Publications by authors named "Lefkothea P Karaviti"

29 Publications

  • Page 1 of 1

Type 1 Doing Well: Pilot Feasibility and Acceptability Study of a Strengths-Based mHealth App for Parents of Adolescents with Type 1 Diabetes.

Diabetes Technol Ther 2020 11 22;22(11):835-845. Epub 2020 May 22.

Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.

We evaluated the feasibility and acceptability of a pilot behavioral intervention delivered to parents of adolescents with type 1 diabetes (T1D) via mobile-friendly web app. The Type 1 Doing Well app aimed to promote supportive family diabetes management by helping parents recognize and reinforce teens' positive diabetes-related behaviors ("strengths"). Parents ( = 80, 74% recruitment) of adolescents (age range = 12-17 years, M = 15.3 ± 1.5 years, 59% female, 56% insulin pump, M hemoglobin A1c (HbA1c) = 9.0% ± 2.1%) were randomized 2:1 to intervention or control (i.e., usual medical care with or without app) for 3-4 months between diabetes appointments. The app prompted parents daily to track adolescents' strengths and generated weekly summaries of their teen's top strengths. Parents could access a library of text messages to praise their teens. Exploratory pre/post data included questionnaires (98% completed) and HbA1c. Parents used the app for M = 106.1 ± 37.1 days, logging in ≥once/day on 80% of days. Ninety-one percent of parents used the app ≥2 days/week on average. Parents viewed M = 5.6 ± 4.7 weekly summaries and "favorited" 15 praise texts in the library. App acceptability ratings (7-point scale) were high: Satisfaction 5.0 ± 1.5, Usefulness 4.8 ± 1.5, Ease of Use 6.2 ± 0.8, and Ease of Learning 6.5 ± 0.8. Parents ( = 48) and adolescents ( = 47) gave positive feedback and suggestions via qualitative interviews. There were no significant between-group differences for change in exploratory outcomes (HbA1c, questionnaires). Type 1 Doing Well was feasible to deliver and highly acceptable and engaging for parents of adolescents with T1D. It may have a larger impact on behavioral or clinical outcomes as part of a multicomponent intervention protocol. Trial Registration: ClinicalTrials.gov NCT02877680.
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http://dx.doi.org/10.1089/dia.2020.0048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698853PMC
November 2020

Patient and Caregiver Attitudes toward Disorders of Sex Development Nomenclature.

J Urol 2020 10 17;204(4):835-842. Epub 2020 Apr 17.

Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.

Purpose: The medical terminology applied to differences/disorders of sex development has been viewed negatively by some affected individuals. A clinical population of patients with differences/disorders of sex development and their caregivers were surveyed regarding current nomenclature, hypothesizing that those unaffiliated with support groups would have more favorable attitudes.

Materials And Methods: We recruited English and Spanish speaking patients 13 years old or older with differences/disorders of sex development and their caregivers at 5 national tertiary care clinics from July 2016 to December 2018. No diagnoses were excluded. Participants completed a survey rating terminology commonly applied to differences/disorders of sex development. Responses were compared between subgroups, including members vs nonmembers of a support group.

Results: Of 185 potential participants approached 133 completed the survey (72% response rate). Congenital adrenal hyperplasia (33%) was the most common diagnosis. "Variation of sex development" was the most liked term (37%) but was not liked more significantly than "disorders of sex development" (27%, p=0.16). No term was liked by a majority of respondents. "Disorders of sex development" (37%) and "intersex" (53%) were the only terms most frequently viewed unfavorably. Support group members were significantly more likely to dislike the term "intersex" (p=0.02) and to like "variation of sex development" (p=0.02).

Conclusions: A clinical population of patients and their caregivers had generally neutral attitudes toward nomenclature applied to differences/disorders of sex development. Members of a support group had clearer terminology preferences. "Variation of sex development" was the most liked term, and "disorders of sex development" and "intersex" were the most disliked. No term was liked by most respondents, and no clear alternative to the present nomenclature was identified.
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http://dx.doi.org/10.1097/JU.0000000000001076DOI Listing
October 2020

Visual Diagnosis: Multiple Falls and a Pigmented Skin Lesion in a 5-year-old Boy.

Pediatr Rev 2020 Jan;41(1):e1-e3

Baylor College of Medicine, Houston, TX.

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http://dx.doi.org/10.1542/pir.2017-0328DOI Listing
January 2020

Case 2: A 4-year-old Boy with Recurrent Vomiting.

