Week 2 Flashcards
(126 cards)
1
Q
Blood supply of thyroid (2)
A
- superior: superior thyroid artery (from external carotid artery)
- inferior: inferior thyroid artery
2
Q
Blood supply of parathyroid glands (2)
A
- inferior thyroid artery
- thyroid ima artery (sometimes is present in patients)
3
Q
Thyroid follicle
1. what is it lined by and what does it produce
2. what is it filled with?
A
- follicular cells - simple cuboidal epithelium that produces colloid
- colloid
4
Q
- What are the important contents inside colloid?
- What is the function of thyroid hormones (general)
- Which hormone made is the more potent hormone and which is more highly produced?
A
- thyroglobulin - part of the process in making thyroid hormone
- regulates basal metabolism and heat production in body
- T3 - more potent + T4 - more highly produced horomone but less potent than T3
5
Q
- Where are parafollicular cells found?
- What do they do?
- What are they also known as?
A
- found between follicles of thyroid - larger cells with lighter cytoplasm
- secrete calcitonin - “tone down calcitonin”
- clear or C cells
6
Q
Chief cells
1. where are they
2. what do they do?
A
- parathyroid gland
- secrete parathryoid hormone (arrows in image). Counteracts action of calcitonin and increases calcium in blood
7
Q
Oxyphil Cells
1. where are they
2. what do they do?
3. unique feature?
A
- parathyroid gland
- have calcium sensors
- non-secretory cells that increase with age (arrowhead)
8
Q
Diffuse vs multinodular goiter
1. typical age group
2. thyroid hormone levels
3. symptoms/effects?
A
Diffuse
1. younger age group
2. usually euthyroid
3. TSH may be slightly elevated
Multinodular
1. older age group
2. euthyroid or subclinical hypothyroid
3. mass effect, often mistaken for neoplasia
If diffuse type is left untreated then it can become multinodular
9
Q
Diffuse and multinodular goiter
1. What is the pathogenesis?
A
- Ineffective synthesis of T4 induces elevated TSH levels -> this induces hyperplasia of follicular cells
- Seen without hyperthyroidis, hypothyroidism, or inflammation - which is why these patients can be euthryoid often
10
Q
Endemic goiter
1. What is it?
Non-endemic goiter
1. what is it?
2. more often found in what patient type?
A
- endemic is lack of iodine in diet so can’t make thyroid hormone
- non-endemic goiter- ingestion of goitrogens or hereditary enzyme defects
- more often in females that are undergoing puberty or young adults
11
Q
Subacute Granulomatous Thyroiditis
1. another name for this?
2. More common in what patient type?
3. pathogenesis?
A
- DeQuervain Thyroiditis
- female 30-50 year old
- self limited inflammation of the thyroid gland. Usually sudden onset and post viral ifnection - peak of incidence in summer.
12
Q
Subacute Granulomatous Thyroiditis
1. common symptoms
2. histology findings
3. Thyroid levels
A
- sudden onset, pain on swallowing, fatigue, fever, malaise, variable thyroid enlargement - recovery in 6-8 weeks
- Granulomatous inflammation with histiocytes, lymphocytes, and giant cells
- Hypothyroidism differential
13
Q
Hashimoto’s Thyroiditis
1. Genetic linkages
2. More common in what patient type?
3. pathogenesis?
A
- HLA-DR5, HLA-DR3 and associated with turners and trisomy 21
- women 45-65 years of age but also cause of goiter in children
- AUTOIMMUE - Autoantibodies against one or more thyroid antigens which then recruit the complement system for destruction + CD4+ T cells release cytokines + CD8+ T cells kill virus infected cells (via perforin granzyme and FAS-FAS ligand)
—– **leads to ** …. gradual destruction of thyroid
— lymphoid and follicular inflammation
— extensive fibrosis in the thyroid gland
14
Q
Hashimoto’s Disease
1. Clinical presentation
2. Histology changes
3. Thyroid levels?
A
- Painless and symmetrical enlargement or thyroid
- Lymphoid chronic inflammation often with extensive fibrosis
- Under hypothyroidism differential but can have transient hyperthyroidism (then euthyroid and then hypothyroid)
15
Q
Subacute Lymphocytic Thyroiditis
1. More common in what patient type?
2. when does this most often occur?
3. thyroid hormone levels
A
- middle age women
- postpartum period
- mild hyperthyroidism - rarely progresses to hypothyroidsim
This is a subtype of DeQuervain type
16
Q
Subacute Lymphocytic Thyroiditis
1. Painful or painless?
2. Time line and risk of progressing to hypothyroidism
A
- PAINLESS VARIANT OF DEQUERVAIN TYPE
- self limited and rarley progresses to hypothyroidism
17
Q
Riedel’s Thyroiditis
1. more common in what patient type
2. How extensive is fribrosis
3. How common is this?
A
- women 40-70 years of age
- Extensive fibrosis that is in and around the thyroid gland (unlike hashimotos which only has inside the gland)
- rare
18
Q
Which “thyroiditis”
1. is painful?
