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PubMed1993

Increased plasma thyroid stimulating hormone in treated congenital hypothyroidism: relation to severity of hypothyroidism, plasma thyroid hormone status, and daily dose of thyroxine.

Plasma thyroid stimulating hormone (TSH) concentrations obtained during the first four years of treatment in 418 children with congenital hypothyroidism, identified by neonatal screening, were examined in relation to paired measurements of plasma thyroxine (n = 1945), free thyroxine (n = 836), triiodothyronine (n = 480), and free triiodothyronine (n = 231), and estimated daily dose of thyroxine at the time of blood sampling. Overall, plasma TSH was above 7 mU/l in 1280 out of 2960 samples (43%); the percentage was not related to severity of hypothyroidism at diagnosis. Mean values for thyroxine and free thyroxine, and to a lesser extent free triiodothyronine, were consistently lower in samples with TSH concentrations over 7 mU/l and this was the case in patients with either severe or less severe hypothyroidism. Raised TSH concentrations were also associated with lower mean doses of thyroxine (micrograms/kg/day) but here the mean doses of thyroxine in children with severe hypothyroidism were higher than in the children with less severe hypothyroidism. The mean dose of thyroxine associated with low/normal TSH values was highest in the first 6 months and fell progressively. Thyroxine dose was significantly related to thyroxine and free thyroxine concentrations but not to triiodothyronine and free triiodothyronine and the latter appeared to be of limited value as measures of plasma thyroid hormone status during treatment.

Child, Preschool↗
PubMed2001

Hypothyroidism and glaucoma. A study of 100 hypothyroid patients.

PURPOSE: To determine whether glaucoma is associated with hypothyroidism, as has previously been suggested. METHODS: This is a cross-sectional study and a noncomparative interventional case series. One hundred consecutive patients with newly diagnosed hypothyroidism were referred for complete ophthalmologic examination, including automated perimetry and examination of the optic disks, to identify the presence of glaucoma. After correction of the hypothyroidism, reexamination was performed. RESULTS: No patient had glaucoma and no correlation was found between intraocular pressure and either thyroid stimulating hormone or free tri-iodothyronine. No statistically significant difference was found between intraocular pressure levels before and after treatment of the hypothyroidism. CONCLUSION: This study does not demonstrate an association between hypothyroidism and glaucoma.

Adolescent↗
PubMed1983

[Profile of autoimmune antibodies in idiopathic hypothyroidism and hypothyroidism following radio-iodine treatment in Basedow's disease: comparison with a group of normal subjects from the female population of Switzerland].

Prevalence of thyroid microsomal antibodies (MCHA) and thyroglobulin antibodies (TGHA), as well as frequency of other autoantibodies (parietal cell antibodies [PZA], adrenal antibodies [NNA], islet cell antibodies [IZA], smooth muscle antibodies [SMA], mitochondrial antibodies [MitA] and antibodies to nuclear antigens [ANF]), are reported for three different female groups in Switzerland in 91 euthyroid controls (group A), in 58 patients with idiopathic hypothyroidism (group B) and in 55 patients with hypothyroidism after administration of radioactive iodine for Graves' disease (group C). Prevalence of MCHA in the three groups was 14.5%, 90%, and 72%, respectively, and TGHA were positive in 6.5%, 56%, and 28%, respectively. Simultaneous occurrence of both thyroid antibodies and their appearance in higher titers were significantly more frequent in group B than in the other two groups. Goitrous forms of idiopathic hypothyroidism show higher MCHA titers than the atrophic forms. There was no association between thyroid antibodies and the presence of endocrine ophthalmopathy in group C. PZA were frequently found in groups B and C (26% and 13.6%, respectively; 4.7% in controls). The higher frequency of other autoantibodies was even more pronounced for ANF (52.1% in group B, 29.7% in group C, and 12.5% in controls). NNA and SMA were also more frequent, but not to a statistically significant degree. Two patients (both in group B) had positive islet cell antibodies. MitA were equally distributed in the three groups. These results suggest a relatively high proportion of asymptomatic autoimmune thyroiditis in the female population of Switzerland, with possible progression to overt hypothyroidism. Determinations of PZA and NNA are mandatory in both Graves' disease and idiopathic hypothyroidism. Cases with positive PZA must be closely monitored in view of the association with autoimmune atrophic gastritis and pernicious anemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1980

Intellectual, school and occupational performance in patients with idiopathic hypothalamo-pituitary hypothyroidism and primary hypothyroidism.

Intelligence quotient (IQ), school and professional performance were reviewed in 33 patients with idiopathic hypothalamo-pituitary hypothyroidism. Diagnosis was based on low T4 values and clinical signs. All were treated with growth hormone (HGH). In some, hypothyroidism became manifest only after HGH therapy. Birth history revealed breech delivery in 24 and perinatal asphyxia in 15 of them. Thyroid treatment was started at a mean age of 9.8 (range 4-18 years). The mean IQ was 103.4 +/- 16.7 (SD). 9 patients had IQs below 90, 8 of them were born by breech delivery, 3 had severe perinatal asphyxia, one recurrent symptomatic hypoglycemia, and one a micropenis. Of those patients who have reached the respective age, 7 attended college, 3 university, and 9 had skilled professions. Only 7 required special education. For comparison, 52 patients with primary hypothyroidism were studied. Their mean IQ was with 89.3 +/- 18.1 (SD) significantly lower (p < 0.001) than the mean IQ of patients with hypothalamo-pituitary hypothyroidism. The best IQ (96.8 +/- 16.9) was attained when thyroid treatment was started before the age of 4 months, the lowest IQ (78.2 +/- 19.2) was found in the group of patients in whom thyroid substitution was initiated between 5 and 12 months. Patients who were treated after one year of age, had a mean IQ of 90.0 +/- 15.7. This group includes patients with ectopic thyroid glands or acquired hypothyroidism such as Hashimoto's thyroiditis.

Adolescent↗
PubMed2004

Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor.

OBJECTIVE: We wished to ascertain whether mutations in the TSH receptor (TSHR) gene were present in two siblings with congenital hypothyroidism with no parental consanguinity. DESIGN: The pituitary-thyroid axis and thyroid gland morphology were investigated in both affected siblings and their parents. The TSHR gene was analysed in each subject. MEASUREMENTS: Basal thyroid function together with circulating thyroglobulin levels were measured in each subject. In addition, a TRH stimulation test was undertaken in each parent. All family members underwent thyroid ultrasonography. The TSHR gene was amplified from genomic DNA using the polymerase chain reaction and receptor mutations were identified by sequence analysis. RESULTS: Two siblings were diagnosed with severe congenital hypothyroidism (total T4 19-21 nmol/l, TSH 160-230 mU/l on neonatal screening). Although radioiodine scanning showed no tracer uptake and ultrasound imaging in both individuals failed to demonstrate thyroid tissue, suggesting complete athyreosis, circulating thyroglobulin levels were measurable. The thyroid status of the parents was discordant: in the father, baseline thyroid function (FT4 13 pmol/l, TSH 4 mU/l), the peak TSH level after TRH stimulation (30 mU/l) were normal and he exhibited an appropriate rise in circulating thyroid hormones in response to the elevated TSH; in contrast, in the mother, baseline thyroid function was abnormal (FT4 10 pmol/l, TSH 15 mU/l), the TSH response to TRH was exaggerated (110 mU/l), with no subsequent rise in circulating thyroid hormones. An eutopic, slightly hypoplastic thyroid gland was visualized on ultrasonography in the mother and her thyroid antibody status was negative. Both children were compound heterozygotes for missense (alanine to threonine at codon 553, A553T) and premature stop (tryptophan at codon 546, W546X) mutations in the fourth transmembrane domain of the TSH receptor. The mother and father were heterozygous for W546X and A553T mutations, respectively. Each mutation is known to abolish the function or cellular surface expression of the TSH receptor. CONCLUSIONS: Inactivating mutations in the TSH receptor can be associated with severe TSH resistance presenting as congenital hypothyroidism with apparent athyreosis. Our observations also suggest that heterozygosity for an inactivating TSHR mutation may be associated with compensated hypothyroidism and thyroid hypoplasia.

