Adrenal Pathology Flashcards
1
Q
What is Addison disease? How do patients typically present?
A
- Addison disease is chronic primary adrenal insufficiency (majority of cases are due to autoimmune adrenalitis)
- the resulting deficiency in aldosterone and cortisol results in hypotension, hyperkalemia, metabolic acidosis, hypoglycemia, fatigue, weakness
- the resulting increase in ACTH results in skin and mucosal hyperpigmentation
- patients have atrophy of all 3 cortical layers (medulla tends to be spared)
2
Q
What is secondary adrenal insufficiency? How can we distinguish it from Addison disease?
A
- secondary adrenal insufficiency is due to an issue with the hypothalamus and/or pituitary, resulting in a decreased ACTH production (thus leading to adrenal insufficiency)
- because of the low ACTH, hyperpigmentation is NOT seen in these patients (vs. in Addison disease)
- additionally, these patients will not develop hyperkalemia or metabolic acidosis because aldosterone secretion is largely normal (aldosterone only needs tonic levels of ACTH, as it mainly responds to angiotensin II) vs. in Addison disease
3
Q
What are the major causes of acute adrenal insufficiency AKA adrenal crisis?
A
- MCC: sudden withdrawal of long-term corticosteroids
- stress in a patient with underlying chronic insufficiency (acute on chronic)
- Waterhouse-Friderichsen syndrome (due to massive adrenal hemorrhage via sepsis and DIC, usually due to Neisseria meningitidis)
4
Q
What is Cushing syndrome? What are the major causes and what are the ACTH levels and image findings of each?
A
- cushings is an excess of cortisol
- MCC: exogenous corticosteroids: low ACTH, bilateral adrenal atrophy
- ACTH-secreting pituitary adenoma (AKA Cushing disease; most common endogenous cause): high ACTH, bilateral adrenal hyperplasia
- ectopic ACTH-secreting tumor (ie in SCLC): very high ACTH, bilateral adrenal hyperplasia
- adrenal adenoma, hyperplasia, or carcinoma: low ACTH, unilateral atrophy of the normal adrenal gland
5
Q
What is the difference between Cushing syndrome and Cushing disease?
A
- syndrome: excess cortisol
- disease: excess ACTH causing excess cortisol; disease involves the hypothalamus and/or pituitary (ectopic ACTH secretion is not considered Cushing disease)
6
Q
How do patients with Cushings present?
A
- HTN
- weight gain (central obesity, moon facies, buffalo hump)
- hyperglycemia
- thin skin, easy bruising, and visible purple striae (because cortisol weakens collagen)
- osteoporosis
- muscle weakness (catabolism is increased to fuel gluconeogenesis)
- immune suppression (reactivation of TB, candidiasis)
- patients with increased ACTH will also develop hyperpigmentation and hirsutism
- note that hyperaldosteronism does NOT occur in cases with increased ACTH because aldosterone requires angiotensin II in addition to tonic levels of ACTH
7
Q
How do we screen and diagnose Cushings?
A
- look for increased free cortisol in 24-hour urine
- use a low-dose dexamethasone suppression test: if ACTH is lower than expected, consider an adrenal tumor; if ACTH is not suppressed at all, consider the other causes and use a high-dose DXM test
- high-dose DXM will suppress ACTH-secreting pituitary adenoma (Cushing disease), but will not be able to suppress ectopic ACTH secretion (SCLC)
8
Q
What is hyperaldosteronism and how do patients present? What are the two types? How do we treat each?
A
- hyperaldosteronism is excess aldosterone secretion resulting in HTN, hypokalemia, and metabolic alkalosis (chronic hyperaldosteronism also causes cardiac fibrosis)
- patients can present with muscle weakness, tingling, polyuria, and tetany
- primary: via adrenal hyperplasia (idiopathic, MCC) or functional adenoma (AKA Conn syndrome); renin is decreased because of the HTN
- secondary: renal perception of low intravascular volume, resulting in overactive RAAS (via renal artery stenosis, CHF, cirrhosis, nephrotic syndrome); renin is increased because of the perception of hypotension
- treat with surgery (for primary) or spironolactone (aldosterone antagonist; for both)
9
Q
Why do some patients with hyperaldosteronism present with tetany and tingling?
A
- hyperaldosteronism results in metabolic alkalosis
- the alkalosis makes albumin even more negative, therefore it sequesters even more Ca2+ than usual
- this drop in free, ionized, active Ca2+ (hypocalcemia) lowers the action potential threshold, resulting in tetany and tingling
10
Q
Why do patients with primary hyperaldosteronism not develop hypernatremia?
A
- you would think hypernatremia would develop in hyperaldosteronism since aldosterone increases Na+ reabsorption
- initially, Na+ levels do increase, but then return to normal after a few days due to “aldosterone escape”
- the mechanism is poorly understood, but this is why edema and increased osmolarity don’t develop
11
Q
How do congestive heart failure, liver cirrhosis, and nephrotic syndrome result in secondary hyperaldosteronism?
A
- all result in edema due to changes in the Starling forces
- more interstitial fluid means less plasma volume, so the kidneys perceive this as hypotension and stimulate RAAS
12
Q
What is a neuroblastoma? How do patients classically present? What can we look at to help the diagnosis?
A
- neuroblastoma is the most common adrenal tumor in kids (occurs in the adrenal medulla); it is malignant
- it is the 3rd most common overall cancer in kids
- patients are usually less than 4 years old (mean age is 18 months), and present with abdominal dissension with a firm, irregular mass
- patients may present with opsoclonus and myoclonus (dancing eyes and dancing feet), which is a poorly understood paraneoplastic syndrome of neuroblastomas
- diagnose with VMA (vanillylmandelic acid, from catecholamines) and HMA (homovanillic acid, from dopamine) urine tests
13
Q
What histological finding is present in neuroblastoma? What is the survival rate?
A
- look for Homer-Wright rosettes (these are neuroblasts surrounding a central space)
- survival rate is not very good at 40% (neuroblastomas commonly metastasize to skin and bones)
- however, the survival rate is 90% in children less than 1 year old
14
Q
What is a pheochromocytoma? How do patients classically present? What can we look at to help the diagnosis?
A
- pheochromocytoma is the most common adrenal medulla tumor in adults; it is benign
- arises from chromatin cells in the medulla
- secretion of epinephrine, norepinephrine, and dopamine
- patients present with episodic HTN, pounding headaches, perspiration, palpitations, pallor and a sense of apprehension (45% of cases are episodic, 55% are sustained)
- look at plasma free metanephrines and urinary VMA (vanillulmandelic acid); these should be increased in pheo; additionally, failure of a clonidine (central alpha-2 receptor agonist) suppression test is indicative of a pheo
15
Q
What are the gross and hisotological findings in a pheochromocytoma?
A
- tumor is yellow-tan and often hemorrhagic, necrotic, and cystic
- exposing the tissue to potassium dichromate turns the chromatin cells dark brown/black
- histo: “salt and pepper” cytoplasm due to increased granules of catecholamines
