It has been reported that receptor-bound blocking type TSH receptor antibody (TRAb) can be converted to the stimulating type by anti-human IgG antibodies. To evaluate the relationship between the conversion of receptor-bound blocking type TRAb to the stimulating type and the biological activity of blocking type TRAb, we compared converting activities of blocking type TRAb from 10 patients with primary nongoitrous hypothyroidism with both the doses of blocking type TRAb which show 50% inhibition of 125I-bTSH binding to the TSH receptor and those which show 50% inhibition of TSH-stimulated cAMP production in cultured rat thyroid cells (FRTL-5). The additions of anti-human IgG antibody to FRTL-5 cell-bound blocking IgGs resulted in the increase in cAMP production in a dose-dependent manner and the converting activities (percent increase of cAMP production) also depended on the doses of blocking IgGs. The converting activities were significantly correlated with the doses of blocking IgGs which showed 50% inhibition of 125I-bTSH binding to the TSH receptor (r = 0.71, p = 0.011). And these converting activities were also significantly correlated with the doses of blocking IgGs which showed 50% inhibition of TSH-stimulated cAMP increase (r = 0.81, p = 0.002), and were negatively correlated with thyroid stimulation blocking antibody activities (r = 0.58, p = 0.02). We have demonstrated that all cell-bound blocking type TRAb were converted to the stimulating type by anti-human IgG antibody and the degree of conversion was negatively correlated with the biological activity of blocking type TRAb.(ABSTRACT TRUNCATED AT 250 WORDS)
Dyshormonogenesis is an uncommon cause of congenital hypothyroidism. The most common abnormality is absent or insufficient thyroid peroxidase enzyme. Maternal intake of antithyroid drug can also lead to elevated thyroid stimulating hormone (TSH) in a neonate, albeit the scenario is temporary. We report one such interesting case where a clinically euthyroid neonate borne to a mother on antithyroid drug presents on 12th day of life with reports of elevated TSH and increased tracer uptake in 99mTc thyroid scan. Disproportionately high TSH in comparison to low maternal antithyroid drug dosage and further elevation of TSH after stopping mother's antithyroid drugs ruled out maternal antithyroid drug-induced congenital hypothyroidism in the baby. Early institution of therapy in these patients can prevent mental retardation and other features of hypothyroidism.
Antithyroid drug; congenital hypothyroidism; dyshormonogenesis
evaluation of thyroid function in neonates born from mothers affected by autoimmune thyroiditis in order to define if a precise follow-up is necessary for these children. The influence of maternal thyroid peroxidase antibody (TPOAb) and L-thyroxine therapy during pregnancy on neonatal thyroid function was also investigated.
129 neonates were tested for thyroid function by measurement of free thyroxine (FT4) and thyroid stimulating hormone (TSH) in 3th day, 15th day and at one month of life. TPOAb were measured in all patients; periodical control of thyroid function were performed until 6 months of life if Ab were positive. Data concerning etiology of maternal hypothyroidism and maternal replacement therapy with L-thyroxine during pregnancy were retrospectively collected.
28% neonates showed at least a mild increase of TSH value at the different determinations. In the majority of them, a spontaneous completely normalisation of TSH value was observed within the first month life. L-thyroxine replacement therapy was started in 3 neonates. TPOAb titer and maternal L-thyroxine replacement therapy were not related to alteration of thyroid hormone function in our study population.
transient mild elevation of serum TSH above the normal reference value for age is frequently observed in the first month of life in infants born from mothers affected by autoimmune thyroiditis. Persistent hyperthyrotropinemia requiring replacement therapy is observed in 2.2% of these neonates. According to our experience, follow-up is recommended in these newborns; the most accurate and not invasive way to carefully monitor these infants after neonatal screening for CH seems to be serum-testing TSH between 2ndand 4th week of life.
To investigate an association between the levels of serum thyroid-stimulating hormone (TSH)-receptor autoantibodies (TRAbs) and Graves' orbitopathy (GO) activity/severity scores, and compare the performance of three different TRAb assays in assessing the clinical manifestations of GO.
