4. Thyroid Gland - Notes taken from the lecture of Mr. Mikhail Valdescona, RMT, MPH PDF

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Summary

THYROID GLAND THYROID GLAND ▪ butterfly-shaped gland ▪ it consist of two lobes—one on the either side of the trachea, located in the lower part of the neck, just below the Larynx ▪ Isthmus: a narrow band that connects the lobes ▪ this gland start to produce a measurable amount of hormone by 11 weeks...

Description

THYROID GLAND THYROID GLAND ▪ buterfy-shaped gland it ▪ consist of two lobes—one on the either side of the trachea, located in the lower part of the neck, just below the Larynx ▪ Isthmus: a narrow band that connects the lobes this ▪ gland start to produce a measurable amount of hormone by 11 weeks of gestation FOLLICLE the▪fundamental & structural unit of the Thyroid gland Types of cells: a. FOLLICULAR ▪secretes T3 & T4 b. PARAFOLLICULAR ▪produces Calcitonin THYROGLOBULINS acts ▪ as a preformed matrix containing Tyrosyl groups & glycoproteins stored ▪ in the follicular colloid of the thyroid gland BIOSYNTHESIS OF THYROID HORMONES: ▪ Iodine: the most important element in the biosynthesis of Thyroid hormones found ▪ in seafood, dairy products, iodine-enriched breads, & vitamins ▪ TrH: stimulates the release of Thyroid hormones Conversion ▪ of T4 to T3 takes place in many tissues, particularly the liver & the kidney Protein-bound ▪ hormones are metabolically inactive, they do not enter the cells & are considered to be biologically inert & function as the storage sites for circulating thyroid hormones ▪ Free hormones (fT3 & fT4): are the physiologically active portions of the Thyroid hormones Iodination ▪ of Tyrosine residues in Thyroglobulin results in formation of Monoiodotyrosine (MIT) & Diiodotyrosine (DIT) ▪ Hypothalamic-Pituitary-Thyroid-Axis: it is the neuroendocrine system that regulates the production & secretion of the Thyroid hormones Thyroid ▪ hormones afect synthesis, degradation, interm. metabolism of adipose tissue & circulating lipids

> TYPE 1: IODOTHYRONIN 5-DEIODINASE the ▪ most abundant form found ▪ mostly in the liver & kidneys responsible ▪ for the largest contribution to the circulating T3 pool > TYPE 2: IODOTHYRONIN 5-DEIODINASE ▪found in the Pituitary gland & Brain maintain ▪ constant levels of T3 in the Central Nervous System its▪activity is decreased when the levels of circulating T4 are high & increased the levels of T4 are low FUNCTIONS OF THYROID HORMONES: it▪ infuences carbohydrate & protein metabolism for ▪ tissue growth for ▪ development of the CNS for ▪ elevating heat production for ▪ control of oxygen consumption ▪for energy conservation THYROID HORMONE BINDING PROTEINS: 1. THYROXINE-BINDING GLOBULIN ▪transports 70-75% of total T4 transports ▪ majority of T3 (affinity for T3 is ↓ than T4) 2. THYROXINE-BINDING PREALBUMIN / TRANSTHYRETIN ▪transports 15-20% of total T4 T3 ▪ has no affinity for prealbumin 3. THYROXINE BINDING ALBUMIN ▪transports T3 & only 10% of T4 THYROID AUTOANTIGENS: are ▪ responsible for autoimmune thyroid disorders 1. TSH RECEPTOR 2. THYROID PEROXIDASE 3. THYROGLOBULINS

MAJOR THYROID HORMONES: 1.TRIIDOTHYRONINE (T3) has▪ the most active thyroid hormonal activity ▪almost 75-80% is produced from the tissue deiodination of T4 ▪used for diagnosing Thyrotoxicosis (Hyperthyroidism) a▪ beter indicator of recovery from Hyperthyroidism as well as the recurrence of Hyperthyroidism an▪ increase in the plasma level is the frst abnormality seen in the cases of Hyperthyroidism Reference values: > In adults = 80-200 ng/dL or 1.2-3.1 nmol/L > In children = 105-245 ng/dL or 1.8-3.8 nmol/L 2. TETRAIODOTHYRONINE (T4) ▪principal secretory product ▪ a prohormone for T3 production major ▪ fraction of organic iodine in the circulation ▪all circulating T4 originates in the thyroid gland the ▪ amount of serum T4 is a good indicator of Thyroid secretory rate elevated ▪ T4 causes inhibition of TSH secretion Reference values: > In adults = 5.5-12.5 ug/dL or 71-161 nmol/L > In neonates = 11.8-22.6 ug/dL or 159-292 nmol/L Clinical Disorders: ▪screening of thyroid disorders is recommended when a person reaches 35 y/o & every 5 years after 1. HYPERTHYROIDISM excess ▪ circulating thyroid hormone Signs & Symptoms: > Tachycardia > Tremors > Weight loss > Heat intolerance > Emotional lability > Menstrual changes > warm, moist skin Kinds of Hyperthyroidism: I. PRIMARY HYPERTHYROIDISM ▪ ↑ T3 & T4 ▪ ↓TRH & TSH II. SECONDARY HYPERTHYROIDISM ▪ ↑ TSH, T3, & T4 due ▪ to primary lesion in the pituitary gland

