ResearchPad - pediatric-endocrine-case-reports-i Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SAT-081 Hidden in Plain Sight: Rethinking Our Approach to Allan-Herndon-Dudley Syndrome]]> Background: Allan-Herndon-Dudley (AHD) is a rare X-linked disorder with neurological manifestations secondary to a mutation in monocarboxylate transporter 8, a protein that transports T3 into nerve cells in the brain. AHD is characterized by increased serum free T3, decreased serum free T4 and normal serum TSH levels as well as the severe neurological manifestations including global developmental delay, hypotonia, and joint contractures (1). A phase 2 trial using triodyothyroacetic acid has shown promise in treating this disorder (2). We report on three children who were diagnosed by whole exome sequencing after presenting with neurological manifestations.

Clinical Cases: Patient 1 presented at 4 months to the neurology clinic for seizures. He had a normal newborn screen. Worsening developmental delays and central hypotonia prompted a brain MRI that revealed delayed myelination for age. At 6 months a chromosomal microarray and metabolic work-up were performed and were nondiagnostic. Whole exome sequencing was obtained at the age of 4.5 years revealing a mutation in the SLC16A2 gene (p.Ser210Tyr). Thyroid studies were consistent with the diagnosis.

Patient 2 presented to neurology at 9 months for developmental delay. A brain MRI was obtained which was within normal limits. At 14 months an acylcarnitine profile was obtained which indicated a possible CPT1 deficiency, which did not fit his clinical picture. Chromosomal microarray as well as work-up for inborn errors of metabolism were performed and were nondiagnostic. Thyroid studies were obtained which showed low free T4 with normal TSH. Whole exome sequencing was obtained at the age of 2.5 years, which revealed a mutation in SLC16A2 (p.R371C).

Patient 3 presented as sibling of patient 2 with known AHD syndrome. Testing for SLC16A2 was performed at the age of 5 months and returned positive for same mutation as sibling (p.R371C).

Conclusion: Allan-Herndon-Dudley syndrome is a rare neurological disease secondary to a mutation in the T3 transporter protein to nervous tissue. A high index of suspicion as well as thyroid studies should be obtained in patients presenting with central hypotonia and global developmental delay with normal newborn screens, particularly in states that use TSH as a screening test. This is especially important as treatments are becoming available that may help prevent neurological devastation seen in these patients.


1. Dumitrescu AM, Fu J, Dempsey MA, Refetoff S. MCT8-Specific Thyroid Hormone Cell-Membrane Transporter Deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993

2. Groeneweg S, Peeters RP, Moran C, et al. Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019;7(9):695-706.

<![CDATA[SAT-077 Two Cases of Hypoparathyroidism Due to Activating Calcium Sensing Receptor Mutation]]> Introduction

The extracellular calcium-sensing receptor (CaSR) expressed mainly in the parathyroid gland and kidneys regulates calcium (Ca+2) homeostasis through parathyroid hormone (PTH) secretion. Activating mutations of CaSR can lead to autosomal dominant hypocalcemia and severe congenital hypoparathyroidism. Constitutively activated CaSR receptors blocks PTH release leading to hypocalcemia, hyperphosphatemia and decreased Ca+2 reabsorption from the kidney.

Case 1:

14 year old male presented for an evaluation of hypocalcemia and hyperphosphatemia found on routine blood work. He denied symptoms of hypocalcemia. He had normal vital signs, positive Chovstek sign but rest of exam was unremarkable. His lab results showed low Ca+2 8.1 mg/dl (8.6–10 mg/dl), high phosphorus 6 mg/dl (2.7–4.5 mg/dl) and inappropriately normal PTH 26.8 pg/ml (10–65 pg/ml). FISH was negative for DiGeorge. Genetic testing showed heterozygous CaSR gene mutation I822T, variant of uncertain significance. His father with primary hypoparathyroidism has the same CaSR gene mutation; mother is healthy and tested negative for this variant. Given the inheritance pattern of the mutation, it is likely a pathologic mutation. He is maintained on Calcium (1500 mg BID) and Calcitriol (0.5 mcg PO BID) and is doing well.

Case 2:

One day old premature 32-week old infant girl was found to have early onset neonatal hypocalcemia 6.1 mg/dl (6.2–11 mg/dl) during NICU admission for respiratory distress, inappropriately normal PTH 18.5 pg/ml and high phosphorus 8.8 mg/dl (4.6–7.9 mg/dl). She had no symptoms of hypocalcemia in the NICU or at home. She did not have any dysmorphic features. FISH was negative for DiGeorge. Genetic testing to sequence genes including AIRE, AP2S1, CASR, GNAS, HADHA, HADHB, PTH1R, SOX3, STX16, TBCE was done and revealed a novel heterozygous mutation in the CaSR gene for a missense variant c.2495T>C

(p.lle832Thr) and STX16 c.644A>T, possibly benign variant. Unfortunately, the parents have not consented to testing yet. Further familial and functional characterization of this new variant is necessary to confirm its possible pathogenetic role in this hypocalcemic patient. Currently she is maintained on ergocalciferol 800 IU, calcitriol 0.25 mcg and sevelamer 3 packets daily and is doing well.


In the workup for primary hypoparathyroidism without dysmorphic features and tests negative for DiGeorge, CaSR mutations should be investigated as part of the differential as we have identified variants in the CaSR gene in 2 children with asymptomatic hypocalcemia, one of which is a novel mutation which has never been reported before.

<![CDATA[SAT-055 A De Novo 1p13.2 Deletion Related to Short Stature, Hypothyroidism and Mild Developmental Delay]]> Background: Chromosomal deletions may lead to variable phenotypic alterations, depending on which loci and genes are deleted. We present the case of a boy with a de novo 1p13.2 deletion which was diagnosed by array-CGH analysis.

Clinical Case: A Greek boy, who was referred for evaluation of growth failure, was investigated. He was delivered at term by cesarean section, with normal birth weight (3.060 kg), birth length (51 cm) and head circumference (35.5 cm). There was no positive family history for short stature. Target height was on the 25th percentile. He presented with growth deceleration since the age of 12 months leading to stature lower than the 3rd percentile at the age of two years, while his weight was at the 3rd percentile. Macrocephaly was appreciated (53 cm, >95th percentile). Dysmorphic facial features resembling Noonan syndrome, such as frontal bossing, depressed nasal bridge and low-set ears were recognized. His motor development was normal. Laboratory examination revealed hypothyroidism and treatment with L-thyroxine was initiated. He had regular follow-ups at 6 months intervals. A mild delay in speech development and motor skills was appreciated. At the age of five years old, as his growth rate remained slow, growth hormone (GH) stimulation tests were performed. GH had a borderline normal peak of 9.9 ng/ml. IGF-1 levels were also within normal range (123.7 ng/ml). Magnetic Resonance Imaging (MRI) of the pituitary gland and the brain was normal. Array-CGH analysis detected a loss of approximately 800 Kb on chromosome 1p13.2; these alterations affect 8 genes in the OMIM database. The deleted segment was mapped at chr1: 115,186,092_115,977,647 region. The genomic coordinates are listed according to genomic build GRCh37/hg19. The genetic material analysis did not show the presence of a deficit in chromosomal region 1p13.2 (chr1: 115,186,092_115,977,647) in neither of the parents, indicating that this finding was created de novo.

Conclusion: We describe a patient with a Noonan like phenotype, due to a 1p13.2 deletion. In the international literature and databases of Database of Genomic Variants and Database of Chromosomal Imbalance and Phenotype in Humans Using Ensemble Resources there are no reports of normal individuals or patients with a similar finding in chromosomal region 1p13.2. Regular follow up of the patient is needed in order to better understand the evolution of the phenotype.

<![CDATA[SAT-063 Polymicrobial Suppurative Thyroiditis Masquerading as Thyroid Storm]]> Introduction:

The thyroid gland is highly resistant to infection due to a robust blood supply, good lymphatic drainage, and high iodine concentration. Suppurative thyroiditis (ST) often presents with fever, tachycardia, leukocytosis, tenderness, and euthyroid labs. However, when ST occurs with thyrotoxicosis, it can meet criteria for thyroid storm, which presents a diagnostic dilemma.

Clinical Case:

A 17 year old female with family history of Graves’ disease presented to the ER with a sore throat. She was diagnosed with viral pharyngitis and treated with dexamethasone. Over the next 2 weeks, she developed fatigue, body aches, nausea, vomiting, and chills. She returned to the ER and was found to have tachycardia, hyperthyroidism [free T4 5.64 ng/dL (0.8 - 2.0 ng/dL), TSH <0.015 uIU/mL (0.5 - 4.5 uIU/mL)], and WBC 11 k/uL (3.5 - 11.5 k/uL). She was prescribed atenolol and referred to Endocrinology. Three days later she developed fever, diaphoresis, ear pain, vomiting, and abdominal pain. In the ER, she was febrile to 101.2°F with a heart rate (HR) of 117 BPM. Labs showed a free T4 6.14 ng/dL, TSH <0.015 uIU/mL, and WBC 20 k/uL. She was treated with methylprednisolone, propylthiouracil, and labetalol with improvement and transferred for concern of impending thyroid storm. Exam showed left-sided thyroid enlargement with tenderness. Thyroid ultrasound showed an enlarged heterogenous left thyroid lobe with 2 nodules, one 25 x 33 x 21 mm heterogenous and one 19 x 11 x 19 mm homogenous, without discrete abscess. That night she developed vomiting, hand tremors, HR in the 130’s BPM, fever to 104.1°F, and a headache. Treatment was initiated with methimazole, SSKI drops, propranolol, and dexamethasone. Symptoms improved save persistent neck tenderness and dysphagia. CT neck demonstrated a left-sided 25 x 17 x 90 mm abscess with concern for 4th branchial apparatus abnormality. She underwent incision and drainage with drain placement. Cultures grew Streptococcus anginosus and Fusobacterium necrophorum. Broad spectrum antibiotics were started and later narrowed to ampicillin-sulbactam. Betablockers and methimazole were discontinued and thyroid labs nearly normalized by discharge [T4 11.8 mcg/dL (4.5-11.5 mcg/dL), free T4 2.0 ng/dL (0.8-2 ng/dL), and total T3 78 ng/dL (100-210 ng/dL)]. Thyroid auto-antibodies were negative.


