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134 Cards in this Set

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List 4 diagnostic criteria for DM.
1. fasting serum glucose > 126mg/dl
2. HbA1c > 6.5%
3. Oral glucose tolerance test > 200 mg/dl
4. Random blood glucose > 200 mg/dl
List 3 diagnostic criteria for pre-diabetes
1. fasting serum glucose b/t 100 - 125 mg/dL
2. Oral glucose tolerance test: b/t 140-199 mg/dL
3. HbA1c: b/t 5.5 - 6.4%
What is the cause of gestational DM?
insulin resistance of pregnancy + Beta cell dysfunction
What 2 hormones support the actions of insulin? describe their actions.
Incretin: enhance insulin secretion and proliferation of beta cells; includes GLP-1 and GIP

Amylin: decrease appetite, slows gastric emptying, decrease glucagon secretion
What immune cells are implicated in the pathogenesis of DM type I? What gene is associated?
T cells:
1. Th1 cells via cytokines IFN-gamma and TNF
2. CD8 cells: direct destruction of beta cells

HLA-DR3
You see birefrigence on islets cells of pancreas, which is Congo red stained, under microscope. What substance is deposited here? Dx?
Amylin is deposited
DM type 2
How does visceral fat exacerbate DM 2? (3 ways)
1. Lipotoxicity: FFA and TG --> inhibit insulin receptors at target tissue
2. dysregulation of adipokine secretion: decrease of leptin and adiponectin (involved in insulin sensitization) and increase in resistin (increase insulin resistance)
3. proinflammatory cytokines from the adipose tissue
List 6 components of metabolic syndrome.
1. obesity
2. dyslipidemia
3. hypercoagulability
4. HTN
5. proinflammatory state
6. Insulin resistance --> dysglycemia
What is the most common cause of death in diabetic patients?

What cancer has an increased risk in diabetic patients?
cardiovascular complications: MI, CVA,

Pancreatic cancer
What are AGEs? Describe how AGEs cause symptoms in Diabetic patients?

What other cellular pathway leads to the same result?
AGEs (advanced glycolytic end-products): glycation to proteins, glycated Hb, amadoi-modified proteins

Cause diabetic microangiopathy and macroangiopathy (atherosclerosis)

PKC pathway leads to micro- and macro-angiopathy
What pathway is responsible for cell deaths of nerves, pericytes, and lens opacification in diabetic patients?
Polyol pathway: intracellular hyperglycemia with disturbances in aldose reductase.
What micro renal vessels is most affected in advanced stage diabetic patients?
afferent arterioles
What is the pathogenesis of hyperosmolar non-ketotic coma? In which group of patients are they seen in?
glycouria --> osmotic diuresis --> severe dehydration --> hyperosmolarity

seen in DM type 2
This is a picture of an eye.
What is the red arrow pointing at?
What is the underlying disease?
"snowflake-like" cataract in diabetic patients
This is a fundoscopic view of the eye.

What is the arrow pointing at?
What complications can this phenomenon lead to? (2)
Retinal neovascularization (formation of neovacular membrane) in advanced diabetic pts.

Can lead to neovascular glaucoma (when grows on the anterior surface of iris into angle) and retinal detachment
This is an Xray image of the knee.

What are the arrows pointing at?
What is the pathogenesis?
Charcot joint seen in diabetic patients.

Peripheral neuropathy --> lose sensation and position sense -- > trauma --> Chacot joint
What is the eventual result of intensive glycemic control in diabetic patients?
Lower HbA1c level, which will lower microvascular and macrovascular related diseases.
Which is more important in weight reduction: diet or exercise?
Diet (90% according Dr. Meriden)
List 3 risks of exercise in diabetic patients.
1. hypoglycemia
2. increased glucose and ketone if poorly controlled
3. CV complications: MI, arrhtymias, and sudden death
What is the first line of drug in treating DM type 2?
Metformin
What is the mechanism of action of Metformin?

What is the most common side effect in metformin?

What is the advantage of using metformin over sulfonylurea?
increase insulin sensitivity and decrease gluconeogenesis.

diarrhea

Unlike sulfonyurea, does not cause hypoglycemia.

Also reduce lipids but increase HDL, no weight gain, and no hyperinsulinemia.
What is the MOA of Pioglitazone?

Most common side effects?

