bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Case of Preterm Ovarian Hyperstimulation Syndrome Presenting With Vaginal Bleeding
Authors: Rana Pratibha , George Lovya 
Published: May 2021

Abstract
Background: Preterm ovarian hyperstimulation syndrome (POHS) is a rare syndrome described in preterm female infants. This is associated with high serum estradiol and gonadotropin levels, multiple follicular ovarian cysts, and edema of the hypogastric, labial and upper leg regions. This usually occurs at 30 to 39 weeks post-conceptional age (PCA). Vaginal bleeding may or may not be present. We present an unusual case of POHS that had a delayed presentation at 5 months of age (45 weeks PCA) with vaginal bleeding. Case presentation: An extremely premature female infant presented with vaginal bleeding at 5 months of age. Workup revealed pubertal gonadotropins indicating ovarian hyperstimulation. She had mild swelling in the hypogastric region. No breast buds were palpable and there was no clitoromegaly. At the time LH (22.2 mu/ml), FSH (8.3 mu/ml), Estradiol (502.2 pg/mL), and Testosterone (111 ng/dL) were all highly elevated. Multiple ovarian follicles were visualized on her pelvic ultrasound, with generous ovarian dimensions: right ovary (3.6 x 1.6 x 1.9 cm, volume 5.7 cc) and left ovary (2.5 x 2.4 x 1.5 cm, volume 4.7 cc). The largest follicle measured 8.8 mm. The uterus was 3.3 x 1.3 x 1.7 cm, with endometrial stripe thickness of 3 mm. There was no endometrial or adnexal mass. Cosyntropin test showed adequate peak cortisol (32.6 mcg/dL). Her newborn screen had been normal. Serial monitoring of her lab work showed a decrease in her gonadotropin and estradiol levels. She had a recurrence of vaginal bleeding about 3 weeks after initial presentation. By 50 weeks PCA the bleeding had resolved and the LH (1.2 mu/ml), FSH (1.5 mu/ml), estradiol (36 pg/ml) had reduced considerably. Complete normalization of LH (1.2 mu/ml), FSH (1.5 mu/ml), E (36 pg/ml), and testosterone (&lt;7 ng/dl) was demonstrated by 55 weeks PCA. Conclusion: POHS has been attributed to the immaturity of the hypothalamic-pituitary-gonadal axis in preterm infants. Vaginal bleeding has been described in one case [1] several weeks after breast enlargement and swelling of clitoral hood, labia majora, hypogastrium and upper legs. In our case the baby presented with vaginal bleeding at 45 weeks that recurred about 3 weeks later and resolved by 50 weeks, with only minimal swelling. This case underlines the need to be aware of this etiology and its varied presentation. [1] Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report. Altuntas et al. J Pediatr Endocr Met; 273(3-4):355-358.
A Case of Psuedohypoparathyroidism Unmasked by COVID-19 and Rhabdomyolysis
Authors: Chan Jacqueline , Mansuri Asif 
Published: May 2021

Abstract
Background: Psuedohypoparathyroidism type 1 b (PHP 1b) is a rare condition characterized by hormone resistance with PTH. It is caused by imprinting defect of the GNAS gene and is acquired as autosomal dominant. Compared with Pseudohypoparathyroidism type 1a (PHP1a), PHP1b does not have the characteristic physical features know as Albright hereditary osteodystrophy or AHO. Results: 12-year-old female with unremarkable past medical history presented with seizures. She has been complaining of leg pain for a week but on the day of presentation noted to have stiffening and shortness of breath. There was no history of cough, fever, leg trauma, headache, dysuria, hematuria or dark urine. She had no significant family history. Work up revealed severe hypocalcemia of 4.6 mg/ dL and elevated phosphorus (7.1mg/dl). There was no hypoglycemia and other electrolytes including renal function were normal. Patient also had normal inflammatory markers, normal fibrinogen, and normal ferritin. Urine was positive for trace protein and was positive for myoglobin. Alkaline phosphatase was normal. Urine toxicology screen was negative. Hand X-rays did not showed the shortening of metacarpal bones and kidney ultrasound was normal. After IV calcium bolus, calcium barely increased at 5.0. Interestingly CK was noted to be elevated at 3,794 U/L. Patient physical exam was normal and there was no signs of Albright hereditary osteodystrophy (AHO). Patient was positive for COVID19. Patient required intensive fluid therapy to correct CK which increased up to 11,223 U/L on 3rd day of admission. It eventually came down back to normal on the 6th day. Creatinine levels remained normal. Patient continued to receive high dose calcium and calcitriol supplement and discharged with calcium of 8.5 mg/dL and phosphorus of 7.8 mg/dL. Additional work up showed PTH of 885 pg/mL consistent with pseudohypoparathyroidism. Vitamin D levels and thyroid function were normal. Genetic testing for pseudohypoparathyroidism is awaited. Conclusion: Psuedohypoparathyroidism type 1 b (PHP 1b) is a rare endocrine disorder presenting with hypocalcemia, hyperphosphatemia and increased PTH values due to a variable resistance to target organs. As in our case it was unmasked by COVID 19 infection and rhabdomyolysis. Best of our knowledge there is no such unusual case reported in children. Severe hypocalcemia likely due to combination of factors including tissue calcium deposition, hyperphosphatemia, and skeletal resistance to PTH. As published in some recent reports, this case also illustrates that rhabdomyolysis could be potential complication of SARS- CoV2 infection in early stage with normal renal function, which warrants further research.
Continuous Glucose Monitoring Facilitates Diazoxide Use in the Management of Glut1 Deficiency Syndrome
Authors: Logel Santhi N , Connor Ellen L , Hsu David A , Engelstad Kristin M , De Vivo Darryl 
Published: May 2021

Abstract
Background: Glut1 deficiency syndrome (Glut1DS) is caused by mutations in SLC2A1 on chromosome 1p34.2, which impairs transmembrane glucose transport across the blood brain barrier resulting in hypoglycorrhachia and decreased glucose availability for brain metabolism. This causes a drug-resistant, metabolic epilepsy due to energy deficiency. Standard treatment for Glut1DS is the ketogenic diet (KD) but treatment options are limited if patients fail the KD. Diazoxide, which inhibits insulin release, was used sparingly in the past for a few Glut1DS patients to increase blood glucose levels and thus intracerebral glucose levels. Unfortunately, their treatment was complicated by unacceptable persistent hyperglycemia with blood glucoses in the 300s to 500s. We investigated the use of a continuous glucose monitor (CGM) to enable titration of diazoxide therapy in a patient with KD-resistant Glut1DS.
Clinical Case: A 14-year-old girl with Glut1DS (c.398_399delGCinsTT:p.Lys133Phe) failed the KD due to severe nausea, vomiting, abdominal pain, and hypertriglyceridemia. Laboratory tests revealed CSF glucose of 36 mg/dL when blood glucose was 93 mg/dL. Over the course of 3 hospitalizations targeting blood glucose levels in the range of 120-180 mg/dL with diazoxide, EEG seizure activity decreased from 3 to 0 absence seizures per hour. CGM placement during the third hospitalization showed an average interstitial glucose of 157 mg/dL with glucose variability of 20.8% on diazoxide dose of 7.3 mg/kg/day. After discharge, CGM has been used to adjust diazoxide doses 2-4 times a week to achieve target interstitial glucoses of 140-180 mg/dL. Repeat laboratory tests revealed CSF glucose of 55 mg/dL when interstitial glucose was 158 mg/dL. Current diazoxide dose is 7.9 mg/kg/day and most recent hemoglobin A1c was 5.4%.
Conclusions: This is the first report demonstrating CGM as a tool facilitating the safe initiation and real-time titration of diazoxide in Glut1DS patients who have failed the KD. Diazoxide addresses neuroglycopenia more physiologically by raising blood glucose levels and subsequently intracerebral glucose levels. CGM allows for more accurate titration of blood glucose with diazoxide while avoiding complications of hyperglycemia and thus introduces the possibility of diazoxide becoming a standard of care for Glut1DS. More broadly, CGM provides a valuable tool for the management of other disorders of glucose transport and carbohydrate metabolism.
Continuous Glucose Monitoring in the Management of Hypoglycemia in TANGO2
Authors: Esper Brecken S , Carson Mallory , Galvin-Parton Patricia , Lane Andrew H , Tafuri Kimberly S 
Published: May 2021

Abstract
Introduction: The TANGO2 gene encodes a transport and Golgi organization protein of unclear function; mutations should be considered in patients presenting with acute metabolic crisis, hypoglycemic episodes, cardiac arrhythmias, and other endocrinopathies. We report the novel use of a continuous glucose monitor (CGM) to help predict and prevent significant hypoglycemic episodes in a patient with TANGO2 mutation.
Clinical Case: A 14-month old previously healthy, developmentally normal female who presented with unresponsive hypoglycemia (glucose 26 mg/dL) was demonstrated by Next Generation Sequencing to have a pathogenic 31.8 kb deletion of exon 3 to 9 in the TANGO-2 gene and a suspected pathogenic hemizygous c.569_592dup, p.Ile190_Leu197dup in TANGO-2. Her hospital course was notable for MRI showing hypoxic ischemic encephalopathy and both physical and electrical cardiac dysfunction. Continuous intravenous dextrose corrected the hypoglycemia, and transient hyperglycemia followed after several days of a glucose infusion rate between 3.2 to 5.8 mg/kg/min. After transitioning to ad lib oral feeds without restrictions, she was discharged.
A second admission for acute unresponsive hypoglycemia and metabolic acidosis (glucose 30 mg/dL) occurred at 17 months of age with no clear inciting cause. Continuous IV dextrose at 9.9 mg/kg/min corrected the hypoglycemia and again resulted in transient hyperglycemia up to 271 mg/dl. Levothyroxine was also started for a TSH of 27 mIU/mL and a T4 of 4.6 ug/dL. Immediately after discharge, a DexCom G6 CGM was placed. Data over 2 weeks shows an average glucose of 104 ng/dL with 99% of the BS in target range. Parents report that CGM predictive low alerts have allowed intervention to abort fasting-related metabolic crises.
Conclusion: In TANGO-2 deficiency, the liver may not adequately store and/or release glycogen in response to glucagon due to abnormal endoplasmic reticulum, Golgi apparatus, and mitochondrial functioning in states of stress or illness. Recent reports are conflicting with some showing reduced mitochondrial respiration in TANGO-2 patients in steady state with others finding normal values, opening the possibility that a combination of factors in the setting of stress may precipitate a metabolic crisis. Our patient quickly returns to near-normal physiological functioning; consequently, we suggest that use of a CGM can help prevent fasting related metabolic crisis in TANGO2 patients and can help guide feeding schedule and food choices to limit hyper- and hypoglycemia. In addition, CGM data can help further investigate if any beta cell dysregulation exists in non-acute states.
References: Bérat CM, ... & de Lonlay P. (2020). Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises.... J Inherit Metab Dis. 2020 Sep 14. doi: 10.1002/jimd.12314.
Isolated Growth Hormone Deficiency as a Cause of Hypoglycemia Past Infancy
Authors: Thakkar Amruta , Aikaterini Nella 
Published: May 2021

Abstract
Introduction: Hypoglycemia is a common manifestation of Growth Hormone (GH) deficiency in infancy, but is rarely seen beyond 1 year of age. Here, we describe the case of a 5 year 6- month- old child with recurrent episodes of hypoglycemia due to GH deficiency in the setting of malnutrition. Experimental Methods / Case Presentation: Case report and literature review Results: A 5y6m girl with history of atypical teratoid rhabdoid tumor, status-post surgical resection and adjuvant therapy with CNS irradiation (50.4 gray), presented with recurrent hypoglycemia despite continuous G-tube feedings. Child had undergone surgery and irradiation approximately 3 years prior to presentation. She was initially followed at the cancer survivor clinic but had been lost to follow up for 2 years. At presentation, whole blood glucose was 51mg/dL. Height was 93.5cm (-4 SDS) and BMI 10.6 kg/m2 (- 7.75 SDS); she appeared malnourished on exam with minimal subcutaneous fat. She was admitted to the hospital where blood glucoses ranged from 59-68 mg/dL, despite continuous enteral feeds. On evaluation, blood ketones were mildly elevated at 0.67 mmol/L (ref range &lt; 0.3mmol/L), growth factors were low: IGF1 15 ng/mL (ref range 37 - 272 ng/mL); IGF-BP3 1.1 mg/L (ref range 1.1 - 5.2 mg/L), and other pituitary hormones were within normal range [stimulation test cortisol peak 31.9 mcg/dL, TSH 2.4 mIU/mL(Ref range: 0.700 - 4.100 uIU/ML), Free T4 1.2 ng/dL (Ref range 1.0-2.4 ng/dL)]. Hypoglycemia resolved within 48 hours of initiating empiric treatment with GH (0.2mg/kg/week) and patient’s feeds were successfully compressed to 16 hours. Child was discharged home after passing an overnight 8-hour safety fast. Conclusion: Growth hormone deficiency can present as recurrent hypoglycemia outside the infantile period in the setting of malnutrition and needs to be considered in the differential diagnosis and evaluation of childhood hypoglycemia. ​
Maffucci Syndrome, Calcium Homeostasis, and Endocrine Challenges in Management
Authors: Ginnard Olivia Z B , Burrage Lindsay C , Karaviti Lefkothea P 
Published: May 2021

Abstract
Maffucci syndrome is a rare disorder characterized by enchondromatosis and hemangiomata. It can occur due to sporadic, de novo, mosaic pathogenic variants in the gene encoding isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2). IDH1 variants are associated with endocrine manifestations, such as pituitary adenomas. However, literature is limited in describing other clinical features and available treatments in severe phenotypes. We report a pediatric patient with uniquely complex and severe Maffucci syndrome. Case: A 5-year-old boy was evaluated by pediatric endocrinology for chronic hypercalcemia as part of a multidisciplinary evaluation of his severe Maffucci syndrome. Past medical history included prematurity, restrictive lung disease, developmental delay, seizures, 2-OH glutaric aciduria, angiomas, and bicytopenia. Physical exam revealed angiomas, scoliosis, and severe bony deformities throughout the entire skeleton. During admission, laboratory assays revealed normal parathyroid hormone, phosphorus, 1,25-OH2D, and C-telopeptide; elevated serum calcium and PTH-related peptide; and low 25-OHD, alkaline phosphatase, and osteocalcin. Low-dose ACTH stimulation test yielded a peak cortisol level of 16.8. A 24-hour urine study confirmed hypercalciuria. Renal ultrasound demonstrated nephrocalcinosis. Skeletal survey revealed diffuse and chondromatous changes of nearly every bone. Whole-exome sequencing detected a presumed, mosaic de novo IDH1 variant. DEXA scan revealed total body BMD z-score of -3.8. Discussion: Hypercalcemia in Maffucci syndrome is a rare phenomenon. The most likely etiology was due to the severe and chronic bony breakdown from the underlying progressive enchondromatosis. Subsequently, the body attempted to adapt to these chronic processes with abnormal mineral homeostasis, as seen in his laboratory assays. Chronic primary hyperparathyroidism was not likely, as his PTH, phosphorus, and 1,25 OH2D levels were not congruent with that diagnosis. Familial hypocalciuric hypercalcemia was not likely, as his urine calcium clearance ratio was &gt;0.01. Finally, his slightly elevated PTHrP level was not due to PTHrP-mediated hypercalcemia of malignancy, as his bone marrow biopsy was negative. The options for short-term hypercalcemia management had their own inherent risks and were not suitable for long-term management. Although there is a lack of pediatric data to guide therapy in Maffucci syndrome, decision was made to proceed with bisphosphonate infusion given the benefits in the setting of his nephrocalcinosis, chronic hypercalcemia, and results of his DEXA scan. Given the rarity of Maffucci syndrome, few characteristics are well-described in the pediatric population. A multidisciplinary approach is necessary to review the severity of the disease and to determine the best treatment approach based on this information.
Metreleptin and Metformin Use in an Infant With Congenital Generalized Lipodystrophy Secondary to AGPAT2 Mutation
Authors: Schweisberger Cintya , Jacobson Jill Diane , Paprocki Emily 
Published: May 2021

Abstract
Background: Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by widespread loss of subcutaneous fat and severe metabolic abnormalities. Metreleptin, a synthetic analog of leptin, is a treatment modality that has been shown to decrease fasting triglycerides, fasting glucose, and HbA1c. Metformin use in infants has only been described in a few case reports of CGL and Donohue syndrome (insulin receptor mutation), and there is no established dosing for this age group. We report metreleptin, insulin, and metformin use in an infant with type 1 CGL who presented with marked hypertriglyceridemia, hypoleptinemia, hyperglycemia, and transaminitis.
