Late Diagnosis of Congenital Hypothyroidism in Young Adult.

Congenital hypothyroidism is the most treatable cause of mental retardation. It is also the most prevalent congenital endocrine disorder in childhood. A dramatic improvement can be made by early detection, diagnosis, and adequate treatment of levothyroxine in patients with congenital hypothyroidism. Severe cognitive impairment is associated with persistent disease in patients who have delayed or no treatment at all. In a modern era with complete healthcare facilities in a big city like Jakarta, the prevalence late-diagnosed congenital hypothyroidism is supposed to be very low. Since many districts have their own public healthcare facilities to screen and diagnose congenital hypothyroidism in children at very young age, a delayed diagnosis in adulthood is actually a rare case.In this medical illustration, we report a case of 21 year-old woman who came to our hospital with abdominal pain. She had mental retardation with no capability to communicate well with other person. She had a short stature (her height was less than 1 meter). She also had mongoloid face with big lips and a very big tongue. There was no goiter or lump on her neck. Her motoric performance was very weak and frail. During abdominal examination, we could see an umbilical bulging on her abdominal wall and on palpation, we could feel an umbilical hernia. By abdominal ultrasound, we could see the umbilical hernia. Unfortunately, no diagnosis of congenital hypothyroidism had been made when she was a newborn, there was also no past or known history of thyroid disease of her and her family. She had a diagnosis of mental retardation with no specific etiology since she was 5-years old. Based on the results of her laboratory examination, we had a confirmed diagnosis of primary hypothyroidism with T4 10.56 nmol/L (normal 60-120 nmol/L) and TSH > 100 mIU/mL. We provided her treatment using levothyroxine based on her body weight (25 mg daily). We arranged her to have abdominal CT Scan and digestive surgery as further management for her umbilical herniation.Some defects are correlated with congenital hypothyroidism when the disease is not treated properly and adequately. Neurocognitive, neuromotoric, growth, and development are some areas which can be disrupted by long-term hypothyroidism condition for patients who had the disease since their early years of life. Congenital hypothyroidism appears to be associated with an increased risk of congenital malformations. Several congenital malformations associated with congenital hypothyrodism are umbilical hernia, congenital heart disease, neurologic abnormalities, genitourinary malformations, cleft palate, and Down's syndrome.Studies concluded that severity of the congenital hypothyroidism has more important role than timing of treatment initiation on long-term cognitive and motor outcomes. Detrimental effects on developmental outcomes in congenital hypothyroidism patients may persist over time; however, early treatment for patients at  very early ages may bring the best cognitive outcomes and neuromotoric development.Regardless of the treatment options, we can say that it is a loss case and a very late diagnosis and treatment of congenital hypothyroidism. The unusual age of detection, delayed diagnosis and treatment are some reminders for primary care physicians in our society to pay greater attention to screening programs.6 Early detection and prompt treatment is an essential part of measures to reduce burden of mental retardation in our society. Delayed diagnosis of congenital hypothyroidism case, which is diagnosed at adulthood, indicates failure in screening program. Early diagnosis and treatment are necessary to prevent long-term catastrophic effects. This a wake-up call of attention and awareness for general public and primary care physicians in our country.

Prenatal diagnosis and successful intrauterine treatment of severe congenital hypothyroidism associated with fetal goiter.

Congenital hypothyroidism with fetal goiter is a rare condition associated with severe, but possibly preventable, intrauterine and postnatal complications. Ultrasound examination after 20 weeks of pregnancy enables prenatal diagnosis and early treatment. Due to limited transplacental transport of thyroid hormones, direct intrauterine treatment is needed. So far, only a few reports of fetal goitrous hypothyroidism have been published and no consensus on adequate management exists. We present a case of severe fetal goitrous hypothyroidism diagnosed at 23 gestational weeks treated by sequential intra-amniotic administration of L-thyroxin. Treatment resulted in significant goiter reduction and normalization of amniotic hormone levels, and enabled uncomplicated vaginal delivery at term. Current knowledge regarding prenatal diagnosis and intrauterine treatment were unified and applied within this case and a recommendation for clinical practice is provided in this report.

Postnatal Serum Total Thyroxine of Very Preterm Infants and Long-Term Neurodevelopmental Outcome.

