Understanding Thyroid Labs Chris Sadler, MA, PA-C, CDE, DFAAPA Senior Medical Science Liaison CVM Janssen Scientific Affairs Diabetes and Endocrine Associates La Jolla, CA Disclosures Employee of Janssen Pharmaceuticals None related to this topic Learning Objectives Participants in this session will learn : To choose appropriate labs for the diagnosis of common thyroid conditions To interpret laboratory values to identify the most likely diagnosis To recognize when additional diagnostic test (lab or imaging) are needed to clarify the diagnosis. To recognize when referral to a specialist is warranted
Question 1 Current labs: TSH: 0.25 (0.4-4.0) Free T4: 1.4 (0.8 1.8) Total T3: 165 (80-180) What is the most appropriate diagnosis based on these labs? A. Hypothyroidism B. Subclinical Hypothyroidism C. Hyperthyroidism D. Subclinical Hyperthyroidism E. I don t know, ask me again later A patient was started on methimazole 4 weeks ago for Graves dz. Current labs: TSH: 0.003 (0.4-4.0) Free T4: 0.30 (0.8 1.8) Total T3: 55 (80-180) What is the most appropriate medication adjustment? A. Increase Methimazole B. Decrease Methimazole C. Keep current dose D. Ask the patient what they prefer Question 2 Prevalence of Thyroid Disorders 21-27 Million in US with thyroid dz over half undiagnosed >360,000 new cases each year Increases with age 40% of patients on thyroid meds have an abnormal TSH Post-partum-thyroiditis on the rise www.thyroid.org
What Does Thyroid Hormone Do? The great SYNERGIZER Increases fetal development (synergy with GH) Increases MVO2, CO, HR Stimulate B-adrenergic Beta receptor in heart Stimulates gut motility and protein catabolism Major impact on menses and fertility Important in thermogenesis Lipid metabolism (T3 mostly) Suspicion/risk of thyroid issues High LFTs CHF, Afib, CAD Dyslipidemia Anemia, hypercalcemia, incr. Prolactin Infertility, menstural issues Autoimmune diseases Amiodarone, lithium, New psychosis, mental instability Newborn and pregnancy Thyroid Disorders & Autoimmune Associations Type 1 DM Vitiligo Addisons Pernicious anemia Celiac RA Psoriasis Sjogrens
TSH?? Free T4 TPO Abs T3 TRAb Hypothyroidism Hyperthyroidism Thyroid nodules/cancer What Can Go Wrong? The problem can be Intrinsic (PRIMARY): thyroid Extrinsic (SECONDARY): H-P disorders Or dietary/ medication/ acute illness problems
T4 Hypothalamic-Pituitary-Thyroid Axis Physiology Hypothalamus TRH Pituitary T3 TSH Thyroid Gland Target Tissues Heart Liver T4 T3 TR Bone Bind to proteins T4 T3 Liver CNS Adapted from Merck Manual of Medical Information. ed. R Berkow. 704:1997. Production of T4 and T3 T4 is the primary hormone released by the thyroid gland, ~9-10x more T4 than T3 T4 is highly protein bound (99%) 75% bound to thyroid binding globulin (TBG) The rest bound to: thyroid binding prealbumin, albumin, and HDL Carrier proteins can be affected by physiologic changes, drugs, and disease T3 released in very small amounts but it is the most potent physiologically (4x > T4) About 80% of circulating T3 comes from deinodination of T4 in peripheral tissues (20% from direct thyroid secretion) Obesity causes decreased T4 to T3 conversion Tests of Thyroid Function TSH Free T4 Total T3 or Free T3 Thyroid scanning
TSH THE screening test cant make dx on this alone New normal range 0.4-4.0 (0.3 2.5 for those without antibodies) to 3 decimal points ( highly-, super-, ultra-sensitive, etc.) Inverse relationship to FT4 (a 2 fold change in FT4 produces 100 fold change in TSH) Everyone has a genetically set point; a normal value may hide subclinical disease Changes slowly in response to Rx; (6-8 weeks, may take up to 12 weeks in elderly) Possible Causes of Low TSH Hyperthyroidism Graves Toxic adenomas or autonomously functioning thyroid nodules Toxic Multinodular goiter (TMNG) Thyroiditis (post-partum, subacute, silent) Pregnancy, Hyperemesis gravidarum Central Hypothyroidism Euthyroid Sick Syndrome Medications (steroids, sympathomimetics, Amiodarone) Ingestion of excess exogenous thyroid hormone (most common) Hypothalamic-Pituitary-Thyroid Axis Physiology Hypothalamus TRH Pituitary T4 T3 TSH Thyroid Gland Target Tissues Heart Liver T4 T3 TR Bone Bind to proteins T4 T3 Liver CNS Adapted from Merck Manual of Medical Information. ed. R Berkow. 704:1997.
