Special Topic: Cortisol and Cushing's Disease Flashcards
Effect of Cortisol on Liver: Normal & Excess Levels
NORMAL: -increases gluconeogenesis, -increases glycogen synthesis and storage (may be protective during stress) CHRONIC: -Diabetes (in conjunction with glucose intolerance)”
Effect of Cortisol on Muscle: Normal & Excess Levels
“Normal: -Decreases glucose uptake in most non-critical tissues, including skeletal muscle -Decreases muscle/increases protein breakdown to provide amino acids Chronic: -glucose intolerance -muscle loss -muscle weakness -muscle bruising “
Effect of Cortisol on Adipose: Normal & Excess Levels
“Normal: -Increases lipolysis in most adipose tissue, increases available free fatty acids. -Increases central, shoulder, facial obesity (mechanism not understood) Chronic: -central obesity, moon faces, buffalo hump -hyperlipidemia -fatty cataracts “
Effect of Cortisol on Immune System: Normal & Excess Levels
“Normal: -suppresses immune system -decreases T>B lymphocytes -decreases cytokines -decreases prostanoids (eicosanoids) Chronic: -frequent infections -persistent infections “
Effect of Cortisol on Bone: Normal & Excess Levels
“Normal: -reduces new bone formation -??possibly increases bone resorption -reduces Ca absorption from the intestine Chronic: -osteopenia -osteoporosis -2o hyperparathyroidism “
Effect of Cortisol on Connective Tissue/Skin: Normal & Excess Levels
“Normal: - reduces collagen -reduces hyaluronate Chronic: - thinning of skin -poor wound healing -tissue tearing, striae “
Effect of Cortisol on Mineralocorticoid Receptor: Normal & Excess Levels
“Normal: -stimulates mineralocorticoid receptor when at high concentration -hypertension Chronic: -suppresses pituitary hormones generally -can alter mood (?hypothalamus) “
Effect of Cortisol on Brain: Normal & Excess Levels
“Normal: psychosis, depression, irritability, mental status changes, memory loss, insomnia Chronic: reduced linear growth in children (reduced growth hormone releasing hormone) “
How do you diagnose a Pituitary vs. an Ectopic vs. an Adrenal Tumor?
remember it fluctuates a lot over a day. It rises in early hours of day 6-8amm and then drops off dramatically and then goes up again in the evening. Therefore, a single measure of blood cortisol is fairly meaningless.
1) Collect urine and check if you have high or regular cortisol output
2) Administor potent glucocorticoid called DEXAMETHASONE and if NO TUMOR then the Cortisol levels will plummet
3) If you find high cortisol levels persist you must distringuish between adrenal, pituitary, and ectopic tumor.
4) Adrenal tumor produces such high levels of Cortisol that is causes a complete suppression of ACTH and therefore unmesasurable ACTH levels. (This is due to negative feedback loop from Adrenal to Pituitary and Hypothalmus?)
5) Pituitary Tumor: Has glucocorticoid receptor and you can cause, with DEXAMETHASONE, some reduction in ACTH output, but you don’t turn off all together. It suppresses ACTH output by 50% or more with DEXAMETHASONE.
6) Ectoppic Tumor: This is rudementary endocrine tissue which has capacity to produce ACTH but it doesn’t have a glucocorticoid receptor. (not sure how to dinstinguis this from an Adreanal tumor)
This takes longer. You must administor 48hrs. of high doses of dexamethasone (potent cousin of cortisol) to suppress ACTH (cortisol) production. The result is that blood levels of ACTH will be completely suppressed if it’s an Adrenal Tumor but an Ectopic or Pituitary tumor will still secreate some ACTH. The Pituitary will secrete will be suppressed more than 50% and the Ectopic tumor will barely be suppressed so it will still secrete ACTH. (ectopic tumors can be found in the lungs and intestines).
Name 3 compounds produced by the Adrenal Cortex and 2 compounds produced by the Adrenal Medulla
“Adrenal Cortex produces: -cortisol which has many activities, esp glucose metabolism -aldosterone which conserves sodium -DHEA and other androgens which may produce pathology in women when in excess. Adrenal Medulla produces: -Epinephrine and norepinephrin which regulate heart rate and vessel tone -Dopamine which regulates renal function “
What type of hormone is cortisol and how is it sythesized?
“Cortisol is aGlucocorticoid. It takes 5 enzymes to modify Cholesterol into Cortisol. -Cholesterol–> 5 Steps–> Cortisol. Adrenal gland is able to make the conversion and is very adept at pulling in steral molecules. “
Describe the Structure of Cortisol and the basic structure of a glucocorticoid
This needs editing…. Cortisol modifies a ring? There is a 3’ Carbon double bond, 11’ OH group, 17’ OH group with Ketone extension that is similar in mineralicorticoids
Draw a diagram showing how Cortisol is regulated by the interaction between the Hypothalmus, Pituitary, and Adrenal Glands
“There is no cell surface receptor -Cortisol diffuses passively into cell -Cortisol binds to Glucocorticoid receptor -Cortisol activated Glucocorticoid receptor displays ZINC fingers, these bind to hormons response elements in DNA and Alter transcription. -Genes are either upregulated or downregulated”
