Gender Issues and Related Social Stigma Affecting Patients with a Disorder of Sex Development in India.

Children with disorders of sex development (DSD) manifest at birth with malformed genitalia or later with atypical pubertal development. Those born with malformed genitalia are often diagnosed at birth. However, in resource-poor countries like India, where not all births are supervised by healthcare workers, some of these children remain undiagnosed until puberty or even later. The aim of this study was to assess the gender issues and psychosocial problems of children with DSD. Participants included 205 children with DSD (103 with 46,XX DSD and 102 with 46,XY DSD). Both the children with DSD and their parents underwent semistructured interviews by a clinical psychologist. The birth of a child with DSD was perceived as a major medical and social problem by parents from all socioeconomic strata. Mothers were distressed as many believed the DSD condition was transmitted through the mother. Children who were not diagnosed and treated during infancy or early childhood experienced considerable social discrimination not only from relatives and friends but also from medical and paramedical staff in hospitals. Several patients had been operated during infancy without an etiological diagnosis and without provision of adequate information to the parents. Some children had problems related to complications of surgery. Most teenage patients with 5α-reductase-2 deficiency reared as females presented with gender dysphoria, while children with androgen insensitivity (except for one) or with gonadal dysgenesis developed a gender identity concordant with their gender of rearing. Parents of children with DSD preferred a male gender assignment for their children (if that was possible) because of the social advantages of growing up male in a patriarchal society.

Evaluation of (68)Ga-DOTANOC PET/CT imaging in a large exclusive population of pancreatic neuroendocrine tumors.

PURPOSE: To evaluate the diagnostic accuracy of (68)Ga-DOTANOC PET/CT imaging in a large exclusive population of pancreatic neuroendocrine tumors (NETs). METHODS: Data of 141 (mean age 46.2 ± 15.2 years) patients who underwent 178 (68)Ga-DOTANOC PET/CT studies for diagnosis/staging (n = 88) and restaging (n = 90) of pancreatic NET were retrospectively analyzed. PET/CT results were compared to conventional imaging (CIM) when available (n = 86). Histopathology and/or clinical/imaging follow-up (minimum 6 months) were used as reference standard. RESULTS: The overall sensitivity, specificity, and accuracy of (68)Ga-DOTANOC PET/CT were 85.7%, 79.1%, and 84.8%. The corresponding values were 73%, 50%, and 70.4% for diagnosis/staging groups and 98.6%, 100%, and 98.8% for restaging groups. The accuracy was significantly higher for restaging as compared to diagnosis/staging (P < 0.0001) and in non-insulinoma tumors than insulinomas (P < 0.0001). The SUVmax of primary tumors was significantly higher than metastatic lesions overall (P = 0.001), as well as in diagnosis/staging (P = 0.041) and restaging (P = 0.0003) subgroups. When available, CIM was less specific than (68)Ga-DOTANOC PET/CT (P < 0.001) and showed fewer lesions. CONCLUSIONS: (68)Ga-DOTANOC PET/CT is useful for diagnosis/staging and restaging of patients with pancreatic NET. It demonstrates more lesions compared to CIM and is more specific.

Diagnostic accuracy of (68)Ga-DOTANOC PET/CT imaging in pheochromocytoma.

