Characteristics and treatment results of patients with gastroenteropancreatic neuroendocrine tumors in a tertiary care centre.

BACKGROUND: Gastroenteropancreatic Neuroendocrine tumors (GEP-NET) are rare neoplasms with limited reported data from the Middle East. Our study aims to report the clinicopathological feature, treatment patterns, and survival outcomes of patients with GEP-NET from our part of the world. METHODS: Medical records of patients diagnosed with GEP-NET between January 2011 and December 2016 at a single center in Saudi Arabia were reviewed retrospectively, and complete clinicopathological and treatment data were collected. Patients' survival was estimated by the Kaplan-Meier method. RESULTS: A total of 72 patients were identified with a median age of 51 years (range 27-82) and male-to-female ratio of (1.1). The most common tumor location was the pancreas (29.1%), followed by small bowel (25%), stomach (12.5%), rectum (8.3%), colon (8.3%), and appendix (6.9%). Forty-one patients (57%) had well-differentiated grade (G)1, 21 (29%) had G2, and 4 (6%) had G3. In five patients, the pathology was neuroendocrine carcinoma and in one it could not be classified. 54.2% of the patients were metastatic at diagnosis. Forty-two patients underwent surgical resection as primary management while 26 underwent systemic therapy, three patients were put on active surveillance, and one was treated endoscopically with polypectomy. The 5-year overall survival and progression-free survivals were 77.2% and 49%, respectively, for the whole group. Patients with G1 and 2 disease, lower Ki-67 index, and surgically treated as primary management had significantly better survival outcomes. CONCLUSION: Our study suggests that the most common tumor locations are similar to western reported data. However, there seems to be a higher incidence of metastatic disease at presentation than in the rest of the world.

Efficacy of Everolimus Combined with 177Lu-Dotatate in the Treatment of Neuroendocrine Tumors.

Background: Both everolimus and peptide receptor radionuclide therapy (PRRT) are approved as monotherapies for advanced neuroendocrine tumors (NETs). Research in animal models showed synergism between the two treatment modalities. This study aimed to evaluate the safety and efficacy of combining everolimus and PRRT in the treatment of unresectable NETs. Methods: Adult patients (≥18 years) with progressing and unresectable histologically confirmed grade 1-2 NETs of all origins were enrolled. Everolimus was started at a 5 mg daily dose and was increased after the initial three patients to 10 mg daily. Patients were treated concurrently with 177Lu-DOTATATE at an 8-week interval, with planned four cycles. Safety was the primary endpoint, with response rate and progression-free survival (PFS) being secondary. Results: Eleven patients were enrolled. The trial was terminated early for poor accrual. The median age was 51 years (18-64), and 4 were males. The median number of cycles of 177Lu-DOTATATE was 3, and the median cumulative dose was 300 mCi. The most frequent grade 1-2 toxicities were stomatitis (90.9%) and nausea (72.7%). Less frequent were fatigue (63.6%), anorexia, diarrhea, and skin changes (each at a 36.4% rate). Grade 3 toxicities occurred in 36% (fatigue, infection, pneumonitis, neutropenia, and stroke). No patient developed grade 4 toxicity. Treatment was stopped because of progression in three patients, and toxicity in another three patients, in addition, in four patients due to therapy interruption and in one patient who developed stroke. One patient achieved partial response, and nine had stable disease. One patient developed disease progression. At a median follow-up of 18.9 months, three died and one was lost to follow-up. The median PFS was 23.3 months. Conclusions: The combination of everolimus at a dose of 10 mg daily and 177Lu-DOTATATE appears not to be feasible. A larger trial at a lower dose of everolimus is warranted.

Using the Appropriate Formula for QT Measurement Can Save Lives.

