Endo-Adrenals Flashcards
(38 cards)
What hormones does the medulla and cortex produce?
Cortex: Androgens, mineralocorticoids, glucocorticoids
Medulla: Catecholamines
What happens to cortisol with Cushing’s syndrome?
Poor suppressibility of cortisol with dexamethasone and loss of normal diurnal variation in cortisol secretion are seen.
What is the most common cause of Cushing’s syndrome?
However, iatrogenic hypercortisolism from the administration of exogenous oral, inhaled, intra-articular, or topical glucocorticoids is often seen in clinical practice and is the most common cause of CS overall.
What dose equivalents of prednisone are likely to cause Cushing Syndrome through suppression of the HPA axis?
Doses equivalent to prednisone 5 mg/d or less are unlikely to cause clinically significant HPA axis suppression, while those in excess of 10 to 20 mg/d commonly do after 3 weeks or more of consecutive use.
What are the two ways that endogenous Cushing’s syndrome occurs? What are the most common etiologies in each?
ndogenous CS can result from ACTH-dependent and ACTH-independent causes.
Dependent: pituitary adenoma, ectopic ACTH source
Independent: adrenal adenomas and carcinomas
What are some causes of pseudo-hypercortisolism? Or disease states that produce hypercortisol mimics?
CS must be differentiated from other disorders and clinical states that are associated with physiologic hypercortisolism (pseudo-Cushing syndrome). Causes of pseudo-Cushing syndrome include severe obesity, polycystic ovary syndrome, pregnancy, anorexia nervosa, depression, alcoholism, and extreme physical stress, as in the setting of infection.
Clinical symptoms of hypercortisolism?
Clinical findings that are highly specific for CS include centripetal obesity, facial plethora, abnormal fat deposition in the supraclavicular or dorsocervical (“buffalo hump”) areas, and wide (>1 cm) violaceous striae
How is Cushing’s syndrome diagnosed?
At least two first-line tests should be diagnostically abnormal before the diagnosis is confirmed. Initial tests include the overnight low-dose dexamethasone suppression test (LDST), 24-hour urine free cortisol (UFC), and late-night (LN) salivary cortisol. All three tests have similar diagnostic utility, but the LDST or LN salivary cortisol tests are more convenient. The 24-hour UFC and LN salivary cortisol tests should be performed at least twice to ensure reproducibility of results.
See figure 6 algorithm
Why can’t random cortisol be used for diagonsis?
Because the secretion of cortisol is pulsatile, measurement of random serum cortisol is neither sensitive nor specific for the diagnosis of CS.
What is the low dose dexamethasone test and how should it be interpreted?
In the overnight LDST, 1 mg of dexamethasone is administered at 11 PM or midnight, and serum cortisol is measured the next morning at 8 AM. With either test, serum cortisol will typically be suppressed to less than 2 μg/dL (55 nmol/L).
When should the low dose dexamethasone test be avoided?
1) proteins are low
2) meds that accelerate dexamethasone metabolism
Standard assays measure total serum cortisol, or that which is bound to cortisol-binding globulin (CBG) and other proteins. Therefore the LDST should not be performed when CBG is likely to be abnormal, such as with malnutrition, cirrhosis, the nephrotic syndrome, and hyperestrogenemia (oral contraceptive pills or pregnancy). There is no clear association between dexamethasone responses and BMI or weight, and therefore the LDST may be used similarly in the obese population. The LDST is best avoided in patients taking medications that could accelerate dexamethasone metabolism, such as antiepileptic drugs (phenytoin, phenobarbital, and carbamazepine), rifampin, or pioglitazone. Concomitant measurement of serum dexamethasone can confirm altered dexamethasone metabolism and patient adherence.
Explain how a LN salivary test is performed
The LN salivary cortisol test is performed between 11 PM and midnight. The normal evening nadir in cortisol secretion is lost in patients with CS, while it is preserved in patients with pseudo-Cushing syndrome. Both emotional and physical stress (for example, exercise) can cause a physiologic increase of salivary cortisol. False-positive results are seen with cigarette smoking or use of chewing tobacco. LN salivary cortisol testing should not be performed in patients with erratic sleep schedules (for example, shift-workers).
How can you distinguish between pseudo-hypercortisolism and real Cushing’s syndrome?
The normal evening nadir in cortisol secretion is lost in patients with CS, while it is preserved in patients with pseudo-Cushing syndrome. Both emotional and physical stress (for example, exercise) can cause a physiologic increase of salivary cortisol.
After Cushing’s syndrome has been confirmed, how do you tell the difference between ACTH dependent or independent causes?
