ResearchPad - Endocrinology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Corrigendum: Fertility Preservation for Child and Adolescent Cancer Patients in Asian Countries]]> https://www.researchpad.co/product?articleinfo=N974a0db9-ab69-4057-88ba-cf298131b8a0 ]]> <![CDATA[OR27-05 Sexual Desire Changes in Transgender Individuals upon Initiation of Hormone Treatment; Results from the Longitudinal ENIGI Study]]> https://www.researchpad.co/product?articleinfo=N7eb804c0-2b46-40a3-89ac-7cdecc8d539a

Abstract

Introduction: Several steps in the transitioning process may affect sexual desire in transgender people. This is often underexposed by those providing gender affirming care. Testosterone therapy in transgender men (TM) generally leads to increasing frequency of desire, masturbation, sexual fantasies and arousal. Studies in transgender women (TW) are inconclusive: some report an increase in the prevalence of hypoactive sexual desire after initiation of hormone therapy, whereas others have shown a positive impact of hormonal therapy on sexual quality of life. The current study prospectively assesses sexual desire during the first three years of hormonal therapy (HT) in transgender people. Methods: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Sexual desire was prospectively assessed in 766 participants (401 TW, 364 TM) by Sexual Desire Inventory (SDI) during a three-year follow-up period, starting at the initiation of hormone treatment (HT). SDI scores were analyzed as total, dyadic and solitary SDI scores. At baseline, psychological questionnaires were administered. Sex steroids were measured at each follow-up visit. Data were analyzed cross-sectionally and prospectively. Results: In TW, total, dyadic and solitary SDI scores decreased during the first three months of HT. However, after 36 months, total and dyadic SDI scores were higher than baseline scores. Solitary scores after 36 months were comparable to baseline scores. In TM, total, dyadic and solitary SDI scores increased over the first three months, remaining stable thereafter. However, total and dyadic SDI scores after thirty-six months were comparable to baseline scores, whereas solitary scores remained higher than baseline. Factors associated with a prospective increase in SDI scores included having undergone gonadectomy, no longer experiencing vaginal bleedings (in TM) or higher gender dysphoria levels at baseline (in TM only). Factors associated with higher cross-sectional SDI scores included being in a relationship, undergoing gonadectomy, no longer experiencing vaginal bleedings (TM), lower gender dysphoria scores (TW only) and lower body dysphoria scores (TW only). Conclusion: Gender affirming hormonal therapy induces short-term changes in sexual desire in transgender people. Over a longer period of time, a net increase in dyadic sexual desire in TW receiving feminizing HT was observed. Sexual desire scores comparable to baseline in TM receiving virilizing HT were found. We observed no correlation between sexual desire and absolute serum testosterone levels. However, other factors, including undergoing gonadectomy, persistence of vaginal bleedings (in TM) and psychological factors may influence sexual desire in transgender people.

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<![CDATA[MON-103 Pattern and Predictors of Thyroid Dysfunction Among Paediatric Endocrine Referrals at Tertiary Care Centre: A Longitudinal Study]]> https://www.researchpad.co/product?articleinfo=Ne9f15cd0-a7ca-43ee-bbe8-1a4e76e29118

Abstract

Background Post iodisation era has experienced gradual change in pattern of thyroid disorders among paediatric population with autoimmunity taking precedence over iodine deficiency disorders and subclinical hypothyroidism (SCH) now more frequently diagnosed but inappropriately managed. Aims This study was conducted to evaluate pattern of abnormal thyroid function among children referred to our tertiary care centre, to ascertain characteristics that influence treatment decisions and to follow them for various outcome measures. Design It was an observational longitudinal follow up study where all children less than 18 years, referred to our outpatient clinic for suspected thyroid disorder were recruited. Demographic data, personal and family history, clinical features were noted and laboratory tests including TT4, TT3, TSH, anti-thyroid peroxidase(antiTPO) and anti-thyroglobulin(antiTG) antibody were conducted in study subjects. Management was based on the clinical judgment of the attending endocrinologist. Patients were followed at 6 week, 3 months, 6 months and one year with clinical and laboratory work up at each visit. Results A total of 241 subjects aged 18 days to 17 years were included out of which 62.25% were females. Initial evaluation revealed SCH in 40% of refereed subjects, overt hypothyroidism (OH) in 33%, congenital hypothyroidism (CH) in 18% and overt thyrotoxicosis in 5%. Autoimmune thyroiditis constituted the major cause of hypothyroidism in the OH group with significantly higher prevalence of anti-TPO and antiTG antibody in comparison of SCH group (61% vs 31%; 45% vs 21.9%, p<0.05) respectively. All subjects in OH group were treated whereas 76% subjects in SCH group were treated and the mean dose of L thyroxine required to treat OH was significantly higher (2.31+1.1ug/kg/day vs 1.76+1.07ug/kg/day; p<0.001) in comparison of SCH group. A major independent predictor of treatment in SCH was initial TSH which was significantly higher in the treated group (11.65 + 3.80 uIU/ml vs 9.24 + 1.31 uIU/ml; p<0.001). Subjects with congenital hypothyroid presented at a mean age of 6 months (18 days to 2 years) with most common aetiology being thyroid hypoplasia and dyshormonogenesis

(20% each). Graves’ disease was diagnosed in 11 out of 12 subjects with thyrotoxicosis and were treated with antithyroid drugs. Overall 85.5% of refereed subjects were treated and after one-year follow up management was found to be adequate in 81% subjects. Conclusions The evolving trend of diagnosing children having nonspecific symptoms with SCH is a matter of concern as many are subjected to the burden of unwanted prolonged treatment and frequent testing as highlighted in our study. Delayed presentation of CH in our study warrants active surveillance of children at birth for thyroid disorders to avoid long term adverse effects on mental development.

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<![CDATA[SAT-081 Hidden in Plain Sight: Rethinking Our Approach to Allan-Herndon-Dudley Syndrome]]> https://www.researchpad.co/product?articleinfo=N68c659ab-8372-4f04-bac2-0fcc876189db

Abstract

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.

References:

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.

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<![CDATA[SAT-553 Use of Optimal Cutting Temperature Compound (OCT)-Embedded Adrenal Tumor Tissue for Intratumoral Steroid Hormone Profiling]]> https://www.researchpad.co/product?articleinfo=Nf1d360d7-889c-4ee1-9bda-7f5673186c66

Abstract

Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension, accounting for 5-8% of all hypertension. PA is most commonly attributed to an aldosterone-producing adenoma (APA) or to bilateral hyperaldosteronism (BHA). Mutations in the inward-rectifying K+ channel (mKCNJ5), which increase autonomous aldosterone production, are most frequently detected in APAs. APAs with mKCNJ5 display aberrant expression of aldosterone synthase (CYP11B2) and 17α-hydroxylase (CYP17A1), which are involved in aldosterone and cortisol synthesis, respectively. Co-expression of these enzymes results in the production of a set of “hybrid” steroids, which have been proposed as serum biomarkers. The relative production of hybrid steroids in adrenal tumors vs. adjacent normal adrenal (NA) tissue has not been investigated. Objectives: To determine the utility of OCT-embedded adrenal tumor tissue for steroid profiling. To use immunohistochemistry (IHC)-guided OCT tumor capture for intratumoral hybrid steroid profiling in mKCNJ5 APA and NA tissue. Methods: OCT-embedded adrenal tissue from 9 patients (8 women, Age 45.9 ± 3.3 years) with APAs harboring known KCNJ5 mutations were used for the study. Where available OCT-embedded normal adrenal (NA) tissue adjacent to APAs were used as controls (n=4). IHC was performed for CYP11B2 and CYP17A1 on OCT tissue allowing guided APA capture from serial sections. Steroids were extracted from APA and adjacent NA tissue, and quantified by liquid chromatography/tandem mass spectrometry. Steroids measured were normalized to the protein content of the extracted tissue. Results: Compared to NA, APA tissue demonstrated 23-, 5.6- and 6.4-fold higher levels of aldosterone, 11-deoxycorticosterone, and 18-hydroxycorticosterone, respectively (P<0.05). In addition, the “hybrid” steroid products, 18-oxocortisol and 18-hydroxycortisol, were significantly elevated in APA vs. NA (P<0.01). Conversely, the adrenal androgens dehydroepiandrosterone and 11-hydroxyandrostenedione were lower in APA as compared with NA (P<0.05). All mKCNJ5 APAs were also found to co-express CYP11B2 and CYP17A1. Conclusion: IHC-guided mKCNJ5 APA capture and steroid extraction identified a distinct intratumoral hybrid steroid signature that associated with co-expression of CYP11B2 and CYP17A1.These findings also demonstrate that OCT-embedded tissue can be used to accurately define intra-tissue steroid profiles, which will have application for steroid-producing and steroid-responsive tumors.

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<![CDATA[Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p]]> https://www.researchpad.co/product?articleinfo=N558cdad7-5acf-4a6f-9ed8-7fa1e3705457

Abstract

Objective: The present study aimed to investigate the regulatory role of long non-coding RNA plasmacytoma variant translocation 1 (PVT1) on high glucose (HG)-induced mouse mesangial cells (MMCs).

Methods: PVT1 expression in diabetic nephropathy (DN) mice and HG-induced MMCs was detected by qRT-PCR. EdU and Colony formation, Annexin V-PI staining, Muse cell cycle, Scratch, and Transwell assays were performed to detect the cell proliferation, apoptosis, cell cycle, migration, and invasion, respectively. The contents of fibrosis factors in cell-culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to detect the expression of factors involved in apoptosis, cell cycle, migration and invasion, fibrosis, and PI3K/Akt/mTOR pathway. The targeting relation between miR-93-5p and PVT1 was predicted by StarBase3.0 (an online software for analyzing the targeting relationship) and identified by Dual-luciferase reporter (DLR) assay.

