scholarly journals Prenatal Diagnosis of Thyroid Hormone Resistance

1999 ◽  
Vol 84 (2) ◽  
pp. 405-410 ◽  
Author(s):  
C. Asteria ◽  
O. Rajanayagam ◽  
T. N. Collingwood ◽  
L. Persani ◽  
R. Romoli ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Thyroid Hormone ◽  
Fetal Development ◽  
Normal Values ◽  
Assay Method ◽  
Common Finding ◽  
Adequate Treatment ◽  
Fetal Goiter ◽  
Tsh Levels ◽  
Biochemical Features

A 29-yr-old woman with pituitary resistance to thyroid hormones (PRTH) was found to harbor a novel point mutation (T337A) on exon 9 of the thyroid hormone receptor β (TRβ) gene. She presented with symptoms and signs of hyperthyroidism and was successfully treated with 3,5,3′-triiodothyroacetic acid (TRIAC) until the onset of pregnancy. This therapy was then discontinued in order to prevent TRIAC, a compound that crosses the placental barrier, from exerting adverse effects on normal fetal development. However, as the patient showed a recurrence of thyrotoxic features after TRIAC withdrawal, we sought to verify, by means of genetic analysis and hormone measurements, whether the fetus was also affected by RTH, in order to rapidly reinstitute TRIAC therapy, which could potentially be beneficial to both the mother and fetus. At 17 weeks gestation, fetal DNA was extracted from chorionic villi and was used as a template for PCR and restriction analysis together with direct sequencing of the TRβ gene. The results indicated that the fetus was also heterozygous for the T337A mutation. Accordingly, TRIAC treatment at a dose of 2.1 mg/day was restarted at 20 weeks gestation. The mother rapidly became euthyroid, and the fetus grew normally up to 24 weeks gestation. At 29 weeks gestation mild growth retardation and fetal goiter were observed, prompting cordocentesis. Circulating fetal TSH was very high (287 mU/L) with a markedly reduced TSH bioactivity (B/I: 1.1 ± 0.4 vs 12.7 ± 1.2), while fetal FT4 concentrations were normal (8.7 pmol/L; normal values in age-matched fetuses: 5–22 pmol/L). Fetal FT3 levels were raised (7.1 pmo/L; normal values in age-matched fetuses: <4 pmol/L), as a consequence of 100% cross-reactivity of TRIAC in the FT3 assay method. To reduce the extremely high circulating TSH levels and fetal goiter, the dose of TRIAC was increased to 3.5 mg/day. To monitor the possible intrauterine hypothyroidism, another cordocentesis was performed at 33 weeks gestation, showing that TSH levels were reduced by 50% (from 287 to 144 mU/L). Furthermore, a simultaneous ultrasound examination revealed a clear reduction in fetal goiter. After this latter cordocentesis, acute complications occured, prompting delivery by cesarean section. The female neonate was critically ill, with multiple-organ failure and respiratory distress syndrome. In addition, a small goiter and biochemical features of hypothyroidism were noted transiently and probably related to the prematurity of the infant. At present, the baby is clinically euthyroid, without goiter, and only exhibits biochemical features of RTH. In summary, although further fetal studies in cases of RTH are necessary to determine whether elevated TSH levels with a markedly reduced bioactivity are a common finding, our data suggest transient biochemical hypothyroidism in RTH during fetal development. Furthermore, we advocate prenatal diagnosis of RTH and adequate treatment of the disease in case of maternal hyperthyroidism, to avoid fetal thyrotrope hyperplasia, reduce fetal goiter, and maintain maternal euthyroidism during pregnancy.

scholarly journals Prognostic value of mitral regurgitation in patients with asymmetric hypertrophic cardiomyopathy

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
M Tesic ◽  
L Travica ◽  
V Giga ◽  
D Trifunovic ◽  
I Jovanovic ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Prognostic Value ◽  
Volume Index ◽  
Common Finding ◽  
Adequate Treatment ◽  
Group 2 ◽  
Group 1

