Thyroid Disorders B&B

Question 1

why does thyroiditis not fit into hypo- or hyper- thryoidism?

Answer 1

both occur, depending on the phase of the disease

initially, inflammation of the thyroid causes thyroid hormone to spill into the bloodstream, raising its levels

in response, however, the thyroid will begin to produce less (neg. feedback), and levels will fall

so both hyper- and hypo-thyroidism occur in thyroiditis

Question 2

myxedema

Answer 2

aka thyroid dermopathy: non-pitting edema of the skin, usually from hypothyroidism

due to hyaluronic acid deposits in the dermis - osmotic agent, pulls water out and causes swelling, usually face/periorbital

[however, note pretibial myxedema over the shins is seen in Grave’s disease, which is hyperthyroidism]

Question 3

myxedema, or thyroid dermopathy, is non-pitting edema of the skin due to _____ deposits

Answer 3

hyaluronic acid - osmotically active, draws water out and causes swelling

Question 4

where would you see skin swelling in patients with hypo- vs hyper-thyroidism, respectively, and what causes this condition?

Answer 4

myxedema: non-pitting edema due to hyaluronic acid deposits (osmotic agent)

hypothyroidism: facial/periorbital swelling

Grave’s disease (hyperthyroidism): pretibial myxedema (over the shins, special form of myxedema)

Question 5

myxedema coma

Answer 5

coma from hypothyroidism

recall myxedema = thyroid dermopathy, non-pitting edema due to hyaluronic acid deposits (osmotic agent)

Question 6

levels of ______ commonly rise in patients with hypothyroid myopathy

Answer 6

creatine kinase (CK) - serum levels usually rise in hypothyroidism, due to low levels of thyroid hormone

hypothyroid myopathy presents with weakness, cramps, myalgias

Question 7

how does hypothyroidism affect sodium levels and what is thought to be the cause of this?

Answer 7

hypothyroidism —> hyponatremia due to high levels of ADH (causes SIADH)

may lead to confusion

Question 8

what kind of drugs are levothyroxine (Synthroid) and liothyronine (Cytomel) and which one is preferred?

Answer 8

levothyroxine (Synthroid): synthetic T4 (thyroxine)
liothyronine (Cytomel): synthetic T3 (triiodothyronine)

levothyroxine preferred because T3 is rapidly absorbed from GI (causes mild hyperthyroidism symptoms like tachycardia, tremor), and T4 is converted to T3 anyway

dose is titrated until TSH is normal

Question 9

Patient is presenting with recent onset of lethargy, dyspnea on exertion, cold intolerance, weight gain with loss of appetite, and constipation. On exam, you note hyporeflexia, bilateral weakness, cool skin, brittle hair, and bradycardia. What are you thinking, and what is the best initial test to run?

Answer 9

hypothyroidism - metabolism slows down

best initial test for suspected thyroid disorder is TSH!
[hypothyroidism presents with HIGH TSH]

Question 10

Patient is presenting with recent weight loss despite increased appetite, diarrhea, and hyperactivity. They went to the ED one week ago for an episode of atrial fibrillation. On exam, you note hyperreflexia, warm and moist skin, fine hair, and tachycardia. The patient notes they feel uncomfortably warm. What are you thinking and what test will you run first?

Answer 10

hyperthyroidism - metabolism speeds up

when patient presents with new onset of atrial fibrillation you must exclude hyperthyroidism

best initial test for suspected thyroid disorder is TSH!
[hyperthyroidism presents with LOW TSH]

Question 11

what causes thyroid storm and how does it present?

Answer 11

life-threatening thyrotoxicosis in a patient with pre-existing hyperthyroid disease, precipitated by an acute event such as surgery/trauma/infection

massive catecholamine surge —> fever, delirium, tachycardia (arrhythmia may cause death), hyperglycemia, hypercalcemia (high bone turnover)

Question 12

Patient is a 34yo F with PMH of hyperthyroid disease presenting to the ED with fever and delirium which developed following an upper respiratory infection. Tachycardia is noted upon admission and labs are significant for hyperglycemia and hypercalcemia. What are you MOST worried about?

Answer 12

patient is presenting with thyroid storm - MOST worried about death from arrhythmia

life-threatening thyrotoxicosis in a patient with pre-existing hyperthyroid disease, precipitated by an acute event such as surgery/trauma/infection —> massive catecholamine surge

Question 13

what causes goiter?

Answer 13

goiter = enlarged thyroid

due to high TSH but inability to produce T3/T4 (bc of low iodine), or thyroid stimulating antibodies (Grave’s)

Question 14

when you suspect a thyroid disorder what is the BEST initial test??

Answer 14

TSH!!

T3/T4 fluctuate, and TSH levels reflect how much thyroid hormone the tissues are actually seeing so it’s much more sensitive

Question 15

what is the cause of central hyper- or hypo- thyroidism?

