Term
| what are the functions of thyroid hormone? |
|
Definition
| increases mitochondrial action, respiratory enzymes, Na-K ATPase and other enzymes --> increases basal metabolic rate, increases o2 consumption, and increases sensitivity of target tissues to catecholamines (elevating lipolysis, glycogenolysis and gluconeogenesis) |
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Term
| how much iodine intake is ideal? what is the level of intake that leads to goiter? |
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Definition
| >200 ug/d is ideal. <50 --> elevation in TSH --> goiter |
|
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Term
| what abnormalities do children born to women with endemic goiter have? |
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Definition
| mental retardation, abnormalities of hearing, gait, and posture, short stature |
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Term
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Definition
| thyroid hormone, dopamine, glucocorticoids |
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Term
| how does TSH control thyroid hormone production? |
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Definition
| increases iodine trapping (expression of sodium/iodide symporter); increases oxidation (expression of TPO); iodination, secretion of T4/T3 and ratio of how much is secreted. |
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Term
| what does TRH cause an increase in? |
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Definition
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Term
|
Definition
|
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Term
| why would we measure serum thyroglobulin? |
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Definition
| mostly exists in colloid, but its released into circ in small amounts and is used to indicate the presence of thyroid tissue. used to monitor the completeness of thyroid tissue removal during tx of thyroid cancer. absence --> no recurrence of cancer. reappearance --> return of cancer |
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Term
| anti-thyroid drugs work in what stages of thyroid hormone synthesis? |
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Definition
| oxidation (decrease TPO) and decrease coupling of iodotyrosines |
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Term
| what is the wolff chaikoff effect? |
|
Definition
| excess of iodine --> inhibits organification of iodine (lasts few days, then organification resumes) used to treat thyroid storm (severe hyperthyroidism) - decreases hormone synthesis acutely while other meds are taking effect |
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Term
| what are the 3 main binding proteins for thyroid hormone? |
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Definition
| thyroid binding globulin, transthyretin, albumin |
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Term
| what things increase thyroid binding globulin? |
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Definition
| pregnancy, estrogen use, acute hepatitis, x-linked familial disorder, phenothiazines (schizo), clofibrate |
|
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Term
| what things decrease thyroid binding globulin? |
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Definition
| chronic hepatitis, androgens, glucocorticoids, protein loss, phenylbutazone, phentoin (seizures) |
|
|
Term
| what supplies peripheral T3? |
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Definition
| 20% released from thyroid as T3; 80% converted peripherally in liver and kidney from T4 |
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Term
| describe type 1 de-iodinase |
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Definition
| found in liver, kidney, and thyroid. converts T4 to T3; supplies T3 to the plasma. activity increased by TSH and it influences the amount of T3 produced; activity decreased by PTU and iopanoic acid used in xray contrast |
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Term
| describe type II de-iodinase |
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Definition
| found in brain, pituitary, thyroid, brown fat, placenta, sk m, and cardiac m. converts T4 to T3; supplies T3 for LOCAL use. ensures adequate active hormone in the brain, involved in intracellular production of T3, important in neg FB regulation of TSH. |
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Term
| describe type III de-iodinase |
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Definition
| found in brain, placenta, and skin. converts T4 to rT3 (in malnutrition, illness) and T3 to T2 (inactivates thyroid hormones) |
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Term
| what are the two terms associated with severe hypothyroidism and severe hyperthyroidism? |
