The effects of amiodarone on thyroid function in pediatric and adolescent patients.

PURPOSE OF REVIEW: Amiodarone-induced thyroid dysfunction is well established. The present review discusses recent literature related to the effects of amiodarone on the thyroid gland and thyroid function in pediatrics. RECENT FINDINGS: Current guidelines in adults treated with amiodarone recommend baseline thyroid function testing followed by initiation of thyroid hormone monitoring after 3 months on therapy. Two retrospective studies to evaluate amiodarone-induced thyroid dysfunction in children and young adults reveal thyroid dysfunction as soon as 2 weeks after amiodarone initiation with a greater percentage of pediatric patients developing amiodarone-induced hypothyroidism rather than thyrotoxicosis. Although additional studies are needed to determine if AIH is associated with negative impact on growth and neurocognitive development, what is clear is that in both adults and pediatrics, there is low compliance with recommended side effect-monitoring guidelines. SUMMARY: Pediatric patients are at similarly high risk to develop amiodarone-induced thyroid dysfunction as are adults. It is hoped that through improved education of providers and patients further research into the incidence, the potential risks of amiodarone therapy and the potential benefits of thyroid hormone replacement therapy in patients with AIH will be investigated and reported.

Cost-effectiveness analysis of sofosbuvir and velpatasvir in chronic hepatitis C patients with decompensated cirrhosis.

BACKGROUND: Current literature indicates that direct-acting antivirals (DAAs) are cost-effective to treat compensated cirrhotic patients with hepatitis C. Although already funded by public payers, it is unknown whether it is economical to reimburse DAAs within the more advanced decompensated cirrhosis population. METHODS: A state-transition model was developed to conduct a cost-utility analysis of sofosbuvir-velpatasvir (SOF/VEL) plus ribavirin regimen for 12 weeks. The evaluated cohort had a mean age of 58 years and Child-Turcotte-Pugh (CTP) class B cirrhosis with decompensated symptoms. A scenario analysis was performed on CTP C patients. We used a payer perspective, a lifetime time horizon and a 1.5% annual discount rate. RESULTS: While SOF/VEL plus ribavirin treatment for 12 weeks increased costs by $156 676, it provided an extra 4.00 quality-adjusted life years (QALYs) compared to best supportive care (no DAA therapy). With an incremental cost-effectiveness ratio of $39 169 per QALY, SOF/VEL plus ribavirin was determined to be cost-effective at a willingness to pay of $50 000 per QALY. SOF/VEL reduced liver-related deaths and reduced progression to CTP C cirrhosis by 20.4% and 21.9%, respectively. On the contrary, SOF/VEL regimen resulted in increases in liver transplants and hepatocellular carcinoma (HCC) by 54.0% and 42.5%, respectively. Similar results were found for CTP C patients. CONCLUSION: This analysis informs payers that SOF/VEL should continue to be reimbursed in decompensated hepatitis C patients. It also supports the recommendations by the American Association for the Study of Liver Diseases to continue screening for HCC in decompensated cirrhotic patients who have achieved sustained virologic response.

Subacute Gummy Vitamin Overdose as a Rare Manifestation of Child Neglect.

ABSTRACT: We present a case of a 20-month-old girl who presented to the emergency department with anorexia, progressive weakness, and lethargy who was found to have severe hypercalcemia (20.7 mg/dL) and vitamin D hypervitaminosis. Further questioning revealed that this was secondary to a subacute toxic ingestion of "L'il Critters" calcium and vitamin D3 gummy vitamins that were being administered by the patient's mother multiple times a day for several weeks or even months. This occurred in the setting of child neglect due to the mother's mental illness. The patient required intensive care unit admission and had a prolonged hospital course complicated by hypomagnesemia, hyperphosphatemia, weight loss, and persistent weakness. Her hypercalcemia was initially refractory to standard treatment of intravenous fluids, prednisone, multiple trials of calcitonin, and zoledronic acid. Our patient had the highest calcium level we are aware of in a toddler and is the only case we know of that occurred as a result of a prolonged, intentional exposure in the setting of child neglect and a complex social situation. This case reviews the causes and management of hypercalcemia and vitamin D intoxication. It also highlights the need for a comprehensive social history and exposes the vulnerabilities of children living in homes afflicted by parental depression and severe mental illness.

Heterozygous recurrent HNF4A variant p.Arg85Trp causes Fanconi renotubular syndrome 4 with maturity onset diabetes of the young, an autosomal dominant phenocopy of Fanconi Bickel syndrome with colobomas.

