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Research Articles and Papers on:

Thyroid Medications


Safety review of liothyronine use: a 20 year observational follow up study

Endocrine Abstracts (2015) 38 OC5.6 | DOI:10.1530/endoabs.38.OC5.6

Enrique Soto-Pedre & Graham Leese

Some patients use liothyronine as thyroid replacement therapy as an alternative to L-thyroxine. Trials have examined the potential benefits, but there is little data looking at the relative safety of these two agents. All patients receiving thyroid replacement therapy between 1993 and 2014 in Tayside were included in a cohort study (n=34 355; 319 500 patient years of follow up). Overall 33 955 patients received only L-thyroxine, and 327 received liothyronine in combination with L-thyroxine and 73 on liothyronine alone (total=400). Using unique patient identification numbers, biochemical, prescribing, hospital admission, radioiodine and general registry office data were linked.

Patients initiating treatment with liothyronine were younger (48 vs 59 years P<0.001), but there was no gender difference (85% female vs 82%). They were more likely at baseline to have had thyroid cancer, have a history of previous hyperthyroidism and be treated with anti-psychotic or anti-depressant medication. They were less likely to have cardiovascular disease or be treated with a statin. During a mean follow up of 9.3 years (±5.6 years) proportional hazards ratios (HR) were reported after adjustment for age, gender, baseline TSH, number of thyroid prescriptions and history of thyroid cancer or hyperthyroidism. For patients taking liothyronine there was no increased risk of death (0.78; 95% confidence interval: 0.54–1.11), fractures (HR 0.79; 0.49–1.27), atrial fibrillation (HR 0.91; 0.47–1.75) or cardiovascular disease (HR 0.90; 0.42–1.92). There was an increased risk of mental health disorders (HR 3.27; 1.02–10.52) for patients taking liothyronine alone, but not for those taking a combination therapy. There was an increased incident use of anti-psychotic medication (HR 2.26; 1.64–3.11).

No increased risk of fractures or atrial fibrillation in patients taking liothyronine compared to L-thyroxine was demonstrated. There was an increased risk of mental health disorders if liothyronine was used alone.




New insights into the variable effectiveness of levothyroxine monotherapy for hypothyroidism

The Lancet - Diabetes & Endocrinology Volume 3, No. 10

Elizabeth A McAninchemail, Antonio C Bianco
Published Online: 09 September 2015

Thyroid hormone replacement has been the mainstay of treatments for hypothyroidism since the 19th century. Animal thyroid preparations, which contain thyroxine (T4) and tri-iodothyronine (T3), were the first pharmacotherapies, and synthetic agents— eg, levothyroxine (also known as LT4)—are the current
standard of care.1 Chemical composition of hormone replacement therapy is important in view of the clinical data suggesting that levothyroxine monotherapy does not consistently normalise serum T3 concentrations1 or universally restore clinical euthyroidism. Although the clinical signifi cance is not clear, increasing serum T3 with a combination of levothyroxine plus iothyronine (also known as LT3) results in weight loss and improves psychological function in some patients.

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UK Trends in Prescribing Thyroid Hormone and Patient Satisfaction Survey

Abstract taken from:
Endocrine Abstracts (2009) 19 P345
AL Mitchell1, B Hickey2, JL Hickey2 & SHS Pearce1
1 University of Newcastle upon Tyne, Newcastle upon Tyne, UK
2 The British Thyroid Foundation, Harrogate, UK

Background: Thyroid hormone replacement is one of the most commonly prescribed and cheapest treatments for a chronic disease. There have been recent changes in community prescribing policies in many areas of the UK that have changed patient access to necessary medications.

Aim: To provide a picture of thyroid hormone usage in the UK and to survey patient opinion about current community prescribing policies for levothyroxine.

Methods: Data on community prescriptions for thyroid hormones in England between 1998 and 2007, provided by the Department of Health, were collated and analysed. A survey of UK members of the British Thyroid Foundation who were taking levothyroxine was carried out.

Results: The amount of prescribed thyroid hormones used in England has more than doubled, from 7 to 18 million prescriptions, over the last 10 years. The mode duration of prescriptions has reduced from 60 to 45 days, over the same time. The professional dispensing fee to the pharmacist is £0.90 per prescription, which is close to the £1.12 cost for 28 levothyroxine tablets. Two thousand five hundred and fifty-one responses to the patient survey were received (42% of the 6083 dispatched). Thirty-eight percent of levothyroxine users reported receiving prescriptions of 28 days’ duration. Seventeen percent had gone without levothyroxine owing to difficulties getting their medication. Fifty-nine percent of respondents reported being dissatisfied with 28-day prescribing. The major reasons stated for dissatisfaction were inconvenience, interference with full-time working, and having a monthly reminder of having a health problem.

Conclusion: Amongst users of levothyroxine there is widespread patient dissatisfaction with 28-day prescription duration. Analysis of the full costs of 28-day dispensing balanced against the potential savings of reduced wastage of thyroid medications suggests that this is unlikely to be a fiscally effective policy.


