ResearchPad - pediatric-endocrine-case-reports-ii Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[MON-072 A 2 -Year Old Girl with Turner Syndrome and Neurofibromatosis Type 1]]> Introduction: Turner syndrome (TS) occurs due to loss of either all or part of the X chromosome, in some or all the cells of the body. The most consistent features of TS are short stature and premature ovarian failure. Neurofibromatosis type 1 (NF1) is an inheritable in an autosomal dominant manner tumor predisposition syndrome and is caused by loss-of-function mutations in the tumor suppressor NF1 gene (neurofibromin 1). Literature review indicated rare cases with NF1 and TS (1). We report the sixth girl with mosaic TS and NF1 who presented with optic nerve glioma.

Case report: A 2-year-old female presented to us due to short stature. Her height was 2,5 SD lower than the mean parental height curve, and her bone age was delayed only by 3 months. She already had a normal (46XX) peripheral blood karyotype (70 mitoses). She had abnormal body proportions and with short limbs with unremarkable café au lait spots. Additionally, to the short stature laboratory investigation we ordered a gene panel to exclude hypochondroplasia, and a Karyotype in fibroblasts culture from oral cavity sample. The results revealed low IGF-1 and mosaic TS in 14%. We preformed 2 provocative tests which revealed low growth hormone peak < 5 ng/ml. A brain and pituitary MRI to exclude pituitary lesions or structural abnormalities revealed gliomas of the optic chiasma and the right optic nerve with characteristic NF1 “spots” (regions of signal abnormality in T2 sequences) involving the basal ganglia, cerebellum and the right temporal lobe. DNA sequencing targeted to a gene panel related to NF1 and NF2 revealed a novel de novo heterozygous NF1 gene mutation in exon 28 [3764Α>G];[=]p.[Gln1255Arg].

Discussion: NF1- Gliomas are most commonly seen in young children, (mean 4.5 years). Only 1/3 of affected children will require therapeutic intervention. However early diagnosis, of optic gliomas is important. Our patient was completely asymptomatic by the time of diagnosis and no other symptom or sign of NF1 was apparent. Ophthalmologic examination was normal, but visual electrophysiologic testing was abnormal as far the right optic nerve is concerned. The oncology team decided to preform chemotherapy. In TS impaired growth is related to resistance in GH. Some studies suggested that there could be a relationship between GHD and NF1 even in the absence of an organic pituitary damage. In our patient it has been decided not to treat with GH and closely track the patient’s growth.

Conclusion: Coexistence of NF1 with TS is rare. Awareness is needed as early identification and treatment of CNS gliomas can prevent visual loss and severe co-morbidities.


Rare Presentation of Neurofibromatosis and Turner Syndrome in a Pediatric Patient. Pediatr Rep. 2017 Jun 26; 9(2): 6810

<![CDATA[MON-LB011 Retrospective Comparison of Cystic Fibrosis Related Diabetes Pediatric Screening Rates]]> Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in those with CF, affecting 20% of adolescents and 40-50% of adults with CF. If uncontrolled, it can cause worsened pulmonary outcomes, increased hospital length of stay, and increased mortality. It is typically clinically silent, and hemoglobin A1C and fasting plasma glucose are not sensitive enough to diagnose it. Per national guidelines, the proper outpatient screening method is oral glucose tolerance test (OGTT), annually beginning age 10. Inpatient diagnosis involves fasting glucose >126 mg/dl or 2 hour postprandial glucose >200 persisting for more than 48 hours. It is believed that national screening guidelines are unfortunately not being met, particularly while inpatient. At our institution, there are 137 pediatric patients with CF; of those, 8 have a diagnosis of CFRD, and 4 have impaired glucose tolerance.

We aim to study the adherence of our institution to the best practice guidelines for CFRD screening in pediatric patients with Cystic Fibrosis.

Retrospective chart review is occurring through our institution’s EMR for inpatient data, and through a CF database (PortCF) for outpatient data. Inclusion criteria includes pediatric patients (below 1 day or above 17 years and 364 days) with CF. Exclusion criteria is those outside this age range, and those with CFRD. Consent is waived, as this is a retrospective data collection. Several variables including demographics, glycemic status, CFTR modulator and class, corticosteroid and vitamin use, and feeding regimen are also being reviewed. REDCap is being used for secure data entry and analysis. Descriptive statistical analysis will be used. Categorical data will be expressed as frequency (percent). Numeric data will be expressed as mean ± standard deviation or median [25th, 75th percentile], depending on normality of the data. Univariate analysis, like Chi square or Fisher’s exact test, will be used between successful and unsuccessful inpatient screens for CFRD.

Thus far, retrospective chart review of all outpatient data is complete. Preliminary analysis of those who should have received OGTT screening shows 11% have never been screened, and 32% were screened more than one year ago. Completion of inpatient data collection and all statistical analysis is anticipated within the next month. Future direction includes increasing inpatient CFRD screening with use of continuous glucose monitoring sensors during CF exacerbation admissions.

<![CDATA[MON-061 A Case of Central Precocious Puberty Patient with Arnold Chiari Malformation, Type I]]> Central precocious puberty (CPP) is caused by early activation of Hypothalamo-Hypophyseal-Gonal (H-P-G) axis. Although the cause of CPP is idiopathic in most cases, small portions of CPP are caused by intracranial lesion such as hypothalamic hamartomas, postencephalitic scars, tubercular meningitis, head trauma, hydrocephalus, tuberous sclerosis, arachnoid cyst, etc. Type I Chiari malformation is a disorder characterized by a displacement of the cerebellar tonsils through the foramen magnum into the upper cervical spinal canal with various neurologic symptom. There have been some reported cases of Arnold-Chiari type I malformations with CPP, however this association is not yet completely understood. We would like to introduce a case of girl experiencing Arnold Chiari type I malformation as well as CPP, who presented with progressive breast budding and acceleration of growth. A 8-year-old girl was presented with 6month history of breast budding and acceleration of growth (5cm/7month). Her family history demonstrated that her mother had been treated with prolactinoma and experienced early menarche. On physical examination, she showed Tanner stage 2(B2, P1). She did not exhibit any neurological signs or symptoms. Thyroid gland was not enlarged and No abnormal skin pigmentation or bony abnormalities were identified. Her height was 124.9cm (37th percentile), weight was 22.4kg (14th percentile), while midparental height was calculated to be 159cm (father: 174cm, mother: 157cm). Her bone age was assessed to be 10 years of age. Luteinizing hormone(LH) showed pubertal response (peak LH: 9.9IU/L) in Luteinizing Hormone Releasing Hormone (LHRH) stimulation test. The abdominopelvic US revealed pubertal response of uterus(length 4.1cm, endometrial echogenicity) without any other abnormality. We performed brain Magnetic Resonance Imaging(MRI) for rule out intracranial lesion, which showed Arnold-Chiari type 1 malformation (downward displacement of the cerebellar tonsil by 6 mm). Following diagnosis, Her parents wanted further neurologic evaluation and treatment in Canada, beacause she was Canadian. In conclusion, Arnold-Chiari type 1 malformation can be a possible cause of CPP without neurological symptoms in children, more cases are needed to clarify the relationship and evaluate reasonable causes of Arnold-Chiari type 1 malformation in the brain, especially in young patients with precocious puberty.

<![CDATA[MON-068 The First Case in Korea, ZC4H2 Gene Mutation in Wieacker-Wolff Syndrome with Recurrent Hypoglycemia]]> Wieacker-Wolff syndrome was first described in 1985 and is a rare congenital syndrome cause by ZC4H2 mutation. It is a X-linked recessive disorder characterized by congenital contracture of the feet, mental retardation, progressive neurologic muscular atrophy, scoliosis, and hypoglycemia. 9-years-old boy with brain atrophy, mental retardation, scoliosis, convulsion and exotropia visited our clinic with recurrent hypoglycemia. Hypoglycemia was developed since infant. Physical examination showed dysmorphism and no hepatomegaly. In the ‘critical sample’, ketoacidosis was present and serum levels of free fatty acid was elevated. Lactate was in the normal range. Hyperinsulinism was excluded with ‘critical sample’ and glucagon stimulation test. Combined pituitary stimulation showed no deficiency of growth hormone and cortisol, respectively. Fatty acid oxidation was excluded by serum levels of acylcarnitines and urine organic acid test. Due to the presence of multiple anomaly and under the suspicion of glycogen storage type 0, whole exome sequencing was performed and p.P154T mutation on the ZC4H2 was observed. Although Sanger sequencing is in processing yet, clinical features are very similar compare to previous cases. In summary, we reported a first Korean male with a novel ZC4H2 mutation, P154T.

<![CDATA[MON-076 Adrenal Hypoplasia Congenita - Is It Possible to Make This Diagnose in Previous “Idiopathic” Adrenal Insufficient Patients? Series of Cases]]> Background: Adrenal hypoplasia congenita (AHC) is a rare disease (1:70.000 men) characterized by reduction in all cortical adrenal hormones and also by hypogonadism. NR0B1 -related AHC includes both X-linked AHC and Xp21 deletion. AHC gene mutation was first described in 1994 and occurs in less than 1% of adrenal insufficiency (AI) cases and it is imperative that clinical endocrinologists increase their knowledge on this condition to recognize it as promptly as they were used to do so in other causes of pediatric AI.Clinical Cases: We describe here two sporadic cases and three familial cases from one family, all of them attending at our Endocrine Unit at HCPA, in the South of Brazil. The median age of AI first symptoms was 1 month old in two patients (acute infantile onset due to a salt wasting crises), and eleven years old in the remaining patients (childhood onset). Their exams confirmed the clinical suspicion of primary AI because of low plasma cortisol (from < 0.5 to 4 mcg/dl - reference range from 7-24 mcg/dl), as well as all adrenal steroids levels, high ACTH levels (from 672 to 2225 pg/ml - reference range from 7-63 pg/ml) and high plasmatic renin (from 92 to 448 mcUI/ml - reference range from 2.8-39.9 mcUI/ml). They were also extensively investigated searching for the AI pathophysiology. After some years of lost follow-up, one of the familial cases that had first been seen in 1993, returned to our hospital and was diagnosed with hypogonadism, leading to NR5OB1 gene evaluation.Regarding the genetic etiology, one of the sporadic cases developed a clinical picture including profound developmental delay, seizures and strabismus suggestive of a contiguous gene syndrome that involves Duchenne muscular dystrophy, glycerol kinase deficiency and AHC. A CGH array was performed and identified a Xp21.3-p21.1 deletion. The affected family had an extensive history suggestive of a genetic disease with X-linked inheritance pattern, as shown by the premature death of 3 uncles and a male cousin. A deleterious variant (c.131_212delinsTGAGACCTGTACCGT) in NR5OB1 gene was identified by Sanger sequencing in hemizygous state in the 46,XY affected patients.Conclusion: Albeit a rare disease, it is crucial that endocrinologist all around the World could be aware about clinical characteristics of this condition in order to properly diagnose it. And it is even possible, as it occurred with one of our patient, to make a late pathophysiologic diagnosis, making possible to treat the associated hypogonadism. Reference: Acherman JC, Vilain EJ. NR0B1- related adrenal hypoplasia congenita. GeneReviews 1993-2019.

<![CDATA[MON-064 Persistent Progressive Clitoromegaly Is Not Always Hormonal: When One Disease Fits All]]> Introduction: Clitoromegaly presenting in childhood can be congenital or acquired. The most common cause is exposure to excess androgens in fetal or neonatal life. However, non-hormonal causes like neurofibromatosis type 1 (NF-1), epidermoid cysts, tumor syndromes have been reported. An asymmetric or irregular appearing clitoris is usually caused by a non-hormonal process.

Clinical Case: A 6-year-old female with NF-1 and right-sided hemihypertrophy was referred to endocrinology due to progressive clitoromegaly since birth. NF-1 features included café-au-lait spots, bilateral optic nerve gliomas, plexiform neurofibroma, Lisch nodule, first degree relatives with NF-1 (sister and mother). At age 1.5, a hormonal work up was negative for hyperandrogenism. At age 2, patient was seen by genetics, and by urology for removal of a bladder neurofibroma, but did not return to these specialties for follow up. Lumbar spine MRI, obtained for back pain, revealed a large sciatic plexiform neurofibroma. She followed with oncology for cancer surveillance and due to parental concern for progressive clitoromegaly was referred to endocrinology at age 6. At the endocrinology visit, parents denied breast development, vaginal discharge or bleeding, axillary or pubic hair, body odor or acne. Her genital exam revealed a clitoris 3 x 1.5 cm in size, Tanner 1 pubic hair, no palpable gonads, no labial fusion but asymmetric labial sizes (right>left). A hormonal workup was normal including 41 ng/dL 17-hydroxyprogesterone (n ≤137 ng/dL), 20 ng/dL androstenedione (n ≤ 45 ng/dl), 42 ng/dL unconjugated DHEA (n ≤ 487 ng/dL), 11 mcg/dL DHEA Sulfate (n ≤ 34 mcg/dL), 3 ng/dL total testosterone (n ≤ 21 ng/dL) and pre-pubertal LH, FSH and estradiol levels. Patient was referred to a multi-disciplinary DSD (Disorders of Sexual Differentiation) clinic for further evaluation and potential surgical options. A pelvic ultrasound and subsequent pelvic MRI revealed that the large sciatic plexiform neurofibroma, detected on the prior MRI, had now extended into the clitoris and right labia. Uterus and ovaries were pre-pubertal in size. Surgical options were discussed in a multi-disciplinary approach. Since clitoral enlargement was contiguous with posterior bladder mass and vital organ functions were not affected, resection was not recommended. Clitoral reduction for cosmetic reasons had a potential risk of recurrence. Since benefits did not outweigh the risks, family chose to not pursue any surgical intervention.

Conclusions: NF-1 is a rare but potential non-hormonal cause of clitoromegaly. In the absence of clinical evidence of hyperandrogenism, clitoromegaly in a patient with NF-1 does not warrant an extensive hormonal work up. Pelvic imaging should be pursued first, to search for local neurofibromas. Decision for surgical interventions requires a multi-disciplinary approach with detailed discussion of benefits vs. risks.

<![CDATA[MON-066 17B-hydroxysteroid dehydrogenase Type 3 Deficiency: An Under-Recognized Cause of 46,XY DSD in the United States?]]> Title: 17β-hydroxysteroid dehydrogenase type 3 deficiency: An under-recognized cause of 46,XY DSD in the United States?

Introduction: The 17β-hydroxysteroid dehydrogenase type 3 (17BHSD3) enzyme, expressed in the testes, converts androstenedione (A) to testosterone (T). 17BHSD3 deficiency causes a 46,XY difference of sex development (DSD), or intersex condition, characterized by lack of prenatal virilization followed by marked virilization at puberty due to peripheral conversation of A to T by other 17BHSD isoenzymes. Diagnosis is suspected with an abnormal T:A ratio of <0.8 and confirmed by HSD17B3 sequencing and deletion/duplication analysis. 17BHSD3 deficiency may present similarly to complete or partial androgen insensitivity syndrome (CAIS, PAIS) due to undervirilization in infancy, and to 5α-reductase deficiency due to virilization during puberty. Previously, only 12 cases of this autosomal recessive disorder have been reported in the US. We report 3 cases of 17BHSD3 deficiency diagnosed at a single pediatric center in the US.

Clinical Cases: Patient A had atypical genitalia at birth and a presumed diagnosis of PAIS though sequencing of AR was normal. He underwent multiple genital surgeries throughout childhood, had significant psychiatric and behavioral concerns, and was referred to our multidisciplinary clinic at age 16 years. Additional diagnostic testing revealed a T:A ratio of 0.29 consistent with 17BHSD3 deficiency; confirmatory genetic testing was deferred per family preference.

Patient B was noted to have testicular tissue present at age 3 years during an inguinal hernia repair and was diagnosed with CAIS. She presented to our institution at age 14 years with clitoromegaly. T:A ratio was 0.29 and genetic testing revealed a pathogenic splice site variant in HSD17B3. She requested gonadectomy due to unwanted virilization inconsistent with her female gender identity. Following gonadectomy at age 16 years, she began estrogen treatment and vaginal dilations.

Patient C presented to our institution at age 18 years with pubertal delay and primary amenorrhea. She was noted to have palpable gonads and clitoromegaly. Evaluation revealed a 46,XY karyotype and a T:A ratio of 0.32. She was raised as a girl and identified as female. She requested gonadectomy to avoid further virilization, after which she began estrogen for pubertal induction. She deferred confirmatory genetic testing.

Conclusions: Previous studies noted 17BHSD3 deficiency to be rare in the US, but the presence of 2 suspected and 1 confirmed diagnoses at a single US institution suggests it is likely more common and may be misdiagnosed as other types of DSD. Differentiating 17BHSD3 deficiency from other causes of 46,XY DSD is essential to inform accurate counseling about sex designation, gender identity, gonadal function, malignancy risk, potential fertility and heritability.

<![CDATA[MON-074 Ketotic Hypercalcemia; A Possible Side Effect of Managing Refractory Epilepsy with Ketogenic Diet]]> Background: Patients with epilepsy have multiple risk factors for low bone mass, including immobility, reduced muscle mass, and use of multiple anticonvulsant medications. The ketogenic diet (KD) has been used as an effective treatment of refractory epilepsy for decades, with multiple reports in medical literature describing adverse effects on bone and mineral metabolism including gradual loss of bone mineral density. There has been only one report of hypercalcemia in three children on the KD for refractory seizures. We now describe another case, highlighting the importance of considering the KD as a cause of hypercalcemia.. Case presentation: A 14-year-old girl with Rett syndrome, epilepsy, global developmental delay and gastrostomy tube dependency presented to the emergency room with marked dehydration. She had been on the KD for several years due to refractory epilepsy. Her parents had recently noticed thick oral secretions. The only change in her management plan was the recent change of her formula from Ketocal 3:1 to Ketocal 2.5:1. Lab studies showed hypercalcemia 15 mg/dL (ref 9.2-10.7) with ionized calcium of 7.99 mg/dL (ref, 4.8-5.2). She had normal serum calcium levels on multiple previous occasions, including 10.2 mg/dL 4 months prior to presentation. Other studies included increased BUN 37 mg/dL (ref, 7-21) and Creatinine 2.31 mg/dL (ref, 0.53-0.8). She had a low normal PTH 14 pg/ml (ref, 8-72), PTH-related peptide 0.6 pmol/l (ref, < 4.2), and 25-hydroxyvitamin D 66 ng/ml (30-100). 1,25-dihydroxyvitamin D level was low at 12.5 pg/ml (ref, 19.9-79.3), with increased urine calcium/creatinine ratio 1.00 mg/mg creat (Ref, 0.02-0.26). Beta Hydroxybutyrate was 3.45 mmol/l (ref, 0.02 - 0.27), without major change over the last year. Renal US was normal. She received IV hydration with improvement in serum calcium, BUN, and creatinine and was discharged on increased intake of free water and adjustment of KD to maintain Beta Hydroxybutyrate around 2 mmol/l. Her serum calcium currently ranges 10.5- 12 mg/dl, and will soon begin therapy with subcutaneous calcitonin. Conclusion: The KD has adverse effects on bone and mineral metabolism, and can lead to severe hypercalcemia and/or hypercalciuria as well as decreased bone density. Agents that decrease bone resorption are highly effective. Providers caring for children on this diet should be aware of such potential association. Reference: Hawkes CP, Levine MA. Ketotic hypercalcemia: a case series and description of a novel entity.J Clin Endocrinol Metab. 2014 May;99(5):1531-6.

