Thyroid disease Flashcards
Graves disease: presentation & etiology
Triopathy of toxic goiter, thyroid eye dz, pretibial mixed edema (+ hyperpigmented skin)
Antibody against THr –> it’s always active!
- it’s a growht factor too –> thyroid becomes enlarged
Risk factors = pregnancy, cigarette smoking, radioatctive iodine therapy
What are the manifestations of thyroid eye dz?
Decreased edemous outflow –> periorbital edema
Enlarged extraocular muscles due to infiltrate with lymphocytes, glucosamine, glycans
Expansion of retroorbital space due to increase in retroorbital fat/muscle –> natural decrompression of the orbits pushe sthe globes forward
What are the treatment goals of graves dz?
o Decrease circulating levels of thyroid hormones
• Surgery or radioactive iodine to destroy thyroid tissue
• Meds to reduce synthesis, release, & conversion of T4 & T3
o Ameliorate sx i.e. anxiety, palpitations, increased HR
o Correct underlying pathophysiological process
Which meds inhibit thyroid hormone synthesis?
Thiocyanite or perchlorate to stop iodide transport
- *Stop oxidation, organic binding**, and coupling with thiourylenes
- competitive inhibitors of thyroid peroxidase: inhibit incorporation of iodine into tyrosine & inhibit coupling of monoiodothyrodine & diiodothryodine to form T3 and T4
- delayed effect: 3-4 weeks
- Propylthiouracil: shorter half life, risk of hepatocyte necrosis, also has extrathyroid effects
- Methiamazole: longer half life, longer duration of action, can take 1x/day, smaller starting dose
- both used as primary therapy for Graves dz & pre-op preparation for definitive therapy with RAI or surgery
- d/c after 6-18 month –> 1/3 stay in remission, 1/3 relapse, 1/3 elastic remission
- SE= rash, transient leukopenia, livery dysfunction, arthralgias, agranulocytosis
- *Stop proteolysis, release & dehalogenation** with iodide: immediate effect, part of normal homeostasis, blocks hormone synthesis transiently as part of the equilibrium of your boyd so when you have too much iodine, you don’t damage your thyroid; also give pre-op to reduce vascularity of thyroid
- lithium: blocks secretion of preformed hormone, increased RAI retention, prompter control of hyperthyroidism “more bang for your buck” SE=CNS effects
What can be used for symptomatic relief of hyperthyroidism?
- *o Beta-adrenergic antagonists** = alleviate hyperadrenergic sx of hyperthyroidism, reduce peripheral conversion of T4 to T3 (propranolol)
- *o Calcium channel blockers**: useful in pt’s who can’t tolerate beta blockers or if they are contraindicated i.e. asthma
What’s definitive treatment of Graves?
• Radioactive iodine: 75-80% of patients get it
o Concerns include: teratogenicity, long term genetic damage (i.e. to ovaries, bc it’s excreted renally & can radiate them), neoplasia, thyroid cancer, infertility, exacerbation of thyroid eye disease, hypothyroidism
o This is a better therapy than the antithyroid drugs: hypothyroidism is the expected outcome & you can just give them TH = safer, cheaper, than giving antithyroid drugs bc they have bad SE
• Surgery: used selectively i.e. in preg woman who fails antithyroid drugs, active eye dz, suspicion of cancer
o Risks: recurrent laryngeal nerve damage, hypoparathyroidism
o Hypothyroidism: expected outcome
What are the major causes of hypothyroidism?
o Autoimmune
o Hashimoto’s
o Natural history of Graves’ disease: burnt out graves dz → hypothyroidism; the treatment with radioactive iodine therapy just speeds up the process but it happens naturally too!
o Thyroiditis (transient) i.e. happens to some women after delivery
o Iatrogeic: caused by medical treatment
o Post-treatment for hyperthyroidism
o Post-treatment for thyroid cancer
o Iodine exposure (transient): 2-3 days, until you clear the excess iodine
What’s the treatment for hypothyroidism?
o Thyroid extract “dessicated” thyroid, “Armour” thyroid = oldest
• Extract from pigs = combo of T4, T3, lots of inert iodinated products
o Thyroxine: preferred therapy
• Precise dosing, constant serum levels, must monitor TSH, converts to T3
• Longer half life: 1 week
o Triiodothyronine (T3): looser protein binding, shorter half life (1 day), larger fluctuation in serum
• Higher absorption
• Serum levels are variable, monitor TSH, T4 levels low: T3 feedback suppresses TSH & lowers T4 levels
• Combined T4 and T3: Some patients report improved sense of well being
Goiter
Any enlargement of they thyroid gland
Can be diffuse or nodular
diffuse: TSH/TSI stimulates hyperplasia
genetic mutations/goitrogenic substance
infiltration by inflammation or malignancy can occur
nodular: hyperplastic cells can involute & fibrose; small percent are malignant; most are stable in size/function (prolonged subclinical hyperthyroidism)
- *toxic** (causes hyperthyroidism) or non-toxic
- nontoxic: can be diffuse or nodular
- i.e. simple goiter not cause by inflammation/neoplasm = most common! can be due to iodine deficiency –> low TH levels, high TSH which promotes thryoid growth & is why you get a goiter. can also be spontaneous in iodine suffieient areas- smoking, drugs (lithium), natural goitrogens, radiation to head/neck, genetics
- Hashimoto’s thyroiditis
- other infiltrative dz: thyroiditis, cancer
- congenital
- physiologic goiter of puberty
can be benign or malignant
Hashimoto’s thyroiditis
Diffuse or nodular goiter in iodine sufficient region
Common cause in US, more common in women
Autoimmune dz: infiltration of lymphocytes –> inflammation & fibrosi
- insidious process with slow progression to hypothyroidism
Decrease in T4/T3 –> TSH production –> further enlargement of thyroid
How do you evaluate a goiter?
