gms thyroid lect 2011
TRANSCRIPT
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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