Improvements in quality of Life in Hypothyroid Patients taking Armour thyroid

Abstract taken from :
Endocrine Abstracts (2008) 15 P359
DH Lewis, J Kumar, P Goulden & DJ Barnes
Maidstone and Tunbridge Wells NHS Trust, Tunbrige Wells, Kent, UK.

Armour thyroid (Armour) is unlicensed in the UK for the treatment of hypothyroidism. It is natural porcine-derived thyroid replacement with 1 grain containing 38 mcg levothyroxine (T4) and 9 mcg L-triiodothyronine (T3), and unspecified amounts of T1, T2 and calcitonin. We have used Armour as a third line agent in selected patients who have not responded adequately to T4 monotherapy, and combination T4/T3 therapy since 2003.

Aim: To assess changes in symptoms of hypothyroidism in patients treated with Armour.

Methods: Forty patients (38 female) who had been prescribed Armour between 2005 and 2006 were identified using hospital Pharmacy records. A simple questionnaire was sent to these patients to assess changes to quality of life whilst they were taking Armour.

Results: Thirty-five patients (88%) returned the questionnaire. All patients had been prescribed either T4 and/or combination T4/T3 therapy before commencing Armour. Twenty-nine were still taking Armour at the time of the questionnaire. Three of these twenty-nine patients did not answer the quality of life questions, one of whom was unable to tolerate T4 and T3 due to nausea.

Of the patients still taking Armour, 72% found improvement in energy levels, 52% dry skin, 52% hair loss and 55% cold intolerance. There was no difference in constipation, arthragia, myalgia or ability to lose weight. Most patients (62%) had improvements in 3 or more symptoms of hypothyroidism.

In the 6 patients who were no longer taking Armour, there were no significant improvements in any parameter.

Conclusion: In appropriately selected hypothyroid patients, Armour appears to improve the quality of life in patients who have either had an inadequate clinical response to conventional T4/T3 therapy or are unable to tolerate such therapy.


Bioequivalence of L-thyroxine tablets and a liquid L-thyroxine solution in the treatment of hypothyroid patients

Abstract summarised from :
Med Klin (Munich). 2004 Nov 15;99(11):639-44.

Grussendorf M, Vaupel R, Wegscheider K.

Background and Purpose: The therapeutic equivalence of L-thyroxine (T(4)) tablets and a new liquid T(4) solution was investigated in patients with hypothyroidism.

Patients and Methods: 136 patients (with autoimmune thyroiditis, after thyroid surgery and/or after therapy with radioiodine), who had been treated with T(4) tablets, were switched to a treatment with a liquid T(4) solution (containing 5 microg T(4) per drop) in the same dosage. TSH was measured after 1, 2, 3, and 6 months; the dose of the T4 solution was adapted to obtain a midnormal TSH level.

Results: The T(4) dose remained constant during the 6 months. Dose needed to be adapted in 19-23% of patients at the different timepoints, with dose reductions and increases, respectively, becoming equally frequently necessary. The average TSH level was 0.79 mU/l at the beginning and 0.81 mU/l after 6 months; similarly, the average levels of free triiodothyronine (fT(3)) and free thyroxine (fT(4)) were equivalent. The liquid T(4) solution was well tolerated: adverse events were noted in three patients (1.8%); one serious adverse event (thyroid carcinoma) showed no correlation to the treatment.

Conclusion: T(4) tablets and liquid T(4) solution have been proven to be therapeutically equivalent; the use of liquid T(4) solutions will have advantages in the treatment of hypothyroid infants or elderly patients with disturbed swallowing, patients who need a differentiated titration of the T(4) dose, as well as patients with an allergy against inactive ingredients of L-thyroxine tablets.


Effects of evening vs morning thyroxine ingestion on serum thyroid hormone profiles in hypothyroid patients

Authors: Bolk, Nienke1; Visser, Theo J.1; Kalsbeek, Andries2; van Domburg, Ron T.3; Berghout, Arie4

Abstract summarised from:
Clinical Endocrinology, Volume 66, Number 1, January 2007 , pp. 43-48(6)

Standard drug information resources recommend that l-thyroxine be taken half an hour before breakfast on an empty stomach, to prevent interference of its intestinal uptake by food or medication. We observed cases in which TSH levels improved markedly after changing the administration time of l-thyroxine to the late evening. We therefore conducted a pilot-study to investigate whether l-thyroxine administration at bedtime improves TSH and thyroid hormones, and whether the circadian rhythm of TSH remains intact.

Patients were studied on two occasions: on a stable regimen of morning thyroxine administration and two months after switching to night-time thyroxine using the same dose. On each occasion patients were admitted for 24h and serial blood samples were obtained.

We investigated 12 women treated with l-thyroxine because of primary hypothyroidism, who used no medication known to interfere with l-thyroxine uptake.

