Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic.

PURPOSE: Congenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown. METHODS: We studied 13 children with sporadic congenital hypopituitarism. Children with non-endocrine, non-familial idiopathic short stature (NFSS) (n = 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach was used to compare the number of candidate variants in the two groups. RESULTS: First, we assessed the frequency of rare, predicted-pathogenic variants in 42 genes previously reported to be associated with pituitary gland development. The average number of variants per individual was greater in probands with congenital hypopituitarism than those with NFSS (1.1 vs. 0.21, mean variants/proband, P = 0.03). The number of probands with at least 1 variant in a pituitary-associated gene was greater in congenital hypopituitarism than in NFSS (62% vs. 21%, P = 0.03). Second, we assessed the frequency of rare, predicted-pathogenic variants in the exome (to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence of the proband's condition with a monogenic etiology (de novo mutation, autosomal recessive, or X-linked recessive) with complete penetrance. There were fewer monogenic candidates in the probands with congenital hypopituitarism than those with NFSS (1.3 vs. 2.5 candidate variants/proband, P = 0.024). We did not find any candidate variants (0 of 13 probands) in genes previously reported to explain the phenotype in congenital hypopituitarism, unlike NFSS (8 of 19 probands, P = 0.01). CONCLUSION: Our findings provide evidence that the etiology of sporadic congenital hypopituitarism has a major genetic component but may be infrequently monogenic with full penetrance, suggesting a more complex etiology.

Diabetic ketoacidosis drives COVID-19 related hospitalizations in children with type 1 diabetes.

BACKGROUND: Diabetes is a risk factor for poor COVID-19 outcomes, but pediatric patients with type 1 diabetes are poorly represented in current studies. METHODS: T1D Exchange coordinated a US type 1 diabetes COVID-19 registry. Forty-six diabetes centers submitted pediatric cases for patients with laboratory confirmed COVID-19. Associations between clinical factors and hospitalization were tested with Fisher's Exact Test. Logistic regression was used to calculate odds ratios for hospitalization. RESULTS: Data from 266 patients with previously established type 1 diabetes aged <19 years with COVID-19 were reported. Diabetic ketoacidosis (DKA) was the most common adverse outcome (n = 44, 72% of hospitalized patients). There were four hospitalizations for severe hypoglycemia, three hospitalizations requiring respiratory support (one of whom was intubated and mechanically ventilated), one case of multisystem inflammatory syndrome in children, and 10 patients who were hospitalized for reasons unrelated to COVID-19 or diabetes. Hospitalized patients (n = 61) were more likely than nonhospitalized patients (n = 205) to have minority race/ethnicity (67% vs 39%, P < 0.001), public insurance (64% vs 41%, P < 0.001), higher A1c (11% [97 mmol/mol] vs 8.2% [66 mmol/mol], P < 0.001), and lower insulin pump and lower continuous glucose monitoring use (26% vs 54%, P < 0.001; 39% vs 75%, P < 0.001). Age and gender were not associated with risk of hospitalization. Higher A1c was significantly associated with hospitalization, with an odds ratio of 1.56 (1.34-1.84) after adjusting for age, gender, insurance, and race/ethnicity. CONCLUSIONS: Higher A1c remained the only predictor for hospitalization with COVID-19. Diabetic ketoacidosis is the primary concern among this group.

Precocious puberty.

Precocious puberty (PP) is a common reason for referral to pediatric endocrinology clinics, with a strong female predominance. PP is a broad term encompassing benign variants of normal development, gonadotropin-dependent precious puberty (GDPP), and gonadotropin-independent precocious puberty (GIPP). This article reviews the definitions, physiology, clinical presentation, evaluation and treatment of these conditions.

Diagnosis and management of hypopituitarism.

PURPOSE OF REVIEW: This review summarizes pituitary function, and the clinical presentation and treatment of hypopituitarism. RECENT FINDINGS: Updates in the field include new guidelines and meta-analyses on the diagnosis and treatment of select hormone deficiencies, novel treatment options, and advances in next generation sequencing technology. SUMMARY: Hypopituitarism is defined as partial or complete loss of a single or multiple pituitary hormones. The clinical presentation of hypopituitarism varies depending on the number and severity of hormone deficiencies. Treatment involves the physiologic replacement of the individual end-organ hormone deficiencies and requires close lifelong monitoring.

