Open Journal Systems

MEDICAL SPECIALITIES

Received: October 21^st 2014

Accepted: March 6^th 2015

Alterations of the thyroid function in patients with morbid obesity

Danely Sabelia Montoya-Morales,^a María de los Ángeles Tapia-González,^a Lisndey Alamilla-Lugo,^a Alejandro Sosa-Caballero,^a Andrés Muñoz-Solís,^a Marisela Jiménez-Sánchez^a

^aDepartamento de Endocrinología, Hospital de Especialidades, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Distrito Federal, México

Communication with: Danely Sabelia Montoya-Morales

Telephone: (55) 5725 5900, extensión 23235; teléfono celular: (72) 2659 1611

Email: danlym@hotmail.com

Background: The morbid obesity (BMI ≥ 40 kg/m²) is associated with dysfunction of the hypothalamus-pituitary-thyroid axis, showing high levels of thyrotropin (TSH), triiodothyronine (T3) total and free, suspecting a real thyroid condition.

Objetive: Describe the alterations in thyroid function in patients with morbid obesity, determining serum levels of TSH, total T3, free T4 and thyroid peroxidase antibodies (TPO).

Methods: Prospective, descriptive, observational, cross-sectional study, we enrolled 52 patients with morbid obesity, at the obesity clinic, from department of Endocrinology, since January 2009 to July 2011. All patients signed a letter of informed consent. Patients with known thyroid disorders and/or under the use of levothyroxine or other medication that causes alteration in thyroid function were excluded. Statistical analysis was performed using measures of central tendency, simple frequencies, percentages and Spearman’s correlation.

Results: The prevalence of primary hypothyroidism was 8 %, 6 % subclinical hypothyroidism and thyroid function alterations secondary to obesity of 23 % (elevated TSH and/or free T4 Total T3 with normal and TPO antibody negative).

Conclusions: Most morbidly obese patients haven’t autoimmune thyroid dysfunction; the alterations in thyroid function are caused by an effect of homeostasis against obesity and can be corrected by reducing weight.

Keywords: Morbid obesity, Thyroid hormone, Body mass index, Thyrotropin, Thyroid peroxidase antibodies.

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It is well described that the hypothalamic-pituitary-thyroid axis is a potent regulator of thermogenesis and of basal and total energy consumption in the short and long term; but the relationship among thyroid abnormalities presented in patients with obesity is still controversial, such as elevated levels of thyrotropin (TSH), total and free T3 with normal free T4 levels; so it continues to be studied whether obesity may influence thyroid function, or if slight alterations in thyroid function in patients with obesity may explain increased weight.^1-3

Several studies have shown that TSH and body mass index (BMI) are positively correlated, however the elevated levels of TSH in obese patients may indicate a thyroid fault line, which in most cases would be of autoimmune etiology.^4-6

The aim of this study was to describe disorders of thyroid function in patients with morbid obesity, describing serum levels of TSH, total T3, free T4, and TPO antibodies.

Methods

A prospective, observational, cross-sectional study, conducted in the Clínica de Obesidad del Departamento de Endocrinología, from January 2009 to August 2011. The protocol was submitted and accepted by the research committee of the Hospital de Especialidades del Centro Médico Nacional La Raza. All patients authorized their participation by signing a letter of informed consent. Inclusion criteria were: being over 18, men and women with morbid obesity (BMI ≥ 40 kg/m²). We excluded patients taking medication that alters thyroid function or thyroid function tests (amiodarone, lithium, dopamine agonists, carbamazepine, furosemide, heparin, glucocorticoids); patients with known hypothyroidism; and with secondary causes of obesity.

Measurements of height and weight were performed and BMI was calculated. With a 12-hour fast glucose, HbA1C, total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and basal insulin were determined. Serum levels of TSH, free T4, total T3, and TPO antibodies were taken by chemiluminescence. The normal range of TSH was 0.4-4.0 μIU/ml, for T3T it was 84-172 ng/dl, and T4L it was 0.8-1.8 ng/dl. The TPO antibodies were reported as positive (> 13 IU/ml), or negative (< 13 IU/ml).

