Muriel H. Nathan

A review of types 1 and 2 diabetes mellitus and their treatment with insulin.

Diabetes is a chronic disease characterized by hyperglycemia, and the prevalence of type 2 diabetes is growing to epidemic proportions in certain populations. Type 1 diabetes is primarily the result of autoimmune destruction of beta cells. Type 2 diabetes is found in those with resistance to the action of insulin, usually as a result of obesity, and deficient insulin secretion. Insulin use not only prevents hyperglycemic emergencies, but also is the best safeguard to prevent the long-term complications of diabetes by correcting fasting and postprandial hyperglycemia. Intensive glycemic control can lead to a substantial decrease in the development of microvascular changes found in patients with diabetes. Human insulin analogs, insulins manufactured by recombinant technology which contain substituted or rearranged amino acids, allow more physiological patterns of insulin replacement, termed the basal-bolus approach. Serious hypoglycemia is the biggest obstacle for patients with diabetes treated with intensive insulin programs. Insulin is now available in prefilled pens or can be delivered by a programmable pump to allow greater flexibility in use and to improve glycemic control. Whereas hyperglycemic emergencies are usually treated with intravenous fluids and an intravenous continuous insulin infusion, patients who are less critically ill can be treated with fluid and subcutaneous insulin analogs.

Celiac Disease and Hypothyroidism

BACKGROUND Celiac disease is more common in patients with hypothyroidism. Malabsorption of levothyroxine has not been studied in this population. We sought to determine if levothyroxine dosing was influenced by the presence and treatment of celiac disease. METHODS This retrospective study was conducted at an academic medical center. Cases had hypothyroidism and celiac disease. Controls had hypothyroidism alone and were selected randomly through the endocrinology clinic records. Celiac disease was defined as representative pathology with positive serology. Age, sex, height, weight, body mass index, creatinine, and medical comorbidity were assessed for cases and controls. The levothyroxine dose and weight-based levothyroxine dose necessary to maintain a euthyroid state was evaluated for controls, and before and after celiac disease therapy for cases. RESULTS Celiac disease was identified in 152 patients, and 22 patients had concomitant hypothyroidism (14.5%). Seven cases met inclusion criteria. Overall, 200 control patients were identified. The mean celiac disease pretreatment levothyroxine dose and weight-based levothyroxine dose needed to maintain a euthyroid state were higher in cases than in controls (154 μg vs 106 μg, P=.007, and 2.6 μg/kg vs 1.3 μg/kg, P <.001). Doses decreased significantly after treatment of celiac disease (154 μg vs 111 μg, P=.03; and 2.64 μg/kg vs 1.89 μg/kg, P=.04). All cases required at least 125 μg of levothyroxine initially to maintain a euthyroid state. CONCLUSIONS Levothyroxine malabsorption likely occurs with hypothyroidism and untreated celiac disease. Absorption may improve after celiac disease treatment. Screening for celiac disease in patients with hypothyroidism requiring elevated levothyroxine doses warrants further investigation.

Celiac disease detection in hypothyroid patients requiring elevated thyroid supplementation: A prospective cohort study☆☆☆

BACKGROUND Celiac disease (CD) is associated with hypothyroidism, but the disease prevalence is not thought to be great enough to warrant testing all hypothyroid patients. We hypothesized that hypothyroid patients with concomitant CD would require elevated doses of levothyroxine, and there is a threshold daily dose, above which, hypothyroid patients should be tested for CD. METHODS Hypothyroid patients presenting to the endoscopy or endocrinology clinics at the University of Vermont Medical Center were included. Patients were categorized by whether or not they required ≥125mcg/day of levothyroxine. A serum tissue transglutaminase (tTG) was performed on enrolled patients. Patients with an elevated serum tTG underwent endoscopy with duodenal biopsies. Symptoms were assessed by the Gastrointestinal Symptom Rating Scale. RESULTS Overall, 500 patients were enrolled and 29% (144 patients) required ≥125mcg/day of levothyroxine. CD was detected in 9 patients. The prevalence of CD ranged from 1.8% in our entire cohort to 12.5% in patients requiring ≥200mcg/day of levothyroxine. Eight patients with CD (89%) required ≥125mcg/day of levothyroxine. Patients who required ≥125mcg/day of levothyroxine had a significantly increased risk of CD (p<0.001). CD was detected in 5.6% of patients requiring ≥125mcg/day of levothyroxine. CONCLUSIONS Hypothyroid patients requiring elevated daily doses of levothyroxine are more likely to have CD. Hypothyroid patients requiring ≥125mcg/day of levothyroxine should undergo serologic testing for CD.

Follicular and Hürthle cell lesions of the thyroid: can inconclusive results be minimized?

OBJECTIVE To assess the cytologic criteria for distinguishing neoplastic from nonneoplastic follicular cell and Hürthle cell thyroid lesions. STUDY DESIGN Ten previously described and commonly used cytologic criteria were evaluated and graded on a 0-4 scale in a consecutive series of thyroid fine needle aspirations (FNAs) reported as follicular or Hürthle cell neoplasms or lesions. Scoring was compared to subsequent surgical outcome. RESULTS A total of 93 (57fo llicular cell and 36 Hühle cell) cases was analyzed. No individual cytologic feature was helpful in distinguishing benign neoplarms from malignancy in either category (p > 0.05), but 4 or more coexistent cytologic features in combination were identified in 50.0% of follicular neoplasms, 13.6% of Hürthle cell neoplasms and none of the nonneoplastic lesions. An unexpected number (13 of 93, 14.0%) of unrecognized papillary carcinomas, some of follicular subtype, was encountered. CONCLUSION In this series, the indeterminate thyroid FNA category could have been reduced by diagnosis of samples with 4 or more of the studied criteria as definite follicular (50% of cases) or Hürthle cell (13.6% of cases) neoplasms and by more astute recognition of papillary carcinomas (14.0% of cases), which blend into this category, often as a result of less-than-optimal sampling or preservation.

Su1435 Hypothyroid Patients Requiring Elevated Doses of Levothyroxine to Maintain a Euthyroid State Should Be Tested for Celiac Disease (CD)

BACKGROUND: Celiac disease is an immune-mediated enteropathy that is secondary to gluten ingestion and is classically associated with gastrointestinal symptoms. Some studies suggest that reproductive disorders may be the first symptoms of Celiac disease in otherwise asymptomatic women. Our objective was to determine the prevalence of Celiac disease in women presenting with infertility. STUDY DESIGN: Prospective cohort study. METHODS: We collected data on demographics, screening test results, and diagnosis among women presenting with infertility from March 2012 through March 2013. Women were screened for Celiac disease using serologic testing for antibodies against tissue transglutaminase (IgAtTG). RESULTS: 1112 women presented for an initial infertility evaluation. 20 women had a previous diagnosis of Celiac disease, 20 were on a self-imposed gluten-free diet, and 839 were screened. Seven women screened positive, yielding an incidence of 0.83% among women presenting with infertility to our clinic. Median age and body mass index as well as screening results are reported in Table 1. The prevalence of Celiac disease among women presenting with infertility was 3.1% (95% CI 2.54.5). The prevalence of Celiac disease among women with unexplained infertility was 5.2% (95% CI 3.1-8.5). CONCLUSION: The prevalence of Celiac disease is approximately 3 times higher in women with infertility than the general U.S. population (0.8%); however, routine screening at the time of infertility evaluation is likely not warranted given the low incidence. Table 1. Characteristics and Laboratory Values Median (interquartile range)

