Long-term oncological outcomes of follicular thyroid cancer in adolescents and young adults: A nationwide population-based study.

BACKGROUND: Follicular thyroid carcinoma (FTC) in adolescents and young adults (AYAs) is rare and data on long-term oncological outcomes are scarce. This study aimed to describe the long-term recurrence and survival rates of AYAs with FTC, and identify risk factors for recurrence. METHODS: This is a retrospective cohort study combining two national databases, including all patients aged 15-39 years, diagnosed with FTC in The Netherlands between 2000 and 2016. Age, sex, tumor size, focality, positive margins, angioinvasion, pT-stage, and pN-stage were included in a Cox proportional hazard model to identify risk factors for recurrence. RESULTS: We included 192 patients. Median age was 31.0 years (IQR 24.7-36.3) and the male to female ratio was 1:4.1. Most patients presented with a minimally invasive FTC (MI-FTC) (95%). Five patients presented with synchronous metastases (2.6%), including two with locoregional metastases (1%) and three with distant metastases (1.6%). During a median follow-up of 12.0 years, three patients developed a recurrence (1.6%), of which one patient developed a local recurrence (33%), and two patients a distant recurrence (67%). Five patients died during follow-up (2.6%). Cause of death was not captured. A Cox proportional hazard model could not be performed due to the low number of recurrences. CONCLUSIONS: FTC in AYAs is generally characterized as a low-risk tumor, as it exhibits a very low recurrence rate, a high overall survival, and it typically presents as MI-FTC without synchronous metastases. These findings underscore the favorable long-term oncological prognosis of FTC in AYAs.

Cardiac function in paediatric patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency.

BACKGROUND: Hyperandrogenism and exogenous glucocorticoid excess may cause unfavourable changes in the cardiovascular risk profile of patients with congenital adrenal hyperplasia (CAH). OBJECTIVE: To evaluate the cardiac function in paediatric patients with CAH. PATIENTS AND METHODS: Twenty-seven paediatric patients with CAH, aged 8-16 years, were evaluated by physical examination, electrocardiogram (ECG), conventional echocardiography, tissue Doppler imaging and two-dimensional (2D) myocardial strain (rate) imaging. Results were compared to 27 age- and gender- matched healthy controls. RESULTS: No signs of left ventricular hypertrophy or dilatation were detected on echocardiography. ECG revealed a high prevalence (25.9%) of incomplete right bundle branch block. Left ventricular posterior wall thickness in diastole (LVPWd) was significantly lower in patients with CAH compared to controls (5.55 vs 6.53 mm; P = .009). The LVPWd Z-score was significantly lower in patients with CAH yet within the normal range (-1.12 vs -0.35; P = .002). Isovolumetric relaxation time was significantly lower in patients with CAH (49 vs 62 ms; P = .003). Global longitudinal, radial and circumferential strain was not significantly different compared to controls. Global radial strain rate was significantly higher compared to healthy controls (2.58 vs 2.06 1/s; P = .046). Global longitudinal strain was negatively correlated with 24-hour blood pressure parameters. CONCLUSION: Cardiac evaluation of paediatric patients with CAH showed no signs of left ventricular hypertrophy or ventricular dilatation. LVPWd was lower in patients with CAH than in controls but within the normal range. A shorter isovolumetric relaxation time in patients with CAH may be a sign of mild left ventricular diastolic dysfunction.

Pancytopenia and Hypothyroidism in a Patient With Leukemic Infiltration of the Thyroid as the First Presentation of Acute Lymphoblastic Leukemia.

We report the case of a 16-year-old female patient with hypothyroidism, goiter, and pancytopenia. Biopsy of the thyroid showed leukemic infiltration. After confirmation of the diagnosis of B-lymphoblastic leukemia, treatment was started. Histologic follow-up at day 33 and 79 showed no residual signs of leukemic infiltration. Hypothyroidism persisted despite successful antileukemic treatment. Leukemic infiltration of the thyroid should be considered as a differential diagnosis in patients with hypothyroidism, goiter, and pancytopenia. We suggest that follow-up of thyroid function and histology should be incorporated in the follow-up of rare patients with acute lymphoblastic leukemia with thyroid infiltration.

