Medical Management of Dental Abnormalities Related to Congenital Hypothyroidism in a Cat.

A 5-month-old intact male domestic shorthair cat presenting for routine vaccinations was diagnosed with congenital hypothyroidism. His primary presenting symptom was incomplete dentition with delayed dental eruption. Congenital hypothyroidism was confirmed by baseline thyroxine (T4), free T4, and thyroid-stimulating hormone testing. The cat was treated with oral thyroid hormone supplementation and 16 weeks after initiation of therapy the cat was clinically normal with age-appropriate dentition. No surgical intervention was necessary to achieve normal dental eruption.

Cases Referred from the Turkish National Screening Program: Frequency of Congenital Hypothyroidism and Etiological Distribution

Objective: The aim of this study was to evaluate cases referred from the congenital hypothyroidism (CH) newborn screening program. Methods: Infants referred to Pediatric Endocrinology between 30.09.2015 - 01.04.2018 because of suspected CH identified by National Neonatal Screening Program were prospectively evaluated. Results: Of the 109 newborns referred to our clinic, 60 (55%) were diagnosed with elevated neonatal thyroid stimulating hormone (TSH). The diagnosis of elevated neonatal TSH was made in 52 (47.7%) and eight (7.3%) infants at initial evaluation and after follow up, respectively of all referrals with 86.7% (52/60) diagnosed at initial visit. The median first and second heel prick times were 1.8 (0-7) and 8.72 (4-30) days. The median age at starting treatment of the infants diagnosed as a result of initial evaluation was 22.13 (7-53) days. Clinical findings associated with CH were present in 19 (36%) of patients. Etiology in patients diagnosed with elevated neonatal TSH on admission was: agenesis in one (2.08%); ectopia in one (2.08%); hypoplasia in 14 (29.16%); normal gland in situ 16 (33.3%); and hyperplasia in 16 (33.3%). The median time to normalization of TSH and free thyroxine concentrations after treatment initiation was 11.02 (4-30) and 9.03 (3-30) days, respectively. Conclusion: The rate of diagnosis in the first month was found to be 87%. The etiological incidence of both dysgenesis and dyshormonogenesis was equal at 33.3%. The majority of cases with normal thyroid gland will be diagnosed with transient hypothyroidism but some of them may be diagnosed with thyroid dyshormonogenesis so the rate of dyshormonogenesis will increase later after final diagnosis.

The etiologies and incidences of congenital hypothyroidism before and after neonatal TSH screening program implementation: a study in southern Thailand.

BACKGROUND: Congenital hypothyroidism (CH) is one of the common causes of intellectual disability which can be prevented by early detection of an elevated thyroid stimulating hormone (TSH) level in the newborn and by treatment with thyroxine. In Thailand, neonatal TSH screening was implemented nationwide in 2005. The objective of the study was to determine the etiologies and the estimated incidences of CH in southern Thailand before and after the implementation of a neonatal TSH screening program in 2005. METHODS: The medical records of pediatric patients who were diagnosed with primary CH at Songklanagarind Hospital during 1995-2013 were retrospectively reviewed. The study was divided into two time periods: study period 1 (SP1) (1995-2004) and study period 2 (SP2) (2005-2013), the time before and after TSH program implementation. RESULTS: The most common form of CH during SP1 was overt permanent CH (66%), mostly caused by athyreosis or ectopic thyroid. In SP2, the most common form of CH was mild permanent CH (39%) (mostly due to dyshormonogenesis), followed by overt CH (32%) and transient CH (29%). The overall annual estimated incidence of CH per 10,000 live births in Songkhla Province was 1.69 (1:5021) in SP1, increasing to 4.77 (1:2238) in SP2; in all 14 provinces in southern Thailand, the estimated incidence was 1.24 (1:8094) in SP1 and 2.33 (1:4274) in SP2. CONCLUSIONS: Neonatal TSH screening has a significant impact on the increased detection of the mild form of permanent and transient CH cases, which may be important for the prevention of brain damage from less severe CH although this remains to be documented.

Etiología y evolución de recién nacidos con hipotiroidismo congénito y glándula eutópica / Etiology and evolution of newborns with congenital hypothyroidism and eutopic thyroid gland

RESUMEN Objetivos Analizar las características clínicas, bioquímicas, estudios complementarios, hallazgos moleculares y la prevalencia de glándula eutópica en neonatos con HC pertenecientes al Programa Provincial de Pesquisa Neonatal de Córdoba, Argentina, entre 1996 y 2015. Analizar la evolución de los pacientes que reunieron criterios para una reevaluación. Pacientes y métodos Se analizaron retrospectivamente las historias clínicas de 237 pacientes detectados por pesquisa neonatal en la provincia de Córdoba, Argentina, entre 1996-2015 con una incidencia promedio de 1/2146 pesquisados. Presentaron glándula eutópica 81 pacientes (34%) F35/M46; se excluyeron 10 con síndromes genéticos asociados. Se analizaron los niveles de: TSH, T4T, T4L, T3, TPOAb / TGAb y Tiroglobulina (ECLIA -ROCHE) (VR: >15 días: 6-83 ng/ ml; <15 días: 29-173 ng/ml), ecografía y centellografía de cuello con Tc-99m. El valor de corte de TSH sérica adoptado para la confirmación diagnóstica fue de ≥10 mUI/ml. Se realizaron estudios de biología molecular en casos seleccionados. Se reevaluaron niños mayores de 3 años, sin bocio, con valores normales de Tiroglobulina y sin requerimiento de incrementos en la dosis de LT4. Resultados: La prevalencia de HC y Tiroides Eutópica se mantuvo constante. El 50% de los pacientes (36/71) mostraron hiperplasia glandular tiroidea. El 84% (n: 60 de 71) presentó niveles de TSH sérica ≥20 uUI/ml (20-1186) y el 75% (n: 53 de 71) >40 uUI/ml (40-1186). TGAb and TPOAb fueron positivos en un niño. La determinación de TG fue normal en el 29% (21/71) de los casos, elevada en el 56% (39/71) y baja en el 14% (10/71). Los estudios de biología molecular resultaron diagnósticos en 26 pacientes de 18 familias, demostrándose mutaciones en los genes de: TPO: 9 pacientes, TG: 12 pacientes, NIS: 2 pacientes, DUOX2: 2 pacientes y TRβ: 1 paciente. Se encontraron 11 nuevas mutaciones: tres en TPO, cinco en TG, dos en NIS y una en DUOX2. Se informaron anomalías congénitas en el 11% (8/71) de los pacientes. Se reevaluó el 11% (8/71) de los niños, resultando: HC transitorio n: 5, permanente n: 2 y una niña con Síndrome de Resistencia a las Hormonas Tiroideas. La prevalencia de lactantes con HC y glándula eutópica se mantuvo constante a lo largo de 19 años del Programa. Conclusiones Nuestros estudios demuestran que la prevalencia de Hipotiroidismo Congénito con glándula eutópica se mantuvo estable en los períodos analizados. Este grupo de pacientes se caracterizó predominantemente por presentar HC de carácter permanente acompañado por fenotipos de moderada a severa intensidad. En el futuro deberá profundizarse el conocimiento respecto a la influencia de factores medioambientales, como posibles agentes de riesgo asociados a la génesis de Hipotiroidismo Congénito.

