Dr. Nihal Thomas

"An interview with Dr Nihal Thomas on "The Need of Multiple Strengths of Levothyroxine in the Management of Hypothyroidism" Dr. Nihal Thomas is currently Reader in Endocrinology at CMC, Vellore and is in charge of Diabetology Section. After having completed MBBS, MD and MNAMS (Endo) at Christian Medical College, Vellore, Dr Thomas has done FRACP (Endo) at Prince of Wales Hospital, Sydney, Australia.

Dr Nihal Thomas was invited Faculty Member of Scientific Committee for the International Conference in Endocrine Disorders in 2001 and was awarded International Young Investigator Award in Clinical Epidemiology in 2003. He is involved in several research projects and multicentric trials at present. He also runs the Diabetes Educator training programme for Peripheral hospitals. His key areas of academic interest are Pituitary Disease, Osteoporosis, Clinical trials in Diabetes Mellitus, and Macroencapsulation techniques in insulin cell line transplantation.

Dr Thomas has to his credit more than 30 indexed papers published in different national and international journals and review articles and one book on Pituitary disease.

Dr Nihal Thomas brings you the answers to the following questions on "The Need of Multiple Strengths of Levothyroxine in the Management of Hypothyroidism"

Q1. When and how should we initiate the treatment of hypothyroidism?

Q2. Which is the most preferred preparation for the treatment of hypothyroidism currently available in India?

Q3.What are the criteria on which you generally base the initial dose of levothyroxine therapy?

Q4. What according to you are the basic guidelines for dosage and titration of levothyroxine therapy?

Q5. Common dose for maintenance is 100 mcg of levothyroxine; can you share your experience when the dose is titrated to higher or lower strengths?

Q6. Are the current TSH assays sensitive enough for accurate titration of levothyroxine therapy?

Q7. What is the importance of monitoring hypothyroid patients on a regular basis to ensure proper thyroxine replacement?

Q8. What is the dose of levothyroxine, which could be used safely to initiate therapy in older patients?

Q9. What guidelines would you offer a patient to provide adequate therapy while minimizing both over- and undertreatment?

Q10. How according to you have multiple strengths of levothyroxine benefited the management of hypothyroidism?

Q1. When and how should we initiate the treatment of hypothyroidism?

Ans. Treatment of hypothyroidism depends on the presence of biochemical abnormalities present at the time of diagnosis, coupled with the clinical diagnosis at that point of time.
The biochemical values that are checked and are crucial to determine therapy are the serum free T4 levels and the TSH levels. Though in India, it seems customary to check serum T3 levels at the same time, this of very little value and is redundant when it comes to the management of hypothyroidism, it is more important for the management of a less common entity called T3-toxicosis. The total T4 levels are also often checked, however these are also not required since the free T4 levels give a better picture of the metabolic effects of the thyroid especially in conditions like pregnancy.

If a patient has low free T4 levels with high TSH levels, irrespective of the severity of the clinical picture, treatment should be initiated early. If the T4 levels are normal and the TSH is elevated, this indicates a condition termed as subclinical hypothyroidism. In subclinical hypothyroidism, when the TSH is less than 10 mIU/ml, treatment is indicated only in specific conditions: - pregnancy or prospective intention to conceive, infertility, elevated LDL cholesterol levels, short stature in childhood, depressive illness, cosmetically significant goitre and positive thyroid peroxidase antibodies.

In severe hypothyroidism, while initiating thyroxine, there may be a transient increase in the hepatic metabolism of cortisol in the liver, which may on occasion precipitate an Addisonian crisis. As a precautionary measure, those patients with florid hypothyroidism need to be covered with a small dose of prednisolone (5 mg AM -2.5 mg PM) during the first two weeks of treatment.

Q2. Which is the most preferred preparation for the treatment of hypothyroidism currently available in India?

Ans. In general, a strength of 100 micg is most commonly utilized, however as mentioned above, since 150micg is a fairly common dosage, some physicians would prefer to use 100 micg plus a 50 micg tablet, of the same brand.

Q3.What are the criteria on which you generally base the initial dose of levothyroxine therapy?

Ans. In subclinical hypothyroidism, starting with 50 micg of thyroxine per day would be most advisable. As mentioned below, in someone with an underlying cardiac problem, starting on a dose of as low as 25 micg may be required and the dose can be gradually increased, under observation and as tolerated.

Q4. What according to you are the basic guidelines for dosage and titration of levothyroxine therapy?