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Since mitral regurgitation (MR) is a very common finding in patients with hypertrophic cardiomyopathy (HCM), the evaluation of the mitral valve anatomy and the degree of MR is of utmost importance in this population. However, data regarding the prognostic value of different degrees of MR in HCM remains scarce. Purpose The aim of this study was to determine whether the presence of a higher degree of MR affects: 1) long term prognosis; 2) clinical and echocardiographic presentation of HCM patients. Material and Methods We included prospectively 102 patients, diagnosed with primary asymmetric HCM. The degree of MR was determined echocardiographicaly according to current recommendations of the American Association of Echocardiography. According to the MR severity, patients were divided into 2 groups: Group 1 (n = 52) with no/trace or mild MR and Group 2 with moderate or moderate to severe MR. All patients had clinical and echocardiographic examination, 24-hour Holter ECG and NT pro BNP analysis performed. The primary outcome was a composite of: 1) HCM related death or sudden death; 2) hospitalization due to acute heart failure; 3) sustained ventricular tachycardia; 4) ischemic stroke. Results Patients with higher MR degree had more frequent chest pain (p = 0.039), syncope (p = 0.041) and NYHA II functional class (p < 0.001). Group 2 patients had mostly obstructive form of HCM (p < 0.001) with more frequent presence of previous atrial fibrillation (AF) (p = 0.032), as well as the new onset of AF (p = 0.014) compared to patients in Group 1. Patients with higher MR degree had significantly more SAM (p < 0.001) resulting in a more frequent eccentric MR jet (p < 0.001), along with calcified mitral annulus (p = 0.007), enlarged left atrial volume index (p < 0.001), and elevated right ventricular pressure (p = 0.001). As a result of higher MR grade, Group 2 had higher E/e" values (p < 0.001), elevated LV filling pressure (lateral E/e’ >10), as well as higher levels of NT pro BNP (p = 0.001). By Kaplan-Meier analysis we demonstrated that the event free survival rate during follow up of median 75 (IQR 48-103) months was significantly higher in Group 1 compared to the Group 2 (79% vs. 46%, p < 0.001), Figure 1. After adjustment for relevant confounders, moderate/moderate to severe MR remained as an independent predictor of adverse outcome (hazard ratio 2.58, 95% CI: 1.08-6.13, p < 0.001). Conclusion Presence of moderate, or moderate to severe MR was associated with poor long-term outcome of HCM patients. These results indicate the importance of an adequate MR assessment and detailed evaluation of the mitral valve anatomy in the prediction of complications and adequate treatment of patients with HCM. Abstract Figure.

Consequences of thyroid hormone deficiency induced by the specific ablation of thyroid follicle cells in adult transgenic mice

1994 ◽  
Vol 143 (1) ◽  
pp. 107-120 ◽  
Author(s):  
H Wallace ◽  
K McLaren ◽  
R Al-Shawi ◽  
J O Bishop
Keyword(s):  
Body Weight ◽  
Thyroid Hormone ◽  
Transgenic Mice ◽  
Follicle Cells ◽  
Hormone Deficiency ◽  
Mrna Levels ◽  
Thyroid Follicle ◽  
Receptor Mrna ◽  
The Many ◽  
Tsh Levels

