Serum Hormone Concentrations in Transgender Youth Receiving Estradiol.

OBJECTIVE: This study aimed to evaluate the serum estradiol levels in gender-diverse youth to compare the efficacy of different estradiol routes in achieving therapeutic blood levels and suppressing serum testosterone levels. METHODS: This was a retrospective chart review of patients who initiated estradiol at an adolescent gender clinic between 2010 and 2019. Data on the route of estradiol administration and antiandrogen use (spironolactone or gonadotropin-releasing hormone agonist) were collected, and laboratory data were analyzed. Scatterplots were used to visualize the relationship between the estradiol dose and testosterone and estradiol laboratory values. RESULTS: A total of 118 patients were included, with a mean (standard deviation [SD]) age of 17.2 (1.6) years. The most common route of estradiol administration was oral only (62.7%), followed by transdermal only (23.7%), multiple routes excluding subcutaneous (8.5%), and any subcutaneous (5.1%). Notable variability was observed in the serum estradiol levels, with means (SDs) of 131.9 (120.4) pg/mL for those on oral estrogen 6 to 8 mg per day, 62.6 (40.3) pg/mL for those on transdermal estrogen 0.1 to 0.15 mg every 24 hours, and 53.6 (42.4) pg/mL for those on subcutaneous estradiol. In patients who received spironolactone, transdermal estradiol was associated with lower testosterone levels than estradiol administered orally or subcutaneously. CONCLUSION: Oral, transdermal, and subcutaneous administrations of estrogen all lead to increased serum estradiol levels and are effective for use in gender-affirming care for youth. Patients on transdermal estrogen tended to have lower serum estradiol levels but also had more suppression of serum testosterone levels.

Gender-affirming endocrine care for youth with a nonbinary gender identity.

Nonbinary individuals, or those who identify outside of the traditional gender binary, are currently present in up to 9% of the general population of youth or up to 55% of gender-diverse youth. Despite the high numbers of nonbinary individuals, this population continues to experience barriers to healthcare due to providers' inability to see beyond the transgender binary and lack of competence in providing nonbinary care. In this narrative review, we discuss using embodiment goals to individualize care of nonbinary individuals, and review hormonal and nonhormonal treatment options for gender affirmation. Hormonal treatments include those often used in binary transgender individuals, such as testosterone, estradiol, and anti-androgens, but with adjustments to dosing or timeline to best meet a nonbinary individual's embodiment goals. Less commonly used medications such as selective estrogen receptor antagonists are also discussed. For nonhormonal options, alterations in gender expression such as chest binding, tucking and packing genitalia, and voice training may be beneficial, as well as gender-affirming surgeries. Many of these treatments lack research specific to nonbinary individuals and especially nonbinary youth, and future research is needed to ensure safety and efficacy of gender-affirming care in this population.

Update on methods to enhance growth.

PURPOSE OF REVIEW: To discuss treatments used to enhance growth in pediatric patients with short stature. RECENT FINDINGS: New data confirm the known efficacy of recombinant human growth hormone (rhGH) in growth hormone deficiency (GHD) and idiopathic short stature. The latest data from the Safety and Appropriateness of Growth hormone Treatment in Europe cohort did not indicate a long-term risk of malignancy in those treated for isolated GHD, but possibly increased risk in those with other diagnoses. Recombinant human insulin-like growth factor 1 is effective in treating patients with pregnancy-associated plasma protein A2 deficiency. Gonadotropin-releasing hormone agonists or aromatase inhibitor treatment to delay puberty remains controversial. They are more likely to augment adult height if combined with rhGH treatment in children already receiving rhGH. Preliminary data indicate that recombinant C-type natriuretic peptide (CNP) is safe in children and increases growth velocity upon 42 months of treatment in achondroplasia. SUMMARY: Recent data confirms previous data on rhGH efficacy and safety. Therapies to delay growth plate closure have greatest efficacy to augment height if combined with GH in select diagnoses. Recombinant CNP holds promise as a medical treatment for short stature associated with achondroplasia.

Benign thyroid nodules in pediatric patients: determining best practices for repeat ultrasound evaluations.

