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Introduction Beckwith-Wiedemann Syndrome (BWS) is the most common overgrowth syndrome with up to 50% of infants found to have hypoglycemia which has been believed to be related to hyperinsulinemia. However, our case report highlights a patient with the unusual presentation of concurrent BWS and T1DM along with the discussion of genetic factors that may contribute to the pathogenesis. Clinical Case We present the case of a 4-year-old African American female with a past medical history of BWS, twin gestation, prematurity, omphalocele, and patent ductus arteriosus. Her BWS had been diagnosed at birth via genetic testing which found a loss of methylation on the maternal chromosome at imprinting center 2 (IC2) on chromosome 11. During her newborn period, she did not have hypoglycemia. She presented to her primary care physician with a 2.4-kilogram weight loss, new-onset headaches, polyuria, and polydipsia for three months. She also had a viral upper respiratory tract infection a month prior to presentation. Her twin sister did not have similar complaints. Her physical exam including vital signs was reassuring. With the concern for diabetes, further work-up was done which showed an elevated serum glucose level of 681 mg/dL, and hemoglobin A1C of 12.4%. She was admitted for new-onset diabetes. Further labs on admission also showed elevated transglutaminase IgG and positive glutamic acid decarboxylase 65 (GAD65) antibody (level: 444 nmol/L, normal: ≤0.02 nmol/L). Notably, no acidosis was detected in the initial investigations and, unfortunately, due to laboratory error the diabetes antibody panel was cancelled. She was started on a basal-bolus insulin regimen with the diagnosis of new-onset T1DM without ketoacidosis. BWS does not have T1DM as a known characteristic. Hypoglycemia secondary to hyperinsulinemia rather than the opposite, such as our case, is associated with BWS. Due to this, our case is rare, and we found a case report from Europe describing a similar phenomenon. Our patient had a GAD65 antibody being positive which explains having T1DM although there are no studies showing the association of BWS with a positive GAD65 antibody. Our patient also had a viral infection prior to the diagnosis of T1DM which may have triggered autoimmunity. Further, IC2 loss of methylation present in our patient regulates the expression of CDKN1C which has been previously reported to be associated with diabetes. Conclusion Further studies will be required to identify the possible case of T1DM in a patient with BWS. We plan on obtaining a diabetes antibody panel to further assess the genetics of our patient.

Introduction: Majority of children and adolescents diagnosed with Type 1 Diabetes Mellitus (T1D) present with the classic symptoms of polyuria, polydipsia and polyphagia, associated with hyperglycemia. Concurrent conditions at the time of T1D diagnosis may alter its presentation and potentially lead to challenges in diagnosis and management. Clinical Case: We present a 17-year-old male with worsening fatigue and unintentional weight loss for two months, then one week of emesis and abdominal pain. Initial work-up by his primary care provider showed sodium 125 mmol/L (133–145), potassium 5.7 mmol/L (3.5–5.1), HCO3 20 mmol/L (21–31), anion gap 13 mmol/L (9–18), random glucose 141 mg/dL (70–199). Due to hyponatremia and dehydration, he was sent to a local emergency room where he was found to be mildly hypotensive at 87/57 mmHg. He received intravenous fluids for hydration and was sent home. On out-patient follow up, he appeared well despite being hypotensive. His additional labs revealed a random glucose of 330 mg/dl and elevated HbA1C of 8.3% (4.4–5.6). His urine was positive for glucose but negative for ketones. He was admitted for further management of new onset diabetes. On admission, he was well appearing and in no acute distress. Blood pressure was 86/57 mmHg, heart rate was 109 bpm, and other physical exam findings were unremarkable. Although his hyperglycemia improved after initiation of insulin therapy, his electrolyte abnormalities persisted, raising suspicion for adrenal insufficiency. An ACTH stimulation test was performed, with both baseline and 60-minute cortisol levels low at 1 ug/dl and 0.9 ug/dl, respectively, confirming adrenal insufficiency. He responded well to glucocorticoid and mineralocorticoid replacement. His electrolytes and blood pressure normalized. Further testing confirmed elevated levels of Glutamic Acid Decarboxylase antibodies 0.19 nmol/L (less than 0.02), Islet Antigen 2 Antibodies: 3.38 nmol/L (less than 0.02), and 21-Hydroxylase antibodies, consistent with T1D with concomitant Addison’s disease (AD). Conclusion: About 0.5% of patients with T1D have AD, but the diagnosis of T1D typically precedes AD for several years, thus the coexistence of both autoimmune conditions at diagnosis is rare.

