Thyroid Gland: Anatomy, Histology, Physiology, and Pathology

THYROID GLAND

Dr. Sassan Hafizi

THIS LECTURE

• Location and histology of the thyroid
• Formation, storage, and release of thyroid hormones
• Control of thyroid hormone secretion
• Actions of thyroid hormones
• Thyroid diseases and treatment

THYROID

HYPOTHALAMUS

PINEAL GLAND

PITUITARY

GLAND

ROID

THYROID GLAND

Trachea

SKIN

THYMUS

Lung

HEART

THYROID GLAND

• 2 lobes connected by isthmus
• Greek: "shield-like" (Wharton 1656)
• Relatively large endocr. gland -
  18-60g in adults
• Location: caudal to larynx,
  adherent to front of trachea
• Able to concentrate iodine
  from blood stream

Hyoid bone

Superior thyroid artery

Superior thyroid vein

Thyroid cartilage of larynx

ea

Internal jugular vein

RIGHT LATERAL LOBE
OF THYROID GLAND
OF THYROID GLAND

Common carotid artery

Middle thyroid vein

ISTHMUS OF THYROID
GLAND

Inferior thyroid artery

Vagus (X) nerve

Subclavian artery

Trachea

Parafollicular (C) cell

Inferior thyroid veins

Sternum

Basement membrane (a) Anterior view of thyroid gland

Follicular cell

Thyroid follicle

Right lateral
lobe

Thyroglobulin (TGB)

Left lateral
lobe

LM
500x

(c) Anterior view of thyroid gland

(b) Thyroid follicles

Thyroid cartilage of larynx

Cricoid cartilage of larynx

RIGHT LATERAL LOBE OF
THYROID GLAND

LEFT LATERAL LOBE OF
THYROID GLAND

ISTHMUS OF
THYROID GLAND

Trachea

Right lung

Arch of aorta

(d) Anterior view

Isthmus

Thyroid
gland

LEFT LATERAL LOBE

HISTOLOGY OF THYROID GLAND

Capsule

Parathyroid

Thyroid

Chief cell

Oxyphil cell

• Parathyroid
  gland

0.
0.
€

Follicular cell

Thyroid gland

Blood vessel

Parafollicular cell

(c) Portion of the thyroid gland (left) and parathyroid gland (right)

• Follicle (acinus) - sac of stored
  hormone (colloid)
• Surrounded by acinar cells that
  produce iodine-containing thyroid
  hormones:
  • Thyroxine (T4; tetraiodothyronine)
  • Triiodothyronine (T3)
• Inactive gland - acinar cells are
  thin, flattened
• Overactive/hyperactive gland -
  acinar cells are tall, columnar
• Other cells: parafollicular cells
  • produce calcitonin (other topic

SUMMARY OF HORMONES BY CHEMICAL CLASS

CHEMICAL CLASS

HORMONES

SITE OF SECRETION

LIPID-SOLUBLE

Steroid hormones

Aldosterone, cortisol, and androgens.

Adrenal cortex.

Calcitriol.

Kidneys.

Testosterone.

Testes.

HO-

Estrogens and progesterone.

Ovaries.

Aldosterone

Thyroid hormones

I
I
H
H
HO
0
-C-C-COOH
H
NH2

Triiodothyronine (T3)

Gas

Nitric oxide (NO).

Endothelial cells lining blood vessels.

WATER-SOLUBLE

Amines

CH-CH2 -NH2
OH
HO
OH

Norepinephrine

Peptides and proteins

Glutamine

Isoleucine

1
Asparagine

Tyrosine

Cysteine-S-S-Cysteine

Proline

Leucine

Glycine

Oxytocin

NH2

Eicosanoids

HO
COOH
OH

A leukotriene (LTB4)

Epinephrine and norepinephrine (catecholamines).

Melatonin.

Histamine.

Serotonin.

All hypothalamic releasing and inhibiting hormones.

Oxytocin, antidiuretic hormone.

Human growth hormone, thyroid-stimulating hormone,
adrenocorticotropic hormone, follicle-stimulating hormone,
luteinizing hormone, prolactin, melanocyte-stimulating
hormone.

Insulin, glucagon, somatostatin, pancreatic polypeptide.

Parathyroid hormone.

Calcitonin.

Dastrin, secretin, cholecystoOInin, OIP
(glucose-dependent insulinotropic peptide).

Erythropoietin.

Ceptin.

Prostaglandins, leukotrienes.

Adrenal medulla.

Pineal gland.

Mast cells in connective tissues.

Platelets in blood.

Hypothalamus.

Posterior pituitary.

Anterior pituitary.

Pancreas.

