thyroid function

控制能量之使用

Thyroid Structure and Function n

Thyroxine: contains iodine n

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Controls development, regulates metabolism Excess -- profuse sweating, weight loss, irritability, high blood pressure Too little -- goiter (swollen neck)

Calcitonin: regulates blood level of calcium, deposits into bone

Metabolic Effects of Thyroid Hormone n

Thermogenesis and O2 consumption ⁄ n n

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Protein synthesis ⁄ : effects on growth Lipid synthesis and breakdown ⁄ : n n

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hyperthyroidism : thermophobia. hypothyroidism : cold sensitivity

hyperthyroidism : hypocholesterolemia. hypothyroidism : hypercholesterolemia.

Control of energy expenditure is the primary function of the thyroid hormones n

Effects on growth n n n

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Effects on the nervous system n

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potentiates G.H essential for ossification essential for organ maturation Central NS: maturation and neuron connections untreated athyreosis cretinism Autonomic NS: potentiates the effects of catecholamines

⁄heart rate, stroke volume and circulation rate

Precursors of Thyroid Hormones n

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Tyrosine MIT: monoiodotyrosine DIT: diiodotyrosine

Glucose synthesis ⁄ : glycemia ⁄ Water and electrolyte metabolism ⁄ : n

hypothyroidism : oedema

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Thyroid Hormones: T3 & T4 T3 is 4~5 times more potent in biological systems than T4

Thyroid Hormones Tyrosine iodinase

Coupling enzyme

rT3, inactive

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Thyroid follicle is the secretory unit This follicle has been stimulated by high TSH :

This follicle lacks TSH stimulation:

Thyroglogulin (Tg) n

Essentially an intravesicular glycoprotein n Protein 19S Thyroid Tg = 660 000 Da Cancer (Tg⁄) n n n n n

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Binding of Thyroid Hormones to Plasma Proteins

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TBG = Thyroxyin Binding Glogulin TBPA = Thyroxin Binding Prealbumin (Transthyretine) = Albumin

Thyroid hormone synthesis matrix Storage of inactive thyroid hormones Iodine storage

Pathways of Thyroid Hormone Metabolism

99.97% T4 99.7% T3

TBP = Thyroxin Binding Proteins

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7 - 12 MIT residues 6 - 10 DIT residues 1 - 4 T4-T3 residues T4 formation site, 5 residues from the N-terminal end T3 formation site, 2 residues from the C-terminal end

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Liver n n n

Deamination Deiodination Esterification

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Regulation: Hypothalamic-pituitary-thyroid axis n

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Thyrotropin releasing hormone (TRH) Thyroid stimulating hormone (TSH) n

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An inverse relationship between TSH and thyroid hormone levels TSH與T4,T3量成反比關係

TSH stimulates the thyroid gland to produce and secrete thyroid hormones (T4 and T3) Once levels of T4 and T3 are adequate, further production of TSH is suppressed according to the familiar negative feedback mechanism

負回饋

Regulation of Thyroid Hormone

In the pituitary thyrotroph:

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Low T3 or T4 gives: n

increased TSH subunit synthesis and thyrotroph hypertrophy n

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High T3 or T4 gives: n

tumour formation (cells then not responsive to high T3 or T4) uncontrolled TSH release thyroid enlargement and overactivity

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Disorders n

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Graves' Disease (Hyperthyroidism) Hashimoto's Thyroiditis Postpartum Thyroiditis Thyroid Cancer (Tg⁄)

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Hyperthyroidism Hypothyroidism

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Expected Test Results

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inactive thyrotrophs may lose the capacity to respond to reduced T3 or T4 levels

Grave's disease

Common (by name) n

decreased TSH subunit synthesis

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Disease Type: Autoimmune Disease Sub-Type: Organspecific Aetiology n

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Unknown, but may involve some of these factors: This is for Autoimmunity in general

Genetic, Human Leukocyte Antigens (HLA, also MHC), Gender, Environmental agents, Bacteria, Viruses

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Hyperthyroidism甲狀腺功能亢進 n

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High T4, T3 => low TSH n except TSH-secreting pituitary tumor Goiter n Thyroid gland enlarged n Grave's disease

Hypothyroidism

Thyroid Lab Tests

甲狀腺功能低下(不足)

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Primary hypothyroidisn n

Tests of Thyroid Hormones n

Total T3, Free T3, Total T4, Free T4

Test of Thyroid Response

Athyreosis, 1/3500-4000 Neonatal screen: T4 & TSH

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Tests of Etiology

Secondary hypothyroidism

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Congenital hypothyroidism n n

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Goitrous, nongoitrous Low T4, T3 => TSH high

Immunologic Assays

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Pituitary or hypothalamus ?? TSH, TRH, or both low Low T4, T3

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TSH TPOAb, TgAb, TRAb

Special Tests n n

T-Uptake, Neonatal TSH, Thyroid Scan Serum Thyroglobulin, TRH Stimulation Test

Minimum: TSH, T4 (total)

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A sensitive TSH assay is now used as the initial test of thyroid function

Thyroid Testing Strategies Ambulatory Patients:

Expected Test Results

Changes in thyroid function tests throughout pregnancy

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Methodology of the T3 Uptake Test

Free Thyroxine Index n

Nonthyroidal Illness (NTI): Euthyroid Sick Syndrome n

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Thyroid hormone excess or deficiency Absence of definitive thyroid disease n

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[TBP], drugs, peripheral resistant to TH Cirrhosis, renal failure, cancer,trauma

The Free Thyroxine Index (FTI) is actually a calculation (Total T4 X T3 Uptake = Free Thyroxine Index) which takes into consideration both the Total T4 and T3 Uptake, and corrects for the elevated T4 due to higher amounts of TBG.

Questions 1. What are the different types of stimuli that may

cause secretion of hormones? 2. What are the different mechanisms for controlling the plasma level of a hormone? 3. How do protein or polypeptide hormones (growth hormone or parathyrin, for example) transmit their message to target cells? 4. What is the difference between primary and secondary endocrine disease?

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Questions 5. How are poorly soluble hormones, such as

cortisol or thyroxine, transported in plasma? 6. What laboratory tests are commonly used for the diagnosis of thyroid disorders?

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