Thyroid

Question 1

What are the antibodies against, in Grave’s disease?

Answer 1

In graves disease, the antibodies are against TSH receptor. But these antibodies STIMULATE TSH—-> hence, there’s ↑ in synthesis as well as release of thyroid hormone (high yield, because it increase BOTH)

It’s a type 2 HSR!!!

Question 2

Histological findings of Grave’s disease?

Answer 2

1. Hyperplasia of follicles (the becomes so large—> the pink material space becomes large)
2. Scalloped colloid (The colloid inside the follicles makes white spaces with its lining, in the shape of scallops)—> HIGH YIELD.

Question 3

Pathophysiology of exophthalmos and pretibial myxedema in Grave’s disease?

Answer 3

Exophthalmos and pretibial myxedema in Grave’s disease—> is not due to increased thyroid in the body. But it is due to the fact that there are TSH receptors behind the eye and on the shin. TSH antibodies in Grave’s disease stimulate these TSH receptors too, and they start producing GAGs—->causes exophthalmos, and dough-like consistency on the shins upon examining (because this edema is not water, it is due to GAG)

Question 4

How does hyperthyroidism increase BMR?

HIGH-YIELD

Answer 4

Increase in BMR manifests as heat intolerance, ↑ sweating, weight loss.
(So obviously, they won’t ask you the cause of increased BMR but one of these things!!!)

↑ thyroid hormone——> INCREASED synthesis of Na+-K+ ATPase——> ↑ basal
metabolic rate—> ↑ calorigenesis

So either they can ask you about Increased calorigenesis, or the pump!!!

Question 5

3 causes of tachycardia in Hyperthyroidism?

High yield because again 2 step!

Answer 5

↑ number and sensitivity of β-adrenergic receptors (They can ask, how does hyperthryoidism cause an increase in sympathetic outflow/ anxiety/insomnia/fine tremors/hyperactivity/restlessness…and that’s how MF)
↑ expression of cardiac sarcolemmal ATPase
DECREASED expression of phospholamban

Question 6

Why is TSH low in Grave’s disease when the antibodies against TSH receptors are actually stimulatory?

Answer 6

TSH receptors are located in AP. back of eye, shins.
But TSH hormone is produced by Hypothalamus. and TRH receptors on Hypothalamus are inhibited due to increased amounts of thyroid in the blood. Hypothalamus then releases less TSH for it to bind less to TSH receptors on AP.

Question 7

What does Thyroid peroxidase do?

Which drug inhibits this enzyme?

Answer 7

It does 3 reactions. (All occur in follicular lumen)
>Oxidation,
>Organification of iodine,
>Coupling of monoiodotyrosine (MIT) and diiodotyrosine (DIT)

Thiomide/PTU/Methimazole.
HIGH YIELD—> PTU also inhibits the peripheral conversion (enzyme is 5-deiodinase) of T4 to T3 (parray hut tuu–> T4 mein sey aik nikaal daeta hai)

Question 8

What is wolff-chaikoff efect and what is its clinical use?

Answer 8

Wolff-Chaikoff effect is when upon taking KI (potassium Iodide)—->excess iodine temporarily turns off thyroid peroxidase production—> Decreases T3/T4 synthesis (protective autoregulatory effect).

This is used when radioactive iodine has been ingested by accident, patients are given KI (uworld)

Question 9

2 classic places where GAGs are deposited in HYPOTHYROIDISM?

Location of myxedema in Hypothyroidism

Answer 9

1>Larynx (causing deepening of lung)

2> Tongue (Protuberant tongue)

Question 10

Mutations associated with Papillary Carcinoma?

Answer 10

RET, PTC, BRAF

Just like pappii–> vomiting/BRAF

Question 11

RET mutation seen in ____________ carcinoma, has a clinical importance.

Answer 11

RET mutation is seen in MEDULLARY carcinoma (Also in Papillary)—> but in medullary carcinoma it has a major clinical significane and that is—> In any scenario, when a RET mutation is seen, thyroid is removed prophylactically because medullary carcinoma in a RET mutation scenario will lead to MEN2A, 2B. In these people, death occurs from medullary thyroid carcinoma so it is better to remove thyroid prophylactically.