Clinically: s/sx of hyperthyroidism (wt loss, heat intolerance, palpitations, tremor, brisk reflex) + sx of goiter (compressive sx, hoarseness, pain); palpate thyroid to see if diffuse/nodular, uninodular/multinodular, hard, fixed, tender?
Lab: TSH to rule out toxic goiter
Ultrasound
Radioactive iodine scan or CT or PET- rarely
Fine needle aspiraiton biopsy- not necessary on every nodule
Which risk factors of a goiter are associated with a goiter?
Male gender
Age M20 or >60
Radiation exposure/fam hist or thyroid cancer
Firm, fixed nodule and/or rapid growth
Hoarseness or vocal cord paralysis
Region lymphadenopathy
What can ultrasonography help you do when imaging a nodular goiter?
Size, evaluate presence of nodules
distinguish between solid & cystic nodules
distinguish benign/ malignant
guidance for fine needle biopsies
doesn’t use ionizing radiation
Benign v malignant nodules
Benign: iso or hyperechogenic on US
coarse calcificatoins
thin, well defined halo
regular margins
no invasive growth
no abnormal lymph nodes
normal vascularity
Malignant: hypoechogenic
microcalcifications
thick, irregular or absent halo
irregular margins
invasive growth
regional lymph nodes
increased vasculariy
Thyroid adenoma
Benign neoplasm, no malignant potential
Can turn into a carcinoma = neoplasm with malignant potential
Grossly solitary, well demarcated, usually 3 cm, gray white to red brown
Microscopically: follicular growth pattern is distinct from adjancet thyroid= lots of tiny follicules growing all over the place
The capsule is intact
No vascular engagement
Thyroid carcinoma: 4 types
Papillary carcinoma:
most common, F>M but men worse prognosis; prognosis age dependent, metastases worse
papillary = finger-like projections, fibrovascular core; intranuclear grooves= invaginations of nuclear membrane
Follicular carcinoma: presents with a nodule; microscopically = like a follicular adenoma- lots of tiny little follicular nodules; capsular invasion and vascular invasion help you distinguish adenoma from carcinoma
**Anaplastic carcinoma **(undifferentiated): uncommon , often present with symptoms, rapidly growing lesion (SOB, hoarseness), high mortality rate; sometimes we see better differentiated areas i.e. underlying papillary or follicular carcinoma this has bizarre cells: spindle shaped cells (oval, large)
Medullary carcinoma: (can be sporadic) - speckled, salt and peppercorn = uniform looking
Treatment for nontoxic simple goiter?
Endemic: iodine replacement
Sporadic/diffuse: lithium, TSH suppression
Sporadic/nodular:
uninodular: if small/nonconcerning features on US, observe; if larger or increased concern for malignancy, biopsy
surgery for concerning pathology, symptoms, cosmetics
Multinodular: biopsy dominant or concerning nodules, if benign, serial US
radioactive iodine to shrink nodules
surgery for concerning pathology, symptoms, cosmetics
Algorithm for nodules
(1) clinical evaluation, US, TSH
If high: FNA biopsy
If low TSH: thyroid scan: hot or cold?
If hot: radioablation or surgery
If cold: FNA biopsy
From biopsy: if benign- observe or surgery
if malignant or suspicious - surgery
How does ardiactive iodine balation work?
131 iodine used to treat toxic uninodiular or multinodular goiters & nontoxic multinodular goiters
Takes advantage of thyroid avidity for iodine
Radioactive iodine destroys thyroid tissue & treats overactive gland or reduces size of NTMNG (nontoxic multinodular goiter)
Causes hypothyroidism in 20-40% of NTMNG
When would you get surgery? What are your options? What are the risks?
When: positive biopsy, rapid decrompression of vital structures, pathological examination, hyperthyroidism, cosmetic
Types: total, subtotal, hemithyroidectomy
Major risks: mortality, recurrent laryngeal nerve injury, hypoparathyroidism, hypothyroidism
What’s the treatment for thyroid cancer?
Surgery= primary treatment for papillary, follicular, medullary carcinomas (not effective in anaplastic)
Total thyroidectomy typically performed; lobectomy is an option for small PTC or FTC
Radioactive iodine ablation: after thyroidectomy to ablate remaining cancer cells
tx= high dose of I-131 to treat metastatic cancer
Synthroid (T4) to suppress TSH in PTC or FTC
