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