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      Serum anti-Müllerian hormone is lower in patients with multiple radioiodine dose for treatment of pediatric thyroid cancer

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          Abstract

          Introduction

          Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility.

          Objective

          The aim was to analyze the association between RAI and serum AMH level in women treated with RAI.

          Methods

          We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured.

          Results

          The study included 47 patients with a mean age of 25.1 years (12.4–50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30–1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01–7.81); the level was 1.57 ng/mL (0.01–7.81) after multiple RAI doses and 2.99 ng/mL (0.01–6.63) after a single RAI dose ( P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39–7.81) than those who received more (1.0 ng/mL, 0.01–6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55–52.2, P = 0.014) after age adjustments.

          Conclusion

          Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

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          Most cited references25

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          Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

          Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed.
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            The physiology and clinical utility of anti-Mullerian hormone in women.

            BACKGROUND The measurement of circulating anti-Müllerian hormone (AMH) has been applied to a wide array of clinical applications, mainly based on its ability to reflect the number of antral and pre-antral follicles present in the ovaries. AMH has been suggested to predict the ovarian response to hyperstimulation of the ovaries for IVF and the timing of menopause, and to indicate iatrogenic damage to the ovarian follicle reserve. It has also been proposed as a surrogate for antral follicle count (AFC) in the diagnosis of polycystic ovary syndrome (PCOS). METHODS This paper is a summary of presentations at a European Society of Human Reproduction and Embryology campus workshop on AMH, with literature cited until September 2013. Published peer-reviewed medical literature about AMH was searched through MEDLINE and was subjected to systematic review and critical assessment by the panel of authors. RESULTS Physiologically, recent data confirm that AMH is a follicular gatekeeper limiting follicle growth initiation, and subsequently estradiol production from small antral follicles prior to selection. AMH assays continue to evolve and technical issues remain; the absence of an international standard is a key issue. The dynamics of circulating AMH levels throughout life can be split into several distinct phases, with a peak in the early 20s before a decline to the menopause, with a strong and positive correlation with non-growing follicle recruitment. There is a more complex rise during childhood and adolescence, which is likely to be more reflective of different stages of follicle development. AMH shows limited short-term variability, but the influence of states such as prolonged oral contraceptive use need to be considered in clinical assessment. There are only very limited data on relationships between AMH and natural fertility at different stages of reproductive life, and while it has a relationship to age at menopause the marked variability in this needs further exploration. AMH may be useful in assessing the need for fertility preservation strategies and detecting post-chemotherapy or surgical damage to the ovarian reserve. Long-term follow-up of patients to ascertain fully the value of post-cancer serum AMH in predicting long-term ovarian function is required. There is a linear relationship between AMH and oocyte yield after ovarian stimulation, which is of value in predicting ovarian hyperstimulation. AMH can also identify 'poor responders', but it seems inappropriate at present to withhold IVF purely on this basis. Women with PCOS show markedly raised AMH levels, due to both the increased number of small antral follicles and intrinsic characteristics of those granulosa cells, and this may contribute to anovulation. The value of AMH in the diagnosis of PCOS remains controversial, but it may replace AFC in the future. CONCLUSIONS For the first time in female reproductive biology, it is possible to measure the submerged part of the iceberg of follicle growth, i.e. the intrinsic, so-called 'acyclic' ovarian activity. An international standard for AMH and improved assay validity are urgently needed to maximize the clinical utility of this very promising biomarker of ovarian function in a large array of clinical situations, both in childhood and adulthood.
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              Anti-Müllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function

              Abstract Context Anti-müllerian hormone (AMH) is produced by granulosa cells of small, growing follicles in the ovary. Serum AMH levels strongly correlate with the number of growing follicles, and therefore AMH has received increasing attention as a marker for ovarian reserve. This review summarizes recent findings and limitations in the application of serum AMH in ovarian reserve assessment. Evidence Acquisition A PubMed search was conducted to find recent literature on the measurements and use of serum AMH as a marker for ovarian reserve. Evidence Synthesis Serum AMH levels are measured to assess the “functional ovarian reserve,” a term that is preferred over “ovarian reserve,” since AMH levels reflect the pool of growing follicles that potentially can ovulate. Serum AMH levels are used in individualized follicle-stimulating hormone dosing protocols and may predict the risk of poor response or ovarian hyperstimulation syndrome but has limited value in predicting ongoing pregnancy. Serum AMH levels are studied to predict natural or disease-related age of menopause. Studies show that the age-dependent decline rates of AMH vary among women. The generalized implementation of serum AMH measurement has also led to an increase in diagnostic assays, including automated assays. However, direct comparison of results remains problematic. Conclusion Serum AMH remains the preferred ovarian reserve marker. However, the lack of an international standard for AMH limits comparison between AMH assays. Furthermore, little is known about endogenous and exogenous factors that influence serum AMH levels, which limits proper interpretation of AMH values in a clinical setting.

                Author and article information

                Journal
                Eur Thyroid J
                Eur Thyroid J
                ETJ
                European Thyroid Journal
                Bioscientifica Ltd (Bristol )
                2235-0640
                2235-0802
                07 March 2024
                30 January 2024
                01 April 2024
                : 13
                : 2
                : e230252
                Affiliations
                [1 ]Department of Oncologic Endocrinology , Instituto Nacional de Câncer – INCA, Rio de Janeiro, RJ, Brazil
                [2 ]Department of Endocrinology , Universidade Federal do Rio de Janeiro – UFRJ, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil
                Author notes
                Correspondence should be addressed to F Vaisman: vaismanfe@ 123456gmail.com
                Author information
                http://orcid.org/0000-0002-6835-7108
                Article
                ETJ-23-0252
                10.1530/ETJ-23-0252
                10959028
                38290210
                d41b83da-0156-42cd-90b8-a4c1f0cb5ccb
                © the author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 04 December 2023
                : 30 January 2024
                Categories
                Research

                anti-müllerian hormone,radiodiodine,pediatric thyroid cancer

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