Background: Hypercalcemia secondary to primary hyperparathyroidism (PHPT) is less common in children than adults. Single parathyroid adenoma is commonly the cause of primary hyperparathyroidism in children. Clinical Case: We present a 15-year-old female with one-week history of abdominal pain despite taking over the counter antacids. Her initial work up by her primary care provider revealed serum calcium of 11.8 mg/dL (9.0–11.5) and creatinine of 0.8 mg/dL (0.4–1.2). A week later, she presented to the emergency department with same complaint. In ED, she was found to have hypercalcemia (12.8 mg/dl) with elevated parathyroid hormone (PTH) at 78.5 pg/mL (15–65). Her random urine calcium creatinine ratio was high at 2.1. Her 25OHD was 25 ng/mL (30–100). She had negative urine pregnancy test but had trace ketones, leukocyte esterase, blood and bacteria. CBC and CMP were otherwise unremarkable. She continued to complain abdominal pain with nausea, decrease appetite, fatigue, and general muscle weakness. There was no known family history of calcium or metabolic bone disorders. Her vital signs and physical exam were normal. Subsequent labs showed mild improvement of calcium between (11–12.3 mg/dL), PTH between 54.5 and 77 pg/mL, normal thyroid function. Ionized calcium was mildly elevated 6.0 mg/dL (4.5–5.3) but her repeat 25OHD was low at18 ng/mL. Serum phosphorus levels were relatively normal with lowest level of 2.5 mg/dL (2.7–4.5). Gliadin Deamidated IgA was detectable 15 U/mL (< 15.0 U/). Ultrasound of abdomen was significant for nonspecific mild hepatomegaly; kidneys were normal in size and appearance. Ultrasound of thyroid was significant for probably intrathyroid parathyroid, measuring 6 x 8 x 8 mm. Tc-Sestamibi scan did not confirm a parathyroid adenoma. Genetic testing for MEN-1 was negative. FHH- related genes (i.e. CASR) was positive for p.R990G variant resulting in a mild gain of function of the calcium-sensing receptor. Although previous Tc-Sestamibi scan was unremarkable, an over read of it raised a concern for questionable uptake in the left superior lobe. SPEC-CT demonstrated possible abnormal parathyroid tissue in the upper pole of the left thyroid. FNA of the left thyroid nodule confirmed likely intrathyroidal parathyroid adenoma. Subsequent follow up and treatment, including parathyroidectomy, was done by another institution. She underwent a left parathyroidectomy with normalization of serum calcium and PTH levels post operatively (10.1 mg/dl and 8 pg/mL, respectively) and has complete resolution of her previous abdominal and gastrointestinal symptoms. Conclusion: PHPT is uncommon in children and adolescents and is typically associated with a single parathyroid adenoma. High index of suspicion is key for early diagnosis of PHPT despite a negative Tc-Sestamibi initially.

Context: GH deficiency is common in childhood cancer survivors. In a previous report, although we did not find an increase in the risk of disease recurrence in survivors treated with GH, GH-treated survivors did have an increased risk of developing a second neoplasm (SN) (rate ratio, 3.21). Objective: In this analysis, we have reassessed the risk of GH-treated survivors developing an SN after an additional 32 months of follow-up. Design and Setting: We conducted a retrospective cohort multicenter study. Patients: Among a total of 14,108 survivors who were enrolled in the Childhood Cancer Survivor Study, a retrospective cohort of 5-yr survivors of childhood cancer, we identified 361 who were treated with GH. Main Outcome: We assessed the risk of developing an SN. Results: During the extended follow-up, five new SN developed in survivors treated with GH, for a total of 20 SN, all solid tumors. Using a time-dependent Cox model, the rate ratio of GH-treated survivors developing an SN, compared with non-GH-treated survivors, was 2.15 (95% confidence interval, 1.3–3.5; P < 0.002). Meningiomas were the most common SN (n = 9) among the GH-treated group. Conclusion: Although cancer survivors treated with GH appear to have an increased risk of developing SN compared with survivors not so treated, the elevation of risk due to GH use appears to diminish with increasing length of follow-up. Continued surveillance is essential.