Thyroid function and control

Second year Physiology

Presented by
Dr Tara Speranza
Department of Physiology, School of Medical Sciences
 The thyroid gland
& metabolism
• The thyroid axis and thyroid gland anatomy

• Synthesis of thyroid hormones T3 and T4

• Stimuli for hormone secretion
• Actions of thyroid hormones
• Facilitation of catecholamine activity
• BMR (basal metabolic rate) and BMI (body mass
index)
 The thyroid gland
& metabolism

• Hypo- and hyper-thyroidism signs & symptoms –

myxedema vs Graves’ disease

• Immune modulation of thyroid gland & diseases

• Synergism in growth

• TH radioimmunoassay & Ab measurements

Figure 23-7 - Overview
A quick word about Calcitonin

Calcitonin

Serum
Ca2+
Osteoblasts
Osteoclasts

Bone
T4 and T3

Figure 23-8
 Steps in synthesis of THs
1. Iodide trap concentrates I-
2. Iodide oxidation to iodine by peroxidase
3. Iodination of tyrosines on thyroglobulin
4. Coupling reaction:
MIT + DIT → T3 DIT + DIT → T4
5. Pinocytosis of TG with all these attached
6. Phagolysosome release of T3, T4, etc.
7. T3 and T4 secretion into blood when
↑TSH/thyrotropin
8. Plasma proteins transport variable %s
Figure 23-9 – Overview
Figure 23-10
 T4 Vs T3
T4>T3
• amount secreted by thyroid gland
• total and free plasma hormone concentration
• % bound to plasma pre-albumin
• half-life in circulation
T4<T3
• volume of distribution - T3 additionally in cells
• amount active in peripheral tissues after
conversion
T4 thus pro-hormone for T3
Table 23-2
 Actions of thyroid hormones
• Stimulate metabolism
Net effect on carb, fat & protein may be anabolic or
catabolic depending on levels
• Increase calorigenesis/heat production
• Promote normal growth
• Promote development and maturation of nervous system
• Increase cardiac function
• Increase respiration & red cell production
• Increase sympathetic/adrenaline actions
• Produce typical patient signs & symptoms
 Thyroid hormone
excess i.e. raised
plasma TH levels or
hyperthyroidism

Calorigenic action
Sympathomimetic action
Increases Na leak into
cells→Na pump/ATP use in Increases actions of Adr via
futile cycle → heat β-receptor up-regulation
Promotes futile cycles of β1 in pacemaker and
Ca2+ (SER) and H+ ventricular cardiac muscle
(mitochondria) latter β2 in vascular smooth
uncouples oxidative muscle and skeletal muscle
phosphorylation→ heat
,

More sympathomimetic More sympathomimetic

More Calorigenic action
Increases metabolism of all
types of substrates, which
Increases heat generation
hence increases BMR
action
Increases HR & contractility
Produces vasodilatation (as
does heat)
Increases blood flow
Decreases TPR
action
Causes muscle tremor
Also increases futile cycles
Net result is increased heat
generation, skin blood flow
Produces heat sensitivity
Figure 23-12
Figure 23-14 - Overview
 Hypothyroidism e.g. myxedema
• Low oxygen consumption and slow metabolic rate →
feel cold
• Decreased protein synthesis
• Slowed reflexes, slow speech and thought processes,
and feelings of fatigue
• Bradycardia
• Effects on gastrointestinal and female reproductive
systems (opposite to hyper)
• Less –FB → ↑TSH → goitre
• Cretinism can result from delayed TH treatment in
hypothyroid infants
Hypothyroidism e.g. myxedema
 Hyperthyroidism (e.g. Graves’
disease)
• Increased oxygen consumption and metabolic heat production
→ feel hot
• Increased protein and fat catabolism and possible muscle
weakness
• Hyperexcitable reflexes and psychological disturbances (e.g.
anxiety)
• Increased cardiac b1-adrenergic receptor and myosin
expression → tachycardia & palpitations
• Increased muscle b2-adrenergic receptors: vascular smooth
muscle relaxation→vasodilatation→↓total peripheral resistance
→↑pulse pressure (↑systolic ↓diastolic) & bounding pulse
skeletal muscle contraction→ tremor
• Abnormal Igs→goitre, exophthalmos (not all hyperthyroidism)
Hyperthyroidism (e.g. Graves’
disease)
 Treatments for hyperthyroidism
•Propylthiouracil (PTU) inhibits TH production by blocking
iodination & the coupling reaction, and interfering with
conversion of T4 to T3
•Beta-blockers prevent adrenergic side-effects of excess TH
•Immunosuppressive drugs inhibit auto-immune antibodies
targeting the thyroid
Note that there are many auto-immune thyroid diseases,
some of which cause hypothyroidism, where treatment would
be hormone replacement therapy with TH
 BMR and BMI
• Basal Metabolic Rate occurs when energy use is at its
lowest level
• BMR is increased by TH
• Body Mass Index = weight (kg)/height(m)2
• When excess TH increases BMR, it would be expected to decrease BMI,
unless there is an increase in calorie intake greater than the increased
energy output

• When lack of TH decreases BMR, it would be expected to increase BMI,

unless there is a decrease in calorie intake greater than the decreased
energy output

• This is the reason why it is important to take a detailed

history of a thyroid patient, as food (& exercise) also→
weight change
 Clinical measurements
• THs are measured by radioimmunoassay
(see The Human Endocrine System practical)
• First test in patients is for TSH, which is simpler
• If raised, most likely due to low TH and less –FB
• If lowered, most likely due to high TH and more –FB
• Treatment to reduce excess TH results in TH and TSH
levels recovering at different rates
• Antibodies can also be measured in those thyroid
diseases which are auto-immune
• These are clustered with other auto-immune diseases,
so having one increases probability of having another
e.g. coeliac disease
 Growth promotion
Dependent on life
cycle stage

Growth hormone Thyroid hormone Androgens

Increase bone growth Develop neural Increase bone

and tissue and
muscle protein Promote GH actions muscle
 Lecture summary:
• The thyroid axis and thyroid gland anatomy.
• Synthesis of thyroid hormones T3 and T4.
• Stimuli for hormone secretion.
• Actions of thyroid hormones.
• Facilitation of catecholamine activity BMR (basal
metabolic rates and BMI (body mass index).
• Hypo- and hyper-thyroidism signs & symptoms –
myxedema vs Graves’ disease.
• Immune modulation of thyroid gland & diseases.
• Synergism in growth.
• TH radioimmunoassay & Ab measurements.

• Calcitonin - synthesis and actions.