V.N. Karazin Kharkiv National University INTERNAL MEDICINE DEPARTMENT Speakers: students of VI course Orotusin Opeyemi Adeola Oyewo Ifeoluwa Tomilayo Scientific advisers: assos.prof. Shevchuk M.I., assis. prof. Zolotarova T.V., assos.prof. Peresypkina T.V. Head of department: prof. Yabluchansky M. I. THYROID GLAND OVERVIEW • The thyroid is a butterfly-shaped gland that is located in the front of the neck just above the trachea; it weighs approximately 15 g to 20 g in the adult human • The thyroid produces and releases into the circulation at least two potent hormones, thyroxine (T4) and triiodothyronine (T3), that influence basal metabolic processes or enhance oxygen consumption in nearly all body tissues • Thyroid hormones also influence linear growth; brain function, including intelligence and memory; neural development; dentition; and bone development https://www.ncbi.nlm.nih.gov/pubmed/15157555 INTRODUCTION 1.5. • In areas of iodine sufficiency, such as Ukraine, the most common cause of hypothyroidism is chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) • Autoimmune thyroid diseases (AITDs) have been estimated to be 5-10 times more common in women than in men https://www.aace.com/files/hypothyroidism_guidelines.pdf INTRODUCTION 2.5. • In the Whickham survey, for example, 5% of women and 1% of men had both positive antibody tests and a serum TSH value >6 • Hashimoto’s thyroiditis increases in frequency with age , and is more common in people with other autoimmune diseases and their families • Goiter may or may not be present • The symptoms of hypothyroidism are nonspecific and mimic symptoms that can be associated with variations in lifestyle, in the absence of disease, or those of many other conditions https://www.aace.com/files/hypothyroidism_guidelines.pdf INTRODUCTION 3.5. APCs –antigen presenting cells http://www.touchendocrinology.com/articles/hashimoto-s-thyroiditis-adolescents INTRODUCTION 4.5. • One of the keys to diagnosing AITDs is determining the presence of elevated antithyroid antibody titers which include antithyroglobulin antibodies (TgAb), antimicrosomal/anti-thyroid peroxidase antibodies (TPOAb), and TSH receptor antibodies (TSHRAb) • In patients with a diffuse, firm goiter, TPOAb should be measured to identify autoimmune thyroiditis https://www.aace.com/files/hypothyroidism_guidelines.pdf INTRODUCTION 5.5. While there is no consensus about population screening for hypothyroidism there is compelling evidence to support case finding for hypothyroidism in: • Those with autoimmune disease, such as type 1 diabetes • Those with pernicious anemia • Those with a first-degree relative with autoimmune thyroid disease • Those with a history of neck radiation to the thyroid gland including radioactive iodine therapy for hyperthyroidism and external beam radiotherapy for head and neck malignancies • Those with a prior history of thyroid surgery or dysfunction • Those with an abnormal thyroid examination • Those with psychiatric disorders • Patients taking amiodarone or lithium https://www.aace.com/files/hypothyroidism_guidelines.pdf OUR PATIENT PROFILE • 32 years old • Female • Book-keeper • Town citizen • Date of admission – 07.08.17 MAIN COMPLAINTS • General weakness https://www.google.com.ua/search?q=hypothyroidism&rlz=1C1GGRV_enUA751UA751&source=lnms&tbm=isch&s a=X&ved=0ahUKEwi57JmX0JjYAhWHbhQKHeLvD9sQ_AUICigB&biw=1366&bih=662#imgrc=VUa6p6yaGm1YFM ANAMNESIS OF THE DISEASE • Listed complaints were over 5 months • For the first time she connected it with seasonal vitamin deficiency and she had been taking polyvitamins for a month • Before this present symptoms she had severe flu and infectious mononucleosis (but there is no true data except for specific changes in CBC) • She remembered the episode of synovitis in the years 2015/2016 ANAMNESIS VITAE • Was born into an extended family • 1997 - viral hepatitis A (Botkin’s Disease) • Denies tuberculosis, malaria, viral hepatitis, • • • • sexually transmitted diseases and AIDS Denies allergic reactions to drugs Denies smoking Denies alcohol consumption Hereditary ( Father – Asthma, IHD; mother AH) OBJECTIVE EXAMINATION 1.2 • The general condition is satisfactory, consciousness is clear, emotionally