Subject Index Vol. 52, 2008

Analytical and Quantitative Cytology and Histology: Volume 29, Number 6 (December 2007), 2008; 52:114–116 Analytical and Quantitative Cytology and Histology: Volume 30, Number 1 (February 2008), 2008;52: 255–258 Analytical and Quantitative Cytology and Histology: Volume 30, Number 2 (April 2008), 2008;52: 373–376 Analytical and Quantitative Cytology and Histology: Volume 30, Number 3 (June 2008), 2008;52:505– 508 Analytical and Quantitative Cytology and Histology: Volume 30, Number 4 (August 2008), 2008;52: 631–634 Analytical and Quantitative Cytology and Histology: Volume 30, Number 5 (October 2008), 2008;52: 736–738 Acid-fast bacilli Role of Modified Bleach Method in Staining of Acid-Fast Bacilli in Lymph Node Aspirates. (Gangane et al), 2008;52:325–328 Adenocarcinoma CK5/6 in Effusions: No Difference Between Mesothelioma and Pulmonary and Nonpulmonary Adenocarcinoma. (Dejmek), 2008;52: 579–583 Cytology of Pseudomyxoma Peritonei Associated with Well-Differentiated Appendiceal Adenocarcinoma. (Siddaraju et al), 2008;52:391–394 (Letter) Diagnosis of Linitis Plastica–Type Gastric Adenocarcinoma by Endoscopic Ultrasound-Guided Fine Needle Aspiration: A Case Report. (Carter et al), 2008;52:725–728 Improved Identification of Malignant Cells in Serous Effusions Using a Small, Robust Panel of Antibodies on Paraffin-Embedded Cell Suspensions. (Grefte et al), 2008;52:35–44 Adenocarcinoma, clear cell Clear Cell Carcinoma in a Background of Endometriosis: Case Report of a Finding in a Midline Abdominal Scar 5 Years After a Total Abdominal Hysterectomy. (Rust et al), 2008;52: 475–480 Adenoma Cytologic Features of Pulmonary Alveolar Adenoma. (González et al), 2008;52:739–740 (Letter) Adenoma, microcytic Preoperative Fine Needle Aspiration Cytology Diagnosis of Microcystic Adenoma of the Pancreas: Fact or Fiction? A Report of 2 Cases. (Fitzhugh et al), 2008;52:240–246 Adenoma, pleomorphic Chondromyxoid Fibroma of the Mandible: A Diagnostic Pitfall on Aspiration Cytology of Parotid. (Daneshbod and Khademi), 2008;52:636–638 (Letter) Fine Needle Aspiration Biopsy of Pleomorphic Adenoma and Adenoid Cystic Carcinoma of the Lacrimal Gland. (Siddaraju et al), 2008;52:515– 517 (Letter) Adenoma, pleomorphic metastazing Pleomorphic Adenoma of the Parotid Gland Metastasizing to the Scapular Region: A Case Report. (Ghosh et al), 2008;52:733–735 Adnexa Cytologic Features of Primary Malignant Tumors of Skin and Adnexae. (Prayaga et al), 2008;52: 702–709 Adolescent Fine Needle Aspiration Cytology of Breast Masses in Children and Adolescents: Experience with 1,404 Aspirates. (Kapila et al), 2008;52:681–686 Adult T-cell leukemia/lymphoma Diagnostic Considerations in Prolymphocytes in Pleural Fluid: A Case Report. (Anand et al), 2008; 52:251–254 Africa Into Africa: Cytology for One World. (Kaminsky), 2008;52:399 Alcian blue Cytology of Pseudomyxoma Peritonei Associated with Well-Differentiated Appendiceal Adenocarcinoma. (Siddaraju et al), 2008;52:391–394 (Letter) Analytical and Quantitative Cytology and Histology

