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Pharmacotherapy II

Spring Semester 2017-18

Thyroid disorders Jimmy Jose M Pharm, PhD

Associate Professor (Pharmacy Practice)

School of Pharmacy

Learning outcomes:

1. Understand the pathophysiology, etiology, clinical

manifestations, diagnostic parameters, and drug and non drug

related management of thyroid disorders

2. Develop the skills for monitoring drug therapy and patient

education in patients with thyroid disorders

3. Develop pharmaceutical care plan for management of patients

with thyroid disorders

4. Develop the skills for identifying drug related problems and

making informed pharmacotherapy decisions (patient focused,

evidence based and clinically sound) in patients with thyroid

disorders

Thyroid disorders (Hyperthyroidism and hypothyroidism)

consists of a variety of disease states affecting thyroid

hormone production or secretion that result in alterations in

metabolic stability.

Thyroid hormone physiology Thyroid gland synthesize –

levothyroxine - T4

triiodo thyronine- T3

Hypothalamus- Thyroid Releasing Hormone (TRH)

Pituitary- TSH (Thyroid stimulating hormone)

Thyroid (T4 /T3)

Periphery (T4, T3)

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Hyperthyroidism (Thyrotoxicosis)

Defined as the production and secretion of excessive amounts

of thyroid hormones

Thyrotoxicosis refers to the clinical syndrome associated with prolonged

exposure to elevated levels of thyroid hormone

Epidemiology: Higher incidence in females. 2- 10 times more likely to develop.

Etiology: Graves disease:

Antibodies to TSH receptor on thyroid gland.

Toxic nodular goiter:

Clear, diffuse or focal autonomous nodule formation

develops in enlarged thyroid

Autonomous thyroid adenomas:

benign well differentiated tumors that secrete excessive amounts of thyroid hormone

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Clinical manifestations Signs and Symptoms

System affected

Skin and

appendages

Nervous system

Hypothyroidism

Dry, cool flaking skin, puffy

face and eyes, coarse brittle

hair, cold intolerance

Slow speech, poor memory,

psychiatric disturbance,

depression

Hyperthyroidism

Warm, moist skin,

Thinning or loss of hair.

Prominence of eyes ,

increase sweating, Heat

intolerance, pretibial

myxoedema

Insomnia, Irritability,

anxiety, psychosis

System affected

Musculoskeletal

GIT

CVS

Hypothyroidism

Muscle pain and

weakness,

Weight gain with

decreased appetite,

constipation

Bradycardia

Hyperthyroidism

Osteoporosis, muscle

weakness and tremor

Diarrhea, weight loss with

increased appetite

Tachycardia, palpitation,

angina, atrial fibrillation

Hypothyroidism Hyperthyroidism 9

Goitre

Thyroid storm is a life-threatening medical emergency characterized by severe thyrotoxicosis, high fever often greater than 39.4°C [103°F]), tachycardia, tachypnea, dehydration, delirium, coma, nausea, vomiting, and diarrhea.

Precipitating factors include infection, trauma, surgery, radioactive iodine (RAI) treatment, and withdrawal from antithyroid drugs.

Thyroid Storm

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Thyroid function tests in different thyroid

conditions

Total T4 Total T3 TSH

Normal 4.5 -10.9 mcg/dl

60-181 ng/dl 0.5-4.7 milli IU/L

Hyperthyroid

Hypothyroid

Thyroid function tests

- Measures the concentration of T 4 and T3

- Integrity of hypothalamic-pituitary thyroid axis -TSH, TRH

Treatment

Standard forms of treatment:

- Antithyroid drugs

- Surgery

- Radioactive iodine

Immediate treatment of thyrotoxicosis:

- Symptoms needs to be addressed and their thyrotoxicosis addressed

- Beta blockers in standard antihypertensive doses are effective within a matter of hours

- Carbimazole (40 mg once daily) or PTU (150 mg twice daily ) will make most patients euthyroid within 6 weeks

- Adjunctive treatment of cardiac disease and anxiety/sleeplessness may be required

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Antithyroid drugs Propyl thiouracil (PTU) , methimazole and carbimazole

Adverse drug reactions

Most common adverse effect is rash and arthropathy with an incidence of -----

Agranulocytosis, Hepatitis, aplastic anemia occur rarely

Agranulocytosis is the most common serious ADR. Incidence and predisposing factor ---------

Usually occurs during first 6 weeks of treatment

Cross sensitivity between carbimazole and PTU is around 10%

Patient counseling points :

Patients to be warned about possible implication of sore throat, mouth ulcers and pyrexia, and instructed to seek an urgent full blood count.

Regimen:

Carbimazole: 20-60 mg daily

Methimazole: 5-15 mg/day

PTU- 100-150 mg/day

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Optimal duration of antithyroid treatment is 12-24 months

T4 concentrations are checked at 6 weeks intervals until

the patient is clinically euthyroid and T4 and T 3 are

normalized.

Pregnancy

Specific situation; tailored dose propylthiouracil to be used

Lowest possible dose of PTU should be used and the fetus closely

monitored for heart rate and growth.