Primary congenital hypothyroidism is a disease associated with low serum thyroxine and elevated thyroid-stimulating hormone (TSH) levels. The processes of screening and treating congenital hypothyroidism, in order to prevent neurodevelopmental impairment (NDI) in newborns, have been well investigated. Unlike term infants, very preterm infants (VPIs) may experience low thyroxine with normal TSH levels (<10.0 µIU/mL) during long-stay hospitalization. In the current literature, thyroxine treatment has been evaluated only for TSH-elevated VPIs. However, the long-term impact of low thyroxine levels in certain VPIs with normal TSH levels deserves more research. Since July 2007, VPIs of this study unit received screenings at 1 month postnatal age (PNA) for serum TSH levels and total thyroxine (TT4), in addition to two national TSH screenings scheduled at 3-5 days PNA and at term equivalent age. This study aimed to establish the correlation between postnatal 1-month-old TT4 concentration and long-term NDI at 24 months corrected age among VPIs with serial normal TSH levels. VPIs born in August 2007-July 2016 were enrolled. Perinatal demography, hospitalization morbidities, and thyroid function profiles were analyzed, and we excluded those with congenital anomalies, brain injuries, elevated TSH levels, or a history of thyroxine treatments. In total, 334 VPIs were analyzed and 302 (90.4%) VPIs were followed-up. The postnatal TT4 concentration was not associated with NDI after multivariate adjustment (odd ratios 1.131, 95% confidence interval 0.969-1.32). To attribute the NDI of TSH-normal VPIs to a single postnatal TT4 concentration measurement may require more research.

Foetal goitrous hypothyroidism - easy to recognise, difficult to treat. Is combined intra-amniotic and intravenous L-thyroxine therapy an option?

INTRODUCTION: Foetal hypothyroidism negatively impacts somatic and neurological child development and can be the cause of serious obstetric and perinatal complications. We present a rare case of a large foetal dyshormonogenetic goitre, causing foetal neck hyperexten-sion, oesophageal compression, and cardiac high-output failure. MATERIAL AND METHODS: A foetal goitre complicated by cardiomegaly and polyhydramnios was diagnosed at 23 weeks of gestation (WG) on a routine ultrasonographic (US) assessment in a healthy nullipara. Foetal blood sampling was performed and a severe foetal hypothyroid-ism was diagnosed. Treatment was undertaken with an intra-amniotic followed by combined intra-amniotic and intravenous injections of L-thyroxine (L-T4). A total of 11 doses of L-T4 were administered between 24-37 WG to the foetus. RESULTS: A complete regression of foetal goitre, cardiomegaly, and polyhydramnios was observed. At 38 WG the patient delivered vagi-nally a male infant with mild hypothyroidism and no signs of goitre or cardiomegaly on postnatal US. Neurological development of the one year old baby is normal. CONCLUSIONS: The effective diminishing of serum TSH concentration and goitre size was reached after combined intra-amniotic and in-travenous L-T4 injections were given. L-T4 requirement in the foetus is equal to or above 15 µg/kg daily and should be given in weekly intervals due to its rapid metabolism by the foetus and by placental type 3 deiodinase. Intra-amniotic L-T4 administration may be inef-fective when a large goitre indisposes amniotic fluid swallowing by the foetus, so then the combined L-T4 injections into the umbilical vein and intra-amniotically in experienced hands seems to be a reasonable and effective option.

Successful intrauterine therapy for fetal goitrous hypothyroidism during late gestation.

We experienced a case of fetal goitrous hypothyroidism in an infant delivered by a 33-year-old woman receiving 300 mg/day of propylthiouracil (PTU) for hyperthyroidism due to Graves' disease. A large fetal goiter (maximum diameter, 60 mm) was detected by magnetic resonance imaging (MRI) at 36 weeks of gestation. Initial fetal blood sampling revealed hypothyroidism with a serum thyroid-stimulating hormone (TSH) of 99 microIU/mL, free triiodothyronine (T(3)) of 1.97 pg/mL, and free thyroxine (T(4)) of 0.29 ng/dL. Consequently, a diagnosis of fetal goitrous hypothyroidism due to transplacental passage of maternal PTU was made. To reduce the risk of perinatal complications, 300 microg of levothyroxine sodium (L-T(4)) was administered into the maternal amniotic fluid twice between 37 and 38 weeks of gestation. Subsequent fetal MRI showed that the size of goiter had decreased. At 38 weeks and 5 days of gestation, a 3042-g male infant was born by cesarean section. There were no severe complications at delivery, although mild tachypnea was observed and the infant's thyroid gland was slightly enlarged. He was treated with L-T(4) for two weeks. At present, his growth and neurological development are normal. This case indicates that intrauterine therapy by the intraamniotic administration of L-T(4) can be effective in treating fetal goitrous hypothyroidism even during late gestation.

