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Thyroid function test , made by dr.boskey,surat


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Thyroid function test , made by dr.boskey,surat

  1. 1. Dr. Boskey . P . Gandhi Consultant pathologist at Jaymala path lab, chhayado trust, surat
  2. 2. SPECTRUM OF THYROID DISEASE Severe mild Subclinical
  3. 3. Epidemiology According to the Indian Thyroid Society, it is estimated that 4.2 crore people in the country are suffering from thyroid disorders with almost 90 per cent undiagnosed. As brand ambassador for the Abbott India Ltd healthcare company, kajol is urging women to take thyroid tests so that they can take timely medical advice and avoid complications. – See more at: thyroid-test#sthash.ewxasQAt.dpuf
  4. 4. Even with the efforts in the past decade, we still have a long way to go in terms of thyroid awareness. As part of a pre cautionary measure, women should check their TSH level as soon as pregnancy has confirmed," said R V Jayakumar, President of The Indian Thyroid Society. Read more at: +Thyroid+/1/97851.html
  5. 5. Oprah win Frey Owner of most famous oprah win Frey talk show in America. Having hashimoto’s thyroiditis.
  6. 6. Anatomy of Thyroid gland The thyroid gland is a butterfly-shaped endocrine gland that is normally located anterior side of the neck lying in front & around the larynx & trachea just below the laryngeal prominence.(Adam’s apple)
  7. 7. *Biosynthesis of thyroid hormones:-
  8. 8. Steps: 1. Iodide (I-) enters the thryroid cell via sodium iodide symporter 2. It enters the colloid through pendrin receptor 3. It is oxidized into Iodine (I0) by peroxidase enzyme 4. Then it is organified into MIT and DIT (mono and di iodo thyronine) 5. Then after coupling it forms T3 (Tri iodo thyronine) and T4 (Thyroxine) 6. T3 and T4 conjugate with TBG (thyroid binding globulin) 7. conjugated TBG is stored in colloid till required 8. While releasing into blood stream, it is first endocytosed into thyroid cell and then de - coupled to form, T3 and T4 with MIT and DIT 9. MIT and DIT can be reutilized for coupling 10. T3 and T4 are released into the blood stream
  9. 9. *What happens to thyroid hormones after release
  10. 10. *Concept of FT3 and FT4 1. Out of the total T3 and T4 in circulation, most of it remains bound to thyroid binding globulin *, prealbumin and albumin. (*note :this is not thyroglobulin) 2. Only about 0.05% of each T3 and T4 remains free in circulation. This is FT3 and FT4. 3. These are better indicators for thyroid function than total T3 and Total T4. (total=bound+free) 4. For example in pregnancy, level of thyroid binding globulin rises; hence though total T3 and total T4 remains same, level of FT3 and FT4 decreases.
  12. 12. Hypothyroidism *Causes: Primary Hypothyroidism ( High TSH, low T3 and T4) 1. Iodine deficiency 2. Goitrogens (excess amount interfere in iodine uptake) SOY products strawberry, Sweet potatoes cabbage, cauliflower, spinach Broccoli Millet e. t .c 3. Hashimoto’s (anti microsomal antibodies) 4. Iatrogenic – surgery Anti thyroid drugs, Radiation
  13. 13. Continue…….. Secondary hypothyroidism (Low TSH with normal TRH i.e. pituitary problem diseases of pituitary Tertiary hypothyroidism (LOW TSH, Low TRH) i.e. hypothalamic problem1. diseases of the hypothalamus Exaggerated response to TSH RH stimulation Rise and Delayed response to TSH-RH stimulation
  14. 14. Common Signs and Symptoms of Hypothyroidism Dry skin Brittle and lustreless hair Weight gain Tiredness Constipation Muscle aches Bradycardia Cold intolerance Depression Memory Loss Mentrual abnormality
  15. 15. Lab abnormalities in hypothyroidism Hyper lipidemia Anemia(mac rocytic-due to vit B12 def) High LDH High CPK Hyper prolactemia Hypo natremia
  16. 16. *Hyperthyroidism Causes: Primary hyperthyroidism Low TSH, High T4 Secondary Hyperthyroidism High TSH, High T4 Pituitary/Para neo plastic syndrome Factitious Hyperthyroidism 1. Grave’s disease 2. Toxicity in Multi nodular goitre 3. toxicity in adenoma 4. Sub acute thyroiditis 1. TSH secreting pituitary adenoma 2. Tropho blastic tumours that secrete TSH (chorio carcinoma, H. mole) Exogenous ingestion of large dose of thyroid hormone.