Patients were admitted to hospital and blood samples were obtained at hourly intervals for 24h. Following this first hospital admission, all women were asked to switch the administration time from morning to bedtime or vice versa. After 2 months they were readmitted for a 24h period of hourly blood sampling. Blood samples were analysed for serum TSH FT4 and T3, T4 and rT3, serum TBG and total protein and albumin.

A significant difference in TSH and thyroid hormones was found after switching to bedtime administration of l-thyroxine. There was no significant change in T4, rT3, albumin and TBG serum levels, nor in the T3/rT3 ratio. The relative amplitude and time of the nocturnal TSH surge remained intact.

l-thyroxine taken at bedtime by patients with primary hypothyroidism is associated with higher thyroid hormone concentrations and lower TSH concentrations compared to the same l-thyroxine dose taken in the morning. At the same time, the circadian TSH rhythm stays intact. Our findings are best explained by a better gastrointestinal uptake of l-thyroxine during the night.



Does synthetic thyroid extract work for everybody?

Gautam Das, Shweta Anand & Parijat De, Diabetes & Endocrine Unit, City Hospital, Birmingham, United Kingdom.
Endocrine Abstracts (2007) 13 P316

The researchers of this study state that thyroxine is the treatment of choice for hypothyroidism and that it is safe, effective and generally well tolerated. They state, however, that some patients cannot tolerate it.  They describe 3 patients who were successfully treated with Armour thyroid after being intolerant to L-Thyroxine.

A 35yr old lady, having been put on thyroxine for autoimmune hypothyroidism found that, even though she was on 150mcg thyroxine and her TSH was in the mid-normal range of 2.62, she still suffered from tiredness, poor memory, headache, and mood swings. She had a Short Synacthen Test (SST), which was normal and her thyroid auto-antibody test was negative.
She was started on Armour thyroid and within a few weeks her symptoms improved significantly. Within 2 months of starting Armour, her FT4 was 15 and TSH 0.67 and she was continued on Armour thereafter.

Another lady, 63 years of age, was diagnosed with hypothyroidism and was started on 25 mcg thyroxine by her GP. She became dizzy, felt nauseous, and had headaches. She had a short synacthen test, which was normal and she had negative thyroid antibodies. She suffered from tiredness and her TSH was 9 mIU/L. She was given some T3 but she couldn’t tolerate this either. She was subsequently started on Armour thyroid, which led to considerable improvement in her symptoms within a few weeks and her TSH normalized to 4.03  and normal FT4 of 9  in three months time.

A 40yr old female was diagnosed with autoimmune thyroiditis and was started on 25 mcg of L-Thyroxine, which was gradually increased to 100mcg. Over the years her symptoms of tiredness, mood swings, poor memory persisted and she claimed to feel more and more unwell and stopped taking her L-Thyroxine. Her thyroid function deteriorated with a TSH of 31.49  within 6 months. She was put on Armour thyroid
extract and within a few months she became biochemically euthyroid and was completely symptom free.

The researchers inform us that, “Currently it has to be imported from the US where it has been used successfully and safely for some time. Although L-Thyroxine remains the treatment of choice in the majority, a trial of Armour could be considered in patients who have not responded to this conventional treatment and who remain symptomatic with raised serum TSH levels.”


Tablet-splitting: a common yet not so innocent practice

Journal of Advanced Nursing
67(1), 26–32. doi: 10.1111/j.1365-2648.2010.05477.x
Charlotte Verrue, Els Mehuys, Koen Boussery, Jean-Paul Remon & Mirko Petrovic
June (2008)

Researchers from Ghent University wanted to find out if the overall weight of tablets decreased when they were split by patients. They say that after a tablet is split, the parts are often not equal in size, and that a portion of a tablet can be lost during splitting if the tablet fragments.

The researchers asked five academic volunteers to split eight different sized tablets using three different techniques. Half of the tablets were split into four segments and half into two.

The three different methods used to split the pills was a specialist splitting device; scissors and manual breakage and a kitchen knife.

The tablets that were split were warfarin, digoxin, metformin, a combined levodopa and carbidopa tablet, phenprocoumon, spironolactone, methylprednisolone and lisinopril.

Warfarin and phenprocoumon were chosen because they are anticoagulants and, therefore, need meticulous dosage adjustment (titration) and frequent splitting. Methylprednisolone and lisinopril were chosen because they are mainly split for economic reasons.

The remaining tablets were chosen because experienced nurses indicated that the tablets often cause problems during splitting.

For all tablets, the pill cutter device was the best for splitting with only a 9.5% reduction in dosage.  The scissors and manual breaking gave a 15.2% reduction  and the kitchen knife gave a 13.7% reduction.

The researchers call for three changes that could improve practice in this area:  the use of a splitting device as a routine method when splitting cannot be avoided; that pharmacists should give clear messages about the risks related to splitting and that manufacturers could avoid the need for splitting by introducing a wider range of tablet doses or liquid formulations.