Purpose There is currently no consensus on which protective strategy is most effective to prevent I-131 uptake in the thyroid during medical interventions in children. We aimed to collect the best available evidence to determine which pharmacological intervention is most effective in protecting the thyroid gland from damage by radioactive iodine (RAI). Methods Literature searches were performed using PubMed, Embase, OLDMEDLINE, and the Cochrane Central Register of Controlled Trials. Only original studies were included (1950–2022). Studies comparing pharmacological prevention of the thyroid against RAI uptake or occurrence of hypothyroidism, thyroid nodule or thyroid cancer were included. Included studies were graded according to the Grading of Recommendations Assessment, Development and Evaluation considerations. Pharmacological interventions were compared for effectiveness on reduction of thyroidal intake or relevant clinical thyroidal outcomes. Results Forty studies were included. Quality of included studies was low and many different outcome variables were used, making meta-analysis impossible. In 81% of studies, the pharmacological intervention could not prevent RAI uptake or thyroid damage. The administration of potassium iodide (KI) 1 h before exposure to RAI seemed most effective to reduce thyroidal uptake, however, hypothyroidism was reported in up to 64% as well as several cases of thyroid carcinoma. The combination of KI, thyroxine and thiamazole reduced RAI uptake and occurrence of hypothyroidism; yet, after follow-up of 9 years, still 50% of patients developed hypothyroidism. KI with potassium perchlorate showed hypothyroidism to occur in up to 12% of patients after short follow-up time. Conclusions The lack of well-designed studies impairs making strong recommendations on the optimal way to prevent thyroid damage when using radioactive coupled ligands for medical interventions. To improve the protection of the thyroid against radiation damage by I-131, well-designed randomized clinical trials with sufficient follow-up time, comparing new protective strategies’ effects on valid and well-defined thyroid outcomes are needed.

Objectives Dioxins and PCBs are highly toxic and persistent environmental pollutants that are measurable in humans worldwide. These persistent organic pollutants are associated with a higher incidence of diabetes mellitus. We hypothesise that perinatal (background) exposure to industrial pollutants like dioxins also influences body mass development and energy metabolism in later life. Study design In The Netherlands, the perinatal exposure (prenatal exposure and postnatal lactational intake) to dioxins has been studied prospectively since 1987. Fasting glucose, insulin, HbA1c and leptin were analysed in 33 children of the original cohort of 60. BMI, glucose:insulin and BMI:leptin ratios were calculated. Prenatal exposure, lactational intake and current serum levels of dioxins (PCDD/F), dl-PCBs and PBDE concentrations were determined using (HR)GC-MS. Results Prenatal dioxin (PCDD/F) exposure was positively correlated to the glucose:insulin ratio (p = 0.024) and negatively correlated to the fasting insulin concentration (p = 0.017) in adolescence. Postnatal lactational PCDD/F intake was also negatively correlated to fasting insulin concentration (p = 0.028). Current serum levels of PCDD/Fs and total TEQ (dl-PCBs+PCDD/Fs) were positively correlated to the fasting serum glucose concentration (p = 0.015 and p = 0.037, respectively).No metabolic effects were seen in association with current serum levels of PBDEs. A positive correlation between the insulin and leptin concentrations (p = 0.034) was observed. No effects were found on leptin levels, BMI:leptin ratio, HbA1c levels or BMI. Discussion/Conclusion This study indicates that prenatal and lactational exposure influences glucose metabolism in adolescents, presumably through a negative effect on insulin secretion by pancreatic beta cells. Additionally, the very low recent background exposure to dioxins in puberty possibly has an effect on the glucose level.

Previous studies have reported changes in the body mass index (BMI) with time in childhood cancer survivors (CCSs) during follow‐up. The limitations of these studies include that they described only a subgroup of survivors or used questionnaires with self‐reported heights and weights. The goal of this study was to examine BMI in a large cohort of long‐term CCSs and relate this to the BMI at diagnosis, age, sex, tumor type, treatment, and endocrine defects.

