Clinical management and outcome of head and neck paragangliomas (HNPGLs): A single centre retrospective study.

CONTEXT: Head and neck paragangliomas (HNPGLs) are rare, usually benign, slow-growing tumours arising from neural crest-derived tissue. Definitive management pathways for HNPGLs have yet to be clearly defined. OBJECTIVE: To review our experience of the clinical features and management of these tumours and to analyse outcomes of different treatment modalities. METHODS: Demographic and clinical data were obtained from The Northern Ireland Electronic Care Record (NIECR) as well from a prospectively maintained HNPGL database between January 2011 through December 2023. RESULTS: There were 87 patients; 50 females: 37 males with a mean age of 52.3 ± 14.2 years old (range 17-91 years old). 58.6% (n = 51) of patients had carotid body tumours, 25.2% (n = 22) glomus vagal tumours, 6.8% (n = 6) tumours in the middle ear, 2.2% (n = 2) in the parapharyngeal space and 1.1% (n = 1) in the sphenoid sinus. 5.7% (n = 5) of patients had multifocal disease. The mean tumour size at presentation was 3.2 ± 1.4 cm (range 0.5-6.9 cm). Pathogenic SDHD mutations were identified in 41.3% (n = 36), SDHB in 12.6% (n = 11), SDHC in 2.2% (n = 2) and SDHA in 1.1% (n = 1) of the patients. Overall treatment modalities included surgery alone in 51.7% (n = 45) of patients, radiotherapy in 14.9% (n = 13), observation in 28.7% (n = 25), and somatostatin analogue therapy with octreotide in 4.5% (n = 4) of patients. Factors associated with a significantly higher risk of recurrence included age over 60 years (p = .04), tumour size exceeding 2 cm (p = .03), positive SDHx variants (p = .01), and vagal and jugular tumours (p = .04). CONCLUSION: The majority of our patients underwent initial surgical intervention and achieved disease stability. Our results suggest that carefully selected asymptomatic or medically unfit patients can be safely observed provided lifelong surveillance is maintained. We advocate for the establishment of a UK and Ireland national HNPGL registry, to delineate optimal management strategies for these rare tumours and improve long term outcomes.

Congenital hypothyroidism in Northern Ireland: 40 years' experience of national screening programme.

OBJECTIVE: The incidence of congenital hypothyroidism (CHT) has progressively increased in several regions around the world but has yet to be evaluated in Northern Ireland (NI). CHT screening programme was introduced in NI in 1980 and has had a relatively unchanged protocol since its inception. The purpose of the study was to evaluate the incidence of CHT in NI from 1981 to 2020 and to explore possible contributing factors to any changes seen over the 40-year period. DESIGN: This was a retrospective database review of children diagnosed with CHT in NI between 1981 and 2020. Data was collected from the patients' medical (paper and electronic) records, including epidemiological, clinical, laboratory, and radiological features as well as outcomes at 3 years. RESULTS: Of 800,404 new-borns who were screened for CHT in NI between January 1981 and March 2020, 471 were diagnosed with CHT. There was a steady and significant increase in incidence of CHT over time with an incidence of 26 cases per 100,000 livebirths in 1981 versus 71 cases per 100,000 in 2019 (p < .001). Of these 471, 77 new-borns (16%) were born preterm. The incidence of CHT was observed twice as much in female compared to male new-borns. Diagnostic imaging including radioisotope uptake and thyroid ultrasound scans were performed in 143 cases (30%). Of these, 101 (70%) cases had thyroid dysgenesis and 42 (30%) cases had thyroid dyshormonogenesis. There were 293 (62%) of 471 patients had confirmed permanent CHT, and 90 patients (19%) had transient CHT. Over that period at least 95% of the population were recorded as having United Kingdom/Ireland as country of birth. CONCLUSION: Our findings demonstrate a nearly tripling of the CHT incidence observed over the last 40 years. This is against a background of a relatively stable population demographics. Future research should focus on the underlying cause(s) of this condition which may include changing environmental exposures in utero.

Iodine status in UK-An accidental public health triumph gone sour.

