Endocrine Dysfunction in Diamond–Blackfan Anemia (DBA): A Report from the DBA Registry (DBAR)

Abstract

Objective Diamond Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome. The mainstays of treatment involve chronic red cell transfusions, long-term glucocorticoid therapy, and stem cell transplantation. Systematic data concerning endocrine function in DBA are limited. We studied patients in the DBA Registry (DBAR) of North America to assess the prevalence of various endocrinopathies. Study design In a pilot study, retrospective data were collected for 12 patients with DBA. Subsequently, patients with DBA aged 1–39 years were recruited prospectively. Combined, 57 patients were studied; 38 chronically transfused, 12 glucocorticoid-dependent and 7 in remission. Data were collected on anthropometric measurements, systematic screening tests of pituitary, thyroid, parathyroid, adrenal, pancreatic and gonadal function and ferritin levels. Descriptive statistics were tabulated and group differences assessed. Results Fifty-three percent of patients had ≥ 1 endocrine disorder, including adrenal insufficiency (32%), hypogonadism (29%), hypothyroidism (14%), growth hormone dysfunction (7%), diabetes mellitus (2%), and/or diabetes insipidus (2%). Ten of 33 patients with available heights had height SD <−2. Low 25(OH)D levels were present in 50%. A small proportion also had osteopenia, osteoporosis or hypercalciuria. Most with adrenal insufficiency were glucocorticoid-dependent; other endocrinopathies were more common in chronically transfused patients. Conclusions Endocrine dysfunction is common in DBA, as early as the teenage years. While prevalence is highest in transfused patients, patients taking glucocorticoids or in remission also have endocrine dysfunction. Longitudinal studies are needed to better understand the etiology and true prevalence of these disorders.

Late Effects Screening Guidelines after Hematopoietic Cell Transplantation for Inherited Bone Marrow Failure Syndromes: Consensus Statement From the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects After Pediatric HCT

“…Significant endocrinopathies including problems with bone health are of particular concern. 66, 67 The impact of iron burden specifically presents one of the major challenges for DBA patients and the importance of optimization of the same prior to transplant cannot be underrated. 68 Iron abatement via chelation must be addressed pre-HCT with additional post-HCT phlebotomy or chelation to prevent cardiac or hepatic complications.…”

A Review of Diamond-Blackfan Anemia: Current Evidence on Involved Genes and Treatment Modalities

“…Chronic red cell transfusion lands the patient in iron overload and its consequent troubles such as hemochromatosis. Endocrine complications in DBA have also been studied [ 25 ]. The highest percentage was determined to be of adrenal insufficiency and hypogonadism [ 25 ].…”

“…Endocrine complications in DBA have also been studied [ 25 ]. The highest percentage was determined to be of adrenal insufficiency and hypogonadism [ 25 ]. The frequency of endocrine dysfunction was more in patients who were transfusion-dependent as compared to those on steroids [ 25 ].…”

Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Cell Transplantation for Inherited Bone Marrow Failure Syndromes: Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation

“…In fact, it is recommended that all patients with DBA are followed routinely by an endocrinologist, regardless of treatment. The incidence of osteopenia is not well reported in DBA; nor is the use of bisphosphonate therapy [84]. However, pathologic fractures have been seen in up to 20% of patients [83].…”