abstract Objectives To describe clinical, biochemical characteristics and complementary studies to diagnosis, molecular findings and the prevalence of eutopic gland in newborn with CH detected through our neonatal screening program in Córdoba, Argentina, between 1996 and 2015. To analyze the evolution of the patients who met criteria for re-evaluation. Patients and methods We retrospectively analysed medical records of 237 patients with CH detected by neonatal screening in Córdoba, Argentina, from 1996 to 2015 with an average incidence of 1/2146 researched. 81 patients (34%) F35/M46 had eutopic thyroid gland; 10 patients with associated genetic syndromes were excluded. TT4, FT4, T3, TSH, TPOAb, TGAb and Thyroglobulin (VR: >15 days: 6-83 ng/ml; <15 days: 29-173 ng/ml) (ECLIA ROCHE), thyroid ultrasonography and 99Tc scan were assessed. The serum TSH cutoff value adopted for diagnostic confirmation was ≥10 mIU/ml. Molecular biology studies were performed in selected cases. Those who had no goiter, with normal thyroglobulin, and had not required increases in L-T4 dose underwent re-evaluation after the age of 3 years. Results The prevalence of HC and thyroid Eutopic remained constant. 50% of the patients (36/71) showed glandular hyperplasia. In 84% (60/71) presented serum TSH levels ≥20 uUI/ml (20-1186) and in 75% (n: 53 of 71) levels >40 uUI/ml (40-1186). TGAb and TPOAb were positive only in one baby. TG levels were: normal in 29% (21/71) of the cases, elevated in 56% (39/71) and low in 14% (10/71). Gene mutations were found in 26 patients from 18 families: TPO: 9 patients, TG: 12 patients, NIS: 2 patients, DUOX2: 2 patients y TRβ: 1 patient. Eleven new mutations were found: three in TPO, five in TG, two in NIS and one in DUOX2. Congenital anomalies were reported in 11% (8/71) patients. The 11% (8/71) of children were re-evaluated resulting in: 5 Transient CH, 2 Permanent CH and 1 with Resistance to Thyroid Hormones. The prevalence of infants with CH and eutopic gland remained constant along 19 years of the Program. Conclusions Our studies show that the prevalence of congenital hypothyroidism with eutopic gland remained stable in the periods analyzed. This group of patients was predominantly characterized by permanent CH accompanied by moderate to severe phenotypes. In the future, knowledge about the influence of environmental factors, as possible risk agents associated with the genesis of Congenital Hypothyroidism, should be deepened.

[Van Wyk-Grumbach syndrome: A case report and literature review].

Van Wyk-Grumbach syndrome (VWGS) is a rare complication of prolonged untreated juvenile hypothyroidism characterized by precocious puberty and enlarged multicystic ovaries. A 13-year-old girl visited our outpatient clinic due to menstrual irregularities. She had precocious puberty, pituitary hyperplasia and multiple cystic ovaries in addition to clinical signs of severe congenital hypothyroidism. After the initiation of L-thyroxine therapy, the symptoms were alleviated in a short time. This rare syndrome is easy to be misdiagnosed as pituitary and ovarian tumor. High degree of suspicion and timely diagnosis can prevent unnecessary surgical procedures because the symptoms can be reversed with thyroid hormone supplementation.

Thyroid Dysfunction in Neonates Born to Mothers Who Have Undergone Hysterosalpingography Involving an Oil-Soluble Iodinated Contrast Medium.

BACKGROUND/AIMS: Patients developing neonatal thyroid dysfunction following maternal hysterosalpingography (HSG) involving the use of oil-soluble iodinated contrast medium (ethiodized oil) have been reported. The present study aimed to investigate the frequency and risk factors for neonatal thyroid dysfunction following HSG. METHODS: We studied 212 infants born to mothers who had become pregnant after undergoing HSG involving the use of ethiodized oil. RESULTS: Five of the 212 infants tested positive during congenital hypothyroidism screening; this frequency (2.4%) was higher than the recall rate among first congenital hypothyroidism screening results (0.7%) in Tokyo, Japan. Two of the 5 screening-positive infants showed hypothyroidism, and 3 showed hyperthyrotropinemia. The urinary iodine concentrations in 4 out of the 5 screening-positive infants were 1,150, 940, 1,570, and 319 µg/l. The subjects were divided into thyroid dysfunction (n = 5) and normal thyroid function (n = 207) groups. The median dosage of ethiodized oil in the thyroid dysfunction group was significantly higher than in the normal thyroid function group (20 vs. 8 ml, p = 0.033). CONCLUSION: When infertile women undergo HSG, the dosage of oil-soluble iodinated contrast medium should be as low as possible to minimize the risk of fetal or neonatal thyroid dysfunction.

Selenium and the thyroid.

PURPOSE OF REVIEW: To provide information on the role of the essential trace element selenium, which enables appropriate thyroid hormone synthesis, secretion, and metabolism, and to discuss supplementation with various selenium compounds, which prevent thyroid diseases such as goiter and exert beneficial effects in thyroid autoimmune diseases. RECENT FINDINGS: Selenium administration in both autoimmune thyroiditis (M. Hashimoto) and mild Graves' disease improves clinical scores and well-being of patients and reduces autoimmune antibody titres in several prospective, placebo-controlled supplementation studies. SUMMARY: Adequate nutritional supply of selenium, together with the two other essential trace elements iodine and iron, is required for a healthy thyroid during development and adolescence, as well as in the adult and aging populations.

[Iodine intake during pregnancy: effects on thyroid function in mother and child]. / Ingesta de yodo durante el embarazo: efectos en la función tiroidea materna y neonatal.

INTRODUCTION: Recent studies in Spain have shown an inadequate iodine intake in a significant proportion of pregnant women. Pregnancy increases thyroid hormone requirements, and adequate iodine intake is therefore needed. MATERIAL AND METHODS: One hundred and forty-seven women in their third trimester (week 37) of pregnancy provided a blood sample and a 24-hour urine sample to test serum and urine iodine levels and completed a food frequency questionnaire to assess iodine intake during pregnancy. Serum TSH levels were measured in the babies born to the 140 mothers in the postpartum group. RESULTS: Only 10.9% of pregnant women consumed more than 250 µg iodine daily, and 24.4% of them consumed less than 100 µg daily. Mean free T4 levels were 9.37 pmol/L, and 74 women (54.41%) had levels below the hypothyroxinemia threshold. TSH levels were normal in 135 newborns (96.4%), while 5 (3.6%) had levels higher than 5 µU/mL.

Congenital hypothyroidism caused by excess prenatal maternal iodine ingestion.

We report the cases of 3 infants with congenital hypothyroidism detected with the use of our newborn screening program, with evidence supporting excess maternal iodine ingestion (12.5 mg/d) as the etiology. Levels of whole blood iodine extracted from their newborn screening specimens were 10 times above mean control levels. Excess iodine ingestion from nutritional supplements is often unrecognized.

The effects of iodine deficiency in pregnancy and infancy.

Iodine requirements are increased ≥ 50% during pregnancy. Iodine deficiency during pregnancy can cause maternal and fetal hypothyroidism and impair neurological development of the fetus. The consequences depend upon the timing and severity of the hypothyroidism; the most severe manifestation is cretinism. In moderate-to-severely iodine-deficient areas, controlled studies have demonstrated that iodine supplementation before or during early pregnancy eliminates new cases of cretinism, increases birthweight, reduces rates of perinatal and infant mortality and generally increases developmental scores in young children by 10-20%. Mild maternal iodine deficiency can cause thyroid dysfunction but whether it impairs cognitive and/or neurologic function in the offspring remains uncertain. Two meta-analyses have estimated that iodine-deficient populations experience a mean reduction in IQ of 12-13.5 points. In nearly all regions affected by iodine deficiency, salt iodisation is the most cost-effective way of delivering iodine and improving maternal and infant health.

Are pregnant women in New Zealand iodine deficient? A cross-sectional survey.

Severe iodine deficiency in pregnancy can result in cretinism. There is growing concern that less severe iodine deficiency may also affect fetal growth and development. A handful of prior small New Zealand studies focussed on pregnant women living in Dunedin. This study utilised biochemical, clinical and dietary indices to assess iodine status of 170 women living throughout New Zealand. The median urinary iodine concentration (UIC) of the women was 38 µg/L, well below the 150 µg/L cut-off value that indicates adequate iodine status; 7% of women had goitre. Not surprisingly, iodine intake was also low at 48 µg/day. The majority of women had TSH and FT4 concentrations within pregnant reference ranges, suggesting that despite the low UIC observed in these women, thyroid hormone production appeared unaffected.

Hypothyroidism due to hepatic hemangioendothelioma: a case report.