Materials and Methods
Cross-sectional study. Medical records of 155 patients diagnosed with GO between January 2008 and December 2010 were reviewed. GO activity was assessed by clinical activity score (CAS) and severity graded with the modified NOSPECS score by a single observer. Serum TRAb was measured by three different methods: 1st generation thyrotropin-binding inhibitor immunoglobulin (TBII) assay (TRAb1st); 3rd generation TBII assay (TRAb3rd); and biological quantitative assay of thyroid-stimulating immunoglobulin (TSI) using Mc4-CHO cells (Mc4-CHO TSI assay). Results were correlated with scores of activity/severity of thyroid eye disease.
All three assays (TRAb1st, TRAb3rd, and Mc4-CHO TSI) yielded results that were significantly positively correlated with CAS (β=0.21, 0.21, and 0.46, respectively; p<0.05) and proptosis (β=0.38, 0.34, and 0.33, respectively; p<0.05). Mc4-CHO TSI bioassay results were significantly positively correlated with all GO severity indices (soft tissue involvement, proptosis, extraocular muscle involvement, and total eye score; β=0.31, 0.33, 0.25, and 0.39, respectively; p<0.05).
Mc4-CHO TSI bioassay was superior over the two TBIIs in assessing active inflammation and muscle restriction due to GO, whereas TBII assay would be sufficient for evaluation of patients with proptosis.
TSH-receptor autoantibody; Graves' orbitopathy; disease activity; severity
AIMS—To define the
aetiology of neonatal transient hypothyroidism (NTH) and recommend
perinatal clinical data on the use of antiseptics, drugs, and contrast
agents containing iodine were collected from 40 subjects. Thyroid
stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4),
thyroglobulin (TG), TSH receptor antibodies, thyroid peroxidase
antibodies and urinary iodine were measured in random neonatal samples.
In the mothers with known or suspected thyroid disorders, TSH, FT4, TSH
receptor antibodies and thyroid peroxidase antibodies were also measured.
aetiology was identified in 85% of cases. More than 50% of the babies
with transient hypothyroidism had been exposed to iodine; maternal
transfer of antibodies had occurred in a third of them.
suggested that the practice of using iodine containing disinfectants
should be withdrawn, and chlorhexidine substituted instead; that
pregnant women should be advised of the adverse effects of using iodine
products; and that thyroid function should be monitored whenever iodine
Thyrotrophin receptor antibodies (TRAb) exist as stimulating or blocking antibodies in the serum (neutral TRAb have been identified recently). The clinical features of GD occur when stimulating TRAb predominate. But the relationship of TRAb to clinical phenotype and outcome is not clear when current assay methods are used. Therefore no consensus exists about its utility in diagnosing and predicting outcome in GD. The most commonly used TRAb assays, measure thyroid binding inhibiting immunoglobulins (TBII or “receptor assays”) and don't differentiate between stimulating and blocking antibodies. However, the more expensive, technically demanding and less freely available “biological assays” differentiate between them by their ability to stimulate cyclic AMP or failure to do so. Failure to differentiate between TRAb types and its heterogeneous molecular and functional properties has limited TBII use to GD diagnosis and differentiating from other forms of thyrotoxicosis. The current 2nd-3rd generation receptor assays are highly sensitive and specific when used for this purpose. TRAb assays should also be done in appropriate pregnant women. Current data do not support its use in outcome prediction as there is a significant variability of assay methodology, population characteristics and study design in published data, resulting in a lack of consensus.
Objective: Iodine deficiency and excess are the most important factors that affect screening and recall rates of congenital hypothyroidism. The purpose of this study was to investigate the urinary iodine status in newborns and their mothers and its effects on neonatal thyroid-stimulating hormone (TSH) levels in a mildly iodine-deficient area.
Methods: A total of 116 newborns and their mothers were included in the study. Urinary iodine levels were measured from healthy mothers and their babies on the 5th day following birth. Neonatal TSH levels were screened, and TSH and free thyroxine (fT4) levels were measured on the15th day in the recall cases. T4 treatment was started in infants with high TSH and low fT4 levels. These measurements were repeated on the 30th day in these newborns.
