Thyroid Disorders Flashcards
1
Q
T3 vs T4
A
- thyroxine (T4) = 90% of hormone secreted rom thyroid
- T4 converted to T3 in peripheral tissues
- Thyroid hormone maintains energy, homeostasis, and regulates metabolism
- target organs include GI, heart, brain, bone liver, skin
- thyroid receptors found in virtually all cells
- T3 is released way less than T4 but is much more metabolically active
- T4 acts as a prohormone for T3
- T4 has a 100 fold lower affinity than T3 for thyroid receptor
- thyroid receptors are found in the nucleus
2
Q
free vs bound thyroid hormone
A
- tightly but reversibly bind to plasma proteins (70% bound to thyroid binding globulin (TBG))
- plasma concentrations of free T4 and T3 reflect amount of hormone actively exerting effect on tissues
- clinically, freeT4 (FT4) is used more than totalT4 (TT4)
3
Q
iodine’s role in thyroid hormone
A
- essential for synthesis of thyroid hormones - obtained from our diet
- dietary iodine = from table salt, ocean fish, seaweed, dairy, grains, kale, spinach
4
Q
factors that increase TBG
A
- estrogens (exogenous or due to pregnancy)
- hypothyroidism
- acute hepatitis
- cirrhosis
- When levels of TBG are increased, more free thyroid hormone is bound so less available to exert effects
- ex) pregnant women needs to have higher dose of T4 or T3
5
Q
factors that decrease TBG
A
- androgens
- cirrhoses
- menopause
- glucocorticoids
- nephrotic syndrome
- cushing’s syndrome
6
Q
labs to assess thyroid hormone
A
- TFTs (thyroid function tests)
- TSH: normal range = 0.4-4.0 –> elevated in hypothyroidism, decreased in hyperthyroidism
- ***TSH ALONE IS THE GOLD STANDARD FOR ASSESSING THYROID CONDITIONS
- free T4: direct measurement of unbound thyroxine
- helpful to look at TSH and T4 together
- start by looking at TSH alone
- free T4 should be obtained to quantify the degree of hyper or hypothyroidism
- T3: serum level useful in dx of autoimmune hyperthyroidism
- thyroid antibodies (TPOAb, TgAb, TSI, TRAb, TBII): useful in diagnosis of autoimmune thyroid dz –> TPOAb and TgAb bositive in Hashimoto’s and Grave’s dz, TBII, TSI, TRAb only found in Grave’s dz
- thyroid scintiscan: not ordered first
- reverse T3: not very helpful unless you suspect euthyroid sick syndrom (common in elderly with sepsis)
7
Q
interpreting labs
A
- serum TSH and FT4 normal –> no further testing
- serum TSH high: low free T4 = primary hypothy, high free T4 = secondary hyperthy (very rare)
- Serum TSH low: low free T4 = secondary hypothy (rare), high free T4 = primary hyperthy
- thyroid uptake and scan: increased uptake = hyperthy, decreased uptake = hypothy
8
Q
hypothyroidism
A
- hypometabolic state from insufficient thyroid hormone
- primary = high TSH with low T4 (thyroid gland problem)
- secondary = low TSH with low T4 (pituitary or hypothalamic - less common)
9
Q
hypothyroidism etiology
A
- most common = dietary iodine deficiency (developing countries)
- autoimmune = destruction of thyroid (hashimoto’s) –> anti-thyroid peroxidase Abs, anti-thyroglobulin Abs
- iatrogenic = results from hyperthyroid or thyroid cancer treatment (RAI, thyroidectomy)
- drug induced = lithium, amiodarone, thalidomide
- primary hypothyroidism = 95% cases
- affects women 4x more than men
- most common in developed countries = Hashimotos
10
Q
Clinical features of hypothyroidism
A
- onset is insidious
- fatigue, lethargy, increased sleep, impaired mental fn, depression, cold intolerance, weakness, myalgias, weight gain, hair loss, skin and nail changes (dry, brittle, scaling), constipation, hoarseness, dysphagia, edema (most is facial and periorbital), menstrual irregularities (increased risk miscarriage, infertility)
- goiter, bradycardia, decreased tendon reflexes, macroglossia
11
Q
Hashimoto’s thyroiditis
A
- chronic lymphocytic thyroiditis
- common cause hypothyroidism (most commonly affects women age 30-60, family hx present)
- high titers autoantibodies (TOPAb and/or TgAb)
- goiter is common finding
- 8x more common in women!
