Thyroid drugs are used to treat hypothyroidism and hyperthyroidism. Hypothyroidism is treated with levothyroxine to replace deficient thyroid hormone, while hyperthyroidism is initially treated with anti-thyroid drugs like methimazole or propylthiouracil to inhibit hormone synthesis. Radioactive iodine may also be used to destroy the thyroid gland in hyperthyroidism, resulting in hypothyroidism. Thyroid storm, a medical emergency, is treated with drugs that block thyroid hormone synthesis, conversion, and release along with beta blockers.

1. Thyroiddrugs
Dr Vijay Prasad

2. Learning objectives:
• Understand the synthesis, factors controlling, release of thyroid
hormone
• Know what thyroid hormone does, as well as what happen if excess
or deficient levels
• Understand the role of iodine in thyroid hormone
• Know the basics of thyroid medications

3. General Information:
• One of the largest endocrine gland
• Butterfly shaped bi-lobed structure, weight 15-20gms.
• It not only synthesis, releases but also store
• Basic unit is follicle, surrounded by colloid (semifluid material).
• Colloid contains thyroglobulin (TGB), which is a high molecular weight
glycoprotein containing 115 tyrosine residues
• A few cells lie embedded between the follicles c/s parafollicular cells (C cells )

5. Synthesis: Various steps: 60µg of iodine need daily

6. Regulation of thyroid hormone: H-P-T axis
• Thyrotropin releasing hormone TRH:
• hypothalamus  stimulates the release of TSH
• TSH Thyroid stimulating hormone:
• Anterior pituitary stimulates the release of Thyroid Hormone
• TH Thyroid hormone: T3 & T4
• SST Somatostatin:
• Inhibitory hormone released by the hypothalamus

7. T4 & T3 difference

8. *Mechanism of action:
• Free form diffuse across the cell bind to intra cellular thyroid receptor.
• T3 bound to receptor change connformation, the co-repressor
complex is suppressed while co-activator complex is recruited.
• This stimulates transcription  resulting in synthesis of proteins 
produce many action

9. Know what thyroid hormone does, as well as what happen if excess or deficient levels:
(decrease mentioned, opposite excess)
Regulates growth (Growth retardation)
Regulates metabolic rate (dec BMI Body weight gain)
Increase cholesterol synthesis & cholesterol excretion into the bile
On GIT: Increase GI motility and secretion of gastric fluids (Constipation)
On CVS:
• Enhance tissue sensitivity to catecholamine
• Increase or decrease need for oxygen in the periphery leading to an increase or decrease
in cardiac output (Angina, Bradycardia, Cardiac failure)

10. CHO metabolism:
• Increase glycogenlysis & gluconeogenesis, Increase glucose absorption from GIT
• Enhance glycolysis – rapid uptake of glucose by the cell.
• Net effect increased blood glucose level
On fat metabolism:
• Increase mobilization of fat
• oxidation of FA  increase FFA
On nervous system:
• Iodine is required for myelination of CNS neurons
• Excitable effect
• Has role on development of brain in fetal & 1st few weeks of postnatal life  depend
on mother T3 and T4
Muscle weakness due to protein catabolism (Increased protein catabolism)
Know what thyroid hormone does, as well as what happen if excess or deficient levels:
(decrease mentioned opposite excess)

11. • Helps regulate temperature (low body temperature Cold
intolerance)
• Helps maintain & release of egg from ovum (Infertility)
Know what thyroid hormone does, as well as what happen if excess or deficient levels:
(decrease mentioned opposite excess)

12. Thyroid disorders:
Hypothyroidism
• Cretinism (in children)
• Myxoedema (in adult)
Hyperthyroidism
• Thyrotoxicosis
• Grave’s disease
Subclinical hypothyroidism: no symptom, only abnormality is an inc. TSH

13. HYPOTHYROIDISM: Resulting from deficiency of thyroid
• Primary hypothyroidism: Inability of thyroid gland itself produce T3 and T4
Causes:
• Autoimmune hypothyroidism (Hashimoto’s (scientist): thyroid gland is attacked by a variety of cell- and
antibody-mediated immune processes.
• Iatrogenic (I123 treatment, thyroidectomy, external irradiation of the neck)
• Drugs: iodine excess, lithium, antithyroid drugs Decrease iodine trapping
• Iodine deficiency
• Infiltrative disorders of the thyroid: amyloidosis, sarcoidosis, haemochromatosis
• Post thyroidectomy
• Secondary hypothyroidism: Hypothalamic or pituitary disease

