Thyroid Clinical

Question 1

hyperthyroidism - defined

Answer 1

*too much thyroid hormone
*elevated T3 and T4
*low TSH

Question 2

hyperthyroidism - symptoms

Answer 2

1. metabolism: heat intolerance, diaphoresis, weight loss, restlessness, hyperactivity, anxiety
2. CV/resp: tachycardia, palpitations, arrhythmias, chest pain
3. derm: warm, moist skin, onycholysis
4. GI: diarrhea
5. MSK: muscle weakness, hand tremors, osteoporosis
6. neuropsych: anxiety, insomnia, psychosis, pressured speech
7. repro: oligomenorrhea, amenorrhea, decreased libido, decreased fertility

Question 3

causes of hyperthyroidism

Answer 3

1. Graves’ Disease (most common cause)
2. other causes include:
   -hyperfunctioning “toxic” adenoma (Plummer’s disease)
   -multinodular goiter
   -thyroiditis
   -hCG-related [pregnancy, cancer]
   -Jod-Basedow phenomenon
   -factitious/iatrogenic use of thyroid hormone
   -TSH secreting adenoma

Question 4

Graves’ disease - overview

Answer 4

*an autoimmune cause of hyperthyroidism; most common cause of hyperthyroidism
*hallmark: + thyroid stimulating immunoglobulins (TSI) or TSH receptor antibodies (TRAb); autoantibodies bind the TSH receptor and stimulate hormone synthesis

Question 5

Graves’ disease - exophthalmos

Answer 5

*exophthalmos (bulging eyes) - only occurs in Graves’ disease
*pathogenesis: TSI activates T cells → lymphocytic infiltration of the retroorbital space which increases inflammatory cytokines → orbital fibroblasts secrete GAGs → increased osmotic muscle swelling/inflammation and adipocyte build up → exophthalmos
*note - exophthalmos associated with HLA-DR3 and HLA-B8

Question 6

Graves’ disease - clinical features

Answer 6

*exophthalmos
*periorbital edema
*lid lag (upper eyelid is high in downward gaze; increased sympathetic stimulation of superior tarsal muscle)
*smooth goiter
*pretibial myxedema (TSI stimulate pretibial dermal fibroblasts → skin thickening)
*Pemberton sign (goiter obstructs jugular venous flow as the thyroid is forced downward with raised arms)

Question 7

Graves’ disease diagnosis - ultrasound

Answer 7

*US shows significantly increased blood flow to the thyroid

Question 8

nuclear uptake & scan (Tc-99 pertechnetate thyroid scintigraphy) - overview

Answer 8

*give pt pertechnetate, which looks a lot like iodine (but isn’t used to make thyroid hormone)
*gets taken up into the thyroid cells
*uptake = gives us a % of how much pertechnetate is taken up
*scan = gives us a picture of where the pertechnetate is taken up

Question 9

Graves’ disease diagnosis: nuclear uptake & scan (Tc-99 pertechnetate thyroid scintigraphy)

Answer 9

*scan reveals pattern of uptake similar to that of a normal thyroid, but much higher % of uptake in Graves’ disease
*homogenous distribution of uptake throughout the thyroid

Question 10

Graves’ disease - treatment

Answer 10

1. medications: inhibit thyroid peroxidase enzyme → blocks thyroid peroxidase → less tyrosine iodination and coupling → prevents formation of T3/T4
   -options for meds: methimazole, propylthiouracil (PTU)
   -ADEs: hepatic failure, agranulocytosis
2. beta blockers (decrease hyperadrenergic sx) = INITIAL therapy to control symptoms
3. other: thyroidectomy, radioactive iodine ablation

Question 11

methimazole - MOA, ADEs

Answer 11

*MOA: inhibit thyroid peroxidase enzyme → less tyrosine iodination and coupling → prevents formation of T3/T4
*used to treat Graves’ disease
*ADEs:
-hepatic failure (jaundice, abdominal pain, elevated LFTs)
-agranulocytosis (low absolute neutrophil count, fever, sore throat)
-teratogenic (avoid in pregnancy)

Question 12

toxic adenoma / toxic multinodular goiter - nuclear uptake & scan (Tc-99 pertechnetate thyroid scintigraphy)

Answer 12

*nodular locations of uptake on scan
*focal patches of follicular cells become hyperfunctioning → hypersecretion of T3/T4 independent of TSH

Question 13

thyroiditis - overview

Answer 13

*inflammation (damage) to the thyroid gland causes premade/stored thyroid hormone to leak into the bloodstream

Question 14

subacute granulomatosis thyroiditis - overview

Answer 14

*aka de Quervain thyroiditis
*usually preceded by infection
*PAINFUL inflammation of the thyroid
*lab trends: hyperthyroid state → euthyroid → hypothyroid state → euthyroid
*typically self-resolves in several weeks

Question 15

postpartum thyroiditis

Answer 15

*a mild, self-limiting variant to Hashimoto thyroiditis < 1 year after delivery

Question 16

Riedel thyroiditis

Answer 16

*aka invasive fibrous thyroiditis
*can be due to IgG4 → progressive fibrosis of the thyroid gland and surrounding structures
*slowly enlarging, hard, fixed, non-tender thyroid gland
*may lead to hypothyroidism
*treatment = surgery; monitor parathyroid function

Question 17

thyroiditis - treatment

Answer 17

*mostly transient process, so does not require methimazole or PTU
*beta blocker may be used to help with symptoms until thyroiditis resolves
*NSAIDs for pain if needed

