Clinical trial NCT02399475: Mechanistic Study of Subclinical Hypothyroidism In the Elderly
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Subclinical Hypothyroidism
Keywords: Levothyroxine
Liothyronine
Thyrotropin Releasing Hormone
Aging
Hypothyroidism
Thyroid diseases
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2015-03-26
Enrollment: 14
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.


Eligibility 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 involving the jejunum and upper ileum
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. chronic or ongoing angina, 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

Primary outcomes:
measure: TSH Area Under the Curve
timeFrame: 0, 5, 10, 15, 20, 30, and 60 min post TRH
measure: TSH Max
timeFrame: Between 0 and 180 min after TRH stimulation
measure: Free T4 Level
timeFrame: An average of 7 months after initiating therapy
measure: Total T3 Level
timeFrame: An average of 7 months
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: The University of Pennsylvania
name: Anne R Cappola, MD, ScM
role: PRINCIPAL_INVESTIGATOR
References: