Post on 08-Jul-2015
Interpreting Interpreting Thyroid Function Thyroid Function TestsTests
DOMMRDOMMR
Rozina MithaniRozina Mithani
Pt Info:Pt Info: CC: palpitationsCC: palpitations
82 y/o F presents with hyperactivity, sweating, 82 y/o F presents with hyperactivity, sweating, palpitations, wt loss, insomnia, moist skin, fine palpitations, wt loss, insomnia, moist skin, fine hair, irregular menses, diarrheahair, irregular menses, diarrhea
PE: tachy, elevated SBP, damp skin, lid lag, PE: tachy, elevated SBP, damp skin, lid lag, hyperreflexive DTRhyperreflexive DTR
Labs: CBC wnl, BMP wnl, TSH <0.01 (L), T4 4.1 Labs: CBC wnl, BMP wnl, TSH <0.01 (L), T4 4.1 (H), T3 wnl(H), T3 wnl
ObjectivesObjectives
PathophysiologyPathophysiology
ThyrotoxicosisThyrotoxicosis
HypothyroidHypothyroid
Hormone RegulationHormone Regulation
TRH TRH TSH TSH iodine uptake, organificationiodine uptake, organification synthesis & release of thyroid hormonesynthesis & release of thyroid hormone
T4/T3 Regulate:T4/T3 Regulate: basal metabolism, thermogenesis, basal metabolism, thermogenesis,
lipogenesislipogenesis fetal CNS developmentfetal CNS development
Thyroid HormonesThyroid Hormones
Thyroxine (T4)Thyroxine (T4) Thyroid glandThyroid gland t1/2: 8 dayst1/2: 8 days
Triiodothyronine (T3)Triiodothyronine (T3) 80% in Periphery80% in Periphery
Liver/kidney remove iodine from T4 Liver/kidney remove iodine from T4
Regulate Thyroid Hormone-Regulate Thyroid Hormone-dependent genesdependent genes
t1/2: 1-1.5 dayst1/2: 1-1.5 days
T4 T4 T3 T3 Decreased:Decreased:
Meds: propranolol, PTU, Meds: propranolol, PTU, corticosteroids, amiodaronecorticosteroids, amiodarone
Illness: cytokine mediatedIllness: cytokine mediated
Binding ProteinsBinding Proteins
T4/T3 99% protein boundT4/T3 99% protein bound Prevents excess tissue uptakePrevents excess tissue uptake Maintains accessible reserveMaintains accessible reserve
Thyroxine-binding globulin (TBG) - 70%Thyroxine-binding globulin (TBG) - 70% Inc: E2, 5-FU, Methadone, TamoxifenInc: E2, 5-FU, Methadone, Tamoxifen Dec: Androgens, Corticosteroids, NiacinDec: Androgens, Corticosteroids, Niacin
Albumin – 15-20%Albumin – 15-20% Transthyretin – 10-15%Transthyretin – 10-15%
TFTsTFTs
TSH
HIGH = HypoCheck free T4
NL =No further Testing
LOW = HyperCheck free T3/T4
FunctionalDisorders
Thyrotoxicosis Hypothyroidism
-Grave’s Disease- Toxic Adenoma
- Toxic Multinodular Goiter-Thyroiditis-Exogenous
-TSH Mediated
-Hashimoto’s Disease- Post-op/Post-ablative
-I deficiency
ThyrotoxicosisThyrotoxicosis
Thyroid excess from any cause:Thyroid excess from any cause: Increased SynthesisIncreased Synthesis Damaged Gland Damaged Gland Exogenous IntakeExogenous Intake
RAIURAIU High (>30%): HyperfunctionHigh (>30%): Hyperfunction NL (10-30%): EuthyroidNL (10-30%): Euthyroid Low (<10%): Thyroiditis, I excess, AmiodaroneLow (<10%): Thyroiditis, I excess, Amiodarone
SymptomsSymptoms
Increased Metabolism:Increased Metabolism: Weight loss, Dec appetiteWeight loss, Dec appetite Warm, sweating, thirst, fever Warm, sweating, thirst, fever Tachycardia, Arrhythmia, Tachycardia, Arrhythmia,
PalpitationsPalpitations Diarrhea Diarrhea Fatigue, Exhaustion Fatigue, Exhaustion GoiterGoiter Difficulty concentratingDifficulty concentrating Panic and anxiety Panic and anxiety Hyperreflexia, Tremors Hyperreflexia, Tremors InsomniaInsomnia