Background The American Thyroid Association (ATA) recommendations for the follow-up of thyroid nodules with benign fine needle aspiration (FNA) cytology in children are largely based on adult data, despite well-characterized differences between thyroid nodules in adults and children. We aimed to determine the optimal time interval for repeat evaluation of an FNA-benign thyroid nodule in a pediatric patient. Methods This is a retrospective chart review of patients <19 years of age from 2003 to 2013 with a benign thyroid nodule by FNA cytology. Results We identified 43 patients with benign thyroid nodule cytology on FNA. The average age at diagnosis was 15.6 years, with female predominance (91%). Initial ultrasound (US) findings showed an average nodule size of 2.5 cm, 10% with calcifications, 37% hyperemia, 29% hypoechogenicity and 7% lymphadenopathy. Follow-up US was done in 42%. The first follow-up US occurred on average at 15 months after the initial US. Four patients had nodules with significant growth over time. One patient with papillary thyroid carcinoma (PTC) on final pathology initially had a decreasing nodule size, and then a subsequent increase in the nodule size after 4.5 years. Thyroid nodules were surgically removed in 33% with the final pathology showing a benign cytology in four patients, follicular adenoma in eight patients and PTC in two patients. Conclusions The majority of patients with benign thyroid nodules had no significant increase in nodule size in the first year of follow-up, including one patient who was subsequently found to have PTC. We recommend follow-up US at 1 year after initial presentation in low-risk pediatric patients with benign thyroid nodule cytology.

SIADH in Systemic JIA Resolving After Treatment With an IL-6 Inhibitor.

Interleukin-6 (IL-6) is implicated in the pathogenesis of both systemic juvenile idiopathic arthritis (SJIA) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but the 2 have not been previously described as occurring together. We report a case of a 6-year-old girl with symptoms of arthralgia, daily fevers, evanescent rash, lymphadenopathy, and laboratory evaluation showing elevated inflammatory markers, consistent with SJIA. At presentation, the patient had hyponatremia with a sodium level of 128 mEq/L. She had low serum osmolality with elevated urine osmolality, consistent with SIADH. Hyponatremia improved temporarily during times of fluid restriction as expected in SIADH, but did not resolve until SJIA was treated successfully with tocilizumab, an IL-6 receptor antibody that inhibits IL-6 activity. The positive response to treatment with tocilizumab supports the role of IL-6 in the pathogenesis of both SJIA and SIADH. Patients with SJIA should be monitored for SIADH to avoid complications of untreated hyponatremia.

AUTONOMOUSLY FUNCTIONING THYROID NODULES IN PATIENTS <21 YEARS OF AGE: THE RHODE ISLAND HOSPITAL EXPERIENCE FROM 2003-2013.

OBJECTIVE: This study evaluates the clinical characteristics, workup, treatment, and outcomes of pediatric patients diagnosed with an autonomously functioning thyroid nodule (AFTN) in a large cohort of patients presenting for evaluation of a thyroid nodule. There are few prior studies on AFTN in pediatrics, with limited data on treatment and outcomes. Rates of malignancy in AFTN are perceived as low, but prior studies have varying reports. METHODS: This is a retrospective chart review of patients less than 21 years of age at Rhode Island Hospital over an 11-year period (2003-2013). We reviewed 354 charts, which yielded 242 patients with a diagnosis of thyroid nodule and 17 patients with AFTN. RESULTS: The prevalence of AFTN in patients presenting with thyroid nodules was 7%. Mean age of patients was 15.8 years at diagnosis, and mean nodule size was 3.3 cm. There was female predominance. Thyroid-stimulating hormone levels were suppressed at diagnosis in 87% of patients. Six patients were treated with surgery, 5 patients with radioactive iodine therapy (RAI), 2 patients with medication, and 1 patient was observed without treatment. Three patients treated with RAI required subsequent treatment for hypothyroidism or continued hyperthyroidism. One patient had papillary thyroid carcinoma based on final surgical pathology. CONCLUSION: Our study found a higher prevalence of AFTN compared to the reported prevalence in adults. We concur with the new guidelines on management of thyroid nodules in recommending surgery for treatment of AFTN, based on the variability of outcomes after treatment with RAI.