123I-Metaiodobenzylguanidine (123I-MIBG) scintigraphy scanning is commonly used in the imaging of phaeochromocytoma (and paraganglioma) to confirm the site of disease and whether any spread has occurred. However, 123I-MIBG imaging is negative in 15% of cases of benign phaeochromocytoma and around 50% of cases of malignant phaeochromocytoma. In recent years, positron emission tomography (PET) scanning using various different radiotracers has been shown to be a good alternative or supplementary investigation in phaeochromocytoma. We present the cases of four patients with symptoms and signs suggestive of phaeochromocytoma, but who had negative 123I-MIBG scans, and illustrate the usefulness of 18-fluoro-dihydroxyphenylalanine PET scanning in their assessment. In one of the patients, we illustrate how fluorodeoxyglucose PETscanning can provide useful information about the extent of malignant disease. These illustrative cases lend further support for the use of PET scanning in the assessment of phaeochromocytoma and suggest that it may have a particularly important role in the investigation of patients in whom 123I-MIBG scanning is negative.
I S Mackenzie, M Gurnell, K K Balan, H Simpson, K Chatterjee and M J Brown
R.J. Heine, M. Ponchner, I. Hanning, P. D. Home, M. Brown, D. Williams and K. G. M. M. Alberti
Abstract. Disturbances of potassium, calcium, phosphate and magnesium homeostasis in diabetes mellitus are well documented. We have compared the effects of semisynthetic human and pancreatic porcine insulin on transmembrane shifts of these ions, and on glucose metabolism, at two insulin infusion rates, 20 and 50 mU/kg/h, during euglycaemic clamping for 2 h in 6 normal volunteers. The glucose requirements and the changes in blood metabolite concentrations were not significantly different during the porcine and human insulin infusions.
Serum potassium levels, however, showed a significant greater decline with infusions of porcine insulin (4.2 ± 0.1 to 3.5 ± 0.1 mmol/l compared with human insulin (4.2 ± 0.1 to 3.7 ± 0.1 mmol/l) 50 mU/kg/h (P < 0.05). Potasssium levels were significantly lower during the porcine insulin infusion at 105 and 120 min and at 15 and 30 min after stopping the infusion.
Electrocardiographic T-wave voltage decreased during the porcine and human insulin infusion by 0.13 ± 0.02 and 0.10 ± 0.01 mV, respectively (P < 0.02). Changes in serum levels of magnesium, calcium, phosphate, and red blood cell concentrations of magnesium and 2,3-DPG, were not significantly different between the insulins.
Thus a small but significant greater decline in potassium levels with similar glucose requirements was found during iv administration of porcine insulin compared with human insulin.
J. B. Ferriss, J. J. Brown, A. M. M. Cumming, R. Fraser, A. F. Lever, M. Peacock and J. I. S. Robertson
Abstract. Two patients with both primary hyperparathyroidism and primary hyperaldosteronism are described. Each presented with high blood pressure and a history of renal calculi. Mild hypercalcaemia was associated with raised plasma parathyroid hormone concentrations and a parathyroid adenoma was excised from each. Both patients also had hypokalaemia, hyperaldosteronism and low plasma renin concentrations. Quadric analysis, adrenal vein plasma aldosterone concentrations, adrenal venography and CT scanning all suggested an adrenal adenoma in each patient. This suspicion was confirmed at operation in one patient; the other patient is unfit for adrenal surgery but her blood pressure and plasma potassium concentration have remained within the normal range during prolonged treatment with either spironolactone or amiloride.
Because of this unusual association a search was made for parathyroid hormone excess in patients with primary hyperaldosteronism and for aldosterone excess in primary hyperparathyroidism. None was found.
E. M. Desmit, W. S. Cost, J. J. Brown, R. Fraser, A. F. Lever and J. I. S. Robertson
3 patients with an unusual type of hypokalaemic alkalosis are described. The findings in these patients are compared with those in similar cases reported by Bartter and others (Bartter's syndrome). It is stressed that all of the abnormalities found in Bartter's syndrome may occur in sodium deficiency in the absence of organic disease.
The pathogenesis of the syndrome in our patients is uncertain but several possibilities are discussed. These include an apparently new aetiological hypothesis, a partial block in the adrenocortical response to stimulation by angiotensin.
Ellen W. Seely, Thomas J. Moore, Meryl S. LeBoff and Edward M. Brown
Hyperparathyroidism has been reported in patients receiving lithium therapy, and lithium alters calcium-regulated PTH release in vitro. Previous studies in vivo have used assays which measure fragments of PTH as well as the intact hormone. To determine if lithium acutely elevates intact PTH levels, we studied 9 subjects who received a single oral dose of lithium carbonate (600 mg). Serum levels of intact PTH, ionized calcium, and lithium were measured before, 2 and 14 h after the dose of lithium. PTH levels rose significantly 2 h following the dose of lithium (before 22 ± 5.0, post 32 ± 7.3 ng/l, p < 0.02). PTH levels had returned to baseline at 14 h (22 ± 3.8 ng/l). There were no significant changes in ionized calcium levels. Therefore, a single oral dose of lithium carbonate acutely elevates intact PTH values in human subjects.