In patients with ST, only 11% present with hyperthyroidism. Current thyroid storm scoring systems are sensitive but not specific so an acute bacterial infection with thyrotoxicosis can easily meet criteria. While ultrasound is standard for assessing for thyroid abscesses, in the setting of high clinical suspicion, further imaging with contrasted neck CT is warranted.

<![CDATA[SAT-059 Congenital Craniopharyngioma: A Rare and Challenging Disease]]> Introduction: Congenital central nervous system tumors are seldomly seen, with just few reported cases of neonatal craniopharyngioma (NCP). Albeit being a benign tumor arising from epithelial vestiges along the adenohypophysis migration, NCP may have an aggressive behavior due to its location.Case Report: We report a two-month-old female infant referred to the Pediatric ward due to recurrent sepsis episodes, uncontrollable crying, large fontanelle and signs of adrenal insufficiency. Laboratory evaluation showed low serum cortisol 0.11 μg/dL(REF: 6.2-19.4 μg/dL), ACTH 6.66 pg/mL(REF: 7.2-63.3pg/mL) and Na 133 mEq/L(REF: 136-145mEq/L), normal Free T4 1.01 ng/dL(REF: 0.93-1.7 ng/dL) and a slightly elevated prolactin 59.43 ng/mL(REF: 4.79-23.3ng/mL). A transfontanelar ultrasound demonstrated a cystic and calcified sellar/suprasellar tumor. Encephalus Magnetic Resonance Imaging described a 36x42x33 mm multicystic sellar/suprasellar mass extending to the middle line and occupying all sellar space, leading to a deformed and compressed third ventricle, and displacing the mesencephalus, the cerebral pedunculus and the optic chiasm. Imaging evaluation suggested a craniopharyngioma. She started hydrocortisone therapy due to hypercortisolism and was submitted to transsphenoidal surgery, but just a partial resection of the tumor was possible. She needed levothyroxine and desmopressin replacement after surgery. On the 10th post-operative day she died due to infectious complications. The histological analysis of the tumor diagnosed an adamantinomatous-type grade I craniopharyngioma.Comments: Central nervous system tumors developing in the first 60 days of life are considered congenital. Besides being a rare condition, NCP are challenging and life-threatening. Although for some groups the complete resection of the tumor is considered the gold standard approach to those patients, sometimes it cannot be performed due to limitations intrinsic to the tumor biology and due to the patient’s age, worsening the prognosis of the infant. Multihormonal deficits and shortened survival of this patient were consequences of the tumor characteristics, delayed diagnosis of craniopharyngioma and the poor results during and after the surgical intervention.

<![CDATA[SAT-061 Severe Hypocalcemia in an Infant with Abnormal Microarray and Dysmorphic Features]]> Introduction:

In pediatrics, hypocalcemia is observed most often in an ICU setting. It can be associated with acute or chronic illnesses. We present a 1 month old male infant with abnormal microarray who presented to the PICU for seizures secondary to severe hypocalcemia.

Case presentation:

A 1 month old male was admitted to PICU with new onset seizures. Past history was remarkable for NICU hospitalization for respiratory distress, dysmorphic features with genetic evaluation revealing chromosome 10p15.3p14 deletion and chromosome 6p25.3p24.3 duplication with normal karyotype, muscular VSD, neonatal cholestasis, left hydronephrosis and congenital hypothyroidism. Labs obtained during NICU stay did not reveal hypocalcemia at the time. Basic lab work-up done at time of admission showed low Ca level of 5.6, elevated Phos of 9.3 and Mag level of 1.6. Thyroid work-up was within normal.

Pediatric endocrinology was consulted for hypocalcemia.

