Embryonal tumors in Canadian children less than 36 months of age: results from the Canadian Pediatric Brain Tumor Consortium (CPBTC).

Embryonal tumors are a heterogeneous group of central nervous system (CNS) tumors whose subgroups have varying incidence and outcome. Despite these differences, they are often grouped as a single entity for study purposes. To date, there are no Canadian multi-institutional studies examining the incidence and outcome of all embryonal subtypes. The current study is an observational study reviewing embryonal tumors in all patients less than 36 months of age diagnosed with a CNS tumor in Canada from 1990 to 2005. Embryonal tumors accounted for 26.9% of all CNS tumors. Medulloblastomas were the highest proportion of the embryonal tumors at 61.5%. Atypical teratoid/rhabdoid tumors (AT/RT) had the second highest proportion of embryonal tumors at 18%. The proportion of primitive neuroectodermal tumors (PNET) was 16%, with 2.6 and 1.9% for congenital medulloepithelioma and ependymoblastoma tumors, respectively. AT/RT and PNET were more common in younger age groups. Medulloblastoma became more prevalent with increasing age, with its highest prevalence in the 25 to 36 month age group. Survival rates for our Canadian population at 18 and 24 months were 0.74 and 0.68 for medulloblastoma, 0.64 and 0.60 for PNET, and 0.36 and 0.29 for AT/RT, respectively. Overall, our data are comparable with published international rates for embryonal tumors. These incidence and outcome figures can guide future research into these rare tumors.

Prevalence of autoimmune disease in patients with prolactinomas and non-functioning pituitary adenomas.

PURPOSE: Prolactin can affect autoimmune response and evidence suggests that hyperprolactinemia can primarily precipitate autoimmunity. We postulate that patients with prolactinomas are more prone to autoimmune disease (AID). METHODS: We conducted a retrospective case-control study comparing prevalence of AID in 100 prolactinoma patients (PRL-P, cases) and 100 age- and gender-matched non-functioning pituitary adenoma patients (NFPA-P, controls) assessed at the Neuroendocrine Clinics of the McGill University Health Centre between January 2005 and December 2014. Comparisons were done using a conditional logistic regression (CLR) analysis. Multiple imputation was used to account for missing data values. RESULTS: Sixty-eight women and 32 men were in each group. Median age was 37 years for PRL-P and 46 years for NFPA-P. AID was diagnosed in 28/100 cases and 16/100 controls. Autoimmune thyroid disease was the most common AID reported in both groups, representing 70 and 61% of the AID diagnoses respectively. CLR analysis revealed a multiplicative interaction effect between AID prevalence and age (p 0.004). Odds ratios for AID in PRL-P compared to NFPA-P increase with age and become significant at age 43, reaching 4.17 (95% CI 1.26, 13.82) at age 45 and 8.09 (95% CI 1.96, 33.43) at age 50 (p 0.05). CONCLUSION: Our data showed a higher prevalence of AID in both PRL-P and NFPA-P than in a reference population. In both groups, prevalence of AID increased with age, given a multiplicative interaction effect. A significant higher prevalence of autoimmunity in PRL-P compared with NFPA-P occurs after age 43. These associations may have significant implications for the management of prolactinoma patients.

A primer on the genetics of medullary thyroid cancer.

Medullary thyroid cancer is a rare type of neuroendocrine tumour that arises from the parafollicular cells (C cells) of the thyroid gland. It accounts for 3%-5% of thyroid cancer cases. Close to 25% of cases are familial, and 75% are considered sporadic. Familial cases are associated with a germline RET mutation; 43%-65% of sporadic cases harbour a somatic event in the gene. Germline RET mutations are associated with the autosomal-dominant inherited multiple endocrine neoplasia (men) 2a and 2b syndromes and the isolated familial medullary thyroid cancer syndrome. More than 100 RET codon mutations have been reported to date, with genotype-phenotype correlations that include the extent and aggressiveness of the medullary thyroid cancer and the presence of other features of the men2 syndromes. The latter include pheochromocytoma-paraganglioma, hyperparathyroidism, cutaneous lichen amyloidosis, and Hirschsprung disease. In this narrative review, we focus on RET proto-oncogene physiology and pathogenesis induced by germline and somatic RET mutations, the genotype-phenotype correlation, and the management and follow-up of patients with germline-mutated medullary thyroid cancer.

