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The Good, the Bad, the Thyroid Gland

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8 ACOFP 55th Annual Convention & Scientific Seminars New Physicians and Residents: The Good, The Bad, The Thyroid Gland Natasha Bray, DO 3/14/2018 Natasha N. Bray, DO, MSEd, FACOI, FACP Visiting Professor of Rural Medicine – Internal Medicine Oklahoma State University College of Osteopathic Medicine ▪ Length: 5 cm ▪ Width: 2 cm ▪ Depth: 2 cm ▪ Weight 10-20 grams 1 3/14/2018 ▪ Active Thyroid Hormone ▪ Thyroxine (T4) and Triiodothyronine (T3) ▪ Iodine is critical to formation of thyroid hormone ▪ Dietary sources – seafood, dairy products, iodized salt ▪ Iodine deficiency in US is rare ▪ Regulation ▪ TSH secretion ▪ Peripheral conversion of T4 to T3 ▪ T4:T3 secretion by thyroid gland 20:1 ▪ Most T3 (80%) results from 5’-deiodination of T4 in peripheral tissue Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. Harrison's Manual of Medicine, 18e; 2014 Available at: http://accessmedicine.mhmedical.com/content.aspx?bookid=1140&sectionid=63503819 Accessed: January 15, 2018 ▪ Thyroxine-binding globulin (TBG) ▪ Transport T3 & T4 ▪ Only free T4 and free T3 are metabolically active ▪ In the serum, 0.04% of total T4 and T3 are in free or active forms ▪ T3 has up to 10 times the potency of T4 2 3/14/2018 TSH Free T4 Hypothyroid High Low Hyperthyroid Los High 3 3/14/2018 ▪ 36-year-old female reports insomnia, weight loss and anxiety over the past 8-10 weeks. She did not get her period this month. ▪ Physical Exam ▪ Alert and oriented ▪ Vital signs are normal ▪ Thyroid gland is diffusely enlarged. No discrete nodule palpated. ▪ No exophthalmos ▪ No pretibial myxedema What lab results would you expect to find? ▪ 36-year-old female reports insomnia, A. Low TSH, low free T4, high T3 weight loss and anxiety over the past 8-10 weeks. She did not get her B. High TSH, high free T4, +TPO period this month. antibodies ▪ Physical Exam ▪ Alert and oriented C. Low TSH, high free T4, +TPO ▪ Vital signs are normal antibodies ▪ Thyroid gland is diffusely enlarged. No discrete nodule palpated. D. High TSH, high free T3, -TPO ▪ No exophthalmos antibodies ▪ No pretibial myxedema E. Low TSH, low free T4, +TPO antibodies 4 3/14/2018 What lab results would you expect to find? ▪ 36-year-old female reports insomnia, A. Low TSH, low free T4, high T3 weight loss and anxiety over the past 8-10 weeks. She did not get her B. High TSH, high free T4, +TPO period this month. antibodies ▪ Physical Exam ▪ Alert and oriented C.Low TSH, high free T4, ▪ Vital signs are normal ▪ Thyroid gland is diffusely enlarged. No +TPO antibodies discrete nodule palpated. D. ▪ No exophthalmos High TSH, high free T3, -TPO ▪ No pretibial myxedema antibodies E. Low TSH, low free T4, +TPO antibodies What is the most likely cause of her hyperthyroidism? ▪ 36-year-old female reports insomnia, A. Toxic multinodular goiter weight loss and anxiety over the past 8-10 weeks. She did not get her B. Graves’ disease period this month. C. Subacute thyroiditis ▪ Physical Exam ▪ Alert and oriented D. Iodine ingestion ▪ Vital signs are normal E. Toxic adenoma (hot nodule) ▪ Thyroid gland is diffusely enlarged. No discrete nodule palpated. ▪ No exophthalmos ▪ No pretibial myxedema 5 3/14/2018 What is the most likely cause of her hyperthyroidism? ▪ 36-year-old female reports insomnia, A. Toxic multinodular goiter weight loss and anxiety over the past 8-10 weeks. She did not get her B. period this month. Graves’ disease ▪ Physical Exam C. Subacute thyroiditis ▪ Alert and oriented D. Iodine ingestion ▪ Vital signs are normal ▪ Thyroid gland is diffusely enlarged. No E. Toxic adenoma (hot nodule) discrete nodule palpated. ▪ No exophthalmos ▪ No pretibial myxedema ▪ Decreased bone density ▪ Increased heart rate ▪ Elevated biochemical markers of bone ▪ Presence of atrial fibrillation resorption: ▪ Increased cardiac contractility ▪ Increased osteocalcin ▪ Increased urinary hydroxyproline ▪ Increased LV mass index ▪ Increased serum glucose ▪ Exophthalmos or specific ophthalmopathy ▪ Increased serum Ca and Alk Phos. ▪ Large, tender thyroid ▪ Decreased LDL and Cholesterol ▪ Restless and irritability ▪ Increased hepatic enzyme and creatine ▪ Weight loss kinase ▪ Finger tremor ▪ Increased sex hormone binding globulin ▪ Increased sweating (altered menses and fertility) 6 3/14/2018 Normal or High Radioiodine Uptake Absent (or near) Radioiodine Uptake ▪ Autoimmune Thyroid Disease ▪ Thyroiditis ▪ Graves’ Disease ▪ Subacute Granulomatous (de Quervain’s) Thyroiditis ▪ Hashitoxicosis ▪ Painless Thyroiditis (silent thyroiditis, lymphocytic ▪ Autonomous Thyroid Tissue thyroiditis) ▪ Toxic Adenoma ▪ Postpartum Thyroiditis ▪ Toxic Multinodular Goiter ▪ Amiodarone (also may cause iodine-induced hyperthyroidism) ▪ TSH-mediated Hyperthyroidism ▪ Radiation Thyroiditis ▪ TSH-producing Pituitary Adenoma ▪ Non-neoplastic TSH-mediated Hyperthyroidism ▪ Palpation Thyroiditis ▪ Mutation in nuclear triiodothyronine (T3) receptor ▪ Exogenous Thyroid Hormone Intake ▪ Mutation of TSH receptor ▪ Excessive Replacement Therapy ▪ Human Chorionic Gonadotropin-Mediated ▪ Intentional Suppressive Therapy Hyperthyroidism ▪ Hyperemesis Gravidum ▪ Factitious Hyperthyroidism ▪ Trophoblastic Disease ▪ Ectopic Hyperthyroidism ▪ Struma ovarii ▪ Metastatic follicular thyroid cancer Uptake Low High Thyroiditis Grave’s Hot Nodules 7 3/14/2018 ▪ Euthyroid hyperthyroxinemia ▪ Abnormal Thyroid hormone-binding hormone ▪ High T4, Normal-High T3, Normal TSH ▪ Low serum TSH without hyperthyroidism ▪ Central hypothyroidism (Low THS, normal FT4 & T3) ▪ Nonthyroidal illness ▪ Recovery from hyperthyroidism ▪ Pregnancy – physiologic lowering of TSH ▪ Healthy older patient – altered set point of the hypothalamic-pituitary-thyroid axis ▪ Biotin Ingestion ▪ Interference with the assay falsely low TSH and high T4 & T3 Sharma A, Baumann NA, Shah P. Biotin-Induced Biochemical Graves Disease: A Teachable Moment. JAMA Intern Med. 2017; 177(4): 571. Hyperthyroidism, goiter, ophthalmopathy (orbitopathy), & pretibial/localized myxedema ▪ Thyrotropin Receptor Simulation Antibodies (TSHR-Ab) ▪ Increase thyroid hormone synthesis, secretion, and hypertrophy of thyroid gland ▪ Treatment – ▪ Anti-thyroid medications (Methimazole or PTU) ▪ MCC of Hyperthyroidism in US ▪ First-line, may induce long-term remission. ▪ No remission achieved by 1-2 years RAI ablation or ▪ Laboratory Findings thyroidectomy may be considered ▪ Elevated T4 & T3 ▪ Beta Blockers ▪ Depressed TSH ▪ Treat symptoms ▪ Positive TSHR-Ab ▪ Propranolol inhibits peripheral conversion of ▪ May have anti-TG and anti-TPO T4 to T3 ▪ Elevated Radioiodine Uptake ▪ Exophthalmos ▪ (I-123 or Tc-99) ▪ Tapering steroid dose (6-12 weeks) ▪ Eye Surgery indicated if diplopia or loss of vision 8 3/14/2018 ▪ Autoimmune Thyroid Disease ▪ Hyperthyroid before deterioration into hypothyroid state ▪ TSH Receptor Blocker & TSH Receptor Stimulation Genes/Ab present ▪ Elderly Women ▪ Focal or diffuse hyperplasia of thyroid follicular cells ▪ Independent of TSH regulation ▪ More common in areas with low iodine intake ▪ Clinical findings: ▪ Mass effect on neighboring structures – airway ▪ Treatment obstruction and dysphagia ▪ Anti-thyroid medication (thionamide) ▪ No exophthalmos or pretibial myxedema ▪ Subtotal thyroidectomy ▪ Lab findings ▪ Radioiodine ablation ▪ Low TSH, High T4 ▪ Increased radioiodine uptake 9 3/14/2018 ▪ Inhibit production of thyroid hormones (organification of iodine to tyrosine and coupling of iodotyrosines to form T3 and T4) ▪ May also inhibit thyroid hormone secretion Principle side ▪ May have immunomodulatory activity on autoimmune disease effects Rash ▪ Methimazole Nausea ▪ Preferred due to less side effects and toxicity, longer duration of action, more