Pheochromocytoma associated with a succinate dehydrogenase subunit B mutation: A minireview and a case report.

Objective. Pheochromocytomas and paragangliomas are rare neuroendocrine tumors that arise from the chromaffin cells of the adrenal medulla or extra-adrenal tissues. These tumors are characterized by an excessive secretion of catecholamines, which are responsible for the clinical manifestation of the disease. Although most of these tumors are sporadic, underlying genetic abnormalities may be present in up to 24% of the cases. A succinate dehydrogenase subunit B (SDHB) mutation represents one of the rare presentations of the disease. In this study, we represent a rare case of pheochromocytoma associated with SDHB mutation. Methods. We performed a retrospective review of our case in addition to reviewing the available literature on the same topic. Results. A 17-year-old patient presented with sustained hypertension. Clinical, laboratory, and radiological evaluations confirmed the diagnosis of catecholamine-secreting tumor. Laparoscopic adrenalectomy was performed. Histopathological and genetic testing confirmed a pheochromocytoma associated with SDHB mutation. No recurrence was detected on two-years of follow up. Conclusion. Pheochromocytoma associated with SDHB mutation is a rare presentation. Genetic testing for suspecting cases is essential to help to establish the appropriate follow-up plan.

Postradioiodine Graves' management: The PRAGMA study.

OBJECTIVE: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies. DESIGN: Retrospective, multicentre and observational study. PATIENTS: Adult patients with Graves' disease treated with RI with 12 months' follow-up. MEASUREMENTS: Euthyroidism was defined as both serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo- and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. RESULTS: Of 812 patients studied post-RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post-RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%-28.7%). No negative outcomes (new-onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. CONCLUSIONS: Dysthyroidism in the 12 months post-RI was common. Differences between post-RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism.

Clinical Presentation and Outcomes of Phaeochromocytomas/Paragangliomas in Neurofibromatosis Type 1.

Introduction: Patients with neurofibromatosis type 1 (NF1) are at risk of developing phaeochromocytomas/paragangliomas (PHAEO/PG). Unlike in other familial PHAEO/PG syndromes, there are no published guidelines regarding screening in asymptomatic or normotensive patients with NF1. This strategy may be associated with preventable morbidities in those patients who ultimately present with symptomatic PHAEO/PG. Objective: To describe the mode of presentation and the incidence of adverse clinical outcomes attributed to PHAEO/PG in NF1. Methods: A retrospective study was performed in a tertiary referral centre in collaboration with a national complex NF1 centre. Hospital records and databases between 1998-2018 were searched. Results: Twenty-seven patients with NF1 and PHAEO/PG were identified. In all but one, PHAEO/PG was diagnosed after NF1. The median age at the time of diagnosis of PHAEO/PG was 43 years (range 22-65) and 21/27 (78%) were females. The diagnosis was mostly incidental in 13/27 (48%) while classical PHAEO/PG symptoms were found in 15/27 (56%), and hypertension was found in 14/27 (52%) of NF1 patients prior to PHAEO/PG diagnosis. No patient had undergone biochemical screening for PHAEO/PG. Metastatic disease was evident in 2/27 patients, 8 suffered potentially avoidable complications attributed to PHAEO/PG (including two deaths). Conclusion: The course of PHAEO/PG in NF1 is associated with an unpredictable presentation and potentially avoidable adverse outcomes. We recommend that routine biochemical screening for PHAEO/PG should be part of the care package offered to all patients with NF1 by regular measurements of plasma free or urinary fractionated metanephrines starting from early adolescence and repeated every 3 years.

Lesson of the month 2: Catecholamine-induced cardiomyopathy - pitfalls in diagnosis and medical management.

Cardiomyopathy as the initial presentation of phaeochromocytoma (PCA) is uncommon. Diagnostic work-up and perioperative management may be challenging within this context. We report three cases of PCA presenting with cardiomyopathy to illustrate the pitfalls in diagnosis and management. None of the patients had typical adrenergic symptoms and all three were established on beta-blockers prior to diagnosis. Their fractionated plasma catecholamine levels were elevated and the diagnosis of PCA was confirmed with various imaging modalities and post adrenalectomy. Interpretation of fractionated catecholamine levels in the context of established cardiomyopathy is difficult as cardiac failure of any aetiology generates an adrenergic response. Hence screening all patients with idiopathic cardiomyopathy is likely to generate a high false-positive rate. However, a high index of suspicion should prompt further diagnostic work-up in patients with idiopathic cardiomyopathy for occult PCAs. Peer-reviewed guidelines are required to guide the investigation and management of suspected catecholamine-induced cardiomyopathy.

Mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy.

OBJECTIVE: Lipid accumulation in skeletal muscle and the liver is strongly implicated in the development of insulin resistance and type 2 diabetes, but the mechanisms underpinning fat accrual in these sites remain incompletely understood. Accumulating evidence of muscle mitochondrial dysfunction in insulin-resistant states has fuelled the notion that primary defects in mitochondrial fat oxidation may be a contributory mechanism. The purpose of our study was to determine whether patients with congenital lipodystrophy, a disorder primarily affecting white adipose tissue, manifest impaired mitochondrial oxidative phosphorylation in skeletal muscle. RESEARCH DESIGN AND METHODS: Mitochondrial oxidative phosphorylation was assessed in quadriceps muscle using 31P-magnetic resonance spectroscopy measurements of phosphocreatine recovery kinetics after a standardized exercise bout in nondiabetic patients with congenital lipodystrophy and in age-, gender-, body mass index-, and fitness-matched controls. RESULTS: The phosphocreatine recovery rate constant (k) was significantly lower in patients with congenital lipodystrophy than in healthy controls (P<0.001). This substantial (∼35%) defect in mitochondrial oxidative phosphorylation was not associated with significant changes in basal or sleeping metabolic rates. CONCLUSIONS: Muscle mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy, a paradigmatic example of primary adipose tissue dysfunction. This finding suggests that changes in mitochondrial oxidative phosphorylation in skeletal muscle could, at least in some circumstances, be a secondary consequence of adipose tissue failure. These data corroborate accumulating evidence that mitochondrial dysfunction can be a consequence of insulin-resistant states rather than a primary defect. Nevertheless, impaired mitochondrial fat oxidation is likely to accelerate ectopic fat accumulation and worsen insulin resistance.

Integrated care pathway for self-harm: our way forward.

BACKGROUND: Balancing pressures of the 4-h wait in Accident and Emergency (A&E) and the National Institute for Clinical Excellence (NICE) requirement for a psychosocial assessment (PSA) before leaving hospital for patients presenting with self-harm is a challenge. This paper suggests a new method for coping with this demand. METHODS: A score of 5 or above on the Modified Sad Persons Scale (MSPS), rated by general hospital staff, would result in an automatic admission to the general hospital for detailed PSA by the dedicated liaison psychiatry team the following day. RESULTS: Most patients are usually admitted due to medical concerns. Only a small number of patients needed further psychiatric inpatient admission. CONCLUSIONS: This integrated care pathway (ICP) is evidence of true multidisciplinary working resulting in mutually beneficial outcomes for both the acute and mental health trusts.