Congenital Hypothyroidism↗
PubMed1990

Transient hypothyroidism in infants born to mothers with chronic thyroiditis--a nationwide study of twenty-three cases. The Transient Hypothyroidism Study Group.

To define the difference in prognosis and the clinical features of transient neonatal hypothyroidism in infants born to mothers with chronic thyroiditis, we conducted a nationwide study of this condition. Sixteen mothers with chronic thyroiditis and twenty-three of their offspring with transient hypothyroidism were registered and reported in this paper. Five (group A) of twenty-two live infants showed physical, mental and/or psychomotor developmental delay (IQ below 80). No significant difference between TSH-binding inhibitor immunoglobulin (TBII) or thyroid-stimulation blocking antibody (TSBAb) activities in groups A and B (normal development) were noted. Moreover, there was no significant difference in thyroid function in the newborn period, ages at the start of thyroid medication or the dose and duration of treatment in the two groups. A striking difference observed between the two groups was the thyroid function of their mothers during pregnancy. In group A, four mothers were hypothyroid during pregnancy, and another mother discontinued thyroid medication in the last trimester and her baby was most delayed at the start thyroid medication. On the other hand, the mothers of only two of seventeen live cases in group B had mild hypothyroidism during pregnancy. There were two sets of siblings whose mother received inadequate treatment during the first pregnancy and adequate treatment during the second pregnancy. The psychomotor, physical and mental developmental delay were observed in their first babies. These findings suggested that maternal thyroid function during pregnancy might be an important factor in the prognosis of infants born to mothers with chronic thyroiditis.

Adolescent↗
PubMed1979

Combined hypothalamic hypothyroidism and secondary adrenal insufficiency. Misdiagnosed as primary hypothyroidism.

A case of combined, selective, hypothalamic hypothyroidism and secondary adrenal insufficiency is described. Serum levels of thyroid-stimulating hormone (TSH), before and after thyrotropin-releasing factor (TRF) administration, were in the range generally considered to be indicative of primary, rather than secondary, hypothyroidism. Hence, the clinical usefulness of serum TSH levels to unequivocally provide an accurate distinction between primary and secondary hypothyroidism must be questioned. The paucity of clinical findings suggestive of adrenal insufficiency in this case is emphasized, and the usefulness of adrenal screening tests in hypothyroid subjects seems clear.

Adrenal Insufficiency↗
PubMed1998

[Long-term study of subclinical hypothyroidism: spontaneous course and predictors of manifest hypothyroidism].

The syndrome of subclinical hypothyroidism is frequent and predominantly affects females over 40. Only limited data on its natural course is available. It was the aim of our prospective trial to analyze the spontaneous evolution of this syndrome, to identify risk factors of the development of overt hypothyroidism and to develop guidelines for the management of such patients. 154 female patients were followed over a mean observation period of 10 years. After 10 years, 34% had developed overt hypothyroidism, 57% remained in the subclinical stage, and in 9% thyroid function had normalized. The initial grading of TSH-concentration (< 6 mU/l, 6-12 mU/l, > 12 mU/l) was highly predictive for thyroid failure: 7.3%, 25% and 78%, respectively, overt hypothyroidism occurred. Further risk factors for thyroid failure included an impaired thyroid reserve (T3-stimulation after TRH) and elevated titers of microsomal antibodies. We therefore recommend to controlling patients with a TSH-concentration < 6 mU/l, start thyroxine hormone replacement therapy in patients with a TSH-concentration > 12 mU/l and, depending on the additional risk factors, either controlling or treating patients with a TSH-concentration of 6-12 mU/l.

Adolescent↗
PubMed1990

Elementary school performance of children with congenital hypothyroidism. New England Congenital Hypothyroidism Collaborative.

