2008-Issue1.indd Haemoglobinopathies encountered at Khoula Hospital, Oman A retrospective study *Gihan Adly, A Rajappa SULTAN QABOOS UNIVERSITY MEDICAL JOURNAL MARCH 2008, VOLUME 8, ISSUE 1, P. 59-62 SULTAN QABOOS UNIVERSITY© SUBMITTED - 23RD JUNE 2007 ACCEPTED - 6TH FEBRUARY 2008 (عمان) مستشفى خولة في بالدم االعتالل اخلضابي حاالت استعادية دراسة رجابا أ. لطيف، عدلي جيهان النتائج ومقارنة ــان) (عم خولة ــفي ملستش احملولني في املرضي (الهيموجلوبني) ــي ــالل اخلضاب االعت حاالت ــار انتش مدي ــص: الهــدف: تقييم امللخ إليها احملولني من أو خولة مبستشفى الداخلني املرضى من سواء 27,403 حالة نتائج تقييم مت احلاالت. الطريقة: من كبير عدد بتقييم أخري بدراسات لديهم. اخلضابى اإلعتالل إنتشار مدى نسبة 2004 لتحديد ــمبر ديس 2001 و حتى يناير من بداية ــنوات س أربع فترة خالل متعددة صحية مراكز من املنجلي الدم فقر حاملي ــبة النتائج: نس . الدم خلضاب الكهربائي الرحالن و الذوبان طريق عن التمنجل اختبار هي ــتخدمة املس الفوحصات اتبرية واضح ترابط %.هناك فكانت0.102 بالدم اخلضابي االعتالل من االخري االنواع نسبة ,أما 0.46% هي املنجلي الدم بفقر املرضي %7.5 و نسبة هي بسلطنة بوزارة الصحة الدراسات و البحوث قسم بواسطة أجريت التي الوراثية الدم الضطرابات الوطني الترصد نتائج بني و الدراسة هذة نتائج بني إهتمام أكثر إعطاء فيجب لذا الدراسه موضوع املرضى عند اخلضابي االعتالل انتشار مدي بوضوح االستعادية الدراسة هذة .اخلالصة: أظهرت عمان . بالسلطنة العامة الصحية املشكلة لتجنب هذه الفحص اجلينى و للتثقيف الصحى عمان. ، الدم خضاب اعتالل ، لِيَّة ِنْجَ امل لَّةُ اخلليةِ خَ ، اخللية املنجلية ، الدم الكلمات: فقر مفتاح Haematology Section, Khoula Hospital Laboratory, Khoula Hospital, Muscat, Sultanate of Oman *To whom correspondence should be addressed. Email: gihanadly@hotmail.com ABSTRACT Objective: The objective of this study was to find out the frequency of abnormal haemoglobins (Hb) in patients referred to Khoula Hospital, Oman and compare the data from other studies by assessing a large number of patients. Methods: The results of 27,403 patients, either admitted to Khoula Hospital or referred to it from different health centres during the 4 years of the study from January 200 till December 2004, were analysed for haemoglobinopathies. The laboratory methods used for detection of abnormal haemoglobins were sickle cell solubility test and haemoglobin electrophoresis. Results: The frequency of sickle cell trait was 7.5%, sickle cell disease 0.46% and other Hb variants were 0.02%. The results correlate well with that of the National Genetic Blood Disor- der Survey carried out by the research and studies department, Ministry of Health, Sultanate of Oman, during a 4 year period from January 200 till December 2004. Conclusion: This retrospective study demonstrates the high prevalence of haemoglobinopathies among the studied group of patients. More attention to the importance of health education and genetic counselling is required for the prevention of this public health problem in the country. Keywords: Anaemia, Sickle Cell; Sickle Cell Trait; Haemoglobinopathies; Oman. Advances in Knowledge - The study shows that haemoglobinopathies are prevalent at a significant rate among the patient group studied. - The study stimulates the need to conduct regular surveys to monitor haemoglobinopathies as well as prevalent genetic blood disorders in Oman. Application to Patient Care - Knowledge gained by researchers and doctors that can be applied both to the early diagnosis of haemoglobin- opathies and to the management of patients with these abnormalities including genetic counselling. C L I N I C A L A N D B A S I C R E S E A R C H G I H A N A D LY, A . R A J A P PA 60 THE COMMONEST GENETIC BLOOD DISORDERS that cause alterations in erythrocyte mor-phology and rheology are sickle cell anaemia, G6PD (Glucose-6 phosphate dehydrogenase enzyme deficiency) and thalassemias.1 These inherited hae- moglobinopathies are the commonest single-gene dis- orders; the World Health Organization estimates that about 