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(Thyroid Gland)
- Scattered among follicular cells and in spaces between the spherical follicles which secrete calcitonin

Parafollicular Cells



– Produce PTH
– Small, polygonal, darkly staining, abundant cells
– Contain lakes of glycogen giving them a water clear appearance

Chief Cells



– Function unknown
– Large, light staining, fewer in numbers
– Only present at age 6 onwards

Oxyntic cells


Percentage synthesized: 93%
Half-life: More (6 days)
Affinity for binding plasma protein: More
Binding to nuclear receptor: Less (10% of the receptors)
Onset of Action: 4x slower (2 days)



Percentage synthesized: 7%
Half-life: Less (1 day)
Affinity for binding plasma protein: Less
Binding to nuclear receptor: More (90% of the receptors)
Onset of Action: 4x faster (12 hours)



Steps in Synthesis of Thyroid Hormones

1. Iodide trapping
2. Formation and secretion of thyroglobulin
3. Oxidation of iodine
4. Organification of thyroglobulin
5. Storage and secretion


- Basal membrane of the thyroid actively pumps iodide to the cell interior (Na-I symporter)
- Concentrates the iodide to about 30 - 250 times its concentration in the blood
- Stimulated by TSH

Iodide Trapping


- Thyroid cell endoplasmic reticulum and Golgi apparatus synthesize the glycoprotein thyroglobulin and secrete to the follicle colloid

Formation of Thyroglobulin


- Conversion of iodide to nascent iodine I0 or I3
- Promoted by PEROXIDASE and its accompanying hydrogen peroxide
- Peroxidase is located in the apical membrane of the cell or attached to it, so the iodine will be readily available
- When peroxidase is blocked or hereditarily absent, the rate of synthesis of thyroid hormone falls to zero

Oxidation of Iodine


- Binding of iodine to thyroglobulin
- Oxidized iodine is associated with IODINASE, which speeds up the binding
- Iodine binds with about 1/6 of the tyrosine molecules in thyroglobulin

“Organification” of Thyroglobulin


- successive stages of iodination of tyrosine
- COUPLING of iodotyrosine molecules
- may occur in a matter of minutes or even days

Final Formation of Thyroxine (T4) and Triiodothyronine (T3)


Release of Hormones from Thyroid Gland

- Apical surface of the cell sends out pseudopods to form pinocytic vesicles that engulf some colloid
- Lysozymes fuse with the vesicles which have proteases that digest thyroglobulin
- T4 and T3 will be in free form then diffuse to basal membrane into surrounding capillaries
- T4 and T3 now enter circulation


Fate of Thyroglobulin

- About ¾ of iodinated tyrosine will not become T3 or T4 and remain only as mono- or diiodotyrosine that are cleaved from thyroglobulin as well
- Iodine is cleaved from these through the DEIODINASE ENZYME, which makes all the iodine available again for hormone synthesis
- Congenital absence of deiodinase enzyme causes iodine deficiency due to failure of recycling


Daily Secretion of T4 and T3

- 93% of hormone released from thyroid is T4, only 7% is T3
- During ensuing days, T4 is slowly deiodinated to T3 which is more readily available in the tissues
- Delivery is about 35 micrograms of T3 per day


Transport of T4 and T3 to Tissues

1. Upon entering the blood, 99% of T4 and T3 bind to transport proteins secreted by the liver:
– Main: Thyroxine-binding globulin
– Less: Thyroxine-binding prealbumin and albumin
– Half of T4 is released to tissues in 6 days

2. Half of T3 is released to tissues in 1 day (due to lower affinity to binding proteins)
3. Upon entering tissues, T4 and T3 bind with intracellular proteins (T4 > T3 binding)
4. Hormones are stored and used slowly in the next few days or weeks


• Unique: can produce and store hormones for up to 3 months
↓TBG: liver & kidney disease
↑TBG: estrogen or pregnancy