The improvement in iodine status among the UK population from the 1930s onwards has been described as an 'accidental public health triumph' despite the lack of any iodine fortification program. However, iodine deficiency in the UK has re-emerged in vulnerable groups and is likely due to a combination of changing farming practices, dietary preferences and public health priorities. The UK is now among only a minority of European countries with no legislative framework for iodine fortification. The experience of folic acid fortification and the 28-year delay in its implementation lays bare the political difficulties of introducing any fortification program in the UK. If iodine fortification is not an imminent possibility, then it is important to explore other options: how to change farming practice especially on organic farms; encourage dairy intake; protect and expand our public health programs of milk provision for vulnerable groups and embark on education programs for women of childbearing potential and healthcare professionals. This review explores how the UK may have arrived at this juncture and how the iodine status of the nation may be improved at this time of major political and public health upheaval.

Iodine status of teenage girls on the island of Ireland.

PURPOSE: The trace element iodine is a vital constituent of thyroid hormones. Iodine requirements increase during pregnancy, when even mild deficiency may affect the neurocognitive development of the offspring. Urinary iodine concentration (UIC) is the means of assessing iodine status in population surveys; a median UIC of 100-199 µg/L is deemed sufficient in a non-pregnant population. Milk is the main dietary source of iodine in the UK and Ireland. METHODS: We surveyed the iodine status of 903 girls aged 14-15 years in seven sites across the island of Ireland. Urine iodine concentration was measured in spot-urine samples collected between March 2014 and October 2015. Food group intake was estimated from iodine-specific food-frequency questionnaire. Milk-iodine concentration was measured at each site in summer and winter. RESULTS: The median UIC overall was 111 µg/L. Galway was the only site in the deficient range (median UIC 98 µg/L). All five of the Republic of Ireland sites had UIC ≤ 105 µg/L. In the two sites surveyed twice, UIC was lower in summer vs winter months [117 µg/L (IQR 76-165) vs 130 µg/L (IQR 91-194) (p < 0.01)]. Milk samples collected from Galway and Roscommon had a lower mean iodine concentration than those from Derry/Londonderry (p < 0.05). Milk intake was positively associated with UIC (p < 0.001). CONCLUSIONS: This is the largest survey of its kind on the island of Ireland, which currently has no iodine-fortification programme. Overall, the results suggest that this young female population sits at the low end of sufficiency, which has implications if, in future, they enter pregnancy with borderline status.

Iodine deficiency among pregnant women living in Northern Ireland.

OBJECTIVE: Mild iodine deficiency has re-emerged among school girls in the UK. We wished to study a contemporaneous pregnant population because a relationship between maternal iodine deficiency and offspring cognitive scores has recently been reported. The WHO has set a median population urinary iodine concentration (UIC) of ≥100 and ≥150 µg/L to define adequacy outside of and during pregnancy, respectively. Iodine creatinine ratio (ICR) is also used to correct for dilution effects (sufficiency ≥150 µg/g creatinine in pregnancy). DESIGN AND METHODS: A total of 241 women were followed across trimesters (T) into the postpartum period (PPP) along with 80 offspring with spot urine sampling and food frequency questionnaires. RESULTS: Median UIC was 73 µg/L in the 1st T (ICR 102 µg/g creatinine) despite 55% taking iodine-containing supplements. Median UICs were 94, 117 and 90 µg/L in the 2nd T, 3rd T and PPP, respectively. Corresponding ICRs were 120, 126 and 60 µg/g creatinine. ICR was associated with volume of milk consumed throughout pregnancy. Median UIC among the offspring was 148 µg/L, with no difference between the breast- and formula-fed babies. CONCLUSIONS: Pregnant women living in Northern Ireland may be at risk of iodine deficiency across pregnancy and into the PPP while the offspring are iodine sufficient. This is the first study of its kind in the UK with data for pregnant women and their offspring. The UK does not provide an iodine fortification programme nor offer routine iodine dietary advice in pregnancy and this requires consideration by public health agencies.