Results: PVT1 was overexpressed in DN kidney tissues and HG-induced MMCs. HG-induced MMCs exhibited significantly increased EdU-positive cells, cell colonies, S and G2/M phase cells, migration and invasion ability, and contents of fibrosis factors, as well as significantly decreased apoptosis rate compared with NG-induced MMCs. HG significantly up-regulated Bcl-2, CyclinD1, CDK4, N-cadherin, vimentin, Col. IV, FN, TGF-β1 and PAI-1, and down-regulated Bax, cleaved caspase-3, cleaved PARP, and E-cadherin in MMCs. Silencing of PVT1 eliminated the effects of HG in MMCs and blocked PI3K/Akt/mTOR pathway. MiR-93-5p was a target of PVT1, which eliminated the effects of PVT1 on HG-induced MMCs.

Conclusions: PVT1 silencing inhibited the proliferation, migration, invasion and fibrosis, promoted the apoptosis, and blocked PI3K/Akt/mTOR pathway in HG-induced MMCs via up-regulating miR-93-5p.

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<![CDATA[SAT-LB92 Sex Hormones Therapy Differentially Modulates HDL Function in Transgender Individuals]]> https://www.researchpad.co/product?articleinfo=N07ce78be-318c-4da0-8ad0-8d426fa74e12

Abstract

Background/aim: The main proposed atheroprotective function of high-density lipoproteins (HDL) lays on their role to promote macrophage cholesterol efflux. An insightful way to learn more about the effects of sex hormones on HDL function is to study changes during hormone therapy. The present study was aimed at evaluating the effects of exogenous sex hormones administration on HDL cholesterol efflux capacity (CEC) within transgender individuals. CEC estimates the ability of HDL to remove cholesterol from cells, i.e. the initial step in reverse cholesterol transport.

Subjects/Methods: Transmen were treated with testosterone gel, a mix of testosterone esters once every three weeks) or testosterone undecanoate once every twelve weeks, whereas transwomen were treated with either oral estradiol valerate or a transdermal application of estradiol (patches). Cyproterone acetate was prescribed as a testosterone-blocking agent to all transwomen. HDL function was evaluated by a radioisotopic technique. Hormone levels, lipids and HDL function were evaluated after one year of follow-up.

Results: In transmen (n= 15), testosterone markedly increased (+ 97%; p < 0.0001), whereas luteinizing hormone (LH) decreased significantly (- 64%; p = 0.049). Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were not affected by testosterone treatment, whilst triglycerides (TG) were raised (+ 11.76%; p = 0.0078) and HDL-C reduced (- 19.6%, p=0.0103). Concerning HDL CEC, only the aqueous diffusion process was lowered (- 9.8%; p = 0.0032), an effect directly correlated with HDL-C changes (r = 0.6242, p = 0.0002). Total-, ATP-binding cassette transporter (ABCA1)-, and ABCG1-mediated CEC were not affected by testosterone treatment. In transwomen (n= 15), estradiol levels were raised (+200%, p=0.013) whereas LH and testosterone significantly reduced, i.e. - 97% for both. Relative to lipids, estradiol supplementation reduced total cholesterol (- 10.7%, p=0.0017), HDL-C (- 14.3%, p = 0.0024) and LDL-C (- 10.9%, p = 0.0058). Total HDL CEC decreased (- 11%, p=0.0001) with a specific decrement in CEC mediated by the ATP-binding cassette transporter (ABCA1) (-24%, p = 0.0003) and aqueous diffusion (-4.7%, p = 0.0014). This last was associated to a reduction in HDL-C (r = 0.4084, p = 0.0251). Conversely, the drop in ABCA1 and total CEC did not associate to reductions in HDL-C levels.

Conclusions: In transmen, testosterone supplementation was associated with a reduction in aqueous diffusion-mediated CEC, an effect potentially dependent to HDL-C changes. In transwomen, estrogen significantly decreased HDL function (CEC), independent of HDL-C levels changes.

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<![CDATA[SAT-559 Patients with Hyperaldosteronism Have Higher Prevalence of Obstructive Sleep Apnea. From the National Inpatient Sample]]> https://www.researchpad.co/product?articleinfo=N4edb7168-4dde-47a9-a88f-1e2442e60f4b

Abstract

Introduction: Previous studies suggested that aldosterone excess may worsen obstructive sleep apnea (OSA) through causing peri-pharyngeal edema. Objective: In this study we sought to examine if hyperaldosteronism is associated with OSA. Methods: The National Inpatient Sample (NIS) data was queried for adults with diagnosis of primary and secondary hyperaldosteronism during the years 2012 - 2015. Patients with hyperaldosteronism were identified using the international classification of disease (ICD-9). Each patient who was diagnosed with hyperaldosteronism was matched to randomly selected controls at a 1:4 ratio by age, gender and year of hospitalization. A multivariable logistic regression model was used to estimate the adjusted odds ratio (aOR) of OSA among patients with hyperaldosternoism. We adjusted for patient demographics, socioeconomic factors, hospital factors and clinical comorbidities. Subgroup analysis was performed based on gender, race and age groups; young adults (aged 18–35 years), middle aged (> 35-<55 years) and older adults (aged > 55 years). Results: There were 23,465 patients diagnosed with hyperaldosteronism identified. The mean age was 59 (standard error of the mean (SEM): 0.1. Females represented 48.5%. Compared to control, patients with hyperaldosteronism had higher prevalence of hypertension, CHF, stroke, obesity, diabetes, renal failure and lower prevalence of tobacco use and COPD. The proportions of African Americans were higher among patients with hyperaldosteronism compared to the control 30.1 vs 15.5, p<0.001. Patients with hyperaldosteronism had higher prevalence of OSA 16.4 vs 8.3, p<0.001. On multivariate analysis, hyperaldosteronism was independently associated with higher odds for OSA with aOR 2.01 (95%CI: 1.81–2.23) p<0.001. On subgroup analysis, similar findings were observed irrespective of gender, age group or race. Conclusion: Prevalence of OSA is higher among patients with hyperaldosteronism. Physicians may need to consider a case detection of hyperaldosteronism in patients with OSA and hypertension. Similarly we suggest to evaluate patients with hyperaldosteronism for OSA.

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<![CDATA[MON-001 Peripartum Sertraline (Zoloft®) Increases Pup Mortality Immediately Postpartum]]> https://www.researchpad.co/product?articleinfo=N1efe9627-f727-4529-be01-2e6ef9b09d9e

Abstract

Peripartum and postpartum depression can be detrimental to both the mother and the developing child. Use of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), is common during the peripartal period and SSRIs have been the leading prescribed antidepressant to treat maternal depression. One of the most commonly prescribed SSRIs is sertraline (Zoloft®) because of the limited fetal teratogenic effects observed, unlike maternal paroxetine (Paxil®) usage which can manifest in fetal cardiovascular defects. Fluoxetine (Prozac®), like sertraline, has previously been shown to have limited teratogenic effects, however, we have shown treatment with fluoxetine for the entire period of pregnancy and lactation in mice compromises pup bones at weaning resulting in decreased long bone length and head circumference. Furthermore, maternal fluoxetine usage results in a sustained reduction in maternal bone mineral density post weaning, which may lead to long-term osteopenia, putting the mother at risk for bone-related disorders later in life. We hypothesized sertraline, like fluoxetine, will compromise maternal bone postpartum and fetal bone development at weaning. Treatment with sertraline in C57BL/6 dams throughout pregnancy and lactation reduced litter size (5.4 pups/dam) and increased pup mortality during the first 24 hours postpartum (20% dead pups/litter) compared to controls (6.8 pups/dam, 5% dead pups/litter, respectively; P < 0.018). Maternal calcium transporters (Orai1 and Serca2) were downregulated in the mammary gland in sertraline-treated dams on day 21 of lactation (P < 0.0032). Together, our data suggests in utero pharmacological exposure to sertraline may induce a failure to thrive in the pups and alters calcium metabolism in the dam. SSRI exposure during pregnancy and lactation may adversely affect the developing neonate(s) as well as have lasting impacts on the mother.

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<![CDATA[Negative pressure wound therapy compared with standard moist wound care on diabetic foot ulcers in real-life clinical practice: results of the German DiaFu-RCT]]> https://www.researchpad.co/product?articleinfo=Nba328c1c-851b-4fb9-a7c1-fe8db5c2232b

Objectives

The aim of the DiaFu study was to evaluate effectiveness and safety of negative pressure wound therapy (NPWT) in patients with diabetic foot wounds in clinical practice.

Design

In this controlled clinical superiority trial with blinded outcome assessment patients were randomised in a 1:1 ratio stratified by study site and ulcer severity grade using a web-based-tool.

Setting

This German national study was conducted in 40 surgical and internal medicine inpatient and outpatient facilities specialised in diabetes foot care.

Participants

368 patients were randomised and 345 participants were included in the modified intention-to-treat (ITT) population. Adult patients suffering from a diabetic foot ulcer at least for 4 weeks and without contraindication for NPWT were allowed to be included.

Interventions

NPWT was compared with standard moist wound care (SMWC) according to local standards and guidelines.

Primary and secondary outcome measures

Primary outcome was wound closure within 16 weeks. Secondary outcomes were wound-related and treatment-related adverse events (AEs), amputations, time until optimal wound bed preparation, wound size and wound tissue composition, pain and quality of life (QoL) within 16 weeks, and recurrences and wound closure within 6 months.

Results

In the ITT population, neither the wound closure rate (difference: n=4 (2.5% (95% CI−4.7% – 9.7%); p=0.53)) nor the time to wound closure (p=0.244) was significantly different between the treatment arms. 191 participants (NPWT 127; SMWC 64) had missing endpoint documentations, premature therapy ends or unauthorised treatment changes. 96 participants in the NPWT arm and 72 participants in the SMWC arm had at least one AE (p=0.007), but only 16 AEs were related to NPWT.

Conclusions

NPWT was not superior to SMWC in diabetic foot wounds in German clinical practice. Overall, wound closure rate was low. Documentation deficits and deviations from treatment guidelines negatively impacted the outcome wound closure.

Trial registration numbers

NCT01480362 and DRKS00003347.

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<![CDATA[SUN-LB13 Idiopathic Infantile Hypercalcemia Secondary to CYP24A1 Mutation: A Rare Case Without Exogenous Vitamin D Supplementation]]> https://www.researchpad.co/product?articleinfo=Nd220ef68-8cc3-4600-9f83-cfcc3e10a03f

Abstract

Background: Mutations in CYP24A1, which encodes 24-hydroxylase, the key enzyme for Vitamin D breakdown, cause symptomatic hypercalcemia and nephrocalcinosis in infants on Vitamin D supplementation. New, symptomatic diagnoses of idiopathic infantile hypercalcemia without exogenous supplementation are rare. Previous case reports describe a seasonal effect with worsening hypercalcemia and hypercalciuria during summertime, attributed to increased sun exposure and endogenous Vitamin D production. Clinical Case: A 10-month-old female presented to endocrine care with hypercalcemia and nephrocalcinosis, detected on renal ultrasound (US) due to history of UTI. Her first renal US and serum calcium (Ca) at 3mo of age were normal. Subsequent renal US at 6mo and 9mo of age demonstrated nephrocalcinosis, prompting nephrology and endocrine evaluation. History was significant for failure to thrive. She was born in the fall, with worsening hypercalcemia and nephrocalcinosis during the summer. Diet consisted of standard infant formula and age appropriate solid foods with no added Vitamin D supplementation (~300 IU/day in her formula). She had no family history of nephrocalcinosis, nephrolithiasis, bone disease, or disorders of Ca regulation. Initial labs were notable for Ca corrected for albumin 11.5 (7.8-11.1 mg/dL), PTH <4 (8.7-77.1 pg/mL), 25-OH-Vitamin D 81 (30-96 ng/mL), 1,25-OH-Vitamin D 23.1 (26.1-95 pg/mL), Urine Ca/creatinine ratio of 0.9 mg/mg (<0.81), normal chromosomal microarray, and normal thyroid function tests. She was started on reduced mineral formula PM 60/40. One week later, repeat Ca level increased to Ca corrected 14.2 (7.8-11.1 mg/dL). She was admitted for IV fluids and pamidronate, and was transitioned to a low Ca and Vitamin D formula (Calcilo), with improvement in Ca levels. Testing revealed an increased ratio of 25-OH-Vitamin D to 24,25-OH-Vitamin D of 192 (normal <25), and genetic testing showed 2 pathogenic missense mutations in CYP24A1 genes: c.1226T>C p.(Leu409Ser) and c.1186C>T p.(Arg396Trp). The Leu409Ser mutation has shown a small amount of 24-hydroxylase activity in previous in vitro analysis. She has continued a low Ca diet with stable Ca corrected of 10.7-10.8 (8.7-9.8 mg/dL) and significantly improved weight gain. Conclusion: This is one of the few documented cases of symptomatic idiopathic infantile hypercalcemia secondary to CYP24A1 mutation in an infant without exogeneous Vitamin D supplementation. Her nephrocalcinosis and hypercalcemia worsened over the summer, suggesting increased sun exposure may have been a contributing factor. This case demonstrates that 1,25-OH-Vitamin D levels may be normal or low in this condition, particularly for individuals with the Leu409Ser mutation who may retain partial 24-hydroxylase function.

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<![CDATA[MON-072 A 2 -Year Old Girl with Turner Syndrome and Neurofibromatosis Type 1]]> https://www.researchpad.co/product?articleinfo=Nce352e8d-4ca2-49d6-9ba2-6b5add376a4e

Abstract

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.

1.

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

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<![CDATA[SUN-001 Identification of Dehydroepiandrosterone-s (DHEA-s) Elevation Due to Performance Enhancing Supplements]]> https://www.researchpad.co/product?articleinfo=N4db3bce9-56a1-451d-a7fc-3a7447ec2cd1

Abstract

Background: Recreational athletes and individuals in certain occupations may utilize supplements with the goal of enhancing their physical performance and strength. These individuals may be reluctant to provide their supplement use history due to the stigma associated with performance enhancing drugs. We report a case of supplement use causing elevated dehydroepiandrosterone sulfate (DHEA-S) levels in a young woman presenting with alopecia. Clinical Case: A 29-year-old Caucasian woman presented for evaluation of progressive alopecia spanning 7 years. She was initially managed by dermatology with topical ketoconazole and clobetasol creams followed by intra-lesional triamcinolone injections. Despite treatment, she had minimal improvement. She reported menarche at age 15 with normal regular monthly menstrual cycles and normal breast development. She has no significant medical history. Physical exam was unremarkable other than localized alopecia and athletic build. She denied any medication use. Routine laboratory screening showed a DHEA-S of 624 ug/dL (ref. 35-430) with repeat DHEA-S at 602.2 ug/dL. Complete blood count, metabolic panel, thyroid function test, total/free testosterone, estradiol, 17-hydroxprogesterone, urinary 17-ketosteroids, prolactin, and iron panel were all within normal limits. Anabolic abuse screen was negative. Adrenal imaging was normal. After discussion on elevated DHEA-S results, patient revealed that she was taking a supplement that contained enobosarm (Ostarine). She was instructed to discontinue the supplement and repeat her labs but she was lost to follow up. Discussion: Developed in 1997, enobosarm is a selective androgen receptor modulator (SARMs) that is increasingly used as a performance-enhancing drug. SARMs have tissue specific androgenic receptor effect and patients on SARMs can present with a completely normal hypothalamic-pituitary gonadal axis without biochemical evidence of hyperandrogenism; which was the case in our patient. Conventional anabolic drug abuse screens do not detect SARMs. There have been multiple studies that have evaluated different performance enhancing supplements and nearly 25% of tested products contained compounds that were not correctly labeled. It is therefore uncertain what may have raised this patient’s DHEA-S levels, but the authors theorize the supplement may have contained exogenous DHEA rather than a direct effect of enobosarm. Unfortunately, there is paucity of data or literature on the effect of SARMs on androgen hormone synthesis and DHEA-S levels. A PubMed search for SARMs and DHEA-S levels led to zero returns. It is important for clinicians to recognize and identify the possibility of SARM or supplement use in order to guide diagnostic and management decisions. Further investigation is needed to understand the impact of SARMs on laboratory data and its long term effects.

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<![CDATA[SAT-077 Two Cases of Hypoparathyroidism Due to Activating Calcium Sensing Receptor Mutation]]> https://www.researchpad.co/product?articleinfo=N6fbfca46-68dc-43ba-816e-5a436a887ec8

Abstract

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.

Conclusion:

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.

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<![CDATA[SAT-567 Hypertriglyceridem...From Mild to Fatal!... Is Time for Awareness]]> https://www.researchpad.co/product?articleinfo=N403a9a08-7737-487a-b02b-3ce87d9aa3e1

Abstract

Hypertriglyceridemia… From mild to fatal! … Is Time for Awareness.

Hypertriglyceridemia can be primary or acquired. High triglycerides are related to complications such as pancreatitis and there is a positive correlation between hypertriglyceridemia and atherosclerotic burden. In this case series we aim to discuss pancreatitis as a hypertriglyceridemia complication and to acknowledge the importance of prevention and management. Is there something we can do to raise awareness and avoid complications as in the cases?

All cases present with chief complaint of epigastric cramp-like abdominal pain, radiating to the back, nausea/vomiting and with highly lipemic blood samples.

38y/o F admitted after been found with lipase 268 U/L (n<60 U/L), amylase 131 U/L (n<100 U/L) and findings of pancreatitis on CT scan. Patient with one-year history of T2DM refers this is the 4th episode of pancreatitis and reports that last time she was told about having triglycerides in 4,000 mg/dL for which she went to her physician that prescribe her Fenofibrate. Patient triglycerides were 7,931 mg/dL (n<199 mg/dL) and found with poorly controlled diabetes with HgbA1c 8.4%. She was properly managed, and triglycerides decrease to 1,309 mg/dL.

31y/o F with elevated lipase (237 U/L, n<60 U/L) and findings of pancreatitis on CT scan was admitted and found with 7,755 mg/dL triglycerides. She refers to have endometriosis for which she uses OCPs for >5years. She develops intractable abdominal pain along with abdominal distension and progress to Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation. She had a prolonged ICU stay and after management triglycerides decrease to 95mg/dL, symptoms resolve, and patient was discharge.

