Opposite Incidence Trends for Differentiated and Medullary Thyroid Cancer in Young Dutch Patients over a 30-Year Time Span (vol 13, 5104, 2021)

Error in Figure In the original article [1], there was a mistake in Figure 1 as published. In this figure, two years are missing (2000 and 2001). The AAPC values as previously published are correct. The corrected Figure 1 appears below. In addition, in the original article, there was a mistake in Figure 2A–C as published. In these figures, two years are missing (2000 and 2001). The AAPC values were correct and do not require adjustment. The corrected Figure 2A–C appears below. The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated. (figure presented)

Een baby met een onduidelijk geslacht

In a neonate with ambiguous genitalia, physical examination revealed a phallus. Ultrasonography showed a vagina and uterus, but no gonads. Because of severe undervirilisation in the presence of a uterus, probably due to 46,XY gonadal dysgenesis, parents were advised female sex assignment. When after a few weeks the phallus had increased in size, abdominal laparoscopy showed an underdeveloped uterus. Gonadal biopsy confirmed gonadal dysgenesis. Sex assignment was reconsidered and changed into the male gende

Fetal Thyrotoxicosis due to Maternal TSH Receptor Stimulating Antibodies Causes Infant Central Hypothyroidism

INTRODUCTION: Women with a current diagnosis or past history of Graves' disease (GD) are at risk of developing fetal thyrotoxicosis (FT) during pregnancy when they are inadequately treated, or because of placental passage of TSH receptor antibodies (TRAb). It is known that FT induced by high maternal thyroid hormone concentrations may result in infant (central) hypothyroidism.CASE PRESENTATION: In a euthyroid woman with a history of GD treated with radioactive iodide (I131), persistently high levels of maternal TRAb resulted in recurrent FT during two separate pregnancies, followed by neonatal hyperthyroidism and infant central hypothyroidism.DISCUSSION: This case demonstrates the novel insight that FT due to high fetal thyroid hormone concentrations stimulated by high maternal TRAb levels might also result in (central) hypothyroidism, requiring long-term evaluation of the hypothalamus-pituitary-thyroid axis in these children.</p

Thyroidectomy in pediatric patients with Graves’ disease: A systematic review of postoperative morbidity

Background: Graves’ disease (GD) is the most common cause of hyperthyroidism. In children, the overall relapse frequency after treatment with antithyroid drugs is high. Therefore, many pediatric GD patients eventually require thyroidectomy as definitive treatment. However, the postoperative complications of thyroidectomy in pediatric GD patients are poorly reported. Objective: To identify the frequency of short- and long-term postoperative morbidities after thyroidectomy in pediatric GD patients. Methods: A systematic review of the literature (PubMed and Embase) was performed to identify studies reporting short- and long-term postoperative morbidities after thyroidectomy in pediatric GD patients according to the PRISMA guidelines. Results: Twenty-two mainly retrospective cohort studies were included in this review evaluating short- and long-term morbidities in 1,424 children and adolescents. The frequency of transient hypocalcemia was 22.2% (269/1,210), with a range of 5.0–50.0%. The frequency of permanent hypocalcemia was 2.5% (36/1,424), with a range of 0–20.0%. Two studies reported high frequencies of permanent hypocalcemia, 20.0 (6/30) and 17.4% (9/52), respectively. The 20% frequency could be explained by low-volume surgeons in poorly controlled GD patients. Only 21 cases of permanent hypocalcemia were reported in the 1,342 patients included in the other 20 studies (1.6%). Transient and permanent recurrent laryngeal nerve injury were reported less frequently, with frequencies between 0–20.0 and 0–7.1%, respectively. Infection, hemorrhage/hematoma, and keloid development were only rarely reported as postoperative complications. Conclusion: The results of this systematic review suggest that thyroidectomy is a safe treatment option for pediatric GD patients. The minority of patients will experience transient and benign morbidities, with hypocalcemia being the most common transient postoperative morbidity. Permanent postoperative morbidities are relatively rare

Comorbidity, hospitalization, and medication use and their influence on mental and motor development of young infants with Down syndrome

OBJECTIVE: Young infants with Down syndrome have an increased occurrence of several well-known medical conditions such as congenital heart and gastrointestinal disease. The aim of this study was to establish consequences like hospitalization and medication use rates and to determine their possible influence on early neurodevelopment. PATIENTS AND METHODS: This study compared 2 years of thyroxine treatment with placebo in 196 neonates with Down syndrome who were included in a previously reported randomized clinical trial. Parents were interviewed about comorbidity, hospitalization, and medication use at random assignment and regularly thereafter. Data were cross-checked with discharge letters when available. The influence of comorbidity on neurodevelopment at 2 years old (Bayley Scales of Infant Development II) was determined by stepwise multiple linear-regression analysis. RESULTS: Before trial entry, 163 infants with Down syndrome had been admitted to hospital for an average of 14.01 days, whereas during the trial, 95 of 181 infants who completed the trial were hospitalized for an average 19.75 days. Main hospitalization reasons during the trial were lung/airway and congenital heart and gastrointestinal disease. The 48 infants operated on for heart or gastrointestinal disease accounted for 1401 of the total number of 1876 hospital admission days during the trial and for 33 of 62 admissions for lung/airway infection. During their second year of life, approximately 60% of the infants were prescribed drugs, mostly antibiotics and pulmonary. Regression analysis showed infantile spasms, "other" central nervous system disease, and gastrointestinal disease necessitating surgery to be associated with greater developmental age delays at 24 months old (mental: 6.87, 3.52, and 1.69 months; and motor: 3.59, 2.54, and 1.68 months, respectively). CONCLUSIONS: Hospital admission and medication use rates in young infants with Down syndrome are still very high, mainly because of congenital heart and gastrointestinal disease and acquired respiratory disease. Central nervous system disease and gastrointestinal disease necessitating surgery were independently associated with a worse developmental outcom

Growth hormone analysis and treatment in Ellis-van Creveld syndrome

Little is known on growth, growth hormone (GH) levels and GH treatment in patients with Ellis-van Creveld syndrome (EvC). The aim of the present study was to assess growth, growth hormone status and the possible effectiveness of GH treatment in literature and in a small series of EvC patients. A review of literature indicated retarded growth for most EvC patients (-2 to -4.5 SDS) and minimal data on GH levels or treatment which did not allow any conclusion. We studied eight EvC patients, seven of whom were treated with GH. Four were GH deficient (GHD) and four were GH sufficient. In all patients treated with GH, first year growth velocity increased. In three of the four GHD and in one GH-sufficient patient a gain in height SDS was noted. In the present small EvC series GHD occurred more often than expected. Patient acquisition through the Growth Hormone Database will have caused a significant bias, but the present results indicate that GH treatment may improve growth in at least some patients with EvC. Therefore we conclude that EvC patients may benefit from being tested for GHD and, if indicated, treated. In addition a prospective study to evaluate GH status and linear growth in patients with EvC as well as the potential effectiveness of GH treatment is warrante

Trisomy 21 causes persistent congenital hypothyroidism presumably of thyroidal origin

OBJECTIVE AND DESIGN: Lowered neonatal plasma thyroxine (T(4)) and mildly elevated thyrotropin concentrations together with developmental benefits from neonatally started T(4) treatment in a randomized clinical trial demonstrated Down syndrome (DS) neonates to be mildly hypothyroid, at least during their first weeks of life. To prove that this hypothyroid state persists beyond this period in all, and to elucidate its etiology, we evaluated the course of the thyroid function determinants in all DS infants participating in this 24-month trial. MAIN OUTCOME: Mean plasma thyrotropin concentrations and thyrotropin frequency distributions of 97 placebo-treated infants were persistently shifted to substantially higher concentrations, while free T(4) frequency distributions were in the lower two thirds of the reference interval. Mean thyroglobulin concentrations were normal. To normalize plasma thyrotropin, T(4)-treated DS infants (N = 99) needed rather high free T(4) concentrations, like T(4)- treated non-DS children with thyroidal congenital hypothyroidism. At ages 12 and 24 months, thyroid peroxidase antibodies were detected in 1.1% and 5.4% of all DS infants. CONCLUSIONS: These findings suggest that as a group DS infants have a novel type of persistent mild congenital hypothyroidism, presumably of thyroidal origin. The group character suggests a direct relation with the trisomic state of chromosome 21, hypothetically through genomic dosage imbalance of dosage-sensitive genes interfering with thyroid hormone productio

The effect of pre-thyroidectomy calcitriol prophylaxis on post-thyroidectomy hypocalcaemia in children