14. Symptoms: General
• Goitre: Due inactivity compensatory mechanism enlarge
• Tiredness and weakness: Muscle weakness and fatigue
• Feeling cold: Dec body temperature and intolerance to cold
• Bradycardia: Due to weak muscle and dec sensitivity of catecholamine’s
• Angina: decrease cardiac output , Serous cavity effusions (pericardial )
• Constipation: Due decrease movement of intestine muscle
• Weight gain with poor appetite : Due decrease BMR
• Hoarse voice: Due enlargement it press voice box
• Anemia: Due to decxrease erythroposis
• Infertility: Due to decrease release of egg from ovum
• Difficulty in concentrating, psychosis and poor memory CNS
• Impaired hearing
• Puffy face, hands and feet (accumulation of interstitial fluid)
• Delayed tendon reflex relaxation
• Carpal tunnel syndrome : Feeling numbness, tingling, or weakness in hand due to compression of nerve
• Dry skin ( dec BMI, dec tissue activity)
• Galactorrhoea (elevated TSH)

15. LAB INVESTIGATIONS:
• TSH , free T4 
• Anti thyroid antibodies – anti-TPO
• S-Cr.Kinase , s-Chol , s-Trigliseride 
• Ultrasound of thyroid – little value
• Normochromic or macrocytic anemia
• ECG: Bradycardia with small QRS complexes

16. Basic thyroid evaluation (Nine square game)
 TSH Normal Range 0.3 - 4.0 mU/L
 Free T4 Normal Range 0.7-2.1 ng/dL

17. Hypothyroid Treatment: T4 why?
Cretinism:
• Due to failure of thyroid development or defect hormone synthesis or
due to extreme iodine deficiency
• ℞ Thyroxine (8-12µg/kg)
• should be started as early as possible, because mental retardation that has
already caused is only partially reversible
Adult thyroidism (Myxoedema):
• ℞ L- thyroxine 50 µg daily
• Change the dose according response
• Liotrix(4:1)

18. Myxoedema coma:
• It is an emergency characterised by progressive mental deterioration,
caries significant mortality.
• Emergency condition so direct T3 will produce fast good response
• ℞ Liothyronine 100 µg loading dose Followed by 25 µg every six hours
or
℞ L- thyroxine 200-500 µg IV followed by 100 µg Oral therapy daily
Hypothyroid Treatment: T3 why?

19. • Thyroid nodules:
• Certain benign function modules regress when TSH is suppressed by T4
• Papillary carcinoma of thyroid:
• Surgery is the definitive management of thyroid cancer.
• In non resectable cases full dose of T4 supress endogenous TSH production
and may induce temporary remission.
Hypothyroid Treatment:

20. Hyperthyroidism: Due to excessive secretion of thyroid hormone
Causes: Gravis disease and toxic nodular goiter
• Grave’s disease: An autoimmune disorder
• Most common type
• TSH stimulating antibodies  in response to T3 and T4 over production
• Normal negative feedback mechanism ( false TSH action)
• T3 and T4, TSH R-Ab elevated while TSH low
Toxic uni or multinodular goiter: Autonomas toxic adenomas of thyroid

21. Hyper thyroidism Symptoms:
• Increased BMR
• Heat intolerance
• Tachycardia, Increased CO, cardiac arrhythmias
• Warm moist skin
• Weight loss (increased appetite)
• Diarrhoea,
• Skeletal muscle weakness with muscle wasting
• Insomnia, hyperreflexia, nervousness
• Hyperglycemia, fine tremors
• Menstrual irregularities
• In addition exopthalmos and dermopathy (peritibial myxoedema) are
characteristic features of Graves’ disease

22. Anti-thyroid drugs: Drugs:
Inhibit iodide trapping (step 1): Thiocyanates, perchlorates, Nitrates
Inhibit hormone synthesis (Thioamides 2-4): Propylthiouracil(s7),
Methimazole, Carbimazole
Inhibit hormone release: Iodine, Iodies of Na, K
Destroy thyroid tissue: Radioactive iodine(131I, 125I, 123I)

23. Other : anti thyroid drugs
• In addition, certain drugs used in high doses for prolonged periods cause
hypothyroidism/goiter as a side effect:
• Sulfonamides, Para-aminosalicyhc acid: inhibit thyroglobulin iodination
and coupling reaction.
• Lithium: inhibits thyroid hormone release
• Amiodarone: inhibits peripheral conversion of T4 to T3; also interferes with
thyroid hormone action
• Phenobarbitone, phenytoin, carbamazepine, rifampin: induce metabolic
degradation of T4/T3

24. Inhibit iodide trapping: Thiocyanates, perchlorates, Nitrates
• Inhibit iodide trapping (Anion inhibitors): Competitive inhibitors of
NA/I symporter .
• They are toxic and not clinically used now.
• Thiocynates associated with liver, kidney, bone marrow and brain
toxicity.
• Perchlorates produce rashes, fever, aplastic anaemia, agranulocytosis

25. Thioamides:
• All drugs have a thiocarbamide group
• Act by inhibiting thyroid peroxidase enzyme. (Step 2,3,4 and PTU additional step 7)
• Perioxidation enzyme and DID I (PTU)
• Clinical improvement starts after 1-2 weeks or more (depending on hormone content
of thyroid gland).

