Julie Hephzibah

Acute pancreatitis and hyperparathyroidism: A case series

Primary hyperparathyroidism is a rare cause of acute pancreatitis. Five consecutive patients with acute or recurrent acute pancreatitis and primary hyperparathyroidism were included. All patients had elevated serum calcium on admission and high levels of circulating parathyroid hormone. Both ultrasonography and Sestamibi scan was used to localize parathyroid adenoma. Except for one, all patients underwent parathyroidectomy and postoperative histology was consistent with parathyroid adenoma. One patient died while on treatment. Metabolic causes of acute pancreatitits, though uncommon, are important as early recognition helps management and prevents recurrence.

Mutational analysis of RET proto-oncogene among patients with medullary thyroid carcinoma and ‘at risk’ carriers from India

Mutations associated with the RET proto-oncogene have been extensively investigated in patients with medullary thyroid carcinoma (MTC) since its first description in 1993. Several germline activating point mutations on exons 10, 11, 13, 14, 15 and 16 of this gene, are known to be associated with multiple endocrine neoplasia type 2 (MEN 2) and familial MTC (FMTC). These mutations are inherited in an autosomal dominant manner necessitating screening of index cases and their families to identify carriers who could benefit from early prophylactic thyroidectomy. In addition to these mutations, several single nucleotide polymorphisms (SNPs) have also been described though it is debatable whether these polymorphisms have either a predisposing or a modifying role in the pathogenesis of MTC. MTC is a malignancy with a good prognosis where patients have reasonable longevity even in the presence of metastases. Our previous experience over a 20-year period has shown that survival rates are favorable even in cases with metastases (43%) at the time of diagnosis. Understanding the mutational profile of MTC in the Indian population is therefore crucial to establishing a diagnosis and performing early prophylactic thyroidectomy before development of disease. However, a detailed report of the mutational profile among Indian patients is lacking. We report RET mutational analysis of the six ‘risk exons’ along with characterization of the four known exonic RET polymorphisms among patients with MTC and among ‘at risk’ carriers. Thirty-six patients with MTC who attended the outpatient clinic between January 2008 to December 2009 were included in the study. The diagnosis of MTC was based on the histopathology of the tumor after thyroidectomy. Peripheral venous blood was collected from all these patients and 11 ‘at risk’ carriers after obtaining consent. Genomic DNA extracted from 200 ll of blood was amplified with primers for exons 10, 11, 13, 14, 15 and 16. PCR products were sequenced using the ABI PRISM 310 genetic analyzer (Applied Biosystems, Foster City, CA, USA). The association between mutational status and various demographic, clinical factors were evaluated by Chi-square test or Fisher’s exact test using stata 10.0 (StataCorp, College Station, TX, USA). The 36 index cases (24 males and 13 females), included cases of MEN IIA (n = 3), MEN IIB (n = 2), FMTC (n = 2) and apparently sporadic MTC (sMTC, n = 29). The mean age of patients included was 47 years (range 19–74 years) and median serum calcitonin was 4650 pg/ml (range 133–97, 8000 pg/ml). Metastases were observed in 72% of patients (n = 26). Mutational analysis showed that 28% (10/36) of patients in this study carried a germline mutation which included all cases of MEN II and FMTCs and three patients (10%; 3/36) who were apparently sporadic cases (Table 1). Mutations at codon 634/exon 11 was most common (n = 5), while two patients had a mutation at codon 618 and one each at codon 804, 891 and 918. Similar sequence analysis was performed for all the 11 ‘at risk’ carriers and six harbored the same mutations as in the index case. Four of them underwent prophylactic thyroidectomy. While the percentage of mutations among the familial and sporadic cases of MTC in this study are comparable to the previous reported studies from other geographic regions of the world, it differs from the only other Indian study which reported a larger number (18/24) of sMTC. Irrespective of these differences, the presence of mutations in sporadic cases and among ‘at risk’ carriers, demonstrates the benefit of routine screening of all patients with MTC and their first degree relatives even in a resource limited setting. Sequences were also analyzed for the four known exonic polymorphisms (G691S/exon 11, L769L/exon 13, S836S/ exon 14 and S904S/exon 15). SNPs at 691 and 769 were more common (47% each) than polymorphisms at 904 (35%) and 836 (20%). Interestingly, nine sporadic cases with no mutations also had the G691S polymorphism, which is the only SNP associated with an amino acid change. Further, all cases that had G691S polymorphism also had S904S polymorphism. Although G691S is not considered an oncogenic mutation, a functional role for this SNP has not been entirely ruled out. In fact Elsei et al. reported a significantly higher allelic frequency of G691S among sMTC when compared to normal controls suggesting a putative role for this SNP as a genetic modifier. However, our study has the drawback of characterizing these polymorphisms only among patients’ with MTCs without

Abnormal Appearance of Spinal Hemangioma Mimicking Metastasis in Bone Scintigraphy and SPECT-CT: Case Report

Study design: Case reports of abnormal appearance of hemangioma in thoracolumbar spine in bone scintigraphy. Objective: To report an unusual presentation of spinal hemangioma mimicking metastasis in bone scintigraphy and SPECT-CT. Summary of back ground data: Spinal hemangiomas are usually incidental findings. Most of them are asymptomatic and bone scintigraphy will be normal in majority of them. In the back ground of an underlying malignancy, an abnormal hot spot in bone scan always arouse a high suspicion of bone metastasis. Methods: Two middle aged ladies, treated for carcinoma cervix and carcinoma breast respectively, were undergoing regular follow ups. One patient had complaints of back pain on and off and her bone scan showed abnormal increase in tracer uptake in L1 vertebra suspicious of metastasis. Second lady had suspected intra abdominal metastatic disease and her bone scan showed abnormal increase in tracer uptake in thoracolumbar spine mimicking metastasis. Results: Both patients underwent further detailed evaluations and MRI study of spine was reported as hemangioma and PET-CT ruled out the possibilities of recurrent or metastatic malignancy. During further follow up, both patients were disease free. Conclusion: Hemangioma of spine appearing as a hot spot in bone scan is rare. In the back ground of a malignancy, a ‘hot’ lesion can be studied better with metabolic imaging with PET – CT which could dispel the suspicion of a metastatic focus quite clearly. MRI could also give a diagnostic clue.

Comparison of glomerular filtration rate measured by plasma sample technique, Cockroft Gault method and Gates' method in voluntary kidney donors and renal transplant recipients

Background: There are numerous methods for calculation of glomerular filtration rate (GFR), which is a crucial measurement to identify patients with renal disease. Aims: The aim of this study is to compare four different methods of GFR calculation. Settings and Design: Clinical setup, prospective study. Materials and Methods: Data was collected from routine renal scans done for voluntary kidney donors (VKD) or renal transplant recipients 6 months after transplantation. Following technetium-99m diethylene triamine penta acetic acid injection, venous blood samples were collected from contralateral arm at 120, 180, and 240 min through an indwelling venous cannula and direct collection by syringe. A total volume of 1 ml of plasma from each sample and standards were counted in an automatic gamma counter for 1 min. Blood samples taken at 120 min and 240 min were used for double plasma sample method (DPSM) and a sample taken at 180 min for single plasma sample method (SPSM). Russells formulae for SPSM and DPSM were used for GFR estimation. Gates’ method GFR was calculated by vendor provided software. Correlation analysis was performed using Pearsons correlation test. Results: SPSM correlated well with DPSM. GFR value in healthy potential kidney donors has a significant role in the selection of donors. The mean GFR ± (standard deviation) in VKD using SPSM, DPSM, camera depth method and Cockroft Gault method was 134.6 (25.9), 137.5 (42.4), 98.6 (15.9), 83.5 (21.1) respectively. Gates’ GFR calculation did not correlate well with plasma sampling method. Conclusions: Calculation of GFR plays a vital role in the management of renal patients, hence it was noted that Gates GFR may not be a reliable method of calculation. SPSM was more reliable. DPSM is reliable but cumbersome. It is difficult to accurately calculate GFR without a gold standard.

Iodine-131MIBG SPECT/CT in neuroendocrine tumours: An institutional experience

Context: Radiolabelled metaiodobenzylguanidine (MIBG) is commonly used for imaging of neuroendocrine tumors (NETs). The hybrid imaging with single photon emission computerized tomography/computerized tomography (SPECT/CT) co-registration can give that additional edge to this functional imaging modality. Aims: To study the additional value of 131I-MIBG SPECT/CT scintigraphy in evaluation of NETs. Settings and Design: We performed a retrospective study of the scintigraphic data of patients referred to our department for detection and follow-up of NETs from 2004 to 2008. Materials and Methods: Total number of studies were 370. Twenty-eight patients with equivocal findings on planar imaging had undergone additional SPECT/CT imaging. The contribution made by SPECT/CT imaging in these studies was analyzed. Results: In 27 of 28 cases, SPECT/CT provided vital additional information. Conclusions: We concluded that SPECT/CT co-registration helps in exclusion, identification, and localization of primary and metastatic NETs. It differentiates physiological from pathological tracer distribution. It helps increase the confidence in reporting, especially in equivocal findings on planar imaging.

Stimulated serum thyroglobulin levels versus unstimulated serum thyroglobulin in the follow-up of patients with papillary thyroid carcinoma

Serum thyroglobulin (Tg) and thyroid whole-body radioiodine scintigraphy (TWBS) are used in the follow-up of patients with papillary thyroid carcinoma (PTC) after total thyroidectomy. Symptoms of hypothyroidism are frequent as patients discontinue levothyroxine 1 month before visit, favoring the use of unstimulated serum Tg (uSTg) only. This study was done to determine the reliability of stimulated serum Tg levels (sSTg) over uSTg. A total of 650 patients with PTC came for follow-up between June 2011 and 2016. In those who had levels of uSTg and sSTg months measured within an interval of median of 3 months (range from 1 to 8 months), risk stratification was done as per the American Thyroid Association guidelines 2015. Intervention was based on a cutoff value of sSTg >10 ng/ml in our institution and the same was used for data analysis. Out of 650 patients, 106 had paired Tg values. Low-, intermediate-, and high-risk groups comprised 40, 31, and 35 patients, respectively. The sSTg >10 ng/ml with uSTg <10 ng/ml in the same patient was noted in 22.5% (9/40) of the low-risk, 41.9% (13/31) of the intermediate-risk, and 14.2% (5/35) of the high-risk groups. The levels were corroborated with tumor burden as determined by additional clinical, ultrasonography neck, and TWBS findings. Our study highlights the superiority of sSTg over uSTg in the follow-up of PTC patients. Follow-up with uSTg alone may result in underestimating the tumor burden.

Diagnostic Utility of PET CT in Thymic Tumours with Emphasis on 68Ga-DOTATATE PET CT in Thymic Neuroendocrine Tumour - Experience at a Tertiary Level Hospital in India

INTRODUCTION 18 Fluorine-fluoro-2-deoxyglucose positron emis-sion tomography/computed tomography (18F- FDG-PET/CT) is of importance in assessing high-risk thymoma and thymic carcinomas. Detection of advanced thymoma versus thymic carcinoma by routine cross sectional anatomical imaging such as computed tomography (CT), magnetic resonance imaging (MRI) often poses a diagnostic dilemma. In this case series we observed the utility of FDG uptake to predict advanced thymoma and distinguish thymoma from thymic cancer. MATERIALS AND METHODS We reviewed 18F- FDG-PET/CT scans of 12 patients (8 males, 4 females); age 24-60yrs with thymic epithelial malignancy from January 2011 to May 2013. FDG activity in lesions was quantified using maximum standardised uptake value (SUVmax) and correlated with Masaoka staging and WHO classification. All patients fasted 4 hr prior to 18F-FDG PET/CT. Images from vertex to mid-thigh were acquired 60min post injection of 3.7 -4.7 MBq/kg (Mega Becquerel)/kilogram of18F-FDG and SUV max of each tumour was measured. One patient underwent DOTATATE scan, received 138MBq of 68Gallium (68Ga)-DOTATATE injection IV and imaging was done after 60 min. RESULTS Higher FDG uptake of SUVmax 7.35 was seen in type B3 thymoma. FDG uptake was higher in thymic carcinoma (20.45 in primary and 17.46 in the node) or neuroendocrine differentiation (NED) than in patients with thymomas (ranged 7.35 - 3.02). No significant association was observed between higher focal FDG uptake and advanced-stage disease in thymoma. In NED 68Ga - DOTATATE imaging identified more lesions than in FDG. CONCLUSION PET CT is a valuable diagnostic tool in evaluation of thymic tumours, to assess in initial workup, for treatment response and for prognostication. 68Ga-DOTATATE PET/CT is beneficial in assessing neuroendocrine thymic tumours. Focal FDG uptake cannot predict advanced thymoma but is helpful in distinguishing thymoma from thymic carcinoma, or the more aggressive thymoma B3.