Cushing’s Disease

• Pituitary adenomas that secrete excess ACTH can lead to high cortisol levels and clinical features of Cushing’s syndrome.

Chronic Stress or Illness

• Prolonged physical or emotional stress, severe infections, or inflammatory states may raise ACTH as the body attempts to boost cortisol production.

Primary Adrenal Insufficiency (Addison’s Disease)

• If the adrenal glands are failing (often from autoimmune destruction or infections), the lack of cortisol feedback may cause ACTH to rise.

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Secondary Adrenal Insufficiency

• Mechanism:
  Insufficient secretion of ACTH from the pituitary—owing to factors such as tumors, pituitary surgery, or autoimmune hypophysitis—leads to low cortisol production.

Hypothalamic Dysfunction

• Mechanism:
  Disrupted signaling from the hypothalamus, for example after head trauma or in certain autoimmune conditions, can result in a reduced release of ACTH.

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Neonates and Children

• Abnormal ACTH levels in neonates and children can significantly affect growth and stress responses, potentially influencing long-term developmental outcomes.

Older Adults

• In older adults, altered secretion or sensitivity to ACTH may contribute to frailty and diminish the overall ability to effectively cope with stress.

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Adrenal Corticosteroid Production and Regulation

All these markers are part of the adrenal corticosteroid system, which is regulated by the hypothalamic–pituitary–adrenal (HPA) axis:

• 11‑Plasma Oxycorticosteroids: These reflect adrenal glucocorticoid production (such as cortisol and related steroids) measured in blood.
• 17‑Plasma Oxycorticosteroids: These indicate another set of adrenal steroids (often including precursors or androgens) in the blood.
• 17‑Urine Ketosteroids: These are urinary metabolites derived primarily from the 17‑hydroxylated adrenal steroids. They provide an integrated view of adrenal steroid production over time.
• Corticotropin (ACTH): This pituitary hormone stimulates the adrenal cortex to produce these corticosteroids.

In essence, ACTH drives the production of various adrenal hormones, which are then measured in blood (11‑ and 17‑oxy compounds) and metabolized to form ketosteroids excreted in urine. Together, these tests offer a comprehensive picture of adrenal function and HPA axis activity.

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