Congenital Hypothyroid Patients Research Articles

High-resolution melt curve analysis: An approach for variant detection in the TPO gene of congenital hypothyroid patients in Bangladesh.

TPO (Thyroid Peroxidase) is known to be one of the major genes involved in congenital hypothyroid patients with thyroid dyshormonogenesis. The present study aims to validate high-resolution melting (HRM) curve analysis as a substitute method for Sanger sequencing, focusing on the frequently observed non-synonymous mutations c.1117G>T, c.1193G>C, and c.2173A>C in the TPO gene in patients from Bangladesh. We enrolled 36 confirmed cases of congenital hypothyroid patients with dyshormonogenesis to establish the HRM method. Blood specimens were collected, and DNA was extracted followed by PCR and Sanger sequencing. Among the 36 specimens, 20 were pre-sequenced, and variants were characterized through Sanger sequencing. Following pre-sequencing, the 20 pre-sequenced specimens underwent real-time PCR-HRM curve analysis to determine the proper HRM condition for separating the three variations from the wild-type state into heterozygous and homozygous states. Furthermore, 16 unknown specimens were subjected to HRM analysis to validate the method. This method demonstrated a sensitivity and specificity of 100 percent in accurately discerning wild-type alleles from both homozygous and heterozygous states of c.1117G>T (23/36; 63.8%), c.1193G>C (30/36; 83.3%), and c.2173A>C (23/36; 63.8%) variants frequently encountered among 36 Bangladeshi patients. The HRM data was found to be similar to the sequencing result, thus confirming the validity of the HRM approach for TPO gene variant detection. In conclusion, HRM-based molecular technique targeting variants c.1117G>T, c.1193G>C, and c.2173A>C could be used as a high throughput, rapid, reliable, and cost-effective screening approach for the detection of all common mutations in TPO gene in Bangladeshi patients with dyshormonogenesis.

Molecular investigation of TSHR gene in Bangladeshi congenital hypothyroid patients.

The disorder of thyroid gland development or thyroid dysgenesis accounts for 80-85% of congenital hypothyroidism (CH) cases. Mutations in the TSHR gene are mostly associated with thyroid dysgenesis, and prevent or disrupt normal development of the gland. There is limited data available on the genetic spectrum of congenital hypothyroid children in Bangladesh. Thus, an understanding of the molecular aetiology of thyroid dysgenesis is a prerequisite. The aim of the study was to investigate the effect of mutations in the TSHR gene on the small molecule thyrogenic drug-binding site of the protein. We identified two nonsynonymous mutations (p.Ser508Leu, p.Glu727Asp) in the exon 10 of the TSHR gene in 21 patients with dysgenesis by sequencing-based analysis. Later, the TSHR368-764 protein was modeled by the I-TASSER server for wild-type and mutant structures. The model proteins were targeted by thyrogenic drugs, MS437 and MS438 to perceive the effect of mutations. The damaging effect in drug-protein complexes of mutants was explored by molecular docking and molecular dynamics simulations. The binding affinity of wild-type protein was much higher than the mutant cases for both of the drug ligands (MS437 and MS438). Molecular dynamics simulates the dynamic behavior of wild-type and mutant complexes. MS437-TSHR368-764MT2 and MS438-TSHR368-764MT1 showed stable conformations in biological environments. Finally, Principle Component Analysis revealed structural and energy profile discrepancies. TSHR368-764MT1 exhibited much more variations than TSHR368-764WT and TSHR368-764MT2, emphasizing a more damaging pattern in TSHR368-764MT1. This genetic study might be helpful to explore the mutational impact on drug binding sites of TSHR protein which is important for future drug design and selection for the treatment of congenital hypothyroid children with dysgenesis.

Different FT3/TSH correlation in acquired and congenital hypothyroid patients reveals a different hypothalamic set-point.

To understand differences in thyroid hormone replacement therapy with levo-thyroxine (l-T4) between acquired and congenital hypothyroid (CH)patients. We compared biochemical thyroid parameters between euthyroid subjects (EU) and both CH adult patients and thyroidectomized patients (TP) under replacement therapy. A retrospective analysis was performed on a series of 98 consecutive adult CH patients (27 males and 71 females) with a median age of 24 years (range 18-58). Serum TSH, FT3, FT4, l-T4 dose and body weight were assessed. For comparison purposes, large series of 461 TP for thyroid cancer and 1852 EU followed at our Thyroid Clinic were used as control groups. The daily weight-based l-T4 dose was significantly higher in CH than TP group (1.9 vs. 1.7 mcg/kg, p = .03). FT3/FT4 ratio was significantly higher in theEU group, intermediate in CH and lower in TP groups (0.32, 0.28 and 0.24, respectively). Linear regression analysis displayed an inverse correlation between FT4 and TSH in all the groups. An inverse correlation between FT3 and TSH was observed in theTP group, but not in theEU and CH group suggesting that CH patients, under replacement therapy, display biochemical thyroid parameters similar to EU subjects. Adult CH patients require a higher daily l-T4 dose than adult TP. However, the different correlation of TSH and FT3 values between CH and TP patients suggests an adaptive and different hypothalamic-pituitary-thyroid axis regulation that may depend on the early timing of the onset of hypothyroidism in CH.

Comparison of Intelligence Quotient between Permanent Congenital Hypothyroid Children and Healthy Children

Background: Congenital hypothyroidism (CH) is the most common curable cause of mental retardation. The aim of this study was to compare the intelligence quotient (IQ) of congenital hypothyroid patients with healthy children. Methods: This two-group cross-sectional study was performed on 30 permanent CH children within the age range of 6-12 years referring to the Endocrine Clinic of Imam Reza Hospital, Mashhad, Iran between April 2017-2019. In addition, 32 healthy children of the same age and gender from the family members of the patients were chosen as the control group. The intelligence test was performed using the revised version of the Wechsler Intelligence Scale for Children and The mean verbal, performance, and total IQ was compared between case and control groups. Results: There was no significant difference between two groups in terms of age and gender. The mean verbal, performance, and total IQ in the case group were obtained as 104.33±13.30, 93.13±7.42, and 98.03±7.94, respectively. With regard to the healthy group, these mean values were respectively estimated at 121.34±16.74, 99.65±11.92, and 110.71±14.15 (the normal range of IQ was 90-109). Accordingly, the results revealed a significant difference between the two groups in terms of verbal (P=0.000), performance (P=0.013), and total (P=0.000) IQ. Furthermore, a relationship was found between early treatment initiation and higher verbal IQ (r=0.521; P=0.032), as well as between lower thyroid-stimulating hormone and higher performance IQ (r=0.559; P=0.020). Conclusion: The permanent CH children that had received timely treatment had normal levels of IQ based on the Wechsler Intelligence test. However, it was significantly lower in the CH children than that in healthy children of the same age, gender, and socioeconomic status.

Ultrasound Elastography in Pediatric Congenital Hypothyroid Patients.

Congenital hypothyroidism (CH) is most frequently encountered in newborns as an endocrine disorder characterized by thyroid hormone deficiency, and is one of the most common reasons for preventable mental retardation. This prospective study was designed to detect the pediatric occurrences of CH followed as euthyroid, with no anomalies detected via US on the gray scale, in comparison with a pediatric group with normal levels. A total of 42 apparently healthy children with no thyroid disorder (Group 1) and 54 euthyroid CH (Group 2) using thyroid hormone were included in this study. Both B-mode gray scale ultrasound (US) and elastography examinations were made using Toshiba Aplio 400 device (Toshiba Medical Systems Corporation, Otawara, Japan), with a 12 MHz linear probe. All the radiological examinations were made by a single radiologic physician with at least 5 years of experience in elastography. In total, 96 occurrences in the right and left lobes of 192 thyroid gland measurements were included in the research. There were 20 males and 22 females in the healthy group (n=42), and 28 males and 26 females in the CH group (n=54). Although, there were no significant differences in the average age or gender (p=0.563), there were significant differences in the strain index (SI) values in the CH group.The receiver operating characteristics (ROC) curve was done to calculate the cut-off value for diagnosing CH with strain index ratio (SIR); the value of the cut-off was 0.695, with 63.1% sensitivity and 50.9% specificity. This was the first study about CH in children. Our study found the SIR of CH to be higher than the normal thyroid parenchyma. It showed that in parenchymal related CH, SE should be used. This study should be a guide for new studies that should be done about the different etiological factors of CH.