Pediatr Rev 2019 Aug;40(8):425-427

Baylor College of Medicine, Houston, TX.

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http://dx.doi.org/10.1542/pir.2017-0280DOI Listing
August 2019

Case 2: 3-month-old Boy with Micropenis.

Pediatr Rev 2018 Jul;39(7):363-365

Department of Pediatrics, Section of Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.

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http://dx.doi.org/10.1542/pir.2017-0067DOI Listing
July 2018

Strengths-Based Behavioral Intervention for Parents of Adolescents With Type 1 Diabetes Using an mHealth App (Type 1 Doing Well): Protocol for a Pilot Randomized Controlled Trial.

JMIR Res Protoc 2018 Mar 13;7(3):e77. Epub 2018 Mar 13.

Section of Psychology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, United States.

Background: Supportive parent involvement for adolescents' type 1 diabetes (T1D) self-management promotes optimal diabetes outcomes. However, family conflict is common and can interfere with collaborative family teamwork. Few interventions have used explicitly strengths-based approaches to help reinforce desired management behaviors and promote positive family interactions around diabetes care.

Objective: The aim of this protocol was to describe the development of a new, strengths-based behavioral intervention for parents of adolescents with T1D delivered via a mobile-friendly Web app called Type 1 Doing Well.

Methods: Ten adolescent-parent dyads and 5 diabetes care providers participated in a series of qualitative interviews to inform the design of the app. The 3- to 4-month pilot intervention will involve 82 parents receiving daily prompts to use the app, in which they will mark the diabetes-related strength behaviors (ie, positive attitudes or behaviors related to living with or managing T1D) their teen engaged in that day. Parents will also receive training on how to observe diabetes strengths and how to offer teen-friendly praise via the app. Each week, the app will generate a summary of the teen's most frequent strengths from the previous week based on parent reports, and parents will be encouraged to praise their teen either in person or from a library of reinforcing text messages (short message service, SMS).

Results: The major outcomes of this pilot study will include intervention feasibility and satisfaction data. Clinical and behavioral outcomes will include glycemic control, regimen adherence, family relationships and conflict, diabetes burden, and health-related quality of life.

Conclusions: This strengths-based, mobile health (mHealth) intervention aims to help parents increase their awareness of and efforts to support their adolescents' engagement in positive diabetes-related behaviors. If efficacious, this intervention has the potential to reduce the risk of family conflict, enhance collaborative family teamwork, and ultimately improve diabetes outcomes.

Trial Registration: ClinicalTrials.gov NCT02877680; https://clinicaltrials.gov/ct2/show/NCT02877680 (Archived by WebCite at http://www.webcitation.org/6xTAMN5k2).
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http://dx.doi.org/10.2196/resprot.9147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871739PMC
March 2018

Bringing Back the Term "Intersex".

Pediatrics 2017 11;140(5)

Section of Endocrinology and Diabetes and.

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http://dx.doi.org/10.1542/peds.2017-0505DOI Listing
November 2017

A Multidisciplinary Approach to Puberty and Fertility in Girls with Turner Syndrome.

Pediatr Endocrinol Rev 2016 Sep;14(1):33-47

Department of Obstetrics and Gynecology. Baylor College of Medicine. Texas Children's Hospital, Houston, TX, USA.

Women with Turner Syndrome (TS) have a variety of medical needs throughout their lives; however, the peripubertal years are particularly challenging. From a medical perspective, the burden of care increases during this time due to growth optimization strategies, frequent health screenings, and puberty induction. Psychologically, girls begin to comprehend the long-term implications of the condition, including their diminished fertility potential. Unfortunately, clear guidelines for how to best approach this stage have not been established. It remains to be determined what is the best age to begin treatment; the best compound, dose, or protocol to induce puberty; how, when or what to discuss regarding fertility and potential fertility preservation options; and how to support them to accept their differences and empower them to take an active role in their care. Given the complexity of this life stage, a multidisciplinary treatment team that includes experts in endocrinology, gynecology, and psychology is optimal.
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http://dx.doi.org/10.17458/PER.2016.CCALM.MultidisciplinaryApproachDOI Listing
September 2016

Evidence-Based Management of Patients with 45,X/46,XY Gonadal Dysgenesis and Male Sex Assignment: from Infancy to Adulthood.

