Hypertensive Crisis in a Patient With a Functioning Mesenteric Paraganglioma: Dramatic Response to Octreotide Treatment.

Background/Objective: To report a dramatic and immediate clinical and biochemical response during treatment with octreotide in a patient with a functioning mesenteric paraganglioma (PGL). Case Report: A 44-year-old woman was admitted with a severe hypertensive crisis and a blood pressure reaching 260/150 mm Hg. She was 2 months postpartum and had been previously diagnosed with pre-eclampsia. Secondary hypertension was suspected. This was confirmed by finding a 6 × 5-cm2 retroperitoneal mass located using 68-Gallium DOTA-octreotate positron emission tomography/computed tomography and a grossly elevated plasma catecholamine level of 93 000 pmol/L (normal reference range: 650-2433 pmol/L). Treatment was immediately started with high doses of long- and short-acting octreotide. After 6 weeks and before surgery, the patient was normotensive, with a blood pressure of 120/70 mm Hg and a norepinephrine level of 6000 pmol/L. The tumor resection was uneventful, and histology confirmed the diagnosis. Following the surgery, the patient remained normotensive without any medications. Discussion: PGLs and pheochromocytomas are neuroendocrine tumors, and most have receptors for octreotide. This case and another patient previously reported responded dramatically to treatment with a high dose of octreotide. Earlier reports of patients failing to respond are likely to have been the result of using a smaller octreotide dose. Conclusion: We conclude that high doses of short- and long-acting octreotide are valuable in severely hypertensive patients. Our experience suggests that octreotide is of value in other patients with PGLs and pheochromocytomas. The response is rapid, sustained, effective, and with minimal reported side effects. To the best of our knowledge, this is the first report of a hypertensive crisis in a functional mesenteric PGL.

Papillary follicular variant thyroid cancer in a malignant struma ovarii: a report of a rare case.

Summary: A 33-year-old female presented in 2013 with left flank pain. Ultrasound and MRI pelvis showed a complex mass 9 × 7 cm arising from the left ovary suggestive of ovarian torsion. She underwent a laparoscopic cystectomy, but the patient was lost to follow-up. Three years later, she presented with abdominal distension. Ultrasound and CT scan revealed a solid left ovarian mass with ascites and multiple peritoneal metastasis. Investigations showed elevated CA 125, CA 19-9. Ovarian malignancy was suspected. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy on November 2016. The histopathology confirmed a well-differentiated thyroid cancer of ovarian origin with features of a papillary follicular variant without evidence of ovarian cancer and the thyroglobulin (Tg) level was elevated, more than 400 consistent with the diagnosis of malignant struma ovarii. The follow-up post-surgery showed normalization of CA 125, CA 19-9 and Tg. The patient underwent total thyroidectomy on January 2017. The histology was benign excluding thyroid cancer metastases to the ovary. She was started on thyroxine suppression, following which she received two ablation doses 131iodine (131I) each 5.3 GBq. The Tg remains slightly elevated at less than 10. 131I WBS showed no residual neck uptake and no distant avid metastasis. She was planned for molecular analysis which may indicate disease severity. We describe a case of malignant struma ovarii with widespread metastatic dissemination and a good response to surgery and 131I treatment without recurrence after 5 years of follow-up. The Tg remains slightly elevated indicating minimal stable residual disease. Learning points: Malignant struma ovarii is a rare disease; diagnosis is difficult and management is not well defined. Presentation may mimic advanced carcinoma of the ovary. Predominant sites of metastasis are adjacent pelvic structures. Thyroidectomy and 131iodine therapy should be considered. The management should be similar to that of metastatic thyroid cancer.

Euthyroid athyroxinemia - a novel endocrine syndrome.