CDK 4/6 inhibitors, in combination with endocrine therapy, are the standard of care for patients with endocrinesensitive advanced breast cancer. This class of drug, however, is associated with QT prolongation, which serves as a surrogate marker for Torsades de Pointes (TdP), a cause of life-threatening ventricular arrhythmias and sudden cardiac death. The ICH E14 guidance document uses the Bazett formula for reporting of cardio-dynamic and safety ECG data in clinical trials. While there is substantial familiarity with the Bazett (QTcB) formula (QT/(RR) 1/2), the Fridericia (QTcF) formula (QT/(RR) 1/3 ) is preferred in the cancer population as it is often more accurate at heart rate extreme. Accordingly, the Fridericia formula is currently the standard adopted by the FDA when submitting QT data for review. At the King Faisal Specialist Hospital and Research Center, a total of 82 patients with advanced breast cancer, had a baseline ECG on day 1 before the initiation of ribociclib based therapy. Of the enrolled 82 patients, 19 (23%) were initially excluded from receiving ribociclib based due to a prolonged QTc >450ms, however, when the QTc-interval was manually measured and recalculated using Fridericia and Framingham formulae using MDCalC (https://www.mdcalc.com),17 of 19 patients successfully received their treatment without any arrhythmogenic effects. Repeat ECG on day14, and day 1 of cycle 2 demonstrated that none of these patients had QTc exceeding 480 ms. Our data highlights the complexities of evaluating the QT interval in oncology patients and the utility of the Fridericia/Framingham formulae in this population. Given these findings, we recommend the adoption of the Fridericia or Framingham formulae for measurement of QTc in all cancer patients exposed to potentially QT-prolonging cancer therapy.

The Impact of COVID-19 Viral Infection on the Hypothalamic-Pituitary-Adrenal Axis.

OBJECTIVE: To study the adrenocortical response to an acute coronavirus disease-2019 (COVID-19) infection. METHODS: Morning plasma cortisol, adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone sulfate levels were measured in 28 consecutive patients with COVID-19 (16 men, 12 women, median age 45.5 years, range 25-69 years) on day 1 to 2 of hospital admission. These tests were repeated twice in 20 patients and thrice in 15 patients on different days. The hormone levels were correlated with severity of the disease. RESULTS: The median morning cortisol level was 196 (31-587) nmol/L. It was <100 nmol/L in 8 patients (28.6%), <200 nmol/L in 14 patients (50%), and <300 nmol/L in 18 patients (64.3%). The corresponding ACTH values had a median of 18.5 ng/L (range 4-38 ng/L), and the ACTH level was <10 ng/L in 7 patients (26.9%), <20 ng/L in 17 patients (60.7%), and <30 ng/L in 23 patients (82.1%). The repeated testing on different days showed a similar pattern. Overall, if a cutoff level of <300 nmol/L is considered abnormal in the setting of acute disease, 9 patients (32%) had cortisol levels below this limit, regardless of whether the test was done only once (3 patients) or 3 times (6 patients). When the disease was more severe, the patients had lower cortisol and ACTH levels, suggesting a direct link between the COVID-19 infection and impaired glucocorticoid response. CONCLUSION: Unexpectedly, the adrenocortical response in patients with COVID-19 infection was impaired, and a significant percentage of the patients had plasma cortisol and ACTH levels consistent with central adrenal insufficiency.

Retinopathy and Uveitis in Congenital Generalized Lipodystrophy with Hypertriglyceridemia and Uncontrolled Diabetes (Berardinelli-Seip Syndrome).

Congenital lipodystrophy syndromes are characterized by a paucity of adipose tissue and are associated with metabolic abnormalities including insulin resistance, diabetes mellitus, and severe hypertriglyceridemia. Herein, we present a case of proliferative diabetic retinopathy with an attack of anterior uveitis in a young female with congenital generalized lipodystrophy - Berardinelli-Seip syndrome. To the best of our knowledge, this is the first description of ocular involvement in Berardinelli-Seip syndrome.

Management of prolactinomas: a survey of physicians from the Middle East and North Africa.

