Thyroid function tests.pptx

Thyroid is a very important hormone which affects the functioning of each and every cell in our body.

1. THYROID FUNCTION TESTS Dr Anu Mariam Varghese 2 nd MD Scholar Dept of Agadatantra GAVC, TVM

2. CONTENTS Thyroid statistics Thyroid gland-Basics Hormones Synthesis of thyroid hormones How it functions Negative feedback system When to suspect thyroid disease Diseases affecting thyroid gland Thyroid function tests-Indications, TSH,TRH,T4,T3 etc. Thyroid examination Thyroid Scan-RAIU test CT Scan, PET Scan FNAC thyroid Biopsy

3. CONTENTS Management Diet in thyroid Thyroid and pregnancy Thyroid and peadiatrics DM and thyroid disorders Thyroid and HTN Thyroid and dermatology Thyroid and dyslipedemia Thyroid and infertility Thyroid –Comorbidities and complications Thyroid and Covid -19 Cases References

4. THYROID STATISTICS 42 millions people in India have thyroid disorders. 2 nd most common endocrine disorder in India Subclinical hypothyroidism is 11%. Hyperthyroidism present in <2% About 12% adults have a palpable goitre. 1/10 adults have hypothyroidism (only 2% in the UK and 4-6% in USA ) Among cancers, thyroid cancer 0.1-0.2 % C ongenital hypothyroidism occurring in 1 out of 2640 neonates (India ) and the worldwide average value of 1 in 3800 subjects.

5. THYOID GLAND Second largest endocrine gland. Small butterfly shaped gland located at the base of neck. C ontrolled by the hypothalamus and pituitary.

6. HORMONES Triodothyronine T3 Tetraiodothyronine / Throxine T4 (produced by follicles) T4 kidney, liver, spleen T3 monodeiodinase T3 is 10x more active than T4

7. TSH Thyrothrophin (TSH) is a pituitary hormone. Controlled by TRH- thyrotrophin releasing hormone from hypothalamus CALCITONIN Produced by thyroid (parafollicular cells) to regulate serum calcium levels

8. SYNTHESIS OF THYROID HORMONES

9. Steps in thyroid synthesis TRH release from hypothalamus Ant Pituitary to release TSH TSH stimulates follicular cells to synthesis TGB(Thyroglobulin) Iodine trapping Oxidation of Iodide (TPO ) Iodination of Tyrosine amminoacid Coupling of DIT’s and MIT’s Endocytosis of TGB with T3 and T4 Lysosomal enzymes cleaves T3 &T4 out of Thyroglobulin Exocytosis T4 &T3 blood plasma

10. FUNCTION Mental growth & maturation BMR Physical growth& maturation Sensitivity to adrenergic system

11. ↓ Cellular ATP ↑ O2 usage ↑ Metabolic rate ↑ Heat production ↑ Number of Mitochondria (Hypertrophy) CELL C6H12O6 +6 O2 6CO2+6H2O+HEAT

12. Glycogenolysis ↑ Glucose in blood Gluconeogenesis ↑ LDL uptake

13. ↑ Cardiac output/BP ↑Heart rate/BP

14. ↑ Dendrites ↑ Myelination ↑ no of synapses

15. Balance b/w osteoblasts & osteoclasts Interstitial growth Regulating endochondral ossification Bone remodelling

16. Lipolysis

17. Protein metabolism balance

18. Sweat production Regulates body temperature

19. ↑ Secretions ↑ Motility

20. Development of RS Synthesis of SHBG Regulates level of sex hormones

21. NEGATIVE FEEDBACK SYSTEM TRH TSH The disruption of any of these mechanisms can cause abnormal levels of T3 and T4 leading thyroid disease. T3 & T4 Thyroid

22. WHEN TO SUSPECT THYROID DISEASE ? Fatigue and sleep disorders Weight changes Mood and mental changes Bowel problems Muscle or joint problems Irregular periods, fertility and libido problems Hair and skin changes Body temperature Cholesterol issues High BP Heart rate Neck enlargement (goitre) Risk factors: Family history, age , gender

23. Diseases affecting thyroid gland? Over functioning Underfunctioning Enlargement (Goitre) uniform, solitary nodule, multiple nodules. Thyroiditis Pregnancy related problems

24. Thyroid Function Tests Blood tests Serum TSH (Ultrasensitive assay) Serum total T3 Serum total T4 Serum free T4 (or T3) Thyroid scanning – USG, Radioactive Iodine/ Tc FNAC CT scanning PET scanning Biopsy.

