What is the difference between hormones and peptides, specifically regarding glucocorticoids (corticosteroids) and Adrenocorticotropic hormone (ACTH)?

Differences Between Hormones and Peptides: Glucocorticoids vs ACTH

Hormones are signaling molecules that can be peptide-based or non-peptide-based (like steroids), while glucocorticoids are steroid hormones produced by the adrenal cortex and ACTH is a peptide hormone produced by the pituitary gland.

Key Differences Between Hormones and Peptides

Hormones: The Broader Category

• Hormones are chemical messengers that can be classified into different types based on their chemical structure 1
• Types of hormones include:
  • Peptide/protein hormones (made of amino acids)
  • Steroid hormones (derived from cholesterol)
  • Amine hormones (derived from amino acids)
  • Eicosanoid hormones (derived from fatty acids)

Peptide Hormones

• Peptide hormones are a specific type of hormone made up of amino acid chains 1
• Examples include:
  • ACTH (adrenocorticotropic hormone)
  • Insulin
  • Glucagon
  • Vasopressin
  • Oxytocin
• Characteristics of peptide hormones:
  • Water-soluble
  • Cannot cross cell membranes easily
  • Typically bind to cell surface receptors
  • Often require second messenger systems
  • Produced by various glands including the pituitary

Glucocorticoids vs ACTH

Glucocorticoids

• Glucocorticoids are steroid hormones (non-peptide) 1
• Produced in the adrenal cortex as the output of hypothalamic-pituitary-adrenal (HPA) axis functioning 1
• Primary examples include cortisol and cortisone 1
• Functions include:
  • Regulating stress response
  • Energy regulation and lipolysis
  • Anti-inflammatory and immune-suppressive effects 1
• Act through binding to intracellular glucocorticoid receptors (primarily type II receptors) 2
• Used therapeutically as replacement therapy in adrenal insufficiency 3

ACTH (Adrenocorticotropic Hormone)

• ACTH is a peptide hormone 1, 4
• Produced by the anterior pituitary gland 1, 3
• Consists of 39 amino acids in its natural form 4
• The biologic activity resides in the N-terminal portion (first 24 amino acids) 4
• Functions:
  • Stimulates the adrenal cortex to produce glucocorticoids (primarily cortisol) 4
  • Regulates adrenal steroid production 1
• Synthetic ACTH (cosyntropin) is used diagnostically to test adrenal function 4

Relationship Between Glucocorticoids and ACTH

Regulatory Feedback Loop

• ACTH stimulates the adrenal cortex to produce glucocorticoids 4
• Glucocorticoids then provide negative feedback to inhibit further ACTH secretion 5
• This feedback occurs through three time frames:
  1. Fast feedback (within minutes)
  2. Intermediate feedback (within hours)
  3. Slow feedback (over several hours to days) 5

Clinical Relevance

• In primary adrenal insufficiency:
  • Low cortisol with high ACTH levels 3
  • Requires both glucocorticoid and often mineralocorticoid replacement 3
• In secondary adrenal insufficiency:
  • Low cortisol with low or normal ACTH levels 3
  • Only requires glucocorticoid replacement 3
• The 250-μg ACTH stimulation test (using synthetic ACTH/cosyntropin) is used to diagnose adrenal insufficiency 3, 4

Common Pitfalls and Clinical Considerations

• When replacing hormones in patients with multiple pituitary hormone deficiencies, always start with hydrocortisone (glucocorticoid) before thyroid hormone to prevent adrenal crisis 1, 3
• Dexamethasone (a synthetic glucocorticoid) should be avoided for long-term replacement therapy 3
• Medications can interfere with the HPA axis:
  • Glucocorticoid therapy can cause secondary adrenal insufficiency 3
  • Antiepileptics/barbiturates may increase hydrocortisone requirements 3
  • Antifungals may alter hydrocortisone metabolism 3

In summary, the fundamental difference is that glucocorticoids are steroid hormones produced by the adrenal glands, while ACTH is a peptide hormone produced by the pituitary that stimulates glucocorticoid production. They work together in a feedback loop that maintains appropriate cortisol levels in the body.