Although hemangioendothelioma (HHE) is a commonly encountered hepatic tumor during infancy, HHE-related hypothyroidism is rare. We present a patient who developed HHE-related hypothyroidism during the neonatal period and showed marked improvement in hypothyroidism by regression of HHE. A 28-day-old boy with TSH level of 77 mIU/mL on neonatal screening and diagnosed as congenital hypothyroidism was started on L-thyroxine (L-T4) (11 µg/kg/day) therapy on the 21(th) day of life. On physical examination, the liver was palpable 5 cm below the right costal margin, and the thyroid gland was nonpalpable. Thyroid ultrasonography was normal. Although L-T4 dose was increased to 15 µg/kg/day, TSH was not suppressed and free T3 level remained low. HHE in both lobes of the liver was detected by abdominal ultrasonography and magnetic resonance imaging. Treatment was started with prednisolone 2 mg/kg/day and alpha-interferon 3 million U/m(2)/3 times per week. Thyroid dysfunction was thought to be due to type 3 iodothyronine deiodinase activity expressed by HHE. L-T4 therapy was changed to Bitiron® tablet, which includes both T4 and T3, and euthyroidism was attained within 1 month. Thyroid hormone requirement was reduced and treatment was discontinued after regression of the HHE. At the most recent visit, the patient was 21 months old and off treatment. His growth and neurological development were normal for age and he was euthyroid. HHE should be considered in cases with severe hypothyroidism resistant to high-dose thyroid hormone replacement. The treatment of HHE in combination with T4 and T3 therapy results in euthyroidism.

Iodine: it's important in patients that require parenteral nutrition.

Iodine deficiency has multiple adverse effects on growth and development because of inadequate thyroid hormone production. Four methods are generally recommended for assessment of iodine nutrition: urinary iodine concentration, thyroid size, and blood concentrations of thyroid-stimulating hormone and thyroglobulin. Iodine intakes < or = 1 mg/d are well tolerated by most adults, because the thyroid is able to adjust to a wide range of intakes. A daily dose of 1 microg iodine/kg body weight is recommended for infants and children receiving parenteral nutrition (PN), but this is far below their requirement. Daily iodine requirements in adults receiving enteral nutrition or PN are estimated to be 70-150 microg, but most PN formulations do not contain iodine. Despite this, deficiency is unlikely because absorption from iodine-containing skin disinfectants and other adventitious sources can provide sufficient iodine. However, if chlorhexidine replaces iodine-containing disinfectants for catheter care, iodine deficiency may occur during long-term PN, and periodic testing of thyroid functions may be prudent. Infants may be particularly vulnerable because of their small thyroidal iodine store, but available data do not yet support routine supplementation of preterm infants with iodine. Adults may be less vulnerable because thyroidal iodine stores may be able to support thyroid hormone production for several months. More studies to clarify this issue would be valuable.

Perinatal goiter with increased iodine uptake and hypothyroidism due to excess maternal iodine ingestion.

BACKGROUND/AIMS: To review cases of fetal/newborn goiter due to excess maternal iodine ingestion. METHODS: We reviewed the medical records of all patients that presented with congenital goiter in 2003. We used the PubMed search engine to conduct a review of publications addressing congenital goiter and excessive iodine intake. RESULTS: Maternal ingestion of large amounts of iodine due to an error in the manufacturing of a prenatal vitamin caused a goiter in her fetus. Seven other women who received the same prenatal vitamin had newborn children with goiters. Three of these children were hypothyroid at the time of initial examination. Three patients (2 hypothyroid and 1 euthyroid) had thyroid scans with radioactive iodine; iodine uptake was elevated (>80%) in all 3, and in 1 the perchlorate washout test was positive. CONCLUSION: The finding of congenital goiter and increased iodine uptake in a newborn is considered diagnostic of dyshormonogenesis, a permanent form of hypothyroidism. Our description is important because it demonstrates that iodine excess during pregnancy may mimic some forms of dyshormonogenesis. The differentiation between the two causes of newborn goiter may prevent the lifelong use of supplemental levothyroxine in patients with a transient abnormality.

Consideraciones sobre el hipotiroidismo congénito a partir del análisis de nuestra casuística / Aspects about congenital hypothyroidism from the analysis of our casuistry