[Correct procedure in the presence of a fetal goiter associated with hypothyroidism. Observations from three cases]. / Conduite à tenir en présence d'un goitre foetal hypothyroïdien. A propos de trois observations.

Fetal goiter is a rare occurrence of which neonatal consequences are not always predictable. Concerning three cases of goiters associated with hypothyroidism discovered in utero, the authors describe the way to take care of in this bad codified situation. They insist upon the major role of ultrasound for goiter diagnosis and its impacts and for control of treatment efficiency. They also discuss intra amniotic L-Thyroxine injection and insist upon the necessity to obtain quick and definite thyroid evaluation after birth before decision to abstain from neonatal therapy.

[Central congenital hypothyroidism due to Graves' disease in the mother]. / Centrale congenitale hypothyreoïdie door ziekte van Graves bij de moeder.

Two male twins were born at a gestational age of 30 weeks. Five days after delivery, the mother was diagnosed with Graves' disease. The thyroid function in the neonates was therefore evaluated, which led to the detection of central congenital hypothyroidism (central CHT), even though the neonatal CHT-screening had been reported to be normal. Both boys were treated with thyroxine up to the age of nine months. It was then established that their development had been uneventful. Maternal Graves' disease can, due to the presence of anti-thyroid stimulating hormone (TSH) receptor antibodies and the maternal use of anti-thyroid drugs, result in thyroid dysfunction in the neonate. Neonates born to mothers with Graves' disease are at risk of developing central CHT. This occurs especially in children of mothers who are not treated or are inadequately treated during pregnancy. In view of the importance of thyroid hormone for brain development, children with central CHT are at risk for neurodevelopmental problems if thyroid dysfunction is not detected and treated early. The Dutch screening for congenital hypothyroidism is based on thyroxine (T4), TSH and thyroid-binding globulin. This makes it possible to detect central CHT. However, in prematurely born infants this disease may be missed because in this subgroup, referral is only based on increased TSH levels, which may not be present.

Transient hypothyroidism associated with viral Human Parechovirus encephalitis in a newborn.

Human Parechovirus type 3 (HPeV-3) is a neurotropic virus which can cause neonatal encephalitis, presenting as encephalopathy with seizures and diffuse white matter lesions on brain imaging. Neurodevelopmental outcome is linked to the extent of white matter abnormalities. We report on a neonate with clinical and biochemical findings of transient central hypothyroidism associated with HPeV-3 encephalitis. The co-occurrence of transient hypothyroidism and viral encephalitis has not been reported in newborns before. Transient suppression of the hypothalamo-pituitary-thyroidal axis is described in critically ill babies as the nonthyroidal-illness syndrome. Assessment of thyroid function in neonatal cases of HPeV-3 infection is required to conclude whether a transient hypothyroidism as in nonthyroidal-illness syndrome may be triggered by viral meningo-encephalitis and if treatment may influence neurodevelopmental outcome.

Effect of l-thyroxine supplementation on infants with transient hypothyroxinemia of prematurity at 18 months of corrected age: randomized clinical trial.

OBJECTIVE: Our objective was to evaluate effects of levothyroxine (l-T4) supplementation against neurodevelopmental outcomes at 18 months of corrected age in very-low-birth-weight (VLBW) infants with hypothyroxinemia but without elevated thyroid-stimulating hormone (TSH) concentration. METHODS: VLBW infants who had plasma TSH concentrations <10 µU/mL and free thyroxine (FT4) concentrations <0.8 ng/dL between 2 and 4 weeks of age were enrolled. They were randomly assigned to either the Treated (n=25) or Untreated group (n=45). The Treated group received l-T4 at a dose of 5 µg/kg/day. We compared growth and neurodevelopmental outcomes at 18 months of corrected age in the two groups. RESULTS: There were no significant differences in growth, the incidences of developmental delay, cerebral palsy, visual impairment, and hearing impairment in the two groups. CONCLUSIONS: In such infants, l-T4 supplementation at a dose of 5 µg/kg/day did not affect FT4 levels and showed no beneficial effect at 18 months of corrected age.

Supplementary iodine fails to reverse hypothyroidism in adolescents and adults with endemic cretinism.

