Mechanistic Study of Subclinical Hypothyroidism In the Elderly

Not Applicable

Completed

• Conditions: Subclinical Hypothyroidism
• Interventions: Drug: Levothyroxine; Drug: Liothyronine; Drug: Thyrotropin-Releasing Hormone

• Registration Number: NCT02399475
• Lead Sponsor: University of Pennsylvania

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01-01
• Study First Submitted: 2015-02-03
• Study First Submitted QC: 2015-03-20
• Study First Posted: 2015-03-26
• Primary Completion: 2019-09-30
• Study Completion: 2019-09-30
• Results First Submitted: 2021-01-21
• Status Verified: 2021-02
• Results First Submitted QC: 2021-02-16
• Last Update Submitted: 2021-02-16
• Results First Posted: 2021-03-09
• Last Update Posted: 2021-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Levothyroxine First	Thyrotropin-Releasing Hormone	Participants will start on the thyroid hormone Levothyroxine prior to crossing over to Liothyronine
Liothyronine First	Thyrotropin-Releasing Hormone	Participants will start on the thyroid hormone Liothyronine prior to crossing over to Levothyroxine
Levothyroxine First	Levothyroxine	Participants will start on the thyroid hormone Levothyroxine prior to crossing over to Liothyronine
Levothyroxine First	Liothyronine	Participants will start on the thyroid hormone Levothyroxine prior to crossing over to Liothyronine
Liothyronine First	Levothyroxine	Participants will start on the thyroid hormone Liothyronine prior to crossing over to Levothyroxine
Liothyronine First	Liothyronine	Participants will start on the thyroid hormone Liothyronine prior to crossing over to Levothyroxine

Primary Outcome Measures

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

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States