2. has fibrosis
3. has granulomatous inflammation
4. has lymphoid and follicular inflammation
5. has lymphid inflammation
6. chronic inflammation
A
- DeQuervain
- Hashimotos and Riedel
- DeQuervain
- Hashimoto
- Subacute Lymphocytic (subtype of DeQuervain)
- Riedel
19
Q
Grave’s Disease
1. Pathophysiology?
A
- Autoimmune disease - has antibodies that stimulate TSH receptor. This leads to low TSH because antibodies act like TSH.
- There is also activation of fibroblasts bc they contain TSH receptors — this leads to secretion of glycosaminoglycans which draw water in (leading to one of the sx of swelling around eyes)
- Most common cause of hyperthyroidism (remember TSH receptor is being stimulated leading to increased thyroid hormone production)
20
Q
Graves Disease
1. Genetic links
2. Clinical symptoms
3. Antibodies (3) - need to know!!
A
- HLA-B8, DR3 or polymorphisms at CTLA-4 gene
- Thyroid enlargement, exophthalmos (eyes bulging out), pre-tibial myxedema, scaley thickening skin, pigmented nodules
- TSI (thyroid stimulating immunoglobulin), TGI (Thyroid growth stimulating immunoglobulin), TBII (TSH-binding inhibitor immunoglobulin)
21
Q
Graves Disease
1. What does TSI autoantibody cause?
2. What does TBII autoantibody cause?
A
- Hyperthyroidism, Ophthalmopathy, Pretibial edema (remember water being drawn in)
- bouts of hypothyroidism (because it is inhibiting binding of TSH)
22
Q
What does hCG do to thyroid hormones?
A
- Stimulates the thyroid even when TSH is suppressed
23
Q
What is the function of TBG (thyroxine binding globulin)?
A
- binding to and transporting thyroid hormones to the necessary tissues
24
Q
24 hour iodide uptake
1. What does normal look like
2. What does high uptake look like and indicate
3. What does low uptake look like and indicate
4. Single “hot” nodule
5. Single “cold” nodule
A
- diffuse even uptake (image)
- Diffuse darker staining in scan
- less darker staining such as in Hashimoto’s
- adenoma
- possible cancer bc most cancers don’t make hormones
25
# most common neoplasm od thyroid
Follicular Adenoma
1. pathogenesis
2. prognosis
1. benign proliferation of follicular cells. It is normal follicular tissue and it is completely surrounded by fibrous capsule
2. most are benign and non-functional
| if it breaks out of capsule it becomes malignant (follicular carcinoma)
26
Papillary Thyroid Carcinoma
1. Most common genetic signature
2. What is the most common cause?
3. Most common patient to have this?
1. BRAF mutation (30-50%), then RET (20%)
2. thyroid irradiation (radiation iodine)
3. mostly 20-40 year olds
27
Papillary Thyroid Carcinoma
1. Three hallmark histology findings
1. psammoma bodies
2. Nuclear clefts
3. Orphan annie nuclei (this one is not required for dx)
28
Papillary Thyroid carcinoma
1. Histology
2. PE findings
1. presence of true papillae. Nuclear features of papillary carcinoma in overlying epithelial cells of thyroid
2. mass in the neck - solid, irregular, or cystic mass - presents as thyroid nodule on CT/MRI but dx if after FNA
29
Out of the thyroid carcinomas which is most common and 2nd most common?
1. papillary thyroid carcinoma
2. follicular thyroid carcinoma
30
Follicular Thyroid Carcinoma
1. Most common patient to have this?
2. Morphology/Histology
3. pattern of spread
1. 40-50 year old woman
2. follicular pattern with invasion BUT none of the big three histology characteristics
3. spreads through the blood but most are just minimally invasive
31
Medullary Thyroid Carcinoma
1. Inheritance patterns
2. pathology?
3. histology findings?