Heterozygous pathogenic variants in HNF4A cause hyperinsulinism, maturity onset diabetes of the young type 1, and more rarely Fanconi renotubular syndrome. Specifically, the recurrent missense pathogenic variant c.253C>T (p.Arg85Trp) has been associated with a syndromic form of hyperinsulinism with additional features of macrosomia, renal tubular nephropathy, hypophosphatemic rickets, and liver involvement. We present an affected mother, who had been previously diagnosed clinically with the autosomal recessive Fanconi Bickel Syndrome, and her affected son. The son's presentation expands the clinical phenotype to include multiple congenital anomalies, including penile chordee with hypospadias and coloboma. This specific pathogenic variant should be considered in the differential diagnosis of Fanconi Bickel Syndrome when genetics are negative or the family history is suggestive of autosomal dominant inheritance. The inclusion of hyperinsulinism and maturity onset of the diabetes of the young changes the management of this syndrome and the recurrence risk is distinct. Additionally, this family also emphasizes the importance of genetic confirmation of clinical diagnoses, especially in adults who grew up in the premolecular era that are now coming to childbearing age. Finally, the expansion of the phenotype to include multiple congenital anomalies suggests that the full spectrum of HNF4A is likely unknown.

The Effects of Amiodarone on Thyroid Function in Pediatric and Young Adult Patients.

CONTEXT: Amiodarone is used in patients with arrhythmias, but thyroid dysfunction [amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH)] is a common adverse effect. As the onset of AIT and AIH has not been studied in children, the timing of dysfunction and long-term monitoring are not known in this population. OBJECTIVE: To describe the incidence and timing of amiodarone-induced thyroid dysfunction in children and adolescents, with a secondary aim to identify risk factors for amiodarone-induced thyroid dysfunction, and to identify variance in thyroid hormone surveillance and treatment. DESIGN: Retrospective review of thyroid dysfunction in children and young adults treated with amiodarone between 2007 and 2018. SETTING: Children's Hospital of Philadelphia. PATIENTS: Children and young adults treated with amiodarone. MAIN OUTCOME MEASURES: Prevalence of amiodarone-induced thyroid dysfunction. RESULTS: Of 484 patients, 190 had thyroid-function testing; 17.3% were found to have subclinical hypothyroidism, and 13.7% testing developed hypothyroidism. Hyperthyroidism occurred in 2.1%. In patients with subclinical hypothyroidism, 63% returned to normal thyroid function without thyroid hormone replacement. Only 26% of patients with hypothyroidism had spontaneous normalization of thyroid function. Twenty-five percent of AIT patients had spontaneous normalization of thyroid function. CONCLUSIONS: This study looks at a pediatric and young-adult population in an effort to describe the natural history of amiodarone-induced thyroid dysfunction. Based on our data, we recommend that a complete thyroid-function panel be obtained within the first week and then at weekly intervals for the first 5 weeks after initiation. The majority of thyroid dysfunction was noted within the first 35 days of treatment.

Mechanical-tactile stimulation (MTS) during neonatal stress prevents hyperinsulinemia despite stress-induced adiposity in weanling rat pups.

Stress in early life negatively influences growth quality through perturbations in body composition including increased fat mass. At term (40 weeks) preterm infants have greater fat mass and abdominal visceral adipose tissue than term-born infants. Mechanical-tactile stimulation (MTS) attenuates the stress response in preterm infants and rodents. We tested the hypothesis that MTS, administered during an established model of neonatal stress, would decrease stress-driven adiposity and prevent associated metabolic imbalances in rat pups. Pups received one of three treatments from postnatal days 5 to P9: Neonatal Stress (Stress; n=20) = painful stimulus and hypoxic/hyperoxic challenge during 60 min of maternal separation; MTS (n=20) = neonatal stress+10 min of MTS; or Control (n=20). Body weight, DXA whole body fat mass (g), MRI subcutaneous and visceral adipose tissue, and fasting adiponectin, leptin, glucose, insulin, and corticosterone were measured at weaning (P21). Stress and MTS weight gain (g/d) were accelerated following neonatal stress with greater fat mass, abdominal subcutaneous adipose tissue, serum adiponectin, leptin, and fasting glucose at weaning (P21). Male Stress and MTS pups had greater visceral adipose tissue depot. Male and female Stress pups were hyperinsulinemic. In summary, neonatal stress compromised body composition by increasing fat mass and abdominal subcutaneous adipose tissue depot, and in males, visceral adipose tissue depot. Importantly, MTS prevented hyperinsulinemia despite of stress-induced adiposity. We conclude that MTS during neonatal stress has the potential to minimize metabolic consequences associated with stress-driven perturbations in fat mass and abdominal adipose depots.