Adult Thyroid - Javorsky Flashcards
What is the most common cause of primary hyperthyroidism?
What are some other causes?
Grave’s Disease
Toxic multinodular goiter, solitary follicular adenoma, and “thyroiditis”
Describe the epidemiology of Grave’s disease.
How does it arise?
More common in females, with a strong familial disposition.
Defect in suppressor T-cells allows T>B sensitization against a thyroid antigen. The produced antibodies stimulate the thyroid, increasing thyroid hormone release despite low TSH.
What ocular findings are seen in Grave’s disease? Why?
How is this assessed, and what is the major sequela?
Proptosis/exophthalmos, mostly due to inflammation of the extraorbital muscles (shares a common antigen with the thyroid).
Measure with a Hertel exophthalmometer. Increased extraocular pressure may damage optic nerve!
What are some typical signs and symptoms of thyrotoxicosis?
Alertness, emotional lability, poor concentration.
Muscular weakness and fatiguability (especially proximal), with fine tremor.
Heart palpitations, tachycardia.
Weight loss despite increased appetite. More bowel movements.
Lid lag & stare, with proptosis and periorbital edema.
Fine, moist skin (especially pretibial thickening)
Cold intolerance.
Following clinical suspicion of primary hyperthyroidism, what test should be ordered?
What will point to Grave’s disease in particular?
TSH levels; these should be low while T3/T4 are high or within reference.
Presence of TSIs (thyroid stimulating immunoglobulins).
What test can distinguish a grave’s disease from a multinodular goiter or follicular adenoma?
Radioiodine uptake scan. Pattern is diffuse and bilateral in Grave’s, solitary or irregular on the others.
Describe the mechanism of action of methimazole.
What are its indications?
Side effects?
Blocks oxidation (& organification) of iodine in the thyroid.
Used for hyperthyroidism in general.
Mild lupus-like symptoms, chance of reversible agranulocytosis.
Contrast propylthiouracil to methimazole in terms of mechanism of action, indication, and side effects.
Same mechanism with the addition of blocking T4 to T3 deiodination.
Both used for hyperthyroidism; methimazole is preferred in general but PTU for 1st trimester pregnancies.
Same side effects as methimazole, plus risk of hepatic failure.
How does iodide treat hyperthyroidism?
What else is it used for?
Side effects?
Iodide directly inhibits thyroid hormone release. It also “shrinks” hyperplastic glands.
Also used pre-op for thyroidectomy and for radioactive iodine fallout.
Acute sensitivity (angioedema / laryngeal edema / serum sickness), head cold.
What radioactive treatment is recommended for most thyroid carcinomas?
Which can it not treat?
131I, given as a single capsule.
Does not treat medullary thyroid carcinomas since they don’t take up iodine (these are made of parafollicular C cells!)
Mild thyrotoxicoses can be treated with treatments other than methimazole/PTU/iodide. Name 3 such treatments.
Beta-blockers (block adrenergic effects of thyroid hormones)
Lugol’s solution (oral iodine)
Cholestyramine (binds thyroid hormones in enterohepatic circulation)
What can cause a secondary hyperthyroidism?
How common is this?
Lab findings?
Pituitary adenoma of the thyrotrophs.
Not common at all.
Elevated TSH despite increased T3/T4.
Most thyroid neoplasias can be treated with surgical removal. What are the risks associated with this procedure?
Damage to the laryngeal nerves and to the parathyroid glands.
Say a patient presents with some weight loss, sweating, and mild heat intolerance. Her TSH is low, and thyroid scans are normal.
What is your diagnosis and treatment?
This is hyperthyroidism resulting from inflammatory destruction of the thyroid gland (“thyroiditis”), treat with only beta blockers and supportive care.
Name the drug that fits the description.
- Can be used pre-operatively for thyroidectomy.
- Used in first trimester pregnancies.
- Blocks organification of iodine.
- May cause angioedema, serum sickness, or just a head cold.
- Ablates the thyroid from within colloids.
- Iodide
- PTU.
- Methimazole and PTU.
- Iodide
- 131I
What is deficient in:
- Primary hypothyroidism?
- Secondary?
- Tertiary?
- Primary = Thyroid gland
- Secondary = Pituitart gland
- Tertiary = Hypothalamus
What is the other name for Hashimoto’s Thyroiditis?
What is the pathogenesis of the disease?
What risk factors are thought to contribute to its development?
