|Year : 2012 | Volume
| Issue : 3 | Page : 81-83
Atypical thyroxine replacement in hypothyroidism: A clinical audit
Sukriti Bhutani1, Jaikrit Bhutani2, Yatan P. S. Balhara3, Sanjay Kalra4
1 Medical Student, MAIMRE, Agroha, India
2 Medical Student, PGIMS, Rohtak, India
3 Assistant Professor of Psychiatry, National Drug Dependence Treatment Centre, AIIMS, New Delhi, India
4 Department of Endocrinology, Bharti Hospital and BRIDE, Karnal, Haryana, India
|Date of Web Publication||11-Aug-2012|
Department of Endocrinology, Bharti Hospital and BRIDE, Karnal, Haryana
Source of Support: None, Conflict of Interest: None
Background: Change in dosage timing and frequency of L-thyroxine administration may decrease the severity of "hypothyroid" symptoms and contribute to patient satisfaction. This clinical audit was planned to assess the patterns of L-thyroxine replacement in hypothyroid patients. Materials and Methods: A pretested, structured questionnaire collecting information about age, gender, duration of disease, concomitant morbidity and therapy, patient concerns, and thyroid control was administered to 100 consecutive hypothyroid patients attending an endocrine clinic in Karnal, Haryana, North India. Analysis was carried out using the SPSS version 19.0. Results: The mean age of patients was 42.14 ± 13.14 yr, with an average duration of hypothyroidism of 5.12 ± 6.87 yr. Thirty-two subjects were euthyroid (thyroid stimulating hormone (TSH) 0.35-5.00 mIU/l).Eleven subjects reported a TSH < 0.35 and 57 reported TSH ≥5.00 mIU/l. The commonest dose of L-thyroxine used was 100 mcg/day (n = 35), followed by 125 mcg/day (n = 20). The mean total daily dose was 101.17 ± 24.91 (range 50-150) mcg/day. The daily dose per body weight was 1.452 ± 0.38 (range 0.67-2.56) mcg/kg). Nine patients were on atypical regimes: five took their medication in divided daily doses, two took it at night, and two preferred a time "two hours after breakfast and two hours before lunch." They shifted from early morning administration of L-thyroxine because of uneasiness (n = 5/9), palpitation (n = 2/9), and increased hunger (n = 1/9) post-tablet ingestion. The symptoms subsided after the timing or frequency of L-thyroxine intake was changed. Conclusions: Changing the time and/or frequency of L-thyroxine dosage helps in alleviating some of the distressful symptoms among the hypothyroid subjects.
Keywords: Clinical inertia in hypothyroidism, hypothyroid patient concerns, patient empowerment, shared decision-making
|How to cite this article:|
Bhutani S, Bhutani J, Balhara YP, Kalra S. Atypical thyroxine replacement in hypothyroidism: A clinical audit. Thyroid Res Pract 2012;9:81-3
|How to cite this URL:|
Bhutani S, Bhutani J, Balhara YP, Kalra S. Atypical thyroxine replacement in hypothyroidism: A clinical audit. Thyroid Res Pract [serial online] 2012 [cited 2020 Oct 23];9:81-3. Available from: https://www.thetrp.net/text.asp?2012/9/3/81/99648
| Introduction|| |
The management of hypothyroidism is thought to be simple and straightforward by many.  At first glance, all that needs to be done is titration of a single daily dose of L-thyroxine, which is administered early morning, before breakfast. This simplistic view, however, obscures the wide diversity of management strategies that have to be utilized, in order to manage hypothyroid patients with varying concerns.
This brief communication reports the findings of a clinical audit performed at an endocrine center in North India, which aimed to assess the patterns of L-thyroxine replacement in hypothyroid patients. Additionally, it highlights the need to address clinical inertia in the management of hypothyroidism, a phenomenon similar to that seen in diabetes mellitus management.  It supports the call for a patient-centered approach to the management of hypothyroidism, involving the elements of patient empowerment, with shared decision-making.
| Materials and Methods|| |
A pretested, structured questionnaire was administered to 100 consecutive hypothyroid patients attending an endocrine clinic in Karnal, Haryana, North India. This was part of a larger study which aimed to evaluate and quantify "patient concerns" of hypothyroid patients and assess clinical correlates of these "felt concerns" at the same center. Informed verbal consent was taken from all the subjects prior to enrolment in the study.