<![CDATA[MON-080 Unusual Association Between Congenital Hyperinsulinism and Neurofibromatosis Type 1]]> Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant multisystemic disorder characterized by an increased risk of benign and malignant tumor formation affecting skin, bone and nervous system. In children with NF1, endocrine manifestations include central precocious puberty, growth hormone deficiency and growth hormone hypersecretion, resulting from complications of optic pathway gliomas involving the hypothalamic and sellar region. A few reports of adults with NF1 have been described to have hypoglycemia due to insulinoma. However, hypoglycemia due to hyperinsulinism has not been described in children with NF1. We present a case of NF1 diagnosed during neonatal period associated with congenital hyperinsulinism.

Case: Patient was delivered at 36 weeks by C- section with birthweight of 2780 grams which was appropriate for her gestational age. There was no maternal history of diabetes. Pertinent exam findings included microcephaly and multiple café-au-lait spots. She developed hypoglycemia at DOL1 with blood glucose of 26 mg/dl which normalized with IV dextrose at a glucose infusion rate of 6 mg/kg/min. At DOL8, an attempt to wean IV dextrose failed and she developed hypoglycemia with blood glucose of 47 mg/dl. Critical sample showed insulin level 3.3 uU/ml, betahydroxybutyrate 0.08 mg/dl (0.2-2.8), cortisol 18.1 mcg/dL and GH 13.2 ng/mL. A glucagon stimulation test showed an increase in glucose of 30 mg/dl. She was diagnosed with hyperinsulinism and started on Diazoxide (8 mg/kg/day) with improvement of blood glucose with prefeed glucose of > 70 mg/dl. She had normal 8- hour fasting tolerance with all BG > 70 while on Diazoxide. Genetic test for known mutations causing hyperinsulinism was negative. Microarray confirmed a 1.42Mb interstitial deletion at chromosome 17q11.2 which encompasses NF1 gene confirming the diagnosis of NF1. Additionally, she has an Xp22.33 duplication of uncertain clinical significance.

Conclusion: Our patient presented with an unusual association between congenital hyperinsulinism and NF1. Further testing needs to be performed to determine whether this association is coincidental or whether congenital hyperinsulinism is a rare manifestation of NF1.

<![CDATA[MON-058 Precocious Puberty and Hypothyroidism in a Pediatric Case]]> Background: Hypothyroidism with secondary sellar/suprasellar mass is rarely associated with precocious puberty. Here we describe a rare case of pediatric hyperprolactinemia and precocious puberty secondary to hypothyroidism, marked TSH elevation, and pituitary hyperplasia.

Clinical Case: A 9-year-old female, with onset of thelarche and menses occurring at age 7 and 8 respectively, presented with primary hypothyroidism (Free T4 <0.11; n=4.9-11.4mcg/mL), elevated TSH (1620.0mU/mL; n=0.3-4.7mU/mL), hyperprolactinemia (108.6ng/mL; n=3.0-23.1ng/mL), and elevated serum estradiol (37.6pg/mL; n=10pg/mL). The patient had coarse scaly skin, diminished energy, and poor growth lasting 1 year. There were no associated gastrointestinal issues, temperature intolerance, nor visual impairments noted during this time.

Magnetic resonance imaging revealed a large mass (1.48cm) with suprasellar extension and a mass effect on the optic chiasm. The patient was then started on Levothyroxine and Cabergoline, to reduce serum prolactin levels. However, upon follow-up two months later, the patient had hypoprolactinemia (2.0ng/mL; n=3.0-23.1ng/mL). The patient was referred to neurosurgery for resection of the sellar mass. Endocrinology was also consulted, at which point Cabergoline was discontinued and Levothyroxine was gradually increased.

Follow up 4 months later showed prolactin levels had normalized to 11.4ng/mL (3.0-23.1ng/mL). Serum LH and FSH were within normal ranges (1.2mIU/mL and 4.2mIU/mL, respectively). TSH, though still elevated (47.35mU/mL; n=0.3-4.7mU/mL), was significantly reduced compared to the prior measurement (1620mU/mL). Serum levels of Free T4 increased to 1.06mcg/mL (n=4.9-11.4mcg/mL). Levothyroxine was titrated up and a repeated pituitary MRI demonstrated a significant decrease in the size of the mass with resolution of the suprasellar extension and mass effect on the optic chiasm. Further, the patient’s menses ceased and thelarche resolved upon correction of T4 and regression of the pituitary mass.

Conclusions: While rare, primary hypothyroidism and TSH-driven pituitary hyperplasia can result in a large mass effect with suprasellar extension, causing secondary hyperprolactinemia by a mass effect and central precocious puberty. This case highlights the benefits for evaluating underlying hypothyroidism as a cause for hyperprolactinemia and sellar/suprasellar mass.

<![CDATA[MON-075 Autonomy and Self-Determination in a Patient with XY Gonadal Dysgenesis]]> Background:

XY gonadal dysgenesis is characterized by the presence of male chromosomes with atypical testes differentiation. Due to an impaired ability to make testosterone, patients are often under-virilized at birth and present with ambiguous genitalia. For multidisciplinary teams specialized in disorders of sex development (DSD), gonadal dysgenesis presents challenges in sex assignment, initiation of hormonal therapy, and timing of surgical interventions. Recent discussions have reconsidered early interventions in favor of preserving self-determination in decisions regarding gender and anatomy.


LT initially presented at 3 years old, after her grandmother noted her abnormal appearing genitalia. Examination revealed clitoromegaly, 1.8 cm in length and 0.8 cm in width, with a blind, open introitus. XY gonadal dysgenesis was diagnosed, based on a pelvic MRI, cystourtheroscopy/vaginoscopy, genetic and hormonal testing.

LT was lost to follow-up for 6 years. At 11 years old, LT had been consistently raised as a female. When asked about gender identity, LT’s understanding of gender identity developed over time. At 11 years old, LT declared her gender identity as a “boy”, because boys are “strong”, and because she did not like make-up. LT denied any desire for breast development and explained that her family told her that breasts ‘make it hard to run fast.’

On follow-up evaluation 6 months later, LT voiced her decision to be a girl, and said that she was very confident in this decision. LT and her parents both desired estrogen therapy for induction of puberty. After discussions regarding the permanent effects of therapy, LT started hormone therapy. Two months after initiation of therapy, she remained firm in her gender identity and expressed a desire to grow her hair long. She independently stated that she did not desire surgery at this time. She will receive formal psychological testing at her next clinical evaluation to evaluate her for body dysmorphia, anxiety, and depression.


LT’s case demonstrates the progression of developmental understanding of gender and expressed gender identity that may occur as learning progresses in patients with DSDs. This case also shows that a delay in surgery may not have significant developmental consequences to these patients as was previously suggested. In general, the American medical system has tended to perform early sex assignments and surgical interventions to align anatomy with the sex assignment. However, after thoughtful discussions regarding human rights concerns, many have recommended to delay surgical interventions until adolescence, when the patient can consent appropriately to interventions that cause permanent anatomic changes. As many of these interventions may be discussed in early adolescence, it is of the utmost importance that information is presented in an understandable and developmentally appropriate manner.

<![CDATA[MON-055 A Rare Case of a Macroadenoma Causing Cushing Syndrome in a Pediatric Patient]]> Background: Pediatric Cushing Syndrome, a rare diagnosis, is almost always caused by pituitary microadenomas less than 5 mm in children older than 6 years old. We report on a 9-year-old girl with a 2.3 cm pituitary macroadenoma, whose ACTH and urinary 24-hour free cortisol were the highest recorded at our institution. Clinical Case: A 9-year-old pre-pubertal female presented with six months of frontal headaches, rapid weight gain, and hirsutism. Two months prior she developed fatigue and proximal muscle weakness and pain. On physical exam, she had plethoric round facies with acne and hirsutism, dorsal fat pad, central adiposity, and violet colored abdominal striae. Her pubertal development was tanner stage 3 for breast and 2 for pubic hair. BMI was 95th percentile and height was 40th percentile, previously 75th and 50th percentile respectively one year prior. 24 hour urinary free cortisol was 40,650 mcg/day [normal:100 mcg/day]. A 48 hour high dose dexamethasone suppression test was done as it is the most accurate in pediatric patients over 40 kg, morning cortisol was 100 mcg/dL [normal: 5-20 mcg/dL], ACTH 868 pg/ml [normal: 9-57 pg/ml], 24 Urinary Free Cortisol was 15,878 mcg/day [normal: 100 mcg/day]. A MRI Pituitary/Sella revealed a 2.3 cm pituitary macroadenoma superiorly displacing and flattening the optic chiasm, invading into the right cavernous sinus. She was referred to Neurosurgery, who did a partial transphenoidal resection, pathology consistent with ACTH producing tumor. Post-operatively she developed central diabetes insipidus and adrenal insufficiency for which she received desmopressin and oral hydrocortisone respectively. Her laboratory values eight months since surgery show normalization of ACTH and cortisol levels. The patient’s general health has improved, headaches have resolved, strength has returned, and her hirsutism is reduced. Her BMI remains elevated at 88% but is declining and growth velocity is increasing back to her pre-disease level. Conclusion: Cushing Syndrome is exceedingly rare in pediatric aged patients and pituitary macroadenomas are atypical in this population.This is a unique case of an ACTH producing macroadenoma in a Pediatric patient, which has seldom been reported in the literature, and should be considered in patients with similar presenting symptoms.

<![CDATA[MON-065 Prevention of 6-Mercaptopurine-Induced Hypoglycemia by Levocarnitine Replacement]]> Background: Symptomatic hypoglycemia has been reported in children less than 6 years of age receiving 6-Mercaptopurine for acute lymphoblastic anemia (ALL); however, the mechanism of 6-Mercaptopurine-induced hypoglycemia has been unclear. Objective: The objective was to investigate the metabolism in a 3-year-old patient with hypoglycemia induced by 6-Mercaptopurine during maintenance therapy for ALL. Methods: We reviewed test results including serum total and free carnitine levels at time of hypoglycemia in a 3-year-old child with ALL who had repeatedly low plasma glucose as a side effect of 6-Mercaptopurine. Hypoglycemia defined as plasma glucose <50 mg/dL was detected using a glucose meter and each time verified in the clinical laboratory. After Levocarnitine was added to 6-Mercaptopurine therapy, the glycemic control was assessed using a glucose meter, the clinical laboratory, and a continuous glucose monitor; serum total and free carnitine levels were repeated when hypoglycemia resolved. Results: Our patient presented with fatigue, tremors and plasma glucose 39 mg/dL to 47 mg/dL, corrected with a sugary beverage. He had plasma ACTH 38 pg/mL, serum cortisol 10 mcg/dL, total carnitine 24 nmol/mL (expected 35 - 84), free carnitine 18 nmol/mL (expected 24 - 63), plasma free fatty acids 1.62 mmol/L (expected >1.5), beta-hydroxybutyrate of 0.2 mmol/L to 0.7 mmol/L (expected >2.0), and urine ketone bodies negative when plasma glucose was between 33 mg/dL and 39 mg/dL. Plasma insulin was undetectable at time of hypoglycemia, and serum glucose increased by less than 30 points in response to Glucagon IV. Serum IGF-1 as measure of growth hormone effect and thyroid function were normal. Hypoglycemia continued to daily recur especially during the night despite bedtime snacks high in complex carbohydrates and was prevented only by Levocarnitine 25 mg/kg/dose every 12 hours PO that raised serum total and free carnitine levels. The patient remained hypoglycemia-free one month after Levocarnitine was added to 6-Mercaptopurine therapy, in particular, he had average glucose 114 mg/dL with standard deviation 30 mg/dL, glucose 70 mg/dL to 140 mg/dL 93% of the time, and glucose <55 mg/dL 0% of the time. Conclusions: Our patient had symptomatic hypoketotic hypoglycemia related to moderately reduced serum total and free carnitine, corrected with Levocarnitine replacement. Increase in plasma free fatty acids without expected increase in plasma and urine ketone bodies may be sign of impaired synthesis of carnitine, which is required for transport of fatty acids into the mitochondria to produce ketone bodies. Measuring serum total and free carnitine in hypoglycemia induced by 6-Mercaptopurine is helpful in identifying children, who may benefit from Levocarnitine replacement.

<![CDATA[MON-062 46 XX DSD Due to POR Deficiency]]> Background

PORD (P450 oxidoreductase deficiency) is a rare form of CAH with marked phenotypic variations due to differences in the degree of steroid hormone excess/deficiency. PORD results in17αhydroxylase/17,20lyase- CYP17, 21αhydroxylase- CYP21, and aromatase- CYP19A1 inhibition. In the absence of characteristic skeletal features of Antley Bixler phenotype, differentiating PORD from other types of CAH is challenging.

Case details

04 day child, second of the non-identical twins, product of 2nd degree consanguinity, third in birth order was brought with abnormal genitalia. The other male twin had no genital ambiguity but had pigmented scrotum. There was no adrenal crisis in index case or maternal virilization. First child is normal female. Child was hemodynamically stable weighed 02 kgs and measured 51 cms, had no hyperpigmentation, skeletal deformities or dysmorphic features. Phallus was 10mm, clitoral index 40mm2 with single urogenital opening and posteriorly fused labia (anogenital ratio 0.6).Gonads were not palpable. Karyotype was 46XX with normal Mullerian structures and non-visualized gonads on ultrasonography. Biochemical workup showed random plasma glucose level of 99mg/dl and normal electrolytes. Baseline serum 8am Cortisol was 1.15 mcg/dl (normal 5-18 mcg/dl) and 17OHP was 20 ng/ml (normal < 02 ng/ml). Serum Androstenedione level was 0.39 nmol/L (normal 0.5-3.4 nmol/L).

In view of clinical, laboratory and imaging findings, presumptive diagnosis of 46 XX DSD due to 21 alpha hydroxylase deficiency CAH was made. Oral Hydrocortisone 15mg/m2 and Fludrocortisone 0.05 mg were initiated. Therapy was monitored with serum 17(OH)P levels and Androstenedione. Genetic testing for 21 alpha hydroxylase gene however came negative.

This led to further genetic mutational analysis, and there was a homozygous R457H POR gene mutation at exon 12 leading to protein change p.Arg457His (nucleotide change c.1370G>A), confirming PORD. Retrospectively, maternal triple test done during the candidate pregnancy showed low serum estriol, suggestive of placental aromatase deficiency. Mineralocorticoid supplements were stopped thereafter.

Conclusions PORD needs to be considered and differentiated from garden variety of CAH in 46 XX DSD when elevation of 17(OH)P is modest with isolated cortisol deficiency and aromatase deficiency (evidenced by low maternal estriol levels and/or virilization), as its course and follow up are different.

