What are the 4 types of thryoid cancer? WHich is most common
**Papillary** (most common and best prognosis), follicular, anaplastic,
medullary
What genes are involved in Papillary thyroid carcinoma?
PTC1, PTC2, and PTC3 oncogenes
Psammoma bodies and optically clear "orphan annie nuclei" are
findings of
Papillary carcinoma of the thyroid.
Follicular thyroid carcinoma: key features
Thickened capsule. More aggressive than papillary thyroid carcinoma.
What thyroid carcinoma has amyloid like presentation (apple green perfringence when viewed under polarized light)
medullary thyroid carcinoma
What is the characteristic thyroid pathology found in all MEN IIa and IIb patients?
medullary thyroid carcinoma
Almost all MEN1 patients have what finding?
parathyroid hyperplasia. 1/3 have pancreatic endocrine tumor, and 1/3 have a pit. adenoma
Pheochromacytoma is seen in 1/2 of case of
MEN2a and MEN2b
What MEN sydrome always has ganglioneuromas associtated with it
MEN 2b
What pathology is present in all cases of MEN 2b (Disease)
ganglioneuroma
What type of thyroid carcinoma can be multinodular
papillary carcinoma
What two drugs could be used to treat a toxic goiter prior to
thyroidectomy
Methimazole or propythiouracil
What is the location of the pathology in Primary, secondary, and
tertiary hypothyroidism?
Primary: intrinsic abnormality of the thyroid. Secondary: Pituitary dz,
Tertiary: Hypothalamic failure
Why effect does lithium and amiodarone have on the thyroid?
Cause hypothyroidism
Antibodies to _______ (Receptor) are fond in autoimmune hypothyroid.
Anti-TSH receptor antibodies
Hypothyroidism in pregnancy has what effects on the child?
childhood cognitive defects, reduced IQ scores, and decreased aptiude/intelligence.
WHat is the effect of congenital hypothyroidism?
retardation. Puffy face, big tongue... etc. due to mucopolysaccharide
deposition.
What is the most common type of hyperthyroidism? Mechanism?
Graves disease (Autoimmune).Thyroid stimulating antibodies (TSIs) that act as agonist on the TSH receptor.
What are the three chactacteristic findings of graves disease?
exopthalmos, pre-tibial myxedma, and acropachy (radial bone deposition)
Contrast hashimotos to graves dz?
hashimotos is an autoimmune condition producing ABs against TSH receptors destroying the thyroid leading to hypothyroid.Graves is an autoimmune condition that creates ABs against TSH rcptrs that *ACT AS AGONISTs* stimulates activity -> hyperthyroid
Clinical presentation of hyperthyroid
Aside from tremors, nervousness. *LID LAG*, PROXIMAL MUSCLE WEAKNESS, onchycholysis (plumbers nail), diarrhea, hypersensitivity to heat.
Pretibial myxedema is seen in what kind of thyroid disorder
HYPERTHYROID. *PRETIBIAL MYXEDEMA* IS EXCLUSIVE TO HYPERTHYROID... other
myxedema is seen in hypothyroid
What is given to treat pt who is presenting with a thyroid storm
Beta blockers to dampen adrenergic effects, iodine drops to block the uptake of iodine (HIGH CONCENTRATIONS OVERWHELM THE TRANSPORT SYSTEM), antithyroid med (propylthiouracil), streoids (block conversion of T4 to T3
Why do high does of iodine supress thyroid function?
overwhelems the transport system
Describe the layers of the adrenal gland, from exterior to interior:
What is the embryonic origin of the adrenal gland?
Two places of origin:
What part of adrenal gland is not present at birth, when does it form?
THe reticularis. It develops around 3 yo
From what part of the adrenal gland are glucocorticoids secreted?
Zona fasciculata.
From waht part of the adrenal gland are sex hormones secreted?
Zona reticularis and zona fasciculata
Where in the adrenal gland are chromaffin cells located? What do they secrete
In the adrenal medulla. They secrete EPE and NE
What is the function of 21-hydroxylase?
converts progesterone and prognenolone in to deoxycorticosterone and deoxycortisol, respectively, these are then convertred to alodsterone and
cortisol by 11B hyhdroxylase
What is the function of 11B hydroxylase
conversion of deoxycorticosterone and deoxycortisol into aldosterone and cortisol.
Pt is born with fused labia and enlarged clitoris. Lab results reveal elevated 17-OH progesterone, decreased cortisol, and increased testosterone.
Dx?
Congenital adrenal hyperplasia (21-hydroxylase deficiency). Failure to produce cortisol results in nonstop ACTH production due to lack of feedback inhibition from cortisol.
What enzyme is defective in congenital adrenal hyperplasia?
Usually 21-hydroxylase (95% of case), 11-hydroxylase deficiency in the remaining 5%.
What group is 21-hydroxylase deficiency most common in ?
alaskan inuit.
Why ion is deficient in the blood of a pt with 21-hydroxylase deficiency?