25. INDICATIONS OF TFT To evaluate integrity of hypothalamic-pituitary-thyroid axis . Diagnosing thyroid disorder in symptomatic person. Screening newborns for hypothyroidism. Monitoring thyroid replacement therapy in hypothyroidism patients. Diagnosis & monitoring female infertility patients. Screening adults for thyroid disorders

26. NORMAL VALUE THYROID FUNCTION TEST MEASUREMENT NORMAL RANGE Total T4 (TT4) Bound & Free T4 5.0-11.0 ug /dL Free T4 (FT4) Free T4 0.9-1.7 ng /dL Total T3 (TT3) Bound & Free T3 100-200 ng /dL T3 Resin Uptake Binding capacity of TBG 22-34% TSH Thyroid stimulating hormone 0.4-4.5 mIU /mL

27. TSH First line test in Thyroid function tests USES Screening in euthyroidism . Screening of hypothyroidism in newborns. Diagnosis of 1 & 2 hypothyroidism. Diagnosis of clinical and subclinical hypothyroidism. Follow up of T3 & T4 replacement therapy in hypothyroidism.

28. METHODS OF TSH ESTIMATION Radioimmunoassay Immunometric assay Chemiluminiscent & flourescent technique (3 rd gen)

29. TSH INCREASE DECREASE * Primary hypothyrodism * 1⁰ Hyperthyroidsm * Addison’s disease * Hashimotto’s *Anti TSH antibodies thyroiditis * PreEclampsia * Hypothyroidism ( 2or3) * Hypothermia, fasting rate sometimes *Pituitary adenoma * Organic brain syndrome *Postoperatively * Drugs- ASA, heparin *Acute psychiatric disease *Thyroiditis * Drugs- Amiodarone , radiographic dyes

30. TSH Best way to initially test thyroid function. Changes in TSH – “early warning system” Symptomatic 1⁰ hypothyroidism- >20mu/L Mild symptomatic 1⁰ hypothyroidism : 10-20 mu/L 1 ⁰ hyperthyroidism :<0.05 mu/L In 2⁰hypothyroidism low TSH levels, prevent making enough TSH to stimulate thyroid.

31. TRH Regulates TSH secretion from pituitary. TSH rise of 5microunits/ml over baseline- euthyroid state Significant increase rule out hyperthyroidism.

32. Difference between T3 and T4 T3 T4 Secretion 30 microgram/day 80 microgram /day Source 20-25% by gland 75-80% by conversion Solely by gland Half life 1 day 7 days Potency 10 times more potent than T4 Potent Binding 0.2% in unbound 0.02% in unbound Binds to Thyroxine binding globulin Thyroxine binding free albumin Albumin Apolipoproteins

33. T4 TESTS Total T4 measure bound and free hormones-change when binding proteins differ. Free T4(FT4) or free T4index (FT4I) –more accurately reflect hypothyroidism Elevated TSH and low FT4 or FTI → 1⁰ hypothyroidism Low TSH and low FT4 or FTI → 2 ⁰ hypothyroidism Low TSH with an elevated FT4 or FTI is found in individuals who have   hyperthyroidism. Increased total serum T4 → hyperthyroidism or increased con of thyroid binding proteins Decreased total serum T4 → hypothyroidism or decreased con of thyroid binding proteins/ non thyroid diseases.