Results: Ninety-nine percent of the mothers included in the study were using iodized salt. The median urinary iodine level in the newborns was 279 µg/L, while it was 84 µg/L in their mothers. The rate of iodine deficiency among the mothers was 56.8%, and the rate of iodine excess was 8.6%. This rate was 10.3% for iodine deficiency and 61.2% for iodine excess in the newborns. The recall rate at the screening was 9.5% (n=11). The urinary iodine levels were above 200 µg/L in three newborns who had transient hyperthyrotropinemia.
Conclusions: Iodine deficiency was more frequently observed in nursing mothers, and iodine excess was more frequently seen in their newborns. The iodine excess noted in the newborns was attributed to the use of antiseptics containing iodine. The iodine excess leads to increases in recall rates, screening costs, and frequency of transient hyperthyrotropinemia.
Conflict of interest:None declared.
Urinary iodine; maternal; neonatal; screening; hyperthyrotropinemia
To assess the psychiatric and endocrinological changes in patients with Graves ophthalmopathy (GO).
A prospective, controlled, University Hospital based study
Subjects and Methods:
The current study comprised 60 patients diagnosed with GO at Mansoura Ophthalmic Center. Thirty five patients of them with moderate to severe GO formed the study group and twenty five patients with negligible to very mild GO formed the control group in the euthyroid state. The study group was further subdivided based on their predominant clinical signs into a proptosis subgroup and a muscle restriction subgroup. Psychiatric changes were assessed with the Middlesex Hospital Questionnaire (MHQ). Biochemical analyses included serum-free thyroxine and thyroid-stimulating hormone (TSH) concentrations, TSH receptor antibody (TRAb) activity and anti-thyroglobulin particle agglutination (TGPA) and antithyroid microsomal particle agglutination (MCPA).
The proptosis group reported significantly higher scores on anxiety, depression, and phobia than the muscle restriction group (P<0.0001). The proptosis and muscle restriction subgroups reported significantly higher scores on all subscales compared to the control group (P<0.05). The scale scores of depression and phobia showed a positive correlation with scores of anxiety (P<0.0001). The serum TRAb activity showed a significant correlation with anxiety, phobia and hysteria (P<0.0001).
The psychiatric aspect of GO should be evaluated during routine follow-up and should be considered when making management decisions. Thyroid specific antibodies may be useful in confirming the diagnosis of GO.
Graves Ophthalmopathy; Psychological Changes; Thyroid Specific Antibodies
Both thyroid stimulating hormone (TSH) and thyroid stimulating antibody (TSAb) negative Graves’s disease (GD) is extremely rare. Here we present such a patient.
The patient was a 76-year-old woman who was diagnosed as having schizophrenia forty years ago. She did not show characteristic symptoms for hyperthyroidism, such as swelling of thyroid, exophthalmos, tachycardia and tremor, however, she showed only psychomotor agitation. Serum free triiodothyronine and free thyroxine levels were elevated and TSH level was suppressed, suggesting the existence of hyperthyroidism. However, both the first generation TSH receptor autoantibody (TRAb1) and the thyroid stimulating autoantibody (TSAb) were negative. Slightly increased blood flow and swelling was detected by thyroid echography. Thyroid scintigraphy demonstrated diffuse and remarkably elevated uptake of 123I uptake. Finally, we diagnosed her as having GD. She was treated by using methimazole, and hyperthyroidism and her psychiatric symptoms were promptly ameliorated.
We experienced a patient with GD who did not show characteristic symptoms except for psychiatric symptoms, and also showed negativity for both TRAb1 and TSAb. Thyroid autoantibody-negative GD is extremely rare. Thyroid scintigraphy was useful to diagnose such a patient.
Delusion; Hyperthyroidism; Scintigraphy; Thyroid stimulating autoantibody; TSH receptor autoantibody
Serum thyrotrophin receptor antibody (TRAb) and thyroid stimulating hormone (TSH) (IRMA) levels were measured in 38 patients at one month after the end of a course of carbimazole/T3 therapy for Graves' disease. Despite the increased sensitivity of the IRMA assay a TSH measurement at this stage was found to be of no predictive value, in contrast to estimation of serum TRAb levels which correctly predicted relapse and remission in 90% of patients.
Thyrotoxicosis is a cause of secondary osteoporosis. High concentrations of triiodotironine (T3) in Graves’ disease stimulate bone turnover, but it is unclear if euthyroidism will always normalize bone metabolism. Thyrotropin (TSH) is known to affect directly the bone metabolism through the TSH receptor and TSH receptor antibodies (TRAb) may have an important role in bone turn-over.
The aim of our study was to determine, in pre and postmenopausal euthyroidism patients with previous overt hyperthyroidism due to Graves’ disease the bone mineral density (BMD) as well as factors that could affect BMD in each group, including TRAb.
Cross-sectional, non-interventional study. Fifty-seven patients with previous hyperthyroidism due to Graves’ disease (premenopausal: 30, postmenopausal: 27) that remained euthyroid for at least 6 months prior to study were included and compared with fifty- two matched respective controls. Thyrotoxine (T4), TSH, TRAb and BMD were measured.
Only euthyroid postmenopausal patients with a history of hyperthyroidism due to Graves’ disease showed lower whole body BMD than matched controls. The BMD expressed as Z-score was less in whole body and lumbar spine in postmenopausal in relation to premenopausal women with previous overt hyperthyroidism due to Graves’ disease.
In the postmenopausal patients, the Z-score of lumbar spine BMD correlated negatively with TRAb (r = −0,53, p < 0.008), positively with the time of evolution of the disease (r = +0.42, p < 0.032) and positively with the time of euthyroidism (r = + 0.50, p < 0.008), but neither with serum T4 nor TSH. In a multiple regression analysis TRAb was the only significant independent variable in relation to lumbar spine BMD (F = 3. 90, p < 0.01).
In euthyroid women with a history of Graves’ hyperthyroidism, BMD was only affected in the postmenopausal group. The negative correlation of Z-score of lumbar spine BMD with TRAb suggests that this antibody may affect the bone metabolism.
To compare clinical characteristics and thyroid-stimulating hormone receptor antibodies (TRAbs) in thyroid-associated ophthalmopathy (TAO) in euthyroid Korean patients with those in hyperthyroid patients.
Clinical activity scores (CASs), modified NOSPECS scores, exophthalmometry values, prevalence of optic neuropathy, restrictive myopathy and lid retraction, and the positivity and levels of TRAb (thyrotropin-binding inhibitor immunoglobulin (TBII) and thyroid-stimulating immunoglobulin (TSI)) were compared in 24 euthyroid (group A) and 139 clinical/subclinical hyperthyroid TAO patients (group B).
Group A presented more clinically unilateral involvement than group B (79.2% vs 27.3%, P<0.001), less active (CAS 1.50 vs 2.26, P=0.014) and less severe clinical course (NOSPECS 3.38 vs 4.13, P=0.037). Lid retraction was more prevalent in group A than group B (91.7% vs 66.2%, P=0.014). Prevalence of optic neuropathy and restrictive myopathy, and the mean value of exophthalmometry were not different. Mean TBII levels were lower (7.20 IU/l) in group A than in group B (44.58 IU/l, P<0.001). A similar difference was found in the TSI bioassay (201.40% vs 425.19%, P=0.001). The positive rate of TBII in group A (34.8%) was significantly lower than in group B (90.8%, P<0.001). The positive rate of TSI was high in both group A (83.3%) and B (91.7%), with no significant difference (P=0.337).
Patients with euthyroid TAO showed a less active and severe clinical course, more unilateral involvement, and lower levels of TRAb than those in patients with hyperthyroid TAO. These distinct clinical and biochemical characteristics might be useful in assessment of euthyroid TAO, and the TSI might be more sensitive for diagnosing these patients.
thyroid-associated ophthalmopathy; euthyroid; hyperthyroid; TSH-receptor antibody
To determine the prevalence of congenital hypothyroidism (CH), permanent and transient CH.
From November 2006 to September 2007, 63031 newborns were screened by measuring serum TSH obtained by heel prick. The neonates who had a TSH≥5mU/L were recalled for measurement of serum T4, thyroid stimulating hormone (TSH) and TSH receptor blocking antibodies (TRBAb) in venous samples. In 43 primarily diagnosed as cases of CH, treatment was discontinued at age 2–3 years for 4 weeks and T4 and TSH were measured again. Permanent or transient CH was determined from the results of these tests and radiologic evaluation.
