Anti-Mullerian Hormone Deficiency in Females With Fanconi Anemia
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 01/2014; 99(5):jc20133559. DOI: 10.1210/jc.2013-3559
Context: In females with Fanconi anemia (FA), infertility is often accompanied by diminished ovarian reserve and hypergonadotropic amenorrhea before the age of 30, suggesting primary ovarian insufficiency (POI). POI is typically diagnosed only after perimenopausal symptoms are observed. Objective: To assess whether serum anti-Müllerian hormone (AMH) levels can serve as a cycle-independent marker for the diagnosis of POI in patients with FA. Design and Setting: This observational study used the National Cancer Institute's (NCI) inherited bone marrow failure syndrome cohort at the National Institutes of Health Clinical Center. Participants: The study included 22 females with FA, 20 unaffected female relatives of patients with FA, and 21 unrelated healthy females under 41 years of age. Main Outcome Measure: Serum AMH, a marker of ovarian reserve, was measured in all participants. Results: Females with FA had very low AMH levels (median=0.05 ng/ml; range: 0-2.32 ng/ml; p<0.001) when compared with unaffected relatives (median=2.10 ng/ml; range: 0.04-4.73 ng/ml) and unrelated healthy females (median=1.92 ng/ml; range: 0.31-6.64 ng/ml). All patients with FA over 25 years of age were diagnosed with POI and had undetectable AMH levels. Conclusions: AMH deficiency appears to be a shared trait across this heterogeneous FA cohort. Substantially reduced AMH levels in females with FA suggest a primary ovarian defect associated with reduced fertility. Measurement of AMH at the time of FA diagnosis and subsequent monitoring of AMH levels at regular intervals may be useful for the timely management of complications related to POI such as subfertility/infertility, osteoporosis, and menopausal symptoms.
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ABSTRACT: Context: Previously, reduced levels of anti-Müllerian hormone (AMH), a circulating marker of ovarian reserve, were found in females with Fanconi anemia (FA). FA, dyskeratosis congenita (DC) and Diamond-Blackfan anemia (DBA) are inherited bone marrow failure syndromes (IBMFS) associated with high risks of bone marrow failure, leukemia and solid tumors. Objective: To assess AMH levels in females with DC or DBA. Design and Setting: This observational study used the National Cancer Institute's inherited bone marrow failure syndrome cohort at the National Institutes of Health Clinical Center. Participants: The study included females with DC, unaffected female relatives of patients with DC, females with DBA, unaffected female relatives of patients with DBA, and unrelated healthy female volunteers younger than 41 years of age. Main Outcome measure: Serum AMH levels. Results: Females with DC had significantly lower levels of AMH (median=0.55 ng/ml) compared with unaffected relatives (median=2.28 ng/ml, p=0.004) or unrelated healthy volunteers (median=2.69 ng/ml, p=0.005). Females with DBA showed a non-significant trend for lower levels of AMH (median=0.89 ng/ml) compared with unaffected relatives (median=1.71 ng/ml, p=0.21) or unrelated healthy volunteers (p=0.11). Patients with DC and DBA had significantly higher levels of AMH (p=0.013, 0.003) compared with FA (median 0.05 ng/ml). Conclusions: Our findings suggest that women with IBMFS have lower levels of AMH than unaffected women. This AMH deficiency could be a primary ovarian defect or a consequence of the pathophysiology of the syndromes. Additional studies of AMH and ovarian function in women with IBMFS are warranted to better understand the underlying biology.
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ABSTRACT: Context: Endocrine problems are common in patients with Fanconi anemia (FA). About 80% of children and adults with FA have at least one endocrine abnormality, including short stature, GH deficiency, abnormal glucose or insulin metabolism, dyslipidemia, hypothyroidism, pubertal delay, hypogonadism, or impaired fertility. The goal of this report is to provide an overview of endocrine abnormalities and guidelines for routine screening and treatment to allow early diagnosis and timely intervention. Evidence acquisition: This work is based on a comprehensive literature review, including relevant articles published between 1971 and 2014, and proceedings of a Consensus Conference held by the Fanconi Anemia Research Fund in 2013. Evidence synthesis: The panel of experts collected published evidence and discussed its relevance to reflect current information about the endocrine care of children and adults with FA before the Consensus Conference and through subsequent deliberations that led to the consensus. Conclusions: Individuals with FA should be routinely screened for endocrine abnormalities, including evaluation of growth; glucose, insulin, and lipid metabolism; thyroid function; puberty; gonadal function; and bone mineral metabolism. Inclusion of an endocrinologist as part of the multidisciplinary patient care team is key to providing comprehensive care for patients with FA.
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