The groups were divided according to the degree of obesity according to the American Association of Clinical Endocrinologists (AACE): Grade 3 with a BMI ≥ 40 kg/m²; Grade 4 as superobesity with a BMI of 50-59 kg/m², and Grade 5 as supersuperobesity with a BMI ≥ 60 kg/m².⁷

Data were analyzed using SPSS version 19 for Windows, and to analyze the results we used descriptive statistics, using measures of central tendency (mean), dispersion (standard deviation), simple frequencies, percentages, and Spearman correlation.

Results

52 patients with clinically severe obesity were assessed, with an average age of 39.9 ± 12.9 years; 36 women (69%) and 16 men (31%); weighing 128.28 ± 22.9 kg; height 1.62 ± 0.8 m, and BMI of the total population was 48.19 ± 6.19 (Table I).

38 patients (73%) were classified in the group of grade 3 obesity, there were 9 (17%) in the grade 4 obesity group, and the grade 5 obesity group had 5 (10%) (Table II).

The overall metabolic profile of the study population was as follows: fasting glucose 95.8 ± 16.4 mg/dl, HbA1c 6.88 ± 0.73%, total cholesterol 177.1 ± 34 mg/dl, HDL cholesterol 38.7 ± 10 mg/dl, LDL cholesterol 104.7 ± 30 mg/dl, triglycerides 172.3 ± 56.9 mg/dl, basal insulin 22.4 ± 16.6 μIU/ml, and HOMA-IR 6.38 ± 7.89 (Table III). 

Comorbidities associated with obesity included: impaired fasting glucose (IFG) in 17 (33%), impaired glucose tolerance (IGT) in 16 (31%), diabetes mellitus 2 (DM2) in 8 (15%), hypertension in 22 (42%), dyslipidemia in 42 (80%), obstructive sleep apnea/hypopnea (OSAH) in 8 (15%), dysthymia in 16 (31%), and insulin resistance syndrome in 39 (75%) patients.

Dyslipidemia was the most frequent comorbidity, and of these mixed hyperlipidemia was the most common, followed by hypoalphalipoproteinemia.

Of our total population, 39 patients (75%) had insulin resistance, based on a HOMA-IR ≥ 2.5.

The total population levels were TSH 3.72 ± 3.1 μIU/ml; total T3 of 131.18 ± 29.9 ng/dl; free T4 1.04 ± 0.21 ng/dl, and TPO antibodies 11.1 ± 28.7 IU/ml, being positive in 9 patients (17%) (Table IV).

In the group of obesity grade 3, TSH levels were 8.68 ± 21.12 μIU/ml; total T3 of 131.11 ± 31.92 ng/dl; free T4 1.02 ± 0.23 ng/dl, and TPO antibodies 14.47 ± 33.28UI/ml, being positive in 9 patients (24%) (Table IV).    

In the group of obesity grade 4, TSH levels were 2.70 ± 1.49 μIU/ml; total T3 of 139.55 ± 23.89 ng/dl; free T4 1.11 ± 0.15 ng/dl, and TPO antibodies 1.68 ± 0.53 IU/ml, being negative in all subjects (Table IV).

In the group of grade 5 obesity, TSH levels were 4.6 ± 2.9 μIU/ml; total T3 of 116.7 ± 20.3 ng/dl; free T4 1.1 ± 0.05 ng/dl, and TPO antibodies 3.1 ± 2.1UI/ml, being negative in all subjects (Table IV).

4 patients (8%) were diagnosed with primary hypothyroidism, 3 (6%) with subclinical hypothyroidism, 12 (23%) with alterations in thyroid profile secondary to obesity, and 33 (63%) with euthyroid.