Disorders of Adrenal Steroidogenesis: Impact on Gonadal Function and Sex Development.

A defect in adrenal steroidogenesis may cause a disorder of sex development (DSD). Importantly, DSD of adrenal origin is not restricted to a genital phenotype but is in most cases accompanied by mild to severe impairment in glucocorticoid and/or mineralocorticoid synthesis. If a patient is suspected of DSD of adrenal origin evaluation of glucocorticoid and mineralocorticoid metabolism is therefore essential to provide adequate medical care in the case of a severe and potentially life-threatening insufficiency. The adrenal steroidogenic defects causing DSD, their clinical features and diagnostic work-up are discussed. In this review we provide an overview of defects in the adrenal steroidogenesis and its impact on gonadal function and sex development.

Characterization of the molecular genetic pathology in patients with 11ß-hydroxylase deficiency.

OBJECTIVE: Steroid 11ß-hydroxylase (CYP11B1) deficiency (11OHD) is the second most common form of congenital adrenal hyperplasia. Nonclassic or mild 11OHD appears to be a rare condition. Our study assessed the residual CYP11B1 function of detected mutations, adding to the spectrum of mild 11OHD, and illustrates the variability of the clinical presentation of 11OHD. PATIENTS AND METHODS: Five patients presented with mild to moderate 11OHD. Two women presented with mild hirsutism and in one case with secondary amenorrhoea. Two men presented with precocious pseudopuberty, gynaecomastia and elevated blood pressure. One 46,XX female patient was diagnosed with virilization of the external genitalia 2 years after birth. Direct DNA sequencing was carried out to perform CYP11B1 mutation analysis. The CYP11B1 mutations were functionally characterized using an in vitro expression system. RESULTS: CYP11B1-inactivating mutations were detected in all patients. Two novel missense mutations (p.P42L and p.A297V) and the previously characterized p.R143W mutation had residual CYP11B1 activities between 10% and 27%. A novel p.L382R and the previously uncharacterized p.G444D mutation both caused complete loss of CYP11B1 enzymatic activity. CONCLUSION: Mutations causing partial impairment of 11ß-hydroxylase activity (residual activity of 10% or above) are associated with a less severe clinical presentation of 11OHD, which can be classified as a nonclassic form. Our data demonstrate that patients with nonclassic 11OHD can present with androgen excess, precocious pseudopuberty and increased blood pressure. Timely diagnosis of nonclassic 11OHD and consequently initiation of personalized treatment is essential to prevent co-morbidities caused by androgen excess and hypertension.

Approach to the Patient: Challenging Cases of Pediatric Thyrotoxicosis.

Graves' disease (GD) is the leading cause of hyperthyroidism in children. However, compared to adults GD in children is a rare condition. In a recent guideline issued by the European Thyroid Association the diagnostic evaluation and treatment of pediatric GD is described extensively. In this article we go beyond the guideline and describe the potential challenges of establishing the right etiology of thyrotoxicosis in children, illustrated by cases of thyroid hormone resistance, autonomous functioning thyroid nodules and subacute thyroiditis with a thyrotoxic phase. In addition, we report therapeutic challenges in pediatric GD such as recurrent immunological flare-ups under anti-thyroid drug (ATD) treatment, innovative ways to improve ATD compliance and the role of definitive treatment in persistent complaints of malaise under ATD treatment.

Iodinated Contrast Induced Hypothyroidism in the Infant After Enteral Contrast Enema: A Case Report and Systematic Review.