Pediatr Endocrinol Rev 2016 Mar;13(3):585-601

45,X/46,XY gonadal dysgenesis is a disorder of sexual differentiation with a wide clinical presentation, ranging from Turner-like females to individuals with genital ambiguity to azoospermic but otherwise normal-appearing males. Hence, patients can be assigned female or male sex. Female patients are managed according to the Turner Syndrome Guidelines, whereas males are managed on a case-by-case basis. Male patients present with multiple medical challenges: undervirilization, hypogonadism, gonadoblastoma risk, and short stature. Many require surgeries and hormonal treatments that are time-sensitive and irreversible. Nonetheless, these therapeutic decisions are made without evidence-based guidelines. This review describes the medical concerns and possible interventions in male patients with 45,X/46,XY dysgenesis for each stage of development. Interventions should be addressed within a patient-centered framework by a multidisciplinary team and after thorough discussion with the family. We use the GRADE system to appraise the existing evidence and provide recommendations based on the available evidence.
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March 2016

Residual manifestations of hypercortisolemia following surgical treatment in a patient with Cushing syndrome.

Int J Pediatr Endocrinol 2015 26;2015(1):19. Epub 2015 Aug 26.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Houston, TX USA.

Context: Cushing Syndrome is difficult to diagnose, and the comorbidities and persistent late effects of hypercortisolemia after treatment of the primary disease are challenging for the patient and the endocrinologist.

Objective: To report the case of a girl with obesity and hypertension, ultimately diagnosed with Cushing syndrome due to primary pigmented nodular adrenocortical disease. In this case, the complications of hypercortisolism persisted short term despite surgical intervention.

Patient: A 4 year old morbidly obese African-American girl with developmental delay presented with hypertensive emergency in the ER and 18-month history of progressive weight gain. Her previous history included premature adrenarche, hypertension, seizures and a random high cortisol with suppressed ACTH. She was subsequently stabilized, and a diagnostic work-up persistently demonstrated elevated cortisol and suppressed ACTH. An abdominal MRI showed bilateral adrenal multinodular disease, consistent with multinodular hyperplasia of the adrenal glands. Based on these findings the patient underwent a bilateral adrenalectomy, which confirmed primary pigmented nodular adrenocortical disease. The patient had a complicated, protracted post-operative course requiring adjustment of therapy for persistent hypertension. Two months after surgery, she was readmitted to the Emergency Department with hyperpyrexia and hypertension and succumbed to the complications of sepsis.

Conclusions And Outcome: This case highlights the significant diagnostic and therapeutic challenges in treating children with Cushing syndrome. Resolution of the source of hypercortisolemia does not imply regression of hypertension or recovery of the immune system. Although the child underwent bilateral adrenalectomy, persistent consequences of prolonged severe hypercortisolism contributed to her death two months later.
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http://dx.doi.org/10.1186/s13633-015-0014-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551381PMC
August 2015

Androgen Insensitivity Syndrome: Management Considerations from Infancy to Adulthood.

Pediatr Endocrinol Rev 2015 Jun;12(4):373-87

Androgen insensitivity syndrome (AIS) is an undervirilization syndrome in individuals with 46, XY karyotype. The undervirilization can be complete feminization or incomplete virilization with grades of ambiguity. AIS is caused by mutations in the androgen receptor, resulting in resistance to the physiologic activities of androgens. Differing degrees of resistance lead to three phenotypes: a complete form with female-appearing external genitalia, a partial form with a wide range of virilization, and a mild form with only minor undervirilization. AIS presents different challenges depending on whether resistance is complete or partial. Challenges include sex assignment, which impacts other medical decisions such as gonadectomy, hormonal replacement, and other surgical interventions. This review describes medical, psychosocial, and ethical concerns for each stage of development in complete and partial AIS, from the neonatal period to adulthood. These aspects of care should be addressed within an ethical framework by a multidisciplinary team, with the patients and families being the stakeholders in the decision-making process. We use the GRADE system when appropriate to appraise the existing evidence and provide recommendations and guidelines for management of AIS and appropriate transition of patients from pediatric to adult care.
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June 2015

Neurocognitive profile of a young adolescent with DK phocomelia/von Voss phocomelia/von Voss Cherstvoy syndrome.

Am J Med Genet A 2015 Jul 21;167(7):1632-6. Epub 2015 Apr 21.

Department of Pediatrics, Section of Psychology, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas.

