Normal Thyroid Hormone Research Articles

The evaluation of function and the ultrasonographic picture of thyroid in children treated for medulloblastoma

Medulloblastoma (MB) is one of the most frequent and sensitive to radiation aggressive brain tumor in children. Abnormalities of the thyroid function are common complications of head and neck irradiation for childhood cancer. The aim of this study was to assess thyroid function in children treated for medulloblastoma according to the treatment protocol phase. Twenty-three children with MB were enrolled to this study. All patients underwent chemotherapy and radiotherapy to the whole craniospinal axis and boost with the conformal therapy restricted to the tumor bed to a total dose of 54 Gy. Thyroid function was evaluated based on thyroid-stimulating hormone (TSH), free thyroxine (fT4) levels controlled before MB treatment, directly after irradiation and at the end of the treatment protocol. Ultrasonography has been used to detect parenchymal abnormalities. All patients presented normal thyroid hormone range before chemotherapy. Hypothyroidism was found in 12 patients in the course of treatment, in 2 patients hormone deficits diagnosed directly after irradiation, in 10 patients such condition was observed at the end of the whole therapy. All of these patients needed thyroid hormone substitution. None of them presented clinical symptoms of hypothyroidism. Ultrasound-detected abnormalities have been found in 20 patients. It is crucial to monitor the functions of the thyroid gland in children treated for medulloblastoma because of the high risk of hypothyroidism resulting from the treatment. The change in the echogenicity of the thyroid gland may be an early marker for a dysfunction of this organ in children treated for medulloblastoma.

Homeopathic and integrative treatment for feline hyperthyroidism – four cases (2006–2010)

Hyperthyroidism is a frequent veterinary problem, particularly in elderly cats. Homeopathic treatment and other integrative modalities were provided for four hyperthyroid cats whose owners did not want conventional treatment. Symptomatic homeopathic treatment with Thyroidinum was helpful in one cat. All cats were prescribed an appropriate individualized homeopathic remedy. All four cats showed resolution of clinical signs; three attained normal thyroid hormone levels. Three cats later received acupuncture and/or herbal medicines; two cats later received symptomatic homeopathic remedies. Two cats are thriving after over 3.5 and 4.25 years of treatment; two were euthanized for unrelated problems after 3 and 4 years of treatment. Homeopathic and complementary therapies avoid the potential side effects of methimazole and surgical thyroidectomy, they are less costly than radioactive iodine treatment, and they provide an option for clients who decline conventional therapies.

Thyroid function and egg characteristics of laying hens in response to dietary methionine levels

This experiment was conducted to evaluate the effects of dietary methionine (met) levels on thyroid function, egg characteristics and protein and energy efficiency of laying hens. A total number of 216 commercial laying hens at 23 weeks of age were randomly allocated to six treatments (four replicates with nine birds in each), and fed 6 dietary have deficiency in met supplement (0.24, 0.29, 0.34, 0.39, 0.44 and 0.49% met). With increasing dietary met level from 0.24 to 0.49%, plasma triiodothyronine (T3) showed an inverted U relationship. Plasma thyroxin (T4) was similar between all treatments. Protein and energy efficiency were increased by increasing dietary Met levels. Egg shape index was significantly higher and lower with 0.29 and 0.39% met levels in diet, respectively. Egg surface area and unit surface shell weight increased by increasing dietary met level from 0.24 to 0.49%, and shell ratio decreased linearly. Shell weight increased significantly by increased met level of diet to 0.34%. Albumin index and Haugh unit were significantly lower in hens which fed the three higher levels of met (0.39 to 0.49%). It is concluded that met deficiency alters normal thyroid hormone metabolism, but the effect was dependent on the degree of deficiency. Furthermore, optimal supplementation of met in diets deficient in met, could improve egg quality of laying hens. Key words: Metionine, egg characteristics, triiodothyronine, thyroxine, laying hens.

