we started the second week of endocrine with a look at parathryoid and calcium issues. calcium levels are regulated hormonally by 3 main agents: PTH from the parathyroid, activated vitamin D from the kidneys, and calcitonin from the thyroid. PTH has four main actions: increases osteoclastic activity, increases reabsorption of calcium in the kidneys, decreases reabsorption of phosphate in the kidneys, and stimulates activation of vitamin D in the kidneys. whereas PTH has the effect of raising serum calcium levels, calcitonin (secreted from the C cells of the thyroid) lowers them by inhibiting osteoclastic bone resorption.
parathyroid hormone can be secreted in excess in many conditions, categorized by 1º, 2º, 3º. 1º is usually due to a parathyroid adenoma and results in osteoporosis, kidney stones, abdominal symptoms, and fatigue (bones, stones, groans, moans). it may also be asymptomatic and found by elevated serum calcium levels. hypercalcemia can also be caused by other conditions such as multiple sclerosis and sarcoidosis, in which case PTH levels would be low due to negative feedback to the parathyroid. 2º hyperparathyroid is often due to renal failure, which causes chronically low levels of calcium, resulting in compensatory PTH secretion. 3º refers to hypercalcemia from autonomous PTH secretion.
on the other end, hypoparathyroidism is mainly caused by surgical procedures-- such as removing part of the thyroid in grave's disease. signs and symptoms might include neuromuscular instability, parkinsons-like movements, and muscle tetany. the characteristic signs on a PE are chvosek (tapping on the TMJ causes contraction of the periorbital or perioral muscles) or trousseau's sign (carpal pedal spasm from occluding forearm blood supply).
the thyroid gland produces thyroid hormone mostly in the form of T4, most of which is bound to TBG in the blood. hypothyroidism can be due to primary causes (autoimmune dysfunction of the thyroid itself), secondary (dysfunction of anterior pituitary secretion of TSH), or tertiary (dysfunction of hypothalamic secretion of TRH), though the latter two are relatively rare. primary hypothyroidism can affect newborns, and cretinism can develop if thyroid hormones are low during the first few weeks of life, resulting in mental retardation, short stature, puffy facial features, among other symptoms.
for adults, hypothyroidism occurs more frequently in females, and is most commonly due to autoimmune disease, although outside the US can also be attributed to iodine deficiency. besides the signs and symptoms related to slowed metabolism (decreased circulation, energy, hair loss, etc), one might also notice follicular hyperkeratosis-- red bumps over the hair follicles on the outer arms, which is related to a defect in vitamin A synthesis, as well as diminished DTR's. lab values would show decreased levels of T4 but increased levels of TSH. secondary hypothyroidism results from pituitary dysfunction, causing low TSH and T4/T3 levels but high TRH levels. patients might present with signs of general pituitary dysfunction, or an intracranial mass (such as pituitary adenoma symptoms).
hyperthyroidism manifests with signs of metabolic excess such as heat intolerance, weight loss, irritability, warm/moist skin, muscle tremors, high cardiac output, etc. the most common cause is autoimmune via antibodies to the thyroid's TSH receptors as in grave's disease. grave's patients might also present with pretibial myxedema, a skin thickening specific to the legs. hyperthyroid states are diagnosed by testing for antibodies against the thyroid as well as checking radioactive iodine uptake. high uptake plus positive antibodies means primary / autoimmune hyperthyroid. high uptake plus negative antibodies can mean plummer's syndrome, toxic thyroid nodules that can stimulate thyroid hormone production. low uptake plus negative antibodies can indicate thyroiditis.
four types of thyroid cancer have been identified: papillary is the most common and has a relatively good prognosis. follicular is more malignant and makes up 15% of thyroid cancers. medullary involves proliferation of c-cells and subsequent elevation of calcitonin levels. anaplastic / undifferentiated type is the most rare and has the worst prognosis.
questions
physiology...
1. what are the three hormones that are in charge of calcium regulation and where are they secreted from?
2. what steps would be taken in order to make a diagnosis of hyperparathyroid from a patient with high calcium levels?
3. what are the four main actions of PTH?
4. what are the actions of calcitonin and where is it secreted from?
hyperparathyroid states...
5. what is 1º hyperparathyroidism usually due to?
6. what are the signs and symptoms of 1º hyperparathyroidism?
7. besides hyperparathyroidism, what are some other causes of hypercalcemia?
8. in general, how high or low are PTH levels in hypercalcemia that is not of parathyroid origin?
9. what is the most common cause of 2º hyperparathyroidism?
10. what is the mechanism of pathogenesis for 2º hyperparathyroidism?
11. what is the hallmark of 3º hyperparathyroidism?
hypoparathyroid...
12. what is the most common cause of hypoparathyroidism?
13. what are the signs / symptoms of hypoparathyroidism?
14. what are the classic PE findings for hypoparathyroidism?
15. describe the first sign from question 14.
16. describe the second sign from question 14.
thyroid physiology review...
17. which cells in which gland is TSH made in?
18. TSH levels are mainly regulated by...
19. what are the three proteins that carry thyroid hormones in the blood?
hypothyroidism intro...
20. what is the difference between primary, secondary, and tertiary hypothyroidism?
21. what is peripheral hypothyroidism?
22. what are some etiologies for primary hypothyroidism?
23. hypothyroid is the number one reversible cause of...
24. what is cretinism and what are its manifestations?
primary hypothyroidism...
25. which gender is hypothyroidism more common in?