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Definition
| severe hypo = myxedematous; severe hyper = thyrotoxic |
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Term
| why can we use beta blockers to treat hyperthyroidism sx (tachy)? |
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Definition
| bc tachycardia is mediated by b-adrenergic stimulation (d/t increased beta receptor concentration or responsiveness) |
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|
Term
| what is thyroid hormones mechanism of action? |
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Definition
| 1. genomic (transcriptional, slow onset) T3 receptors bind DNA with RXRs as heterodimer --> T3 binding to this heterodimer causes coactivation and gene transcription. 2. non-genomic (direct membrane and cytosolic actions, occur within minutes) through P13 kinase. binding causes mitochondrial respiration probably secondary to nuclear effects but possibly direct effects as well |
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Term
|
Definition
| measure of how many binding sites for T3 (and T4) are available on thyroid binding globulin. (more available binding sites --> lower resin uptake. less available binding sites (thyrotoxicosis) --> increase resin uptake of TH) |
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Term
| what is the most useful tool to distinguish the different causes of hyperthyroidism? |
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Definition
| nuclear scans (they are NOT helpful in dx of hypothyroidism) |
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Term
| what can we treat with radioactive iodine? |
|
Definition
| high doses to tx graves disease and toxic multinodular goiters; even higher doses for malignancy |
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|
Term
| what accounts for 98% of hypothyroidism? |
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Definition
|
|
Term
| what is hashimoto's thyroiditis? |
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Definition
| slow irreversible autoimmune destruction of the thyroid. autoantibodies to TPO and thyroglobulin |
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Term
| describe subacute thyroiditis etiology and course |
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Definition
| thyroid post-viral inflammation, usually hx of URI (granulomatous, lymphocytic, post-partum); 3 self-limited phases (hyper, hypo, eu) and hypo phase is transient, so life long rx unnecessary; cells are injured --> release preformed TH --> thyrotoxic (increased T4, normal T3, TSH suppressed) --> inflammation resolves --> mild hypothyroidism |
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Term
| which drugs are assoc with hypothyroidism? |
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Definition
| lithium, iodides, high iodine intake, amiodarone, propylthiouracil, methimazole, INFa or INFb |
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|
Term
| what is JOD-BASEDOW phenomenon? |
|
Definition
| iodine deficient patient --> chronic elevation and overstimulation with TSH --> supply large amount of iodine --> thyroid overproduces --> hyperthyroidism or hyperthyroid crisis |
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|
Term
| what kind of patients are at risk for chronic lymphocytic thyroiditis? |
|
Definition
| downs syndrome (50%) tx with thyroxine while young can help with growth and development |
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|
Term
| what is the long term effect of hypothyroidism on the pituitary? |
|
Definition
| hypertrophy. may result in hyperprolactinemia and galactorrhea (can be mistaken for pituitary tumor) |
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|
Term
| what is the etiology of thyroid hormone resistance syndrome? |
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Definition
| rare, autosomal-dominant disorder caused by inherited mutations in thyroid hormone receptor (abolish ability of receptor to bind to TH) |
|
|
Term
| what expected levels of T3/T4 and TSH in TH receptor resistance syndrome? |
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Definition
| high for both. high TSH because receptors on pituitary for neg FB are also resistant |
|
|
Term
| what are 2 things that can precipitate myxedema coma? |
|
Definition
| cold exposure, sepsis, other stressful situations |
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|
Term
| what lab tests help distinguish myxedema coma from sick euthyroid syndrome? |
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Definition
| SES = increased T3R, decreased cholesterol and decreased TSH; Myxedema = myxadematous appearance, low T3R, high cholesterol, high TSH |
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Term
| tx for primary hypothyroidism? |
|
Definition
