Prevalence of thyroid malignancy and hormonal dysfunction following radiation exposure in childhood.

INTRODUCTION: Childhood radiation exposure is a known risk factor for thyroid malignancy and dysfunction. However, local data are limited and there is no consensus on the modality and frequency of screening in this high-risk group. METHODS: Retrospective analysis study evaluating patients with childhood radiation exposure in 2006-2016 and minimum of 1-year follow-up. RESULTS: Of the 132 childhood cancer survivors in the study, thyroid malignancy was detected in 2 cases (1.5%) and thyroid nodules in 13 (9.8%). The earliest thyroid malignancy was detected 5 years post-radiotherapy via ultrasound. Of the 84 patients who had screening thyroid function test, 26 (31.0%) were detected with abnormal test results post-radiation, majority being subclinical hypothyroidism. CONCLUSION: Regular screening via clinical examination for thyroid nodules should be performed at least annually. Where feasible and if resources permit, consideration should be given to using ultrasound for thyroid nodule(s) and malignancy screening at 5 years post-radiation therapy. Screening for thyroid dysfunction can be considered from 6-12 months post-radiotherapy.

A short report on current fertility preservation strategies for boys.

BACKGROUND: Advances in cancer treatment have led to improved long-term survival after childhood cancer, but often at a price of impaired future fertility. Fertility preservation (FP) in male children and early adolescents poses unique challenges as efficacy is unproven. OBJECTIVES: To describe characteristics of testicular tissue cryopreservation (TTCP) specimens taken from paediatric and adolescent patients, stratified by age, and prior chemotherapy, if any, and to demonstrate evidence for germ cells. MATERIALS AND METHODS: Retrospective review of gonadal biopsies and clinical records of patients consented into the Royal Children's Hospital FP programme between 1987 and 2015. Tissue was sliced into blocks, with one section sent for histopathology prior to cryopreservation. In boys ≥12 years where spermatogenesis could be expected, a portion of tissue was disaggregated completely to look for mature sperm and if found, additional tissue was dissected and the resulting suspension frozen. RESULTS: Testicular tissue cryopreservation specimens in 44 males (0.3-16.8 years) provided an average of 7.8 slices per patient. All the specimens were taken at the same time as another necessary surgical procedure, under one general anaesthesic. There was only one complication of scrotal wound dehiscence. Seven of the forty-four (15.9%) patients had chemotherapy prior to testicular biopsy, while the rest were chemotherapy naïve. Five of these were prepubertal, and two were pubertal patients. Eleven subjects had tissue dissected with mature sperm found in eight. Of these eight patients where sperm were found, all were pubertal with testicular size of more than 10 mL and showing histological evidence of spermatogenesis. No histologic specimen demonstrated any malignant cells. CONCLUSIONS: Testicular tissue cryopreservation can be performed in young patients without delay, preferably prior to cancer treatment. As testicular tissue contains germ cells from which haploid spermatozoa are ultimately derived, future technologies may allow their utilization for fertility in humans. This may be the only hope for biological offspring in some patients undergoing fertility compromising treatment. Retrieval of mature sperm from some pubertal patients, however, offers realistic hope to these patients of future fertility.

Sirolimus therapy in a child with partially diazoxide-responsive hyperinsulinaemic hypoglycaemia.

Hyperinsulinaemic hypoglycaemia (HH), which causes persistent neonatal hypoglycaemia, can result in neurological damage and it's management is challenging. Diazoxide is the first-line treatment, albeit not all patients will fully respond to it, as episodes of hypoglycaemia may persist and it entails unpleasant adverse effects. Sirolimus, an mTOR inhibitor, has reportedly been successful in treating children with severe diffuse HH, thus obviating the need for pancreatectomy. We report a girl with HH, with a novel heterozygous ABCC8 gene missense mutation (c.4154A>T/ p.Lys1385Thr), who was initially responsive to diazoxide therapy. After 11 months of diazoxide treatment, she developed intermittent, unpredictable breakthrough episodes of hypoglycaemia, in addition to generalized hypertrichosis and weight gain from enforced feeding to avoid hypoglycaemia. Sirolimus, which was commenced at 15 months of age, gradually replaced diazoxide, with significant reduction and abolition of hypoglycaemia. The hypertrichosis resolved and there was less weight gain given the reduced need for enforced feeding. Sirolimus, which was administered over the next 15 months, was well tolerated with no significant side effects and was gradually weaned off. After stopping sirolimus, apart from hypoglycaemia developing during an episode of severe viral gastroenteritis, the capillary glucose concentrations were maintained >3.5 mmol/L, even after a 10 h fast. Sirolimus may have a role in the treatment of partially diazoxide-responsive forms of HH who experience breakthrough hypoglycaemia, but the long-term safety and efficacy of sirolimus are not established. LEARNING POINTS: Conventional treatment of diffuse HH with diazoxide is not always effective in controlling hypoglycaemia and can be associated with unpleasant side effects.Sirolimus was successfully used to abolish recurrent hypoglycaemia in partially diazoxide-responsive HH, with resolution of unacceptable diazoxide-associated side effects.Sirolimus was well tolerated with no clinically significant side effects.Shortly after stopping sirolimus, the capillary glucose levels remained normoglycemic.

Thyroid carcinoma in children, adolescents and adults, both spontaneous and after childhood radiation exposure.

UNLABELLED: Thyroid carcinoma is the most common second malignancy for childhood cancer survivors. Radiation exposure is linked to risk. Thyroid nodules in children have a high risk for malignancy, whether spontaneous or after radiation. Due to the extremely limited available paediatric data, we sought to review a series of patients with thyroid carcinoma, seen over 25 years. Forty-six patients were identified. Thirty-nine (84.8 %) had papillary thyroid carcinoma, five (10.9 %) follicular carcinoma and 2 (4.3 %) medullary thyroid carcinoma (MEN2B). Thirty-three (71.7 %) had childhood radiation exposure (17 females) with thyroid malignancy occurring 6-37 years later. The smallest nodule size found on surveillance to have thyroid malignancy was 4 mm. Thyroid cancer in patients 16 years and under was seen in 22 patients (47.8 %). All had total thyroidectomy, with initial central node clearance from 2005. Diagnostic rTSH stimulated I(123) scan was followed by ablative I(131) if any uptake was seen. Sixteen (32.6 %) had metastases. Twenty-four (52.2 %) had I(131), four requiring multiple courses. Forty-two remain alive and well. CONCLUSION: Ultrasound screening is required for early diagnosis as small nodule size is not predictive of benign histology or absence of metastases. Central node clearance provides better outcome. Despite metastatic disease at presentation for some, prognosis is favourable. WHAT IS KNOWN: • Incidence of thyroid cancer has been increasing and radiation exposure in childhood cancer survivors is clearly linked to risk. • Published guidelines in many places can only provide very low level evidence due to extremely limited available paediatric data. What is New: • Paper provides good evidence to confirm existing views with the largest cohort of thyroid cancer reported to date in the paediatric age group in Australia, and the largest cohort in Australia where there have been specific high risks of radiation exposure. The only other reported larger studies have come from the Children's Oncology Group and Childhood Cancer Survivor Study [24]. • Using diagnostic rTSH stimulated I(123) scan 6 weeks after surgery helps to determine if radioactive iodine ablation is necessary and limits unnecessary bone marrow exposure for young patients in whom future leukaemia is of greater concern.