1. most are sporadic but some are due to MEN2 disorders in younger patients
2. Neuroendocrine tumor of the C cells outside of follicles that produce calcitonin.
3. Amyloid deposits are found in thyroid
32
Anaplastic Thyroid Carcinoma
1. typical patient type and history of patient
2. prognosis
3. Histology
4. sx
1. elderly but mean age is 65 years - 50% is associated with history of multinodular goiter
2. highly malignant, survival <1 year
3. undifferentiated cells - no papilla, no follicles, no amyloid
4. cough, dysphagia, hoarseness, SOB
33
1. parathyroid hormone is secreted in response to what? (3)
1. low calcium (fastest response)
2. high phosphate levels
3. low vitamin D
34
1. What can lower PTH levels? (2)
2. what can inhibit PTH release
1. high calcium
2. high magnesium ( can activate calcium sensing receptor)
------
1. very low Mg can inhibit PTH release bc it is needed for normal calcium sensing receptor function
35
Parathyroid Hormone
1. effectss on bone
2. effects on kidney
3. effects on phosphate
4. effects on vitamin D
5. effects on the gut
1. increases bone resorption - to release calcium
2. increases calcium resorption in kidney (tubular resorption) + increases renal production of 1,24 (OH)2 vitamin D
3. increases urinary phosphate excretion - to lower serum phoshate
4. increases vitamin D enzyme 1 alpha hydroxylase (catalyzes the synthesis of active form of vitamin D)
5. augments GI absorption of calcium
36
Vitamin D
1. What is its function for calcium homeostasis
1. increases calcium absorption from the gut and reabsorption of calcium in the kidney
2. Increases mineralization of bone - to increase calcium
37
Calcitonin
1. What is its function in calcium homeostasis
1. inhibits osteoclasts - to tone down calcium
38
Fibroblast growth factor 23
1. What is its function?
2. How does FGF23 affect vitamin D?
3. Where is it often found?
1. FGF-23 is a peptide hormone produced by osteocytes that regulates increased serum phosphate levels. The primary effect of FGF-23 is to inhibit the Na-phosphate cotransporter in the proximal tubule, reducing phosphate reabsorption thereby promoting urinary phosphate excretion.
2. It also inhibits the expression of 1α-hydroxylase in the proximal tubule, thereby decreasing calcitriol production.
2. osteocytes (a bone cell)
| essentially it decreaes Vitamin D and blood caclium
39
Hyperparathyroidism
1. What is the general pathology
2. Types
1. Elevated concentrations of PTH
2. primary, secondary, tertiary, or pseudohyperparathyroidism
40
Primary Hyperparathyroidism
1. Pathogenesis?
2. demographic
3. What are the two common molecular defects
4. Sx
1. overactive glands due to hyperplasia or functional tumor (adenoma - most cases) that secrete inappropriate amount of PTH -high levels of calcium due to high levels of PTH
2. disease of adult women
3. Cyclin D1 gene inversions + MEN1 mutations
4. often asymptomatic but if there are sx think stones (kidney), bones, groans (abdominal pain), and psychiatric overtones (anxiety)
41
Secondary Hyperparathyroidism
1. Pathogenesis?
2. changes to parathyroid gland
1. This is overactive glands due to hypocalcemia. It is caused by any syndrome that leads to long term hypocalcemia. (such as renal failure - failure to remove extra phosphate leads to more phosphate that inhibits the enzyme to activate vitamin D needed for calcium absorption)
2. hyperplasia
42
Tertiary Hyperparathyroidism
1. pathogenesis?
2. changes to parathyroid gland?
3. how is this usually fixed
1. This is continued increased secretion of PTH after a defect in calcium metabolism has been corrected. Most commonly its chronic renal disease where PTH remains elevated after vitamin D is corrected.
2. hyperplasia + may have decreased expression of calcium sensing receptors and vitamin D receptors
3. parathyroidectomy
43
Pseudohypoparathyroidism
1. pathogenesis?
2. When does it present
3. sx or clinical presentations
4. gene mutation associated with this
1. a rare genetic disorder which gland has no response to PTH
2. in childhood
3. low calcium, elevated phosphate, high PTH hormone, cataracts, dental imperfections, numbness, seizure, tetany
4. most common gene mutations iGNAS
44
What treatment is given to someone with hypoparathyroidism?
1. calcium and calcitriol (vitamin D3)
2. recombinant PTH available too
45
PTHrP - why is this marker important?
1. a tumor marker that is often elevated in hypercalcemia due to malignancy
46
1. Drug cinacalet -> what does it tx?
1. increases the sensitivity of the parathyroid calcium sensors -> *lowering PTH*
47
1. What is chvostek sign
2. What is trousseau sign
3. With what level of calcium do these occur
1. facial muscle spasms by tapping the nerve
2. carpal sapasms by occlusion of arm circulation
3. These occur with hypocalcemia
48
What classical signs are seen with hypocalcemia?
