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1.
Pediatrics ; 151(1)2023 01 01.
Article in English | MEDLINE | ID: mdl-36827521

ABSTRACT

ABSTRACT: Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Prompt diagnosis by newborn screening (NBS) leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet established in all countries globally. Seventy percent of neonates worldwide do not undergo NBS.The initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism.Newborn screening alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.


Subject(s)
Congenital Hypothyroidism , Infant, Newborn , Infant , Humans , Child , Child, Preschool , Thyroxine , Thyrotropin , Thyroid Function Tests , Neonatal Screening
2.
Pediatrics ; 151(1)2023 01 01.
Article in English | MEDLINE | ID: mdl-36827523

ABSTRACT

Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Newborn screening (NBS) for CH should be performed in all infants. Prompt diagnosis by NBS leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet practiced in all countries globally. Seventy percent of neonates worldwide do not undergo NBS. The recommended initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and with free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding the detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth-weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism. NBS alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.


Subject(s)
Congenital Hypothyroidism , Infant, Newborn , Infant , Humans , Child , Child, Preschool , Thyroxine , Thyrotropin , Thyroid Function Tests , Neonatal Screening
3.
AJR Am J Roentgenol ; 220(1): 144-145, 2023 01.
Article in English | MEDLINE | ID: mdl-35731099

ABSTRACT

On March 30, 2022, the U.S. FDA issued a drug safety communication recommending that infants and young children through 3 years of age undergo monitoring of thyroid function within 3 weeks of intravascular administration of iodine-based contrast media. This article considers the literature that was referenced for this decision and provides an outlook on thyroid monitoring after diagnostic imaging from pediatric radiology and pediatric endocrinology perspectives.


Subject(s)
Iodine , Radiology , Humans , Infant , Child , Child, Preschool , Infant, Newborn , Thyroid Gland/diagnostic imaging , Iodine/adverse effects , Contrast Media/adverse effects
4.
Best Pract Res Clin Endocrinol Metab ; 37(1): 101715, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36404191

ABSTRACT

Thyroid cancer is rare in children but its incidence is increasing. Recent data have clarified important similarities and differences between thyroid cancers originating in childhood and in adulthood. The genetic drivers of pediatric thyroid cancers are similar to those in adult tumors but comprise more gene fusions and fewer point mutations. Clinically, despite frequent metastatic spread, pediatric thyroid cancer has an excellent prognosis and mortality is rare. Therefore, treatment approaches must weigh carefully the morbidity of thyroid cancer treatments against their benefits. Current key questions include which children require total thyroidectomy rather than more limited-and safer-lobectomy, and in which children does the benefit of radioactive iodine therapy outweigh its risk of inducing a secondary malignancy. Finally, molecular therapies targeting genetic drivers of thyroid cancer now provide effective treatment for children with progressive, radioiodine-refractory disease, as well as opportunities to explore novel neoadjuvant uses that facilitate therapeutic surgery or radioactive iodine.


Subject(s)
Thyroid Neoplasms , Adult , Humans , Child , Thyroid Neoplasms/pathology , Iodine Radioisotopes/therapeutic use , Treatment Outcome , Prognosis , Thyroidectomy
5.
Thyroid ; 32(9): 1109-1117, 2022 09.
Article in English | MEDLINE | ID: mdl-35950619

ABSTRACT

Background: It is uncertain whether the presence of autoimmune thyroiditis (AIT) increases the risk of thyroid cancer in children with thyroid nodules. This study evaluated the association between AIT and thyroid cancer in pediatric patients with thyroid nodules. Methods: A cross-sectional study was performed of pediatric patients (<19 years old) with a thyroid nodule (≥1 cm) who underwent fine-needle aspiration in an academic pediatric thyroid center. AIT was defined by the presence of thyroid autoantibodies or diffusely heterogeneous sonographic echotexture. The primary outcome was diagnosis of thyroid cancer. The association of AIT with thyroid cancer was evaluated with univariable and multivariable logistic regression. Associations of AIT with subject and nodule characteristics were also assessed. Results: Four hundred fifty-eight thyroid nodules in 385 patients (81% female) were evaluated at a median age of 15.5 years (interquartile range 13.5-17.0). Thyroid cancer was present in 108 nodules (24%). AIT was present in 95 subjects (25%) and was independently associated with an increased risk of thyroid cancer (multivariable odds ratio [OR] 2.19, 95% confidence interval [CI] 1.32-3.62). Thyroid cancer was also independently associated with younger age, nodule size, and solitary nodules, but was not associated with serum thyrotropin concentration. AIT was not associated with the likelihood of subjects undergoing thyroid surgery (p = 0.17). AIT was less commonly associated with follicular thyroid carcinoma than with papillary thyroid carcinoma (OR 0.22, CI 0.05-1.06). Among papillary thyroid carcinomas, AIT was strongly associated with the diffuse sclerosing variant (OR 4.74, CI 1.33-16.9). AIT was not associated with the extent of local, regional, or distant disease at thyroid cancer diagnosis. Conclusions: AIT is independently associated with an increased risk of thyroid cancer in children with thyroid nodules. These findings suggest that the evaluation of thyroid autoantibodies and thyroid echotexture may inform thyroid cancer risk assessment and surgical decision-making in children with thyroid nodules.


Subject(s)
Hashimoto Disease , Thyroid Neoplasms , Thyroid Nodule , Thyroiditis, Autoimmune , Adolescent , Autoantibodies , Cross-Sectional Studies , Female , Hashimoto Disease/complications , Humans , Male , Retrospective Studies , Thyroid Cancer, Papillary/complications , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/epidemiology , Thyroid Nodule/complications , Thyroid Nodule/diagnostic imaging , Thyroiditis, Autoimmune/complications , Thyrotropin
7.
Am J Gastroenterol ; 117(7): 1166-1168, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35333786

ABSTRACT

INTRODUCTION: Ultrasound screening for thyroid cancer is recommended in familial adenomatous polyposis (FAP). This study investigated the prevalence of thyroid neoplasia in children with FAP. METHODS: Cross-sectional study of children with FAP at an academic hospital. Clinical and ultrasound data were analyzed for the prevalence of thyroid nodules and cancer. RESULTS: Of 37 children with FAP, 8 (22%) had thyroid nodules and 2 (5%) had thyroid cancer. Nodules (30%) and cancer (9%) were more common among female subjects and rare among male subjects. DISCUSSION: Thyroid ultrasound screening in adolescence may benefit female subjects with FAP but has limited utility in male subjects.


Subject(s)
Adenomatous Polyposis Coli , Thyroid Neoplasms , Thyroid Nodule , Adenomatous Polyposis Coli/diagnostic imaging , Adenomatous Polyposis Coli/epidemiology , Adolescent , Child , Cross-Sectional Studies , Female , Humans , Male , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/epidemiology , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/epidemiology
8.
Cancer Cytopathol ; 130(5): 330-335, 2022 05.
Article in English | MEDLINE | ID: mdl-35119774

ABSTRACT

BACKGROUND: Thyroid nodules with atypia of undetermined significance (AUS) are challenging to manage because of their intermediate risk of malignancy. Subclassification of atypia can refine malignancy risk in adult AUS nodules but has not been evaluated in children. METHODS: This was a retrospective cohort study of pediatric patients (<19 years old) who underwent fine-needle aspiration (FNA) of a thyroid nodule with resulting AUS cytology. Atypia was subclassified as nuclear only, architectural only, nuclear and architectural, or oncocytic. The primary outcome was the association between atypia subtype and malignancy. A secondary outcome was the association of atypia subtype with repeat FNA cytology. RESULTS: Sixty-eight AUS nodules in 61 patients were analyzed. The median age at FNA was 16.2 years (range, 9.8-18.9 years). Twenty-four nodules (35%) were malignant. Nuclear atypia only was present in 17 nodules (25%), architectural atypia only was present in 27 nodules (40%), nuclear and architectural atypia was present in 20 nodules (29%), and predominantly oncocytic features were present in 4 nodules (6%). The presence of nuclear atypia was associated with a significantly increased rate of malignancy (22 of 37 [59%] vs 2 of 31 [6.5%]; P < .001), whereas architectural atypia was not associated with malignancy (P = .8). Repeat FNA was performed in 42 of 68 nodules (62%). In nodules with initial nuclear and architectural atypia, benign repeat cytology had a high false-negative rate (3 of 6; 50%). CONCLUSIONS: Pediatric AUS nodules with nuclear atypia have a high rate of malignancy, but architectural atypia is not associated with malignancy. In nodules with nuclear atypia, repeat FNA may inform clinical decisions regarding the need for resection. In the absence of suspicious clinical features, nodules without nuclear atypia might be considered for observation rather than resection or repeat FNA.