Introducción: El hipotiroidismo congénito (HC) es la enfermedad endocrinológica más frecuente en la edad pediátrica y la causa más frecuente de retraso mental prevenible. La rápida detección e instauración del tratamiento son indispensables para la normalización del proceso de desarrollo psicomotor. Pacientes, métodos y objetivos: Estudio retrospectivo y fundamentalmente descriptivo sobre diversos aspectos de la enfermedad (epidemiología, manifestaciones clínicas, diagnóstico, tratamiento y evolución) en 51 pacientes diagnosticados y tratados en nuestro centro hospitalario, y comparación de los mismos entre los 2 subgrupos principales: hipotiroidismo congénito permanente (HCP) y transitorio (HCT). Resultados: Las manifestaciones clínicas observadas en neonatos que deben hacernos sospechar con mayor frecuencia un posible HC son la ictericia prolongada, fontanela posterior abierta, estreñimiento y hernia umbilical. El uso de antisépticos yodados durante la cesárea y cuidados neonatales favorece el desarrollo de HCT (P=0,039). Los valores de TSH obtenidos en el screening son significativamente menos elevados en los casos de HCT que en los de HCP (p=0,006). El estado de la maduración ósea al nacimiento se encuentra significativamente más alterado en los casos de HCT que en los HCP (P<0,001). Las dosis de levotiroxina requeridas en el tratamiento de los casos de HCT son significativamente menores que en los casos de HCP (p=0,025 al diagnóstico y p≤0,001 en sucesivos controles). Conclusiones: Con escaso tiempo de evolución e incluso en el momento del diagnóstico de un caos de HC, existen ciertas características que nos aproximan a predecir la transitoriedad o no de la afección (AU)

Background: Congenital hypothyroidism (CH) is the most common pediatric endocrinological disorder, and the most frequent cause of avoidable mental retardation, Early detection and treatment are indispensable for development normalization. Participants, methods and objectives: Retrospective and mainly descriptive study about several aspects of this disorder (epidemiology, clinical manifestations, diagnosis, treatment and evolution) over 51 patients diagnosed and treated in our workplace, and comparison between the two main subgroups: permanent congenital hypothyroidism (PCH) and transient congenital hypothyroidism (TCH). Results: Clinical expressions observed in newborns that more frequently must make us suspect CH are prolonged jaundice, wide back fontanel, constipation and umbilical hernia. Iodized antiseptics used during caesarean and neonatal cares contribute to TCH appearance (p=0,039). Thyrotropin (TSH) values obtained in screening are less high in TCH than PCH (p=0,005). In the same way, at this moment thyroxine (L-T4) values are less reduced in TCH relative to PCH (p=0,006). Initial bone development is significantly more affected in TCH than PCH (p<0,001). Levothyroxine dose required in TCH treatment is significantly fewer than in PCH (p=0,025 at diagnosis time and p≤0,001 in following tests). Conclusions: When a case of CH is diagnosed, there are some features that can help to predict the transience or not of this disorder (AU)

Iodine requirements and the risks and benefits of correcting iodine deficiency in populations.

Iodine deficiency has multiple adverse effects on growth and development due to inadequate thyroid hormone production that are termed the iodine deficiency disorders (IDD). IDD remains the most common cause of preventable mental impairment worldwide. IDD assessment methods include urinary iodine concentration, goiter, thyroglobulin and newborn thyrotropin. In nearly all iodine-deficient countries, the best strategy to control IDD is salt iodization, one of the most cost-effective ways to contribute to economic and social development. When salt iodization is not possible, iodine supplements can be targeted to vulnerable groups. Introduction of iodized salt to regions of chronic IDD may transiently increase the incidence of thyroid disorders, and programs should include monitoring for both iodine deficiency and excess. Although more data on the epidemiology of thyroid disorders caused by differences in iodine intake are needed, overall, the relatively small risks of iodine excess are far outweighed by the substantial risks of iodine deficiency.

[Reflections on mental retardation and congenital hypothyroidism: effects of trace mineral deficiencies]. / Réflexions sur le retard mental et le crétinisme de l'hypothyroïdie congénitale et de la carence des minéraux à l'état de traces.