Answer 15

rare disorders of the pituitary or hypothalamus which cause thyroid disease

most often hypothalamic-pituitary tumors which either block TRH/TSH secretion (—> hypothyroidism) or secrete TSH (—> hyperthyroidism)

or due to pituitary resistance to thyroid hormone and thus lack of negative feedback (—> hyperthyroidism)

Question 16

when is it useful to measure reverse T3 levels?

Answer 16

reverse T3: isomer of T3 also derived from T4, usually parallels T4 levels

except for in euthyroid sick syndrome - decreased TSH and T3/T4 in critically ill patients due to their disease, NOT central hypothyroidism… rT3 will RISE due to impaired clearance

low rT3 —> central hypothyroidism
high rT3 —> sick euthyroid syndrome

Question 17

how can central hypothyroidism be distinguished from euthyroid sick syndrome?

Answer 17

central hypothyroidism: hypothalamic pituitary axis is cause of low TSH/T3/T4

euthyroid sick syndrome: critically ill patients with low TSH/T3/T4

measure reverse T3: isomer of T3 also derived from T4, will be low in central hypothyroidism but RISE in euthyroid sick syndrome due to impaired clearance

Question 18

what causes Grave’s disease?

Answer 18

thyroid stimulating antibodies which act like TSH —> hyperthyroidism

(autoimmune disease)

Question 19

what are the 2 unique exam findings of Grave’s disease and why do these occur?

Answer 19

1. exophthalmos (bulging eyes) - proptosis (eye protrusion) + periorbital edema
2. pretibial myxedema (shin swelling)

both caused by T-cell activation of fibroblasts, which contain TSH receptor —> stimulate causes secretion of hyaluronic acid (glycosaminoglycan), which is osmotic agent that draws out water and causes swelling

Question 20

how is Grave’s disease diagnosed?

Answer 20

hyperthyroid labs + exophthalmos (bulging eyes, unique to Grave’s)

can also measure “thyroid stimulating immunoglobulins” (TSH receptor antibodies)

Question 21

methimazole vs propylthiouracil (PTU)

Answer 21

both are thionamides

methimazole: inhibits thyroid peroxidase (TPO), blocking organification of iodine and coupling of MIT/DIT

propylthiouracil (PTU): inhibits TPO and also 5’-deiodinase, thus also blunting peripheral conversion of T4–>T3

Question 22

what are the adverse effects (3) of thionamides such as methimazole and propylthiouracil (PTU)? which one is of most concern?

Answer 22

1. skin rash (common)
2. agranulocytosis - rare drop in WBC that presents as fever/infection after starting the drug, possible aplastic anemia - most concerning side effect
3. hepatotoxicity

Question 23

which hyperthyroid drug should NOT be used in pregnant women?

Answer 23

methimazole (inhibits TPO) - teratogen, associated with congenital malformations

however ionizing thyroid ablation is also not safe, so propylthiouracil (PTU) often used during early pregnancy

Question 24

how are the following used in the treatment of thyroid storm?
a. propranolol
b. thionamides
c. SSKI (saturated solution of potassium iodide)
d. steroids

Answer 24

a. propranolol (beta blocker): treats tachycardia but also is weak inhibitor of 5’-deiodinase, blocking T4–>T3 conversion

b. thionamides: methimazole blocks TPO, PTU blocks TPO + 5’-deiodinase

c. SSKI (saturated solution of potassium iodide): iodide load shuts down T4 production via Wolff-Chaikoff effect

d. steroids: reduce T4–>T3 conversion, suppress autoimmune damage, treat possible concomitant adrenal insufficiency (cortisol depleted in thyroid storm)

Question 25

toxic multinodular goiter

Answer 25

nodules in thyroid that function independently, but usually have mutated TSH receptor so do not respond to TSH

if only 1 nodule, it’s called toxic adenoma

tx: radioactive iodine or surgery

Question 26

how can radioactive iodine be used to distinguish between toxic multinodular goiter and cancer?

Answer 26

toxic multinodular goiter: nodules in thyroid that function independently, do not respond to TSH but continually produce thyroid hormone

thyroid (“hot”) nodules will take up radioactive iodine to make thyroid hormone, while cancer “cold” nodule) will not

much higher doses of radioactive iodine can also be used for thyroid ablation

Question 27

Jod-Basedow phenomenon

Answer 27

iodine-induced hyperthyroidism, occurs in regions of iodine deficiency - many of these patients probably have toxic adenomas already

can also occur when patients with toxic adenomas (in non-deficient regions) are given drugs with high iodine content, expectorants (contain potassium iodide), CT contrast dye, or amIODarone (class III anti-arrhythmic)

Question 28

A patient on your floor being treated for a toxic adenoma of the thyroid developed a cold. They were given an expectorant for their symptoms. Soon after, they develop symptoms of hyperthyroidism, despite their condition being well-controlled before. What is going on?

