High Ghrelin Levels in Post-treatment Euthyroid Patients with Hashimoto’s Thyroiditis: a Case-control Preliminary Study

N. Malandrino; A. Miceli; L. Leggio; G. Mingrone; E. Capristo

doi:10.1055/s-0034-1376965

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2014; 122(09): 540-543
DOI: 10.1055/s-0034-1376965

Article

High Ghrelin Levels in Post-treatment Euthyroid Patients with Hashimoto’s Thyroiditis: a Case-control Preliminary Study

N. Malandrino

¹Institute of Internal Medicine, Metabolic Diseases Outpatient Unit, Catholic University of Rome, Rome, Italy

,

A. Miceli

²Humanitas Clinical and Research Center, Rozzano (MI), Italy

,

L. Leggio

³Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism (NIAAA), NIH, Bethesda, Maryland, USA; Intramural Research Program, National Institute on Drug Abuse (NIDA), NIH, Baltimore, Maryland, USA; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, Rhode Island, USA

,

G. Mingrone

¹Institute of Internal Medicine, Metabolic Diseases Outpatient Unit, Catholic University of Rome, Rome, Italy

,

E. Capristo

¹Institute of Internal Medicine, Metabolic Diseases Outpatient Unit, Catholic University of Rome, Rome, Italy

› Author Affiliations

Abstract

Rationale: Hashimoto’s thyroiditis is a chronic inflammatory condition often associated with changes in appetite and body composition. Ghrelin is an orexigenic peptide involved in the regulation of appetite and food intake. A possible role of ghrelin in mediating inflammation has been suggested. A few contrasting published data are available on the relationship between thyroid status and circulating ghrelin in patients affected by Hashimoto’s thyroiditis. The aim of the present case-control study was to provide additional evidence on the relationship between thyroid status and plasma ghrelin levels in post-treatment euthyroid female patients with Hashimoto’s thyroiditis, compared to healthy controls.

Methods: 25 women [age 46.6±10.6 years; Body Mass Index 26.3±3.8 kg/m²] affected by overt hypothyroidism due to Hashimoto’s thyroiditis were studied after thyroid hormones and body weight were already normalized for at least 2 months following L-thyroxine replacement. 25 healthy women (age 40.2±6.4 years; Body Mass Index 26.2±4.0 kg/m²) served as the control group. Blood levels of thyroid hormones, thyroid peroxidase antibodies, thyroglobulin antibodies and ghrelin were determined. Fat mass, fat-free mass and high-density lipoprotein cholesterol were also assessed.

Results: Circulating ghrelin levels were significantly higher in patients vs. control subjects (p<0.001). No differences were found in metabolic parameters (body mass index, fat mass, fat-free mass, high-density lipoprotein cholesterol) between groups.

Conclusion: The present study provides additional evidence of hyperghrelinemia status in post-treatment euthyroid patients affected by Hashimoto’s thyroiditis.