IN the severe (Salt wasting) from (~2/3 of caseS), the lack of aldosterone production leads to salt wasting.
What is the result of an 11-B hydroxylase deficiency?
CONG. ADRENAL HYPERPLASIA (the rarer form - 21-hydroxylase def. is more common) FEMALE VIRILIZATION / early male puberty (due to androgen xs) and Retention of Na and htn due to accum. of 11-deoxycorticosterone (aldosterone precursor that has similar fx)
describe type 2 polyglandular autoimmune syndromes
More common in female age 20-40 yo. POLYGENIC INHERITENCE on HLA DR3 and HLA DR4. Type 1 DM, Adrenal insufficiency, hypothyroid, graves disease, hypogondadism, hypophystis, MG,
Type 1 vs type 2 polyglandular autoimmune syndrome: which is more common
in females?
Type II
Increased band cells suggests:
acute severe infection. Band cells are immature leukocytes
In the presence of hyponatremia/hyperkalemia, what test can be performed to dx acute adrenal failure?
ACTH stimulation test
Upon suspicion of adrenal failure, what is the first step?
give cortisol, hydrocortison and IV saline. THis is a medical emergency. Treatment should be given on suspicion.
Cushings dz vs cushing syndrome?
Cushing's disease is due a problem with the pituitary producing excess ACTH, Cushing syndrome is a collection of symptoms DUE TO EXCESS CORTISOL but does not necessarily have to have to be due to ACTH excess.
What is the most common cause of cushing *syndrome* in the US? Cushing disease?
Treatment with corticosteroids is the most common cause of cushing syndrome. The most common cause of cushing disease is pituitary overproduction of ACTH
Adrenal cortical adenomas reveal what cell type?
Cells of the zona fasciculata (ZF). Adrenal cortical carcinoma is extremely rare.
Clinical presentation of cushings
truncal obesity, purple striae, hirsuitism, thinning of the skin, osteoperosis, emotional lability
What is the series of tests performed ot dx hypercortisolism?
Urine free cortisol + low dose DXM suppression test. If UFC is normal and cortisol is supressed, cushings is unlikely. Increased UFC an no Cortisol suppression: measure the ACTH to determine cause of hypercortisol
What is Conn syndrome?
Primary hyperaldosteronism.
Lab findings of Conn syndrome:
Aldosterone elevated, renin supressed, decreased K
What is the most common cause of primary hyperaldosteroneism (conn syndrome)
aldosterone secreting tumor
What is the most common cause of secondary hyperaldosteroneism?
renovascular htn, estrogen therapy, abuse of laxative, renal tubular acidosis.
How is primary hyperaldosteronism differentiated from secondary hyperaldosteronism
Primary: High aldosterone, low renin. Secondary: High aldsterone, *HIGH RENIN!*
What changes in ACTH findings are seen with hyperaldosteronism
None... aldosterone does not have much effect on ACTH
What is the tx for hyperaldosteronism?
spirolactone.
Key lab finding of pheochromocytoma?
Increased VMA in urine
Elevated VMA in urine in an adult... likely dx?
pheochromocytoma. Will also have high plama free metanephrine and normetanephrine
Pheochromocytoms is seen in MEN1 or MEN2?
MEN2
What color is a pheochromocytoma tumor?
yellow-red-brown (brown due to necrosis and hemorrhage. Also turns brown when potasium dichromate is poured onto tumor.
What kind of thyroid cancer is associated with multiendocrine neoplasia (MEN)
medullary thyroid carcinoma
What gene is associated with MEN1&2
RET gene
Elevated neuron specific enolase, along with elevated urine HVA and VMA with low VMA:HVA ratio is suggestive of:
neuroblastoma
What is the best drug to use to treat fetus with abnormally low level of 21B-hydroxylase? What is the fucntion of the drug?
Dexamethasone. This will protect the fetus from genetic abnormalities as it is at high risk for congenital adrenal hyperplasia due to 21Bhydroxylase
deficiency
How is cushings disease differentiated from ectopic ACTH secretion?
High dose dexamethasone.
What is sheehan syndrome?
seondary adrenal dysfunction due to failure of pituitary to produce ACTH
Neonate shows signs of virilization and a 46,xx karyotype due to an autosomal recessive disorder. What is the likely developmental anomaly?
congenital adrenal hyperplasia
Raccoon eyes, lethargy, and decreased appetite in a 4 year old is suggestive of what disease?
Neuroblastoma
What lab is used to measure progress of a pt with neuroblastoma?
Urine vanillymandellic acid (VMA)
What gene is commonly involved in neuroblastoma ?
N-MYC (neuro myc)
APECED gene mutation. Dz?
Type 1 polyglandular autoimmune syndrome
What is the only way to differentiate a pituitary adenoma from a pituitary hyperplasia?
Breakdown of reticular structure takes place with an adenoma.