In 1980s Western Europe, human perinatal exposure to background levels of dioxins was rather high. We therefore evaluated the neurodevelopment of our cohort during the prepubertal period and in adolescence.At prepubertal age (7-12 years) 41 children were tested. Both neuromotor functioning and psychological testing were performed (Dutch version of the Wechsler Intelligence Scale for Children (WISC-R) and the Dutch version of the Child Behavior Checklist for ages 4-18 years (CBCL 4-18) and the Teacher Report Form (TRF)). Neurophysiological tests were performed using magnetoencephalography and electroencephalography.In adolescence (14-18 years) the behavior of 33 children was studied again (CBCL and TRF). And the levels of dioxins and dioxin-like PCBs (dl-PCBs) were measured in serum.Results: At prepubertal age no association was found between perinatal dioxin exposure and verbal, performal and total IQ or with the Touwen's test for neuromotor development. There were behavioral problems associated with both prenatal and postnatal dioxin exposure. In adolescence there were problems associated with the current dioxin levels and dioxin-like-PCBs.Neurophysiological tests revealed clear negative dysfunction. An increase in latency time after a motion stimulus (N2b) of 13 ms (= a delay of 10%) is associated with the higher prenatal dioxin exposure. A similar delay was measured in testing cognitive ability by analyzing the odd ball measurements, N200 and P300, together with an amplitude decrease of 12%. The delay is indicative of a defective myelinisation and the decrease in amplitude of a loss of neurons.Conclusion: We found effects on behavior in association with the perinatal dioxin exposure and in adolescence in association with the current dioxin levels.Neurophysiological testing is instrumental in the detection of effects of perinatal background levels of chemicals on brain development in normal, healthy children. The clinical, neurological and psychological tests commonly used are not sensitive enough to detect important effects. (C) 2014 Elsevier B.V. All rights reserved.

To describe the Dutch neonatal screening programme for congenital hypothyroidism (CH). Descriptive study. Data on neonatal screening for CH in the period 1 January 1981 through 31 December 2011 were obtained from the Department for Vaccine Supply and Prevention Programmes of the Dutch National Institute for Public Health and the Environment (RIVM), laboratories and paediatricians to whom babies with abnormal screening results were referred. The screening procedure has been amended several times. In the period 1981-1994, only T4 and TSH were measured in heel prick blood, for example. From 1995, thyroxine-binding globulin (TBG) was added to the screening protocol. The participation rate was 99.7%. Before 1995 the sensitivity, specificity and positive predictive value were 94%, 99.51% and 6%, respectively. From 1995 these percentages were 98%, 99.85% and 21%, respectively. The total prevalence of CH was 1:2670 (prevalence of CH of thyroidal origin was 1:3100 and CH of central origin was 1:21,600). The percentages of patients with severe CH treated before day 15 in the periods 1981-1990, 1991-2000 and 2001-2011 were 24% (63/263), 63% (170/269) and 96% (176/184), respectively. The sensitivity and specificity of the screening procedure has considerably increased since 1995 compared with the period before 1995. In recent years patients with severe CH were treated considerably earlier than in the first years of the screening. Neonatal screening for CH may be considered as an important success for public health care

Doel Beschrijving van de Nederlandse neonatale screening op congenitale hypothyreoidie (CH). Opzet Descriptief onderzoek. Methode We verzamelden gegevens over de neonatale screening op CH in de periode 1 januari 1981-31 december 2011 van de Dienst Vaccinvoorziening en Preventieprogramma’s van het RIVM, van laboratoria en van kinderartsen naar wie pasgeborenen met een afwijkende uitslag werden verwezen. De screeningsprocedure werd verscheidene keren bijgesteld. In de periode 1981-1994 werden bijvoorbeeld alleen de waarden van T4 en TSH bepaald uit het hielprikkaartje. Vanaf 1995 werd ook de waarde van thyroxinebindend globuline (TBG) meegenomen. Resultaten De deelname was 99,7%. Tot 1995 was de sensitiviteit 94%, de specificiteit 99,51% en de positief voorspellende waarde 6%; vanaf 1995 was dit respectievelijk 98%, 99,85% en 21%. De totale prevalentie van CH was 1:2670 (prevalentie CH van thyreoidale oorsprong: 1:3100 en centrale CH: 1:21.600). De percentages kinderen met ernstige CH bij wie in de perioden 1981-1990, 1991-2000 en 2001-2011 voor de 15e levensdag met thyroxinebehandeling werd gestart, waren respectievelijk 24 (63/263), 63 (170/269) en 96 (176/184). Conclusie De sensitiviteit en specificiteit van het screeningsprogramma is vanaf 1995 aanzienlijk hoger dan voor 1995. In de recente jaren worden patienten met ernstige CH aanzienlijk vroeger behandeld dan in de beginjaren. De neonatale screening op CH kan als een belangrijk succes van de openbare gezondheidszorg worden beschouwd.

