Thyroid Abnormalities in Patients With Extreme Insulin Resistance Syndromes

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2019 Jan 19

PMID 30657911

Citations 9

Authors

Yevgeniya S Kushchayeva

Sergiy V Kushchayev

Megan Startzell

Elaine Cochran

Sungyoung Auh

Yuhai Dai

Marissa Lightbourne

Monica Skarulis

Rebecca J Brown

Affiliations

Soon will be listed here.

Abstract

Context: Insulin and leptin may increase growth and proliferation of thyroid cells, underlying an association between type 2 diabetes and papillary thyroid cancer (PTC). Patients with extreme insulin resistance due to lipodystrophy or insulin receptor mutations (INSR) are treated with high-dose insulin and recombinant leptin (metreleptin), which may increase the risk of thyroid neoplasia.

Objective: The aim of this study was to analyze thyroid structural abnormalities in patients with lipodystrophy and INSR mutations and to assess whether insulin, IGF-1, and metreleptin therapy contribute to the thyroid growth and neoplasia in this population.

Design: Thyroid ultrasound characteristics were analyzed in 81 patients with lipodystrophy and 11 with INSR (5 homozygous; 6 heterozygous). Sixty patients were taking metreleptin.

Results: The prevalence of thyroid nodules in children with extreme insulin resistance (5 of 30, 16.7%) was significantly higher than published prevalence for children (64 of 3202; 2%), with no difference between lipodystrophy and INSR. Body surface area-adjusted thyroid volume was larger in INSR homozygotes vs heterozygotes or lipodystrophy (10.4 ± 5.1, 3.9 ± 1.5, and 6.2 ± 3.4 cm2, respectively. Three patients with lipodystrophy and one INSR heterozygote had PTC. There were no differences in thyroid ultrasound features in patients treated vs not treated with metreleptin.

Conclusion: Children with extreme insulin resistance had a high prevalence of thyroid nodules, which were not associated with metreleptin treatment. Patients with homozygous INSR mutation had thyromegaly, which may be a novel phenotypic feature of this disease. Further studies are needed to determine the etiology of thyroid abnormalities in patients with extreme insulin resistance.

Citing Articles

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INSULIN RESISTANCE AND PATHOGENESIS OF POSTMENOPAUSAL OSTEOPOROSIS.

Greere D, Grigorescu F, Manda D, Lautier C, Poiana C Acta Endocrinol (Buchar). 2024; 19(3):349-363.

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The Relationship between Thyroid-Stimulating Hormone and Insulin Resistance in Incipient Elderly Type 2 Diabetics with Normal Thyroid Function.

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Thyroid Function Alteration in Obesity and the Effect of Bariatric Surgery.

Cordido M, Juiz-Valina P, Urones P, Sangiao-Alvarellos S, Cordido F J Clin Med. 2022; 11(5).

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References

Kimura T, Dumont J, Fusco A, Golstein J . Insulin and TSH promote growth in size of PC Cl3 rat thyroid cells, possibly via a pathway different from DNA synthesis: comparison with FRTL-5 cells. Eur J Endocrinol. 1999; 140(1):94-103. DOI: 10.1530/eje.0.1400094. View

Dang C, Semenza G . Oncogenic alterations of metabolism. Trends Biochem Sci. 1999; 24(2):68-72. DOI: 10.1016/s0968-0004(98)01344-9. View

Deleu S, Pirson I, Coulonval K, Drouin A, Taton M, Clermont F . IGF-1 or insulin, and the TSH cyclic AMP cascade separately control dog and human thyroid cell growth and DNA synthesis, and complement each other in inducing mitogenesis. Mol Cell Endocrinol. 1999; 149(1-2):41-51. DOI: 10.1016/s0303-7207(99)00005-2. View

Kasagi K, Shimatsu A, Miyamoto S, Misaki T, Sakahara H, Konishi J . Goiter associated with acromegaly: sonographic and scintigraphic findings of the thyroid gland. Thyroid. 1999; 9(8):791-6. DOI: 10.1089/thy.1999.9.791. View

