Thyroid Disorders Flashcards

1
Q

What is colloid composed of?

A

Thyroglobulin, which is made of tyrosine residues that serve as sites for TH synthesis

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2
Q

3 things that inhibit TRH

A

Glucocorticoids, DA, somatostatin

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3
Q

4 steps of TH synthesis

A
  • 1) Iodide transport (trapping) through Na-iodide symporter (NIS)
  • 2) Oxidation / incorporation into TG (organification). Regulated by thyroid peroxidase (TPO). TPO is upregulated by TSH.
  • 3) Coupling of MIT (monoiodotyrosine) and DIT to form T3 and T4
  • 4) TSH stimulates TPO and transcription of TG
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4
Q

What 2 things inhibit proteolysis / release of TH?

A

Excessive iodine and lithium

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5
Q

3 TH binding proteins

A

Thyroid binding globulin, transthyretin, and albumin

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6
Q

What increases thyroid binding globulin concentration?

A

Hyperestrogenic states: pregnancy, exogenous estrogens

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7
Q

What decreases thyroid binding globulin? (5)

A

Androgens, glucocorticoids, protein malnutrition, nephrotic syndrome, cirrhosis.

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8
Q

What inhibits 5’MDI? (6)

A

Illness, caloric deprivation, malnutrition, glucocorticoids, beta-blockers, amiodarone, and PTU

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9
Q

Half life for T4/3

A

T4 is 7 days

T3 is 1 day

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10
Q

Wolff-Chaikoff Effect

A

Protects against iodine excess. Thyroid peroxidase (TPO) is shut down so TH isn’t made in excess. Normally, a subsequent decrease in I → escape from this effect and resumption of normal TH synthesis. However, if there is no escape from this effect, I-induced hypothyroidism may occur.

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11
Q

Jod-Basedow Phenomenon

A

When pxs who have accommodated to chronic iodine deficiency are exposed to high doses of iodine → hyperthyroidism.

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12
Q
TH effects
Neurogenesis
Metabolism
Weight
Cholesterol
Heart
Bone
Childhood growth
GI
GU
Renal
A
  • Neurogenesis: absence during early life → irreversible MR (cretinism). TH regulates transcription of myeline basic protein.
  • Metabolism: increases metabolic rate, O2 consumption, heat production, glucose absorption, GNG, glycogenolysis, hepatic LDL receptors, lipolysis, and metabolism of cholesterol to bile acids.
  • Hyperthyroidism doesn’t cause universal weight loss b/c it stimulates appetite. Also causes muscle wasting.
  • Hypothyroidism may involve weight gain of 10-20 lbs (not obese)
  • Hypercholesterolemia occurs w/ hypothyroidism
  • Heart – stimulates contractility, increases O2 consumption, enhances sensitivity to catecholamines. Hyperthyroid causes tachycardia and increased contraction force.
  • Bone – stimulation of bone formation and resorption (increased urine / serum Ca), but overall resorption prevails. Hyperthyroid → osteoporosis.
  • Hypothyroidism may blunt growth in childhood.
  • GI – stimulates gut motility. Hyperthyroid → hyperdefecation. Hypothyroid → constipation.
  • GU – TH affects ovulation, so excess / deficiency → menstrual irregularities / infertility. High TRH stimulates hyperprolactinemia → anovulation
  • Renal – necessary for normal renal free water excretion
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13
Q

T3/4 levels in primary hypothyroidism

A

T4 is low. T3 often remains normal.

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14
Q

Indications for TSH screening (10)

A

Women > 60 y/o (older women have highest rates of thyroid disease), family hx, sxs of hyper / hypothyroidism, goiter, hyperprolactinemia, hypercholesterolemia, infertility / menstrual irregularity, cardiomyopathy / arrhythmia, osteoporosis, before getting pregnant.

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15
Q

Apathetic thyrotoxicosis
Population
2 main sxs

A

More common in older pxs. Usually involves cardiac problems (A fib, CHF), and / or osteoprosis

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16
Q

Thyroid storm
3 main characteristics
Causes (5)
Treatment (5)

A
  • Severe thyrotoxicosis + mental status changes + fever.
  • Caused by underling hyperthyroidism plus acute precipitant: not taking meds, surgery, MI, CVA, infection.
  • Treatment
  • PTU – decreases production and blocks T4 → T3
  • Propranolol – treats hyperadrenergic sxs and blocks T4 → T3
  • Potassium iodide AFTER PTU – blocks TH release
  • Glucocorticoids – blocks T4 → T3 conversion
  • Supportive care
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17
Q

Does hyper stimulation of TSH receptor cause high or low iodine uptake?

