Levothyroxine Dose and Titration

1. Writing the Dose

Marketed strengths are 12.5, 25, 37.5, 50, 62.5, 75, 88, 100, 125 and 150 mcg. Any dose in between is written as two strengths, for example 100 mcg plus 12.5 mcg, and never as a total the chemist cannot dispense. The 50 mcg tablet is colourant free and is the one to use if a dye reaction is suspected.

To sit between two steps, keep one strength daily and add an extra tablet on a stated number of days in the week. This is also how the pregnancy increase is usually written.

Keep one brand. Any change of formulation, brand to generic or generic to generic, is followed by a repeat TSH at steady state.

2. Other Routes and Preparations

The weekly regimen was tested in a randomised crossover of 12 patients. The pre-dose TSH was higher, 6.61 against 3.92, and the peak free T4 was 2.71 against 1.59 ng/dL, with no change in tissue markers and no demonstrable toxicity. It is a way of treating a patient who would otherwise go untreated, not a routine alternative.

3. When to Take It

Best absorption first, from the consolidated timing studies:

1. 60 minutes or more before breakfast. Mean TSH 1.06 mIU/L, and the most consistent readings.
2. Bedtime, three or more hours after the evening meal. Mean TSH 2.19.
3. About 30 minutes before breakfast. Workable if breakfast is the same each day.
4. With breakfast. Mean TSH 2.93. Absorption falls from about 80 per cent to about 64 per cent.

Coffee, dietary fibre and soya all reduce absorption. Grapefruit juice does not.

4. Drug Interactions

5. When the Dose Is Not Working

Take these in order.

1. Adherence. The commonest cause, and the only one a larger prescription makes worse.
2. Timing. Taken with breakfast, with tea or coffee, or at a different hour each day.
3. Co-administered drugs. Calcium and iron are the two that matter most.
4. Gastrointestinal disease. Helicobacter pylori or atrophic gastritis, coeliac disease, bariatric surgery or resection, lactose intolerance. Treating Helicobacter took the mean TSH from 30.5 to 4.2 mIU/L in patients considered unresponsive to high doses. Recheck the dose after any of these is treated.
5. Other causes of a rising requirement. Nephrotic syndrome, through urinary loss of binding proteins. Cirrhosis and renal failure need no adjustment.

The guideline asks for a gastrointestinal cause to be sought when the requirement is much higher than expected, and gives no figure for how much higher. This tool flags a requirement above 1.9 mcg/kg or 200 mcg a day, and that mark is its own.

1. Why the Weight Basis Matters

1.6 to 1.8 mcg/kg of actual body weight is the figure in the national workflow and in the 2014 guideline. Deiodination happens in muscle, liver and skin, not in adipose tissue, so extra fat adds dose without adding capacity to use it.

In 720 adults on a stable dose, the dose per kg of actual weight fell as body mass index rose, 1.73 to 1.51 to 1.33, and fell with age and after the menopause. Per kg of lean body mass it did not move on any of the three, at about 2.3 mcg/kg. Per kg of ideal body weight it rose with body mass index, so no single coefficient exists for it. This tool leads with lean body mass only where the patient is overweight or obese and the two answers are more than one tablet step apart, and always shows both.

2. Subclinical Hypothyroidism: Four Positions

Confirm first. Both the Indian and the European statements ask for a repeat TSH, free T4 and thyroid peroxidase antibodies before treatment, at 8 to 12 weeks and at 2 to 3 months respectively, because most mildly raised readings normalise.

Progression to overt disease runs at about 2.6 per cent a year without thyroid peroxidase antibodies and 4.3 per cent with them, which is a reason to set the follow-up interval by the antibody result.

3. The Target Rises With Age

The TSH distribution shifts right with age in people who have no thyroid disease. The 97.5th centile in healthy elderly people is 7.5 mIU/L. The 2014 guideline calls it reasonable to raise the target to 4 to 6 mIU/L above 70 to 80 years. The national workflow prints its own bands, rising to 7.0 to 8.0 mIU/L by 80.

The elderly box on that sheet is internally inconsistent: it is headed elderly patients and then labels its first row under 60 years, and its comparison symbols do not agree between rows. This tool reads the three figures as upper limits at 60, 70 and 80 years and says so on the result.