Question 18

hCG-mediated hyperthyroidism - overview

Answer 18

*TSH, hCG, LH, and FSH all share the same alpha subunit, but have different beta subunits
*at high levels, hCG can bind to TSH receptors
*human chorionic gonadotropin (hCG) is made almost exclusively by the placenta but also by some neoplasms; therefore, seen in pregnancy, molar pregnancy, choriocarcinoma
*transient, no treatment needed

Question 19

Jod-Basedow phenomenon - overview

Answer 19

*iodine-induced hyperthyroidism
*occurs when a pt with an underlying thyroid disorder is given excess iodine → excess hormone production by an abnormal thyroid gland that doesn’t respond to normal regulation
*pertinent history: excess source of iodine, such as administration of IV contrast, amiodarone, iodine supplements

Question 20

other causes of hyperthyroidism

Answer 20

1. iatrogenic use of thyroid hormone
2. TSH secreting adenoma (very rare, sx of pituitary mass with hyperthyroidism, tx = surgery)
3. struma ovarii (thyroid hormone-secreting ovarian teratoma: hyperthyroidism + pelvic mass)

Question 21

thyroid storm - overview

Answer 21

*rare but life-threatening complication of hyperthyroidism (untreated or incompletely treated hyperthyroidism + acute stressor such as infection, trauma, surgery)
*presentation: agitation, delirium, fever, coma, tachyarrhythmias
*treatment:
-beta blocker
-PTU or methimazole
-glucocorticoids
-iodine

Question 22

hypothyroidism - defined

Answer 22

*too little thyroid hormone
*low T4 and T3
*elevated TSH

Question 23

hypothyroidism - symptoms

Answer 23

1. metabolism: cold intolerance, weight gain, hyponatremia, hyperlipidemia
2. CV/pulm: bradycardia, dyspnea on exertion
3. derm: dry, cool skin, coarse brittle hair, alopecia
4. GI: constipatiion
5. MSK: proximal muscle weakness, carpal tunnel, myoedema
6. neuropsych: fatigue/lethargy, depression, hyporeflexia
7. repro: abnormal uterine bleeding, decreased libido, infertility

Question 24

hypothyroidism - features

Answer 24

*periorbital edema
*edema, tongue swelling
*goiter
*Queen Anne’s sign (thinning of distal 1/3 of the eyebrow)

Question 25

causes of hypothyroidism

Answer 25

***Hashimoto thyroiditis** (most common) *congenital hypothyroidism *central hypothyroidism *iodine deficiency *medication-induced *surgery/radiation

Question 26

Hashimoto thyroiditis - overview

Answer 26

*most common cause of hypothyroidism in iodine-sufficient countries *an **autoimmune cause** of hypothyroidism

Question 27

Hashimoto thyroiditis - pathogenesis

Answer 27

***thyroid peroxidase (TPO) antibodies destroy follicular cells** → decreased thyroid hormone production *initial normal/high thyroid hormone levels followed by permanent hypothyroidism

Question 28

Hashimoto thyroiditis - risk factors

Answer 28

*female *PMH/FHx of autoimmune disease *Down Syndrome, Turner Syndrome *HLA-DR5 haplotype

Question 29

congenital hypothyroidism - overview

Answer 29

*most common cause worldwide = **iodine deficiency** *most common cause in USA = **thyroid dysgenesis/agenesis** *thyroid hormone affects axon proliferation, dendrite branching, synaptogenesis, myelination, cell migration, growth, skeletal development ***undiagnosed/untreated congenital hypothyroidism → irreversible intellectual disability** -this is an emergency; newborn screening programs essential

Question 30

congenital hypothyroidism - clinical presentation

Answer 30

*aka cretinism *classically presents with 6 P's: **pot-bellied, pale, puffy-faced child with protruding umbilicus, protuberant tongue, and poor brain development** *undiagnosed/untreated, leads to irreversible intellectual disability

Question 31

central hypothyroidism - overview

Answer 31

*thyroid gland is normal but **signal from pituitary/hypothalamus is absent,** so thyroid hormone isn't produced *labs = **low TSH and low T4** *less common than primary hypothyroidism *look for hx of pituitary disorders

Question 32

other causes of hypothyroidism

Answer 32

1. iodine deficiency: no iodine → no organification → no T3/T4 production 2. medication induced: **amiodarone, lithium** inhibits thyroid hormone synthesis + release 3. surgery/radiation

Question 33

hypothyroidism - treatment

Answer 33

*goal = replace thyroid hormone 1. **levothyroxine = T4** (Synthroid is the brand name) 2 liothyronine = T3; can add to levothyroxine regimen, but not prescribed alone

Question 34

myxedema coma - overview

Answer 34

*severe, potentially fatal **complication of hypothyroidism** *hypothyroid state + stressor (infection, MI, stroke, surgery) *severe hypothyroidism → **decreased mental status, hypothermia, hypoglycemia, hyponatremia, hypoventilation, bradycardia, puffy hands/face** *elderly pts with hypothyroidism have highest risk

Question 35

amiodarone & thyroid

Answer 35

***amiodarone: class III anti-arrhythmic drug rich in iodine**; can do anything to the thyroid: -hypothyroidism: decreased conversion of T4 to T3 -hyperthyroidism: trigger autoimmune hyperthyroidism -thyroiditis: can cause destruction of thyroid gland