INTRODUCTION: Transient or permanent hypoparathyroidism is one of the most well-known complications of total thyroidectomy and may lead to symptomatic hypocalcaemia. In children treatment of post-thyroidectomy hypocalcaemia usually consists of postoperative calcium and/or vitamin D supplementation. In 2013 we implemented prophylactic pre-thyroidectomy calcitriol supplementation for all children undergoing total thyroidectomy at the Amsterdam UMC. The objective of this study was to evaluate the efficacy of this prophylactic calcitriol supplementation in preventing post-thyroidectomy hypocalcaemia in children. METHODS: In a retrospective case study we included all children (age < 18 years), who underwent a total or completion thyroidectomy in the Amsterdam UMC, between 2000 and 2020. Patients were divided into two groups, patients with preoperative calcitriol supplementation, and those without (controls). Hypocalcaemia was defined as total serum calcium concentration of < 2.0 mmol/l. Primary outcome measure was the occurrence of hypocalcaemia in the first 72 hours after surgery. Secondary outcome measures were occurrence of symptomatic hypocalcaemia and need for medical intervention within the first 72 hours after surgery, and length of hospitalization. RESULTS: A total of 51 patients were included; 26 with calcitriol prophylaxis and 25 controls. There was no significant difference in occurrence of hypocalcaemia (17/26 prophylaxis group; 18/25 control group). Median post-operative calcium concentrations in the first 72 hours were significantly higher in the group with prophylaxis at 30-35 hours (2.26 vs 2.01 mmol/l) and 36-41 hours (2.17 vs 1.92 mmol/l). Occurrence of symptomatic hypocalcaemia, need for medical intervention and length of hospitalization were not significantly different between the groups. CONCLUSION: Calcitriol prophylaxis resulted in somewhat higher postoperative calcium concentrations, but did not reduce the occurrence of hypocalcaemia or affect clinical outcome measures such as occurrence of symptomatic hypocalcaemia and length of postoperative hospitalization

Statin treatment in children with familial hypercholesterolemia - The younger, the better

Background - We previously demonstrated in a randomized placebo- controlled trial that 2-year pravastatin treatment induced a significant regression of carotid intima-media thickness (IMT) in 8- to 18-year-old children with familial hypercholesterolemia. Subsequently, we continued to follow up these children to explore the relation between the age of statin initiation and carotid IMT after follow- up on statin treatment. We also examined safety aspects of statin therapy during this long-term follow-up. Methods and Results - All 214 children who initially participated in the previous placebo-controlled study were eligible for the follow- up study. After completion of the placebo-controlled study, all children continued treatment with pravastatin 20 or 40 mg, depending on their age. Blood samples were taken on a regular basis for lipids and safety parameters, and a carotid IMT measurement was performed after an average treatment period of 4.5 years. Follow-up data for 186 children were available for the statistical analyses. Multivariate analyses revealed that age at statin initiation was an independent predictor for carotid IMT after follow-up with adjustment for carotid IMT at initiation of statin treatment, sex, and duration of treatment. Early initiation of statin treatment was associated with a subsequently smaller IMT. Furthermore, no serious laboratory adverse events were reported during follow- up, and statin treatment had no untoward effects on sexual maturation. Conclusions - These data indicate that early initiation of statin treatment delays the progression of carotid IMT in adolescents and young adults. The present study shows for the first time that early initiation of statin therapy in children with familial hypercholesterolemia might be beneficial in the prevention of atherosclerosis in adolescenc

Gonadal steroids, gonadotropins and DHEAS in young adults with familial hypercholesterolemia who had initiated statin therapy in childhood

Statins are currently the preferred pharmacological therapy in children with familial hypercholesterolemia (FH) with the aim to prevent premature cardiovascular disease (CVD). However, concerns have been raised that lowering cholesterol levels with statins could interfere with hormone production. In this study hormone concentrations were assessed in young adult FH subjects before and 10 years after the initiation of statins, and compared with their unaffected siblings. All 214 FH children (8-18 years) who were previously randomized into a placebo-controlled trial evaluating the 2-year efficacy and safety of pravastatin, and their 95 unaffected siblings, were eligible. Women using oral contraceptives were excluded. Fasted blood samples were taken to measure lipids and testosterone (males), estradiol (females), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and dehydroepiandosterone (DHEAS). After ten years, gonadal steroid and gonadotropin concentrations were within the reference interval and did not differ between FH subjects (n = 88) and unaffected siblings (n = 62). Mean DHEAS concentrations (±standard deviation) in the FH subjects and female siblings were normally distributed within the reference interval, whereas male siblings had a higher mean DHEAS concentration than their FH brothers (12.9 [± 4.9] vs. 8.4 [± 3.0] μmol/L, respectively, p < 0.0001). After ten years of statin treatment, testosterone, estradiol, LH and FSH concentrations in young adult FH patients are within the reference interval and comparable to their unaffected siblings. These results strengthen current guidelines that statins in FH subjects could be safely used from childhood onwards to prevent premature CV