ABSTRACT
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.
ABSTRACT
INTRODUCTION: Phaeochromocytomas/paragangliomas (PHAEO/PG) are linked to hereditary syndromes including neurofibromatosis type 1 (NF-1). Current guidelines do not recommend biochemical screening for PHAEO/PG in asymptomatic or normotensive patients with NF-1. This strategy may miss preventable morbidities in those patients who ultimately present with symptomatic PHAEO/PG. Our aim was to review the literature and extract data on mode of presentation and the incidence of reported adverse outcomes. METHODS: PubMed and EMBASE literature search using the keywords "Phaeochromocytoma", "Paraganglioma" and "Neurofibromatosis" was performed looking for reported cases from 2000 to 2018. RESULTS: 73 reports of NF-1 patients with PHAEO/PG were found. Patients were predominately women (n=40) with a median age of 46 years (range 16-82). PHAEO/PG was found incidentally in most patients, 36/73 did not present with typical symptoms while 27 patients were normotensive at diagnosis. 31 patients had adverse outcomes including metastases and death. CONCLUSION: Given the protean presentation of PHAEO/PG, relying on symptomology and blood pressure status as triggers for screening is associated with adverse outcomes. Further studies are required to ascertain whether biochemical screening in asymptomatic and normotensive patients with NF-1 can reduce the rate of adverse outcomes.
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Metastasis of neuroendocrine tumor to the myocardium is rare. We present a case of 64-year-old woman, who presented initially with abdominal pain and large adnexal mass. The image-guided biopsy showed low-grade neuroendocrine tumor with Ki67 less than 2% within the ovarian tissue. CT staging revealed bilateral adnexal masses, liver metastases, and primary lesion in the terminal ileum. Octreoscan showed marked tracer uptake within the lower esophagus not related to obvious mass on CT scan; the echocardiography confirmed the presence of a 2.7 cm LV/LA mass. In this case, close correlation between ECHO and the octreoscan obviated need for myocardial biopsy.
Subject(s)
Carcinoid Tumor/diagnostic imaging , Gastrointestinal Neoplasms/diagnostic imaging , Heart Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Carcinoid Tumor/pathology , Female , Gastrointestinal Neoplasms/pathology , Heart Neoplasms/secondary , Humans , Middle AgedABSTRACT
OBJECTIVE: Somatostatin (SST) analogues are a key option in the management of a variety of conditions, including acromegaly. Tachyphylaxis to SST analogues is not documented in acromegaly. We describe such a phenomenon. DESIGN AND METHODS: A 74-year-old female with acromegaly previously treated with (90)Y implant, external radiotherapy and thrice daily s.c. octreotide had stable GH levels of 19 mU/l. GH progressively rose following switches to lanreotide and depot octreotide as Sandostatin LAR: from 29 to 126 mU/l. Magnetic resonance imaging and (111)In-pentetreotide scanning revealed no tumour growth or alteration in SST receptor (SSTR) status. Tachyphylaxis to SST analogues was considered. Therapy was discontinued and re-introduced in daily 200 microg/24 h increments by continuous s.c. infusion, to a maximum of 1000 microg/24 h, and maintained over 3 weeks with daily, followed by weekly, GH profiles. Competitive (125)I-octreotide radioligand binding assays measured in vitro bio-activity of anti-SST analogue antibodies. In vitro SSTR binding studies utilised SSTR-expressing rat cortex membrane. RESULTS: Median GH fell by 93% from 504 to 39.5 mU/l and rose reproducibly on continued infusion to 120 mU/l. Octreotide withdrawal for 16 h produced a 64% increase in sensitivity. High-affinity IgG anti-lanreotide (IC(50)=187 pmol/l) and anti-octreotide (IC(50)=82 nmol/l) antibody, with no crossreactivity with natural SST, was demonstrated. In vitro inhibition of (125)I-octreotide SSTR binding by anti-SST analogue crossreacting antibody was observed at 1:1 serum dilution. CONCLUSIONS: This is the first report of tachyphylaxis to SST analogues in acromegaly. We believe that the short time course of resensitisation following acute octreotide withdrawal is suggestive of an effect(s) on receptor function or on the receptor signal transduction cascade at sites further downstream, rather than an immune-mediated phenomenon.