A

High

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18
Q

Does leak of TH cause high or low iodine uptake?

A

Low

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19
Q

What percentage of iodine is normally taken up by the gut?

A

25%

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20
Q
Graves' Disease
I uptake
Population
Which cells make TSI?
What increases risk of orbitopathy?
Signs / sxs of orbitopathy (8)
Risk if untreated
Treating dermopathy
A
  • High I uptake
  • More common in younger people. 9x more common in women.
  • TSI is made in B lymphocytes.
  • Smoking increases risk of orbitopathy.
  • Sxs / signs include proptosis / exophthalmos, eye irritation / pain, dryness, photosensitivity, periorbital edema, exposure keratopathy, diplopia / gaze paralysis, loss of color vision
  • If untreated, risk of A fib, bone loss, and thyroid storm.
  • Treat dermopathy w/ corticosteroids
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21
Q
Toxic multinodular goiter (TMNG) / Solitary hyperfuctioning nodules
I uptake level
Population
Presentation
Cause
A
  • High I uptake
  • More often seen in older pxs.
  • May present as “apathetic hyperthyroid”. Hot and cold areas seen on nuclear imaging.
  • May be due to activating mutations of TSH receptor.
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22
Q
TSH secreting tumors
I uptake level
Elevated levels of what?
Sx
Treatment (2)
A
  • High iodine uptake.
  • Normal / high TSH, high T4, high alpha subunit.
  • May have visual field defects.
  • Tx w/ tumor resection and somatostatin analogs.
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23
Q

Thyroid hormone resistance
I uptake level
Inheritance
Treatment

A

High I uptake
Autosomal dominant.
Tx usually not necessary. May use BB’s to control HTN.

24
Q

Excess hCG
I uptake level
Effect on thyroid function

A

High I uptake if from tumor.

Stimulates TSH receptor.

25
Q

3 main strategies for treating high I uptake hyperthyroidism

A

Anti-thyroid drugs (PTU, MMI), radioactive I, and total thyroidectomy

26
Q
2 anti-thyroid drugs
Mechanism / Use
Timing of onset, and why
Which acts faster?
Which is used for thyroid storm?
Which is used during pregnancy?
A
  • Propylthiouracil, methimazole
  • Mechanism / Use
  • PTU and MMI interfere w/ hormone synthesis (inhibit iodination of tyrosyl groups in thyroglobulin and coupling to form T4/3).
  • Does not impact release, explaining delayed onset of action, b/c stores have to be depleted first.
  • PTU also blocks peripheral conversion of T4 → T3. Acts faster than methimazole and is preferred tx for thyroid storm. Also tx of choice during 1st trimester of pregnancy b/c MMI may result in aplasia cutis (lack of scalp). After 1st trimester, MMI is used due to lower risk of hepatotoxicity.
27
Q

Side effects of PTU and MMI (4)

A
  • Agranulocytosis – most severe side effect. Check CBC routinely if px has fever or sore throat.
  • PTU has risk of liver failure. Check LFTs routinely
  • Urticaria / rash – most common side effect
  • Arthralgias
28
Q
Radioactive Iondine
Uses (5)
Mechanism
Timing of onset
Requirements (2)
Side effects (3)
A
  • Uses – Graves’, toxic multinodular goiter, toxic adenoma, thyroid cancer, and diagnosis
  • Mechanism – emits beta (short range / destructive) and gamma rays (longer range, detected by nuclear camera).
  • Cytotoxic effect is delayed for 1-2 months. Peaks at 2 months.
  • Anti-thyroid drugs must be stopped for 3 weeks prior to administration. Low I diet for 1-2 weeks prior to tx.
  • Side effects – dry mouth (acts on salivary gland), altered taste, dry eyes (lacrimal glands)
29
Q

What should be done before a total thyroidectomy?

A

Pre-treatment w/ anti-thyroid drugs may reduce surgical risk

30
Q

3 things that cause low I uptake hyperthyroidism

A

Thyroiditis, struma ovarii, meds

31
Q
Thyroiditis
I uptake level
Pathogenesis
Presentation
Treatment (4)
A
  • Low I uptake.
  • Involves increased TH release, not increased production.
  • Presents w/ neck pain after URI.
  • SELF-LIMITED. May have transient phase of hypothyroidism. Supportive tx w/ NSAIDs / prednisone for pain control and BB’s to control HR.
32
Q

Silent thyroiditis

A

No neck pain, but still inflammation of thyroid

33
Q

Treatment of post-partum thyroiditis

A

Self-limited

34
Q

Struma ovarii
Description
I uptake level

A

Rare ovarian tumor that produces TH. I uptake is low in neck but high in ovaries.

35
Q

3 meds that induce hyperthyroidism

I uptake level

A

Low I uptake
•High I levels –> Jod-Basedow phenomenon
•Amiodarone – rich in iodine
•Thyroid hormone (levothyroxine)

36
Q
Myxedema coma
Population
Features (6)
Cause (4)
Treatment (4)
A
  • Life-threatening hypothyroidism. Most common in older women.
  • Main features: mental status changes, hypothermia, respiratory failure. May have associated hypotension, bradycardia, and hyponatremia
  • Precipitated by omission of T4 replacement therapy, MI, CVA, or sepsis
  • Treatment – glucocorticoids (prophylaxis in case of adrenal insufficiency, must be given prior to thyroid hormone), levothyroxine, liothyronine (beware in cardiac pxs), supportive care
37
Q

5 drugs that cause hypothyroidism

A
  • Lithium – impairs release of T4/3
  • Amiodarone – Wolff-Chaikoff effect
  • PTU, methimazole
  • Interferon – causes presentation similar to Hashimoto’s
38
Q

Liothyronine
What is it?
When is it used?

A

Liothyronine = T3 – rarely used. Used when a faster onset of action is required and in rare cases of impaired T4 → T3 conversion (defect in 5’ deiodinase)

39
Q

Side effects of Levothyroxine / Liothyronine (3)

A

Changes in estrogen status or weight. Hyperthyroidism sxs (arrhythmia, bone loss)

40
Q

6 things that decrease absorption of exogenous TH

A

Iron, Ca, soy, sucralfate (antacid), chromium, coffee

41
Q

4 things not related to the thyroid that cause low TSH

A

Acute illness, exogenous / endogenous glucocorticoids, exogenous DA, or catecholamines.

42
Q

What has a poor prognosis during acute illness?

A

Low T4

43
Q

What is common during non-thyroidal illness?

A

Low T3

44
Q

Why is rT3 high during illness?

A

Mainly due to decreased clearance.

Partly due to increased production

45
Q

Evaluation of thyroid nodules (5)

A
  • First check TSH level. If TSH is normal or high (indicates a cold nodule), then do FNA.
  • FNA – Initial diagnostic study for euthyroid pxs w/ thyroid nodules. Can diagnose papillary, medullary, and anaplastic cancer, but cannot differentiate follicular adenoma from follicular carcinoma.
  • Thyroid scan w/ Tc99 obtained if TSH is low or if FNA shows evidence of follicular neoplasia.
  • US – determines size of nodules and helps guide FNA. Differentiate b/w solid and cystic nodules.
  • I-131 uptake (only used in presence of low TSH and hyperthyroidism)
46
Q

What percentage of thyroid nodules are malignant?

A

10%

47
Q

Warning signs for thyroid cancer (8)

A

Under age 20 or >60, rapid growth, hard / fixed mass, cold nodule in setting of Graves’, hoarseness (laryngeal nerve invasion), hx of childhood head / neck radiation, family hx of thyroid cancer, cervical LAD.

