Obesity, energy regulation and thyroid function

Summary

Several population-based studies have shown a significant association between TSH-level and BMI (body mass index). About 30% of the rest energy expenditure are regulated by thyroid hormones, which generated the hypothesis that thyroid hormone substitution with TSH-titration into the lower reference levels may prevent body weight gain. The opposite effect of thyroid hormones is appetite stimulation, which may be responsible for body weight gain in case of substitutive medication.

The association between TSH and BMI has become a complex topic in the light of the endocrine activity of adipocytes. Adipocytes are not a silent fat mass, but increase the hormone level of leptin, which influences neurones in the hypothalamus, the thyreotropic axis and TSH secretion. BMI is positively correlated with serum leptin. Elevated leptin levels, endogenous in individuals with high BMI or exogenous after leptin injection for treatment of hypothalamic amenorrhoea, shift TSH in the upper reference level. Borderline elevated TSH levels are reversible in case of body weight reduction in obese persons. It remains unclear whether high TSH levels or high leptin level are responsible for obesity or represent secondary phenomenon.

Recommendation for daily practice: Borderline elevated TSH-levels in obese patients will decrease in case of body weight reduction without hormone medication. After definitive treatment of hyperthyroidism patient's history for use of carbohydrates (increased during hyperthyroidism) should be noticed and substitution with thyroid hormones aims at TSH in the lower reference level. As body weight gain is observed in all TSH groups, a special concept for prevention and therapy of obesity (diet, daily exercise, behaviour training) should be initiated early and additionally to medication.

Zusammenfassung

Mehrere Populationsstudien wiesen eine signifikante Assoziation zwischen TSH-Spiegel und BMI (Body-mass-Index) nach. Da etwa 30% des Ruhe-Energieumsatzes von Schilddrüsenhormonen abhängen, besteht die Vorstellung, dass eine Schilddrüsenhormon-Substitution mit TSH-Titration in den niedrig-normalen Referenzbereich der Gewichtszunahme entgegenwirkt. Der konkurrierende Effekt einer Appetitsteigerung durch Schilddrüsenhormone gilt als mögliche Erklärung, warum es in der Praxis trotzdem zu einer Gewichtszunahme kommt.

Die Assoziation zwischen TSH und BMI ist im Licht der endokrinen Aktivität der Adipozyten inzwischen ein facettenreiches Thema geworden. Die Adipozyten bilden kein ruhendes Fettdepot, sondern führen u. a. zu einem erhöhten Hormonspiegel für Leptin, das über Neurone im Hypothalamus die thyreotrope Achse und damit die TSH-Sekretion beeinflusst. So korreliert der BMI positiv mit dem Leptin- Spiegel im Serum. Erhöhte Leptin-Spiegel, endogen bei hohem BMI oder unter exogener Zufuhr von Leptin in der Behandlung einer hypothalamischen Amenorrhoe, verschieben den TSH-Spiegel in den oberen Referenzbereich. Hoch-normale TSH-Werte sind bei der Adipositas reversibel, falls eine Gewichtsreduktion gelingt. Insgesamt lässt es die Datenlage offen, inwiefern hoch-normale TSH-Spiegel oder hohe Leptin-Spiegel ursächlich für eine Adipositas sind oder Sekundärphänomene darstellen.

Empfehlungen für die Praxis: Grenzwertig hohe TSH-Werte bei adipösen Patienten normalisieren sich nach Gewichtsreduktion ohne Hormonsubstitution. Nach definitiver Beseitigung der Hyperthyreose ist eine gezielte Ernährungsanamnese (Kohlenhydratzufuhr während der Hyperthyreose gesteigert) zu erheben, bei der Substitution mit Schilddrüsenhormonen sollte der TSH-Spiegel in den unteren Referenzbereich eingestellt werden. Da in allen TSHGruppen eine Gewichtszunahme beobachtet wurde, ist zusätzlich zu einer Schilddrüsenhormonmedikation frühzeitig das Basisprogramm in der Prävention und Therapie der Adipositas einzuleiten, das aus Ernährungs-, Bewegungsund Verhaltenstherapie besteht.

