Source / episode info
- **Episode:**73
- **Title:**Divine Intervention Episode 73 – Endocrine Physiology and Pharmacology Part 2 (Final Part)
- **Published:**2019-01-12
- Source:Episode page
One-liner
This episode covers the pharmacology of anti-diabetic agents (Sulfonylureas, GLP-1 agonists, SGLT2 inhibitors), details the complex physiology and diagnostic testing for adrenal insufficiency using ACTH analogs and enzyme inhibitors (Metyrapone), and reviews growth hormone excess management.
High-yield summary
- Adrenal Gland Structure: The cortex is organized into three zones: Glomerulosa (outermost, {Mineralocorticoids} -> Aldosterone); Fasciculata (middle, {Glucocorticoids} -> Cortisol); Reticularis (innermost, {Androgens}).
- Sulfonylureas: These drugs stimulate insulin release by blocking ATP-sensitive potassium channels, leading to cell depolarization and calcium influx. They carry a high risk of hypoglycemia and are associated with sulfur allergies.
- SGLT2 Inhibitors: Drugs like canagliflozin block the SGLT2 transporter in the proximal convoluted tubule, causing glucosuria (glucose loss in urine) and reducing blood glucose levels; they increase the risk of UTIs/genital infections.
- Adrenal Insufficiency Workup: In primary adrenal insufficiency (Addison's disease), ACTH stimulation will fail to raise cortisol because the adrenal gland itself is damaged. The diagnostic test involves administering an ACTH analog (e.g., cosyntropin).
- Metyrapone Mechanism: Metyrapone inhibits 11-hydroxylase, causing a predictable rise in {ACTH} and precursors ({11-deoxycortisol}) but a fall in cortisol, allowing differentiation of pituitary vs. adrenal failure.
Learning objectives
- Differentiate the mechanisms of action and side effects of various anti-diabetic agents (Sulfonylureas, GLP-1 agonists, SGLT2 inhibitors).
- Describe the normal physiological function and structural organization of the adrenal cortex and its hormones.
- Interpret ACTH stimulation testing results to diagnose the site of adrenal insufficiency failure (primary vs. secondary/tertiary).
- Understand the role of 11\beta-hydroxylase in cortisol synthesis and how inhibitors like Metyrapone alter the HPA axis feedback loop.
- Recognize the clinical consequences of mineralocorticoid excess, such as those caused by licorice or chronic steroid use.
Board exam buzzwords