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Michel Procopiou, Hazel Finney, Scott A Akker, Shern L Chew, William M Drake, Jacky Burrin and Ashley B Grossman

Objective

To define the test characteristics of an enzyme immunoassay (EIA) for plasma-free metanephrines (metanephrine and normetanephrine) in the diagnosis of pheochromocytoma and paraganglioma.

Design

Prospective observational design from a single University Hospital. Twenty-four hour urine for catecholamines and plasma for free metanephrines were collected from patients with a clinical suspicion of pheochromocytoma or paraganglioma. Patient records were reviewed for clinical data, follow-up, imaging and laboratory results to establish or exclude the diagnosis of pheochromocytoma.

Patients and methods

Out of 178 consecutive patients, 10 had a paraganglioma and 12 had a pheochromocytoma: 156 were finally judged not to harbour active tumors and were therefore considered as controls. The main outcome measure was the diagnosis or exclusion of paraganglioma or pheochromocytoma and test characteristics of plasma-free metanephrines measured by EIA.

Results

Urinary epinephrine had a sensitivity of 45.5% and norepinephrine a sensitivity of 75% (98.8% specificity) for the diagnosis of pheochromocytoma. Plasma-free metanephrine and normetanephrine both had a sensitivity of 66.7% and a specificity of 100%, but when combined (either positive) they demonstrated a 91.7% sensitivity with a preserved specificity of 100%. For the diagnosis of paraganglioma, urinary norepinephrine gave slightly better results than plasma-free metanephrines, but combined testing was of no additional value.

Conclusions

Plasma-free metanephrines measured by EIA have better diagnostic test characteristics than urinary catecholamines in the diagnosis of pheochromocytoma. The EIA offers a simple and effective measurement of plasma-free metanephrines.

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Michel Procopiou, Hazel Finney, Scott A Akker, Shern L Chew, William M Drake, Jacky Burrin and Ashley B Grossman

The authors and journal apologize for the error in the above paper which appeared in 161 (1) 131–140. The kits for the assay of free metanephrines were supplied by both Immunodiagnostic Systems Ltd (IDS), Tyne and Wear, UK and also Biotech-IgG (UK) Ltd, Wilmslow, UK.

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Richard Sheaves, Jonathan Goldin, Rodney H Reznek, Shern L Chew, Janet E Dacie, David G Lowe, Richard JM Ross, John AH Wass, G Michael Besser and Ashley B Grossman

Sheaves R, Goldin J, Reznek RH, Chew SL, Dacie JE, Lowe DG, Ross RJM, Wass JAH, Besser GM, Grossman AB, Relative value of computed tomography scanning and venous sampling in establishing the cause of primary hyperaldosteronism. Eur J Endocrinol 1996;134:308–13. ISSN 0804–4643

The purpose of this study was to evaluate the relative merits of the postural stimulation test, adrenal computed tomography (CT) and venous sampling in the differential diagnosis of patients presenting with primary hyperaldosteronism. The records of 20 patients presenting with primary hyperaldosteronism were reviewed retrospectively. There were 15 patients with a unilateral aldosterone-producing adenoma (APA), four patients with idiopathic hyperaldosteronism (IHA) and one patient with primary adrenal hyperplasia (PAH). The postural stimulation test was based on measurements of plasma aldosterone and renin activity at 08.00 h and at noon after 4 h of ambulation. The CT scans of the adrenals were reviewed by a single radiologist. Bilateral venous sampling of adrenal veins was attempted in all patients and blood collected for aldosterone and cortisol assay. Plasma aldosterone concentration increased after 4 h of standing in all cases of hyperplasia but was also demonstrated in 10/15 patients with a surgically-proven APA, If one defines a significant postural rise as being greater than 30%, then 8/15 patients with APA can be considered as being posturally responsive. Computed tomography scanning correctly identified all 15 cases of APA and also classified correctly the remaining five cases of hyperplasia (four cases of IHA and one case of PAH). Venous sampling failed technically in 4/15 cases of APA and in one case of IHA; a total of 5/20 (25%), A correct diagnosis of APA or IHA was established in all the remaining cases. However, the one case of PAH was treated successfully by adrenalectomy following venous sampling, which suggested a unilateral adrenal lesion: this one result was the only instance where venous sampling altered clinical decision-making. Computed tomography scanning may be used alone to confirm the cause of hyperaldosteronism where postural studies suggest an adrenal adenoma, and such patients may be considered for early surgery. Venous catheterization studies are not necessary routinely, but may still be useful in selected patients, particularly when CT scanning shows no clear lesion.

