Elevated thyroid stimulating hormone is associated with elevated cortisol in healthy young men and women

Thyroid Research - 2012
Kimberly N. Walter1, Elizabeth J. Corwin2, Jan S. Ulbrecht1, Laurence M. Demers1, Jeanette M. Bennett1, Courtney A. Whetzel1, Laura Cousino Klein1
1Department of Biobehavioral Health, The Pennsylvania State University, 219 Biobehavioral Health Bldg, University Park, PA, 16802, USA
2Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, 30322, USA

Tóm tắt

Abstract Background Recent attention has been given to subclinical hypothyroidism, defined as an elevation of TSH (4.5-10 uIU/L) with T4 and T3 levels still within the normal range. Controversy exists about the proper lower limit of TSH that defines patients in the subclinical hypothyroidism range and about if/when subclinical hypothyroidism should be treated. Additional data are needed to examine the relationship between markers of thyroid function in the subclinical hypothyroidism range, biomarkers of health and ultimately health outcomes. Objective We aimed to assess the relationship between serum TSH levels in the 0.5-10 uIU/L range and serum cortisol in a cohort of healthy young men and women without clinical evidence of hypothyroidism. Based on data in frank hypothyroidism, we hypothesized that serum TSH levels would be positively correlated with serum cortisol levels, suggesting derangement of the cortisol axis even in subclinical hypothyroidism. Methods We conducted a cross sectional study in 54 healthy, young (mean 20.98 +/− 0.37 yrs) men (19) and women (35). Lab sessions took place at 1300 hrs where blood was drawn via indwelling catheter for later assessment of basal serum TSH, free T3, free T4, and cortisol levels. Results All but 1 participant had free T3 levels within the normal reference intervals; free T4 levels for all participants were within the normal reference intervals. Linear regression modeling revealed that TSH levels in the 0.5-10 uIU/L were significantly and positively correlated with cortisol levels. This positive TSH-cortisol relationship was maintained below the accepted 4.5 uIU/L subclinical hypothyroid cutoff. Separate regression analyses conducted by systematically dropping the TSH cutoff by 0.50 uIU/L revealed that the TSH-cortisol relationship was maintained for TSH levels (uIU/L) ≤4.0, ≤3.5, ≤3.0, and ≤2.5 but not ≤2.0. Linear regression modeling did not reveal a relationship between free T3 or free T4 levels and cortisol levels. Conclusions Results suggest a positive relationship between TSH and cortisol in apparently healthy young individuals. In as much as this relationship may herald a pathologic disorder, these preliminary results suggest that TSH levels > 2.0 uIU/L may be abnormal. Future research should address this hypothesis further, for instance through an intervention study.

Từ khóa


Tài liệu tham khảo

Boelaert K, Franklyn JA: Thyroid hormone in health and disease. J Endocrinol 2005, 187: 1–15. 10.1677/joe.1.06131

Canaris GJ, Manowitz NR, Mayor G, Ridgway EC: The Colorado thyroid disease prevalence study. Arch Intern Med 2000, 160: 526–534. 10.1001/archinte.160.4.526

Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE: Serum TSH, T-4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metabol 2002, 87: 489–499. 10.1210/jc.87.2.489

Demers LM, Spencer CA (Eds): Laboratory Medicine Practice Guidelines: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease. Washington, DC: National Academy of Clinical Biochemistry; 2002. www.nacb.org

Fatourechi V: Subclinical Hypothyroidism: An Update for Primary Care Physicians. Mayo Clin Proc 2009, 84: 65–71. 10.4065/84.1.65

Spencer CA, Hollowell JG, Kazarosyan M, Braverman LE: National health and nutrition examination survey III thyroid-stimulating hormone (TSH)-thyroperoxidase antibody relationships demonstrate that TSH upper reference limits may be skewed by occult thyroid dysfunction. J Clin Endocrinol Metabol 2007, 92: 4236–4240. 10.1210/jc.2007-0287

Surks MI, Goswami G, Daniels GH: The thyrotropin reference range should remain unchanged. J Clin Endocrinol Metabol 2005, 90: 5489–5496. 10.1210/jc.2005-0170

Wartofsky L, Dickey RA: The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metabol 2005, 90: 5483–5488. 10.1210/jc.2005-0455