Contraindication?
PPAR alpha and gamma activator --> increase insulin sensitivity in peripheral tissue
But no actions on pancreas and intestine

side effects: edema and weight gain

Contraindicated in pts with advanced heart failure
What are GLP-1 and GIP? What are their actions?
They both are incretins.

GLP-1: increase insulin secretion AND suppress glucagon secretion

GIP: only increase insulin secretion
What is the MOA of Exenatide?
GLP-1 mimetic

increase insulin and decrease glucagon
what is the definition of HTN in diabetic pts?

What drug is indicated?
>130/80

recommend ACE inhibitors and ARBs
Name 2 inhibitory inputs to the beta cells of Pancreas.
somatostatin and sympathetic activity
What 2 HLA subtypes associated with DM type 1?
HLA DR3 and DR4
What are 3 types of antibodies used to confirm the diagnosis of DM type 1?
Insulin autoantibody (IAA)
glutamic acid decarboxylase antibody (GADA)
tyrosine phosphatase-2 protein antibody (IA2A)
Which type of diabetes has stronger family hx?
type 2 DM
A 25 YO diabetic pt presents with vomiting, abdominal pain, and dyspnea. He is hypotensive, tachypneic, and has abdominal tenderness. His history reveals a recent pneumonia. What is dx? Is surgery indicated for abdominal pain?
Dx: diabetic ketoacidosis

No, surgery is not indicated.
What happens to the serum levels of glucose, fatty acids, and amino acids in insulin deficiency?

What can change in each macromolecule cause?
Glucose, fatty acid, and AA all increase.

Increased glucose --> polyuria and dehydration and eventually renal failure.

Increased fatty acid: ketone formation --> DKA

increased AA: muscle wasting and increased gluconeogenesis
The following are insulin analogues. Group them in terms of duration of action.

Determir, Glargine, Lispro, NPH, Aspart, Glulisine.
Short acting (4-5 hrs): lispro, asprt, glulisin

intermediate (12-16 hrs): NPH

long acting: Determir (14 hrs), Glargine (24 hrs)
What is the purpose of short-acting insulin? long acting insulin?
Short acting insulin is used to prevent hyperglycemia after meals

long acting insulin is used to maintain basal levels of insulin
What is the most common complication of insulin therapy?
hypoglycemia
What is Somogyi phenomonon?
Occurs as a complication of insulin therapy

rebound hyperglycemia after hypoglycemia b/c of actions of couterregulartory hormones
What is Pramlintide used for? what is its mechanism of action?
Used for diabetes mellitus

MOA: injectable amylin analogue
slows gastric emptying, suppresses glucagon and increases satiety
What is the main thing you want to do in diabetic ketoacidotic pts? why?
push fluid b/c they are volume-depleted.

Low volume is concentrating the glucose and keeps them hyperglycemic even with application of insulin
In the first 24 hours, how is the glucose level maintained in the newborn after the umbilical is clamped off?
Insulin level drops and insulin opposing hormones are increased (epinephrine, glucagon and GH) to increase to serum level of glucose.
Describe the body's adaptation to fasting in the first 24 hours hormonally. What processes are driven by these hormones?
First 8 hrs: increase in glucagon and epinephrine --> glycogenolysis

hrs 8-24: increase in Epi, glucagon, GH, and cortisol (in order) to drive gluconeogenesis
A newborn was born prematurely and the immediate blood work shows glucose level of 45 mg/dl. What happened?
Most likely transitional hypoglycemia of the newborn.

Premature babies glycogen/fat reserve and enzymes involved in gluconeogenesis and fatty acid to increase the glucose level.

early feeding stimulates these enzymes.
What 2 drugs are indicated for infants of diabetic mothers to lower high insulin level.
Ca channel blockers and K channel opener (diaxozide)

they both prevent insulin release
What is the most common and most severe form of hypoglycemia in early infancy?

How do you dx it?
What gene is involved?
persistant neonatal hyperinsulinemia

Dx by increased 18f DOPA uptake in the pancreatic head

ABCC8 gene is involved (indicated in K channel)
What enzyme is deficient in glycogen storage disease type I? type III? types VI/IX?

which one is more severe clinically? mildest?
type 1: glucose-6-phosphatase; most severe

type 3: debranching enzyme, amylo-1,6 glucosidase

types VI/IX: hepatic phosphorylase; mildest
A 24 months old boy presents with hypoglycemia and low levels of ketone level. The baby is also jaundiced and hypotonic. What do you suspect?
fatty acid oxidation disorder
What would you expect in terms of blood glucose level in pts with hypopituitarism?
Low b/c counterregulartory hormones (GH, cortisol) to insulin are low.
A child with high ketones and hypoglycemia. Has normal history and physical. dx?
idiopathic ketotic hypoglycemia
A 2 YO boy presents with hypoglycemia. He did not respond to glucose infusion and diaxozide? dx?
insulinoma
A 25 YO female presents with galactorhea, amenorrhea, and loss of libido. you suspect a pituitary tumor. What is the dx?

What is clinically significant of the serum concentration of secreted hormone?

What accounts for libido and amenorrhea?
Prolactinoma

secretes prolactin and its concentration is correlated with the tumor size.

prolactin opposes GnRH
What 2 hormones are the most frequent combination presented in pituitary adenoma?
growth hormone and prolactin (mammosomatotrophs)
A 50 YO female was diagnosed with Cushing's syndrome and underwent bilateral adrenalectomy. She now has patches of hyperpigmented skin and weakness.

What is the dx?
Nelson's syndrome: rapidly growing ACTH pit tumor due to loss of negative feedback from cortisol
What is the most common cause of hypopituitarism?
Null cell tumor (non-secretory)
A 25 YO had a baby 2 weeks ago and now presents with a sudden cessation of lactation. What is the dx?
Sheehan syndrome: post-partum anterior pituitary necrosis
What is pituitary apoplexy?
ischemic necrosis of pituitary adenoma due to sudden enlargement
What is the syndrome called when the subarachnoid space extends into the sella?

Sxs?
empty sella syndrome.

hypopituitarism
What is the most common cause of hypopituitarism in chilren?

Describe the pathogenesis of this disease.
Craniopharyngioma

developed from vestigial remnants of Rathke cleft cyst
This is a tumor seen in children with hypopituitarism.

Dx? be specific
Craniopharyngioma adamantinomatous type (has calcification in a cystic mass)
Name a transcription factor involved in development of all anterior pituitary cells except corticotropes.

how about a factor involved in early pituitary development
LHX3

HESX1
Name 3 hormones that stimulate prolactin secretion.

1 hormone that inhibit prolactin secretion?

What 2 anterior pituitary hormone secretion is inhibited by prolactin?

What 2 anterior pituitary hormone secretion is inhibited by somatostatin?
stimulate prolactin secretion: TRH, VIP, oxytocin

inhibit prolactin secretion: dopamine

inhibited by prolactin:( GnRH), LH, and FSH

inhibited by somatostatin: GH and TSH
What anterior pituitary hormones bind to G protein receptors? how about class 1 cytokine receptors?
G protein receptors: FSH, LH, ACTH, TSH (FLAT)

Cytokine receptors: prolactin and GH
What time of the day does ACTH/CRH level peak?

how about TSH?
ACTH/CRH: b/t 4-8 AM

TSH: late evening before sleep
How do you test for pituitary function.
Insulin function test to induce hypoglycemia and see if there is a rise of TSH, GH, and ACTH/cortisol
In early puberty, what time of the day is LH/GnRH pulse frequency/amplitude the highest?

How about testosterone?
LH/GnRH: in the late afternoon/evening hours

Testosterone: in the morning
What is the most common cause of amenorrhea in women?

what other sxs are seen in this condition?
Turner's (XO)

primary ovarian failure
SHOX haploinsufficiency
coarctation of aorta
horseshoe kidney
What stages of sleep are associated with an increase in GH? how about a decrease in GH?
stages 3/4: increased GH

REM sleep: decreased GH
What endogenous hormone from the stomach increases GH secretion, appetite and gastric emptying?
ghrelin
What is the action of IGF-1?
What stimulates the secretion of IGF-1?
increased chondrogenesis (skeletal growth), increased protein synthesis and increased cell proliferation
Anti-insulin actions


GH stimulates IGF-1 secretion
Phenothiazeins, haloperidol, and metoclopriamide.

What are they?
What endogenous hormone secretion is increased?

Name 3 other agents that can increased the same hormone.
they are dopamine antagonist
Increase the secretion of prolactin

Cimetidine, opioid, monoamine Oxidase inhibitors (anti-depressants)
What syndrome is associated with anosmia and hypogonadism?

What genes is associated?
Kallmann syndrome

KAL gene on X chrom or FGFR1 on chrom 8p
A mild increase in prolactin is seen. What do you suspect?
medications that can increase prolactin such as dopamine antagonists.
What drug is used to treat hyperprolactinemia? which one is the first line of treatment?
dopamine antagnosts

cabergoline: first line of tx
bromocriptin: causes headaches
Name this syndrome:

action of G protein at several sites
presents with GH-secreting tumor in 40% of pts
has big and irregularly bordered cafe-au-lait spots.
McCune-Albright syndrome
A neonate is born with ambiguous genitalia. Physical exam reveals a palpable mass in the labioscrotal folds. The karyotype shows 46, XX.

At puberty, this person goes through breast development and virilization.

What do you suspect?
ovotesticular DSD (true hermaphrodite)
A male newborn presents with diarrhea and vomiting. Blood work shows metabolic acidosis, hyponatremia.

What do you suspect?

What tests do you do to confirm? (2)
Congenital adrenal hyperplasia due to 21 hydroxylase deficiency.

Do karyotyping and serum 17alpha- progesterone level.
A 4 YO girl presents with accelerated growth for her age and clitoral enlargement. Blood shows increased 17alpha progesterone.

What do you suspect?
Predict her bone age.
MIld case of 21 hydroxylase deficiency.

Advanced bone age
A newborn presents with severe dehydration, lethargy and shock. blood work shows low Na, High K, low glucose and high DHEA. The genitalia looks ambiguous.

What do you suspect?
3 beta hydroxysteroid dehydrogenase deficiency
A 16 YO girl comes to your office because she has not started her menstrual cycle yet. Physical exam shows no pubic/axillary hair. Ultrasound reveals no uterus but a mass in the inguinal region.

What do you suspect?
androgen insensitivity syndrome
What is the first step of treatment in 21 hydroxylase deficient patients?
replace adrenal hormones first then replace sex hormones
Write a formula to calculate correct serum Ca.
correct serum calcium = 0.8 (expected serum albumin - actual serum albumin) + measured serum calcium

expected serum albumin = 4
What are 2 classic findings of hypocalcemia?
Trousseau sign: hand spasm when blood pressure cuff is held above systolic BP for over 3 min

Chvostek's sign: contraction of facial muscles after tapping the facial nerve just anterior to the ear
What is the most common reason of low PTH measure in a hypocalcemic patient?
surgical removal of the parathyroid glands
A patient has hypocalcemic symptoms but the blood PTH level is high.

What do you suspect?
Albright's hereditary osteodystrophy
How does acute respiratory alkalosis change serum Ca level?
alkalosis increases Ca binding to albumin --> hypocalcemia
What is the most likely reason for hypercalcemia in out patients? how about in hospitalized patients?
Out-pts: hyperPTH

in-pts: malignancy
What are 3 most common cancers causing hypercalcemia?
breast cancer
multiple myeloma
lung cancer
A pt presents with hypercalcemia, metabolic alkalosis, and renal insufficiency.

this is the 3rd leading cause of hypercalcemia.

What is the dx?
milk-alkali sydnrome
What diuretic can cause hypercalcemia?
thiazide
Does osteoporosis produce "abnormal" bone?

What are the sxs of osteoporosis?
No osteoporosis produce normal bone content but has less mineral density

NO symptoms unless it results in a fracture.
How do you diagnose osteoporosis?
Diagnose with hip BMD using DEXA scan.

Plain films are not a diagnostic tool. it only discovers severe osteoporosis
How is osteoporosis defined?
BMD that is 2.5 SD below that of a young adult

Uses the T score
What is the most common cause of Cushing's syndrome?
excessive exogenous cortisol
A patient presents with hypertension, hypokalemia, metabolic alkalosis and low plasma renin.

What do you suspect?
Conn's syndomre due to primary hyperaldosteronism
What is adrenal crisis?

What is the most common cause of adrenal crisis?
Adrenal crisis is acute adrenocortical insufficiency.

Most commonly due to rapid withdrawal from exogenous corticosteroids.
what bacteria can cause adrenal crisis?

What is this called?
Waterhouse-Friderichsen syndrome

Bacteremia and sepsis due to Neiserria meningitidis
A pt presents with chronic hypotension, metabolic acidosis, hyponatremia, hyperkalemia, and skin hyperpigmentation.

What do you suspect?
Addison's disease due to primary adrenocortical insufficiency
A pt presents with HTN, headache, perspiration, and palpitation. His urine has high metanephrine levels.