10-20% women have reduced TSH with HCG peak 28 yo female at 10 weeks gestation has a suppressed TSH of 0.24 (0.4-4.0) She is asymptomatic for hyperthyroidism. You should: A. Refer to Endocrinology B. Check Free T4 C. Reassure, repeat TSH in 2 nd Trimest D. Order thyroid scan 10 Possible Causes of High TSH Hypothyroidism Thyroiditis Central Hyperthyroidism
T4 Hypothalamic-Pituitary-Thyroid Axis Physiology Hypothalamus TRH Pituitary T3 TSH Thyroid Gland Target Tissues Heart Liver T4 T3 TR Bone Bind to proteins T4 T3 Liver CNS Adapted from Merck Manual of Medical Information. ed. R Berkow. 704:1997. Free T4 THE test to monitor the acute response to therapy; changes rapidly To confirm meaning of a low or high TSH Everyone has a genetically set point; a normal value may hide subclinical disease Avoid FTI (Total T4/T3 Resin Uptake) Not a direct measurement of T4 but a calculation and prone to interference Why FT4 and not Total T4 (factors increasing total T4) High estrogen states Hyperemesis gravidarum Lab error Autoimmunity Acute illness Acute psychiatric problems Familial thyroid binding abnormalities Generalized resistance to thyroid hormone Drugs
When FT4 and TSH Seem Discordant Usually means early or subclinical disease Often occurs after initiating a therapy that changes thyroid function (e.g. starting L-thyroxine or starting anti-thyroid meds); FT4 will change before TSH Sign of Pituitary or Hypothalamic dysfunction (central hypo or hyperthyroidism) -Refer
Total or Free T3 Assess for T3 toxicosis To clarify subclinical thyroid conditions Assess response to therapy when using T3 in your replacement dose Assessing response to anti-thyroid medication when T3 was elevated prior to Rx Most accurate when elevated, poor performance in normal and low ranges (Total T3 more reliable assay) Adjunctive Tests Antibodies: (Tg, TPO): thyroiditis, goiter, nodules, Hashimoto s dz Thyroid Receptor Antibodies (TRAb): TSI- Thyrotropin stimulating immunoglobulin TBII- Thyrotropin binding inhibitory immunoglobulin Reverse T3: confirms euthyroid sick syndrome when elevated only order in hospitalized pts. Thyroglobulin: cancer marker post thyroidectomy Thyroid Scanning: labeled iodine travels to functioning parts of thyroid Thyroid Uptake: How rapidly the iodine gets in Adjunctive Tests (TRAB s) Free T4 Total T3, T3 toxicosis, euthyroid sick TSH Receptor Auto Antibodies (TRAb) TBII (thyrotropin binding inhibitory immunoglobulin) TSI (thyroid stimulating immunoglobulin) ENDOCRINE PRACTICE Vol 17 No. 3 May/June 2011
Thyroid Uptake/Scan Thyroiditis (low uptake) Graves (increased uptake, when other signs lacking) Looking for hot/cold nodules Percent uptake to prepare for I-131 Normal/Cold Nodule Toxic MNG
Toxic Hot Nodule Thyroiditis Thyroid Uptake Associated With Elevated Radioiodine Uptake Graves disease Toxic Adenoma/Nodule Toxic MNG Associated With Depressed Radioiodine Uptake Thyroiditis acute subacute Painless Post-partum Hashitoxicosis Iodine ingestion Fisher, J South Med J 2002
CASE 1 70 yo male with fatigue, (pulse 95 bpm) TSH: 0.098 (0.35-4.00) What do you do next? More Labs? I-123 Uptake and Scan? Ultrasound? CASE 1 What do you do next? It depends Any clues from physical exam? Free thyroid hormone levels Thyroid antibody tests? Imaging (US, Uptake, Scan) Diagnosis of Hypo/Hyperthyroidism Weight and blood pressure Thyroid palpation and auscultation (to determine size, tenderness, nodularity and vascularity) Cardiovascular (pulse rate, rhythm) Neuromuscular exam (muscle weakness, hyperreflexia, tremor, delayed ankle DTR) Eye exam (exophthalmos, stare, edema) Dermatologic (nails, diaphoresis, dry skin, myxedema)
CASE 1 Exam is normal except for high normal pulse of 95 bpm. When would you order an Ultrasound of the Thyroid? Asymmetrical gland or palpable nodule If cold area(s) on Scan suggestive of nodule(s) Note: Thyroid cancer and Graves disease although rare, are not mutually exclusive Toxic Nodule
CASE 1 Free T4: 1.58 (0.8-1.80) Total T3: 166 (60-180) Uptake/Scan: slightly elevated uptake at 6 and 24 hrs, with even distribution of tracer TSI: 150% (<130%) What s the diagnosis? CASE 1 1) Graves disease 2) Subclinical Hyperthyroidism CASE 2 37 yo female with type 1 diabetes, h/o hypothyroidism since age 12. Currently on 100 mcg of levothyroxine, normal TFT s for many years on this dose. She is asymptomatic with normal exam. Routine labs reveal: TSH: 0.042 (0.4 4.0) Free T4: 1.54 (0.89 1.80)
Case 2 Her dose is decreased every 6-8 weeks but her TSH remains suppressed until the dose is down to 25 mcg TSH: 1.15 (0.4 4.0) Free T4: 1.08 (0.89 1.8) Case 2 10 months later on 25 mcg daily TSH: 0.004 (0.4 4.0) FT4: 1.43 (0.89 1.8) Plan: D/C levothyroxine 25 mcg 2 months later TSH: 0.004 FT4: 1.13 What would you do next? A.Check TRAB s B.Order thyroid uptake C.Thyroid Ultrasound D.Check Free T3 level Correct answer is A or B. 10
Case 2 Labs TRAB 5.18 (0-1.75) TPO Ab 330 (<40) TG Ab 103 (<40) Thyroid Uptake: 46% 24 hour uptake (normal 10-30%) Case 2 DX: Graves Disease/Subclinical Hyperthyroidism Plan: Begin Methimazole 5 mg daily 6 weeks later TSH: 6.070 (0.4 4.0) FT4: 0.72 (0.89 1.8) Case 2 Conclusion: Pt. was weaned off methimazole over the next 2 months and then D/C d. Patient has remained with normal TFT s off of all thyroid medication for 2 years
Summary TSH still the best initial screening test for thyroid dysfunction Clinical exam findings can help guide the diagnostic work-up Adjunctive labs including Free T4, T3, Thyroid Abs help to clarify diagnosis of hyperthyroidism Thyroid uptake/scan helpful when clinical picture is not clear Free T4 and T3 more accurately reflect acute changes in thyroid hormone status Current labs: TSH: 0.25 (0.4-4.0) Free T4: 1.4 (0.8 1.8) Total T3: 165 (80-180) What is the most appropriate diagnosis based on these labs? A. Hypothyroidism B. Subclinical Hypothyroidism C. Hyperthyroidism D. Subclinical Hyperthyroidism Correct answer is D. 10 A patient was started on methimazole 4 weeks ago for Graves dz. Current labs: TSH: 0.003 (0.4-4.0) Free T4: 0.30 (0.8 1.8) Total T3: 55 (80-180) What is the most appropriate medication adjustment? A. Increase Methimazole B. Decrease Methimazole C. Keep current dose D. Change to PTU Correct answer is B. 10
Q&A Resources www.thyroid.com - physician/patient information source www.aace.com American Association of Clinical Endocrinologists www.thyroid.org American Thyroid Association www.endo-society.org - The Endocrine Society