Parathyroid glands.

Thyroid gland (parafollicular cells).

Stomach and small intestine
(enteroendocrine cells).

Kidneys.

Adipose tissue.

All cells except red blood cells.

CH2OH
Il C=0
H-C

T3 (triiodothyronine) and T4 (thyroxine).

Thyroid gland (follicular cells).

PRODUCTION OF
THYROID HORMONE

IODINATION OF TYROSYL RESIDUES
BY THE THYROPEROXIDASE-H2O2 COMPLEX

-e
OH
I-
Thyroperoxidase H2O2
C
H2N
H
COOH
4
H
5
31
6
21
CH
1
C
C
HON
H
COOH
HON
H
COOH
Tyrosine
Tyrosine radical
Monoiodotyrosine
OH
OH

Portion of thyroid follicle

Follicular
cell

Colloid

4
Iodination
of tyrosine

Blood
capillary

5
Coupling
of T, and T2

Tyrosine
T.
T2
T4

3
Oxidation
of iodide

Colloid
T2
TGB

6
Pinocytosis
and digestion
of colloid

3.
Secretory
vesicles

Lysosome

Golgi complex

Ta
TA

r
2
Synthesis
of TGB

Ta
TA

Rough ER

1
Iodide
trapping

X

7
Secretion
of thyroid
hormones

T3
TBG

Blood
plasma

T.
TBG

8
Transport
in blood

Key:
['= Iodide; 12 = Iodine
TGB = thyroglobulin
Blood capillary
TBG = thyroxine-binding globulin

PRODUCTION OF THYROID
HORMONE

1. Follicular cells
   • Trap iodide, active, against steep concn grad
   • Na+/I- symporter (NIS) and I-/CI- porter (pendrin, PDS)
   • Synthesise glycoprotein thyroglobulin (TGB)
   • Release TGB into colloid
2. Iodination of tyrosine in colloid
3. Formation of T3 & T4 by coupling:

SYNTHESIS OF THYROID HORMONES

Thyroid hormones formed within the structure of thyroglobulin (TGB):

• 40/125 Tyr residues in TGB available for iodination
  • Proportion related to I- concn
• Tyr in TGB is iodinated to form monoiodotyrosine (MIT)
• MIT is iodinated to form diiodotyrosine (DIT)
• Coupling then occurs: MIT+DIT = T3; DIT+DIT = T4

Thyroid hormones

Monoiodotyrosine
Diiodotyrosine
Thyroxine (T4)
Triiodothyronine (T3)

OH
OH
1
3
3
6
2
6
2
1'
O
O
1
4
4
5
3
6
2
1
CH2
CH2
C
C
H2NH COOH
H2NH COOH
OH
OH
1
1
1
CH2
C
C
·N
H
C
·N
H
H
0
0
6
2
1
5
3
H
CH2

Portion of thyroid follicle

Follicular
cell

4
Iodination
of tyrosine

Blood
capillary

5
Coupling
of T, and T2

Tyrosine
T.
T2
T4

3
Oxidation
of iodide

Colloid
T3
TGB

6
Pinocytosis
and digestion
of colloid

Secretory
vesicles

Lysosome

Golgi complex

Ta
TA

1
2
Synthesis
of TGB

Ta
TA

Rough ER

1
Iodide
trapping

X

7
Secretion
of thyroid
hormones

T3
TBG

Blood
plasma

T.
TBG

8
Transport
in blood

Key:
['= Iodide; 12 = Iodine
TGB = thyroglobulin
Blood capillary
TBG = thyroxine-binding globulin

PRODUCTION OF THYROID
HORMONE

1. Follicular cells
   • Trap iodide, active, against steep concn grad
   • Na+/I- symporter (NIS) and I-/Cl- porter (pendrin, PDS)
   • Synthesise glycoprotein thyroglobulin (TGB)
   • Release TGB into colloid
2. Iodination of tyrosine in colloid
3. Formation of T3 & T4 by coupling:
   • MIT (T1) + DIT (T2)
   • Extracellular "depot" of hormone
4. Uptake & digestion of colloid containing TGB
   by follicle cells (TGB degraded)
5. Secretion of thyroid hormone into blood
   • 80-90% T4, 10-20% T3
   • Only 0.03% T4 & 0.3%T3 free (unbound)
   • Most bound to thyroxine-binding globulin (also
     transthyretin, albumin)

r
Colloid

CONTROL
OF THYROID HORMONE SECRETION

CONTROL OF THYROID HORMONE
SECRETION

HORMONE

SECRETED BY

RELEASING HORMONE
(STIMULATES SECRETION)

INHIBITING HORMONE
(SUPPRESSES SECRETION)

Human growth hormone (hGH)
or somatotropin

Somatotrophs.