Chronic Lymphocytic Thyroiditis
Autoimmune destruction of the thyroid gland via cytokine release and inflammation following autoimmuine lymphocyte sensitization and activation
Risk factors:
- Environmental factors
- Viral or bacterial infection
- High iodine intake
- Genetic factors
- e.g. Treg defects, etc.
Antibodies against what thyroidal antigens can be seen in Hashimoto’s Thyroiditis?
- Thyroglobulin
- Thyroid peroxidase
- TSH receptor
Aside from Hashimoto’s, what are some other causes of primary hypothyroidism?
- Partial or total thyroidectomy [duh]
-
Reversible autoimmune thyroiditis
- silent and postpartum thyroiditis
- Irradiation
- Infiltrative & infectious disease
- Thyroid dysgenesis
- Iodine deficiency
- Iodine excess (Wolff-Chaikoff effect)
- Drugs
- Antithyroid agents
- Lithium
What is the Wolff-Chaikoff effect?
How is this concept applicable therapeutically?
(not discussed in class materials, but the concept is simple and seems high yield down the road…)
- Autoregulatory reaction of thyroid in response to a large iodine ingestion
- **Decrease **in iodine organification and thyroid hormone production & release
- Eventual downregulation of Na+-I- symporter (NIS) on thyroid follicular cell
- Prevents excessive thyroid hormone formation following high iodine intake
-
Therapeutic uses of this principle:
- Iodine was used to treat hyperthyroidism before newer agents
- Including Grave’s (Grave’s thyroid esp. sensitive to this effect)
- The basis of giving iodine to those exposed to nuclear fallout
- Prevent thyroid uptake of damaging radioactive iodine
- Iodine was used to treat hyperthyroidism before newer agents
(All from Wiki)
Name some causes of secondary or tertiary hypothyroidism
- Tumors
- Trauma
- Infiltrative diseases
- Sarcoidosis
- Hemochromatosis
- Drugs
- Dopamine
- Glucocorticoids
- Inactivating mutations of genes in the hormonal axis
Hypothyroidism has a boatload of potential symptoms. Name as many as you can.
[Memorizing all is likely low-yield]
- Hair loss
- Periorbital puffiness
- Ptosis
- Loss of outer third of eyebrow
- Macroglosia
- Hoarseness
- Lack of facial expression
- Depression
- Fatigue
- Pallor
- Weight gain
- Constipation + decreased bowel sounds
- Bradycardia
- Hypoventilation
- Menstrual irregularities
- Infertility
- Pain & cramps
- Cold intolerance, Hypothermia
- Nonpitting edema
- Cool, rough, dry skin
- Peripheral neuropathy
How can TSH be within the reference range in some instances of secondary/tertiary hypothyroidism?
- Again, recall the principal that TSH may be in the reference range, but it is innappropirately not elevated given the low free T3 & T4.
- Recall the reference range is technically only applicable to patients who are healthy!
What two drugs are used to treat hypothyroidism?
Which is more commonly used?
- Levothyroxine (recombinant T4) - most commonly used
- Liothyronine (recombinant T3)
(Quick mnemonic: Levo = 4 letters = T4. Lio = 3 letters = T3.)
Compare levothyroxineandliothyronine in terms of:
- Relative potency
- Oral bioavailability
- Elimination half-life
- Daily doses
- What is severe hypothyroisism referred to as?
- Why can it be life-threatening?
- What is the typical clinical case?
- Myxedema coma
- Concerns:
- Multiorgan dysfunction
- Profound hypothermia
- Hypoventilation
- Hypotension
- CNS symptoms
- An elderly patient with a history of hypothyroidism developed myxedema coma after a stressful precipitating event, e.g. infection, MI, or stroke.
- What is the first test typically ordered when thyroid disease is expected: TSH or T4?
- Why is it not the other one?
- TSH is done first
- T4 and TSH share a log-linear relationship: a small change in T4 will result in a large change in TSH via the strength of the feedback. Thus, abnormalities in TSH levels are typically more easily detected.
- What is the goal TSH range for patients taking levothyroxine?
- How long does it take a patient beginning levothyroxine therapy to reach steady-state levels?
- How much is a typical dose of levothyroxine once steady state is reached?
- 0.5 - 4 mU/L
- ~5-6 half-lives. T4 t1/2 = 7 days. So about 5-6 weeks.
- 1-2ug/kd/day
What are the side effects of taking levothyroxine?
When monitored well and kept within physiologic levels:
NO reported side effects