48
Q

Indications for biopsy

A

> 1cm, solid / hypoechoic on US, microcalcifications, irregular borders, central blood flow, hx of radiation

49
Q
Papillary thyroid carcinoma
How common?
Poor prognostic factors
Mutations
Where is it found?
Histology
Metastases
Treatment (3)
Tumor marker
A
  • Accounts for 75%
  • Poor prognosis: >4 foci, age >45, tall cell variant, BRAF mutation
  • Caused by mutations in NTRK, RET, and BRAF
  • BRAF mutation → decreased expression of NIS and TPO → decreased I trapping and organification → less responsive to radioactive iodine. Bad prognosis.
  • RET rearrangements are associated w/ younger age and radiation-induced tumors. May cause constitutive activity of a tyrosine kinase.
  • Multifocal: often found in both lobes.
  • Histology: Papillary architecture, hypercellular, overlapping nuclei, cleaved / grooved nuclei, NUCLEAR CLEARING (GROUND GLASS, ORPHAN ANNIE EYES [WHITE IN MIDDLE]), intranuclear cytoplasmic inclusions (represent cytoplasmic invagination), prominent nucleoli, fibrovascular floors, PSAMMOMA BODIES (laminated calcifications; large purple things).
  • Metastasizes via lymphatics, but this does not increase mortality rate.
  • Treat w/ thyroidectomy, I-131, and T4 suppression. I-131 and T4 suppression (levothyroxine) not required for low grade cancers.
  • Use thyroglobulin as tumor marker.
50
Q
Follicular carcinoma
Histology requirements
Other histo findings
Diagnosis
Which variant is more aggressive?
Metastases
Treatment (3)
Tumor marker
A
  • MUST have capsular invasion and / or vascular invasion.
  • Small follicles w/ a thick fibrous capsule.
  • May have cytologic atypia: enlarged nuclei, prominent nucleoli.
  • FNA is not capable of differentiating follicular adenoma from carcinoma
  • Hurthle cell variant is more aggressive.
  • Metastasizes hematogenously → more likely to spread to lungs / liver / bone / brain.
  • Treatment is similar to papillary: thyroidectomy, I-131, T4 suppression
  • Follow thyroglobulin.
51
Q
Anaplastic carcinoma
Population
Presentation
Histology
Mutation
Treatment
A
  • More common in elderly
  • Presents as rapidly expanding, fixed, and hard thyroid mass. Often doubles in size in 1 week.
  • Sheets of pleomorphic giant cells, look similar to osteoclasts. Many mitoses. Necrosis. Very dedifferentiated
  • BRAF mutations are found in 50%
  • Treatment is palliative
52
Q
Medullary carcinoma
Always preceded by what?
Tumor markers
Doubling rate
Mutation
Prophylaxis
Diagnosis
Histology
Treatment
A
  • Always preceded by C-cell hyperplasia.
  • Tumor markers: calcitonin or CEA
  • Doubling rate: Calcitonin doubling w/in 6 months is a bad sign. If it does not double w/in 2 years, pxs often live at least 10 years (good prognosis).
  • Mutation in RET oncogene. Genetic screening for germline mutation recommended for ALL pxs diagnosed w/ medullary cancer. If positive, screen 1st deg relatives. If catch early (familial screening), then prophylactic thyroidectomy may be done.
  • Diagnosed w/ FNA
  • Histology - Monotonous cells: polygonal, PLASMACYTOID (eccentric nucleus; look similar to plasma cells) or spindle-shaped cells in nests, cords, or follicles. Round / oval nuclei w/ “salt and pepper chromatin”. Granular cytoplasm. AMYLOID DEPOSITION – seen w/ congo red stain.
  • Treat w/ thyroidectomy. No I-131 tx b/c C cells do not produce TH.
53
Q

What does MEN stand for?

A

Multiple endocrine neoplasia

54
Q

MEN 1
Gene
Inheritance
Mnemonic

A
  • Loss of function mutation in MENIN gene (tumor suppressor).
  • Autosomal dominant.
  • Mnemonic PPP: Parathyroid hyperplasia (most common feature), pancreatic islet cell tumors / neuroendocrine tumors, pituitary tumors.
  • If you see parathyroid disease in a young patient, think of MEN1
55
Q

MEN 2a
Mutation
Inheritance
3 characteristics

A
  • Gain of function mutation in RET oncogene. Autosomal dominant.
  • Medullary thyroid cancer (100%), bilateral pheochromocytoma (50%), parathyroid hyperplasia (40%)
56
Q
MEN 2b
Mutation
Inheritance
4 characteristics
Prognosis
A
  • Also a gain of function mutation in RET oncogene. Autosomal dominant.
  • Medullary thyroid cancer (100%), pheochromocytoma (50%), NOT parathyroid hyperplasia, Marfanoid habitus (tall / lanky), mucosal neuromas (often 1st sign)
  • Poor prognosis. 50% are de novo mutations so hard to identify.