26. what are the most common causes of adult hypothyroidism in the US and the world?
27. what is follicular hyperkeratosis and what is it due to?
28. what is a common PE finding for hypothyroidism?
29. what are the lab values for the thyroid hormones in hypothyroidism?
secondary hypothyroidism...
30. what is a condition associated with secondary hypothyroidism?
31. what are the signs / symptoms of a patient with secondary hypothyroidism?
32. what åre the typical lab values for a patient with secondary hypothyroidism?
33. what is a contraindication for thyroid hormone replacement therapy?
hyperthyroidism...
34. what are some of the symptoms of hyperthyroidism?
35. what are some PE findings for hyperthyroidism?
36. what is the most common cause of hyperthyroidism?
37. what is the mechanism for the condition in question 36?
38. what is a symptom associated with the condition in question 36 that manifests on the extremities?
39. how is the cause of hyperthyroidism determined diagnostically?
40. according to the method in question 39, primary hyperthyroid would be characterized by...
41. according to the method in question 39, plummer's syndrome would be characterized by...
42. according to the method in question 39, thyroiditis would be characterized by...
other thyroid pathologies...
43. what are the 4 types of thyroid cancer?
44. which thyroid cancer is the most common?
45. which is more malignant, follicular or papillary?
46. the medullary type is characterized by proliferation of which cell?
47. how does anaplastic thyroid cancer present?
answers
1. PTH from parathyroid, calcitonin from thyroid, and activated vitamin D from the kidneys.
2. recheck. check for high ionized calcium levels. check for high PTH levels.
3. stimulates osteoblastic activity
inhibits reabsorption of phosphate in the kidneys
stimulates reabsorption of calcium in the kidneys
stimulates activation of vitamin D in the kidneys
4. secreted from C cells of the thyroid, decreases serum calcium by decreasing bone resorption via osteoclasts.
5. parathyroid adenoma.
6. bones, stones, abdominal moans, groans.
7. multiple sclerosis, paget's disease, vitamin D intoxication, sarcoidosis.
8. low because of negative feedback to the parathyroid.
9. renal disease.
10. depressed serum calcium leads to overcompensation via PTH secretion.
11. development of autonomous hypersecretion of PTH, causing hypercalcemia.
12. surgically induced.
13. neuromuscular instability, parkinsons-like movements, tetany.
14. chvosek and trousseau's sign.
15. tapping around the TMJ causes contraction of muscles around the mouth or eyes.
16. "carpal pedal spasm" resulting from occluding blood supply to forearm for several minutes.
17. thyrotroph cells of the anterior pituitary.
18. T3 levels.
19. TBG, transthyretin, albumin.
20. primary is a dysfunction in secretion of the thyroid gland itself, secondary is dysfunction in secretion of TSH from AP, tertiary is dysfunction in secretion of TRH from hypothalamus.
21. peripheral resistance to thyroid hormones, or reduced T4 to T3 conversion, or excess rT3.
22. congenital
iodine deficiency related (goitrogens)
thyroid ablation
23. depression.
24. primary hypothyroid during the first few weeks of life, resulting in mental retardation, short stature, puffy facial features, dry skin, myxedema.
25. females.
26. autoimmune, and iodine deficiency.
27. red bumps over the hair follicles on the outer arm, due to vitamin A synthesis defect.
28. diminished DTR's
29. high TSH, low T4.
30. sheehan's.
31. symptoms of deficiency of other pituitary hormones, or intracranial mass.
32. high TRH, low TSH, low T4 and T3.
33. adrenal cortisal insufficiency / addison's, MI, thyrotoxicosis
34. heat intolerance
irritability
weight loss
exophthalmos
35. may have goiter
warm, moist skin
conjunctival injection
high cardiac output
tremor
fast DTR's
36. grave's disease.
37. antibody against TSH receptor causes constant stimulation of thyroid gland.
38. skin thickening on the legs: pretibial myxedema.
39. testing for antibodies to thyroid plus radioactive iodine uptake.
40. high uptake and positive antibodies.
41. high uptake and negative antibodies.
42. low uptake and negative antibodies.
43. papillary, follicular, medullary, anaplastic.
44. papillary.
45. follicular.
46. c cells that produce calcitonin.
47. rapid and painful enlargement of the thyroid, poor prognosis.
Showing posts with label thyroid. Show all posts
Showing posts with label thyroid. Show all posts
Monday, May 10, 2010
Saturday, March 20, 2010
lab dx II: thyroid function tests
a review of the thyroid in the context of lab diagnosis in the context of cramming for finals.
the synthesis of thyroid hormones begins in the follicles of the thyroid, filled with a protein rich colloid where iodine is incorporated into thyroglobulin molecules to form mostly T4 (90%) and T3 (10%, the biologically active form). the thyroid is stimulated to release T4/T3 by TSH, which is released by the pituitary via stimulation by TRH, which is released by the hypothalamus. once released, T4 is converted to T3 in the periphery and mediate cellular growth, differentiation and metabolism.
in the periphery T4 and T3 are either free or bound; if bound they are most likely bound to TBG, or TBPA (20% of T4), or albumin (10% T4, 30% T3). T4 is converted to T3 mainly in the liver and skeletal muscle, which then has a ten times greater affinity for nuclear receptors within cells which mediate metabolic activity. only about 40% of T4 is converted directly to T3; the remaining T4 can be converted either to reverse T3 or T3AC, both of which are inactive isomers of T3 that can be activated by intestinal sulfatases.
more detail on T4: when in the blood, T4 is mostly bound (99.98%) rather than free. thus when levels of the main carrier for T4 goes up, TBG (as can happen in pregnancy), T4 levels may appear to be falsely elevated- however free, unbound T4 levels will remain normal. T4 levels less than 2.0 ug/mL are equivalent to "myxedema hypothyroidism" and can be caused by primary, secondary, or tertiary hypothryoidism-- lack of production at the level of the thyroid, pituitary, or hypothalamus, respectively. T4 greater than 20 ug/ml is considered a "thyroid storm" and can be from primary hyperthyroid (most commonly grave's disease), acute thyroiditis, struma ovarii, or a TBG increase.
a test that can provide an indirect measurement of T4 is the T3 resin uptake test, which measures relative saturation of TBG- because the T4 in the blood is nearly all bound to TBG. if T4 levels are elevated in hyperthyroidism or struma ovarii, TBG will be more saturated and not able to accommodate much T3, which will result in higher levels of T3 bound to resin rather than TBG-- leading to a high T3RU. conversely, hypothyroid states will leave TBG less saturated, allowing T3 to bind to it rather than to the resin-- leading to a low T3RU.
testing TSH levels is useful for differentiating between different types of hypothyroidism-- primary hypothyroid would present with high TSH levels and would not be responsive to exogenous TSH, whereas secondary or tertiary hypothyroid would have near zero TSH levels and would be responsive to exogenous TSH.
some more lab markers and what they indicate: total T3 levels (bound plus free) are useful for measuring hyperthyroidism. free T4 or T3 useful for patients with protein abnormalities. reverse T3 levels high in hyperthyroidism and with stressed physiology. autoantibodies can also be measured, to the thyroid gland (results in hyperthyroid), or TPO and thyroglobulin (hypothyroid).
primary hypo and hyperthyroid and most commonly caused by antibodies to the thyroid; in primary hyperthyroid, this results from defective suppressor genes which ultimately allow b cells to create anti TPO and TGLB antibodies. grave's can manifest with marked exophthalmos due to the targeting of TSH receptors in the retro orbital area by the anti thyroid antibodies. on the other end of the spectrum, hashimoto's is the result of an anti TPO antibody, and might initially present as hyperthyroidism, then progress to hypothyroidism with low T4, T3RU, and high TSH. compared to grave's, hashimoto's has a higher level of anti TPO antibodies.
questions
thyroid hormone synthesis...
1. what type of cell in the thyroid produces thyroid hormone?
2. what is contained inside the follicles?
3. what do the parafollicular cells produce?
4. what is the role of the hypothalamus and pituitary in thyroid function?
5. what form is thyroid hormone secreted in and which form is biologically active?
6. what is the role of TPO in the colloid of the follicles?
7. what is the T4:T3 ratio in the colloid?
8. what are the three fundamental physiological processes that thyroid hormones affect?
thyroid hormones in the wilderness...
9. which protein binds most T3 and T4 in the blood?
10. what does TBPA carry?
11. what does albumin carry?
12. which tissues does T4 conversion generally take place in?
13. compare the biological potency of T4 vs. T3.
14. under normal circumstances, what is T4 converted into besides T3?
15. are T3s and T3AC biologically active?
T4...
16. what percentage of T4 is protein bound?
17. what conditions might show falsely elevated T4 levels? how does this appear as a lab result?
18. what are congenital defects that can result from low T4 levels?
19. what are the critical high and low values for T4?
20. what are the most common factors for increased T4 levels?
21. what are the most common causes for decreased T4 levels?
T3RU...
22. what is T3RU a measure of?
23. what would be the T3RU for hyperthyroidism and why?
24. what would be the T3RU for hypothyroidism and why?
25. is T3RU better for assessing hyper or hypothyroidism?
26. what else can cause increased T3RU besides hyperthyroidism?
27. what else can cause decreased T3RU besides hypothyroidism?
28. what is the formula for FTI and what does it represent?
TSH...
29. TSH aids in the diagnosis of...
30. what are TSH levels in primary, secondary, tertiary hypothyroidism?
31. describe the diurnal variation seen in TSH levels.
32. what causes increased TSH levels?
33. what causes decreased TSH levels?
34. what does TRH assess?
total T3, free T4/T3, reverse T3, thyroid antibodies...
35. are total T3 levels better for diagnosing hyper or hypothyroidism?
36. what is T3 toxicosis and how does it present?
37. when are free T4 or T3 levels useful to measure?
38. when are reverse T3 levels high?
39. what did Dr. Dennis Wilson, MD propose in relation to reverse T3?
40. what are some examples of autoantibodies to the thyroid gland?
grave's and hashimoto's...
41. what is grave's disease?
42. what is the "suppressor defect" in the context of grave's disease?
43. what are the autoantibodies that are commonly seen in grave's?
44. why does grave's disease manifest with exophthalmos?
45. what is hashimoto's?
46. which gender is more likely to get hashimoto's?
47. early stages of hashimotos might present as...
48. early labs of hashimotos might show...
49. compare the antibody titer levels in grave's vs. hashimotos.
euthyroid sick syndrome...
50. what is ESS?
51. what are three specific physiogical processes that can cause ESS?
answers
1. follicular epithelium.
2. protein rich colloid, high in thyroglobulin.
3. calcitonin.
4. hypothalamus releases TRH, which stimulates release of TSH from pituitary, which is the main mediator of thyroid gland function.
5. 90% secreted as T4, then converted to biologically active T3 in cells.
6. thyroid peroxidases oxidize iodide to iodine for use in T3/T4.
7. 5:1.
8. cellular growth, differentiation, metabolism.
9. TBG, 70%.
10. 20% of T4 and no T3.
11. 10% of T4, 30% T3.
12. liver and skeletal muscle.
13. T3 has a 10 times greater affinity for DNA transcription factor receptors than T4.
14. 40% T3, 20% reverse T3, 20%T3S.
15. not unless they encounter sulfatases in the GI tract.
16. 99.98%.
17. pregnancy and oral contraceptives. high TBG but normal free T4.
18. cretinism, mental retardation.
19. less than 2.0 ug/ml- myxedema coma
more than 20 ug/ml- thyroid storm
20. primary hyperthyroid (grave's disease)
acute thyroiditis
struma ovarii
TBG increase
21. primary hypothyroid (hashimoto's)
secondary hypothyroid (pituitary dysfx)
tertiary hypothyroid (hypothalamus dysfx)
protein malnutrition
22. an indirect measurement of the amount of free binding sites on TBG and TBPA.
23. hyperthyroidism -> high T4 levels -> more saturated TBG -> more T3 bound to resin instead of TBG -> higher T3RU.
24. hypothyroidism -> low T4 -> more unsaturated TBG -> more T3 bound to TBG -> lower T3RU.
25. better for hyperthyroidism-- only 60% accurate for hypo.
26. hypoproteinemia, struma ovarii.
27. any factor that increases TBG like pregnancy, hepatitis / cirrhosis.
28. FTI=(T4*T3RU)/100, is an estimate for total T4 levels.
29. hypothyroidism.
30. primary- high TSH. secondary + tertiary: TSH almost 0.
31. lowest at 10AM, highest at 10PM.
32. primary hypothyroid
thyroiditis
thyroid agenesis
congenital cretinism
excess iodine intake
33. secondary, tertiary hypothyroid
hyperthyroid
self medication with T4
34. responsiveness of anterior pituitary to secrete TSH upon injection of TRH.
35. hyperthyroid.
36. normal T4 and high T3.
37. useful to measure thyroid functioning in patients who have protein abnormalities.
38. hyperthyroidism.
39. a stressed body might have a predisposition to converting T4 to rT3 instead of T3.
40. thyroid stimulating antibodies, resulting in hyperthyroidism. anti TPO antibody, inhibits thyroid peroxidase. anti TGLB, inhibits thyroglobulin.
41. most common form of hyperthyroid that results from TSI's stimulating TSHR's.
42. a defect in a suppressor gene allows t helper cells to interact with thyroid antigens, which then stimulate b cells to create thyroid stimulating immunoglobulin.
43. anti TPO, anti TGLB.
44. the TSH antibodies produced in grave's bind to TSH receptors in the retroorbital tissues which produces inflammation and swelling.
45. the most common cause of acquired hypothyroid.
46. females 8:1.
47. hyperthyroid.
48. normal T4 and TSH + anti TPO ab.
49. much higher in hashimotos.
50. thyroid dysfunction secondary to nonthyroidal systemic illness.
51. decreased peripheral conversion of T4 to T3,
decreased clearance of reverse T3
decreased binding of thyroid hormones to TBG
[conversion, clearance, binding]
the synthesis of thyroid hormones begins in the follicles of the thyroid, filled with a protein rich colloid where iodine is incorporated into thyroglobulin molecules to form mostly T4 (90%) and T3 (10%, the biologically active form). the thyroid is stimulated to release T4/T3 by TSH, which is released by the pituitary via stimulation by TRH, which is released by the hypothalamus. once released, T4 is converted to T3 in the periphery and mediate cellular growth, differentiation and metabolism.
in the periphery T4 and T3 are either free or bound; if bound they are most likely bound to TBG, or TBPA (20% of T4), or albumin (10% T4, 30% T3). T4 is converted to T3 mainly in the liver and skeletal muscle, which then has a ten times greater affinity for nuclear receptors within cells which mediate metabolic activity. only about 40% of T4 is converted directly to T3; the remaining T4 can be converted either to reverse T3 or T3AC, both of which are inactive isomers of T3 that can be activated by intestinal sulfatases.
more detail on T4: when in the blood, T4 is mostly bound (99.98%) rather than free. thus when levels of the main carrier for T4 goes up, TBG (as can happen in pregnancy), T4 levels may appear to be falsely elevated- however free, unbound T4 levels will remain normal. T4 levels less than 2.0 ug/mL are equivalent to "myxedema hypothyroidism" and can be caused by primary, secondary, or tertiary hypothryoidism-- lack of production at the level of the thyroid, pituitary, or hypothalamus, respectively. T4 greater than 20 ug/ml is considered a "thyroid storm" and can be from primary hyperthyroid (most commonly grave's disease), acute thyroiditis, struma ovarii, or a TBG increase.
a test that can provide an indirect measurement of T4 is the T3 resin uptake test, which measures relative saturation of TBG- because the T4 in the blood is nearly all bound to TBG. if T4 levels are elevated in hyperthyroidism or struma ovarii, TBG will be more saturated and not able to accommodate much T3, which will result in higher levels of T3 bound to resin rather than TBG-- leading to a high T3RU. conversely, hypothyroid states will leave TBG less saturated, allowing T3 to bind to it rather than to the resin-- leading to a low T3RU.
testing TSH levels is useful for differentiating between different types of hypothyroidism-- primary hypothyroid would present with high TSH levels and would not be responsive to exogenous TSH, whereas secondary or tertiary hypothyroid would have near zero TSH levels and would be responsive to exogenous TSH.
some more lab markers and what they indicate: total T3 levels (bound plus free) are useful for measuring hyperthyroidism. free T4 or T3 useful for patients with protein abnormalities. reverse T3 levels high in hyperthyroidism and with stressed physiology. autoantibodies can also be measured, to the thyroid gland (results in hyperthyroid), or TPO and thyroglobulin (hypothyroid).
primary hypo and hyperthyroid and most commonly caused by antibodies to the thyroid; in primary hyperthyroid, this results from defective suppressor genes which ultimately allow b cells to create anti TPO and TGLB antibodies. grave's can manifest with marked exophthalmos due to the targeting of TSH receptors in the retro orbital area by the anti thyroid antibodies. on the other end of the spectrum, hashimoto's is the result of an anti TPO antibody, and might initially present as hyperthyroidism, then progress to hypothyroidism with low T4, T3RU, and high TSH. compared to grave's, hashimoto's has a higher level of anti TPO antibodies.
questions
thyroid hormone synthesis...
1. what type of cell in the thyroid produces thyroid hormone?
2. what is contained inside the follicles?
3. what do the parafollicular cells produce?
4. what is the role of the hypothalamus and pituitary in thyroid function?
5. what form is thyroid hormone secreted in and which form is biologically active?
6. what is the role of TPO in the colloid of the follicles?
7. what is the T4:T3 ratio in the colloid?
8. what are the three fundamental physiological processes that thyroid hormones affect?
thyroid hormones in the wilderness...
9. which protein binds most T3 and T4 in the blood?
10. what does TBPA carry?
11. what does albumin carry?
12. which tissues does T4 conversion generally take place in?
13. compare the biological potency of T4 vs. T3.
14. under normal circumstances, what is T4 converted into besides T3?
15. are T3s and T3AC biologically active?
T4...
16. what percentage of T4 is protein bound?
17. what conditions might show falsely elevated T4 levels? how does this appear as a lab result?
18. what are congenital defects that can result from low T4 levels?
19. what are the critical high and low values for T4?
20. what are the most common factors for increased T4 levels?
21. what are the most common causes for decreased T4 levels?
T3RU...
22. what is T3RU a measure of?
23. what would be the T3RU for hyperthyroidism and why?
24. what would be the T3RU for hypothyroidism and why?
25. is T3RU better for assessing hyper or hypothyroidism?
26. what else can cause increased T3RU besides hyperthyroidism?
27. what else can cause decreased T3RU besides hypothyroidism?
28. what is the formula for FTI and what does it represent?
TSH...
29. TSH aids in the diagnosis of...
30. what are TSH levels in primary, secondary, tertiary hypothyroidism?
31. describe the diurnal variation seen in TSH levels.
32. what causes increased TSH levels?
33. what causes decreased TSH levels?
34. what does TRH assess?
total T3, free T4/T3, reverse T3, thyroid antibodies...
35. are total T3 levels better for diagnosing hyper or hypothyroidism?
36. what is T3 toxicosis and how does it present?
37. when are free T4 or T3 levels useful to measure?
38. when are reverse T3 levels high?
39. what did Dr. Dennis Wilson, MD propose in relation to reverse T3?
40. what are some examples of autoantibodies to the thyroid gland?
grave's and hashimoto's...
41. what is grave's disease?
42. what is the "suppressor defect" in the context of grave's disease?
43. what are the autoantibodies that are commonly seen in grave's?
44. why does grave's disease manifest with exophthalmos?
45. what is hashimoto's?
46. which gender is more likely to get hashimoto's?
47. early stages of hashimotos might present as...
48. early labs of hashimotos might show...
49. compare the antibody titer levels in grave's vs. hashimotos.
euthyroid sick syndrome...
50. what is ESS?
51. what are three specific physiogical processes that can cause ESS?
answers
1. follicular epithelium.
2. protein rich colloid, high in thyroglobulin.
3. calcitonin.
4. hypothalamus releases TRH, which stimulates release of TSH from pituitary, which is the main mediator of thyroid gland function.
5. 90% secreted as T4, then converted to biologically active T3 in cells.
6. thyroid peroxidases oxidize iodide to iodine for use in T3/T4.
7. 5:1.
8. cellular growth, differentiation, metabolism.
9. TBG, 70%.
10. 20% of T4 and no T3.
11. 10% of T4, 30% T3.
12. liver and skeletal muscle.
13. T3 has a 10 times greater affinity for DNA transcription factor receptors than T4.
14. 40% T3, 20% reverse T3, 20%T3S.
15. not unless they encounter sulfatases in the GI tract.
16. 99.98%.
17. pregnancy and oral contraceptives. high TBG but normal free T4.
18. cretinism, mental retardation.
19. less than 2.0 ug/ml- myxedema coma
more than 20 ug/ml- thyroid storm
20. primary hyperthyroid (grave's disease)
acute thyroiditis
struma ovarii
TBG increase
21. primary hypothyroid (hashimoto's)
secondary hypothyroid (pituitary dysfx)
tertiary hypothyroid (hypothalamus dysfx)
protein malnutrition
22. an indirect measurement of the amount of free binding sites on TBG and TBPA.
