PHARMACOLOGY OF

THYROID GLANDS

Dr. Yunita Sari Pane, MSi

Bagian Farmakologi dan Terapeutik,

Fakultas Kedokteran
Universitas Sumatera Utara 1
INTRODUCTION

Due to its anatomic prominence thyroid

was one of the first of the endocrine
glands to be associated with the clinical
conditions caused by its malfunctions

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Thyroid Gland Physiology
Synthesis and secretion of thyroid hermones.

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Metabolism of Thyroid Hormones

TH  circulates bound to plasma

protein  1. Thyroid binding
globulin (TBG)
2. Transthyretin.
T4 : predominant in the blood, but
T3 : has 4 times the physiologic
activity of T4 on target tissues.

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Peripheral metabolism of thyroxine

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Enzymes for deiodination : 
iodothyronine 5’ – deiodinase.
3 subtypes
1. Type I deiodinase
- expressed in the liver and
kidneys.
- important for converting T4 to T3
in the serum.
2. Type II deiodinase
- expressed in pituitary, brain and
brown fat.
- located intra cellularly
- Converted T4 to T3 locally.
3. Type III deiodinase 6
T4 presence in blood acts like a buffer or
reservoir for thyroid hormone effect.

t ½ T4 in plasma :  6 days
t ½ T3 :
 1 days

 Changes in thyroid hormone –

regulated functions caused by
pharmacologic intervention are generally
not observed for a perriod of 1 to 2 weeks.
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HYPOTHALAMIC – PITUITARY –
THYROID AXIS

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MECHANISM OF T.H. ACTION

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EFFECTS OF T.H.

T.H. are responsible for optimal :

- Growth
- Development
of all body tissues
- Function
- Maintenance

Excess  thyrotoxicosis or
hyperthyroidism.

Inadequate  hypothyroidism
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T.H. is important in infancy for growth
and development of the nervous
system

Congenital deficiency of TH.

Cretinism  mental retardation

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In adult :
TH regulates general body metabolism and
energy expenditure, and also some enzymes :
- Na+ - K+ - ATPase
- For catabolic and anabolic  body
temperatur increases
- Resemble the effects of symphathetic
stimulation.
Low level of TH.
- Lethargy
- Myxedema  -
Hypometabolic
- Dry skin
- Coarse voice 13
TREATMENT OF HYPOTHYROIDISM
T3 or T4 ?

More active
 Lower activity but is the most
TH in blood

as a buffer
 t ½ of T4 6 days  single dose

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TREATMENT OF HYPERTHYROIDISM

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Inhibitors of Iodide uptake
- Perchlorate (Cl O4-)
- Thiocyonate (SCN-) 
- Pertechnetate
Compete with iodide for uptake
via Na+/ I- symporter.

Iodide for TH synthesis

- Effect not appear for over a week
- Can cause aplastic anaemia

- Thioamine is more effective.

- Be careful with radiopaque 16
contrast.
Inhibition of organification and
hormone release.
I. Iodides

1. I-  a radioactive iodide isotope

131

emits strongly -rays toxic to cells.

 Na+ / I- channel cannot
distinguish 131 I- from 127 I-
131
I- will destroy the thyroid gland.
Concern 
- May develop to hypothyroidism
- Long-term side-effect : thyroid17
I. IODIDE
2. Stable inorganic iodide  high levels of
iodide inhibit synthesis & release 

Wolff – Chaikoff effect

- reversible, transient
not useful for long-term theraphy.
- Reduces the size & vascularisation of
the thyroid gland

- Often administered before gland

surgery 18
II. THIOAMINES
Mekanisme kerja :
1. Berkompetisi dengan
thyroglobulin (TG) terhadap
oxidized iodide sehingga proses
organification and coupling
menjadi terganggu,  produksi
TH menurun.
2. Iodinated thioamine may also
bind to TG  TH
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TH production  TSH upregulation 
thyroid gland stimulation

Thyroid gland hypertrophy

goiter

Substances or drugs that produced

goiter  goitrogens.

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 Thioamines pharmacokinetics
Prophylthiouracil Methimazole

Abs. - rapid,  peak of - Variable

absorb in  1 hour
Biovail, - 50 – 80% - Complex
Vol. Dist. - Total body water - id
- Accum. in thyroid - id
Metab. - Glucuronidation - id
Excr. - Kidney - id but.
slower
t½ - 1,5 hours - 6 hours
Dose : 6 – 8 hours Single dose
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Side effects :

- Occur in 3 – 12 %
- Maculopapular skin rash +
fever.
- Rarely : urticarial rash +
vasculitis, + lupus-like
jaundice, lymphadenopathy,
acute arthralgia.
- Agranucytosis  0,3 – 0,6 %

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Propylthiouracil
- Prototype of thioamine.
- Can also inhibit peripheral T4 to T3
conversion.
- Can also deplete the level of
prothorombin.
Methimazole.
- Is reported to cause fetal defects.
- More potent than PTU 
hypothroidism.

PTU is preferred 23
Inhibitors of Peripheral thyroid hormone
metabolism
- Propylthiouracil *
-  - adrenergic blockers.
- Radiocontrast agents.
 - adrergic blockers.
- Symptoms of thyrotoxicosis mimic those of
sympathetic stimulation :
- Sweating
- Tremor
- Nervousness
- Tachycardia
Propranolol : most widely used and studied.
Esmolol : preferred because
- Rapid onset of action 24
- Short t ½ (9 minutes).
Radiocontrast agents :

- Iodinated contrast agents :

- Ipodate
P.O.
- Iopanoic acid
- Diatrizoate  I. V.

- Rapidly in hibit T4 to T3 conversion by

inhibiting 5’ – deiodinase.
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Preparation available :

I. THYROID AGENTS :
- Levothyroxine (T4)
- Liothyronine (T3)
- Liotrix (a combination of a 4 : 1 ratio
of T4 : T3)
- Thyroid desiccated (USP)

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II. ANTI THYROID AGENTS

1. Propyl thiouracil (PTU)

2. Methimazole (Tapazole)
3. Iodide (131I) sodium
4. Ipodate sodium
5. Potassium Iodide
- generic oral sol.
- Lugol’s solution :
- 100 mg/ml KY + 50 mg/ml iodine.

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