gms thyroid lect 2011

8/7/2019 GMS Thyroid Lect 2011

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` Introduction to Thyroid Hormone

` Thyroid Gland to Periphery: Hormone Biosynthesis, Serum

Transport, and Entry into Cells

` Thyroid Hormone Regulation

` Thyroid Hormone Action: Effects on Tissues, Organs &

Physiological Processes

` Thyroid Hormone Dysfunction: Clinical Correlations


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Some Clinical Aspects of Thyroid Disease

the most common endocrine dysfunction

Prevalence 5x greater in women and increases with age

Frequent autoimmune component

Hypothyroidism is 5x more common than hyperthyroidism

Severity ranges from subclinical to potentially fatal conditions

Affects approximately 8% of the U.S. population

Worldwide, the most common thyroid condition is iodine deficiency;

prophylactic use of iodized salt and routine testing of newborns has

made iodine deficiency rare in most parts of the U.S.


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A 28-year-old Ecuadoran woman with endemic cretinism

(from Porterfield, 2nd ed.)


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The Thyroid Gland

richly innervated

highly vascularized

responsive to tropic stimuli


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Goiter: Enlargement of the thyroid gland


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Goiter can have many causes, including:

lack of dietary iodine

hyperthyroidism hypothyroidism

inflammation of the thyroid gland

So for proper diagnosis and treatment

You need to understand thyroid physiology!


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Thyroid hormone is derived from tyrosine:

tyrosine

1) Iodinated2) Ring coupled

(thyronine =

2 tyrosine rings)


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Iodothyronines occur in three forms:

3,5,3-triiodotyrosine (T3) 3,3,5-triiodotyrosine, reverse T3 (rT3)

3,5,3,5-tetraiodotyrosine, thyroxine (T4)

biologically active biologically inactive

biologically inactive


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TSH action at the

thyroid gland


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The Thyroid Follicle


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Thyroid Follicles

Intense TSH stimulationBasal TSH levels


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Hormone Biosynthesis, Serum

Transport, and Entry into Cells


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biosynthetic precursor materials into and out of follicular cells (Fig. 5).

Thyroid Hormone Biosynthesis

H2O2


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Iodine Flux in Thyroid Follicular Cells

PendrinNa+/I- Symporter(NIS)

Na+/K+ATPase


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Radioactive iodine uptake measurements


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Thyroid

Radioiodine

Scans


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Thyroid Hormone Transport and Uptake Into Cells

1. Transport proteins act as reservoirs to buffer

circulating levels of thyroid hormone.

2. Most of the serum TH is bound by thyroxin-binding

globulin (TBG).

3. T4 binds much more tightly than T3 to transport

proteins.


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Serum Half-lives of T3 and T4


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Molecular Mechanism of T3 Genomic Effects


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Regulatory mechanisms of thyroid hormone activity

Hypothalamic-pituitary-thyroid axis

Deiodinase activities

Wolff-Chaikoff auto-regulation responsive to iodine

excess


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Thyroid hormone axis


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Effects of TRH, T3, T4 on Pituitary Thyrotrope

Stimulatory

(TRH)

Inhibitory (T3,T4)

TSH


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Deiodinases in Thyroid Hormone Physiology

Promote hormone action by converting T4T3

Decrease hormone action by degrading T3

Degrade unused thyronines for iodide recycling

Many require the trace element selenium, which diet

must provide


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Wolff-Chaikoff inhibition:Acute high iodide levels

turn off hormone production

by inhibiting TG organification

X

Escape from Wolff-Chaikoff inhibition: NIS down-regulation permits adaptation to

chronic high iodide levels by reducing entering iodide and restoring normal hormone

production

NIS

Auto-regulation of TH Production throughWolff-Chaikoff Mechanism

High

Iodide


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Effects on Tissues, Organs &Physiological Processes


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Thyroid hormone plays many important roles

oxidative metabolism

determining rates of anabolic and catabolic cellular processes

permissive for many other hormone activities

system function, e.g. cardiovascular, respiration, renal, liver

growth and development, especially brain & nervous system

adjusting sensitivity of target tissues to catecholamines


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increases oxygen consumption in most tissues

regulates basal metabolic rate (BMR)

increases thermogenesis (body heat production)

promotes mobilization of endogenous carbohydrate,protein, and fat stores

TH effects on metabolism


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Hyperthyroid Hypothyroid

Cardiac Output Contractility, cardiac muscle

Stroke Volume

Systolic BP

Heart Rate Electrical activity

Peripheral Resistance Metabolites, vasodilation

Diastolic BP

Pulse pressure (Sys-Dias BP)

Cardiovascular Effects of Thyroid Hormone


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TH effects on skeletal muscle

protein synthesis

blood flow contractility

oxygen consumption

metabolite production


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TH effects on liver and kidney

blood flow

clearance rates

vasoactive mediators

protein synthesis

clearance functions other metabolic

processes


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TH effects on growth, brain, and nervous system

Critical for normal development early in life

Regulates genes for myelin basic protein and other key

proteins and growth factors

Significantly affects mood and cognition

IncreasesGH and IGF secretion

Increases tissue responsiveness to catecholamines


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Children of same age

Hypothyroid Normal


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Effect of TH on Bone Maturation


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Clinical Correlations


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Causes of Thyroid Dysfunction

Dietary iodide deficiency or excess

Selenium deficiency

Genetic defects in hormone biosynthesis

Autoimmune disease

Infection of thyroid gland

Thyroid cancer

Excessive radiation exposure

Surgical destruction of thyroid tissue

Secondary endocrine dysfunction

Resistance to TH (general, pituitary)

Hormonogenesis

Gland Pathology

Extrathyroidal


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Symptoms of Hypothyroidism

Basal metabolic rate q

Weakness, fatigue, lethargy

Somnolence

Mental slowness

Muscle aches

Cold intolerance

Decreased sweating

Dry, cold skin

Prolonged reflex times

Weight gain

Constipation

Myxedema (generalized edema frominterstitial GAG accumulation)

Goiter

Slow speech

Hoarseness

Amenorrhea

Depression

Psychosis (myxedema madness)

ECG

changes Thin, brittle hair

Infertility

Endocrine emergency myxedema coma


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Symptoms of Hyperthyroidism

Nervousness

Heat intolerance

Palpitations

Muscle weakness Increased appetite

Moist, warm skin

Bruit over thyroid

Goiter

Tremor Fatigue

Eye problems: exophthalmos (Graves

disease) lid retraction

eye irritation Corneal ulceration Pretibial myxedema (Graves

disease) Menstrual abnormalities Infertility Diarrhea

Endocrine emergency thyroid storm


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Thyroid-stimulating autoimmune antibodies of

Graves disease

Thyroid gland


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Good sources of information

American Thyroid Association

The Hormone Foundation

American Association of Clinical Endocrinologists (AACE)

National Institutes of Health (NIDDK)

National Endocrine and Metabolic Diseases Information

Service (also NIDDK)

The Endocrine Society

Graves Disease Foundation

gms thyroid lect 2011

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