Chapter 77

CHAPTER 77 - Thyroid Metabolic Hormones

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UNIT XIV
CHAPTER 77 - Thyroid Metabolic Hormones
Basic knowledge of the concept and understanding
● Synthesis and Secretion of the Thyroid Metabolic Hormones
– Describe the physiologic anatomy of the thyroid gland?

Ans. Physiologic Anatomy of the Thyroid Gland

1. Location & Structure
• Lies anterior to the trachea
• 2 lobes + isthmus (butterfly shape)
• Rich blood supply → 3–5x the thyroid’s weight per minute
2. Functional Unit: Thyroid Follicle
• Follicle: Spherical structure filled with colloid (stores thyroglobulin)
• Follicular cells:
• Synthesize and secrete T3 and T4
• Parafollicular (C) cells:
• Secrete calcitonin (↓ blood Ca²⁺)
3. Unique Feature
• Stores hormones extracellularly in colloid (unlike other endocrine glands)

Qn. Importance of Iodine in Thyroid Hormone Synthesis

1. Essential Component
• Iodine is required to form T3 (triiodothyronine) and T4 (thyroxine).
• T3 has 3 iodine atoms, T4 has 4 iodine atoms.
2. Role in Synthesis
1. Iodine is absorbed as iodide (I⁻) from the gut
2. Thyroid follicular cells actively trap iodide (iodide pump)
3. Iodide → Iodine (oxidized) by thyroid peroxidase
4. Iodination of tyrosine residues on thyroglobulin → MIT & DIT
 5. Coupling forms T3 (MIT+DIT) and T4 (DIT+DIT)
3. Clinical Importance
• Iodine deficiency → ↓ T3/T4 → ↑ TSH → Goiter
• Adequate iodine prevents hypothyroidism and supports normal growth & CNS
development

Qn. Definition of the following terms:

● lodide trapping
● • Organification

1. Iodide Trapping
• Definition:
• Active transport of iodide (I⁻) from the blood into thyroid follicular cells
via the sodium-iodide symporter (NIS).
• Importance:
• First step in thyroid hormone synthesis → concentrates iodide 30–250×
plasma level.

2. Organification (Iodination)
• Definition:
• Process of binding iodine to tyrosine residues of thyroglobulin in the
follicular lumen to form:
• MIT (Monoiodotyrosine) – 1 iodine
• DIT (Diiodotyrosine) – 2 iodines
• Enzyme: Thyroid peroxidase (TPO)
• Importance:
• Essential for forming T3 (MIT+DIT) and T4 (DIT+DIT)

Qn Role of thyroglobulin and function, storage?

Thyroglobulin: Role, Function & Storage
1. What is Thyroglobulin?
• Large glycoprotein produced by thyroid follicular cells.
• Secreted into the colloid inside thyroid follicles.

Functions
1. Scaffold for Hormone Synthesis
• Provides tyrosine residues where iodine is attached (organification).
• Forms MIT, DIT → T3 and T4 while still part of thyroglobulin.
2. Hormone Storage
• Stores T3 and T4 in an inactive form within the follicular colloid.
• Thyroid can store a 2-3 month supply of hormone.
3. Release
• Upon stimulation by TSH, thyroglobulin is endocytosed, digested → free T3 and T4 enter
the blood.

Qn Explain the physiological process: How thyroid hormones are synthesized and transported into
the blood?

Synthesis & Transport of Thyroid Hormones (T3 & T4)

A. Synthesis (in Follicular Cells & Colloid)

1. Iodide Trapping
• Iodide (I⁻) actively transported into follicular cells via Na⁺-I⁻ symporter
(NIS).
2. Oxidation of Iodide
• I⁻ → I⁰ (active iodine) by thyroid peroxidase (TPO) at the apical membrane.
3. Organification (Iodination)
• Iodine binds to tyrosine residues on thyroglobulin in colloid → forms
• MIT (1 iodine)
• DIT (2 iodines)
4. Coupling of Iodotyrosines
• MIT + DIT → T3
 • DIT + DIT → T4
5. Storage in Colloid
• T3 & T4 remain attached to thyroglobulin in follicle lumen until needed.

B. Secretion & Transport to Blood

6. Endocytosis & Proteolysis
• TSH stimulates thyroglobulin uptake → lysosomes cleave free T3 & T4.
7. Release into Blood
• T3 & T4 diffuse into circulation.
• MIT & DIT are deiodinated → iodine recycled.
8. Transport in Blood
• >99% bound to plasma proteins (TBG, transthyretin, albumin) → long
half-life
• Free fraction (active):
• T3 (~0.3%) – active form
• T4 (~0.03%) – prohormone, converted to T3 in tissues

Qn What is the rate of daily secretion of thyroid hormones?