While deficiencies of trace minerals and vitamins are rare in humans eating a variety of food, they can occur in premature infants and those with disturbances in dietary behavior for physical or psychological reasons and during parenteral or enteral nutrition. Some deficiencies - such as iron and iodine - cause such serious specific disorders that they must be considered separately. Congenital hypothyroidism induced by iodine deficiency is a major problem. Its public health importance comes from the neurological complications that lead to the most severe forms of endemic congenital hypothyroidism (cretinism). In areas without iodine deficiency, the standard incidence of this disease in the West is 1/4,500 live births. In areas with iodine deficiency, however, its incidence varies from 1 to 5%! It is nonetheless underestimated, because the screening methods revolutionized 20 years ago are still not applied systematically. Additional factors include the thiocyanates in cassava, the selenium deficiency resulting in selenium-dependent glutathione peroxidase deficiency, and the natural goitrogens in some foods: milk, millet, walnuts, and bacterial and chemical water pollutants. Adolescents and adults need 100 microg/day, children aged 1-10 years 60-100 microg, and babies under one year, 35-40 microg, but these daily requirements are not necessarily met. This threat weighs on a billion people, 50-100 million in Europe, especially pregnant women, fetuses, newborns, and young children whose cerebral development may be negatively affected in the womb and in early life. According to some authors, subjects with cretinism syndrome should be found in places where goiter prevalence exceeds 20%. Evaluation of diffuse intellectual impairment in the population would require tools too specific for most studies. Generations of children are the victims throughout wide swaths of the African ecosystem in which it is endemic and associated with poor adaptation to the environment. But studies of isolated places cannot be transposed to entire populations. Because pregnancy in women with hypothyroidism is often thought to have a very negative prognosis, the two cases we report merit attention. In one case, despite certainly insufficient thyroid hormone replacement treatment, the child was born alive and healthy. In the second case, where hypothyroidism followed a thyroidectomy in a woman with Graves disease, a hydrocephalic child was liveborn, without any replacement treatment. In her next pregnancy, she received optimal hormonal treatment and delivered a healthy liveborn child. The disorders due to severe iodine deficiency did not affect our two patients. In a series of 166 cases of congenital hypothyroidism in newborns, only two cases had maternal antithyroid antibodies. Elsewhere, 9 women with hypothyroidism had 11 pregnancies, 9 normal children, 1 premature child (mother had eclampsia), and 1 with Down syndrome and an Ostium primum defect (mother aged 41 years). Ontogenesis of the hypothalamo-pituitary-thyroid axis of the fetus still appears today to develop independently of the mother in cases of hypothyroidism. An important role is played by type III deiodinase, which is especially active in the placenta during pregnancy, probably involving the T3 activity on nuclear and also mitochondrial receptors. The maturation of these receptors is not well understood.

Loss of integrity of thyroid morphology and function in children born to mothers with inadequately treated Graves' disease.

CONTEXT: Central congenital hypothyroidism (CH-C) in neonates born to mothers with inadequately treated Graves' disease usually needs T(4) supplementation. The thyroid and its regulatory system have not yet been extensively studied after T(4) withdrawal, until we observed disintegrated thyroid glands in some patients. OBJECTIVE: The aim was to study the occurrence and pathogenesis of disintegrated thyroid glands in CH-C patients. DESIGN, SETTING, PATIENTS, PARTICIPANTS: Thyroid function was measured and thyroid ultrasound imaging was performed in 13 children with CH-C due to inadequately treated maternal Graves' disease after T(4)-supplementation withdrawal (group Aa). In addition, thyroid ultrasound imaging was performed in six children with CH-C born to inadequately treated mothers with Graves' disease, in whom T(4) supplementation was not withdrawn yet (group Ab) or never initiated (group Ac), in six euthyroid children born to adequately treated mothers with Graves' disease (group B), and in 10 T(4)-supplemented children with CH-C as part of multiple pituitary hormone deficiency (group C). MAIN OUTCOME MEASURES: Thyroid function and aspect (volume, echogenicity, echotexture) were measured. RESULTS: In group A, five children had developed thyroidal hypothyroidism characterized by persistently elevated TSH concentrations and exaggerated TSH responses after TRH stimulation. In the majority of patients in groups A and C, thyroid echogenicity and volume were decreased, and echotexture was inhomogeneous. Thyroid ultrasound imaging was normal in group B children. CONCLUSIONS: Inadequately treated maternal Graves' disease not only may lead to CH-C but also carries an, until now, unrecognized risk of thyroid disintegration in the offspring as well. We speculate that insufficient TSH secretion due to excessive maternal-fetal thyroid hormone transfer inhibits physiological growth and development of the child's thyroid.