The aim of this study was to determine whether hypothyroid children treated early as a result of diagnosis after neonatal screening progressed normally in school. The New England Congenital Hypothyroidism Collaborative studied 72 of its patients at the ages of 9 or 10 years after they had completed 3 years of schooling beyond kindergarten. Control subjects were 96 classmates of the same sex and age as the patients and 32 siblings of appropriate age for the testing. Intelligence quotients (IQs) were measured by the Wechsler Intelligence Scale for Children-Revised abbreviated to five items, and school achievement by the Peabody Individual Achievement Test. In addition, a series of neuropsychologic tests was administered to both patients and control subjects. Educational histories were obtained from the parents for 74 patients, 87 of their siblings, 96 classmates, and 96 siblings of the classmates. The IQ of the control subjects (mean +/- SEM) was 109 +/- 1.2 versus 106 +/- 1.4 for the patients. The mean overall achievement score was 109 +/- 0.93 for the control subjects and 108 +/- 1.3 for the patients. These differences are not statistically significant. The regression lines relating overall Peabody Individual Achievement Test scores or subtests thereof to IQ did not differ among the patients and the control groups. Within the groups the regression lines for IQ and the different subtests of school achievement were also identical. The percentages of children repeating a grade, needing extra tutoring, or in special classes were the same for patients and control groups. We conclude that children with hypothyroidism have no apparent specific impediments to learning unrelated to intelligence.

Child↗
PubMed1994

Correlation of cognitive test scores and adequacy of treatment in adolescents with congenital hypothyroidism. New England Congenital Hypothyroidism Collaborative.

PURPOSE: To measure the frequency of noncompliance and its possible effect on school achievement test and cognitive test scores in our older patients with congenital hypothyroidism. METHODS: Fifty patients born from 1976 through 1978 were studied at home when they were 14 years of age. Each patient was given a battery of psychometric and school achievement tests, and blood for hormonal assays was drawn without forewarning from 36 of the patients on the day of examination. Efforts were made to improve control after the second year. During the third summer the tests were repeated in 25 of the 29 patients who had been tested at the age of 14; thyrotropin and thyroxine concentrations were measured in 23 of these 25 patients. RESULTS: At the age of 14 years 16 of the 36 children had poorly controlled hypothyroidism, as defined by thyrotropin values greater than 15 mU/L. Of these 16 patients, 13 also had thyroxine concentrations of less than 85 nmol/L (6.6 micrograms/dl). A second examination at 15 or 16 years of age disclosed significant improvements in hormonal concentrations without changes in thyroxine dosage. Poor control was demonstrated on at least one occasion in 74% of 27 children older than 12 years of age who had 3 to 8 thyrotropin measurements during a period of 9 months. Cognitive test results in the patients did not differ from those in control subjects or from previous test results in the same children. The improved hormonal concentrations at the age of 15 or 16 years, however, were accompanied by significant improvement in cognitive test results; mean IQ increased from 106 to 112 (p = 0.002). Patients with greater improvement in hormonal values had significantly greater improvement in IQ. CONCLUSIONS: The prevalence of noncompliance in the adolescent children of our cohort with congenital hypothyroidism was high. Subsequent improvement in thyroid control was associated with significant improvement in psychometric test scores.

Adolescent↗
PubMed2002

Low TSH congenital hypothyroidism: identification of a novel mutation of the TSH beta-subunit gene in one sporadic case (C85R) and of mutation Q49stop in two siblings with congenital hypothyroidism.