Transient hypothyroxinemia, brain injury and neuroethology in preterm infants

Objective To analyse the associativity among serum thyroid hormone level,brain injury and neuroethology in preterm infants by testing the thyroid hormone level and neuro-behaviour assessment.Methods Fifty-two preterm infants were continuously admitted in neonatal department of Shanghai Children's Hospital from Dec 2009 to Apr 2010. Radio-immunity was used to determine the serum level of T3,T4, TSH within 6 h after birth. Each case received cranial ultrasonic examination within 3 d after birth and rechecked every week. Before discharge, every infant received a cranial MRI examination. The 52 cases were devided into three groups according to the result of ultrasound and MRI:no brain damage group (33 cases),intraventricular hemorrhage greup (10 cases) ,and white matter injury group (9 cases). At the corrected gestation age 40±2 weeks,every infant received a neonatal behavioral neurological assessment (NBNA). Results The level of serum TSH in all the three groups of preterm infants were normal, which could reject congenital hypothyroidism. Eight preterm infants(15.4% ,8/52) had normal thyroid hormone level,another 44 preterm infants(84. 6% ,44/52) got lower thyroid functions. The levels of T3 and T4 were higher in the no brain damage group than those in intraventricular hemorrhage group and white matter injury group. And the preterm infants who had white mauer injury got the lowest level of thyroine hormone T3 and T4. Thyroxine hormone levels had significant difference among three groups (P ＜ 0. 05). The preterm infants who had no brain damage got higher scores in capability, passive muscle tonus,initiative muscle tonus and total score than the other two groups. Intraventricular hemorrhage group always got higher scores in NBNA than the white matter injury group (P ＜ 0. 05). The NBNA scores had significant difference among three groups (P ＜ 0. 05). Conclusion Premature infant who has more severe brain injury always has lower levels of thyroxine hormone. Premature infants with brain injury get lower scores in NBNA test than those without brain injury. Key words: Transient hypothyroxinemia; Periventricular leukomalacia; Neonatal behavioral neurological assessment ; Premature infants

Small-Molecule Thyrotropin Receptor Agonist Activates Naturally Occurring Thyrotropin-Insensitive Mutants and Reveals Their Distinct Cyclic Adenosine Monophosphate Signal Persistence

Subclinical hypothyroidism (SHT), characterized by normal thyroid hormone levels maintained by elevated thyrotropin (TSH), predisposes patients to health problems as they age. Some cases arise from mutations of the TSH receptor (TSHR) that confer TSH resistance. This resistance might be circumvented by TSHR agonists with different modes of binding compared with TSH. We hypothesized that the recently discovered small-molecule TSHR agonist C2, with its unique mode of receptor binding, would activate mutant TSHRs associated with SHT, facilitating their study. HEK-EM293 cells transiently expressing TSHR variants-wild-type TSHR or mutants C41S, L252P, L467P, or C600R-were analyzed for TSH or C2-induced cyclic adenosine monophosphate (cAMP) signaling to establish C2 as a mutant TSHR agonist. These cells were also pretreated with TSH or C2 to characterize each mutant receptor's ability to maintain and desensitize cAMP signaling. We showed that C2 could activate the TSH-unresponsive TSHR ectodomain mutants C41S and L252P but had no effect on the serpentine mutant L467P. We found that TSH and C2 could acutely activate the serpentine mutant C600R. Preincubation with C2 caused persistent cAMP signaling and receptor desensitization in wild-type TSHR and cAMP signal persistence with no detectable desensitization in the cases of C41S and L252P. The small-molecule agonist C2 is a useful pharmacological tool for the study of mutant TSHRs. It revealed that some naturally occurring TSH-insensitive mutants can mediate induction of cAMP elevation upon stimulation with C2 and that this signal is differentially maintained within cells.

Deterioro cognitivo e hiperparatiroidismo primario: resultado favorable después de cirugía: Caso clínico

We report a 79-year-old male patient presenting with progressive memory loss associated with anxiety and muscular pain. An extensive biochemical control revealed high serum calcium and parathormone levels, and normal thyroid hormones. Cognitive assessment prior to surgery was compatible with mild cognitive impairment, showing significant improvement two months after parathyroidectomy. Our case suggests that, although rare, primary hyperparathyroidism should be considered as a possible cause of cognitive decline in the elderly.