Thyroid Hormone



– Thyroxine Binding Globulin :70%
– Transthyretin or Thyroxine Binding Prealbumin : 20%
– Thyroxine Binding Albumin: 10%
– Free Thyroxine : 0.03%


Latency of Thyroid Hormones

- After injection of thyroxine to the blood, the basal metabolic rate only increases after 2 to 3 days
- Once activity begins, it lasts for 10-12 days then decreases with a half-life of 15 days
- Triiodothyronine has a latency of 6-12 hours
- Maximal cellular activity happens in 2-3 days
- Latency is due to binding to protein and their slow release and from how these are used in the cell


- Thyroid hormone receptors are located in the DNA
- Forms a heterodimer with retinoid X receptor (RXR) on DNA
- On binding with thyroid hormones, they initiate transcription and eventual translation into intracellular proteins
- Whole process takes about minutes to hours (explains latency)

Thyroid Hormones Activate Nuclear Receptors


Actions of Thyroid Hormones

- Increases O2 consumption and Basal Metabolic Rate (BMR) >> Increases mitochondria and Na-K-ATPase pump activity
- Stimulates carbohydrate, fat and protein metabolism
- Increases requirements for vitamins
- Increases blood flow, Cardiac Output, Heart Rate, Heart Strength


How does Thyroid Hormone stimulate carbohydrate, fat and protein metabolism?

- Increases glucose uptake, gluconeogenesis, glycogenolysis
Decreases cholesterol, phospholipids and triglycerides but increases fatty acids
- Increases cholesterol secretion to bile and number of liver LDL receptors
- Increase protein synthesis
- Needed for Growth


Actions of Thyroid Hormones

- Increases respiration
- Increases gastrointestinal motility
- Increases cerebration
- Increases muscle vigor (reason for Fine Muscle Tremors)
- Increases risk for somnolence
- Loss may cause loss of libido, impotence, menstrual changes


- Hyperthyroidism following administration of iodine or iodide, either as a dietary supplement or as contrast medium
- Typically occurs with comparatively small increases in iodine intake, in people who have thyroid abnormalities that cause the gland to function without the control of the pituitary

Jod-Basedow Effect


- Reduction in thyroid hormone levels caused by ingestion of a large amount of iodine
- Autoregulatory phenomenon that inhibits organification in the thyroid gland (inhibition of peroxidase), the formation of thyroid hormones inside the thyroid follicle, and the release of thyroid hormones into the bloodstream
- Lasts several days (around 10 days), after which it is followed by an "escape phenomenon“

Wolff-Chaikoff Effect


– Resumption of normal organification of iodine and normal thyroid peroxidase function
– Due to decreased inorganic iodine concentration secondary to down-regulation of sodium-iodide symporter (NIS) on the basolateral membrane of the thyroid follicular cell

Escape phenomenon


- Increased metabolic rate
- Excitability, restlessness
- Exophthalmos (sometimes but not always)
- Increased appetite but with weight loss, protein wasting and muscle weakness (thyrotoxic myopathy)
- Pre-tibial Myxedema (20% of patients)
- Tachycardia, increased Cardiac output
- Fine Tremors
- Diarrhea



- Decreased metabolic rate
- Slow thought process, poor memory
- Elevated plasma cholesterol and other lipids (atherosclerosis)
- Fatigue, increased somnolence, weight gain
- Whole body myxedema
- Prolonged relaxation phase of Deep Tendon Reflexes (DTRs)
- Hoarse voice
- Constipation



– Autoimmune disease, anti-TSH receptor antibodies
– Classic Triad:
• Exophthalmos
• Goiter
• Pre-Tibial Myxedema

Graves Disease


– Plummer’s Disease
– Most common cause of hyperthyroidism in those >50 y.o.

Toxic Multinodular Goiter


– Results from congenital lack of thyroid gland, genetic defect of the thyroid gland or lack of iodine in the diet
– Skeletal growth