Growth hormone-releasing hormone
(GHRH), also known as somatocrinin.

Growth hormone-inhibiting hormone
(GHIH), also known as somatostatin.

Thyroid-stimulating hormone (TSH)
or thyrotropin

Thyrotrophs.

Thyrotropin-releasing hormone (TRH).

Growth hormone-inhibiting hormone
(GHIH).

Follicle-stimulating hormone (FSH)

Luteinizing hormone (LH)

Prolactin (PRL)

Gonadotrophs.

Gonadotropin-releasing hormone (GnRH).

Gonadotrophs.

Gonadotropin-releasing hormone (GnRH).

Lactotrophs.

Prolactin-releasing hormone (PRH);
TRH.

Adrenocorticotropic hormone (ACTH)
or corticotropin

Corticotrophs.

Corticotropin-releasing hormone (CRH).

Melanocyte-stimulating hormone

Corticotrophs.

Corticotropin-releasing hormone (CRH).

-

-

Prolactin-inhibiting hormone (PIH),
which is dopamine.

-

Dopamine.

• Thyrotropin-releasing hormone (TRH) from
  hypothalamus
• Thyroid-stimulating hormone (TSH) from anterior
  pituitary (thyrotroph cells):

1
Low blood levels of T3
and T3 or low metabolic
rate stimulate release of

Hypothalamus
TRH

2
TRH, carried
by hypophyseal
portal veins to
anterior pituitary,
stimulates
release of TSH
by thyrotrophs

TSH

5
Elevated
T3inhibits
release of
TRH and
TSH
(negative
feedback)

3
TSH released into
blood stimulates
thyroid follicular cells

Anterior
pituitary

Thyroid
follicle

4
T3 and T4
released into
blood by
follicular cells

ACTIONS OF THYROID HORMONES

0
Follicular
cells

Thyroid
follicle

O T3 & T4 cause:

• î Metabolic rate
• î Protein synthesis
• î Breakdown of fats
• î Use of glucose for ATP production

Thyroid
follicle

Parafollicular
cells

"C" cells

o Calcitonin

• From the parafollicular cells
• Responsible for building of bone

Other topic

IMPORTANCE OF THYROID HORMONES

o Administration of thyroid hormones:

• Î BASAL METABOLIC RATE (BMR) in adults

o Concentration of circulating thyroid hormones relatively constant

• Contrast to most other hormones

o Essential for normal growth and development

o In adult, virtually every body tissue requires thyroid hormones

• Principal site of action is cell nucleus

ACTIONS OF THYROID HORMONES

Calorigenic - increases oxygen consumption of most tissues

o Effect on nerves - brain maturation during foetal development

o Synergistic with catecholamines (adr., noradr.) - 1 heart rate

C
Effect on carbohydrates - increase uptake from GI tract

o Growth & development - need for correct growth

o Effect on skeletal muscle - need for muscle strength

O
Effect on heart muscle - heart v. sensitive to thyroid hormones

O
Cholesterol lowering - lowers blood cholesterol

THYROID HORMONE PROPERTIES

o Thyroid secretes mostly T4 (80 µg/d) in adult
human (T3, 4 ug/d)

o T3 probably the true hormone

• more active
• faster turnover
• better T3 receptor binding

Thyroxine (T4)
Triiodothyronine (T3)

OH
OH
-
5'
3
3
6'
2
6
2
1
1
O
1
-
1
-
5
3
5
3
6
2
6
2
.1
1
CH2
CH2
C
.C
HẠNH
I
COOH
H2N H
COOH

o T3 activates T3 receptor in cell nucleus, turning
on protein synthesis

o T4 largely a prohormone

• Easily converted to T3 (deiodinase)
• Up to 80% T4 converted to T3 outside
  thyroid (liver, kidney, spleen)

4

PROPERTIES OF THYROID HORMONES

T3
T4

Ty, in blood
2 days
6 days

Start of action (nucleus)
4h
24h

Maximum effect
2-3 days
10 days

% bound in blood
99.8
99.98

Free level in plasma
0.4 ng/dl
2 ng/dl

Total level in plasma
0.15 µg/dl
8 ug/dl

O2 consumption in
humans
3-5x effect of T4 on
a molar basis

THE EFFECT OF EQUIMOLAR DOSES OF T3 AND T4 ON
BASAL METABOLIC RATE IN A HYPOTHYROID SUBJECT

+5

Basal metabolic rate

600 µg T3

-5

-15

720 µg T4

-25

-35
0
4
8
12
16
20
Days after injection