Case presentation on hyperthyroidism

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 T
3 and T
4
•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 T
3 and T
4 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 T
3, T
4 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
T
3 210 ng/dl 60-181 ng/dl Elevated
T
4 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
T
3 and T
4

17. PHARMACOKINETICS
•Absorption: 75% orally
•Distribution: 80-855 protein bound
•Metabolism: Liver via glucuronide conjugation
•Excretion: Via urine (t
1/2 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. 7
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New Delhi, India: Jaypee Brothers Medical Publishers Pvt. Ltd.
•SEMBULINGAM, K., (2012). Essentials of Medical Physiology. 6
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New Delhi, India: Jaypee Brothers Medical Publishers Pvt. Ltd.
•KATZUNG, B.G., TREVOR, A.J., MASTERS, S.B., (2012). Basic & Clinical
Pharmacology. 12
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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. 11
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Edition. USA: The McGraw-Hill Companies, Inc.
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