A new literature review published in EJNMMI Reports argues that the safeguards meant to prevent that outcome are inconsistent across the world’s nuclear medicine societies, and it proposes a standardized protocol built around serum testing, a two-week abstinence window, and a written attestation signed on the day of treatment.
The review, conducted by Stephen J. Sozio, David Cohen, William Y. Raynor, and Jeffrey S. Kempf, was performed in March 2026 using PubMed/MEDLINE and covered peer-reviewed publications from 1970 to 2025, including professional society guidelines, consensus statements, and studies of pregnancy test performance. The authors examined two questions: what the major guidelines actually recommend before radioiodine administration, and how reliably the available tests detect an early pregnancy. Because no patients were enrolled or analyzed, institutional review board approval was not required.
The biological rationale for strict screening is well established. Iodine-131 is a radioactive isotope used to treat hyperthyroidism and to ablate residual thyroid tissue and cancer cells after thyroidectomy in papillary and follicular thyroid carcinoma. Its beta radiation concentrates in cells expressing the sodium-iodide symporter, which is abundant in thyroid follicle cells and well-differentiated thyroid cancer cells, though the symporter also occurs in the lacrimal glands, salivary glands, gastrointestinal tract, genitourinary tract, and placenta. Radioiodine crosses the placenta and concentrates in fetal thyroid tissue as early as 8 to 10 weeks of gestation.
The timing matters enormously. The fetal thyroid gland first develops around 8 weeks of gestation and acquires the ability to take up iodine between weeks 10 and 13, making it particularly vulnerable because of its high mitotic activity and higher affinity for iodine than the adult gland. Exposure at or after 10 weeks of gestation will almost certainly result in fetal hypothyroidism, according to the review. After birth, that condition may present with macroglossia, lethargy, hypotonia, poor feeding, constipation, and hypothermia, and if untreated can lead to irreversible neurocognitive impairment, motor delay, speech and language deficits, short stature, and delayed puberty. Exposure before 8 to 10 weeks may instead cause fetal demise through radiation-induced progenitor cell apoptosis, but among surviving fetuses the authors found no reported cases of radioiodine-attributed extra-thyroidal birth defects, since major organogenesis has not yet occurred.
Against that backdrop, the performance characteristics of pregnancy tests become central. Pregnancy testing detects human chorionic gonadotropin, one of the earliest hormones secreted during pregnancy, produced by placental trophoblast cells after implantation. In uncomplicated intrauterine pregnancies, hCG levels initially double every 48 to 72 hours, typically reaching a serum concentration of approximately 10 mIU/mL by 10 to 11 days after conception. Serum tests can detect hyperglycosylated hCG at roughly 10 mIU/mL, yielding positive results in up to 98 percent of uncomplicated pregnancies by 11 days after conception. Standard urine tests detect hCG at approximately 25 mIU/mL, producing positive results by 15 to 17 days after conception. Serum testing is therefore about 2.5 times more sensitive than standard urine testing and can detect a pregnancy several days earlier.
Even that advantage has limits. The review emphasizes that all tests have a biological window during which very early pregnancy may be undetectable. Newer high-sensitivity urine tests, sometimes marketed as early result or enhanced sensitivity tests, can detect urine hCG as low as 10 mIU/mL and may offer sensitivity equivalent to serum testing. Yet in one study cited by the authors, Wilcox and colleagues sequentially assayed more than 150 women planning pregnancy using ultrasensitive immunoradiometric urine assays roughly one hundred times more sensitive than standard tests, and still failed to detect approximately 10 percent of pregnancies on the day after a missed period and about 3 percent on the seventh day after a missed period. False-positive results can also occur, driven by heterophilic antibodies, trophoblastic disease, and physiologically elevated hCG secretion in menopausal women.
When the authors compared eight current society guidelines and recommendations, they found unanimous agreement on one point: pregnancy must be ruled out in all female patients of reproductive potential before radioiodine is administered. Beyond that, the recommendations diverge considerably. All guidelines align on testing no earlier than 72 hours before therapy, but the preferred timing varies widely. The SNMMI Practice Standard for Thyroid Cancer Scintigraphy recommends testing on the day of therapy with either serum or urine analysis, while the SNMMI Practice Guideline for Therapy of Thyroid Disease with I-131 3.0 advises testing within 24 hours prior to therapy. The ACR-ACNM-ARS-SNMMI-SPR Practice Parameter permits testing up to 72 hours beforehand if the patient practiced abstinence, though it does not specify the duration. Both EANM guidelines and ATA guidelines recommend testing as early as 72 hours before treatment. Serum hCG is explicitly preferred by the SNMMI I-131 guideline, the SNMMI/ACNM Radiopharmaceuticals guideline, and the EANM guideline on benign thyroid disease, while other guidelines either accept both modalities or state no preference.