Key words

ghrelin - thyroid hormones - Hashimoto’s thyroiditis - inflammation - metabolism

Full Text

References

References
1 Seppel T, Kosel A, Schlaghecke R. Bioelectrical impedance assessment of body composition in thyroid disease. Eur J Endocrinol 1997; 136: 493-498
2 Langdahl BL, Loft AG, Eriksen EF et al. Bone mass, bone turnover and body composition in former hypothyroid patients receiving replacement therapy. Eur J Endocrinol 1996; 134: 702-709
3 Kojima M, Hosoda H, Date Y et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402: 656-660
4 Korbonits M, Kojima M, Kangawa K et al. Presence of ghrelin in normal and adenomatous human pituitary. Endocrine 2001; 14: 101-104
5 Gnanapavan S, Kola B, Bustin SA et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 2002; 87: 2988-2991
6 Baldanzi G, Filigheddu N, Cutrupi S et al. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol 2002; 23: 1029-1037
7 Gualillo O, Caminos J, Blanco M et al. Ghrelin, a novel placental-derived hormone. Endocrinology 2001; 142: 788-794
8 Date Y, Nakazato M, Hashiguchi S et al. Ghrelin is present in pancreatic α-cells of humans and rats and stimulates insulin secretion. Diabetes 2002; 51: 124-129
9 Mori K, Yoshimoto A, Takaya K et al. Kidney produces a novel acylated peptide, ghrelin. FEBS Letters 2000; 486: 213-216
10 Tena-Sempere M, Barreiro ML, González LC et al. Novel expression and functional role of ghrelin in rat testis. Endocrinology 2002; 143: 717-725
11 Wren AM, Seal LJ, Cohen MA et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001; 86: 5992-5995
12 Wren AM, Small CJ, Ward HL et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000; 141: 4325-4328
13 Dhillo WS, Bloom SR. Gastrointestinal hormones and regulation of food intake. Horm Metab Res 2004; 36: 846-851
14 Sainsbury A, Cooney G, Herzog H. Hypothalamic regulation of energy homeostasis. Best Practice & Research Clinical Endocrinology and Metabolism 2002; 16: 623-637
15 Shintani M, Ogawa Y, Ebihara K et al. Ghrelin an endogenous growth hormone secretagogue is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 2001; 50: 227-232
16 Hattori N, Saito T, Yagyu T et al. GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J Clin Endocrinol Metab 2001; 86: 4284-4291
17 Dixit VD, Schaffer EM, Pyle RS et al. Ghrelin inhibits leptin- and activation induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest 2004; 114: 57-66
18 Capristo E, Farnetti S, Mingrone G et al. Reduced plasma ghrelin concentration in celiac disease after gluten-free diet treatment. Scand J Gastroenterol 2005; 40: 430-436
19 Karmiris K, Koutroubakis IE, Xidakis C et al. Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease. Inflamm Bowel Dis 2006; 12: 100-105
20 Toussirot E, Streit G, Nguyen NU et al. Adipose tissue, serum adipokines, and ghrelin in patients with ankylosing spondylitis. Metabolism 2007; 56: 1383-1389
21 Berilgen MS, Bulut S, Ustundag B et al. Patients with multiple sclerosis have higher levels of serum ghrelin. Neuro Endocrinol Lett 2005; 26: 819-822
22 Maruna P, Gurlich R, Frasko R et al. Ghrelin and leptin elevation in postoperative intra-abdominal sepsis. Eur Surg Res 2005; 37: 354-359
23 Caminos JE, Seoane LM, Tovar SA et al. Influence of thyroid status and growth hormone deficiency on ghrelin. European Journal of Endocrinology 2002; 147: 159-163
24 Kokkinos A, Mourouzis I, Kyriaki D et al. Possible implications of leptin, adiponectin and ghrelin in the regulation of energy homeostasis by thyroid hormone. Endocrine 2007; 32: 30-32
25 Biyikli HH, Arduc A, Isik S et al. Assessing the Relationship between Serum Ghrelin Levels and Metabolic Parameters and Autoimmunity in Patients with Euthyroid Hashimoto’s Thyroiditis. Endocr Pract 2014;
26 Emami A, Nazem R, Hedayati M. Is association between thyroid hormones and gut peptides, ghrelin and obestatin, able to suggest new regulatory relation between the HPT axis and gut?. Regul Pept 2014; 189C: 17-21
27 Altinova AE, Toruner F, Karakoc A et al. Serum Ghrelin Levels in patients with Hashimoto’s thyroiditis. Thyroid 2006; 16: 1259-1264
28 Giménez-Palop O, Giménez-Pérez G, Mauricio D et al. Circulating ghrelin in thyroid dysfunction is related to insulin resistance and not to hunger, food intake or anthropometric changes. Eur J Endocrinol 2005; 153: 73-79
29 Tanda ML, Lombardi V, Genovesi M et al. Plasma total and acylated ghrelin concentrations in patients with clinical and subclinical thyroid dysfunction. J Endocrinol Invest 2009; 32: 74-78
30 Gjedde S, Vestergaard ET, Gormsen LC et al. Serum ghrelin levels are increased in hypothyroid patients and become normalized by L-thyroxine treatment. J Clin Endocrinol Metab 2008; 93: 2277-2280
31 Brąclik M, Marcisz C, Giebel S et al. Serum leptin and ghrelin levels in premenopausal women with stable body mass index during treatment of thyroid dysfunction. Thyroid 2008; 18: 545-550
32 Kosowicz J, Baumann-Antczak A, Ruchała M et al. Thyroid hormones affect plasma ghrelin and obestatin levels. Horm Metab Res 2011; 43: 121-125
33 Gurgul E, Ruchała M, Kosowicz J et al. Ghrelin and obestatin in thyroid dysfunction. Endokrynol Pol 2012; 63: 456-462
34 Schmidt M, Voell M, Rahlff I et al. Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) treated with levothyroxine. Thyroid 2008; 18: 755-760
35 Barkan AL, Dimaraki EV, Jessup SK et al. Ghrelin secretion in humans is sexually dimorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels. J Clin Endocrinol Metab 2003; 88: 2180-2184
36 Beaumont NJ, Skinner VO, Tan TM et al. Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase. J Biol Chem 2003; 278: 8877-8880
37 Vestergaard ET, Hansen TK, Gormsen LC et al. Constant intravenous ghrelin infusion in healthy young men: clinical pharmacokinetics and metabolic effects. Am J Physiol Endocrinol Metab 2007; 292: E1829-E1836
38 Larsen PR, Davies TF. Hypothyroidism and thyroiditis. In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS. (eds.). Williams Textbook of Endocrinology. Elsevier Science (USA). Press; Philadelphia: 2003: 423-449
39 Saravanan P, Chau WF, Roberts N et al. 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: 577-585
40 Ruhla S, Arafat AM, Osterhoff M et al. Levothyroxine medication is associated with adiposity independent of TSH. Exp Clin Endocrinol Diabetes 2012; 120: 351-354
41 Hoogwerf BJ, Nuttall FQ. Long-term weight regulation in treated hyperthyroid and hypothyroid subjects. Am J Med 1984; 76: 963-970
42 Tamboli RA, Breitman I, Marks-Shulman PA et al. Early weight regain after gastric bypass does not affect insulin sensitivity but is associated with elevated ghrelin. Obesity (Silver Spring) 2014;