Final height in Italian patients with congenital hypothyroidism detected by neonatal screening: a 20-year observational study

BackgroundLinear growth and final height are reported as normal in congenital hypothyroid patients in the neonatal screening era.MethodsWe evaluated the final height in 215 patients with congenital hypothyroidism to assess if it improved over the last 2 decades.ResultsFinal height (-0.1 ± 1.0 SDS) was higher than target height (-0.8 ± 1.0 SDS, p < 0.001) and not different among the 4 quartiles for birthdate. It was correlated with target height (r2 = 0.564, p < 0.001) and height at puberty onset (r2 = 0.685, p < 0.001), but not with age at diagnosis or the starting LT4/kg/day dose. The curve fitting analysis showed that the age at diagnosis progressively decreased during the 20-year study period, while the target height and the starting LT4/kg/day increased. Final height was not affected by the birthdate, the age at diagnosis, the starting LT4 dose.ConclusionsThe final height is higher than the target height, but despite the improvement in the screening and the treatment, it did not improve over the last 20 years. These findings are in keeping with the described secular trend and suggest that earlier diagnosis and replacement therapy do not significantly modify final height in these patients.

Male congenital hypothyroid Pax8−/− mice are infertile despite adequate treatment with thyroid hormone

Severe forms of congenital hypothyroidism lead to serious clinical symptoms if thyroid hormone replacement therapy is not instituted immediately after birth. In this study, Pax8(-/-) mice that are born without a thyroid gland were used as an animal model to study the consequences of congenital hypothyroidism. As expected, adequate treatment of these animals with thyroxine restored the general deficits of congenital hypothyroidism; however, Pax8-deficient male mice were infertile. We report here that in these mice, the efferent ducts and epididymides are either absent or the efferent ducts exhibit a reduced lumen and extensive connective tissue, which appears to impair testicular drainage and subsequently leads to complete absence of spermatozoa from the epididymis. The results suggest that, starting with the onset of pubertal testicular fluid secretion, a backpressure is created in the testis by the absence of efferent ducts or constriction of their tubule lumen when present. This subsequently leads to secondary disorganization of the seminiferous epithelium that increases with age, resulting in mixed atrophy of the testis in the adult. Serum testosterone levels as well as mRNA expression of anterior pituitary hormones are in the normal range, indicating that the observed infertility is not due to hormonal imbalance, but rather to a developmental defect of the efferent ducts. The demonstration of Pax8 expression in the epithelia of the epididymis and the efferent ducts suggests a direct morphogenic role of Pax8 in the development of these organs. It remains to be elucidated whether congenital hypothyroid male patients with mutations in the Pax8 gene are similarly affected.

Congenital Hypothyroid Female Pax8-Deficient Mice Are Infertile Despite Thyroid Hormone Replacement Therapy

Absence of the Pax8 gene results in congenital hypothyroidism in mice, and mutations of the Pax8 gene have been associated with thyroid hypoplasia in humans. As in humans, treatment of congenital hypothyroid Pax8 null mice with thyroxine normalizes the known deficits. However, we report here that thyroxine-substituted female Pax8(-/-) mice are infertile because they lack a functional uterus revealing only remnants of myometrial tissue. In addition, the vaginal opening is absent. Interestingly, oviduct, cervix, and upper parts of the vagina are not affected, although Pax8 expression has been described in the entire Müllerian duct before. Because the natural outflow of the oviduct is impaired, a hydrosalpinx develops frequently. Folliculogenesis, ovarian hormone production, and transcription of pituitary hormones are in a normal range. Thus, infertility in Pax8(-/-) mice seems to be due to a defect in development of the Müllerian duct rather than to hormonal imbalance, pointing to a direct morphogenic role for Pax8 in uterine development. Because we demonstrated Pax8 expression not only in the uterine epithelium of mice but also in the human endometrium, it remains to be elucidated whether adequate development of the uterus may also be affected in congenital hypothyroid female patients with mutations in the Pax8 gene.

