Serum Thyroid-Stimulating Hormone Concentration and Morbidity from Cardiovascular Disease and Fractures in Patients on Long-Term Thyroxine Therapy

• Published in: The journal of clinical endocrinology and metabolism 2010-01, Vol.95 (1), p.186-193
• Main Authors: Flynn, Robert W, Bonellie, Sandra R, Jung, Roland T, MacDonald, Thomas M, Morris, Andrew D, Leese, Graham P
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Comorbidity; Endocrinopathies; Feeding. Feeding behavior; Female; Fractures, Bone - blood; Fractures, Bone - epidemiology; Fractures, Bone - etiology; Fundamental and applied biological sciences. Psychology; Hormone Replacement Therapy - adverse effects; Humans; Hypothyroidism - blood; Hypothyroidism - drug therapy; Hypothyroidism - epidemiology; Male; Medical sciences; Middle Aged; Osmolar Concentration; Osteoporosis - blood; Osteoporosis - complications; Osteoporosis - epidemiology; Thyrotropin - blood; Thyroxine - adverse effects; Thyroxine - therapeutic use; Time Factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2009-1625

Context: For patients on T4 replacement, the dose is guided by serum TSH concentrations, but some patients request higher doses due to adverse symptoms. Objective: The aim of the study was to determine the safety of patients having a low but not suppressed serum TSH when receiving long-term T4 replacement. Design: We conducted an observational cohort study, using data linkage from regional datasets between 1993 and 2001. Setting: A population-based study of all patients in Tayside, Scotland, was performed. Patients: All patients taking T4 replacement therapy (n = 17,684) were included. Main Outcome Measures: Fatal and nonfatal endpoints were considered for cardiovascular disease, dysrhythmias, and fractures. Patients were categorized as having a suppressed TSH (≤0.03 mU/liter), low TSH (0.04–0.4 mU/liter), normal TSH (0.4–4.0 mU/liter), or raised TSH (>4.0 mU/liter). Results: Cardiovascular disease, dysrhythmias, and fractures were increased in patients with a high TSH: adjusted hazards ratio, 1.95 (1.73–2.21), 1.80 (1.33–2.44), and 1.83 (1.41–2.37), respectively; and patients with a suppressed TSH: 1.37 (1.17–1.60), 1.6 (1.10–2.33), and 2.02 (1.55–2.62), respectively, when compared to patients with a TSH in the laboratory reference range. Patients with a low TSH did not have an increased risk of any of these outcomes [hazards ratio: 1.1 (0.99–1.123), 1.13 (0.88–1.47), and 1.13 (0.92–1.39), respectively]. Conclusions: Patients with a high or suppressed TSH had an increased risk of cardiovascular disease, dysrhythmias, and fractures, but patients with a low but unsuppressed TSH did not. It may be safe for patients treated with T4 to have a low but not suppressed serum TSH concentration. It may be safe for patients on thyroxine replacement to have a low but not suppressed TSH.