DK phocomelia/von Voss Cherstvoy syndrome is a rare condition characterized by upper limb and urogenital abnormalities and various brain anomalies. Previously reported cases have noted significant developmental delays, although no formal testing of cognitive abilities has been reported. In this paper we describe results from a comprehensive neuropsychological evaluation of a 12-year-old male with DK phocomelia syndrome. Test findings indicated mild impairment in intellectual functioning, with more significant impairment in adaptive skills and academic achievement. The neuropsychological profile converged with neurological findings, showing a distinct pattern of strengths and weaknesses that suggests functional compromise of posterior brain regions with relatively well-preserved functioning of more anterior regions. Specifically, impairments were evident in perceptual reasoning, visual perception, and visuomotor integration, whereas normal or near normal functioning was evident in memory, receptive language, social cognition, attention, and most aspects of executive functioning. To our knowledge this is the first report to describe the neurocognitive profile of an individual with DK phocomelia syndrome.
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http://dx.doi.org/10.1002/ajmg.a.37039DOI Listing
July 2015

State of the art review in hypospadias: challenges in diagnosis and medical management.

Pediatr Endocrinol Rev 2014 Sep;12(1):46-54

Hypospadias is a common congenital malformation in males, the cause of which may be genetic, hormonal, or environmental, although it usually is idiopathic or possibly multifactorial. Determining the optimal diagnostic testing and management remains a challenge. Hypospadias is corrected with surgery, and androgen therapy often is used preoperatively as an adjunctive therapy, although its use, timing, and effectiveness are unclear. No standardized approach has been established for the diagnostic testing for hypospadias or for preoperative androgen therapy. We reviewed current literature and used the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence and provide recommendations for a diagnostic testing algorithm from an endocrine and genetic perspective and for the optimal use of preoperative androgen therapy. These recommendations are an important step towards standardizing the use of diagnostic testing and the management of patients with hypospadias.
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September 2014

Intrauterine growth restriction and hypospadias: is there a connection?

Int J Pediatr Endocrinol 2014 15;2014(1):20. Epub 2014 Oct 15.

Section of Pediatric Diabetes and Endocrinology, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.

Hypospadias is one of the most common congenital malformations of the genitourinary tract in males. It is an incomplete fusion of urethral folds early in fetal development and may be associated with other malformations of the genital tract. The etiology is poorly understood and may be hormonal, genetic, or environmental, but most often is idiopathic or multifactorial. Among many possible risk factors identified, of particular importance is low birth weight, which is defined in various ways in the literature. No mechanism has been identified for the association of low birth weight and hypospadias, but some authors propose placental insufficiency as a common inciting factor. Currently, there is no standardized approach for evaluating children with hypospadias in the setting of intrauterine growth restriction. We reviewed the available published literature on the association of hypospadias and growth restriction to determine whether it should be considered a separate entity within the category of disorders of sexual differentiation.
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http://dx.doi.org/10.1186/1687-9856-2014-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203859PMC
October 2014

Ectopic adrenocorticotropic hormone and corticotropin-releasing hormone co-secreting tumors in children and adolescents causing cushing syndrome: a diagnostic dilemma and how to solve it.

J Clin Endocrinol Metab 2015 Jan;100(1):141-8

Section on Endocrinology and Genetics (A.S.K., J.B., M.F.K., C.L., M.B.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Section of Radiology and Imaging Sciences (G.Z.P., N.J.P.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Laboratory of Pathology (M.M.Q., M.M.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Thoracic and Gastrointestinal Oncology Branch (D.S.S.), Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892; Endocrine Oncology Branch (E.K.), Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892; Randall Children's Hospital at Legacy Emanuel (M.K.H.), Children's Diabetes and Endocrine Center, Portland, Oregon 97227; Department of Pediatrics (M.R.A., L.P.K., A.E.B.), Section of Diabetes and Endocrinology, Baylor College of Medicine, Houston, Texas 77030.

Context: Ectopic ACTH/CRH syndrome is a rare cause of Cushing syndrome (CS), especially in children. The localization, work-up, and management of ACTH/CRH-secreting tumors are discussed.

Setting: A retrospective study was conducted of patients under 21 years of age evaluated at the National Institutes of Health (NIH) for CS and diagnosed with ectopic ACTH/CRH-secreting tumors during the period 2009-2014.

Patients: Seven patients with ectopic ACTH/CRH CS are included in this study with a median age 13.6 years (range 1-21), and 3 are female.

Measurements: Clinical, biochemical, radiological features, treatment, and histological findings are described.

