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
2
Q
3 things that inhibit TRH
A
Glucocorticoids, DA, somatostatin
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
4
Q
What 2 things inhibit proteolysis / release of TH?
A
Excessive iodine and lithium
5
Q
3 TH binding proteins
A
Thyroid binding globulin, transthyretin, and albumin
6
Q
What increases thyroid binding globulin concentration?
A
Hyperestrogenic states: pregnancy, exogenous estrogens
7
Q
What decreases thyroid binding globulin? (5)
A
Androgens, glucocorticoids, protein malnutrition, nephrotic syndrome, cirrhosis.
8
Q
What inhibits 5’MDI? (6)
A
Illness, caloric deprivation, malnutrition, glucocorticoids, beta-blockers, amiodarone, and PTU
9
Q
Half life for T4/3
A
T4 is 7 days
T3 is 1 day
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.
11
Q
Jod-Basedow Phenomenon
A
When pxs who have accommodated to chronic iodine deficiency are exposed to high doses of iodine → hyperthyroidism.
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
13
Q
T3/4 levels in primary hypothyroidism
A
T4 is low. T3 often remains normal.
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.
15
Q
Apathetic thyrotoxicosis
Population
2 main sxs
A
More common in older pxs. Usually involves cardiac problems (A fib, CHF), and / or osteoprosis
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
17
Q
Does hyper stimulation of TSH receptor cause high or low iodine uptake?
A
High
18
Q
Does leak of TH cause high or low iodine uptake?
A
Low
19
Q
What percentage of iodine is normally taken up by the gut?
A
25%
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
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.
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.
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
3 main strategies for treating high I uptake hyperthyroidism
Anti-thyroid drugs (PTU, MMI), radioactive I, and total thyroidectomy
26
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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?
```
* 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
Side effects of PTU and MMI (4)
* 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
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Radioactive Iondine
Uses (5)
Mechanism
Timing of onset
Requirements (2)
Side effects (3)
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* 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
What should be done before a total thyroidectomy?
Pre-treatment w/ anti-thyroid drugs may reduce surgical risk
30
3 things that cause low I uptake hyperthyroidism
Thyroiditis, struma ovarii, meds
31
```
Thyroiditis
I uptake level
Pathogenesis
Presentation
Treatment (4)
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* 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
Silent thyroiditis
No neck pain, but still inflammation of thyroid
33
Treatment of post-partum thyroiditis
Self-limited
34
Struma ovarii
Description
I uptake level
Rare ovarian tumor that produces TH. I uptake is low in neck but high in ovaries.
35
3 meds that induce hyperthyroidism
| I uptake level
Low I uptake
•High I levels --> Jod-Basedow phenomenon
•Amiodarone – rich in iodine
•Thyroid hormone (levothyroxine)
36
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Myxedema coma
Population
Features (6)
Cause (4)
Treatment (4)
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* 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
5 drugs that cause hypothyroidism
* Lithium – impairs release of T4/3
* Amiodarone – Wolff-Chaikoff effect
* PTU, methimazole
* Interferon – causes presentation similar to Hashimoto’s
38
Liothyronine
What is it?
When is it used?
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
Side effects of Levothyroxine / Liothyronine (3)
Changes in estrogen status or weight. Hyperthyroidism sxs (arrhythmia, bone loss)
40
6 things that decrease absorption of exogenous TH
Iron, Ca, soy, sucralfate (antacid), chromium, coffee
41
4 things not related to the thyroid that cause low TSH
Acute illness, exogenous / endogenous glucocorticoids, exogenous DA, or catecholamines.
42
What has a poor prognosis during acute illness?
Low T4
43
What is common during non-thyroidal illness?
Low T3
44
Why is rT3 high during illness?
Mainly due to decreased clearance.
| Partly due to increased production
45
Evaluation of thyroid nodules (5)
* 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
What percentage of thyroid nodules are malignant?
10%
47
Warning signs for thyroid cancer (8)
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
Indications for biopsy
>1cm, solid / hypoechoic on US, microcalcifications, irregular borders, central blood flow, hx of radiation
49
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Papillary thyroid carcinoma
How common?
Poor prognostic factors
Mutations
Where is it found?
Histology
Metastases
Treatment (3)
Tumor marker
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* 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
```
Follicular carcinoma
Histology requirements
Other histo findings
Diagnosis
Which variant is more aggressive?
Metastases
Treatment (3)
Tumor marker
```
* 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
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Anaplastic carcinoma
Population
Presentation
Histology
Mutation
Treatment
```
* 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
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Medullary carcinoma
Always preceded by what?
Tumor markers
Doubling rate
Mutation
Prophylaxis
Diagnosis
Histology
Treatment
```
* 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
What does MEN stand for?
Multiple endocrine neoplasia
54
MEN 1
Gene
Inheritance
Mnemonic
* 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
MEN 2a
Mutation
Inheritance
3 characteristics
* Gain of function mutation in RET oncogene. Autosomal dominant.
* Medullary thyroid cancer (100%), bilateral pheochromocytoma (50%), parathyroid hyperplasia (40%)
56
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MEN 2b
Mutation
Inheritance
4 characteristics
Prognosis
```
* 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.
