Flashcards in Pathology of Pituitary and Adrenal Glands Deck (63):
What is a pituitary adenoma?
- benign tumor of ANTERIOR pituitary cells
- may be FUNCTIONAL (produces hormones) or NONfunctional (does not produce hormones)
**** How do NONfunctional pituitary adenomas present?
with mass effect:
- BITEMPORAL HEMIANOPSIA (due to proximity of optic chiasm to sella turcica).
How do FUNCTIONAL pituitary adenomas present?
- features based on hormone produced.
**** What is a Prolactinoma?
most common type of functional pituitary adenoma causing:
- galactorrhea and amenorrhea due to prolactin's inhibition of GnRH, decreasing FSH and LH (females)
- decreased libido and headache (males)
- may undergo DYSTROPHIC CALCIFICATION (calcium deposition with normal serum calcium) with psammoma bodies
- AMYLOID deposition (apple green birefringence)
- PERINUCLEAR CRESCENTS of prolactin immunopositivity
How do you treat a prolactinoma?
- dopamine agonists; bromocriptine (inhibits prolactin secretion) or surgery
*** What is a Growth Hormone adenoma?
functional pituitary adenoma causing:
- GIGANTISM in children
- ACROMEGALY in adults
- T2DM (GH causes decreased glucose uptake in cells)
*** How do you diagnose Growth Hormone adenoma?
- elevated GH and IGF-1
- oral glucose will NOT suppress GH release.
How do you treat GH adenoma?
- OCTREOTIDE (somatostatin analog that blocks the response of the anterior pituitary to GHRH).
- GH receptor antagonists
What are some other FUNCTIONAL pituitary adenomas?
- ACTH cell adenomas= secrete ACTH leading to hypersecretion of cortisol (Cushing disease). Hyperpigmentation due to ACTH precursor products on melanocytes.
- Thyrotroph= TSH
*LH and FSH-producing adenomas are rare.
What is HYPOpituitarism?
- insufficient production of hormones by anterior pituitary.
**** What can cause HYPOpituitarism?
- pituitary adenoma (adults)
- CRANIOPHARYNGIOMAS (children)= slow growing cystic tumors (cholesterol crystals, keratin, peripheral palisading) arising from suprasellar regions, causing headaches and visual problems.
- SHEEHAN SYNDROME= infarcted pituitary due to increase in size during pregnancy, but lack of blood flow increase; women present with poor lactation and loss of pubic hair.
- EMPTY SELLA SYNDROME= defect in the diaphragm sella allowing the arachnoid mater CSF to herniate into the sella, expanding the sella and compresses the pituitary, leading to PANHYPOPITUITARISM (hypothyroidism, adrenal insufficiency, amenorrhea).
*** What are the POSTERIOR pituitary pathologies?
- central diabetes insipidus
*** What is Central Diabetes Insipidus?
- increased urination (polyuria) and increased thirst (polydipsia) due to ADH deficiency (due to hypothalamic or posterior pituitary pathology).
- hypernatremia and high serum osmolality.
- low urine osmolality and specific gravity.
How do you diagnose Central Diabetes Insipidus?
- water deprivation fails to increase urine osmolality.
How do you treat Central Diabetes Insipidus?
- Desmopressin (ADH analog).
*** What is nephrogenic diabetes insipidus?
- impaired renal response to ADH due to inherited mutations or drugs (lithium).
*similar to central DI, but there is no response to desmopressin.
*** What is SIADH (syndrome of inappropriate ADH secretion)?
- excessive ADH secretion leading to hyponatremia, low serum osmolality, mental status change, and seizures (from cerebral edema).
*** What can cause SIADH?
- ectopic production (small cell carcinoma of the lung).
- CNS trauma
- pulmonary infection or pathology (COPD)
- drugs (cyclophosphamide)
How do you treat SIADH?
- free water restriction
- demeclocycline (blocks effect of ADH).
What is pituitary apoplexy?
- bleeding into an adenoma
What genetic components lead to pituitary adenomas?
- G alpha proteins generating cAMP, which is a mitogenic stimulus due to GNAS mutation interfering with intrinsic GTPase activity, which hydrolyzes GTP (required for cAMP generation) to GDP.
What genetic products are associated with familial pituitary adenomas?
- CDKN1B= MEN like syndromes
- PRKAR1A= Carney's syndrome
- AIP= GH adenomas
What is the morphology of adenomas?
- cellular monomorphism and absence of a reticulin network.
What is hypopituitarism?
- decreased secretion of pituitary hormones.
What percentage of parenchyma must be lost for hypofunction of the anterior pituitary to occur?
