Hypothalamic-Pituitary and Other Endocrine Surveillance Among Childhood Cancer Survivors.

2021

2021 Nov 20

1945-7189

<p>Endocrine disorders in survivors of childhood, adolescent, and young adult (CAYA) cancers are associated with substantial adverse physical and psychosocial effects. To improve appropriate and timely endocrine screening and referral to a specialist, the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) aims to develop evidence and expert consensus-based guidelines for healthcare providers that harmonize recommendations for surveillance of endocrine disorders in CAYA cancer survivors. Existing IGHG surveillance recommendations for premature ovarian insufficiency, gonadotoxicity in males, fertility preservation, and thyroid cancer are summarized. For hypothalamic-pituitary (HP) dysfunction, new surveillance recommendations were formulated by a guideline panel consisting of 42 interdisciplinary international experts. A systematic literature search was performed in MEDLINE (through PubMed) for clinically relevant questions concerning HP dysfunction. Literature was screened for eligibility. Recommendations were formulated by drawing conclusions from quality assessment of all evidence, considering the potential benefits of early detection and appropriate management. Healthcare providers should be aware that CAYA cancer survivors have an increased risk for endocrine disorders, including HP dysfunction. Regular surveillance with clinical history, anthropomorphic measures, physical examination, and laboratory measurements is recommended in at-risk survivors. When endocrine disorders are suspected, healthcare providers should proceed with timely referrals to specialized services. These international evidence-based recommendations for surveillance of endocrine disorders in CAYA cancer survivors inform healthcare providers and highlight the need for long-term endocrine follow-up care in subgroups of survivors and elucidate opportunities for further research.</p>

10.1210/endrev/bnab040

Endocr Rev

34962573

Endocrine Health in Childhood Cancer Survivors.

2020

1171-1186

2020 Dec

1557-8240

<p>Endocrine late effects, including reproductive disorders and secondary thyroid cancer, have been reported in up to 50 %childhood cancer survivors (CCS) more than&nbsp;5&nbsp;years after treatment. Most endocrine disorders are amenable to treatment; awareness of symptoms is therefore of great importance. Recognition of these symptoms may be delayed however because many are nonspecific. Timely treatment of endocrine disorders improves quality of life in CCS and prevents possible consequences, such as short stature, bone and cardiovascular disorders, and depression. At-risk CCS must therefore be regularly and systematically monitored. This article provides a summary of the most commonly reported endocrine late effects in CCS.</p>

10.1016/j.pcl.2020.08.002

Pediatr Clin North Am

33131540

Radiation Dose and Volume to the Pancreas and Subsequent Risk of Diabetes Mellitus.

2019

2019 Jul 22

1460-2105

<p><strong>BACKGROUND: </strong>Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for diabetes mellitus but the association between risk and radiation dose and volume is unclear.</p>

<p><strong>METHODS: </strong>Participants included 20,762 five-year survivors of childhood cancer (4,568 exposed to abdRT) and 4,853 siblings. For abdRT, we estimated maximum dose to abdomen, mean doses for whole pancreas, pancreatic head, body, tail, and percent pancreas volume receiving ≥10, ≥20, and ≥30Gy. Relative risks (RRs) were estimated with a Poisson model using generalized estimating equations, adjusted for attained age. All statistical tests were two-sided.</p>

<p><strong>RESULTS: </strong>Survivors exposed to abdRT (median age=31.6 years, range=10.2-58.3) were 2.92-fold more likely than siblings (95% confidence interval [CI]=2.02 to 4.23) and 1.60-times more likely than survivors not exposed to abdRT (95%CI=1.24 to 2.05) to develop diabetes. Among survivors treated with abdRT, greater attained age (RR(per 10 years)=2.11, 95%CI=1.70 to 2.62), higher body mass index (RR(BMI 30+)=5.00, 95%CI=3.19 to 7.83 with reference(BMI 18.5-24.9)), and increasing pancreatic tail dose were associated with increased diabetes risk in a multivariable model; an interaction was identified between younger age at cancer diagnosis and pancreatic tail dose with much higher diabetes risk associated with increasing pancreatic tail dose among those diagnosed at the youngest ages (p&lt;.001). Radiation dose and volume to other regions of the pancreas were not statistically significantly associated with risk.</p>