BACKGROUND: Prolactinomas are the commonest functional tumors of the pituitary gland. There are still controversies regarding medical therapy in specific clinical situations. Patients may be managed by different specialists in the Middle East and North Africa (MENA) region and no data exist on patterns of clinical management. OBJECTIVES: To ascertain the diagnostic and therapeutic approaches to prolactinomas among relevant professionals from the MENA region. METHODS: An online survey of a large sample of physicians was conducted. The questionnaire covered various aspects of diagnosis and treatment of prolactinomas. 468 respondents were included; 36 % were endocrinologists; 49 % worked in public facilities and 81 % graduated more than 10 years. 40 and 30 % would have seen 1-5 and more than 5 suspected or confirmed prolactinomas over a 6 months period, respectively. RESULTS: Regarding the diagnosis, 30 % of the respondents considered that prolactin levels <100 ng/ml exclude the presence of a prolactinoma. 21 % of respondents considered prolactin levels >250 ng/ml compatible with macroprolactinomas only, whereas others accepted this to be compatible also with microprolactinomas, macroprolactinaemia and drug-induced hyperprolactinemia (50, 42 and 36 % respectively). 71 % of respondents favored the screening for macroprolactin in asymptomatic individuals with hyperprolactinemia. Regarding the treatment, 84 % of respondents would treat microprolactinomas even in the absence of symptoms whereas 72 % of the respondents would treat microprolactinomas only if symptoms exist. 60 and 49 % of the respondents chose cabergoline as the drug of choice to treat macroprolactinomas and microprolactinomas respectively. Similar proportions had no preference of either cabergoline or bromocriptine as the best treatment for macroprolactinoma (27 %) and microprolactinomas (32 %). 46 and 75 % of respondents favored treatment withdrawal 2-3 years after prolactin normalization in patients with macroprolactinomas and microprolactinomas, respectively whereas 10 % of respondents withdraw treatment after menopause in either case. 94 % of respondents considered medical therapy as the primary treatment for microprolactinomas. In case of pregnancy, 49 % considered bromocriptine as the drug of choice for women who wish to become pregnant. 65 and 38 % of respondents advocated discontinuation of treatment with dopamine agonists in patients with microprolactinomas and macroprolactinomas, respectively. Finally, 48 % would allow breast-feeding without restriction, 28 % would restrict it to patients with microprolactinomas and 25 % would not recommend it for women with prolactinomas. CONCLUSIONS: This is the first study of the clinical management of prolactinomas in the MENA region. Some of the practices are not in line with the latest Endocrine and Pituitary Societies guidelines. These warrant further discussions of contemporary guidelines in regional forums.

2015 Guidelines for Osteoporosis in Saudi Arabia: Recommendations from the Saudi Osteoporosis Society.

BACKGROUND AND OBJECTIVES: To provide guidelines for medical professionals in Saudi Arabia regarding osteoporosis. DESIGN AND SETTINGS: A panel of 14 local experts in osteoporosis assembled to provide consensus based on the strength of evidence and expert opinions on osteoporosis treatment. PATIENTS AND METHODS: The Saudi Osteoporosis Society (SOS) formed a panel of experts who performed an extensive published studies search to formulate recommendations regarding prevention, diagnosis, and treatment of osteoporosis in Saudi Arabia. Both local and international published studies were utilized whenever available. RESULTS: Dual x-ray absorptiometry (DXA) scanning is still the golden standard for assessing bone mineral density (BMD). In the absence of local, country-specific fracture risk assessment tool (FRAX), the SOS recommends using the USA (White) version of the FRAX tool. All women above 60 years of age should be evaluated for BMD. This is because the panel recognized that osteoporosis and osteoporotic fractures occur at a younger age in Saudi Arabia. Hormone replacement therapy (HRT) is not recommended for treating postmenopausal women with osteoporosis. BMD evaluation should be performed 1-2 years after initiating intervention, and the assessment of bone turnover biomarkers should be performed whenever available to determine the efficacy of intervention. CONCLUSION: All Saudi women above the age of 60 years must undergo a BMD assessment using DXA. Therapy decisions should be formulated with the use of the USA (White) version of the FRAX tool.

Increasing trends and significance of hypovitaminosis D: a population-based study in the Kingdom of Saudi Arabia.

