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Rapid Responses: Rapid Responses published:
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Sublinical hypothyroidism and hyponatremia
- Lester M Baskin (22 July 2008)
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Affect of patient weight on deciding to treat subclinical hypothyroidism?
- Dr John Andrew Lockton, Dr Peter Hale, Consultant Physician (31 July 2008)
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You've identified the knowledge gaps - so what are the research questions?
- Andrew Cook (6 August 2008)
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Is the age an important factor for screening for subclinical hypothyroidism?
- Cesar Augusto Guevara-Cuellar (13 August 2008)
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Individuality
- Diana M Holmes (24 September 2008)
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Lester M Baskin, internist Portland, Oregon, USA 97210
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I have known repeated unexplained hyponatremia and low plasma osmolality, with less than maximally dilute urine, respond nicely to thyroid replacement with almost complete normalization of serum sodium. The only finding on initial labs was a mild elevation of thyroid stimulating hormone, which also normalized with thyroid replacement. Competing interests: None declared |
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Dr John Andrew Lockton, Clinical assistant Lime House, Poplar Grove, Stepping Hill Hospital, Stockport, SK2 7JE, UK, Dr Peter Hale, Consultant Physician
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On 16th July an article by Cung B Pham and Allen F Shaughnessy discussed treatment of subclinical hypothyroidism. Many patients with subclinical hypothyroidism suggest that the condition is contributing to their obesity and request treatment on this basis. What is the evidence that subclinical hypothyroidism contributes to weight gain and that treatment assists with control of weight? It is well established that overt hypothyroidism is associated with reduced metabolic rate and consequent weight gain. Studies report that TSH variability within the normal range is positively associated with historical weight change1 and is also a predictor of subsequent weight gain2. It would seem logical therefore that subclinical hypothyroidism might be associated with weight gain. Indeed one study confirmed this by including subjects with subclinical hypothyroidism1. Unsurprisingly the prevalence of subclinical hypothyroidism is reported to be higher in obese subpopulations, for example, in a group of metabolic syndrome patients with a mean BMI of 32.4 kg/m2 compared with a control group with a mean BMI of 26.4 kg/m2 (16.4% v 5.8%; p=0.001)3. However in obesity tri-iodothyronine4 as well as TSH rise suggesting a resetting of the HPA axis. Further in a group of morbidly obese subjects who also had subclinical hypothyroidism Roux-en-Y surgery improved TSH values suggesting that obesity can cause elevations of TSH rather than the converse5. A recent double-blind, placebo-controlled, crossover study of the benefit of treatment with thyroxine with subclinical hypothyroidism showed a benefit on weight6. In 100 subjects randomized to treatment with 100ug thyroxine or placebo for 12 weeks subjects waist-hip ratio improved from 0.83 to 0.81 and was associated with a small weight loss (0.7 kg). By comparison placebo treated subjects lost 0.5 kg which was statistically significantly different p=0.02. In this case the weight loss was small and in other, albeit smaller, studies weight loss has not occurred7. Cung B Pham and Allen F Shaughnessy conclude that ‘a short trial of treatment’ may be justified in some patients. In view of the above we would be interested to hear the authors views specifically on whether to treat patients presenting with difficulty controlling weight who have subclinical hypothyroidism. 1. Knudson N, Laurberg P, Rasmussen LB, Bulow I, Perrild H, Ovesen L, Jorgensen T. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. JCEM 2005; 90: 4019-4024. 2. Fox CS, Pencina MJ, D’Agostino RB, Murabito JM, Seely EW, Pearce EN, Vasan RS. Relations of thyroid function to body weight. Arch Intern Med 2008; 168: 587-592. 3. Uzunlulu M, Yorulmaz E, Oguz A. Prevalence of subclinical hypothyroidism in patients with metabolic syndrome. Endocrine journal 2007; 54: 71-76. 4. Bray GA, Fisher DA, Chopra IJ. Relation of thyroid hormones to body weight. Lancet 1976; 7971: 1206-1208. 5. de Moraes CMM, Mancini MC, de Melo ME, Figueiredo DA, Villares SMF, Rascovski A et al. Prevalence of subclinical hypothyroidism in a morbidly obese population and improvement after weight loss induced by Roux-en-Y gastric bypass. Obesity Surgery 2005; 15: 1287-1291. 6. Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function and quality of life in subclinical hypothyroidism: Randomised crossover trial. JCEM 2007; 92: 1715-1723. 7. Kong WM, Sheikh MH, Lumb PJ, Freedman DB, Crook M, Dore CJ, Finer N. A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. Am J Med 2002; 112: 348-345. Neither author has any conflicting interests Competing interests: None declared |
