Acute and chronic suprarenal insufficiency. Etiology, pathogenesis and clinico-pathological correlations.
The adrenal glands are paired endocrine organs with a cortex and medulla. The cortex synthesizes three steroids:
- Glucocorticoids (mainly cortisol - regulates metabolism, reduces inflammation)
- Mineralocorticoids (most important is aldosterone - conserves sodium and water)
- Sex steroids (estrogens and androgens)
The Medulla synthesizes catecholamines (mainly epinephrine - increase BP, muscle, HR).
Adrenal insufficiency is the decreased synthesis and secretion of the above hormones. This can be primary or secondary (deficiency of ACTH secreted from the pituitary). There are three general categories of insufficiency:
- Primary acute
- Primary chronic (Addison's disease)
- Secondary
Primary acute insufficiency:
- Usually as a result of Waterhouse-Friderichsen syndrome (sepsis causing adrenal haemorrhage), withdrawal of corticosteroid therapy or stress in patients with underlying disease
Waterhouse-Friderichsen syndrome: both adrenals enlarged and dark red from bilateral haemorrhagic necrosis (scale in cm).
Image: “Waterhouse-Friderichsen. IMG 2912” by Amadalvarez, CC BY-SA 4.0, via Wikimedia Commons.
Example: a child with Neisseria meningitidis septicaemia develops a purpuric rash, DIC and shock; at autopsy both adrenals are massively haemorrhagic - Waterhouse-Friderichsen syndrome, a cause of acute adrenal crisis.
Primary chronic insufficiency
- May be autoimmune, TB related, metastatic disease, systemic amyloidosis, fungal infection or sarcoidosis
- Autoimmune is the most common
Secondary insufficiency
- Any disorder of the hypothalamus or pituitary (e.g. metastatic cancer, infarction, infection, radiation) can reduce ACTH output and lead to reduced adrenal hormone secretion
Morphologically, secondary hypoadrenalism changes the adrenals to small, flattened structures with atrophy of cells. In primary autoimmune adrenalitis we see irregularly shrunken glands with lymphoid infiltrate into the cortex.
The clinical manifestations of all of these forms of insufficiency are:
- Progressive weakness
- Fatigability
- GI disturbances
- Vomiting
- Weight loss
- Diarrhea
- In primary adrenal disease - hyperpigmentation of skin and mucosa
Remember: hyperpigmentation occurs only in primary insufficiency: low cortisol removes feedback, the pituitary makes more POMC, and its products (ACTH and MSH) stimulate melanocytes. In secondary insufficiency ACTH is low, so the skin is not pigmented.