A 55-year-old female was referred with abnormal thyroid function tests (TFTs); the free thyroxine level (FT4) was undetectable <3.3 pmol/L (normal: 7.9-14.4), while her FT3, TSH and urinary iodine levels were normal. She was clinically euthyroid with a large soft lobulated goitre that had been present for more than thirty years. She received an injection of recombinant human TSH (rhTSH) following which there was a progressive rise of the FT3 and TSH levels to 23 pmol/L and >100 mIU/L respectively at 24 h, The FT4 however remained undetectable throughout. Being on thyroxine 100 µg/day for one month, her FT4 level increased to 15 pmol/L and TSH fell to 0.08 mIU/L. Four years earlier at another hospital, her FT4 level had been low (6.8 pmol/L) with a normal TSH and a raised Tc-99 uptake of 20% (normal<4%). We checked the TFTs and Tc-99 scans in 3 of her children; one was completely normal and 2 had euthyroid with soft lobulated goitres. Their Tc-99 scan uptakes were raised at 17% and 15%, with normal TFTs apart from a low FT4 7.2 pmol/L in the son with the largest thyroid nodule. This is a previously unreported form of dyshormonogenesis in which, with time, patients gradually lose their ability to synthesize thyroxine (T4) but not triiodothyroxine (T3). LEARNING POINTS: This is a previously unreported form of dyshormonogenetic goitre.This goitre progressively loses its ability to synthesize T4 but not T3.The inability to synthesize T4 was demonstrated by giving rhTSH.

Lesson of the month 1: Subacute thyroiditis: a rare cause of fever of unknown origin.

Fever of unknown origin (FUO) is sometimes a diagnostic dilemma for clinicians. Endocrine causes reported in the literature include subacute thyroiditis, thyrotoxicosis, adrenal insufficiency and pheochromocytoma. Among these, subacute thyroiditis is often overlooked as it can occasionally lack typical symptoms. This case illustrates the fact that subacute thyroiditis should be considered as a possible cause of fever even if signs and symptoms of hyperthyroidism and thyroid tenderness are absent.

Paget's Disease in an Omani: Long-term Improvement Following a Single Injection of Zoledronic Acid.

Paget's disease of bone is a patchy skeletal disorder characterized by an increase in bone resorption and formation in the affected areas. It affects up to 3% of individuals of Anglo-Saxon origin over the age of 40 years but is rare in Arabs. Although most patients are asymptomatic, a variety of symptoms and complications may develop directly from bone involvement or secondarily to compression by bone expansion and increased blood flow. The disease can be treated by using medications that inhibit bone resorption, such as calcitonin and the bisphosphonates. Here we describe the case of an Omani patient with the disease, involving the skull, spine, pelvis, and tibia. He presented to the endocrine clinic in Sultan Qaboos University Hospital with a six-year history of headache, bone pain, progressive skull enlargement, and left-sided deafness. His alkaline phosphatase (ALP) level was 1500 U/L. His disease responded gradually to six months of subcutaneous and nasal calcitonin followed by a single 5 mg intravenous injection of zoledronic acid. This resulted in a further progressive reduction of his bone pain, skull size, and improvement in his hearing, as well as normalization of his serum ALP levels after one-year. This effect has been sustained for 3 years.

Adrenocorticotropic Hormone-Dependent Cushing's Syndrome: Use of an octreotide trial to distinguish between pituitary or ectopic sources.

OBJECTIVES: Adrenocorticotropic hormone (ACTH) overproduction is usually due to a pituitary tumour which is often not visible on magnetic resonance imaging (MRI). However, ACTH overproduction may be due to an ectopic source. This study aimed to develop a simple non-invasive technique to differentiate these sources. METHODS: This study took place in King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia, and Sultan Qaboos University Hospital, Muscat, Oman, between 1988 and 2012. Serum cortisol levels were measured in nine patients with ACTH-dependent Cushing's syndrome before and during a 72-hour trial of octreotide. All patients underwent computed tomography (CT) scans. MRI scans were performed on six patients. RESULTS: CT scans were abnormal in three patients with ectopic ACTH production. MRI scans showed that three patients had pituitary microadenomas. Serum cortisol levels returned to normal in those with confirmed ectopic ACTH production. No response was found in the other six patients. CONCLUSION: A 72-hour trial of octreotide is recommended for patients with ACTH-dependent Cushing's syndrome and a normal pituitary MRI. This trial will be a useful alternative to petrosal sinus sampling.