1. Chvostek sign (remember hypocalcemia increases excitability by decreasing the threshold needed for activation of neurons)
2. Trousseau sign
3. Mental status changes
4. Calcifications of basal ganglia
5. Long QT syndromes
6. Dental abnormalities
49
Common causes for hypocalcemia
1. surgical removal of glands
2. chronic renal disease (no vitamin D to allow for Ca absorption)
3. Low serum mg (needed for calcium sensing receptors)
4. others that are more uncommon
50
1. What is heat conduction?
2. Convection?
3. Radiation?
1. moving heat to another object or air
2. the transfer of heat from one place to another due to the movement of air
3. heat moved through waves
51
1. What body part is responsible for setting the core body temp?
2. What determines a shift from heat production to heat lost (or vice versa)
1. hypothalamus
2. Hypothalamus recieves signals from thermoreceptors and the total input changes what the hypothalamus will direct: heat production or heat loss
52
What special changes to core body temp occurs with a fever?
1. exogenous pyrogens (substances that cause a fever) induce an immune response and the release of PGE2
2. PGE2 inhibits warm-sensitive receptors and disinhibits cold-activated neurons
3. This makes the hypothalamus interpret a higher temp as the correct/new core body temp
4. mechanisms are activated to conserve heat, produce heat (remember cold-activated neurons are activated so body thinks they need to work against the cold)
5. Clearance of exogenous pyrogens eventually occurs and this stoms the warm-sensitive receptor inhibition
6. Hypothalamic set point returns to normal
7. Heat dissipation mechanisms are activated to return to regular body temp
53
1. How does shivering allow for conservation of heat?
2. What about brown adipose tissue?
3. What about thyroxine output?
1. ATP is hydrolzyed but no work is done so energy produced is released as heat
2. thought to help infants more - brown adipose has UCP1 protein that uncouples the ATP synthesis pathway in mitochondria - so heat can now dissipate instead of making ATP
3. increases rate of cellular metabolism throughout body - slower response so may be better for long-term adaptation
54
1. how do osteoclast resorbed bone?
2. How does osteoblast build bone?
1. dissolve hydroxyapatite deposited around collagen with hydrolytic enzymes and acid that are secreted from osteoclasts
2. lay down osteoid in area that was broken down by osteoclasts - then controlled mineralization
55
1. Function of RANK
2. Function of RANKL (ligand)
3. Function of OPG
1. RANK is on osteoclasts and need to bind to RANKL on osteoblasts to become activated (for the osteoclasts to activate)
2. RANKL is on the osteoblasts and activate osteoclasts once they bind to RANK on osteoclasts
3. OPG is a protein that is made by osteblasts and these bind to RANKL to prevent binding to RANK and thus inhibits osteoclast activation
56
1. How does excess PTH stimulate osteoclastogenesis?
2. How does excess thyroid hormone stimulate osteoclast activity?
3. How does glucocorticoids favor osteoclast activation?
1. increases RANKL expression and decreases OPG production
2. T3 increases osteoblast differentiation (need this for RANKL presence which activates osteoclasts)
3. suppresses OPG secretion and upregulates RANKL expression BUT it also decreases GI Ca2+ uptake so increases PTH levels and induces bone resorption (so not entirely good- can cause osteoporosis)
57
How do these stimulate or favor osteoblast activity?
1. calcitriol
2. calcitonin
3. growth hormone
4. estrogen
5. testosterone
1. maintains serum Ca to support bone mineralization so stimulates formation of osteoblasts
2. wants to reduce serum Ca so it inhibits osteoclasts and favors osteoblast function
3. promotes linear bone growth - proliferates osteoblasts and reduces osteoblast apoptosis
4. leads to apoptosis of osteoclasts to limit bone resorption
5. Inhibits osteoclastogenesis via inhbiting RANKL expression
6.
58
1. What cells does TSH bind to and what second messenger system does it activate to increase T3/T4 release?
1. follicular cells
2. cAMP/PKA 2nd messenger system
59
Effects of TSH
1. immediate effects
2. intermediate effects
3. long term effects
1. release of T3 and T4
2. increased protein expression
3. hypertrophy and hyperlasia of follciular cells (goiter), increased capillary formation
60
1. How does T4 released from thyroid do on the spot negative feedback on anterior pituitary?
1. thyrotrope cells in the anterior pituitary express deiodinase enzyme which converts T4 to T3
2. T3 then can exert negative feedback at anterior pituitary
61
1. What is the Wolff-Chaikoff Effect?
2. What is the escape in this effect?
3. What patient does not experience the escape?
1. When there is an increase in iodide in the diet the body does autoregulation of thyroid hormone production (to not make too much TH)
2. high iodide concentration in thyroid gland inhibits TPO (thyroid peroxidase) and thus suppresses TH formation
3. The escape occurs 2 days later - meaning TH production is started back up after being inhibited
3. This escape process does not occur in fetal/neonatal patients so after too much iodide then they continue to not make TH and experience hypothyroidism
62
1. What is the importance of NIS in Thyroid Hormone synthesis?
1. This is how iodine is taken up by follicular cells - NIS (Na/Iodine symporter)
2. NIS can also pick up ClO4- and TcO4 since they are negatively charged ions as well.
3. They are competitive inhibitors of iodine (I-)
63
After NIS allows for Iodine to be taken up by follicular cells.... explain the process up until T3/T4 are released?