Factors predicting final height in early treated congenital hypothyroid patients

To evaluate pubertal development and final height (FH) in early treated patients with congenital hypothyroidism (CH) and to identify the main factors predicting FH. Retrospective. Eighty-five patients with early diagnosed and treated CH. Evaluation of length/height at diagnosis (mean age 26.6 days), at onset of puberty, and at the end of linear growth. Mean FH was 161.7 cm in females and 173.8 cm in males, within +/- 0.9 cm of the 50th percentile of Italian growth charts, 5 cm higher than the mean target height (TH). Linear growth did not differ according to thyroid imaging findings. In males, height at onset of puberty was 0.16 standard deviation score (SDS), not statistically different from FH (-0.09 SDS). In females, height both at onset of puberty (0.39 SDS) and at menarche (0.57 SDS) was significantly higher (P < 0.001) than FH (-0.10 SDS). Puberty started at a mean chronological age of 10.2 and 11.6 years in females and males, respectively, with a corresponding bone age. FH correlated with TH and height at diagnosis, at onset of puberty, and at menarche. Multiple regression analysis showed that height at onset of puberty and TH are the most important factors explaining FH variability, although height at onset of puberty is slightly more important. Our results, obtained in the largest reported available group of congenital hypothyroid patients, show that final height is higher than target height in both sexes and that height at onset of puberty is the main factor affecting final height.

Thyroid hormones cannot restore female fertility in congenital hypothyroid Pax8-/- mice

Congenital hypothyroidism (CH) is a common disorder affecting 1 in 3600 newborns. If not treated immediately after birth with thyroid hormones (TH), severe CH leads to mental retardation and motor dysfunction. The Pax8-/- mouse provides an ideal animal model for CH since these animals are athyroid during postnatal life. As in humans, TH replacement in mice generally normalizes the deficits of CH. Surprisingly, however, although adequately treated with TH, female Pax8-/- mice are infertile. Our analysis revealed that infertility of these mice is caused by an almost complete absence of the uterus. In T4 substituted Pax8-/- mice ovaries show normal histology and characteristics of ovulation, and serum estrogen and progesterone levels as well as transcript expression of all pituitary hormones are in a normal range. However, remnants of myometrial tissue, as identified by staining for alpha-smooth muscle actin, can be found surrounded by fat tissue in Pax8-/- mice. Since these tissue remnants lack a lumen, the natural outflow of secretory products of the oviduct is impaired. As a consequence, a hydrosalpinx develops in many cases. Whereas cervix and vagina are normally differentiated, vaginal opening is absent in T4 treated Pax8-/- mice. Thus, this infertility is obviously not due to hormonal imbalance, but to a defect in uterine development from the Müllerian duct where Pax8 has been shown previously to be expressed. This points to a direct morphogenic role of the Pax8 gene. Interestingly, Pax8 mRNA is still expressed in the uterine epithelium of adult wildtype mice. Furthermore, we could also demonstrate expression of the Pax8 gene in uterine epithelium in humans. Thus, it remains to be elucidated whether fertility may be similarly affected in congenital hypothyroid female patients with mutations in the Pax8 gene.

Treatment for Congenital Hypothyroidism: Thyroxine Alone or Thyroxine Plus Triiodothyronine?

To compare the effects of therapy with thyroxine (T4) plus triiodothyronine (T3) versus T4 alone from the first days of life in screened congenital hypothyroid (CH) infants. We examined 14 CH infants diagnosed by neonatal screening and a group of control infants. CH patients were divided randomly into 2 groups, 1 treated with T4 alone (group 1) and the other treated with T4 plus T3 (liothyronine; group 2). In all patients electrocardiography and thyroid hormone evaluations were performed before and 15 and 30 days and 3, 6, and 12 months after the beginning of therapy. Psychological tests were also performed at 6 and 12 months of age in CH patients and in other matched controls. After 15 days of treatment, serum thyrotropin (TSH) levels become normal in 5 of 7 cases of group 1 (median TSH level 10.7 micro U/ml) and in 1 of 7 cases of group 2 (median TSH level 72.5 micro U/ml). At the same period, serum-free thyroid hormone levels were within the normal range in both groups, but free T4 values were significantly higher in group 1 than in group 2 and in controls. At the subsequent examinations, free T4 values were within the upper normal limit in group 1, whereas they remained within the normal range in group 2. No clinical or electrocardiographic signs of heart disease were found in any of the patients. The psychometric quotient in CH infants was significantly lower than in controls, but similar in patients of group 1 and group 2. The combined treatment with T4 plus T3 seems not to show significant advantages, at least in our experimental conditions, compared with the traditional treatment with T4 alone in early treated CH infants. A further longer and more extensive follow-up is mandatory.

