A Rare Case of Partial Peripheral Thyroid Hormone Resistance Due to a Point Mutation in the Membrane Integrin Α(V)Β(3) and Concomitant Hashimoto`s Thyroiditis


  • Martina Savovska Student
  • Sinisa Stojanoski Institute for Pathophysiology and Nuclear medicine ``Isak Tadzer``, University of ``St. Cyril and Methodius``, Medical faculty – Skopje, R. Macedonia
  • Nevena Manevska Institute for Pathophysiology and Nuclear medicine ``Isak Tadzer``, University of ``St. Cyril and Methodius``, Medical faculty – Skopje, R. Macedonia




peripheral resistance, hypothyroidism, secondary hyperthyroidism, Hashimoto’s thyroiditis


BACKGROUND: Peripheral resistance to thyroid hormones is a type of unresponsiveness of the peripheral cells or tissues to FT3 and/or FT4. Generalised resistance to thyroid hormones affects the pituitary gland and most of the peripheral tissues. Selective pituitary resistance or central resistance to thyroid hormones include unresponsiveness of the pituitary gland, but the peripheral tissues are responsive. Selective peripheral resistance involves peripheral tissue or cellular resistance to thyroid hormones, but the pituitary gland is responsive.
CASE PRESENTATION: We present a rare case of a female patient with partial peripheral resistance to thyroid hormones due to a point mutation coding for the beta subunit of the integrin molecule α(V)β(3) and concomitant Hashimoto`s thyroiditis. Clinically, the patient`s symptoms were in favour of hypothyroidism, and the laboratory results were in favour of the secondary hyperthyroid state. PCR protein amplification detected a point mutation coding for the membrane receptor, which mediates a signal via the MAPK pathway when bonded with thyroid hormones.
CONCLUSION: Peripheral resistance to thyroid hormones is a very rare condition and can often be misdiagnosed due to the broad spectrum of clinically similar differential diagnostic entities. Molecular analysis is required to confirm the exact underlying cause for the impaired peripheral sensitivity to thyroid hormones syndrome.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Bianco, AC, Kim BS. Pathophysiological relevance of deiodinase polymorphism. Curr Opin Endocrinol Diabetes Obes. 2018; 25(5):341-346.

Singh BK, Sinha RA, Yen PM. Novel transcriptional mechanisms for regulating metabolism by thyroid hormone. Int J Mol Sci. 2018; 19(10): 3284. https://doi.org/10.3390/ijms19103284 PMid:30360449 PMCid:PMC6214012

Cyril S. Anyetei-Anum, Vincent R. Roggero, Lizabeth A. Allison. Thyroid hormone receptor localization in target tissues. J Endocrinol. 2018; 237(1):19-34. https://doi.org/10.1530/JOE-17-0708 PMid:29440347 PMCid:PMC5843491

Rohit A. Sinha, Brijesh K. Singh, Paul M. Yen. Direct effects of thyroid hormones on hepatic lipid metabolism. Nat Rev Endocrinol. 2018; 14(5):259-269. https://doi.org/10.1038/nrendo.2018.10 PMid:29472712 PMCid:PMC6013028

Refetoff S. et al. Classification and Proposed Nomenclature for Inherited Defects of Thyroid Hormone Action, Cell Transport, and Metabolism. Thyroid. 2014; 24(3):407-409. https://doi.org/10.1089/thy.2013.3393.nomen PMid:24588711 PMCid:PMC3950730

Takada Y, Ye X, Simon S. The integrins. Genome Biology. 2007; 8:215. https://doi.org/10.1186/gb-2007-8-5-215 PMid:17543136 PMCid:PMC1929136

Leith JT, Mousa SA, Hercbergs A, Lin HY, Davis PJ. Radioresistance of cancer cells, integrin αvβ3 and thyroid hormone. Oncotarget. 2018; 9(97):37069. https://doi.org/10.18632/oncotarget.26434 PMid:30651936 PMCid:PMC6319341

Krashin E, Piekiełko-Witkowska A, Ellis M, Ashur-Fabian O. Thyroid hormones and cancer: A comprehensive review of preclinical and clinical studies. Frontiers in endocrinology. 2019;10. https://doi.org/10.3389/fendo.2019.00059 PMid:30814976 PMCid:PMC6381772