7% of the world population are carriers.2 Because of their worldwide distribution, the disorders resulting from abnormal haemoglobin structure (haemoglobin- opathies) are of enormous clinical importance.3 These haemoglobin disorders occur in homozygous as well as heterozygous forms and involve the β-chain or the α-chain. In the homozygous state, Hb A is totally lacking, and clinical manifestations are of variable se- verity. Individuals so affected have anaemia, for exam- ple, sickle cell anaemia. In the heterozygotes, because they rarely have phenotypic expressions of clinical sig- nificance, they are said to have the trait for abnormality, for example, sickle cell trait.1 The thalassaemias are a heterogenous group of in- herited conditions characterised by defects in the syn- thesis of one or more of the globin chains that form the haemoglobin tetramer. The clinical syndromes as- sociated with thalassaemia arise from the combined consequences of inadequate haemoglobin production and of unbalanced accumulation of one type of globin chains.4 The main objective of this study was to estimate the prevalence of the most common haemoglobinopathies reported at Khoula Hospital and compare the data with other studies performed in Oman. Some studies were done before to estimate the prevalence of haemoglobinopathies in Oman. Khoula Hospital is a tertiary hospital and is the national trau- ma centre. It therefore gets referrals from many other hospitals in Oman, in addition to the referrals from the local health centres in Muscat; so a large number of cases is assessed every year. This provided a good op- portunity for further assessment and evaluation of hae- moglobinopathies, especially those investigations that were already requested by the treating doctors in the hospital departments and health centres, as this meant no additional costs or patient disturbance. M E T H O D S In this study, we used the laboratory records to col- lect data on blood samples sent to the laboratory from Khoula Hospital and Wattayah Polyclinic and also those referred from health centres over a period of four years from January 2001 to December 2004. Ours is a tertiary hospital and the National Trauma Centre of the Sultanate of Oman receiving referrals from differ- ent regions and different health centres. 27,403 patients had investigations done for them as in-patients in the hospital or outpatients from different health centres. The investigations were already requested by the treat- ing doctors in different departments in the hospital and health centres so there were no additional costs or ad- ditional financial funds needed for the study and also no additional burden on the patients either physically or financially. All cases of haemoglobinopathies detected in the laboratory were tabulated noting the solubility sickle cell screening test results and their confirmation us- ing the haemoglobin electrophoresis, HbL4, by Helena method.4 For thalassemia confirmation, samples were sent to the laboratory at the Royal Hospital, Muscat, where the high performance liquid chromatography (HPLC) method is done.4 During the period of study, a total number of 27,403 cases were screened by the sickle cell solubility method and 3,158 cases were subjected to haemoglobin elec- trophoresis. R E S U L T S The results are charted in Figures 1, 2 and Table 1. The total number of patients assessed was 27,403 cases. Of these 90.5% were Omanis and expatriates 9.5% (Indians 6.2%; Egyptians 1.4%; Bangladeshis 0.7%, Sri Lankans 0.3% and Gulf Cooperation Council citizens 0.3%). Out of these, according to our laboratory results, 2,057 cases (7.5%) had sickle cell trait with only a small numbers of patients having sickle cell disease itself: 128 cases (0.46%). Other small groups of patients, 21 cases (0.102%), had a combination of sickle cell with abnor- mal haemoglobin. Sickle thalassemias were