Thyroid Hormones

&
Related Drugs

Dr. Sandip Jadav

Department of Pharmacology
BJMC
09/21/21 1
• Thyroid hormone action and regulation

• Disorders of thyroid hormone

• Thyroid drugs

• Antithyroid drugs

• Management in thyroid storm and myxoedema coma

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 Thyroid Hormones
• Thyroxine (Tetraiodothyronine,T4)
• Triiodothyronine ( T3 )
– both produced from thyroid follicles
– similar biological activity
– ‘thyroid hormones’

• Calcitonin:
– Produced by interfollicular ‘c’ cells
– Chemically and biologically different
– Role in calcium balance
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 Synthesis
1. Iodide is trapped by sodium-iodide symporter
2. Iodide is oxidized by thyroidal peroxidase to iodine
3. Tyrosine in thyroglobulin is iodinated and forms MIT & DIT
4. Iodotyrosines condensation

MIT+DIT→T3
DIT+DIT→T4

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Regulation of thyroid function

TRH: thyrotropin-releasing hormone

TSH: thyroid-stimulating hormone
Physiological actions of thyroid hormones

 To normalize growth and development, body temperature, and

energy levels

 Lipid, carbohydrate and protein metabolism

 To enhance CNS excitability & sensitivity of CVS to NA

 Indirectly on reproduction

＃ T3 is 3 to 4 times more potent than T4 in heat production

＃ T4 in colloid is about 4 times more numerous than T3

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 T3, via its nuclear
• Some of T4 are receptor, induces
converted to T3 in new proteins
kidney and liver generation which
produce effects
• The actions of T3 on
several organ systems
are shown

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Thyroid Disorders

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 hyperthyroid

cretinism
myxoedema
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Drugs for Thyroid Disorders

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 Thyroid drugs

 levothyroxine (L-T4)
 liothyronine (T3)
 liotrix (T4 plus T3)

Pharmacokinetics
T3 is more potent than T4
Oral easily absorbed
Should be taken at empty stomach
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 Clinical use
1. Cretinism :
• Failure of thyroid development/ defective synthesis (sporadic cretinism)/ severe
iodine deficiency (endemic cretinism)
• T4 thyroxine - 12.5–50 mcg (6–8 mcg/kg)/ day; life long

2. Myxoedema:
• Most common, in adults
• Autoimmune Thyroiditis/ thyroidectomy/ drugs/ Iodine deficiency
• T4 - DOC

3. Non toxic goiter:

• Endemic (iodine deficiency) or Sporadic (defective synthesis) - raised TSH levels
• T4 (100-200 mcg/day) - decreases size of goiter
• Good response- recent, diffuse, soft goiter cases
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• Poor response- old, fibrotic, nodular goiter
4. Myxoedema coma:
• Emergency treated in ICU
• Progressive mental deterioration, high mortality
• Rapid thyroid replacement – crucial
• T4/T3- IV, Steroids, Antibiotics

5. Papillary carcinoma of thyroid

• TSH dependent carcinoma
• Suppression of TSH is the basis of use of T4
• After surgery or radiotherapy for temporary regression

6. Other uses : Refractory anaemias, mental depression,

menstrual disorders, infertility, chronic/non-healing ulcers,
constipation.
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Antithyroid Drugs

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 Thyroid Inhibitors

Class Drugs
Inhibit hormone synthesis Propylthiouracil,
(Antithyroid drugs) Methimazole, Carbimazole

Inhibit iodide trapping Thiocyanates (–SCN),

(Ionic inhibitors) Perchlorates (–ClO4),
Nitrates (–NO3).
Inhibit hormone release Iodine, Iodides of Na and K,
Organic iodide.
Destroy thyroid tissue Radioactive iodine (I131 ,I125
,I123) 20
Mechanism of action

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 Antithyroid drugs
• Bind to the thyroid peroxidase and prevent oxidation
of iodide/iodotyrosyl residues, thereby;
 Inhibit iodination of tyrosine residues in thyroglobulin
 Inhibit coupling of iodotyrosine residues to form T3 and T4
(low dose)

 Characteristics
• Result appears slowly: in 3-4 w hyperthyroid ameliorated, and
in 2-3 months BMR normalized;
• Long-term use leads to hypothyroidism 22
 Difference between propylthiouracil and
carbimazol
Propylthiouracil Carbimazol
• Less potent • 3 times more potent
• High plasma protein bound • Less bound
• No active metabolite
• Produces active metabolite-
• Inhibits peripheral Methimazole
conversion T4 to T3 • Does not inhibits T4 to T3

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For Hyperthyroidism (Graves disease and
toxic nodular goiter)
1. Definitive treatment
– Grave’s disease- remission in 50% of patients in 1-2 yrs
– Toxic goiter-remission is rare- RA131I, surgery preferred
– In frail elderly patients with multinodular goiter who are less
responsive to RA131I, permanent therapy with antithyroid drugs can be
given

• Indicated in-
– Children, young adults, recent small goiter, frail elderly
– Pregnant woman- Propylthiouracil is preferred

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2. Preparation before thyroidectomy-
• To render the patient euthyroid before surgery to avoid
thyrotoxic crisis (surgical storm) in post operative period;
followed by iodides for 10 days prior to surgery

3. With radioactive iodine-

• Initial control with anti-thyroid drugs till the action of RAI
starts i.e. 2-3 months
• Antithyroid drugs 1-2 wks gap RAI ATDs after 1 wk
started  gradually withdrawn over 3 months

