Poster Session : PS 0155 ; Diabetes : Associated Polymorphisms in Type 2 Diabetes of Early Initiation in Mexico

( Roberto Monreal Robles ),( Hugo L Gallardo Blanco ),( Fernando J Lavalle Gonzalez ),( Ricardo M Cerda Flores ),( Pavel Carrillo Molina ),( Minerva G Martinez Cavazos ),( Laura E Martinez Garza ),( J 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Currently there are a growing number of individuals with type 2 diabetes (T2D) imposing a signifi cant public health burden due to disability and premature death. Diabetes is the most common cause of death in Mexico. It is estimated that 11.7 million Mexicans will have diabetes by the year 2025. The risk of developing T2D is determined by genetic and environmental factors. However, large differences in prevalence between ethnic groups exist and seem to depend on genetic factors. Nearly 40 different T2D susceptibility loci, mainly in Europeans have been identifi ed. The aim of this study was to identify susceptibility loci related to T2D in our population. Methods: We studied 128 SNPs in or near 42 genes, most of which had been replicated in other populations. A case-control association study comprising 186 controls, 211 early-onset T2D (diagnosed before 45 years of age) and 173 late-onset T2D individuals was conducted. Actually we preliminary reported the genotypifi cation analyses of 256 individuals. Results: Subjects with T2D independently of age at diagnosis have higher mass body index than controls (27.5 vs 25.7 kg/m2, P= <0.0001). The median age for early-onset T2D, late-onset T2D and controls individuals were 46, 61 and 62 years, respectively. Age at diagnosis for early-onset and late-onset T2D individuals was 35 and 52 years, respectively. The allelic variants of genes KCNJ11 (rs5219), LEPR (rs11208654), IGF2BP2 (rs4402960), VLDLR (rs2242103), KCNQ1 (rs2237892), RPTOR (rs12946115), SLC25A18 (rs1296819) show association with T2D in this preliminary analysis. These polymorphism previously mentioned affect directly or indirectly over insulin release and peripheral sensitivity. Conclusions: We found our population to have an important genetic predisposition to T2D. The associated susceptibility loci for T2D support the hypothesis that insulin release defects and peripheral resistance are the main mechanisms predisposing to T2D in Mexican population.

Poster Session : PS 0470 ; Nephrology ; Acute Toluene Intoxication: Prospective Observational Study

( Rene Rodriguez Gutierrez ),( Roberto Monreal Robles ),( Carlos R Camara Lemarroy ),( Jose G Gonzalez Gonzalez ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Toluene is one of the most widely abused inhaled drugs and dangerous metabolic abnormalities are associated to its acute intoxication. It has been previously reported that rhabdomyolysis and acute hepatorenal injury could be hallmarks of the disease, and could constitute risk factors for poor outcomes. The objective was to describe the clinical presentation, to characterize the renal and liver abnormalities, the management and prognosis associated to acute toluene intoxication. Methods: We prospectively assessed 20 patients that were admitted to a single center`s emergency department from 2007-2014 with clinical and metabolic alterations due to acute toluene intoxication. Results: Patients were severely acidotic on admission (mean pH: 7.14 ± 0.09) with a mean anion gap of 16 ± 6.9 mmol/L and mean potassium level of 2.19 mmol/L ± 1.32. The main clinical presentation consisted of weakness associated to severe hypokalemia and acidosis. Renal glomerular injury (proteinuria) was ubiquitous. Serum creatine-phosphokinase levels were elevated in 16 cases, with a mean elevation of 6 times the upper normal limit (1,544 ± 1,864 U/L). Liver function tests were normal, except for ALP, which was elevated in 15 patients. Gamma-glutamyl transpeptidase was elevated in all patients, with a mean of 103.9 ± 66.9. Rhabdomyolysis occurred in 80% of patients, probably due to hypokalemia and hypophosphatemia. There were three deaths, all associated with altered mental status, severe acidosis, hypokalemia and acute oliguric renal failure. The causes of death were cardiac rhythm abnormalities. Conclusions: The hallmarks of acute toluene intoxication are hypokalemic paralysis and metabolic acidosis. Liver injury and rhabdomyolysis are common. Altered mental state on admission, renal failure, severe acidemia and female gender could be associated with a poor outcome, and patients with these characteristics should be treated in an intensive care unit.

Poster Session:PS 0197 ; Endocrinology : Severe Hypercalcemia: Chronic Tophaceous Gout the Responsible Cause?