26. Comparison
Propylthiouracil Carbimazole
Don’t cross placenta * Pregnancy Cross placenta
Protein binding 75% Protein binding less
Less potent More potent (*10 time grater that PTU)
No active metabolite Active metabolite (Methimazole)
Half-life 75min 4-6 hours
Peripheral T4- T3 conversion inhibitor No peripheral T4- T3 conversion inhibitor
Side effects higher ( less frequent but high
mortality) Fulminant hepatitis
Less ( Regular use)
Not secreted through the milk

27. Carbimazole side effect during pregnancy:
• Fetal hypothyroidism
• Psychomotor delay
• Facial abnormality
• Nasal, Oesophageal atresis
• Hypoplastic phalanges
• Scalp or patchy hair defect
• Tracheo esophageal fistula

28. Therapeutic Uses:
Grave’s disease:
• Remission may occur in up to half of the patients of grave’s disease after 1-2 years of
treatment.
• If symptoms recur –treatment is reinstituted.
• This is preferred in young patients with a short history of Graves' disease and a small
goiter.
Thyrotoxicosis: lifelong
Pre operatively:
• To make euthyroid & preparation of patient for surgical subtotal thyroidectomy
• *B blockers used to reduce catecholamine sensitivity induced by hyperthyroidism
Along with 131I:
• Initial control with anti-thyroid drug  l to 2 weeks gap Radioiodine dosing of 131
I resume anti thyroid drug after 5-7 days  gradually withdraw over 3 months as
the response to 131I develops..

29. Advantage:
• No surgical risk, scar or chances of injury to parathyroid glands or
recurrent laryngeal nerve.
• If hypothyroidism develops then therapy can be stopped  normal
function
Side effect common: The most dangerous – agranulocytosis
(granulocyte count <500 cells/mm2)

30. Inhibit hormone release: Iodine
• These are fastest acting but short duration anti-thyroid drugs.
• Iodides are required for thyroid synthesis  but at high concentration
limits its own transport (Step1)
• Endocytosis of the colloid and proteolysis of thyroglobulin [step 5] 
inhibits release of T3 and T4:inhibited (thyroid constipating agents)
• Also attenuates TSH and cAMP induced thyroid stimulation.
• It makes the gland less vascular and more compact
Preparations and dose:
• Lugol’s iodine (5% iodine in 10% potassium iodide solution).
• Iodide (sodium/potassium): 100-300 mg/day (therapeutic), 5-10
mg/day (prophylactic) in endemic goiter.

31. Uses: preoperatively, thyroid storm, prophylaxis in endemic goiter,
antiseptic
ADRs: Acute reaction:
• Hypersensitivity reaction: Swelling of lips and eyelids, angiooedma of larynx,
fever, joint pain, petichial haemorrhage,
• thrombocytopenia, lymphadenopathy  further exposure to iodine should
be stopped immediately.
Chronic overdose (Iodism):
• Major symptoms are inflammation of mucus membrane, increase in
secretions (salivation, lacrimation, rhinorrhoea), headache, rashes,
gastrointestinal distress.
• Flaring up of acne in adolescents

32. Radioactive Iodine
• 131I is the most commonly used radioactive iodine with half life of 8
days.
• Actively taken up by thyroid gland and stored in the colloid (as sodium
salt of 131I orally) emits x rays and β particles
• β particles can penetrate only 0.5-2 mm of the tissue and destroy
the gland from within.( undergo pyknosis, necrosis followed by
fibrosis)
Uses:
• Diagnostic: 25-100 u curie
• Therapeutic: average therapeutic dose 3-6 m curie response is
slow start after 2 weeks, gradually increases peak seen around 3
months repeat if necessary.

33. Advantages:
• Treatment with 131Is simple, conveniently given on outpatient basis and
inexpensive.
• No surgical risk, scar or injury to pararathyroid / recurrent laryngeal nerves.
• Once hyperthyroidism is controlled, cure is permanent
Disadvantages:
• If hypothyroidism develops it is permanent.
• Long latent period of response
• Contraindicated during pregnancy foetal thyroid will also destroyed
resulting in cretinism, other abnormalities if given during 1st trimester.
• Not suitable for young patients

34. Drugs useful in thyroid storm: 5Bs
• Block synthesis: PTU 200-300 mg oral 6 hrly
• Block conversion: PTU
• Block release: Iopanoic acid (0.5 to 1 g OD oral)
• Block entrohepatic circulation: Cholestramine
• Beta blockers : propranolol 1-2 mg iv followed by 60-80 mg oral.
• Rehydrarion, external cooling, anxiolytics, appropriate antibiotics are
the other measures
• Corticosteroids