Ashley Grossman, Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London ECIA 7BE, UK

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Krystallenia I Alexandraki, Gregory A Kaltsas, Andrea M Isidori, Scott A Akker, William M Drake, Shern L Chew, John P Monson, G Michael Besser and Ashley B Grossman

Objective

Cyclical Cushing's syndrome may render the diagnosis and management of Cushing's disease difficult. The aim of the present study was to investigate the prevalence of cyclicity and variability in patients with Cushing's disease, and to identify putative distinctive features.

Design

Retrospective case-note study.

Methods

We analysed the case records of 201 patients with Cushing's disease in a retrospective case-note study. Cyclicity was considered as the presence of at least one cycle, defined as a clinical and/or biochemical hypercortisolaemic peak followed by clinical and biochemical remission, followed by a new clinical and/or biochemical hypercortisolaemic peak. The fluctuations of mean serum cortisol levels, as assessed by a 5-point cortisol day curve, defined the variability.

Results

Thirty (14.9%; 26 females) patients had evidence of cyclicity/variability. ‘Cycling’ patients were older but no difference in sex or paediatric distribution was revealed between ‘cycling’ and ‘non-cycling’ patients. The median number of cycles was two for each patient, and 4 years was the median intercyclic period. A trend to lower cure rate post-neurosurgery and lower adenoma identification was observed in ‘cycling’ compared with ‘non-cycling’ patients. In multivariate analysis, older patients, longer follow-up, female sex and no histological identification of the adenoma were associated with an increased risk of cyclic disease.

Conclusions

This large population study reveals that cyclicity/variability is not an infrequent phenomenon in patients with Cushing's disease, with a minimum prevalence of 15%. Physicians should be alert since it can lead to frequent problems in diagnosis and management, and no specific features can be used as markers.

Free access

Tara Barwick, Iain Murray, Hakim Megadmi, William M Drake, P Nick Plowman, Scott A Akker, Shern L Chew, Ashley B Grossman and Norbert Avril

Objective

The aim of the study was to assess the diagnostic performance of co-registered single photon emission computed tomography (SPECT)/computed tomography (CT) compared to Iodine-123 whole body gamma camera (WBGC) imaging and to SPECT alone in patients with differentiated thyroid cancer.

Methods

WBGC and SPECT/CT (n=85) imaging of the neck and thorax was performed in 79 consecutive patients. Three experienced observers reviewed: i) WBGC images followed by ii) SPECT alone, and iii) co-registered SPECT/CT. Foci of increased radioiodine uptake were classified on a five-point scale. Biopsy, other imaging modalities, and clinical follow-up served as the reference standard.

Results

Twenty-two patients had local recurrence or metastatic thyroid cancer (11 were radioiodine negative), 9 had remnant thyroid tissue, and 54 had no evidence of disease. When classifying equivocal, probably, and definitely malignant findings as positive for malignancy, the sensitivity, specificity, positive predictive value, and negative predictive value were as follows: 41, 68, 31, and 77% for WBGC imaging; 45, 89, 59, and 82% for WBGC plus SPECT imaging; and 50, 100, 100, and 85% for WBGC plus SPECT/CT imaging respectively. The specificity was improved by the addition of SPECT (P=0.0002) and SPECT/CT (P<0.0001) than to WBGC imaging. SPECT/CT was also more specific than WBGC plus SPECT imaging (P=0.016). In a study-based analysis, SPECT/CT provided additional diagnostic information in 42% (36/85) of cases. SPECT/CT provided further characterization in 70% (63/90) of foci and improved the diagnostic confidence of all three observers.

Conclusion

The addition of SPECT/CT significantly improved the diagnostic information over Iodine-123 WBGC imaging and WBGC plus SPECT imaging alone.

Free access

Krystallenia I Alexandraki, Gregory A Kaltsas, Andrea M Isidori, Helen L Storr, Farhad Afshar, Ian Sabin, Scott A Akker, Shern L Chew, William M Drake, John P Monson, G Michael Besser and Ashley B Grossman

Objective

To investigate the early and late outcomes of patients with Cushing's disease (CD) submitted to a neurosurgical procedure as first-line treatment.

Design

In this single-centre retrospective case notes study, 131 patients with CD with a minimum follow-up period of 6 years (124 operated by transsphenoidal surgery (TSS) and seven by the transcranial approach) were studied. Apparent immediate cure: post-operative 0900 h serum cortisol level <50 nmol/l; remission: cortisol insufficiency or restoration of ‘normal’ cortisol levels with resolution of clinical features; and recurrence: dexamethasone resistance and relapse of hypercortisolaemic features.