Isolated congenital hypothyroidism resulting from mutation of the TSH beta-subunit gene, has rarely been reported. In the present article, we report a new mutation (C85R) in exon 3 of the TSH beta-subunit gene in one sporadic case and the mutation Q49stop in two siblings with congenital hypothyroidism. The novel mutation is a T to C transition at codon 85, resulting in a change of cysteine to arginine (C85R) of the ss-subunit. Because the cysteine residues of all glycoproteins are highly conserved, this mutation is expected to result in conformational changes of the ss-subunit, rendering it incapable to form a functional heterodimer with the alpha-subunit. The second mutation described is a C to T transition resulting in a premature stop at codon 49 (Q49stop), leading to the formation of a truncated protein. Although the two siblings reported herein carried the same mutation, they had slightly modified clinical and biochemical phenotype. The mutation C85R and the previously described E11stop have, thus far, exclusively been detected in Greek patients. The Q49stop mutation initially detected in Greek patients was subsequently identified in an Egyptian girl and most recently in two Turkish siblings. These three reports possibly indicate the presence of a mutational hot spot on the TSH beta-subunit gene. Hence, with the novel mutation herein reported, a total of five mutations of the TSH beta-subunit gene are recognized as a cause of low-TSH congenital hypothyroidism worldwide.

Adolescent↗
PubMedDate not supplied

[A model for clinical diagnosis-treatment of the newborn with an abnormal screening test for hypothyroidism and in children with congenital hypothyroidism].

Congenital hypothyroidism occurs in 1:4000 newborns. Mass screening for congenital hypothyroidism constitutes a major progress in the prevention of mental retardation. The neonatal screening programme in Poland was established and implemented by the National Research Institute of Mother and Child from the middle of the 70. and reorganised in 1997. Recall examinations in the infants, substitute therapy with l-thyroxine and the follow-up of hypothyroid infants and children are presented.

Child↗
PubMed1980

[Postnatally acquired hypothyroidism in an infant a variant of congenital hypothyroidism (author's transl)].

We are reporting a case of hypothyroidism in an infant which developed at the end of the second quarter of the first year of life on the basis of a dysgenetic thyroid gland. By the time of its diagnosis in the ninth month of life it had led to bone age retardation and dysgenesis of the second lumbar vertebra. Clinical picture, longitudinal growth and psychomotor development were minimally or not affected. Pathogenetically this case of relatively mild postnatally acquired hypothyroidism has to be classified under the spectrum of congenital hypothyroidism. Clinically it is important that it would not have been picked up by a neonatal screening program and still might have led to impairment of the cerebral development.

Age Factors↗
PubMed1992

Subclinical hypothyroidism, overt thyrotoxicosis and subclinical hypothyroidism: the subsequent phases of thyroid function in a patient chronically treated with amiodarone.

In a patient chronically treated with amiodarone, subclinical iodine-induced hypothyroidism occurred as a result of excess iodine released from the amiodarone molecule. The patient was maintained on amiodarone and developed thyrotoxicosis as a result of a destructive process into the thyroid follicles. Amiodarone was withdrawn and methylprednisolone and methimazole treatment was started with resolution of the thyrotoxic phase. Months later, off therapy, the patient developed subclinical hypothyroidism. This is the first description of hypo- and hyperthyroidism in the same patient caused by amiodarone therapy. This unusual observation suggests that patients treated with amiodarone are at risk to develop hyperthyroidism even if they show laboratory findings consistent with hypothyroidism.

Amiodarone↗
PubMed1997

Flow-mediated, endothelium-dependent vasodilation is impaired in subjects with hypothyroidism, borderline hypothyroidism, and high-normal serum thyrotropin (TSH) values.

Patients with hypothyroidism are considered to have an increased risk of developing atherosclerosis; because endothelial dysfunction is an early sign of atherosclerosis, we investigated whether endothelial dysfunction is present in patients with hypothyroidism. Thirty-five subjects with various TSH levels were investigated by high-resolution ultrasound imaging of the brachial artery to assess endothelial and smooth muscle responses. Flow-mediated, endothelium-dependent vasodilatation was significantly higher in subjects with TSH 0.4-2 microIU/mL (11.8 +/- 2.7%), compared with subjects with TSH 2.01-4 microIU/mL (6.8 +/- 2.9%), 4.01-10 microIU/mL (5.2 +/- 6.3%) and >10 microIU/mL (4.0 +/- 4.4%); TSH levels correlated inversely to endothelium-dependent dilatation. Thus, flow-mediated vasodilatation, a marker of endothelial function, is impaired not only in patients with mild hypothyroidism but also in subjects with "high-normal" serum TSH levels (ie, 2.01-4.0 microIU/mL) that may be characterized as possibly abnormal.