What is a Rathke cleft cyst??
- cysts lined by ciliated cuboidal epithelium, which can expand and compress the normal gland.
Are most metastatic pituitary tumors symptomatic?
NO, they are mostly asymptomatic.
What are the 3 layers of the ADRENAL CORTEX?
1. Glomerulosa= aldosterone (mineralocorticoids)
2. Fasiculata= cortisol (glucocorticoids)
3. Reticularis= sex steroids
*remember GFR and all hormones are synthesized from cholesterol here ("gets sweeter as you get deeper").
**** What is CUSHING Syndrome and what are the clinical features? (PICMONIC)
Excess cortisol causing:
- muscle weakness with thin extremities (due to breaking down muscle for gluconeogenesis).
- moon facies, buffalo hump, and truncal obesity (due to excess glucose in the blood causing excess production of insulin leading to excess storage of fat).
- abdominal striae (cortisol impairs the synthesis of collagen, leading to easily ruptured blood vessels).
- HTN (cortisol upregulates alpha 1 receptors on arterioles increasing the effect of norepinephrine)
- Immune suppression
*** What are the 3 mechanisms by which cortisol results in immune suppression?
1. inhibits phospholipase A2, preventing synthesis of arachidonic metabolites.
2. inhibits IL-2 (important T cell growth factor)
3. inhibits release of histamine from mast cells.
** How do you diagnose Cushing Syndrome?
- increased 24-hour URINE cortisol levels, late night salivary cortisol level (increased), and low-dose dexamethasone suppression test.
**** What are the 4 major causes of Cushing Syndrome?
1. EXOGENOUS CORTICOSTEROIDS (aka we caused it by prescribing the pt these; MOST COMMON cause)= both the right and left adrenal glands will become atrophic because excess cortisol will shut down the production of ACTH in the anterior pituitary, resulting in the shrinking of both adrenal glands.
2. PRIMARY ADRENAL ADENOMA, HYPERPLASIA, or CARCINOMA= one adrenal gland larger than the other).
3. ACTH-secreting PITUITARY ADENOMA= both adrenal glands enlarged.
4. PARANEOPLASTIC ACTH secretion (ectopic corticotropin syndrome)= both adrenal glands enlarged.
**** How do you distinguish a primary adrenal adenoma from an ACTH-secreting pituitary adenoma, if they both cause enlargement of the adrenal glands?
- high-dose DEXAMETHOSONE test= suppresses ACTH production by pituitary adenoma (detected by decreased cortisol levels), but fails to suppress ectopic ACTH production by for example a small cell lung carcinoma.
*** What is the clinical presentation of hyperaldosteronism?
- HTN, HYPERNATREMIA, HYPOKALEMIA, and METABOLIC ALKALOSIS caused by increased Na+ reabsorption for the DCT and collecting duct.
*remember principle cells (absorb Na+ in exchange for K+) and alpha-intercalated cells (dump H+ ions in response to aldosterone).
*** What is PRIMARY hyperaldosteronism?
- excess aldosterone caused by a primary problem WITHIN the ADRENAL gland (most commonly due to adrenal adenoma; CONN SYNDROME).
*can less likely occur due to hyperplasia and carcinoma.
How do you distinguish PRIMARY hyperaldosteronism?
- HIGH aldosterone and LOW renin (caused by the kidney recognizing high volume, and decreasing renin in response).
- SPIRONOLACTONE BODIES= laminated cytoplasmic inclusions when treated with spironolactone
*** What is SECONDARY hyperaldosteronism?
- excess aldosterone secondary to activation of renin-angiotensin system (e.g. renovascular HTN).
- usually due to arteriolar nephrosclerosis and renal artery stenosis, making the kidneys think there is hypovolemia.
How do you distinguish SECONDARY hyperaldosteronism from primary?
- HIGH aldosterone and HIGH renin.
*contributes to endothelial dysfunction by decreasing levels of glucose-6-phosphate dehydrogenase levels, which reduces endothelial nitric oxide synthesis and causes oxidative stress.
What is CONGENITAL adrenal hyperplasia?
- enzymatic defects (AR) in cortisol production leading to high ACTH (due to decreased negative feedback) and thus bilateral adrenal hyperplasia.
- will see EXCESS SEX STEROIDS.
**** What is the most common cause of CONGENITAL adrenal hyperplasia?
- 21-HYDROXYLASE deficiency= required for production of mineralocorticoids (ALDOSTERONE) and CORTISOL from cholesterol, but NOT SEX STEROIDS, so you will get excess of sex steroids (progesterone, DHEA, testosterone) as the pathway from cholesterol to pregnenolone to sex steroids. Deficiency of cortisol thus leads to increased ACTH, which results in bilateral adrenal hyperplasia.