Further work-up showed Ca of 7.2, drawn after calcium gluconate riders and on calcium infusion rate at 5 mg/kg/hr, Mg of 1.8, Phos of 6.4, PTH of 36.2 and vitamin D-25 OH of 10, which was most consistent with hypoparathyroidism, likely due to his underlying genetic mutation, given inappropriately normal PTH. We recommended to continue Ca infusion as needed up to 80 mg/kg/day to maintain normal Ca levels and to provide 2000 units of vit D for 6-12 weeks and Calcitriol 0.25 mcg daily for 1 week with monitoring of levels.

Patient’s remainder of hospital course was complicated by need for intubation, arrhythmia unrelated to hypocalcemia, sepsis, acute tubular necrosis, which prolonged patient’s need for IV calcium and length of hospitalization. Patient’s electrolytes were normalized and he was able to transition to 25 mg/kg/day PO supplements and 1000 units of vit D with improved levels. He was discharged on these supplements with follow-up.


This is a case of severe hypocalcemia secondary to primary hypoparathyroidism from underlying genetic mutation with chromosome 10p15.3p14 deletion. Patient’s complicated hospital course including sepsis and acute tubular necrosis had prolonged the need for calcium infusion until he was eventually transitioned to PO calcium supplementation. It is interesting that to note the association of his underlying genetic mutation and hypoparathyroidism as there has not been any specific pediatric case described with patient’s genetic mutation.


<![CDATA[SAT-054 Gigantism and Hypothalamic Obesity: Rare Endocrine Manifestations of Neurofibromatosis Type 1]]> Background: Neurofibromatosis type 1 (NF-1) is a heritable, autosomal dominant, multisystem disorder caused by mutations or deletions in NF1, with approximately 30-50% of cases arising from de novo mutations. In the pediatric population, growth hormone deficiency is among one of the most commonly described endocrine sequelae, although aberrations of pubertal development are also commonly seen.

Clinical Case: A 3-year-old female, who was clinically diagnosed with NF-1 at the age of 4 months based on the presence of multiple café-au-lait macules, underwent screening MRI, which noted a left optic glioma and a hypothalamic mass favored to represent a hypothalamic glioma. Review of her growth chart showed a height much greater than the 99th percentile, with an increase in height velocity beginning 1 year prior. Weight was also noted to be much greater than the 99th percentile, with an increase in weight gain coinciding with the timing of alterations in linear growth. Mid-parental height is at the 95th percentile, and the patient’s height had tracked between the 86th and the 99th percentiles until age 2 years. Weight had tracked between the 68th and the 95th percentiles during that period. Initial laboratory evaluation showed an IGF-1 of 644 ng/mL (26-164 ng/mL). Gonadotropins were prepubertal; prolactin and thyroid studies were normal. ACTH stimulation demonstrated a rise in serum cortisol from 6.8 mcg/dL to 30.2 mcg/dL at 60 minutes. Growth hormone failed to suppress following an oral glucose load with a baseline GH of 4.4 ng/mL and values of 3.7, 6.5, 6.8, and 9.0 ng/mL at time +30, +60, +90, and +120 minutes respectively. Leuprolide stimulation did not show significant rises in gonadotropins. Bone age was advanced by more than 1 year. The patient was started on subcutaneous octreotide with a decrease in IGF-1 to 258 ng/mL after 1 month of therapy. On treatment, linear growth velocity slowed with no interval height gain over the initial 1-month period; however, the patient’s weight continued to increase with a gain of 1.8 kg. Parents additionally reported hyperphagia, which prompted concern for hypothalamic obesity in the setting of her known hypothalamic mass. Thyroid function remained normal on somatostatin therapy. To date, there has been no concern for diabetes insipidus.

Conclusion: Growth hormone excess may rarely complicate a diagnosis of NF-1 in the setting of intracranial gliomas. Increased height velocity and/or tall stature for family should raise clinical suspicion and prompt evaluation. Hyperphagia and significant increases in weight in the setting of hypothalamic gliomas in patients with NF-1 should raise suspicion for hypothalamic obesity and prompt lifestyle modifications to curb ongoing weight gain.

<![CDATA[SAT-057 A Novel IGSF1 Variant in a Boy with Central Hypothyroidism and Epiphyseal Dysplasia]]> Background: IGSF1 deficiency syndrome, also known as X-linked central hypothyroidism and testicular enlargement (CHTE) syndrome, is caused by mutations in the immunoglobulin superfamily, member 1 gene. Recently recognized as the most common genetic cause of isolated central hypothyroidism (CH), its cardinal features include CH and adult macroorchidism. We describe a boy with CH and epiphyseal dysplasia found to have a novel IGSF1 variant.

Clinical case: A male with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, obsessive compulsive disorder and obesity was evaluated at age 9y for high total and LDL cholesterol and low T4 with normal TSH. He had short stature for family, high BMI, high sitting height ratio, and short arm span. Laboratory investigation revealed persistently mildly high total and LDL cholesterol, low T4, normal cortisol response to low-dose Cortrosyn stimulation, and normal IGF-1 and IGF-BP3. Bone age at 9y1m chronological age was 8y0m. Skeletal survey showed abnormal epiphyses of the femoral heads, knees, and humeral capitella suggesting primary epiphyseal dysplasia; he was referred to genetics. Growth improved after starting levothyroxine for CH. Multiple epiphyseal dysplasia gene panel (with reflex to clinical exome) did not find any variants known to be pathogenic for his condition. He was found to be a carrier of autosomal recessive Bartter syndrome. Heterozygous variants of unknown significance were found in RMRP, FGFR1, CDT1 and APOB. Whole exome sequencing showed hemizygosity for the p.Q743X (c.2227C>T) variant in IGSF1.

Discussion: The p.Q743X IGSF1 variant has not been reported in the literature and is not present in population databases. It is predicted to cause loss of normal protein function and is considered pathogenic. CH is found in all males with IGSF1 deficiency syndrome. Macroorchidism, another defining feature, develops in adulthood; age of testicular growth onset is normal, but pubertal testosterone rise is delayed. Our patient remains prepubertal at age 11y. Other features sometimes present include hypoprolactinemia (which was found in this child) and transient partial GHD (not seen in this case). Overweight and the metabolic syndrome are common; this child’s cholesterol abnormalities may be due to weight and/or APOB variant found on genetic testing. ADHD has been seen in some patients with this syndrome; this child also has extensive psychiatric/behavioral problems, which have not been described. The skeletal findings in this case have not been previously noted in IGSF1 deficiency syndrome; whether this is a rare feature of IGSF1 deficiency syndrome or a separate entity is unclear. This case adds to the growing list of disease-causing variants in IGSF1. Endocrinologists should consider IGSF1 deficiency syndrome when diagnosing isolated CH in boys, as the characteristic macroorchidism is not present in childhood.

<![CDATA[SAT-060 Unusual Case of Short Stature and Poor Growth in Childhood]]> Background: Néstor-Guillermo progeria syndrome (NGPS; OMIM 614008) is caused by biallelic pathogenic variants in BANF1 (barrier-to-autointegration factor 1) on chromosome 11q13. It characterized by early onset and slow progression of symptoms including poor growth, lipoatrophy, pseudo-senile facial appearance, and normal cognitive development. Two adult patients have been reported. This is the first reported case of a child with NGPS who presented to endocrine clinic with failure to grow.

Clinical Case: Two year, 8 month old Hispanic female born at 40 weeks gestation with birth weight 3.5 kg. At 1 year, she had short stature, poor weight gain, and thinning hair. There were no developmental concerns. Family history was remarkable for consanguinity. At presentation, her weight was 8.5 kilograms) and height 80 centimeters (both <1st percentile) and head circumference 45.5 centimeters (3rd percentile). Hair was sparse and fine with large areas of scalp alopecia. She had a small face with overhanging brow ridge, flattened midface, narrow nose, small mouth and bilateral lower eyelid ectropion. Fingers were shortened with thickened knuckles, widened fingertips, and distally set nails. Skin was tight throughout, particularly notable on the legs and hands with light discoloration of skin over the hand joints and reticulated dark macules over the lower abdomen. Her cardiac, respiratory, abdominal, genitourinary, neuro and joint examinations were unremarkable. Routine labwork was normal. Her bone age was normal at 2 year and 7 months but there was hypoplasia of the distal phalanges. Full skeletal survey revealed small mandible, thinning of the cranial vault, apparent crowding of the teeth, short stature, acroosteolysis-like changes involving the distal phalanges most evident in the hands, pointed distal phalanx of the great toes, and resorption of the distal clavicles. Her echocardiogram was normal. Sequencing and deletion/duplication analysis of LMNA was not diagnostic. Trio-based whole exome sequencing (WES) was performed after obtaining informed consent. WES revealed homozygosity for a pathogenic missense variant in BANF1 c.34G>A (p.Ala12Thr) inherited from each of the unaffected parents.

Conclusion: Progeria syndromes are unusual but diagnosable causes of failure to grow and can be diagnosed based on clinical suspicion. This patient represents the first child reported with NGPS.

<![CDATA[SAT-056 Autosomal Dominant Hypophosphatemic Rickets in Premature Twins Resolved with Iron Supplementation]]> Introduction

Autosomal dominant hypophosphatemic rickets (ADHR) is a condition with variable phenotype in terms of age of presentation, severity, and possible resolution. ADHR is caused by mutations of FGF23, preventing its cleavage, producing high levels of FGF23, which leads to renal phosphate wasting. Studies in mice and adult humans, have shown a correlation between low iron levels and increased FGF23 levels. To our knowledge, three pediatric patients with ADHR resolved with iron supplementation have been reported in the literature.