34. Free T4 index Total Serum T4(mg/dl) x T3 resin uptake(%) High in hyperthyroidism Low in hypothyroidism.

35. T3 TESTS T3 tests –diagnosis/ determine the severity of hyperthyroidism . In some individuals - low TSH, only T3 is elevated and FT4 or FTI is normal . T3 testing-rarely helpful in hypothyroidism , since it is last test to become abnormal. Measurement of free T3 is possible, but is often not reliable - not typically helpful. Reverse T3 -biologically inactive- not clinically useful Total T3 –used to detect T3 toxicosis (increase T3 &normal T4)

36. Serum T3 resin uptake Thyroid hormone binding ratio The T3 resin uptake is high when thyroid binding protein is low and viceversa . Increase in T3 resin uptake – consistent with hyperthyroidism Decrease in T3 resin uptake – consistent with hypothyroidism

37. THYROID ANTIBODY TESTS  A thyroid antibodies test is used to help diagnose autoimmune disorders of the thyroid . + ve Anti-thyroid peroxidase (TPO) and / or Anti-thyroglobulin antibodies( Tg ) - Hypothyroidism - Hashimoto’s thyroiditis . Stimulatory TSH receptor antibody (TSI). Thyrotropin receptor antibody test (TSHR or TRAb ), which detects both stimulating and blocking antibodies Hyperthyroidism-Grave’s disease .

38. NORMAL VALUES   TPO   antibody : S erum   level  should be less than 9 IU/ mL. Anti- Tg   antibody : Serum   level  should be less than 4 IU/ mL.   Thyroid -stimulating immunoglobulin  antibody  (TSI): This  value  should be less than 1.75 IU/L.

39. DISEASES Hypothyrodism – Under activity Prevalence Affect 5-17 % of population Females > Males Higher in >60 years old Types –Primary, Secondary,Teritary Hashimoto’s thyoditis Postoperative hyporthyrodism Postpartum hyporthyrodism Iatrogenic hyporthyrodism

40. CAUSES OF HYPOTHYROIDISM PRIMARY ( 95%) SECONDARY ( 5%) TERTIARY ( RARE) Iodine deficiency Excess iodide intake Thyroid ablation Hashimoto’s thyroiditis Sub acute thyroiditis Genetic abnormalities Goiterogenic food Drugs -Lithium - Amiodarone Idiopathic Hypopituitarism - Adenoma - congenital - neoplasms - Ablative therapy - Pituitary destruction Pituitary necrosis (Sheehan’s syndrome) Hypothalamic dysfunction

41. Hyperthyroidism [ Thyrotoxicosis]– Over activity Prevalence Affect 5-17 % of population Females > Males More common in younger persons Types -Primary ,Secondary Graves disease Thyroid storm Toxic thyroid nodule Thyroiditis Iatrogenic hyperthyroidism

42. CAUSES OF HYPERTHYROIDISM PRIMARY SECONDARY Graves’s disease Toxic multinodular goitre Solitary toxic adenoma Thyroiditis - Subacute -Postpartum Iodide-induced Follicular carcinoma TSH induced TSH secreting pituitary adenoma - Choriocarcinoma - Hydatidiform mole Iatrogenic hyperthyroidism Ectopic thyroid issue

43. THYROID EXAMINATION WHAT ALL THINGS TO LOOK FOR IN A PATIENT WITH SUSPECTED THYROID DISEASES ? Proper history from the patient General examination Thyroid examination System examination

44. INSPECTION Anterior Approach and Lateral Approach Behaviour Hands Pulse Face Eyes Thyroid

45. PALPATION Normally thyroid gland is not palpable . Examination is best carried out from behind, with neck slightly extended Ask pt to slightly flex their neck. Assess * size *Symmetry *Consistency *Masses *Palpable thrill

46. PROCEDURE 1.Place the 3 middle fingers of each hand along the midline of the neck below the chin 2.Locate the upper edge of the thyroid cartilage( A dam’s apple). 3.Move inferiorly until you reach the cricoid cartilage/ring 4.The first two rings of the trachea are located below the cricoid cartilage and the thyroid isthmus overlies this area. 5.Palpate the thyroid isthmus using the pads of your fingers(index fingers) 6.Palpate each lateral lobe of the thyroid including inferior border in turn by moving your fingers down and slightly laterally from the isthmus. 7.Ask the patient to swallow some water , whilst you feel for symmetrical elevation /superior movement of the thyroid lobes. 8.Ask the patient to protrude their tongue once more. If mass note- Assess – position,shape,tenderness,consisteny,mobility

47. PERCUSSION Percuss downwards from the sternal notch. AUSCULTATION Auscultate each lobe of the thyroid for a bruit.

48. THYROID SCAN

49. ADVANTAGES Information regarding size, shape, position of gland Functional classification of nodules To differentiate various causes of thyrotoxicosis. In ectopic or metastatic sites. Distinguishes diffuse glandular activity from patchy pattern seen in goitre. In association with thyroid suppression regimes, TSH dependent or autonomous nature of hot nodules.

50. CONTRAIND INDICATIONS Thyroid nodules Diffuse or multinodular goitre Clinical hypo-or hyperthyroidism Evaluation of substernal mass R/O Ectopic thyroid issue Subacute thyroiditis, early phase Patient with previous h/o of H&N radiation CONTRAINDICATIONS Pregnancy Lactation

51. Radioactive iodine uptake (RAIU) test RAIU test with thyroid scan. A radioactive material called a radioisotope, or radionuclide “tracer,” is given before the test through an injection, a liquid, or a tablet tracer releases gamma rays when it’s in your body A gamma camera or scanner can detect this type of energy from outside your body The camera scans your thyroid area Process images and interpet

52. Normal scan

53. CT SCAN The  CT scan  is an x-ray test that makes detailed cross-sectional images . It can help determine the location and size of  thyroid   cancers and whether they have spread to nearby areas Preoperative planning in patients with symptomatic goitre .

54. PET SCAN  F luorine-18-fluorodeoxyglucose (FDG) P ositron E mission T omography ( PET ) Used to detect local recurrence  and  distant metastases of  thyroid  carcinoma, especially in those patients who present with high serum Tg , but negative I-131.

55. FNAC THYROID INDICATIONS Diagnosis of diffuse non toxic goitre, solitary or dominant thyroid nodule. Thyroid nodule over 1 cm in diameter. Confirmation of clinically obvious malignancy. For defining prognostic parameters. LIMITATIONS Inability to distinguish between follicular adenoma and carcinoma CONTRAINDICATIONS Nil.

56. COMPLICATIONS Local hemorrhage and hematoma. Transient laryngeal nerve paresis. Tracheal puncture. Rarely, needling causes formation of a hot nodule. MATERIALS Syringes and syringe holder 22-25 gauge needle Cotton swabs Alcohol bottles for wet fixation.

57. Rapid smearing Air dried stained with giemsa Alcohol fixed smears stained with Pap Analysis

58. BIOPSY INDICATIONS Nodule size > 2cm diameter. Regional adenopathy . To find cause of nodule/goitre. Presence of distant metastases. Prior head or neck irradiation. Rapidly growing lesion. Development of hoarseness, progressive dysphagia, or shortness of breath. Family history of papillary  thyroid  cancer.

59. T YPES Fine needle aspiration (FNA) biopsy.  Core needle biopsy.  Surgical biopsy. 

60. Management Symptomatic management Drug therapy –Anti thyroid / Synthetic TH supplements Surgery

61. DIET IN THYROID WHAT WE HAVE TO GET * Iodine * Tyrosine * Selenium OTHERS INTERFERE * Vit D * Calcium

62. Iodine Tyrosine Selenium Cheese Cows milk Eggs Frozen Yogurt Ice Cream Iodine-containing multivitamins Iodized table salt Saltwater fish Seaweed (including kelp, dulce , nori ) Shellfish Yogurt Poultry Seaweed Peanuts Pumpkin seeds Avacados Bananas Chicken Turkey Almonds Sesame seeds Brown rice Mustard seeds Oats Brazil nuts Crimini mushrooms Sunflower seeds Whole wheat bread Pinto beans Shitake mushrooms Tuna Beef, Pork Eggs Chicken Fish, shelfish lentils Cottage cheese

63. AVOID…. Cabbage Cauliflower Broccoli Coffee Alcohol even red wine Soy foods Carbonated drinks Fast foods Raddish Horse raddish chocolates Millet Sweet potatoes Potatoes Maple syrup Dried fruits White bread White rice White pasta Sweets Cafffeinated energy drinks

64. Thyroid and pregnanacy INCIDENCE Hyperthyroidism- 2 per 1000 pregnancies Hypothyroidism first time Dx in pregnancy Hypothyroid women either discontinue thyroid therapy or who need larger doses. Hyperthyroid women on excessive amount of antithyroid drugs. T3 &T4 can cross placenta, TSH not

65. Thyroid stimulating antibodies in maternal Cross placenta Produce neonatal thyrotoxicosis with increased neonatal death. Gestational transient thyrotoxicosis (1 st trimester) High hCG levels TSH receptor stimulation and temporary hyperthyroidism 20 week gestation -Reduced hepatic clearance Estrogen –induced change in the structure of TBG that prolongs serum half-life Plasma TBG increases 2.5 fold 25-45% increase in serum total T4 Total T3 icreases by about 30% in 1 st trimester and by 50% to 65 % later

66. Complications MATERNAL Anemia Miscarriage Preterm labour Preeclampsia Congestive cardiac failure. Placenta abruptio Thyroid storm Infection Postpartum hemorrhage FOETAL Mental retardation Still birth IUGR Prematurity Hyper/Hypothyroidism Increased morbidity and mortality

67. PEADIATRICS AND THYROID T hyroid hormones growth, development, maturation and brain functions are unique to pediatric age group. Congenital and acquired disorders of thyroid gland - constituting nearly 25-30% of all endocrinopathies . The three major clinical forms of thyroid disorders are Primary hypothyroidism (75%) Goiters ( thyromegaly )- of which nearly 20%, no alterations in thyroid function. Hyperthyroidism or thyrotoxicosis in 5%

68. CONGENITAL HYPOTHYDOISM- CRETINISM Thyroid dysgenesis - Aplasia, hypoplasia - Ectopic or lingual thyroid gland. I odine deficiency. Autoimmune thyroiditis- antibody mediated destruction Iatrogenic - Antithyroid drugs and goitrogens -Irradiation -Post thyroidectomy

69. CONGENITAL HYPERTHYRODISM Rare compared to hypo CAUSES – Antibody mediated –maternal graves disease - Pendred syndrome - Bamfroth Lazarus syndrome - Brain lung thyroid syndrome.

70. DM and Thyroid disorders Both are disorders of endocrine system. Thyroid plays imp role glucose metabolism – Glycogenolysis and gluconeogeneis , insulin secretion Hyperthyroidism Hyperglycemia Hypothyroidism Hypoglycemia , also  increase susceptibility to hypoglycemia thus complicating diabetes management . Hypothyroidism cause insulin resistance further can also leads to hypergycemia ie Type II Diabetes mellitus

71. Hyperthyroidism due to autoimmune causes leads to Type 1 Diabetes mellitus

72. Thyroid and HTN HYPERTHYROIDIM elevated T3 & T4 can cause 1. ↑ HR 2.↑ NE, E receptor sensitivity Increase contractibility, vasoconstriction Increase BP HYPOTHYROIDISM Low T3 & T4 Acts on kidney causes Sodium retention Na retention ↑ ses Blood volume ↑ ses Increased BP ,T3 &T4 also increases diastolic BP.