Extreme and Cyclical Blood Pressure Elevation in a Pheochromocytoma Hypertensive Crisis.

Pheochromocytomas are rare adrenal neoplasms characterized by excess secretion of catecholamines. We describe the case of a 65-year-old man, known for hypertension, with no family history of hereditary pheochromocytoma syndromes. He reported a two-year history of flushing, systolic blood pressure surges to 200 mmHg, headaches, tremors, and syncope. His initial workup revealed elevated 24h urine catecholamines and metanephrines. An adrenal MRI in March 2017 showed a large 7.6 cm heterogeneous right adrenal lesion. Given orthostatic hypotension, his final preoperative dose was limited to a low dose of terazosin and metoprolol. In the operating room, shortly after intubation and Foley insertion, his blood pressure rose to 350 mmHg. Surgery was cancelled and he was admitted to the intensive care unit, where intravenous phentolamine, nitroprusside, and nicardipine were started. His systolic blood pressure would oscillate between 60 mmHg and 350 mmHg at 2-3 minutes' intervals. After 3 days, he was weaned off intravenous medications. His oral medications were uptitrated to high doses of phenoxybenzamine, metoprolol, and nifedipine. Three weeks later, he underwent successful open right adrenalectomy. This case outlines the importance of preoperative preparation of pheochromocytomas and raises the question if phenoxybenzamine is the alpha-blocker of choice for larger tumours with significant hormonal secretion.

Cytomegalovirus-mononucleosis-induced thyroiditis in an immunocompetent patient.

Enteroviruses, including coxsackieviruses and Echovirus, are well known pathogens responsible for the development of thyroiditis. We describe the case of a 49-year-old woman with no personal or family history of thyroid disease who presented to the emergency room with a two-week history of daily fevers up to 39°C, a sore throat, occasional palpitations and diaphoresis, decreased appetite and an unintentional 10 kg weight loss over the same time course Physical examination revealed mild tachycardia, an intention tremor and a normal-sized, nontender thyroid gland without palpable nodules. The remainder of the physical examination was unremarkable and without stigmata of Graves' disease. Her initial blood tests revealed overt thyrotoxicosis, elevated liver enzymes, an elevated C-reactive protein, a negative monospot and a positive CMV IgM antibody. Thyroid sonography revealed areas of hypoechogenicity and relatively low vascularity. Fine-needle biopsy showed a lymphocytic infiltrate. The patient was treated symptomatically with propranolol. On follow-up, the patient became euthyroid, and her liver enzymes normalised. Previous cases of CMV-induced thyroiditis occurred in immunosuppressed patients. This is the first reported case of a CMV-mononucleosis-induced thyroiditis in an immunocompetent adult patient and serves as a reminder that viral illnesses are a common cause of thyroiditis with abnormal liver enzymes. LEARNING POINTS: The differential diagnosis of thyrotoxicosis with abnormal liver enzymes includes severe hyperthyroidism and thyroid storm caused by Graves' disease as well as the thyrotoxic phase of a thyroiditis, usually caused by a virus such as coxsackievirus or, in this case, cytomegalovirus.Cytomegalovirus appears to be a recently recognized causal agent for thyroiditis, both in immunosuppressed and immunocompetent patients.Careful follow-up of thyroid function tests in patients with thyroiditis allows clinicians to determine if patients' thyroid hormone secretion normalizes or if they remain hypothyroid.