Background Congenital central hypothyroidism occurs either as isolated thyroid-stimulating hormone (TSH) defi ciency or in conjunction with other pituitary hormone defi cits.Undetected central hypothyroidism is associated with developmental delay in children and adverse cardiometabolic sequelae in adults.Hitherto, mutations in the thyrotropin-releasing hormone receptor gene (TRHR) or the TSHb subunit gene (TSHB) are the only known causes of isolated TSH defi ciency.Methods Using whole exome and candidate gene sequencing, we have studied 11 unrelated families with males exhibiting isolated TSH defi ciency, testicular enlargement, and variably low serum prolactin levels.Findings We have identifi ed eight distinct mutations and two whole gene deletions disrupting the X-linked immunoglobulin superfamily member 1 gene (IGSF1) in aff ected males.IGSF1 encodes a pituitary-enriched plasma membrane glycoprotein; disease-associated mutations block traffi cking of IGSF1 from the endoplasmic reticulum to the membrane, consistent with loss-of-protein function.Adult male IGSF1 null mice exhibit central hypothyroidism with decreased pituitary TSH content and circulating T3 levels; TSH secretion in response to TRH is blunted and pituitary TRHR mRNA levels are decreased, suggesting that impaired TRH signalling may provide the basis for hypothyroidism.Interpretation Our observations delineate a novel X-linked syndrome in which loss-of-function mutations in IGSF1 cause central hypothyroidism, testicular enlargement, and variable prolactin defi ciency, and identify a previously unsuspected role for IGSF1 in hypothalamic-pituitary control of thyroid and testicular function.Variable biochemical penetrance in these families highlights the importance of genetic ascertainment in this syndrome, so that asymptomatic aff ected individuals can benefi t from early initiation of thyroxine treatment.

Congenital central hypothyroidism occurs either in isolation or in conjunction with other pituitary hormone deficits. Using exome and candidate gene sequencing, we identified 8 distinct mutations and 2 deletions in IGSF1 in males from 11 unrelated families with central hypothyroidism, testicular enlargement and variably low prolactin concentrations. IGSF1 is a membrane glycoprotein that is highly expressed in the anterior pituitary gland, and the identified mutations impair its trafficking to the cell surface in heterologous cells. Igsf1-deficient male mice show diminished pituitary and serum thyroid-stimulating hormone (TSH) concentrations, reduced pituitary thyrotropin-releasing hormone (TRH) receptor expression, decreased triiodothyronine concentrations and increased body mass. Collectively, our observations delineate a new X-linked disorder in which loss-of-function mutations in IGSF1 cause central hypothyroidism, likely secondary to an associated impairment in pituitary TRH signaling.

1 Department of Paediatrics and Neonatology, Emma Children’s Hospital Academic Medical Center, Amsterdam, The Netherlands 2 IBED/ESS, University of Amsterdam, POBox 94240, 1090GE, Amsterdam, The Netherlands 3 Ecobaby Foundation, Loenersloot, The Netherlands 4 KWR Watercycle Research Institute, PO Box 1072, 3430 BB Nieuwegein, The Netherlands 5 Department of Paediatrics and Neonatology, Westfriesgasthuis, Maelsonstraat 3, 1624 NP Hoorn, The Netherlands

There are good reasons to describe congenital hypothyroidism and hyperthyroidism separately from acquired thyroid diseases because the risks of a disturbed thyroid hormone supply in young children are clearly different from the risks in older children or adults. For adequate metabolism, vertebrates with a higher degree of development, or a more complex ontogeny, are highly dependent on thyroid hormone. Nevertheless, humans appear to be able to ‘vegetate’ for years in the absence of this hormone. After resumption of hormone supply the metabolism normalizes again. However, brain development in young children does not. With the exception of the development of the neural tube, thyroid hormone is involved in regulation of later events, such as cell migration and the formation of cortical layers, and in neuronal and glial cell differentiation. Thyroid hormone also controls differentiation of not only neurons and oligodendrocytes, but also astrocytes and microglia (1).

