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Typical symptoms which should lead to suspicion of hyperthyroidism are unintentional weight loss, tachycardia, and palpitations, heat intolerance, and hyperactivity. It is diagnosed by suppressed thyroid-stimulating hormone (TSH) with elevated thyroid hormone (TH) levels. Graves' disease (GD) due to antibodies stimulating the TSH receptor is the leading cause, and first-line treatment is with methimazole (MMI). Emerging data suggest MMI treatment, up to 8 years is effective and safe in improving the rate of remission. Radioactive iodine (RAI) and thyroidectomy offer definitive treatment and induce permanent hypothyroidism. Thyroid storm is a life-threatening condition with systemic decompensation and hyperpyrexia. Neonates of mothers with current or past GD are at risk for neonatal hyperthyroidism (NH). Appropriate identification and follow-up of at-risk neonates will reduce complications.

Purpose of review This review is intended to highlight recent studies which provide new data on the epidemiology and management of children with hyperthyroidism, including neonates. Recent findings A French study demonstrates differences in age-related trends in incidence of hyperthyroidism in males versus females and suggests the overall incidence may be increasing. New studies confirm the effectiveness and safety of long-term medical therapy (up to 10 years), including from the first randomized trial of short-term versus long-term therapy. Radioiodine ablation (RAI) is the main alternative therapy, though surgery may have some advantages if done in a high-volume center; using higher weight-based doses of I-131 (250 μCI/g thyroid tissue) could increase proportion of patients achieving hypothyroidism and decrease repeat ablations. Maternal or neonatal thyroid-stimulating hormone (TSH) receptor antibodies in children of mothers with Graves' disease, and TSH at 3-7 days of age are good predictors of which neonates will have problems. Summary More research is needed on the epidemiology of Graves' disease. Long-term medical therapy well past two years should be considered an option in compliant patients to decrease the number who need definitive therapy. For those receiving RAI, a dose of about 250 μCI/g thyroid tissue should result in fewer cases of persistent hyperthyroidism than lower doses.

Introduction Only about 30% of pediatric patients with Graves’ hyperthyroidism achieve remission with medical therapy, and therefore radioactive iodine (RAI) therapy is often used as a definitive treatment. Although the goal of RAI is permanent hypothyroidism, this is not consistently achieved. We conducted a chart review to determine the factors associated with the success of RAI. We also tried to determine optimal follow-up post RAI and if there was an optimal L-thyroxine dose that would normalize the hypothyroid state quickly. Methods This is a retrospective chart review of Graves’ patients who underwent RAI between 2008 and 2017. We included age, sex, time from diagnosis, thyroid gland size, total dose of I-131 and dose in μCi/g of thyroid tissue. Patients were grouped based on outcome and analyzed using univariate and multivariate logistic regression. Follow-up thyroid levels post RAI and after starting l-thyroxine were analyzed. Results There were 78 ablations including six repeat ablations. Seventy-three percent became hypothyroid, 23% remained overtly or subclinically hyperthyroid, and 4% were euthyroid. Smaller thyroid size (36.5 vs. 47.4 g; p = 0.037) and higher dose of I-131 (242 vs. 212 μCi/g thyroid tissue; p = 0.013) were associated with a higher likelihood of hypothyroidism. Most patients remained hyperthyroid at 1 month post RAI, but by 3 months the majority became hypothyroid. There was no clear L-thyroxine dose that normalized hypothyroidism quickly. Conclusions An I-131 dose close to 250 μCi/g of thyroid tissue has a higher likelihood of achieving hypothyroidism. Testing at 2–3 months after RAI is most helpful to confirm response to RAI.

PurposeThe purpose of this paper is to describe a successful model of shared medical leadership within an academic division of an urban children’s hospital.Design/methodology/approachExperience and outcomes were tracked over a three-year period during which two physicians shared the role of interim division chief of pediatric endocrinology and diabetes, resulting in a working model of shared leadership.FindingsAn evolutionary trajectory occurred over three years in which the strengths of the leaders were combined to optimize decision making in a complex medical division. Improvements in team satisfaction and additional positive outcomes were achieved.Practical implicationsBenefits of and challenges tackled by the strategic approach to shared leadership are identified to inform other medical institutions, particularly those with many team members or combined programs that include strong clinical and research components.Originality/valueLittle has been written within medical literature regarding shared leadership. The shared leadership model described in this paper can be implemented by others in a complex academic setting and will hopefully lead to more robust divisions.

A 13-year-old girl with type 1 diabetes presented to the emergency department (ED) after being found unresponsive at home by her mother with a capillary blood glucose (CBG) of 1.488 mmol/L (26.8 mg/dL) (Figure 1). She was given intramuscular (IM) glucagon and intravenous (IV) dextrose by emergency medical services, and her CBG increased to 4.628 mmol/L (83.4 mg/dL) by the time of her ED arrival. FIGURE 1. Timeline of glucose and insulin levels during admission. The line is glucose levels, squares are insulin levels, and arrows indicate times of glucagon doses given, 1 mg each. At presentation, she was diaphoretic and somnolent, with an otherwise unremarkable exam, body temperature 37°C (98.6°F), heart rate 93 beats/min, respiratory rate 22 breaths/min, blood pressure 103/62 mmHg, and oxygen saturation 99%. Other significant admission laboratory values were sodium 139 mmol/L, potassium 3.6 mmol/L, carbon dioxide 23 mmol/L, creatinine 32 μmol/L, magnesium 0.86 mmol/L, phosphorus 1.35 mmol/L, alanine aminotransferase 95 units/L, and aspartate aminotransferase 75 units/L. While in the ED, her CBG value repeatedly fell to 10 mg/kg/min to maintain euglycemia. She was admitted to the intensive care unit (ICU) for further management and careful monitoring. In the ICU, she received intermittent doses of IM glucagon (1 mg each) because of continued hypoglycemia even on continuous dextrose infusion with a GIR of 10 mg/kg/min (Figure 1). With her first glucagon dose, her glucose level rose from 2.09 mmol/L (37.7 mg/dL) to 9.97 mmol/L (179.6 mg/dL) after 20 minutes. On hospital day 2, her dextrose infusion was slowly weaned. At 55 hours from admission, her dextrose infusion was discontinued, and she maintained euglycemia with frequent …

BackgroundMidkine (MDK), one of the heparin-binding growth factors, is highly expressed in multiple organs during embryogenesis. Plasma concentrations have been reported to be elevated in patients with a variety of malignancies, in adults with obesity, and in children with short stature, diabetes, and obesity. However, the concentrations in healthy children and their relationships to age, nutrition, and linear growth have not been well studied.Subjects and methodsPlasma MDK was measured by immunoassay in 222 healthy, normal-weight children (age 0-18 yrs, 101 boys), 206 healthy adults (age 18-91 yrs, 60 males), 61 children with BMI ≥ 95th percentile (age 4-18 yrs, 20 boys), 20 girls and young women with anorexia nervosa (age 14-23 yrs), and 75 children with idiopathic short stature (age 3-18 yrs, 42 boys). Body fat was evaluated by dual-energy X-ray absorptiometry (DXA) in a subset of subjects. The associations of MDK with age, sex, adiposity, race/ethnicity and stature were evaluated.ResultsIn healthy children, plasma MDK concentrations declined with age (r = -0.54, P < 0.001) with values highest in infants. The decline occurred primarily during the first year of life. Plasma MDK did not significantly differ between males and females or between race/ethnic groups. MDK concentrations were not correlated with BMI SDS, fat mass (kg) or percent total body fat, and no difference in MDK was found between children with anorexia nervosa, healthy weight and obesity. For children with idiopathic short stature, MDK concentrations did not differ significantly from normal height subjects, or according to height SDS or IGF-1 SDS.ConclusionsIn healthy children, plasma MDK concentrations declined with age and were not significantly associated with sex, adiposity, or stature-for-age. These findings provide useful reference data for studies of plasma MDK in children with malignancies and other pathological conditions.