Other:Other: Pregnancy-related problems Pregnancy-related problems Arthralgias Arthralgias Skin: hives, itching, vitiligoSkin: hives, itching, vitiligo Hair loss Hair loss Finger/nail changesFinger/nail changes Eye: bulging, dry, painEye: bulging, dry, pain Depression, irrational anger Depression, irrational anger
ThyrotoxicosisThyrotoxicosis
Increased SynthesisIncreased Synthesis
Damaged Gland Damaged Gland
Exogenous IntakeExogenous Intake
Increased Synthesis: Increased Synthesis: HyperthyroidismHyperthyroidism High T4 & Low TSHHigh T4 & Low TSH
Increased T4/T3 release:Increased T4/T3 release: Grave’sGrave’s Toxic MNGToxic MNG Toxic AdenomaToxic Adenoma
High RAIUHigh RAIU
Grave’s DiseaseGrave’s Disease
Most common cause in USMost common cause in US AutoAb against TSH receptorAutoAb against TSH receptor
Diffuse Goiter, Thyrotoxicosis, High RAIUDiffuse Goiter, Thyrotoxicosis, High RAIU Thyroid Scan: Increased activityThyroid Scan: Increased activity Ophthalmopathy, Dermopathy, Ophthalmopathy, Dermopathy,
AcropathyAcropathy
Grave’s Disease - Grave’s Disease - treatmenttreatment Medication: 50% remission @ 1 yearMedication: 50% remission @ 1 year
MethimazoleMethimazole PTUPTU BB while toxicBB while toxic
Radioactive Iodine AblationRadioactive Iodine Ablation Not for pts with severe ophthalmopathyNot for pts with severe ophthalmopathy
Surgical RemovalSurgical Removal
Toxic Multinodular Toxic Multinodular GoiterGoiter Sporadic Goiter Sporadic Goiter Multinodular Multinodular
Euthyroid Euthyroid Subclinical Subclinical Overt Thyrotoxicosis Overt Thyrotoxicosis
Increased RAIU (autonomous production)Increased RAIU (autonomous production) Rest of Gland suppressedRest of Gland suppressed
Treatment: Radioactive IodineTreatment: Radioactive Iodine
Toxic AdenomaToxic Adenoma
HOT Nodule: Autonomous functionHOT Nodule: Autonomous function Activating Mutation of TSH ReceptorActivating Mutation of TSH Receptor Size = Hormone productionSize = Hormone production
>3 cm >3 cm
Treatment: Treatment: HemithyroidectomyHemithyroidectomy Radioactive IodineRadioactive Iodine
ThyrotoxicosisThyrotoxicosis
Increased SynthesisIncreased Synthesis
Damaged Gland Damaged Gland
Exogenous IntakeExogenous Intake
Damaged GlandDamaged Gland
Low RAIULow RAIU
Subacute Thyroiditis: BB & NSAIDsSubacute Thyroiditis: BB & NSAIDs Firm & painful glandFirm & painful gland Post-viralPost-viral
Drug-InducedDrug-Induced Amiodarone, Lithium, Amiodarone, Lithium, αα-IFN, IL-2-IFN, IL-2
Postpartum ThyroiditisPostpartum Thyroiditis
Amiodarone-InducedAmiodarone-Induced
3% of patients in US3% of patients in US Type 1: high iodine content (JodBasedow)Type 1: high iodine content (JodBasedow)
Pre-existing thyroid autonomyPre-existing thyroid autonomy High RAIUHigh RAIU Treatment: methimazoleTreatment: methimazole
Type 2: direct toxic effectType 2: direct toxic effect No Pre-existing thyroid autonomyNo Pre-existing thyroid autonomy Low RAIU, Inc InflammationLow RAIU, Inc Inflammation Treatment: Prednisone, NSAIDsTreatment: Prednisone, NSAIDs
ThyrotoxicosisThyrotoxicosis
Increased SynthesisIncreased Synthesis
Damaged Gland Damaged Gland
Exogenous IntakeExogenous Intake
Surreptitious IntakeSurreptitious Intake
Low TSHLow TSH Low RAIULow RAIU Low TG levelLow TG level
Thyroid StormThyroid Storm
IatrogenicIatrogenic Radioiodine therapy, Contrast dyesRadioiodine therapy, Contrast dyes
Abrupt cessation of Antithyroid drugsAbrupt cessation of Antithyroid drugs SurgerySurgery Acute Nonthyroidal IllnessAcute Nonthyroidal Illness
