Abnormal Thyroid Stimulating Hormone Values That Are Not due to Common Causes of Primary Hypothyroidism or Thyrotoxicosis

  • Zsu-Zsu ChenEmail author
  • James V. Hennessey


Thyroid stimulating hormone (TSH) levels are now commonly used as the initial screening lab to assess thyroid function in patients. However, it is important for the clinician to remember that not all abnormal serum TSH values are due to common causes of primary hypothyroidism or thyrotoxicosis. Some are due to normal physiology, like TSH level variability due to age and ethnicity, or due to issues surrounding laboratory measurement of serum TSH. Other abnormal values can be transient and do not require thyroid replacement or ablative treatment, such as nonthyroidal illness. Still other causes, such as central hypothyroidism or a TSH secreting pituitary adenoma, once diagnosed will require further hormonal evaluation and possible genetic workup. It is important to have the correct differential diagnosis so that the appropriate diagnostic workup and treatment plan can be pursued. This chapter will give an overview of the different causes of abnormal serum TSH values not due to primary thyroid dysfunction (several of which are outlined in Fig. 6.1). It will also briefly discuss the clinical symptoms, biochemical findings, and treatment for these conditions.


Thyroid stimulating hormone TSH abnormalities Low TSH High TSH TSH normal range Age effect on TSH Ethnicity effect on TSH TSH heterophile antibody TSH autoantibodies Biotin Amiodarone Iodine Nonthyroidal illness Sick euthyroid Central hypothyroidism Isolated central hypothyroidism Combined congenital hypothyroidism Resistance to TSH Thyrotropin-releasing hormone Resistance to TRH Thyroid hormone resistance THR mutation TSH secreting tumor 

Suggested Reading

  1. Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, et al. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncol. 2018;4(2):173–82.CrossRefGoogle Scholar
  2. Beck-Peccoz P, Rodari G, Giavoli C, Lania A. Central hypothyroidism - a neglected thyroid disorder. Nat Rev Endocrinol. 2017;13:588–98.CrossRefGoogle Scholar
  3. Bonomi M, Busnelli M, Beck-Peccoz P, Costanzo D, Antonica F, Dolci C, et al. A Family with Complete Resistance to Thyrotropin-Releasing Hormone. N Engl J Med. 2009;360(7):731–4.CrossRefGoogle Scholar
  4. Demir K, van Gucht ALM, Büyükinan M, Çatlı G, Ayhan Y, Baş VN, et al. Diverse Genotypes and Phenotypes of Three Novel Thyroid Hormone Receptor-α Mutations. J Clin Endocrinol Metab. 2016;101(8):2945–54.CrossRefGoogle Scholar
  5. Estrada JM, Soldin D, Buckey TM, Burman KD, Soldin OP. Thyrotropin isoforms: implications for thyrotropin analysis and clinical practice. Thyroid. 2014;24(3):411–23.CrossRefGoogle Scholar
  6. Fliers E, Bianco AC, Langouche L, Boelen A. Endocrine and metabolic considerations in critically ill patients 4. Lancet Diabetes Endocrinol. 2015;3(10):816–25.CrossRefGoogle Scholar
  7. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18(6):988–1028.CrossRefGoogle Scholar
  8. Piketty M-L, Polak M, Flechtner I, Gonzales-Briceño L, Souberbielle J-C. False biochemical diagnosis of hyperthyroidism in streptavidin-biotin-based immunoassays: the problem of biotin intake and related interferences. Clin Chem Lab Med. 2017;55(6):780–8.CrossRefGoogle Scholar
  9. Refetoff S, Weiss RE, Usala SJ. The syndromes of resistance to thyroid hormone. Endocr Rev. 1993;14(3):348–99.PubMedGoogle Scholar
  10. Tenenbaum-Rakover Y, Almashanu S, Hess O, Admoni O, Hag-Dahood Mahameed A, Schwartz N, et al. Long-term outcome of loss-of-function mutations in thyrotropin receptor gene. Thyroid. 2015;25(3):292–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Beth Israel Deaconess Medical Center, Department of Endocrinology, Diabetes and MetabolismBostonUSA
  2. 2.Beth Israel Deaconess Medical Center, Harvard Medical School, Division of Endocrinology, Diabetes and MetabolismBostonUSA

Personalised recommendations