Question 12

Follicular Carcinoma has a (hematogenous/lymphatic spread)?

Answer 12

Follicular carcinoma metastasize hematogenous.
There are only 4 carcinomas that metastasize hematogenous and they are:

> RCC via Renal Vein
Hepatocellular carcinoma via hepatic vein
Follicular Carcinoma
Choriocarcinoma

Question 13

Histology of each type 4 types of thyroid carcinoma?

Answer 13

Follicular—> Looks like follicular adenoma, but the difference is that carcinoma is not encapsulated, and FNA cannot tell a follicular adenoma and a follicular carcinoma apart. (HIGH-YIELD)

Papillary—> Papiiii and Moma adopts Orphan Annie-eye. Psammoma bodies seen, orphan annie eye nucleus (empty/white nuleus with slight rim of peripheral chromatin)

Medullary–> Malignant cell sheets in AMYLOID stroma.
(Amyloid deposition is seen because of INCREASED calcitonin in this.)

Anaplastic–> undifferentiated.

Question 14

Hurthle cells are what and seen in which condition?

Answer 14

Hurthle cells are basically LARGE follicular cells of thyroid, which are basically oncocytic cells—> oncocytic cells ka matlab very pinkish/eosinophilic and large due to altered mitochondrial accumulation.

Hurthle cells are seen in Hashimotos Thyroiditis.

Question 15

Hashimotos Thyroiditis can lead to which neoplasm?

Answer 15

Hashimotos Thyroiditis is associated with Non-hodgekin’s lymphoma/Marginal zone lymphoma.

Question 16

HLA and thyroid conditions?

Answer 16

Hashimotos–> HLA-DR3, HLA-DR5

Grave’s—>HLA-DR3 ,HLA-B8

Question 17

From the channel, of 12daysinmarch–>

How do you diagnose a thyroid problem? What’s your story?

Answer 17

First and foremost, look at the TSH.
TSH tells the thyroid is hyperthyroid, euthyroid or Hypothyroid.
Hyperthyroidism in Grave’s–> TSH is low.
Euthyroid—> TSH is normal—> can be in problems related to TBG.
In low, TBG—-> Normal TSH, Normal FREE T4. Decreased total T3,T4
in HIGH TBG—-> Normal TSH, Normal free T4. Increased total T3, T4.
Undetectable levels of TBG–> Hyperthyroidism with NO TBG—> Exogenous Thyroxine intake/levothyroxine abuse.

Question 18

Radioiodine uptake scan is done in a patient of hyperthyroid? How will the RIU scan appear in different conditions?

Answer 18

In RIU scan–> shows how much is the thyroid synthesizing Thyroid hormone.
>Grave’s disease–> lights up black like a christmas tree.
>Toxic adenoma—-> Small circular part turns black.
>Thyroiditis (Dequervein’s after a viral infection or lymphocytic in postpartum or autoimmune disease)—> shows no blackness.—> The hyperthryoidism in these conditions, is due to damaged thyroid follicles pouring out all of their contents—-> causes increased TBG too!
>Surreptitious use of thryroid hormone—> Nothing on RIU scan, and UNDETECTABLE levels of TBG.

Question 19

Exceptions in which TSH doesn’t tell the function of thyroid gland?

Answer 19

TSH increased–> T4 is also elevated (I KNOW SHOCKING)—> TSH secreting adenoma!
TSH decreased—–> T4 is also decreased—-> Hypopituitarism (Sheehan’s Syndrome)

Question 20

What do they want you to know about Proptosis?

Answer 20

Proptosis means Grave’s disease.
(Lid lag is a common sign of hyperthyroidism, but PROPTOSIS ONLY OF GRAVE’S DISEASE)

Proptosis/Orbitopathy is CYTOKINE-MEDIATED.
T cells secrete cytokines which stimulate fibroblasts to produce and deposit GAGs.