12
Q
Tx of Hypothyroidism
A
- thyroid hormone replacement: levothyroxin (synthroid, levoxyl, levothyroid, tirosint) –> dosing = 1.7 mcg/kg po qd (best taken on empty stomach
- conservative initial tx; incremental increase to slowly achieve restoration of normal metabolism (used in children, elderly, cardiac pts
- full clinical response takes several months, repeat labs every 4-6 weeks
- typically start adults at 25-50 mcg dose (unless they need full thyroid replacement)
- other tx = dessicated pig thyroid gland - includes T4 and T3
- LEVOTHYROXINE is first line due to data, safety
13
Q
complications of hypothyroidism: myxedema coma
A
- severe hypothyroidism, often fatal
- more typically in edlerly with long term untreated hypothyroidism
- usually preceded by event (PNA, peritonitis, MI, CVA, trauma)
- EMERGENCY - high mortality rate
- rarely seen due to use of TSH assays and early detection
14
Q
clinical features of myxedema coma
A
- myxedema = general skin and soft tissue swelling (abnormal deposits of mucin –> proteins produced by epithelial tissues, maintains mucosal barriers)
- scaling, dry, cold; appear “doughy”, yellow-orange discoloration; periorbital edema, nonpitting edema throughout
- sinus bradycardia, hypotension, hypoventilation, pericardial effusion, pleural effusion, ascites
- decreased mental status, slowed speech, ataxia
15
Q
hyperthyroidism
A
- overproduction of thyroid hormone
- MCC is autoimmune –> Grave’s disease
- other causes = toxic nodular goiter (single or multinodular), thyroiditis (subacute, painles, postpartum), TSH producing adenoma (rare)
16
Q
clinical presentation
A
- weight loss, insomnia, anxiety, irratability, heat intolerance, palpitations, tremors, frequent bowel movements, muscle weakness, hair loss, oily skin, amenorrhea
- on exam: tachycardia, diaphoresis, goiter, thyroid bruit (due to increased blood flow in goiter), fine tremor, proptosis, lid retraction, chemosis (edema of conjunctiva)
- cardiac findings: sinus tachycardia, systolic flow murmurs, atrial fibrillation, prominent API
17
Q
Grave’s dz
A
- autoimmune hyperthyroidism
- MCC of hyperthyroidism
- MC in young women 20-40, family hx of autoimmune thyroid dz
- labs show low TSH, high T3 and T4, positive thyroid Abs
- Etiology: autoantibodies to TSH receptor (TRAb, TSHRAb, TSI, TBII) –> Abs bind and activate TSH receptors to stimulate thyroid hormone production
- OPTHALMOPATHY is unique to this dz!!! (not found in other causes of hyperthyroidism)
18
Q
infiltrative opthalmopathy
A
- volume of extraocular mm. and retroorbital CT and adipose tissue is increased d/t inflammation and accum. of hydrophilic glycosaminoglycans (GAG), prinicipally hyaluronic acid
- GAG secretion by firboblasts increased by activation by T cell cytokines (i.e.TNF alfa and interferon gamma)
- accumulation of GAG changes osmotic pressure, leads to fluid accumulation –> increase in pressure in orbit
- THIS ALL PUSHES EYE FORWARD
- selenium can help, smoking makes it worse
19
Q
Grave’s dz tx
A
- refer to endo
- thionamides (propylthiouracil (PTU) and methimazole inhibit thyroid hormone synth –> methimazole preferred b/c qd, more rapid efficacy, fewer ADEs); TSH, FT4, FT3 monitored after 3-4 wks and then q2-3 mos
- once euthyroid is achieved, can proceed with radioactive iodine ablation (RAI)
- beta blockers (atenolol, proranolol) –> sx relief (tachycardia, anxiety, tremulousness, heat intolerance)
20
Q
side effects of methimazole, PTU
A
- methimazole: agranulocytosis/neutropenia (neut usually occurs during first couple months, increased dose increases likelihood)
- PTU: hepatotoxicity and agranulocytosis –> need to monitory LFT’s, CBC –> Methimazole is better for 1st line tx d/t hepatotoxicity
21
Q
RAI tx
A
-usually 2 parts: 1) pt has radioactive iodine uptake and scan to determine extent of hyperactivity of gland. 2) nuclear med radiologist determines appropriate dose of iodine for radioactive iodine ablation (pt returns 1-2 days later for ablation)
22
Q
complications of hyperthyroidism
A
- atrial fib: too much thyroid hormone irritates heart
- CHF: increased HR, palpitations causes ventricular hypertrophy and decreased CO
- bone loss: thyroid hormone increases bone turnover –> more osteoclast activity
- thyroid storm
23
Q
thyroid storm
A
- rare, life threatening
- develops with long-standing untreated hyperthyroid
- precipitated by event (surgery, trauma, infection, acute iodine load, childbirth)
- clinical features: tachycardia, cardiac arrhythmia, hyperpyrexia, n/v/d; may progress to delirium, psychosis, coma
- most likely occur in setting of untreated Grave’s dz
- mortality = 20-30%
24
Q
toxic multinodular goiter
A
- hyperthyroid
- hypersensitive to TSH stimulation
- one or more nodules synthesize excessive amounts thyroxine
- toxic nodule common causes of hyperthyroidism after Graves dz
- more common in elderly
- dx: thyroid uptake and scan determines presence of “hot” nodules