Fluctuation in the Levels of Immunoglobulin M and Immunoglobulin G Antibodies for Cardiolipin and ß2-Glycoprotein among Healthy Pregnant Women.

OBJECTIVES: Antiphospholipid antibodies fluctuate during a healthy normal pregnancy. This study aimed to investigate the levels of both immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies for cardiolipin and ß2-glycoprotein (ß2GP) among healthy pregnant women. METHODS: This study was conducted between May 2010 and December 2012. A total of 75 healthy Omani pregnant women with no history of autoimmune disease were investigated during their pregnancy and 90 days after delivery at the Armed Forces Hospital in Muscat, Oman. A control group of 75 healthy Omani non-pregnant women were also investigated as a comparison. Levels of IgM and IgG antibodies for both anti-cardiolipin antibodies (ACAs) and ß2GP were measured using a standard enzyme-linked immunosorbent assay. RESULTS: The ACA IgM levels were significantly higher in the control group compared to the pregnant women (P <0.001). No significant differences were observed in the ACA IgM levels between the control group and the pregnant women after delivery. In contrast, ACA IgG levels were significantly higher during pregnancy and after delivery compared with those of the healthy control group (P = 0.007 and 0.002, respectively). The levels of ß2GP IgG were significantly higher during pregnancy than after delivery and in the control group (P = 0.001 and <0.001, respectively). CONCLUSION: In this study, ACA IgG levels increased during healthy pregnancies and after normal deliveries whereas ß2GP IgG levels increased transiently during the pregnancies. Both phenomena were found to be significantly associated with a transient decline in the levels of IgM specific for these antigens. Therefore, the levels of these antibodies may be regulated during a healthy pregnancy.

Radioactive iodine-131 therapy in the management of ectopic thyroid tissue.

The occurrence of ectopic lingual thyroid tissue was first reported over 100 years ago. We report an unusual presentation of ectopic thyroid tissue occurring in the submental area. A 27-year-old female presented to the Sultan Qaboos University Hospital in Muscat, Oman, in October 2011 with an 8 × 6 cm mass which caused difficulty in talking and a feeling of heaviness in the jaw. She was clinically and biochemically euthyroid upon presentation. The clinical diagnosis was confirmed by a technetium(-99m) thyroid scan, magnetic resonance imaging and fine needle aspiration. A single dose of 976 megabecquerels of radioactive iodine-131 resulted in hypothyroidism after three months and the complete disappearance of the swelling and associated symptoms. At a two-year follow-up, the patient was healthy and continuing lifelong replacement therapy with thyroxine.

Insulin resistance and its correlation with risk factors for developing diabetes mellitus in 100 omani medical students.

OBJECTIVES: The aim of this study was to assess the prevalence of insulin resistance (IR) in healthy young Omanis and relate this with their body mass index (BMI) and family history (FH) of diabetes mellitus (DM). METHODS: This study was conducted between May 2009 and February 2010 at Sultan Qaboos University, Muscat, Oman. A detailed questionnaire was completed by 50 male and 50 female medical students between 20-25 years old. Fasting blood samples were obtained for serum glucose and insulin measurements. IR was calculated using the homeostasis model assessment-estimated insulin resistance (HOMA-IR) formula (fasting insulin x fasting glucose/22.5) and a value above 2.5 was considered elevated. The results were analysed using the Statistical Package for the Social Sciences (SPSS). RESULTS: PARTICIPANTS WERE CLASSIFIED INTO THE FOLLOWING BMI CATEGORIES: 59% were normal (18.5-24.9 kg/m(2)), 26% were overweight or obese (>24.9 kg/m(2)) and 15% were underweight (<18.5 kg/m(2)). A FH of DM was present in 74%. The HOMA-IR index was elevated in 16% and was directly correlated to the BMI (P = 0.003). There was no correlation between IR and a positive FH of DM. CONCLUSION: There is a high prevalence of IR (16%) and obesity (26%) in healthy young Omani medical students. Counselling is recommended for all overweight and obese individuals in an attempt to prevent or delay the onset of DM in the future.