1. Iodine is oxidized in follicular cell to I2 via thyroid peroxidase enzyme (TPO)
2. Iodine (I2) is taken out of follicular cell and into follicle lumen. There it is combined to tyrosine (attached to thyroglobulin) with the help of TPO and this creates MIT and DIT
3. Now you have MIT and DIT attached to thyroglobulin
4. TPO acts on MIT and DIT again and creates T3 or T4. T3 and T4 are still attached to thyroglobulin
5. T3 and T4 on thyroglobulin enter follicular cell where it undergoes proteolysis and finally able to to release T3 and T4 when requested
64
1. Where is T3 mostly synthesized from T4
2. what enzymes allows for this?
1. peripheral tissues
2. 5' deiodinase (deiodinase enzymes) converts T4 into T3
65
Effects of T3 on..
1. metabolism and heat production
2. sympathethic NS
3. bone growth
4. brain development
5. hair follicle
6. sebaceous and sweat gland
1. increases - speeds up the basal metabolic rate
2. increases fight or flight sx (increased CO, RR, mental alertness)
3. increases long bone growth
4. helps with brain development
5. increases hair follicle growth
6. increases sebaceous and sweat gland secretion
66
1. when in circulation what do thyroid hormones T3 and T4 bind to?
1. Thyroid binding globulin (TBG) - these are not active hormones so it is always important to get labs for free TH as well
67
1. What is the process by which thyroid hormones induce an effect on cells/tissues?
1. T3 and T4 are transported through cell membrane via monocarboxylate transport proteins
2. bind to nuclear receptors to induce gene expression
68
Metabolic effects of Thyroid Hormone?
1. Carbohydrate
2. Fat
3. Na/K ATPase pumps
4. Basal metabolic rate
1. increased carb metabolism - increased glycogenolysis, gluconeogenesis
2. increased fat metabolism - increased lipolysis, decreased concn of cholesterol and triglycerides, decreased LDL, increased cholesterol in bile (liver)
3. increased Na/K ATPase pumps - more ATP consumed bc more energy is being used up
4. increased metabolic rate
69
1. What is the effect of Thyroid hormone on the cardiovascular system?
2. effect on respiratory system?
3. effect on muscles?
4. effect on bone?
5. effect on reproductive system?
6. effect on brain function?
1. increases CO, HR, Stroke volume, increases beta 1 receptors on heart
2. increases respiratory rate, increase minute ventilation
3. increases glycogenolysis and glycolysis - decreases glycogen storage - **increases ATP usage** in muscles for thermogenesis - **increases protein degredation** to release AA from muscle
4. TH is needed for normal bone growth
5. TH is needed for normal reproductive function
6. TH is needed for normal CNS maturation
70
1. What is cretinism?
2. is it treatable?
3. When do symptoms show?
1. stunted growth, intellectual disability due to iodine deficiency, thyroid dysgenesis, or inborn errors of hormone synthesis --> dont have enough thyroid hormome
2. very treatable! Newborns are screened for this and then treated if they have it.
3. Need to be screened bc babies may seem normal at birth due to mothers thyroid hormone supply but later show symptoms.
71
1. What is the drug of choice for hypothyroidism?
2. How long until TSH returns to normal after this tx?
3. Changes in pregnant women?
1. levothyroxine (T4)
2. 6-9 months
3. increase dose because there is more TBG meaning free T4 will be lower so you want to give more to off balance this
72
1. When is Liothyronine (T3) used over levothyroxine (T4)?
2. Which is better for maintenance therapy?
1. used when there is impaired absorption of levothyroxine.
2. levothyroxine - has longer half life. Plus Liothyronine is not has higher incidence of adverse effects.
73
Thiomides (PTU, methimazole)
1. MOA
2. When is it used?
3. Which is more potent?
4. What does PTU do that methimazole does not do?
1. blocks synthesis of thyroid hormones by inhibiting thyroid peroxidase system (TPO)
2. Hyperthyroidism
3. Methimazole is more potent
4. PTU also inhibits peripheral conversion of T4 to T3
74
Thiomides (PTU, methimazole)
1. what patient populations is this used in?
2. How does dose change in therapy timeline?
3. Adverse reactions
4. How soon until hyperthyroid sx are diminished?
1. children, young adults, pregnancy, thyroid storm (but PTU not recommended in pediatric population)
2. dose adjustments monthly and once euthyroid, dose should be reduced or discontinued. Tx only lasts 12-18 months.
3. Rash, hepatotoxicity
4. by 4-8 weeks of onset of therapy.
75
If patient is tx with thiomides and then tx is discontinued but later relapses again with hyperthyroidism - what is next tx steps?
1. Radioactive iodine therapy or surgery
76
Radioactive I 131 (RAI)
1. MOA
2. Adverse effects
3. clinical reason for use
4. Onset of action?
1. disrupts hormone synthesis initially and then leads to destruction of the follicles and surrounding area
2. Mild thyroidal pain and tenderness, dysphagia, thinning of air, hypothyroidism
3. When pt relapses after thiomide tx for hyperthyroidism
4. delayed onset of action, maybe 6-8 weeks for improvement and 3-6 months to become euthyroid
77
Iodide (Lugol solution) - adjunct therapy
1. MOA
2. length of use
3. Clinical use for this tx?
1. inhibits thyroid hormone release and production
2. short acting and short term uses only - improvement seen within 2-7 days
3. used to prepare pt for surgery or in thyroid storm (hyperthyroidism)
78
Beta Blockers (propanolol) - adjunct therapy
1. MOA
2. Clinical use for this tx?
1. partially blocks conversion of T4 to T3
2. used to tx symptoms that come up in thyroid storm like palpitations, anxiety, tremor, heat intolerance
79
1. what is the pathogenesis of Grave's Disease?
2. hypo or hyperthyroidism
1. B cells release antibodies that are stimulatory on thyroid follicular cells. This helps their survival and production of more follicular cells -> leading to hyperthyroidism
80
What does histology of Grave's look like?
1. increased number of follicular cells (hyperplasia) - follicles themselves are small and less colloid inside
81
What does histology of thyroid look like in Hashimoto's disease?
1. follicular cells look smaller
2. Extensive fibrosis CONFINED to areas in the gland NOT to tissues surrounding gland
82
1. What are the two antibodies associated with Hashimoto's disease?
1. anti-thryoglobulin antibodiy
2. anti-thyroid peroxidase antibody
83
What are some complications of Hashimoto's?
1. autoimmune phenomenon - increased frequency of autoimmune disease (this is also seen in Grave's)
2. increased risk of developing B cell non-hodgkin lymphoma
84
1. What causes the nodularity in multinodular goiter?
1. with reduced TH production there is compensatory hyperplasia and goitrous enlargement of the thyroid gland
2. Recurrent episodes of hyperplasia and involution when the TH need is met results nodules of the thyroid (multinodularity)
85
Papillary Neoplasm of Thyroid
1. what is the genetic mutation in this?
2. what is a risk factor for this?
3. How does it spread
4. What does histology show
5. Clinical features
1. BRAF point mutation OR RET/PTC translocation
2. ionizing radidation
3. lymphatics
4. Papillae (finger like projections), Nuclear features like orphan annie eye, intranuclear inclusions, nuclear grooves, + psammoma bodies
5. painless mass in neck
## Footnote
Reminder: this is a thyroid cancer and most common
86
Follicular Carcinoma of Thyroid
1. Risk Factor
2. How does it present in imaging
3. What is usually found on histology to make it carcinoma
4. How and to where does it spread?
1. Dietary iodine deficiency
2. Solitary cold thyroid nodule
3. the mass is seen to be invading/breaking the capsule. Uniform cells forming small follicles.
4. hematgenous spread to lungs, bone, and liver.
## Footnote
Reminder: this is a thyroid cancer
87
Medullary Carcinoma
1. sporadic vs familial?
2. clinical presentation
3. pattern of spread
1. sporadic mostly
2. neck mass sometimes with dysphagia or hoarseness. Sxs may be related to secretion of peptide hormone.
3. To lymph nodes
88
Medullary Carcinoma
1. What cells does this arise from?
2. What does histology show?
1. arises from C cells (the ones that make calcitonin)
2. may contain amyloid deposites (red parts in image), necrosis and hemorrhage in larger lesions, polygonal or spindle shaped cells in nests, and more
## Footnote
Reminder: this is a thyroid cancer
89
Anaplastic Carcinoma
1. type of patient most likely to have this
2. clinical features
3. pattern of spread
4. prognosis?
1. older age - mean is 65
2. h/o or concurrent well differentiated thyroid carcinoma, rapid growth locally with compromise of vital neck structures
3. invasion of local structures and distant mets
4. poor - mortality approaches 100%
90
Anaplastic Carcinoma
1. Histology hallmarks?
1. Anaplastic cells that may be large and pleomorphic, invades adjacent neck structures
91
In parathyroid hyperplasia what changes are seen in chief cells and adipocytes?
1. Increased number of chief cells
2. Decreased adipocytes
92
Parathyroid adenoma vs hyperplasia vs carcinoma
1. How to tell the difference in histology?
2. when parathyroid adenoma is taken out what changes to PTH should be seen to differentiate it from hyperplasia
1. Adenoma shows clear division from normal tissue, Hyperplasia shows less adipose and more chief cells, carcinoma shows invasive growth beyond capsule
2. decrease in PTH by atleast 50% if not then it may be hyperplasia
93
What is the low calcium tetany phenomenon?