Ans Rate of Daily Secretion of Thyroid Hormones

• Thyroxine (T4) → ~80–100 µg/day
• Triiodothyronine (T3) → ~6 µg/day

Note:
• Most hormone secreted is T4 (inactive) → converted to T3 (active) in tissues.
• T3 is ~4 times more potent than T4 but secreted in much smaller amount

.. Regulation of Thyroid Hormone Secretion

•
Qn. How is the thyroid hormone secretion regulated?

Regulation of Thyroid Hormone Secretion

Main control: Hypothalamic-Pituitary-Thyroid (HPT) Axis
1. TRH (Hypothalamus)
• Thyrotropin-releasing hormone → stimulates anterior pituitary.
2. TSH (Anterior Pituitary)
• Thyroid-stimulating hormone → acts on thyroid to:
• ↑ Iodide trapping
• ↑ T3/T4 synthesis and release
• ↑ Follicular cell growth
3. T3 & T4 (Negative Feedback)
• High levels inhibit TRH and TSH secretion → prevent overproduction.

Other Influences
• Cold exposure → ↑ TRH & TSH → ↑ T3/T4 (in infants)
• Stress & infection → Can ↓ thyroid function
• Iodine deficiency/excess → Affects hormone synthesis

Memory Tip:
TRH → TSH → Thyroid → T3/T4 → Negative feedback to pituitary & hypothalamus

Explain the feedback control mechanism of TSH secretion?

Feedback Control of TSH Secretion

Main Mechanism: Negative feedback via the Hypothalamic-Pituitary-Thyroid (HPT) axis

Steps
1. Hypothalamus
• Secretes TRH (Thyrotropin-releasing hormone) → stimulates anterior
pituitary.
 2. Anterior Pituitary
• Secretes TSH (Thyroid-stimulating hormone) → stimulates thyroid gland:
• ↑ Iodide trapping
• ↑ Thyroglobulin synthesis
• ↑ T3/T4 release
3. Thyroid Gland
• Produces T3 and T4 → enter blood
4. Negative Feedback
• High T3 & T4 → inhibit TRH (hypothalamus) and TSH (pituitary)
• Low T3 & T4 → remove inhibition → ↑ TSH secretion

Clinical Correlation
• Primary hypothyroidism: ↓ T3/T4 → ↑ TSH
• Primary hyperthyroidism (Graves’): ↑ T3/T4 → ↓ TSH

Memory Tip:
TRH → TSH → T3/T4 → Negative feedback

Clinical correlation / Synthesis

● Physiological Functions of the Thyroid Hormones
Functions and effects of thyroid hormones
● On sleep, body composition, metabolic rate, growth
● Other endocrine glands, plasma and fats
● Other body systems: Cardiovascular, respiratory, GI, CNS, skeletal muscles
Sexual function

Metabolic Effects
• ↑ Basal Metabolic Rate (BMR) (60–100%)
• ↑ O₂ consumption & heat production → ↑ body temperature
• ↑ Carbohydrate & fat metabolism → weight loss if excess
⸻

2. Growth & Development

• Essential for normal growth (works with GH & IGF-1)
• Critical for CNS development in infants (deficiency → cretinism)

3. Effects on Body Composition & Sleep

• Excess T3/T4 → ↓ weight, ↑ protein breakdown → muscle wasting
• Deficiency → weight gain, sluggishness
• Sleep: Hyperthyroid → insomnia; Hypothyroid → somnolence

4. Effects on Other Endocrine Glands & Plasma

• ↑ Glucose absorption & insulin requirement
• ↑ Cortisol metabolism
• ↑ LDL breakdown → low cholesterol in hyperthyroidism

5. Effects on Major Body Systems

Cardiovascular
• ↑ HR, ↑ cardiac output, ↑ systolic BP (hyperthyroid → tachycardia)

Respiratory
• ↑ Respiration rate to meet ↑ O₂ demand

Gastrointestinal
• ↑ Motility (hyperthyroid → diarrhea; hypothyroid → constipation)

CNS
• Excess → nervousness, anxiety
• Deficiency → lethargy, slow reflexes

Skeletal Muscles
 • Mild ↑ → strength
• Excess → weakness due to protein catabolism

