Mechanistic Study of Subclinical Hypothyroidism In the Elderly

NCT02399475 | Completed Results

• 2 other identifiers: 821564K24AG042765-01A1
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Subclinical Hypothyroidism

Keywords

Levothyroxine; Liothyronine; Thyrotropin Releasing Hormone; Aging; Hypothyroidism; Thyroid diseases

Outcome Measures

Primary Outcomes (4)

• 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

• TSH Max

  The maximum concentration of TSH after TRH stimulation when TSH is at goal

  Between 0 and 180 min after TRH stimulation

• Free T4 Level

  Free thyroxine level when TSH level is at goal on therapy.

  An average of 7 months after initiating therapy

• Total T3 Level

  Total triiodothyronine level when TSH is at goal on therapy

  An average of 7 months

Study Arms (2)

Levothyroxine First

EXPERIMENTAL

Participants will start on the thyroid hormone Levothyroxine prior to crossing over to Liothyronine

Drug: Levothyroxine; Drug: Liothyronine; Drug: Thyrotropin-Releasing Hormone

Liothyronine First

EXPERIMENTAL

Participants will start on the thyroid hormone Liothyronine prior to crossing over to Levothyroxine

Drug: Levothyroxine; Drug: Liothyronine; Drug: Thyrotropin-Releasing Hormone

Interventions

Levothyroxine DRUG

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

Also known as: Synthroid

Levothyroxine First; Liothyronine First

Liothyronine DRUG

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

Also known as: Cytomel

Levothyroxine First; Liothyronine First

Thyrotropin-Releasing Hormone DRUG

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).

Levothyroxine First; Liothyronine First

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• men and women aged 70 and older
• TSH between 4.5 and 19.9 mU/L as an outpatient
• ability to provide informed consent

You may not qualify if:

• Laboratory Tests:
• 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
• thyroid peroxidase (TPO) antibody positive
• abnormal liver function tests (LFTs \>3 x upper limit of normal)
• hemoglobin \<11 g/dL
• Surgeries or Procedures:
• thyroid surgery
• pituitary surgery
• bariatric surgery
• bowel resection involving the jejunum and upper ileum
• radioactive iodine therapy
• radiation treatments to head or neck
• Medical Conditions:
• diagnosis of pituitary disease
• diagnosis of amyloidosis, sarcoidosis, hemochromatosis

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Hypothyroidism; Thyroid Diseases

Interventions

Thyroxine; Triiodothyronine; Thyrotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Thyronines; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Dr. Anne Cappola
• Organization: University of Pennsylvania

acappola@pennmedicine.upenn.edu

2155375359

Study Officials

• Anne R Cappola, MD, ScM

  The University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: March 26, 2015
• Study Start: January 1, 2015
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: March 9, 2021
• Results First Posted: March 9, 2021

Record last verified: 2021-02

Locations

US (1)