23. hyperthyroidism -> high T4 levels -> more saturated TBG -> more T3 bound to resin instead of TBG -> higher T3RU.
24. hypothyroidism -> low T4 -> more unsaturated TBG -> more T3 bound to TBG -> lower T3RU.
25. better for hyperthyroidism-- only 60% accurate for hypo.
26. hypoproteinemia, struma ovarii.
27. any factor that increases TBG like pregnancy, hepatitis / cirrhosis.
28. FTI=(T4*T3RU)/100, is an estimate for total T4 levels.
29. hypothyroidism.
30. primary- high TSH. secondary + tertiary: TSH almost 0.
31. lowest at 10AM, highest at 10PM.
32. primary hypothyroid
thyroiditis
thyroid agenesis
congenital cretinism
excess iodine intake
33. secondary, tertiary hypothyroid
hyperthyroid
self medication with T4
34. responsiveness of anterior pituitary to secrete TSH upon injection of TRH.
35. hyperthyroid.
36. normal T4 and high T3.
37. useful to measure thyroid functioning in patients who have protein abnormalities.
38. hyperthyroidism.
39. a stressed body might have a predisposition to converting T4 to rT3 instead of T3.
40. thyroid stimulating antibodies, resulting in hyperthyroidism. anti TPO antibody, inhibits thyroid peroxidase. anti TGLB, inhibits thyroglobulin.
41. most common form of hyperthyroid that results from TSI's stimulating TSHR's.
42. a defect in a suppressor gene allows t helper cells to interact with thyroid antigens, which then stimulate b cells to create thyroid stimulating immunoglobulin.
43. anti TPO, anti TGLB.
44. the TSH antibodies produced in grave's bind to TSH receptors in the retroorbital tissues which produces inflammation and swelling.
45. the most common cause of acquired hypothyroid.
46. females 8:1.
47. hyperthyroid.
48. normal T4 and TSH + anti TPO ab.
49. much higher in hashimotos.
50. thyroid dysfunction secondary to nonthyroidal systemic illness.
51. decreased peripheral conversion of T4 to T3,
decreased clearance of reverse T3
decreased binding of thyroid hormones to TBG
[conversion, clearance, binding]
Wednesday, June 3, 2009
organ systems III: thyroid
this lecture (sadly, dr. brons' last lecture during our time here) covered the thyroid anatomy and thyroid hormones release and physiological effects on the body. the thyroid hormone is situated between the thyroid cartilage and the 6th tracheal cartilage ring and is composed of functional units called follicles. these follicles are vesicles that are lined with cuboidal cells which take in iodine and secrete it, along with thyroglobulin, into the lumen of the follicles. in the lumen, iodine combines with thyroglobulin and tyrosine to form mono and di-iodotyrosine, which can be combined to form the main thyroid hormones T3 and T4, which are stored in the lumen of the follicles.
the release of T3 and T4 from the thyroid gland is mediated by the HPA axis; the hypothalamus releases TRH (thyrotropin releasing hormone) into the portal veins and anterior pituitary, which then releases TSH (thyroid stimulating hormone) into the circulation. the thyroid reacts to TSH by endocytosing T3/T4 from the lumen into follicle cells, where thryoglobulin is removed from T3/T4 via phagolysosomes. T3/T4 then enter general circulation in the approximate ratio of 10:1 T4:T3. high T3 levels allow for feedback inhibition of the hypothalamus, causing it to downregulate TRH receptor sites as well as disrupting synthesis of TSH, homeostatically lowering T3 levels.
in peripheral cells, T4 is converted to T3; T3 has a host of effects on virtually all organs and tissues in the body. on a cellular level, it functions as a modulator of cell metabolism (rather than an on-off switch, it simply amplifies existing metabolic processes) by acting as a transcription factor which can upregulate certain metabolic proteins; such as the ATP-ase Na+/K+ pump. the net effect of T3 on cells is to increase basal metabolic rate, oxidative metabolism (except in the brain, spleen, and testes) by increasing O2 consumption, facilitating hormonal actions on metabolic fuels (such as glucose, fatty acids, etc), and increasing cardiac output by upregulating beta-receptors. due to this close relationship to metabolism, the release of thyroid stimulating hormones is regulated by body temperature; higher body temperatures will inhibit release of TSH and lower body temperatures will stimulate TSH release.
hyperthyroidism is an excess production of T3/T4 and the accompanying metabolic frenzy, and is either caused by reduced feedback inhibition or an immune dysfunction where antibodies produced against the thyroid stimulates excess release of T3/T4; in this case, the high levels of T3/T4 would cause feedback inhibition and thus low levels of TSH. hyperthyroidism results in a goiter due to hyperplasia of thyroid cells, heat intolerance, weight loss, exophthalamos, nervousness, irritability, tachycardia, arrhythmia. hypothyroidism is the opposite condition of low T3/T4 levels which can be the result of autoimmune destruction of thryoid, iodine deficiency, or excess consumption of goitrogens. the symptoms include lethargy/sluggishness, colloid goiter, cold intolerance, delayed tendon reflexes, high cholesterol, hair loss, enlarged liver/kidney/tongue, and myxedema, among other things.
questions
thyroid anatomy and functional anatomy...
1. what is the endocrine axis that regulates release of thyroid hormone?
2. what is TRH? how is it released?
3. what is TSH? how is it released?
4. how does the thyroid respond to TSH?
5. where is the thyroid gland located?