The incidence of congenital hypothyroidism was found to be 1:1465 with a female to male ratio of 1.19:1. The most common clinical findings were prolonged jaundice (73%), large anterior fontanel (56%) and wide posterior fontanel (55%). In 43 patients with CH, prevalence of permanent and transient form of the disorder was 53.6% and 46.4% respectively. Permanent CH was associated with higher initial TSH level than transient hypothyroidism (P<0.001). The most common etiology of permanent CH was dyshormonogenesis (57%). TRBAb was found in 6.8% of the total 43 cases.
Congenital hypothyroidism in Iran may have different etiologies. Due to higher rate of transient CH than other similar researches, it is reasonable to follow these patients for a longer period to rule out the possibility of permanent hypothyroidism.
Congenital Hypothyroidism; TSH Receptor; Dyshormonogenesis; Thyroid Dysgenesis
PURPOSE: To evaluate the effect of temporal clear corneal phacoemulsification on intraocular pressure (IOP) in eyes that had prior trabeculectomy. DESIGN: Retrospective case-control study. PATIENTS: Forty consecutive patients (cases; TRAB-PHACO group) who underwent temporal corneal phacoemulsification subsequent to trabeculectomy were identified. Forty patients (controls; TRAB group) who had trabeculectomy alone were matched to the cases for length of follow-up, age, IOP, number of anti-glaucoma medications, number of 5-fluorouracil (5-FU) injections, race, sex and diagnosis. MAIN OUTCOME MEASURES: Comparison of IOP before and one year after phacoemulsification in the TRAB-PHACO group, and comparison with the TRAB group. Survival analysis of IOP control after trabeculectomy in the TRAB-PHACO and TRAB groups. RESULTS: In the TRAB-PHACO group, IOP one year after phacoemulsification was not significantly different from the pre-phacoemulsification IOP value (p = 0.65). Kaplan-Meier survival analysis showed that the rates of IOP control at 3, 6 and 9 years after trabeculectomy in the TRAB-PHACO group were 80%, 66% and 44%; in the TRAB group these were 79%, 69% and 55%. These survival curves were not statistically different (p = 0.55). CONCLUSIONS: Cataract surgery by temporal clear corneal phacoemulsification in eyes with filtering blebs after trabeculectomy does not adversely affect long term IOP control.
In a screening programme for neonatal hypothyroidism an otherwise healthy female infant was found to have a high concentration of thyroid stimulating hormone in a filter paper blood spot and in serum. A high concentration was also found in the maternal serum. Mother and baby were both biochemically euthyroid with normal serum thyroxine concentrations. The apparently high concentration of thyroid stimulating hormone in the mother was due to the presence of an IgG antibody that bound to human but not bovine thyroid stimulating hormone. Maternal serum inhibited the action of human thyroid stimulating hormone in an in vitro bioassay for the hormone. It is suggested that the baby acquired the antibody transplacentally, especially as the concentration of thyroid stimulating hormone subsequently fell. It is concluded that maternal serum should be assayed for thyroid stimulating hormone when a neonate is found to have a high concentration of the hormone and a normal concentration of thyroxine to establish the incidence of this finding and to avoid inappropriate replacement treatment.
Skin disinfection with povidine-iodine (PVP-I) is widely used in obstetrics. We evaluated the influence of PVP-I in mothers at delivery on the serum thyroid stimulating hormone concentrations of their infants at the time of screening for congenital hypothyroidism. The study covered 4745 infants who were either breast fed (3659, 77%) or bottle fed (1086, 23%); 3086 (65%) of them were born to mothers with no iodine overload (controls) and 1659 (35%) to mothers with iodine overload. Compared with the control group, the breast and bottle fed infants born to mothers with iodide overload had a shift of neonatal thyroid stimulating hormone concentration towards high values. The shift was maximal in the breast fed infants with a 25 to 30 fold increase in the recall rate at screening for congenital hypothyroidism (serum thyroid stimulating hormone greater than 50 mU/l) while in the bottle fed infants, the recall rate was barely modified. In conclusion, the use of PVP-I in mothers at delivery induces a transient impairment of thyroid function in their infants, especially if breast fed. This situation is detrimental to screening for congenital hypothyroidism. Consequently PVP-I is not recommended in obstetrics.
