Mechanistic Study of Subclinical Hypothyroidism In the Elderly

University of Pennsylvania

Status: Completed

Conditions: Subclinical Hypothyroidism

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02399475

K24AG042765-01A1 (U.S. NIH Grant/Contract)

821564

Details and patient eligibility

About

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.

Enrollment: 14 patients

Sex: All

Ages: 70+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

14 participants in 2 patient groups

Levothyroxine First

Experimental group

Description:

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

Treatment:

Drug: Thyrotropin-Releasing Hormone

Drug: Levothyroxine

Drug: Liothyronine

Liothyronine First

Experimental group

Description:

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

Treatment:

Drug: Thyrotropin-Releasing Hormone

Drug: Levothyroxine

Drug: Liothyronine