Click-evoked otoacoustic emissions recorded from untreated congenital hypothyroid newborns

Thyroid hormone plays an important role in hearing development. Both a genetic or non-genetic hypothyroidism is often associated with congenital hearing loss. The exact incidence of hearing impairment in untreated congenital hypothyroid (CH) patients is unknown. This paper will present the results of measuring of the transient-evoked otoacoustic emissions (TEOAE) in a population of 29 newborns, who tested positive on a screening test for hypothyroidism (CH group) and in 68 well babies (control group) randomly chosen from all the newborns, classified as PASS, included in the Hearing Screening Program of the San Raffaele Hospital in Milan. TEOAE were recorded in all newborns within 1 month after birth and before beginning L-thyroxine treatment with conventional commercial instrumentation. Both temporal and time–frequency analyses of the emitted responses were conducted by means of a wavelet transform. The comparison of the characteristics of the temporal and frequency content of the responses of the two groups (CH and control) showed no statistically significant difference. No correlation was found between outer hair cell dysfunction and hypothyroidism.

Incidence of febrile convulsions in children with congenital hypothyroidism

Brain excitability has been inconsistently reported to be increased both in hypo‐ and hyperthyroidism, but there have been few studies on the effects of thyroid hormones on brain excitability in children. With this in mind, we investigated the incidence of febrile convulsions (FCs) among patients with congenital hypothyroidism, who have been taking L‐ thyroxine since the age of 1 month. The incidence of FCs among congenital hypothyroid patients was 1.6% (1/63) which was significantly low (p &lt; 0:05) compared with that of normal control children who visited our hospitals as outpatients (28/341, 8.2%) and that of others (322/3301, 9.8%) investigated 33 years ago in the same area. The incidence of FC among siblings of the 63 patients (7/74, 9.5%) was not statistically different from the controls. At least 8 of the 126 parents (6.4%) had experienced FC, however, only one child was affected in the 8 families. In conclusion, it seems likely that patients with congenital hypothyroidism on regular L‐T4 replacement are less prone to experience FC. More studies on the incidence of convulsive disorders in children with thyroid diseases are needed to clarify the effects of thyroid hormones on brain excitability.

Incidence of febrile convulsions in children with congenital hypothyroidism

Brain excitability has been inconsistently reported to be increased both in hypo- and hyperthyroidism, but there have been few studies on the effects of thyroid hormones on brain excitability in children. With this in mind, we investigated the incidence of febrile convulsions (FCs) among patients with congenital hypothyroidism, who have been taking L-thyroxine since the age of 1 month. The incidence of FCs among congenital hypothyroid patients was 1.6% (1/63) which was significantly low (p < 0.05) compared with that of normal control children who visited our hospitals as outpatients (28/341, 8.2%) and that of others (322/3301, 9.8%) investigated 33 years ago in the same area. The incidence of FC among siblings of the 63 patients (7/74, 9.5%) was not statistically different from the controls. At least 8 of the 126 parents (6.4%) had experienced FC, however, only one child was affected in the 8 families. In conclusion, it seems likely that patients with congenital hypothyroidism on regular L-T4 replacement are less prone to experience FC. More studies on the incidence of convulsive disorders in children with thyroid diseases are needed to clarify the effects of thyroid hormones on brain excitability.

Bone mass in children with congenital hypothyroidism treated with thyroxine since birth.

To determine whether the large doses of thyroxine treatment early in life adversely affect bone mass, we measured bone mass of 20 congenital hypothyroid (CH) patients (8.4 +/- 2.2 years) who were diagnosed and treated since birth. Starting thyroxine dose and current dose were 8.5 +/- 1.9 micrograms/kg/day and 3.1 + 1.2 micrograms/kg/day respectively. Thyroid function and serum biochemical tests for calcium homeostasis were normal at the time of study. Bone mass was measured by dual energy X-ray absorptiometry. Nine siblings served as controls. The patients' bone mineral density was within the normal range of population controls, and was not different from the sibling controls. The patients also had height-adjusted bone mineral content equal to the expected height-adjusted values in the siblings. Our studies indicate that the large doses of thyroxine therapy for CH do not cause osteopenia in childhood.

Neurophysiologic studies and cognitive function in congenital hypothyroid children.