What do you suspect?

What histological feature do you expect to see in the pathological tissue?
Pheochromocytoma

Cluster of chromaffin cells (Zellballen) + endocrine atypia
If pheochromocytoma arises outside the adrenal gland, what is the condition called?

List 2 common regions.
Paragangliomas

Paravertebral sympathetics: Organs of Zuckerkandi and urinary bladder

Aorticopulmonary regions: carotid body tumor and jugulotympanic body
what is the 2nd most common solid malignancy in children?

What tumor marker is present in the urine?

What gene indicates poor prognosis in this malignancy?

what histology do you see in the pathologic tissue?
Neuroblastoma of the adrenal gland.

C-MYC indicates poor prognosis

small, round, blue cell tumor and sometimes Homer-Wright pseudorossettes
what do you suspect when a pt experiences a hypertensive crisis during micturition?
Paraganglioma of the bladder.
This picture is from the pituitary gland of a pt suffering form Cushing's syndrome.

What is the arrow indicating?
What is the cause of this histological change?
Crooke hyaline change (accumulation of intermediate filaments) due to excessive negative feedback from high cortisol level
What 2 features of Addison's disease contribute to postural hypotension?
1. low cortisol --> a lack of maintaining BP
2. salt diuresis
What is highly indicated in patients with Addison's disease, who are about to undergo a major surgery? why?
high levels of cortisol to cover stress of the surgery.

These pts can undergo hypotensive shock
What enzyme blocker is used to diagnose Addison's disease?
Metyrapone: 11hydroxylase blocker

these pts show increased ACTH but no increase in 11-beta deoxycortisol
The following are the result of Dexamethasone suppresion test. Diagnose each case.

Case 1: high cortisol in both low and high dexa suppression; low ACTH

Case 2: high cortisol in both low and high dexa suppression; high ACTH

Case 3: high cortisol in low dexa suppression, low cortisol in high dexa suppression, and normal ACTH
Case 1: primary adrenal tumor that secretes cortisol

Case 2: ectopic ACTH tumor (e.g. small cell lung carcinoma)

case 3: Cushing's disease
What hormone is only synthesized in adrenal medulla? why?
Epinephrine

Synthesis of Epi requires cortisol, which induces the enzymes that converts norepi to epi.

Adrenal medulla receives its blood supply from the adrenal cortex
A long-time diabetic patient with advanced complications experience postural hypotension and frequent hypoglycemic episodes.

What accounts for this?
Adrenomedulla hypofunction due to autonomic neuropathy
What is this syndrome called?

Nerufibromatosis, cafe-au-lait spots, Lisch nodules and pheochromocytoma
Von Recklinghausen syndrome
this is a microscopic picture of adrenal gland from a 2 YO boy. He recently suffered a septic bacteremia due to pseudomonas infections.

What is shown?
What is the dx?
Hemorrhage and necrosis of adrenal gland.

Waterhouse-Friderischen syndrome
this histological picture is found in the liver of a 2 YO boy. He had elevated levels of urinary HVA and VMA.

What is the arrow pointing at?
What is the dx
Homer-Wright pseudorossettes

Medullary neuroblastoma
What is the most common cause of hyperthyroidism?

What is the most common cause of hypothyroidism in the US?
Hyper: Grave's disease

hypo: Hashimoto's thyroditis
What are 2 types of cells present in Hashimoto's thyroiditis?

What neoplasm can develop from Hashimotos?
Hurthle cells: Eosinophilic cells lining the follicles

lymphoid follicle with lymphoid cells

Can develop B cell lymphoma
A 30 YO female presents with painful enlargement of thyroid. She has a flu a week ago.

What is the dx? Tx?

What histological feature would you expect from a biospy?
Subacute thyroiditis (DeQuervain's)

no treatment; self-limiting

granulomatous lesion with multinucleated giant cells
A 25 YO female has a painless enlargement of the thyroid gland. History reveals she just had a baby a week ago.

What is the dx? tx?
subacute lymphocytic thyroiditis

Treatment: none; self limiting
A 50 YO female a fixed, hard, and painless goiter. Histology from the biopsy reveals multi-directional fibrosis.

What is the dx?
Riedel's thyroiditis
What is the most common cause of simple goiter, especially in developing nations?