Summary Pubertal gynecomastia is common, can be seen in 65% of the adolescent boys and is considered physiological. It is thought to be due to transient imbalance between the ratio of testosterone and estradiol in the early stages of puberty. It resolves in 1–2 years and requires no treatment. However, more persistent and severe pubertal gynecomastia is less common and can be associated with pathological disorders. These can be due to diminished androgen production, increased estrogen production or androgen resistance. We report a case of persistent pubertal gynecomastia due to partial androgen insensitivity syndrome (PAIS), classical hormone findings and a novel mutation in the androgen receptor (AR) gene. Learning points: Laboratory testing of follicle-stimulating hormone (FSH), leutinizing hormone (LH) and testosterone for pubertal gynecomastia is most helpful in the setting of undervirization. The hormonal finding of very high testosterone, elevated LH and estradiol and relatively normal FSH are classical findings of PAIS. Gynecomastia due to PAIS will not resolve and surgery for breast reduction should be recommended.

The extrathyroid manifestations of Graves disease (GD) include thyroid orbitopathy, dermopathy, and acropachy. Thyroid dermopathy (TD), also known as pretibial myxedema, classically presents as nonpitting edema or plaquelike lesions on the pretibial region, while thyroid acropachy (TA) is seen in cases of severe TD, characterized by soft tissue swelling and clubbing of fingers and toes, as well as a periosteal reaction of the bones of the hands and feet. Both TD and TA are rare manifestations of thyroid disease and uncommonly reported in pediatric patients. Our aim was to increase awareness of dermatological manifestations associated with pediatric GD and review the literature of pediatric thyroid dermopathy as well as report a case of acropachy in a child.

BACKGROUND: Prolactin-secreting macroadenomas are generally not life-threatening and often present with visual impairment. Medical management with a dopamine agonist is typically the treatment of choice, which significantly reduces the tumor size and improves symptoms without surgical morbidity. In this report, we present a case of an acidophilic stem cell adenoma (ASCA) that was slowly responsive to medical management, but exhibited marked visual recovery after surgical resection. RESULTS: A 15 year-old previously healthy male presented with significantly decreased peripheral vision but no other neurologic or endocrinologic symptoms. Initial magnetic resonance imaging of the brain/spine revealed a mass in the suprasellar and sellar regions with extension into the cavernous sinus and a prolactin level of 644, leading to a presumptive diagnosis of macroprolactinoma. Medical management with cabergoline resulted in some decrease of the prolactin level, but no radiographic improvement or visual recovery after two months. He subsequently underwent endoscopic endonasal transsphenoidal resection with near-total restoration of his peripheral vision post-operatively and significant improvement of his prolactin level. Pathology was consistent with an ASCA (staining positively with prolactin, growth hormone (a-subunit), and pituitary-specific positive transcription factor 1), a rare pituitary adenoma that tends to be invasive and often requires more aggressive therapy; the patient thus underwent focal consolidative proton beam irradiation. CONCLUSION: This case highlights the importance of considering acidophilic stem cell adenomas in the differential of medically-resistant pituitary macroadenomas and early consideration of resection in cases where significant visual or other symptoms exist, as timely intervention may substantially improve functional outcomes.

Endocrine emergencies require prompt identification and intervention to prevent morbidity and mortality. This chapter addresses the presentation, diagnosis, initial management, and disposition of patients suffering the following endocrine emergencies: diabetic ketoacidosis, adrenal crisis, hypernatremia secondary to diabetes insipidus, thyroid storm, and hypoglycemia.

Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.

Low-cost, translatable interventions to promote adherence in adolescents with type 1 diabetes are needed. This study evaluated a brief physician-delivered intervention designed to increase parent–adolescent communication about blood glucose monitoring. Thirty adolescent–parent dyads completed baseline questionnaires and received the physician-delivered intervention. Participants completed follow-up questionnaires at 12 weeks; HbA1c and glucometer data were abstracted from medical charts. Parent-reported conflict surrounding diabetes management decreased from pre- to postintervention. Participants who reported adhering to the intervention plan (n = 15) demonstrated an increase in blood glucose monitoring frequency and trends in improved HbA1c and parental diabetes collaboration from pre- to postintervention. Participants and physicians reported overall satisfaction with the program. Results demonstrate initial feasibility as well as a trend toward improvement in diabetes-specific health indicators for parent–adolescent dyads who adhered to program components. Frequent joint review of glucometer data can be a useful strategy to improve type 1 diabetes–related health outcomes and parent–adolescent communication.

Hyperthyroidism is much less common in children To compare the mean MMI dose needed to normalize free T4 in younger (Based on chart review (2004–2012), patients were divided into groups based on age at diagnosis: 12 years (n=40). Follow-up visits were reviewed until free T4 normalized.The mean dose of MMI (mg/kg/day) needed to normalize free T4 was 0.71 (±0.29) in the Hyperthyroid children diagnosed before age 7 required higher initial doses of MMI and took a longer time to become euthyroid than older patients. Clinicians should consider starting with higher weight-based MMI doses when treating younger patients to more rapidly normalize free T4.

BACKGROUND Premature adrenarche (PA) is often associated with bone age (BA) advanced by ≥2 years, which increases the concern for underlying pathology, but the frequency and clinical significance of this is unknown. Our objective was to identify the proportion of PA patients with very advanced BA and normal BA and compare the clinical characteristics of the two groups. METHODS Charts of 427 patients aged 5-9 years, referred for early puberty over a 2-year period, were reviewed for clinical diagnosis, growth, parental heights, hormone levels and BA. We divided the PA patients into three separate groups based on degree of BA advancement. Predicted adult heights (PAH) were calculated and compared to mid-parental target height (TH). RESULTS Of 427 patients, 266 (62%) had PA (82% female). Of the 121 with BA, 30.6% had very advanced BA (≥2 years) and this group was taller (Ht SD+1.72 vs. +0.72, p

Current guidelines recommend an initial L-thyroxine (L-T4) dose of 10-15 μg/kg/day for the treatment of congenital hypothyroidism (CH). We analyzed our data for the treatment outcome at 1 month after we noted a frequent overtreatment even at the lower end of this dose range.A 3-year chart review of 55 patients with confirmed CH was performed. The patients were divided to three groups based on L-T4 dose: Group 1 (6-9.9 μg/kg), Group 2 (10-11.9 μg/kg), and Group 3 (12-15 μg/kg). Overtreatment was defined as T416 μg/dL/free T42.3 ng/dL±thyroid-stimulating hormone (TSH)0.5 μIU/L and undertreatment was defined as TSH6 μIU/L at 1 month.At 1 month, 45.8%, 37.5%, and 16.6% in Group 1, 30%, 55%, and 15% in Group 2, and 0%, 75%, and 25% in Group 3 had target labs, overtreatment, and undertreatment, respectively.An initial L-T4 dose of 10-11.9 μg/kg for TSH100 μIU/L and 8-10 μg/kg for TSH100 μIU/L at diagnosis met and often exceeded the target thyroid levels at 1 month. More frequent overtreatment was seen when12 μg/kg was given.

AIM Although subnormal TSH between 0.1-0.4 mIU/L is fairly common and benign, suppression of TSH to < 0.1 mIU/L with normal free T4 is less common and more worrisome. We have conducted a retrospective chart review of a collection of such cases and have summarized the features and outcome on follow up. METHODS We studied 23 consecutive patients referred from 2005-07 to our pediatric endocrine clinic with TSH < 0.1 mIU/L and free T4 in the range of 0.8-2 ng/dl. We collected historical, clinical and laboratory data, and analyzed their outcome. RESULTS The natural evolutions of these subjects were separated into 4 groups. Group 1, 14 subjects, (61%) became euthyroid within a mean of 3.7 months. Group 2, 4 subjects, (17%) became hypothyroid within a mean of 2.8 months. Group 3, 2 subjects (9%) progressed to overt hyperthyroidism. Group 4, 3 subjects (13%) had persistently suppressed TSH, 8-14 months after initial testing, of which one had a multinodular goiter and had a thyroidectomy. Elevated thyroid peroxidase antibody (TPO) was seen in 54.5% of those tested. CONCLUSION Only 2/23 in our series became overtly hyperthyroid. Substantial number of subjects had a short period of transient TSH suppression that resolved spontaneously. Markers suggestive of autoimmune thyroid disease were consistently seen in group 2 and less so in others. It is prudent to observe such cases in the short term with serial follow up TSH, free T4 and T3, and to reserve further testing and treatment for those who become symptomatic or do not resolve.