Keywords

Obesity - body mass index - thyroid - TSH - leptin

Schlüsselwörter

Adipositas - Body-mass-Index - Schilddrüse - TSH - Leptin

• Literatur

• 1 Abid M, Billington CJ, Nuttall FQ. Thyroid function and energy intake during weight gain following treatment of hyperthyroidism. J Am Coll Nutrition 1999; 18: 189-193.
• 2 Al-Adsani H, Hoffer LJ, Silva JE. Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement. J Clin Endocrinol Metab 1997; 82: 118-1125.
• 3 Andersen S, Bruun NH, Pedersen KM. et al. Biologic variation is important for interpretation of thyroid function tests. Thyroid 2003; 13: 1069-1078.
• 4 Bastemir M, Akin F, Alkis E. et al. Obesity is associated with increased TSH level, independent of thyroid function. Swiss MedWkly 2007; 137: 431-434.
• 5 Biersack HJ, Hartmann F, Rodel R. et al. Long term changes in serum T4, T3, and TSH in benign thyroid disease: proof of a narrow individual variation. Nuklearmedizin 2004; 43: 158-160.
• 6 Brabant G, Horn R, von zur Mühlen A. et al. Free and protein bound leptin are distinct and independently controlled factors in energy regulation. Diabetologia 2000; 43: 438-442.
• 7 Cettour-Rose P, Theander-Carrillo C, Asensio C. et al. Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion. Diabetologia 2005; 48: 624-633.
• 8 Chan JL, Heist K, DePaoli AM. et al. The role of falling leptin in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. JClin Invest 2003; 111: 1409-1421.
• 9 Chikunguwo S, Brethauer S, Nirujogi V. et al. Influence of obesity and surgical weight loss on thyroid hormone levels. Surg Obes Relat Dis 2007; 3: 631-635.
• 10 De Pergola G, Ciampolillo A, Paolotti S. et al. Free triiodothyronine and thyroid stimulating hormone are directly associated with waist circumference, independently of insulin resistence, metabolic parameters and blood pressure in overweight and obese women. Clin Endocrinol 2007; 67: 265-269.
• 11 Dietlein M, Dressler J, Eschner W. et al. Procedure guidelines for radioiodine therapy of differentiated thyroid cancer. Nuklearmedizin 2007; 46: 213-219.
• 12 Dietlein M, Moka D, Reinholz U. et al. Who might benefit from administration of additional inactive iodine during radioiodine therapy for Graves' disease ?. Nuklearmedizin 2007; 46: 77-87.
• 13 Dietlein M, Wegscheider K, Vaupel R. et al. Management of multinodular goiter in Germany (Papillon 2005). Nuklearmedizin 2007; 46: 65-75.
• 14 Dietlein M, Wegscheider K, Vaupel R. et al. Survey of management of solitarythyroid nodules in Germany. Nuklearmedizin. 2008 47. doi: 10.3413/nukmed-0136.
• 15 Eliakim A, Barzilai M, Wolach B. et al. Should we treat elevated thyroid stimulating hormone levels in obese children and adolescents?. Int J Pediatr Obes 2006; 1: 217-221.
• 16 Ettinger MP, LittlejohnT W, Schwartz SL. et al. Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults. JAMA 2003; 289: 1826-1832.
• 17 Feldt-Rasmussen U. Thyroid and leptin. Thyroid 2007; 17: 413-418.
• 18 Grover G J, Mellstrom K, Malm J. Therapeutic potential for thyroid hormone receptor-beta selective agonists for treating obesity hyperlipidemia and diabetes. Curr Vasc Pharmacol 2007; 5: 141-154.
• 19 Haluzik M, Nedvidkova J, Bartak V. et al. Effects of hypo- and hyperthyroidism on noradrenergic activity and glycerol concentrations in human subcutaneous abdominal adipose tissue assessed with microdialysis. J Clin Endocrinol Metab 2003; 88: 5605-5608.
• 20 Hauner H, Buchholz G, Hamann A. et al. Prävention und Therapie derAdipositas. Evidenzbasierte Leitlinie. Version. 2007
• 21 Heymsfield SB, Greenberg AS, Fujioka K. et al. Recombinant leptin for weight loss in obese and leanadults: arandomised, controlled, dose-escalating trial. JAMA 1999; 282: 1568-1575.
• 22 Iacobellis G, Ribaudo MC, Zappaterreno A. et al. Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women. Clin Endocrinol 2005; 62: 487-491.
• 23 Iglesias P, Diez JJ. Influence of thyroid dysfunction on serum concentrations of adipocytokines. Cytokine 2007; 40: 61-70.
• 24 Knudsen N, Laurberg P, Rasmussen LB. et al. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab 2005; 90: 4019-4024.
