Endocrine Abstracts

Background: The rapid advancements in the field of allogenic hematopoietic stem cell transplantation (allo-HSCT) and better management of acute postprocedural complications have led to increased life expectancy, but at the same time to higher incidences of long-term complications. Conditioning regimens (chemotherapy, total body irradiation), immunosuppresive treatments and immune dysregulation threaten endocrine and metabolic functions, leading to late effects, including hypogonadism and infertility, thyroid dysfunction or steroid-induced diabetes and dyslipidemia, associated with increased cardio-vascular risk. Even though, thyroid function abnormalities are one of the most prevalent conditions encountered after HSCT, Graves’ disease is rarely seen, but can appear as a result of immune reconstitution syndrome, either by transfer of pathogenic auto-reactive lymphocyte clone from donor to recipient or by loss of immunotolerance secondary to graft-vs-host disease (GVHD).

Case report: A 20-year old female received an allo-HSCT from a related donor(brother) for acute myeloid leukemia without maturation (M1) in November 2019. The conditioning regimen included cytarabine, idarubicine, etopozide and methylprednisolone. In August 2021, the patient developed an active form of cutaneous chronic graft-vs-host disease with morphea-like lesions, for which high doses of methylprednisolone were started. In December 2021, she presented to our departement for premature ovarian failure secondary to chemotherapy and evaluation for other endocrine and metabolic complications. Continuous combined hormone replacement therapy was introduced for menopausal symptoms. Subsequently, the patient developed hematocolpos secondary to vulvovaginal cGVHD for which she underwent dilatation. At the next follow-up in our department, her thyroid function tests revealed a TSH level of 0.059 µIU/ml (0.3-3.6 µIU/ml), fT4 1.08ng/dl (0.8-1.7ng/dl) and fT3 60.7 ng/dl (76.3-220.8 ng/dl). Her thyroid ultrasound was normal. Even though, her thyroid function abnormalities are consistent with the effects of high dose corticosteroids, subclinical hyperthyroidism caused by Graves’ disease in connection with a post-transplant immune reconstitution syndrome cannot be excluded, as thyrotropin receptor antibodies were found increased (TRAb=5.06 UI/l, normal 0-1.75 UI/l). Nevertheless, we were not able to perform TSI for differential diagnosis. Moreover, diabetes mellitus (fasting glucose=132 mg/dl) and dyslipidemia (total cholesterol = 476 mg/dl, triglycerides = 716 mg/dl) were diagnosed.

Conclusions: As survivorship after HSCT increases and endocrine complications become more frequent, emphasis should be placed on the importance of a long-term multidisciplinary follow-up, in order to recognise and treat endocrinopathies before clinical impact, thus optimizing quality of life. Furthermore, HSCT offers an unique insight into the pathogenesis of autoimmune disease, such as Graves’ disease.