Iatrogenic myxoedema madness following radioactive iodine ablation for Graves' disease, with a concurrent diagnosis of primary hyperaldosteronism.

UNLABELLED: Myxoedema madness was first described as a consequence of severe hypothyroidism in 1949. Most cases were secondary to long-standing untreated primary hypothyroidism. We present the first reported case of iatrogenic myxoedema madness following radioactive iodine ablation for Graves' disease, with a second concurrent diagnosis of primary hyperaldosteronism. A 29-year-old woman presented with severe hypothyroidism, a 1-week history of psychotic behaviour and paranoid delusions 3 months after treatment with radioactive iodine ablation for Graves' disease. Her psychiatric symptoms abated with levothyroxine replacement. She was concurrently found to be hypertensive and hypokalemic. Primary hyperaldosteronism from bilateral adrenal hyperplasia was diagnosed. This case report serves as a reminder that myxoedema madness can be a complication of acute hypothyroidism following radioactive iodine ablation of Graves' disease and that primary hyperaldosteronism may be associated with autoimmune hyperthyroidism. LEARNING POINTS: Psychosis (myxoedema madness) can present as a neuropsychiatric manifestation of acute hypothyroidism following radioactive iodine ablation of Graves' disease.Primary hyperaldosteronism may be caused by idiopathic bilateral adrenal hyperplasia even in the presence of an adrenal adenoma seen on imaging.Adrenal vein sampling is a useful tool for differentiating between a unilateral aldosterone-producing adenoma, which is managed surgically, and an idiopathic bilateral adrenal hyperplasia, which is managed medically.The management of autoimmune hyperthyroidism, iatrogenic hypothyroidism and primary hyperaldosteronism from bilateral idiopathic adrenal hyperplasia in patients planning pregnancy includes delaying pregnancy 6 months following radioactive iodine treatment and until patient is euthyroid for 3 months, using amiloride as opposed to spironolactone, controlling blood pressure with agents safe in pregnancy such as nifedipine and avoiding ß blockers.Autoimmune hyperthyroidism and primary hyperaldosteronism rarely coexist; any underlying mechanism associating the two is still unclear.

Central nervous system atypical teratoid rhabdoid tumours: the Canadian Paediatric Brain Tumour Consortium experience.

BACKGROUND: Atypical teratoid rhabdoid tumours (ATRT) are aggressive brain tumours mostly occurring in early childhood. Largest published series arise from registries and institutional experiences (1-4). The aim of this report is to provide population-based data to further characterise this rare entity and to delineate prognostic factors. PATIENTS AND METHODS: A national retrospective study of children ⩽18years diagnosed with a central nervous system (CNS) ATRT between 1995 and 2007 was undertaken. All cases underwent central pathology review. RESULTS: There were 50 patients (31 males; median age at diagnosis of 16.7months). Twelve patients were >36months. Infratentorial location accounted for 52% of all cases. Nineteen patients (38%) had metastatic disease. Fifteen (30%) underwent gross total resection (GTR). Ten patients (20%) underwent palliation. Among the 40 remaining patients, 22 received conventional chemotherapy and 18 received high dose chemotherapy regimens (HDC); nine received intrathecal chemotherapy and 15 received adjuvant radiation. Thirty of the 40 treated patients relapsed/progressed at a median time of 5.5months (0-32). The median survival time of the entire cohort was 13.5months (1-117.5months). Age, tumour location and metastatic status were not prognostic. Patients with GTR had a better survival (2years overall survival (OS): 60%±12.6 versus 21.7%±8.5, p=0.03). HDC conferred better outcome (2years OS 47.9%±12.1 versus 27.3%±9.5, p=0.036). Upfront radiation did not provide survival benefit. Six of the 12 survivors (50%) did not receive radiation. CONCLUSION: The outcome of CNS ATRT remains poor. However, the use of HDC provides encouraging results. GTR is a significant prognostic factor. The role of adjuvant radiation remains unclear.