We found a correlation between levels of TSH and levels of HDL, with r -.287, p < 0.05. The rest of the correlations were not statistically significant.

Discussion 

Morbidly obese patients, in most cases, had normal thyroid function (63%), in 23% we found disorders in thyroid function secondary to obesity, such as elevated TSH and/or elevated total or free T3 with normal free T4 and negative TPO antibodies, which reflect an adaptive process.

There are several theories explaining thyroid disorders presented in patients with obesity:

• Neuroendocrine dysfunction, with an abnormal rate of TSH secretion or secretion of bioinactive TSH.
• Hormonal peripheral resistance, as the expression of TSH and thyroid hormones, is reduced in the adipocytes of obese subjects compared to those of normal weight, altering the negative feedback on TSH.
• Increased activity of deiodinases with a high conversion of T4 to T3, increasing levels of total T3 and free T3, considered as a defense mechanism to counter the accumulation of fat, increasing energy expenditure.
• The synthesis of cytokines (IL-1, TNF-alpha, IL-6), which characterizes the inflammatory state in obesity, can inhibit the expression of sodium symporter/Iodine (NIS), compensating for it with elevation of TSH.^8-11

As for autoimmune thyroid disease, literature reports a prevalence of hypothyroidism in the general population of 1-2% and subclinical hypothyroidism 6-8%; and in obese patients with full and subclinical hypothyroidism, up to 19.5%.^1,12-14 However, the Third National Health and Nutrition Examination Survey (NHANES III) showed that the prevalence of positive tests for thyroid antibodies and normal serum levels of TSH, does not differ in patients with morbid obesity and the general population.⁶ We found an increased prevalence of autoimmune thyroid disease in patients with severe obesity, confirming what is suggested Duntas and Biondi,¹⁵ that obesity may increase susceptibility to autoimmunity. In our group, the prevalence of primary hypothyroidism was 8%, subclinical hypothyroidism was presented by 6%, similar to that reported in a previous study in patients with severe obesity by Michakali et al.,¹² which reported a prevalence of newly diagnosed primary hypothyroidism of 11% and subclinical hypothyroidism of 7.7%. We only determined the TPO antibodies, since these levels correlate with autoimmune thyroid disease, and patients with Hashimoto's thyroiditis have these antibodies and may have no antibodies against thyroglobulin.¹⁶

Disorders in thyroid function in patients with severe obesity are reversible, as Sari et al.¹⁷ reported if a weight loss of more than 10% is achieved. Another study reported that after a major weight loss, the expression of the TSH receptor and thyroid hormone receptor (TR-alpha 1) in the subcutaneous adipose tissue increase, leading to a reduction in circulating levels of TSH and free T3.⁸

We did not establish a correlation between TSH and BMI as previous studies have established, one possible cause is that many of our patients were managed with metformin, which, without knowing the mechanism of action, has shown lower levels of TSH in patients with dysfunction of the thyroid axis.^19-21

Another important aspect is that different degrees of obesity could not be considered as a single entity and each of these could present their own characteristics.²²

Conclusions

We conclude that most morbidly obese patients have normal thyroid function (63%), so finding an elevated TSH in patients with severe obesity does not always reflect a background thyroid disorder, but rather an effect of homeostasis, which is it corrected by a weight loss of at least 10%.