Clinical case

We report on identical twins born at 28 weeks and 5 days by cesarean section due to premature rupture of membranes with complicated pregnancy due to twin-to-twin transfusion syndrome. Birth weights were 780 grams (2nd percentile) for twin A, 1,200 grams (50th percentile) for twin B. Hypophosphatemia was documented starting at 2 weeks of life and during the first 6 of months of life, with phosphorus levels between 2.9-3.9 mg/dL for twin A and between 2.4-5.1 mg/dL for twin B.

During their NICU admission phosphorus had a positive relationship with the hemoglobin level, which was more severe on twin A. Both were treated with calcitriol and a low dose of phosphorus starting on their 2nd month of life.

At 6 months of age, both had persistent hypophosphatemia, more prominently in twin A (2.7mg/dL) with high alkaline phosphatase (1,209 IU/L) and high FGF23 (343 RU/dL). At that time his hemoglobin was 9.8 g/dL and his hematocrit was 29.5%. Both were started on Polyvisol with iron.

At 14 months of life phosphorus and calcium were within normal limits, therefore calcitriol and phosphate were discontinued. At 15 months of age their hemoglobin, hematocrit, iron level, and TIBC levels were normal for both twins. Phosphorus was 4.6 and 4.3 mg/dL, alkaline phosphatase reduced significantly to 819 and 413IU/L, and FGF23 normalized to 100 RU/dL and 32 RU/dL on twin A and B respectively.

Upon physical examination at 15 months of age, twin A was at the 0.02% for length and weight/length at the 31%; twin B was at the 5% for length and weight/length at the 50%. Both twins had high arched palates. Twin A had craniosynostosis, left renal agenesis, bilateral epicanthal folds, overlapping 2nd toes, and clinodactyly of the fifth digits. Note the donor kid (twin A) had a more severe presentation.

Genetic testing showed heterozygous mutation c536G>a (p.Arg179GLN) in the FGF23 gene. This is the same mutation previously reported to be related with ADHR resolved with iron supplementation


The study of patients with hypophosphatemia and hypophosphaturia should include evaluation of iron status (ferritin, TIBC). Treating iron deficiency on these patients might normalize phosphate levels. This would avoid cumbersome treatment with phosphate and calcitriol.

Laboratory values

Phosphorus:4-8 mg/dL

Alkaline Phosphatase: 130-317 IU/L

FGF23: 44-215 RU/dL

<![CDATA[SAT-074 A Rare Endocrine Cause of Pseudotumor Cerebri]]> Introduction: Idiopathic intracranial hypertension, also known as pseudotumor cerebri, can be associated with various medications, obesity, systemic conditions, and inherited disorders. To the best of our knowledge, this is the second pediatric case of a GnRH agonist reported to cause pseudotumor cerebri.

Case presentation: Our patient, a 12 5/12-year-old transgender male (birth-assigned female), started depot leuprolide acetate to suppress puberty at 11 10/12 years of age (early Tanner 2 breast development). He received Lupron Depot® 7.5 mg intramuscularly for 4 doses, then 22.5 mg intramuscular every 13 weeks thereafter. Five months after his first injection, a routine eye examination revealed bilateral papilledema and enlarged blind spots, which was confirmed by a Pediatric Ophthalmologist. He was asymptomatic. There was no marked weight gain in the previous year with a BMI of 24.5 kg/m2 (+1.85 SD). His blood pressure was 110–123 mmHg systolic and 71–85 mmHg diastolic. Neurological examination was normal. CT head was normal. Cranial MRI showed slight flattening of the optic nerve heads, mild engorgement of optic nerve sheath fluid, and no space-occupying mass. Sedated lumbar puncture revealed elevated opening pressure of 31 cm H2O. CSF analysis, including pathology, was benign. He was managed with acetazolamide. Based on these findings, he was diagnosed with pseudotumor cerebri secondary to the GnRH agonist. Follow-up by the Ophthalmologist one month after starting acetazolamide showed significant improvement of the papilledema.

Conclusion: This case highlights that patients on GnRH agonist therapy are at risk for pseudotumor cerebri, and we recommend periodic ophthalmologic surveillance.

<![CDATA[SAT-071 Autoimmune Polyglandular Syndrome Type 1 with Common Variable Immunodeficiency]]> BACKGROUND:

Autoimmune polyglandular syndrome (APS) is a rare disorder. It’s co-existence with common variable immunodeficiency (CVID) was reported in 5 cases before but, none of them was APS type 1up to our knowledge. The overlap between the 2 conditions indicates a possible association between Autoimmunity and immunodeficiency.


