13. Thyroid CIS

3. What special enzyme doe tissues hold to convert thyroid hormone to the active form? 4. Do individuals with hypothyroidism have issues with activating thyroid hormone?

3. Tissues contain deiodinases to convert T4 to T3 4. NO! People without thyroid function will have T3 upon treatment with T4 only

1. What would a graphic representation look like for someone with hyperthyroidism when challenged with radioactive iodine? 2. What about someone with hypothyroidism? Where is most of the iodine going?

Distribution of Radioactive Iodine Graphs 1. Check it out 2. going into the pee hole

Welcome

Here is a meme for your troubles... Go ahead and flip that deck back.

Here is a pic of a 4-yr/old with cretinism.

Made the point that between the two photos, thyroid hormone replacement has started with on the right and the child is already looking more alert and better muscle tone

If you want to know where the PTU will inhibit thyroid hormone production, you can check them out on the flip side

Steps 3. Oxidation of I-* - thyroid peroxidase 4. Organification of iodine into MIT and DIT*; MIT = monoiodothyronine, DIT = diiodothyronine 5. Coupling reaction*; DIT + DIT = T4, DIT + MIT = T3

What what type of hyperthyroidism would you see a high T4 levels with a high TSH? How would the condition be classified? Would you see a change in PRL in this case?

With a *thyrotroph adenoma*. We would have over production of TSH and thus T4; this would be considered a *secondary hyperthyroidism*. *NOPE*!! NOT HERE GUY! DONT THINK SO BUDDY!

Check out this figure for Euthyroid sick syndrome

this is a normal physiological response to severe illness.

The absence of iodine for an extended period of time will result in which changes to thyroid laboratory values? A. Increased TSH, Decreased T4 and T3 B. Increased TSH, T4, T3 C. No change in TSH, Decreased T4, T3 D. Decreased TSH, Increased T4 and T3.

*A.* We know that thyroid hormone would be deficient due the lack of iodine and the hypothalamus/pituitary axis would be increasing the amount of TSH to increase the amount of T4 and T3 in the blood.

Mrs. Omaya has low T4 and TSH. How would you classify her thyroid deficiency? A. Primary hypothyroidism B. Secondary hypothyroidism C. Tertiary hypothyroidism D. Tissue resistance to thyroid hormone

*B.* Loss of function of the pituitary gland.

A 35 y/o female presents with galactorrhea, amenorrhea, headaches, fatigue, and weight gain. Laboratory evaluation reveals the following: prolactin 58 ng/ml (nl, 2-25); free T4 0.2 ng/dL (nl, 4.5-12); TSH 100 mU/L (nl, 0.5-5.0). She has an enlarged pituitary gland on MRI scan. What is the probable diagnosis? A. Prolactinoma B. Hypothyroidism C. Silent thyroiditis D. Thyrotroph adenoma E. Median eminence laceration

*B.* T4 is low which stimulates the hypothalamus to increase thyroid hormone. *TRH increases, which then signals to not only increase TSH but PRL as well*; increase in PRL would inhibit GnRH and thus cause the amenorrhea and galactorrhea. TSH would increase. A is incorrect because we wouldnt see any changes in TSH and T4 levels in the body. C is incorrect, we would expect a low T4 but the TSH levels would also be VERY low. Should not see any increase in PRL. D is incorrect because you would see a high T4 level (one exception to hyperthyroidism). E. is incorrect because PRL would still be high (again, it is under negative control) with all the other levels being markedly decreased.

A 39 y/o HIV-positive male with Pneumocystis carinii pneumonia has the following serum thyroid hormone values: T4 = 4.0 µg/dL (nl, 4.5-12.0), T3 = 60 ng/dL (nl, 90-200), and TSH = 1.3 mU/L (nl, 0.5-5.0). What is the most likely endocrine diagnosis? A. Primary hypothyroidism B. Secondary hypothyroidism C. Euthyroid sick syndrome D. Thyroid hormone resistance E. Subacute thyroiditis from HIV infection

*C. In euthryoid sick syndrome* you would see drop in T4 and T3 with no change in TSH with a rise in rT3 in response to a serious illness. A would show with drastically increased TSH B would show decreased TSH D would be a genetic disorder with TRH, TSH, and thyroid hormone being very elevated E

Testing shows a suppressed TSH and an increased homogeneous radioactive iodine uptake. Which finding would be likely in the patient? A. Surreptitious use of thyroid hormone B. A painful thyroid gland C. Elevated thyroid stimulating immunoglobulins D. A low T3 E. A high thyroxine binding globulin (TBG)

*C.* This is Grave's disease A is incorrect (see next slide) B is incorrect and would see this in granulomatous thyroiditis (its viral) D is incorrect, we would see increased T3 E is incorrect, would see this in a few states, but most commonly see this in pregnancy.

What laboratory findings are expected (what would her TSH, T4 and T3 levels look like)?

*Increased TSH, decreased T4 and T3*. Due to low levels of T3 and T4 in the body, hypothalamus/pituitary gland are over producing thyrotopic stimulating hormone in order to increase T4 and T3; with the obliteration of the thyroid, it wouldnt react.

Administration of thyroid hormone to a patient with primary hypothyroidism will have which effect? A. Increase TSH levels B. Decrease TSH levels C. Increase iodide uptake by the thyroid D. Increase thyroglobulin levels E. Induce thyroid gland hyperplasia

*Warning! Long explanations! No need to read all of them if you already understand* *B.* The new thyroid hormone would feed back on the hypothalamus/pituitary axis to tell it that the T4 and T3 levels are sufficient and do not need TSH. A is incorrect because this is the opposite of what would happen as explained above. C is incorrect because Iodine intake would decrease due to orally administered thyroid hormone. D is incorrect due to lack of thyroid hormone being made in the thyroid gland, so there is no need for thyroglobulin to increase. E is incorrect because we would see atrophy in the thyroid instead of hyperplasia (it is no longer making thyroid hormone).

Lets review Sheehan's syndrome. -What is it? -How does the AP change throughout pregnancy? -What is the correlations with Mrs. Omaya's blood loss and this condition?

- postpartum pituitary necrosis; with the increased size there is an increased demand for O2 through the hypothalamic-hypophyseal portal system. - AP incrases due to increase in hypertrophy of lactotrophs. -due to the increased demand of O2 in the AP (because of hyperplasia and hypertrophy) the blood loos could hypoperfuse the AP and cause necrosis of the gland

If someone was hiding the fact they were taking extra thyroid hormone, what else would they present with (answer A from the previous card)?

-Atrophy of the thyroid gland -Low TSH levels -Wouldnt expect to see exophthalmous

Surgery for treatment of Grave's Disease -What are the draw backs of surgery of the thyroid gland?

-damage to the parathyroid gland -highly vascular organ which can increase the complications of the surgery.

*Thyroid Case #1* Karen is a 35 year-old female who complains of sweating, palpitations and a 15 lb weight loss over the past two months. Her vital signs are P 110, RR 15, BP 145/95, and T 37°C. On physical exam there is a small goiter. 1. What is the most likely diagnosis concerning thyroid function? 2. What other symptoms and signs would you expect to find?

1. *Hyperthyroidism*. Due to weight loss and palpitations. *Thyroid hormone raises metabolic rate and increases chrontropic and ionotropic effects on the heart.* 2. exophthalmos, anxiety, weight loss in-spite of good appetite, goiter, autoantibodies, amenorrhea, if *on hormonal birth control - would burn through birth control and could be ineffective*, thinning of hair, pretibial myxedema (Grave's dermopathy), tremors.

What is the difference between thyrotoxicosis and hyperthyroidism?

1. *Thyrotoxicosis*- elevation in thyroxine, triiodothyronine, or both, from any cause 2. *Hyperthyroidism*- causes of thyrotoxicosis in which the thyroid gland is actively overproducing thyroid hormone

What are the three different antibody interactions (binding patterns) on cell receptors and what do they cause?

1. Agonist antibody - cell stimulation 2. antagonist antibody - cell blockage 3. neutral antibody - differential signal transduction

*Developmental Role of Thyroid Hormone* 1. What does endemic iodine deficiency lead to? 2. What happens to mental state of infants with low thyroid hormone if hormone intervention isnt started within days of birth? Can it be corrected? 3. What happens to their growth? Can it be corrected?

1. Endemic iodine deficiency leads to cretinism 2. Mental disability- permanent if hormone replacement is not started within days of birth 3. Growth delay leads to dwarfism which can be partially corrected

*Grave's Disease* 1. What is the most common cause of Grave's disease? 2. What is the most common age group and gender it occurs in? 3. What is the triad of clinical finding for Grave's?

1. Hyperthyroid→ most common cause is Grave's Disease: 2. occurs more commonly in women age 20-40 3. Triad of clinical finding a. *Hyperthyroidism*- hyperfunctional, diffuse enlargement of the thyroid gland, TSH ↓ but T3, T4 and thyroid size ↑ b. Infiltrative ophthalmopathy with *exophthalmos* c. Localized, infiltrative dermopathy (*pretibial myxedema*)

*Hashimoto Thyroiditis* 1. (Inflammation/atrophy) of the thyroid gland. 2. Most common in what gender and age group? 3. T or F: this is the most common disorder of hypothyroidism, but only in iodine deficient areas. 4. What cell type attacks the thyroid gland in Hashimotos? What are the 4 molecules/cell receptors that autoantibodies are made against in the thyroid?

1. Inflammation of the thyroid gland 2. More common in women (age 45-65) 10:1 to 20:1. Clusters in families 3. FALSE: Most common disorder of hypothyroidism in iodine *sufficient* areas 4. T cell-mediated with presence of autoantibodies: Autoantibodies against: -thyroglobulin -*thyroid peroxidase* -TSH receptor -iodine transporter

*Thyroiditis* 1. What is this? 2. What are the 2 classifications of Thyroiditis?

1. Inflammation of the thyroid gland- compromised of a group of diverse conditions 2. Granulomatous thyroiditis 3. Subacute lymphocytic thyroiditis

1. What are normal levels of T3 and T4? 2. What is total serum T4 influenced by? (2 main things) 3. What is the normal free T4 levels?

1. Normal levels: -Total T4 5-12 μg/dL -T3 70-190 ng/dl 2. Total Serum T4 is influenced not only by the amount of hormone but also the amount of TBG 3. Free T4: normal 0.58-1.64 ng/dl; Low levels but can be assayed.

*Hypothyroidism* 1. Where are the points of interruption (primary, secondary, etc)? 2. What condition is characterized by primary hypothyroidism? 3. What cell type is acting on the thyroid to cause the hypothyroidism in #2? 4. How is it treated?

1. Points of interruption a. Thyroid gland- primary b. Pituitary- secondary c. Hypothalamus- tertiary d. Tissue resistance- rare 2. Hashimoto's (5-10% of population)- 3. T cell-mediated but antibodies can also be present (α-TPO) 4. Radioactive ablation of the thyroid

*8 Steps in Thyroid Hormone Synthesis Pathway* REVIEW 1. What is the first step of this pathway? 2. What ion is transported into the cell? With or against its concentration gradient? 3. What rxn does this ion undergo? By which enzyme? 4. What happens to the ion after step 3?

1. Synthesis of thyroglobulin (TG) and exocytosis to the lumen 2. Transport of I- into cell- against chemical and electrochemical gradients 3. Oxidation of I-* - thyroid peroxidase 4. Organification of iodine into MIT and DIT*; MIT = monoiodothyronine, DIT = diiodothyronine

1. How does T3 and T4 circulate in the blood (2 proteins)? 2. Which is the more active form of thyroid hormone? How much high affinity to the thyroid receptor than the other? What is the ratio of T3:T4?

1. T4 and T3 circulate bound to *thyroid-binding globulin (TBG)* and to a lesser extent *albumin* and *transthyretin (TTR)* -TBG buffers hormone levels in the blood -99.98% of T4 is bound in circulation and 99.5% of T3 is bound 2. T3 is the more active thyroid hormone as it has a higher affinity for thyroid receptor (10 fold); however the ratio of T4 to T3 is 10:1.

*Hyperthyroidism* 1. What do TSH levels look like in hyperthyroidism? What bout T4 levels? 2. What type of a disease is Grave's? 3. What is a "hot nodule"? 4. What is a toxic nodular goiter? 5. What imaging test can be used in the differential diagnosis for hyperthyroidism?

1. TSH will be decreased compared to normal and T4 will be increased compared to normal. 2. Grave's disease- autoimmune thyroid disease (0.5% of population) 3. Toxic adenoma "hot nodule"- overproduction of thyroid hormone by the nodule with low TSH and gland atrophy surrounding the nodule 4. Toxic nodular goiter (toxic multinodular goiter) 5. Radioactive iodine uptake scan can be useful

*Lymphocytic thyroiditis in transient thyrotoxicosis* 1. What is the change in thyroid function as lymphocytes begin to deposit in the thyroid? 2. Does the individual always regain thyroid function? 3. So how long does all of this take (weeks, months, years)?

1.Hyperthyroidism→ euthyroidism→ hypothyroidism→ euthyroidism 2. She said that no, they dont always regain thyroid function. 3. This is on a month timeline (take a look at the graph

*Thyroiditis* 3. What is Granulomatous thyroiditis? What is the progression of this condition? 4. What is subacute lymphocytic thyroiditis? What is an example of this?

3. viral in etiology with painful gland Hyperthyroidism→ euthyroidism→ hypothyroidism→ euthyroidism 4. *silent or painless thyroiditis* (believed to be autoimmune in etiology) with non-tender gland- transient. Ex postpartum thyroiditis

*Grave's Disease* 4. What type of disease is Grave's disease? What is acting on the thyroid to cause Grave's disease? Where are they specifically binding. 5. What eye changes take place? 6. What is the treatment? (4)

4. Autoimmune disease. Autoantibodies are directed against the TSH receptor (activating) (thyroid-stimulating antibodies- TSAb or TSI) 5. Eye changes: Volume of retro-orbital connective tissue and extraocular muscles is increased due to inflammation 6. Treatment: immune suppression, antibody clearance, *blocking thyroid function*, or *gland removal*

4. What is the normal serum TSH level? 5. What is the most valid and useful assessment of thyroid function?

4. Serum TSH: normal 0.5-5.0 μU/ml 5. The most valid and useful assessment of thyroid function is TSH

*8 Steps in Thyroid Hormone Synthesis Pathway* 5. What are the two subunits from #4 that make up T4? What about T3? 6. Where is the product of #5 then taken? 7. What is one of the final steps before the product is released into the blood stream? 8. *What is done with the left over product/byproducts?*

5. Coupling reaction*; DIT + DIT = T4, DIT + MIT = T3 6. Endocytosis of TG 7. Proteolysis of iodinated thyroglobulin; releases T3 and T4 8. Deiodination of residual MIT and DIT; recycling of I- and TG

*Hashimoto Thyroiditis* 5. Is this a rapid or gradual failure? 6. What are some symptoms that are in a common presentation? 7. What would TSH/TRH levels look like compared to T3 and T4? 8. What is the treatment?

5. Gradual thyroid failure 6. Classical presentation: goiter, skin change, peripheral edema, constipation, headache, fatigue, and anovulation 7. TSH and TRH ↑ but T3 and T4 ↓ 8. Treatment: replacement therapy with levothyroxine (T4)

*Hypothyroidism* 5. What condition is characterized by secondary hypothyroidism? What is an example of this? 6. What condition is characterized by tertiary hypothyroidism?

5. Secondary: Pituitary insufficiency - Sheehan Syndrome 6. Tertiary: Hypothalamic disease

*Case #3 Mrs. Omaya* cc: *Mrs. Omaya has been fatigued since giving birth 9 months ago.* Hx: She had been in good health up to and throughout the pregnancy (her second). She was able to nurse for only 1 month because her *milk production was scant.* She has *not begun menstruating* again since the delivery. She has been *unable to lose the weight* she gained during her pregnancy. She also notes that her *skin has become rough and her voice deeper since the birth of her child*. Mrs. Omaya's delivery was difficult and she *required a blood transfusion* with 6 units of blood. VS: T 37⁰C, BP 100/70 mm Hg, P 60/min PE: a coarse skin texture was present; physical exam otherwise normal.

Check out these lab values as well!

Check out this histology slide of lymphocytic thyroiditis in transitient thyrotoxicosis!

Crazy!

A 24 y/o pregnant women and her 3 y/o child are seen in a medical mission clinic in the Sudan. The child is short in stature, has a potbelly, enlarged protruding tongue, and is developmentally delayed. Iodine is prescribed for mother and child. In the absence of iodine during fetal development, biosynthesis of which hormone is inhibited resulting in the child's presentation? A. Insulin B. Cortisol C. Growth hormone D. Thyroid hormone E. IGF-I

D.

Also, what is happening here....?

I've heard of this type of thing, those crazy college boys getting all stir crazy....

Shalom!

Just a little Jew humor here...

Flip the deck!

Just for this one...

*Radioactive Thyroid Scans* 1. What would a thyroid scan look like for someone with diffuse thyroid enlargement? 2. What would it look like for someone with an enlarged thyroid with hyperfunctioning nodules? 3. What about a cold nodule?

Radioactive Thyroid Scans Check out these beaUTies!

A. Graves Disease B. Hypothyroidism

What is the thyroid conditions that these presentations are characterized by? A? B?

Josephine is 28 years old and comes to see you for a checkup 4 months after an uneventful pregnancy. She was seen by her obstetrician 6 weeks after delivery. At that time she felt *tired and was not sleeping well*, which she attributed to having to wake up frequently to breast-feed her baby. She *lost all the weight she had gained during the pregnancy*, and also noticed *marked hair loss*. In the last couple of weeks she has been *sleeping better but has been even more fatigued*, and now *complains of constipation*. On exam, you notice a *small goiter*, *delayed relaxation of the deep tendon reflexes and dry skin.* You suspect that she has a thyroid problem and you order a *TSH level, which is high at 15 mIU/L (normal 0.5-5)*. a. what is the most likely diagnosis? b. Name one other condition that is also possible in this situation.

a. hypothyroidism b. Hoshimotos disease and postpardom thyroiditis (subacute lymphocitic thyroiditis)

c. Is a radioactive iodine scan helpful in this situation? d. What treatment may be offered to this patient?

c. No, she is breastfeeding AND the thyroid is underproducing so it wouldnt be a great test to use. d. thyroid replacement

A couple of years later, Karen comes back to see you. Since her last visit 2 years ago, *she has been on thyroid hormone replacement*. A blood test done 2 months after that visit had shown *normal thyroid hormone levels*, and she has not seen a physician since that time. *She had been feeling well until the last 2 or 3 months*, when she began *having sweating and palpitations*. She has been losing weight and attributes that to her regular exercise routine. She recalls having those symptoms when she was first diagnosed with hyperthyroidism and is *concerned that she may need to be treated for this again*. On exam, you notice *lid lag, tremor and a fast pulse*. A blood test shows a suppressed TSH level of 0.03. i)What additional findings on physical exam would be present in each of the following possibilities? a. Recurrence of hyperthyroidism b. Over-replacement with thyroid hormone ii)What tests may be helpful in establishing the diagnosis in each case?

i) a. enlarged thyroid, could do another radioactive iodine uptake, check levels of the thyroid stimulating immunoglobulins. b. *check for gland atrophy* would indicate that she is not struggling with Grave's anymore and that she is being over-replaced with thyroid hormone. *Check TSH levels*. ii) TSH, TSI levels, radioactive iodine uptake

Karen returns to see you 6 months later. She was treated with radioactive iodine 5 months before. She reports that many of her previous symptoms subsided within a few weeks, and she felt great for a couple of months (so she did not make an appointment to see you sooner, as had been recommended) but she is now complaining of lethargy and fatigue. i) What is the radioactive iodine for? iI) What is the likely diagnosis? iiI) Which additional symptoms and signs would be likely to be found at this time?

i) used to kill off the thyroid ii) hypothyroidism iii) weight gain, cold intolerance, constipation (changes in GI), brittle hair and dry skin, increased edema, anovulation with amenorrhea