Adrenal Pathophysiology

Adrenal Pathophysiology

1. Adrenal Disorders

   • HYPERfunction
     • Hypercortisolism (Cushing's Syndrome)
       • Most commonly caused by exogenous corticosteroids. Most commonly occurs in women.
       • Etiologies
         • Iatrogenic
           • ↓cortisol, ↓ACTH, ↓CRH
         • Cushing's Disease (pituitary adenoma)
           • ↑cortisol, ↑ACTH, ↓CRH
         • Adrenal Adenoma/Carcinoma
           • ↑cortisol, ↓ACTH, ↓CRH
         • Ectopic ACTH-Secreting Tumor
           • ↑cortisol, ↑ACTH, ↓CRH
         • Ectopic CRH-Secreting Tumor
           • ↑cortisol, ↑ACTH, ↑CRH
       • Clinical Effects: Hyperglycemia, T2DM, "Buffalo Hump", "Moon Face", skin atrophy, HTN, Acne, Infertility, Hirsutism (females), depression
     • Primary Hyperaldosteronism (Conn's Disease)
       • Due to an aldosterone-secreting adrenal adenoma
         • Results in: HTN (end-organ-effects: retinopathy, nephropathy, left ventricular hypertrophy), Hypokalemia, Hypervolemia
     • Secondary Hyperaldosteronism
       • Due to increased renin production (Heart Failure, CKD, Cirrhosis, etc.)
   • HYPOfunction
     • Primary Adrenal Insufficiency (Addison's Disease)
       • Autoimmune: accounts for 80% of adrenal insufficiency
       • Clinical Effects: Skin bronzing occurs as a result of the up-regulation of ACTH
     • Secondary Adrenal Insufficiency
       • Adrenal Crisis: cortical hormones at levels below that which are necessary for survival; Life-Threatening!!!
         • Treat Immediately!!!
       • Causes: Infection, Infarction, Iatrogenic Events

2. Adrenal Cortex: Produces 3 types of Corticosteroid Hormones

   • 1. Glucocorticoids (CORTISOL)
     • A stress hormone that INCREASES BLOOD PRESSURE, which activates...
       • Also activates the release of steroids within the liver
   • 3. Mineralocorticoids (ALDOSTERONE)
     • Increases sodium and water reabsorption
       • Increases blood volume, INCREASING BLOOD PRESSURE
         • This antidiuretic effect increases arterial perfusion pressure in the kidneys is what regulates renin release
   • 2. Adrenal Androgen Precursors (DHEA)

3. Co-Workers

   • Hypothalamic-Pituitary-Adrenal (HPA) Axis
     • Regulates glucocorticoids and adrenal androgens
     • Hypothalamus
       • -- Corticotropin Releasing Hormone (CRH )-->
     • Anterior Pituitary
       • -- Adrenocorticotropic Hormone (ACTH) -->
     • Adrenal Cortex
   • Renin-Angiotensin-Aldosterone System (RAAS)
     • Regulates mineralocorticoids
     • Kidney
       • -- Renin -->
         • Renin + Angiotensinogen
           • --> Angiotensin 1
             • Angiotensin 1 + ACE
               • --> Angiotensin 2
                 • Binds to and activates AT2 Receptor
                   • --> Stimulates release of...
                   • Causes vasoconstriction, INCREASING BLOOD PRESSURE
                     • Also activates the release of steroids within the liver
     • Lungs
       • -- Angiotensin Converting Enzyme (ACE) -->
     • Liver
       • -- Angiotensinogen -->