Adult↗
PubMed1979

Comparative effectiveness of dextrothyroxine and levothyroxine in correcting hypothyroidism and lowering blood lipid levels in hypothyroid patients.

Data reported here establish that treatment regimens of 4 mg dextrothyroxine and 0.15 mg levothyroxine in hypothyroid subjects produce similar degrees of lowering of serum TSH, cholesterol, triglycerides, and phospholipid levels and equal stimulation of metabolic rate. The Murphy-Pattee total T4 determination applied to blood samples drawn 24 h after the last dose of dextrothyroxine can be used to assess adequacy of treatment. Correction of hypothyroidism requires high serum levels of dextrothyroxine than of levothyroxine. Serum T3 levels increase in patients treated with dextrothyroxine. In the treatment of hypothyroidism, the cholesterol-lowering and metabolic rate-stimulating effects of dextrothyroxine do not appear to be dissociated. Further studies are needed to determine whether such an effect can be demonstrated in euthyroid hypercholesterolemic subjects with doses established herein as equivalent in terms of the stimulating effect on metabolic rate.

Basal Metabolism↗
PubMed2000

Selenium deficiency and hypothyroidism: a new etiology in the differential diagnosis of hypothyroidism in children.

Three female children presented with different clinical symptoms that could be related to impaired thyroid function. They underwent an accurate pediatric-endocrinologic diagnosis. Laboratory tests revealed no pathological findings, except latent hypothyroidism and selenium deficiency. Hypothyroidism was diagnosed by elevated basal TSH and by a pathological i.v.-TRH-stimulation test. After treating the children with sodium selenite orally for 4 wk, their metabolism had returned to normal and we saw a marked improvement of all clinical symptoms. For the first time, we have been able to describe hypothyroidism caused exclusively by selenium deficiency, the pathophysiology of which may be expressed as a malfunction of human 5'-deiodinases.

Child↗
PubMed1995

Serum thyrotropin in primary hypothyroidism. A possible predictor of optimal daily levothyroxine dose in primary hypothyroidism.

BACKGROUND: Pretreatment thyrotropin levels may be a reliable predictor of the optimal daily dose of levothyroxine sodium in patients with primary hypothyroidism. However, the older method of serum thyrotropin determination, with the reference range of less than 1 to 8 mU/L, has given way to a newer, supersensitive thyrotropin assay, with a reference range of 0.5 to 5.0 mU/L. Thus, at present, the previously established relationship between the levothyroxine dose and the pretreatment serum thyrotropin concentration may not be reliable in predicting the optimal daily dose of levothyroxine. METHODS: We reassessed the relationship between the optimal daily levothyroxine dose and the pretreatment serum thyrotropin concentration as determined by the newer assay in 192 consecutive patients with primary hypothyroidism referred to an endocrinology clinic over a period of 4 years. RESULTS: The optimal daily dose of levothyroxine sodium ranged from 25 to 225 micrograms, with most patients (65%) requiring 100 to 150 micrograms/d and a median dose of 125 micrograms. Multiple regression analysis documented a significant curvilinear correlation between the mean pretreatment serum thryrotropin concentration and the optimal daily levothyroxine dose for individual groups divided according to available tablet strengths (r = .994, P < .001). A simple linear regression was also significant (r = .92, P < .001), although with an intercept much higher than the minimum levothyroxine sodium dose of 25 micrograms/d. However, the relationships markedly improved when the linear regressions were determined separately for two further subgroups at the median daily dose of 125 micrograms, providing equations to predict even the smallest optimal daily dose of levothyroxine. CONCLUSION: Pretreatment thyrotropin levels determined by new assays may also provide a useful guideline in determining the optimal daily maintenance dose of levothyroxine in patients with primary hypothyroidism.

Adult↗