6. what is the functional unit of the thyroid and what does it consist of?
T3, T3 synthesis, release, feedback...
7. describe the synthesis of T3 and T4.
8. how long can T3 and T4 be stored in the lumen of thyroid follicles?
9. describe the release of T3 and T4 from the thyroid into the blood.
10. what is the ratio of T4 to T3 at release from the thyroid?
11. in cells, what happens to T4?
12. describe the feedback inhibition of T3.
13. how does temperature affect T3/T4 release?
physiological and metabolic effects of T3...
14. which organs does T3 affect?
15. describe the role that T3 plays in regulating cellular functioning.
16. what is cretinism and what does it result in?
17. in peripheral cells, T3 enhances...
18. in which tissues does T3 not enhance oxidative metabolic functioning?
19. describe T3's effects on metabolism.
pathologies...
20. what is hyperthyroidism and what are its causes?
21. describe relative levels of T3/T4 and TSH in hyperthyroidism that results from autoimmune dysfunction.
22. what are some of the symptoms of hyperthyroidism?
23. what is hypothyroidism and what are its causes?
24. describe the relative levels of T3/T4 and TSH in hypothyroidism.
25. what are the symptoms of hypothyroidism?
answers
1. HPA axis.
2. thyrotropin releasing hormone is released from the PVN of the hypothalamus into the portal veins and anterior pituitary.
3. thryoid stimulating hormone is released from the anterior pituitary into general circulation.
4. by releasing T3 and T4 into the circulation.
5. between the thyroid cartilage to the 6th tracheal cartilage ring.
6. a follicle which is a vescicle surrounded by cuboidal cells that incorporate iodine and synthesize thyroglobulin, and a colloid interior where T3 and T4 are synthesized and stored, bound to thyroglobulin.
7. iodine is pumped into follicular cells and subsequently into the lumen of the follicles, along with thyroglobulin. in the lumen, thyroglobulin is combined with iodine and tyrosine to form mono and di-iodo tyrosine (MIT and DIT), and T3 and T4 are formed by combining MIT and DIT or two DIT's.
8. 2-3 months.
9. T3 and T4 are endocytosed back into follicle cells where the thyroglobulin is degraded into amino acids via phagolysosomes. T3 and T4 are then released into the circulation.
10. 10:1
11. it is converted to T3.
12. high T3 levels can act on the anterior pituitary to downregulate TRH receptors as well as inhibiting signal transduction in the TSH pathway, ultimately reducing the level of T3/T4 that is released from the thyroid.
13. high temperature inhibit T3/T4 release and cold temperatures stimulate T3/T4 release via hypothalamic temperature centers.
14. all organs.
15. acts as a modulator of cell function rather than an on/off switch.
16. an early thyroid deficiency; abnormal development of bones and CNS. results in stunted bones, malformation of facial bones and mental retardation.
17. basal metabolic rate, oxidative metabolism, upregulation of ATP-ase sodium/potassium pump.
18. brain, spleen, testes.
19. increases O2 consumption, facilitates hormonal actions on metabolic fuels (glucose, lipids, etc.), increases cardiac output by upregulating beta-receptors.
20. increased synthesis of T3/T4, caused by reduced feedback inhibition or autoimmune dysfunction, where antibodies to thyroid gland stimulate excess release of T3/T4.
21. high T3/T4 levels and low TSH levels due to feedback inhibition of the anterior pituitary.
22. goiter due to hyperplasia of thyroid cells, heat intolerance, weight loss, exophthalamos, nervousness, irritability, tachycardia, arrhythmia.
23. decreased synthesis of T3/T4 due to autoimmune destruction of thyroid, iodine deficiency, or goitrogens in the diet such as turnips or cabbage (but only in ridiculous, comical quantities according to dr. brons)
24. low levels of T3/T4 but high levels of TSH; results in increased colloid volume in thyroid due to synthesis and storage of T3/T4 without release.
25. colloid goiter, cold intolerance, fatigue/somnolescence, delayed tendon reflexes, bradycardia, high cholesterol, hair loss, enlarged liver/kidney/tongue, myxedema (mucopolysaccharide gel in skin osmotically holding water).
the release of T3 and T4 from the thyroid gland is mediated by the HPA axis; the hypothalamus releases TRH (thyrotropin releasing hormone) into the portal veins and anterior pituitary, which then releases TSH (thyroid stimulating hormone) into the circulation. the thyroid reacts to TSH by endocytosing T3/T4 from the lumen into follicle cells, where thryoglobulin is removed from T3/T4 via phagolysosomes. T3/T4 then enter general circulation in the approximate ratio of 10:1 T4:T3. high T3 levels allow for feedback inhibition of the hypothalamus, causing it to downregulate TRH receptor sites as well as disrupting synthesis of TSH, homeostatically lowering T3 levels.
in peripheral cells, T4 is converted to T3; T3 has a host of effects on virtually all organs and tissues in the body. on a cellular level, it functions as a modulator of cell metabolism (rather than an on-off switch, it simply amplifies existing metabolic processes) by acting as a transcription factor which can upregulate certain metabolic proteins; such as the ATP-ase Na+/K+ pump. the net effect of T3 on cells is to increase basal metabolic rate, oxidative metabolism (except in the brain, spleen, and testes) by increasing O2 consumption, facilitating hormonal actions on metabolic fuels (such as glucose, fatty acids, etc), and increasing cardiac output by upregulating beta-receptors. due to this close relationship to metabolism, the release of thyroid stimulating hormones is regulated by body temperature; higher body temperatures will inhibit release of TSH and lower body temperatures will stimulate TSH release.