Data were collected regarding the age, gender, duration of disease, concomitant morbidity and therapy, patient concerns, and level of thyroid control of all subjects. This was correlated with the total daily dose (TDD) and dose per kg body weight (DBW) of L-thyroxine, as well as the frequency and timing of administration of the hormone. Focused interviewing was carried out to assess the reasons and effects of atypical frequency or timing of L-thyroxine.
Analysis was carried out using the SPSS version 19.0. Descriptives of various variables were calculated and student's t-test was used for in-between group comparisons. Level of statistical significance was kept at P < 0.05 for all the tests.
| Results|| |
Of the 100 subjects enrolled, 88 were females. The mean age was 42.14 ± 13.14 yr, with an average duration of hypothyroidism of 5.12 ± 6.87 yr. Thirty-two subjects had a current (within the past one month) euthyroid thyroid stimulating hormone (TSH) value (0.35-5.00 mIU/l), while 11 reported TSH <0.35 and 57 reported TSH 5.00 mIU/l. TSH was done commercially, from the same laboratory, using chemiluminescence immunoassay.
All patients were on L-thyroxine supplementation. The commonest dose used was 100 mcg/day (n = 35), followed by 125 mcg/day (n = 20). The mean TDD was 101.17 ± 24.91 mcg/day with a range of 50-150 mcg/day. The DBW was 1.452 ± 0.38 mcg/kg (range 0.67-2.56 mcg/kg). No difference was noted in DBW in men and women (male: 1.29 ± 0.46, female: 1.47 ± 0.37; R = −1.515, P = 0.133). No difference was noted in the dose prescribed to well controlled (1.44 mcg/kg/day) and poorly controlled (1.46 mcg/kg/day) patients (R = −0.347, P = 0.729).
Frequency of administration was once daily in 95 patients, with five patients taking divided doses twice a day. When timing was assessed, the results were as follows, 91 patients took L-thyroxine once daily, at least 30 min before breakfast. Two patients took their dose "2 hours after breakfast and 2 hours before lunch," while another two followed a bed time regime. Five patients preferred to take L-thyroxine in doses divided between early morning and at bed time.
Detailed interviewing was to determine the reasons for atypical administration of L-thyroxine in all cases, shared decision-making between treating endocrinologist and patients was clearly obvious.
Patients had requested change in early morning administration of L-thyroxine because of uneasiness (n = 5/9), palpitation (n = 2/9), and increased hunger (n = 1/9) after ingesting the tablet. One patient could not remember the reason why she had shifted to a twice daily regime. In all cases, the symptoms subsided after time or frequency of intake was changed. All nine patients wished to continue the atypical regime they were following. No sense of "intrusion" into normal lifestyle by the time of administration of therapy was reported by any of them. The nine patients (one male and females) with atypical administration of L-thyroxine did not differ from the rest of the cohort with respect to age, gender, duration of hypothyroidism, comorbid conditions, or concomitant medication.
| Discussion|| |
L-thyroxine is usually administered once daily, on an empty stomach. The replacement of thyroxine in hypothyroid patients is considered a relatively simple matter by most physicians, leaving little room for innovation or improvisation in therapeutic regimens. A few authors, however, have reported using L-thyroxine in weekly doses or in doses less frequent than once daily. 
At the same time, it is obvious to most practicing endocrinologists that patients are not satisfied with the treatment of hypothyroidism that they reserve. Improvements in diagnosis treatment and monitoring have not necessarily improved satisfaction levels of patients. ,
We have earlier raised the issue of whether to treat patients according to their biochemical levels or their symptoms. , It has also been pointed out that we should try to find reasons rather than being "unsympathetic and dismissive of their symptoms." 
One reason for symptoms may be iatrogenic. It is not absolutely necessary that a patient who is euthyroid on L-thyroxine supplementation will have constant levels of T3 and T4 throughout the day. Individual variations in absorption of thyroxine, a variation in bioavailability and alterations in tissue concentration of thyroid hormones may contribute to varying symptomatology.
L-thyroxine is absorbed from the stomach and small intestine. Absorption is slightly increased if taken as an empty stomach and variability in TSH is reduced in thus manner. Though serum T4 levels peak two to four hours after ingestion, the seven day plasma half life is long enough to minimize fluctuations in T4 levels.  This means that omission of a single dose does not have a major effect on TSH or free T4 levels. It also means that one can divide the daily dose requirement into smaller parts or can complete the requirement as a combined weekly dose.