4. Overtreatment Is the Harm You Cause

Hence the recommendation to avoid subnormal values, and below 0.1 in particular, in older people and after the menopause.

5. Starting Low, and When It Is Necessary

• Known coronary artery disease: always 12.5 to 25 mcg a day, increased gradually. Thyroid hormone is inotropic and chronotropic and can precipitate angina.
• Above 80 years: the same, with increments every 3 to 4 weeks.
• 65 to 80 years without cardiac disease: the sources differ. The workflow says start low; the 2014 guideline records a randomised trial in which elderly patients free of cardiovascular disease were safely started on the full dose. This tool starts low and prints both.
• Young and otherwise healthy: the full calculated dose at once.

6. What Changed in Pregnancy

The 2026 guideline replaced the 2017 one. The first-trimester TSH ceiling of 2.5 mIU/L is now a treatment target, not a diagnostic threshold: where no laboratory interval exists the reference interval offered is 0.1 to 4.0 mIU/L, and treatment is indicated at 6 or above. Indian normative data run about 1 mIU/L higher again.

• Already treated: about 25 per cent more by week 12, 50 per cent by week 20, started on the positive test.
• New overt diagnosis: 1.5 to 1.7 mcg/kg a day plus a further 20 to 30 per cent.
• New subclinical diagnosis: 25 to 75 mcg a day by the TSH and the weight.
• Subclinical disease known before conception: no standard 25 per cent increase.
• At delivery, back to the prepregnancy dose, and test after six weeks.
• Iodine 150 mcg a day before conception, in pregnancy and while breastfeeding.

Two things that guideline says not to do: levothyroxine for euthyroid thyroid peroxidase antibody positivity, on three randomised trials, and levothyroxine for isolated hypothyroxinaemia started in the second trimester, on two.

7. The Two Situations That Change the Answer Completely

Critical illness without established hypothyroidism. Abnormal tests here are the non-thyroidal illness syndrome, and the recommendation against treating it is strong. A patient who was already hypothyroid stays on treatment, with two cautions: dopamine and dobutamine lower the TSH, and gut oedema, tube feeds and proton pump inhibitors make the enteral dose unreliable.

Adrenal insufficiency, known or suspected. The glucocorticoid goes first. Thyroid hormone accelerates cortisol metabolism and can precipitate a crisis. The same order applies in myxoedema coma, where a stress-dose intravenous glucocorticoid precedes the levothyroxine, and in central hypothyroidism, where the workflow gives 1.3 mcg/kg a day after the adrenal insufficiency has been treated.

8. Myxoedema Coma

Treatment starts on clinical suspicion and is not delayed for the tests. Glucocorticoid first, then levothyroxine 200 to 400 mcg intravenously as a loading dose, less for a smaller or older patient or one with coronary disease or arrhythmia, then 1.6 mcg/kg a day reduced to 75 per cent while given intravenously. Liothyronine may be added at 5 to 20 mcg then 2.5 to 10 mcg eight-hourly, avoiding high doses.

Where the intravenous preparation cannot be obtained, the published alternative is an oral loading dose of 300 to 500 mcg followed by a taper over 3 to 5 days, from a series of 14 patients of whom 13 survived. No liothyronine regimen exists for that route and none is printed. Endpoints are clinical: mental state, cardiac function and pulmonary function.

9. Suppression After Thyroidectomy for Cancer

A higher dose, 2.1 to 2.7 mcg/kg, aimed at a suppression target rather than a normal TSH. The initial target follows the risk of recurrence and the long-term target follows the response to therapy, which are two separate recommendations.

Suppression below 0.03 mIU/L may add nothing, and the harms are those of subclinical thyrotoxicosis. Where the patient has ischaemic heart disease, an arrhythmia or osteoporosis, the target is a balance rather than a lookup.

10. What This Tool Does Not Print

• A maximum daily dose. No guideline read for it gives a ceiling.
• A number that defines malabsorption.
• A coefficient for ideal body weight, which varies with body mass index.
• A dose for the first days of an acute coronary syndrome. The coronary artery disease rule is printed instead.
• A dose change for acute infection outside intensive care.
• A liothyronine regimen for the oral myxoedema route.
• A dosing rule for amiodarone, lithium or a checkpoint inhibitor.

Each is an absence stated on purpose rather than a gap filled with something plausible.