Subject(s)
Adenocarcinoma, Follicular , Thyroid Neoplasms , Thyroid Nodule , Adenocarcinoma, Follicular/pathology , Adult , Biopsy, Fine-Needle/methods , Child , Cytodiagnosis , Humans , Retrospective Studies , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroid Nodule/pathology , Young Adult
9.
Cancer Med ; 11(8): 1745-1752, 2022 04.
Article in English | MEDLINE | ID: mdl-35174967

ABSTRACT

PURPOSE: Multigene panels allow simultaneous testing of genes involved in cancer predisposition. Thyroid cancer (TCa) is a component tumor of several cancer predisposition syndromes, but the complete landscape of germline variants predisposing to TCa remains to be determined. METHODS: Clinical information and genetic test results were reviewed from over 170,000 individuals who had multigene panel testing for hereditary cancer at a single diagnostic laboratory. Germline pathogenic and likely pathogenic variants ("pathogenic variants") were examined among individuals with TCa. A cohort with breast cancer (BCa) was examined to serve as a comparison group and to determine the added contribution of TCa to the ascertainment of genetic risk. RESULTS: Of 3134 individuals with TCa, 291 (9.3%) were found to have one or more pathogenic variant(s). Among 904 individuals with TCa alone, 7.5% had one or more pathogenic variant(s), similar to those with BCa alone (8.4%). In all groups, CHEK2 was the gene with the highest number of pathogenic variants identified, with a significantly increased frequency among individuals with a history of both thyroid and BCa compared to BCa alone. CONCLUSIONS: A high prevalence of germline pathogenic variants was observed among individuals with TCa referred for hereditary cancer genetic testing, even in the absence of other cancer diagnoses. These data suggest that TCa may be an under-recognized component of cancer predisposition syndromes.


Subject(s)
Germ-Line Mutation , Thyroid Neoplasms , Genetic Predisposition to Disease , Genetic Testing/methods , Germ Cells , Humans , Syndrome , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/genetics
11.
N Engl J Med ; 385(22): 2059-2065, 2021 11 25.
Article in English | MEDLINE | ID: mdl-34818480

ABSTRACT

The integration of genomic testing into clinical care enables the use of individualized approaches to the management of rare diseases. We describe the use of belzutifan, a potent and selective small-molecule inhibitor of the protein hypoxia-inducible factor 2α (HIF2α), in a patient with polycythemia and multiple paragangliomas (the Pacak-Zhuang syndrome). The syndrome was caused in this patient by somatic mosaicism for an activating mutation in EPAS1. Treatment with belzutifan led to a rapid and sustained tumor response along with resolution of hypertension, headaches, and long-standing polycythemia. This case shows the application of a targeted therapy for the treatment of a patient with a rare tumor-predisposition syndrome. (Funded by the Morin Family Fund for Pediatric Cancer and Alex's Lemonade Stand Foundation.).


Subject(s)
Adrenal Gland Neoplasms/drug therapy , Basic Helix-Loop-Helix Transcription Factors/antagonists & inhibitors , Indenes/therapeutic use , Paraganglioma/drug therapy , Polycythemia/drug therapy , Adolescent , Adrenal Gland Neoplasms/genetics , Adrenal Glands/diagnostic imaging , Adrenal Glands/drug effects , Adrenal Glands/pathology , Basic Helix-Loop-Helix Transcription Factors/genetics , Biomarkers/blood , Chromogranins/blood , Female , Gain of Function Mutation , Humans , Indenes/adverse effects , Magnetic Resonance Imaging , Normetanephrine/blood , Paraganglioma/genetics , Polycythemia/genetics , Signal Transduction , Syndrome , Whole Genome Sequencing
13.
J Clin Endocrinol Metab ; 106(10): e4242-e4250, 2021 09 27.
Article in English | MEDLINE | ID: mdl-33780538