Stroke, PE, DKA, Trauma, InfectionStroke, PE, DKA, Trauma, Infection
Thyroid Storm - Thyroid Storm - treatmenttreatment
•Blocks T4T3Hydrocortisone/
Dexamethasone
•Blocks new hormone synthesis•Blocks hormone release
Iodine
•Blocks T4T3 in high dosesPropanolol/
Esmolol Infusion
•Blocks new hormone synthesis•Blocks T4T3
PTU/Methimazole
Drug
Subclinical Subclinical ThyrotoxicosisThyrotoxicosis Low TSH & High NL T4Low TSH & High NL T4
ComplicationsComplications Arrhythmia, OsteoporosisArrhythmia, Osteoporosis esp >65y/o with TSH <0.1 mU/Lesp >65y/o with TSH <0.1 mU/L
FunctionalDisorders
Thyrotoxicosis Hypothyroidism
-Grave’s Disease- Toxic Adenoma
- Toxic Multinodular Goiter-Thyroiditis-Exogenous
-TSH Mediated
-Hashimoto’s Disease- Post-op/Post-ablative
-I deficiency
HypothyroidismHypothyroidism
Low T4 & High TSHLow T4 & High TSH
More common than ThyrotoxicosisMore common than Thyrotoxicosis
Treatment: Synthroid - goal TSH 1-2 mU/LTreatment: Synthroid - goal TSH 1-2 mU/L
SymptomsSymptoms
Slow Metabolism:Slow Metabolism: Weight GainWeight Gain ConstipationConstipation Hypothermia/Cold Hypothermia/Cold
IntoleranceIntolerance Fatigued, LethargyFatigued, Lethargy Slow Movements/speechSlow Movements/speech Delayed DTRsDelayed DTRs BradycardiaBradycardia
Accumulation of Matrix Accumulation of Matrix Substance:Substance:
Skin: coarse/dry, scalySkin: coarse/dry, scaly Hair: coarse/dry, brittle, lossHair: coarse/dry, brittle, loss HoarsenessHoarseness Edema of eyes and faceEdema of eyes and face
Other:Other: ArthralgiasArthralgias Irregular menstrual cyclesIrregular menstrual cycles DepressionDepression
Monitoring Monitoring ReplacementReplacement
TSH
HIGH = Not EnoughINC Dose
NL = Continue Dose
LOW = Too MuchDEC Dose
Medication Medication ControversyControversy ? T3? T3
1999: improved mood 1999: improved mood & psych testing with & psych testing with combo therapycombo therapy
Four subsequent Four subsequent studies refutedstudies refuted
? Generic Synthroid? Generic Synthroid Not all bioequivalent Not all bioequivalent
when FDA approvedwhen FDA approved
Hashimoto’sHashimoto’s
Most common cause in North AmericaMost common cause in North America Positive anti-TPO AbPositive anti-TPO Ab Increase Autoimmune EndocrinopathyIncrease Autoimmune Endocrinopathy
Addison’s, DM1, Premature ovarian failureAddison’s, DM1, Premature ovarian failure
No further w/uNo further w/u
Myxedema ComaMyxedema Coma
Obtundation, HypothermiaObtundation, Hypothermia
CV Changes: CV Changes: Dec HR, Contractility, SBP, CODec HR, Contractility, SBP, CO Inc SVR, DBPInc SVR, DBP Pericardial EffusionPericardial Effusion
Precipitant: Infection, trauma, cold, sedativePrecipitant: Infection, trauma, cold, sedative
Myxedema Coma - Myxedema Coma - treatmenttreatment IV Levothroxine replacementIV Levothroxine replacement Corticosteroids – adrenal insufficiencyCorticosteroids – adrenal insufficiency MV – CO2 retention, hypoxiaMV – CO2 retention, hypoxia Treat precipitating causeTreat precipitating cause
Subclinical Subclinical HypothyroidismHypothyroidism High TSH & Low NL T4High TSH & Low NL T4 Most have Hashimoto’sMost have Hashimoto’s
Systemic symptoms, elevated LDL, Systemic symptoms, elevated LDL, Cardiac changesCardiac changes
ObjectivesObjectives
PathophysiologyPathophysiology
ThyrotoxicosisThyrotoxicosis
HypothyroidHypothyroid