Neonatal TSH levels in Northern Ireland from 2003 to 2014 as a measure of population iodine status.

OBJECTIVE: The re-emergence of iodine deficiency in the UK has recently been reported in a large cohort of teenage girls including from Northern Ireland (NI) using the gold standard spot urinary iodine concentration. We wished to explore and confirm this by analysing neonatal thyroid-stimulating hormone (nTSH) levels in the NI population. DESIGN: We analysed the nTSH heel prick tests results from the NI national screening database between 2003 and 2014. The WHO proposes a definition for population iodine sufficiency at <3% of the population with nTSH results >5 mIU/L. METHODS: Anonymized results from 288 491 nTSH tests were retrieved, and prevalence rates of results at increasing cut-offs including >2 mIU/L and >5 mIU/L calculated. We also assessed for possible seasonal variation in nTSH results. RESULTS: An overall population prevalence of 0.49% with TSH >5 mIU/L was found, indicating population iodine sufficiency with no year attaining a prevalence >3%. The prevalence of nTSH >2 mIU/L decreased to 4.1% in 2007 and subsequently increased to 9.8% in 2014. Modest seasonal variation was also detected, with higher levels among April/May births. CONCLUSIONS: The neonatal TSH database suggests iodine sufficiency in the NI population. However, the rising frequency of results >2 mIU/L may indicate an emerging mild iodine deficiency. This is one of the largest and longest studies of its kind in the UK and the first carried out in NI. The summer months may be a time of increased risk of iodine deficiency in our pregnant women whose requirements are increased and who are not currently targeted by any iodine fortification programme in the UK.

Insights on epidemiology, morbidity and mortality of Cushing's disease in Northern Ireland.

Cushing's disease is a rare condition that occurs due to an adrenocorticotrophin-producing corticotrophinoma arising from the pituitary gland. The consequent hypercortisolaemia results in multisystem morbidity and mortality. This study aims to report incidence, clinicopathological characteristics, remission outcomes and mortality in a regional pituitary neurosurgical cohort of patients diagnosed with Cushing's disease in Northern Ireland (NI) from 2000 to 2019. Clinical, biochemical and radiological data from a cohort of patients operated for Cushing's disease were retrospectively collected and analysed. Fifty-three patients were identified, resulting in an estimated annual incidence of Cushing's disease of 1.39-1.57 per million population per year. Females accounted for 72% (38/53) of the cohort. The majority (74%, 39/53) of corticotrophinomas were microadenomas and in 44% (17/39) of these no tumour was identified on preoperative magnetic resonance imaging. Histopathological characterisation was similarly difficult, with no tumour being identified in the histopathological specimen in 40% (21/53) of cases. Immediate postoperative remission rates were 53% and 66% when considering serum morning cortisol cut-offs of ≤ 50 nmol/L (1.8 µg/dL) and ≤ 138 nmol/L (5 µg/dL), respectively, in the week following pituitary surgery. Approximately 70% (37/53) of patients achieved longer-term remission with a single pituitary surgery. Three patients had recurrent disease. Patients with Cushing's disease had a significantly higher mortality rate compared to the NI general population (standardised mortality ratio 8.10, 95% CI 3.3-16.7, P < 0.001). Annual incidence of Cushing's disease in NI is consistent with other Northern European cohorts. Functioning corticotrophinomas are a clinically, radiologically and histopathologically elusive disease with increased mortality compared to the general population.

Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action and quality of life in hypopituitary females: a double-blind, placebo-controlled study.