UNLABELLED: Vitamin D deficiency is highly prevalent in Saudi Arabia, particularly among young women and is emerging as public health threat of epidemic proportions. Prevalence of severe hypovitaminosis D is expected to rise exponentially without primary intervention. This largest study encompasses extent of vitamin D deficiency and recommendations to reduce significant health care burden. INTRODUCTION: The aim of the study was to determine the prevalence and significance of vitamin D deficiency in Saudi population and to help develop national consensus for its prevention, screening, and management. METHODS: This was a retrospective observational study which involved 10,709 patients, recruited from the Department of Family Medicine and Polyclinic, King Faisal Specialist Hospital and Research Center (KFSH&RC), Saudi Arabia, over a period of 5 years. The endpoints included overall status of vitamin D level and severity of vitamin D deficiency. Serum measurements included 25 hydroxyvitamin D (25(OH)D), parathormone, calcium, phosphate, alkaline phosphatase, albumin levels, eGFR levels, bone mineral density. RESULTS: A total of 10,709 patients were analyzed; 31.4 % were males and 68.6 % were females, with a preponderance of Saudis (68.5 %) compared to non-Saudis (31.5 %). The prevalence of vitamin D deficiency was 83.6 % (31.9 % severe, 32.0 % moderate, and 19.7 % mild), when cut points of less than 25, 50, and 75 nmol/l, respectively, were used. Mean serum 25(OH)D was 44.58 ± 34.80 standard deviation (SD) nmol/l. There was significant difference in severity of vitamin D deficiency stratified by age, gender, and nationality. More females had severe 25(OH)D deficiency compared to males (35.6 vs. 23.7 %, p < 0.000). Severe 25(OH)D deficiency was markedly high among adolescents as compared to other age groups (49.2 vs. 30.9 %, p < 0.000). More Saudis were found to be vitamin D deficient compared to non-Saudis (37.2 vs. 20.3 %, p < 0.000). CONCLUSION: The prevalence of hypovitaminosis D is significantly high among Saudi population, especially among women, despite abundant sunshine. It is a major public health concern and requires a robust health policy for vitamin D supplementation and implementation of dietary public health measures. Vitamin D screening is strongly recommended at an earlier age especially among women and children.

Molecular characterization of a novel p.R118C mutation in the insulin receptor gene from patients with severe insulin resistance.

CONTEXT: Mutations of the insulin receptor gene (INSR) can cause genetic syndromes associated with severe insulin resistance. OBJECTIVES: We aimed to analyse INSR mutations in Saudi patients with severe insulin resistance. DESIGN: Ten patients with Type A insulin resistance syndrome from five unrelated Saudi families were investigated. The entire coding region of INSR was sequenced. The founder effect was assessed by microsatellite haplotype analysis. The functional effect of the mutation was investigated by in vitro functional assays. RESULTS: A novel biallelic c.433 C>T (p.R118C) mutation was detected in all patients. The c.433 C>T (p.R118C) sequence variation was not found in 100 population controls. The arginine residue at position 118 is located in the ligand-binding domain of INSR and is highly conserved across species. Microsatellite haplotype analysis of these patients indicated that p.R118C was a founder mutation created approximately 2900 years ago. The wild-type and mutant (R118C) INSR were cloned and expressed in CHO cells for functional analysis. Specific insulin binding to the mutant receptor was reduced by 83% as compared to wild-type (WT), although the mutant receptor was processed and expressed on the cell surface. Insulin-mediated receptor autophosphorylation was also significantly reduced in CHO(R118C) cells. CONCLUSIONS: Biallelic c.433 C>T (p.R118C) mutation of INSR causes significant damage to insulin binding and insulin-mediated signal transduction. p.R118C is a founder mutation frequently present in the Saudi patients with severe insulin resistance.

A novel deletion of the MEN1 gene in a large family of multiple endocrine neoplasia type 1 (MEN1) with aggressive phenotype.

CONTEXT: The MEN1 syndrome is associated with parathyroid, pancreatic and pituitary tumours and is caused by mutations in the MEN1 gene. In general, there is no genotype-phenotype correlation. OBJECTIVES: To characterize a large family with MEN1 with aggressive tumour behaviour: malignant pancreatic endocrine tumours were present in five affected subjects and were the presenting features in three subjects. DESIGN: The coding region of MEN1 was sequenced. Gene copy number analysis was performed by multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). Loss of heterozygosity (LOH) in tumour tissue was studied by microsatellite analysis. Insulin-like growth factor II (IGF-II) and CDKN1C/p57KIP2 expression were investigated by immunohistochemistry. RESULTS: Mutation screening by conventional PCR sequence analysis of patients' peripheral blood DNA did not reveal any mutation in the MEN1 or CDKN1B gene. Gene copy number analysis by MLPA and aCGH demonstrated a novel monoallelic deletion of 5 kb genomic DNA involving the MEN1 promoter and exons 1 and 2. LOH analysis indicated somatic deletion of maternal chromosome 11, including MEN1 locus (11q13) and 11p15 imprinting control regions (ICR). Methylation analysis of ICR demonstrated ICR1 hypermethylation and ICR2 hypomethylation in the tumour specimens. ICR1 and ICR2 control the expression of IGF-2 and CDKN1C/p57KIP2, respectively. Immunohistochemistry showed that expression of paternally expressed IGF-2 was up-regulated and the maternally expressed CDKN1C/p57KIP2 was lost in the pancreatic endocrine tumours. CONCLUSIONS: Gene copy number analysis by MLPA should be considered in patients with negative conventional mutation screening. Although large MEN1 deletion causes MEN1, disruption of imprinted CDKN1C/p57KIP2 and IGF-2 gene expression may contribute to tumour progression and aggressive phenotype.

Updated recommendations for the diagnosis and management of osteoporosis: a local perspective.

Postmenopausal osteoporosis and osteoporosis in elderly men are major health problems, with a significant medical and economic burden. Although osteopenia and osteoporosis are more common locally than in the West, fracture rates are generally less than in Western countries. Vitamin D deficiency is common in the region and contributes adversely to bone health. Vitamin D deficiency should be suspected and treated in all subjects with ostopenia or osteoporosis. The use of risk factors to determine fracture risk has been adopted by the World Health Organization and many international societies. Absolute fracture risk methodology improves the use of resources by targeting subjects at higher risk of fractures for screening and management. The King Faisal Specialist Hospital Osteoporosis Working Group recommends screening for women 65 years and older and for men 70 years and older. Younger subjects with clinical risk factors and persons with clinical evidence of osteoporosis or diseases leading to osteoporosis should also be screened. These guidelines provide recommendations for treatment for postmenopausal women and men older than 50 years presenting with osteoporotic fractures for persons having osteoporosis-after excluding secondary causes-or for persons having low bone mass and a high risk for fracture. The Working Group has suggested an algorithm to use at King Faisal Specialist Hospital that is based on the availability, cost, and level of evidence of various therapeutic modalities. Adequate calcium and vitamin D supplement are recommended for all. Weekly alendronate (in the absence of contraindications) is recommended as first-line therapy. Alternatives to alendronate are raloxifene or strontium ranelate. Second-line therapies are zoledronic acid intravenously once yearly, when oral therapy is not feasible or complicated by side effects, or teriparatide in established osteoporosis with fractures.

Biallelic p.R2223H mutation in the thyroglobulin gene causes thyroglobulin retention and severe hypothyroidism with subsequent development of thyroid carcinoma.

CONTEXT: Dyshormonogenesis due to genetic defect in thyroglobulin (Tg) synthesis and secretion can lead to congenital hypothyroidism. OBJECTIVES: The aim of the study was to analyze the TG gene for the presence of mutations and to study the underlying mechanisms leading to dyshormonogenesis. CASES: Two siblings aged 25 and 31 yr presented with recurrent goitrous hypothyroidism with undetectable serum Tg. The older sibling was diagnosed with follicular variant of papillary thyroid carcinoma (FVPTC) at age 21 and metastatic FVPTC 8 yr later. METHODS: The entire coding region of TG gene was sequenced. BRAF, RAS, and P53 mutations or PAX8/PPAR-gamma rearrangement were screened in the FVPTC. Tg expression was studied by immunohistochemistry. RESULTS: Biallelic c.6725G>A (p.R2223H) and c.6396C>T (p.S2113L) sequence variations were detected in both patients and monoallelic variations in their family members. The c.6396C>T (p.S2113L) sequence variation was found in 14% of 100 population controls, whereas c.6725G>A variation was not present in the controls. Two previously reported polymorphisms (c.2200T>G and c.3082A>G) were present in all the family members. Strong cytoplasmic immunostaining of Tg was observed in the hyperplastic thyroid epithelial cells and weak or no staining in the follicular lumen. Cytoplasmic staining was localized in the endoplasmic reticulum. Reduced staining was found in the FVPTC. Neither RAS, BRAF, or P53 gene mutation nor a PAX8/PPAR-gamma rearrangement was detected in the tumor tissue. CONCLUSIONS: Biallelic c.6725G>A (p.R2223H) mutation causes Tg retention in the endoplasmic reticulum, resulting in dyshormonogenesis. Prolonged TSH stimulation may promote malignant transformation and development of thyroid cancer. The c.6396C>T (p.S2113L) is a novel polymorphism.

Recurrent thyroid storm induced by heretofore unrecognised causes in a patient with thyroid cancer.

An unusual encounter of a thyroid storm, on two separate occasions, is reported in a patient with metastatic differentiated thyroid cancer following initially direct trauma to, and later tumour embolisation of, a metastatic skeletal lesion. Shortly after a fall, our patient presented with pain and swelling in the right shoulder, high fever, change in mental status, anorexia, nausea and vomiting, tachycardia and dehydration. The laboratory tests were consistent with hyperthyroidism. As the patient improved, arterial embolisation of the large right humerus metastasis was performed to decrease the tumour burden. The patient, however, developed a similar clinical and biochemical picture to that at her presentation, with a very high free thyroxine (T(4)) level, a few days after successful embolisation. Treatment of the thyroid storm was initiated and the patient eventually improved. Awareness of such occurrences is helpful in early diagnosis and effective management of this potentially fatal complication.

Genotype-phenotype correlation in a family with primary cortisol resistance: possible modulating effect of the ER22/23EK polymorphism.

OBJECTIVE: Glucocorticoid resistance is a rare sporadic or familial condition that is characterized by generalized, partial resistance to glucocorticoids. It is caused by a mutation in the glucocorticoid receptor-alpha (GR-alpha) gene. We aimed to understand the reasons for different phenotypes (severe to asymptomatic) observed in a family with primary cortisol resistance. DESIGN: The genotype leading to cortisol resistance in the family members was investigated and correlated to the clinical phenotype. METHOD: Three siblings were presented with clinical cortisol resistance, featuring severe hypertension, hypokalemia and hyperandrogenism. Three other siblings and both parents were asymptomatic. Genomic DNA from peripheral lymphocytes was isolated from family members. The entire GR-alpha coding sequence (exons 2-9) was amplified by PCR and sequenced. RESULTS: A homozygous G679S mutation was present in the three clinically affected subjects. Heterozygous G66A (E22E) and G68A (R23K) polymorphisms and G2035A (G679S) mutation were found in the father and two siblings. Mother and one sibling had only heterozygous G679S mutation. The clinically unaffected subjects showed two different responses to dexamethason. Those with heterozygous G679S mutation and ER22/23EK polymorphism had normal cortisol suppression, whereas those with only heterozygous G679S mutation failed to suppress normally. CONCLUSIONS: A homozygous G679S mutation of the GR-alpha gene is associated with severe cortisol resistance, whereas a heterozygous mutation of the same gene can lead to subclinical cortisol resistance. The effect of the heterozygous mutation was abolished in subjects carrying the ER22/23EK polymorphism.

Hurthle cell neoplasm of the thyroid gland.

