• It was treated with animal thyroid extracts in the past
  
• This was followed by development of purified thyroid hormone preparations.

Available thyroid hormone preparations are

• Thyroxine sodium (T4)
  
• Tri-iodothyronine (T3)
  
• Combination of synthetic T3 and T4
  
• Thyroid USP (desiccated animal thyroid containing T3 and T4 in the form of thyroglobulin)
  
• The mostly widely used and preferred preparation is synthetic T4, thyroxine sodium.

Initial dosage may be based on

• Age of patient
  
• Severity and duration of hypothyroidism
  
• Presence of associated disorders like ischaemic heart disease, adrenal insufficiency paediatric hypothyroidism
  
• The dosage of thyroxine sodium for paediatric hypothyroidism varies with age and body weight. Thyroxine should be given at a dose that maintains the serum total T4 or free T4 concentrations in the upper half of the normal range and serum TSH in the normal range.
  
• Thyroxine sodium therapy is usually initiated at the full replacement dose. Infants and neonates with very low or undetectable serum T4 levels
  ( < 5 mcg/ dL) should start at the higher end of the dosage range (e.g. 50 mcg daily).

A lower starting dosage (e. g. 25 mcg daily) should be considered for neonates at risk of cardiac failure, increasing every few days until a full maintenance dose is reached.

In children with severe, long-standing hypothyroidism, thyroxine sodium should be initiated gradually, with an initial dose of 25 mcg for two weeks, and then increasing the dose by 25 mcg every 2 to 4 weeks until the desired dose

Age Daily dose per kg.	Growth and puberty complete 10 - 15 mcg
Body weight* 0 - 3 mos 0 - 6 mos 6 - 12 mos 1 - 5 yrs 6 - 12 yrs > 12 yrs	8 - 10 mcg 6 - 8 mcg 5 - 6 mcg 4 - 5 mcg 2 - 3 mcg 1.6 mcg
* To be adjusted on the basis of the clinical response and laboratory test based on serum T4 and TSH levels is achieved.

Adults

• Young, healthy adults with no cardiac/respiratory disease are started with 1.6 mcg/kg/day of thyroxine sodium administered once daily.
  
• In elderly patients or in younger patients with cardiovascular disease dose required is lower than the usual adult dose i.e. <1mcg/kg/day, administered once a day. To start with in elderly patients 12.5 to 50 mcg of thyroxine sodium are given daily and increment of 12.5 to 25 mcg are made at 3-6 week intervals if required.
  
• Women who are maintained on thyroxine sodium during pregnancy may require increased doses.
  
• Treatment of subclinical hypothyroidism, when indicated may require lower than usual replacement doses; (1mcg/kg/day). Patients for whom treatment is not initiated should be monitored yearly for changes in clinical status, TSH and thyroid antibodies.
  
• In patients with associated adrenal insufficiency, low doses of thyroxine sodium are started only after initial treatment with glucocorticoids.
  

• Thyrotoxicosis due to thyroid hormone
  
• Increased intracranial pressure
  
• Craniosynastosis

• Adults

• Accelerates bone loss in postmenopausal women
  
• Increased heart rate
  
• Increased left ventricular wall thickness and contractibility

Drug Interactions

• Pregnancy

II • Drugs leading to decreased absorption of thyroxine

• Sucralfate
  
• Aluminium hydroxide
  
• Ferrous sulphate

• Drugs leading to increased clearance of thyroxine

• Rifampicin
  
• Carbamazepine
  
• Phenytoin

• Drugs that prevent conversion of T4 to T3

• Glucocorticoids
  
• Amiodarone

• Titration of dosage of thyroxine is done to maintain TSH in normal range of 0.2-5mIU/L and in cases of central hypothyroidism to maintain T4 levels in normal range (5- 13.5 mg/dl)
  
• Follow up of these patients is done with TSH testing at 6-8 weeks intervals
  
• In severe hypothyroid patients, older patients or in young patients with a history of a cardiovascular disease TSH testing is done at 3-6 weeks interval
  
• In central hypothyroidism FT4 /T4 testing at 4-6 week intervals
  
• Once the dose is titrated and TSH /T4 maintained within normal limits, patient should be followed up at 6 months or yearly intervals

Infants and Neonates :

• Serum T4 and TSH measurements should be evaluated at the following intervals, with subsequent dosage adjustment to normalize serum total T4 or FT4 and TSH
  
• 2 and 4 weeks after the initiation of Thyroxine sodium treatment ;
  
• Every 1 to 2 months during the first year of life;
  
• Every 2 to 3 months between 1 & 3 years of age;
  
• Every 3 to 12 months thereafter until growth is completed

Evaluation at more frequent intervals is advisable when compliance is poor or abnormal values are obtained. Patient evaluation is also advisable approximately 6 to 8 weeks after any change in thyroxine sodium dose.

• Cold months
  
• Pulmonary events
  
• Cerebrovascular accidents
  
• Congestive heart failure
  
• Metabolic derangements
  
• Drugs - sedatives, narcotics, antidepressants

II Cardinal Features

• Hypothermia
  
• Unconsciousness
  
• Other signs of hypothyroidism

III Treatment

• Treatment of underlying cause
  
• Ventilatory support
  
• Correction of electrolyte imbalance hypothermia, hypotension
  
• Steroid treatment - injection hydrocortisone 100mg, 8 hourly parenterally during initial 7-10 days then tapered off
  
• Once patient is stable, consider evaluation of adrenal status

Thyroid Hormone Therapy (Thyroxine Sodium)

• Initial dose (loading dose), 100-500mcg followed by maintenance dose of 50-100mcg/ day
  
• Parenteral preparations if not available thyroxine tablets to be used through nasogastric tube, 500-1000 mcg initial dose followed by 50-100 mcg /day. Care to be taken if patient has ischaemic heart disease
  
• Due to illness, T4 given may not be converted to T3 so some advise T3 therapy