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Andrew Cook, Consultant in Public Health Medicine NCCHTA, University of Southampton, SO16 7NS
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This summary of what is unknown about the management of clinical hypothyroidism is interesting, but the authors appear to have missed a prime opportunity to identify the key research questions which would address this evidence gap - preferably in a PICO format. (1) The authors - who have conducted a systematic review on this topic - are best placed to know the evidence gaps, and hence identify the research questions which need answering. Even if they themselves had no inclination to do the research, publication here would enable researchers to take those questions, find funding, and answer them. As is, the recommendations on how to deal with subclinical hypothyroidism constitute a mix of common sense (don't screen for this condition), best guesses (try treating it for a few months) and ignorance of the natural history of subclinical hypothyroidism (check TSH every year). There is a big evidence gap here - amenable to being filled by robust research. 1. BMJ 2006;333:804-806 (14 October), doi:10.1136/bmj.38987.492014.94 Competing interests: None declared |
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Cesar Augusto Guevara-Cuellar, Assistant Professor University of Valle
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Although some scientific associations recommend routine screening for subclinical hypothyroidism (SCH) in adults, pregnant women and those contemplating pregnant, several governmental organization do not recommend because there is weak evidence with respect of benefit with levotiroxine supplementation. . However a recent meta analysis (1) that included 2531 patients with subclinical hypothyroidism founded that patients younger than 65 years have greater risk of ischemic heart disease (odds ratio: 1,57 confidence interval: 1,19-2,06) and cardiovascular/all cause mortality was elevated (odds ratio: 1,37 confidence interval: 1,04-1,79) compared with patients with SCH greater than 65 years. It is necessary more studies to determine the utility of age or other factors (ie. abnormal serum lipids levels) as criteria for screen in these patients. (1) Razvi S, Shakoor A, Vanderpump M, Weaver JU, Pearce SH The Influence of Age on the Relationship between Subclinical Hypothyroidism and Ischemic Heart Disease: A Metaanalysis. J Clin Endocrinol Metab. 2008;93(8):2998-3007. Competing interests: None declared |
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Diana M Holmes, Lay Researcher Gailey, Staffordshire, ST19 5PZ
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As the authors state ‘subclinical hypothyroidism’, is a laboratory definition with a raised thyroid stimulating hormone (TSH) and yet ‘normal’ concentrations of free thyroid hormones, without specific symptoms of hypothyroidism. With current protocol with regard to the diagnosis and management of subclinical hypothyroidism there is no room for individuality. Professor Ralph Gräsbeck one of the developers of the concept of the reference range warned the medical profession in 1990 not to use incorrect terminology such as the word ‘normal’(1). Individuality presents as - what is normal for one person is not normal for another person. Patients cannot be made to fit into a set of parameters. The words ‘normal’, cut off levels’, ‘upper limits and lower limits’, and ‘border line’ all affect decision making with regard to a diagnosis. If the terminology ‘cut off levels’ was abandoned there would be no ‘borderline’ cases. The patient is either hypothyroid or not hypothyroid. Worldwide, new guidelines have been set for the TSH reference interval. In 2004 the National Academy for Clinical Biochemistry (USA) set the reference interval for TSH at 0.4 mU/l to 2.5 mU/l (2). However, in 2006 the British Thyroid Association raised the TSH reference interval to >10 mU/l for both primary hypothyroidism and subclinical hypothyroidism, although no guidelines have been set by the National Institute for Clinical Excellence. With regard to specific signs and symptoms for subclinical hypothyroidism there appears to be the same grey area as for specific signs and symptoms in primary hypothyroidism. Continual exhaustion, weight gain, and hair loss are classed by many in the medical profession as non-specific signs and symptoms for hypothyroidism. Then there are the silent signs for e.g. depression, high cholesterol levels, and or cardiovascular conditions, many times these are treated as separate conditions because the results of thyroid function tests are returned within the reference interval. Much more clarity is needed for diagnosis and management of thyroid conditions. References 1. Scand J Clin Lab Invest Supp 1990; 201:45-53 2. The Endocrine Society, Volume 29, Number 2, April 2004 Competing interests: None declared |
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