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To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years.Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups.A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic.The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.

Two patients with homozygous mutations in PDX1 presented with pancreatic agenesis, chronic diarrhea, and poor weight gain, the causes of which were not identified through routine clinical testing. We aimed to perform a deep analysis of the stomach and intestine using organoids derived from induced pluripotent stem cells from PDX1Gastric fundic, antral, and duodenal organoids were generated using induced pluripotent stem cell lines from a PDX1Patient-derived PDX1These patients will now be monitored for the progression of metaplasia and gastrointestinal complications that might be related to the reduced gastric and intestinal endocrine cells. This study demonstrates the utility of organoids in diagnosing uncovered pathologies.

BACKGROUND Few studies focus on pediatric thyroid nodules categorized under indeterminate diagnostic categories. The current study was conducted to assess the risk of malignancy of indeterminate pediatric thyroid nodules. METHODS A search of the institutional electronic pathology database from 01/2011 to 09/2018 was performed to identify pediatric (

Objective: To evaluate the relationship of six diabetes self-management habits with Hemoglobin A1c (HbA1c) and by race and insurance. Methods: Using the electronic health record (EHR), we incorporated six patient-level diabetes self-management metrics into the clinical workflow for visits. Patients were classified as “performing the habit” if they checked glucose ≥4 times/day or used a continuous glucose monitor; administered ≥3 insulin boluses/day; used an insulin pump; bolused insulin before meals; reviewed data between visits; and changed insulin doses between visits. We then calculated a total habit score. Results: Of 1344 T1D patients seen in 2019, we excluded patients who were new onset (n=57), not on insulin (n=2); missing HbA1c (n=9); or missing documentation (n=64); leaving 1212. HbA1c was significantly lower for those who performed each habit compared with those who did not. For every one-unit increase in total habit score, we found a 0.7% (8 mmol/mol) reduction in HbA1c overall with similar reductions by race and insurance. Conclusions: The six habits are significantly associated with glycemia and will be adopted by T1D Exchange Quality Improvement Collaborative centers to support interventions to improve glycemic outcomes. Disclosure J. M. Lee: Advisory Panel; Self; GoodRx. A. Garrity: None. E. Hirschfeld: None. I. H. Thomas: None. N. Rioles: None. O. Ebekozien: None. S. Corathers: None. Funding T1D Exchange; Brehm Center for Diabetes Research

SummaryTwo patients with mutations in PDX1 presented with pancreatic agenesis, chronic diarrhea and poor weight gain, the causes of which were not identified through routine clinical testing. We generated patient derived organoids as a novel diagnostic strategy and observed that PDX1188delC/188delC antral organoids convert to an intestinal phenotype, while intestinal organoids undergo gastric metaplasia with significant reduction in enteroendocrine cells. This prompted a re-examination of gastric and intestinal biopsies from both PDX1188delC/188delC patients, which recapitulated organoid phenotypes. Antral biopsies had increased parietal cells and lacked G-cells suggesting loss of antral identity. These patients will now be monitored for the progression of metaplasia. This study demonstrates the utility of organoids for patient diagnoses and treatment.