Results: Seven patients were found to have ACTH/CRH-secreting tumors, all with neuroendocrine features. The site of the primary lesion varied: pancreas (3), thymus (2), liver (1), right lower pulmonary lobe (1). PATIENTS underwent biochemical evaluation for CS, including diurnal serum cortisol and ACTH levels, urinary free cortisol levels (UFC), and CRH stimulation tests. All patients underwent radiological investigations including MRI, CT, and PET scan; imaging with octreotide and 68 gallium DOTATATE scans were performed in individual cases. Five patients underwent inferior petrosal sinus sampling; 4 patients had sampling for ACTH and CRH levels from additional sites. Three patients underwent trans-sphenoidal surgery (TSS), and 3 patients required bilateral adrenalectomy. Three patients (43%) died due to metastatic disease, demonstrating the high mortality rate. One of the unique findings in these seven patients is that in each case, their neuroendocrine tumors were ultimately proven to be co-secreting ACTH and CRH. This explains the enigmatic presentation, in which 3 patients initially thought to have Cushing's disease (CD) with corresponding pituitary hyperplasia underwent TSS prior to the correct localization of the causative tumor.

Conclusions: Ectopic ACTH/CRH co-secreting tumors are extremely rare in children and adolescents. The diagnosis of this condition is frequently missed and is sometimes confused with CD due to the effect of CRH on the pituitary.
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http://dx.doi.org/10.1210/jc.2014-2945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283025PMC
January 2015

A new family with an activating mutation (G431S) in the TSH receptor gene: a phenotype discussion and review of the literature.

Int J Pediatr Endocrinol 2014 17;2014(1):23. Epub 2014 Nov 17.

Department of Medicine, The University of Chicago, Chicago, IL 60637 USA.

Germline nonautoimmune hyperthyroidism due to an activating mutation in the thyroid stimulating hormone receptor gene is an uncommon disease. To date 32 different mutations have been described. The severity of the hyperthyroid symptoms is variable and phenotype differences have been described in subjects harboring the same mutation. This paper describes a family with a mutation in codon 431 of the thyroid stimulating hormone receptor gene. This is the most common activating mutation in the thyroid stimulating hormone receptor gene with total of 13 patients harboring the mutation in four families. The similarities and differences among patients with the mutation in codon 431 are discussed. Furthermore all previously reported activating mutations in the thyroid stimulating hormone receptor gene are reviewed.
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http://dx.doi.org/10.1186/1687-9856-2014-23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396564PMC
April 2015

Assessing sex assignment concordance with genotype and phenotype.

Int J Pediatr Endocrinol 2013 Mar 14;2013(1). Epub 2013 Mar 14.

Department of OBGYN, Division of Pediatric and Adolescent Gynecology, Baylor College of Medicine, Houston, TX, 77030, USA.

Objectives: To catalogue patients with DSD and to assess the concordance of genotype and phenotype with sex assignment at birth compared to sex assignment before and following assessment by a Gender Medicine Team (GMT) at one institution, as an initial step in formulating standardized guidelines for management of these conditions.

Design: After obtaining IRB approval, a retrospective chart review was conducted patients seen in the Gender Medicine Clinic (GMC) between 2006-2009 at Texas Children's Hospital (TCH), Houston, Texas. McNemar's test and Kappa agreement provided associations of various factors with sex assignment at birth prior to GMT assessment and after GMT assessment.

Participants: Forty-seven patients seen in the GMC with confirmed DSD.

Results: Forty-seven patients met the inclusion criteria. The mean age of the patients at the time of GMT evaluation was 9.1+/-6.1 years; 61.7% had male karyotype, and 38.3% had female karyotype; 51.1% had a male external phenotype, 42.6% had a female external phenotype, and 6.4% had phenotypic ambiguity. Sex assignment was concordant with genotype and phenotype in 63.8% and 86.4%, respectively of cases at the time of birth and in 76.6% and 97.7%, respectively, of cases after assessment by GMT.

Conclusion: Long-term outcomes are needed to establish standardized practice guidelines for decision-making.
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http://dx.doi.org/10.1186/1687-9856-2013-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608956PMC
March 2013

Activation of cyclic AMP signaling leads to different pathway alterations in lesions of the adrenal cortex caused by germline PRKAR1A defects versus those due to somatic GNAS mutations.

J Clin Endocrinol Metab 2012 Apr 18;97(4):E687-93. Epub 2012 Jan 18.

Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Building 10, CRC, Room 1-3330, 10 Center Drive, MSC1103, Bethesda, Maryland 20892, USA.

Context: The overwhelming majority of benign lesions of the adrenal cortex leading to Cushing syndrome are linked to one or another abnormality of the cAMP or protein kinase pathway. PRKAR1A-inactivating mutations are responsible for primary pigmented nodular adrenocortical disease, whereas somatic GNAS activating mutations cause macronodular disease in the context of McCune-Albright syndrome, ACTH-independent macronodular hyperplasia, and, rarely, cortisol-producing adenomas.

Objective And Design: The whole-genome expression profile (WGEP) of normal (pooled) adrenals, PRKAR1A- (3) and GNAS-mutant (3) was studied. Quantitative RT-PCR and Western blot were used to validate WGEP findings.

Results: MAPK and p53 signaling pathways were highly overexpressed in all lesions against normal tissue. GNAS-mutant tissues were significantly enriched for extracellular matrix receptor interaction and focal adhesion pathways when compared with PRKAR1A-mutant (fold enrichment 3.5, P < 0.0001 and 2.1, P < 0.002, respectively). NFKB, NFKBIA, and TNFRSF1A were higher in GNAS-mutant tumors (P < 0.05). Genes related to the Wnt signaling pathway (CCND1, CTNNB1, LEF1, LRP5, WISP1, and WNT3) were overexpressed in PRKAR1A-mutant lesions.

Conclusion: WGEP analysis revealed that not all cAMP activation is the same: adrenal lesions harboring PRKAR1A or GNAS mutations share the downstream activation of certain oncogenic signals (such as MAPK and some cell cycle genes) but differ substantially in their effects on others.
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http://dx.doi.org/10.1210/jc.2011-3000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319183PMC
April 2012

Early onset obesity and adrenal insufficiency associated with a homozygous POMC mutation.

Int J Pediatr Endocrinol 2011 6;2011(1). Epub 2011 Jul 6.

Endocrinology section-Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Isolated hypocortisolism due to ACTH deficiency is a rare condition that can be caused by homozygous or compound heterozygous mutations in the gene encoding proopiomelanocortin (POMC). Loss of function mutations of POMC gene typically results in adrenal insufficiency, obesity and red hair. We describe an 18 month old Hispanic female with congenital adrenal insufficiency, a novel POMC mutation and atypical clinical features. The patient presented at the age of 9 months with hypoglycemia and the endocrine evaluation resulted in a diagnosis of ACTH deficiency. She developed extreme weight gain prompting sequence analysis of POMC, which revealed a homozygous c.231C > A change which is predicted to result in a premature termination codon. The case we report had obesity, hypocortisolism but lacked red hair which is typical for subjects with POMC mutations. Mutations of POMC should be considered in individuals with severe early onset obesity and adrenal insufficiency even when they lack the typical pigmentary phenotype.
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http://dx.doi.org/10.1186/1687-9856-2011-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159139PMC
November 2011

Pituitary and systemic autoimmunity in a case of intrasellar germinoma.

Pituitary 2011 Dec 26;14(4):388-94. Epub 2009 May 26.

Department for Neurosurgery, Georg August University Göttingen, Göttingen, Germany.

Germinomas arising in the sella turcica are difficult to differentiate from autoimmune hypophysitis because of similar clinical and pathological features. This differentiation, nevertheless, is critical for patient care due to different treatments of the two diseases. We report the case of an 11-year-old girl who presented with diabetes insipidus and growth retardation, and was found to have an intra- and supra-sellar mass. Initial examination of the pituitary biopsy showed diffuse lymphocytic infiltration of the adenohypophysis and absent placental alkaline phosphatase expression, leading to a diagnosis of hypophysitis and glucocorticoid treatment. Because of the lack of clinical and radiological response, the pituitary specimen was re-examined, revealing this time the presence of scattered c-kit and Oct4 positive germinoma cells. The revised diagnosis prompted the initiation of radiotherapy, which induced disappearance of the pituitary mass. Immunological studies showed that the patient's serum recognized antigens expressed by the patient's own germinoma cells, as well as pituitary antigens like growth hormone and systemic antigens like the Sjögren syndrome antigen B and alpha-enolase. The study first reports the presence of pituitary and systemic antibodies in a patient with intrasellar germinoma, and reminds us that diffuse lymphocytic infiltration of the pituitary gland and pituitary antibodies does not always indicate a diagnosis of autoimmune hypophysitis.
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http://dx.doi.org/10.1007/s11102-009-0187-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291822PMC
December 2011

X-linked hypophosphatemic rickets associated with respiratory failure.