The efficacy of supplemental iodine in correcting hypothyroidism in adults and older children with endemic myxedematous cretinism is not known. To investigate this issue we administered im iodized oil (1.5 mL) to 28 hypothyroid endemic cretins (TSH, greater than 5 mIU/L) from western China, aged 14-52 yr (mean = 29 SD = 11 yr). Clinical examination, intelligence testing (Hiskey Nebraska Test of Learning Aptitude and the Griffiths Mental Development Scales), and thyroid function tests were performed before and 6 months after iodine supplementation. We found that signs of thyroid hormone deficiency, dwarfism, and delayed sexual maturity persisted after iodine supplementation. Further, mental disability and other clinical features of neurological damage were not altered by treatment. The mean serum concentration of total T4 before treatment was 75 nmol/L (SD = 40) and fell after iodized oil administration to 56 nmol/L (SD = 29; P less than 0.001). Mean serum levels of TSH before and after iodine showed a paradoxical fall [85 mIU/L (SD = 102) and 46 mIU/L (SD = 46), respectively]. Serum TSH levels decreased into the normal range (less than 5 mIU/L) in only 1 of 28 patients (4%). We conclude that iodine supplementation does not reverse thyroid hormone deficiency or its sequelae in adolescents and adults with endemic myxedematous cretinism. Iodized oil in this age group of patients with endemic cretinism does not appear to be beneficial and should be used with caution.

Unusual course of congenital hypothyroidism and route of the L-thyroxine treatment in a preterm newborn.

Congenital hypothyroidism (CH) is the most common endocrine pathology in neonates. Inappropriate treatment of CH is complicated by irreversible brain damage or low IQ score. Hormone replacement therapy with L-thyroxine (L-T4) is sufficient for a very large proportion of patients. However, during treatment, the patient needs to be carefully monitored for presence of factors which might affect the absorption or bio-availability of the drug as well as its dose. Herein, we report a preterm newborn with CH who presented with gastrointestinal problems mimicking necrotizing enterocolitis. The clinical course was also complicated by cholestasis. The L-T4 replacement treatment was switched from oral route to parenteral. After resolution of the cholestasis, L-T4 treatment was continued successfully by the oral route.

Prenatal diagnosis and treatment perspective of fetal hypothyroidism with goiter.

We describe two cases of fetal goiter in women with no history of thyroid disease. Diagnosis of fetal goiter during antenatal care was made by ultrasound and MRI. Congenital hypothyroidism was confirmed by fetal blood sampling that was treated with weekly intra-amniotic injections of L-thyroxin. One fetus was initially treated with four weekly intra-amniotic injections of 200 µgms of L-thyroxin, later increased to 400 µgms. The other fetus was treated with only three weekly intraamniotic injections of 400 µgms of L-thyroxin. Therapeutic response was monitored by repeated ultrasound and MRI along with fetal blood sampling. At birth, none of the babies had goiter and were put on oral thyroxin. Post-natal studies were suggestive of congenital hypothyroidism due to dyshormogenesis. No abnormality was detected at follow-up. These cases highlight the role of intra-amniotic thyroxine in management of fetal hypothyroidism with goiter.

Unawareness of the effects of soy intake on the management of congenital hypothyroidism.

It has been established that soy products can interfere with thyroid hormone absorption resulting in continued hypothyroidism in individuals receiving recommended levothyroxine replacement. It has also been reported that achievement of euthyroidism in hypothyroid patients using soy products requires increased doses of levothyroxine. We have observed 2 patients with congenital hypothyroidism who continued to manifest clinical hypothyroidism while receiving recommended doses of hormone and ingesting soy products. The first patient was diagnosed by newborn screening (thyroid-stimulating hormone [TSH] =169 µIU/mL) and treated with 50 µg of levothyroxine since 6 days of age while simultaneously starting soy formula. At 3 weeks of age, she was clinically and biochemically hypothyroid (thyroxine = 4.0 µg/dL, TSH = 216 µIU/mL). We stopped her soy formula and decreased her levothyroxine dose. Three weeks later signs of hypothyroidism were resolving, and, by 10 weeks of age, she was clinically and biochemically euthyroid. Another patient was diagnosed by newborn screening, received levothyroxine, and did well. She was lost to us for 2 years. During this interval she began consuming soy milk and became profoundly hypothyroid (free thyroxine <0.4 ng/dL, TSH = 248 µIU/mL), even though the primary care physician had increased her levothyroxine dose to 112 µg/day. She was switched to cow milk, and her thyroid function slowly normalized with decreasing doses of levothyroxine. These 2 patients reinforce the importance of remembering that soy products interfere with levothyroxine absorption and can endanger infants and young children with congenital hypothyroidism who are at risk for developmental and growth delay.

European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism

"OBJECTIVE: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). EVIDENCE: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. CONSENSUS PROCESS: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. RECOMMENDATIONS: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy."