An Approach to: Thyroid Function Tests. Rinkoo Dalan Consultant Department of Endocrinology Tan Tock Seng Hospital

Transcription

1 An Approach to: Thyroid Function Tests Rinkoo Dalan Consultant Department of Endocrinology Tan Tock Seng Hospital

2 Regulation of Thyroid axis Hypothalamus TRH T3,T TRH Median Eminence (base of brain) T3, T4 TSH Anterior Posterior TSH Pituitary Pituitary T3, T4 TSH Body

3 Within the thyroid gland Peripheral action of T3 T4 Tg Io MIT,DIT + Tg T3 T4 C-amp Na Io Io TSH TSH_R T3 T4 T4 T4 T4 T4 T4

4 6 combinations possible High Free T4 Normal Free T4 Decreased Free T4 Decreased Free T4 Normal Free T4 Increased Free T4 TSH Normal with either increased or decreased free T4

5 High Free T4 Common causes: Primary Hyperthyroidism : Graves s Disease, toxic nodule or toxic MNG Relatively Common with low RAI uptake: Transient thyroiditis-postpartum, Silent (lymphocytic), post viral granulomatous subacute De Quervan s Rare: Thyroxine ingestion, Ectopic thyroid tissue (struma ovari), Iodine Induced, Amiodarone. Rare with positive HCG: Pregnancy with hyperemesis gravidarum. HCG producing tumor; Familial gestational hyperthyroidism Rare familial or resistant to treatment : Activating germline TSH-receptor mutation

6 Case 1: The lady with Pain in the 46 yrs old lady presents with prolonged fever for 6/52 associated with anterior neck pain. URTI 4/52 earlier On palpation Small diffuse,firm goitre tender. Neck Tests Value RI Free T4 44pM 8-21pM TSH <0.001mIU/L ESR 100 mm 3-5 TrAb 4 IU/L <2 Thyroid gland is not visible

7 Case 2: The depressed Lady A 46 yrs lady was started on Lithium for depression. She presented with symptoms of heat intolerance, weight loss and palpitations. O/E : small diffuse non tender goitre Tests Value RI Free T4 25 pm 8-21pM TSH <0.001mIU/L Free T3 8 pm ( ) TrAb Not detectable <2 Lithium was discontinued. Subsequently 3 months later: Free T4: 18pM; TSH: 1.0 miu/l Disturbed iodine kinetics with Expansion of intrathyroidal iodine pool, Escape phenomenon Overflow of thyroid hormones

8 Case -3: Lady who was persistently vomiting A 28 years old lady presented with severe Nausea and vomiting Did not resolve with regular medication Pregnancy with hyperemesis Gravidarum Free T4= 30 pm (8-21) TSH= 0.01mIU/L ( ) On further questioning: No past h/o thyroid problems No goitre Totally asymptomatic. Menstrual cycle: regular but has not had menses the last 2 cycles.

9 Case 4: The Giddy Lady 65 yrs old lady Giddiness and palpitations Apathetic No goitre palpable Tests Value RI Free T4 65 pm 8-21pM TSH <0.001mIU/L Free T3 24 pm ( ) TrAb >40 <2 Diagnosis : Thyrotoxicosis secondary to Graves Disease

10 6 combinations possible High Free T4 Normal Free T4 Decreased Free T4 Decreased Free T4 Normal Free T4 Increased Free T4 TSH Normal with either increased or decreased free T4

11 Normal Free T4 Common Causes: Subclinical Hyperthyroidism T3 Toxicosis Thyroxine ingestion Normal Pregnancy Rare Causes: Steroids therapy Dopamine/Dobutamine infusions NTI

12 Case 5: 65 yrs old lady Giddiness and palpitations Right thyroid nodule palpable Tests Value RI Free T4 18 pm 8-21pM TSH <0.001mIU/L Free T3 12 pm ( ) TrAb Not detectable <2 T3 Toxicosis secondary to Toxic Nodule

13 Case 6: A 28 years old lady Healthy-no medical problems at all. Newly enrolled in a school as a teacher Required to do health screening preemployment. Tests Value RI Free T4 15 pm 8-21pM TSH 0.14 miu/l TrAb Not detectable <2 On further questioning: No past h/o thyroid problems No goitre Totally asymptomatic. Menstrual cycle: regular but has not had menses the last cycle. Normal Pregnancy : Physiological

14 Case 7 A 70 years old lady is admitted with complains of fever, giddiness, confusion increased urinary frequency. She is tachycardic at 120 /min and febrile with Temp:39 C. Because of acute confusion the HO ordered the ff : Ca, Mg, PO4, Thyroid panel Free T4 : 16 pmol/l (8-21) TSH 0.24 miu/l ( ) Free T3 : Low Diagnosis : Non-thyroidal illness. 2 months later repeat thyroid function : Free T4: 9 pmol/l, TSH:2.34 miu/l

15 NTI

16 Case 8 A 70 yrs old Chinese lady seeks advice as a routine screening: She had an episode of AF when she was admitted for Pneumonia but reverted to normal after that. BMD : Osteopenia T score-2.1 SD at hip No Goitre Free T4 : 15 pmol/l TSH: 0.01 miu/l

17 An algorithm that outlines a proposed plan for the evaluation and therapy of subclinical hyperthyroidism. *, Based on data showing higher mortality,atrial fibrillation, bone loss, symptoms or reduced quality of life by Endocrine Society Cooper D S JCEM 2007;92:3-9

18 6 combinations possible High Free T4 Normal Free T4 Decreased Free T4 Decreased Free T4 Normal Free T4 Increased Free T4 TSH Normal with either increased or decreased free T4

19 Decreased Free T4 Common: Non Thyroidal illness Recent Treatment for hyperthyroidism Rarer: Secondary Hypothyroidism Congenital TSH or TRH hormone deficiency

