Adrenal Insufficiency

Definition

Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol, and in some cases, aldosterone. It can be classified as primary (Addison's disease), secondary, or tertiary adrenal insufficiency, depending on the level of the hypothalamic-pituitary-adrenal (HPA) axis that is affected.

Aetiology

Adrenal insufficiency can be caused by various factors:

Primary Adrenal Insufficiency (Addison's Disease): Caused by damage to the adrenal glands due to autoimmune destruction, infections (e.g., tuberculosis, HIV), metastatic cancer, or adrenal haemorrhage.
Secondary Adrenal Insufficiency: Caused by pituitary gland dysfunction, which leads to inadequate production of adrenocorticotropic hormone (ACTH). Common causes include pituitary tumours, surgery, radiation, or pituitary apoplexy.
Tertiary Adrenal Insufficiency: Results from hypothalamic dysfunction, often due to chronic exogenous steroid use that suppresses the hypothalamus-pituitary-adrenal axis.

Pathophysiology

The adrenal glands produce glucocorticoids (cortisol), mineralocorticoids (aldosterone), and adrenal androgens. In adrenal insufficiency, the lack of cortisol affects metabolism, immune response, and stress response, while aldosterone deficiency leads to sodium loss, hyperkalemia, and hypotension. The deficiency in adrenal hormones disrupts the normal physiological functions regulated by these hormones.

Risk Factors

Autoimmune diseases
Family history of adrenal insufficiency or autoimmune disorders
Infections (e.g., tuberculosis, HIV)
Adrenal or pituitary gland surgery
Prolonged use of corticosteroids
Adrenal haemorrhage or infarction

Signs and Symptoms

Symptoms of adrenal insufficiency can be nonspecific and may include:

Chronic fatigue
Muscle weakness
Loss of appetite and weight loss
Abdominal pain
Low blood pressure, orthostatic hypotension
Hyperpigmentation (in primary adrenal insufficiency)
Salt craving
Hypoglycemia
Nausea, vomiting, and diarrhoea

Investigations

Clinical history and physical examination
Serum cortisol and ACTH levels: Low cortisol and high ACTH indicate primary adrenal insufficiency, while low ACTH suggests secondary or tertiary causes
ACTH stimulation test: To assess adrenal gland response to ACTH
Electrolytes: To check for hyponatremia and hyperkalemia
Imaging studies: CT or MRI of the adrenal glands and pituitary gland to identify structural abnormalities
Autoantibody tests: To detect autoimmune adrenalitis

Management

Primary Care Management

Education: Informing patients about the condition, its symptoms, and the importance of medication adherence
Hydrocortisone replacement: Administering oral hydrocortisone to replace deficient cortisol
Mineralocorticoid replacement: Fludrocortisone may be required in primary adrenal insufficiency to replace aldosterone
Stress dose adjustment: Increasing steroid doses during periods of illness or stress to prevent adrenal crisis
Emergency kit: Providing patients with an emergency injection kit containing hydrocortisone for use during adrenal crises

Specialist Management

Referral to endocrinologist: For confirmation of diagnosis, ongoing management, and monitoring
Monitoring: Regular follow-up to assess symptoms, biochemical markers, and medication side effects
Management of adrenal crisis: Immediate intravenous hydrocortisone and fluid resuscitation for patients presenting with adrenal crisis
Addressing underlying causes: Treating infections, adjusting or discontinuing medications that may contribute to adrenal insufficiency

References

NICE. (2024). Adrenal Insufficiency: Diagnosis and Management. Retrieved from NICE
NHS. (2023). Adrenal Insufficiency. Retrieved from NHS
Endocrine Society. (2022). Clinical Practice Guidelines for Adrenal Insufficiency. Retrieved from Endocrine Society
British Thyroid Foundation. (2021). Management of Adrenal Insufficiency. Retrieved from British Thyroid Foundation