S. L. Chew

Treatment of metastatic carcinoid tumours, phaeochromocytoma, paraganglioma and medullary carcinoma of the thyroid with 131I-meta-iodobenzylguanidine (131I-mIBG)

OBJECTIVE Meta‐iodo‐benzyl‐guanidine labelled with 131‐iodine (131I‐mIBG) has been used extensively for imaging tumours originating from the neural crest but experience with its therapeutic use is limited, particularly for non‐catecholamine secreting tumours. In order to assess the therapeutic response and potential adverse effects of the therapeutic administration of 131I‐mIBG, we have reviewed all patients who had received this form of treatment in our department.

Pancreatic lesions in von Hippel–Lindau disease

objective Von Hippel–Lindau disease is an inherited neoplasia syndrome. The main endocrine manifestations are phaeochromocytoma and paraganglioma. The presence of pancreatic disease has also been variably reported. This study was undertaken to describe the prevalence, nature, natural history and clinical associations of pancreatic lesions in von Hippel–Lindau disease.

Optimal dosage interval for depot somatostatin analogue therapy in acromegaly requires individual titration

The recent introduction of the depot somatostatin analogues octreotide LAR and lanreotide represent major advances in the medical treatment of acromegaly. However, it is uncertain whether the recommended dose intervals of 4 weeks and 10–14 days, respectively, are applicable to all patients.

Tumour surveillance imaging in patients with extrapituitary tumours receiving growth hormone replacement

Objective  GH replacement is widely used in the management of patients with adult‐onset (AO)‐GH deficiency (GHD). In most cases, AO‐GHD arises as a result of pituitary/peripituitary tumours and/or their treatment, but the effect of GH replacement on recurrence/regrowth of these tumours is unknown. The aim of this study was to examine the effect of GH replacement in a group of patients with primary tumours of the parasellar region, many of which (e.g. craniopharyngioma, glioma or germ cell tumours) might be anticipated to have a higher recurrence rate than secretory and nonsecretory anterior pituitary tumours.

Repeated colonoscopic screening of patients with acromegaly: 15-year experience identifies those at risk of new colonic neoplasia and allows for effective screening guidelines

OBJECTIVE It is suggested that patients with acromegaly have an increased risk of colorectal cancer and pre-malignant adenomatous polyps. However, the optimum frequency with which colonoscopic screening should be offered remains unclear. DESIGN To determine the optimum frequency for repeated colonoscopic surveillance of acromegalic patients. METHODS We retrospectively reviewed the case records of all patients with acromegaly seen in our centre since 1992: 254 patients had at least one surveillance colonoscopy, 156 patients had a second surveillance colonoscopy, 60 patients had a third surveillance colonoscopy and 15 patients had a fourth surveillance colonoscopy. RESULTS The presence of hyperplastic or adenomatous polyps was assessed in all patients, while one cancer was detected at the second surveillance. At the third surveillance, mean (+/-s.d.) serum IGF1 levels (ng/ml) in patients with hyperplastic polyps were significantly higher than those with normal colons (P<0.05). The presence of an adenoma rather than a normal colon at the first colonoscopy was associated with a significantly increased risk of adenoma at the second (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.9-10.4) and at the third (OR 8.8, 95% CI 2.9-26.5) screens. Conversely, a normal colon at the first surveillance gave a high chance of normal findings at the second (78%) or third surveillance (78%), and a normal colon at the second colonoscopy was associated with normality at the third colonoscopy (81%). CONCLUSIONS Repeated colonoscopic screening of patients with acromegaly demonstrated a high prevalence of new adenomatous and hyperplastic colonic polyps, dependent on both the occurrence of previous polyps and elevated IGF1 levels.

Suprasellar germ cell tumours: specific problems and the evolution of optimal management with a combined chemoradiotherapy regimen

objective Suprasellar germ cell tumours are rare, and there are few series of patients outlining the problems in diagnosis and management, and providing clear guidelines for optimal therapy. We have therefore reviewed our own series of 11 such patients who were managed in a joint endocrinology/clinical oncology setting.

Screening children at risk of developing inherited endocrine neoplasia syndromes.

The familial endocrine neoplasia syndromes, multiple endocrine neoplasia (MEN) types 1 and 2 and von Hippel Lindau disease (VHL), are autosomal dominant disorders which most commonly present clinically in early adulthood and onwards. They can, however, cause significant disease in childhood. The discovery of the causative genes for these disorders now allows the identification, by genetic mutation analysis, of most individuals at risk, at least in principle. Subjects found to be carriers of a mutation are at risk of developing the disorder and can be clinically monitored and treated in childhood so that appropriate targeted management may prevent the devastating complications which may develop, e.g. haemorrhage from retinal angiomas, sudden death from phaeochromocytoma and the development of medullary thyroid carcinoma from preexisting C cell hyperplasia. Furthermore, genetic screening allows the children from affected families who have not inherited the mutation to be reassured and avoid regular clinical monitoring. Genetic testing raises many issues over informed consent, counselling and confidentiality; these are reviewed elsewhere (Reilly et al., 1997). Epidemiological and clinical information on the penetrance of familial endocrine neoplasia in childhood is derived mainly from clinical case reports of children presenting with manifestations of these disorders and not from screening data. This paper will review the screening and clinical management strategies for MEN1, MEN2 and VHL. We discuss, using illustrative case reports from our own experience, the role and nature of DNA testing, and review the relevant investigations and their timing in children at risk of endocrine neoplasia syndromes. Multiple endocrine neoplasia type 1

Rapid desensitisation of the GH secretagogue (ghrelin) receptor to hexarelin in vitro.