BACKGROUND: A clinicopathological analysis and long-term follow up of 32 patients with Hurthle cell neoplasm (HCN) was undertaken to contrast the clinical and histological features between benign versus malignant HCN of thyroid and to examine the effect of treatment on the outcome. METHODS: This is a retrospective study of 32 patients with HCN who were identified out of an archival clinical/pathological/imaging database of 3752 thyroid cancer patients seen between 1976 and June 2006. All patients underwent thyroid surgery. Data for the non-surgical treatment along with follow up were also analysed. RESULTS: Seventeen patients were classified as malignant HCN (MHCN) and 15 as benign HCN (BHCN). Among the MHCN, there were 11 women and 6 men, whereas among BHCN there were 14 women and 1 man. Three patients designated MHCN presented with metastases, one with pulmonary metastases and two others with skeletal metastases who developed lung metastases 9-19 months later. The mean tumour size was 4.43 +/- 0.66 cm for MHCN, and 2.57 +/- 0.32 cm for BHCN (P = 0.03). Multicentric tumour foci were evident in five cases (29%) of MHCN but none among the BHCN (P = 0.03). At neck exploration cervical lymph node dissection was carried out in nine MHCN patients with findings of tumour metastases in 33%. Postoperatively, three MHCN patients had no thyroid remnant on ultrasound and computed tomography of neck and undetectable serum thyroglobulin; these were considered to be in remission. Fourteen other MHCN patients with postoperative thyroid remnant and/or distant metastases received 131I treatment. Eight of these patients had negative whole-body scans after 131I treatment and undetectable thyroglobulin. Accordingly, 11 MHCN patients (64.7%) showed evidence of remission and 6 patients did not respond to 131I treatment. After a mean follow up of 35 months, all BHCN patients are alive with no evidence of disease. Of the MHCN, 11 (64.7%) were in remission and 35% had evidence of persistence/recurrence. One patient who had recurrence is dead. A lack of effectiveness of 131I therapy in two patients with distant metastases is an important finding. CONCLUSION: Features of MHCN consisted of a large tumour size, unequivocal capsular and vascular invasion, multicentric tumour foci, metastatic lymph node deposits in one-third of patients and presence of distant metastasis in a few. Findings of dominant Hurthle cell cytology in a fine-needle aspiration biopsy from a thyroid nodule should prompt surgical resection of the lesion to assess malignancy.

Continuous subcutaneous insulin infusion in type 1 diabetic Saudi children. A comparison with conventional insulin therapy.

OBJECTIVE: To assess the efficacy and effectiveness of continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetic Saudi children in comparison with conventional insulin (CI) therapy. METHODS: Continuous subcutaneous insulin infusion was initiated in 14 Saudi children with type 1 diabetes mellitus (T1DM) through insulin pump therapy between October 2002 and June 2004. All children were followed at the Diabetes Clinic, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia. The patients were initially on CI therapy, which is usually defined as 2 or fewer insulin injections per day before shifting them to CSII. The patients were trained on carbohydrates counting and started on continuously basal insulin infusion aside from the meal and high blood glucose correction insulin boluses. RESULTS: The patients included in the study had T1DM for a mean duration of 6 years. The age of the children ranged from 4-18 years. They were followed on insulin pump therapy for a mean duration of 10 months. There was a significant reduction in hemoglobin A1c, mean blood glucose level, total insulin requirement, frequency of hypoglycemic episodes and frequency of diabetic ketoacidosis (DKA) events during CSII therapy. CONCLUSION: Continuous subcutaneous insulin infusion improved the glycemic control in diabetic Saudi children with decreased frequency of hypoglycemic episodes and DKA events. Long follow-up studies are needed to confirm these results.

The hook effect in prolactin immunoassays.

We describe a young female patient with giant invasive sellar and suprasellar tumor and modest elevation of prolactin to 165 ng/ml (normal range 3-29). A diagnosis was made of non functional pituitary adenoma with stalk effect, causing moderate prolactin elevation. A surgery for the removal of the tumor was advised but the patient declined. Treatment with a dopamine agonist was not offered. The patient presented 2 years later with deterioration of her vision and serum prolactin of >16000 ng/ml. Debulking transsphenoidal surgery was performed. The staining of tissue confirmed prolactinoma. Medical treatment with bromocriptine was initiated. We believe that the discrepancy between the 2 values of serum prolactin, is most probably caused by a hook effect in the initial prolactin assay. The mechanism of the hook effect and its occurrence with prolactin immunoassays and methods to eliminate this effect is discussed. Hook effect needs to be suspected in every patient with a giant pituitary or parasellar mass and serum prolactin <200 ng/ml. Assaying a diluted serum will usually unmask this phenomenon and allow accurate diagnosis and management.