CASE 1320: RAI Uptake and Serum Prolactin in Thyroid Cancer

Breast Uptake on Radioiodine Scan and Serum Prolactin in Thyroid Cancer Patients Prepared by Thyroid Hormone Withdrawal or Recombinant Human Thyrotropin: A Prospective Study

Radioactive iodine (RAI) is a radioisotope used to ablate thyroid gland remnant after thyroidectomy in patients diagnosed with differentiated thyroid carcinoma (DTC). A whole body scan (WBS) is performed to not only evaluate for iodine uptake by the native thyroid tissue but also to observe for uptake in other areas of the body, which could be physiological or indicative of iodide-avid metastases. Research has shown a correlation between breast cancer and thyroid cancer. Patients with DTC have been found to have elevated levels of serum prolactin, which could lead to mammary gland dysfunction.

In patients with DTC undergoing RAI scanning or therapy, it has been previously observed that patients prepared by thyroid hormone withdrawal have significantly higher breast uptake on whole body scan compared to those prepared by rh-TSH. Considering the impact of prolactin on breast tissue, this study aims to correlate these findings with the lab values and the method of preparation.

Accordingly, the research question is as follows: does the method of WBS preparation impact prolactin levels and how does that correlate with breast uptake in patients with DTC undergoing RAI WBS?

Study Overview

• Status: Active, not recruiting
• Conditions: Thyroid Cancer

Detailed Description

Radioactive iodine (RAI) is a radioisotope used to ablate thyroid gland remnant after thyroidectomy in patients diagnosed with differentiated thyroid carcinoma (DTC). A whole body scan (WBS) is performed to not only evaluate for iodine uptake by the native thyroid tissue but also to observe for uptake in other areas of the body, which could be physiological or indicative of iodide-avid metastases. Research has shown a correlation between breast cancer and thyroid cancer. Patients with DTC have been found to have elevated levels of serum prolactin, which could lead to mammary gland dysfunction. As such, this study will evaluate for breast uptake on the RAI WBS. Research has shown that patients with DTC may have uptake on RAI WBS.

There is a concern in the molecular imaging community and oncology community that increased I-131 retention in breast tissue may increase the risk of future breast malignancy. The notion that increased serum prolactin concentration increases iodine uptake in breast tissue comes mostly from case series. A correlation between high prolactin as a result of withdrawal from thyroid hormone treatment vs stimulation by recombinant human thyrotropin and uptake by thyroid tissue is the main research question. This research will not be able to answer the question of whether such breast uptake is associated with the future risk breast malignancy. The later research question should be undertaken by other researchers in a larger study with longer follow up. Metastases to the breast from thyroid cancer are rare. Uptake in a discrete lesion in the breast will need to be investigated. It is unclear whether breast adenocarcinoma will concentrate iodine.

In a previous retrospective study of 194 patients with DTC and no breast cancer, it was demonstrated that patients prepared by withdrawal from thyroid hormone had 5-fold higher peak I-131 uptake in breast tissue on post-therapy scan compared to patients prepared by recombinant human thyrotropin (rh-TSH). In other research, DTC patients with hyperprolactinemia have been found to have increased uptake by the mammary gland. The hypothesis is that patients prepared by withdrawal would have increased serum prolactin compared to patients prepared by rh-TSH who are not made hypothyroid. This study plans to prospectively evaluate serum prolactin and breast uptake on the RAI WBS and assess the impact of pre-scan preparation on those variables. This would be the first prospective study of its kind in this set of patients to look at whether the method of pre-RAI scan preparation might impact RAI uptake with correlation to prolactin levels.

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Group 1: Female patients with differential thyroid cancer prepared for radioactive iodine whole body scan by withdrawal from thyroid hormones Group 2: Female patients with differential thyroid cancer prepared for radioactive iodine whole body scan by rh-TSH.

Description

Inclusion Criteria:

• Female patients with diagnosis of differentiated thyroid carcinoma who have had thyroidectomy performed previously
• Patients able to understand and sign informed consent for imaging
• Patients already scheduled to undergo radioactive iodine whole body scanning (RAI WBS)

Exclusion Criteria:

• Males
• Patients with a history of breast cancer
• Patients with a known history of hyperprolactinemia
• Patients receiving medications known to raise serum prolactin

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Thyrogen (rh-TSH); Group 1: Female patients prepared for radioactive iodine treatment by rh-TSH (Thyrogen)
Withdrawal from thyroid hormone; Group 2: Female patients prepared for radioactive iodine treatment by withdrawal from thyroid hormones

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breast uptake of I-131 on whole body radioactive iodine scan	Breast uptake of I-131 on whole body radioactive iodine scan	10 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum prolactin concentration	Change in prolactin levels in thyroid hormone withdrawal group	6 weeks
Serum prolactin concentration	Change in prolactin levels in thyrogen preparation group	3 days
Prolactin level and breast uptake of I-131	Correlation between serum prolactin level and breast uptake of I-131	Day 46 of thyroid hormone withdrawal group
Prolactin level and breast uptake of I-131	Correlation between serum prolactin level and breast uptake of I-131	Day 26 of thyrogen preparation group

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Alexandra Mikhael, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2020
• Primary Completion (Actual): July 27, 2022
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: July 30, 2020
• First Posted (Actual): August 3, 2020

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms
• Other Study ID Numbers: IRB 20-488

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No