Diseases under Hyperthyroidism: a. THYROTOXICOSIS ▪ ↑ free T3 & T4 in the circulation ▪ ↑ FT3 & FT4 (or N) ▪ ↓ TSH ▪ Plummer’s Disease: “T3 Thyrotoxicosis” b. GRAVE’S DISEASE / DIFFUSED TOXIC GOITER most ▪ common cause of Thyrotoxicosis ▪an autoimmune disease in which Ab are produced that activate TSH receptor Ab ▪ Clinical Features: > Exophthalmia (bulging of the eyes) > Pretibial Myxedema ▪ Diagnostic test: TSH receptor Ab test c. RIEDEL’S THYROIDITIS thyroid ▪ turns into a woody/stony hard mass d. SUBCLINICAL HYPERTHYROIDISM ▪has no clinical symptoms ▪ ↓ TSH ▪ Normal lvls of FT3 & FT4 e. SUBACUTE GRANULOMATOUS THYROIDITIS associated ▪ with neck pain, low grade fever, & swings in Thyroid function test ▪ has no Thyroid Peroxidase Ab ▪ ↑ ESR & Thyroglobulin 2. HYPOTHYROIDISM develops ▪ whenever insufficient amount of Thyroid hormone are available to tissue treated ▪ with Thyroid Hormone Replacement Therapy Signs & Symptoms: > Bradycardia >Weight gain > Cold intolerance > Mental dullness > Coarsened skin Kinds of Hypothyroidism: I. PRIMARY HYPOTHYROIDISM due ▪ to defciency of elemental iodide caused ▪ by destruction or ablation of the Thyroid gland ▪ ↓ T3 & T4 ▪ ↑ TSH other causes: > Surgical removal of the gland > Radiation exposure > Drugs such as Lithium >use of Radioactive Iodine for Hyperthyroidism

Diseases under Primary Hypothyroidism: a. HASHIMOTO’S DISEASE ▪ “Chronic Autoimmune Thyroiditis” Thyroid ▪ is replaced by a nest of lymphoid tissuesensitized T lymphocyte/Autoantibodies bind to cell membrane causing lysis & infammatory reaction associated ▪ with enlargement of the Thyroid gland ▪ Diagnostic test: > TPO Ab test = (+) result > ↑ TSH b. MYXEDEMA ▪describes the peculiar nonpitng swelling of the skin ▪skin becomes infltrated by Mucopolysaccharide ▪ Myxedema coma: severe form of 1° Hypothyroidism Clinical features: > “pufy” face > weight gain > slow speech >thin eyebrows > dry & yellow skin > Anemia II. SECONDARY HYPOTHYROIDISM due ▪ to pituitary destruction / adenoma ▪ ↓ T3 & T4 ▪ ↓ TSH III. TERTIARY HYPOTHYROIDISM ▪due to Hypothalamic disease ▪ ↓ T3 & T4 ▪ ↓ TSH Diseases under Tertiary Hypothyroidism: a. CONGENITAL HYPOTHYROIDISM / CRETINISM defects ▪ in the development or function of the Thyroid gland Retarded ▪ Physical & mental development of the child ▪ Screening test: free T4 test ▪ Confrmatory test: TSH test b. SUBCLINICAL HYPOTHYROIDISM ▪ (Normal) T3 & T4 ▪slightly ↑ TSH THYROID FUNCTION TEST: 1. TRH STIMULATION TEST measures ▪ the relationship between TRH & TSH secretion used ▪ to diferentiate Euthyroid & Hyperthyroid patients who both had undetectable TSH levels

may ▪ also be helpful in the detection of Thyroid hormone resistance syndrome ▪used to confrm borderline cases of Euthyroid & Grave’s disease ▪ Dose needed: 500 ug TRH via IV ▪ ↑ levels: Hypothyroidism ▪ ↓ levels: Hyperthyroidism 2. TSH TEST most ▪ important thyroid function test best ▪ screening test most ▪ clinically sensitive assay for the detection of Primary thyroid disorders helps ▪ in the early detection of Hypothyroidism Used ▪ to diferentiate Primary from Secondary Hypothyroidism used ▪ to monitor & adjust Thyroid hormone replacement therapy ↑ TSH 1° Hypothyroidism Hashimoto’s Thyroditis Thyrotoxicosis (due to Pituitary tumor) TSH Antibodies Thyroid Hormone Resistance