Background/Aims: It is not exactly known how many children develop the triphasic response (diabetes insipidus (DI)/hyponatremia/DI) immediately after surgery for childhood craniopharyngioma; neither is it known which factors predict this. We studied the occurrence of the triphasic response after primary surgery for craniopharyngioma in children, and aimed to identify possible predictors. Methods: Patients <18 years old who had undergone a primary craniopharyngioma resection between January 1990 and February 2010 in either of the 2 academic centers in Amsterdam were studied retrospectively. Results: Twenty-one patients (5 males) fulfilled the inclusion criteria. Median age at surgery was 9.1 (range: 4.0–15.1) years. Six patients developed a triphasic response (29%). Of all factors, only the duration of surgery was found to be a predictor of a triphasic response: 8.5 (6.0–11.0) versus 4.6 (3.5–11.5) h in patients who did not develop a triphasic response (p = 0.03). Conclusion: After primary surgery for a craniopharyngioma, a considerable number of patients develop a triphasic response in the regulation of the sodium and water balance. This is predicted by (factors associated with) a longer duration of surgery. Other predictors could not be identified, which may be due to the small sample size.

Objective To study the relationship between maternal thyroid function at each pregnancy trimester and neonatal screening results.Background Overt maternal thyroid dysfunction during gestation is associated with poor neonatal thyroid function. However, research on the relationship between suboptimal maternal thyroid function (assessed at three trimesters) and neonatal thyroid screening outcome is scarce.Design/Patients Prospective follow-up study during three trimesters of gestation in 886 Dutch Caucasian healthy pregnant women followed from 12-week gestation until term delivery (>37 weeks) and their neonates.Measurements The relation between neonatal data from the Congenital Hypothyroidism (CH) screening and maternal thyroid determinants [TSH, FT4 and thyroid peroxidase (TPO)-Ab] assessed at 12-, 24- and 36-week gestation.Results Boys have lower screening TT4 levels and their mothers have higher TSH levels at 24- and 36-week gestation. Higher maternal TSH levels (>97.5th percentile, as defined in 810 women without TPO-Ab at 12 weeks) at one or more times during pregnancy (O.R: 2 26, 95% CI: 1.20-4.29) and lower gestational age (O.R: 1.22, 95% CI: 1.05-1.41) are independently related to lower screening TT4 levels.Conclusions Maternal thyroid function during gestation is related to neonatal TT4 at screening. The finding of both lower neonatal TT4 levels in boys and higher TSH levels in mothers carrying boys is worthy of further investigation, as both observations may be meaningfully related.

Protection of the thyroid from radioactive contamination by the administration of stable iodide was investigated in chimpanzees aged 2 to 98 weeks. The uptake of iodide in the thyroid was measured with 123I-. The animals were subjected to a control measurement first, and subsequently the thyroid uptake of 123I- was determined twice; once at the start and once at the end of 11 days of ingestion of 0.5, 1.5 or 5.0 mg of stable iodide per kg body weight per day. The three doses of iodide reduced the control thyroid iodide uptake of 10 to 30% to lower than 1% when ingested 1 h before exposure to the tracer and to 2-4% when ingested 20 h before exposure. In the latter experiments 0.5 mg iodide/kg was less effective than doses of 1.5 mg/kg or higher. The physiological state of the thyroid of control infant chimpanzees does not differ from that of human infants. Incidentally, an increased level of TSH was found during the ingestion of iodide, but with unaltered thyroxine levels. Therefore, it is concluded that a daily dose of 1.5 mg stable iodide/kg body weight and higher offers optimal protection of the thyroid against exposure to radioactive iodine in infants and that, when used during 10 days, it leaves the thyroid unaffected.

To the Editor: Permanent neonatal diabetes mellitus (PNDM) is mainly caused by activating mutations in the KCNJ11 or ABCC8 genes, encoding respectively the Kir6.2 and sulfonylurea receptor (SUR)1 subunits of the KATP channels in the pancreatic beta cells [1–3]. Developmental delay, epilepsy and neonatal diabetes syndrome (DEND) represents the most severe clinical form of PNDM [4]. Besides diabetes mellitus patients exhibit severe developmental delay, hypotonia and therapy-resistant epilepsy. As KCNJ11 and ABCC8 are expressed in neuronal tissue the neurological features in DEND syndrome are postulated to result from mutated KATP channels in the brain. Only a few cases of DEND syndrome have been described. More common is a milder clinical picture, without generalised epilepsy and with less severe developmental delay, referred to as intermediate DEND. Since 2006 many patients with PNDM due to KCNJ11 and ABCC8 mutations have been completely transferred from insulin to sulfonylurea drugs [5, 6]. However, in DEND syndrome only cases of intermediate DEND were sulfonylurea-responsive [7, 8]. Shimomura and colleagues reported the first patient with severe DEND syndrome, due to a KCNJ11 mutation, who did completely switch to sulfonylurea drugs [4]. Here we report a case of DEND syndrome due to a novel ABCC8 mutation and successful transfer to sulfonylurea treatment. A boy was born as second child of non-consanguineous white parents following an uneventful pregnancy and spontaneous term delivery. His birthweight was low (2,700 g, −2 standard deviation score [SDS]). At 7 weeks of age he presented with failure to thrive (weight 3,140 g, −3.8 SDS), severe hyperglycaemia (blood glucose 42 mmol/l), glucosuria, and ketoacidosis. Physical examination revealed severe generalised hypotonia without dysmorphic features or other abnormalities. Islet cell auto antibodies, serum insulin and C-peptide were undetectable. Abdominal ultrasound examination demonstrated a normally developed pancreas. Neonatal diabetes mellitus was concluded and continuous intravenous insulin therapy was started followed by continuous subcutaneous insulin pump therapy. This resulted in good glycaemic control without significant hypoglycaemia. At the age of 5 months HbA1c was 7.2% and catch-up growth (weight −2 SDS) was observed. On the tenth day of admission, at the age of 2 months, he developed frequent subtle seizures unresponsive to increasing doses of the anti-epileptic drug phenobarbital. EEG examination showed a burst-suppression pattern (abnormal for the age of 8.5 weeks) and epileptic discharges later on. At the age of 3 months the seizures progressed to infantile spasms and EEG examination demonstrated a slowed high-voltage background pattern with multifocal epileptic discharges consistent with hypsarrhythmia and unresponsive to various antiepileptic drugs (phenobarbital, nitrazepam, adrenocorticotropic hormone and vigabatrin). At age 5 months the boy was severely hypotonic, with no visual contact, no babbling, hardly any facial expression and a psychomotor developmental age of 1 month. Magnetic resonance imaging of the brain at that age demonstrated no structural abnormalities but mild atrophy of frontal–temporal regions. DEND syndrome was suspected and the boy was tested for KATP channel defects. Genomic DNA isolated from peripheral lymphocytes was analysed by direct sequencing of all coding sequences as well as the relevant intron/exon boundaries. The KCNJ11 sequence was wild type. In exon 1 of the ABCC8 gene a monoallelic missense mutation was present (c.145A > T) that changed amino acid residue 49 from isoleucine to phenylalanine (p.I49F). This nucleotide change was not previously reported in any single-nucleotide polymorphism or mutation database, was absent in 70 control alleles and also absent in genomic DNA from both parents, indicating a de novo mutation. In an attempt to influence both glycaemic control and neurological abnormalities, at the age of 5.5 months oral glibenclamide therapy was started in a daily dose of 0.2 mg/kg body mass in two doses followed by weekly increments of 0.2 mg/kg−1 day−1. The insulin dose could gradually be reduced and after 2 months, at a glibenclamide dose of 1.6 mg/kg, insulin therapy was stopped. Side effects of glibenclamide treatment were not noticed, and there were no episodes of hypoglycaemia. Gradually the daily glibenclamide dose was tapered and at the age of 17 months he continued to have excellent glycaemic control with 1.0 mg/kg (HbA1c 5.6%). No improvement was observed in seizure control despite anti-epileptic drug treatment with high dose vigabatrin and levetiracetam. At the age of 26 months his functional psychomotor age was 3 months and he continued to have infantile spasms with unchanged EEG hypsarrhythmia. To our knowledge, this is the first report of a DEND patient with an ABCC8 mutation who successfully transfers to sulfonylurea therapy. Although functional studies were not performed the mutation is likely to be the molecular origin of the patient’s DEND syndrome, as it is a de novo mutation in a child of unaffected parents and affects an amino acid residue that shows evolutionary conservation across species. Based on the topology suggested by Conti and colleagues, amino acid residue 49 is located either in the N-terminal extracellular region or in the first predicted transmembrane domain [9]. The in silico prediction programs SIFT and PolyPhen both predicted that substitution at position 49 from isoleucine to phenylalanine would affect protein function. The excellent response to sulfonylurea treatment provides further evidence for the pathogenicity of the mutation. Shimomura and colleagues reported the first patient with severe DEND syndrome, due to a KCNJ11 mutation, who completely switched to sulfonylurea drugs [4]. Their patient also showed neurological improvement on a dose of 2.3 mg/kg, suggesting that such extremely high doses might influence neurological symptoms. In our case glucose values dropped to 3.5 mmol/l with a sulfonylurea dose of 1.6 mg/kg and further increasing the sulfonylurea dosage was thought to be contraindicated by the risk of hypoglycaemia. As the main aim in the treatment of DEND syndrome is to influence neurological dysfunction, perhaps increasing sulfonylurea doses should have been considered together with an additional treatment to prevent hypoglycaemia. Furthermore it could be speculated that rather than a drug that targets both SUR1 and SUR2 isoforms, such as glibenclamide, a SUR1-specific drug, such as gliclazide, might influence neurological symptoms more effectively as only SUR1 isoforms are present in neuronal KATP channels. It is not clear to what extent sulfonylurea drugs are hindered by the blood–brain barrier. Administering sulfonylurea drugs at a very young age, when the blood–brain barrier is still immature, might lead to better brain penetration than at later ages. This case report emphasises the importance of early genetic analysis in all cases of neonatal diabetes mellitus, including the most severely affected patients with DEND syndrome as in this group, sulfonylurea treatment may also completely restore glucose homeostasis. The effect on neurological features is a field of future research perhaps aiming at improved blood–brain barrier penetrance of sulfonylurea drugs and allowing higher doses by alternatively handling hypoglycaemia.

