Term
| When would a physician entertain a high index of suspicion of Cushing's syndrome in a patient? |
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Definition
| When diabetes and hypertension are present. |
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Term
| What are classical features of Cushing's Syndrome? |
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Definition
- Central obesity
- Hypertension/edema/hypokalemia
- Hirsutism/amenorrhea/acne
- Purple cutaneous striae
- Ecchymoses
- Proximal myopathy
- Diabetes mellitus
- Osteoporosis
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Term
| What are some of the effects of cortisol? |
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Definition
- Cortisol counteracts the effects of insulin on glucose and favores gluconeogenesis & breakdown of proteins.
- Cortisol increases proteolysis (increase in urinary nitrogen excretion) in multiple organs (thinned skin with purplish striae; muscle weakness with reduced mass and reduced bone matrix).
- Cortisol inhibits the positive effect of vitamin D on calcium absorption by the intestine.
- Cortisol increases calcium excretion and inhibits bone formation.
- Cortisol is vasoprotective, immunosuppressant, decreases threshold for epileptic seizures and emotional lability.
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Term
| What are the 3 types of spontaneous Cushing's? |
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Definition
- pituitary tumor, often (up to 40%) below the CAT and NMR detection limit.
- adrenal tumor, usually benign.
- ectopic ACTH- or CRH- producing tumor (most often small cell cancer of the lung or carcinoid).
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Term
| What is the single most common cause of Cushing's syndrome? |
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Definition
| Use of supraphysiologic doses of synthetic glucocorticoids (prednisone, dexamethasone, others) to treat patients w/chronic inflammatory or autoimmune disorders. |
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Term
| What is the most common endogenous etiology of Cushing's? |
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Definition
| small benign tumor (microadenoma) of the pituitary gland hypersecreting ACTH. |
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Term
| What do screening tests for Cushing's attempt to document? |
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Definition
- Excessive production of cortisol
- Abnormal HPA feedback
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Term
| What are screening tests for Cushing's syndrome? |
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Definition
- Overnight dexamethasone (1 mg at midnight) Suppression test Normal: 8:00 AM plasma cortisol <1.8 ug/dl
- Urinary free cortisol:Normal: <100 ug/day
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Term
| What two conditions can elevate cortisol levels measured in Cushing's screening tests? |
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Definition
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Term
| If a patient tests positive for any of the screening tests for Cushings, what would be a confirmatory test? |
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Definition
| The prolonged (2-day) low-dose (.5mg) dexamethasone suppression test. This test confirms Cushing's, but doesn't identify its cause. |
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Term
| If screening tests were positive for Cushing's, what test results thereafter are most consistent w/an autonomous overproduction of cortisol by an adrenal tumor? |
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Definition
- Low ACTH in plasma
- Absent response to high dose dexamethasone.
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Term
| Why is the high does dexamethasone test able to differentiate a pituitary adenoma hypersecreting ACTH from the other two common etiologies (ectopic & adrenal)? |
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Definition
| Most pituitary ACTH hypersecreting tumors are semiautonomous, meaning that they respond to feedback inhibition by rising cortisol levels; wherease the other two tumor types are completely autonomous and are not regulated. |
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Term
| Failure of high dose dexamathasone to suppress urinary exretion of cortisol or serum cortisol by >50% is evidence against what type of source of Cushing's syndrome? |
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Definition
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Term
| What makes testing using CRH stimulation of ACTH a good test for differentiating between a pituitary and an ectopic source of ACTH? |
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Definition
| Most ACTH secreting pituitary tumors are hyperresponsive to CRH relative to the normal pituitary and most tumors producing ectopic ACTH do not secrete ACTH in response to CRH. |
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Term
| What is used in conjunction to CRH infusion for determination of the source of an ACTH secreting tumor? |
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Definition
| Selective venous sampling from the petrosal sinuses, which receive venous blood from the pituitary, is often employed to confirm the pituitary as the source of excess ACTH secretion. |
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Term
| What kind of petrosal aCTH gradient confirms a positive result consistent with a pituitary source of ACTH? |
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Definition
| petrosal to peripheral ACTH gradient of ≥ 3:1 after CRH is a positive result. (85% sensitive, 100% specific). |
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Term
| Why would the adrenal display hyperplasia in the context of an ACTH secreting tumor (be it pituitary or ectopic)? |
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Definition
| The 'T' in ACTH stand for 'Trophic', meaning that it stimulates growth as well. |
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Term
| What is Cushing's Disease? |
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Definition
| Cushing's Syndrome due to a pituitary tumor. |
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Term
| Who should be screened for Cushing's Syndrome? |
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Definition
- Obese, poorly controlled diabetics even if they do not have all of the typical CS features
- Women with hyperandrogenism or symptoms of PCOS (irregular menses, hirsutism, weight gain, acne) particularly if hx of sudden onset in adulthood
- Patients with abnormal weight gain and osteoporosis / non-traumatic fractures
- Patients with sudden onset of hypokalemia, hypertension, and muscle weakness (ectopic ACTH)
- Patients with hx of incidentally discovered adrenal adenoma or pituitary adenoma who have any signs or symptoms of CS
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Term
| How is Cushing's Disease treated? |
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Definition
| Transsphenoidal resection of the pituitary adenoma is the treatment of choice by an experienced surgeon. |
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Term
| What is the best postoperative index of remission of resection of a pituitary adenoma? |
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Definition
| A low serum cortisol post-op. (<1.8μg/dl within 14 days after surger) |
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Term
| What options exist for patients with failed resection of a pituitary adenoma? |
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Definition
- Reoperation, but success of only 50-71%.
- Medical therapy w/ketoconazole, which is an adrenal steroidogenesis inhibitor, blocks synthesis of cortisol early in the pathway.
- Biolateral adrenalectomy
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Term
| Apart from surgical risk, what disadvantages does bilateral adrenalectomy have? |
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Definition
- Requiring lifelong replacement of both glucocorticoid and mineralocorticoid hormones.
- Concern that it increases the risk of Nelson's syndrome ( which is malignant growth of residual ACTH-secreting adenoma due to lack of cortisol feedback inhibition).
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Term
| What is Nelson's Syndrome and what predisposes to its developement? |
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Definition
Malignang growth of residual ACTH-secreting adenoma due to lack of cortisol feedback inhibition. This occurs as a complication of bilateral adrenalectomy.
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Term
| What are the top 3 sites for development of an ectopic ACTH secreting tumor? |
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Definition
Small cell carcinoma of the lung. Bronchial carcinoid tumor. Thymic carcinoid tumor. |
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