encoun- tered at a very low rate (0.01%). D I S C U S S I O N In a previous survey study done by the Research and Studies Department of the Oman Ministry of Health, 6,342 children under 5 years of age were taken by their parents to neighbourhood hospitals or health centres for blood collection. The study showed that the preva- lence of sickle cell trait was 6%, B-thalassemia trait (het- erozygous) was 2%, B-thalassaemia homozygous was 0.07% and sickle cell disease 0.2%. The combination of A B N O R M A L H A E M O G L O B I N S E N C O U N T E R E D AT K H O U L A H O S P I TA L , O M A N : A R E T R O S P E C T I V E S T U D Y 61 Figure 1: Values in numbers of the different haemoglobinopathies Year No. % Nor Hb AA SC Trait AS SC Disease SS Total Proc. FS SE AFS FSD S- S-OM S-Dho AD AE DD HBL4 2001 No 179 465 18 - - 1 - 1 2 1 1 - - 668 % 26.8 69.6 2.69 - - 0.15 - 0.15 0.3 0.15 0.15 - - - 2002 No 255 522 33 2 - - - - - - - 1 1 814 % 31.3 64.1 4.05 0.25 - - - - - - - 0.12 0.12 - 2003 No 141 461 31 - - - 1 - - - 2 - 1 637 % 22.1 72.3 4.87 - - - 0.16 - - - 0.31 - 0.16 - 2004 No 368 609 46 7 1 - 1 2 - - 4 1 - 1039 % 35.4 58.6 4.43 0.67 0.1 - 0.1 0.19 - - 0.38 0.1 - - Totals No 943 2057 128 9 1 1 2 3 2 1 7 2 2 3158 % 29.8 65.1 4 0.03 0.03 0.03 0.06 0.01 0.007 0.003 0.025 0.007 0.007 - AA-Normal Haemoglobin; AS-Sickle Cell Trait; SS - Sickle Cell Disease; FS-Fetal and Sickle Haemoglobin ; SE-Sickle and Haemoglobin D; AFS- Adult, Fetal and Sickle Haemoglobin ; FSD-Fetal Haemoglobin and Sickle Cell Disease; S-Th-Sickle Cell and β-Thalassemia ; S-OM-Sickle Cell-Oman; S-Dho-Sickle Cell-Dhofar region Oman; AD-Adult and Haemoglobin D; AE-Adult and Haemoglobin E; DD-Haemoglobin D ; HBL4 -Haemoglobin Electrophoresis Table 1: Tables of values and percentages for the different haemoglobinopathies Figure 2: Percentage values of the different haemoglobinopathies G I H A N A D LY, A . R A J A P PA 62 sickle cell with other abnormal haemoglobins was also detected at a very low prevalence rate. Among the stud- ied children, three quarters (74.5%) were found to be free from haemoglobinopathies and G6PD normal, the other quarter of children, either had haemoglobin ab- normalities (7.5%), G6PD (16%) or had a combination of G6PD with at least one abnormal haemoglobin (2%). The prevalence rate of the total haemoglobinopathies in Oman is 9.5%.5 Other abnormal haemoglobins de- tected in this survey were: Hb D(0.6%), Hb E(0.3%), Hb C (0.02%).The combination of sickle cell with abnormal Hb was also detected at low prevalence.5 In the study done by White et al, the frequencies of four major red cell genetic defects: sickle haemoglobin (HbS), glucose 6 phosphate dehydrogenase (G6PD), and α and β- thalassemia, were determined in nearly 5,000 subjects from the three major peninsular Arab states, namely Yemen, the United Arab Emirates, and Oman. The frequencies of these in Oman were 0.389, 0.328, 0.024, and 0.038 respectively.6 In the Khoula laboratory study, the prevalence rate of haemoglobinopathies was found to be 8.09%; sickle cell trait formed 7.5 %, while sickle cell disease formed 0.46 % of this total. The other variants encountered (HbD, E, S-Oman, S-thalassemia, etc.) were 0.102%. Our results are consistent with previous studies per- formed in Oman. Knowledge of the distribution of these genetic blood disorders is useful in health care planning and manage- ment of resources.7 In populations in which there is a significant incidence of severe forms of thalassemia or sickle cell anaemia, women should be screened early in pregnancy for thalassemia and the sickle cell trait. If both parents are carriers, prevention of severe disease is possible through genetic counselling and offering prenatal diagnosis through fetal blood analysis or am- niocentesis and performing fetal DNA analysis.8 Also, the major objective of screening for genetic blood disorders is the identification of individuals who would benefit from genetic counselling. Testing for haemoglobinopathies is best coordinated with compre- hensive health screening programmes and integrated with meaningful education and ethical counselling.1 The technique chosen for screening should be geneti- cally diagnostic and should clearly differentiate be- tween sickle cell trait and those disorders of haemo- globin having implications for health.9 Genetic blood disorder diseases can be prevented by establishing a proper preventive programme which includes health education, genetic counselling for het- erozygotes, the improvement of curative and blood transfusion services, as well as newborn screening. The Ministry of Health in the Sultanate of Oman has rec- ognised that genetic blood diseases are a public health problem in the country and need attention.5 Many of the components of a genetic blood disorder prevention programme have already been successfully implement- ed in Oman, for example, neonatal screening, premari- tal examination and genetic counselling. C O N C L U S I O N In conclusion, this retrospective study over 4 years demonstrated clearly the high prevalence of haemo- globinopathies among the studied group of patients. Moreover, prompt and full implementation of the ge- netic blood disorder disease prevention programme is likely to reduce the numbers of homozygous patients and help early detection. R E F E R E N C E S 1. Wintrobe’s Clinical Haematology, Vol. 1. 9th ed. Phila- delphia: Lea & Febiger, 1993. 2 . Hoffbrand AV, Catovsky D, Tuddenham EGD. Postgrad- uate Haematology, Vol. 1. 5th ed. Oxford: Blackwell Pub- lications, 2005. 3. Henry JB. MD. Clinical Diagnosis and Management by Laboratory Methods. 19th ed. Philadelphia: WB Saun- ders Company, 1999. 4. Dacie JV, Lewis SM. Practical Haematology. 9th ed. Edin- burgh: Churchill Livingstone, 2001. 5. Al Riyami A, Ebrahim GJ. National Genetic Blood Dis- orders Survey - Ministry of Health, Sultanate of Oman. J Trop Pediatr 2003; 49:1-20. 6. White JM, Byrne M, Richards R, Buchanan T, Katsoulis E,Weerasingh K. Red cell genetic abnormalities in Penin- sular Arabs: Sickle haemoglobin, G6PDdeficiency, and alpha and beta thalassemia. J Med Genet 1986; 23:245- 251. 7. Guidelines – The Laboratory Diagnosis of Haemoglobin- opathies. Br J Haematol 1998; 101:783–792. 8. Weatherall DJ, Clegg JB. The Molecular basis of Blood Disease, 2nd ed. Philadelphia: WB Saunders Company, 1994. 9. Serjeant GR. Historical Review – The emerging under- standing of Sickle Cell Disease. Br J Haematol 2001; 112: 3-18. Insulinoma: A Rare Cause of a Common Metabolic Disorder - Hypoglycaemia *Omayma El Shafie,1 Dilip Sankhla,2 Nayil Al-Kindy,3 Aisha Al-Hamadani,4 Christopher Grant,3 Nicholas Woodhouse1 SULTAN QABOOS UNIVERSITY MEDICAL JOURNAL MARCH 2008, VOLUME 8, ISSUE 1, P. 63-67 SULTAN QABOOS UNIVERSITY© SUBMITTED - 20SH JUNE 2007 ACCEPTED - 14TH JANUARY 2008 C A S E R E P O R T األيضي لالضطراب نادر سبب : (انسولينوما) زيرِيّ اجلَ رَمٌ الوَ الدم سكر نقص - االنتشار واسع (االستقالبي) وودهاوز جرانت، نيكوالس كريستوفر احلمداني، عائشة الكندي، نايل سانخال، ديليب الشافعي، أميمة املنظار. ــطة بواس البنكرياس غدة ذيل مع ــتئصاله اس والذي مت اجلزيري الورم من يعاني عماني ملريض عمان ــلطنة س في حاله أول عن تقرير امللخص: يعانون الذين الدم للمرضى في السكر نسبة فحص التقرير أهمية هذا يوضح كما . عائلته و/أو املريض تثبت أهمية اخذ تاريخ املرض من احلالة هذه االنسولني طليع ج – وبيبتايد ــولني األنس هرمون ــبة ونس املعمل في ــكر الس ــبة نس من للتأكد دم أخرى عينات ، وكذلك اخذ املتكرر الوعي من فقدان ، ميكن حينذاك الورم بالضبط موقع حتديد املغناطيسي الرنني ــتطاعة باس يكن لم واذا لذلك. ضرورة هناك كانت اذا - ــلفونيل الس يوريا ــتويات ومس اذا البنكرياس في الورم ــكان م باالوكتيرويد لتحديد ــوم املوس الثالثي االنديوم ــتخدام باس رُّس بالتَفَ أو ، لِيّ اخِ الدَّ بالتَّنْظيرِ ى دَ طيطُ الصَّ بتَخْ ــص الفح باالوكتيرويد. للعالج الدم من انخفاض سكر