Type 1 iodothyronine deiodinase in human physiology and disease

Thyroid hormone is essential for the normal function of virtually all tissues. The iodothyronine deiodinases catalyze the removal of an iodine residue from the pro-hormone thyroxine (T4) molecule, thus producing either the active form triiodothyronine (T3; activation) or inactive metabolites (reverse T3; inactivation). Type I deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on normal thyroid hormone metabolism and pathological processes. Although peripheral D1-generated T3 production contributes to a portion of plasma T3 in euthyroid state, pathologically increased thyroidal D1 activity seems to be the main cause of the elevated T3 concentrations observed in hyperthyroid patients. On the other hand, D1-deficient mouse models show that, in the absence of D1, inactive and lesser iodothyronines are excreted in feces with the loss of associated iodine, demonstrating the scavenging function for D1 that might be particularly important in an iodine deficiency setting. Polymorphisms in the DIO1 gene have been associated with changes in serum thyroid hormone levels, whereas decreased D1 activity has been reported in the nonthyroid illness syndrome and in several human neoplasias. The current review aims at presenting an updated picture of the recent advances made in the biochemical and molecular properties of D1 as well as its role in human physiology.

P03-345 - Thyroid dysfunction in chronic schizophrenia in albania

BackgroundThyroid dysfunction is relatively common in patients with schizophrenia.This study seeks to determine the prevalence and pattern of thyroid dysfunction and thyroid antibodies presence in a group of adult psychiatric inpatients with chronic schizophrenia.MethodsThyroid function tests and thyroid antibodies measurement were performed on 88 patients hospitalized in Psichiatric Clinic of UHC “Mother Teresa” from december 2006 to december 2007.55 of them (62,5%) were females and 33 of them (37,5%) males. A median age of 43 years (range16 to 70 years) and a median duration of hospitalization of 10 years (range 1 to 30 years) was assessed.ResultsTAb were found in 22 patients (25%), of which 18 females and 4 males. 16% of them resulted with positive anticorps for Hashimoto Thyroiditis; 9% for Graves‘disease.According to thyroid function tests70% had normal test, 8% had elevated TSH: 3% of them with low thyroid hormones and 5% with normal thyroid hormones. 20% of cases had low TSH: 5% of them with high level of thyroid hormones, 15% with normal thyroid hormones. Hypothyroidism was more frequent in elderly patients ( > 60 years old), and in those treated with Risperidone. Most of cases (73%) with thyroid disorders resulted from endemic geographic areas. 37% of them mentioned familial history for thyroid pathology, and 23% for diabetes mellitus type 1.ConclusionThyroid abnormalities are common in patients with chronic schizophrenia.This fact call for caution in the use and interpretation of thyroid function tests in these patients.

“Hypoechoic Triangle”: A New Sonographic Sign or Marker of Advanced Autoimmune Thyroiditis

Ultrasonography (US) changes have been noted in patients with autoimmune thyroiditis (AT). Here, we report that some patients with late stage AT have a distinctive, previously unreported finding on US that we call the "hypoechoic triangle sign" (HET). On US, the HET sign was characterized as a well-defined area of low echogenicity, about 10 mm in diameter, between the lateral margin of one or both thyroid lobes, the medial wall of the carotid artery, and, posteriorly, the prevertebral muscles. Twenty-six patients with AT who had the HET sign (Group 1) were compared with 71 patients with AT who had normal serum thyrotropin (TSH) and free thyroid hormones levels (Group 2) and with 154 normal controls (Group 3). TSH was tested at least twice, first as part of their regular clinical care and then in follow-up. The groups were similar in terms of age, sex, and body mass index. Thyroid volume by US, TSH, free triiodothyronine, free thyroxine, antithyroid antibodies, and l-thyroxine treatment were evaluated. Sonographic gray-scale analysis and three-dimensional reconstruction of HET region were performed in five of the Group 1 patients. Thyroid volume was significantly smaller (p < 0.01) in Group 1 than in Groups 2 and 3 (6.9 ± 2.18 vs. 10.4 ± 2.1 and 9.8 ± 2.5 mL, respectively). In Group 1, 61.5% of subjects were taking l-thyroxine for hypothyroidism; none of the Group 2 or 3 patients was taking thyroid hormone. Serum TSH was significantly higher (p < 0.01) in Group 1 versus Groups 2 and 3 (3.6 ± 1.3 vs. 2.18 ± 1.4 and 1.9 ± 1.1 mIU/L, respectively). None of the Group 2 or 3 patients had the HET sign. Gray-scale US demonstrated an overlap between HET zone and the surrounding muscle tissue. The HET sign seems to be specific for overt thyroid failure in patients with AT as it was not noted in patients with AT not having overt thyroid failure. The incidental finding of the HET sign during cervical US examination should prompt obtaining thyroid function tests to rule out hypothyroidism. Our study provides data regarding specificity but not sensitivity of the HET sign for AT and thyroid failure because a consecutive group of AT patients with thyroid failure was not studied. In addition, the specificity of the HET sign for AT needs to be evaluated further by studying a diverse group of thyroid diseases.

New Insights into Subclinical Hypothyroidism and Cardiovascular Risk

Subclinical hypothyroidism (SH) is a frequent condition affecting millions of people around the world. Defined by increased thyrotropin-stimulating hormone (TSH) and accompanied by normal thyroid hormone levels, SH reflects a mild tissue hypothyroidism that has been associated with metabolic derangements and-although this issue is still contentious-possibly with increased cardiovascular risk. Depending on the degree of TSH elevation, SH has accordingly been associated with hyperlipidemia, arterial hypertension, and cardiovascular disease (CVD), as well as, increasingly, newly emerging CVD risk factors such as serum C-reactive protein and retinol binding protein 4 levels. There have also been reports of abnormalities in glucose metabolism and of hemostatic parameters, mainly underscored by the increased activity of factor VII. This review discusses the results of the latest studies on the various parameters affected by SH while highlighting the need for timely treatment with levothyroxine.

Hashimoto's disease in a bilateral benign cystic ovarian teratoma: a case report

A wide array of tissues derived from all the three germinal layers is seen in ovarian teratomas. Among these, thyroid tissue is present in 10% cases of all mature cystic teratomas. We report this case of Hashimoto's thyroiditis in a clinically euthyroid patient who tested positive for antithyroid peroxidase antibodies in spite of normal thyroid hormone profile. While the histological features of several disorders of thyroid tissue may be discovered, Hashimoto's thyroiditis is extremely rare finding in ovarian teratomas.

Thyroid and pregnancy.

Thyroid and pregnancy.

Pregnancy in women heterozygous for MCT8 mutations: risk of maternal hypothyroxinemia and fetal care

Monocarboxylate transporter 8 (MCT8 or SLC16A2) mutations cause X-linked Allan-Herndon-Dudley syndrome. Heterozygous females are usually asymptomatic, but pregnancy may modify thyroid function and MCT8 is expressed in the placenta, suggesting that maternal and fetal abnormalities might develop even in the absence of MCT8 fetal mutation. Genetic counseling is so far based on X-linked transmission, and prenatal diagnosis is rarely performed. To describe thyroid function and the prenatal diagnosis in pregnant mothers harboring heterozygous MCT8 mutations and management of the persistent maternal hypothyroxinemia. Patients Two women heterozygous for MCT8 mutations (c.1690G>A and c.1393-1G>C) were monitored throughout pregnancy. Prenatal diagnosis included sex determination, direct MCT8 sequencing, and familial linkage analysis. Ultrasonography and hormonal assays for maternal thyroid function evaluation were performed serially during pregnancy. Neonatal thyroid hormonal status was assessed. None of the three fetuses (two males and one female) carried MCT8 mutations. One of the two heterozygous mothers revealed gestational hypothyroxinemia, prompting early levothyroxine (l-T₄) therapy until delivery. The second heterozygous mother showed normal thyroid function but was preventively traited by l-T₄ and all of the three neonates had normal thyroid hormone levels and thyroid gland at birth, suggesting advantages of prenatal care and/or compensatory mechanisms. Heterozygous MCT8 women should be monitored for requirement of l-T₄ therapy to prevent fetal and neonatal hypothyroidism and to avoid risk of potential cognitive delay due to gestational hypothyroxinemia. Moreover, when the disease-causing mutation is known and/or the first child is affected, prenatal diagnosis for male fetuses should be assessed early for MCT8 mutations by direct sequencing.

Myxedema Coma in a Patient with Subclinical Hypothyroidism

Myxedema coma is the extreme manifestation of hypothyroidism, typically seen in patients with severe biochemical hypothyroidism. Its occurrence in association with subclinical hypothyroidism is extremely unusual. We describe a patient with subclinical hypothyroidism who developed clinical manifestations of myxedema coma. A 47-year-old woman presented to our endocrine clinic with complaints of fatigue and biochemical findings of subclinical hypothyroidism. She was started on treatment with thyroxine (T4) but remained unwell and was later admitted to hospital with hormone profile showing persisting subclinical hypothyroidism (elevated thyrotropin and normal free T4 [FT4] and free triiodothyronine [FT3]): FT4 10.7 pmol/L (reference range 10.3-24.5), FT3 2.7 pmol/L (reference range 2.67-7.03), and thyrotropin 6.09 mU/L (reference range 0.4-4.0). She subsequently developed hypothermia (temperature 33.2°C), circulatory collapse, and coma. Biochemical profile showed hyponatremia, elevated creatinine phosphokinase, metabolic acidosis, and renal failure. An echocardiogram revealed a moderate-sized pericardial effusion. We diagnosed myxedema coma and started treatment with intravenous T3. She responded dramatically with improvement in level of consciousness and normalization of metabolic parameters. We found no explanation other than hypothyroidism to account for the presentation. Adrenocorticotrophic hormone (ACTH) stimulation tests excluded adrenal insufficiency, and serum gonadotrophins were within the normal reference range. FT4 estimation by equilibrium dialysis excluded analytical interference, and molecular analysis for the thyroid hormone receptor β gene associated with thyroid hormone resistance was negative. To the best of our knowledge this is the first report of myxedema coma in a patient with subclinical hypothyroidism. The reason for normal thyroid hormone levels is unclear but may reflect deviation from a higher pre-morbid set-point. The case highlights the importance of careful clinical evaluation in patients with disparate clinical and laboratory findings.

Ventricular fibrillation associated with early repolarization in a patient with thyroid storm

We present a case of a 69-year-old male who was hospitalized for the treatment of thyroid storm due to Grave's disease, who presented with unexpected ventricular fibrillation (VF). The possible etiology was early repolarization (ER), characterized by J-point elevation in inferior and posterolateral leads, unmasked by the attenuation of beta-adrenergic effect with normalization of thyroid hormones and following the administration of a beta-blocker. Our case focuses attention on the occurrence of VF in a patient with ER during the treatment of hyperthyroidism, which to our knowledge is the first such report.

Cardiac arrhythmia and thyroid dysfunction: A novel genetic link

Inherited Long QT Syndrome (LQTS), a cardiac arrhythmia that predisposes to the often lethal ventricular fibrillation, is commonly linked to mutations in KCNQ1. The KCNQ1 voltage-gated K + channel α subunit passes ventricular myocyte K + current that helps bring a timely end to each heart-beat. KCNQ1, like many K + channel α subunits, is regulated by KCNE β subunits, inherited mutations in which also associate with LQTS. KCNQ1 and KCNE mutations are also associated with atrial fibrillation. It has long been known that thyroid status strongly influences cardiac function, and that thyroid dysfunction causes abnormal cardiac structure and rhythm. We recently discovered that KCNQ1 and KCNE2 form a thyroid-stimulating hormone-stimulated K + channel in the thyroid that is required for normal thyroid hormone biosynthesis. Here, we review this novel genetic link between cardiac and thyroid physiology and pathology, and its potential influence upon future therapeutic strategies in cardiac and thyroid disease.

