In:
Journal of the Endocrine Society, The Endocrine Society, Vol. 6, No. Supplement_1 ( 2022-11-01), p. A31-A31
Abstract:
Congenital leptin deficiency (CLD) is a rare autosomal recessive form of monogenic obesity caused by loss-of-function mutations in the leptin gene. Targeted therapy is available in the form of recombinant human leptin (metreleptin). We previously reported baseline characteristics of one of the first cases of CLD diagnosed in the United States, a patient with a comorbid diagnosis of Hodgkin lymphoma prior to initiation of therapy. Metreleptin has a black box warning for risk of T-cell lymphoma, which has been reported in acquired generalized lipodystrophy patients, both treated and untreated with metreleptin. Clinical Case A 20 yr old female (Pt B) was referred for evaluation of obesity (BMI 45.0 kg/m2) with a history of hyperphagia and excessive weight gain by three months of life. Pt B is of Pakistani origin with a family history of consanguinity. She was treated with combination OCPs in adolescence due to primary amenorrhea and hypogonadotropic hypogonadism. At the time of her initial evaluation, serum leptin levels were undetectable. Pt B was homozygous for the pathogenic variant c398delG in exon 3 of the leptin gene (LEP), which causes a frameshift/premature stop codon. On MR elastography performed for hepatic steatosis, she had an incidental finding of axillary lymphadenopathy. Surgical biopsy and staging work-up confirmed diagnosis of nodular lymphocyte predominant Hodgkin lymphoma, Stage II disease. She was treated with 2 cycles of R-ABVD followed by adjuvant radiation (2000 cGy) to the right supraclavicular and axillary region, achieving clinical remission. Pt B was then treated with 3.75-5 mg metreleptin once daily in an observational treatment protocol for 18 months. With therapy, pt B lost 39.1 kg or 33% of initial body weight. Clinically significant improvements in related parameters were observed, including percent body fat (-18%), estimated visceral adipose tissue (-53%), HOMA2 IR (-80%), ALT (-91%), total cholesterol (-10%), triglycerides (-26%), HDL (+6%), LDL (-19%), and high-sensitivity C-reactive protein (-84%). In addition, prediabetes (with abnormal 2 hour OGTT) resolved, hepatic steatosis improved, bone mineral density increased (+0.6 SD), and pt B developed spontaneous regular menses. She tolerated metreleptin well without serious adverse effects and her lymphoma remained in remission throughout the study. Conclusion To our knowledge, this is the first report of lymphoma in a patient with CLD, occurring prior to treatment with metreleptin. Pt B achieved clinical remission prior to initiation of therapy with metreleptin, with no recurrence on 18 months of therapy. She experienced substantial weight loss and marked improvements in body composition, glucose metabolism, insulin sensitivity, lipid metabolism, liver and reproductive health. Untreated CLD has been associated with impaired lymphocyte production and function. The risk for lymphoma associated with metreleptin may relate to preexisting autoimmunity or immunologic abnormalities related to leptin deficiency rather than medication adverse effect. Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
Type of Medium:
Online Resource
ISSN:
2472-1972
DOI:
10.1210/jendso/bvac150.065
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2022
detail.hit.zdb_id:
2881023-5
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