73. THYROID AND DERMATOLOGY HYPOTHYROIDISM 1.Ichthyotic skin Resembles ichthyosis vulgaris skin cold and pale first clinical manifestation 2.Facies Broad nose, thick lips, upper lid droop, face expressionless. May have melasma like pigmentation. 3.Hair Dry , coarse , brittle hair Alopecia –patchy or diffuse ( first symptom of hypothyroidsm ) Supraciliary madarosis typical

74. HYPERTHYROIDISM 1.Skin Cold, moist, smooth Palmoplantar hyperhidrosis 2.Flush Persistant flush Palmar erythema 3.Pigmentary changes Hyperpigmentaion of face , vitiligo – occassional Pretibial myxedema

75. THYROID AND DYSLIPIDEMIA Thyroid hormones regulates Lipolysis, LDL uptake Hyperthyroidism Hypolipidemia Hypothyroidism Hyperlipidemia

76. THYROID AND INFERTILITY Prevalence of hypothyroidism in women in reproductive age is 2% and 4%. Males –rare -0.1% Increased TSH ↑ ses prolactin ↑ ses FSH ,LH ↓ ses estrogen, Testosterone Males - ↓ ses sperm production, Sexual drive ↓ ses , Libido Females - Decreased ovulation, anovulation, menstrual abnormalities (amenorrhea, oligomenorrhea ) INFERTILITY

77. Hyperthyroidism High T3 & T4 act on liver produce TBG Binds with T4 produce other globulin SHBG Binds estrogen & Testosterone ↓ es circulating estrogen and testosterone in blood Males - ↓ ses sperm production, low libido, ↓ ses masculinisation Females-Anovulation, Amenorrhea, Oligmenrhea INFERTILITY

78. THYROID - CO MORBIDITIES & COMPLICATION Myxedema Coma Thyroid storm Heart problems Mental health issues Peripheral neuropathy Infertility Metabolic syndromes HTN, DM, Dyslipidemia

79. THYROID AND COVID -19 There is no association b/w novel corona virus and thyroid abnormalities so far. Vaccination do not interfere with thyroid medications.

80. CASE 1  A 50 year old housewife complains of progressive weight gain of 20 pounds ( 9 kg) in 1 year, fatigue, slight memory loss, slow speech, dry skin, constipation, and cold intolerance . Physical examination : moderately obese, speaks slowly, puffy face, with pale, cool, dry, and thick skin. The thyroid gland is slightly enlarged, firm, not nodular, mobile, and not tender. The deep tendon reflex time is delayed. Laboratory studies : CBC and differential WBC are normal. Serum T4 - 3.8 ug /dl, serum TSH is 23.0 uU /ml Diagnosis : Primary hypothyroidism

81. CASE 2 :A 35 year old nurse complained of nervousness, mood swings, weakness, and palpitations with exertion for the past 6 months. Recently, she noticed excessive sweating and wanted to sleep with fewer blankets than her husband. Menstrual periods had been regular but there was less bleeding . Physical examination : Pulse - 92/minute and BP - 130/60 . She appeared anxious, with a smooth, warm, and moist skin, a fine tremor, she couldn't rise from a deep knee bend without aid Laboratory studies : Serum T4=15.6 ug /dl and serum T3=185 ng /dl. Diagnosis : Primary Hyperthyroidism

82. REFERENCES American thyroid association guidelines European thyroid association guidelines Thyroid disorders, Kottakkal Ayurveda Series 167. Wikipedia Davidson’s principles &practice of medicine-22 nd edition Illustrated synopsis of Dermatology and sexually transmitted diseases,Neena Khanna-6 th Edition; page no 399 Desai PM. Disorders of the Thyroid Gland in India. Indian J Pediatr 1997;64:11-20 Principles of Anatomy and Physiology –Gerald J Tortora-12 th edition IAP Textbook of peadiatrics-7 th edition Usha Menon V, Sundaram KR, Unnikrishnan AG, Jayakumar RV, Nair V, Kumar H. High prevalence of undetected thyroid disorders in an iodine sufficient adult south Indian population. J Indian Med Assoc 2009;107:72-7

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