rapid efficacy Hepatitis ▪ Starting dose 10-15 mg daily (larger goiter/sever symptoms 20-30 mg/day) Vasculitis ▪ Maintenance dose is 5 – 15 mg daily Agranulocytosis ▪ Duration of therapy generally 12 to 18 months, but has been used for up to 10 years safely more common ▪ Permanent remission after cessation of therapy in only 20-30% of patients with PTU ▪ Propylthiouracil (PTU) ▪ Drug of choice in pregnancy patients due to teratogenic effects of methimazole ▪ Dosage 300 – 450 mg daily initially in 2 to 3 doses ▪ Maintenance dose is 50 – 300 mg in 2 to 3 doses Radioiodine Ablation Surgery ▪ Therapy of Choice in US (69%) ▪ Indicated for: ▪ Used less in Europe (22%) & ▪ Obstructive goiter Japan (11%) ▪ Pregnant women ▪ I-131 capsule (or oral ▪ Iodine allergy solution) ▪ Refusal of radiation therapy ▪ Ablation requires 6-18 weeks for euthyroid state ▪ 20% will need second round of treatment 10 3/14/2018 ▪ A 32-year-old man is evaluated for a 1-week history of severe neck pain. He also has heat intolerance, palpitations, and insomnia. Medical history is significant only for a viral upper respiratory tract infection 3 weeks ago. He takes no medications. ▪ Physical examination ▪ Anxious, sweating ▪ T - 36.9 °C (98.6 °F), BP - 124/64 mm Hg, P - 118/min, RR - 12/min ▪ No proptosis or lid lag ▪ Heart: Regular, tachycardic, no murmur ▪ Lungs: Clear to auscultation bilaterally ▪ Thyroid gland: normal-sized, very tender to palpation. No thyroid nodules palpated. ▪ Laboratory Evaluation ▪ TSH: <0.008 µU/mL (0.008 mU/L) ▪ Free-T4: 3.2 ng/dL (41.3 pmol/L) ▪ Total T3: 310 ng/dL (4.8 nmol/L) ▪ Thyroid-stimulating immunoglobin index: <1.3 (normal, <1.3) ▪ 24-hour radioactive iodine uptake: 5% (low) ▪ A 32-year-old man is evaluated for a 1- week history of severe neck pain. He also has heat intolerance, palpitations, and insomnia. Medical history is significant only for a viral
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  • Hypothyroidism: Mimicker of Common Complaints Matthew C

    Hypothyroidism: Mimicker of Common Complaints Matthew C

    Emerg Med Clin N Am 23 (2005) 649–667 Hypothyroidism: Mimicker of Common Complaints Matthew C. Tews, DOa, Sid M. Shah, MD, FACEPb,*, Ved V. Gossain, MD, FACP, FACEPc aCollege of Osteopathic Medicine, Emergency Medicine Residency Program, Michigan State University–Lansing, P.O. Box 30480, Lansing, MI 48909, USA bMichigan State University, Attending Physician Emergency Medicine, Ingham Regional Medical, Center 401 W. Greenlawn Avenue, Lansing, MI 48910, USA cDivision of Endocrinology, Department of Medicine, Michigan State University, Lansing, MI 48909, USA Patients with hypothyroidism may present with vague symptoms such as fatigue, arthralgias, myalgias, muscle cramps, headaches, and ‘‘not feeling well.’’ These are also among the more common complaints encountered by the emergency physicians. The disease spectrum of hypothyroidism ranges from an asymptomatic, subclinical condition to the rare, life-threatening myxedema coma, and thus can be a challenging diagnosis to make. A progressive and chronic disease, hypothyroidism results from diminished thyroid hormone production. It slows metabolic functions in every organ system in the body. Commonly, clinical presentation of hypothyroidism can be confused with effects of aging in the elderly, musculoskeletal or a psychiatric illness such as depression in the younger patients. Spontaneously occurring hypothyroidism is relatively common, with prevalence between 1% to 2%, and is 10 times more common in women than in men [1]. The probability of developing spontaneous hypothyroidism increases with age, with women having a mean age at diagnosis of around 60 years [2]. A recent survey showed that 9.5% out of nearly 26,000 visitors to a statewide health fair in Colorado had elevated circulating thyroid stimulating hormone (TSH) levels, indicating underlying hypothyroidism [3].