Treastment of pituitary microadenoma?
dopamine agonist (bromocriptin or cabergolin) to shrink tumor, surgical resection or radiotherapy radiotherapy
What regular screening is essential for anyone with somatotroph adenoma?
somatotroph adenoma = GH secreting adenoma) Colonoscopy to check for colon cancer and polyps
What is the high dose dexamethasone test used for? Low dose:
Low Dose: initial test to determine if hypercortisol is due to primary or secondary cushings. High Dose: to determine the cause of the secondary
cushings, whether it is due to an ectopic ACTH Secreting tumor or a pituitary adenoma
High dose dexamethasone test is administered to a patient with hypercortisolism. ACTH levels dropped upon administration of the dexamethasone.
What is the dx?
Pituitary adenoma. If ACTH did not change it would be an ectopic ACTH secreting tumor.
If low dose DXM test is given and urine cortisol levels are still high, but ACTH is supressed, what is the likely dx?
adrenal tumor. if ACTH did not change a high dose DXM test would have to be given to determine whether it was pituitary tumor or ectopic ACTH.
What are the lab findings of a adrenal ACTH secreting tumor
low dose DXM test revealing supressed ACTH but no change in cortisol
What is the gross appearance of the adrenal glands in Conn syndrome?
conn syndrome = aldosterone secreting tumor. The cortex of the adrenal will be normal (cortisol secreting tumor will have an atrophic adrenal cortex due to loss of feedback inhib from the pituitary. because feedback loop to ant pit via cortisol is intact.
When calcification is observed in the sella tursica region in a child, the likely diagnosis is:
craniopharyngioma. Hypopituitarism is often observed causing decreased growth, amennorhea. pituitary is destroyed. May often destroy the posterior pituitary.
What is the site of infarct in sheehan syndrome?
artery feeding the post. pituitary.
Compare the myxedema seen in hyperthyroidism to hypothyroidism.
Hyperthyroidism presents with myxedema local only to the pretibial region, while hypothyroidsm has generalized myxedema
What non-thyroid tumor may contain functional thyroid tissue?
ovarian tumor may contain functional thyroid tissue, which will cause hyperthyroidism,
What is the cause of the hyperthyroidism sometimes observed with ovarian cancer?
Ovarian tumors contain functional thyroid tissue
Compare the diagnoses of a diffusely enlarged thyroid enlargement that is 1) firm, 2) hard, 3) tender.
1) a FIRM diffusely enlarged thyroid suggests graves disease or hashimotos, 2) a hard diffusely enlarged thyroid suggests reidel's thyroiditis,
and 3) tender suggests de quervain's thyroiditis
How is an enlarged thyroid differentiated from an enlarged LN during PE
ask pt to swallow. If it moves it is thyroiditis, if it does not is likely an enlarged LN
pt presents with lethargy, depression and weight gain with hoarseness of voice and diffusely enlarged thyroid. What test should be ordered to aid in
diagnosis?
FNAC (fine needle aspiration cytology)
Confirtmatory test for hashimotos?
FNAC (fine needle aspiration cytology)
What is the expected thryoid lab findings during pregnancy?
normal free T4, high total T4 due to increased thyroid binding globulins
What is the diagnostic test of thyroid levels?
FREE T3 / T4 (bound T4 is not biologicaly available for use by the body)
What is the biggest concern with a pt who is pregnant and suffering from hypothyroid?
creatinism in the baby.Even subclinical hypothyroidism in the mother can cause creatinism and hypothyroidism in the baby
When is thyroid scan indicated?
When a solitary nodular enlargement in found. If the scan reveals a cold nodule: perform FNAC to determine whether it is carcinoma, adenoma, or a colloid cyst. If it is hot, treat with radio iodine.
What action is taken if a thyroid scan reveals a cold nodule? hot nodule?
cold nodule: FNAC todetermine identity. Hot nodule: treat by radio-iodine destruction
What is the prognosis of a papillary carcinoma of the thyroid
very good prognosis
What role does metastasis play in the prognosis of a papillary thyroid carcinoma?
metastastis does not change prognosis.
What is elevated (lab finding) in pheochromocytoma?
VMA in uirne
pt complains of episodic attacks of hypoglycemia. What is the best test to determine the cause?
a test for adequit insuline secretion (c-peptide test)
What hormone increases insulin levels even before glucose is elevated?
Incretins (from the GI)
What is the function of the incretin system?
incretins (GLP-1) are GI hormones that increase the amount of insulin released from the beta cells after eating, even before glucose levels become elevated. Also increase islet cell proliferation and neogenesis, and decreased islet cell apoptosis
What type of thyroid carcinoma may sometimes produce symptoms early in disease due to paraneoplastic phenomenon?
medullary carcinoma (produces 5-HT, which causes flushing.)
in a bx, how is an follicular thyroid adenoma differentiated from a follicular thyroid carcinoma?
Adenoma will have a capsule and will not have the invasion and metastasis seen with carcinoma.
