A presentation on a case of hyperthyroidism (Graves disease) along with explanations in the pathophysiology and drug of choice.

1. CASE PRESENTATION ON
HYPERTHYROIDISM
PRESENTED BY
ROHIT AGRAWAL
B.PHARMACY

2. BACKGROUND
• Hyperthyroidism simply means hyperfunction
or hyperactive state of thyroid gland
• It is associated with thyrotoxicosis i.e. a hyper
metabolic state caused by elevated circulating
levels of free T3 and T4
• Hyperthyroidism might not be the only cause
for thyrotoxicosis
• In hyperthyroidism, there is depressed levels
of TSH due to negative feedback mechanism

3. There are three common causes of
thyrotoxicosis associated with hyperthyroidism:
• Diffuse toxic goiter, Grave’s disease
• Toxic Multinodular goiter
• Toxic adenoma

4. GRAVE’S DISEASE
• Also called as diffuse toxic goiter, is an
autoimmune disease of thyroid and most
common cause of endogenous
hyperthyroidism
• It is characterized by triad of manifestations
– Thyrotoxicosis, caused by diffusely enlarged
hyperfunctional thyroid
– Ophthalmopathy, with resultant exophthalmus
– Dermatopathy

5. PATHOGENESIS
• Autoantibodies are produced against thyroid
antigens, the major one being TSI
• Thyroid Stimulating Immunoglobulin (TSI) is
antibody to TSH-R antigen and mimics action of
thyroid hormones i.e. stimulate growth and
biosynthetic activity of thyroid cell
• It results in hypertrophy and hyperplasia of thyroid
follicles
• Opthalmopathy arises due to infiltration of
retroorbital space by T cells, accumulation of ECM
and increased no. adipocytes along with
inflammatory edema and swelling of extraocular
muscles, all leading to protrusion of eyeball
(exopthamos)

7. Exopthalmos

8. CLINICAL SYMPTOMS
• Due to thyrotoxicosis,
– Emotion instability, nervousness, fatigue, perspiration,
heat intolerance, fine tremors
– Weight loss despite of good appetite
– Menstrual disturbances
– Cardiac: Tachycardia, Palpitations
– Increased levels of T3 and T4 but depressed levels of
TSH
• Due to ophthalmopathy
– Abnormal protrusion of eyeball
– Wide, starring gaze

9. MANAGEMENT
NON-PHARMACOLOGICAL APPROACH
• Eating well (berries, dairy products, protein, fats)
• Exercise
• Easing stress
• Applying cool compress to eyes
• Use lubricating eye drops
• Elevate head
• Don’t smoke

10. PHARMACOLOGICAL APPROACH
• Anti thyroid drug therapy: Most useful in
young patients with small glands and mild
disease. e.g. Propylthiouracil, methimazole
• Thyroidectomy: Usually done in case of large
glands or goiter
• Radioactive Iodine: Preferred for patients
above 21 yrs of age
• β blockers (for symptomatic treatment)

11. CASE
A 19 years old women develops secondary
amenorrhoea followed by symptoms of
palpitations, nervousness, heat intolerance and
swelling. There is a strong family history of
autoimmune disease. One examine she appears
anxious and sweaty, her pulse in 120 beats/minute
and there is a smooth goiter with a soft bruit. There
is tremors of outstretched fingers and lid lag is
present. A pregnancy test is positive. Blood was
sent to laboratory for T3, T4 and TSH investigations

12. CASE SUMMARY
• Age: 22 years Sex: Female
• Signs and symptoms:
– Palpitations, nervousness, heat intolerance, amenorrhoea
• Physical examination:
– Smooth goitre with soft bruit
– Lid lag present
– Pulse rate: 120 beats/minute
• Laboratory Investigations:
Obtained value Normal value Inference
T3 210 ng/dl 60-181 ng/dl Elevated
T4 15.6 μg/dl 4.8-10.4 μg/dl Elevated
TSH 0.8 μIU/ml 0.4-4 μIU/ml Low
TSI 145% <125%) Elevated
• Diagnosis: Grave’s Disease
• Treatment: Propylthiouracil

13. PROPYLTHIOURACIL
• It is an antithyroid drug that inhibits the
hormonal synthesis
• It is widely used in Grave’s disease and other
conditions of hyperthyroidism

14. MECHANISM OF ACTION
• It binds to the thyroid peroxidase and prevent
oxidation of iodide/iodotyrosyl residues,
thereby:
– Inhibit iodination of tyrosine residues in
thyroglobulin
– Inhibit coupling of iodotyrosine residues in form of
T3 and T4

17. PHARMACOKINETICS
• Absorption: 75% orally
• Distribution: 80-855 protein bound
• Metabolism: Liver via glucuronide conjugation
• Excretion: Via urine (t1/2 1-2 hrs and Duration
of action is 4-8 hrs)

18. INDICATION
• Grave’s Disease
• Toxic Nodular Goiter
• Thyrotoxic Crisis
• It is reserves for those cases unable to tolerate
other treatments
• Treatment of choice during and just before the
first trimester of pregnancy

19. DOSE
• Grave’s Disease
– 50-150 mg PO q8hr initially
– Maintenance: 50mg PO q8-12hr for upto 12-18
months; then taper and discontinue if
euthyroidism restored in normal
• Thyrotoxic Crisis
– Initial 200-300 mg/day PO divided q8hr intially
– Maintenance: 100-150 mg/day divided q8hr

20. ADVERSE REACTIONS
• Hypothyroidism and goiter due to overtreatment
• Agranulocytosis
• Aplastic anemia
• Dermatologic reactions
• Hepatitis
• Polyarthritis
• Drowsiness, fever, headache
• Alopecia
• Rashes
• Loss of taste
• Leukopenia, Thrombocytopenia

21. CAUTIONS
• Liver disease, Bleeding disorders
• Bone marrow depressions
• Pregnancy: Risk of foetal hypothyroidism and
goiter but low in case of propylthiouracil due
to its greater protein binding and less tranfer
to foetus

22. CONTRAINDICATIONS
• Hypersenstivity
• With sodium iodide

23. DRUG INTERACTIONS
• Sodium iodide
– Decrease level or effect of sodium iodide
• Carbamazepine, Clozapine, Methimazole
– Increase toxicity of the other by synergism
(Increased risk of agranulocytosis)

24. REFERENCES
• TRIPATHI, K.D., (2014). Essentials of Medical Pharmacology. 7th Edition.
New Delhi, India: Jaypee Brothers Medical Publishers Pvt. Ltd.
• SEMBULINGAM, K., (2012). Essentials of Medical Physiology. 6th Edition.
New Delhi, India: Jaypee Brothers Medical Publishers Pvt. Ltd.
• KATZUNG, B.G., TREVOR, A.J., MASTERS, S.B., (2012). Basic & Clinical
Pharmacology. 12th Edition. USA: McGraw-Hill Companies, Inc.
• BRUNTON, L.L., PARKER, K.L., BLUMENTHAL, D.K., BUXTON, I.L.O, (2006).
Goodman and Gilman’s Manual of Pharmacology and Therapeutics. 11th
Edition. USA: The McGraw-Hill Companies, Inc.
• RITTER, J.M. et. al. (2008). A Textbook of Clinical Pharmacology and
Therapeutics. 5th Edition. London, UK: Hodder Arnold, part of Hachette
Livre
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