OBJECTIVE: Addition of dehydroepiandrosterone sulphate (DHEAS) to standard pituitary replacement may improve quality of life and glucose metabolism. Conflicting results from the previous work probably relate to differences in populations studied and assessment techniques used. We examined the effects of DHEAS on insulin action and the quality of life in female patients with hypopituitary hypoadrenalism. DESIGN: Randomized, double-blind, placebo-controlled, crossover design was used. Patients received either DHEAS 50 mg daily or placebo for 12 weeks. PATIENTS: Fourteen hypopituitary females on stable standard replacement therapy and with low DHEAS were enrolled. MEASUREMENTS: Insulin action by euglycaemic hyperinsulinaemic clamp and extensive quality of life parameters were assessed after each treatment. RESULTS: Serum DHEAS (DHEAS 5·4 ± 0·8 vs placebo <0·8 ± 0·0 µm; P < 0·001) and androstenedione (DHEAS 4·1 ± 0·8 vs placebo 1·3 ± 0·2 nm; P < 0·05) rose to within the normal range after DHEAS 50 mg daily. There were no differences between treatments in testosterone, sex hormone-binding globulin (SHBG) or IGF-1. Quality of life measures were unchanged after DHEAS. There were no differences between treatments in fasting glucose, serum insulin, HbA1c or in insulin action (glucose infusion rates required to maintain euglycaemia; DHEAS 21·9 ± 2·5 vs placebo 24·5 ± 2·1 µmol/kg/min; P = 0·4). Triglyceride concentrations were lower following DHEAS (DHEAS 1·24 ± 0·18 vs placebo 1·41 ± 0·19 mm; P < 0·05) but other lipid parameters remained unchanged. CONCLUSION: There were no differences compared with placebo in quality of life or insulin action after DHEAS replacement therapy for 12 weeks. These results do not provide evidence for the addition of DHEAS to standard hypopituitary replacement therapy.

A review of current knowledge about the importance of iodine among women of child-bearing age and healthcare professionals.

Iodine is required for thyroid hormone synthesis and fetal neurogenesis. Recent population studies in the United Kingdom (UK) have found iodine deficiency among schoolgirls, women of child-bearing age and pregnant women. This review explores knowledge and awareness of iodine among women of child-bearing age and healthcare professionals (HCPs) in the UK, set within a global context. We aimed to identify gaps in iodine knowledge in the current UK setting of iodine deficiency without iodine fortification and where iodine is not included in antenatal guidelines. The search terms 'iodine knowledge' and 'iodine awareness' were used to identify relevant papers. Iodine knowledge is poor among women of child-bearing age in the UK according to four studies using questionnaires and qualitative methods. They were unsure of dietary sources of iodine and were not consistently provided with relevant information from HCPs during clinical care. Midwives have been recognised as the main providers of dietary information during pregnancy and, although they recognised the importance of their role in providing nutrition advice, they did not feel equipped to do so and lacked confidence in addressing nutritional concerns. Globally, there was a similar lack of knowledge, however, this was somewhat improved by the inclusion of iodine in antenatal care guidelines. Midwives' knowledge of iodine was poor, as was knowledge among women of child-bearing age. Improved HCP knowledge and effective communication of information to pregnant women and women planning to conceive may help to improve iodine status which is of particular concern in pregnancy.

Thyroglobulin levels among iodine deficient pregnant women living in Northern Ireland.

BACKGROUND: Iodine deficiency has re-emerged among pregnant cohorts in the UK. Thyroglobulin (Tg) is a protein produced uniquely by the thyroid gland which appears to mount a U-shaped response to extremes of iodine status. Tg has been suggested as an alternative marker for chronic iodine deficiency but the value of Tg in pregnancy has not been fully elucidated. A recent non-European study suggested a median Tg ≤10 µg/L with <3% of values >44 µg/L was indicative of sufficiency in the second trimester of pregnancy. METHODS: We measured serum Tg levels in each trimester in 241 pregnant women living in Northern Ireland, a population with mild iodine deficiency at all stages of pregnancy as defined by urinary iodine concentration (UIC) and iodine: creatinine ratio (ICR). Women with Tg antibodies (6% in 1st trimester) were excluded. RESULTS: The median UIC in this cohort was in the deficient range at 73, 94 and 117 µg/L in sequential trimesters (adequacy ≥ 150 µg/L). Corresponding median Tg levels were 19, 16 and 16 µg/L respectively. Median Tg for all samples was 17 µg/L (IQR 11-31) suggestive of iodine deficiency. Tg was >44 µg/L in 14.3%, 9.4% and 12.4% of women in sequential trimesters respectively. Women with either UIC/ICR below the cut-offs 150 µg/L and 150 µg/g creatinine had higher Tg concentrations in 1st and 2nd trimester (p < 0.01; p < 0.001) but not in 3rd trimester. CONCLUSION: This study adds to the evolving evidence that Tg measurement is of value in reflecting iodine status in pregnancy.