*** What are the clinical features of 21-hydroxylase deficiency (type of congenital adrenal hyperplasia?
- salt wsting with hyponatremia, hyperkalemia, and hypovolemia.
- life-threatening hypotension.
- clitoral enlargement (females) or precocious puberty (males)
What is 11-hydroxylase deficiency?
- biochemically similar to 21-hydroxylase deficiency, but weak mineralocorticoids (DOC) are increased.
What are the clinical manifestations of 11-hydroxylase deficiency?
- hypertension (sodium retention) with mild hypokalemia.
- renin and aldosterone are low.
What is 17-hydroxylase deficiency?
- decreased cortisol and androgens.
- weak mineraolocroticoids (DOC) are increased leading to hypertension and mild hypokalemia; renin and aldosterone are low.
- decreased androgens (adrenal and gonads) lead to primary amenorrhea and lack of pubic hair in females or pseudohermaphroditism.
How do we screen for CONGENITAL adrenal hyperplasia?
serum 17-hydroxyprogesterone levels:
- INCREASED in 21- and 11-hydroxylase deficnecy.
- DECREASED in 17-hydroxylase deficiency.
How do we treat CONGENITAL adrenal hyperplasia?
- glucocorticoids; mineralocorticoids (21-hyroxylase deficiency) or sex steroids (17-hydroxylase deficiency) may also be needed.
What is adrenal insufficiency?
- lack of adrenal hormones.
*** What is most common ACUTE adrenal insufficiency (abrupt withdrawal of glucocorticoids)?
- Waterhouse-Friderichsen syndrome.
**** What is Waterhouse-Friderichsen syndrome?
- ACUTE adrenal insufficiency characterized by hemorrhagic necrosis of the adrenal glands, classically due to DIC in young children with NEISSERIA MENINGITIDIS infection.
- lack f cortisol exacerbates hypotension, often leading to death.
*** What is CHRONIC adrenal insufficiency (ADDISON'S DISEASE)?
- slow, progressive destruction of the adrenal glands.
What are the 3 major causes of CHRONIC adrenal insufficiency?
1. autoimmune destruction (most common in the WEST).
3. metastatic carcinoma
**** What cancer loves to metastasize to the adrenal glands?
- LUNG cancer
What are the clinical features of Addison's disease (chronic adrenal insufficiency)?
- hyponatremia, hypovaolemia, hyperkalemia
- metabolic acidosis
- hyperpigmentation (due to lack of negative feedback from cortisol, causing increased ACTH; derived from POMC, which also produces melanocyte stimulating hormone).
- vomiting and diarrhea
What cells make up the adrenal medulla, and from where are they derived?
- chromaffin cells, derived from neural crest.
*main physiologic source of catecholamines (epinephrine and norepi)
*** What is the key pathology of the adrenal medulla?
- PHEOCHROMOCYTOMA= tumor of chromaffin cells
*also Zellbellen= nests of tumor cells.
*** What are the clinical features of a PHEOCHROMOCYTOMA?
- episodic hypertension, headache, palpitations, tachycardia, and sweating.
*all due to increased serum catecholamines.
*** How do you diagnose a PHEOCHROMOCYTOMA?
- incrased serum metanephrines (metabolite of epinephrine) and increased 24-hour urine metanephrines and vanillylmandelic acid (VMA).
*** How do you treat a pheochromocytoma?
- surgical excision.
*must give PHENOXYBENZAMINE first (irreversible alpha-blocker) to prevent a hypertensive crisis, bc catecholamines may leak into the bloodstream upon manipulation of the tumor.
*** What are the additional features of pheochromocytoma (rule of 10s)?
- 10% bilateral
- 10% familial
- 10% malignant
- 10% located outside of adrenal medulla (BLADDER wall or organ of Zuckerkandl at the inferior mesenteric artery root).
*** What are the 3 associated disorders of pheochromocytoma?
- MEN2A and 2B
- von Hippel-Lindau disease= also increased risk of hemangioblastoma of the cerebellum and increased risk of renal carcinoma
- neurofibromatosis type 1
What type of hyaline change will you see in the pituitary gland with Cushing syndrome?
- Crooke's hyaline change= replacement of anterior pituitary cells with homongenous paler cells, produced form the accumulation of intermediate keratin filaments in the cytoplasm.
** What is a neuroblastoma?
- cancer that forms in nerve tissue (most frequently starts from one of the adrenal glands).
*HOMER-WRIGHT PSEUDOROSETTES= eosinophilic fibrils