This pharmacokinetic profile, therefore, allows the treating endocrinologists to change the frequency and timing of L-thyroxine tablets, if warranted by the patient's clinical picture. It also allows the endocrinologist to practice shared decision-making with the patient, while maintaining scientific accuracy, in an attempt to improve patient compliance.
It makes sense, therefore, to conduct therapeutic trials with atypical times and frequency of administration of L-thyroxine, in the select few hypothyroid patients also complain of "hyperthyroid" or non-specific symptoms while maintaining normal TSH levels on L-thyroxine supplementation. In the absence of randomized controlled trials to answer this question, an observational trial or a cross-sectional study is the best way of assessing the utility of these typical regimes.
In the current study, 9% patients preferred to follow atypical regimes, including: twice daily, bed time, and post-meal administration of L-thyroxine. These regimes had been suggested after a process of shared decision-making and were necessitated by the presence of symptoms, such as uneasiness, palpitations, and increased hunger after L-thyroxine ingestion, in patients who were biochemically euthyroid.
This cross-sectional study was initially designed as a clinical audit, to assess patient concerns, and management trends, in hypothyroid patients at an endocrine center in north India. The small sample size, unicentric design, and lack of controls are limiting factors of the study. Detailed investigations for surrogate markers of hypothyroidism were not carried out. The unexpected clinical inertia  (similarity in doses of well controlled and poorly controlled patients) is another limiting factor, which needs to be addressed by the clinical team.
| Conclusions|| |
The sole aim of the treating doctor is to ensure the complete well being of the patient, by both decreasing the symptoms and controlling the underlying disease. This study reveals that changing the time and/or frequency of thyroxine dosage helped in alleviating some of the distressful symptoms among the hypothyroid subjects. A placebo effect of "patient mental satisfaction" and "convenience," or satisfaction with the process of shared decision-making cannot be ruled out, and these clinical observations do need to be replicated in large, well-designed studies. Also, the concept of tissue hypothyroidism may explain many of the clinical features that biochemically euthyroid patients present with. Using simple shared decision-making strategies, clinical and laboratory tools, we can ensure benefit and satisfaction to patients of hypothyroidism. 
Further, large-scale studies must be performed on measures to reduce the clinical morbidity despite of normal biochemical parameters in hypothyroid patients. Until results of such studies are available; however, we can consider some of the applied and studied simple therapeutic strategies in select patients who continue to remain symptomatic or develop new symptoms, while on L-thyroxine supplementation.
| References|| |
|1.||Vaidya B, Pearce SH. Management of hypothyroidism in adults. BMJ 2008;337:a801 . |
|2.||Phillips LS, Branch WT, Cook CB, Doyle JP, El-Kebbi IM, Gallina DL, et al. Clinical inertia. Ann Intern Med 2001;135:825-34. |
|3.||Grebe SK, Cooke RR, Ford HC, Fagerström JN, Cordwell DP, Lever NA, et al. Treatment of hypothyroidism with once weekly thyroxine. J Clin Endocrinol Metab 1997;82:870-5. |
|4.||Saravaven P, Cahu WF, Roberts N, Vedhara K, Greenwood R, Dayon CM. Psychological well-being in patients on 'adequate' doses of L-Thyroxine: Results of a large, controlled community - based questionnaire study. Clin Endocrinol (Oxf) 2002;57:577-85. |
|5.||Kalra S, Khandelwal SK. Why are our hypothyroid patients unhappy? Is tissue hypothyroidism the answer? Indian J Endocrinol Metab 2011;12:S95-8. |
|6.||Skinner GR, Thomas R, Taylor M, Sellarajah M, Bolt S, Krett S, et al. Thyroxine should be tried in clinically hypothyroid but bio-chemically euthyroid patients. BMJ 1992;314:1764 . |
|7.||Robert ND. Psychological problems in thyroid disease. Br Thyroid Found Newsl 1996;18:3 . |
|8.||Bach-Huynh TG, Nayak B, Loh J, Soldin S, Jonklaas J. Timing of levothyroxine administration affects serum thyrotropin concentration. J Clin Endocrinol Metab 2009;94:3905-12. |