Beliefs and Intentions of Anesthesia Physicians Toward Providing Culturally Competent Care to Transgender Patients.

Purpose: Anesthesiologists have limited relationships with their patients before delivering care and have little time for patient interactions. Yet, they should possess the knowledge and skills to treat all patients in an equitable, culturally competent manner, including transgender patients. The study's purpose was to determine behavioral factors influencing culturally competent care by anesthesia physicians with transgender patients. Methods: A two-phase design was utilized in 2020 to examine the attitudes, subjective norms, and perceived behavioral control of anesthesia physicians, both in training and practicing independently. Phase 1 allowed exploration of themes related to facilitators and barriers of the provision of culturally competent care to transgender patients. Phase 2 involved the creation and deployment of a 51-question survey informed by phase 1 to 100 anesthesia physicians at a single academic medical center in the southeastern United States. Results: Thematic analysis was performed on results from the phase 1 elicitation survey, which informed the creation of the survey for phase 2. One hundred phase 2 surveys were distributed, with a 70% response rate. Analyses were conducted to determine the largest influence of intent to interact with transgender patients in a culturally competent manner, as well as to establish the reliability of the tool. Conclusion: Attitude followed by subjective norms were positive influencers of intent, while lack of knowledge was a negative influencer. Strengthening attitudes and subjective norms, while implementing programs to increase knowledge, competence, and humility, would be goals for future studies and actions toward improving healthcare of transgender individuals.

A case report to assess the safety and efficacy of Burosumab, an investigational antibody to FGF23, in a single pediatric patient with Epidermal Nevus Syndrome and associated hypophosphatemic rickets.

Epidermal Nevus Syndrome (ENS), also known as Cutaneous Skeletal Hypophosphatemia Syndrome or Linear Sebaceous Nevus Syndrome, is caused by a mosaic somatic mutation of RAS (Rat Sarcoma genes) which leads to abnormally elevated levels of fibroblast growth factor 23 (FGF23). FGF23 is a major regulator in phosphate homeostasis. There are multiple disorders, along with Epidermal Nevus Syndrome (ENS), that result in unusually high circulating levels of FGF23. This increase ultimately leads to renal phosphate wasting and reduced levels of 1,25-dihydroxy vitamin D. Across these disorders, the clinical symptoms are similar and often include osteomalacia (hypophosphatemic rickets in children), muscle weakness, fatigue, joint deformities, bone pain, and fractures. Burosumab (KRN23), is an IgG1 monoclonal antibody that binds to the FGF23 receptor and inhibits the activity of FGF23. This leads to an increase in serum phosphate levels. Burosumab emerged as a potential therapy in FGF23 overactivity disorders. Burosumab was successful in the treatment of X-linked hypophosphatemia (XLH) and is now FDA-approved for its treatment. Studies have indicated that Burosumab therapy in subjects with XLH consistently increases and sustains serum phosphorus levels and tubular reabsorption of phosphate without a major impact on urine calcium levels or vitamin D metabolism. We studied the effect of Burosumab treatment in a single pediatric patient with Epidermal Nevus Syndrome. Serum phosphorus rose gradually as we titrated the dose of Burosumab upwards. During treatment, a persistent elevation of parathyroid hormone levels was noted along with a persistent elevation of serum calcium. We presumed the patient had tertiary hyperparathyroidism. However, after the removal of three parathyroid glands, the pathology came back with a single enlarged parathyroid adenoma. Subsequently, his calcium and PTH, and phosphorus levels stabilized while taking only Burosumab. ClinicalTrials.gov NCT04320316.

Incidental Pituitary Cysts in Children: Does Growth Hormone Treatment Affect Cyst Size?

OBJECTIVE: To evaluate the response of incidentally discovered pituitary cysts to growth hormone (GH) treatment. METHODS: A retrospective chart review was performed of children with pituitary cysts on magnetic resonance imaging (MRI) over a 5-year period. Records and images were reviewed, and the results were analyzed using descriptive statistics. Children with pituitary cysts who received GH treatment were compared with those without. RESULTS: We identified 109 children with pituitary cysts, 24 were treated with GH therapy. The average age was 8.5 ± 5.1 years. Children whose initial MRI scan was to evaluate growth hormone deficiency were more commonly male and non-Hispanic White compared with those with scans for other indications (male, 18 of 24 vs 35 of 85, P = .003; White, 23 of 24 vs 58 of 85, P = .004). Among patients who received GH treatment, 12 had follow-up MRI. Six had no change in cyst size and 6 had a decrease in cyst size. We observed no difference in the likelihood of cyst growth between those who received GH and those who did not (0 of 12 cysts with GH vs 1 of 15 cysts without GH showed growth at follow-up). No patient had neurologic deficits attributable to the pituitary cyst at any time. CONCLUSION: In a single-institution, retrospective study, we find no evidence of growth in pituitary cysts in response to GH therapy.