Effect of L-carnitine supplementation on myocardial free fatty acid oxidation,in vitro, in offsprings born of hypothyroid and hyperthyroid mothers was studied in rats. L-carnitine supplementation stimulated myocardial fatty acid oxidation during gestational period in offspring born of control and hyperthyroid mothers. In contrast L-carnitine supplementation induced stimulation in myocardial fatty acid oxidation was very less in fetuses born of hypothyroid mothers. However, in neonates born of hypothyroid mothers L-carnitine stimulated myocardial fatty acid oxidation to a great extent. The results suggested that during maternal hypothyroidism low availability of thyroid hormones to fetuses through maternal circulation and availability of less carnitine to neonates due to hypolactation might be responsible for decreased myocardial free fatty acid utilization. In neonates born of hypothyroid mothers and with cardiac energy insufficiency parenteral carnitine supplementation might be of great help to prevent mortality and morbidity of such offsprings.
Maternal; Thyroid; Fetal; Heart; FFA
Ophthalmopathy is the most common extrathyroidal manifestation of Graves’ disease. However, in approximately 5% of cases this autoimmune eye disorder occurs in the apparent absence of Graves’ hyperthyroidism: the so-called euthyroid Graves’ disease (EGD).
Seven patients with EGD were followed for evidence of thyroid and orbital autoimmunity, for up to 10 years. Calsequestrin and collagen XIII antibodies were measured by enzyme linked immunosorbent assay (ELISA), and TSH-receptor (TSH-r) antibodies were measured as TSH-r-binding antibody (TRAb) and thyroid-stimulating immunoglobulin (TSI). Eye signs were characterized and quantified as clinical activity score (CAS), NOSPECS classes, Nunery types 1 and 2, and margin-reflex distance (MRD).
Calsequestrin antibodies were detected on at least one occasion in three of the seven patients and collagen XIII antibodies were detected one or more times in five patients. In one patient with isolated congestive ophthalmopathy who was studied intensely, collagen XIII antibodies were initially positive and then became negative as the eye disease stabilized, while antibodies targeting calsequestrin were always negative. TRAb was not detected in any patient, but TSI was detected in three patients on one occasion each. Ultrasound abnormalities were found in four of the six patients for whom this was carried out, but there was no clear evidence for thyroiditis in any of these patients. For comparison, 13 patients were studied with typical Graves’ ophthalmopathy. There were no significant differences compared to EGD in respect to the prevalence of positive calsequestrin or collagen XIII antibodies, but these patients included more smokers (eight out of 13 versus none out of seven).
Earlier studies suggesting that patients with EGD eventually develop thyroid dysfunction have not been confirmed here, although follow-up continues, and the possibility that such patients have had thyroid autoimmunity in the past, or that they will develop it in the future cannot be excluded. Overall, it is likely that the ophthalmopathy associated with Graves’ hyperthyroidism is the same disease as that observed in patients – such as those reported here – in whom thyroid dysfunction and thyroid autoimmunity are not present during the period of follow- up. The role of autoimmunity against the TSH-r in euthyroid patients with ophthalmopathy has not been proven and the significance of the orbital antibodies is unclear.
ophthalmopathy; thyroid eye disease; collagen XIII; calsequestrin; euthyroid Graves’ disease
The cloning and sequencing of thyroid-stimulating hormone (TSH) receptor (TSHR), combined with advances in molecular techniques, have facilitated the understanding of the interaction of the TSHR antibodies (TSHRAbs) with the TSHR at the molecular level and have allowed the delineation of their clinical role. TSHRAbs in vivo are functionally heterogeneous; the stimulating TSHRAbs cause hyperthyroidism and diffuse goiter in patients with Graves' disease, whereas, the blocking TSHRAbs cause hypothyroidism in some patients with autoimmune hypothyroidism and are the cause of transient neonatal hypothyroidism. Measuring TSHRAbs has potential clinical implications in differential diagnosis of Graves' disease, predicting the outcome of Graves' disease after antithyroid drug treatment, and predicting the fetal/neonatal hyperthyroidism or neonatal hypothyroidism. The existence of epitope heterogeneity in a patient, i.e., of stimulating TSHRAbs with epitopes other than on the N-terminal region of the extracellular domain, is significantly associated with favorable long-term clinical response to antithyroid drug treatment. Measuring these subtypes for thyroid-stimulating antibody (TSAb) has potential clinical implications, for example, in predicting responsiveness to treatment in untreated patients with Graves' disease.