Hypercalcemia, hyperkalemia and supraventricular tachycardia in a patient with subcutaneous fat necrosis.

BACKGROUND: Subcutaneous fat necrosis (SCFN) is a rare, self-limiting condition that has been associated with several complications including hypercalcemia. CASE PRESENTATION: We present the case of a 6-week-old male who presented to his pediatrician with a dime-sized erythematous nodule consistent with SCFN, who was also found to have supraventricular tachycardia (SVT). Laboratory findings revealed hypercalcemia and hyperkalemia. Extensive evaluation for the electrolyte disturbances revealed no other etiology. This case reinforces that SCFN should be considered in newborns with hypercalcemia of unknown etiology. Additionally, this case is the first to suggest a connection between SCFN and hyperkalemia. Electrolyte abnormalities can potentially contribute to arrhythmogenesis and may have triggered the arrhythmia in our patient. CONCLUSIONS: Our case highlights the importance of remaining vigilant in the workup of atypical rashes of the infant, which should include early assessment of serum electrolytes.

Pituitary Hypoplasia.

This article summarizes pituitary development and function as well as specific mutations of genes encoding the following transcription factors: HESX1, LHX3, LHX4, POU1F1, PROP1, and OTX2. Although several additional genetic defects related to hypopituitarism have been identified, this article focuses on these selected factors, as they have been well described in the literature in terms of clinical characterization of affected patients and molecular mechanisms of action, and therefore, are very relevant to clinical practice.

National study of continuity clinic satisfaction in pediatric fellowship training.

BACKGROUND: A national online survey was conducted to evaluate pediatric subspecialty fellow satisfaction regarding continuity clinic experience. METHODS: An anonymous online survey (SurveyMonkey™) was developed to evaluate demographics of the program, clinic organization, and patient and preceptor characteristics, and to compare fellow satisfaction when fellows were the primary providers with faculty supervision versus attending-run clinics assisted by fellows or a combination of the two models. Pediatric subspecialty fellows in a 3-year Accreditation Council for Graduate Medical Education accredited program in the United States (excluding emergency medicine, neonatology, and critical care) were invited to participate. RESULTS: There were 644 respondents and nearly half (54%) of these had fellow-run clinics. Eighty-six percent of fellows responded that they would prefer to have their own continuity clinics. Higher satisfaction ratings on maintaining continuity of care, being perceived as the primary provider, and feeling that they had greater autonomy in patient management were associated with being part of a fellow-run clinic experience (all P < 0.001). Additionally, fellow-run clinics were associated with a feeling of increased involvement in designing a treatment plan based on their differential diagnosis (P < 0.001). There were no significant associations with patient or preceptor characteristics. CONCLUSION: Fellow-run continuity clinics provide fellows with a greater sense of satisfaction and independence in management plans.

Foster care and type 1 diabetes in the Bronx: a case series.

OBJECTIVE: The objective of this retrospective study was to describe the health status of children with type 1 diabetes mellitus (T1DM) in foster care. RESEARCH DESIGN AND METHODS: A retrospective chart review of children with T1DM in foster care at the Children's Hospital at Montefiore (CHAM) in Bronx, NY, USA, was performed. RESULTS: All patients were either African American or Hispanic and raised by single mothers. The majority of referrals were for medical neglect. The time spent in foster care ranged from 1 to 7 years, with 1-12 placements. Only two children were reunified with their biological mothers. Extensive financial burdens on the health-care system for children with diabetes including prolonged hospitalizations awaiting placement, frequent hospital admissions, and support services were noted. CONCLUSIONS: To our knowledge, this is the first report on children with T1DM in foster care. Poor glycemic control and suboptimal social outcomes were noted in the children we report in our case series. Programs geared to improve and reform foster care for children with diabetes are needed.

Reversed seasonal variation in maternal vitamin D levels in southern Louisiana.

Vitamin D is critical in bone and mineral homeostasis, particularly in the prevention of rickets in children. Levels of vitamin D in cord blood were measured in a population from New Orleans as an index of maternal vitamin D status at the time of delivery. Cord blood samples from infants born during the summer and winter showed lower 25-hydroxyvitamin D levels compared with those from infants born during fall and spring, indicating an unusual pattern of seasonality where vitamin D levels were among the lowest in the season with the greatest sunlight. It is important to establish screening and supplementation guidelines based on observed regional trends and risk factors, in addition to considerations based on global recommendations.