Answer 28

Jod-Basedow phenomenon: iodine-induced hyperthyroidism, seen in patients with toxic adenomas (thyroid nodules) who are exposed to high levels of iodine

many expectorants contain potassium iodide

Question 29

type I vs type II amiodarone-induced hyperthyroidism

Answer 29

amIODarone: class III antiarrhythmic, contains 2 iodine atoms

type I: occurs in patients with pre-existing thyroid disease, iodine input results in excess hormone production

type II: direct toxic effect of the drug causes destructive thyroiditis which leads to release of T4/T3 (without increased hormone synthesis), can occur in patients without pre-existing illness

[note amiodarone can also cause hypothyroidism via Wolff-Chaikoff effect]

Question 30

where is “endemic goiter” most common?

Answer 30

aka iodine deficiency, constant elevation in TSH results in enlarged thyroid (goiter)

common in mountainous areas, where iodine is depleted from the environment via water run-off

Question 31

what chemical used in psychiatry is a known goitrogen?

Answer 31

goitrogens: substance that inhibit thyroid hormone production

[most common is iodine via Wolff-Chaikoff effect]

lithium also has this effect (used in psychiatry)

Question 32

name 2 foods that are known goitrogens?

Answer 32

goitrogens: substance that inhibit thyroid hormone production

[most common is iodine via Wolff-Chaikoff effect]

cassava and millet are foods that have this effect

Question 33

explain how amiodarone can cause hypothryoidism, aside from the ways it can cause hyperthyroidism (type I and II)

Answer 33

amIODarone contains 2 iodine atoms (class III anti-arrhythmic)

excess iodine can induce Wolff-Chaikoff effect (suppression of thyroid hormone synthesis, protective measure) - normal patients “escape” in a few weeks, but patients with pre-existing subclinical thyroid disease may have “failure to escape”

amiodarone also mimics T4 —> competitively inhibits 5’-diodinase (converts T4 to T3)

Question 34

most common cause of non-dietary hypothyroidism

Answer 34

Hashimoto’s thyroiditis (chronic autoimmune thyroiditis): lymphocytes attack thyroid gland, associated with HLA-DR5

Question 35

what are the histological findings of Hashimoto’s thyroiditis? (3)

Answer 35

1. massive lymphocytic infiltrate - may form germinal centers
2. Hurthle cells - enlarged eosinophilic follicular cells
3. anti-TPO or anti-thyroglobulin antibodies - uninvolved in pathology, but can be measured

Question 36

what do the following findings indicate:
- symptoms of hypothyroidism
- thyroid biopsy shows germinal centers and Hurthle cells
- genetic analysis shows HLA-DR5

Answer 36

Hashimoto’s thyroiditis (chronic autoimmune thyroiditis): lymphocytes attack thyroid gland, most common non-dietary cause of hypothyroidism

Hurthle cells - enlarged eosinophilic follicular cells

Question 37

patients with Hashimoto’s thyroiditis are at an increased risk for developing what kind of cancer?

Answer 37

Hashimoto’s thyroiditis (chronic autoimmune thyroiditis): lymphocytes attack thyroid gland, most common non-dietary cause of hypothyroidism

increased risk of non-Hodgkin B cell lymphoma (this makes sense given lymphocytes are involved in the pathology)

Question 38

de Quervain’s thyroiditis

Answer 38

aka granulomatous or subacute thyroiditis: granulomatous inflammation of the thyroid, presents with tender / enlarged thyroid, occurs in young women

usually resolves in a few weeks

Question 39

Pt is a 23yo F presenting with concerns about tenderness in her neck. Upon palpitation, you note an enlarged thyroid gland. Upon questioning, pt denies any symptoms of hypothyroidism. She is worried it’s cancer. What will you tell her?

Answer 39

most likely granulomatous or subacute or de Quervain’s thyroiditis: granulomatous inflammation of the thyroid, presents with tender / enlarged thyroid, occurs in young women

usually resolves in a few weeks

Question 40

Riedel’s thyroiditis

Answer 40

“rock hard” thyroid due to fibroblast activation —> collagen deposition

associated with IgG4 plasma cells

often extends beyond thyroid to parathyroids (hypoparathyroidism), recurrent laryngeal nerve (hoarseness), and trachea (difficulty breathing)

Question 41

Pt is presenting with difficulty breathing and hoarseness. Upon palpitation, you note a “rock hard” thyroid. Biopsy shows IgG4 plasma cells. What is your diagnosis?

Answer 41

Riedel’s thyroiditis: fibroblast activation —> collagen deposition, associated with IgG4 plasma cells

often extends beyond thyroid to parathyroids (hypoparathyroidism), recurrent laryngeal nerve (hoarseness), and trachea (difficulty breathing)

Question 42

what causes “painless thyroiditis”?

Answer 42

aka lymphocytic thyroiditis: variant of Hashimoto’s - lymphocyte infiltration of thyroid gland, but self-limited and resolves in a few weeks

causes transient hyperthyroidism, sometimes followed by hypothyroidism