stable, optimistic mood • Height = 156 cm, Weight = 56 kg, BMI = 23 kg/m • Skin is dry • Peripheral lymph nodes are not palpable • Bilateral enlargement of the thyroid gland I degree, smooth, elastic structure OBJECTIVE EXAMINATION 2.2 • Respiratory system : - Pulmonary percussion-resonant sound - Pulmonary auscultation-vesicular breathing (no adventitious sounds) • Cardiovascular system : -Apex in 5th intercostal space, no enlargement of heart boarders -HR=65 bpm -Auscultation revealed no abnormalities -BP sin=120/75mmHg, BP dextra=116/75mmHg PRELIMINARY DIAGNOSIS • AUTOIMMUNE HYPOTHYROIDITIS WITH HYPOTHYROIDISM RECOMMENDED EXAMINATION • • • • • • • TSH , free T3, free T4, AB TPO Ultrasound of the thyroid gland Complete blood test General urine test Lipid profile ECG Biochemical blood test THYROID FUNCTION TEST (08.08.17) MEASURE Free T4 RESULT 6.08 NORMAL RANGE Under 60 years : 10.0-25.0 mcmol/L Over 60 years : 10.021.0 mcmol/L Free T3 TSH TPOAb 2.69 >20 86.3 2.5-5.8 mcmol/L 0.23-3.40 mcmol/L 30.0U/mL Conclusion: manifested hypothyroidism, elevated autoAb ULTRASOUND OF THE THYROID Conclusion: normal volume of both lobes, heterogeneous echotexture of thyroid (areas of hypoechoic, linear hyperechogenic of the marks), diffuse increased blood flow (looks like puff pastry or Napoleon, Spongiform appearance) COMPLETE BLOOD TEST (23.05.17) RBC Hemoglobin HCT MCV MCH MCHC RDW-CV PLT PCT MPV PDW 4,5 133 39,8 87,1 29,1 33,4 14,3 269 0.3 5.7 17.3 4,00 – 5,00 (10^12/L) 120 – 140 (g/l) 35,0 – 54,0 % 76,0 – 96,0 (fL) 27,0 – 33,0 (pg) 32 – 36(g/dl) 12,0 – 15 (%CV) 180 – 360 [10^9/L[ (0.10 –0.5) (%) (5.0 – 10.0) [fL] (12.0 – 18.0) [%] Basophils ESR Eosinophils 1,11 10,8 0,02 21 MEASURE WBC Neutrophils Lymphocytes Monocytes RESULT 10,29 5, 88 1, 94 1,34 RATE 4,0 - 9,0 (10^9/L) 1,56 – 6,13 (10^9/L) 1,19 – 3,74 (10^9/L) 0,24 – 0,82 (10^9/L) 3-10 % 0,04 – 0,36 (10^9/L) 0,5-5,0 % 0,01 – 0,08 (10^9/L) ≤20,0 mm|h 13 Conclusion: leukocytosis with absolute monocytosis COMPLETE BLOOD TEST (09.08.17) RBC Hemoglobin HCT MCV MCH 4,5 126 44,2 89,8 31,1 4,00 – 5,00 (10^12/L) 130 – 160 (g/l) 40,0 – 48,0 % 80,0 – 100,0 (fL) 28,0 – 36,0 (pg) MCHC RDW-CV PLT PCT MPV PDW 346 13,6 296 0.17 11 12.8 310 – 370 (g/l) 10,0 – 16,5 (%CV) 180 – 320 [10^9/L[ (0.10 –0.5) (%) (6.0 – 13.0) [fL] (10.0 – 20.0) [%] Conclusion: normal GENERAL URINE TEST (09.08.17) MEASURE SPECIFIC GRAVITY REACTION PROTEIN GLUCOSE LEUCOCYTES EPITHELIUM TRANSITION BACTERIA RESULT 1,024 6,0 absent absent 2-3 Not detected Not detected NORMAL RANGE 1,001-1,040 5,0-7,0 to 0.033 g / l Absent 6-8 Not detected Not detected Conclusion: normal BIOCHEMICAL BLOOD TEST (09.08.17) MEASURE AsAt AlAt 16 18 RESULT NORMAL RANGE <37 u/L <41 u/L Total bilirubin Fasting glucose Creatinine 10 5.57 80 8,6-25,5 mcmol/L 4,2-6,1 mmol/l 80-115 mcmol/L Conclusion: normal CLINICAL DIAGNOSIS OF THYROID DISEASE ACCORDING TO CURRENT CLASSIFICATION ABRIDGED CLASSIFICATION OF THYROID DISEASES 1.3 I. Diseases characterized by (tissue) euthyroidism II. Diseases characterized by (tissue) hyperthyroidism III. Diseases characterized by (tissue) hypothyroidism IV. Thyroid-associated ophthalmopathy V. Abnormal thyroid parameters without thyroid diseases (nonthyroidal illness, deficit of TBG, etc.) https://academic.oup.com/jcem/article/88/4/1428/2845096 ABRIDGED CLASSIFICATION OF THYROID DISEASES 2.3 A. With thyroid gland hypofunction 1. Primary hypothyroidism a. Adult (iatrogenic (surgery, I therapy, external radiotherapy), chronic autoimmune thyroiditis (in the hypothyroid phase), Graves’ disease (end-stage), diffuse and nodular goiter, iodine deficiency b. Neonatal congenital (ectopia, agenesis, dyshormonogenesis) https://academic.oup.com/jcem/article/88/4/1428/2845096 ABRIDGED CLASSIFICATION OF THYROID DISEASES 3.3 2. Secondary: hypothalamic-pituitary hypothyroidism (or central) 3. Dyshormonogenetic congenital goiter B. Without hypothyroidism 1. Generalized and peripheral resistance to thyroid hormones (receptor and postreceptor defects) C. Transient hypothyroidism https://academic.oup.com/jcem/article/88/4/1428/2845096 MAIN DIAGNOSIS • PRIMARY HYPOTHYROIDISM: AUTOIMMUNE HYPOTHYROIDITIS (HASHIMOTO’S), MANIFASTATED STAGE TREATMENT • Lifestyle modification • Dietary