<![CDATA[MON-079 Prepubertal Gynecomastia Secondary to Excessive Soy Consumption]]> Enlargement of breast tissue in males, or gynecomastia, is a rare condition in prepubescent boys. While the majority of cases are idiopathic, we describe an 8-year-old patient who developed unilateral gynecomastia secondary to marked dietary soy consumption. Soy products, particularly those consumed by our patient, contain high levels of phytoestrogens which have been documented in limited case studies to contribute to abnormal development of breast tissue in adolescent and adult males. To our knowledge, this is the first documented case of gynecomastia occurring in a prepubescent patient resulting from excessive intake of dietary soy. Importantly, we also report a complete resolution of gynecomastia upon exclusion of dietary products containing significant amounts of soy. While soybeans and soy-derived products can be an important source of nutrition for some, those with abnormal sensitivity to phytoestrogens may benefit from limiting dietary soy consumption to avoid potential adverse effects, including gynecomastia.

<![CDATA[MON-078 WFS1 Related Disorder in A 4-Month Old Girl]]> Background: Idiopathic early-onset central diabetes insipidus (CDI) may be due to mutations of arginine vasopressin-neurophysin II (AVP-NPII (AVP)) or wolframin (WFS1/2) genes (1).

Clinical Case: A 4-month old girl presented to our pediatric endocrinology clinic due to severe polydipsia-polyphagia and polyuria. Plasma and urine glucose and HbA1c were normal and 24h monitoring of urinary output was elevated (4.2ml/kg/h). We proceeded to a modified 5-h water deprivation test followed by 0.1 mcg DDAVP IM. Results were compatible with partial central DI: at 5-hrs weight loss 5%, urine osmolality 155 from 111 at 0΄and 355 mOsm/kg 2hrs after DDAVP administration.

Pituitary MRI was normal with presence of posterior pituitary bright spot and normal pituitary stalk.

We initiated therapy with oral desmopressin acetate titrated at the dose of 70mcg x 3/day under close clinical and biochemical surveillance. Hyponatremia, with high natriuresis >100 mmol/L and elevated BNP occurred the 3rd day. Fludrocortisone 100 mcg x 2/day controlled natriuresis and supplemental oral NaCl 15% 15ml/day was needed to restore normal electrolytes (2).

Marked catch-up growth was observed already at 1 month for height, weight and head circumference.

Methods: Whole exome sequencing was performed targeted to a gene panel related to DI, containing AVP gene, WFS1/2 genes and AVPR2/AQP2 genes.

Result: Two heterozygous variants were revealed: WFS1:NM_001145853:exon8:c. G997A:p.V333I,WFS1:NM_006005:exon8:c.G997A:p.V333I and WFS1:NM_00114585 3:exon8:c.G1832A:p.R611H,WFS1:NM_006005:exon8:c.G1832A:p.R611H reported as possibly damaging in 1/6 and 4/6 prediction programs respectively. These variants will be checked in both parents to confirm the presumed compound heterozygosity pattern in the child.

Conclusion: We present a 4-month old girl with two heterozygous variants of WFS1 gene which may cause early-onset central diabetes insipidus and possibly a WFS1 related disorder (1).


(1) Perrotta S et al. Early-onset central diabetes insipidus is associated with de novo arginine vasopressin-neurophysin II or Wolfram syndrome 1 gene mutations. Eur J Endocrinol. 2015 Apr;172(4):461-72

(2) Papadimitriou DT, Spiteri A, Attilakos A, Papadimitriou A. Cerebral Salt Wasting Complicated by Central Diabetes Insipidus and Growth Hormone Deficiency. Indian J Pediatr. 2018 Jul;85(7):580-581

<![CDATA[MON-077 A Case of Growth Hormone Deficiency in Sturge-Weber Syndrome]]> <![CDATA[MON-067 A Perplexing Case of Hyponatremia and Abdominal Pain]]> <![CDATA[MON-073 Hyperinsulinemic Hypoglycemia Responsive to Diazoxide Due to a Previously Unknown ABCC8 Dominant Mutation]]> A (p.Val1351Met) variant in ABCC8, classified as “of uncertain significance”. However, an entry in the ClinVar database (RCV000714711.1) exists from a research lab and was classified as likely pathogenic. Analysis of parental samples showed that the mother was heterozygous for the same genetic variant. She did not have a history of hypoglycemia. Patient was started on diazoxide (8 mg/kg/day) and chlorothiazide with resolution of hypoglycemia. At a follow up visit at 5 months of age, there was no history of hypoglycemia, and no need for adjustments of the diazoxide dose by weight (dose at that time of 7.4 mg/kg/day). Conclusion: The ABCC8 reported here is a dominant mutation causing hyperinsulinemic hypoglycemia responsive to diazoxide with a milder phenotype later in infancy. Longitudinal follow up of the case is warranted to understand the long term progress in patients with this particular mutation. Reference: Adam MP, Ardinger HH, Pagon RA, Wallace SE, et al. None. 1993. Familial hyperinsulinism. ]]> <![CDATA[MON-056 Rare X Chromosome Pericentric Inversion Associated with Ovotesticular Disorder of Sex Development]]>