Ghrelin, the recently identified hormone with GH-secreting and appetite-inducing effects, acts on the GH secretagogue receptor (GHS-R). GHS-R belongs to the G protein-coupled 7 transmembrane domain receptors and activates the phospholipase C pathway; it then leads to the release of GH from somatotroph cells via an elevation of intracellular calcium concentration. Both in vivo and in vitro studies demonstrated that the effect of GH secretagogues (GHS) could be desensitised similar to most receptor stimulation systems. We have studied whether acute desensitisation of the GHS-R occurs in response to the GHS hexarelin in vitro in terms of intracellular calcium concentration. Chinese hamster ovary cells were transiently transfected with cDNA encoding the human type 1a GHS-R. The presence of messenger RNA was confirmed with RT-PCR, while no GHSR was observed in mock-transfected cells. Calcium responses to the peptide GHS analogue hexarelin were measured using the fluorescent indicator fura-2. Cells were stimulated with the peptide GHS, hexarelin, at concentrations between 10−10 and 10−7 M. Cells transfected with the GHS-R cDNA demonstrated a significant and specific calcium response to hexarelin that was not observed in mock-transfected cells. Marked desensitisation of the calcium response to hexarelin was observed 2-5 min after the first dose of hexarelin (10−7 M) was administered. These data show directly for the first time the desensitisation of the GHS receptor signal at the second messenger level. The desensitisation of the receptor may play a major role in the regulation of effect of circulating or locally produced ghrelin both in the GH and in the appetite-regulating system or in other systems where ghrelin has been shown to be active, such as the cardiovascular system or cell proliferation.

Growth Hormone Deficiency and Replacement in Patients with Treated Cushing’s Disease, Prolactinomas and Non-Functioning Pituitary Adenomas: Effects on Body Composition, Glucose Metabolism, Lipid Status and Bone Mineral Density

Background/Aims: This study was designed to determine whether previous Cushing’s disease (CD) or prolactinoma (PRL) could exert adverse effects additional to those of growth hormone (GH) deficiency as a consequence of variable degrees of prior hypogonadism or hypercatabolism. We report the effects of 5 years GH treatment in 124 GH deficiency adults; 42 patients with non-functioning pituitary adenomas (NFPA), 43 with treated PRL and 39 with treated CD. Methods: Fasting plasma glucose, HbA1c, lipoprotein profile, anthropometry and bone mineral density (BMD) were measured at baseline, 6 months and annually up to 5 years. Results: Mean body mass index remained unchanged in the PRL group and tended to increase in the NFPA group. In contrast, body mass index decreased in the CD group. Decreases in waist and waist/hip ratio were seen in all groups at 6 months. Decreases in total cholesterol and low-density lipoprotein cholesterol were seen in all groups and remained sustained at 5 years. Plasma glucose and HbA1c increased at 6 months. Subsequently, plasma glucose returned to baseline values at 5 years; in contrast, HbA1c remained unchanged at the end of the study. Baseline lumbar spine and hip BMD were lower in the PRL and CD groups than in the NFPA group, decreased over 1 year in all groups and subsequently increased by 2 years in NFPA with a subsequent increase in lumbar spine BMD in PRL and CD groups delayed to 3–5 years. Conclusions: Baseline characteristics and response to GH replacement are qualitatively similar in NFPA, PRL and CD patients. Because improvements in BMD occur later in PRL and CD patients, an extended trial of GH therapy may be indicated in those patients who were commenced on GH therapy as an additional treatment for reduced BMD.

The appearance of the adrenal glands on computed tomography in multiple endocrine neoplasia type 1

AIMS To review the morphology of the adrenal glands in multiple endocrine neoplasia type 1 (MEN1) on computed tomography (CT) to compare the results with established normal values for adrenal size and nodularity and to correlate adrenal size with serum cortisol secretory dynamics. MATERIALS AND METHODS Two observers independently reviewed the adrenal CT in 28 patients with MEN1, measuring the maximum width of the body of the gland and the medial and lateral limbs. Incidence and location of nodules >5 mm within the gland were recorded. Following exclusion of known cases of Cushings syndrome, adrenal gland size was compared with previously documented normative data. Adrenal gland size was compared between patients with normal and abnormal cortisol dynamics. RESULTS Comparison of mean adrenal size in MEN1 patients with normative data showed that the adrenal limbs were significantly larger in MEN1 than normal (P<0.0001 in all four limbs). Adrenal body was also significantly larger (P<0.05). Nodules were demonstrated in 17 (60%) of patients (versus 0.4-2% in the normal population). No statistically significant correlation was demonstrated between adrenal limb hyperplasia and abnormal cortisol dynamics. CONCLUSIONS In patients with MEN1, adrenal limb hyperplasia and adrenal nodules are significantly more common than in the normal population, a phenomenon not previously documented in a quantitative manner. There was no significant correlation between adrenal limb hyperplasia and abnormal cortisol dynamics.