Background: The transition from pediatric to adult care is a high risk time for young adults with diabetes associated with poor glycemic control and psychosocial challenges. However, little is known about how to prospectively identify patients most at risk during transition. Thus, we screened young adults for diabetes distress as part of a multidisciplinary diabetes transition program and identified correlations between distress and patient outcomes. Methods: Diabetes distress was measured during enrollment in the Michigan Medicine Diabetes Transition Program (MMDTP) using the Problem Areas in Diabetes (PAID) questionnaire, a validated diabetes distress screening tool. Patients with high distress were referred to the program social worker. We performed a retrospective chart review on MMDTP participants who were screened from 7/2017 to 12/2018. Results: Fifty-eight young adults (age 17-23 years) completed distress screening, with PAID scores ranging from 0 to 82.5 (median 11.9). 13.8% of patients had high distress (PAID>40). Mean HbA1c prior to transition was 9.7 ± 2.3% and did not correlate with PAID scores nor did distress correlate with insulin pump or continuous glucose monitor use. Among 48 patients >1 year from first adult endocrine visit, those attending at least 3 visits in the first year (n=35) had lower median PAID scores than those attending 2 or fewer visits (10.0 vs. 26.2, p=0.02). Those attending at least 3 visits also had significantly lower mean HbA1c prior to transition (9.0% vs. 12.2%, p Discussion: Here we report the successful implementation of diabetes distress screening for young adults during the transition to adult care. While distress scores were lower than anticipated based on prior studies, we still found 13.8% of our patients had high distress levels. High distress and HbA1c levels at program entry both correlated with reduced visit frequency in the first year post-transition. Future interventions will aim to improve clinic attendance in patients with high distress. Disclosure K. Rodeman: None. A. Rao: None. A. Konigsberg: None. L. Ang: None. I.H. Thomas: None. S. Soleimanpour: None. J.J. Iyengar: None.

Pancreas and gastrointestinal (GI) tract development is guided by several transcription factors, including pancreatic and duodenal homeobox gene-1 (PDX1). While it is well known that PDX1is essential for pancreatic development and beta cell function, its role in GI development and function is not fully understood. We identified a patient with a homozygous point mutation in PDX1 causing total loss of PDX1 protein resulting in pancreatic agenesis. We differentiated induced pluripotent stem cells from the patient into human antral gastric (HAGO) and intestinal (HIO) organoids as a novel diagnostic approach to identify new GI pathologies. Immunofluorescence staining revealed that portions of the PDX1-null HAGOs lost the gastric marker claudin18 and increased intestinal villin1 expression, signifying that regions of the antrum are converting to an intestinal phenotype. Similarly, PDX1-null HIOs lost the intestinal marker cadherin17 and increased claudin18, indicating that regions of the intestine are undergoing gastric metaplasia. Examination of functional markers revealed an increase in acid producing parietal cells, complete lack of gastrin producing endocrine cells in HAGOs, and an increase in gastric surface mucin in HIOs. These in vitro results were further validated using endoscopy biopsies from two patients with PDX1 mutations, which showed a similar disruption in gastric and intestinal identity. CRISPR/Cas9-mediated correction of the PDX1 mutation reversed the observed PDX1-null metaplasic phenotypes in HAGOs and HIOs and also allowed for the successful generation of pancreatic tissue indicating unambiguously that the PDX1 mutation is responsible for these pathologies. Based on these findings, these PDX1-null patients will have additional screening to monitor the progression of metaplasia into gastric and intestinal cancer. This study further demonstrates the utility of organoids in improving patient diagnoses and treatment. Disclosure M. Krishnamurthy: None. T.R. Broda: None. D.O. Kechele: None. X. Zhang: None. J.J. Palermo: None. M.H. Collins: None. I.H. Thomas: None. A. Heider: None. A. Dauber: None. J. Wells: None. Funding American Diabetes Association (1-19-PDF-036 to M.K.)

Most ovarian steroid cell tumors arise sporadically. However, they can also be observed as a rare manifestation of von Hippel Lindau disease. Here, we present a clinical, pathological and molecular characterization of a steroid cell tumor in a VHL patient. A 14 year old girl with molecularly confirmed diagnosis of VHL developed hirsutism and amenorrhea. Initial clinical hormonal evaluation was notable for elevated 17-OHP of 406ng/dl, androstenedione 275ng/dl, and testosterone 102ng/dl. In order to exclude congenital adrenal hyperplasia as a common cause of hirsutism in adolescents, ACTH stimulation was performed, but no increase in 17-OHP was observed. Anti Muellerian hormone, inhibin (INH) A and INH B were normal. Imaging revealed a bilobed 6cm left adnexal mass. The mass was resected en bloc via a left oophorectomy. Pathological evaluation showed multinodular steroid cell tumor with clear cytoplasm and delicate vascular meshwork. Immunoprofiling demonstrated positivity for inhibin and calretinin; while renal cell carcinoma markers were negative. All laboratory values normalized post-surgery. In addition to clinical measurements pre- and post-surgery, steroid profiles were evaluated by LC-MS/MS. Quantitative RT-PCR analysis showed robust tumor expression of enzymes facilitating the production of androgens, but not estrogens. Further preliminary analysis by exome sequencing confirmed the known germline pathogenic variant in VHL, but no additional obvious somatic driver mutations were identified. Interestingly, the NGS analysis of different specimens from the same tumor revealed multiple different single base pair variants in the VHL gene as a second hit. In summary, hirsutism in VHL patients should raise the suspicion for unusual ovarian tumors. In contrary to the usual theory of a monoclonal expansion after loss of the wt VHL allele, this tumor appeared to be oligoclonal as evidenced by different somatic VHL mutations. This could be either explained by initial parallel occurrence of several clones or that the VHL second hit is not an initial event, but the mutation instead supports tumor expansion following initial steps of tumorigenesis.

Importance A low-burden electronic health record (EHR) workflow has been devised to systematize the collection and validation of 6 key diabetes self-management habits: (1) checks glucose at least 4 times/day or uses continuous glucose monitor (CGM); (2) gives at least 3 rapid-acting insulin boluses per day; (3) uses insulin pump; (4) delivers boluses before meals; (5) reviewed glucose data since last clinic visit, and (6) has changed insulin doses since the last clinic visit. Objective To describe the performance of these habits and examine their association with hemoglobin A1c (HbA1c) levels and time in range (TIR). Design, setting, and participants This cross-sectional study included individuals with known type 1 diabetes who were seen in a US pediatric diabetes clinic in 2019. Main outcomes and measures Habit performance, total habit score (sum of 6 habits per person), HbA1c levels, and TIR. Results Of 1344 patients, 1212 (609 [50.2%] males; 66 [5.4%] non-Hispanic Black; 1030 [85.0%] non-Hispanic White; mean [SD] age, 15.5 [4.5] years) were included, of whom 654 (54.0%) were using CGM and had a TIR. Only 105 patients (8.7%) performed all 6 habits. Habit performance was lower among older vs younger patients (age ≥18 years vs ≤12 years: 17 of 411 [4.1%] vs 57 of 330 [17.3%]; P Conclusions and relevance These findings suggest that a focus on increasing adherence to the 6 habits could be critical for improving disparities in glycemic outcomes; these metrics have been adopted by the Type 1 Diabetes Exchange Quality Improvement Collaborative for continuous quality improvement.

Metformin is a widely prescribed medication that has been used to treat children with type 2 diabetes in the United States for the past 15 years. Metformin now has a variety of clinical applications in pediatrics, and its potential clinical uses continue to expand. In addition to reviewing the current understanding of its mechanisms of action including the newly discovered effects on the gastrointestinal tract, we will also discuss current clinical uses in pediatrics, including in type 1 diabetes. Finally, we examine the existing state of monitoring for metformin efficacy and side effects and discuss prospective future clinical uses.

Sex assignment at birth remains one of the most clinically challenging and controversial topics in 46,XY disorders of sexual development (DSD). This is particularly challenging in deficiency of 5-alpha reductase type 2 given that external genitalia are typically undervirilized at birth but most individuals virilize at puberty to a variable degree. Historically, most individuals with 5-alpha reductase deficiency were raised females. However, reports that over half of patients who underwent a virilizing puberty adopted an adult male gender identity have challenged this practice. Consensus guidelines on assignment of sex of rearing at birth are equivocal or favor male assignment in the most virilized cases. While a male sex of rearing assignment may avoid lifelong hormonal therapy and/or allow the potential for fertility, female sex assignment may be more consistent with external anatomy in the most severely undervirilized cases. Herein, we describe five patients with 46,XY DSD due 5-alpha-reductase type 2 deficiency, all with a severe phenotype. An inter-disciplinary DSD medical team at one of two academic centers evaluated each patient. This case series illustrates the complicated decision-making process of assignment of sex of rearing at birth in 5-alpha reductase type 2 deficiency and the challenges that arise when the interests of the child, parental wishes, recommendations of the medical team and state law collide.

Pancreas and gastrointestinal (GI) tract development is guided by several transcription factors, including Pancreatic and duodenal homeobox gene-1 (PDX1). While it is well known that PDX1 is essential for pancreas development, its role in GI development and function in humans has not been investigated. We have identified two patients with a homozygous point mutation in PDX1 (c.188delC(p.P63fs)), causing total loss of protein function. These patients have additional GI complications however endoscopy and histological analysis of gastric and ?intestinal biopsies did not? reveal any pathologies. We used patient derived GI organoids from induced pluripotent stem cells (iPSCs) as a novel diagnostic approach and identified a myriad of undiagnosed GI pathologies. Analyses of human antral gastric organoids (HAGO) using immunofluorescence staining demonstrated a loss of gastric marker? claudin18 (CLDN18) and increased intestinal villin expression in PDX1-null? organoids, signifying that regions of the antrum are converting to an intestinal?phenotype. Similarly, human intestinal organoids (HIO) demonstrated a loss of intestinal marker ?Cadherin17 and an increase in gastric marker? CLDN18, indicating that regions of the intestine are undergoing gastric metaplasia. We also observed an increase in parietal cells in HAGOs, a lack of gastrin hormone in HAGO, and an increase in mucin production in HIOs. Based on this data we re-analyzed antral and duodenal biopsies of both patients and confirmed gastric and intestinal metaplasia increased parietal cells, decreased gastrin and increased mucin production. Because of our findings, these patients will have additional screening to monitor for development of gastric and intestinal cancer. This clearly demonstrates the utility of organoids in improving patient diagnoses and developing new clinical treatment plans. Disclosure M. Krishnamurthy: None. T.R. Broda: None. X. Zhang: None. J.J. Palermo: None. I.H. Thomas: None. A. Heider: None. D.B. Steien: None. A. Dauber: Consultant; Self; Novo Nordisk Inc. Research Support; Self; Novo Nordisk Inc. J. Wells: None. Funding American Diabetes Association (1-19-PDF-036 to M.K.)

Mutations in GATA6, GATA4 and PDX1 cause congenital diabetes and pancreatic hypoplasia (PH) or agenesis. We investigated clinical features and treatment of 10 PH patients through the University of Chicago National Monogenic Diabetes Registry. Data was self-reported or extracted from medical records. Similar to previous cohorts, congenital heart defects, gallbladder agenesis, and exocrine pancreatic insufficiency were often present, whereas features such as recurrent infections and epilepsy have not been reported previously (Figure 1). Weight gain and glycemic control were often poor, yet there were no episodes of DKA over 110 patient-years (Figure 2). Close multi-subspecialty follow-up of these complex patients may improve frequent difficulties with weight gain and highly labile blood sugars. Disclosure A.M. Denson: None. M. Freemark: Research Support; Self; Rhythm Pharmaceuticals, Inc. I.H. Thomas: None. H. Abdullatif: None. J.B. Nogueira: None. R. Benjamin: None. L.R. Letourneau: None. R.N. Naylor: None. S.W. Greeley: None. Funding American Diabetes Association (1-17-JDF-008 to S.A.W.G.); National Institutes of Health (R01DK104942, P30DK020595, UL1TR002389)

Hypocalcemia occurs frequently after a total thyroidectomy in pediatric patients. Four hour postoperative PTH monitoring predicts the need for calcium supplementation in the adult thyroidectomy population. We evaluated the role of the 4 h postoperative PTH level in determining the need for calcium supplementation after thyroidectomy in the pediatric population.This is a retrospective review of children undergoing total thyroidectomy by a single pediatric surgeon from July 2011 through July 2018. Intact PTH obtained four hours postoperatively determined the need for calcium supplementation for patients beginning in November 2014 onward. Serum total calcium levels were monitored concurrently with serum intact PTH levels. Serum calcium levels were followed in our Multispecialty Pediatric Endocrine Surgery clinic within the month following thyroidectomy.From July 2011 through July 2018, there were a total of 56 total thyroidectomies at our institution. Prior to November 2014, all pediatric total thyroidectomies received calcium supplementation per our institutional protocol. Based on ionized calcium levels, 26.3% (5/19) of children developed hypocalcemia. From November 2014 to July 2018, 37 pediatric patients required total thyroidectomies. 29.7% (11/37) had low 4-h postoperative PTH levels. 72.7% (8/11) patients with low 4-h postoperative PTH levels had corresponding postoperative day 1 total calcium levels less than 8.5 or ionized calcium levels less than 1.12, and five children (45.5%) developed symptomatic hypocalcemia. 70% (26/37) of children had normal 4-h postop PTH levels, with only 5 (19%) ever developing hypocalcemia. No patients with a normal postop PTH level developed symptomatic hypocalcemia or required IV calcium repletion. A single 4-h postoperative PTH10 pg/dl for identifying hypocalcemia has a sensitivity of 81% and specificity of 91%, with AUC 0.81.The 4-h postoperative serum PTH level can help determine the need for calcium supplementation in pediatric patients undergoing total thyroidectomy, thereby reducing unnecessary calcium supplementation and serial lab draws to monitor for postoperative hypocalcemia.Level II.

Objective To describe the clinical characteristics, treatment approaches, clinical outcomes, and co-morbidities of youth with type 2 diabetes (T2D) enrolled in the Pediatric Diabetes Consortium (PDC) T2D Registry. Methods PDC enrolled 598 youth

Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount, structure, or processing. The disease is characterized by an increased susceptibility to bony fracture. In addition to the skeletal phenotype, common additional extraskeletal manifestations include blue sclerae, dentinogenesis imperfecta, vascular fragility, and hearing loss. Medical management is focused on minimizing the morbidity of fractures, pain, and bone deformities by maximizing bone health. Along with optimizing Vitamin D status and calcium intake and physical/occupational therapy, individualized surgical treatment may be indicated. Pharmacological therapy with bisphosphonate medications is now routinely utilized for moderate to severe forms and appears to have a good safety profile and bone health benefits. New therapies with other anti-resorptives as well as anabolic agents and transforming growth factor (TGF)β antibodies are in development. Other potential treatment modalities could include gene therapy or mesenchymal cell transplant. In the future, treatment choices will be further individualized in order to reduce disease morbidity and mortality.

Carriers of isodicentric Y (idicY) mosaicism exhibit a wide range of clinical features, including short stature, gonadal abnormalities, and external genital anomalies. However, the phenotypic spectrum for individuals carrying an idicY and a 46, XX cell line is less clearly defined. A more complete description of the phenotype related to idicY is thus essential to guide management related to pubertal development, fertility, and gonadoblastoma risk in mosaic carriers. Findings from the evaluation of twin females with an abnormal karyotype, 48, XX, +idic(Yq) x2/47, XX, +idic(Yq)/46, XX, are presented to highlight the importance of interdisciplinary care in the management of multifaceted disorders of sex development.

To evaluate biomechanical corneal properties in children with osteogenesis imperfecta (OI).A prospective, observational, case-control study was conducted on children 6-19 years of age diagnosed with OI. Patients with OI and healthy control subjects underwent complete ophthalmic examinations. Additional tests included Ocular Response Analyzer (ORA) and ultrasonic pachymetry. Primary outcomes were central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF). Intraocular pressure (IOP) was measured directly by either iCare or Goldmann applanation and indirectly by the ORA (Goldmann-correlated and corneal-compensated IOP). Statistically significant differences between OI and control groups were determined using independent samples t test.A total of 10 of 18 OI cases (mean age, 13 ± 4.37 years; 8 males) and 30 controls (mean age, 12.76 ± 2.62 years; 16 males) were able to complete the corneal biomechanics and pachymetry testing. Children with OI had decreased CH (8.5 ± 1.0 mm Hg vs 11.6 ± 1.2 mm Hg [P 0.001]), CRF (9.0 ± 1.9 mm Hg vs 11.5 ± 1.5 [P 0.001]) and CCT (449.8 ± 30.8 μm vs 568 ± 47.6 μm [P 0.001]) compared to controls. The corneal-compensated IOP was significantly higher in OI cases (18.8 ± 3.1 mm Hg) than in controls (15.0 ± 1.6 mm Hg, P 0.004), but there was no significant difference in Goldmann-correlated IOP (16.3 ± 4.2 mm Hg vs 15.8 ± 2.2 mm Hg).Collagen defects in OI alter corneal structure and biomechanics. Children with OI have decreased CH, CRF, and CCT, resulting in IOPs that are likely higher than measured by tonometry. These corneal alterations are present at a young age in OI. Affected individuals should be routinely screened for glaucoma and corneal pathologies.

Parents of young children with type 1 diabetes (T1DM) maintain full responsibility for their child's daily diabetes self-care and thus may be vulnerable to experiencing parenting stress. This study examined several psychological correlates of pediatric parenting stress in parents of young children with T1DM. Parents of 39 young children with T1DM (ages 2-7 years) completed measures of pediatric parenting stress, mealtime behavior problems, depressive symptoms, and fear of hypoglycemia. For parents of young children, higher stress frequency and difficulty were associated with higher parental depressive symptoms and fear. Regression analyses identified that 58% of the variance in stress frequency was associated with parental depressive symptoms. For stress difficulty, 68% of the variance was associated with parental depressive symptoms and fear. Pediatric parenting stress is common in parents of young children with T1DM. Stress and the psychological correlates measured in this study are amenable to intervention and should be regularly assessed in parents of young children with T1DM.

We studied the genetic and clinical features of diabetic subjects in a five-generation Michigan-Kentucky pedigree ascertained through a proband with pancreatic agenesis and homozygous for the IPF1 mutation Pro63fsx60. Diabetic and nondiabetic family members were genotyped and phenotyped. We also carried out genetic studies to determine the history of the IPF1 mutation in the Michigan-Kentucky family and a Virginia family with the same mutation. We identified 110 individuals. Thirty-four are currently being treated for diabetes and ten of these are Pro63fsX60 carriers (i.e. MODY4). Subjects with MODY as well as those with type 2 diabetes are characterized by obesity and hyperinsulinemia. Genetic studies suggest that the IPF1 mutation was inherited from an ancestor common to both the Michigan-Kentucky and Virginia families. MODY4 and type 2 diabetes in the Michigan-Kentucky pedigree are associated with obesity and hyperinsulinemia. Obesity and hyperinsulinemia have been observed occasionally in other subtypes of MODY suggesting that hyperinsulinemia may be a general phenomenon when obesity occurs in MODY subjects. Hypoinsulinemia in non-obese MODY subjects appears to be due to a functional defect in the beta cell. Genetic testing should be considered in multigenerational obese diabetic subjects, particularly when such families contain young diabetic members.

