The Endocrine System: Thyroid

The Endocrine System
Thyroid
Department of Physiology Diponegoro University Faculty of Medicine

Thyroid Gland
 The largest endocrine gland, located in the anterior

neck, consists of two lateral lobes connected by a
median tissue mass called the isthmus
 Composed of follicles that produce the glycoprotein
thyroglobulin
 Colloid (thyroglobulin + iodine) fills the lumen of
the follicles and is the precursor of thyroid hormone
 Other endocrine cells, the parafollicular cells,
produce the hormone calcitonin
Thyroid Gland

Thyroid Hormones
 Thyroid hormone – the body’s major metabolic
hormone
 Consists of two closely related iodine-containing
compounds
 T4 – thyroxine; has two tyrosine molecules plus
four bound iodine atoms
 T3 – triiodothyronine; has two tyrosines with three
bound iodine atoms
 Calcitonin

Thyroid Hormones
OH OH
I I I
O O
I I I I
CH2 CH2
NH2CHCOOH NH2CHCOOH
Thyroxine (T4) Triiodothyronine (T3)

Synthesis of T3 and T4
 Thyroglobulin is synthesized and discharged into the
lumen
 Iodides (I–) are actively taken into the cell, oxidized
to iodine (I2), and released into the lumen
 Iodine attaches to tyrosine, mediated by peroxidase
enzymes, forming T1 (monoiodotyrosine, or MIT),
and T2 (diiodotyrosine, or DIT)
 Iodinated tyrosines link together to form T3 and T4
 Colloid is then endocytosed and combined with a
lysosome, where T3 and T4 are cleaved and diffuse
into the bloodstream
I + tyrosine monoiodotyrosine (MIT)
MIT + I diiodotyrosine (DIT)
DIT + DIT thyroxine (T4)
DIT + MIT triiodothyronine (T3)
hormones still attached to thyroglobulin

Synthesis of Thyroid Hormone

Thyroid hormone synthesis

Transport and Regulation of TH
 T4 and T3 bind to thyroxine-binding globulins

(TBGs) produced by the liver
 Both bind to target receptors, but T3 is ten times
more active than T4
 T3 also being produced in the peripheral tissues by
deiodination of T 4 (~ 80% of T 3 )
 reverse T 3 (rT 3 ) is inactive
 Mechanisms of activity are similar to steroids
 Regulation is by negative feedback
 Hypothalamic thyrotropin-releasing hormone (TRH)
can overcome the negative feedback
T3 and T4
• Bound to carrier proteins in the plasma

- thyroid binding globulin (TBG)
- albumin (10%)
- transthyretin (20%)
• Mainly thyroxine (t4) is released

- T4:T3 ratio = 25
- T3 is formed by the deiodination of T4

Iodine metabolisme
• The minimum adult daily requirement to maintain
thyroid function ±100-150 µg
• The thyroid secretes ±80 µg of I- per day as T3 &
T4, of which ±60 µg is metabolised in the liver
with release of I- into the ECF
• The total I- added to the plasma per day :
 500 µg - average dietary intake
 60 µg - from the liver metabolism of T3
& T4
 40 µg - diffusion from the thyroid to the
ECF

Iodine metabolisme
About 600 µg of iodide is distributed throughout

the ECF daily:
•Thyroid takes up ~ 20% or ~ 120 µg/day
•Remaining 80% is taken up by the kidney and
excreted in the urine

Physiological Actions of Thyroid Hormones
• effects of T3 and T4 are nearly identical except for

latency and potency
• essential for growth in childhood
• various metabolic effects:
- increase breakdown of carbohydrates

- increase breakdown of lipids
- determine metabolic rate
- level of heat production
Role of Thyroid Hormone
 Glucose oxidation
 Increasing metabolic rate
 Heat production
 Maintaining blood pressure
 Regulating tissue growth
 Developing skeletal and nervous systems
 Maturation and reproductive capabilities