Roberts CGP, Ladenson PW: Hypothyroidism. Lancet 2004, 363: 793–803. 10.1016/S0140-6736(04)15696-1

Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, Franklyn JA, Hershman JM, Burman KD, Denke MA, Gorman C, Cooper RS, Weissman NJ: Subclinical thyroid disease - Scientific review and guidelines for diagnosis and management. J Am Med Assoc 2004, 291: 228–238. 10.1001/jama.291.2.228

Iranmanesh A, Lizarralde G, Johnson ML, et al.: Dynamics of 24-hour endogenous cortisol secretion and clearance in primary hypothyroidism assessed before and after partial thyroid hormone replacement. J Clin Endocrinol Metabol 1990, 70: 155–161. 10.1210/jcem-70-1-155

Kirschbaum C, Kudielka BM, Gaab J, Schommer NC, Hellhammer DH: Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosom Med 1999, 61: 154–162.

McHale SM, Blocklin MK, Walter KN, Davis KD, Almeida DM, Klein LC: The role of daily activities in youth’s stress physiology. J Adol Health 2012. [published online ahead of print May 16 2012]. http://dx.doi.org/10.1016/j.jadohealth.2012.03.016

Whetzel CA, Corwin EJ, Klein LC: Disruption in Th1/Th2 immune response in young adult smokers. Addict Behav 2007, 32: 1–8. 10.1016/j.addbeh.2006.03.007

Almeida C, Brasil MA, Costa AJL, Reis FAA, Reuters V, Teixeira P, Ferreira M, Marques AM, Melo BA, Teixeira L, Buescu A, Vaisman M: Subclinical hypothyroidism: psychiatric disorders and symptoms. Revista Brasileira De Psiquiatria. 2007, 29: 157–159. 10.1590/S1516-44462007000200013

Heffelfinger AK, Newcomer JW: Glucocorticoid effects on memory function over the human life span. Dev Psychopathol 2001, 13: 491–513. 10.1017/S0954579401003054

Sapolsky RM: Why stress is bad for your brain. Science 1996, 273: 749–750. 10.1126/science.273.5276.749

Bell RJ, Rivera-Woll L, Davison SL, Topliss DJ, Donath S, Davis SR: Well-being, health-related quality of life and cardiovascular disease risk profile in women with subclinical thyroid disease - a community-based study. Clin Endocrinol 2007, 66: 548–556.

Bartalena L, Martino E, Petrini L, Velluzzi F, Loviselli A, Grasso L, Mammoli C, Pinchera A: The nocturnal serum thyrotropin surge is abolished in patients with adrenocorticotropin (ACTH)-dependent or ACTH-independent Cushing’s syndrome. J Clin Endocrinol Metabol 1991, 72: 1195–1199. 10.1210/jcem-72-6-1195

Brabant G, Brabant A, Ranft U, Ocran K, Köhrle J, Hesch RD, von zur Mühlen A: Circadian and pulsatile thyrotropin secretion in euthyroid man under the influence of thyroid hormone and glucocorticoid administration. J Clin Endocrinol Metabol 1987, 65: 83–88. 10.1210/jcem-65-1-83

Samuels MH, Luther M, Henry P, Ridgway EC: Effects of hydrocortisone on pulsatile pituitary glycoprotein secretion. J Clin Endocrinol Metabol 1994, 78: 211–215. 10.1210/jc.78.1.211

Samuels MH, McDaniel PA: Thyrotropin levels during hydrocortisone infusions that mimic fasting-induced cortisol elevations—a clinical research center study. J Clin Endocrinol Metabol 1997, 82: 3700–3704. 10.1210/jc.82.11.3700

Samuels MH: Effects of variations in physiological cortisol levels on thyrotropin secretion in subjects with adrenal insufficiency: a clinical research center study. J Clin Endocrinol Metabol 2000, 85: 1388–1393. 10.1210/jc.85.4.1388

Samuels MH: Effects of metyrapone administration on thyrotropin secretion in healthy subjects—a clinical research center study. J Clin Endocrinal Metabol 2000, 85: 3049–3052. 10.1210/jc.85.9.3049

Thông tin
Thông tin xuất bản

Thyroid Research

Thông tin tác giả