Clin Pediatr (Phila) 2008 Apr 5;47(3):293-5. Epub 2007 Dec 5.

Department of Pediatric Endocrinology and Metabolism, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.

We report a 5-year-old girl who presented to our emergency room with respiratory arrest and limb deformities and was subsequently diagnosed with X-linked hypophosphatemic rickets. On normalization of the serum phosphorus concentration, her respiratory distress resolved, illustrating that untreated X-linked hypophosphatemic rickets can lead to life-threatening respiratory distress.
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http://dx.doi.org/10.1177/0009922807308174DOI Listing
April 2008

Rapid resolution of consumptive hypothyroidism in a child with hepatic hemangioendothelioma following liver transplantation.

Ann Clin Lab Sci 2007 ;37(3):280-4

Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.

We report a unique case of a 3-mo-old female with consumptive hypothyroidism and liver hemangioendothelioma who required pharmacological doses of thyroid hormones and was cured following liver transplantation. Liver hemangioendotheliomas are capable of producing an excess of the thyroid hormone inactivating enzyme, type-3 iodothyronine deiodinase. The increased tumoral enzyme activity leads to rapid degradation of thyroid hormones, resulting in consumptive hypothyroidism. Review of similar cases indicated variable outcomes. We focus on our patient's clinical course and describe in detail the thyroid hormone replacement therapy and a unique outcome of this rare type of hypothyroidism. This first example of a prompt and complete resolution of consumptive hypothyroidism in an infant after liver transplantation confirms the concept and the reversibility of consumptive hypothyroidism and provides novel insights into the rapidity of response of the infant's hypothalamic-pituitary-thyroid axis to thyroid hormone replacement.
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October 2007

Ethical and legal implications of genetic testing in androgen insensitivity syndrome.

J Pediatr 2007 Apr;150(4):434-8

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

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http://dx.doi.org/10.1016/j.jpeds.2006.12.037DOI Listing
April 2007

Osteopenic effects of MgSO4 in multiple pregnancies.

J Pediatr Endocrinol Metab 2006 Oct;19(10):1225-30

Department of Pediatric Endocrinology and Metabolism, Texas Children's Hospital, Houston, TX, USA.

Objective: To describe the effects of prolonged maternal treatment with MgSO4 in infants who were products of multiple pregnancies.

Study Design: Case series of infants presenting with osteopenia secondary to MgSO4 administration for preterm labor.

Results: Ten premature infants with hypermagnesemia (4.5+/-0.2 mg/dl), hypocalcemia (6.0 +/-0.3 mg/dl), and high serum alkaline phosphatase (574+/-96 U/l) underwent imaging studies that showed diffuse osteopenia of the long bones and probable rib fractures. All mothers had isolated premature labor, for which they were given MgSO4; (average dose 3.66+/-0.08 kg/ pregnancy over 10.0+/-0.5 weeks). On follow-up (to 9 months), all infants had complete or near complete resolution of the osteopenia.

Conclusions: Premature infants who are exposed to large doses of MgSO4, especially those of multiple pregnancies, have an increased risk of developing hypocalcemia, osteopenia, and fractures. Our findings indicate that these infants should be identified at birth and managed prospectively.
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http://dx.doi.org/10.1515/jpem.2006.19.10.1225DOI Listing
October 2006

Variable presentation of precocious puberty associated with the D564G mutation of the LHCGR gene in children with testotoxicosis.

J Pediatr 2006 Aug;149(2):271-4

Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA.

We report on a family with familial male-limited precocious puberty (FMPP) due to a D564G mutation of the LHCGR gene. Family members show a varied phenotypic expression from severe precocity unresponsive to therapy with compromise of the predicted final height in some members, to attainment of tall final stature in other members who never received medical treatment. DNA amplification and sequencing of exon 11 of the LHCGR gene was done for the three affected male members and their mother. DNA analysis revealed a D564G mutation in the third cytoplasmic loop of the LHCGR receptor. All three males had precocious puberty with elevated testosterone levels. The index case developed central precocious puberty and evidence of compromised final height while on therapy. In contrast, the untreated older siblings attained a tall final height. This report underscores the possibility that the effects of the mutant luteinizing hormone/choriogonadotropin receptor on phenotypic expression of FMPP, such as adult final height, are modified by other factors.
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http://dx.doi.org/10.1016/j.jpeds.2006.03.017DOI Listing
August 2006

Insulin pump therapy in preschool children with type 1 diabetes mellitus improves glycemic control and decreases glucose excursions and the risk of hypoglycemia.