20 Case 9: A 68 years old Taxi driver Presented with headache,nausea and malaise. Minor accidents usually knocks down with pavements on the sides Tests Value RI Free T4 8pM 8-21pM TSH 0.21mIU/L Free T3 2 pm 4-6 pm Prolactin 69,000 miu/l

21 A 30 years old Indonesian Presented with short height, constipation, low intelligence Born normal but began to lag behind in growth and intelligence at 5 years of age. No puberty and no secondary sexual characteristics. Height 148 cm Bone age years Epiphyses not fused Case 10: Tests Value RI Free T4 8 pm 8-21pM TSH 0.21mIU/L Free T3 2 pm 4-6 pm LH <1 FSH <1 IGF-1 10

22 PROP-1 Mutation leading to combined multiple hormonal deficiencies Secondary hypothyroidism Hypogonadotrophic hypogonadism GH deficiency. Long history and the multiplicity of disorders suggests that he has a mutation in one of the genes encoding the transcription factors that are responsible for anterior pituitary development. MRI Pituitary :Looks hypoplastic to normal in appearance.

23 6 combinations possible High Free T4 Normal Free T4 Decreased Free T4 Decreased Free T4 Normal Free T4 Increased Free T4 TSH Normal with either increased or decreased free T4

24 Common Chronic autoimmune thyroiditis Post radioiodine Post thyroidectomy Hypothyroid phase of transient thyroiditis Congenital hypothyroidism Thyroid agenesis/dysgenesis Iodide organification defects TSH receptor defects/resistance Decreased Free T4 Rare (anti-tpo negative, no radioiodine or surgery) 1. Post external-beam irradiation to the neck 2. Drugs: amiodarone, lithium, interferons, interleukin-2 3. Iodine deficiency 4.Iodine excess-iodide goitre in Japan (water purification units) 5. Goitrogens 6. Amyloid goitre (large, firm goitre with systemic amyloidosis) 6. Riedel s thyroiditis

25 Case 11 A 24 years old lady Presents with dysmenorrhoea and increased flow. Also has weight gain Cold intolerance Constipation O/E : small diffuse goitre Thyroid Function Test: Free T4= 6 pmol/l (RI:8-21) TSH =50 miu/l Anti TPO ab : positive Diagnosis: Hashimoto s Thyroiditis with Primary Hypothyroidism

26 6 combinations possible High Free T4 Normal Free T4 Decreased Free T4 Decreased Free T4 Normal Free T4 Increased Free T4 TSH Normal with either increased or decreased free T4

27 Normal Free T4 Common: Subclinical autoimmune hypothyroidism Rare: Heterophile (interfering) antibody Intermittent T4 therapy for hypothyroidism Drugs: amiodarone, sertraline, cholestyramine Recovery phase after non-thyroidal illness Congenital TSH-receptor defects Resistance to TSH associated with other (unspecified) defects Pendred s syndrome some cases (associated with sensorineural deafness and goitre)

28 Case 12 A 83 years old gentleman has baseline hyperlipidemia very well controlled on Simvastatin 20 mg daily. He seeks advice regarding starting thyroxine Free T4=13 pmol/l TSH = 7.1 miu/l 6/12 later: Free T4 : 12 pmol/l TSH: 15 miu/l Diagnosis: Subclinical Hypothyroidism

29 Persistently raised TSH Concentration TSH 5-9 miu/l TSH >10 miu/l Consider treatment in young, Middle aged patients especially if child bearing age group females, goitre present or antibodies positive or symptomatic. Treat with Thyroxine Goal TSH conc miu/l No treatment in patients >85yrs age. In patients older than 65 if treating target TSH<7 miu/l Treat with Levothyroxine Goal TSH <60 yrs miu/l Goal TSH>60 yrs 4-6 miu/l

30 6 combinations possible High Free T4 Normal Free T4 Decreased Free T4 Decreased Free T4 Normal Free T4 Increased Free T4 TSH Normal with either increased or decreased free T4

31 Increased Free T4 Rare with discordant free T4 versus free T3 Interfering antibodies to thyroid hormones (anti-tpo antibodies usually also present) Familial dys-albuminaemic hyper-thyroxinaemia Amiodarone Rare other Intermittent T4 therapy or T4 overdose Resistance to thyroid hormone TSH secreting pituitary tumour (hyperthyroid) Acute psychiatric illness (first 1 3 week)

32 Case 13 A 65 years old lady presents after fracture neck of femur. Weight loss 1/12 AF diagnosed 2 months ago Small goitre Free T4= 22 pmol/l (8-21) TSH= 8.64 miu/l ( ) Free T3=12 pmol/l (4-6) 3/12 repeat at another centre Free T4= 64 pmol/l (8-21) TSH= 8.69 miu/l ( ) Free T3=12 pmol/l (4-6) Differential diagnosis: Heterophilic antibodies Non thyroidal illness TSH resistance syndrome TSH producing pituitary adenoma

33 TRH Stimulation test-200 mcg O min : 7.48 miu/l 15 min: 7.13 miu/l 30 min: 7.47 miu/l 45 min: 7.16 miu/l 60 min: 7.16 miu/l Diagnosis: TSH producing pituitary adenoma

34 6 combinations possible High Free T4 Primary hyperthyroidism Normal Free T4 Subclinical hyperthyroidism Decreased Free T4 Central hypothyroidism Decreased Free T4 Primary hypothyroidism Normal Free T4 Subclinical hypothyroidism Increased Free T4 TSH Normal with either increased or decreased free T4 TSH resistance/ TSH producing pituitary adenoma

35 Reference Colin M Dayan. Interpretation of thyroid function tests. Lancet 2001; 357:

36 Thank You