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. Design: Register-based cross-sectional study. Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

What is the best approach to suspected cyclical Cushing syndrome? Strategies for managing Cushing's syndrome with variable laboratory data.

Cyclical Cushing's syndrome is a pattern of hypercortisolism in which the biochemistry of cortisol production fluctuates rhythmically. This syndrome is often associated with fluctuating symptoms and signs. It is now being increasingly recognized. The phenomenon is important because it can, if not recognized, lead to errors in diagnosis and differential diagnosis of the syndrome and in assessment of therapeutic outcomes. The techniques and criteria, protocols and dynamic biochemical tools to detect cycling in patients with hypercortisolism are discussed as are the strategies for diagnosing and managing this important subgroup of patients with hypercortisolism.

Knowledge about iodine requirements during pregnancy and breastfeeding among pregnant women living in Northern Ireland.

BACKGROUND: Iodine is an essential micronutrient important for foetal nerve and brain development, especially in the early stages of pregnancy. The re-emergence of mild to moderate iodine deficiency has recently been reported in the United Kingdom (UK). The level of knowledge amongst pregnant women regarding iodine nutrition is poorly understood. The aim of this study was to determine the level of knowledge about iodine nutrition during pregnancy among pregnant women living in Northern Ireland (NI). METHODS: A cross-sectional study in pregnant women was carried out in Royal Jubilee Maternity Hospital Belfast, from March to June 2015. Two hundred pregnant women were provided with a short questionnaire on iodine knowledge during routine clinic visits and comparisons were made across trimester and parity. RESULTS: Only 20% of women were aware of the potentially increased iodine requirements during pregnancy and breast feeding; 45% were unable to identify any foods they thought would be iodine rich. The three main sources of dietary iodine in the UK are fish, dairy and eggs and 30, 9 and 15% correctly identified these as good sources respectively. When asked about whether they felt they had been given sufficient advice about folic acid and iodine in pregnancy, 90% felt this was so for folic acid, but only 5% for iodine. CONCLUSIONS: This study suggests that iodine knowledge among pregnant women living in NI is poor. In the absence of any iodine fortification programme, women in the UK may be vulnerable to iodine deficiency in pregnancy. At present they are poorly equipped to make positive dietary changes to meet their increasing iodine requirements during pregnancy and breastfeeding. Public health strategies should be considered to target this population group.

What is the availability of iodised salt in supermarkets on the Island of Ireland?

Iodine deficiency remains a global nutritional public health challenge, with evidence suggesting borderline adequate or even deficient status for UK and Irish subpopulations such as schoolgirls and pregnant women. The solution, according to the WHO, is salt iodisation, but it is not known how widely available iodised salt is in supermarkets. Iodised salt availability was determined by a shelf survey of 89 supermarket stores on the island of Ireland (n = 30 in Northern Ireland and n = 59 in the Republic of Ireland) from September 2018 to January 2019, to take into account factors such as store type, location, population density, socioeconomic status and ethnicity. Availability was calculated as the number of stores selling iodised salt as a percentage of the total. Iodised salt was only available in 11 stores (12%), of which 10 were ethnic stores. This indicates a lack of access for the majority of the Irish and Northern Irish populations.

Twenty-four-hour growth hormone profiling in the assessment of acromegaly.