6. Sexual Function
• Women: Irregular or absent menses in both hyper & hypothyroidism
• Men: Low libido, possible infertility in extremes

Memory Tip:
T3/T4 = “Heat, Heart, Height, Head, Hormones”
• Heat → ↑ metabolism
• Heart → ↑ cardiac output
• Height → growth & bone development
• Head → CNS function
• Hormones → affect other endocrine gland

4 Drugs that suppress thyroid secretions. How?

Thiocyanate
Propylthiouracil (PTU)
Inorganic iodides

Drugs that Suppress Thyroid Secretion & Their Mechanism

1. Thiocyanate (and Perchlorate)

• Mechanism:
• Compete with iodide for the Na⁺-I⁻ symporter (iodide trapping) → ↓
iodide entry into follicular cells
• Effect:
• ↓ T3 & T4 synthesis (no iodine available)
• Note: Does not block hormone release
⸻

2. Propylthiouracil (PTU)
• Mechanism:
1. Inhibits thyroid peroxidase (TPO) → ↓ iodination & coupling
2. Blocks peripheral conversion of T4 → T3
• Effect:
• ↓ Synthesis of new thyroid hormones and ↓ active T3

3. Inorganic Iodides (High Dose)

• Mechanism:
• Wolff-Chaikoff effect: Excess iodide inhibits iodide organification and
hormone release
• Effect:
• Temporary suppression of T3/T4 secretion
• Clinical Use:
• Short-term in thyroid storm or before thyroid surgery

Summary

Drug Main Action Step Blocked

Thiocyanate Competes for iodide Iodide trapping
transport
PTU Inhibits TPO & T4→T3 Organification &
conversion coupling
Inorganic iodides Wolff-Chaikoff effect Hormone release
(↓ organification &
release)
Qn. Explain the pathogenesis of the following conditions. Cause and effect (symptoms), diagnostic
test, treatment
• Hyperthyroidism
Hypothyroidism
Exophthalmos
Myxedema
Cretinism
Goiter

Ans. 1. Hyperthyroidism (Thyrotoxicosis)

• Cause:
• Graves’ disease (autoimmune ↑ TSH-receptor stimulation), toxic nodular
goiter
• Effect / Symptoms:
• ↑ Metabolism → weight loss, heat intolerance, tachycardia, tremor
• Diagnostic Test:
• ↓ TSH, ↑ T3/T4
• Treatment:
• Antithyroid drugs (PTU, Methimazole), β-blockers, radioiodine, surgery

2. Hypothyroidism
• Cause:
• Hashimoto’s thyroiditis, iodine deficiency, post-thyroidectomy
• Effect / Symptoms:
• Fatigue, weight gain, cold intolerance, bradycardia, constipation
• Diagnostic Test:
• ↑ TSH, ↓ T3/T4
• Treatment:
• Levothyroxine (T4 replacement)

3. Exophthalmos
 • Cause:
• Autoimmune Graves’ disease → antibodies stimulate fibroblasts in orbit →
tissue & fat swelling
• Effect / Symptoms:
• Bulging eyes, corneal drying, diplopia
• Diagnostic Test:
• Clinical exam + thyroid function tests
• Treatment:
• Treat hyperthyroidism + steroids if severe

4. Myxedema (Severe Adult Hypothyroidism)

• Cause:
• Long-standing hypothyroidism (Hashimoto, iodine deficiency)
• Effect / Symptoms:
• Puffy face, periorbital edema, thick skin, slow reflexes
• Diagnostic Test:
• ↑ TSH, ↓ T4
• Treatment:
• Urgent thyroid hormone replacement (IV if coma)

5. Cretinism (Congenital Hypothyroidism)

• Cause:
• Iodine deficiency in mother, congenital thyroid failure
• Effect / Symptoms:
• Severe growth retardation, mental delay, large tongue, umbilical hernia
• Diagnostic Test:
• Neonatal TSH/T4 screening
• Treatment:
• Early thyroid hormone replacement to prevent mental retardation

6. Goiter
• Cause:
 • Iodine deficiency (endemic), autoimmune stimulation (Graves), TSH
stimulation
• Effect / Symptoms:
• Visible thyroid enlargement ± hyper- or hypothyroid symptoms
• Diagnostic Test:
• Thyroid function tests + ultrasound
• Treatment:
• Based on cause (iodine, antithyroid drugs, or surgery)

Memory:
• Hyper = Hot & Fast
• Hypo = Cold & Slow
• Cretinism = Kids
• Myxedema = Mature