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 Advantage & Disadvantage of antithyroid
drug over surgery or I131
Advantages:
• No surgical risk or scar or chances of injury to parathyroid
gland or nerve
• Hypothyrodism is reversible
• Can be used in children and young
Disadvantages:
 Prolonged treatment – Relapse rate is high
 Compliance
 Drug toxicity
Note: Pregnant women Propylthiouracil preferred
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• Propylthiouracil: 50–150 mg TDS followed by 25–
50 mg

• Methimazole: 5–10 mg TDS initially, maintenance

dose
5–15 mg daily in 1–2 divided doses.
• Carbimazole: 5–15 mg TDS initially, maintenance
dose
2.5–10 mg daily in 1–2 divided doses

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 Iodides (NaI, KI)
Pharmacological action
•All facets of thyroid function affected
•Inhibition of T3 & T4 release(Constipation) and synthesis
• Fastest acting
•Decrease of size & vascularity of the hyperplastic gland
Clinical uses
1. Operation preparation for thyroidectomy
2. Thyrotoxic crisis,
3. Expectorant, Antiseptic

Adverse reactions
1. Acute reaction (fever, allergy)
2. Overdose (Swollen salivary glands, mucous membrane ulcerations)
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Preparations and dose
• Lugol’s solution (5% iodine
in 10% Pot. iodide solution)

• Iodide (Sod./Pot.) 100–300 mg/day

(therapeutic), 5–10 mg/day (prophylactic) for
endemic goiter.

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 Radioactive iodine (I131)
• Isotopes: I131
•X- rays - tracer study
β – rays – treatment
•given orally, Slow onset, repeat dose
Used in
hyperthyroidism (Graves’ disease or toxic nodular goiter)
Diagnostic, Metastatic papillary carcinoma of thyroid

Advantage:
Simple, convenient, low cost, OPD
No surgical risk, permanent cure

Disadvantages:
Hypothyroidism (long term treatment required)
Delayed onset of action
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Pregnancy or lactation, young patients - contraindicated!
 β- adrenergic blockers

• Effective in treatment of thyrotoxicosis.

• Propranolol - most widely used.
• Relieve symptoms (palpitation, anxiety, tremors)
• Uses:
• Response to propylthiouracil/ carbimazole/I131
• Along with iodide for preoperative preparation
• Before subtotal thyroidectomy.
• Thyroid storm (thyrotoxic crisis)
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 Management
in
Thyroid Storm
and
Myxoedema Coma
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 Myxoedema Coma
• “Body can no longer tolerate the changes caused by severe
hypothyroidism, so it decompensates.”
• Sign and symptoms can include:
– decreased breathing (respiratory depression),
– lower than normal blood sodium levels
– hypothermia (low body temperature), confusion or mental slowness
– Shock, low blood oxygen levels, high blood carbon dioxide levels
– Coma, seizures

• Can cause death often due to complications from infection,

bleeding, or respiratory failure.
• More common in women and people over the age of 60.
• Can occur during pregnancy as well.
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• Causes:
– an autoimmune condition, including Hashimoto’s disease
– surgical removal of thyroid
– radiation therapy for cancer
– certain medications, such as lithium or amiodarone 
– iodine deficiency or an excess of iodine
– pregnancy
– Chemotherapy
• Low T4 and high TSH

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 Management
• O2 +/- intubation / ventilation if resp. failure
• Cautious slow rewarming (scalp, groin, & axilla
warm packs, +/- NG lavage)
• Hydrocortisone 100 to 250 mg IV then 25-50 mg 8
hourly
• Thyroxine (T4) 500 mcg IV loading dose, then 50 – 100
mcg IV daily / NGT route
• Liothyronine (T3) loading dose of 10-20 mcg IV,
followed by 10 mcg IV every 4-6 hours for the first 48 hours

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• Fluid management
– If Hypoglycemic - 5% dextrose IV.
– Check for serum Na level
- 0.9% NaCl IV (120-130 mEq/mL)
-3% NaCl IV (below 120 mEq/mL) with furosemide
• Watch for fluid overload
• Antibiotics
• Search and treat cause

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 Thyrotoxic Crisis (Thyroid Storm)
"Exaggerated or florid state of thyrotoxicosis"
"Life threatening, sudden onset of thyroid hyperactivity"
– Most cases secondary to Graves' disease
– Some due to toxic multinodular goiter
– Rare causes : Acute thyroiditis, Malignancies (most do not efficiently
produce thyroid hormones)
•Important defining features :
– High fever (> 40 C), significantly abnormal mental status
– Agitation, confusion, psychosis, coma
– May also exhibit : Marked tachycardia,Vomiting, diarrhea
– Jaundice (in 20 %), Associated signs of Graves' disease
•HIGH T4 and T3 but low TSH 37
 Management
• Hospitalisation – ICU
• High flow Oxygen, IV fluids
• Manage temperature – ice packs, cooling
blanket, antipyretics (avoid aspirin)
• Antithyroid drugs
– methimazole, 15-25 mg orally every 6 hours or
propylthiouracil, 150-250 mg orally every 6 hours
• Oral Iodides [potassium iodide 10 drops three
times daily orally] /iopanoic acid 38
• Propranolol 0.5-2 mg intravenously
every 4 hours or 20- 120 mg orally /
Calcium channel blockers/ esmolol
• Hydrocortisone 100 mg IV then 50 mg
orally / dexamethasone
• Antibiotics
• Treat precipitating cause
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 References
1. Sharma HL, Sharma KK: Principles of Pharmacology: 2nd edn; Paras
Medical Publisher, Hyderabad, 2011
2. Tripathi KD. Essentials of Medical Pharmacology. 7th edition. New
Delhi: Jaypee Brothers Medical Publishers (P) LTD; 2013
3. Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G editors. Rang
and Dale’s Pharmacology. 7th edition.Elsevier Churchill Livingstone;
2012

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