Historical Mechanism of ACTH in Minimal Change Disease (1960s)
Direct Steroidogenic Effect
In the 1960s, ACTH was thought to benefit minimal change disease primarily through its ability to stimulate endogenous cortisol production from the adrenal cortex, essentially functioning as an indirect method of delivering high-dose corticosteroid therapy. 1
Physiological Rationale
The mechanism was understood through the hypothalamic-pituitary-adrenal axis:
- ACTH directly stimulates the zona fasciculata of the adrenal cortex to produce and release cortisol, the dominant glucocorticoid in humans 1
- The hormone triggers cortisol secretion that can increase up to five-fold (approximately 100 mg per day) compared to baseline production of 20 mg daily 1
- This endogenous cortisol production was believed to provide the anti-inflammatory and immunosuppressive effects necessary to induce remission in minimal change disease 1
Clinical Application Context
The use of ACTH in the 1960s reflected the era's understanding:
- ACTH was employed as an alternative to oral glucocorticoids for patients who could not tolerate direct steroid administration 1
- The treatment was particularly considered for polyarticular inflammatory conditions where systemic corticosteroid effects were desired 1
- Parenteral ACTH (40-80 units given intravenously, intramuscularly, or subcutaneously) was the typical dosing approach used during this period 1
Important Historical Caveat
The 1960s understanding was limited to ACTH's steroidogenic mechanism alone—the concept that ACTH might have direct melanocortin receptor-mediated effects on podocytes or immune cells independent of cortisol production was not recognized until decades later 2, 3. This explains why ACTH was essentially viewed as a "corticosteroid delivery system" rather than as a distinct therapeutic agent with unique mechanisms.