1. When there is decreased calcium in the body it decreases the threshold to cause AP so thats what causes tetany.
94
1. Where is most of total body calcium found?
2. How is calcium excreted?
1. 99% in bones
2. GI tract (feces) and kidney (urine)
95
1. PTH binds to the (Blank A) on osteoblasts in bone to stimulate the release of paracrine factors that upregulate osteoclast formation
2. Osteoclast lead to bone resoprtion releasing (Blank B) and (Blank C) into serum
1. Blank A - PTH/PTH-related peptide receptor
2. Blank B - Calcium; Blank C- Pi
96
1. PTH leads to resorption of bone to increase calcium serum levels but how does it also affect Calcium and Phosphate levels via the kidney?
1. Increases Calcium reabsorption in the **distal tubule**
2. Decreases Pi reabsorption in **proximal tubule** by inhibiting the Na-phosphate co-transporter
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What is pseudohypocalcemia?
1. when it appears that serum calcium is low but it is because hypoalbuminemia (or other loss of proteins) occurs but free calcium may be normal or high
98
How does frequent emesis lead to low calcium tetany?
1. with emesis you are losing acid -> leading to alkalosis in stomach
2. This efflux of H takes H off of albumin and then this frees up albumin to bind to calcium. This diminishes the amount of free calcium and presents as hypocalcemia
3. Then tetany phenomenon occurs
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Phosphate
1. How does this interact with calcium?
1. can complex with calcium to form insoluble calcium. this can cause soft tissue calcification and kidney stones!
100
1. What cells is PTH is secreted from?
2. What three main things stimulate PTH secretion?
1. chief cells of the parathyroid gland
2. low serum calcium, mild decrease in serum magnesium, high serum phosphate
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1. How is PTH connected to Vitamin D (calcitriol) and thus increase in Calcium levels (3)
1. PTH stimulates secretion of 1 alpha hydroxylase which creates active vitamin D at the kidney. Active vitamin D (calcitriol) then induces renal Calcium reabsorption
2. Vitamin D is needed for GI absorption of Calcium.
3. Vitamin D stimulates osteoblast to express RANKL which then activate osteoclasts for bone resorption.
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1. What is the name of the most active form of Vitamin D
2. What are the sources of vitamin D
1. calcitriol
2. Vitamin D3 (inactive) can be formed in keratinocytes by UV light exposure. + Vitamin D2 (inactive) can be obtained from diet
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1. What are the 2 steps to fully process vitamin D into active vitamin D
1. Hydroxylation occurs in the liver via 25-hydroxylase enzyme
2. Fully active in proximal tubule via 1 alpha hydroxylase
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Deficiency in vitamin D leads to what in
1. children
2. adults
3. Explain overall pathogenesis
1. rickets
2. osteomalacia
3. If decrease Ca and P absorption from GI tract and kidney occur then -> this leads to low Ca and thus PTH release. PTH liberates Ca and P from bone which. PTH also allows for P to be excreted in urine causing (hypophosphatemia). ULTIMATELY total serum Ca-phosphate is low leading to low bone mineralization
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1. What is the purpose of FGF23?
2. What is it secreted by?
1. **secreted by osteocytes** in response to high serum phosphate. Act to decrease serum phosphate levels.
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Effect of FGF23 on
1. GI absorption
2. Kidney
3. Calcitriol production
1. Inhibit expression of 1-alpha-hydroxylase to stop calcitriol production and thus stopping GI absorption of phosphate.
2. Inhibit P reabsorption in proximal tubule of kidney -> increasing excretion
3. inhibits calcitriol production
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1. What induces calcitonin secretion?
2. How do c cells know when to act?
3. Actions of calcitonin?
4. What is uncertain about calcitonin?
1. high calcium levels
2. they have sensing receptors to monitor Ca blood levels
3. Inhibit bone resorption, inhibit renal Ca reabsorption
4. physiological importance is uncertain because excess or complete absence of calcitonin does not alter Ca levels.
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Bisphosphonates
1. drug names
2. MOA
3. clinical use/indications (2 main ones)
4. Adverse effects
5. Contraindications
1. alendronate, pamidronate, end in -dronate)
2. analog of pyrophosphate which bind calcium and accumuulate in bone. They are then taken up by osteoclasts and inhibit osteoclast activity.
3. osteoporosis and postmenopausal women
4. Upper GI upset (reflux, esophagitis), flu like sx, etc
5. Renal impairment
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Denosumab
1. MOA
2. Clinical indications
3. Adverse effects
4. Contraindications
1. monoclonal RANKL antibody - prevents RANKL on osteoblasts from activating osteoclasts.
