Characteristics of patients with classic congenital adrenal hyperplasia missed on the newborn screen.

BACKGROUND: Newborn screening for congenital adrenal hyperplasia (CAH) has been in place in the USA for over 20 years. However, not all patients with classic CAH are diagnosed as neonates. OBJECTIVES: Our aim was to characterize patients with classic CAH who were missed on the newborn screen (NBS) in Indiana and determine if discriminating features were present that might have led to earlier detection. METHODS: Medical records of children diagnosed with classic CAH due to 21-hydroxylase deficiency seen at Riley Hospital for Children in Indiana between January 2005 and December 2020 were reviewed. Patient characteristics, visit information and lab results were collected. Statistical analysis was performed using SPSS version 28. RESULTS: A total of 64 patients were identified of whom 12 (19%) were missed on the NBS. Mean age at diagnosis was 21.7 months (range: 2-74 months), 67% were girls and 66% were salt wasters. Eight (67%) presented with clinical evidence of hyperandrogenism, including clitoromegaly (n=7), posterior labial fusion (n=5) and pubic hair (n=2). Screening was pursued due to a family history of CAH in the remaining 4. Genetic confirmation was present in 50%. There was no history of antenatal steroid exposure in any of the missed patients. No differences were seen with regard to sex, ethnicity, gestational age, birth weight, type of CAH or serum 17-hydroxyprogesterone (17OHP) level at diagnosis in patients who were missed compared with those diagnosed on the NBS (14,948 ng/dL vs 16,701 ng/dL, p=0.74). However, the mean testosterone level at diagnosis was lower in patients who were missed compared with those who were diagnosed earlier (68 ± 60.28 vs 196.2 ± 206.0, p=0.02). Positive family history of CAH was present in 42% of the missed patients. Timing of the NBS collection was not different between the two groups, p=0.36. CONCLUSION: Nearly one-fifth of our patients with classic CAH were missed on the NBS. No specific features were identified that distinguished these children from those who were detected at birth. It is critical to maintain a high index of suspicion for CAH in order to recognize these patients as early as possible so as to avoid adverse effects and potential life-threatening adrenal crises.

Rhabdomyolysis: A Rare Presentation of Hashimoto Thyroiditis in an Adolescent Boy and Review of the Literature.

INTRODUCTION: Hypothyroidism-induced rhabdomyolysis without precipitating factors is extremely rare, particularly in pediatric patients. We describe a previously healthy adolescent boy who came to our institution with vague symptoms and was found to have rhabdomyolysis secondary to hypothyroidism due to Hashimoto thyroiditis. We also summarize previously published cases in children and adolescents. CASE PRESENTATION: A 16-year-old boy presented to the emergency department at Riley Hospital for Children with a 2-week history of bilateral eye and lip swelling, fatigue, and slowing of speech initially attributed to angioedema. His laboratory studies were significant for acute kidney injury secondary to rhabdomyolysis. Additional evaluation revealed profound primary hypothyroidism and positive TPO antibodies. Although his free T4 was undetectable, his TSH was only 32.2 mcU/mL. He received IV hydration and thyroid replacement, and his symptoms improved after several months of treatment. DISCUSSION: Rhabdomyolysis without any risk factors is very rare, especially in children. Our patient was not on any medications, had no family history of neuromuscular disorders, and no history of trauma, infection, or strenuous exercise. The reason behind the disproportionately mild elevation of TSH in the setting of an undetectable free T4 is unclear. CONCLUSION: It is important for clinicians to be aware that rhabdomyolysis may be a presenting sign of severe hypothyroidism, as delay in diagnosis and treatment can be detrimental.

Nonketotic hyperglycemic hemichorea-hemiballismus in a pediatric patient: A case report.

Nonketotic hyperglycemic hemichorea-hemiballismus (NHHH) is an infrequent complication of diabetes mellitus, and rarely occurs in children. We present an adolescent boy with recent diagnosis of type 1 diabetes who presented with hemichorea and brain imaging findings consistent with NHHH. His symptoms resolved with euglycemia and valproic acid after few weeks.

Genetic Counseling, Screening and Risk-Reducing Surgery in Patients with Primary Breast Cancer and Germline BRCA Mutations: Unmet Needs in Low- and Middle-Income Countries.

