Dr.

Seaton

Physiology of Thyroid Hormone

Thyroid Physiology Lecture Outline

 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
 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.
A 28-year-old Ecuadoran woman with endemic
cretinism (from Porterfield, 2nd ed.)
The Thyroid Gland

richly innervated
highly vascularized
responsive to tropic stimuli
Goiter: Enlargement of the thyroid gland
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!
 Thyroid hormone is derived from tyrosine:

tyrosine

1) Iodinated (thyronine =
2) Ring coupled 2 tyrosine rings)
 Iodothyronines occur in three forms:

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

biologically inactive

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

biologically active biologically inactive

TSH action at the
thyroid gland
The Thyroid Follicle
 Thyroid Follicles

Basal TSH levels Intense TSH stimulation

Thyroid Gland to Periphery

Hormone Biosynthesis, Serum

Transport, and Entry into Cells
 Thyroid Hormone Biosynthesis

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

H2O2
 Iodine Flux in Thyroid Follicular Cells

Pendrin
Na+/I- Symporter
(NIS)

Na+/K+ ATPase
Radioactive iodine uptake measurements
Thyroid
Radioiodine
Scans
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.
Serum Half-lives of T3 and T4
Molecular Mechanism of T3 Genomic Effects
Regulation of Thyroid Hormone
Regulatory mechanisms of thyroid hormone activity

 Hypothalamic-pituitary-thyroid axis
 Deiodinase activities
 Wolff-Chaikoff auto-regulation – responsive to iodine
excess
Thyroid hormone axis
 Effects of TRH, T3, T4 on Pituitary Thyrotrope

Inhibitory (T3,T4)

Stimulatory
(TRH)

TSH
Deiodinases in Thyroid Hormone Physiology

• Promote hormone action by converting T4→T3

• Decrease hormone action by degrading T3

• Degrade unused thyronines for iodide recycling

• Many require the trace element selenium, which diet

must provide

 
Auto-regulation of TH Production through Wolff-Chaikoff Mechanism

High
Wolff-Chaikoff inhibition:
Iodide Acute high iodide levels
turn off hormone production
by inhibiting TG organification

NIS
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
Thyroid Hormone Action:
Effects on Tissues, Organs &
Physiological Processes
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

 TH effects on metabolism

• 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
 Cardiovascular Effects of Thyroid Hormone

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) ↑ ↓

TH effects on skeletal muscle

 protein synthesis
 blood flow
 contractility
 oxygen consumption
 metabolite production
 TH effects on liver and kidney

 blood flow  protein synthesis

 clearance rates  clearance functions
 vasoactive mediators  other metabolic
processes
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
 Increases GH and IGF secretion
 Increases tissue responsiveness to catecholamines
Children of same age

Hypothyroid Normal
Effect of TH on Bone Maturation
Thyroid HormoneDysfunction

Clinical Correlations
 Causes of Thyroid Dysfunction

Hormonogenesis • Dietary iodide deficiency or excess

• Selenium deficiency
• Genetic defects in hormone biosynthesis

Gland Pathology • Autoimmune disease

• Infection of thyroid gland
• Thyroid cancer
• Excessive radiation exposure
• Surgical destruction of thyroid tissue

Extrathyroidal • Secondary endocrine dysfunction

• Resistance to TH (general, pituitary)
 Symptoms of Hypothyroidism

 Basal metabolic rate 

 Myxedema (generalized edema from
interstitial GAG accumulation)
 Weakness, fatigue, lethargy  Goiter
 Somnolence  Slow speech
 Mental slowness  Hoarseness
 Muscle aches  Amenorrhea
 Cold intolerance  Depression
 Decreased sweating  Psychosis (“myxedema madness”)
 Dry, cold skin  ECG changes
 Prolonged reflex times  Thin, brittle hair
 Weight gain  Infertility
 Constipation

Endocrine emergency — myxedema coma

 Symptoms of Hyperthyroidism

 Nervousness  Eye problems:

 Heat intolerance • exophthalmos (Graves’ disease)
 Palpitations • lid retraction
 Muscle weakness
• eye irritation
• Corneal ulceration
 Increased appetite  Pretibial myxedema (Graves’
 Moist, warm skin disease)
 Bruit over thyroid
 Menstrual abnormalities
 Infertility
 Goiter  Diarrhea
 Tremor
 Fatigue

Endocrine emergency — thyroid storm

Thyroid-stimulating autoimmune antibodies of
Graves’ disease

Thyroid gland
 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