The review also documents why verbal questioning alone is insufficient. In a case described by Berlin, a woman who was unknowingly 15 weeks pregnant received 2 mCi of I-131 for thyroid scintigraphy after verbally stating she was not pregnant during pre-examination questioning. She later stated in an affidavit that she never recalled being asked about pregnancy, no written documentation was obtained, and no pre-examination pregnancy test was performed. The fetus subsequently developed severe hypothyroidism because the exposure was calculated to have occurred well beyond 10 weeks of gestation, and the resulting lawsuit was settled for what was described as a substantial payment to the mother and child. The authors argue that testing should always be performed in all female patients capable of pregnancy, ideally coupled with a written statement signed by the patient affirming she is not pregnant.
The proposed institutional protocol model follows directly from these findings. The authors recommend advising patients to abstain from intercourse for at least two weeks before therapy, because traditional urine tests remain unreliable for at least 8 to 10 days after implantation, and abstinence reduces the risk of false-negative results during the biological window of invisibility. Patients should provide a written declaration on the day of therapy confirming adherence to that abstinence period. As an additional safety measure, therapy should ideally be scheduled during the follicular phase of the menstrual cycle, ensuring no ovum is available to be fertilized, although the authors acknowledge that cycle-based scheduling is often impractical given variability in cycle length and irregularity common in thyroid disease. Pregnancy testing should be performed within 72 hours prior to therapy, ideally within 24 hours, with serum quantitative hCG preferred for its higher sensitivity. The test should be ordered by the primary responsible specialist, with results verified by both the ordering provider and the treating nuclear medicine physician before administration. If a result is inconclusive, for example a serum quantitative hCG of 0.1 to 10 mIU/mL, the authors recommend delaying therapy and repeating serum hCG within 48 to 72 hours, aligned with the typical doubling time in an uncomplicated intrauterine pregnancy.
The protocol also extends to counseling around the therapy itself. Current guidelines advise avoiding pregnancy for 6 to 12 months after treatment to allow post-therapy radiation clearance and stabilization of thyroid function, and the authors stress that the exact interval should be set through joint decision-making between patient and provider, informed by individual biokinetic data such as the distribution and retention of I-131. For patients with Graves’ disease who wish to conceive sooner, alternatives such as anti-thyroid medications or thyroidectomy should be discussed. Patients should also be counseled about the potential for temporary menstrual irregularities and infertility following ablation, thought to be related to therapy-related ovarian radiation exposure; dosimetric studies show ovarian absorbed doses are generally below thresholds associated with permanent ovarian failure, though cumulative exposure may result in permanent effects, particularly in younger patients or those requiring repeated treatments. The authors conclude that inadvertent fetal exposure to I-131 is rare but potentially devastating and preventable, and they call for future prospective studies to establish more uniform societal guidelines and standardized institutional protocols that balance maternal and fetal safety with clinical feasibility.
Subject of Research: Pregnancy testing recommendations prior to iodine-131 thyroid therapy
Article Title: Pregnancy testing prior to iodine-131 thyroid therapy: a literature review of current recommendations
Article References: Sozio, S. J., Cohen, D., Raynor, W. Y., & Kempf, J. S. (2026). Pregnancy testing prior to iodine-131 thyroid therapy: a literature review of current recommendations. EJNMMI Reports, 10(1), Article 54. https://doi.org/10.1186/s41824-026-00313-8
Image Credits: AI Generated
DOI: 10.1186/s41824-026-00313-8
Keywords: iodine-131, radioiodine therapy, pregnancy testing, hCG, thyroid cancer, fetal hypothyroidism, serum hCG, urine pregnancy test, nuclear medicine guidelines, abstinence, thyroid ablation, medical-legal risk
News Source: Harold Sullivan. (October 28, 2026). Pregnancy testing before radioactive iodine therapy: review urges serum hCG within 24 hours and two weeks of abstinence. Scienmag.