hyperthyroidism is an excess production of T3/T4 and the accompanying metabolic frenzy, and is either caused by reduced feedback inhibition or an immune dysfunction where antibodies produced against the thyroid stimulates excess release of T3/T4; in this case, the high levels of T3/T4 would cause feedback inhibition and thus low levels of TSH. hyperthyroidism results in a goiter due to hyperplasia of thyroid cells, heat intolerance, weight loss, exophthalamos, nervousness, irritability, tachycardia, arrhythmia. hypothyroidism is the opposite condition of low T3/T4 levels which can be the result of autoimmune destruction of thryoid, iodine deficiency, or excess consumption of goitrogens. the symptoms include lethargy/sluggishness, colloid goiter, cold intolerance, delayed tendon reflexes, high cholesterol, hair loss, enlarged liver/kidney/tongue, and myxedema, among other things.
questions
thyroid anatomy and functional anatomy...
1. what is the endocrine axis that regulates release of thyroid hormone?
2. what is TRH? how is it released?
3. what is TSH? how is it released?
4. how does the thyroid respond to TSH?
5. where is the thyroid gland located?
6. what is the functional unit of the thyroid and what does it consist of?
T3, T3 synthesis, release, feedback...
7. describe the synthesis of T3 and T4.
8. how long can T3 and T4 be stored in the lumen of thyroid follicles?
9. describe the release of T3 and T4 from the thyroid into the blood.
10. what is the ratio of T4 to T3 at release from the thyroid?
11. in cells, what happens to T4?
12. describe the feedback inhibition of T3.
13. how does temperature affect T3/T4 release?
physiological and metabolic effects of T3...
14. which organs does T3 affect?
15. describe the role that T3 plays in regulating cellular functioning.
16. what is cretinism and what does it result in?
17. in peripheral cells, T3 enhances...
18. in which tissues does T3 not enhance oxidative metabolic functioning?
19. describe T3's effects on metabolism.
pathologies...
20. what is hyperthyroidism and what are its causes?
21. describe relative levels of T3/T4 and TSH in hyperthyroidism that results from autoimmune dysfunction.
22. what are some of the symptoms of hyperthyroidism?
23. what is hypothyroidism and what are its causes?
24. describe the relative levels of T3/T4 and TSH in hypothyroidism.
25. what are the symptoms of hypothyroidism?
answers
1. HPA axis.
2. thyrotropin releasing hormone is released from the PVN of the hypothalamus into the portal veins and anterior pituitary.
3. thryoid stimulating hormone is released from the anterior pituitary into general circulation.
4. by releasing T3 and T4 into the circulation.
5. between the thyroid cartilage to the 6th tracheal cartilage ring.
6. a follicle which is a vescicle surrounded by cuboidal cells that incorporate iodine and synthesize thyroglobulin, and a colloid interior where T3 and T4 are synthesized and stored, bound to thyroglobulin.
7. iodine is pumped into follicular cells and subsequently into the lumen of the follicles, along with thyroglobulin. in the lumen, thyroglobulin is combined with iodine and tyrosine to form mono and di-iodo tyrosine (MIT and DIT), and T3 and T4 are formed by combining MIT and DIT or two DIT's.
8. 2-3 months.
9. T3 and T4 are endocytosed back into follicle cells where the thyroglobulin is degraded into amino acids via phagolysosomes. T3 and T4 are then released into the circulation.
10. 10:1
11. it is converted to T3.
12. high T3 levels can act on the anterior pituitary to downregulate TRH receptors as well as inhibiting signal transduction in the TSH pathway, ultimately reducing the level of T3/T4 that is released from the thyroid.
13. high temperature inhibit T3/T4 release and cold temperatures stimulate T3/T4 release via hypothalamic temperature centers.
14. all organs.
15. acts as a modulator of cell function rather than an on/off switch.
16. an early thyroid deficiency; abnormal development of bones and CNS. results in stunted bones, malformation of facial bones and mental retardation.
17. basal metabolic rate, oxidative metabolism, upregulation of ATP-ase sodium/potassium pump.
18. brain, spleen, testes.
19. increases O2 consumption, facilitates hormonal actions on metabolic fuels (glucose, lipids, etc.), increases cardiac output by upregulating beta-receptors.
20. increased synthesis of T3/T4, caused by reduced feedback inhibition or autoimmune dysfunction, where antibodies to thyroid gland stimulate excess release of T3/T4.
21. high T3/T4 levels and low TSH levels due to feedback inhibition of the anterior pituitary.
22. goiter due to hyperplasia of thyroid cells, heat intolerance, weight loss, exophthalamos, nervousness, irritability, tachycardia, arrhythmia.
23. decreased synthesis of T3/T4 due to autoimmune destruction of thyroid, iodine deficiency, or goitrogens in the diet such as turnips or cabbage (but only in ridiculous, comical quantities according to dr. brons)
24. low levels of T3/T4 but high levels of TSH; results in increased colloid volume in thyroid due to synthesis and storage of T3/T4 without release.
25. colloid goiter, cold intolerance, fatigue/somnolescence, delayed tendon reflexes, bradycardia, high cholesterol, hair loss, enlarged liver/kidney/tongue, myxedema (mucopolysaccharide gel in skin osmotically holding water).
Subscribe to:
Posts (Atom)