PURPOSE: The purpose of the present study was to evaluate the diagnostic accuracy of (68)Ga-DOTANOC positron emission tomography (PET)/CT in patients with suspicion of pheochromocytoma. METHODS: Data of 62 patients [age 34.3 ± 16.1 years, 14 with multiple endocrine neoplasia type 2 (MEN2)] with clinical/biochemical suspicion of pheochromocytoma and suspicious adrenal lesion on contrast CT (n = 70), who had undergone (68)Ga-DOTANOC PET/CT, were retrospectively analyzed. PET/CT images were analyzed visually as well as semiquantitatively, with measurement of maximum standardized uptake value (SUVmax), SUVmean, SUVmax/SUVliver, and SUVmean/SUVliver. Results of PET/CT were compared with (131)I-metaiodobenzylguanidine (MIBG) imaging, which was available in 40 patients (45 lesions). Histopathology and/or imaging/clinical/biochemical follow-up (minimum 6 months) was used as reference standard. RESULTS: The sensitivity, specificity, and accuracy of (68)Ga-DOTANOC PET/CT was 90.4, 85, and 88.7%, respectively, on patient-based analysis and 92, 85, and 90%, respectively, on lesion-based analysis. (68)Ga-DOTANOC PET/CT showed 100% accuracy in patients with MEN2 syndrome and malignant pheochromocytoma. On direct comparison, lesion-based accuracy of (68)Ga-DOTANOC PET/CT for pheochromocytoma was significantly higher than (131)I-MIBG imaging (91.1 vs 66.6%, p = 0.035). SUVmax was higher for pheochromocytomas than other adrenal lesions (p = 0.005), MEN2-associated vs sporadic pheochromocytoma (p = 0.012), but no difference was seen between benign vs malignant pheochromocytoma (p = 0.269). CONCLUSION: (68)Ga-DOTANOC PET/CT shows high diagnostic accuracy in patients with suspicion of pheochromocytoma and is superior to (131)I-MIBG imaging for this purpose. Best results of (68)Ga-DOTANOC PET/CT are seen in patients with MEN2-associated and malignant pheochromocytoma.

Comparison of the prognostic values of 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT in patients with well-differentiated neuroendocrine tumor.

PURPOSE: To determine the prognostic value of (68)Ga-DOTANOC PET/CT in patients with well-differentiated neuroendocrine tumor (NET), and to compare the prognostic value with that of (18)F-FDG PET/CT and other conventional clinicopathological prognostic factors. METHODS: Data from 37 consecutive patients (age 46.6 ± 13.5 years, 51% men) with well-differentiated NET who underwent (68)Ga-DOTANOC PET/CT and (18)F-FDG PET/CT were analyzed. All patients underwent a baseline visit with laboratory and radiological examinations. Clinical and imaging follow-up was performed in all patients. Progression-free survival (PFS) was measured from the date of the first PET/CT scan to the first documentation of progression of disease. RESULTS: (68)Ga-DOTANOC PET/CT was positive in 37 of the 37 patients and (18)F-FDG PET/CT was positive in 21. During follow-up 10 patients (27%) showed progression of disease and 27 (73%) showed no progression (24 stable disease, 3 partial response). The median follow-up was 25 months (range 2 - 52 months). Among the variables evaluated none was significantly different between the progressive disease and nonprogressive disease groups, with only SUVmax on (68)Ga-DOTANOC PET/CT being borderline significant (P = 0.073). In the univariate analysis for PFS outcome, SUVmax on (68)Ga-DOTANOC PET/CT (HR 0.122, 95% CI 0.019 - 0.779; P = 0.026) and histopathological tumor grade (HR 4.238, 95% CI 1.058 - 16.976; P = 0.041) were found to be associated with PFS. Other factors including age, sex, primary site, Ki-67 index, TNM stage, (18)F-FDG PET/CT status (positive/negative), SUVmax on (18)F-FDG PET/CT and type of treatment were not significant. In multivariable analysis, only SUVmax on (68)Ga-DOTANOC PET/CT was found to be an independent positive predictor of PFS (HR 0.122, 95% CI 0.019 - 0.779; P = 0.026). CONCLUSION: SUVmax measured on (68)Ga-DOTANOC PET/CT is an independent, positive prognostic factor in patients with well-differentiated NET and is superior to SUVmax on (18)F-FDG PET/CT and conventional clinicopathological factors for predicting PFS.

Morning plasma cortisol is low among obese women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common cause for androgen excess in women. It is associated with wide variety of metabolic disorders. The present study assessed morning plasma cortisol in women with PCOS. One hundred and ninety seven cases and 55 controls were enrolled for this study. The mean age of patients and controls were 23 ± 5.6 years and 25 ± 4.3 years. One hundred twelve (56%) women with PCOS had BMI >25. Serum cortisol levels were significantly higher in lean PCOS women compared to controls (13.4 ± 5.1 versus 11.3 ± 4.5, p < 0.01) and over-weight PCOS women group (13.4 ± 5.1 versus 9.3 ± 3.2, p < 0.01). There was a trend for less acne and hirsutism with increase in BMI. Morning plasma cortisol was lower among obese women with PCOS. Morning plasma cortisol correlated negatively with BMI in PCOS women with normal glucose tolerance.

Prospective evaluation of 68Ga-DOTA-NOC PET-CT in phaeochromocytoma and paraganglioma: preliminary results from a single centre study.

OBJECTIVE: To evaluate the role of (68)Ga-labelled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI(3)-Octreotide ((68)Ga-DOTA-NOC) whole body positron emission tomography-computed tomography (PET-CT) as a functional imaging approach for phaeochromocytoma and paraganglioma. METHODS: Thirty-five unrelated patients (Median age-34.4 years; range: 15-71) were evaluated in this prospective study. PET-CT was performed after injection of 132-222 MBq of (68)Ga-DOTA-NOC. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as quantitatively (standardised uptake value-SUVmax). In addition we compared the findings with (131)I Metaiodobenzylguanidine (MIBG) scintigraphy, which was available for 25 patients. Histopathology and/or conventional imaging with biochemical markers were taken as the reference standard. RESULTS: 44 lesions were detected on (68)Ga-DOTA-NOC PET-CT imaging with an additional detection of 12 lesions not previously known, leading to a change in management of 6 patients. Sensitivity, specificity and accuracy were 100%, 85.7%, and 97.1% on a per patient basis and 100%, 85.7% and 98% on per lesion basis, respectively.(131)I MIBG scintigraphy was concordant with (68)Ga-DOTA-NOC PET-CT in 16 patients and false negative in 9 patients. CONCLUSION: (68)Ga-DOTA-NOC PET-CT is highly sensitive and specific for the detection of phaeochromoctyomas and paragangliomas. It seems better than (131)I MIBG scintigraphy for this purpose. KEY POINTS: • ( 68 ) Ga-DOTA-NOC PET-CT seems useful in patients with phaeochromocytoma and paraganglioma. • This prospective single centre study showed that it has high diagnostic accuracy. • (68) Ga-DOTA-NOC PET-CT seems superior to (131) I-MIBG in these patients.

Effect of metformin and spironolactone therapy on OGTT in patients with polycystic ovarian syndrome - a retrospective analysis.

BACKGROUND: Metformin (an insulin sensitizer) and spironolactone (an antiandrogen) are both used for treatment of polycystic ovary syndrome. We analyzed the effect of 6 months of therapy with these drugs on body weight and glucose tolerance. RESULTS: This was a retrospective analysis of polycystic ovarian syndrome (PCOS) cases on treatment. There were 88 patients with PCOS-42 were on metformin 1 g daily and 46 were taking spironolactone 50-75 mg daily. 21 of 42 had abnormal glucose tolerance (AGT) in the metformin group and 13 of 46 had AGT in the spironolactone group. Patients on metformin reported a greater reduction in body weight, whereas there was no change in body weight with spironolactone therapy (67.6-63.7 versus 59.6-59.2 kg). There was a significant reduction in the 1 and 2 h glucose and insulin levels with metformin therapy in those with AGT. However, fasting glucose increased in those with normal glucose tolerance. There was no change in either body weight or insulin levels with spironolactone. But, there was a significant reduction in both the 0 and 2 h glucose with spironolactone also in those with AGT. CONCLUSION: Spironolactone and metformin had similar effect in reducing the glucose levels in PCOS patients with AGT. PCOS patients with normal glucose tolerance had higher fasting plasma glucose at the end of 6 months of metformin therapy inspite of weight reduction.

Sex of rearing seems to exert a powerful influence on gender identity in the absence of strong hormonal influence: report of two siblings with PAIS assigned different sex of rearing.

There is an ongoing debate regarding the relative contribution of nurture over nature in development of gender identity. Patients with partial androgen insensitivity syndrome (PAIS) have ambiguous genitalia and are known to be reared as male or female. Familial cases of PAIS sharing common hormonal defects are usually reared in the same sex. Here, we describe two siblings with PAIS, one reared as a male and the other as female. These two siblings presented at adolescence. Gender identity was concordant with the sex of rearing for both. The male sibling was distressed with gynecomastia that had disrupted his social life. The sex of rearing seems to have played a predominant role in the formation of gender identity in these two patients with PAIS.

Type 2 diabetes increases risk for obesity among subsequent generations.

BACKGROUND: Childhood obesity is increasing worldwide. Although the prevalence of obesity is low in India, it is being perceived as an emerging problem among affluent urban Indian children. There is little information regarding the profile of obese Indian children. The aim of this study was to assess the clinical profile of children and adolescents attending our hospital (a tertiary-care center) with the main complaint of obesity or overweight. STUDY DESIGN: Children and adolescents attending our pediatric and adolescent endocrine clinic with the main complaint of overweight or obesity were included in this study. All subjects underwent detailed history, physical examination, hemogram liver function tests, oral glucose tolerance test, plasma insulin, and body fat estimation. RESULTS: One hundred nine children (70 boys and 39 girls), ranging in age from 5 to 18 years (mean 13.8 +/- 2.9 years), were enrolled for the study. Twenty boys and 13 girls were overweight, while 50 boys and 26 girls were obese. Twenty-five of these children had hypertension, 48 had dyslipidemia, and 27 had abnormal glucose tolerance. Plasma insulin levels were significantly higher than what is observed in healthy lean controls. The most significant observation was that 75 children had grandparents and/or parents with diabetes mellitus. Possible reasons for this association are discussed. CONCLUSIONS: Children from families with diabetes mellitus are at risk for obesity. Hyperinsulinemia, by its action on the brain, induces behaviors and lifestyles conducive to obesity.

Mother-to-son transmission of a luteinizing hormone receptor activating mutation in a prepubertal child with testotoxicosis.

AIM: To identify the LHR gene mutation in a prepubertal child with testotoxicosis. METHODS: Standard RIA procedure was used for estimating LH, FSH and testosterone levels. Molecular analysis was done by standard PCR using different sets of primers and reaction conditions specific for the LHR gene. Direct sequencing was done using the ABI Prism Dye terminator sequencing kit and the ABI 310 sequencing apparatus. RESULTS: We found a heterozygous mutation of the LHR gene in exon 11 of the second transmembrane region, Met-->Thr at the 398 position (M398T). The same mutation was also found in the proband's mother. CONCLUSION: To our knowledge, this is the first molecular characterization of maternally inherited testotoxicosis in a 5 1/2-year-old boy from the Indian subcontinent.

Comparison of gliclazide with insulin as initial treatment modality in newly diagnosed type 2 diabetes.

AIM: This study was designed to compare effectiveness and remission rate between gliclazide and insulin as initial treatment in newly diagnosed, drug-naive patients with type 2 diabetes. METHODS: Newly diagnosed, drug-naive subjects with type 2 diabetes having mean fasting blood glucose >200 mg/dL were enrolled into either of two groups (gliclazide or insulin). The former received gliclazide modified-release 60 mg daily, while the insulin group received 16 units of premixed insulin as two divided doses along with medical nutrition therapy. Premeal blood glucose was monitored, and the dose was adjusted accordingly. Glycosylated hemoglobin (HbA1c), lipid profile, and postmeal C-peptide were estimated at baseline and 6 months. Remission was defined as euglycemia off drug for a minimum duration of 1 month. RESULTS: Baseline and 6-month blood glucose, HbA1c, and lipid profile were comparable between groups. Blood glucose levels normalized in 2-6 weeks in both groups. At 6 months, one of 30 (3.33%) in the gliclazide group and 24 of 30 (80%) in the insulin group were in remission. Ten of 16 (62.5%) in the insulin group and one of 20 (.5%) in the gliclazide group continued to maintain euglycemia off all pharmacological treatment at 12 months. At 6 months, C-peptide increased in the insulin group (3.21+/-1.61 ng/mL at baseline vs. 5.82+/-2.23 ng/mL at 6 months), while it remained unchanged in the gliclazide group (3.4+/-1.87 ng/mL at baseline vs. 3.82+/-1.78 ng/mL at 6 months) (P=0.0003). CONCLUSIONS: Comparable glycemic control could be achieved with both insulin and oral hypoglycemic agent in newly diagnosed type 2 diabetes subjects. Insulin treatment exceeded gliclazide in the remission (drug-free) rate.

Molecular diagnosis of 5alpha-reductase-2 gene mutation in two Indian families with male pseudohermaphroditism.

AIM: To identify the genotype of two Indians with male pseudohermaphroditism. METHODS: Standard radioimmunoassay procedure was used for estimating hormonal levels. Conventional cytogenetic analysis was carried out for diagnosing the genetic sex in these subjects with genital ambiguity. Molecular analysis was carried out by standard polymerase chain reaction procedure using different sets of primers and reaction conditions specific for the 5alpha-reductase type 2 gene (SRD5A2) gene. Direct sequencing was carried out using the ABI Prism dye terminator sequencing kit and the ABI 310 sequencing apparatus. RESULTS: We found an SRD5A2 gene mutation in exon 5, where arginine is substituted with glutamine (R246Q), in two males with pseudohermaphroditism and ambiguous genitalia from unrelated families. This is the first time this mutation has been reported in individuals from India. CONCLUSION: Identification of the R246Q mutation of the SRD5A2 gene from two unrelated Indian families possibly extends the founder gene effect.

Insulin response to oral glucose in healthy, lean young women and patients with polycystic ovary syndrome.

BACKGROUND AND AIM: Insulin resistance and consequent hyperinsulinemia are common among patients with polycystic ovary syndrome (PCOS). Ethnicity and dietary habits affect insulin levels. There is little published information from India on insulin levels in PCOS patients. Thus the present study aimed to determine the insulin response to oral glucose in women with PCOS and healthy women. METHODS: In a case-control study design, women with PCOS and lean healthy women without a family history of diabetes mellitus underwent oral glucose tolerance testing. Samples were collected at 0, 1 and 2 h after glucose ingestion. RESULTS: Two hundred and eighty-five women with PCOS and 27 lean healthy young women were enrolled into the study. The mean age of controls was 22.8 +/- 4.5 years (range 15-32 years) and their mean body mass index (BMI) was 19.7 +/- 2.6 kg/m(2). Mean blood glucose at 0, 1 and 2 h was 88.2 +/- 7.2, 115.5 +/- 25.5 and 91.8 +/- 20.5 mg/dl, respectively. Corresponding plasma insulin levels were 5.8 +/- 1.1, 32.7 +/- 26.5 and 14.6 +/- 9.6 mIU/l. Peak insulin levels were seen at 1 h and these came down to less than 40% of the peak value by 2 h. Glucose/insulin ratio at 0, 1 and 2 h was 15.6 +/- 3.1, 7.0 +/- 3.1 and 11.4 +/- 7.0. Homeostasis model assessment of insulin resistance (HOMA-IR) was 1.2 +/- 0.2. The age of the PCOS women ranged from 15 to 40 years (mean 23.4 +/- 6.2 years) and their BMI ranged from 16.4 to 50.4 kg/m(2) (mean 27.7 +/- 6.3 kg/m(2)). One hundred and seventy-six (62%) PCOS patients had normal glucose tolerance (NGT), 39 (14%) had impaired fasting glucose (IFG), 49 (17%) had impaired glucose tolerance (IGT) and 21 (7%) had type 2 diabetes mellitus (T2DM). Insulin response was higher in women with PCOS. Peak insulin was observed at 1 h. The difference between 1-h and 2-h post-glucose insulin decreased with worsening glucose tolerance. Both plasma insulin and BMI showed a rising trend from NGT to IFG to IGT. There was no further increase in either insulin or BMI from IGT to T2DM. Glucose/insulin ratio at 0, 1 and 2 h was lower (8.3 +/- 4.2, 2.0 +/- 1.6 and 3.2 +/- 3.5) than that of healthy controls. HOMA-IR was 3.1 +/- 3.0. CONCLUSION: Women with PCOS had an exaggerated insulin response to glucose. Thirty-eight percent of PCOS women had some form of abnormal glucose tolerance. Greater insulin response was seen with impairment of glucose tolerance. Obesity had no effect on fasting insulin or insulin response to oral glucose in PCOS women with NGT.

Fertility among women with classical congenital adrenal hyperplasia: report of seven cases where treatment was started after 9 years of age.

BACKGROUND AND AIM: Androgen excess is believed to be one of the major factors responsible for poor fertility outcomes in females with congenital adrenal hyperplasia (CAH). Some believe that the adverse effect of androgens on fertility could have its origins as early as the antenatal years. To assess the impact of prolonged androgen exposure on fertility in CAH patients, we compiled the data of females with CAH followed in our clinic during the last 25 years who were sexually active and had not been initiated on steroids until age 9 years. STUDY DESIGN AND PATIENTS: This was an observational case study on seven patients with classical CAH who fulfilled the inclusion criteria. The age at initiation of therapy in these females ranged from 9 years to 29 years. RESULTS: All patients had varying degrees of genital ambiguity. The most common presenting complaints were genital ambiguity, non-development of secondary sexual characteristics, hirsutism and primary amenorrhea. Genital surgery was performed in all patients at ages ranging from 12 to 29 years, except for one patient who underwent surgery at age 5 years without a diagnosis of CAH being made. Breast development ensued within 2 to 12 months and periods started in all patients within 2-24 months of steroid initiation. There were 13 pregnancies (seven normal vaginal deliveries, two spontaneous abortions and four pregnancies were medically terminated). CONCLUSIONS: Late initiation of steroid therapy did not affect fertility in our cohort of CAH women. Androgen excess in situations of subnormal cortisol may not adversely affect fertility in females with CAH.

Gender identity of children and young adults with 5alpha-reductase deficiency.

Male pseudohermaphroditism (46,XY DSD) due to 5alpha-reductase deficiency has been recognized for the last few decades. There is scant literature on this entity in India. We compiled data on five patients with this disorder. Four of our five patients were reared as females. Our assessment of these children reveals that they had male gender identity from childhood. Three of the four reared as females chose to change gender role at adolescence, while the fourth is still prepubertal. We conclude that all these patients had male gender identity from early childhood. The parents took note of this only after the appearance of male secondary sexual characteristics at puberty, thereby giving an impression of change in gender identity and gender role.

Insulinoma: reversal of brain magnetic resonance imaging changes following resection.

Insulinoma presents with myriad manifestations and severe neurological deficit may develop due to delay in diagnosis. We report a lady who presented with Glasgow coma scale of E1 M2 V1, which did not improve after correction of hypoglycemia. There was complete reversal of neurological deficit and brain magnetic resonance imaging changes of hypoglycemia on follow-up after resection of pancreatic insulinoma. This is the first report which shows reversal of hypoglycemic changes in MRI after resection of insulinoma. Insulinoma, pre and post surgery provides a model for study of the effect of hypoglycemia and its improvement after euglycemia.

Effect of Different Insulin Response Patterns During Oral Glucose Tolerance Test on Glycemia in Individuals with Normal Glucose Tolerance.