ABSTRACT

CONTEXT: Total thyroidectomy is recommended for children with papillary thyroid carcinoma, partly because of a high prevalence of bilateral disease. Identifying characteristics that predict bilateral disease might identify candidates for more limited surgery. OBJECTIVE: Investigate associations of preoperative or histopathological characteristics with bilateral disease in children with differentiated thyroid cancer. METHODS: Retrospective cohort study (1998-2020) at 2 academic hospitals. Patients <19 years who underwent total thyroidectomy for differentiated thyroid cancer were included. Clinical, sonographic, and histopathological characteristics were evaluated. The presence of bilateral disease on histopathology was assessed by univariable analysis and multivariable logistic regression. RESULTS: One hundred and fifteen subjects were analyzed (90% with papillary carcinoma). Median (range) age at diagnosis was 15.0 (8.1-18.9) years. Bilateral disease was present in 47/115 subjects (41%). Bilateral disease was associated with solid parenchyma, calcifications, irregular margins, and abnormal lymph nodes detected by ultrasound, Bethesda class V/VI cytology, papillary histology, tumor multifocality in the primary lobe, extrathyroidal extension, lymphovascular invasion, and nodal metastases. In multivariable analysis, only multifocality in the primary lobe was independently associated with bilateral disease (OR 7.61, 95% CI 2.44-23.8, P < .001). Among clinically node-negative subjects with papillary carcinoma who did not have tumor multifocality in the primary lobe, bilateral disease was present in 5/32 (16%). CONCLUSIONS: In children with differentiated thyroid cancer, tumor multifocality in the primary lobe is associated with bilateral disease and should prompt consideration of completion thyroidectomy after initial lobectomy. Clinically node-negative children with tumors that are unifocal in the primary lobe have a low likelihood of contralateral disease.


Subject(s)
Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/pathology , Thyroidectomy , Adolescent , Child , Female , Humans , Logistic Models , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Male , Retrospective Studies , Thyroid Cancer, Papillary/surgery , Thyroid Gland/pathology , Thyroid Neoplasms/surgery
14.
J Pediatr Endocrinol Metab ; 34(3): 401-406, 2021 Mar 26.
Article in English | MEDLINE | ID: mdl-33675208

ABSTRACT

OBJECTIVES: Graves' disease (GD) is rare in children under age five years. Antithyroid drugs are typically first-line therapy but carry the risks of agranulocytosis and liver dysfunction. CASE PRESENTATION: A male infant with multiple congenital anomalies, left ventricular hypertrophy, and neurologic dysfunction developed GD at five months of life. The presence of chronic hepatitis complicated medical management. Potassium iodide was effective temporarily, but urgent thyroidectomy was required at nine months of age. Postoperatively, the patient developed a thyroid function pattern consistent with impaired pituitary sensitivity to thyroid hormone (TH) that responded to the addition of liothyronine. Exome sequencing revealed a heterozygous de novo duplication of the ATAD3 gene cluster, suggesting a possible mitochondrial disorder. CONCLUSIONS: This case describes the youngest child to date to be diagnosed with endogenous GD and to successfully undergo definitive treatment with thyroidectomy. An underlying defect in mitochondrial function is suspected, suggesting a potential novel pathophysiologic link to early-onset thyroid autoimmunity. Additionally, this case illustrated the development of impaired pituitary sensitivity to TH following thyrotoxicosis of postnatal onset, which may contribute to our understanding of hypothalamic-pituitary-thyroid (HPT) axis development.


Subject(s)
Graves Disease/therapy , ATPases Associated with Diverse Cellular Activities/genetics , Graves Disease/genetics , Graves Disease/metabolism , Humans , Infant , Male , Membrane Proteins/genetics , Mitochondrial Proteins/genetics , Thyroidectomy , Thyroxine/blood
15.
Eur J Endocrinol ; 184(5): 657-665, 2021 May.
Article in English | MEDLINE | ID: mdl-33635830

ABSTRACT

OBJECTIVE: Surgical resection is recommended for cytologically indeterminate pediatric thyroid nodules due to their intermediate malignancy risk. We evaluated the utility of ultrasound characteristics for refining malignancy risk to inform the management of these nodules. DESIGN: Retrospective cohort study (2004-2019). METHODS: We analyzed consecutive thyroid nodules with indeterminate fine-needle aspiration cytology (Bethesda category III, IV, or V) in pediatric patients (<19 years). We assessed the association of demographic and sonographic characteristics with malignancy risk among all indeterminate nodules and within each Bethesda category. RESULTS: Eighty-seven cytologically indeterminate nodules were identified in 78 patients. Bethesda category was III in 56 nodules (64%), IV in 12 (14%), and V in 19 (22%). The malignancy rate was 46/87 (53%) overall, and 23/56 (41%), 8/12 (75%), and 15/19 (79%) in Bethesda III, IV, and V nodules, respectively. Malignancy rate was higher in solitary nodules (67% vs 37%, P = 0.004) and nodules with irregular margins (100% vs 44%, P < 0.001) or calcifications (82% vs 43%, P = 0.002). American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) risk level TR5 was associated with a higher rate of malignancy than lower TI-RADS risk levels (80% vs 42%, P = 0.002). Within individual Bethesda categories, TI-RADS risk level was not associated with malignancy. No sonographic feature had a negative predictive value for malignancy greater than 80%. CONCLUSIONS: In pediatric thyroid nodules with indeterminate cytology, some sonographic features - including higher ACR TI-RADS risk level - are associated with malignancy, but these associations are unlikely to alter clinical management in most cases.


Subject(s)
Thyroid Neoplasms/diagnosis , Thyroid Nodule/diagnosis , Ultrasonography , Adolescent , Age of Onset , Biopsy, Fine-Needle , Child , Cohort Studies , Diagnosis, Differential , Female , Humans , Male , Margins of Excision , Predictive Value of Tests , Radiotherapy, Adjuvant , Retrospective Studies , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/pathology , Thyroid Neoplasms/therapy , Thyroid Nodule/epidemiology , Thyroid Nodule/pathology , Thyroid Nodule/therapy , Thyroidectomy
16.
J Clin Endocrinol Metab ; 106(5): e2129-e2136, 2021 04 23.
Article in English | MEDLINE | ID: mdl-33492396

ABSTRACT

CONTEXT: Thyroid function may be assessed in children before cardiac surgery because of concerns that hypothyroidism or thyrotoxicosis might adversely affect cardiac function perioperatively. However, the relationship between preoperative thyroid dysfunction and surgical outcomes is unknown. OBJECTIVE: Determine the relationship between preoperative thyroid dysfunction and outcomes of pediatric cardiac surgery. METHODS: Retrospective cohort study (January 2005 to July 2019). SETTING: Academic pediatric hospital. PATIENTS: All patients <19 years old who underwent cardiac surgery with cardiopulmonary bypass and had thyrotropin (TSH) measured within 14 days preoperatively. Exclusion criteria included neonates (≤30 days), preoperative extracorporeal life support, salvage operations, or transplantation procedures. MAIN OUTCOME MEASURES: Subjects were stratified by preoperative TSH concentration (mIU/L): low (<0.5), normal (0.5-5), mildly high (5.01-10), or moderately high (>10). Outcomes were compared among subjects with normal TSH (control) and each group with abnormal TSH concentrations. The primary outcome was 30-day mortality. Secondary outcomes included time to extubation, intensive care unit and hospital length of stay, and operative complications. RESULTS: Among 592 patients analyzed, preoperative TSH was low in 15 (2.5%), normal in 347 (58.6%), mildly high in 177 (29.9%), and moderately high in 53 (9.0%). Free thyroxine was measured in 77.4% of patients and was low in 0 to 4.4% of subjects, with no differences among TSH groups. Thirty-day mortality was similar among TSH groups. There were no differences in any secondary outcome between patients with abnormal TSH and patients with normal TSH. CONCLUSION: Preoperative mild to moderate subclinical hypothyroidism was not associated with adverse postoperative outcomes in children undergoing cardiopulmonary bypass procedures.


Subject(s)
Cardiac Surgical Procedures/mortality , Heart Diseases/surgery , Preoperative Care , Thyroid Diseases/physiopathology , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Heart Diseases/pathology , Humans , Infant , Male , Prognosis , Retrospective Studies , Survival Rate , Young Adult
17.
J Clin Endocrinol Metab ; 106(3): e1121-e1130, 2021 03 08.
Article in English | MEDLINE | ID: mdl-33347563

ABSTRACT

CONTEXT: Thyroid ultrasound screening is recommended in children with PTEN hamartoma tumor syndrome (PHTS) due to increased risk of thyroid neoplasia, but the natural history of thyroid disease in children with PHTS is unclear. OBJECTIVE: Determine the prevalence and natural history of thyroid disease in children with PHTS. METHODS: Retrospective cohort study (1998-2019) in an academic pediatric hospital of individuals with genetically confirmed PHTS diagnosed before age 19 years. Clinical, thyroid ultrasound, and laboratory characteristics are described. Primary outcomes were the prevalence of thyroid nodules ≥10 mm diameter and time course and risk factors for nodule development assessed by Cox regression analysis. Secondary outcomes included thyroid nodule requiring biopsy, other ultrasound findings, and prevalence of autoimmune thyroid disease. RESULTS: Among 64 subjects with PHTS, 50 underwent thyroid ultrasound. A thyroid nodule ≥10 mm was diagnosed in 22/50 (44%) subjects at median (range) age 13.3 (7.0-22.9) years. Nodules were diagnosed earlier in females than in males (10.8 [7.0-17.9] vs 14.2 [9.9-22.9] years, P = .009). In multivariate analysis, risk of thyroid nodules was significantly associated with female sex (hazard ratio 2.90, 95% CI 1.16-7.27, P = .02) and inversely associated with the presence of neurologic findings of PHTS (HR 0.27, 95% CI 0.10-0.69, P = .007). Abnormal-appearing lymph nodes with echogenic foci were observed by ultrasound in 20% of subjects, but these were not associated with malignancy. Autoimmune thyroid disease was present in 10/33 (30.3%) of subjects in whom it was assessed. CONCLUSION: Thyroid disease is common in children with PHTS. This study supports current consensus recommendations for ultrasound screening.


Subject(s)
Hamartoma Syndrome, Multiple/epidemiology , Hamartoma Syndrome, Multiple/pathology , Thyroid Diseases/epidemiology , Thyroid Diseases/pathology , Adolescent , Adult , Child , Cohort Studies , Disease Progression , Female , Hamartoma Syndrome, Multiple/complications , Hamartoma Syndrome, Multiple/genetics , Humans , Male , PTEN Phosphohydrolase/genetics , Prevalence , Retrospective Studies , Risk Factors , Thyroid Diseases/diagnosis , Thyroid Diseases/etiology , Ultrasonography , United States/epidemiology , Young Adult
18.
J Clin Endocrinol Metab ; 106(2): e757-e762, 2021 01 23.
Article in English | MEDLINE | ID: mdl-33245743

ABSTRACT

CONTEXT: Proteinuria can cause or exacerbate hypothyroidism, possibly due to urinary loss of protein-bound thyroid hormone. However, the precise relationship between proteinuria and hypothyroidism remains unclear. OBJECTIVE: This work aimed to determine the prevalence of hypothyroidism in patients with proteinuria and the relationship between hypothyroidism and degree of proteinuria. DESIGN: A retrospective cohort study was conducted from December 1979 to March 2015. SETTING: This study was conducted at a large academic hospital. PATIENTS: All paired samples of urine protein and serum thyrotropin (TSH), measured within 24 hours, were obtained from adults (age > 18 years) with at least one instance of urine protein greater than 0.2 g/day or mg/mg creatinine. MAIN OUTCOME MEASURES: Samples were stratified by urine protein tertile. Mean TSH and risk of TSH elevation were compared among tertiles using analysis of covariance and generalized estimating equations controlled for age, sex, samples per patient, and levothyroxine treatment. RESULTS: A total of 2676 samples were identified from 2136 patients. Mean ±â€…SE TSH (mIU/L) was increased in the highest tertile of urine protein (> 1.75g/day) compared to the lower 2 tertiles (2.09 ±â€…0.07 vs 1.59 ±â€…0.07, 1.59 ±â€…0.06, P < .001). The highest tertile had a greater prevalence of TSH greater than 5 mIU/L (17.2% vs 10.5%, 11.9%, P < .001) but a similar risk of TSH greater than 5 mIU/L (odds ratio [OR] 1.44; 95% CI, 0.67-3.09, P = .35). The highest tertile also had a higher prevalence (6.2% vs 3.4%, 2.6%, P = .003) and risk (OR 1.72; 95% CI, 1.05-2.84, P = .008) of TSH greater than 10 mIU/L. Similar results were observed when comparing samples with nephrotic-range proteinuria (> 3.5g/day) to those with lesser proteinuria. CONCLUSION: Hypothyroidism is common among adults with proteinuria, and the risk of hypothyroidism is directly related to the severity of proteinuria.


Subject(s)
Hypothyroidism/epidemiology , Proteinuria/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , History, 20th Century , History, 21st Century , Humans , Hypothyroidism/etiology , Male , Massachusetts/epidemiology , Middle Aged , Prevalence , Proteinuria/complications , Proteinuria/pathology , Retrospective Studies , Risk Factors , Severity of Illness Index , Thyroid Function Tests , Young Adult
20.
J Clin Endocrinol Metab ; 105(10)2020 10 01.
Article in English | MEDLINE | ID: mdl-32706870

ABSTRACT

CONTEXT: Children with brain tumors may have pubertal onset at an inappropriately young chronologic age. Hypothalamic-pituitary irradiation ≥18Gy has been found to be a risk factor; age at irradiation is associated with pubertal timing. However, the underlying mechanisms are unknown. OBJECTIVE: To determine the impact of body mass index (BMI) and catch-up growth on pubertal timing in females treated for medulloblastoma and other embryonal tumors. DESIGN, SETTING, AND PATIENTS: Retrospective cohort analysis of 90 female patients treated for medulloblastoma and other embryonal tumors at Dana-Farber Cancer Institute/Boston Children's Hospital from 1996 to 2016. Eighteen individuals met inclusion criteria, with a mean ± SD follow-up period of 11.9 ± 3.4 years. MAIN OUTCOME MEASURES: Multiple linear regression models for age at pubertal onset and bone age discrepancy from chronologic age at pubertal onset assessed the joint influences of age at irradiation, hypothalamic irradiation dose, undernutrition duration, BMI standard deviation score (SDS) at pubertal onset, and catch-up BMI SDS. RESULTS: The mean ± SD age of pubertal onset was 9.2 ± 1.3 years and hypothalamic radiation dose was 31.9 ± 9.9 Gy. There was a direct relationship between age at irradiation and age at pubertal onset (ß = 0.323 ± 0.144 [standard error] year per year; P = 0.04) that was significantly attenuated after adjusting for BMI SDS at pubertal onset (P = 0.5) and catch-up BMI SDS (P = 0.08), suggesting that BMI is a mediator. CONCLUSIONS: Both absolute and catch-up BMI SDS at pubertal onset are significant mediators of pubertal timing and bone age discrepancy in pediatric medulloblastoma and other embryonal tumors, and thus, are targetable risk factors to optimize pubertal timing.


Subject(s)
Brain Neoplasms/radiotherapy , Cancer Survivors/statistics & numerical data , Cranial Irradiation/adverse effects , Hypothalamo-Hypophyseal System/radiation effects , Malnutrition/epidemiology , Medulloblastoma/radiotherapy , Puberty, Precocious/epidemiology , Adolescent , Age Factors , Body Height , Body Mass Index , Brain Neoplasms/mortality , Child , Child, Preschool , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Humans , Hypothalamo-Hypophyseal System/physiopathology , Malnutrition/etiology , Medulloblastoma/mortality , Puberty, Precocious/etiology , Puberty, Precocious/physiopathology , Radiotherapy Dosage , Retrospective Studies
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