Phaeochromocytoma and functioning paraganglioma in childhood and adolescence: role of iodine 131 metaiodobenzylguanidine

Phaeochromocytomas and functioning paragangliomas are rare tumours in childhood and adolescence. We review our experience of 43 cases (24 men, 19 women) who were first diagnosed at the age of ⩽ 18 years. All patients were evaluated at some point in their illness with iodine 131 metaiodobenzylguanidine ( 131 I-mIBG) scintigraphy. Eight patients (19%) had bilateral adrenal tumours, 12 (28%) had solitary extra-adrenal tumours, and 8 (19%) had multiple tumours. In 10 patients (23%), the tumours were associated with a familial neurocristopathic syndrome. Thirteen of 24 (54%) unifocal tumours which were initially considered to be benign ultimately proved to be multi-focal and/or malignant. The final prevalence of malignancy was 60% − 26 patients, of whom only 15 (57%) had obviously malignant tumours at the time of diagnosis. Primary tumour size ⋝5 cm was more commonly associated with a malignant course in adrenal but not extra-adrenal tumours. No other clinical, biochemical or morphological characteristic was significantly associated with malignancy. Although the high prevalence of malignancy in this series at least partly reflects referral bias, the need for lifelong follow-up of these patients is underscored. 131 I-mIBG scintigraphy was positive in 36 patients (84%), with a somewhat lower false-negative rate (12%) than X-ray computed tomography (20%). Eight patients with malignant tumours received therapeutic doses of 131 I-mIBG, with partial tumour responses in 3. Thus, 131 I-mIBG is an efficacious, non-invasive, localising agent and may be considered as a palliative therapeutic agent when alternatives have failed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46831/1/259_2005_Article_BF02262730.pd

Myocardial perfusion scans

This article forms part of our ‘tests and results’ series for 2013, which aims to provide information about common tests that general practitioners order regularly. It considers areas such as indications, what to tell the patient, what the test can and cannot tell you and interpretation of the result

Thyroid scans

This article forms part of our 'Tests and results' series for 2012, which aims to provide information about common tests that general practitioners order regularly. It considers areas such as indications, what to tell the patient, what the test can and cannot tell you and interpretation of results

Cerebral perfusion (SPECT) studies

This article forms part of our ‘Tests and results’ series for 2013, which aims to provide information about common tests that general practitioners order regularly. It considers areas such as indications, what to tell the patient, what the test can and cannot tell you, and interpretation of the results

Failure of reflex venoconstriction during exercise in patients with vasovagal syncope

In this study, we tested two hypotheses. First, we tested the hypothesis that reflex constriction of the venous capacitance beds in patients with vasovagal syncope is impaired during both subhypotensive lower-body negative pressure. Second, we proposed that splenic venoconstriction may be impaired during exercise in patients with vasovagal syncope

A novel mutation of the primary protein kinase C phosphorylation site in the calcium-sensing receptor causes autosomal dominant hypocalcemia

Objective: The calcium-sensing receptor (CASR) is a key controller of calcium homeostasis by regulating parathyroid hormone (PTH) secretion and renal calcium reabsorption. CASRT888 is a protein kinase C (PKC) phosphorylation site in the receptor's intracellular domain that has previously been identified as a critical negative regulator of CASR downstream signaling in vitro, but whose importance in vivo is unknown. Case report: The proband presented with mild symptomatic hypocalcemia following treatment for nephrotic syndrome due to minimal change glomerulonephropathy. Laboratory tests revealed inappropriately normal PTH concentrations and relative hypercalciuria typical of autosomal dominant hypocalcemia. His asymptomatic father had similar laboratory test results. Design and methods: The CASR gene was sequenced. To investigate the molecular consequences of CASRT888M mutation, site-directed mutagenesis was used to modify the wild-type (wt)-CASR gene, with the resulting mutant being transfected transiently into HEK-293 cells. Results: A novel CASR missense mutation, T888M, was identified in both cases. The CASRT888M mutant exhibited enhanced sensitivity to extracellular calcium concentration, both for intracellular calcium (Cai2+) mobilization and for ERK phosphorylation, despite having unaltered levels of cell surface expression. Furthermore, CASRT888M elicited sustained Ca i2+ mobilization rather than high frequency Ca i2+ oscillations, and, unlike the wt-CASR, the response was resistant to acute inhibition by the PKC activator, phorbol 12-myristate 13-acetate. Conclusions: The clinical and functional data provide the first genotype-phenotype correlation for a mutation at T888, indicating its critical physiological importance in CASR signaling. Thus, CASRT888 represents a functionally important, inhibitory phosphorylation site that contributes to the control of PTH secretion. © 2011 European Society of Endocrinology