Any thyroid related sxs? Complications?
Iodine deficiency
Usually euthryoid

can progress to toxic, multinodular goiter, which can be mistaken for tumor.
A single discrete nodule is present on the thyroid gland. Grossly, the nodule is completely encapsulated. Histology shows follicular size variation and the nodule is "cold"

What is the dx?
Is there any potential for malignancy?
thyroid adenoma

No adenomas rarely become malignant
A bx from thyroid is taken. HIstology shows psamomma bodies, Orphan Annie nuclei.

What do you suspect?
Papillary carcinoma of thyroid
What thyroid tumor is derived from parafollicular C cells?

What syndromes are associated?
What oncogene is implicated?
Prognosis?
Medullary carcinoma of the thyroid

MEN types 2A and 2B
RET oncogene

This is an aggressive tumor, so thyriodetomy is performed if the pt is a gene carrier
What thyroid carcinoma has the worst prognosis.
undifferentiated carcinoma of the thyroid (anaplastic thyroid cancer)
Name 2 enzymes involved in Iodine metabolism and iodine trapping.

Describe the actions of each.
Na/I symporter (NIS): transport Na and I on the basal side

Thyroidal peroxidase (TPO): oxidize I to I- AND couples MIT and DIT to T4 and T3
How are T4/T3 metabolized and excreted?
Metabolized in the kidney and liver via deiodination and conjugation to glucoronides.

Excreted via bile
What 2 conditions result in "hot" thyroid nodules?

What 3 conditions result in "cold" thyroid nodules?
Hot: multinodular toxic goiter and Grave's

cold: thyroid adenoma, cyst, and cancer
List a late manifestation of Grave's disease.
pretibial myxedema or thyrotoxic demopathy
What is the pathogenesis of Grave's disease?
stimulatory Antibodies against TSH receptor.

TSI (thyroid stimulating immunoglobulin)
LATS (long-acting stimulators)
How do you confirm the dx of Hashimoto's thyroditis?
tests for antibodies:
1. thyroglobuiln antibody (TgAb)
2. Thyroidal peroxidase antibody (TPO Ab) or anti-microsomal ab
3. TSH receptor blocking antibody
What is Plummer's disease?
Multinodular, toxic nodules of thyroid.

TSH independent and Hot nodules
Name 4 carcinomas of thyroid in the order of decreasing frequency.
papillary > follicular > medullary > anaplastic
Define subclinical hypothyroidism and subclinical hyperthyroidism.

What clinical findings are observed in each?
Sublinical hypothyroidism: high TSH > 5 mU/L but normal T3/T4; subtle neuropsychiastric sxs

Subclinical hyperthyroidism: low TSH <0.1 mU/L but normal T3/T4; associated with bone loss and fracture in postmenopausal women
What is the diagnosis?

Low T4/T3, low TSH, and high reverse T3. Euthryoid
Euthyroid sick syndrome (ESS)
What is the clinical difference b/t a true follicular adenoma of thyroid and a follicular variant of papillary carcinoma?

How do you distinguish the 2?
True follicular adenoma has poorer prognosis.

Distinguish them histologically. True follicular adenoma has NO psamomma bodies and Orphan Annie nuclei.
What is the histological precursor lesion to familial medullary thyroid carcinoma?
C-cell hyperplasia
This is a biopsy of the thyroid gland from a hypothyroid patient.

What are the arrows indicating? What is the most likely dx?
What other histological feature would you expect?
Arrows are pointing and Hurthle cells (or oncocytes)
Hashimoto's thyroiditis
Lymphoid follicles will also present
This is a biopsy of a solitary lesion on the thyroid gland.
What are the arrows pointing at?
What is the dx?
What other histological features would you expect?
What is a common risk factor?
Arrows are pointing at Orphan Annie nuclei.
Also has psamomma bodies
papillary thyroid carcinoma
associated with childhood head and neck irradiation
This is a section of thyroid tissue.

What are the green arrows indicating? What is the clinical significance of green arrows?

What are the red arrows indicating?

what is the diagnosis?
Green arrows: papillary nature of the tumor; all papillary pattern thyroid tumors are malignant

red arrows: Psamomma bodies

Papillary thyroid carcinoma
This is a biopsy of thyroid nodule.

What is indicated by "A"?
Describe the histology.
What is the dx?
A: amyloid derived from altered calcinotin molecule

histology: sheets and nests of small, dark, blue-stained cells

Dx: medullary carcinoma of thyroid