1. CASE A- THYROID FUNCTION TESTS MYLINH TRUONG. JEN CRAZE, KELLY STEWART,

2. CASE A  Ms YW  Age: early 20s  History of weight loss, heat intolerance, nervousness, increased bowel frequency and oligomenorrhoea.  Current symptoms: tremor, sinus tachycardia, proximal myopathy, large goitre (14cm), mild proptosis w/out diplopia.

3. What is THYROTOXICOSIS?  Thyrotoxicosis refers to the hypermetabolism and increased sympathetic nervous activity associated with increased concentrations of free T4 and T3 hormones, irrespective of the source.  Symptoms can be vague and the clinical presentation can range from minimal symptoms to life-threatening thyroid storm.

4. Clinical Manifestations  Amenorrhoea or oligomenorrhoea.  Heat intolerance  Excessive sweating  Weight loss  Fatigue and appetite changes  Palpitations  Atrial fibrillation  CCF  Fine tremor  Exophthalmos  Goitre  Muscle weakness  Diarrhoea  Osteoporosis

5. GRAVE’S DISEASE  Most common cause of hyperthyroidism among patients btw 20-50 yrs of age.  More common among women.  Thyrotoxicosis associated with Grave’s disease is due to stimulation of TSH receptors by TSH receptor antibodies ->excess hormone production and secretion.  S&S: goitre, opthalmopathy, dermopathy.

6. TFT results  Initially:  FT4 65(10-25) pmol/L  FT320(3-8) pmol/L  TSH suppressed  Carbimazole15 mg tds for 1 month  FT4 reduced to 30 pmol/L  REDUCED dose to 10mg bd  After 3 mths: FT4 is 9 pmol/L and TSH is suppressed

7. Why has FT4 decreased but symptoms of thyrotoxicosis still remain and TSH is still suppressed?

8. ?????  After correction of hyperthyroidism, TSH may fail to respond (months) to a fall in FT4 ->if this time lag is overlooked, the patient may be over treated, resulting in biochemical hypothyroidism with clinical thyrotoxicosis.  T4 and T3 may need to be measured.

9. What additional TFTs are required in light of YW suppressed TSH?

10. Additional TFTs  FTI - Free thyroxine index  T4  T3

11. What TFTs should be measured in patients receiving antithyroid treatment?

12. Monitoring  Total T3  Total T4  Free T4  Thyroid scan  TSAb

13. “Describe the analytical principles behind the sensitive TSH assay and its advantages and disadvantages compared to the clinical utility of this measurement.”

14. Measurement of TSH Ivery, 2003 – lecture notes MethodsPrincipleComments RIACompetetive binding of radiolabled TSH and non-labeled TSH to limited binding sites on the antibody Being phased out Immunoradiometric assay Binding of TSH to radiolabeled antibody Utilises 2 antibodies – sandwhich method

15. The sensitive TSH assay  Also known as sTSH  All utilise antibodies for the β subunit of TSH. The α subunit is common for TSH, FSH, LH and CG  Mid-1980s, 2 nd generation immunometric assays developed with lower detection rate than RIA methods – enabled differentiation between hyperthyroid patients with subnormal TSH and normal subjects  Third generation assays, recently developed – assay functional sensitivities reported as 0.01-0.02 mU/l  Sandwich assays with two antibodies. The use of the second antibody gives better sensitivity.  Sensitive chemiluminescent enyzymeimmunoassay – analytical sensitivity of 0.0016 mU/l

16. The clinical TSH assay  RIA method  Doesn’t have the sensitivity to detect much below euthyroid  Currently being phased out

17. Advantages/disadvantages  2 nd generation permits detection of TSH levels below euthyroid  3 rd generation permits differentiation between complete suppression and incomplete suppression of pituitary TSH output

18. Clinical utility of TSH measurement TSHThyroxine Subclinical hypothyroidism ElevatedNormal Subclinical hyperthyroidism UndetectableNormal Overt hypothyroidism ElevatedLow Overt hyperthyroidism UndetectableElevated Helfand et al, 1998

19. Subnormal TSH… Subnormal TSH levels are apparent in patients with  overt thyrotoxicosis  T4 therapy  treated hyperthyroidism  subclinical Graves’ disease  autonomously functioning thyroid nodule  central hypothyroidism  psychiatric illness  nonthyroidal illness Kasagi et al, 1999

20. Early detection and monitoring The early detection of thyroid dysfunction if important to.. The early detection of thyroid dysfunction if important to..  ensure the necessary treatment is commenced as soon as possible  patients with subclinical thyroid dysfunction are monitored and that any changes to their status are detected and treated as early as possible.  The clinical TSH assay does not have enough sensitivity to detect these small changes and cannot detect TSH levels below euthyroid.  It is important to detect subnormal levels of TSH as well as high levels. Kasagi et al, 1999

21. References  Helfand, M. et al Screening for thyroid disease. Annals of internal medicine, 1998; 129(2):141-143.  Ivery, M. Thyroid function lecture notes. Clinical pathology B, 2003.  Kasagi, K. et al Comparison of serum thyrotrophin concentrations determined by a third generation assay in patients with various types of overt and subclinical thyrotoxicosis. Clinical Endocrinology, 1999; 50(2):185-189.