Weiss RE, Weinberg M, Refetoff S. Identical mutations in unrelated families with generalized resistance to thyroid hormone occur in cytosine-guanine-rich areas of the thyroid hormone receptor beta gene. Analysis of 15 families. J Clin Invest. 1993; 91 (6): 2408-2415. https://doi.org/10.1172/JCI116474 PMid:8514853 PMCid:PMC443299

McDermott MT, Ridgway EC. Thyroid hormone resistance syndromes. Am J Med. 1993; 94 (4): 424-432. https://doi.org/10.1016/0002-9343(93)90155-I

Dumitrescu AM, Refetoff S. The syndromes of reduced sensitivity to thyroid hormone. Biochim Biophys Acta. 2013; 1830 (7): 3987-4003. https://doi.org/10.1016/j.bbagen.2012.08.005 PMid:22986150 PMCid:PMC3528849

Gonçalves AP, Aragüés JM, Nobre E, Barbosa AP, Mascarenhas M. A case of thyroid hormone resistance: a rare mutation. Arq Bras Endocrinol Metabol. 2014; 58(9): 962-966. https://doi.org/10.1590/0004-2730000003297 PMid:25627054

Fan W, Tandon P, Krishnamurthy M. Oscillating hypothyroidism and hyperthyroidism - a case-based review. 2014. J Community Hosp Intern Med Perspect. 2014; 4 (5): 10. https://doi.org/10.3402/jchimp.v4.25734 PMid:25432652 PMCid:PMC4246140

Wong M, Inder W. Alternating hyperthyroidism and hypothyroidism in Graves' disease. Clin Case Rep. 2018 Sep; 6 (9): 1684-1688. https://doi.org/10.1002/ccr3.1700 PMid:30214742 PMCid:PMC6132101

Drummond J, Roncaroli F, Grossman AB, Korbonits M. Clinical and pathological aspects of silent pituitary adenomas. The Journal of Clinical Endocrinology & Metabolism. 2018; 104(7):2473-89. https://doi.org/10.1210/jc.2018-00688 PMid:30020466 PMCid:PMC6517166

De Leo S, Lee YS, Braverman EL. Hyperthyroidism. Lancet. 2016; 388 (10047): 906-918. https://doi.org/10.1016/S0140-6736(16)00278-6

Teng X, Jin T, Brent GA, Wu A, Teng W, Shan Z. A patient with a thyrotropin-secreting microadenoma and resistance to thyroid hormone (P453T) J Clin Endocrinol Metab. 2015; 100(7):2511-2514. https://doi.org/10.1210/jc.2014-3994 PMid:25867808 PMCid:PMC5393528

Kobayashi S, Yoshimura Noh J, Shimizu T, Sato T, Kurihara I, Sugino K, Itoh H, Ito K. A case of familial dysalbuminemic hyperthyroxinemia (FDH) in Japan: FDH as a possible differential diagnosis of syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH). Endocr J. 2017; 64: 207-212. https://doi.org/10.1507/endocrj.EJ16-0135 PMid:27904073

Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiological reviews. 2014; 94(2):355-82. https://doi.org/10.1152/physrev.00030.2013 PMid:24692351 PMCid:PMC4044302

Jiao Fu, Alexandra M. Dumitrescu. Inherited defects in thyroid hormone cell-membrane transport and metabolism. Best Pract Res Clin Endocrinol Metab. 2014 March; 28 (2): 189-201. https://doi.org/10.1016/j.beem.2013.05.014 PMid:24629861 PMCid:PMC3959653

Rivas MA, Lado-Abeal J. Thyroid hormone resistance and its management. Proc (Bayl Univ Med Cent). 2016; 29:209-211. https://doi.org/10.1080/08998280.2016.11929421 PMid:27034574



How to Cite

Savovska M, Stojanoski S, Manevska N. A Rare Case of Partial Peripheral Thyroid Hormone Resistance Due to a Point Mutation in the Membrane Integrin Α(V)Β(3) and Concomitant Hashimoto`s Thyroiditis. Open Access Maced J Med Sci [Internet]. 2019 Jun. 29 [cited 2023 Dec. 6];7(12):1991-7. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2019.582



C- Case Reports

Most read articles by the same author(s)