( Rene Rodriguez Gutierrez ),( Roberto Monreal Robles ),( Maria Azucena Zapata Rivera ),( Karla V Rodriguez Velver ),( Fernando Jj Lavallegonzalez ),( Jose Gerardo Gonzalez Gonzalez ),( Jesus Zacarias 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background and Description: The association of chronic tophaceous gout with severe hypercalcemia is extremely rare and has been usually associated with calcitriol secretion. PTHrP has never been described as the responsible cause. A 42-year old man with a long stand history of chronic gout initiated a week before admission with polyuria, polypsia and progressive altered mental status. Neurological examination revealed only lethargy. Characteristic, multiple, non-tender tophi were obvious at inspection (Figures 1-3). Initial laboratory work up revealed a uric acid of 14.0 mg/dl, calcium of 14.5 mg/dl, phosphorous of 6.3 mg/dl, creatinine of 5.4 mg/dl, blood nitrogen urea of 56, a MDRD GFR of 16 ml/min. Diagnostic and Therapeutic Approach: PTH was suppressed (< 3.0 pg/ml), 25-dihydroxyvitamin D was normal, PTHrP was elevated 45.0 pg/ml, and calcitriol normal (19.6 pg/ml). Radiographs revealed bone erosions (Figure 1-3). Bone scan and a PET-CT were negative for metastasis and malignancy. Treatment was initiated with calcitonin, hydration and prednisone. PTH, 25-dihydroxyvitamin D, PTHrP, and calcitriol returned to normal values. At 6 months follow-up he referred no pain, tophi had improved and calcium levels were within normal range. Discussion and Conclusion: A systemic research on PubMed, Medline, Embase and MedConsult with the search criteria: “Tophaceous gout”, hypercalcemia”, “calcitriol”, “PTHrP”, was made. The proposed mechanism has being an enhanced 1a-hydroxylation of vitamin D in a proliferative chronic synovitis. In this case calcitriol levels were normal. PTHrP had never been, until now, described as the responsible cause of hypercalcemia in gout. In our case baseline PTHrP and calcium values were elevated and after medical treatment both returned to normal values. Immobilization is another well-known cause of mild calcium elevations. It is likely that in this case this was an exacerbating rather than the primary factor.

Poster Session:PS 0198 ; Endocrinology : Giant Cystic Prolactinoma in a Woman: Do Not Forget the Hook Effect

( Rene Rodriguez Gutierrez ),( Karla V Rodriguez Velver ),( Maria Azucena Zapata Rivera ),( Roberto Monreal Robles ),( Fernando J Lavalle Gonzalez ),( Jose G Gonzalez Gonzalezz ),( Jesus Zacarias Vill 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background and Case Presentation: Cystic prolactinomas correspond to = 1% of all prolactinomas and its association with a giant pituitary macroadenoma in a woman has been seldom reported. A 43-year old woman was evaluated for a suprasellar tumor. She had absence of menses since 2 years. Three months before she started to have progressive headache. She also referred asthenia, adynamia, fatigue, dry hairiness, decreased libido, vaginal atrophy, and chronic constipation. Hair in armpits and pubic area was insignificant and osteotendinous reflex relaxation phase was slow. Galactorrhea was absent and presented bitemporal hemianopsia. Diagnostic and Therapeutic Approach: MRI scan revealed a 5 x 3.5 cm suprasellar mass and a 8.1 x 3.6 cm cystic component (Figures 1-3). Cortisol level 2.2 mg/dl, FSH and LH were low, estradiol < 0.05 pg/mL, IGF-1 normal and a serum prolactin of 125 ng/mL. Serial dilutions 1:10 and 1:100 were made. Diluted prolactine was 12,500 ng/mL (hook effect). Treatment with cabergoline, prednisone and levothyroxine were initiated. At two months follow-up prolactin serum levels decreased to 32.1 ng/mL. Discussion and Conclusion: A systemic research on PubMed, Medline, Embase and MedConsult with the search criteria: “Giant Cystic Prolactinoma”, “prolactin”, “prolactioma and “hook effect” was made. Due to the clinical signs of hypogonadism, the image in the MRI and the low/moderate high serum prolactin levels serial dilutions of prolactin were made. Serum prolactin assays can greatly underestimate extremely high levels of hormone, the so called “hook effect”. In present case, a high level of suspicion along with low/moderate prolactin levels and the MRI image consistent with a pituitary adenoma made us ask for diluted prolactin samples. If missed, this would have delayed the diagnosis and consequently would have changed the treatment plan and prognosis of the patient.

Poster Session : PS 0323 ; Hematology : Apixaban as a Therapeutic Option in Heparin-Induced Thrombocytopenia in a Patient on Hemodialysis

( Hector Raul Ibarra Sifuentes ),( Guillermo Ruben Garcia Delgado ),( Roberto Monreal Robles ),( Daniel Gallegos Arguijo ),( Perla Rocio Colunga Pedraza ),( Luis Javier Marfil Rivera ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

A 50-years-old woman came to the emergency room due to uremic syndrome; she was referred to start renal replacement therapy. Her past medical history was signifi - cant for long-standing type 2 diabetes and hypertension (evolving over 4 years), both conditions irregularly treated. On the night of her admission, a right femoral Mahurkar catheter was placed through an ultrasonography guided technique, and hemodialysis was thus started. Unfractionated heparin (UFH) was used as a bolus at the start of the session, subcutaneous UFH was also used as thromboprophylaxis during her hospital stay. On day 4 the second hemodialysis was performed. She clinically improved after 6 days of hospitalization, and was switched from hemodialysis to peritoneal dialysis. At admission, moderate thrombocytopenia (118 K/uL) was found, which was exhaustively investigated without identifying its cause. On day 10, showed at the physical examination painful, pitting edema, and limitation in walking. Deep venous thrombosis was then diagnosed by color Doppler ultrasonography, and anticoagulation with UFH and warfarin was started. The next day platelet count (PC) fell by 67% (absolute PC: 23. 6 K/uL), so early-onset HIT was suspected. According to the 4Ts score, our patient had a high pretest probability for HIT, therefore UFH and warfarin were discontinued. Treatment options were discussed with the patient in detail; we obtained an informed consent from her, and started her on apixaban. On day 15 her PC improved to 75 K/uL; and on day 18 to 128 K/uL. A low-dose warfarin (5 mg qd) was started together with apixaban for fi ve days. The INR was maintained within the therapeutic range during her hospital stay. On day 22 apixaban was discontinued, and she continued solely on warfarin. Prior to discharge her PC was entirely recovered (231 K/uL).