48y/o F with pancreatitis, lipase levels 1,452 U/L, amylase 744 U/L and positive imaging findings. Patient with uncontrolled diabetes (HgbA1c 11.0%) and breast mass s/p lumpectomy for which she used tamoxifen for the last 2 years. Triglycerides 7,444mg/dL on Gemfibrozil started due to previous levels found >4,000 mg/dL on outpatient evaluation. She deteriorates clinically and develops renal failure, abdominal compartment syndrome, respiratory distress and hypotension requiring mechanical ventilation and vasopressors. On repeated abdominal CT pancreas changes were suggestive of fulminant pancreatitis. Patient did not respond to treatment and passed away 48 hours after admission.

Hypertriglyceridemia complications can be mild or fatal as in these cases. They were evaluated by a primary care physician before complications occur and had secondary causes that predispose them to hypertriglyceridemia, but they were not addressed, reason for which these scenarios raise concern of how much we know? How much we are doing to prevent these outcomes?... Awareness of hypertriglyceridemia management and adverse effects is necessary to avoid complications and fatal outcomes. Is time!

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<![CDATA[SUN-083 Screening of Vitamin D and Calcium Concentrations in Neonates of Mothers at High Risk of Vitamin D Deficiency]]> https://www.researchpad.co/product?articleinfo=N91dff92b-0cd1-4b70-8bee-76eb53e09203

Abstract

Objective: The aim of this study was to determine, retrospectively, the serum 25OHD and calcium concentrations of screened neonates of mothers at high risk of 25OHD deficiency (maternal 25OHD < 25 nmol/L or unknown vitamin D concentrations and risk factors for vitamin D deficiency) and critically analyse whether their measurements contributes to the management of these neonates.

Methods: Serum 25OHD and calcium concentrations from 600 samples of umbilical cord blood or venous blood collected from neonates over a 12-month period were analysed. 25OHD concentrations were reported for all while both the corrected calcium concentrations and vitamin D concentrations were available for 569 samples.

Results: There was little or no evidence of association between neonatal 25OHD concentrations and gender, gestational age or birth weight. There was a high prevalence of vitamin D insufficiency (27.6%, 30–50 nmol/L) and deficiency (21.3%, < 30 nmol/L) in neonates from high-risk maternal groups. There was a statistically positive but weak correlation (ρ = 0.22, P < 0.0001) between serum calcium and 25OHD concentrations. Only 7 neonates out of 569 (1.2%) had calcium levels in the hypocalcaemic range; however, a significant number (47.6%) were reported to be in the hypercalcaemic range. Nearly all of these were venous samples collected in first 24 hours after birth. We calculated the reference interval for corrected calcium from our data of venous samples in first 24 hours and the upper limit was significantly higher (2.38–3.04 mmol/L) than the standard reference range used.

Conclusion: Vitamin D deficiency is prevalent in neonates of high-risk mothers but the risk of hypocalcaemia due to vitamin D deficiency at birth is low. Screening neonates entails blood testing which can cause distress to neonates and their parents, substantial impost on staff and financial burden on the health care system. 25OHD deficiency is corrected relatively easily in neonates with supplementation and vitamin D supplementation of neonates from birth without routine screening appears to offer better value of care. Also, the data from this study suggest that the paediatric reference range for corrected calcium concentrations in neonates is higher and the paediatric reference range should be reconsidered.

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<![CDATA[SUN-LB1 Atypical Presentation Of Myocardial Infarction In A Young Patient With Polycystic Ovarian Syndrome]]> https://www.researchpad.co/product?articleinfo=Ndfe7c0dd-4cdf-4291-8bec-fd2f6c08246a

Abstract

Background: Polycystic ovarian syndrome (PCOS) is a very common and complex endocrine problem in women of childbearing age, with a prevalence of 4 to 12% globally. Myocardial infarction (MI) is the leading cause of death in women worldwide. PCOS increases the risk of MI because of chronic inflammation, endothelial dysfunction, impaired pulse wave velocity and its association with metabolic syndrome, and hormonal imbalance.

Clinical Case: A 36-year-old female with a history of PCOS, hirsutism, severe acne on spironolactone, presented to ER with a chief complaint of lower back pain for 10 days that started after lifting a 60-pounds printer. The pain was attributed to musculoskeletal type, one dose of ketorolac intramuscularly was given and she was discharged on cyclobenzaprine. The next morning, she presented with worsening back pain and new-onset vomiting. Physical exam was normal except for BMI 34.6kg/m2; vitals were stable. Lab work showed elevated troponin of 1.43 which rose to 10.6 ng/ml (normal 0.00-0.034), cholesterol 125 mg/dL (less than 200), HDL 33 mg/dL (normal 40-59), LDL 164 mg/dL (normal 100-129). Electrocardiogram showed sinus tachycardia with Q wave changes in leads III and V1 to V3. Echocardiogram showed hypokinesia of left ventricular wall in the mid to apical anterior septum. Computed tomography (CT) scan of the thoracic spine was negative for abscess or fracture. CT of abdomen and pelvis as well as CT angiography chest were negative. Urine drug screening was also negative.