Abstract The herpes simplex type 1 virus thymidine kinase (HSV1-TK) reporter gene was coupled to a bovine thyroglobulin promoter (TG-tk construct). Within the thyroid glands of transgenic mice expression was confined to thyroid follicle cells. Infusion of Ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl]guanine) to 8 to 12 week transgenic females led to the complete loss of thyroid HSV1-TK activity (at 3 to 4 days) and thyroid follicles (between 7 and 14 days). During the first 5 days of treatment a single reciprocal oscillation in circulating thyroxine (T4) and TSH levels occurred. By 14 days the circulating triiodothyronine (T3) and T4 levels of all treated animals were below the detection limits of the assays, while TSH levels were elevated ten-fold and continued to increase thereafter. During 14 days of treatment the thyroids regressed, protein content fell by 80–90% and the C cells, normally dispersed within the central region of each gland, came together in aggregates. Pituitary GH levels in females rose and fell back to normal within 14 days and between 14 and 28 days fell to a level comparable with that of GH-deficient lit/lit mice. The levels of hepatic GH receptor mRNA and the predominant 6·6 kb T3 receptor mRNA were unaffected by thyrocyte ablation. Thyrocyte ablation had no effect on the level of prolactin (Prl) receptor mRNA in females, but increased Prl receptor mRNA levels in males and eliminated group 1 major urinary protein (MUP) mRNA in females. T4 replacement reversed the effects of thyrocyte ablation on MUP mRNA in females and on Prl receptor mRNA in males. Despite the many physiological changes induced by thyrocyte ablation, ablated mice have been maintained for up to 1 year without thyroid hormone supplementation. T4-deficient females were normally fertile and carried pups to term. Although transgenic males expressed HSV1-TK ectopically in spermatids and spermatozoa at levels similar to thyrocyte levels, a rate of Ganciclovir infusion which successfully ablated the thyrocytes did not affect the testis. As an alternative to infusion by minipump, thyrocyte ablation could be achieved by 6 twice-daily injections of Ganciclovir, at a level of 112 μg Ganciclovir/g body weight per day, and fetuses in utero could be thyrocyte ablated by administering 50 or 15 μg/g body weight per day to pregnant females between days 14 and 18 of gestation. These data demonstrate the potential value of transgenic thyrocyte ablation in the study of the effects of thyroid hormone deprivation. Journal of Endocrinology (1994) 143, 107–120

scholarly journals Prevalence of a Iodothyronine Deiodinase 2 gene single nucleotide polymorphism in children with congenital hypothyroidism from Western Romania and impact on TSH levels

2019 ◽  
Vol 27 (2) ◽  
pp. 169-178
Author(s):  
Niculina Mang ◽  
Liviu Athos Tămas ◽  
Otilia Mărginean ◽  
Cătălin Marian ◽  
Sorin Ursoniu ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Statistical Difference ◽  
Normal Values ◽  
Healthy Controls ◽  
Nucleotide Polymorphism ◽  
Iodothyronine Deiodinase ◽  
Single Nucleotide ◽  
Western Romania ◽  
Gene Single Nucleotide Polymorphism ◽  
Tsh Levels

Abstract The aim of this study was to evaluate the prevalence of the Iodothyronine Deiodinase 2 gene Thr92Ala polymorphism in children from West of Romania with congenital hypothyroidism (CH) and association with TSH levels in response to levothyroxine monotherapy. Genotyping in 50 children with CH and 52 healthy controls was done using real time PCR. The results showed that there was no statistical difference between the frequencies of genotypes in patients vs. controls. Patients were treated with L-thyroxine and most had normal values for fT3 and fT4. However, high TSH values were found in 21 patients (42%) after treatment. Among patients with high TSH values, AA genotypes were significantly more prevalent (p = 0.044) than TT and AT genotypes. Our results suggest that for the D2 gene Ala92Thr polymorphism, the AA genotype may be detrimental for achieving euthyroidism in patients with CH and levothyroxine monotherapy, therefore polytherapy could be considered as a better approach in these patients.

scholarly journals Multiple Hürthle cell adenomas in a patient with thyroid hormone resistance

2013 ◽  
Vol 2013 ◽  
Author(s):  
Gemma Xifra ◽  
Silvia Mauri ◽  
Jordi Gironès ◽  
José Ignacio Rodríguez Hermosa ◽  
Josep Oriola ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Nodules ◽  
List Type ◽  
Hormone Resistance ◽  
Subsequent Growth ◽  
Thyroid Hormone Resistance ◽  
Hürthle Cell ◽  
First Case ◽  
Increased Risk ◽  
Tsh Levels

Summary Background: Thyroid hormone resistance (RTH) is a rare cause of thyroid dysfunction. High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules with subsequent growth and malignancy. Patient findings: In 2006, a 29-year-old Caucasian man presented with a palpable mass in the neck. Increased free thyroxine and triiodothyronine levels were found in the context of unsuppressed TSH levels, despite no signs or symptoms of hyperthyroidism. Ultrasonography revealed a multinodular and enlarged goitre, and fine-needle aspiration cytology revealed suspicious features of malignancy. After excluding pituitary tumour and levothyroxine (l-T4) treatment, the patient was diagnosed with generalized RTH. Screening for all the known mutations in thyroid hormone receptor-β (TR β (THRB)) was negative. Thyroidectomy disclosed five Hürthle adenomas and three hyperplasic nodules. Euthyroidism was achieved after surgery with 6.1 μg/kg per day of l-T4. Conclusion: RTH may be a risk factor that predisposes to the development of multiple Hürthle cell adenomas. To our knowledge, this is the first case of multiple Hürthle cell adenomas in a patient with RTH. Learning points High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules, with subsequent growth and malignancy. The exact role of TR β mutants in thyroid carcinogenesis is still undefined. We report the first case of multiple Hürthle cell adenomas associated with RTH.

