Presentation is loading. Please wait.

Presentation is loading. Please wait.

Thyroid Roger L. Bertholf, Ph.D. Associate Professor of Pathology

Similar presentations

Presentation on theme: "Thyroid Roger L. Bertholf, Ph.D. Associate Professor of Pathology"— Presentation transcript:

1 Thyroid Roger L. Bertholf, Ph.D. Associate Professor of Pathology
Director of Clinical Chemistry & Toxicology

2 Thyroid hormones Tetraiodothyronine (T4, Thyroxine)
3,5,3´ Triiodothyronine (T3) 3,3´,5´ Triiodothyronine (reverse T3)

3 Effects of thyroid hormones
Calorigenic ( O2 consumption) Growth, development, sexual maturation, CNS maturation  HR and contraction  Protein synthesis, C(H2O)n metabolism, lipid turnover  Sensitivity of -adrenergic receptors to catecholamines Brain, retina, lungs, spleen, testes appear to be unaffected by thyroid hormones

4 Regulation of thyroid hormones
TRH TSH T4 (T3) T3 (rT3)

5 Thyroid hormone production
Follicle Colloid TPO T1 T2 Thyroglobulin Iodide (I-) NIS* I- (40X) T4 TBG Alb TBPA T3 T4 Thyroglobulin T4 T3 Thyroglobulin TSH *Sodium/Iodide Symporter protein

6 Thyroid hormone synthesis
Thyroglobulin Free thyroxine

7 Peripheral T4 metabolism

8 Peripheral thyroxine metabolism
T4 production is exclusively thyroidal 70-90% of T3 is produced extrathyroidally 95-98% of rT3 is produced extrathyroidally Most peripheral de-iodination occurs in the liver T3 accounts for most of the thyroid hormone activity in peripheral tissues 3-4 times more potent than T4 Some researchers have questioned whether T4 has any intrinsic biological activity rT3 is biologically inactive

9 Circulating thyroid hormones
TBG Alb TBPA T3 fT4 (0.03%) fT3 (0. 3%) Only free hormone is active! 99.7% T3

10 Affinities of thyroid binding proteins
TBG >>> TBPA >> Alb 68% of T4 80% of T3 Low conc. (0.27 M) High affinity (K=1010) 54 kDa 11% of T4 9% of T3 Low conc. (4.6 M) Low affinity (K=107) 15.5 kDa 20% of T4 11% of T3 High conc. (640 M) Low affinity (K=105) 66 kDa A small fraction of thyroid hormones is bound to lipoproteins

11 Increased protein binding
 TBG Genetic, NTI (HIV, hepatitis, estrogen-producing tumors, AIP), pregnancy, drugs  Prealbumin (TBPA) (euthyroid thyroxine excess) Albumin variant (familial dysalbuminemia hyperthyroxinemia) T4 autoantibodies

12 Decreased protein binding
 TBG Genetic, NTI (NS), drugs, nephrosis  Prealbumin (TBPA)  TBG binding capacity (competing drugs such as salicylate and phenytoin)

13 Thyroglobulin (Tg) 660 kd protein that is the intra-thyroidal carrier of thyroid hormones Synthesized in the thyroid follicular cells; secreted into the lumen Stored mostly in the colloid Synthesis, colloidal uptake, and proteolysis (to release T4 and T3) regulated by TSH

14 Thyrotropin (TSH) One of several hormones synthesized in the anterior pituitary Others are LH, FSH, Prolactin, ACTH, GH  (common with LH, FSH, hCG) and  subunits MW=30 kDa Binds to a TSH receptor on the thyroid follicular cells to activate adenylyl cyclase/cAMP protein kinase A and Ca++ protein kinase C pathways

15 Sick Euthyroid Healthy Sick T3 T3 Peripheral T4 rT3 rT3

16 Sick Euthyroid rT3 TSH Concentration  fT4 T4 T3 Phase of illness
Normal range fT4 Concentration  T4 T3 Mild Moderate Severe Recovery Phase of illness

17 Hypothyroidism A deficiency in thyroid hormone activity
Occurrence as high as 15%, with ♀preference Myxedema is severe form Untreated congenital hypothyroidism results in severe developmental deficits Can be structural or functional 1° = deficiency in thyroid hormone production 2° (or “central) = pituitary or hypothalamic failure Hypothalamic failure sometimes called “3°”

18 Primary Hypothyroidism
Iodine deficiency (most common worldwide) Hashimoto’s thyroiditis (most common in developed countries) Autoimmune (α-TG or α-TPO) Non-goitrous causes Radioactive I2 therapy/exposure; surgical ablation Congenital (1 per 3500 to 4000 live births)

19 Secondary Hypothyroidism
Pituitary (TSH) or hypothalamic (TRH) failure. Isolated TSH deficiency is rare; usually associated with panhypopituitarism. Sheehan’s Syndrome Endocrine-inactive adenomas Other space-occupying lesions

20 Stages of Hypothyroidism
Stage of disease TSH fT4 T3 Sub-clinical nl Early Mature

21 Hyperthyroidism (thyrotoxicosis)
Increased thyroid hormone production Graves’ Disease (most common; α-TSH receptor) Toxic multi-nodular goiter Solitary toxic adenoma or pituitary adenoma Normal thyroid hormone production Thyroiditis (thyroid hormone leakage) Thyrotoxicosis facticia Metastatic thyroid carcinoma or struma ovarii

22 Stages of Hyperthyroidism
Stage of disease TSH fT4 T3 Sub-clinical nl T3 toxicosis Classic pattern

23 Summary of thyroid autoantibodies
Autoantibody Target antigen HT GD Thyroid microsomal autoantibody (TMA) Thyroperoxidase (TPO) Thyroglobulin autoantibody (TGA) Thyroglobulin (TG) TSH receptor autoantibody (TRAb) TSH receptor Thyroid-stimulating immunoglobulin (TSI) TSH receptor (agonist) Thyrotropin-binding inhibitory immunoglobulin (TBII) TSH receptor (inhibitory)

24 Effects of Drugs on Thyroid Hormones
TSH fT4 T3 Inhibit TSH secretion dopamine, glucocorticoids Inhibit synthesis iodine, lithium Inhibit T4  T3 amiodarone, propranolol glucocorticoids Inhibit protein binding salicylate, NSAIDs phenytoin, carbamazepine nl

25 Laboratory Evaluation of Thyroid Function
nl TSH Euthyroid ND Hyperthyroid? Hypothyroid? Borderline fT4 if N, T3 fT4, T3 TRH? fT4

Download ppt "Thyroid Roger L. Bertholf, Ph.D. Associate Professor of Pathology"

Similar presentations

Ads by Google