Three siblings with self‐resolving congenital hyperthyrotropinaemia secondary to thyrotropin receptor blocking antibodies

Thyrotropin receptor blocking antibodies are a rare cause of hyperthyrotropinaemia and more rarely of congenital hypothyroidism. We report a case of hyperthyrotropinaemia but normal thyroid hormone in the newborn of a mother with hypothyroidism treated with thyroxine. Two older siblings had similar high thyrotropin and normal thyroid function in the newborn period which did not require hormone treatment and resolved spontaneously. Demonstration of thyrotropin receptor antibodies in the child confirmed our diagnosis. Our case was not treated with thyroid replacement hormone and has remained biochemically euthyroid, with thyrotropin levels returning to normal over a period of months.

Subclinical thyroid disorders: significance and clinical impact

Subclinical thyroid diseases are defined by abnormal serum thyroid stimulating hormone (TSH) levels associated with normal thyroid hormone concentrations. The diagnosis of these conditions depends on defining the ‘normal’ euthyroid...

Iodine excess

Several mechanisms are involved in the maintenance of normal thyroid hormone secretion, even when iodine intake exceeds physiologic needs by a factor of 100. The sodium-iodide symporter system contributes most to this stability. Faced with an iodine excess, it throttles the transport of iodide into the thyroid cells, the rate-limiting step of hormone synthesis. Even before the iodine symporter reacts, a sudden iodine overload paradoxically blocks the second step of hormone synthesis, the organification of iodide. This so-called Wolff-Chaikoff effect requires a high (>or=10(-3) molar) intracellular concentration of iodide. The block does not last long, because after a while the sodium-iodide symporter shuts down; this allows intracellular iodide to drop below 10(-3) molar and the near-normal secretion to resume. In some susceptible individuals (e.g., after radio-iodine treatment of Graves' disease or in autoimmune thyroiditis), the sodium-iodide symporter fails to shut down, the intracellular concentration of iodide remains high and chronic hypothyroidism ensues. To complicate matters, iodine excess may also cause hyperthyroidism. The current explanation is that this happens in persons with goitres, for example, after long-standing iodine deficiency. These goitres may contain nodules carrying a somatic mutation that confers a 'constitutive' activation of the TSH receptor. Being no more under pituitary control, these nodules overproduce thyroid hormone and cause iodine-induced hyperthyroidism, when they are presented with sufficient iodine. These autonomous nodules gradually disappear from the population after iodine deficiency has been properly corrected. More recent studies suggest that chronic high iodine intake furthers classical thyroid autoimmunity (hypothyroidism and thyroiditis) and that iodine-induced hyperthyroidism may also have an autoimmune pathogenesis.

P03-288 - Thyroid axis activity and suicidal behavior in depressed patients

ObjectivesThe aim of this study was to investigate the relationship between suicidal behavior and hypothalamic-pituitary thyroid (HPT) axis activity in depressed patients.MethodsThe serum levels of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were evaluated before and after 8 AM and 11 PM TRH challenges, on the same day, in 95 medicationfree DSM-IV euthyroid major depressed inpatients and 44 healthy hospitalized controlsResultsCompared to controls: 1)patients with a positive suicide history (PSH; n=53) showed lower basal FT4 (at 8AM: p&lt; 0.005; at 11PM: p&lt; 0.03), but normal FT3 levels, while patients with a negative suicide history (NSH; n=42) showed normal FT4 and FT3 levels;2)TSH responses to TRH (delta TSH) were blunted in NSHs (at 8 AM: p&lt; 0.03; at 11PM: p&lt; 0.00001), but not in PSHs.Compared to NSHs, basal FT4 levels were reduced in PSHs (at 8AM: p&lt; 0.002; at 11PM: p&lt; 0.006). HPT parameters were not significantly different between recent suicide attempters (RSA; n=32) and past suicide attempters (PSA; n=21). However, compared to controls, RSAs showed lower 11PM-deltaTSH (p&lt; 0.04) and lower basal FT4 values (at 8AM: p&lt; 0.002; at 11PM: p&lt; 0.008).ConclusionsOur results indicate that various degrees of HPT axis dysregulation are associated with the history of suicide. In NSHs, one may hypothesize that hypersecretion of hypothalamic TRH (as reflected by decreased TRH receptor responsiveness) represents a compensatory mechanism to maintain normal thyroid hormone secretion. In PSHs this mechanism is ineffective.