Approach to thyroid dysfunction Alice Y.Y. Cheng, MD, FRCPC Twitter: @AliceYYCheng
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Learning Objectives By the end of this presentation, you will be able to: 1.Identify and investigate thyroid dysfunction 2.Appropriately manage thyroid dysfunction
Thyroid Bi-lobed, butterfly shape anterior neck Overlies trachea, below cricoid cartilage Location of a bowtie
Thyroid Follicular cells: Make thyroid hormone (T4, T3) Parafollicular cells Make calcitonin Colloid = protein
Thyroid Physiology TSH release T4 & T3 (T4 >> T3) Majority protein-bound in plasma (99.97% T4, 99.7% T3) = inactive biologically most active = free T3 T4 converted to T3 in periphery by 5 - deiodinase
Thyroid Hormone Action Nuclear receptor alter gene transcription BMR, oxygen use, sympathetic system Hyperthyroidism: Tachycardia, tremor, restlessness, heat intolerance, sweating, hyperdefecation, weight loss etc. Hypothyroidism: Bradycardia, fatigue, weight gain, cold intolerance, dry hair, menorrhagia etc.
Primary hyperthyroidism T3 and T4 low TSH Primary hypothyroidism T3 and T4 high TSH Secondary hyperthyroidism TSH T3 and T4 Secondary hypothyroidism TSH T3 and T4
Hyperthyroidism
Where might things go wrong? T3/T4 Tissue
Differential Diagnosis Graves disease Thyroiditis Toxic adenoma Toxic multinodular goitre Iatrogenic / exogenous Struma ovarii Choriocarcinoma Hydatiform mole
Graves Disease Common cause of 1 o hyperthyroidism in adults and children Autoimmune, familial disposition Thyroid stimulating antibodies (TSAb) or thyroid stimulating immunoglobulins (TSI) mimic TSH autonomous stimulation
Hypothalamus Pituitary Thyroid + + + + TSAb Serum T3 / T4
Graves disease Continuous stimulation high T3/T4 and increase thyroid size Ophthalmopathy: pathogenesis unclear? Cross-reactive antigen, protein depositions Dermopathy: deposition of mucopolysaccharide (?why)
Treatment Antithyroid medications (PTU, methimazole) inhibit TPO block iodination of tyrosine inhibit 5 -deiodinase block peripheral conversion of T4 to T3 Radioactive iodine: destroy gland Surgery: remove gland Symptomatic relief with beta blockers
Thyroiditis (subacute, painless, postpartum) Acute inflammation of thyroid (?viral) damage to gland release of T3 & T4 initially patient is hyperthyroid with high T3 and T4 but may become hypothyroid
Hypothalamus Pituitary Thyroid Serum T3 / T4 Gland destruction
Treatment Symptomatic relief with beta blockers Watchful waiting
Question A thyroid uptake and scan should be part of the routine work up of thyroid dysunction TRUE FALSE
Uptake: Nuclear Medicine tests Test of FUNCTION and not structure Useful if HYPERTHYROID Scan: Test of STRUCTURE and not function Useful if HYPERTHYROID and NODULE Only useful finding = hot
What tests to consider? Radioactive iodine UPTAKE Ultrasound Radioactive iodine SCAN only if there is a STRUCTURAL abnormality!!
Iodine UPTAKE Antibodies Natural History Treatment Graves High TSII TSAb Worsen PTU / Tapazole I131 Thyroiditis Low or Anti-TPO Resolve Time Normal Anti-TG hypo Symptomatic
Differential Diagnosis Graves disease Thyroiditis Toxic adenoma Toxic multinodular goitre Iatrogenic / exogenous Struma ovarii Choriocarcinoma Hydatiform mole
Hypothyroidism
Where might things go wrong? T3/T4 Tissue
Hashimoto s thyroiditis Most common cause of 1 0 hypothyroidism Autoimmune, familial predisposition Antibodies against thyroid (anti-tpo, anti-thyroglobulin) chronic inflammation, lymphocytic infiltration, malfunction of thyroid gland Treatment:
Hypothalamus Pituitary TRH TSH Thyroid Gland inflammation Serum T3 / T4
Other Possible Causes Primary Secondary Tertiary Ectopic (?) Tissue Receptor
Clinical Tips TSH > 10 or symptoms or child-bearing 1.7 ug / kg (usual start = 0.1mg) Adjust q 6-8 weeks Caution with CALCIUM, IRON
Ramadhan A, Tamilia M. CMAJ 2012;184(2):205-209.
Ramadhan A, Tamilia M. CMAJ 2012;184(2):205-209.
Case 29F, 1 month history of heat intolerance, palpitations, 8 lb weight loss, sweating, poor sleep, tremour denies any significant eye/skin symptoms her mother had similar symptoms in her 20 s and was treated with radioactive iodine
Case (cont d) What would you expect her labs to show? TSH? ft4? ft3? Antibodies? What is most likely cause? What would you do next?
Case (cont d) How would you treat? 3 years later pregnant Could her symptoms return? Natural history? Could baby get Graves? How could a hypothyroid woman give birth to a child with neonatal Graves?
Pregnancy
What happens in normal pregnancy? 1 st trimester: low TSH, normal ft4 HCG is similar to TSH Hyperemesis gravidarum can make it worse Do NOT refer low TSH in 1 st trimester just watch Refer if SUPPRESSED TSH and high ft4 American Thyroid Association. Stagnaro-Green, Abalovich, et al., Thyroid 21(10): 1081-1125, 2011.
Pregnancy (hypothyroid) Treat to TSH < 2.5 in T1 Treat to TSH < 3.0 in T2 and T3 American Thyroid Association. Stagnaro-Green, Abalovich, et al., Thyroid 21(10): 1081-1125, 2011.
Sick Euthyroid Syndrome (Nonthyroidal Illness Syndrome)
Sick Euthyroid Syndrome T3 ( rt3) 5 -monodeiodinase (cortisol, cytokines) TSH normal low Transient central hypothyroidism Cortisol, medications, cytokines Total T4 low due to low TBGs but as sicker low free T4 poor prognosis Van den Bergh G. Thyroid 2014;24(1):1456-65.
Treatment of SES NONE! Van den Bergh G. Thyroid 2014;24(1):1456-65.
Summary Thyroid function tightly regulated (TRH, TSH, T3, T4) Primary dysfunction most common (TSH is sensitive marker) Sick euthyroid syndrome is common in hospital!
Summary Primary hyper vs hypothyroidism Uptake if function problem Scan if structural problem Differentiate Graves vs Thyroiditis Tips with thyroid replacement Pregnancy: okay to have low TSH early Do not treat sick euthyroid syndrome