Minor neurologic and intellectual impairments have been described in some congenital hypothyroid (CH) children in spite of early detection by neonatal screening. The aim of our study was to assess cognitive functions as well as neurophysiologic parameters in hypothyroid children and to compare children detected by neonatal screening (group A) versus hypothyroid patients clinically diagnosed before the beginning of the screening program (group B). Group A consisted of 15 children (13 girls, mean age at the beginning of treatment 33 d). Group B consisted of 11 patients (7 girls, mean age at the start of treatment 10.1 mo). Twenty age-matched healthy children were studied as a control group for neurophysiologic tests. Neurophysiologic tests (Auditory P 300, long latency somatosensory evoked potentials (LL-SEP) were performed along with IQ evaluation. Abnormalities of neurophysiologic tests were detected in 82% of clinically diagnosed hypothyroid children. Surprisingly, 47% of the children detected by neonatal screening, having normal mental development index, showed at least one abnormal neurophysiologic test. LL-SEP latencies were found significantly increased in both groups of CH patients compared with controls. Our data are suggestive for a prenatal or perinatal CNS damage in some children with congenital hypothyroidism, despite early treatment.

Personality traits and mental prognosis in patients with congenital hypothyroidism not treated from early life.

Congenital hypothyroidism, if not treated in very early life, severely impairs the neuropsychological development of affected subjects. We have carried out a detailed analysis of cognitive functioning and personality traits in 18 congenital hypothyroid patients treated late and/or unproperly. Significant cognitive defects were observed, the most important being a defective learning ability and an impaired capacity to judge socially significant events and to project complex actions in a temporal perspective. A mental retardation (IQ less than 70) was observed in 8/18 (44.4%) of these patients, a moderate intellective deficit in 5/18 (27.8%) and an IQ greater than 85 in the remaining 5 patients (27.8%). These data indicate that the mental defect of congenital hypothyroid patients may be overestimated. The patients personality was characterized by dependence on the mother, worrying about their body, maladjustment and socialization problems. Since the intellective prognosis of these patients may significantly improve when the environmental conditions are optimized, social and psychological help must always be suggested.

Thyroid-stimulating hormone, prolactin, and growth hormone response to thyrotropin-releasing hormone in treated children with congenital hypothyroidism.

The purpose of the present study was to assess thyroid-stimulating hormone (TSH), prolactin, and growth hormone responses to TRH stimulation in 12 congenitally hypothyroid children adequately treated with L-thyroxine from the first weeks of life. Although clinically euthyroid, six of these children were found to have abnormally high basal serum TSH concentrations despite clinical euthyroidism. Serum triiodothyroxine and L-thyroxine concentrations were normal and did not differ whether the children had elevated or normal basal serum TSH. All six of the children with high basal TSH had an exaggerated TSH response to TRH and 4 of them also had an augmented prolactin response to TRH. The children with normal basal TSH concentrations had normal TSH and prolactin responses to TRH. An abnormal ("paradoxical") elevation of growth hormone concentration in response to TRH was found in four of seven children in a separate group of patients who had prolonged, untreated primary hypothyroidism, but such responses were not found in any of the adequately treated children. These findings suggest the following conclusions: 1) the phenomenon of high serum concentrations of TSH in conjunction with normal L-thyroxine and triiodothyronine levels (and clinical euthyroidism), is prevalent in congenital hypothyroid patients. 2) These patients have an exaggerated response of their pituitary thyrotroph and lactotroph cells to TRH, presumably caused by selective and relative resistance of these cells to the inhibitory effects of thyroid hormones. 3) Congenital hypothyroidism is not associated with abnormal somatotroph cell responses to TRH.

A retrospective study of audiological function in a group of congenital hypothyroid patients

A retrospective survey has been carried out on audiological function in 46 congenital hypothyroid cases; mental and physical development were also assessed, as well as the adequacy of substitutive therapy. Using traditional audiometry it was found that 50% of the congenital hypothyroid patients were hypocusic. Severe and profound hearing loss (5 cases) was found in the group of hypothyroid patients with dyshormonogenesis, whereas only one-third of patients with thyroid agenesis presented a mild or moderate hearing loss not related to the time of diagnosis and treatment. The hearing loss was twice as frequent in the patients with clinical hypothyroidism. Using electro-physiological techniques, the early or slow potentials were comparable between hypocusic or normocusic patients; however a longer latency of the slow vertex responses was observed in the hypothyroid group as compared to the normal population. The mean estimated I.Q. was about 2 standard deviations below the average; however 30% of subjects had normal or above normal intellectual level, this percentage rises to 55% if only patients below 16 years are considered. The height was significantly shorter only in the late treated patients (1 year). No correlations were found among audiological and psychological variables, nor between these variables and height. All patients were on desiccated thyroid, but therapy was inadequate in 26% of cases and subclinical hypothyroidism was found in 33% of cases.