Permanent neonatal diabetes mellitus is a rare disorder known to be caused by activating mutations in KCNJ11 or ABCC8, inactivating mutations in INS, or very rarely in GCK or insulin promotor factor-1 (IPF-1) genes. We report a patient with permanent neonatal diabetes mellitus and severe exocrine pancreatic insufficiency. Ultrasound examination revealed pancreatic agenesis with a suggestion of a small amount of tissue in the head of the pancreas. Genetic testing revealed that the neonate had a homozygous Pro63fsX60 IPF-1 mutation. This is the second reported case of neonatal diabetes mellitus secondary to a homozygous mutation in the IPF-1 gene and supports the previously proposed biological role of IPF-1 in the pancreatic development in human.

To describe the clinical characteristics, treatment approaches, clinical outcomes, and co-morbidities of youth with type 2 diabetes (T2D) enrolled in the Pediatric Diabetes Consortium (PDC) T2D Registry.PDC enrolled 598 youth21 yr of age with T2D from February 2012 to July 2015 at eight centers. Data were collected from medical records and interviews with participants and/or parents and included glycated hemoglobin (HbA1c), diabetes treatments, prevalence of diabetes comorbidities (hypertension (HTN), dyslipidemia (DL), microalbuminuria (MA), and nonalcoholic fatty liver disease (NAFLD).Insulin use was observed in 45% of those with T2D duration1 yr, 44% for 1-2 yr, 55% for 2-3 yr and 60% for ≥4 yr. Median HbA1c was 6.7% (50 mmol/mol), 8.5% (69 mmol/mol), 9.6% (81 mmol/mol), and 9.7% (82 mmol/mol) in those with disease duration1, 1-2, 2-3 and ≥4 yr, respectively. Only 33 and 11% of those with HTN and DL respectively, were being treated. MA and NAFLD were observed in 5-6% of the participants. Prevalence of HTN was associated with higher BMI (p 0.001), DL with higher HbA1c (p 0.001), and MA with longer diabetes duration (p = 0.001).Frequency of insulin therapy in youth with T2D was associated with increased disease duration and those with longer duration rarely achieve target HbA1c level. This highlights the aggressive course of T2D in youth and adolescents. Additionally, co-morbidities are not being adequately treated. Follow up data from the PDC will provide additional important information about the natural history of T2D and patterns of gaps in treatment.

We describe a 13-year-old male with multiple endocrine neoplasia syndrome type 2B with medullary thyroid carcinoma who was diagnosed with ectopic adrenocorticotropin-dependent Cushing syndrome. This report highlights the importance of monitoring for paraneoplastic syndrome in MEN and clues to the diagnosis of this complication provided by growth patterns.

BACKGROUND. The purpose of the current study was to determine the prevalence of low bone mineral density (BMD) (ie, osteopenia) and identify factors associated with low BMD in young adult survivors of childhood acute lymphoblastic leukemia (ALL). METHODS. Dual energy x-ray absorptiometry was used to evaluate BMD in 74 randomly selected, long-term childhood ALL survivors initially treated in Minneapolis/St. Paul, Minnesota. Growth hormone (GH)-releasing hormone–arginine stimulation testing was conducted to evaluate peak GH level, and insulin-like growth factor I (IGF-I) and other markers of endocrine functioning were also evaluated in relation to BMD. RESULTS. The mean age at the time of interview was 30 years, and the mean time since diagnosis was 24 years. Low BMD (Z-score, ≤−1) was present in 24% of subjects, including 1 with osteoporosis. Low BMD was substantially more prevalent in men than in women and was strongly associated with short height. The mean height Z-score for those with low BMD was −1.44, compared with a height Z-score of −0.39 (P < .01) for those with normal BMD. GH insufficiency, low IGF-I Z-score, and current smoking were also suggestive risk factors for low BMD. CONCLUSIONS. In this long-term follow-up study of childhood ALL survivors, low BMD was found to be more prevalent than expected based on population normative data, specifically in men. The health consequences of early-onset BMD problems in childhood ALL survivors need to be carefully monitored. Cancer 2008. © 2008 American Cancer Society.