الذي يعاني املريض استجاب البنكرياس. استئصال باملنظار ، اجلراحة ، الدم سكر انخفاض ، ج - الكلمات: بيبتايد مفتاح Departments of 1Medicine, 2Radiology and Molecular Imaging, 3Surgery, 4Pathology, College of Medicine & Health Sciences, Sultan Qaboos Univer- sity, Muscat, Sultanate of Oman. *To whom correspondence should be addressed. Email: omayma0@hotmail.com HYPOGLYCAEMIA IS A COMMON METABOLIC problem and may result from increased peripheral uptake of glucose, failure of glu- cose production or a combination of both. By far the commonest cause is increased peripheral glucose up- take resulting from stimulation of the insulin receptor (INS-R) by endogenous overproduction or exogenous administration of excess insulin. Rarely, hypoglycaemia is caused by increased circulating levels of molecules resembling insulin such as insulin like growth factors (IGFs) or antibodies directed against the INS-R. Hy- poglycaemia also occurs in patients with advanced liv- er disease resulting from a failure of gluconeogenesis. The role of the kidney is less certain; glucose uptake and synthesis is high normally and renal failure often results in hypoglycaemia. As insulin is degraded by the kidney, hypoglycaemia may in part be due to prolonga- tion of its actions.1-5 Hypoglycaemia has a potential for serious neuro- nal damage and death. The patient described here had recurrent symptoms for two years that were initially thought to result from epilepsy and later a conversion reaction. Insulinoma is rare with an incidence of only 4 per 1 million persons per year, but it is the common- ABSTRACT We describe the first patient diagnosed with an insulinoma in Oman and successfully managed with a distal laparoscopic pancreatectomy. The importance of obtaining a good history from the patient and/or his family is stressed. All patients with loss of consciousness must have a Reflow check carried out and, if hypoglycaemic, this should be documented in the laboratory and a simul- taneous serum sample stored for measurement of insulin, C-peptide proinsulin and sulphonylurea levels, if subsequently indicated. If magnetic resonance imaging fails to locate the tumour, endoscopic ultrasound of the pancreas, or indium  labelled octreotide scanning is indicated if the patient’s hypoglycaemia has previously responded to treatment with octreotide. Key words: Insulinoma; C-peptide; Hypoglycaemia; Laparoscopy; Pancreatectomy. O M AY M A E L S H A F I E , D I L I P S A N K H L A , N AY I L A L - K I N D Y, A I S H A A L - H A M A D A N I , C H R I S T O P H E R G R A N T, N I C H O L A S WO O D H O U S E 64 est cause of hypoglycaemia in otherwise healthy adults who are not taking antidiabetic drugs. The median age is 47 years with a slight female preponderance of 59%. 87% of insulinomas are single benign tumours, 6% are malignant and 7% are multiple benign tumours and associated with multiple endocrine neoplasia type 1 (MEN-1).1, 2 C A S E R E P O R T A 23 year old Omani male had a 2 year history of recur- rent loss of consciousness and convulsions. On the first day of Ramadan (Islamic month of fast- ing) in 2006, he presented to the Accident and Emer- gency Department of Sultan Qaboos University Hospi- tal, Oman, with loss of consciousness. His blood glucose was measured by Reflocheck, a blood glucose monitor, and was found to be 1.5mmol/L. On receiving intrave- nous dextrose, he regained consciousness. He was then discharged with a referral letter to the endocrine clinic. This delayed his admission by two months. His attacks had started in Ramadan 2005, when he was unable to fast for more than 10 days. A year later in Ramadan 2006, fasting became impossible for more than a few hours hence his hospital visit. The family reported that frequent meals made him less liable to attacks. There was no family history of diabetes and he was not known to have diabetes. His parents and ten siblings