| replace/normalize thyroxine. pill once a day. for young people can normalize with higher dose pill right away. for older people, need to start low because too high of a dose could precipitate tachycardia |
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Term
| how to treat secondary hypothyroidism? |
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Definition
| replace thyroixine. replace adrenal steroids too if needed, bc increasing metabolism with thyroid hormone replacement can increase metabolism of adrenal hormones and pt may become suddenly hypoadrenal) |
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|
Term
| what are the 3 features of graves disease |
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Definition
| diffuse hyperplasia of thyroid and thyrotoxicosis; dermopathy; infiltrative ophthalmopathy |
|
|
Term
| what HLA haplotypes is graves associated with? |
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Definition
|
|
Term
| what would we expect to see on nuclear imaging for graves disease? |
|
Definition
| symmetrical homogenous increased uptake of radionuclide |
|
|
Term
| describe the 3fold tx plan for graves |
|
Definition
| 1. immediate decrease in thyroid hormone (PTU and methimazole inhibit TPO --> prevent oxidation of trapped iodine, prevent coupling of iodotyrosines, and PTU inhibits conversion of T4 to T3, no effect on preformed TH; Iodine blocks release of preformed TH) 2. decrease sx related to increased adrenergic tone (tachy, palpitations. use b blockers - propanolol prevents conversion of t4 to t3) 3. long term anti-thyroid (meds, radioactive ablation of gland, surgery) |
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|
Term
| major AE of antithyroid meds? |
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Definition
| agranulocytosis (go to ER if have fever or sore throat) |
|
|
Term
| how do we treat thyroid storm? |
|
Definition
| hydrate, antithyroid meds to stop synthesis, iodine to block release, glucocorticoids, avoid aspirin (dissoc thyroid hormone from binding globulin), tx underlying cause |
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|
Term
| describe solitary toxic thyroid nodule |
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Definition
| 3cm nodules, overactive, produce T3/T4, low TSH, suppress remainder of gland. d/t activating mutation of TSH receptor? |
|
|
Term
| how do we treat solitary toxic thyroid nodule |
|
Definition
| no spontaneous resolution; use radioactive iodine (use antithyroid meds to pre-treat before RAI or surgery) |
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Term
| describe toxic mulit-nodular goiter |
|
Definition
| at least 2 autonomously functioning nodules w/signs and sx of thyrotoxicosis (occasionally not); sometimes precipitated by pharm doses of iodine in ppl with underlying non-toxic multi-nodular goiters (common in areas of iodine deficiency) |
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|
Term
| what would we expect to see on a nuclear scan of toxic multinodular goiter? |
|
Definition
| heterogenous areas of high and low uptake |
|
|
Term
| how do we treat toxic multinodular goiter? |
|
Definition
| antithyroid drugs to pre-tx before radioactive iodine tx; radio-ablation; surgery |
|
|
Term
| what is the tx for jod-basedow syndrome? |
|
Definition
| self-limiting once source of iodine stopped |
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|
Term
| describe painful subacute thyroiditis (de quervains)? |
|
Definition
| viral origin, assoc with HLA B35; giant nucleated cells; fever, malaise, thyroidal pain extending down the ears or anterior chest wall (uni or bilateral), s/s of thyrotoxicosis, VERY tender thyroid, firm and irregular; mild hyperthyroidism (T4>T3 because d/t release of hormone, not synthesis) |
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Term
| what does radio scan look like for de quervains? |
|
Definition
| low iodine uptake (reflects destructive nature of process) |
|
|
Term
| how do we tx de quervains? |
|
Definition
| aspirin or nsaid (4-8 wks), steroids if severe, b blockers if thyrotoxicosis is severe, may have transietn hypothyroidism; NO antithyroid drugs |
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|
Term
| describe painless lymphocytic thyroiditis aka hashimotos hyperthyroid phase |
|
Definition
| s/s thyrotoxicosis, mildly enlarged thyroid, followed by hypothyroidism, ~50% dev long term hyperthyroidism, increased anti-TPO and anti-tg abs, assoc with other autoimmune diseases |
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|
Term
| how do we tx painless lymphocytic thyroiditis? |
|
Definition
| b blockers for thyrotoxicosis, long term problems may require thyroxine replacement rx; NO antithyroid meds |
|
|
Term
| what are the 2 hyperthyroid problems assoc with pregnancy? |
|
Definition
| 1. postpartum thyroiditis (hyper or hypo); 2. excess b-hcg from a molar pregnancy or choriocarcinoma (bhcg x-reacts with tsh bc of structural similarity --> pt becomes hyperthyroid with decreased TSH) |