supplements • Hormone replacement therapy https://www.aace.com/files/hypothyroidism_guidelines.pdf LIFE STYLE MODIFICATION • Stress Management (too much stress can cause receptor cells to resist thyroid hormone and weaken immune system) • Exercise: stick with low-impact aerobic exercise such as walking, riding a stationary bike or yoga DIETARY SUPPLEMENTS 1.3. • The majority of dietary supplements (DS) fail to meet a level of scientific substantiation deemed necessary for the treatment of disease • DS are generally thought of as various vitamins, minerals, and other “natural” substances, such as proteins, herbs, and botanicals DIETARY SUPPLEMENTS 2.3. • Selenium (Se) is an essential dietary mineral that is part of various selenoenzymes • The thyroid is the organ with the highest Se content per gram of tissue • Se has been investigated as a modulator of autoimmune thyroid disease and thyroid hormone economy • Se is present in soil and enters the food chain through plants; foods rich in Se are Brazil nuts, oysters, tuna, whole-wheat bread, sunower seeds, most kinds of meat (pork, beef, lamb, turkey, mushrooms and rye) http://www.nuclmed.gr/wp/wp-content/uploads/2017/04/10.pdf DIETARY SUPPLEMENTS 3.3. • The current recommended dietary intake of Se in adults is between 55 and 75g per day • Se administration (as 200 µg/d selenomethionine) was associated with a reduction in autoimmune thyroid disease, postpartum thyroiditis, and hypothyroidism • Se supplementation was associated with decreased anti-TPO titers and improved well-being or mood, but there were no significant changes in thyroid gland ultrasonographic morphology or L-thyroxine dosing https://www.aace.com/files/hypothyroidism_guidelines.pdf HORMONE REPLACEMENT THERAPY • L-thyroxine monotherapy has become the mainstay of treating hypothyroidism, replacing desiccated thyroid and other forms of L-thyroxine and L-triiodothyronine • L-thyroxine doses on the basis of the initial serum TSH values as follows: -25 µg for TSH 4.0-8.0 mIU/L, -50 µg for TSH 8-12 mIU/L, -75 µg for TSH >12 mIU/L. • Instructing patients to consistently take it with water between 30 and 60 minutes prior to eating breakfast https://www.aace.com/files/hypothyroidism_guidelines.pdf ADJUSTMENT DOSE FOR HYPOTHYROIDISM • Dose adjustments are guided by serum TSH determinations 4-8 weeks following initiation of therapy, dosage adjustments, or change in the L-thyroxine preparation • While TSH levels may decline within a month of initiating therapy with doses of L-thyroxine such as 50 or 75 µg, making adjustments with smaller doses may require 8 weeks or longer before TSH levels begin to plateau https://www.aace.com/files/hypothyroidism_guidelines.pdf TREATMENT OF OUR PATIENT • L- thyroxine – 75 mg per day during 3 months then tests were rechecked • Se - 200 µg everyday for 3 months ( now the patient has stopped it) 3 MONTHS AFTER TREATMENT MAIN COMPLAINTS • The hair loss has stopped and start grow back, skin is normal, denies memory problems, feels more active every day 3 month later THYROID FUNCTION TEST (06.11.17) MEASURE Free T4 RESULT 19.91 NORMAL RANGE Under 60 years : 10.0-25.0 mcmol/L Over 60 years : 10.021.0 mcmol/L 0.23 - 3.40 mcU/mL TSH 0.15 Conclusion: mild subclinical hyperthyroidism ULTRASOUND 3 MONTHS AFTER TREATMENT 1.2. Looks like puff pastry or Napoleon, Spongiform appearance ULTRASOUND 3 MONTHS AFTER TREATMENT 2.2. Conclusion: normal volume of both lobes, sites of different echogenicity (areas of hypoechoic, linear hyperechogenic of the marks), diffuse increased blood flow TREATMENT OF OUR PATIENT 3 MONTH AFTER • L-thyroxine – 50 mg per day under control of TSH and T4 every 3 month CONCLUSION • The most reliable therapeutic endpoint for the treatment of primary hypothyroidism is the serum TSH value • Confirmatory total T4, free T4, and free T3 levels do not have sufficient specificity to serve as therapeutic endpoints by themselves, nor do clinical criteria • Moreover, when serum TSH is within the normal range, free T4 will also be in the normal range • Considering the asymptomatic course of hypothyroidism, more careful monitoring of the course of the disease in dynamics is necessary https://www.aace.com/files/hypothyroidism_guidelines.pdf