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This Concept Map, created with IHMC CmapTools, has information related to: Thyroid, Thyroid Hyperthyroidism Thyrotoxicosis -hypermetabolic state -due to excess T3, T4 -nonhyperactive thyroid -leakage of hormones Hyperthyroidism- -high T3, T4due to thyroid hyperfcn -eg Graves (85%) -hyperfcnal moltinod goiter -hyperfcnal adenoma -exogenous thyroid hor. -thyroiditis, Thyroid Goiter DIFFUSE NONTOXIC (Simple) GOITER -aka colloid goiter Endemic-low iodine - mtns -goiters in ᡂ% -Alps, Andes, Himalayas -low I2->high TSH->more cells -Goitrogens-high Ca++, veggies (cabbage, cauli, Brussels, turnips) -Cassava (inhibits I transport) Sporadic-less often -FEMALES AT PUBERTY -goitrogens or enz defects 1. I transport defect 2. organification defect 3. dehalogenase defect 4. iodotyrosine coupling defect MORPH-hyperplastic THEN colloid involution -some distended foliics, some not -involution if enough I available or dec'd dmd, Thyroid GRAVES DISEASE MORPH-SYMMETRICALLY ENLARGED -hypercellular, papillary infoldings -NO fibrovasc cores -scalloped margins in colloid -some lymphoid aggregates of B cells -preTx alters histology -hypertrophic heart CLINICAL- -audible bruit to thyroid LAB-high T4, T3, low TSH, INCREASED I2 UPTAKE Tx: ablation, surgery, propylthiouracil, Thyroid Hypothyroidism CRETINISM-in neonate -from dietary I def -China, Africa -or sporadic IEMs ->impaired mental, MS development: -severe MR -short stature -course facial features -protruding tongue -umb hernia From thyroid def in utero -MR proportional to def -T3, T4 cross placenta -if mom w/ def, worse MR -gland develops later, Thyroid Hyperthyroidism HASHITOXICOSIS -Graves on top of Hashimoto -hyperthy for couple wks at beginning of Hashimoto, Thyroid Thyroiditis SUBACUTE (GRANULOMATOUS) THYROIDITIS (DeQuervain) -30-50yo, F:M=5:1 SUMMER -2nd most common thyroiditis -via VIRAL infx or post-infx inflam -H/O URI BEFORE THYROIDITIS -coxsackie, mumps, measles, adenovirus, etc. ->provides antigen->CTLs -limited process can be in waves -STRONG HLA-B35 MORPH-bi- or unilaterally enlarged, firm -microabscesses early w/ neutrophils -then lymphocytes, histio, plasma cells -collapsed, dmged follicles -giant cells around colloid -can ->fibrosis CLINICAL-sudden or gradual -neck pain->jaw, throat, ears -fever, fatigue, malaise, anorexia, myalgia -inflam and HYPERthyroid for 2-6wks -can->HYPOthyroidism for 2-8wks ->complete recovery LAB-high T3, T4, low TSH, low I uptake, Thyroid Thyroiditis SUBACUTE LYMPHOCYTIC (Painless) THYROIDITIS-1-10% of hyperthy -middle-aged women -mild hyperthyroidism &/or goiter -HLA-DR3, DR5 (Hashimoto variant) -Tg, TPO ABs MORPH-small lymphos, follicle collapse -if plasma cells, GCs, prob Hashimoto CLINICAL-hyperthyroidism for 2-8wks -nontender, enlarged thyroid LAB-high T4, T3, low TSH, I uptake, Thyroid Hypothyroidism MYXEDEMA-older child, adult -intermediate Sx -insidious in adult-can mimic depression SSx-slowed physical/mental activity -generalized fatigue -apathy, mental sluggishness -slowed speech, listless, overweight -reduced CO->SOB, dec'd exercise -pale, cold, dry skin, constipation -matrix accum-GAGs, hyal acid -in skin, subQ, visceral ->edema, coarse facies, big tongue, deep voice, Thyroid Neoplasms FOLLICULAR CA-10-20% -40s-50s WOMEN-more malig than Pap -increased in endemic goiter areas -might predispose - 1/2 w/ RAS mutations MORPH-calcification, hemorr, fibrosis -colloid-filled follics -mostly uniform, small follics -some w/ Hurthle cells -NO psammoma or orphan annie CLINICAL-slowly enlarging, painless -COLD on scintiscans -some hyperfcnal if well-diff'd-WARM -stim'd by TSH if well-diff SPREAD -lymph uncommon, BLOOD COMMON -to bone, lungs, liver, etc., Thyroid Hypothyroidism General -most common cause-Hashimoto -worldwide-iodine deficiency -radioiodine, resection, irradiation -Rx-methimazole, propylthiouracil, lithium, amiodarone -Dzs- hemochromatosis, amyloid, sarcoid Secondary-low TSH Tertiary-low TRH, Thyroid Hypothyroidism Lab Tests Free T4, TSH initially T4 levels ALWAYS dec'd, Thyroid Thyroiditis REIDEL THYROIDITIS -not true thyroiditis -middle-aged women -idiopathic, extensive fibrosis of thyroid, other neck -can be w/ retroperit fibrosis -mediastinal fibrosis -sclerosing cholangitis -retroorbital pseudotumor -wood-like hardness "Ligneous Thyroiditis", Thyroid Goiter MULTINODULAR GOITER -recurrent hyperplasia & involution -almost all long-standing simple -can be nontoxic or ->toxicosis -cells have diff prolif potential -may have oncogene activation -both mono and polyclonal ->disorganized->rupture, hemorr ->fibrosis, calcifications MORPH-can->intrathoracic/plunging -colloid-rich -flattened, inactive follic epith -can have fibrosis, cystic change CLINICAL-MASS EFFECTS -mostly euthyroid -some w/ hyperFCN nodule ->HYPERTHYROIDISM-toxic -PLUMMER SYNDROME -few w/ HYPOthyroidism TESTS-uneven radioactive I uptake, Thyroid Neoplasms ADENOMAS -mostly follicular epith -NOT forerunners of CA Pathogenesis -somatic muts in cAMP signalling pathway -chronic activation -exaggerated stim by TSH MORPH-solitary, spherical -encapsulated Macrofollicular (simple coll) Microfoll (fetal)-flat epith Trabecular-sparse follicles Atypical-spindle cells -pleomorphic cells, varied nuc ->examine capsule-invasion Hurthle cell-follicular type -large granular eo'philic cells Papillary-large follicles, cysts Clear Cell Follic Adenoma Signet-Ring cell follic adenoma CLINICAL-painless mass -don't take up RA Iodine -rarely hyperfunctional-HOT ->dec'd TSH->NL tissue is quiescent, Thyroid Neoplasms Risk Factors -IONIZING RADIATION -esp ងyo -in kids in Chernobyl -rearrange chrom 10 (RET) -nodular goiter -Hashimoto -RET oncogene (Chrom 10) -rearrangement->RET/PTC -muts in 95% of MEN-II fam -most unlikely to have FHx, Thyroid Hyperthyroidism Testing Initial Screen: TSH, Free T4 -TSH low if primary TRH stimulation test -see if NL rise in TSH ->rule out secondary Radioactive I2 uptake If high T3, low TSH, NL T4 -T3 thyrotoxicosis -Graves or primary -too much periph conversion, Thyroid Neoplasms MEDULLARY CA-5% -neuroendocrine-C cells ->calcitonin -also CEA, VIP, 5-HT, somatostatin -80% sporadic - 40-50s -others w/ MEN IIA,IIB or fam -IIA-95% RET oncogene muts -MEN II cases in younger pts -most likely fam CA of thyroid MORPH-unilateral in sporadic -bilateral in familial -AMYLOID DEPOSITS-altered calcitonin molecules -C cell hyperplasia in FAM only CLINICAL-mass in neck, hoarse -can be paraneoplastic syn -VIP->diarrhea -can screen families for cal'nin -spor, MEN-IIB-ᡪ% 5-yr survival -fam usually indolent, Thyroid Hyperthyroidism S/Sx: Nervousness Palpitations, tachycardia, inc CO -cardiac-earliest SSx -CHF, A.Fib Fatigability, PROXIMAL mm weakness Wt loss, good appetite Diarrhea, warm skin, sweating HEAT intolerance Osteoporosis Emotional lability Menstrual changes Fine tremor of outstretched hand Eye changes-wide gaze (lid lag) (SNS) Thyroid gland enlargement, Thyroid Thyroiditis INFECTIOUS -acute or chronic -direct seeding or hematogenous -mycobac, fung, Pneumocystic in immunocomp. -Acute-sudden neck pain -fever, chills, etc. -usually no sequelae, +/- scarring, Thyroid Neoplasms ANAPLASTIC CA-mean 65yo ɝ% thyroid CA -aggressive - no Tx, always fatal -can eat thru trachea -mort ~100% -1/2 w/ h/o multinod goiter -20% w/ h/o better-diff'd CA -COMMON loss of p53 MORPH- 1 of 3: -large, pleomorphic giant cells -spindle, sarcomatous cells -small anaplastic (may be medullary or lymphoma) -can have foci of pap or follic CLINICAL-RAPIDLY enlarging -mets to LUNG by presentation