Diabetes Technol Ther 2005 Dec;7(6):876-84

Pediatric Endocrinology and Metabolism Section, Clinical Care Center, Texas Children's Hospital, Baylor College of Medicine, Houston 77030-2399, USA.

Background: Hypoglycemia in preschool children limits the effectiveness of insulin therapy. Continuous subcutaneous insulin infusion (CSII) is not widely used in this group.

Objectives: This study was designed (1) to test the hypothesis that compared with twice-daily insulin injection, CSII decreases the SD of the mean daily blood glucose (BG) and improves glycemic control and (2) to evaluate the effect of CSII on parental anxiety using the Parental Stress Index (PSI) scale.

Methods: Ten subjects <6 years of age and receiving insulin injections were recruited. Each underwent two 72-h CGMS (Medtronic Minimed, Northridge, CA) monitoring periods and then was started on CSII and re-monitored 3 and 6 months later. We assessed the effects of CSII on the mean BG and SD of BG values, A1c, PSI scores, and number, distribution, and duration of hypoglycemic episodes.

Results: Pooled pre- and post-CSII data were compared. There was a 22% decrease in the BG variability (mean +/- SD 93 +/- 19 mg/dL vs. 72 +/- 5 mg/dL; P = 0.02) and a 13% decrease in A1c (8.6 +/- 0.8% vs. 7.5 +/- 0.7%; P = 0.01). There was a decrease in the 24-h median number and duration of hypoglycemic episodes [1.16 vs. 0 episodes/24 h (P = 0.01) and 1.19 vs. 0.05 h/24 h (P = 0.01), respectively], as well as the median number and duration of nighttime episodes [0.83 vs. 0 episode/night (P = 0.008) and 0.98 vs. 0 h/night (P = 0.008), respectively]. We found no statistically significant change in the PSI score.

Conclusions: CSII in preschool children is feasible and safe. Pump therapy reduced the glycemic excursions and decreased hypoglycemia duration and frequency.
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http://dx.doi.org/10.1089/dia.2005.7.876DOI Listing
December 2005

Continuous glucose monitoring and the reality of metabolic control in preschool children with type 1 diabetes.

Diabetes Care 2004 Dec;27(12):2881-6

Texas Children's Hospital, Clinical Care Center, Suite 1020, 6621 Fannin St., CC 1020.05, Houston, TX 77030, USA.

Objective: To determine using the MiniMed continuous glucose monitoring system (CGMS) 1) whether twice-daily insulin injection therapy achieves adequate control in preschool children with type 1 diabetes and 2) whether the CGMS is more informative than self-monitoring of blood glucose (SMBG) regarding glucose control and well tolerated by preschool children and their families.

Research Design And Methods: Ten children <6 years of age with type 1 diabetes were monitored twice using the CGMS. The distribution of glucose values was analyzed, particularly the frequency, duration, and distribution of hypoglycemia. We analyzed the accuracy of the CGMS in detecting hypoglycemia as well as the clinical relevance of the difference between CGMS and SMBG values.

Results: Although hypoglycemia was more frequent during the night (0.8 nighttime episodes . subject(-1) . 24 h(-1) vs. 0.3 daytime episodes . subject(-1) . 24 h(-1)), the difference did not reach statistical significance (P=0.07). However, nighttime episodes lasted longer than daytime episodes (1.2 vs. 0.2 h . subject(-1) . 24 h(-1), P=0.006). Hypoglycemia accounted for 7% and normoglycemia for 24%, while hyperglycemia occurred 64% of the time, with postprandial hyperglycemia being an almost universal feature (94 +/- 7% of all postmeal values). The CGMS correlated well with SMBG without significant clinical discrepancy. The CGMS sensitivity to detect hypoglycemia was 70% with a specificity of 99%; however, the CGMS detected twice as many total episodes as SMBG (82 vs. 40).

Conclusions: Twice-daily insulin injection rarely achieves control in preschool children with type 1 diabetes. The CGMS is well tolerated by patients and has the advantage of revealing daily glucose trends missed by SMBG.
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http://dx.doi.org/10.2337/diacare.27.12.2881DOI Listing
December 2004