Flashcards in Pathology Deck (141):
What is the mechanism of Cushing syndrome?
Increased cortisol due to a variety of causes
What causes bilateral adrenal atrophy and is the most common cause of Cushing syndrome?
Exogenous steroid use
Atrophy of uninvolved adrenal gland in Cushing syndrome points to what cause?
Primary adrenal adenoma, hyperplasia or carcinoma
What is Cushing disease?
An ACTH-secreting pituitary adenoma
What are some paraneoplastic causes of increased ACTH?
Small cell lung cancer or bronchial carcinoids
What is the affect of increased endogenous ACTH on adrenal glands?
What is responsible for the majority of endogenous cases of Cushing syndrome?
What needs to be done if adrenal tumor is suspected?
Adrenal CT to confirm
What is next step if ACTH levels are elevated on low-dose dexamethasone test?
High-dose dexamethasone test and CRH stimulation test
What test results are consistent with Cushing disease?
Adequate suppression with high-dose dexamethasone and increased ACTH and cortisol with CRH stimulation
What test results are consistent with ectopic ACTH secretion?
No suppression with high-dose dexamethasone and no increase in ACTH and cortisol with CRH stimulation
What is next step with adequate suppression with high-dose dexamethasone and increased ACTH and cortisol with CRH stimulation?
MRI of pituitary
What is next step with no suppression with high-dose dexamethasone and no increase in ACTH and cortisol with CRH stimulation?
CT of the chest/abdomen/pelvis
Inability of the adrenal glands to generate enough glucocorticoids
Acute primary adrenal insufficiency due to hemorrhage associated with septicemia form N. meningitidis, DIC or endotoxic shock
Hypotension, hyperkalemia, metabolic acidosis with skin and mucosal hyperpigmentation points to what disease?
Primary adrenal insufficiency
Shock or hemorrhage causing hypovolemia leading to ischemia of the adrenal glands causes what type of adrenal insufficiency
Acute primary adrenal insufficiency
What is the most common cause of chronic primary adrenal insufficiency in the Western world?
What is the most common cause of chronic primary adrenal insufficiency in the developing world?
Adrenal atrophy or destruction by disease either from autoimmune or TB is called what?
Chronic primary adrenal insufficiency or Addison disease
What cortisol and ADH levels are seen in primary adrenal insufficiency?
What cortisol and ADH levels are seen in secondary adrenal insufficiency?
Decreased cortisol and ACTH
What is a common cause of tertiary adrenal insufficiency?
Exogenous steroid use
How is aldosterone synthesis affected in tertiary adrenal insufficiency?
What prevents edema in hyperaldosteronism?
Aldosterone escape mechanism
What are lab findings in primary hyperaldosteronism?
Increased aldosterone, sodium reabsorption and potassium excretion
What is the cause of primary hyperaldosteronism?
What is the cause of 2ndary hyperaldosteronism?
Renovascular HTN, juxtaglomerular cell tumors and edema
What is the most common tumor of the adrenal medulla in children?
Neuroblastomas originate from what cell line?
Neural crest cells
What type of tumors can occur anywhere along the sympathetic chain?
Abdominal distention and a firm, irregular mass that can cross the midline points to what disease?
Abdominal distention with a smooth mass that is unilateral, points to what disease?
Child with history of "dancing eyes-dancing feet" and an abdominal mass that crosses the midline with normal BP points to what disease?
What are common findings in urine in someone with Neuroblastoma?
Increased catecholamines (homovanillic and vanillylmandelic acid)
Histology with Homer-Wright rosettes and Bombesin and NSE positive indicates to what disease?
What oncogene is associated with neuroblastomas?
Most common tumor of the adrenal medulla in adults?
Pheochromocytoma is derived from what cells?
Chromaffin cells of the adrenal medulla
What germline mutations are associated with pheochromocytoma?
NF-1, VHL, RET (MEN2A and MEN2B)
What is the rule for pheochromocytomas?
Rule of 10s:
10% extra-adrenal (bladder wall, organ of Zuckerandl)
What are common symptoms of pheochromocytomas?
Relapsing and remitting symptoms of 5 Ps:
Pressure (increased BP) - increased catecholamines
What are common findings in pheochromocytomas?
Increased catecholamines: Epi, NE, dopamine in urine and plasma
What is a worry in someone with history of chronic exogenous steroid use who stops using immediately?
Tertiary adrenal insufficiency
What is the treatment for pheochromocytoma?
Irreversible a-antagonists (phenoxybenzamine) and B-blockers prior to tumor resection
Why is a-blockade needed before giving B-blockers?