Breast feeding:

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Counseling points for patients on antithyroid

drugs

- Identify anticipated duration of treatment

- Explain the use of adjuvant therapy; beta blockers

- Encourage reporting of adverse effects as skin rashes, sore throat or

mouth ulcers

- Stress on the need for regular review

- Discuss management of relapse

Beta blockers: provide symptomatic relief and are useful adjuncts with

other agents

- Propanolol – 20-40 mg 2-4 times/day is effective for most patients

(heart rate less than 90 beats/min)

- Relives palpitations, anxiety, sweating, tremor and diarrhea

Beta Blockers

Iodide used usually as an adjunctive therapy

Potassium iodide is available as a saturated solution or as Lugol’s

solution,

Iodides

Thyroid ablative therapy

- Required for all patients with toxic nodular goitres, those who have relapsed or

are likely to relapse after drug therapy for Graves disease and those who are

allergic to thionamides

Surgery - Thyroidectomy

Surgical removal of the thyroid gland should be considered in patients

with a large gland (>80 g), severe ophthalmopathy, or a lack of remission

on antithyroid drug treatment.

Make the patient biochemically euthyroid before surgery

- Thyroid storm may develop

Complications of surgery:

Hypoparathyroidism, hypothyroidism, vocal cord abnormalities

Radioactive iodine (RAI)

Sodium iodide 131 is an oral liquid that concentrates in the thyroid and initially

disrupts hormone synthesis.

Pregnancy and breast feeding is a contraindication

to the use of RAI.

- Usually avoided in children

β-Blockers are the primary adjunctive therapy to RAI

Commonest complication- hypothyroidism

- Antithyroid drugs must be withdrawn (around 7 days) before radioiodine is given

and should not be restarted for at least 3 days afterwards

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Treatment of thyroid storm

Following therapeutic measures should be instituted promptly:

1) Suppression of thyroid hormone formation and secretion

2) Antiadrenergic therapy

3) Administration of corticosteroids

4) Treatment of associated complications or coexisting factors that may

have precipitated the storm

Evaluation of therapeutic outcomes

After therapy for hyperthyroidism initiated, patient to be evaluated on a monthly

basis until they reach a euthyroid condition

Clinical signs of continuing thyrotoxicosis or development of hypothyroidism

should be noted

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Hypothyroidism Clinical state that results from decreased production of

thyroid hormones, or, very rarely from their decreased

action at the tissue level

Epidemiology

- 2-4/1000 persons

- At any age, usually b/w 30-60

- More common in women

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Etiology: Classification of hypothyroidism

Primary hypothyroidism (>95% of cases)

- Congenital hypothyroidism

- Antithyroid drugs

- Post operative

- After radioactive iodine

Secondary hypothyroidism

- Hypopituitarism

- Selective TSH deficiency

Tertiary hypothyroidism

- Hypothalamic disorders

Peripheral hypothyroidism

- Tissue insensitivity to action of thyroid hormones

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Other classification:

- Goitrous/Non goitrous

Non antithyroid drugs and thyroid disorder:

Amiodarone – Hyper and hypothyroidism

Lithium - Hypothyroidism

Glucocorticoids - Hypothyroidism

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Treatment

Aims:

- Ensure that the patient receive a dose that will restore well being and usually returns TSH to within the range

- Avoid under or over treatment

Thyroid replacement therapy

- Initial dose of T4 depends on

Age, severity, duration of disease, coexistence of cardiac disease

- T4 treatment of choice, except in myxoedema where in T3 is preferred

- Before starting T4 replacement, the diagnosis of glucocorticoid deficiency must be excluded to prevent precipitation of a hypoadrenal crisis.

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Usual starting dose: Young

Starting dose: 50-100 microgram/day

Dosing range- 100- 200 microgram/day

Once daily preferably in the morning

After 6 wks check Thyroid function tests

TSH is the best indicator of thyroid state, and should be

used for further dose adjustment

Pregnancy: Higher dose is required

Elderly: should be introduced cautiously especially those with a cardiac disease

Coronary artery disease: may be unable to tolerate because of palpitations, angina or heart failure

Start with a 25 microgram daily and increased slowly by 25 microgram every 4-6 weeks.

Excessive doses of thyroid hormone may lead to heart failure, angina and MI. Use of beta blockers: In some patients, T4 may be better tolerated if a beta-blocker such as propranolol is given concomitantly.

Duration of thyroid replacement therapy:

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Myxoedema coma

- A rare but potential complication of severe untreated hypothyroidism

- Coma is precipitated by – cold weather, stress, infection, trauma, drugs like beta blockers, anesthetic agents, narcotics, phenothiazine's and hypnotics

Rx of myxedema coma:

- 5-10 microgram of T3 BID

- Possible under activity to be treated with hydrocortisone 100 mg TID

- Sources of infection to be sought and treated

- Monitor body temp

- Electrolyte imbalance to be monitored and treated

PATIENT COUNSELING POINTS FOR THYROID REPLACEMENT

THERAPY (LAB SESSION)

Evaluation of therapeutic outcomes

Symptoms improvement

TSH and T4 concentration to he checked every 6 weeks until a euthyroid

state is achieved.

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