Dexamethasone Therapy of Congenital Adrenal Hyperplasia and the Myth of the “Growth Toxic” Glucocorticoid

The use of long-acting glucocorticoids in the treatment of individuals with Congenital Adrenal Hyperplasia (CAH) has been greeted with controversy. Avoidance of dexamethasone therapy is in part due to the mistaken assumptions that dexamethasone is 30-fold more potent than hydrocortisone in suppressing adrenal activity, resulting in the overtreatment and the “growth toxic” label. However, as shown more than 50 years ago, dexamethasone is 80- to 100-fold (or greater) more potent than hydrocortisone in suppressing adrenal androgen production. When children are treated with low doses of dexamethasone once daily in the morning (0.15–0.3 mg/m2/day of dexamethasone versus 10–25 mg/m2/day of hydrocortisone), studies involving infants and children show that normal growth and skeletal maturation can be achieved, along with appropriate suppression of adrenal androgen secretion. Due to its high potency, the potential for overtreatment remains high with dexamethasone. Thus, it is imperative that dexamethasone-treated children be closely monitored

63 Years and 715 Days to the “Boxed Warning”: Unmasking of the Propylthiouracil Problem

715 days after potential problems related to PTU use in children were presented in a debate in front of the Lawson Wilkins Pediatric Endocrine Society (LWPES), the US Food and Drug Administration issued a “black-box” warning about the hepatotoxicity risk of the antithyroid drug propylthiouracil (PTU). This safety advisory followed the collective actions of academic societies, medical publishers, the National Institutes of Health, and the FDA. Considering that surgery and radioactive iodine are the legitimate treatment options for Grave Disease (GD), and are now the preferred alternative therapy in individuals who developed toxic reactions to MMI, the use of PTU should now be limited to exceptional circumstances and pregnancy. Long-term PTU therapy, especially in children, is not justifiable. The current advisory comes 63 years after the introduction of PTU for clinical use in 1947

Low-Dose Dexamethasone Therapy from Infancy of Virilizing Congenital Adrenal Hyperplasia

Objective. To assess the growth and control of adrenal androgen secretion in children with virilizing congenital adrenal hyperplasia (CAH) treated with dexamethasone. Method. We examined doses used, control of adrenal androgen secretion, and growth and skeletal maturation of 8 children with CAH treated with dexamethasone beginning in infancy. Results. 3 boys and 5 girls with classical CAH (17-hydroxyprogesterone at diagnosis >20,000 ng/dL) were treated with dexamethasone beginning at diagnosis (<10 days of age). Patients were also treated with fludrocortisone and sodium chloride. The average initial medication dose was 0.1 mg (0.28 ± 0.015 mg/m2); all doses were given in the morning using a dosing syringe to administer a 0.1 mg/mL elixir. The children were treated for 6.5 ± 2.0 years over which time the change in bone age to chronological age ratio (ΔBA/ΔCA) was 0.9 ± 0.06. Most recent height Z' scores were +0.5 ± 0.2, and body mass index (BMI) scores were 18 ± 0.2. Late afternoon levels of 17-hydroxyprogesterone, androstenedione, and testosterone were 780 ± 238 ng/dL (23.4 ± 7 nmol/L), 42 ± 10 ng/dL (1.4 ± 0.3 nmol/L), and 11.5 ± 3 ng/dL; (0.4 ± 0.1 nmol/L), respectively. Conclusions. These observations show that low doses of dexamethasone can be used to effectively treat CAH beginning in infancy

Prenatal Virilization Associated with Paternal Testosterone Gel Therapy

Transdermal testosterone gels are used in the treatment of hypoandrogenism of males. Virilization due to exposure to testosterone gels has been reported in children resulting in a US Food and Drug Administration (FDA) warning about secondary exposure to these products. At present, we are unaware of prenatal virilization associated with unintentional testosterone gel exposure. We report prenatal virilization in a female infant due to secondary maternal exposure to the father's testosterone gel. We also describe postnatal virilization of the child's twin sister

Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use

Propylthiouracil (PTU) was introduced for clinical use in July 1947 for Graves' disease (GD) treatment. Over the 60 years that this medication has been used, reports of PTU-related liver failure and death have accumulated. On October 28, 2008, an expert panel evaluated PTU drug safety in children at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) It is estimated that about 4000 pediatric patients per year with GD are being treated with antithyroid drugs (ATDs) in the United States, and up to 30% of pediatric patients with GD are being treated with PTU. The risk of severe PTU-induced liver failure is estimated as 1 in 2000–4000 children. The number of children developing reversible PTU-induced liver injury is estimated to be at least 1 in 200. Routine biochemical surveillance of liver function and hepatocellular integrity is not useful in identifying children who will develop liver failure. Children appear to be at higher risk for PTU-induced liver injury than adults. PTU should not be used as first line therapy for the treatment of GD in children. Current PTU use in children taking this medication should be stopped in favor of alternate therapies

Adverse Events Associated with Methimazole Therapy of Graves' Disease in Children

Objective. Graves' disease is the most common cause of hyperthyroidism in the pediatric population. Antithyroid medications used in children and adults include propylthiouracil (PTU) and methimazole (MMI). At our center we have routinely used MMI for Graves' disease therapy. Our goals are to provide insights into adverse events that can be associated with MMI use. Methods. We reviewed the adverse events associated with MMI use in our last one hundred consecutive pediatric patients treated with this medication. Results. The range in the patient age was 3.5 to 18 years. The patients were treated with an average daily dose of MMI of 0.3±0.2 mg/kg/day. Adverse events attributed to the use of the medication were seen in 19 patients at 17±7 weeks of therapy. The most common side effects included pruritus and hives, which were seen in 8 patients. Three patients developed diffuse arthralgia and joint pain. Two patients developed neutropenia. Three patients developed Stevens-Johnson syndrome, requiring hospitalization in 1 child. Cholestatic jaundice was observed in 1 patient. No specific risk-factors for the development of adverse events were identified. Conclusions. MMI use in children is associated with a low but real risk of minor and major side effects

The shifting impact and response to COVID-19 in Florida

The first cases of COVID-19 in Florida were diagnosed on March 1, 2020. Three years later, more than 7.3 million people have had COVID-19 in Florida, and more than 93,000 individuals have died from this illness. When considering the impact of COVID-19 on Florida, several key factors need to be considered, including that Florida was one of the most medically vulnerable states due to a substantial proportion of older individuals and those with underlying medical conditions. Florida also has a centralized Department of Health and Division of Emergency Management structure that facilitated response activities. Looking at the impact of COVID-19 on Florida, two distinct phases need to be considered: the pre-Delta variant phase from March 2020 to July 2021 and the Delta variant and beyond phase that began July 2021 and still continues. During the 16-month first phase, about 38,000 people died. Yet, 24,000 people died during the 5-months of the Delta variant wave from July to November 2021. During the Omicron waves that followed Delta, an additional 31,000 people died. Florida thus went from ranking 26th in death per capita in the United States at the end of the first phase to 10th a few months into the Delta wave and now ranks 8th. Why did these phases differ so dramatically in terms of mortality? During the first phase of the pandemic, adherence to established nonpharmacological and older adult protection measures was recommended. When COVID-19 vaccines became available in December 2020, there was an aggressive campaign to promote COVID-19 vaccination, and public acceptance was high. The second phase followed political opposition to CDC and public health expert guidelines, the rise of anti-vaccine sentiment and misinformation, and falling vaccination rates. These factors contributed to considerable population vulnerability to severe disease when the Delta variant hit. As the former State Surgeon General and Secretary of Health of Florida from June 2019 to September 2021, this report provides perspective on the shifting impact and response to COVID-19 in Florida, which is the third most populous state in the United States. This perspective shows the clear consequences of shifting from standard public health practices and vaccine promotion to attacks on public health and vaccines