2. Hypercalcemia, osteoporosis
3. Hypocalcemia
4. Contraindicated in hypocalcemia and pregnancy
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Raolxifene
1. MOA
2. Indications
3. Adverse effects
1. SERM (selective estrogen receptor modulator) - estrogen actions on bone (inhibit bone resorption) but anti-estrogen effects in breast/uterus
2. Osteoporosis in postmenopausal women
3. hot flashes, DVT/PE-clots
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Teriparatide
1. MOA
2. indications
3. adverse effects
1. recombinant form of PTH - low dose once daily bolus leads to increased bone mass and increased osteoblast bone formation
2. osteoporosis
3. brief rise in serum calcium
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Romosozumab
1. MOA
2. Indications
3. Adverse effects
1. Anti-sclerostin antibody (this is helpful against osteoporosis because sclerostin usually increases osteoclast activity)
2. osteoporosis in postmenopausal women at high risk of fracture or pts who don't respond to other meds
3. arthralgia, headache
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Calcimimetic (Cinacalcet)
1. MOA
2. Indication
3. Adveres effect
1. acts like calcium to stimulate Ca sensing receptor agonist and inhibit PTH secretion
2. this is meant to be used to level out/temporize the PTH levels in pts who have very high PTH (due to 2ndary hyperparathyroidism in CKD, parathyroid carcinoma, etc) and cannot be tx with surgery
3. nausea, hypocalcemia
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Vitamin D (D3 or D2 supplements)
1. MOA
2. Indications
3. other names for D3 and D2
1. increases intestinal Ca absorption, increases bone resorption, decreases renal Ca excretion
2. vitamin D deficiency, osteoporosis
3. D3 (cholecalciferon) + D2 (ergocalciferon)
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Activated Vitamin D
1. names of drugs (2)
2. Indication
1. calcitriol, paricalcitol
2. secondary hyperparathryoidism in CKD - kidney dysfuntion doesn't allow it to convert D3 or D2 into calcitriol so just need the fully active for as medication
116
1. How does hypothyroidism affect lipid levels?
2. How does hyperthyroidism affect lipid levels?
1. Hypothyroidism - **elevated** total cholesterol and LDL due to decreased LDL receptor on liver and decreased lipoprotein lipase
2. Hyperthyroidism - levels of total cholesterol, LDL tend to be **decreased**. There are increased LDL receptor expression in liver.
117
1. How does contraceptives affect total T3 and T4 and Free T3 and T4
1. Contraceptives increase estrogen leading to increased Total T3 and T4
2. Free T3 and T4 stay the same
118
Levels of TSH and Free T4 in...
1. Overt hyperthyroidism
2. subclinical hyperthyroidism
3. Over hypothyroidism
4. Subclinical hypothyroidism
5. Pituitary hypothalamic
1. Suppressed TSH and increased Free T4
2. Suppressed TSH and normal Free T4
3. Increased TSH and low Free T4
4. Increased TSH and normal Free T4
5. Decreased TSH and free T4
119
1. What changes in TSH levels are seen with age
1. The upper end of normal TSH levels are increased
120
1. overt hyperthyroidism is associated with what changes in bone?
2. What about subclinical hyperthyroidism?
1. accelerated bone remodeling, reduced bone density, osteoporosis, increase in fracture rate
2. small reduction in BMD and increased risk of fracture but only in men and postmenopausal women
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What happens to PTH secretion with...
1. Decreased serum calcium
2. Increased serum phosphate
3. Increased calcitriol
1. increased PTH
2. increased
3. decreased
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1. primary hyperparathyroidism
2. secondary hyperparathyroidism
1. Increased PTH and increased Calcium
2. Increase of PTH in response to vitamin D deficiency. This never causes hypercalcemia.
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1. what is the frax score?
2. what does a significant score indicate?
1. A FRAX (Fracture Risk Assessment Tool) score is used to determine a person's 10-year risk of major osteoporotic fracture—that is, their risk of fracturing their spine, hip, forearm, or shoulder over the next decade.
2. screening needs to be done - usually via DXA (dual energy X-ray absorptiometry)
124
1. What T score in DXA indicates osteoporosis
2. what about osteopenia?
3. How is plain films (not DXA) used for osteoporosis dx?
1. -2.5 or lower
2. between -1 and -2.5
3. Plain films can only discover severe osteoporosis - not effective dx tools for screening
125
Genetic mutations for
1. papillary carcinoma of thyroid
2. Follicular and anaplastic carcinoma of thyroid
3. Follicular carcinoma of thyroid only
1. BRAF and RET/PTC
2. RAS, PI3K, PTEN
3. PAX8:PPARG Fusion
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