Factors predicting endocrine late effects in childhood cancer survivors from a Japanese hospital

Abstract

We retrospectively analyzed endocrine late effects in 81 childhood cancer survivor (CCS) patients who had been referred to our endocrinology department in Chiba Children's Hospital between January 1, 2008 and December 31, 2016. Among 69 eligible patients (33 male, 36 female), endocrine late effects were identified in 56 patients (81.1%). The median age at the last visit to our endocrinology department was 17.4 years (range: 7.1-35.3 years). The most common primary cancer was acute lymphoblastic leukemia (22 patients, 31.8%). Forty-four patients (64%) were treated using radiation therapy. A primary brain tumor and high doses (≥6 g/m 2 ) of cyclophosphamide were significantly associated with growth hormone deficiency (GHD). Our present study suggests that high doses of cyclophosphamide is a risk factor for GHD. Adult heights and pubertal growth spurts of patients treated with radiation therapy were significantly lower than patients not treated with radiation therapy. Our retrospective study reconfirmed that hematopoietic stem cell transplantation and chronic graft versus host disease (GVHD) were associated with elevated risks of primary hypothyroidism. However, it is unclear whether GVHD induces thyroid dysfunction. Gonadal radiation and busulfan were associated with primary hypogonadism as reported in previous studies. We found high doses of cyclophosphamide to be involved in pituitary disorders. We suggest that pediatric endocrinologists should discuss the potential effects of radiation therapy on adult height and pubertal growth spurt in CCS patients. Moreover, patients who have been treated with high doses of cyclophosphamide or have chronic GVHD require long-term follow-up for endocrine late effects.

Autoimmune thyroid disease following hematopoietic stem cell transplantation in childhood cancer survivors

“…We previously confirmed that HSCT and chronic GVHD are risk factors for primary hypothyroidism and subclinical hypothyroidism (7). Previous studies have reported that HSCT is associated with a risk of thyroid dysfunction, and the prevalence of primary hypothyroidism among CCSs who have undergone HSCT is 23.1-45.1% (8,9).…”

Incidence of thyroid dysfunction in children after HSCT with reduced intensity conditioning (RIC) or myeloablative conditioning (MAC)

“…With a median follow‐up of almost 2 years, 10% of individuals developed new thyroid dysfunction after HSCT. However, as most long‐term studies have longer median duration to detection of thyroid dysfunction (at least 3–6 years), 13‐21 including our prior study, with median follow‐up of 4 years, 1 continued annual screening of this cohort of patients may reveal the true long‐term incidence of new thyroid disease post‐transplant in a modern cohort and better inform discussions of risk versus benefit for transplant overall and for the use of RIC or MAC.…”

“…roid dysfunction (at least 3-6 years), [13][14][15][16][17][18][19][20][21] including our prior study, with median follow-up of 4 years, 1 continued annual screening of this cohort of patients may reveal the true long-term incidence of new thyroid disease post-transplant in a modern cohort and better inform discussions of risk versus benefit for transplant overall and for the use of RIC or MAC.…”

Endocrine late effects in survivors of infantile acute lymphoblastic leukemia

“…In general, radiation therapy is a risk factor for growth disorder, GH deficiency, hypogonadism, hypothyroidism, and abnormalities in glucose and lipid metabolism in childhood cancer survivors, high-dose alkylating agents are risk factors for hypogonadism, and corticosteroids are risk factors for abnormalities in glucose, lipid, and bone metabolism (11)(12)(13). According to previous reports on childhood cancer survivors (CCS), including those with solid tumors, endocrine late effects were observed in more than half of the patients and were related to a combination of radiation therapy, surgical treatment, and HSCT in addition to chemotherapy (11,14,15). In Japan, Shimazaki et al reported that 56 (81.1%) of 69 patients with CCS had endocrine late effects, 13 (18.8%) experienced GH deficiency, 14 (20.2%) experienced hypothyroidism, and 25 (36.2%) experienced hypogonadism (11).…”