Mechanistic Study of Subclinical Hypothyroidism In the Elderly

Subclinical Hypothyroidism Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02399475
• Other study ID #: 821564
• Secondary ID: K24AG042765-01A1
• Status: Completed
• Phase: N/A
• Start date: January 1, 2015
• Est. completion date: September 30, 2019

Study information

• Verified date: February 2021
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: September 30, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypothyroidism
• Subclinical Hypothyroidism

Intervention

Drug:
• Levothyroxine
Oral levothyroxine with a total starting dose of 0.7mcg/kg/day split into three daily doses will be titrated to a target TSH level of 0.5 -1.5mU/L
• Liothyronine
Oral liothyronine with a starting dose of 1/3 of the weight-based LT4 dose divided into three daily doses titrated to a target TSH level of 0.5 -1.5mU/L
• Thyrotropin-Releasing Hormone
200 µg intravenous TRH will be given at study visit 1 (baseline), study visit 2 (on first thyroid treatment), and study visit 3 (on second thyroid treatment).

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TSH Area Under the Curve	TSH area under the curve within 60 minutes of TRH stimulation when TSH is at goal	0, 5, 10, 15, 20, 30, and 60 min post TRH
Primary	TSH Max	The maximum concentration of TSH after TRH stimulation when TSH is at goal	Between 0 and 180 min after TRH stimulation
Primary	Free T4 Level	Free thyroxine level when TSH level is at goal on therapy.	An average of 7 months after initiating therapy
Primary	Total T3 Level	Total triiodothyronine level when TSH is at goal on therapy	An average of 7 months