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MPBP 301: ENDOCRINOLOGYTHYROID
OBJECTIVES: THYROIDDescribe the major signs and symptoms of excess or reduced thyroid hormone levels.Explain the key phrases used to summarize the actions of thyroid hormone:
Differentiation.Basal metabolic Rate.
Describe the major signs and symptoms of excess or reduced thyroid hormone levels.Draw and explain the control system for thyroid hormone.Define key signals that regulate thyroid hormone secretion.Describe how and why thyroid hormone levels are affected by caloric status.Explain the production, physiologic significance and regulation of T3 and rT3 production from T4.Describe the utility of palpation of the thyroid gland as a diagnostic tool.Describe the basis and utility of radio-isotopic scanning of the thyroid gland as a diagnostic tool.Describe the thyroid follicular cell and the mechanisms and control of thyroid hormone synthesis and release.Describe the mechanisms by which thyroid hormone influences Basal Metabolic Rate (BMR).Describe the relationship between thyroid hormone and the autonomic nervous system and the mechanism involved.Describe the effects of thyroid hormone on fat metabolism.Describe the effects of thyroid hormone on carbohydrate metabolism.Describe the effects of thyroid hormone on protein metabolism.Describe the binding of thyroid hormone to proteins in the blood, its purpose and how the phenomenon can complicate interpretation of measurements of thyroid hormone levels.Describe the essential steps required to evaluate the thyroid feedback control system.
HUMAN STRUCTURE - FUNCTION ENDOCRINOLOGY
THYROID
SUMMARY OF EFFECTS OF THYROXINE/TRIIODOTHYRONINE (T4, T3)
BMR Brain Development
Increased (much of this due to an Required for normal braindevelopment,increase in Na/K-ATPase). Especially nerve myelination.Cretinism, if hormone is missing duringembryonic
development. Carbohydrate1. Gastrointestinal glucose uptake increased increased gluconeogenesis.
Fat Protein1. Mobilization of fat stores. 1. Required for normal growth.2. Blood cholesterol decreased. 2. Increased levels causecatabolism,3. Blood phospholipids decreased. These especially muscle. are decreased despite triglyceride mobilization from fat stores because lipid breakdown to make ATP is increased even more.4. Many of the effects on lipid metabolism are due to changes in Autonomic Nervous System (ANS) function.
Miscellaneous:1. Synergistic involvement with the ANS.2. High doses unmask diabetes mellitus.3. High doses unmask failing heart.
Signs of Excess (adult): Signs of Deficit (adult):1. heat intolerance 1. Lipemia2. CNS changes 2. Cholesterolemia3. sweating 3. Cold Intolerance4. hyperglycemia 4. Myxedema (sometimes)5. muscle catabolism 5. Obesity6. exopthalmos (possibly due to TSH) 6. Slow Speech7. cardiovascular axis activity 7. Poor cardiovascular axis
function increased but efficiency decreased8. BMR increased
KEY PHRASES: THYROID HORMONE
DEVELOPMENT BMR SYNERGY WITH THE ANS
THE THYROID FOLLICULAR CELL
MECHANISM OF ACTIONTHYROID STIMULATING HORMONE
Surface receptors that work through multiple second messenger systems
KEY PHRASES: THYROID HORMONE
DEVELOPMENTBMRSYNERGY WITH THE ANS
THYROID HORMONE ANDDEVELOPMENT
Embryogenesis: tadpoles and frogs
CNS Maturation: Cretinism
THYROID HORMONE ANDFOODSTUFF METABOLISM