Ans. The initiation of thyroxine depends on the age of the patient where treatment is being commenced, in the young adult, one tends to be less cautious as to dose titration, and in significant hypothyroidism or in a euthyroid individual with a significant goitre, the initiation would generally be that of 100 micg once a day. Always administer the dose on an empty stomach, with a glass of water. Other foodstuffs, even tea for that matter should be taken only after half an hour of taking the dose of thyroxine.

Q5. Common dose for maintenance is 100 mcg of levothyroxine; can you share your experience when the dose is titrated to higher or lower strengths?

Ans. Generally, the maximum dose of thyroxine required in an adult with hypothyroidism is in the range of 100 to 150micg per day. Rarely 200 mcg per day may be required, in fact in Indian patients, owing to their lower body weight; this is unlikely to be the case. In case a patient seems to require higher doses, it indicates a problem of noncompliance in most cases or that the medication is being taken after meals rather than on an empty stomach. Cationic drugs like iron and calcium preparations in particular may bind to thyroxine in the gut hindering its absorption, and hence a spacing of more than 2 hours away from thyroxine should be given when these drugs are administered.

Q6. Are the current TSH assays sensitive enough for accurate titration of levothyroxine therapy?

Ans. The more sensitive third generation TSH kits are obviously the best for monitoring patients with thyroid disease. Unfortunately, a number of commercial laboratories in India barely possess 1st generation TSH kits. Essentially, the issue in discussion is diagnosis of hyperthyroidism, for which third generation TSH kits are good. In patients on thyroxine therapy, the worry is in some cases- are we over treating these patients and precipitating iatrogenic hyperthyroidism. This iatrogenic hyperthyroidism is subclinical in some cases and concern is as to whether one may precipitate arrhythmias in the elderly and osteoporosis with long-term treatment. From a clinical and practical perspective however, 2nd generation assays that are available with reasonable freedom are good enough to delineate early subclinical iatrogenic hyperthyroidism. The treating physician should ensure that the laboratory where he checks his thyroid function tests is part of a well-recognized quality control programme.

Q7. What is the importance of monitoring hypothyroid patients on a regular basis to ensure proper thyroxine replacement?

Ans. When treating patients with thyroxine, it is important to monitor them by with thyroid function tests. A point should be given to the cost-effectiveness of testing. Bear in mind that the half-life of thyroxine is one week. It takes 5-half life for most drugs that follow linear kinetics to achieve a steady state. Based on this, on commencing therapy, the first test should be performed after 6 weeks, waiting a little longer to stabilize the T4-TSH axis is also advisable, hence thyroid functions are best repeated after 2 months, provided no frequent dosage changes are performed, within this period of time. If hypothyroidism is being treated, then the most cost-effective test to perform to see if stabilization has occurred would be the TSH alone. Only if iatrogenic hyperthyroidism is suspected, or if the patient is swinging from hypothyroidism to hyperthyroidism as may occur with some patients with Hashimoto's thyroiditis, need free T4 be checked in addition. Once the TSH has been stabilized in the normal range, it needs to be repeated only annually, thereafter.

Q8. What is the dose of levothyroxine, which could be used safely to initiate therapy in older patients?

Ans. In an older individual, one should be more cautious while administering thyroxine. Theoretically, one third of the population above the age of 60 years has ischaemic heart disease- in many this may be silent or asymptomatic. In the elderly, those with known angina and those with left ventricular failure; thyroxine should be administered at a small dose, starting with 25 micg once a day and gradually increasing the dose by 25 micg every two weeks, monitoring the patient carefully for symptoms of angina or worsening cardiac failure. In fact in some individuals, the treating physician may be forced to leave the patient on therapy that may be sub optimal, without normalization of thyroid function tests.

Q9. What guidelines would you offer a patient to provide adequate therapy while minimizing both over- and undertreatment?

Ans. Insisting on regularity of therapy is the most important point. The other precautions, like taking the medication on an empty stomach, without other drugs have already been mentioned. If compliance is a problem, the patient should be asked to maintain a dairy and record, his/ her daily dosage. In case of children and those patients who are mentally challenged, it should be insisted that a parent or caregiver be given the responsibility of administering the medication.

Q10. How according to you have multiple strengths of levothyroxine benefited the management of hypothyroidism?

Ans. In childhood, precise dose calculation and titration are required; hence the smaller strengths like 25 micg and 50 micg play a major role. While starting a patient in old age or adulthood, the precautionary measure of starting with the lowest dose and gradually increasing the dose over a matter of weeks to months to avoid precipitating angina, entails the use of multiple strengths of thyroxine.