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Flashcards in Cushing's Syndrome Deck (27)
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1. What are the 3 layers of the Adrenal Cortex and what do they produce?

1. Glomerulosa (mineralocorticoids – aldosterone for example), Fasciculata (glucocorticoids – i.e. cortisol), Reticularis (Sex Steroids).

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2. The parent compound of all of the hormones made by the Adrenal Cortex is the...

1. Cholesterol, thus the adrenal cortex looks yellow.

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3. General idea of “Cushing's Syndrome?”

1. There is an excess of Cortisol. It is any condition that produces elevated levels of glucocorticoids.

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4. What are the subclasses of Cushing's Syndrome?

1. Exogenous (iotragenic – administration of glucocorticoids via drug) causes and Endogenous causes (further divided into ACTH dependent and ACTH independent).

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5. Clinical Features of “Cushing's Syndrome?” Why do they occur?

1. Muscle weakness with central obesity, peripheral wasting.
1. Cortisol breaks down muscle to provide for the amino acids necessary for gluconeogenesis.
2. Specifically the fast twitch (type 2) muscle fibers are targetted for atrophy
2. Moon faces, Buffalo hump, truncal obesity.
1. Due to the excess sugar produced by gluconeogenesis, the pancreas will produce more insulin → stimulates storage of, specifically on the face, on the back and on the trunk.
2. Also glucocorticoids, while inducing gluconeogenesis, it doesn't allow cells to uptake the glucose and therefore causes secondary diabetes with diabetic symptoms.
3. Abdominal Striae.
1. Cortisol impairs the synthesis of collagen → blood vessels ruptures easily → striae (which basically represents ruptured blood vessels.
4. HTN
1. Cortisol upregulates the alpha 1 receptors on the blood vessels (specifically arterioles) which potentiates the effect of norepinephrine
2. Increased cortisol → Increased alpha 1 receptors → increased response to norepinephrine → increased vasoconstriction → HTN
5. Osteoperosis and Immune Suppression
1. Osteoperosis due to bone reabsorption induced by the glucocorticoids, due to all this catabolic effects.

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6. How do cortisol suppress the immune system?

1. It suppresses Phospholipase A2 → No arachodonic acid metabolites → No mediators of inflammation.
2. Inhibition of IL-2, which is an essential T-cell growth factor.
3. Inhibition of Histamine release from Mast cells → No vasodilation, no increased vascular permeability.

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7. Other symptoms of Cushing's Syndrome?

1. Hirsutism, decreased libido, decreased linear growth in children, menstrual irregularity, depression/emotional liability, easy bruising and weakness.

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8. How do you detect Cushing's Syndrome?

1. A 24 hour urine cortisol levels.

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9. Etiology of Cushing's Syndrome? For the Exogenous?

1. Exogenous corticosteroids ← most common cause.
1. This causes both the right and the left adrenal glands to atrophy
1. Increased cortisol levels in the blood leads to the cortisol going to the anterior pituitary and shutting down the release of ACTH → this is needed for adrenal glands to be maintained, and without it the result is adrenal glands to atrophy

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Etiology of the most common ACTH Independent inducer of Cushing's Syndrome?

2. Primary adrenal adenoma, hypertrophy, or carcinoma ← this is the most common cause of ACTH independent Cushing's syndrome.
1. This will lead to increased production of cortisol from ONE of the adrenal glands to be large due to the pathology, and it will release cortisol which will go to the anterior pituitary and shut down the release of ACTH → Results in THE OTHER ADRENAL GLAND TO ATROPHY!
2. The carcinoma tends to have a more marked increase in cortisol than the adenomas.

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3. What is Cushing's Disease? What happens here and how is this manifesting?

1. ACTH secreting pituitary adenoma. Pituitary adenoma is Cushing's Disease, which can rarely be also caused by CRH dependent pituitary hyperplasia.
1. 70% of all endogenous Cushing's syndrome is caused by this. Hits women x4 more frequently than men and particularly young adults, mostly due to microadenoma's as, rarely some macroadenomas.
2. This will result in an increased release of ACTH in the blood which will cause both the adrenal glands to hypertrophy and release increased cortisol into the blood → Cushing's syndrome

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2. How do corticotroph cell hyperplasia occur without a discrete adenoma in the pituitary?

1. Might be primary, or secondary in which case it is due to excessive stimulation of the ACTH release by hypothalamic corticotrophin releasing hormone CRH producing tumors.

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What is "Ectopic Corticotropin Syndrome?"

4. Paraneoplastic ACTH secreting tumors ← This is called Ectopic Corticotropin Syndrome
1. Random tumor anywhere (classically small cell carcinoma of the lung) that secretes ACTH → both adrenals hypertrophy → more cortisol produced → Cushing's Syndrome.

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10. How can you distinguish between a ACTH secreting pituitary adenoma from a Paraneoplastic ACTH secreting tumor, if both of them results in increased size of both adrenal glands?

1. High-dose Dexamethasone administration → this is a cortisol analog and it has the ability to shut down ACTH production in the pituitary adenoma but not the ectopic ACTH producing tumor (i.e. small cell carcinoma from the lung.
2. Follow up with blood cortisol levels. If it was a pituitary adenoma then the ACTH production would've stopped thus decreased cortisol. If ectopic tumor ACTH production, then Dexamethasone will have no effect and you will still have elevated cortisol.

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11. How would you figure out if the Cushing's Syndrome is ACTH dependent or independent?

1. If ACTH independent, then blood serum will reveal elevated cortisol levels with decreased ACTH levels.

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12. What is “Crooke Hyaline Change?”

1. A histologic change where the normal granular, basophilic ACTH producing cells in the anterior pituitary becomes homogenous and pale ← due to accumilation of intermediate keratin filaments in the cytoplasm.
2. Change in the anterior pituitary occurs regardless of the cause of Cushing's Syndrome.

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What is the general problem with Cushing's syndrome?

Excess Cortisol, and as a result the unwanted effects of too much cortisol.

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Why do patients with Cushing's have muscle weakness with thin extremeties?

Cortisol can break down muscle to provide amino acids needed for gluconeogenisis.

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Why do Cushing's patients have moon faces, buffalo humps and truncal obesity?

Due to the efforts of cortisol to increase blood sugar, the pancreas reacts by making insulin whose job is to store fat. Fat is stored in the face (moon face), in the trunk (truncal obesity) and in the back (buffalo hump).

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Why is there abdominal striae in cushing's?

Cortisol impairs the production of collagen, thus weak collagen in the blood vessels which will rupture easily as a result. Ruptured BV's are presented as abdominal striae.

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Why do we see HTN in cushing's?

Cortisol will upregulate the alpha 1 receptors of blood vessels which amplifies the effects of NorEpi.

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How does cortisol maintain vascular tone?

Upregulation of alpha 1 receptors in the arterioles.

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How does cortisol result in immune suppression (3 pronged mech).

1. Inhibits Phospholipase A2, the precursor to the arachadonic acid and cox, which is needed for the COX enzymes and inflammation.
2. Inhibits IL-2, a T cell growth factor.
3. Inhibits histamine from mast cells, so no vasodilation and increased vascular permeability.

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What does a bilateral cortical atrophy imply?

Probably an effect of exogenous corticosteroid administeration, which goes to the anterior pituitary and shuts off ACTH production, thus both adrenal cortex atrophies.

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What does one big adrenal gland and one atrophic adrenal gland imply?

Primary adrenal adenoma, hyperplasia or carcinoma, because that will make cortisol and shut off anterior pituitary production of ACTH. The normal adrenal cortex will respond to no ACTH and atrophy, whereas the abnormal one will still have its supply (due to the fact its a tumor).

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What will we suspect if BOTH the adrenals are enlarged?

ACTH secreting Anterior pituitary adenoma, which will induce both adrenal cortex to hypertrophy with its constant supply of ACTH. Also can be due to a paraneoplastic ACTH secretion, where a small cell lung carcinoma can secrete ACTH and the result will be the same.

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After high dose dexamethasone administration, cortisol levels in the blood has not changed. What's this diagnostic of?

It is used to distinguish between a paraneoplastic tumor secreting ACTH vs a adrenal pituitary tumor secreting ACTH. High dose dexamethasone should've shut off the AP production of ACTH, but since the cortisol levels are the same as it was before in the blood, it must be paraneoplastic, most commonly a small cell carcinoma of the lung. (Adenoma of the pituitary is benign, small cell lung carcinoma is malignant and will not respond to anything).