In Iran thyroid-stimulating hormone (TSH) based neonatal screening program is included in health care services from 2005 for detection of patients with primary congenital hypothyroidism (CH). This study was performed for a critical evaluation of the screening program primary congenital hypothyroidism in Fars province, Iran.
From November 2006 to September 2007, TSH serum concentrations of 63031 newborns, 3 to 5 days old born in Fars province, were measured by heel prick. The newborns with TSH ≥5mIU/L were recalled for measurement of serumT4 and TSH in venous blood samples
Of 127 recalled subjects, 43 were confirmed to be hypothyroid, showing a prevalence of 1:1465 with F:M ratio of 1.05:1. The most common clinical and radiological findings were prolonged jaundice (73%), large anterior fontanel (56%), wide posterior fontanel (55%), absence of distal femoral epiphysis (20%), and umbilical hernia (11%). Scintigraphy of the thyroid with 99mTC revealed eutopia (67.4%), hypoplasia (23.3%), agenesis (4.7%) and ectopia (2.3%).
It is concluded that a cut off value of TSH≥5mIU/L overestimates recalling the number of patients with CH. The most common cause of congenital hypothyroidism is not dysgenesis of the gland and perhaps dyshormonogenesis in Iran is more common than what is reported in other countries.
Congenital Hypothyroidism; Thyroxin; Thyroglobolin; Thyroid Dysgenesis; Fars province
The clinical manifestations of Graves’ ophthalmopathy (GO) stem from a combination of increased orbital fat and extraocular muscle volume within the orbital space. Fibroblasts residing within these tissues are thought to be targets of autoimmune attack in the disease. Thyrotropin receptor (TSHr) mRNA and functional protein have been demonstrated in orbital fibroblasts from both normal individuals and GO patients, with higher levels present in the latter. Autoantibodies directed against TSHr or the insulin-like growth factor-1 (IGF-1) receptor have been implicated in GO pathogenesis. Evidence from our laboratory suggests that monoclonal TSHr autoantibodies (TRAbs) are potent stimulators of adipogenesis in GO orbital cells. Therefore, it is possible that circulating TRAbs in Graves’ patients both stimulate overproduction of thyroid hormones and increase orbital adipose tissue volume. Antibodies to the IGF-1 receptor appear to impact GO pathogenesis through recruitment and activation of T-cells and stimulation of hyaluronan production, processes that play key roles in the development of inflammation and increased orbital tissue swelling. Although originally thought to represent another causative agent, antibodies to extraocular muscles are now generally thought to be secondary to extraocular muscle inflammation and damage.
The purpose of our pilot study was to explore the relationship between serum thyroid stimulating hormone (TSH) levels during overt hypothyroidism (OH) and hypothyroid-related neuropsychological symptoms. We hypothesized that TSH level may reflect the degree of ‘brain hypothyroidism’ such that an inverse correlation may exist between serum TSH and cognitive function in patients experiencing overt hypothyroidism (OH), and sought to explore this hypothesis.
Eleven thyroidectomized patients underwent neuropsychological and thyroid function testing while overtly hypothyroid, and again following thyroid hormone replacement. Their test performance was compared with that of eleven healthy controls at a similarly separated two points in time, and the change over time for the patient group and the controls was likewise assessed and compared. The patients’ neuropsychological test scores were then correlated with their serum TSH levels while hypothyroid.
The patients’ performance while hypothyroid was worse than that of the controls in only one neurocognitive measure--Working Memory Index. The subjects improved similarly or to a greater degree than the controls, when the subjects were thyroid hormone replaced, on all but one neurocognitive measure--Thurstone Word Fluency. TSH level during hypothyroidism was inversely proportional to the patients’ performance on these same two measures, but no others.