Szanto I, Kahn C . Selective interaction between leptin and insulin signaling pathways in a hepatic cell line. Proc Natl Acad Sci U S A. 2000; 97(5):2355-60. PMC: 15805. DOI: 10.1073/pnas.050580497. View

van den Brandt P, Spiegelman D, Yaun S, Adami H, Beeson L, Folsom A . Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol. 2000; 152(6):514-27. DOI: 10.1093/aje/152.6.514. View

WERTHEIMER E, Shen S, Bak A, Accili D, Sampson S . Increased IGFR activity and glucose transport in cultured skeletal muscle from insulin receptor null mice. Am J Physiol Endocrinol Metab. 2001; 281(1):E16-24. DOI: 10.1152/ajpendo.2001.281.1.E16. View

Clement S, Refetoff S, Robaye B, Dumont J, Schurmans S . Low TSH requirement and goiter in transgenic mice overexpressing IGF-I and IGF-Ir receptor in the thyroid gland. Endocrinology. 2001; 142(12):5131-9. DOI: 10.1210/endo.142.12.8534. View

Seto-Young D, Zajac J, Liu H, Rosenwaks Z, Poretsky L . The role of mitogen-activated protein kinase in insulin and insulin-like growth factor I (IGF-I) signaling cascades for progesterone and IGF-binding protein-1 production in human granulosa cells. J Clin Endocrinol Metab. 2003; 88(7):3385-91. DOI: 10.1210/jc.2002-021965. View

10.

Cochran E, Musso C, Gorden P . The use of U-500 in patients with extreme insulin resistance. Diabetes Care. 2005; 28(5):1240-4. DOI: 10.2337/diacare.28.5.1240. View

11.

Garofalo C, Surmacz E . Leptin and cancer. J Cell Physiol. 2005; 207(1):12-22. DOI: 10.1002/jcp.20472. View

12.

Fruhbeck G . Intracellular signalling pathways activated by leptin. Biochem J. 2005; 393(Pt 1):7-20. PMC: 1383660. DOI: 10.1042/BJ20051578. View

13.

Taniguchi C, Emanuelli B, Kahn C . Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol. 2006; 7(2):85-96. DOI: 10.1038/nrm1837. View

14.

Slaaby R, Schaffer L, Lautrup-Larsen I, Andersen A, Shaw A, Mathiasen I . Hybrid receptors formed by insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant. J Biol Chem. 2006; 281(36):25869-74. DOI: 10.1074/jbc.M605189200. View

15.

Irwin R, Lin H, Motyl K, McCabe L . Normal bone density obtained in the absence of insulin receptor expression in bone. Endocrinology. 2006; 147(12):5760-7. DOI: 10.1210/en.2006-0700. View

16.

Rezzonico J, Rezzonico M, Pusiol E, Pitoia F, Niepomniszcze H . Introducing the thyroid gland as another victim of the insulin resistance syndrome. Thyroid. 2008; 18(4):461-4. DOI: 10.1089/thy.2007.0223. View

17.

Kjeldsen T, Andersen A, Wiberg F, Rasmussen J, Schaffer L, Balschmidt P . The ligand specificities of the insulin receptor and the insulin-like growth factor I receptor reside in different regions of a common binding site. Proc Natl Acad Sci U S A. 1991; 88(10):4404-8. PMC: 51668. DOI: 10.1073/pnas.88.10.4404. View

18.

Gursoy A . Rising thyroid cancer incidence in the world might be related to insulin resistance. Med Hypotheses. 2009; 74(1):35-6. DOI: 10.1016/j.mehy.2009.08.021. View

19.

Zhang H, Zhang C . Adipose "talks" to distant organs to regulate insulin sensitivity and vascular function. Obesity (Silver Spring). 2010; 18(11):2071-6. PMC: 2946982. DOI: 10.1038/oby.2010.91. View

20.

Lu Z, Mu Y, Zhu H, Luo Y, Kong Q, Dou J . Clinical value of using ultrasound to assess calcification patterns in thyroid nodules. World J Surg. 2010; 35(1):122-7. DOI: 10.1007/s00268-010-0827-3. View