This paper compared patients started on a calculated full replacement dose of levothyroxine against starting at 25 micrograms and incrementing every four weeks.
Since this paper - and others - the idea of starting on full replacement dose has permeated the guidelines in several countries.
Unfortunately, it appears that cost saving is a significant part of the rationale.
My own belief is that somewhere between the two extremes is probably the best for the patient. But that might also be the most expensive in terms of tests and prescription changes - as well as doctor time.
(I just posted this in a reply on another thread but realised it might be of general interest.)
August 8/22, 2005
The Starting Dose of Levothyroxine in Primary Hypothyroidism Treatment - A Prospective, Randomized, Double-blind Trial
Annemieke Roos, MD; Suzanne P. Linn-Rasker, MD; Ron T. van Domburg, PhD; et alJan P. Tijssen, PhD; Arie Berghout, MD, PhD, FRCP
Author Affiliations Article Information
Author Affiliations: Department of Internal Medicine, Medical Centre Rijnmond-Zuid, Rotterdam (Drs Roos, Linn-Rasker, and Berghout), Department of Cardiology, Erasmus Medical Centre, Rotterdam (Dr van Domburg), and Department of Cardiology, Academic Medical Centre, Amsterdam (Dr Tijssen), the Netherlands.
Arch Intern Med. 2005;165(15):1714-1720. doi:10.1001/archinte.165.15.1714
Background The treatment of hypothyroidism with levothyroxine is effective and simple; however, recommendations for the starting dose vary considerably. To our knowledge, the levothyroxine starting dose has never been studied prospectively.
Methods We conducted a prospective, randomized, double-blind trial that compared a full starting levothyroxine dose of 1.6 μg/kg with a low starting dose of 25 μg (increased every 4 weeks) in patients with newly diagnosed cardiac asymptomatic hypothyroidism. Safety was studied by documenting cardiac symptoms and events, and efficacy was studied by monitoring thyrotropin and free thyroxine levels and by assessing improvement of signs and symptoms and quality of life.
Results Seventy-five consecutive patients were enrolled, of whom 50 underwent randomization. At baseline, the severity of hypothyroidism and age were comparable in the full-dose (n = 25) vs the low-dose group (n = 25): thyrotropin, 61 vs 48 mIU/L; free thyroxine, 0.56 vs 0.64 ng/dL (7.2 vs 8.2 pmol/L); and age, 47 vs 47 years. No cardiac complaints or events were documented during treatment or at bicycle ergometry at baseline, 12 weeks, or 24 weeks. Euthyroidism was reached in the full-dose vs the low-dose group in 13 vs 1 (4 weeks), 19 vs 3 (8 weeks), 19 vs 9 (12 weeks), 20 vs 14 (16 weeks), 20 vs 18 (20 weeks), and 21 vs 20 (24 weeks) patients (P = .005). However, signs and symptoms of hypothyroidism and quality of life improved at a comparable rate.
Conclusion A full starting dose of levothyroxine in cardiac asymptomatic patients with primary hypothyroidism is safe and may be more convenient and cost-effective than a low starting dose regimen.
Primary hypothyroidism is a common disorder, most prevalent in women and most often caused by autoimmune thyroiditis. Overt hypothyroidism can present with classic symptoms of fatigue, weight gain, cold intolerance, and constipation. Fatigue, one of the major complaints, together with depression,1 neuromuscular signs and symptoms,2 and diastolic dysfunction3 can all lead to an impaired quality of life in patients with hypothyroidism. Furthermore, abnormalities of lipid metabolism, hyperhomocysteinemia, and arterial hypertension occur with increased frequency in hypothyroidism4,5 and are associated with an increased risk of premature atherosclerotic vascular disease.6,7
Although the treatment of hypothyroidism with levothyroxine, one of the most commonly prescribed drugs, seems effective and simple, recommendations for the starting dose of levothyroxine vary considerably: from 50 μg to a full replacement dose of 1.6 or 1.7 μg/kg in healthy adult patients younger than 65 years and from 25 to 50 μg/d in older patients and patients with known ischemic heart disease.8-13 The safety and efficacy of different initial doses of levothyroxine have, to our knowledge, never been studied prospectively. Moreover, in daily practice, many physicians still promote the dogma of “start low and go slow” irrespective of age or patient. This dogma is based on the association of hypothyroidism with ischemic heart disease.14,15 Interestingly, and in contradiction to this dogma, high doses of levothyroxine have been given to patients with myxedema coma, a patient group in whom a high prevalence of cardiac ischemia would be expected, without untoward effects.16 However, when levothyroxine was combined with triiodothyronine (T3) in the treatment of such severely ill patients, fatal outcome has been reported.9 Several case series and retrospective studies, dating back 4 to 6 decades, have shown considerable variability in the cardiac responses of patients with hypothyroidism to thyroid hormone therapy, ranging from precipitating acute coronary syndromes in patients without previous cardiac symptoms14,17 to controlling or even abolishing preexisting angina.17,18 These studies can be criticized for being retrospective, cross-sectional, or uncontrolled; for having small numbers of patients; or for using desiccated thyroid preparations that contain differing and therefore unpredictable amounts of both levothyroxine and T3. Levothyroxine is converted into T3 by type 1 deiodinase in the liver.19 The evidence for local deiodination of total thyroxine (T4) in the human heart by type 2 deiodinase20,21 and the increased expression of type 2 deiodinase in the mouse heart during hypothyroidism22 could indicate mechanisms of adaptation in case of low or high serum levels of T4.
Most reviews report a period of 4 to 6 months before normalization of plasma thyrotropin and free thyroxine (FT4) levels is attained.8-12 A more rapid normalization could be of great benefit to patients with hypothyroidism regarding the reduction of cardiac risk factors, improvement of quality of life, and being less cumbersome for regular visits to the clinics. However, the efficacy and safety of different initial doses of levothyroxine have surprisingly never been studied prospectively in patients with primary hypothyroidism. This prompted us to compare a full initiating treatment dose of levothyroxine (1.6 μg/kg)23 with the classic approach of “start low and go slow” in a prospective, randomized, double-blind study. The aim of the study was to prove that restoration of plasma thyrotropin and FT4 levels within the normal reference range can be performed with a straightforward high-dose regimen without any increased risk of major adverse cardiac events.
Full paper accessible here:
I think we need to realise that the best approach might well be one which tested every single day. (Possibly even more often very early. To catch the situations in which the thyroid hormone seems to run out well before the next dose.) That would allow blood levels and clinical assessment to go together and raise dose fairly fast, but not too fast for the individual. Of course, the cost of so doing is prohibitive.
But that is behind my hope that some technological development would allow indirect assessment of thyroid status - if not actual measurement of thyroid hormones.