A 21-year-old lady was diagnosed to have CVID since infancy, as she was presenting to the hospital with recurrent infections and sepsis. At the age of 7 months, she was diagnosed with type 1 diabetes and was started on insulin. Furthermore, at 2 years of age she was found to have primary hypothyroidism and in her teenage she was diagnosed with primary adrenal insufficiency. Her history became more complicated when she also started to develop recurrent oral and esophageal candidiasis that required systemic anti-fungal therapy. Later in her life, she was incidentally found to have hypoparathyroidism when her labs showed hypocalcemia with inappropriately normal parathyroid hormone. She had chronic diarrhea which was thought to be due to celiac disease based on intestinal biopsy showing villous atrophy. With her IgA deficiency, her Tissue transglutaminase IgA antibodies were not reliable. Splenic atrophy was also detected on abdominal imaging. She never reached puberty and elected with her parents to not start combined hormonal therapy.

With the constellation of these features, we concluded that she has type 1 APS along with CVID.


Autoimmunity and immunodeficiency might be interconnected. Early diagnosis will affect the quality of life and early targeted treatment will prevent morbidity and early mortality.

KEY WORDS: Autoimmune Polyglandular Syndrome, Common Variable Immunodeficiency.

<![CDATA[SAT-079 Is There an Association Between the Detection Method for Pediatric Thyroid Nodules and the Risk of Malignancy?]]> Background

Thyroid nodules are less common in children compared to adults, but have a higher likelihood of malignancy. There are few studies, particularly in the pediatric population, examining the association between how and by whom the nodule is detected and the risk of malignancy. Several adult studies have suggested a high rate of malignancy in incidentally discovered thyroid nodules (1,2). However, this was not similarly seen in pediatric thyroid nodules according to one study (3). As fine needle aspiration (FNA) in pediatric patients may be more labor intensive and diagnostic excision is the recommendation for nodules with indeterminate or potentially malignant cytology, if the detection method can be a predictive measure of malignancy, it may enhance the evaluation of pediatric thyroid nodules.


The aim of this study is to determine if there is an association between how and by whom a thyroid nodule is detected and the risk of malignancy in the pediatric population.

Study Design and Methodology

We retrospectively reviewed the medical records of pediatric patients (≤21 years of age) who had a thyroid nodule with definitive cytologic or pathologic diagnosis from January 2010 to June 2019. Patients were categorized into 3 groups based on how and by whom the nodule was detected: (1) patient or parent, (2) provider, or (3) imaging obtained for non-thyroid indications (incidental). Characteristics that were evaluated included rate of malignancy, size of the nodule, location of the nodule, and size of the cancer (if present).


A total of 78 patients with concerning thyroid nodules were analyzed. Within the study, the cancer rate was 27% (21/78), which is comparable to the reported malignancy rate of pediatric thyroid nodules in the literature (22-26%) (4), suggesting that our sample population may be representative of the general pediatric thyroid nodule population. In our study, though the absolute numbers were small, there was a higher rate of malignancy in the incidental group (3/5, 60%) compared to the patient/parent (9/34, 26%) and provider (9/39, 23%) groups. The average size of the thyroid nodule was similar in all 3 groups. The strength of this study was the inclusion of only patients with definitive diagnosis of the thyroid nodule and the possibility of the findings being applicable to the general pediatric population.


In our sample study, incidentally discovered pediatric thyroid nodules had a higher rate of malignancy as compared to those discovered by patients/parents or providers.



Kang HW, et al. Thyroid 2004; 14(1):29-33.


Liebeskind A, et al. J Ultrasound Med 2005; 24(5):629-634.


Gupta A, et al. J Pediatr 2014; 164(3):658-660.


Francis GL, et al. Thyroid 2015; 25(7):716-758.

<![CDATA[SAT-069 Advantages of Next Generation Sequencing (NGS) in Hypophosphatemic Disorders Diagnosis. First Case of SLC9A3R1 Gene Pathogenic Variant Detected in a Pediatric Patient]]> Background: Hereditary hypophosphatemic rickets (HHR) is a group of inherited disorders characterized by hypophosphatemia due to renal-phosphate wasting and impairment of vitamin D metabolism, rickets and disproportioned short stature. Different genetic defects are known to cause HHR, but similar clinical and biochemical features were reported. Dominant-X-linked HR (XLHR) is the most frequent form, with an incidence of 1 in 20.000, although dominant and recessive autosomal forms are also described. XLHR is caused by inactivating mutations in the PHEX gene (located at Xp22.1), encoding a endopeptidase which regulates the phosphaturic secretion. Affected individuals present with a broad phenotypic spectrum, ranging from isolated hypophosphatemia up to severe symptoms of rickets. Therefore NGS studies represent an useful tool for molecular diagnosis characterization Aim: to develop a reliable NGS diagnostic tool for HHR and related disorders.