OBJECTIVES AND BACKGROUND: Recent guidelines recommend insulin-like growth factor (IGF-1), random growth hormone (GH) and nadir GH on an oral glucose tolerance test (OGTT) for assessment of acromegaly. At this Regional Centre, the 24-hour GH profile has also been used. DESIGN PATIENTS AND MEASUREMENTS: We evaluated 57 GH profiles from 34 patients from 2008 to 2012. Samples were drawn every 2 hour and matched with 0800 GH, nadir GH after OGTT and IGF-1. RESULTS: Correlations between the mean 13-point profiles and mean 5-point profile, OGTT nadir and 0800 GH were as follows: r = .99, .99 and .90, respectively (P < .01 for all). The correlation between the mean 13-point profiles and IGF-1 was r = .32 P = .02.Of 5 patients with very high 0800 GH preoperatively (≥20 µg/L), mean 13-point GH reduced by 88%-99% postoperatively. IGF-1 did not normalize in these patients, and all required extra treatment. Preoperatively, all patients had concordant 0800 GH and IGF-1. Postoperatively, 6 patients had 0800 GH <1 µg/L and high IGF-1; only 2 of these had a 13-point mean >1 µg/L, but 5 required further treatment. CONCLUSIONS: Growth hormone profiling is not necessary for assessing the majority of patients with acromegaly if there is confidence in the local IGF-1 assay. When undertaken, a 5-point profile is adequate. In patients with very high 0800 GH, 24-hour profiling was useful in demonstrating partial therapeutic success but did not alter management. Further work is needed to explore the possible role of GH profiling in stratifying patients with discordant IGF-1 and GH results.

Levels of infants' urinary arsenic metabolites related to formula feeding and weaning with rice products exceeding the EU inorganic arsenic standard.

Early childhood inorganic arsenic (i-As) exposure is of particular concern since it may adversely impact on lifetime health outcomes. Infants' urinary arsenic (As) metabolites were analysed in 79 infants by inductively coupled plasma-mass spectrometric detection (IC-ICP-MS) to evaluate i-As exposure pre- and post-weaning. Levels of i-As in rice-based weaning and infants' foods were also determined to relate to urinary As levels. Higher As levels, especially of monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were found in urine from formula fed infants compared to those breastfed. Urine from infants post-weaning consuming rice-products resulted in higher urinary MMA and DMA compared to the paired pre-weaning urine samples. The European Union (EU) has regulated i-As in rice since 1st January 2016. Comparing infants' rice-based foods before and after this date, little change was found. Nearly ¾ of the rice-based products specifically marketed for infants and young children contained i-As over the 0.1 mg/kg EU limit. Efforts should be made to provide low i-As rice and rice-based products consumed by infants and young children that do not exceed the maximum i-As level to protect this vulnerable subpopulation.

Intestinal microsomal triglyceride transfer protein in type 2 diabetic and non-diabetic subjects: the relationship to triglyceride-rich postprandial lipoprotein composition.

BACKGROUND: Microsomal triglyceride transfer protein (MTP) is responsible for the assembly of the triglyceride-rich lipoproteins (TRLs) and is increased in diabetic animal models. Human intestinal MTP expression has not been previously reported. This study examined the relationship between intestinal MTP gene expression and postprandial TRL composition in diabetic and non-diabetic subjects. Since the MTP promoter region has a sterol response element the effect of statins on intestinal MTP mRNA was analysed. METHODS: Twenty-seven diabetic and 24 non-diabetic subjects were examined. Duodenal biopsies were taken during gastroscopy and MTP mRNA was measured by RNase protection assay. Postprandial lipoprotein composition was determined. RESULTS: Diabetic subjects had significantly higher MTP mRNA than non-diabetic subjects. Statin therapy was associated with lower MTP mRNA in both groups. In the untreated diabetic patients compared to the untreated non-diabetic patients MTP mRNA was 25.0 +/- 25.1 amol/microg versus 13.1 +/- 5.6 amol/microg total RNA (p < 0.05). In the statin-treated diabetic group compared to statin-treated non-diabetic group MTP mRNA was 17.7 +/- 8.6 amol/microg versus 5.8 +/- 4.1 amol/microg total RNA (p < 0.05). In the whole group there was a positive correlation between the MTP mRNA and postprandial chylomicron cholesterol/B48 (r = 0.36, p < 0.01). CONCLUSIONS: This is the first study to demonstrate increased MTP expression in diabetic subjects. MTP mRNA expression was lower in statin-treated patients confirming the suggestion that the insulin and sterol response elements of the MTP gene are important regulators of MTP transcription in diabetes. Our results show that MTP plays a central role in regulating the cholesterol content of the chylomicron particle.

