Study of Resistance to Thyroid Hormone After Long-term Exposure in People With Thyroid Cancer

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase

Withdrawn

Phase 1

Conditions

Thyroid Cancer

Treatments

Drug: Thyrotropin Releasing Hormone (TRH)

Drug: levothyroxine

Other: Hypothyroidism QOL questionnaire

Study type

Interventional

Funder types

Other

Identifiers

NCT04868045

20-079

Details and patient eligibility

About

The purpose of this study is to find out whether people who have had thyroid cancer develop resistance to treatment with thyroid hormones after having received high doses of thyroid drugs for many years.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 18 or older
Due to a diagnosis of thyroid cancer, patient underwent a total thyroidectomy based on pathology.
No evidence of active disease based on routine surveillance testing showing no suspicious findings on neck ultrasound and low thyroglobulin levels (≤1.0 ng/ml) with negative thyroglobulin antibodies within one year of study enrollment. For the study patients, this response can be evaluated after five years of TSH suppression. For control subjects, this response can be evaluated after two years of surveillance.
Two groups:
- 8 patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years
- 8 patients with no history of TSH suppression
Normal TSH level based on the laboratory reference range for at least 6 months at the time of study enrollment.
Blood pressure range of >90/60 and <180/100. Patients may be included in the study if blood pressure has been treated with medication and normalized.

Exclusion criteria

Patient reported history of symptomatic heart disease including unstable angina or NYHA stage III or IV heart failure.
Patient reported history of one of the following cardiac arrhythmias: atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular fibrillation, or ventricular tachycardia.
Patient reported history of uncontrolled hypotension (<90/60) or hypertension (>180/100).
History of renal dysfunction with creatinine more than 1.5 times the upper limit of normal based on recent laboratory testing
Known hypersensitivity to the drug
Pregnant or breast feeding
Prior history of seizures or brain damage
Patients on chronic therapy with levodopa
Patients on therapeutic doses of acetylsalicylic acid (2 - 3.6 gm/day)
Patients with conditions that result in disruption of the hypothalamic-pituitary axis (i.e. hypophysectomy, hypopituitarism, pituitary tumor/surgery, head irradiation, or head trauma).

Trial design

Primary purpose

Diagnostic

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

0 participants in 2 patient groups

Patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years

Experimental group

Description:

Study subjects will be given 200mcg of TRH as a single intravenous (IV) bolus in endocrine clinic on Day 1 and Day 5. LT3 will be administered orally, twice a day (12 hours apart i.e. 8 AM and 8 PM) at a dosage of 10 mcg on Day 2-4. Levothyroxine will be taken after the TRH stimulation tests on Day 1 and day 5. Levothyroxine will be taken on Days 2-4 of the study. \*Patients will take their own LT4 that they are prescribed by their endocrinologist. The dose of Levothyroxine is titrated for each patient.

Treatment:

Other: Hypothyroidism QOL questionnaire

Drug: levothyroxine

Drug: Thyrotropin Releasing Hormone (TRH)

Patients with no history of TSH suppression

Experimental group

Description:

Treatment:

Other: Hypothyroidism QOL questionnaire

Drug: levothyroxine

Drug: Thyrotropin Releasing Hormone (TRH)