Patients and Methods: we develop a NGS panel including 13 genes related with HHR or other hypophosphatemic disorders, using Illumina TruSeq Custom Amplicon technology.

We analyzed 12 patients which have been sent to our laboratory for molecular genetic testing under suspicion of HHR based on clinical phenotype and laboratory studies but with no proven mutation in PHEX gene by Sanger sequencing or MLPA analysis or other hypophosphatemic disorder.

Results: A previously reported pathogenic variant (p.Arg153Gln) was found in SLC9A3R1 gene encoding NHERF1cotransporter, which interact with phosphate and sodium renal transporter NaPi2a in a 13 months old girl. There are only 5 reported cases with alterations in this gene and all of them were adult patients with nephrolithiasis. The patient was referred to our hospital due to hypercalcemia. She had poor weight gain and laboratory findings showed high serum calcium (16,6 mg/dl), mild serum phosphate (3.9 mg/dl), very low parathyroid hormone (PTH) (< 3 ng/ml), normal 25OHvit D (40 ng/ml) levels, and elevated urinary calcium/ creatinine rate (2), and low phosphate tubular reabsorption (85%). Ultrasound showed nephrolithiasis. Since she had hypophosphatemia and renal phosphate wasting with symptomatic severe PTH independent hypercalcemia probably secondary to excessive calcitriol production with hypercalciuria, a molecular alteration of CYP24A1 or SLC34A1genes was suspected.

Conclusion: NGS allowed to report for the first time the identification of a mutation in the SLC9A3R1 gene in a pediatric patient. An early diagnosis might improve long term outcome starting the right therapy to avoid progression of nephrolithiasis and nephrocalcinosis and chronic renal failure.

<![CDATA[SAT-070 Nutritional Deficiency of Calcium Mimicking P Seudohypoparathyroidism]]> <![CDATA[SAT-068 Bewilderment! Sex Chromosome Non-Invasive Prenatal Screening (NIPS) Results Differ from Phenotype and Postnatal Karyotype]]> <![CDATA[SAT-072 A Case of Solitary Hyperfunctioning Thyroid Nodule Harboring Papillary Thyroid Carcinoma in a Pediatric Patient]]> <![CDATA[SAT-058 A Rare Case of Primary Hyperparathyroidism in a Pediatric Patient]]> A) of unknown clinical significance. Case presentation: A 10-year-old male with a history of constipation presented to the emergency department with five days of abdominal pain and emesis. Initial workup revealed high serum calcium (Ca) of 17.3 mg/dL (8.7-10.7) and ionized Ca (ICal) of 2.01 mmol/L (0.95-1.32). Further evaluations revealed low phosphorus level 3.5 mg/dL (4.5-6.5) and high parathyroid hormone level (iPTH) of 329.2 pg/mL (8.0-85.0). These findings were consistent with PHPT. Neck US demonstrated a cervical mass in the mid-right thyroid measuring 0.5 x0.3 x0.5cm, questionable for parathyroid adenoma, which was confirmed with 99mTc-MIBI scintigraphy and neck CT. His Ca level initially responded to fluid resuscitation and Lasix, with Ca level decreasing to 13.6. However, on hospital day two, his Ca level became refractory to all interventions, rising to 16 and prompting the use of bisphosphonates. The patient underwent neck exploration with partial parathyroidectomy and lymph node excision. Pathology revealed hypercellular parathyroid tissue consistent with parathyroid hyperplasia. Intraoperatively iPTH was reduced from 3,134.7 to 79.8 and remained within normal limits since. Postoperatively course was uncomplicated, and the patient was discharged home on oral Ca carbonate and vitamin D. A genetic evaluation was remarkable for a change in the RET gene (3.2C>A), a finding of unknown clinical significance. This change has not been seen in association with an individual who fulfills the clinical diagnosis of MEN2A. To further determine if the variant identified in the RET gene is a benign variant, the mother was tested for MEN2A and was negative. Father could not be tested, but family history was significant for thyroid malignancies. The patient is currently doing well four months postoperatively. His Ca level remains normal. Due to the genetic finding and the concern of MEN2A syndrome, the patient is followed closely by pediatric endocrinology and genetics. Conclusion: PHPT is a common endocrine disorder in adults but rare in children. The diagnosis of pediatric PHPT is almost always delayed due to atypical presentation and rarity of the disease. As secondary organ damage is common, a multi-organ assessment is mandatory. Due to the association with other syndromes, a genetic evaluation should be performed. ]]> <![CDATA[SAT-078 Griscelli Syndrome and Late Endocrine Effects After Stem Cell Transplant]]> <![CDATA[SAT-075 Pulmonary Hypertension in a Patient with Neonatal Graves Disease]]>