To avoid a hypertensive crisis
What are the cholesterol levels in hypothyroidism?
Hypercholesterolemia due to decreased LDL receptor expression
What are the CK levels in hypothyroidism?
Increased CK levels
What are the TSH levels in hypothyroidism?
Increased TSH levels if primary
What are the T3 and T4 levels in hypothyroidism?
Decreased T3 and T4
What are the CK levels in hyperthyroidism?
Normal CK levels
What is the TSH level in hyperthyroidism?
Decreased TSH levels
What are the free T3 and T4 levels in hyperthyroidism?
Increased T3 and T4 levels
What are the cholesterol levels in hyperthyroidism?
Hypocholesterolemia due to increased LDL receptor expression
Causes of nodular thyroid goiters
Toxic multi-nodular goiter
Causes of smooth/diffuse thyroid goiters
TSH-secreting pituitary adenoma
What is the most common cause of hypothyroidism in iodine-sufficient regions?
What are antibodies are associated Hashimoto thyroiditis?
Anti-thyroid (anti-microsomal) peroxidase and anti-thyroglobulin antibodies
What malignancy is associated with Hashimoto thyroiditis?
Non-Hodgkin lymphoma (B-cell origin)
Hashimoto thyroiditis may present as hyperthyroid early in disease course - why?
Thyrotoxicosis during parafollicular rupture
Presents as a non-tender, moderately enlarged thyroid with decreased T3 and T4 and Hurthle cells with lymphoid aggregates and germinal centers on histology.
What malignancy can present as an enlarging gland in Hashimoto thyroiditis?
Marginal zone lymphoma
What is the most common cause of congenital hypothyroidism in the U.S?
What is the cause of congenital hypothyroidism?
Severe fetal hypothyroidism due to maternal hypothyroidism, thyroid agenesis, thyroid dysgenesis, iodine deficiency, dyshormonogenetic goiter
What are the findings in congenital hypothyroidism?
Pot-bellied, Pale, Puffy, Protruding umbilicus, Protuberant tongue, and Poor brain development
Self-limited disease often following a flu-like illness presenting with increased ESR, jaw pain, and very tender thyroid
de Quervain (subacute granulomatous thyroiditis)
What is the histology of subacute granulomatous thyroiditis?
How does subacute granulomatous thyroiditis present early on in disease course?
Hyperthyroid early on, followed by hypothyroid
Thyroid replaced by fibrous tissue with inflammatory infiltrate and may extend to surrounding structures mimicking anaplastic carcinoma
Young female presents with fixed, hard, rock-like painless goiter points to what disease?
Thyroid gland down-regulation in response to increased iodine seen in hypothyroid diseases - what effect is this?
What drugs can cause hypothyroidism and presents as goitrogens?
Amiodarone and lithium
What is the most common cause of hyperthyroidism?
What type of hypersensitivity reaction is Graves disease?
Type II; IgG thyroid stimulating immunoglobulin
What HLA subtypes are associated with Graves disease?
HLA-DR3 and HLA-B8
What histological findings are seen in Graves disease?
Tall crowded follicular cells and scalloped colloid
What lymphocytes are associated with Graves disease?
Increased osmotic swelling, muscle inflammation and adipocyte count in retro-orbital space causes what in Graves disease?
What symptoms are seen in Graves disease?
Exophthalmos, pretibial myxedema
What causes pretibial myxedema in Graves disease?
What mediates exophthalmos?
Infiltration of activated T-cells in the retro-orbital space leading to increased cytokines like TNF-a and IFN-y
Focal patches of hyperfunctioning follicular cells distended with colloid and working independently of each TSH
Toxic multinodular goiter
What is the cause of toxic multinodular goiters working independently of TSH?
TSH receptor mutations
What are T3 and T4 levels in toxic multinodular goiter?
Increased T3 and T4 levels
What is usual cause of toxic multinodular goiters?
Uncommon but serious complication that occurs when hyperthyroidism is incompletely treated or undertreated, and then significantly worsens in the setting of acute stress such as infection, trauma or surgery
Commonly presents with agitation, delirium, fever, diarrhea, coma and tachyarrhythmias from incomplete treatment of hyperthyroidism after acute illness
What lab findings are typically seen in thyroid storm?
What is the treatment for thyroid storm?
Propranolol, PTU, Prednisone, and Potassium iodine
A patient with an autonomous nodule who is iodine deficient is given iodine and develops thyrotoxicosis
Asymptomatic benign solitary growth of the thyroid that is non-functional rarely causing hyperthyroidism
What is the histology or thyroid adenoma?
Follicular with absence of capsular or vascular invasion
What is the treatment for thyroid cancer?
