Mechanistic Study of Subclinical Hypothyroidism In the Elderly

Condition(s) targeted: Subclinical Hypothyroidism

Intervention: Levothyroxine (Drug); Liothyronine (Drug); Thyrotropin-Releasing Hormone (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: University of Pennsylvania

Official(s) and/or principal investigator(s):
Anne Cappola, MD, ScM, Principal Investigator, Affiliation: The University of Pennsylvania

Overall contact:
Paige Meizlik, MD, Phone: 215-746-1151, Email: paige.meizlik@uphs.upenn.edu

Subclinical hypothyroidism, defined as an elevated TSH in the setting of normal thyroid hormone levels, is a common diagnosis in the elderly. The purpose of this study is to examine the hypothalamic-pituitary-thyroid axis in men and women aged 70 years and older with persistent subclinical hypothyroidism. To evaluate the mechanism behind this condition, participants will undergo thyrotropin releasing hormone stimulation testing at 3 visits: baseline and while taking two different thyroid hormone preparations, levothyroxine and liothyronine. The investigators will also assess physiologic responses to these two different thyroid hormone medications to help us understand how the thyroid works in advanced age.

Official title: The Thyroid Axis in Older Individuals With Persistent Subclinical Hypothyroidism: a Mechanistic, Randomized, Double-Blind, Cross-Over Study of Levothyroxine and Liothyronine Administration

Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator)

Primary outcome:

TSH area under the curve

TSH Max

Free T4 Level

Total T3 Level

TSH bioactivity measurement

Secondary outcome:

Unstimulated TSH bioactivity

Resting energy expenditure (REE) evaluation

Weight

Body Fat Percent

Body Fat Total

Free Fat Mass

Bone Density

Lipid Profile

SF-36

Heart Rate

Physical Activity

Digit Symbol Substitution Test

Body Temperature

Hypothyroid Symptom Questionnaire

Minimum age: 70 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. men and women aged 70 and older 2. TSH between 4. 5 and 19. 9 mU/L as an outpatient 3. ability to provide informed consent Exclusion Criteria: Laboratory Tests: 1. TSH <4. 5 mU/L or >20 mU/L on repeat testing at least four weeks later or free T4 level outside the reference range 2. thyroid peroxidase (TPO) antibody positive 3. abnormal liver function tests (LFTs >3 x upper limit of normal) 4. hemoglobin <11 g/dL Surgeries or Procedures: 1. thyroid surgery 2. pituitary surgery 3. bariatric surgery 4. bowel resection 5. radioactive iodine therapy 6. radiation treatments to head or neck Medical Conditions: 1. diagnosis of pituitary disease 2. diagnosis of amyloidosis, sarcoidosis, hemochromatosis 3. diagnosis of adrenal insufficiency 4. obesity with BMI > 35 mg/kg2 5. history of stroke 6. history of myocardial infarction, coronary artery bypass graft surgery or percutaneous coronary angioplasty, angina, atrial fibrillation, Class II or higher congestive heart failure, or uncontrolled hypertension with current blood pressure greater than 160/100 7. diabetes mellitus with hemoglobin A1C level greater than 8. 0% in the past six months 8. celiac sprue, Crohn's disease, ulcerative colitis, Zollinger-Ellison syndrome 9. renal insufficiency with calculated glomerular filtration rate <45 cc/min 10. cognitive impairment with Mini Mental State Exam[30] <24/30 11. history of any seizures 12. unstable medical or psychological condition in the judgment of the principal investigator Medications: 1. thyroid hormone preparations 2. antithyroid drugs 3. medications that interfere with the absorption or metabolism of thyroid hormone 4. medications that interfere with the TRH stimulation test 5. proton pump inhibitors

Paige Meizlik, MD, Phone: 215-746-1151, Email: paige.meizlik@uphs.upenn.edu

University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States; Recruiting

Starting date: January 2015
Last updated: March 20, 2015