T3 REGULATES THE RATE AT WHICH METABOLIC PATHWAYS ARE OPERATING
SYNTHESIS DEGRADATION
SYNTHESIS DEGRADATION
NORMAL
ELEVATED T3
PATHWAYS FOR SYNTHESIS ANDDEGRADATION BOTH REQUIRE ATP
THYROID HORMONE AND FAT METABOLISM
BLOOD FATLEVELS FALL
MORE BATHTUBS
T3 AND CARBOHYDRATE
T3 AND PROTEIN
GLUCONEOGENESIS(At the Expense of Muscle)
APPETITE
INCREASED TURNOVERLARGER INCREASE IN DEGRADATION(Therefore, NET LOSS)
CHANGING BMR
ENERGY CHARGE A THE KEY DETERMINANTOF THE RATE OF METABOLISM
Energy Charge = [ATP] / [ADP] + [AMP]
PUSHING vs PULLING
REALLY KEY CONCEPTSYNERGY BETWEEN THYROID HORMONEAND THE AUTONOMIC NERVOUS SYSTEM
BETA ALPHA-2
+ _
GiGS
CMB HSF: ANS
T3 REDUCES LEVELSOF Gi-α
MECHANISM OF ACTIONTHYROID HORMONE
ACTS LIKE A STEROID HORMONE
KEY PHRASES: THYROID HORMONE
DEVELOPMENTBMRSYNERGY WITH THE ANS
BLOOD BINDING PROTEINS
T3 + BP T3-BP
THE NITTY GRITTY
T3 + BP T3-BP
THE NITTY GRITTY
NORMAL FEEDBACKKEEPS THIS CONSTANT
T3 + BP T3-BP
ACCOUNTING FOR BINDING PROTEINS
T3 RESIN UPTAKE: MEASURES“PARKING SPACES”
THE NITTY GRITTY
NORMAL FEEDBACKKEEPS THIS CONSTANT
T3 + BP T3-BP
Many Conditions AffectBinding Proteins
PregnancyStarvationKidney DiseaseDrugs (e.g. Aspirin)Liver Disease
TESTING THE FEEDBACK LOOP
1. SIGNS AND SYMPTOMS
2. KEY MEASUREMENTS- TROPHIC HORMONE (TSH)- HORMONE ITSELF (T3)
3. TWEAK THE FEEDBACK LOOP- CHALLENGE THE CONTROL SYSTEM AND SEE IF IT RESPONDS APPROPRIATELY
THYROID FEEDBACK MODULE
BLACKBOARD
Summer Course
WEEK 2: Monday – Wednesday - Endocrinology
THYROID FEEDBACK MODULE
TWO UNIQUE THYROID TESTS
OTHER POTENTIAL TESTS
Give TSH and watch for increase in T3
If primary hypo – little or no rise
Give T3 and watch for a fall in TSHIf secondary hyper – no reduction
Give TRH and watch for a rise in TSH and eventually T3
A SINGLE TEST THATREVEALS “EVERYTHING”
Give TRH and watch what happens to TSH
THYROID FUNCTION TESTS
YOUR GOAL: BE ABLE TO EXPLAIN THIS
RTRH
TRH
PITUITARY FEEDBACK: NORMAL vs HIGH FEEDBACK
TSH
TRH TRH
RTRH
TRH TRH TRH
RTRH RTRH
+ + + +
T3 T3
__AP Cell AP Cell
TSH
NORMAL ELEVATED T3
TRHTRH
TRHTRH
TRH = Thyrotrophic Releasing HormoneTSH = Thyroid Stimulating Hormone
RTRH RTRH
RTRH
TRH
PITUITARY FEEDBACK: NORMAL vs LOW FEEDBACK
TSH
TRH TRH
RTRH
TRH TRH TRH
RTRH RTRH
+ + + +
T3
T3
__AP Cell AP Cell
TSHNORMAL REDUCED T3
TRHTRH
TRHTRH
TRH = Thyrotrophic Releasing HormoneTSH = Thyroid Stimulating Hormone
RTRH RTRH
RTRH
RTRH
RTRH
RTRH
RTRH
RTRH
THE TRH TEST:HYPERTHYROID DISEASE
Normal Range:hatched
Importance of knowing normal values on an individual basis
THE TRH TEST:HYPERTHYROID DISEASE
Primary Hyper:
TSH low
TSH Responseto TRH LOW
Twodifferentcases
THE TRH TEST:HYPERTHYROID DISEASE
Secondary Hyper:
TSH High
TSH Responseto TRH HIGH*
*Note break in curve
THE TRH TEST:HYPOTHYROID DISEASE
Primary Hypo:
TSH High
TSH response to TRH HIGH*
*Note break in top curve
2 Cases
THE TRH TEST:HYPOTHYROID DISEASE
Secondary Hypo:
TSH Low
TSH responseto TRH LOW
TRH TEST: PRIMARY AND SECONDARY DISEASE
OTHER ABNORMAL CONDITIONS
1. Exogenous thyroid hormone
2. Iodide Deficiency
3. Antibody that activates TSH receptor
4. Antibody that blocks the TSH receptor
5. Ectopic production of TSH
EXPLAINED IN THYROID MODULE: NOT ON EXAM
TESTING THE / ANYFEEDBACK LOOP
1. Signs and Symptoms
2. Key Measurements- Tropic Hormone (TSH)- Hormone itself (T3)
3. Tweak the Feedback Loop- Challenge the control system and see if it responds appropriately