OBJECTIVE: Worldwide genetic counseling practices are variable and often not reported in low- and middle-income countries (LMICs). We present the follow-up genetic counseling, breast screening, risk-reducing salpingo-oophorectomy (RRSO) and contralateral prophylactic mastectomy (CPM) in a cohort of study patients with either BRCA pathogenic mutations or BRCA variant of unknown significance (VUS). MATERIALS AND METHODS: Chart review and phone calls for the collection of information. Out of a cohort of 250 patients, 14 had deleterious mutations and 31 had a VUS, of whom 19 had primary early breast cancer. We collected information about genetic counseling, screening, CPM and RRSO. RESULTS: Fourteen patients with deleterious mutations (7 BRCA1 and 7 BRCA2) and 19 patients with VUS mutations (20 VUS, 4 BRCA1, 16 BRCA2; 1 patient had both) were surveyed. Of 14 patients with deleterious BRCA mutations, 57.14% (8/14 patients) received genetic counseling from their oncologist. Subsequently 85.71% (12/14) are undergoing mammography screening and 35.71% (5/14) breast screening magnetic resonance imaging (MRI). Furthermore, 50% of them underwent CPM and 57.14% underwent RRSO. Of 19 patients with VUS mutations, 10.5% received genetic counseling from their oncologist; 78.9% were undergoing regular screening mammogram and 31.5% were undergoing breast MRI; one patient underwent CPM and two patients RRSO. CONCLUSION: Within three years from knowing they have a mutation, 50% of patients with germline BRCA mutations had undergone CPM and 60% RRSO, the majority of them had screening mammography surveillance but only 50% had screening MRI. Follow-up of patients with VUS with mammography was 78% but MRI was only 31%. Lack of MRI surveillance reflects both limited resources and insufficient counseling. Genetic counseling was done by medical oncologists, which reflects a trend in LMIC. Our Data shows the importance of the need for professional genetic counselors and optimal surveillance in Lebanon and other LMICs.

Cardiovascular Health of Youth During Gender-Affirming Testosterone Treatment: A Review.

PURPOSE: Many birth-assigned female/transgender male and nonbinary people (identified as masculine spectrum here) begin gender-affirming testosterone therapy by the age of 24 years. Few data inform assessment of cardiovascular health of masculine spectrum youth as a specific subgroup of the 1.5 million transgender people in the United States. The purpose of this review is to help youth-serving practitioners consider, understand, and evaluate cardiovascular health in adolescent and young adult masculine spectrum patients receiving gender-affirming testosterone treatment. METHODS: This is a narrative review intended to synthesize a broad body of clinical and research literature. RESULTS: Common cardiovascular health changes associated with testosterone include increased red blood cell mass and likely insignificant changes in high-density lipoprotein and low-density lipoprotein levels. Changes in heart mass, heart electrophysiology, and endothelial reactivity are likely, based on extrapolation of data from adults. Testosterone may have indirect effects on cardiovascular health through influences on depression, anxiety, stress, and anorexia nervosa as well as on behaviors such as tobacco use. CONCLUSIONS: Testosterone contributes importantly to the cardiovascular health and well-being of masculine spectrum gender-diverse youth. We need to do a better job of supporting these young people with data on cardiovascular health over the life span.

Non-GH Agents and Novel Therapeutics in the Management of Short Stature.

Short stature is one of the most common reasons for referral to pediatric endocrinologists. The vast majority of short children do not have growth hormone (GH) deficiency or another pathologic process that is interfering with normal growth. While GH has been approved in the US for several etiologies of non-GH deficient short stature, its high cost and need for daily injections represent barriers for many families. Alternative agents for the management of short stature include the use of gonadotropin releasing hormone analogs (GnRHas) to delay puberty, and aromatase inhibitors (AIs) in boys to postpone epiphyseal fusion. The results of studies employing GnRHas as either monotherapy or combined with GH are mixed, and there is a dearth of rigorously designed clinical trials that have followed patients to adult height. While AIs have been found to result in modest increases in adult height in some studies, important questions about their long-term safety exist. The C-type natriuretic peptide analog vosoritide is an experimental agent that is emerging as a potential treatment for a few specific conditions including achondroplasia, although its efficacy in attenuating disproportionality is as yet unproven. While each of these therapeutic strategies holds promise, none are currently considered standard of care and several important questions remain. These include the impact of these interventions on quality of life as well as long-term outcomes.

ESOPHAGEAL PERFORATION FOLLOWING OROGASTRIC SUCTION CATHETER INSERTION IN AN ELDERLY PATIENT.

Esophageal rupture has been described following iatrogenic manipulation. In this report, we present an elderly lady admitted to the operative theater for laparoscopic cholecystectomy. Multiple intra-operative attempts to place a flexible orogastric tube were unsuccessful because of failure to advance. Post-operatively, the patient developed sepsis and a right pleural effusion. She was transferred to the Intensive Care Unit and she was treated with antibiotics. Radiologic evaluation confirmed an esophago-pleural fistula. Surgical repair was urgently performed for closure of fistula and lung decortication. The patient recovered and was discharged home.