Effects on Organ Systems
• HEART – increases rate, decreases force
• VASCULAR – vasodilation
• GI – increased motility and absorption
• SKELETAL – increased bone turnover
• NEUROMUSCULAR – hyperactivity, increased

muscle contraction

Regulation of Thyroid Hormone Release
Production and secretion of T3 and T4 is controlled

by thyroid stimulating hormone (TSH) released from
the anterior pituitary
• increasing plasma TSH causes:

• release of formed T3 and T4
• increased rate of iodide uptake
• increased rate of synthesis
• increased size and number of follicles
• TSH release under feedback control
Thyroid Hormone Control Pathways
Department of Physiology Diponegoro University Thyroid

Faculty hormone pathway
of Medicine
Additional Mechanism of T3/T4 Release
Cold exposure:
• a decrease in temperature acts via the
hypothalamic thermoregulatory centre to
increase release of TRH
• an increase in temperature has the reverse

effect

• Increase in thyroid binding globulin due to increase in
estrogen (stimulation of hepatic production and
decreased degradation)
 Increase in total T4 and T3
• Increase in GFR leads to increase in renal iodine
clearance
• HCG has similar properties to TSH therefore has
intrinsic thyroid stimulating activity
 Increase FT4 and FT3 levels during first trimester

• TSH upper reference limit (2.5–3.0 mIU/L).
Below 2.5 mIU/L in the first trimester and
preconception and 3.0 mIU/L in the second and
third trimesters
• The range of normal serum total T4 changes
during pregnancy
• Rapid increases in TBG levels  T4 increase
• Total T4 level 50% higher than non-pregnant
levels (5–12 μg/dL or 50–150 nmol/dL)
• In the second and third trimester multiply this
range by 1.5-fold.
Thyroid Dysfunctions

Hypothyroidism

Hyperthyroidism

Hypothyroidism: Cretinism
Congenital absence of T3 and T4 or chronic iodine

deficiency during childhood
- Retarded growth
- Sluggish movements
- Mental deficiencies
- Big tongue

Adult hypothyroidism
- Low rate of
metabolism and
lethargy
- Decreased body temp
- Decreased heart rate
- Outer skin becomes
scaly
- Myxedema – non
pitting edema due to
swelling of
subcutaneuous
connective tissues
Myxedema

Hyperthyroidsm
 Hyperthyroidism: the thyroid becomes over-active and

produces too much of its hormones  thyrotoxicosis
 Hyperthyroidism  over-activity of the organs resulting
in symptoms such as sweating, feeling hot, rapid
heartbeats, weight loss, and sometimes eye problems.
 Thyroid storm: the levels of thyroid hormones become
very high in a patient who has hyperthyroidism.
One major sign of thyroid storm is a marked elevation of

body temperature ≥ 41o C. It is a life-threatening
emergency.
Adult hyperthyroidism -
Grave’s disease
• Tall stature
• Hyperactive
• High rate of
metabolism
• High body
temperature
• High heart rate

Exophthalmus
edematous swelling at the rear of eye socket

Goiter
• swelling in neck due to thyroid
hypertrophy
• both hypo- and hyperthyroidism

Calcitonin
 A peptide hormone produced by the parafollicular,

or C, cells
 Lowers blood calcium levels in children
 Antagonist to parathyroid hormone (PTH)

Calcitonin
 Calcitonin targets the skeleton, where it:

 Inhibits osteoclast activity (and thus bone
resorption) and release of calcium from the bone
matrix
 Stimulates calcium uptake and incorporation into
the bone matrix
 Regulated by a humoral (calcium ion concentration

in the blood) negative feedback mechanism

Parathyroid Glands
 Tiny glands embedded in the posterior aspect of the

thyroid
 Cells are arranged in cords containing oxyphil and
chief cells
 Chief (principal) cells secrete PTH
 PTH (parathormone) regulates calcium balance in

the blood

Parathyroid Glands

Effects of Parathyroid Hormone
 PTH release increases Ca2+ in the blood as it:

 Stimulates osteoclasts to digest bone matrix
 Enhances the reabsorption of Ca2+ and the secretion

of phosphate by the kidneys
 Increases absorption of Ca2+ by intestinal mucosal
cells
 Rising Ca2+ in the blood inhibits PTH release

Effects of Parathyroid Hormone

Calcium balance

Hormonal regulation of the blood Calcium concentration

Disorders of Parathyroid gland

PTH excess – hypercalcemia
• Caused by either excessive bone resorbtion or

increased calcium absorption
• Hard to diagnose, often asymptomatic
 groans (constipation)  fatigue
 moans (psychotic noise)  anorexia, nausea,
 bones (bone pain, vomiting
especially if PTH is  increased urination
elevated)  abnormal heart
 stones (kidney stones) rhythms
 psychiatric overtones
(including depression and
confusion)

PTH excess – hypercalcemia
• High calcium blood values (12.0 mg/dl or 3

mmol/l).
• Severe hypercalcemia (above 15–16 mg/dl
or 3.75-4 mmol/l) is considered a medical
emergencycoma and cardiac arrest

PTH inssuficient – Hypocalcemia
• Hypocalcemia : low serum calcium levels in the

blood < 2.1 mmol/L or 9 mg/dl or an ionized
calcium level mm < 1.1 mmol/L (4.5 mg/dL)
• PTH or vitamin D deficiency
• Calcium receptor deficiency

Hypocalcaemia sign
Chvostek sign Trousseau sign

Tapping the skin over the facial Place a blood pressure cuff on the
nerve immediately in front of patient’s arm and inflate to 20 mm
the external auditory meatus Hg above systolic blood pressure for
will cause an ipsilateral 3-5 minutes. A flexion of the wrist
contraction of the facial muscles and metacarpal phalangeal joints can
be observed with extension of the
interphalangeal joints and adduction
of the thumb (carpal spasm).
Hypocalcaemia sign – carpopedal spasm
Werkudara


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The Endocrine System

Department of Physiology Diponegoro University Faculty of Medicine

 The largest endocrine gland, located in the anterior

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine

MIT + I diiodotyrosine (DIT)

DIT + DIT thyroxine (T4)

DIT + MIT triiodothyronine (T3)

hormones still attached to thyroglobulin

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine

 T4 and T3 bind to thyroxine-binding globulins

• Bound to carrier proteins in the plasma

• Mainly thyroxine (t4) is released

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine

About 600 µg of iodide is distributed throughout

Department of Physiology Diponegoro University Faculty of Medicine

• effects of T3 and T4 are nearly identical except for

• essential for growth in childhood

• various metabolic effects:

- increase breakdown of carbohydrates

Department of Physiology Diponegoro University Faculty of Medicine

• HEART – increases rate, decreases force

• GI – increased motility and absorption

• SKELETAL – increased bone turnover

• NEUROMUSCULAR – hyperactivity, increased

Department of Physiology Diponegoro University Faculty of Medicine

Production and secretion of T3 and T4 is controlled

• increasing plasma TSH causes:

Department of Physiology Diponegoro University Thyroid

• an increase in temperature has the reverse

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine

Congenital absence of T3 and T4 or chronic iodine

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine

 Hyperthyroidism: the thyroid becomes over-active and

One major sign of thyroid storm is a marked elevation of

Department of Physiology Diponegoro University Faculty of Medicine

edematous swelling at the rear of eye socket

Department of Physiology Diponegoro University Faculty of Medicine

 A peptide hormone produced by the parafollicular,

 Antagonist to parathyroid hormone (PTH)

Department of Physiology Diponegoro University Faculty of Medicine

 Calcitonin targets the skeleton, where it:

 Regulated by a humoral (calcium ion concentration

Department of Physiology Diponegoro University Faculty of Medicine

 Tiny glands embedded in the posterior aspect of the

 PTH (parathormone) regulates calcium balance in

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine

 PTH release increases Ca2+ in the blood as it:

 Enhances the reabsorption of Ca2+ and the secretion

 Rising Ca2+ in the blood inhibits PTH release

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine