Improvements in cancer therapy have resulted in an expanding population of early-onset cancer survivors. In contrast to childhood and adolescent cancer survivors, there is still a lack of data concerning late morbidities among young adult (YA) cancer survivors. Thus, our aim was to investigate cardiac and vascular morbidity among early-onset cancer survivors with a special interest in YA cancer survivors. In a population-based setting, we explored the risk of cardiovascular disease in early-onset cancer survivors compared to healthy siblings. Patients diagnosed with cancer below 35 years of age since 1975 were identified from the Finnish Cancer Registry, and 5-year survivors were included in our study (N 5 13,860). Information on cardiovascular morbidity was collected from the national hospital discharge registry. Compared to siblings, cancer survivors aged 0-19 and 20-34 at diagnosis had significantly elevated hazard ratios (HRs) for the studied outcomes: HR 13.5 (95% CI 8.9-20.4) and 3.6 (95% CI 2.8-4.6) for cardiomyopathy/cardiac insufficiency; HR 3.4 (95% CI 2.3-5.1) and 1.7 (95% CI 1.4-2.0) for atherosclerosis/brain vascular thrombosis; HR 3.3 (95% CI 1.7-6.5) and 1.8 (95% CI 1.5-2.1) for myocardial infarction/cardiac ischemia and HR 1.7 (95% CI 1.2-2.6) and 1.4 (95% CI 1.2-1.7) for cardiac arrhythmia. In both groups, depending on the outcome, the HR for adverse events was highest among lymphoma, brain tumor, leukemia and testicular malignancy survivors. Our results regarding late effects of childhood cancer survivors confirmed previous findings. Additionally, our study provides novel information concerning the YA cancer survivor population. Hence, our data may help in planning the risk-based longterm follow-up of early-onset cancer survivors.Over the past four decades, survival rates for childhood and early adulthood cancer have increased significantly. The use of advanced diagnostic modalities, improvements in surgical techniques and radiation therapy regimes, combination chemotherapy and supportive care have all contributed to this success.Currently, more than 80% of patients diagnosed with a malignancy below the age of 25 are likely to survive for 5 years or more. This growing population of survivors faces considerable morbidity and mortality owing to late effects of their initial anticancer therapy. 1 As a result, monitoring for short-and long-term health risks of these patients represents a new challenge to physicians. 2,3 Long-term childhood cancer survivors are at increased risk of developing life-threatening conditions such as second malignant neoplasms (SMNs), cardiovascular disease, pulmonary complications as well as renal and endocrine dysfunction. [2][3][4][5][6] Excess mortality has been attributed not only to the relapse of primary cancer but also to SMNs, and cardiovascular and cerebrovascular diseases as the leading causes. [7][8][9] Although it is known that more than 60% of survivors of childhood cancer may develop at least one long-term adverse outcome, 2,3 there are few published data o...

To date, only few studies have been published documenting late mortality among early onset cancer survivors, especially regarding young adulthood (YA) malignancies. Our nation-wide population-based registry study provides information concerning cause-specific long-term mortality among 16,769 5-year survivors of early onset cancer (aged 0-34 years at diagnosis), with follow-up for death extending from 1971 through 2012. A sibling cohort and population data were used as reference. The overall standardized mortality ratio (SMR) of cancer patients was 4.6-fold, (95% CI 4.4-4.8). Highest SMRs were found for malignancies (12.8,3), infectious (4.8, 95%CI 2.9-6.7) and cardiovascular diseases (1.9, 95% CI 1.7-2.1). Malignancies and cardiovascular diseases accounted for the largest number of deaths. Childhood and YA cancer survivors with the same primary cancer site had a similarly elevated overall SMR with the exception of markedly higher SMRs after childhood Hodgkin lymphoma. The highest cumulative non-malignancy-related mortality was due to cardiovascular disease with a steady rise throughout the follow-up, but strongly dependent on the primary cancer site and age at diagnosis. In childhood cancer survivors, the cumulative cardiovascular mortality did not reduce over time. However, overall and malignancyrelated mortality showed a declining tendency towards the most recent periods after both, childhood and YA cancer. Our findings on non-malignancy-related mortality stress the need to set up long-term individual follow-up with a focus on cardiovascular late effects for early onset cancer survivors, especially for YA cancer survivors still lacking those.Advances in therapies for early onset cancer have lead to a substantial increase in 5-year survival rates. 1-3 Thus far the main focus of late effect research has been on the morbidity and mortality of childhood cancer survivors aged up to 21 years at cancer diagnosis. [4][5][6][7][8][9] Only few studies have investigated those topics for the survivors of young adult (YA) cancer patients aged from 20 to 34 years at cancer diagnosis. [10][11][12] Previous studies have found elevated risks for chronic health conditions which contribute to higher mortality among survivors of childhood cancer patients compared to the general population. 5,9,13,14 Patterns of increased excess mortality after childhood cancer have been shown to be dependent on time from cancer diagnosis and cause of death. 4,7,11 The success of improved cancer survival is overshadowed by the life-threatening chronic health outcomes that cancer survivors are more likely to suffer from. Thus, the growing population of early onset cancer survivors has a strong need for adequate individualized follow-up to detect and possibly reduce treatment-related morbidities and mortality. 15 After the survival of childhood cancer, the adoption of a healthy lifestyle including physical activity may lower especially the risk of developing late cardiovascular sequelae. 16 Thus, promoting the control of known cardiovascular risk fa...

Background: Congenital hypothyroidism (CH) is defined as the lack of thyroid hormones at birth. Mutations in at least 15 different genes have been associated with this disease. While up to 20% of CH cases are hereditary, the majority of cases are sporadic with unknown etiology. Apart from a monogenic pattern of inheritance, multigenic mechanisms have been suggested to play a role in CH. The genetics of CH has not been studied in Finland so far. Therefore, multigenic sequencing of CH candidate genes was performed in a Finnish patient cohort with both familial and sporadic CH.Methods: A targeted next-generation sequencing (NGS) panel, covering all exons of the major CH genes, was applied for 15 patients with sporadic and 11 index cases with familial CH.Results: Among the familial cases, six pathogenic mutations were found in the TPO, PAX8, and TSHR genes. Furthermore, pathogenic NKX2.1 and TG mutations were identified from sporadic cases, together with likely pathogenic variants in the TG, NKX2.5, SLC26A4, and DUOX2 genes. All identified novel pathogenic mutations were confirmed by Sanger-sequencing and characterized in silico and/or in vitro.Conclusion: In summary, the CH panel provides an efficient, cost-effective, and multigenic screening tool for both known and novel CH gene mutations. Hence, it may be a useful method to identify accurately the genetic etiology for dyshormogenic, familial, or syndromic forms of CH.

The purchase of medications associated with MetS was increased after early onset cancer and highly dependent on the age at cancer diagnosis and the cancer diagnosis. Prevention strategies are imperative for reducing potentially life-threatening cardiovascular complications after early onset cancer.

Thyroid function is controlled by thyroid-stimulating hormone (TSH), which binds to its G protein-coupled receptor [thyroid-stimulating hormone receptor (TSHR)] on thyrocytes. TSHR can potentially couple to all G protein families, but it mainly activates the G- and G-mediated signaling cascades. To date, there is a knowledge gap concerning the role of the individual G protein cascades in thyroid pathophysiology. Here, we demonstrate that the thyrocyte-specific deletion of G-protein α subunit (Gα) in adult mice [tamoxifen-inducible G protein α subunit deficient (iTGαKO) mice] rapidly impairs thyrocyte function and leads to hypothyroidism. Consequently, iTGαKO mice show reduced food intake and activity. However, body weight and the amount of white adipose tissue were decreased only in male iTGαKO mice. Unexpectedly, hyperplastic follicles and papillary thyroid cancer-like tumor lesions with increased proliferation and slightly increased phospho-ERK1/2 staining were found in iTGαKO mice at an older age. These tumors developed from nonrecombined thyrocytes still expressing Gα in the presence of highly elevated serum TSH. In summary, we report that partial thyrocyte-specific Gα deletion leads to hypothyroidism but also to tumor development in thyrocytes with remaining Gα expression. Thus, these mice are a novel model to elucidate the pathophysiological consequences of hypothyroidism and TSHR/G/cAMP-mediated tumorigenesis.-Patyra, K., Jaeschke, H., Löf, C., Jännäri, M., Ruohonen, S. T., Undeutsch, H., Khalil, M., Kero, A., Poutanen, M., Toppari, J., Chen, M., Weinstein, L. S., Paschke, R., Kero, J. Partial thyrocyte-specific Gα deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma-like lesions in mice.

Despite improved survival rates, childhood and young adult (YA) cancer survivors face elevated risks for life-threatening morbidities, especially cardiovascular complications. Our nationwide Finnish registry study investigated the purchases of cardiovascular medication from 1993 to 2011 in patients diagnosed with cancer aged below 35 years (N 5 8,197) between 1993 and 2004 compared to siblings (N 5 29,974) via linkage to the drug purchase registry. The cumulative incidence for purchasing cardiovascular medications was higher in childhood and YA cancer patients compared to siblings with a rising trend over time. After childhood cancer, the highest hazard ratio (HR) was found for purchasing anticoagulants (HR 19.8,). The HRs for any cardiovascular medication (HR 7.2, 95% CI 5.1-10.1) and cardiac medication (HR 4.8, were markedly elevated after childhood cancer as well. Regarding YA cancer patients, the respective HRs were 2.5 (95% CI 2.0-3.2) for anticoagulants, HR 1.7 (95% CI 1.5-1.9) for any cardiovascular medication and HR 1.5 (95% CI 1.3-1.7) for cardiac medication. Among cancer patients, highest HRs for cardiovascular medication were observed after childhood acute lymphoblastic leukemia (ALL) and bone tumors (HR 10.2, 95% CI 6.8-15.5 and HR 7.4, 95% CI 4.0-13.7) and YA ALL and acute myeloid leukemia (HR 5.1, 95% CI 3.5-7.1 and HR 2.8, 95% CI 1.8-4.0). Our study demonstrated increased HRs for purchasing cardiovascular medication after early-onset cancer compared to siblings reflecting elevated cardiovascular morbidity. Thus, the implementation of long-term cardiovascular disease screening is imperative to prevent, detect and adequately treat cardiovascular late effects after cancer at a young age.At present, the diagnosis with childhood or young adult (YA) cancer is not an instantaneous death sentence anymore thanks to survival approaching 80%.1,2 However, virtually any organ system may be susceptible to adverse effects of cancer therapy involving chemotherapy, radiation or surgery. 3-5 Nearly twothirds of childhood cancer survivors have reported to experience health drawbacks after the initial defeat over malignancy: longterm morbidities that may eventually lead to a reduced life expectancy. 5 Late cardiovascular morbidity has been demonstrated to be the leading nonmalignant cause of death after childhood and YA cancer in patients aged below 34 years at cancer diagnosis. [6][7][8] Up to date, information on the use of cardiovascular medication after childhood and YA cancer remains limited. Only one study reported that childhood cancer survivors have more likely been treated for hypertension than their siblings. 9As a consequence of the great impact of cardiovascular adverse effects after cancer, a new clinical field has emerged to specifically deal with cardiovascular complications: cardiooncology.10 Cardio-oncology aims at reducing or preventing cardiovascular damage during cancer therapy, detecting cardiovascular late effects in early, reversible stages and treating cardiovascular complications effectively...

According to previous studies, childhood cancer survivors have an elevated risk for late mental health effects. However, only few studies exist on young adulthood (YA) cancer survivors' mental health outcomes. In our study, we examined first time antidepressant (AD) medication purchases of childhood and YA cancer patients compared to siblings. The first time AD medication purchases of 7,093 cancer patients aged 0-34 years at diagnosis and a sibling cohort (N = 26,882) were retrieved from the Social Insurance Institution of Finland (Kela) since 1.1.1993. Cancer patients diagnosed between 1.1.1994 and 31.12.2004 were identified from the Finnish Cancer Registry and sibling controls via the Population Registry Centre. Statistical analyses were performed via the Cox regression model, and the hazard ratios (HR) were adjusted for age and gender. Increased hazard ratios for AD purchases were found in the younger (0-19 years at cancer diagnosis) [HR 5.2, 95%CI (3.7-7.2)] and older (age 20-34 years at cancer diagnosis) [HR 4.5, 95%CI (3.9-5.2)] cancer patient groups compared to siblings. The gender effect was similar in patients and controls, showing that females have higher risk for AD purchases than males. Males in the younger patient group had highest HR (5.6) for AD purchases compared to siblings. Patients with sarcoma or CNS tumor in the younger age group and leukemia or CNS malignancy in the older age group had the highest risk for AD medication purchases. The frequency and risk for AD purchases has been increasing during recent decades in both cancer patient age groups compared to siblings. Thus, cancer patients' psychological support should be properly assessed already after primary treatment. Certain diagnostic groups as well as female patients may require more psychological support than others.

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