Background: Excessive iodine intake triggers the Wolff-Chaikoff effect resulting in downregulation of thyroid hormone synthesis to prevent hyperthyroidism. Failure to escape the Wolff-Chaikoff effect can be seen especially in (premature born) infants and may result in prolonged iodine induced hypothyroidism. We describe a rare case of a preterm infant who developed severe iodinated contrast induced hypothyroidism after the use and prolonged stasis of enteral iodinated contrast media (ICM). In addition a systematic literature search was performed to evaluate all available data on this complication. Methods: A systematic literature search was performed in PubMed and Embase. Studies describing the effect of enteral ICM on thyroid function were considered eligible. The primary outcome was to determine the frequency of contrast induced hypothyroidism in infants after administration of enteral ICM. Results: The premature infant in our center developed severe iodinated contrast induced hypothyroidism after enteral ICM. In total, only two studies met our eligibility data, reporting eight patients. Out of these eight patients, four premature infants developed a contrast induced hypothyroidism after enteral administration of ICM. Conclusion: Data on severity, length and frequency of contrast induced hypothyroidism after exposure to enteral ICM is very scarce. The herein reported case and literature search illustrate the potential severity of the complication and underline the necessity of future studies on this topic. We recommend standardized monitoring of thyroid function after exposure to enteral ICM in newborns to prevent delayed diagnosis of severe contrast induced hypothyroidism until evidence based recommendations can be made.

The Definition of Recurrence of Differentiated Thyroid Cancer: A Systematic Review of the Literature.

Background: Recurrence is a key outcome to evaluate the treatment effect of differentiated thyroid carcinoma (DTC). However, no consistent definition of recurrence is available in current literature or international guidelines. Therefore, the primary aim of this systematic review was to delineate the definitions of recurrence of DTC, categorized by total thyroidectomy with radioactive iodine ablation (RAI), total thyroidectomy without RAI and lobectomy, to assess if there is a generally accepted definition among these categories. Methods: This study adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. In December 2023, a systematic literature search in MEDLINE and EMBASE was performed for studies reporting on the recurrence of DTC, from January 2018 to December 2023. Studies that did not provide a definition were excluded. Primary outcome was the definition of recurrence of DTC. Secondary outcome was whether studies differentiated between recurrence and persistent disease. Two independent investigators screened the titles and abstracts, followed by full-text assessment and data extraction. The study protocol was registered in PROSPERO, CRD42021291753. Results: In total, 1450 studies were identified. Seventy studies met the inclusion criteria, including 69 retrospective studies and 1 randomised controlled trial (RCT). Median number of patients in the included studies was 438 (range 25-2297). In total, 17 studies (24.3%) reported on lobectomy, 4 studies (5.7%) on total thyroidectomy without RAI, and 49 studies (70.0%) with RAI. All studies defined recurrence using one or a combination of four diagnostic modalities cytology/pathology, imaging studies, thyroglobulin (-antibodies), and a predetermined minimum tumor-free time span. The most common definition of recurrence following lobectomy was cytology/pathology-proven recurrence (47.1% of this subgroup), following total thyroidectomy with RAI was cytology/pathology-proven recurrence and/or anomalies detected on imaging studies (22.4% of this subgroup). No consistent definition was found following total thyroidectomy without RAI. Nine studies (12.9%) differentiated between recurrence and persistent disease. Conclusion: Our main finding is that there is no universally accepted definition for recurrence of DTC in the current studies across any of the treatment categories. The findings of this study will provide the basis for a future, international Delphi-based proposal to establish a universally accepted definition of recurrence of DTC. A uniform definition could facilitate global discussion and enhance the assessment of treatment outcomes regarding recurrence of DTC.

A 15-year-old Girl with a Lateral Neck Mass Turning Out to Be Papillary Thyroid Carcinoma-Lateral Ectopic Papillary Thyroid Carcinoma or Lymph Node Metastasis?

Lateral neck lesions in children are common and involve various infectious or inflammatory etiologies as well as embryological remnants such as branchial cleft cysts. Although unusual, ectopic thyroid tissue can also present as a lateral neck mass. Here, we present an unusual case of a 15-year-old girl treated for an asymptomatic lateral neck mass that after surgical removal was found to be papillary thyroid carcinoma (PTC). However, after removal of the thyroid gland, no primary thyroid tumor was found. The question arose whether the lateral neck lesion was a lymph node metastasis without identifiable primary tumor (at histological evaluation) or rather malignant degeneration of ectopic thyroid tissue. Total thyroidectomy was performed with postoperative adjuvant radioactive iodine ablation. Even though PTC in a lateral neck mass without a primary thyroid tumor has been described previously, pediatric cases have not been reported. In this report we share our experience on diagnosis, treatment and follow-up, and review the existing literature.