were healthy. His physical examination was un- remarkable. He was admitted and started on a 72 hour fast. After 8 hours, his blood glucose fell to 1.5 mmol. (Reflocheck). Blood samples were taken for laboratory confirmation of the plasma glucose, and levels of insulin, C-peptide, pro-insulin and sulphonylureas. The fast was termi- nated and he was given intravenous glucose. Treatment Glucose 1.5 (3.5 – 5.0) mm/l Insulin 9.0 (1.9 – 23) miu/L C-peptide 2 (1.5 – 4.5) ug/L Pro-insulin 21 (6.4 – 9.4) pm/l Time (minutes) -15 0 30 60 120 Glucose mmol/L 1.4 1.7 1.8 1.4 1.0 Insulin mIU/L 2.1 3.4 0.3 1.9 2.0 Table 1: Simultaneous blood sampling of patient when hypoglycaemic Table 2: Octreotide trial 100 micrograms s/c time 0 Figure 1: A therapeutic trial of octreotide (SMS) in 3 patienrs with insulinomas. Insulin secretion can be inhibited, with normalisation of the blood sugar level, only in those patients whose tumours have receptors for octreotide (<50%). Only patient 1 responded I N S U L I N O M A : A R A R E C AU S E O F A C O M M O N M E TA B O L I C D I S O R D E R - H Y P O G LY C A E M I A 65 Figure 3: Patient’s pancreatic tumour Figure 2: The Patient’s CT scan was normal but an MRI revealed a 1.5 x 2 cm tumour localized in the tail of the pancreas (Arrows) Figure 5: Insulin staining. On left normal staining, on right patient’s tumour Figure 4: Microscopic view of tumour - Well differentiated endocrine tumours - Well differentiated (low grade maligant) carcinoma with gross local invasion or distant metastasis - Poorly differentiated endocrine carcinoma small cell neuroendocrine carcinoma Table 3: WHO classification of pancreatic endo- crine tumours O M AY M A E L S H A F I E , D I L I P S A N K H L A , N AY I L A L - K I N D Y, A I S H A A L - H A M A D A N I , C H R I S T O P H E R G R A N T, N I C H O L A S WO O D H O U S E 66 was started with diazoxide 50 mg three times a day, and thereafter he remained asymptomatic. The results in Table 1 show an inappropriately high insulin concentration for the level of blood glucose. The detectable C-peptide excludes the injection of ex- ogenous insulin as commercial insulins contain no C- peptide.1, 2 Sulphonylurea was not detected. These re- sults confirm excessive and inappropriate endogenous insulin overproduction. Normally, circulating proinsu- lin levels account for less than 22% of the serum insulin value, but the ratio of more than 24% is seen in 90% of all insulinomas when greater than 40% malignancy is usually indicated. Our patient’s value was more than 50% and he has to be carefully followed up. An octre- otide trial [Table 2] produced no significant change in blood glucose or insulin levels and therefore an octre- otide scan was not done. Only 50% of insulinomas have octreotide receptors and in these cases the drug can be used therapeutically6 [Fig 1] or to locate the tumour by scanning with indium III labelled hormone. Two weeks later, he was admitted for further as- sessment. There had been no attacks of hypoglycaemia since starting on diazoxide. He underwent laparoscopic distal pancreatectomy7 and the tumour was localized by intraoperative laparoscopic ultrasound during surgery.8 The surgery was uneventful and the histopathology confirmed an insulinoma [Figs. 4-5] of “uncertain be- haviour” by WHO classification [Tables 3 & 4]. Since surgery, the patient has been very well with no hypoglycaemic attacks and he is looking forward to the next Ramadan moon to undertake his fast. D I S C U S S I O N This case illustrates the necessity of good history tak- ing. The patient’s symptoms very clearly improved by taking food. The family gave a vivid description of how he was often too weak to walk to the table for his meals. He would sometimes sink to the ground and the fam- ily would restore him by bringing food to him. During Ramadan, by midday, he would be weak and confused until