BACKGROUND: Research is still going on for detecting the earliest glucose homeostasis derangements in individuals, which is crucial for the prevention of glucose intolerance. This cross-sectional study analyzes different insulin response patterns during the oral glucose tolerance test (OGTT) and their implications on glycemia in normoglycemic individuals. SUBJECTS AND METHODS: The sample frame was the "Offspring of Individuals with Diabetes Study" database. All participants underwent OGTT. Blood samples were collected at 0, 30, 60, and 120 min for measurement of insulin, C-peptide, and proinsulin levels. Normal glucose tolerant individuals were selected for analysis. RESULTS: Four hundred fifty subjects (mean age, 25 years) were included and divided into two groups according to timing of plasma insulin peaking during OGTT: Group 1, peaking at 30 min; and Group 2, peaking at 60 or 120 min. Body mass index (BMI) and insulin resistance were comparable between the groups; however, Group 2 showed a significantly higher 60- and 120-min glucose level and lower disposition index. Based on the magnitude of the insulin levels, Group 1 was subdivided into Group N (normal pattern) and Group E (exaggerated pattern) with a 30-min insulin cutoff of 74 µU/mL (Group E, ≥74 µU/mL). Group 2 was subdivided into Group DL (delayed and limited pattern; 60-min insulin <73.0 µU/mL and 120-min insulin <80.0 µU/mL) and Group DE (delayed and exaggerated pattern; 60-min insulin ≥73.0 µU/mL or 120-min insulin ≥80.0 µU/mL). Group DE showed a significantly higher area under the curve (AUC) of glucose compared with the other groups and had a lower disposition index and high-density lipoprotein levels. Group DL had significantly lower insulin resistance and BMI compared with Group E but showed a similar AUC of glucose. CONCLUSIONS: A delayed insulin pattern was associated with higher postprandial glucose levels. Individuals with delayed and exaggerated insulin secretion may have a higher risk for glucose intolerance.

Accuracy of 68Ga DOTANOC PET/CT Imaging in Patients With Multiple Endocrine Neoplasia Syndromes.

OBJECTIVE: The aim of this study was to evaluate the role of 68Ga DOTANOC PET/CT imaging in patients with multiple endocrine neoplasia (MEN) syndromes. PATIENTS AND METHODS: Data of 33 patients (age, 33.5 [13.8] years; male 14/female 19) with MEN syndromes (MEN 1, 9; MEN 2A, 19; MEN 2B, 5) who underwent 41 68Ga DOTANOC PET/CT studies were retrospectively analyzed. Twenty PET/CTs were done for staging and 21 for restating. PET/CT images were evaluated in consensus by 2 nuclear medicine physicians, qualitatively and semiquantitatively (SUV(max)). A combination of histopathology, clinical, and biomarker follow-up was taken as reference standard. RESULTS: Of the total 41 68Ga DOTANOC PET/CTs, 34 were interpreted as positive for neuroendocrine tumors (NETs) and 7 as negative. The patientwise sensitivity of PET/CT was 94% (95% confidence interval [CI], 80-99), specificity was 71% (95% CI, 29-96), positive predictive value was 94% (95% CI, 80-99), negative predictive value was 71% (95% CI, 29-96), and accuracy was 90%. A total of 74 disease sites were demonstrated on PET/CT, including 41 primary NETs (pancreas, 10; stomach, 2; pheochromocytoma, 10; medullary thyroid carcinoma, 19), 31 metastatic sites (lymph node, 15; liver, 10; bone, 4; lung, 1; breast, 1), and 2 parathyroid adenomas. Lesionwise sensitivity, positive predictive value, and accuracy of PET/CT were 93%, 96%, and 90% overall, 89%, 95%, and 85% for primary tumors, and 100%, 97%, and 97% for metastasis, respectively. Among primary tumors, the SUV(max) of medullary thyroid carcinoma was significantly lower than gastro pancreatic NETs (P = 0.003) and pheochromocytomas (P = 0.003). No site-specific difference was seen in SUV(max) of metastatic lesions. CONCLUSIONS: 68Ga DOTANOC PET/CT shows high diagnostic accuracy in MEN syndrome and can demonstrate both primary and metastatic NETs in these patients.

68Ga-DOTATOC PET-CT in the localization of source of ectopic ACTH in patients with ectopic ACTH-dependent Cushing's syndrome.

Localization of the source of adrenocorticotrophic hormone (ACTH) in ectopic ACTH-induced Cushing's syndrome is of paramount importance as definitive management mainly involves surgical resection of tumor. Many of these are occult, not identified by conventional structural imaging. Accurate localization and assessment of their functional status has become feasible with the use positron emission tomography-computerized tomography using (68)Ga-DOTATOC (1,4,7,10-tetraazacy-clododecane-NI,NII,NIII,NIIII-tetraacetic acid(D)-Phe1-thy3-octreotide), aiding in proper planning for their definitive management.