↓ TSH 1° Hyperthyroidism 2° & 3° Hypothyroidism Treated Grave’s Disease Euthyroid Sick Disease Over replacement Hormone in Hypothyroidism

a. 2nd GENERATION TSH IMMUNOMETRIC ASSAY ▪ 0.1 mu/L of TSH screening ▪ test for Hyperthyroidism rd b. 3 GENERATION TSH CHEMILUMINOMETRIC ASSAY ▪ 0.01 mu/L of TSH used ▪ to diferentiate Euthyroid & Hyperthyroid; & Hyperthyroidism & Hypothyroidism its sensitivity ▪ has led to the ability to detect subclinica disease (a mild degree of Thyroid disfunction) ▪ Reference value: 0.5-5 µU/mL 3. RADIOACTIVE IODINE UPTAKE (RAIU) used ▪ to measure the ability of the Thyroid gland to trap iodine helpful ▪ in establishing the cause of Hyperthyroidism High ▪ uptake indicates metabolically active hormone production ▪High uptake + TSH defciency = Autonomous Thyroid Activity Laboratory Results: > RAI is conc. on the Thyroid gland = hot nodules > RAI is distributed all over the body = cold nodules

4. THYROGLOBULIN ASSAY normally ▪ used as post-operative of Thyroid cancer used ▪ in monitoring the course of recurrence/metastasis of Thyroid cancer ▪when measuring Thyroglobulin as a tumor marker for Thyroid cancer, always check a simultaneous sample for Thyroglobulin Ab Reference values: > In adults = 3-42 ng/mL > In infants = 38-48 ng/mL Diagnostic Methods: > Double antibody RIA > ELISA > IRMA > ICMA Laboratory Results: * Increased levels > untreated & metastatic diferentiated Thyroid cancer > Hyperthyroidism * Decreased levels > Infants with Goiterous Hypothyroidism > Thyrotoxicosis factitia 5. REVERSE T3 (rT3) used ▪ to assess borderline or conficting lab results identifes ▪ patient with Euthyroid Sick Syndrome rT3 ▪ id formed by removal of one iodine from the inner ring of T4 & end product of T4 metabolism ▪ Reference values: 38-44 ng/dL 6. FREE THYROXINE INDEX indirectly ▪ assess the level of free T4 in the blood ▪based on equilibrium relationship of bound T4 & FT4 important ▪ in correcting Euthyroid individuals ↑ ▪ in Hyperthyroidism; ↓ Hypothyroidism ▪ Reference method: Equilibrium Dialysis ▪ Formula: FT4I = TT4 x T3U or TT4 x THBR 100 7. TOTAL T3 (TT3), FT3, & FT4 used ▪ to diferentiate drug-induce ↑ TSH & Hypothyroidism ▪ Reference method: Equilibrium Dialysis (FT4) 8. T3 UPTAKE TEST measures ▪ the number of available binding sites of the Thyroxine-binding proteins, most notably TBG ▪ ↑ TBG results to ↓ T3 uptake (& vice versa) ▪ ↑ Estrogen TBG while ↓ Androgen TBG

it▪ only refects the level of TBG a▪known amount of radiolabeled T3 is added to the test serum ▪ Reference values: 25-35% ▪ Laboratory Results: a. Increased levels > Hyperthyroidism > Euthyroidism > Chronic liver disease b. Decreased levels > Hypothyroidism > Oral contraceptives > Pregnancy > Acute hepatitis 9. THYROXINE BINDING GLOBULIN (TBG) TEST used ▪ to confrm results of FT3 or FT4 or abnormalities in the relationship of the total Thyroxine & THBR test useful ▪ to distinguish between Hyperthyroidism causing ↑ Thyroxine levels & Euthyroidism with ↑ binding by TBG & ↑ T4 Total ▪ serum T3 & T4 are dependent on the amount of TBG Laboratory Results: * Increased levels >Hypothyroidism > Pregnancy > Estrogen * Decreased levels > Anabolic steroids > Nephrosis 10. THYGLOBULIN ASSAY 11. FINE NEEDLE ASPIRATION most ▪ accurate tool in the evaluation of Thyroid nodule 12. RECOMBINANT HUMAN TSH used ▪ to test patients with Thyroid cancers for the presence of residual/recurrent disease 13. TANNED ERYTHROCYTE HEMAGGLUTINATION TEST a▪ test for Anti-thyroglobulin antibodies 14. SERUM CALCITONIN TEST tumor ▪ marker for detecting residual Thyroid metastasis in Medullary Thyroid Carcinoma...