Clinical Case: A 2-month-old African American female born SGA at term presented to her primary care physician for a well child check where she was noted to have poor weight gain, hyperphagia, and abdominal distension. She was subsequently admitted for failure to thrive with weight z-score of -2.17 and length z-score of -0.15. Initial labs were notable for triglycerides of 5,167 mg/dL, HDL 10 mg/dL, blood glucose 324 mg/dL, ALT 212 units/L, AST 215 units/L, and bicarbonate of 17 mmol/L. A random insulin level was elevated at 257 mcIU/mL. Adiponectin was undetectable and leptin was low at 0.3 ng/mL. Hemoglobin A1c was in diabetes mellitus range at 8.9%. She was started on detemir 1.0 units/kg/day on day 1 (titrated to a maximum dose of 4.4 units/kg/day) and metformin 50 mg/kg/day on day 3 of hospitalization. By day 4, triglycerides decreased to 758 mg/dL, AST to 119 units/L and ALT to 124 units/L. Pre-prandial glucoses improved ranging from 113 to 138 mg/dL. As her insurance denied coverage for detemir, she was discharged home on glargine 0.7 units/kg/day and metformin suspension. One month later, she was started on subcutaneous metreleptin, and glargine was discontinued. At 5 months of age, she had triglycerides 229 mg/dl, normal liver enzymes, and normal blood glucoses while on 0.056 mg/kg/day of subcutaneous metreleptin and metformin. Medications were well tolerated without side effects. She had improved growth and met all developmental milestones. Genetic evaluation revealed that she was homozygous for a pathogenic variant, c.589-2A&gt;G; p.Gln196fs*228 (rs116807569), in the AGPAT2 gene.
Conclusion: Leptin is important in regulation of lipid and glucose metabolism, and patients with CGL are deficient due to lack of adipose tissue. Metabolic abnormalities, including stabilization of glucoses and improved hypertriglyceridemia, in our patient markedly improved with initiation of metreleptin, metformin, and insulin. We present successful dosing of these treatment modalities without adverse reactions in an infant with CGL.
Paternalism in DSD Management: A Real and Present Threat
Authors: Moryan-Blanchard Kristen , Karaviti Lefkothea P , Axelrad Marni , Austin Paul , Mann David 
Published: May 2021

Abstract
In 1965, a botched circumcision left Bruce Reimer, a healthy, 8-month old XY male, with a disfigured penis. At the recommendation of Dr. John Money and physicians at Johns Hopkins, the infant was reassigned to female sex and underwent an orchiectomy and vaginoplasty. The family renamed the child “Brenda.” Unaware of her history, Brenda struggled with significant gender identity, psychological, and behavioral issues throughout her childhood and adolescence. When made aware of this history, she transitioned to male gender and assumed the name “David.” After years of psychological distress, David Reimer committed suicide in 2004. Despite the myriad lessons gleaned from this tragic story, medical and surgical management of children with atypical genitalia still remains often misguided, as providers continue to assume paternalistic roles in determining sex assignment and surgical interventions. A fifteen year old XY male with Robinow Syndrome presented for evaluation of hypogonadism and urinary incontinence. At birth, the patient was discovered to have a micropenis and perineal hypospadias and was diagnosed with hypogonadotropic hypogonadism. At the recommendation of the medical team, the infant underwent bilateral orchiectomy at eight months of age followed by urethroplasty and vaginoplasty at six years of age. The child was then given a female sex assignment. At twelve years of age, the child felt discordant from the sex of rearing and wished to be identified as male—his natal, genetic sex. He transitioned to male gender and began testosterone injections. He had history of recurrent UTIs and severe incontinence requiring diaper use. He strongly desired neophallus and urethral reconstruction for improved quality of life. The patient endorsed prior depression and desires to self-harm. He had significant concerns regarding his gender presentation and transition. He shared his difficulties in continuing in the same school system with peers who knew him as a female prior to transition and was concerned about peers knowing his medical history. In the years since the famous David Reimer case, the medical system has made tremendous strides in recognizing the need for patient autonomy and shared decision-making in patients with Differences of Sex Development and genital atypia. However, the paternalistic history of this field continues to leave its indelible mark more than 20 years since David Reimer’s case made headlines, as physicians continue to recommend definitive sex assignments and surgical interventions. As with the David Reimer case, the bodily integrity of this XY infant was altered in a permanent fashion with inadequate education of his family and little to no credence given to the autonomy of the child himself. We, as physicians, cannot continue to paternalistically apply John Money’s concept of gender neutrality and rigidly mandate sex assignments and early surgical interventions.