Glucocorticoids

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Glucocorticoids

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USMLE® Step 2 style questions USMLE

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A 43-year-old woman presents to an outpatient clinic for evaluation of a new facial rash. The rash worsens with sun exposure. The patient has also experienced painful oral ulcers, joint pain, and hair loss. She has no significant past medical history. Her mother has a history of rheumatoid arthritis. Physical examination reveals a bright red butterfly-like rash on the cheeks and nose, sparing the nasolabial folds. ANA titer is 1:320. She was diagnosed with systemic lupus erythematosus and started on oral prednisone. Which of the following best describes the mechanism by which glucocorticoids exert their anti-inflammatory and immunosuppressive effect?

External References

First Aid

2024

2023

2022

2021

B cells p. 409

glucocorticoid effects p. 118

Glucocorticoids

acute gout attack p. 724

adrenal insufficiency p. 353

adrenal steroids and p. 336

arachidonic acid pathway p. 494

calcium pyrophosphate deposition disease p. 473

Cushing syndrome diagnosis p. 352

diabetes mellitus p. 352

fat redistribution with p. 249

gout p. 473, 496

myopathy p. 249

rheumatoid arthritis p. 472

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Glucocorticoids are a group of steroid hormones, which are secreted by the two adrenal glands that sit like hats, one on top of each kidney. Each one has an inner layer called the medulla and an outer layer called the cortex. The adrenal cortex secretes different corticosteroid hormones: like glucocorticoids under the control of adrenocorticotropic hormone, or ACTH.

Normally the hypothalamus, located at the base of the brain, secretes corticotropin releasing hormone, known as CRH, which stimulates the anterior pituitary gland to secrete adrenocorticotropic hormone, known as ACTH. ACTH then travels to the pair of adrenal glands and binds to the ACTH receptors on adrenocortical cells. This causes the adrenocortical cells to release the glucocorticoids from the zona fasciculata, which have powerful anti-inflammatory and metabolic effects. These glucocorticoids have a negative feedback effect on the hypothalamic-pituitary-adrenal axis, meaning excess corticosteroids suppress the release of both CRH and ACTH into the circulation.

Now, once made, glucocorticoids enter the circulation and travel via the blood to reach the target cells. Steroids are lipophilic molecules, so they cross the cell membrane, enter inside the cell, and bind with a cytoplasmic receptor protein, called a ‘glucocorticoid receptor’. Now, this ‘glucocorticoid-receptor complex’ undergoes some structural changes, which allow them to enter inside the nucleus and bind with the ‘glucocorticoid response elements’ or GRE on the chromatin. Now, this induces transcription of specific mRNA that’s used to synthesize different proteins, which in turn modifies various cell functions and metabolic effects in the body.

The most important glucocorticoid in humans is cortisol, and it’s generally released during times of stress, like during an illness or starvation. Cortisol helps to regulate both the immune response as well as cellular metabolism like gluconeogenesis. With regard to the immune response, cortisol promotes an overall anti- inflammatory state by inhibiting the two main products of inflammation - prostaglandins and leukotrienes - as well as inhibiting interleukin-2 production by white blood cells.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Adrenal insufficiency - recognition and management" Clin Med (Lond) (2017)
  5. "Clinical Pharmacology of Corticosteroids" Respiratory Care (2018)
  6. "Treatment with Synthetic Glucocorticoids and the Hypothalamus-Pituitary-Adrenal Axis" International Journal of Molecular Sciences (2017)
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