P. Leduque, C. Gespach, J. C. Brown, G. Rosselin and P. M. Dubois
The appearance and distribution of the gastro-intestinal hormone, gastric inhibitory peptide (GIP) were examined in the gastro-entero-pancreatic system of human foetuses, aged 5–24 weeks, by immunocytochemistry or radioimmunoassay. The first immunoreactive cells were observed in the gut from 16 weeks of gestation. The GIP-containing cells were localized preferentially in the villous epithelium of the small intestine. In the radioimmunoassay, the highest concentrations of immunoreactive GIP (IR-GIP) were detected from 13 to 21 weeks of gestation. The tissue concentration of IR-GIP was 68.10 ± 10.70 ng/g wet weight of duodenum, 30.29 ± 3.96 ng/g wet weight of jejuno-ileum and 3.05 ± 1.97 ng/g wet weight in the colon. Measurable amounts of IR-GIP (4.93 ± 1.57 ng/g wet weight of organ) were found from 9 to 12 weeks in the jejuno-ileal region. The ontogenic development of IR-GIP was studied in this region. From 13 to 21 weeks of gestation, the IR-GIP content per g of organ increased about 6-fold. In the endocrine pancreas, GIP antiserum No. R07 was potent in staining A cells from 14 weeks of gestation. In radioimmunological tests, no cross-reactions of the anti-GIP sera R 07 and GP 01 with heterologous peptides were observed. Labelling of paraffin and semi-thin sections was subjected not only to the usual specificity tests, but also to particularly extensive cross-reaction studies. GIP-like immunoreactivity was not inhibited by absorptions against heterologous peptides added at varying concentrations. The immunocytological and radioimmunological results are consistent with an eventual implication of GIP in the endocrine regulation of metabolism or in the development of the gastro-entero-pancreatic system during the intrauterine life in man.
B. M. Fisher, G. J. A. MacPhee, D. L. Davies, S. G. McPherson, I. L. Brown and A. Goldberg
Abstract. A 40 year old woman presented with a 10 year history of watery diarrhoea and an acute quadriparesis. On clinical examination there was severe muscle weakness and a nodule was palpable in the thyroid gland. Biochemical testing revealed a hypokalaemia at 1.6 mmol/l. Plasma levels of VIP were raised at 202 pmol/l. CT scanning demonstrated a mass in the area of the left adrenal gland, and isotope scanning of the thyroid gland showed a 'cold' nodule. The plasma catecholamines and calcitonin were elevated. The patient also presented with psychiatric symptoms, and the relevance of these to her condition has been discussed. At operation a left adrenal tumour was removed. Post-operatively the patient's symptoms disappeared and the plasma hormone levels returned to normal values. Histological examination of the tumour revealed a well differentiated phaeochromocytoma which contained VIP and calcitonin. The thyroid nodule was excised and showed histological features of autoimmune thyroid disease. It is suggested that in all cases of the WDHA syndrome where the tumour is in an extra-pancreatic site patients should be screened for phaeochromocytoma.
W. Vale, C. Rivier, M. Brown, P. Plotsky, L. Swanson, T. Bruhn, F. Bloom, G. Koob, J. Spiess, M. Thorner and J. Rivier.
J.J. Brown, A.M.M. Cumming, B. Leckie, A.F. Lever, A. Mackay, A. Millar, J.J. Morton, P.L. Padfield, J.I.S. Robertson, P.F. Semple and M. Tree
C M Ogilvie, P L Brown, M Matson, J Dacie, R H Reznek, K Britton, R Carpenter, D Berney, W M Drake, P J Jenkins, S L Chew and J P Monson
Objective: The role of preoperative localisation of abnormal parathyroid glands remains controversial but is particularly relevant to the management of patients with recurrent or persistent hyperparathyroidism and familial syndromes. We report our experience of the use of selective parathyroid venous sampling (PVS) in the localisation of parathyroid disease in such patients.
Design: We report a retrospective 10-year experience (n = 27) of the use of PVS in complicated primary hyperparathyroidism and contrast the use of PVS with neck ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) and sestamibi imaging modalities.
Results: In 14 out of 25 patients who underwent surgery PVS results were completely concordant with surgical and histological findings and 88% of patients achieved post-operative cure. Out of 13 patients referred after previous failed surgery, 12 underwent further surgery which was curative in 9. In total PVS yielded useful positive (n = 13) and/or negative information (n = 6) in 19 out of 25 patients undergoing surgery. Using histology as the gold standard, 59% of PVS studies were entirely consistent with histology, as compared with 39% of ultrasound scans, 36% of sestamibi scans and 17% of MRI/CT scans.
Conclusions: PVS is a valuable adjunct to MRI/CT and sestamibi scanning in selected patients with complicated hyperparathyroidism when performed in an experienced unit.