After CS has been confirmed biochemically, further testing is required to distinguish ACTH-dependent or -independent causes, and consultation with an endocrinologist is recommended. The first step is to measure plasma ACTH on two separate occasions. With adrenal (ACTH-independent) CS, plasma ACTH is usually less than 5 pg/mL (1.1 pmol/L), whereas values greater than 20 pg/mL (4.4 pmol/L) are typically seen with ACTH-dependent causes
After Cushing’s syndrome has been determined, and then ACTH independence has been established… what next?
The next step in the evaluation of ACTH-independent CS is with imaging of the adrenal glands, such as dedicated adrenal imaging with thin-section CT or MRI. Both studies have equal sensitivity; however, MRI is more costly. Adrenal adenomas and carcinomas can usually be distinguished from one another radiographically
What is the treatment for ACTH independent Cushing syndrome?
Surgery is considered first-line treatment for adrenal adenomas and nonmetastatic adrenocortical carcinomas (ACCs). When surgery is delayed for patients with overt CS, adrenal enzyme inhibitors (metyrapone, ketoconazole, and etomidate) can be used to reduce cortisol levels and decrease the risk of complications, such as opportunistic infections and cardiovascular events.
Following adrenalectomy, patients with adrenal CS will often develop acute adrenal insufficiency because of HPA axis suppression and contralateral adrenal atrophy from long-standing elevated cortisol levels. All patients should therefore be treated with stress-dose glucocorticoids during the perioperative period and continued on physiologic replacement until HPA axis recovery has been confirmed. Following successful surgery, the physical changes associated with CS can take up to 1 year to resolve.
How is a pheochromocytoma diagnosed?
The diagnosis of pheochromocytoma and paraganglioma is based on confirmation of the excessive secretion of catecholamines or their metabolites, as measured in the plasma or urine.
What most u test for if you incidentally find an adrenal mass?
Pheochromocytoma!
How do you diagnose a pheo? What are tests and how are they best used?
The sensitivity of plasma free metanephrines is the highest of any screening test (96%-100%); however, its specificity is relatively low (85%-89%). Therefore, plasma free metanephrines will reliably exclude a pheochromocytoma when negative, but further testing is needed to confirm the diagnosis unless the result is markedly abnormal (above 4 times the upper limit of normal). The sensitivity and specificity of 24-hour urine fractionated metanephrines and catecholamines are 91% to 98%. Due to the lower frequency of false-positive results, 24-hour urine measurements are recommended when the pre-test probability of disease is relatively low (adrenal mass without typical radiographic appearance), while measurement of plasma free metanephrines is preferred when clinical suspicion is higher (known hereditary syndrome).
After biochemical test confirmation, what is next in the diagnostic workup of a pheo?
Following the biochemical diagnosis of pheochromocytoma or catecholamine-secreting paraganglioma, radiographic localization is needed. Because most catecholamine-secreting tumors are located in the abdomen, CT or MRI of the abdomen and pelvis is the best initial study. If negative, iodine 123 (123I)-metaiodobenzylguanidine (MIBG) scanning can be performed. Adjunctive diagnostic tests are CT or MRI of the chest or head and neck region.
What is the preoperative management of someone with a pheochromocytoma?
1) alpha blockade: phenoxybenzamine
2) beta blockade
Preoperative pharmacologic treatment is mandatory for pheochromocytomas and paragangliomas to prevent life-threatening cardiovascular complications related to the massive release of catecholamines during surgery. Preoperative blockade of α-adrenoceptors, usually with phenoxybenzamine, is first-line medical therapy. The dosage is titrated to achieve a blood pressure below 130/80 mm Hg seated and greater than 90 mm Hg (systolic) standing. Commonly used but non-FDA approved alternatives include calcium channel blockers and selective α1-blockers (terazosin or doxazosin). β-Adrenoceptor blockers (metoprolol or propranolol) are added later to treat reflex tachycardia, but should never be started before adequate α-blockade has been achieved due to the risk of hypertensive crisis from unopposed α-receptor stimulation. A heart rate of 60 to 70/min seated and 70 to 80/min standing can be targeted in most patients.
Once resected laparoscopically, what next for people who have had a pheo? What is their follow-up?
Pheochromocytomas and paragangliomas require lifelong surveillance for recurrence with annual plasma free metanephrine measurement.
What do you see on a BMP with primary hyperaldosteronism?
Additional signs of PA include hypokalemia and metabolic alkalosis. Without treatment, excess cardiovascular morbidity and mortality are seen.
What are the most common causes of hyperaldosteronism?
Aldosterone-producing adrenocortical adenomas (APA; aldosteronomas) cause approximately 40% of PA, whereas nearly all other cases are due to bilateral adrenal hyperplasia. Unilateral adrenal hyperplasia and aldosterone-secreting adrenocortical carcinomas (ACCs) are rare. Familial hyperaldosteronism is also uncommon.