Results

In patients operated by TSS, remission of hypercortisolaemia was found in 72.8% of 103 microadenomas and 42.9% of 21 macroadenomas, with recurrence rates 22.7 and 33.3% respectively with a 15-year mean follow-up (range, 6–29 years). Of 27 patients with microadenomas operated after 1991, with positive imaging and pathology, 93% obtained remission with 12% recurrence. In multivariate analysis, the time needed to achieve recovery of hypothalamo-pituitary–adrenal axis was the only significant predictor of recurrence; all patients who recurred showed recovery within 3 years from surgery: 31.3% of patients had total hypophysectomy with no recurrence; 42% of patients with selective adenomectomy and 26.5% with hemi–hypophysectomy showed recurrence rates of 31 and 13% respectively (χ 2=6.275, P=0.03). Strict remission criteria were not superior in terms of the probability of recurrence compared with post-operative normocortisolaemia.

Conclusions

Lifelong follow-up for patients with CD appears essential, particularly for patients who have shown rapid recovery of their axis. The strict criteria previously used for ‘apparent cure’ do not appear to necessarily predict a lower recurrence rate.

Free access

Maralyn R Druce, Vasantha M Muthuppalaniappan, Benjamin O'Leary, Shern L Chew, William M Drake, John P Monson, Scott A Akker, Michael Besser, Anju Sahdev, Andrea Rockall, Soumil Vyas, Satya Bhattacharya, Matthew Matson, Daniel Berney and Ashley B Grossman

The authors apologise for an error in the author list of the article titled above published in the journal, volume 162 on page 971. R H Reznek should be the penultimate author. The full list of authors and their affiliations for this article is as follows:

Maralyn R Druce1, Vasantha M Muthuppalaniappan1, Benjamin O'Leary1, Shern L Chew1, William M Drake1, John P Monson1, Scott A Akker1, Michael Besser1, Anju Sahdev2, Andrea Rockall2, Soumil Vyas3, Satya Bhattacharya3, Matthew Matson2, Daniel Berney4, R H Reznek2 and Ashley B Grossman1

Departments of 1Endocrinology, 2Radiology, 3Surgery and 4Histopathology, Barts and the London Medical School, St Bartholomew's Hospital, London EC1A 7BE, UK.

Free access

Maralyn R Druce, Vasantha M Muthuppalaniappan, Benjamin O'Leary, Shern L Chew, William M Drake, John P Monson, Scott A Akker, Michael Besser, Anju Sahdev, Andrea Rockall, Soumil Vyas, Satya Bhattacharya, Matthew Matson, Daniel Berney and Ashley B Grossman

Context

Preoperative localisation of insulinoma improves cure rate and reduces complications, but may be challenging.

Objective

To review diagnostic features and localisation accuracy for insulinomas.

Design

Cross-sectional, retrospective analysis.

Setting

A single tertiary referral centre.

Patients

Patients with insulinoma in the years 1990–2009, including sporadic tumours and those in patients with multiple endocrine neoplasia syndromes.

Interventions

Patients were identified from a database, and case notes and investigation results were reviewed. Tumour localisation by computed tomography (CT), magnetic resonance imaging (MRI), octreotide scanning, endoscopic ultrasound (EUS) and calcium stimulation was evaluated.

Main outcome measure(s)

Insulinoma localisation was compared to histologically confirmed location following surgical excision.

Results

Thirty-seven instances of biochemically and/or histologically proven insulinoma were identified in 36 patients, of which seven were managed medically. Of the 30 treated surgically, 25 had CT (83.3%) and 28 had MRI (90.3%), with successful localisation in 16 (64%) by CT and 21 (75%) by MRI respectively. Considered together, such imaging correctly localised 80% of lesions. Radiolabelled octreotide scanning was positive in 10 out of 20 cases (50%); EUS correctly identified 17 lesions in 26 patients (65.4%). Twenty-seven patients had calcium stimulation testing, of which 6 (22%) did not localise, 17 (63%) were correctly localised, and 4 (15%) gave discordant or confusing results.

Conclusions

Preoperative localisation of insulinomas remains challenging. A pragmatic combination of CT and especially MRI predicts tumour localisation with high accuracy. Radionuclide imaging and EUS were less helpful but may be valuable in selected cases. Calcium stimulation currently remains useful in providing an additional functional perspective.