Contributors Index Vol. 52, 2008

Abascal-Agorreta M (see Vera-Alvarez et al). 2008;52: 264–266 (Letter) Abdali K (see Shamsi et al). 2008;52:187–190 Abdul-Karim FW (see Farag et al). 2008;52:294–296 Abnet CC (see Pan et al). 2008;52:14–23 Abraham EK (see Ramadas et al). 2008;52:396–398 (Letter) Adán A (see Saro et al). 2008;52:87–90 Afarid M (see Mostaghni et al). 2008;52:597–601 Aisner S (see Fitzhugh et al). 2008;52:240–246 Akbulut M, Zekioglu O, Kapkac M, Erhan Y, Ozdemir N. Fine Needle Aspiration Cytology of Glycogen-Rich Clear Cell Carcinoma of the Breast: Review of 37 Cases with Histologic Correlation. 2008;52:65–71 Akbulut M, Zekioglu O, Ozdemir N, Kapkac M. Fine Needle Aspiration Cytology of Mammary Carcinoma with Choriocarcinomatous Features: A Report of 2 Cases. 2008;52:99–104 Aktepe F (see Tokyol et al). 2008;52:235–239 Al-Abbadi M (see Vella et al). 2008;52:377–378 (Letter) Al-Abbadi MA (see Feng et al). 2008;52:434–438 Al-Agha OM, Khader SN, Cajigas A, Blank W, Grafstein N, Seymour AW. Fine Needle Aspiration of Urethral Recurrence of Urothelial Carcinoma After Radical Cystectomy Presenting as a Perineal Mass: A Case Report. 2008;52:94–98 Al-Ayadhy B (see Kapila et al). 2008;52:681–686 Al-Mosawy FA (see Kapila et al). 2008;52:681–686 Al-Sebeih K (see Palmieri et al). 2008;52:691–696 Aledavud A (see Daneshbod et al). 2008;52:387–389 (Letter) Ales A (see Terčelj et al). 2008;52:584–590 Almeida JD, Lima CF, Brandão AAH, Cabral LAG. Evaluation of Staining Methods for Cytologic Diagnosis of Oral Lesions. 2008;52:697–701 Altay M (see Demir et al). 2008;52:309–312 Alvarez-Santín C. Endometrial Adenocarcinoma: Prevention and Early Diagnosis. 2008;52:748 (Book Review) Amadori PL (see Bonzanini et al). 2008;52:541–548 Amano S (see Komatsu et al). 2008;52:591–596 Ambaye AB (see Sherman et al). 2008;52:659–664 Anand M, Sharma S, Kumar R, Raina V. Diagnostic Considerations in Prolymphocytes in Pleural Fluid: A Case Report. 2008;52:251–254 Ang L-C (see Keith et al). 2008;52:260–263 (Letter) Angeloni C (see Maccallini et al). 2008;52:568–574 Anshu (see Gabhane et al). 2008;52:354–356 Anshu (see Gangane et al). 2008;52:325–328 Anshu (see Gangane et al). 2008;52:619–622 Antonelli C (see Maccallini et al). 2008;52:568–574 Apice G (see Fulciniti et al). 2008;52:612–618 Arabi MA (see Daneshbod et al). 2008;52:268–270 (Letter) Argüelles M (see González et al). 2008;52:490–494 Armbruster C, Bernhardt K, Setinek U. Pulmonary Tumorlet: A Case Report of a Diagnostic Pitfall in Cytology. 2008;52:223–227 Aron M (see Mathur et al). 2008;52:740–743 (Letter) Arora VK (see Mathur et al). 2008;52:740–743 (Letter) Arundhati (see Garbyal et al). 2008;52:204–206 Arundhati (see Ghosh et al). 2008;52:733–735 Ashfaq R (see Patino et al). 2008;52:718–720 Ashraf MJ (see Azarpira et al). 2008;52:220–222 Ashraf MJ, Azarpira N, Vasei M, Tavakol MH, Khademi B. Thyroid Paraganglioma: Diagnostic Pitfall in Fine Needle Aspiration Biopsy. 2008;52: 745–747 (Letter) Assiri AH (see Mokhtar et al). 2008;52:169–177 Asthana AK (see Ghosh et al). 2008;52:733–735 Athanassiadou P, Grapsa D. Value of Endoscopic Retrograde Cholangiopancreatography–Guided Brushings in Preoperative Assessment of Pancreaticobiliary Strictures: What’s New? 2008;52:24–34 Azarpira N (see Ashraf et al). 2008;52:745–747 (Letter) Azarpira N, Ashraf MJ, Shishegar M. Fine Needle Aspiration Findings in Angiofollicular Hyperplasia with Eosinophilia: A Case Report. 2008;52:220–222