<p><strong>CONCLUSIONS: </strong>Among survivors treated with abdRT, diabetes risk was associated with higher pancreatic tail dose, especially at younger ages. Targeted interventions are needed to improve cardiometabolic health among those at highest risk.</p>

10.1093/jnci/djz152

J. Natl. Cancer Inst.

31329225

Endocrine Late Effects in Childhood Cancer Survivors.

2018

JCO2017763268

2018 Jun 06

1527-7755

<p>Endocrine complications are highly prevalent in childhood cancer survivors. Approximately 50% of survivors will experience at least one hormonal disorder over the course of their lives. Endocrine complications often are observed in survivors previously treated with radiation to the head, neck, or pelvis. We provide an overview the most common endocrine late effects seen in survivors, including hypothalamic-pituitary dysfunction, primary thyroid dysfunction, obesity, diabetes mellitus, metabolic syndrome, and decreased bone mineral density. Primary gonadal injury is discussed elsewhere in this series. Given a variable latency interval, a systematic approach where individuals are periodically screened on the basis of their risk factors can help to improve health outcomes by prompt diagnosis and treatment of evolving endocrinopathies. These recommendations must be revised in the future given changes and improvements in cancer treatment over time.</p>

10.1200/JCO.2017.76.3268

J. Clin. Oncol.

29874130

Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

2016

2016 Jul 5

1527-7755

<p><strong>PURPOSE: </strong>The development of endocrinopathies in survivors of childhood cancer as they age remains understudied. We characterized endocrine outcomes in aging survivors from the Childhood Cancer Survivor Study on the basis of therapeutic exposures.</p>

<p><strong>PATIENTS AND METHODS: </strong>We analyzed self-reported conditions in 14,290 5-year survivors from the Childhood Cancer Survivor Study, with a median age 6 years (range, &lt; 1 to 20 years) at diagnosis and 32 years (range, 5 to 58 years) at last follow-up. Identification of high-risk therapeutic exposures was adopted from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cumulative incidence curves and prevalence estimates quantified and regression models compared risks of primary hypothyroidism, hyperthyroidism, thyroid neoplasms, hypopituitarism, obesity, diabetes mellitus, or gonadal dysfunction between survivors and siblings.</p>

<p><strong>RESULTS: </strong>The cumulative incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors (P &lt; .01 for all). Risk was significantly higher in survivors exposed to high-risk therapies compared with survivors not so exposed for primary hypothyroidism (hazard ratio [HR], 6.6; 95% CI, 5.6 to 7.8), hyperthyroidism (HR, 1.8; 95% CI, 1.2 to 2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2 to 7.5), thyroid cancer (HR, 9.2; 95% CI, 6.2 to 13.7), growth hormone deficiency (HR, 5.3; 95% CI, 4.3 to 6.4), obesity (relative risk, 1.8; 95% CI, 1.7 to 2.0), and diabetes mellitus (relative risk, 1.9; 95% CI, 1.6 to 2.4). Women exposed to high-risk therapies had six-fold increased risk for premature ovarian insufficiency (P &lt; .001), and men demonstrated higher prevalence of testosterone replacement (P &lt; .001) after cyclophosphamide equivalent dose of 20 g/m(2) or greater or testicular irradiation with 20 Gy or greater. Survivors demonstrated an increased risk for all thyroid disorders and diabetes mellitus regardless of treatment exposures compared with siblings (P &lt; .001 for all).</p>

<p><strong>CONCLUSION: </strong>Endocrinopathies in survivors increased substantially over time, underscoring the need for lifelong subspecialty follow-up of those at risk.</p>

10.1200/JCO.2016.66.6545

J. Clin. Oncol.

27382091