Anatomy of female puberty: The clinical relevance of developmental changes in the reproductive system.

Puberty is the period of biologic transition from childhood to adulthood. The changes that occur at this time are related to the increasing concentrations of sex steroid hormones. In females, most pubertal changes are caused by estrogen stimulation that results from the onset of central puberty. Significant development occurs in the organs of the female reproductive system and results in anatomic changes that characterize reproductive maturity. Adrenal and ovarian androgens also increase during puberty, affecting change that includes the promotion of certain secondary sex characteristics. The ability to recognize normal pubertal anatomy and distinguish between estrogen and androgen effects is important in the ability to diagnose and treat disorders of sex development, precocious puberty, pubertal delay, and menstrual irregularities in children and adolescents. An understanding of this developmental process can also help clinicians identify and treat reproductive pathology in adults and across all female life stages.

Parental separation anxiety and diabetes self-management of older adolescents: a pilot study.

Parents of high school seniors with type 1 diabetes mellitus are faced with many concerns and fears as their adolescent prepares to assume primary disease management responsibility and leave the parental residence. The purpose of this study was to explore the relationship between parental separation anxiety and adolescent self-management and glycemic control. A second aim was to assess the relationship between adolescent self-management and glycemic control. Twenty-three families who had adolescents 16 to 18 years of age in or entering in their senior year of high school were recruited. Adolescents from higher income families reported better self-management skills than those from poorer families (r = 0.410, p = 0.05). Length of time since diabetes diagnosis was inversely related to glycemic control (r = 0.448, p = 0.02), indicating that adolescents who had the disease longer had poorer control. Parental separation anxiety was not related to adolescent self-management. Adolescent self-management was negatively related to glycemic control (r = -0.370, p = 0.08), suggesting that adolescents who demonstrated better self-management skills had improved glycemic control in comparison to adolescents who did not demonstrate effective self-management skills. Paternal, not maternal, separation anxiety demonstrated a significant relationship with glycemic control (r = 0.639, p < 0.001).

Parents' experiences supporting self-management of middle adolescents with type 1 diabetes mellitus.

The purpose of this article is to describe the experiences of parents regarding the fostering of self-management of diabetes mellitus with their middle adolescents with type 1 diabetes mellitus (T1DM). A purposive sample of parents of 16- to 18-year-old adolescents with T1DM from 23 families who attended the endocrinology clinic of a children's hospital were interviewed about their experience with their adolescent's diabetes management and how they supported or inhibited their adolescent's diabetes self-management. Qualitative description was used to analyze the transcripts of audio-recorded interviews. Parents often described having negative experiences involving struggle, frustration, and worry about adolescent self-management. Parents supported their adolescent's self-management primarily by reminding, recognizing positive aspects of the adolescent's diabetes management, and granting more freedom. Conversely, parents inhibited their adolescents' diabetes management by scolding and judging, checking and nagging, and becoming emotional. Clinicians can help parents share their experiences, cope with their emotions, and practice effective strategies to motivate adolescent diabetes self-management in the transition to later adolescence.

Prevalence of hypovitaminosis D in early infantile hypocalcemia.

AIM: To further define the pathogenesis of infantile hypocalcemia, the prevailing vitamin D status, and treatment outcomes. METHODS AND RESULTS: Of the 23 infants admitted with infantile hypocalcemia, 21 had biochemical evidence of hypocalcemia and hyperphosphatemia and the other two had isolated hypocalcemia. The majority of these infants had relatively low serum intact parathyroid hormone responses against the backdrop of hypocalcemia. Thirteen (56.5%) of these infants had low 25-hydroxyvitamin D (25-OHD) levels, of whom 69% were Hispanic and 23% were African American. Infantile serum vitamin D status reflected that of the mother in all the 16 instances in which it was measured. Treatment with calcitriol hastened recovery from hypocalcemia in our series. CONCLUSIONS: Relative hypoparathyroidism is the etiology in the majority of cases of late onset and early infantile hypocalcemia. We identified vitamin D deficiency in a significant percentage of infants with hypocalcemia, especially Hispanics and African Americans. Maternal 25-OHD concentrations should be ascertained if the infant has low 25-OHD levels.

Reversible subclinical hypothyroidism in the presence of adrenal insufficiency.