Successful Management of Phaeochromocytoma using Preoperative Oral Labetalol and Intraoperative Magnesium Sulphate: Report of four cases.

Phaeochromocytoma is a rare neuroendocrine catecholamine-secreting tumour. This type of tumour poses multidimensional anaesthetic challenges as it has an unpredictable clinical course during surgical resection. The alpha-blocking agent phenoxybenzamine remained the mainstay in preoperative preparation before the introduction of beta-blocking agents. We report four cases operated between 2009-2012 at Sultan Qaboos University Hospital, Muscat, Oman. The cases were prepared with oral labetalol, as the alpha-blocking drug phenoxybenzamine was not immediately available. Responses to simulated stress were tested in the theatre before surgery. Anaesthesia was induced under invasive arterial pressure monitoring and magnesium sulphate infusion. Rare intraoperative surges in blood pressure during tumour manipulation were treated with sodium nitroprusside infusions and phentolamine boluses. All of the patients had an uneventful postoperative recovery. Preoperative treatment with labetalol has rarely been reported and can be considered as a potential therapeutic option with optimal patient monitoring if phenoxybenzamine is unavailable.

Familial Clustering of Type 2 Diabetes among Omanis.

OBJECTIVE: The aim of this study was to screen Omani individuals for the familial aggregation of type 2 diabetes mellitus. METHODS: A random cohort of 1182 Omani individuals visiting the Family Medicine Clinic at Sultan Qaboos University Hospital (SQUH), Muscat, Oman, for regular medical checkup, aged ≥40 years, were sampled. Patients were categorized into three groups: (1) individuals who claim not to have diabetes and had no family history of diabetes; (2) individuals who claim not to have diabetes but had family history of diabetes; (3) individuals with diabetes. Only 16% of these Omani individuals had no diabetes and no family history of diabetes. Another separate random cohort of 234 Omani type 2 diabetes mellitus patients, from the Diabetes Clinic at SQUH, were interviewed and questioned about their family history of type 2 diabetes mellitus. RESULTS: Ninety five percent of the patients had a family history of diabetes. Eighty percent had first degree relatives with diabetes and 46% had second degree relatives with diabetes. At least one parent with diabetes was reported among 55% of these diabetics, while maternal diabetes (55%) was found to be higher than paternal diabetes (47%). However, only 15% had both parents with diabetes. Furthermore, almost half of the 234 diabetics were having at least one of the following relatives with diabetes: brother, sister, aunt or an uncle. CONCLUSION: The findings of this study confirm familial aggregation of diabetes among the Omani population. Compared to other populations, familial aggregation of type 2 diabetes mellitus among Omanis is relatively very high, and is perhaps due to the very high degree of consanguinity among Omanis. Since almost everyone seems to have a genetic predisposition to diabetes, the dramatic lifestyle changes over the past 25 years, could tip the population into an epidemic of type 2 diabetes mellitus.

Vitamin D Status in Pregnant Omanis: A disturbingly high proportion of patients with low vitamin D stores.

OBJECTIVES: The objective of this study was to determine the vitamin D status of pregnant Omanis by measurement of their circulating 25 hydroxy vitamin D levels. METHODS: Blood samples were obtained from a cohort of 103 consecutive healthy pregnant Omanis at the Armed Forces Hospital, Muscat, on their first antenatal visit. The study took place in May, June and July 2010. RESULTS: Vitamin D deficiency was present in 34 (33%) of patients (25OHD3 <25 nmol/L), 'at risk' levels were found in 67 (65%) patients (25OHD3 25-50 nmol/L); two patients (1.9%) had values between 50 and 75 nmol/L, and no patients in the optimal range >75 nmol/L. CONCLUSION: If confirmed, these findings indicate the need for vitamin D replacement during pregnancy and lactation. Although not evidence based we recommend at least 1000 IU of cholecalciferol, (vitamin D3) daily.

VIPoma Crisis: Immediate and life saving reduction of massive stool volumes on starting treatment with octreotide.

We report the case of a 57-year-old male physician who presented with a life threatening secretory and refractory diarrhoea of around 20 L/day. This was complicated by severe hypotension, hypokalaemia, hypercalcaemia, renal failure requiring dialysis, metabolic acidosis, cardiorespiratory arrest and ventilation for 12 days. His diarrhoea responded immediately to the first dose of a therapeutic trial of subcutaneous octreotide 100 mcg 8 hourly which was started on clinical grounds alone before any investigations were carried out. After one day he was extubated and his blood pressure returned to normal. When a functioning neuroendocrine tumour is suspected clinically, the use of octreotide can, as in this case, be life saving.

Clinically-Defined Maturity Onset Diabetes of the Young in Omanis: Absence of the common Caucasian gene mutations.

OBJECTIVES: We are seeing a progressive increase in the number of young patients with clinically defined maturity onset diabetes of the young (MODY) having a family history suggestive of a monogenic cause of their disease and no evidence of autoimmune type 1 diabetes mellitus (T1DM). The aim of this study was to determine whether or not mutations in the 3 commonest forms of MODY, hepatic nuclear factor 4α (HNF4α), HNF1α and glucokinase (GK), are a cause of diabetes in young Omanis. METHODS: The study was performed at Sultan Qaboos University Hospital (SQUH), Oman. Twenty young diabetics with a family history suggestive of monogenic inheritance were identified in less than 18 months; the median age of onset of diabetes was 25 years and the median body mass index (BMI) 29 at presentation. Screening for the presence of autoimmune antibodies against pancreatic beta cells islet cell antibody (ICA) and glutamic acid decarboxylase (GAD) was negative. Fourteen of them consented to genetic screening and their blood was sent to Prof. A. Hattersley's Unit at the Peninsular Medical School, Exeter, UK. There, their DNA was screened for known mutations by sequencing exon 1-10 of the GCK and exon 2-10 of the HNF1α and HNF4α genes, the three commonest forms of MODY in Europe. RESULTS: Surprisingly, none of the patients had any of the tested MODY mutations. CONCLUSION: In this small sample of patients with clinically defined MODY, mutations of the three most commonly affected genes occurring in Caucasians were not observed. Either these patients have novel MODY mutations or have inherited a high proportion of the type 2 diabetes mellitus (T2DM) susceptibility genes compounded by excessive insulin resistance due to obesity.

Multiple Bone Metastases in a Patient with Differentiated Thyroid Cancer (DTC): Complete resolution following thyroidectomy and four ablation doses of I-131.

Multiple bone metastases from a differentiated thyroid cancer are usually incurable. We report the case of a young Omani woman who presented with 8 discrete skeletal lesions three years after a total thyroidectomy. Following four ablation doses of I-131 she has remained in clinical and biochemical remission for over five years. An extraordinary aspect of this case was the persistent refusal of her husband to use contraception either for himself or his wife. This resulted in her treatment being delayed for more than 6 years during which time the patient delivered and breastfed four additional healthy babies.

The Diagnosis and Management of Severe Hypercalcaemia: A simplified approach - Report of five cases.

Hypercalcaemia is a common medical problem, can be a manifestation of many diseases and, when severe, can represent a life-threatening medical emergency. Making the correct diagnosis is important to prevent unnecessary investigations and parathyroidectomies. At Sultan Qaboos University Hospital, Oman, we have recently seen five patients with severe hypercalcaemia (calcium ≥3.5 mmol/L), most of whom had been misdiagnosed for months or even years. The clinical examination, evaluation of the fasting serum calcium, phosphate, creatinine and 24-hour urine calcium levels together with a review of their radiographs accurately predicted the pathophysiology of the disorder and successfully guided our investigative procedures well before the results of hormone assays became available.

Quality of Diabetes Care: A cross-sectional observational study in Oman.

OBJECTIVES: The objective of this study was to evaluate the quality of diabetes care in Oman. METHODS: This was a cross-sectional observational study. Fifty percent of all those attending six general health centres in June 2005 were systematically selected for the study. Descriptive statistics were used to describe the data. RESULTS: A total of 430 diabetic subjects were included. Just over 61% percent of the subjects were female (n = 263). The overall mean age of the cohort was 52 ± 12 years ranging from 6 to 84 years. Only 40% (n = 171) and 39% (n = 169) of the diabetics had their random blood sugar (RBS) and fasting blood sugar (FBS) documented, respectively. However, 79% (n = 339) had either RBS or FBS done according to the records. Documentation for the other measurements ranged from 74% (n = 317) for HbA1c and LDL (low density lipoproteins)-cholesterol to 95% (n = 409) for systolic and diastolic blood pressure (SBP/DBP) readings. A total of 58% (n = 249) of patients had non-missing values of HbA1c, SBP/DBP, total cholesterol, LDL-cholesterol, HDL (high density lipoproteins)-cholesterol, and triglycerides. Only 2.4% (6 out of 249 diabetics) were simultaneously within goal for HbA1c (<7%), SBP/DBP (<=130/80mmHg), total cholesterol (<5.2mmol/L), LDL-cholesterol (<3.3mmol/L), HDL-cholesterol (>1.1 - <1.68mmol/L), and triglycerides (<1.8mmol/L). CONCLUSION: There was good documentation of values for the indicators used in the assessment of quality. However, the proportion (2.4%) of those meeting internationally recognised goals for the three diabetes-related factors was extremely low.

Insulinoma: a rare cause of a common metabolic disorder - hypoglycaemia.

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 simultaneous 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 111 labelled octreotide scanning is indicated if the patient's hypoglycaemia has previously responded to treatment with octreotide.

Graves' Disease following Interferon Therapy for Chronic Hepatitis C Infection.

We describe the first case of Graves' disease occurring at Sultan Qaboos University Hospital, Oman, in a patient who was under treatment with interferon alfa for HCV infection. INF-α is now being widely used to treat patients with a variety of disorders including infection with hepatitis C virus. Clinical thyroid disease, hypo and hyperthyroidism can occur in up to 15% of patients. We emphasize the need for thyroid function screening before and during therapy to identify patients early in the course of their disease..

Familial mineralocorticoid induced hypertension in the sultanate of oman.

OBJECTIVES: In Oman, many hypertensive patients with a family history of the disease respond to treatment with spironolactone, a mineralocorticoid receptor (MC-R) blocking agent thus suggesting a high prevalence of mineralocorticoid (MC) induced disease. The aim of this study was to document the prevalence of MC induced disease in patients with a positive family history of hypertension (HTN). METHODS: Serum calcium, potassium, creatinine, aldosterone and renin levels were measured under standard conditions in all patients together with an abdominal ultrasound scan and an adrenal computed tomography (CT) scan in four patients. RESULTS: In this small study, we show that 18 of the 27 patients (66%) had undetectable (suppressed) renin levels with usually normal aldosterone values (14 patients) and respond to treatment with spironoactone. CONCLUSION: We suggest that MC induced hypertension is likely to be common in the Middle East. In evolutionary terms, this makes sense as the ability to conserve salt in hot climates might be expected to confer a definite survival advantage.