Optimal treatment of hypothyroidism is usually anticipated to require a daily dose of 1.61.8 μg/kg (body weight)/day of levothyroxine (L-T4) in order to restore the TSH within the normal range. Patients who require significantly larger doses of L-T4 than anticipated, e.g., >2 μg/kg body weight of L-T4/day with a persistently elevated TSH warrant further investigation. Biological causes should be excluded, however sub-optimal compliance with medication remains the main cause of treatment failure.
Absorption of oral L-T4 takes place within the small intestine (6080% of ingested dose) and is maximal when the stomach is empty, peaking within the first 3 hours of absorption. Food, dietary fibre, and express coffee may interfere with T4 absorption as may commonly used drugs, e.g., bile acid sequestering agents, ferrous sulphate, aluminum containing antacids, calcium carbonate, raloxofene, and proton pump inhibitors. Drugs that may increase the excretion or turnover of T4 include phenytoin, rifampicin, and carbamazepine. Malabsorptive disorders, e.g., coeliac disease and inflammatory bowel disease reduce the fraction of the ingested L-T4 dose that is absorbed. Other causes include atrophic gastritis, Helicobacter pylori, liver disease, and previous gastrointestinal surgery.
Non-compliance with medication is a challenging situation that must be explored with a sensitive and non-judgemental approach. Patients health beliefs, understanding of their condition and fears of adverse side effects of medication may need to be addressed. Directly observed therapy in a supportive environment over an agreed timeframe may be suitable for some patients. If non- compliance is suspected by the clinician but denied by the patient, a L-T4 absorption test helps to demonstrate that L-T4 can be absorbed into the systemic circulation. Options may include using a supervised 1 mg bolus of oral L-T4 or a weeks supply of a weight related bolus dose of oral L-T4 with measurement of TSH and fT4 samples at baseline and post dose as per protocol.
This weekly administration was conducted for 4 consecutive weeks. TSH is rechecked 1 week after the final dose. Measurement of fT4 120 min after the ingestion of a weight related dose can be used to show maximal T4 absorption.
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