|
|
Term
| how do we treat excess beta-hcg hyperthyroidism? |
|
Definition
| remove trophoblastic tissue |
|
|
Term
| what is thyrotoxicosis factitia |
|
Definition
| excess ingestion of thyroid hormone (usually t3) |
|
|
Term
|
Definition
| thyroid hormone production in the ovary (rare); thyroid nuclear scanning shows decreased uptake in the neck and increased uptake in the pelvic regions; tx by removing ovarian tumor |
|
|
Term
| what are parafollicular cells responsible for? |
|
Definition
| (C cells) synthesize and secrete calcitonin (inhibits bone resorption by osteoclasts) |
|
|
Term
| what does hashimotos look like histologically? |
|
Definition
| lymphocitic infiltrate, germinal centers, atrophic thyroid follicles, hurthle cells (metaplastic, eosinophilic) |
|
|
Term
| describe subacute thyroiditis symptoms? |
|
Definition
| sudden or gradual, neck pain esp with swallowing |
|
|
Term
| what does subacute thyroiditis look like grossly and histologically |
|
Definition
| grossly: enlarged, firm, yellow/white; histo: aggregations of lys, histiocytes and plasma cells, multinucleate giant cells enclose on pools of colloid (no germinal centers, no hurthle cells) |
|
|
Term
| what does graves look like grossly and histologically? |
|
Definition
| gross: symmetrical enlargement, hypertrophy, hyperplasia, soft and muscle-like; histo: papillae, scalloped edge of colloid, T cells, some germinal centers |
|
|
Term
|
Definition
| decrease sx of hyperthyroidism, reduce TH synthesis with drugs (or radiation, surg) |
|
|
Term
| describe (nontoxic) diffuse and multinodular goiters |
|
Definition
| impaired TH synthesis --> enlarged thyroid (usually d/t iodine deficiency). increase in glandular mass usually restores pt to euthyroid state. can be hypothyroid if compensatory increase in TSH is not adequte (congential defects in TH synthesis or inadequate access to iodine). can be hyperthyroid (if nodules hyperfunction --> toxic multinodular goiter) |
|
|
Term
| describe the gross and histo apperance of multinodular goiters |
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Definition
| gross: exreme assymetric enlargement, compress trachea or esophagus. sometimes grows behind sternum/clavicles to produce plunging goiter. histo: well defined nodules lined by atrophied follicular epithelium (pushed back by abundant colloid) and no papillations |
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|
Term
| what distinguishes follicular adenoma from carcinoma? |
|
Definition
| (both are unilateral painless mass, cold on scan) difference is that adenomas are well-encapsulated, whereas the carcinomas show capsular invasion (vs. papillary carcinomas can be solitary or multifocal, encapsulated or infiltrative) |
|
|
Term
| what is the major risk factor for follicular carcinoma? |
|
Definition
| exposure to ionizing radiation, particularly in first 2 decades of life |
|
|
Term
| most common type of thyroid cancer? |
|
Definition
| papillary carcinoma (then follicular) |
|
|
Term
| how do we distinguish follicular carcioma from papillary? |
|
Definition
| follicular nuclei lack the features of papillary carcioma (longitudinal nuclear grooves and "annie eye" nuclei) |
|
|
Term
| which carcinoma spreads vascularly? which spreads lymphatically? |
|
Definition
| follicular = vascular; papillary = lymph |
|
|
Term
| microscopic dx of papillary carcinoma? |
|
Definition
| finger-like papillae, orphan annie eye (optically clear nuclei), longitudinal grooves, psammoma bodies (laminated calcified structures = remains of necrotic papillae) |
|
|
Term
| 3 important variants of papillary carcinoma |
|
Definition
| follicular (characteristic nuclei, follicular architecture); tall cell (no characteristic nuclei, tall columnar cells eosinophilic staining); microcarcinoma (typical, <1cm) |
|
|
Term
| whats the diff b/w MEN2a and MEN2b? |
|
Definition
| 2a= medullary carcinoma of thyroid + pheochromocytoma; 2b= medullary carcinoma of thyroid and pheochromocytoma + mucocutaneous neuromas |
|
|
Term
| what do medullary carcinomas look like histologically |
|
Definition
| polygonal to spindle shaped cells (nests, trabeculae or folicles), amyloid deposits (from altered calcitonin molecules - look glassy pink and stain with congo red); membrane-bound electron-dense granules |
|
|
Term
| describe what sets anaplastic carcinomas apart from other thyroid carcinomas as far as presentation and prognosis |
|
Definition
| RAPIDLY enlarging bulky neck mass. 100% mortality. no tx, death in <1yr. |
|
|
Term
| what does anaplastic carcinoma look like histologically |
|
Definition
| highly anapalstic cells, large pleomorphic giant cells, spindle cells, sarcomatous appearance |
|
|
Term
| secondary hyperparathyroidism is almost always secondary to what? |
|
Definition
| depressed levels of serum calcium caused by renal failure |
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