References

1. Verma A, Jayaraman M; Kumar HK, Modi KD. Hipothyroidism and obesity. Cause of effect?. Saudi Med J. 2008;29:1135-38.
2. Liu YY, Brent GA. Thyroid hormone crosstalk with nuclear receptor signaling in metabolic regulation. Trends Endocrinol Metab. 2009;21:166-73.
3. Muscogiuri G, Sorice G, Mezza T, Prioletta A, Lassandro A, et al. High-Normal TSH values in obesity: Is it insulin resistence or adipose tissue´s guilt?. Obesity. 2013;101-06.
4. Iglesias P, Diez JJ. Influence of thyroid dysfunction on serum concentrations of adipocytokines. Cytokine. 2007;40:61-70.
5. Iacobellis G, Ribaudo MC, Zappaterreno A, Iannucci CV, Leonetti F. Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women. Clin Endocrinol. 2005;62:487-91.
6. Rotondi M, Magri F, Chiovato L. Thyroid and obesity: not a one-way interaction. J Clin Endocrinol Metab. 2011;96:344-46.
7. Mechanick J, Kushner R, Sugerman H, Gonzalez-Campoy M, Collazo-Clavell M, Spitz A, et al. American Association of Clinical Endocrinologists, The Obesity Society and American Society for Metabolic & Bariatric Surgery Medical Guidelines for Clinical Practice for the Perioperative Nutritional Metabolic and Nonsurgical Support of the Bariatric Surgery Patient. 2009.
8. Bergoglio L, Mestman J. NACB: Guía de Consenso para el Diagnóstico y Seguimiento de la Enfermedad Tiroidea. Thyroid. 2003;13:4-126.
9. Reinehr T. Obesity and thyroid function. Mol Cell Endocrinol. 2010;316:165-171.
10. Krotkiewski M. Thyroid hormones in the pathogenesis and treatment of obesity. Eur J Pharmacol. 2002; 440:85-98.
11. Longhi S, Radetti G. Thyroid Function and Obesity. J CLin Res Pediatr Endocrinol. 2013;5:40-44.
12. Michalaki M, Vagenakis A, Leonardou A, Argentou M, Habeos I, Makri M, et al. Thyroid function in humans con morbid obesity. Thyroid. 2006;16:73-77.
13. Marzullo P, Minocci A, Tagliaferri MA, Guzzaloni G, Di Blasio A, De Medici C, et al. Investigations of Thyroid Hormones and Antibodies in Obesity: leptinlevels are associated with thyroid autoinmunity independent of bioanthropometric, hormonal and weight-related determinants. J Clin Endocrinol Metab. 2010;95:3965-72.
14. Vanderpump MP. The epidemiology of thyroid disease. Br Med Bull. 2011;99:39-51.
15. Duntas L, Biondi B. The interconnections between obesity, thyroid function, and autoimmunity: the multifold role of leptin. Thyroid. 2013;23:646-53.
16. Ohtaki S, Nakagawa H, Nakamura M, Kotani T. Thyroid Peroxidase: Experimental and Clinical Integration. Endocrine Journal.1996;43:1-14.
17. Sari R, Kemal M, Altunbas H, Karayalcin U. The effect of body weight and weight loss on thyroid volume and function in obese women. Clinical Endocrinology. 2003;59:258-62.
18. Nannipieri M, Cecchetti F, Anselmo M, Camastra S, Niccolini P, Lammacchia M et al. Expression of thyrotropin and thyroid hormone receptors in adipose tissue of patients with moprbid obesoty and/or type 2 diabetes: effects of weight loss. International Journal of Obesity.2009;33:1001-06.
19. Kouidhi S, Berhouma R, Ammar M, Rouissi K, Jarboui S, et al. Relationship of thyroid function with obesity and type 2 diabetes in euthyroid Tunisian subjects. Endocrine Research. 2013;38:15-23.
20. Cappelli C, Rotondi M, Pirola I, Agosti B, Gandossi E, et al. TSH-Lowering effect of metformin in type 2 diabetic patients. Diabetes Care. 2009;32: 1589-90.
21. Vigersky R, Filmore-Nassar A, Glass A. Thyrotropin suppression by metformin. J Clin Endocrinol Metab. 2006;91:225-27.
22. Rotondi M, Leporatti P, La Manna A, Pirali B, Mondello B, Fonte R et al. Raised serum TSH levels in patients with morbid obesity: is it enough to diagnose subclinical hypothyroidism?. European Journal of Endocrinology. 2009;160:403-408.

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