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The Evolution of ACTH Therapy: From Medical Breakthrough to Modern Understanding

In the early 1950s, a hormone called ACTH was making headlines. A November 1951 issue of Reader’s Digest featured an article titled The Power and the Glory of ACTH, describing a treatment that had captured the attention of physicians, researchers, and the public. At the time, ACTH was being investigated for conditions ranging from rheumatoid arthritis and asthma to inflammatory and allergic disorders. More than 75 years later, our understanding of ACTH, inflammation, the adrenal system, and the immune system has evolved considerably. The history of ACTH offers an interesting look at how a major medical discovery can change over time as researchers learn more about how the body works.

What Is ACTH?

ACTH stands for adrenocorticotropic hormone. It is a hormone produced by the pituitary gland, a small gland located at the base of the brain. One of ACTH’s primary roles is signaling the adrenal glands to produce cortisol and other adrenal hormones. Cortisol is involved in several important processes throughout the body, including the stress response, metabolism, immune activity, and regulation of inflammation. This connection between the pituitary gland, adrenal glands, and inflammation would eventually become the foundation for decades of research into ACTH and corticosteroid therapies.

The Early Years of ACTH Research

Scientific interest in the pituitary-adrenal system developed during the first half of the 20th century. By the late 1930s and 1940s, researchers were beginning to isolate and better understand hormones produced by the pituitary and adrenal glands. Physicians were also investigating an intriguing observation: some people with rheumatoid arthritis experienced dramatic changes in their symptoms under certain physiological conditions. That research eventually led investigators to explore both adrenal corticosteroids and ACTH. In 1948 and 1949, researchers at the Mayo Clinic reported striking improvements in patients with severe rheumatoid arthritis treated with cortisone. ACTH produced similar effects in some early patients. The findings attracted enormous attention.

A Medical Breakthrough Makes Headlines

By 1951, ACTH and cortisone had become widely discussed medical discoveries. The Reader’s Digest article shared with us provides a fascinating snapshot of that moment in history. Its language reflects just how extraordinary these treatments appeared at the time, describing experiences involving rheumatoid arthritis, asthma, lupus, inflammatory eye conditions, and other illnesses. Importantly, these historical accounts should be read in context. Medical research standards, available treatments, and our understanding of inflammatory disease have changed tremendously since 1951. Some claims made in popular publications at the time were much broader or more enthusiastic than would be appropriate based on today’s evidence. Even the original researchers urged caution. Early investigators recognized that these therapies were not cures and that high doses and prolonged treatment could create significant adverse effects.

The Discovery Earned a Nobel Prize

The importance of this period in medicine was recognized almost immediately. In 1950, Philip S. Hench, Edward C. Kendall, and Tadeus Reichstein received the Nobel Prize in Physiology or Medicine for discoveries involving hormones of the adrenal cortex, their structures, and their biological effects. Their work helped establish a much deeper understanding of the relationship between hormones and inflammatory disease. It also helped open the door to an entirely new era of anti-inflammatory medicine.

Then Corticosteroids Changed the Landscape

The excitement surrounding ACTH was soon followed by another major shift. Corticosteroid medications became increasingly available and practical. Prednisone was introduced in the 1950s, and corticosteroids eventually became standard treatments for many inflammatory and autoimmune conditions. As these medications became more widely used, ACTH became less prominent for many conditions. Historical reviews note that corticosteroid therapy eventually replaced ACTH in many areas of clinical practice. But ACTH did not disappear entirely.

Scientists Learned ACTH May Be More Complex Than Originally Thought

The original explanation for ACTH’s effects was relatively straightforward:

ACTH → stimulates the adrenal cortex → increases corticosteroid production → reduces inflammation

Today, researchers understand that the story may be more complicated. ACTH belongs to a broader family of signaling molecules associated with the melanocortin system. Research has identified five melanocortin receptors located in different tissues and cell types throughout the body. Modern research into repository corticotropin injection suggests its activity may involve both steroidogenic and nonsteroidogenic pathways, including effects involving melanocortin receptors on immune cells. In other words, researchers have continued investigating whether ACTH-related therapies can influence inflammation through mechanisms extending beyond simply telling the adrenal glands to produce cortisol.

ACTH Therapy Today

ACTH-based therapy still has specific medical applications, but it is not a general wellness treatment or an appropriate therapy for everyone. One prescription form, repository corticotropin injection, has FDA-approved indications involving certain inflammatory and autoimmune conditions. Its history dates back to FDA approval in 1952, although its indications and the evidence supporting its use have evolved substantially over the decades. Modern treatment decisions need to consider the specific condition being treated, available alternatives, medical history, potential risks, and the evidence supporting treatment. That is very different from the sweeping excitement surrounding ACTH in the early 1950s.

What a 1951 Article Can Teach Us About Medicine

Perhaps the most interesting part of looking back at The Power and the Glory of ACTH is seeing medicine in the middle of a major discovery. Researchers had uncovered something important, but they did not yet understand everything about it.

Over the decades that followed:

  • Hormone science advanced.
  • Corticosteroids transformed inflammatory medicine.
  • The immune system became better understood.
  • Melanocortin receptors were characterized.
  • New treatments became available.
  • Researchers continued investigating how ACTH exerts its effects.

That evolution is a reminder that medicine is rarely a finished story.

From 1951 to Today

What was described as an extraordinary new therapy more than seven decades ago ultimately became part of a much larger scientific story involving endocrinology, immunology, rheumatology, and inflammatory disease. The old Reader’s Digest pages are a fascinating piece of that history. But modern medicine gives us something physicians in 1951 did not have: decades of additional research to help separate early observations from established evidence and better understand where a therapy may, and may not, belong.

At You First Health & Wellness, we believe understanding the science behind health is just as important as following the latest trend. Our goal is to look at the whole person, consider the available evidence, and help patients make informed decisions about their health.

References

  1. Hench PS. Potential reversibility of rheumatoid arthritis. Nobel Lecture, December 11, 1950. Nobel Prize.
  2. Reichstein T. Chemistry of the adrenal cortex hormones. Nobel Lecture, December 11, 1950. Nobel Prize.
  3. Fleseriu M, et al. Acthar® Gel Treatment for Patients with Autoimmune and Inflammatory Diseases: An Historical Perspective and Characterization of Clinical Evidence. Drugs. 2023.
  4. History of Adrenal Research: From Ancient Anatomy to Contemporary Molecular Biology. Endocrine Reviews. 2023.
  5. de Kruif P. The Power and the Glory of ACTH. Condensed from Today’s Health. Reader’s Digest, November 1951.

***Disclaimer: This article is for educational purposes only and is not intended to replace medical advice. Historical descriptions of ACTH therapy reflect the medical knowledge and reporting of their time and should not be interpreted as current treatment recommendations. If you have questions about your health or treatment options, please speak with a qualified healthcare provider.***