Addison's disease Flashcards
Addison’s Disease (Primary Adrenal Insufficiency)
Definition:
Caused by destruction of adrenal cortex, leading to reduced production of glucocorticoids (Cortisol), mineralocorticoids, and adrenal androgens.
Causes of Addison’s Disease
Autoimmunity (90% in western countries), long-term corticosteroid use, congenital adrenal hyperplasia, infections like tuberculosis.
Clinical Presentation of Addison’s Crisis
Sudden onset precipitated by illness or stress, featuring hypotension, hypovolemic shock, abdominal pain, vomiting, reduced consciousness.
Emergency Management of Addison’s Crisis
Immediate hydrocortisone administration, transfer to hospital, never delay for investigations.
Symptoms Indicative of Addison’s Disease
Fatigue, hyperpigmentation, GI symptoms, salt craving, postural hypotension, muscle weakness, cramps.
Diagnostic Tests for Addison’s Disease
Serum cortisol <100 nmol/L indicates likely admission, 100-500 nmol/L warrants endocrinology referral. ACTH stimulation test confirms diagnosis.
Treatment of Addison’s Disease
Initiated by endocrinologist, lifelong therapy essential. Hydrocortisone for glucocorticoid, fludrocortisone for mineralocorticoid replacement.
Management Strategies for Addison’s Disease
Increase steroid coverage during stress, recognize adrenal crisis symptoms, carry steroid treatment card and MedicAlert identification
Differentiating Causes of Adrenal Insufficiency
While Addison’s disease results from adrenal cortex destruction, other causes include prolonged corticosteroid use or hypothalamus/pituitary gland disorders.
Causes of Adrenal Insufficiency
Long-term corticosteroid use or disorders of the hypothalamus or pituitary gland can cause adrenal insufficiency, distinct from Addison’s disease.
Pathophysiology of Addison’s Disease
Destruction of adrenal cortex reduces cortisol, aldosterone, and adrenal androgen production, leading to increased ACTH due to reduced negative feedback
Causes of Secondary Adrenal Insufficiency
Insufficient pituitary ACTH production, leading to reduced cortisol and adrenal atrophy. Causes include pituitary tumors, subarachnoid hemorrhage, traumatic brain injury.
Secondary Adrenal Insufficiency
Occurs when
pituitary ACTH production is insufficient due to intracranial disorders, leading to decreased cortisol production and adrenal atrophy
Causes of Tertiary Adrenal Insufficiency
Disruption of hypothalamic corticotropin-releasing hormone production, leading to insufficient ACTH from the anterior pituitary. Causes include long-term corticosteroid use, tumors, radiotherapy, or surgery affecting the hypothalamus
Tertiary Adrenal Insufficiency
Results from
disrupted hypothalamic CRH production, leading to insufficient ACTH, commonly due to long-term corticosteroid use or hypothalamic tumors
Common Causes of Addison’s Disease in Western Countries
Autoimmunity accounts for about 90% of cases, with approximately 40% affecting the adrenal gland alone and 60% occurring as part of multi-organ autoimmune polyendocrine syndrome.
Other Causes of Primary Adrenal Insufficiency
congenital adrenal hyperplasia (most common in children), genetic conditions like adrenoleukodystrophy, infections such as tuberculosis, meningococcus, haemophilus influenzae, cryptococcosis, CMV, and HIV.
Tuberculosis as a Cause of Primary Adrenal Insufficiency
Significant in endemic regions, contributing to adrenal insufficiency due to infection-related destruction of the adrenal gland.
Less Common Causes of Primary Adrenal Insufficiency
adrenal metastases, amyloidosis, hemochromatosis, iatrogenic factors like bilateral adrenalectomy, adrenal hemorrhage, and use of immune checkpoint inhibitors in cancer therapy.
Conditions associated with Addison’s disease include
autoimmune thyroid disease, pernicious anaemia, vitiligo, and type 1 diabetes mellitus.
Adrenal Crisis in Addison’s Disease
Severe complication occurring during physical stress when the adrenal glands fail to produce enough cortisol, leading to life-threatening symptoms like dehydration, hypotension, shock, altered consciousness, seizures, stroke, or cardiac arrest.
Causes of Adrenal Crisis in Addison’s Disease
Include gastrointestinal illness (23%), other infections (25%), perioperative period (10%), and physiological stress/pain (9%).
Complications of Addison’s Disease
Include reduced quality of life, adverse maternal and neonatal outcomes, and premature ovarian insufficiency (POI).
Reduced Quality of Life in Addison’s Disease
Factors include fatigue, loss of energy, depression, anxiety, reduced ability to cope with daily activities, and loss of libido, especially in women.
Adverse Maternal and Neonatal Outcomes in Addison’s Disease
Poorly managed Addison’s disease during pregnancy associated with increased risk of maternal mortality, miscarriage, preterm delivery, impaired fetal growth, and congenital abnormalities.
Premature Ovarian Insufficiency (POI) in Addison’s Disease
10-20% of women with autoimmune Addison’s disease develop POI before age 40, with higher risk in autoimmune polyendocrine syndrome type 1 (up to 50-70% in some studies).