Serum TSH level during hypothyroidism was inversely proportional to performance on the only two neurocognitive measures evidencing an adverse effect from hypothyroidism in our cohort. This suggests that serum TSH level may reflect the severity of ‘brain hypothyroidism’ during the overt stage of this condition.
thyroid stimulating hormone; cognition; hypothyroidism; depression; working memory
We have previously shown that a long noncoding RNA transcript Heg is negatively correlated with TSH receptor autoantibodies (TRAb) in patients with untreated Graves' disease and with CD14 mRNA in treated patients and controls. Thus patients with high concentrations of Heg RNA have low levels of TRAb or CD14 mRNA, respectively. Here we show that an additional factor, gene expression of Cdk1 in mononuclear cells, is positively related to concentrations of TRAb in patients with untreated Graves' disease. Cdk1 mRNA is very important for regulation of cell cycle activity. It is well known that TRAb decrease significantly during treatment with antithyroid drugs. This decrease during treatment cannot be explained by Heg RNA, which remains unchanged. Cdk1 mRNA decreased significantly during treatment to values below values obtained in normal subjects. Thus both Heg RNA and Cdk1 mRNA may influence the level of TSH receptor autoantibodies but by different mechanisms.
Thyroid-stimulating hormone receptor (TSHR) loss-of-function (LOF) mutations lead to a wide spectrum of phenotypes, ranging from severe congenital hypothyroidism (CH) to mild euthyroid hyperthyrotropinemia. The degree of TSH resistance depends on the severity of the impairment of the receptor function caused by the mutation and on the number of mutated alleles In this review data about genotype-phenotype correlation and criteria for clinical work-up will be presented and discussed. Complete TSH resistance due to biallelic LOF TSHR mutations must be suspected in all patients with severe not syndromic CH and severe thyroid hypoplasia diagnosed at birth by neonatal screening. Partial forms of TSH resistance show a more heterogeneous hormonal and clinical pattern . In these cases TSH serum levels are above the upper limit of normal range for the age but with a very variable pattern, free thyroxine (T4) concentrations are within the normal range and thyroid size can be normal or hypoplastic at ultrasound scan. An early substitutive treatment with L-T4 must be mandatory in all patients with severe CH due to complete uncompensated TSH resistance diagnosed at birth by neonatal screening. The usefulness of substitutive treatment appears much more controversial in patients with subclinical hypothyroidism due to partial TSH resistance in whom the increased TSH concentration should be able to compensate the mild functional impairment of the mutant receptor. Together with standard criteria we recommend also an accurate clinical work-up to select patients who are candidates for a LOF TSHR mutation.
Conflict of interest:None declared.
Thyrotropin receptor gene mutations; congenital hypothyroidism; Neonatal screening; Subclinical hypothyroidism
Background. For unknown reasons, the prevalence of thyroid autoimmune disorders is higher in patients with Down's syndrome than in the general population. The present case strongly supports a recent evaluation of propagating screening for thyroid disease in this group of patients to assure early diagnosis of hypothyroidism. Methods. In a 25-year-old man diagnosed with Down's syndrome, clinical manifestations of hypothyroidism were lacking, but profound biochemical abnormalities were found with particularly high levels of thyroid stimulating hormone (TSH). Antigenic properties of TSH were characterized using a panel of anti-TSH antibodies.
Results. Technical problems not infrequently associated with TSH measurements are convincingly ruled out. Antigenic characterization of the patient's circulating TSH revealed circulating forms of TSH different from pituitary TSH which closely resembled TSH recombinant human hormone. Conclusions. It appears counterintuitive that the bioactivity of TSH decreases in the hypothyroid state as higher bioactivity of TSH is anticipated in hypothyroidism promoted by an increased hypothalamic TRH drive. In contrast, diminished negative thyroid hormone feedback will enhance posttranslational glycosylation of TSH subunits and increase sialylation of the carbohydrate side chains. Both exert a negative effect on TSH bioactivity, only compensated by the very high levels of the hormone as in the present case.