Thyroid consequences of the Chernobyl nuclear accident

It is well recognized that the use of external irradiation of the head and neck to treat patients with various non-thyroid disorders increases their risk of developing papillary thyroid carcinoma years after radiation exposure. An increased risk of thyroid cancer has also been reported in survivors of the atomic bombs in Japan, as well as in Marshall Island residents exposed to radiation during the testing of hydrogen bombs. More recently, exposure to radioactive fallout as a result of the Chernobyl nuclear reactor accident has clearly caused an enormous increase in the incidence of childhood thyroid carcinoma in Belarus, Ukraine, and, to a lesser extent, in the Russian Federation, starting in 1990. When clinical and epidemiological features of thyroid carcinomas diagnosed in Belarus after the Chernobyl accident are compared with those of naturally occurring thyroid carcinomas in patients of the same age group in Italy and France, it becomes apparent that the post-Chernobyl thyroid carcinomas were much less influenced by gender, virtually always papillary (solid and follicular variants), more aggressive at presentation and more frequently associated with thyroid autoimmunity. Gene mutations involving the RET proto-oncogene, and less frequently TRK, have been shown to be causative events specific for papillary cancer. RET activation was found in nearly 70% of the patients who developed papillary thyroid carcinomas following the Chernobyl accident. In addition to thyroid cancer, radiation-induced thyroid diseases include benign thyroid nodules, hypothyroidism and autoimmune thyroiditis, with or without thyroid insufficiency, as observed in populations after environmental exposure to radioisotopes of iodine and in the survivors of atomic bomb explosions. On this basis, the authors evaluated thyroid autoimmune phenomena in normal children exposed to radiation after the Chernobyl accident. The results demonstrated an increased prevalence of circulating thyroid antibodies not associated with significant thyroid dysfunction. This finding is consistent with the short period of follow-up, but it is highly likely that these children will develop clinical thyroid autoimmune diseases in the future. Therefore, screening programmes for this at-risk population should focus, not only on the detection of thyroid nodules and cancer, but also on the development of thyroid autoimmune diseases.     

Management of pediatric differentiated thyroid cancer: An overview for the pediatric oncologist

Differentiated thyroid cancer (DTC) is the most common childhood thyroid malignancy. The standard of care for pediatric DTC is total thyroidectomy followed by radioactive iodine (RAI) treatment when indicated. Molecular changes and potential therapeutic targets have been recently described in pediatric thyroid cancer. Pediatric oncologists are increasingly involved in the evaluation of thyroid nodules in childhood cancer survivors and in the management of advanced thyroid cancer. In 2015, the American Thyroid Association published management guidelines for children with DTC. We provide an overview of the current standard of care and highlight available targeted therapies for progressive or RAI refractory DTC.     

Thyroid-stimulating hormone receptor levels and binding affinity in the thyroid gland of growth-retarded mice

Growth-retarded (grt/grt) mice are congenitally primary hypothyroid. Our previous study indicated that thyroid-stimulating hormone (TSH) responsiveness was defective in the grt/grt thyroid gland. We now report additional studies of impaired grt/grt thyroid function. Semiquantitative RT-PCR confirmed that TSH receptor (TSHR) mRNA expression in the grt/grt thyroid was significantly decreased compared with +/+ thyroids. Scatchard analysis revealed that grt/grt and +/+ mice have only one type of TSH binding site. grt/grt thyroids had fewer TSH binding sites, although this did not apparently affect the affinity of TSH for its receptor. The present data suggest that reduced TSHR levels or defects in TSHR signaling could be one of the possible defective sites in the grt/grt thyroid gland.     

Iodine and thyroid status during pregnancy and risk of stillbirth: A population-based nested case–control study

Prior research suggests that severe iodine deficiency in pregnancy may be associated with stillbirth. However, the relationship between mild to moderate iodine insufficiency, which is prevalent even in developed countries, and risk of stillbirth is unclear. We thus examined associations of iodine status and risk of stillbirth in a prospective population-based nested case–control study in Finland, a mild to moderately iodine insufficient population. Stillbirth cases (n = 199) and unaffected controls (n = 249) were randomly selected from among all singleton births in Finland from 2012 to 2013. Serum samples were collected between 10 and 14 weeks gestation and analysed for iodide, thyroglobulin (Tg) and thyroid-stimulating hormone (TSH). Odds ratios (ORs) and 95% confidence intervals (CIs) for stillbirth were estimated using logistic regression. After adjusting for maternal age, prepregnancy body mass index, socio-economic status and other factors, neither high nor low serum iodide was associated with risk of stillbirth (Q1 vs. Q2–Q3 OR = 0.92, 95% CI = 0.78–1.09; Q4 vs. Q2–Q3 OR = 0.78; 95% CI = 0.45–1.33). Tg and TSH were also not associated with risk of stillbirth in adjusted models. Maternal iodine status was not associated with stillbirth risk in this mildly to moderately iodine-deficient population. Tg and TSH, which reflect functional iodine status, were also not associated with stillbirth risk. The lack of associations observed between serum iodide, TSH and Tg and risk of stillbirth is reassuring, given that iodine deficiency in pregnancy is prevalent in developed countries.     

Changing face of paediatric and adolescent thyroid cancer

OBJECTIVES: The aims of our study were to review the Royal Children's Hospital cohort of children having thyroidectomy for thyroid nodules over the last 8 years and to report the changing pattern of thyroid cancer seen in our institution over that time. METHODS: We undertook a retrospective case-note review of all patients who underwent thyroid surgery between 1997 and 2004. RESULTS: Of 69 patients identified, the pathological diagnoses were 51 benign tumours, 14 thyroid cancers and four cases of multiple endocrine neoplasia type 2, who were treated with prophylactic thyroidectomy. Sixteen of the 69 patients had a history of childhood cancer and 10/16 had cancer treatment which included direct or scatter radiation. Of the 10 patients who received irradiation, four had follicular adenomas and six developed thyroid cancer. All six patients were euthyroid: one patient was presented with a palpable nodule and the other five were detected on surveillance ultrasound. CONCLUSIONS: Our results confirm a high detection of malignancy in thyroid nodules in childhood. Compared to an earlier study at this institution, the number of thyroid malignancies appears to be increasing. Surveillance at the Royal Children's Hospital has changed, with increased long-term cancer survival. Prospective 2-yearly evaluation of those with a past history of radiation exposure has resulted in earlier detection of benign and malignant thyroid lesions. Nodular changes are usually not clinically apparent for many years and lifelong surveillance is necessary for cancer detection in this group.     

Effects of low level radiation from the Chernobyl accident in a population with iodine deficiency

To determine the effects of low dose radiation from ¹³¹I and ¹³⁷Cs resulting from the Chernobyl disaster on the expression of endemic goiter in children, we studied children in regions with and without evidence of radiocontamination but comparable iodine insufficiency. We included 89 children in the study (radiocontaminated) region (SR) and 116 in the control region (CR) because they were either fetuses, infants, or pre-adolescents at the time of exposure. We evaluated thyroid dimensions by clinical examination and ultrasound; thyroid function by hormonal levels, and thyroglobulin measurement; histology of the thyroid by fine needle aspiration; and thyroid autoimmunity. SR subjects had 5 times the frequency of thyroid enlargement as those from CR, greatest in the younger patients. There were no instances of clinically apparent thyroid dysfunction. Antithyroid microsomal and antithyroglobulin antibodies were present in a markedly greater percentage of SR subjects. Fine needle biopsy demonstrated greater cellular proliferation in samples from SR. Conclusions We have demonstrated findings of autoimmune thyroid disease at markedly increased frequency in a population of children with poor iodine nutriture who were exposed to low level radiation, compared to a more iodine deficient population not so exposed. These results suggest that low level radiation may induce thyroid gland changes in children who have inadequate iodine intake nutriture and reinforce the importance of adequate dietary iodine. Received: 14 June 1996 / Accepted in revised form: 20 June 1997     

Transient primary hypothyroidism in the newborn: Experience of the Victorian Neonatal Thyroid Screening Programme

Abstract Between May 1977 and December 1986, the Victorian Thyroid Screening Programme tested approximately 570 000 newborns for congenital hypothyroidism. One hundred and sixty-six cases of primary hypothyroidism, confirmed by formal thyroid function tests, were identified, of which 24 were later found to be transient. In addition, there were two patients with permanent dyshormonogenesis who passed through a stage of being biochemically euthyroid and so could have been diagnosed mistakenly as transient hypothyroidism. Fourteen of the transient cases were due to excessive intake of iodine. In two, this was due to maternal ingestion of iodide during pregnancy and in 12 the babies received large amounts of topical iodine antiseptic. Two cases were caused by maternal anti-thyroid antibodies and in eight instances the cause was unknown. The large number of cases due to the topical application of iodine antiseptic emphasizes the need for caution when using this substance in neonates.     

Papillary thyroid carcinoma of childhood and adolescence: a 30-year experience at the Istituto Nazionale Tumori in Milan

BACKGROUND: Survival rates are reportedly excellent for papillary thyroid carcinomas (PTCs) in childhood/adolescence, despite their strong tendency to spread. The aim of this study was to verify this assumption in a single-institution series spanning a 30-year period with a very long follow-up. PROCEDURE: From 1968 to 2001, 74 cases of thyroid carcinoma were collected. The papillary histological type was confirmed in 42 cases with available slides; we recorded the sex, age at diagnosis, age of menarche, tumor side and size, TNM/pTNM classification, multicentricity, vascular invasion, type of surgery, post-operative complications, post-surgical therapies and outcome up to May 31, 2004. RESULTS: The female/male ratio was 2.2; pT4, pN1 and M1 cases were 52%, 95%, and 12% (four in lungs and one in bone), respectively. Total thyroidectomy was performed in 33 patients, hemithyroidectomy in 8, and a biopsy in 1 inoperable case. Nine patients (21%) relapsed, six in the cervical lymph nodes and three in the lungs. After a median follow-up of 189 months, all patients were alive, two of them with evidence of disease. Overall and progression-free survival curves were independent of sex, age, TNM/pTNM classification, or type of surgery. Overall survival was also independent of recurrence. CONCLUSIONS: Unlike its adult counterpart, PTC of childhood and adolescence is a cancer with a high frequency of spread, but an excellent outcome irrespective of sex, age at diagnosis, TNM/pTNM classification, type of surgery, recurrence. Since pediatric PTCs proved highly responsive to hormone manipulation, it is worth considering a different therapeutic approach from adult cases.     

Radiation Exposure and the Risk of Pediatric Thyroid Cancer

It has been more than three years since the unprecedentedly massive earthquake and tsunami struck eastern Japan on March 11, 2011, and the large accident occurred at the Fukushima Daiichi Nuclear Power Plant. To investigate the influence of radiation exposure, thyroid ultrasonography has been provided preliminarily for 360,000 children who lived in Fukushima Prefecture at the time of the accident. As of September 2013, 59 children had been diagnosed with thyroid cancer by fine-needle aspiration cytology, and 34 children had been treated surgically and ultimately diagnosed with papillary thyroid cancer. Here, I would like to describe the characteristics of pediatric thyroid cancer and typical thyroid images obtained by ultrasonography.     

Papillary carcinoma of the thyroid gland in a child of thyrotoxicosis patient receiving radioactive iodine therapy: report of a case

Herein we present the case of a 9-year-old girl who had an enlarged right lobe of the thyroid gland and sub-clinical hypothyroidism (thyroid stimulating hormone at 9.24 mIU/L). The patient had a history of unintentional exposure to radiation while her mother was receiving radionuclide therapy for diffuse toxic goiter. Ultrasonography of the young girl showed right lobe enlargement with diffuse coarse heterogenous echogenicity, compatible with a microcalcification pattern identified in both lobes of the thyroid gland. Histopathology of the tissue from a thyroidectomy revealed papillary thyroid carcinoma in the right lobe and chronic lymphocytic thyroiditis in the remaining tissue. Molecular pathology demonstrated an RET/PTC1 rearrangement in both tumor and non-tumorous tissue harboring thyroiditis. Considering the history of exposure and the characteristics of the thyroid pathology together, the PTC in this patient was likely a secondary-to-genetic alteration induced by external radiation. This case emphasizes the importance of stringent restrictions when giving radioactive iodine therapy to a patient with small children.