  17. 17. Common Signs and Symptoms of Hyper thyroidism Worm moist skin Hair loss Weight loss Nervousness Increased bowel movements Muscle weakness Tachycardia Heatintolerance insomnia Difficulty in concentrating Light or Absent periods
  18. 18. Laboratory findings in Hyperthyroidism • TSH nearly undetectable • Elevated FT4 or FT3 • Mild leuko penia • N/N anemia • ESR elevated • ↑ed hepato cellular enzymes • Mild ↑ Ca++ • ↓ Albumin • ↓ Cholesterol
  19. 19. TRH Stimulation test Indication: To rule out secondary or tertiary hypo/hyper thyroidism Baseline sample collected for estimation of basal serum TSH levels ↓ Inject TRH (200 to 500 ug i.v) ↓ Measure TSH at 20 & 60 mins
  20. 20. Baseline TSH 20 min TSH 60 min TSH interpretation Normal Rise of >2mU/L Small decline normal Hypothyroidi sm Elevated Further rise Small decline Primary hypothyroidism Low No rise Secondary hypothyroidism (pituitary) Low rise Further rise (delayed) Hypothalamic hypothyroidism Hyperthyroi dism elevated rise Thyroid hormone resistance elevated No rise Pituitary adenoma/ para neoplastic
  21. 21. Subclinical Thyroid Disease Asymptomatic Among the group with sub clinical thyroid disease, 73.8% are hypothyroid and 26.2% are hyperthyroid. TSH outside the reference interval but normal serum levels of T3 and T4 The prevalence of SCH is about 4% to 10% in the general population and may be as high as 20 percent in women older than 60 years Anti thyroid antibodies can be detected in 80% of patients with SCH. 80% of patients with SCH have a serum TSH of less than 10 mIU/L. To treat or not to treat –Strict follow up
  22. 22. Suspicion of thyroid disease based on clinical signs and symptoms Screening for thyroid disease Evaluation of treatment for thyroid disease.
  23. 23. Thyroid Disease – Who Is At Risk ? All newborns (neonatal screening) personal history of thyroid disease strong family history of thyroid disease Have an autoimmune disease, such as Type 1 Diabetes Some genetic conditions (e.g. Down, Turner syndromes) past history of neck irradiation drug therapies such as lithium and amio darone Investigation and Management of Primary Thyroid Dysfunction. Toward Optimized Practice Program, Edmonton: AB, 2008 Update.
  24. 24. Contd… women over age 35 elderly patients Pregnant women during the first trimester women 6 weeks to 6 months post-partum Have elevated lipid levels
  25. 25. THYROID FUNCTION TESTING IN AMBULATORY PRACTICE Suspected case ↓ normal ← S.TSH →high ↓ ↓ euthyroid low ↓ Sub clinical hyper← low/normal ← Order FT4→high→Overt hyper ↓ ↓ Order TT3 Confirm with TT3 ↓ ↓ ↓ High low normal ↓ ↓ ↓ T3 central follow up Thyro hypo toxicosis
  26. 26. Continue……. S.TSH ↓ high ↓ Overt hypo← Low← Order FT4→normal→Subclinical hypo ↓ high ↓ normal/low ← Order TT3→high→Secondary hyper ↓ T4 Assay interference ↓ Repeat with diff method
  27. 27. To screen or not to screen for thyroid dysfunction American Association of Clinical Endocrinologist (AACE), American Academy of Family Physicians (AAFP), The American College of Physician (ACP) and the American Thyroid Association (ATA) vary greatly in their recommendations. ATA recommending routine screening at age 35 then every five years.
  28. 28. BLOOD test to evaluate thyroid disease: TSH ,T4 ,T3 FT4 , FT3: Free hormone(Active metabolite) rT3 :(inactive metabolite)high in NTI , newborn, hyperthyroidism Thyro globulin mesurement Thyroid antibodies: AntiTPO antibodies, (microsomal) TSH receptor Abs Anti TG antibodies Urinary iodine mesurement Thyroxine binding globulin:
  29. 29. • RadioimmunoassayRIA • Enzyme-linked immunosorbant assayELISA • Chemiluminescent immunoassayCLIA • Fluorescent immunoassayFIA
  30. 30. Principle of FT4 measurement by immunoassay method. High affinity hormone Abs measure free hormone as a fraction of binding site occupancy. Means ( unoccupied Abs sites are inversely proportional to free hormone.) Hormone labeled tracer quantified free hormone level & passing signals which are converted to concentration using calibrators.
