and cardiac arrest
  • Reduced quality of life
  • Osteoporosis due to corticosteroid use and potentially due to low androgen use

Prognosis

  • If untreated, Addison’s disease is always fatal
  • Even with treatment, the mortality rate of those with Addison’s disease may be higher than that of the general population

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