Hyponatremia with hyperkalemia in infancy is an uncommon but life-threatening occurrence. In the first weeks of life, this scenario is often associated with aldosterone deficiency due to salt-wasting congenital adrenal hyperplasia. However, alternative diagnoses involving inadequate mineralocorticoid secretion or action must be considered, particularly for infants one month of age or older. We report four infants who presented with profound hyponatremia accompanied by urinary tract infection, ultimately leading to the diagnosis of transient pseudohypoaldosteronism. Our cases provide support for the idea that the renal tubular resistance to aldosterone is due to urinary tract infection itself rather than to underlying urinary tract anomalies typically found in these infants. Awareness of this condition is important so that serum aldosterone, urine sodium, and urine cultures may be obtained immediately in any infant presenting with hyponatremia and hyperkalemia in whom a diagnosis of congenital adrenal hyperplasia was not found. Adequate replacement with intravenous saline and antibiotic therapy is sufficient to correct sodium levels over 24–48 hours.

In this study, the destruction of the contrast agent Sonazoid (GE Healthcare, Oslo, Norway) was measured in vitro as a function of centre frequency (2-3 MHz), acoustic amplitude (0.66-1.6 MPa), pulse length (2-16 cycles) and PRF (0.5-8.0 kHz). Up to 82% of microbubbles were destroyed after exposure to a single 1.6 MPa acoustic pulse (16 cycles, 2.5 MHz and PRF of 1.0 kHz), while at a low amplitude of 0.66 MPa, fractional destruction increased gradually from 0 to 40% after exposure to 9 (identical) pulses. Fractional destruction increased from approximately 8 to 66% as pulse length was changed from 2 to 16 cycles following exposure to a single 2.5 MHz, 1.3 MPa pulse. As the PRF was increased from 0.5 to 8.0 kHz, shorter exposure time intervals (from 4.8 to 1.2 ms) were needed to achieve the same fractional destruction of 80%. Conversely, as the transmit frequency was increased from 2 to 3 MHz the fractional destruction decreased (by more than half within the first 3 pulses). The influence of changes in acoustic pressure and duty cycle on the destruction of Sonazoid microbubbles was highly statistically significant (por = 0.01) with a threshold around 0.67 MPa for a duty cycle of 0.0064. In conclusion, the fractional destruction increases with the duty cycle and the acoustic pressure amplitude and decreases with ultrasonic transmit frequency. Better understanding of the influence of the ultrasound transmit parameters on the destruction of contrast microbubbles should help improve existing contrast-assisted imaging modalities and may help develop new techniques for better use of contrast agents.

OBJECTIVE: To describe the practices in intensive care units in Mumbai hospitals regarding limitation and withdrawal of care at the end of life. DESIGN: Review of prospectively collected data. SETTINGS: Intensive care units of four major hospitals (two private tertiary referral general hospitals, one mixed public and private cancer referral hospital, and one large public hospital). PATIENTS: Hospital and intensive care unit patients who died during the study period. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We measured the percentage of hospital deaths occurring inside and outside intensive care units and the incidence of withholding intubation, withholding other therapy, and withdrawing therapy for deaths in the intensive care unit. The proportion of hospital deaths that occurred in an intensive care unit was 14% in the cancer hospital, 23% in the public hospital, and 58-73% in the two private hospitals (chi-square test for trends, p < .0001). Of the 143 deaths that occurred in intensive care unit, limitation of care occurred in 49 patients. Twenty-five percent of these patients were not intubated terminally, 67% were initially intubated and ventilated but failed to recover and subsequently had no further escalation of therapy, and 8% had withdrawal of therapy. Therapy was limited in 19% of deaths in the public hospital intensive care unit (odds ratio, 0.44; 95% confidence interval, 0.2-0.97) vs. 40%, 41%, and 50% of deaths in the other three intensive care units. CONCLUSIONS: Therapy is limited in a significant proportion of intensive care unit patients. Significant differences in the practice of limitation of therapy exist between public and private hospitals. Lack of access to a limited number of intensive care unit beds, especially in the public hospital, may constitute implicit limitation of care.