- tx: beta blocker, thionamides (will not induce remission), permanent solution is RAI, surgery
25
thyroid scintigraphy
- uptake and scan
- useful to distinguish between causes of hyperthyroidism, and hyperthyroidism vs. thyroiditis
- iodine uptake and scan (administer Iodine 131 or 123), pt returns 24 hrs later to have "uptake" measured which measures level of radioactivity emitting from thyroid
26
thyroiditis
- thyroid inflammation
| - subacute, painless/silent, pospartum
27
subacute thyroiditis
- self-limited, non suppurative, abrupt onset pain that radiates to ear, jaw, and neck
- thought to be caused by virus or postviral inflammation
- presents with fever, fatigue and lethargy with mild hyperthyroidism initially followed by transient hypothyroidism
- full recovery is common
- tx = symptomatic --> NSAID, prednisone
28
painless/silent thyroiditis
- transient and mile hyperthyroidism sometimes followed by hypothyroidism, then recovery
- thyroid not painful or tender
- tx is symptomatic (beta blocker, short course thyroxine)
29
Postpartum thyroiditis
- variant of hashimoto's thyroiditis (+TPOAb)
- occurs w/in 1 yr of parturition
- often mistaken for depression
- hyperthyroid phase followed by hypothyroid phase
- most recover completely, but 30% have permanent hypothyroid
- some women (20-40% with thyroiditis) only have hyperthyroidism, while others (40-50% with thyroiditis) only have hypothyroidism
30
thyroid nodules
- 90% are benign adenomas/cysts (50% population 30-60yo)
- 10% are lesions w/ varying levels of malignancy
- aggressive thyroid cancer is rare
31
solitary thyroid nodules
- most are benign with hypofunction
- folicular may have normal or increased function
- US is indicated
- thyroid uptake and scan to identify hot (active) vs. cold (inactive) nodules
- can be difficult to palpate
- growth of the nodules can be dependent on TSH or autocrine
32
Dx of thyroid nodule
- US needed to confirm size, consistency, characteristic, and number of nodules
- nodule needs to be monitored, biopsy may be indicated
- US guided fine needle aspiration (FNA): if benign w/ normal TFTs, no tx necessary; if cystic, aspirate every 6-12 mos; if FNA cytology positive for cancer, begin aggressive tx
33
Thyroid carcinoma
- MC malignant neoplasm of endocrine system
- increased risk in pts w/ hx of irradiation to head and neck, family hx of thyroid cancer
- routine screening is key to early dx
- suspicious features on US - solid nodules w/ increase in size from prior study, presence of microcalcifications
34
Classification of thyroid carcinoma
- IN ORDER OF LEAST TO MOST DEADLY
- papillary (mean age dx = 45)
- follicular (mean age dx = 55)
- Medullary
- Anaplastic (mean age dx = 65)
- ALL THYROID CANCER PTS GO TO ENDO, NOT ONCOLOGY
35
papillary carcinoma
- most common (80%) and benign of thyroid cancers
- etiology: genetic, radiation exposure
- enlarged neck lymph nodes in >50% cases
- distant spread (to lungs, bones) very uncommon
- cure rate very high (close to 100% for small nodules)
- tx: total thyroidectomy followed by RAI ablation, TSH suppression (to prevent TSH stimulation and regrowth of remaining tissue) --> ATA guidelines say no TSH suppression in low risk pts
36
follicular carcinoma
- second most common
- peak onset - 40-60yo (female:male = 3:1)
- rarely associated w/ radiation exposure
- prognosis directly related to tumor size --> less than 1cm = good prognosis
- angioinvasive with hematogenous spread
- spread to lymph nodes (~10%) and distant spread uncommon
- tx: same as papillary --> total thyroidectomy followed by RAI ablation, TSH suppression
- cure rate = 95% for small lesions in young pts
37
medullary carcinoma
- 3-5% all thyroid cancers
- neuroendocrine tumor --> produces calcitonin
- females>males
- not associated with radiation
- regional metastases early, distant metastasis late
- poor prognostic factors: age>50, male, distant metastases
- associated w/ other endo tumors due to MEN syndrome (multiple endocrin neoplasia --> genetic, families w/ one or more endocrine glands are overactive or form a tumor. Endo glands MC involved = pancreas, parathyroid, pituitary)
- tx: total thyroidectomy is tx of choice, no response to TSH suppression
- residual dz or recurrence can be detected by measuring calcitonin
- age at time of dx is important factor that influences prognosis: 5 and 10 yr dz free survival rates higher in pts = 40yo compared to those over 40yo (95% vs 65%, 75% vs 50% respectively)
38
anaplastic carcinoma
- 1% all thyroid carcinomas
- male>female, peak onset >60yo
- most invasive and fatal (death within 6-12 mos)
- may present after yrs of radiation exposure
- presentation: rapidly growing hard neck mass, long-standing goiter that suddenly grows, pain, dysphagia, hoarseness, breathing obstruction (tracheal deviation)
- spread to lymph nodes of neck present in >90% cases
- distant spread (to lungs or bones) common when first diagnosed
- aggressive tx plan with surgical resection, radiation, chemo
- 5 YEAR SURVIVAL RATE = 5%