How is thyroid cancer diagnosed?
Fine needle aspiration
What nerve can be damaged in thyroidectomy?
Recurrent laryngeal nerve
Hypocalcemia after thyroidectomy is cause by damage to what structure?
Removal of parathyroid glands
What nerve can be damaged during ligation of inferior thyroid artery in thyroidectomy?
Recurrent laryngeal nerve
What nerve can be damaged during ligation of superior laryngeal artery in thyroidectomy?
Superior laryngeal nerve
What is the most common thyroid cancer?
What is the histology of papillary carcinoma?
Empty-appearing nuclei with central clearing (Orphan Annie eyes), psammoma bodies, and nuclear grooves
What mutations increase risk of papillary carcinoma?
RET and BRAF mutations
What is a major cause of papillary carcinoma in childhood?
What is the prognosis of papillary carcinoma?
Presents with uniform follicles on histology, invades thyroid capsule and vasculature with a good prognosis?
Follicular carcinoma of the thyroid
What mutation is associated with follicular carcinoma?
How does follicular carcinoma spread?
Thyroid cancer from parafollicular cells that produces calcitonin in sheets of cells in an amyloid stroma
What stain is used in Medullary carcinoma?
Congo red stain for amyloid stroma
What mutations are associated with medullary carcinoma?
MEN 2A and 2B RET mutations
What is done if RET mutations detected in someone with thyroid cancer?
Has medullary carcinoma so prophylactic thyroidectomy
Thyroid cancer that is common in older patients presenting with dysphagia and respiratory compromise with invasion of local structures and has a very poor prognosis?
What is lymphoma of the thyroid associated with?
Accidental surgical excision of parathyroid glands, autoimmune destruction, or DiGeorge syndrome can all cause what condition?
What are common findings in Hypoparathyroidism?
Tetany, hypocalcemia and hyperphosphatemia
Contraction of facial muscles with tapping of facial nerve on the check is called what?
Occlusion of brachial artery with BP cuff causing carpal spasm is called what?
Common procedures done to test for Hypoparathyroidism are what?
Chvostek and Trousseau sign
Unresponsiveness of kidney to PTH causing hypocalcemia despite increased PTH level is called what?
Pseudohypoparathyroidism type 1A or Albright hereditary osteodystrophy
What are common findings in Albright hereditary osteodystrophy?
Shortened 4th/5th digits and short stature
What is the inheritance pattern of Albright hereditary osteodystrophy?
What is the mechanism of end-organ resistance to PTH in Albright hereditary osteodystrophy?
Defective Gs protein a-subunit
How is the defect inherited in Albright hereditary osteodystrophy?
From mother due to imprinting
How is the defect inherited in pseudopseudohypoparathryroidism?
Inherited from father due to imprinting
What is the mechanism of pseudopseudohypoparathryroidism?
Defective Gs protein without end-organ resistance
What are the PTH levels in pseudopseudohypoparathryroidism?
What are the causes of primary hyperparathyroidism?
Carcinoma, adenoma, hyperplasia
What are lab findings seen in primary hyperparathyroidism?
Hypercalcemia, hypercalciuria, hypophosphatemia
Increased PTH, ALP, cAMP in urine
Disease that presents with weakness and constipation, abdominal/flank pain, and depression
What is the mnemonic for primary hyperparathyroidism?
Stones, thrones, bones, groans and psychiatric overtones
What is the cause of osteitis fibrosa cystica?
Cystic bone spaces filled with brown fibrous tissue with increased PTH levels?
Osteitis fibrosa cystica
What is contained in the cysts seen in osteitis fibrosa cystica?
Osteoclasts and deposited hemosiderin from hemorrhages
What is the most common cause of 2ndary hyperparathyroidism
Chronic renal disease
2ndary hyperplasia due to decreased calcium absorption and/or increased phosphate
What are common findings in 2ndary hyperparathyroidism?
Hypovitaminosis D, Hypocalcemia, Hypophosphatemia
Increased ALP, PTH
What are common findings in 2ndary hyperparathyroidism due to chronic renal failure?
Hypovitaminosis D, Hypocalcemia
Increased ALP, PTH
What is the cause of tertiary hyperparathyroidism?
Refractory hyperparathyroidism from chronic renal failure
What are common lab findings in tertiary hyperparathyroidism?
Markedly increased PTH and increased calcium
What disease is caused by a defective G-coupled sensing receptor in multiple tissues requiring higher than normal calcium levels to suppress PTH
Familial hypocalciuric hypercalcemia
What lab findings are seen in familial hypocalciuric hypercalcemia?
Hypercalcemia, low urine calcium, normal to increased PTH