breaking his fast. Hypoglycaemia was not, how- ever, suspected and he was referred to neurology and psychiatric clinics. In the Mayo Clinic series of 224 cas- es of insulinoma as many as 20% of patients had been misdiagnosed as having neurological or psychiatric disorders.2 In this article, we have outlined a systematic ap- proach to the investigation and management of patients with spontaneous hypoglycaemia.9 The largest series in the literature is from the Mayo Clinic2 where, in an 80-year period, 224 cases were seen. 87% were benign tumours, 6% were malignant, and 7% were associated with MEN-1. Their follow up shows a higher recur- rence rate in patients with MEN-1 [Figure 6]. Patients with benign insulinomas had a survival rate which did not differ from that expected in the general population. This is not the case in those with malignant insulino- mas [Figure 7]. MEN-1 is excluded in our patient as the pituitary CT scan and bone profile were normal. He is now free of symptoms since surgery done in November 2006. In the Mayo Clinic series, a cure has been defined as being totally free of symptoms for 6 months after removal of the insulinoma.2 The next Ramadan fast will be used to confirm the success or otherwise of his treatment. C O N C L U S I O N The symptoms of hypoglycaemia may include loss of consciousness, convulsions and personality changes. In such a patient, hypoglycaemia should be looked for and, if found by Reflocheck, two venous samples must be taken immediately; one for laboratory confirmation of the glucose and insulin level and the other stored for C- peptide, pro-insulin and sulphonylurea measurement, if indicated. This must not delay the administration of intravenous glucose, which should be given without awaiting a result. If in such a patient hypoglycaemia is found by finger prick sampling, it is essential to take two venous samples immediately. One sample should Benign - No extrapancreatic spread - No vascular invasion <2cm - <2 mitoses/10HPF - <2% ki-67 positive cells Table 4: Characteristics of well differentiated endocrine tumours Uncertain behaviour - No extrapancreatic extension - BUT with one or more of these features: >2cm in size angioinvasion >2% ki-67 positive cells I N S U L I N O M A : A R A R E C AU S E O F A C O M M O N M E TA B O L I C D I S O R D E R - H Y P O G LY C A E M I A 67 be taken for laboratory confirmation of the glucose and insulin levels. The other should be stored for other pos- sible investigations (C-peptide, pro-insulin and sulpho- nylurea). You should then take a history from your re- covering patient. R E F E R E N C E S 1. Siperstein A, Clark OH, Rushakoff RJ. Tumor Syndromes: Insulinoma and other Hypoglycemias. In: Goldine ID, Rushakoff RJ, eds. Diabetes and Carbohydrate Metabo- lism. From http://www.endotext.org/diabetes/index. htm. Accessed June 2007. 2. Service FJ. Diagnostic Approach to Hypoglycemia in Adults. From http://www.uptodate.com. Accessed June 2007. 3. Service, FJ. Hypoglycemic disorders. N Engl J Med 1995; 332:1144-1152. 4. Vortmeyer AO, Huang S, Lubensky I, Zhuang Z. Non- islet origin of pancreatic islet cell tumours. J Clin Endo- crinol Metab 2004; 89:1934-1938. 5. Minn AH, Kayton, M, Lorang, D, et al. Insulinomas and expression of insulin splice variant. Lancet 2004; 363:363- 367. 6. Romeo S, Milione M, Gatti A, Fallarino M, Corleto V, Morano S, et al. Complete Clinical Remission and Dis- appearance of Liver Metastases after Treatment with Somatostatin Analogue in a 40-Year-Old Woman with a Malignant Insulinoma Positive for Somatostatin Recep- tors Type 2. Horm Res 2006; 65:120-125. 7. Ayav A, Bresler L, Brunaud L, Boissel P, SFCL (Société Française de Chirurgie Laparoscopique), AFCE (Associ- ation Francophone de Chirurgie Endocrinienne). Lapar- oscopic approach for solitary insulinoma: a multicentre study. 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