Recurrence of Phaeochromocytoma and Abdominal Paraganglioma After Initial Surgical Intervention.

BACKGROUND: Clinical and biochemical follow up after surgery for phaeochromocytoma is essential with long term studies demonstrating recurrence frequencies between 6% and 23%. AIM: To examine the characteristics and frequency of tumour recurrence in a regional endocrine referral centre, in patients with surgical resection of phaeochromocytoma (P) and abdominal paraganglioma (AP). METHODS: We identified a cohort of 52 consecutive patients who attended our Regional Endocrinology & Diabetes Centre and retrospectively reviewed their clinical, biochemical and radiological data (between 2002 and 2013). After confirmation of early post-operative remission by negative biochemical testing, tumour recurrence was defined by demonstration of catecholamine excess with confirmatory imaging. RESULTS: Phaeochromocytoma was confirmed histologically in all cases (43:P, 9:AP, mean-age:53 years). Open adrenalectomy was performed in 20 cases and laparoscopically in 32. Hereditary phaeochromocytoma was confirmed by genetic analysis in 12 (23%) patients. Median follow up time from initial surgery was 47 months, (range: 12 - 296 months), 49 patients had no evidence of tumour recurrence at latest follow-up. Three patients (6%) demonstrated tumour development, one in a patient with VHL which occurred in a contralateral adrenal gland, one sporadic case had local recurrence, and an adrenal tumour occurred in a patient with a SDHB gene mutation who had a previous bladder tumour. After initial surgery, the tumours occurred at 8.6, 12.0 and 17.7 years respectively. CONCLUSION: In this study tumour development occurred in 6% of patients. Although tumour rates were low, careful and sustained clinical and biochemical follow up is advocated, as new tumour development or recurrence may occur long after the initial surgery is performed.

Outcome of 131I therapy in hyperthyroidism using a 550MBq fixed dose regimen.

BACKGROUND: Radioiodine is the treatment of choice for relapsed hyperthyroidism although the optimum protocol is uncertain. Fixed dose radioiodine is increasingly popular but responses may vary. AIM: To assess the outcome of 131I therapy in hyperthyroidism using a standard dose regimen in a regional referral centre and to explore factors influencing outcome. METHODS: We studied 449 patients (M:F 82:367; age range 13-89 y, median 42 y) with hyperthyroidism treated between 2003 and 2007 with a standard dose of 550 MBq 131I. Patients were classified as either Graves' disease, toxic multinodular goitre or indeterminate aetiology. Antithyroid drugs were routinely stopped at least 1 week before radioiodine. RESULTS: One year after radioiodine 334 (74%) were hypothyroid, 85 (19%) were euthyroid and 30 (7%) had required a further dose of 131I. Patients with Graves' disease were more likely to become hypothyroid than those with toxic multinodular goitre (78% v 37%, p<0.001) and less likely to become euthyroid (11% v 55%, p<0.001). Free T4 >80 pmol/L (normal range 9.0 - 19.0 pmol/L) at presentation was associated with an increased failure rate (17% compared with 5% and 3% for 40-79 pmol/L and <40 pmol/L respectively; p=0.01). Patients with either a small or no goitre were more likely to be successfully treated by a single dose (96%) than those with a medium/large goitre (85%, p<0.001). Anti-thyroid medication was taken by 345 (77%) (carbimazole n=319) patients up to 1 week prior to 131I and was associated with an increased failure rate (8% v 2%, p=0.027) compared to those who had not had antithyroid medication. Logistic regression showed free T4 at presentation to be the only independent risk factor for failure of the first dose of radioiodine (OR 2.5; 95% CI, 1.2-5.1, p=0.012). CONCLUSION: A single standard dose of 550 MBq 131I is highly effective in treating hyperthyroidism. The aetiology, severity of hyperthyroidism at diagnosis, goitre size and prior antithyroid medication all had a significant effect on outcome.