• 25 Kobe C, Eschner W, Sudbrock F. et al. Graves' disease and radioiodine therapy: is success of ablation dependent on the absorbed dose above 200 Gy?. Nuklearmedizin 2008; 47: 13-17.
• 26 Kobe C, Weber I, Eschner W. et al. Graves' disease and radioiodine therapy: Is success of ablation depend on the choice of thyrostatic medication?. Nuklearmedizin. 2008 47. doi: 10.3413/nukmed-0145.
• 27 Kok P, Roelfsema F, Langendonk JG. et al. Highcirculating thyrotropin levels in obese women are reduced by after body weight loss induced by caloric restriction. J Clin Endocrinol Metab 2005; 90: 4659-4663.
• 28 Kokoeva MV, Yin H, Flier JS. Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science 2005; 310: 679-683.
• 29 Lambert PD, Anderson KD, Sleeman MW. et al. Ciliary neurotropic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistent obesity. Proc Natl Acad Sci USA 2001; 98: 4652-4657.
• 30 Lönn L, Stenlöf K, Ottosohn M. et al. Body weight and body composition changes after treatment of hyperthyroidism. J Clin Endocrinol Metab 1998; 83: 4269-4273.
• 31 Lomenick JP, El-Sayyid M, Smith WJ. Effect of levo-thyroxine treatment on weight and body mass index in children with acquired hypothyroidism. J Pediatr 2008; 152: 96-100.
• 32 Manji N, Boelaert K, Sheppard MC. et al. Lack of association between serum TSH or free T4 and body mass index in euthyroid subjects. Clin Endocrinol 2006; 64: 125-128.
• 33 Misiolek M, Marek B, Namyslowski G. et al. Sleep apnea syndrome and snoring in patients with hypothyroidism with relation to overweight. J Physiol Pharmacol 2007; 58 (Suppl 1) 77-85.
• 34 Montague CT, Farooqi IS, Whitehead JP. et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387: 903-908.
• 35 Nyrnes A, Jorde R, Sundsfjor d. Serum TSH is positively associated with BMI. Int J Obes 2006; 30: 100-106.
• 36 Onur S, Haas V, Bosy-Westphal A. et al. L-T3 is a major determinant of resting energy expenditure in underweight patients with anorexianervosa and during weight gain. Eur J Endocrinol 2005; 152: 179-184.
• 37 Oppenheimer JH, Schwartz HL, Lane JT. et al. Functional relationship of thyroid hormone-induced lipogenesis, lipolysis, and thermogenesis in the rat. J Clin Invest 1991; 87: 125-132.
• 38 Pijl H, de Meijer PHEM, Langius J. et al. Food choice in hyperthyroidism. J Clin Endocrinol Metab 2001; 86: 5848-5853.
• 39 Reinehr T, de Sousa G, Andler W. Hyperthyrotropinemia in obese children is reversible after weight loss and is not related to lipids. J Clin Endocrinol Metab 2006; 91: 3088-3091.
• 40 Roos A, Bakker SJL, Links TP. et al. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab 2007; 92: 491-496.
• 41 Ruscica M, Dozio E, Gandini S. et al. Total, free and bound leptin and thyroid function in elderly women with different body weights. Clin Endocrinol (Oxf). 2007 Nov 19 epub.
• 42 Sari R, Balci MK, Altunbas H. et al. The effect ofbo- dy weight on thyroid volume and function in obese women. Clin Endocrinol (Oxf) 2003; 59: 258-262.
• 43 Scheidhauer K, Odatzidu L, Kiencke P. et al. Body weight gain after radioiodine therapy of hyperthyroidism. Nuklearmedizin 2002; 41: 47-51.
• 44 Seeley RJ. More neurons, less weight. Nature Med 2005; 11: 1276-1278.
• 45 Silva JE. The thermogenic effect of thyroid hormone and its clinical implications. Ann Intern Med 2003; 139: 205-213.
• 46 Spilker L, Happel C, Döbert N. et al. Is radioiodine therapy conducted too late in patients suffering from thyroid autonomy?. Nuklearmedizin 2008; 47: 8-12.
• 47 Tagliaferri M, Berselli ME, Calò G. et al. Subclinical hypothyroidism in obese patients: relation to resting energy expenditure, serum leptin, body composition, and lipid profile. Obes Res 2001; 9: 196-201.
• 48 Villicev CM, Freitas FRS, Aoki MS. et al. Thyroid hormone receptor β-specific agonist GC-1 increases energy expenditure and prevents fat-mass accumulation in rats. J Endocrinol 2007; 193: 21-29.
• 49 Welt CK, Chan JL, Bullen J. et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 2004; 351: 987-997.