OBJECTIVE: To describe 3 different scenarios of reversible hypothyroidism in young patients with adrenal insufficiency. METHODS: We present 3 case reports of patients with adrenal insufficiency--one with delayed puberty, the second with type 1 diabetes and poor weight gain, and the third with hypoglycemia-related seizures and glucocorticoid deficiency--who had biochemical evidence of hypothyroidism. RESULTS: Our first patient (case 1) initially had a mildly elevated thyrotropin (thyroid-stimulating hormone or TSH) level and a normal free thyroxine (FT4) level that, on follow-up assessment, had progressed to persistent mild elevation of TSH and low FT4 concentration. The other 2 patients (cases 2 and 3) had low FT4 and mildly elevated TSH values at the time of diagnosis of adrenal insufficiency. In all 3 patients, the results of thyroid function tests normalized with use of physiologic doses of adrenal hormone replacement therapy, without thyroid hormone replacement. All 3 patients remained euthyroid after 4, 3, and 1 year of follow-up, respectively. CONCLUSION: These observations add insights into the complexities of the thyroadrenal interactions. These examples are important because thyroid hormone replacement in the setting of adrenal insufficiency could be unwarranted.

Autosomal dominant resistance to thyrotropin as a distinct entity in five multigenerational kindreds: clinical characterization and exclusion of candidate loci.

CONTEXT: Resistance to TSH (RTSH) is an inherited disorder of variable hyposensitivity to TSH. The metabolic consequences can range from euthyroid hyperthyrotropinemia to severe congenital hypothyroidism with thyroid hypoplasia. Although subclinical and mild hypothyroidism fitting the RTSH phenotype is common in the population, the role of genetic factors is far from being understood. Only in rare cases has RTSH been attributed to TSHR or PAX8 gene mutations. OBJECTIVE, SETTING, AND PARTICIPANTS: Toward the identification of novel RTSH genes, we studied five large, unrelated families comprising 102 individuals, 56 of whom were affected. RESULTS: Inheritance of RTSH in these families followed an autosomal dominant pattern without evidence for incomplete penetrance, yet expressivity was variable. Considering only fully phenotyped generations, 64% of the progeny was affected, with a 1:1.4 male-to-female ratio. Of 18 affected individuals tested in the neonatal period, two were undetected because of borderline results. The thyroid phenotype was indistinguishable from that observed with PAX8 and TSHR defects. In four families, untreated affected subjects of all ages had elevated serum thyroglobulin levels, consistent with a defect in the thyroid follicle cells. Linkage of RTSH to TSHR and PAX8 was excluded in all five families. For the largest families, we likewise excluded a contribution of genes previously only associated with syndromic forms of RTSH, namely TITF1, GNAS, and FOXE1. CONCLUSIONS: These kindreds represent a distinct etiological entity of autosomal dominant RTSH. According to the clinical presentation of these families, genetic causes of mild hyperthyrotropinemia in the general population may be more common than currently appreciated.

Effect of insulin on plasma vascular endothelial growth factor in children with new-onset diabetes.

CONTEXT: Considerable experimental evidence inculpates vascular endothelial growth factor (VEGF) as one of the candidate factors providing a mechanistic link between hyperglycemia and diabetic complications. AIM: The aim of the study was to assess the effect of insulin treatment and glycemic control on plasma VEGF levels in children with new-onset diabetes. METHODS: This prospective study assessed the changes in plasma VEGF levels after treatment of diabetes with insulin. We also aimed to ascertain whether there was any correlation between plasma VEGF levels and simultaneous random plasma glucose. The study comprised 19 children with new-onset diabetes mellitus between the ages of 3 and 18 yr. The control group comprised 55 healthy nondiabetic children with idiopathic short stature. RESULTS: Plasma VEGF concentrations were significantly elevated in children at diagnosis of diabetes, compared with healthy controls (P < 0.0002). Plasma VEGF levels (P < 0.01) and hemoglobin A(1C) (P < 0.0001) declined in diabetic children after insulin treatment. There was a highly significant correlation between reduction in plasma VEGF levels and hemoglobin A1C levels (r = 0.65, P = 0.0037). We did not find any correlation between the simultaneous plasma glucose values and basal VEGF. CONCLUSIONS: Presence of hyperglycemia and/ or insulin deficiency in children with new-onset of diabetes is associated with plasma VEGF elevation, even at the outset of disease, and this can be mitigated by insulin therapy.

Unusual case of neonatal diabetes mellitus due to congenital pancreas agenesis.

Congenital absence of the pancreas is an extremely rare condition. We participated in the care of a patient with an unusual presentation of neonatal diabetes attributable to agenesis of the pancreas. Additional clinical features of the patient included cardiac septal defects, gall bladder agenesis and duodenal malrotation. Appropriate institution of insulin, exocrine pancreatic supplements and surgical repair of the cardiac and intestinal anomalies resulted in the infant's survival. Of the reported cases of congenital pancreas agenesis, two cases have been ascribed to mutations in the insulin promoter factor-1(Ipf-1) gene. Deletion of the Ipf-1-homolog pdx-1 in mice results in the failure of pancreas to develop. Analysis of both exons of the Ipf-1 coding sequence from the presented patient's genomic DNA, however, did not identify a mutation. These results suggest that a congenital or genetic perturbation occurred in this infant most likely before the appearance of dorsal pancreatic bud in the 3 mm long embryonic stage, around the embryonic day 25 in human development, before the onset of Ipf-1 expression.

Neuroendoscopic findings in patients with intracranial germinomas correlating with diabetes insipidus.

OBJECT: Intracranial germinomas commonly occur in the pineal region, the floor of the third ventricle (hypothalamus), or both, and they are often associated with diabetes insipidus (DI). The authors conducted a study to correlate preoperative DI with the endoscopic and magnetic resonance (MR) imaging evidence of tumor on the third ventricle floor. METHODS: The authors reviewed hospital records, office charts, and MR imaging studies obtained in patients in whom a biopsy sampling procedure was performed with or without endoscopic third ventriculostomy (ETV) at Children's Hospital, Birmingham, Alabama between May 1998 and July 2002. Ten patients with the pathological diagnosis of pure germinoma were identified. Preoperative MR imaging findings and presenting symptoms were correlated with intraoperative neuroendoscopic findings. Seven patients presented with symptomatic hydrocephalus and underwent concomitant ETV. Six patients presented with DI and MR imaging evidence of involvement of the third ventricle floor. Two patients presented with DI and no initial MR imaging evidence of neoplastic involvement of the third ventricle floor; in both there was endoscopic evidence of neoplastic involvement of the floor of the third ventricle. In two children without DI, neither MR imaging nor endoscopic evidence of involvement of the third ventricle floor was observed. CONCLUSIONS: In the authors' experience with intracranial germinoma, endoscopic tumor biopsy sampling, and ETV provide an effective, safe, and minimally invasive means of obtaining diagnostic tissue and treating any concomitant hydrocephalus. The authors found that preoperative DI is an absolute predictor of neoplastic involvement of the hypothalamus regardless of MR imaging findings. Therefore, in the setting of DI and intracranial germinoma without neuroimaging evidence of hypothalamic involvement, germinomatous involvement of the hypothalamus should be assumed present, if not confirmed endoscopically at the time of biopsy sampling or third ventriculostomy, when devising adjuvant treatment plans for such patients.

Posterior cranial fossa volume in patients with rickets: insights into the increased occurrence of Chiari I malformation in metabolic bone disease.

OBJECTIVE: Some have proposed that the calvarial thickening seen in patients with rickets results in an increased rate of Chiari I malformation (CIM) in these patients. The present study measures the posterior fossa volume in children with rickets to verify previous case reports indicting a small posterior fossa as the cause for an increased rate of CIM in children with rickets. METHODS: Patients were chosen by use of a computer database to search for individuals diagnosed with rickets. Nineteen patients were identified with this diagnosis. Seven patients were found from this cohort to have imaging of the head. Axial computed tomographic and magnetic resonance images were analyzed by use of the Cavalieri method to define posterior fossa volumes. These data were then compared with those from age-matched control subjects. RESULTS: Mean volumes of the posterior fossa were significantly reduced in all patients compared with age-matched control subjects (P < 0.0001). CONCLUSION: We have found that the volume of the posterior fossa is significantly smaller in children with rickets versus age-matched control subjects. Furthermore, 29% of our study group had an associated CIM. We may hope that these data will aid in the further understanding of the pathophysiology of CIM in cases of metabolic bone disease.

Refining the staging evaluation of pineal region germinoma using neuroendoscopy and the presence of preoperative diabetes insipidus.

Treatment strategies for CNS germinoma are currently evolving. Current approaches include reducing the volume and dose of radiation by adding pre-irradiation chemotherapy. Very accurate staging is necessary with such an approach to prevent failures. Eight consecutive patients with pineal germinoma at one institution underwent endoscopic surgery for tumor biopsy, direct visualization of the third ventricular region, and third ventriculostomy for those with hydrocephalus. All patients were treated with 4 cycles of chemotherapy. Conformal field radiation therapy followed, with the dose to the tumor bed dependent on the response to chemotherapy. Patients who had MRI, endoscopic, or cerebrospinal fluid evidence of multicentric or disseminated disease also received craniospinal radiation. Six patients had diabetes insipidus (DI) at presentation. All 6 had tumor studding the floor of the third ventricle on endoscopic visualization, while only 4 of those patients had MRI evidence of disease in that region. All patients have completed therapy and are alive, with no evidence of disease at median follow-up of 31.5 months from diagnosis. Direct endoscopic visualization of the third ventricular region may be more sensitive than MRI for evaluating the presence of suprasellar disease and appears to add important information. This parameter should be added to the staging evaluation when feasible. In this series, the presence of DI was 100% predictive of suprasellar disease, even when the MRI was negative for involvement of that region. Patients should be evaluated for DI as part of the initial staging, and if it is present, the patients should be treated for suprasellar disease regardless of MRI findings.