As her presentation was attributed to MI, patient was started on heparin drip, aspirin, atorvastatin, and metoprolol. She underwent cardiac catheterization that showed 99% ostial left anterior descending artery stenosis; a drug-eluting stent was successfully placed. After intervention her back pain resolved. She was discharged on dual antiplatelet therapy (aspirin and Prasugrel) along with atorvastatin, metoprolol and nitroglycerin.

Conclusion: This case suggests an association of PCOS with MI. A meta-analysis has shown a two-fold increase in risk of coronary artery disease in patients with PCOS (1). Future studies are need to examine opportunities for cardiovascular disease risk reduction in PCOS patients.

Reference:1. de Groot PCM, Dekkers OM, Romijn JA, Dieben SWM, Helmerhorst FM. PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis. Human Reproduction Update 2011. 17 495-500.

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<![CDATA[SAT-029 AMH Is Higher Across the Menstrual Cycle in Early Post-Menarchal Girls Than in Ovulatory Women]]> https://www.researchpad.co/product?articleinfo=N65ec8755-10f0-440a-b354-aceb0dc4ae7e

Abstract

Ovaries of young girls contain healthy and degenerating follicles from the primordial to antral stage, suggesting coordination of growth and atresia. At age 6 yrs, antral follicle (AF) number and size increase; by late puberty, AF count is higher than at any other life stage. The discovery of AMH, a biomarker of AFs, has facilitated the study of the immature ovary. AMH, a granulosa cell product of pre-antral and small AFs, inhibits primordial follicle growth and AF selection. As a marker of AF count, AMH should be highest during puberty, yet cross-sectional studies suggest that AMH peaks in the mid-20’s. In the current studies we compared AMH levels in early post-menarchal girls and regularly cycling adults. The rich phenotypic data available for this adolescent cohort (Sun 2019) was used to investigate further the relationship between AMH, LH, FSH, and sex steroids, and the propensity for anovulatory cycles (ANOV) in girls. 23 healthy girls (12.8–17.6 yrs;1.7±0.2 yrs post-menarche; 56% overweight/obese [OB]) underwent hormone measurements and pelvic ultrasounds during 2 consecutive menstrual cycles. Cycles were classified as ovulatory (OV) based on an LH and E2 peak and P4 >1.65 ng/mL (Sun 2019). AMH was measured in a random subset of samples (5x/subject) with the Ansh ultrasensitive ELISA. Maximum average ovarian volume (VOL) was calculated in the absence of a dominant follicle. Hormones were compared with data from 32 historic adult controls (18–34 yrs; 44% OB) with regular cycles (Lambert-Messerlian 2016). In adults, AMH was measured during the follicular and luteal phase of an OV (5x/subject) using the Ansh assay. AMH was compared among groups using a mixed model. AMH (in adults), LH (in both) and androgens (in girls) were natural log-transformed (ln) before analysis. 11 girls had 2 OV, 5 girls had 1 OV, and 5 girls had no OV; 2 could not be classified due to loss to follow-up. Girls had higher AMH than women (5.2 ± 0.3 vs. 3.3 ± 0.4 ng/mL; p<0.01) and girls with more OV tended to have lower AMH than those with ANOV (2 OV 4.5 ± 0.2, 1 OV 5.7 ± 1.1, 0 OV 6.8 ± 1.1 ng/mL; p=0.1). In girls, AMH correlated with ln_LH (r=0.4, p=0.02), ln_a’dione (r=0.4, p=0.04), ln_testosterone (r=0.5, p=0.02) and VOL (r=0.6, p=0.01) but not with FSH, E2, or BMI. In women, AMH correlated with E2 (r=-0.4, p=0.03) and not with ln_LH or BMI. Within-person variability in AMH was similar in girls and adults (CV 18%). During the early post-menarchal years, AMH levels exceed those of adults with OV, particularly among girls with ANOV, and correlate with LH and androgens. The finding of higher AMH in adolescents is consistent with previous studies demonstrating a peak in AF count during this stage of development. Investigation into how the normal ovary matures and is pruned of excess AFs, either by increased recruitment and growth or by atresia, may provide insights into the pathogenesis of PCOS, wherein follicles are arrested at the pre-antral and antral stage.

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<![CDATA[MON-076 Adrenal Hypoplasia Congenita - Is It Possible to Make This Diagnose in Previous “Idiopathic” Adrenal Insufficient Patients? Series of Cases]]> https://www.researchpad.co/product?articleinfo=Nd041173b-11a5-4bd0-97ff-958e81a2aeca

Abstract

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.

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<![CDATA[MON-068 The First Case in Korea, ZC4H2 Gene Mutation in Wieacker-Wolff Syndrome with Recurrent Hypoglycemia]]> https://www.researchpad.co/product?articleinfo=N6a2ba340-dbe4-45ae-9ffb-8ed6ea9915d7

Abstract

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.

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