  31. 31. Factors limit the validity of free T4 IMMUNO ASSAY method 1.Dilution effects & protein dependence: dissociation of bound ligand occurs with sample dilution 2.Anomalous protein binding of tracer: Certain tracer used in FT4 assay have high binding capacity to protein(albumin)→ so in serum less tracer available for free Abs binding site→ false high FT4;while (in dialysis pts ,low protein →more tracer bind to Abs→ False Low FT4.) 3.Heparin effect: Heparin induce sample→↑ed lipase activity(if TG is high, Albumin is low, temp is prolong at 37C→high non esterified fatty acid →inhibit binding of T4 to serum protein in vitro only→ false high FT4. 4.Dysalbuminemic hyper thyroxinemia pts have abnormal proteins which bind T4 ,so spurious result of FT4 varies depending on labs. Most accurate methods are: Equilibrium dialysis(time consumable), Ultra filtration(avoid dilution effect) , mass spectroscopy. When FT4 is not correlate persistently with other parameter, method should be change.
  32. 32. Thyro globulin measurement Thyroglobulin: One kind of organ specific protein. Increased in Thyroid mass , injury , inflammation , TSH stimulation. Indication in practice: 1.congenital hypothyroidism(thyroid dysgenesis(low)/dyshormonogenesis(high)) 2.endemic goiter area, to monitor iodine supplementation. 3.Differentiated thyroid cancer cases ,after Sx to monitor recurrence 4.Thyrotoxicosis factitia: endogenous thyrotoxicosis(↑TG),exogenous ingestion of thyroid hormone(↓TG)
  33. 33. Normal range of TG :10-13ug/L in euthyroid subject. Method: immunoassay , RIA By immunoassay : minimal Tg abs in sample interfere with TG(low) measurement. So TGAb should be measure in all sample priror to TG analysis. If Abs present, RIA method S/b used.(low interference)
  34. 34. Thyroxin binding globulin Main carrier protein of T3 &T4 Measure by immunoassay Normal Range:12 to 28 gm/dl. Indicated ,when T3,T4 level do not agree with other parameter. Increase TBG Decrease TBG Liver disease Liver failure Pregnancy, new born Malnutrition, nephrotic SX Genetic disease Genetic disease Drugs: Estrogen, 5-florouracil, clofibrate , methadone Drugs: Androgens, gluco corticoids
  35. 35. Drugs alter thyroid function test Alter secretion of T3,T4 ↑ TBG ↓ TBG Competitio n with binding protein Induction of metabolism Activation from T4 to T3 Centrl TSH suppresio n Thionamid e Estrogen Andro gen Aspirin Phenytoin Amio darone Dopamine Ethiona mide Narcotics Danazol Heparin Carbema zepine Propyl thiourecil Dobuta mine Lithium 5-FU Nicotini c acid Furosemide (high dose) Pheno barbitone Dexameth asone Octreotide Clofibrat e L- asparagi nase Rifampicin Radio graphic agent Oxcarbema
  36. 36. Sick Euthyroid Syndrome Thyroid related changes that occur during systemic illness in the absence of intrinsic thyroid disease The syndrome is acute, reversible, and occurs commonly after surgery, starvation and in many acute febrile illnesses, These changes may be observed in up to 75% of hospitalized patients Any abnormality in hormone level is possible, usually low fT3 and tT3 Thyroid Disorders in Elderly Patients, S Med J 2005;98(5):543-549
  37. 37. Critically ill pt (hospitalization) stage i.e 1. infections 2. liver diseases 3. malignancies 4. trauma 5. surgery 6. renal failure 7. cardiac failure Decresed D1→T4 to T3 conversion inhibited. →high T4,low T3 Incrased D3→inactivation of t4 to rt3 →high rT3 TSH will remain normal. All parameters are normal on recovery.
  38. 38. THYROID FUCTION TEST DURING PREGNANCY Physiologial changes during pregnancy: (TSH ↓, T3,T4↑) Because: hepatic & estrogen induce TBG ↑ ed B- hcg mimicking TSH, Stimulate Thyroid gland ↑ plasma volume→↑ T4 & T3 pool size. High iodine clearance →more demand ↑D3 from placental mass → more degradation of T3,T4
  39. 39. Gestational variation of TFT 0 1 2 3 4 5 6 10weeks 20weeks 30weeks 40weeks TSH FT3 FT4
  40. 40. Trimester specific referance range of TFT TSH(mIu/L) FT3(pmol/L) FT4(pmol/L) Trimester-1 2.1(0.6-5) 4.4(1.9-5.8) 14.4(12-19.4) Trimester-2 2.4(0.4-5.7) 4.3(3.2-5.7) 13.4(9.4-19.4) Trimester-3 (Roche-cobas- e411/Elecsys) instrument specific 2.1(0.7-5.7) 4.1(3.3-5.1) 13.2(11.3-17.7)
  41. 41. According to endocrine society of india In lab report ,ref range s/b trimester specific & depands upon instrument Method use by lab Ethicity Iodine status of population Age
  42. 42. Subclinical hypothyroidism with pregnancy Associated with hypertension and toxaemia Subclinical hypothyroidism is associated with ovulatory dysfunction and infertility.. Undetected SCH during pregnancy may adversely affect the neuropsychological development ,survival of the fetus
  43. 43. Screening of TFT during pregnancy According to endocrine society of india: S/S of thyroid disease previous H/O of thyroid disease Family history of thyroid disease. Autoimmune dis: i.e Hashimoto,type-1 diabetes, H/O irradiation Previous H/O miscarriage, infertility, preterm delivery. Although Studies suggest that All pregnant women s/b screen for TSH & AntiTPO(more responsible for post partum thyroiditis) in 1st trimester.
