Thyroid Function Tests Flashcards
What are the steps in the formation and release of thyroid hormones
Trapping of iodide
●Oxidation of iodide to iodine
●Incorporation of iodine into tyrosyl residues
●Coupling of iodo-tyrosyl residues
●Release of T3 and T4 from thyroglobulin
What is dyshormonogenesis
“Blocks” or difficulty in making thyroid hormones
What are some enzymes used in thyroid formation
Trapping enzyme
Peroxidase
Iodinase
Coupling enzyme
Give some examples of substances that inhibit iodinases
Carbimazole
Propylthiouracil
Sulphonamides
Give some examples of substances that inhibit peroxidases
Thiourea
Methimazole
Carbimazole
Give an example of substances that inhibit coupling enzyme
Thiouracil
Give an example of substances that inhibit trapping enzyme
Perchlorate
Thiocyanate
Pertechnetate
What is endemic goitre
Iodine deficiency⇒ Low T3 and low T4 ⇒ High TSH
●TSH stimulates all physiological processes of the thyroid gland ⇒ hyperplasia / hypertrophy of the thyroid
What is Sick euthyroid syndrome:
(Euthyroid sick syndrome)
In the very old, starving, severely ill, acutely ill and after trauma (e.g. surgery) and drugs: (propranolol, amiodarone, radio contrast media), there is:
●Increased metabolism of T4 to RT3
●Plasma T3 level falls
●There is minimization of BMR
NB: 20% of T3 is made by the thyroid gland and 80% is made by mono-deiodination of T4
How are thyroid hormones transported
They are transported as protein-bound and free hormone in equilibrium
●99.95% T4 and 99.5% T3 is protein bound
●Protein binding is so strong that only 0.05% of T4 and 0.5% T3 is free hormone
What percentage of T3 and T4 are bound to Thyroxine binding pre-albumin (TBPA, Transthyretin)
15
What percentage of T3 and T4 are bound to Albumin (Alb)
10
What percentage of T3 and T4 are bound in Thyroxine binding globulin (TBG)
75
What is hereditary TBG excess
Causes an increase in TT4 and TT3 levels
●Benign
●Needs to be recognized to prevent unnecessary treatment
What are some factors that increase TBPs
Pregnancy (TBPs are 30-40% higher than in the non-pregnant)
●Oestrogens (including high levels in the newborn)
●Oestrogen containing contraceptives
●Hereditary TBG excess
What are some factors that decrease the TBPs leading to low TT4 levels
Chronic liver disease
●Nephrotic syndrome
●Malnutrition
●Drugs that displace T3 and T4 from TBPs
●Intake of androgens or danazol
●Severe or chronic illness especially in the elderly
●Inherited TBG deficiency (rare)
What are some other causes of low TT4
Increased peripheral metabolism of T4
●Androgens
●Corticosteroids
●Some anticonvulsants (e.g. phenytoin)
Inhibition of secretion of thyroid hormones
●Lithium
●Phenylbutazone
What is the importance of free T3 and T4
They are diffusible
●They are responsible for the metabolic effects of thyroid hormones
●They regulate the output of TSH
●They are kept fairly constant by homeostatic mechanisms
Give some examples of thyroid function tests
Total thyroxine, TT4
●Total tri-iodothyronine, TT3
●Free thyroxine, FT4
●Free tri-iodothyronine, FT3
(Instant)Thyroid stimulating hormone, TSH
●Tests of H-P-Th axis, TSH and TRH dynamic tests
●In vivo radio-active uptake tests using 131I 132I and 99Tc
●Thyroid auto-antibodies, TSI, LATS, LATSP, colloid antibodies
What is total thyroxine
Changes in the levels of TBPs can cause misleadingly high or low results
●TBP-T4 ⇋ FT4 + U-TBP
●>99.9% of T4 is present as TBP-T4
●Therefore TT4 effectively measures TBP-T4
What is total tri-iodothyronine (TT3)
There is little cross-reaction with T4
●Main use is in the diagnosis of hyperthyroidism
●In most cases of thyrotoxicosis TT4, FT4, TT3 , FT3
● In a few cases of thyrotoxicosis TT4, FT4 , TT3 , FT3 (T3 toxicosis)
Total tri-iodothyronine (TT3) is usually in hypothyroidism
●It is less sensitive for hypothyroidism than plasma TT4
●Hypoactive thyroid glands produce an proportion of T3
●There are levels of T3 in the old, severely ill, after trauma and in certain acute illnesses (e.g. MI)
What are free thyroid hormones (FT3, FT4)
More accurate, (i.e. sensitive and specific) tests of thyroid status than TT3, and TT4
Measured by:
●Equilibrium dialysis with RIA, EMIT, IMA
Estimated by:
●Free thyroxine index (FTI)
●Total T4 : TBG ratio
●Because FT4 is now readily measured, only a few laboratories still determine FTI and TT4: TBG ratio
What is TSH
Some methods cannot distinguish between subnormal and low normal TSH levels (cannot be used in diagnosing hyperthyroidism)
●Valuable measurement in early 1 hypothyroidism: Plasma T3 (F/T),T4 (F/T) and in-vivo radio-active uptake tests are normal but TSH
●Also important in 2 hypothyroidism: TSH
What are In vivo radio-active uptake tests
Measure the uptake of an oral dose of radioactive iodine (131I; half-life 8 days 132I; half-life 140 min)
●I.V. Technetium 99m (99mTc; half-life, 6h)
What are the uses of an in vivo radio-active uptake test
●Help with calculation of dose of radio-activity required in treatment of hyperthyroidism (99mTc unsuitable)
●Monitor thyroid function in patients treated with anti-thyroid drugs
●With scanning of the thyroid to determine if a nodule is “hot” or “cold”
●Determine if there is extra-thyroidal functioning thyroid tissue
What are thyroid antibodies
Complement-fixing antibodies specific for thyroid tissue
Present in >80% of patients with
Hashimoto’s disease
(anti-TPO, anti-Tg, TSH receptor blocking antibodies)
Antibodies to thyroglobulin:
●Can be detected in most cases of early or incipient hypothyroidism
●80% of hyperthyroid patients also have antibodies to thyroglobulin in the serum
●Thyroglobulin antibodies found in a small proportion of healthy individuals
●Thyroid microsomal antibodies are found in Grave’s and Hashimoto’s diseases
●Antibodies to a second colloid antigen is reported in all forms of auto-immune thyroiditis and in de Quervain’s thyroiditis
Thyroid stimulating immunoglobulins (TSI formerly known as LATS)
●In Grave’s disease IgG antibodies directed against TSH receptors are present: binding to receptors leading to thyroxine production
●Others; thyroid growth immunoglobulins (TGI) stimulate thyroid growth but not hormone production
What are some miscellaneous tests to take
●Basal metabolic rate (BMR)
●Glucose tolerance tests
●Plasma calcium
●Plasma LDL-cholesterol
●Plasma creatine kinase
What is the reference interval for FT3
3.0-8.6 pmol/L
What is the reference interval for FT4
9-23 pmol/L
What is the reference interval for TT4
55-140 nmol/L
What is the reference range for TSH
0.2-5.5 mU/L
What are the reference intervals for TT3
1.2-3.4 nmol/L
What is the thyroid-binding globulin
7-17 mg/L