ThyroidVol. 19, No. 6 Letters to the EditorCentral Hypothyroidism in an Infant Born to an Adequately Treated Mother with Graves' Disease: An Effect of Maternally Derived Thyrotrophin Receptor Antibodies?Nitash Zwaveling-Soonawala, Paul Van Trotsenburg, and Thomas VulsmaNitash Zwaveling-SoonawalaSearch for more papers by this author, Paul Van TrotsenburgSearch for more papers by this author, and Thomas VulsmaSearch for more papers by this authorPublished Online:5 Jun 2009https://doi.org/10.1089/thy.2008.0348AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Central Hypothyroidism in an Infant Born to an Adequately Treated Mother with Graves' Disease: An Effect of Maternally Derived Thyrotrophin Receptor Antibodies?." , 19(6), pp. 661–662FiguresReferencesRelatedDetailsCited ByThyroid Disorders19 November 2021Neonatal Thyroid Function and DisordersClinical Obstetrics & Gynecology, Vol. 62, No. 2Endocrine Diseases of PregnancySecondary and tertiary preventions of thyroid disease10 January 2018 | Endocrine Research, Vol. 43, No. 2Central congenital hypothyroidism caused by maternal thyrotoxicosis22 March 2018 | BMJ Case Reports, Vol. 1722017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum Erik K. Alexander, Elizabeth N. Pearce, Gregory A. Brent, Rosalind S. Brown, Herbert Chen, Chrysoula Dosiou, William A. Grobman, Peter Laurberg, John H. Lazarus, Susan J. Mandel, Robin P. Peeters, and Scott Sullivan1 March 2017 | Thyroid, Vol. 27, No. 3Management of Neonates Born to Mothers With Graves’ Disease1 April 2016 | Pediatrics, Vol. 137, No. 4Severe fetal and neonatal hyperthyroidism years after surgical treatment of maternal Graves’ disease23 January 2014 | Journal of Obstetrics and Gynaecology, Vol. 34, No. 2Endocrine Diseases of PregnancyGuidelines for the Diagnosis and Management of Thyroid Disease during Pregnancy and PostpartumJournal of Korean Thyroid Association, Vol. 7, No. 1Management of Hyperthyroidism in Pregnancy: Comparison of Recommendations of American Thyroid Association and Endocrine SocietyJournal of Thyroid Research, Vol. 2013Thyroid disorders in pregnancy25 September 2012 | Nature Reviews Endocrinology, Vol. 8, No. 11TSH and Thyrotropic Agonists: Key Actors in Thyroid HomeostasisJournal of Thyroid Research, Vol. 2012Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum The American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum , Alex Stagnaro-Green, Marcos Abalovich, Erik Alexander, Fereidoun Azizi, Jorge Mestman, Roberto Negro, Angelita Nixon, Elizabeth N. Pearce, Offie P. Soldin, Scott Sullivan, and Wilmar Wiersinga23 September 2011 | Thyroid, Vol. 21, No. 10Neonatal Graves' Disease Associated With Severe Metabolic Abnormalities1 July 2011 | Pediatrics, Vol. 128, No. 1 Volume 19Issue 6Jun 2009 InformationCopyright 2009, Mary Ann Liebert, Inc.To cite this article:Nitash Zwaveling-Soonawala, Paul Van Trotsenburg, and Thomas Vulsma.Central Hypothyroidism in an Infant Born to an Adequately Treated Mother with Graves' Disease: An Effect of Maternally Derived Thyrotrophin Receptor Antibodies?.Thyroid.Jun 2009.661-662.http://doi.org/10.1089/thy.2008.0348Published in Volume: 19 Issue 6: June 5, 2009PDF download

Several groups of investigators have reported an increased incidence of congenital anomalies in patients with congenital hypothyroidism. Furthermore, in patients with congenital hypothyroidism and mutations in genes known to be involved in thyroid development, specific extra-thyroidal abnormalities have been observed. The goal of the present study was to gain insight in the types and patterns of morphological characteristics depending on the type of congenital hypothyroidism of thyroidal origin (CH-T). In 242 Dutch CH-T patients with a thyroid agenesis, a dystopic thyroid rudiment or a eutopic thyroid gland, we performed a careful physical examination of the body surface directed to visually detectable morphological abnormalities; results were compared to a group of 1,007 Dutch control subjects. The percentage of patients with one or more major abnormalities in the total CH-T cohort (33.1%) and in patients with CH-T dystopic thyroid (37.2%) was significantly higher than in the control population (21.8%; P < 0.001). Especially in the CH-T dystopic thyroid group specific major malformations (bilateral ear pits; oligodontia) were found more frequently. Also, the percentage of patients in the total CH-T group with one or more minor anomalies (96.3%) was significantly higher than in the control group (82.5%). The careful grouping of patients according to their CH-T etiology and the types and patterns in morphological findings may be helpful in the search for novel genes involved in thyroid development.

CONTEXT:The Dutch neonatal congenital hypothyroidism (CH) screening program detects infants with CH of central origin (CH-C). These infants have a high likelihood of multiple pituitary hormone deficiencies. ACTH deficiency especially poses an additional risk for brain damage and may be fatal.OBJECTIVE:Our objective was to evaluate different tools for assessment of the integrity of the hypothalamus-pituitary-adrenocortex (HPA) axis in young infants, aiming for a strategy for reliable and timely diagnosis.DESIGN, SETTING:This is a Dutch nationwide prospective study (enrollment 1994-1996). Patients were included if neonatal CH screening results were indicative of CH-C and HPA axis function could be tested within 6 months of birth.PATIENTS:Nine male and three female infants with CH-C and four infants with false-positive screening results or transient hypothyroidism were included in the study.MAIN OUTCOME MEASURES:CRH test results, multiple cortisol plasma concentrations, and cortisol excretion in 24-h urine were measured.RESULTS:Six (50%) of the CH-C patients had abnormal CRH test results. Three of them had discordant test results: impaired increase of plasma cortisol in response to CRH, despite substantial increase of plasma ACTH. The other three infants, with concordant impaired responses of both ACTH and cortisol to CRH, had a very low urinary cortisol excretion in comparison with the subjects with normal CRH test results.CONCLUSIONS:The CRH test proves to be a fast and reliable tool in the assessment of HPA axis (dys)function. It enables timely diagnosis in (asymptomatic) neonates at risk for serious morbidity and mortality. The discordant response type, which has not been described before, may be an early phase of HPA axis dysfunction. Alternatively, patients with this response type may constitute a separate pathogenetic subset of HPA axis-deficient patients.