  44. 44. THYROID FUNCTION IN INFANTS changes of thyroid hormone in first 120 hrs of life 0 1 2 3 4 5 6 Born 24hrs 48hrs 72hrs 96hrs 120hrs TSH RT3 T3 T4
  45. 45. Normal range of TFT in infant & children Age FT4(n g/dl) T4(ug/ dl FT3(pg/d l) T3(ng/ ml TSH(mu/ L) TBG(mg/d l) Cord blood 0.9-2.2 7.4-13.0 15-75 1.0-17.4 2.5-5.1 1-4 days 2.2- 5.3↑ 14.0- 28.4↑ 180-760 100-740↑ 1.0-39.0↑ 2-20weeks 0.9- 2.3↓ 7.2- 15.7↓ 185-770 105-245↓ 1.7-9.1↓ 2.1-6.0 5-24 months 0.8- 1.8↓ 7.2-15.7 215-770 105-269 0.8-8.2 2-7 years 1.0- 2.1↑ 6.0-14.2 215-700 94-241 0.7-5.7↓ 2.0-5.3 8-20 yrs o.8-1.9 4.7- 12.4↓ 230-650 80-210 0.7-5.7 1.8-4.2 21-45 years 0.9-2.5 5.3- 10.5↓ 210-440 70-204 0.4-4.2 1.8-4.2
  46. 46. SCREENING OF INFANTS-WHY? S/S not develop up to 3-6 months Most common cause congenital hypothyroidism is thyroid dysgenesis / dys hormono genesis. It affects neuro psychological status & growth of body. In united states ,its routine screening World wide 25% newborn babies undergo screening tests. Some program screen at 2-5 days, while others screen at 2-6 weeks of life.
  47. 47. SCREENING OF INFANTS 2 APPROCHES: 1. Initial T4 measuring followed by TSH , if T4 is low 2. Primary TSH determination.
  48. 48. Pre term babies Preterm term baby has their own unique set of thyroid function tests & its directly co relate with gestation age & birth wts. Usually preterm babies have” low T4-non elevated TSH “ result in screening programe. Because 1.discontinuation of maternal T4. 2.immaturity of hypothalamic-pitutary stimulation(low TSH surge). 3.immaturity in thyroid hormone production. . 4.low iodine intake( due to i.v fluids). repeat test is indicated in most cases.
  49. 49. Cancer thyroid Thyroid carcinoma occurs relatively infrequently compared to the common occurrence of benign thyroid disease Thyroglobulin Assays:  Determines the amount of thyroid tissue after a thyroidectomy ie there should be no thyroglobulin after complete thyroid gland removal.  Used to monitor the recurrence of the common thyroid cancers (follicular cell–derived tumors)  Tg measurements should always be interpreted in the context of simultaneous measurement of Tg autoantibodies (TgAB). TgAB occur in about 20% of thyroid cancer patients and can lead to falsely low Tg measurements Calcitonin Assay: Used to detect and monitor the recurrence of medullary thyroid cancer
  50. 50. NEW UPDATES 1.NAFLD,Female,obesity----Hypo thyrodism S/b rule out.(metabolic syndrome) 2.Chronic HCV infection in children →mimic structure thyroid cells → Anti TPO, Anti TG antibodies produce→ Sub clinical hypothyroidism →Overt hypothyroidism → So screening is mandatory before starting treatment 3.Steroid responsive nephrotic syndrome relaps pts may have hypothyroidism(temporary) because (they have oxidative stress in body ↘ affect kidney↘↑ed permeability of GBM↘ loss of TG↘low T3,T4 ↘high TSH) Improve with remission No need for thyroid treatment.
  51. 51. Take home message When FT4 level dose not match with other parameter ,it should be repeated by more accurate method. Trimester specific reference range should be included in report. In case of thyrotoxicosis factatia ,TG is more useful parameter. AntiTgAb S/b screen in all samples demand for TG measurement by immunoassay method. Sick euthyroid Sx is identified by high rT3 level.
  52. 52. Referances Todd & Henry Springer Indian thyroid society manual Internet