EFFECT OF THYROID STATUS ON THE THYROTROPHIN-RELEASING HORMONE-DEGRADING ACTIVITY OF RAT SERUM

1976 ◽  
Vol 71 (1) ◽  
pp. 13-19 ◽  
Author(s):  
N. WHITE ◽  
S. L. JEFFCOATE ◽  
E. C. GRIFFITHS ◽  
K. C. HOOPER
Keyword(s):  
Thyroid Hormone ◽  
Human Serum ◽  
Thyroid Function ◽  
Thyroid Status ◽  
Rat Serum ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Tsh Levels

SUMMARY The TRH-degrading activity of rat serum in vitro is five times more potent than that of human serum. In rats, it is significantly reduced in hypothyroidism (thiouracil-induced) and significantly increased in hyperthyroidism (T3 or T4-induced). This suggests a possible role in the regulation of adenohypophysial-thyroid function which is probably, in turn, dependent on thyroid hormone, rather than TSH, levels.

Thyrotrophin-producing pituitary adenomas

1982 ◽  
Vol 57 (4) ◽  
pp. 515-519 ◽  
Author(s):  
Stephen A. Hill ◽  
James M. Falko ◽  
Charles B. Wilson ◽  
William E. Hunt
Keyword(s):  
Thyroid Hormone ◽  
Pituitary Adenomas ◽  
Preoperative Diagnosis ◽  
Pituitary Tumors ◽  
Recurrent Tumor ◽  
Hormone Production ◽  
Content Type ◽  
Aggressive Tumor ◽  
Tsh Levels ◽  
Fine Print

✓ Hyperthyroidism due to thyrotrophin (TSH)-secreting pituitary tumors is rare. Four cases are described, with the features that allow preoperative diagnosis. In all the patients, thyroid hormone production was consistently elevated despite antithyroid therapy, and TSH levels were inappropriately elevated. All patients were treated with both surgery and irradiation. Each patient had recurrent tumor with suprasellar, intrasphenoidal, or intraorbital spread. The combination of a recurrent, aggressive tumor complicated by thyrotoxicosis makes this a complex and difficult surgical problem.

Early Treatment of Congenital Hypothyroidism

PEDIATRICS ◽  
1989 ◽  
Vol 83 (5) ◽  
pp. 785-789
Author(s):  
D. A. FISHER ◽  
B. L. FOLEY
Keyword(s):  
Thyroid Hormone ◽  
School Performance ◽  
Congenital Hypothyroidism ◽  
Neonatal Period ◽  
Effective Means ◽  
Newborn Infants ◽  
Motor Dysfunction ◽  
Adequate Treatment ◽  
Functional Assessments ◽  
Normal Mean

Mass population screening of newborn infants for congenital hypothyroidism was introduced in 1974 and now is a routine and effective means of early diagnosis of congenital hypothyroidism throughout most of the industrialized world. A large number of affected infants and children have been treated with replacement thyroid hormone, and several reports of IQ measurements and functional assessments of 5-to 7-year-old treated children now are available. These reports document normal mean IQ values, satisfactory school performance, and minimal motor dysfunction in treated children. However, there have been reported correlations between lower IQ values and biologic parameters of the hypothyroid state in the neonatal period among several reported studies, and it is not yet clear whether early adequate treatment will reverse all of the effects of congenital hypothyroidism.

HOMOZYGOUS FACTOR XII CONGENITAL DEFICIENCY: STUDY OF 10 NEW FAMILIES.

1987 ◽  
Author(s):  
G Castaman ◽  
F Rodeghiero ◽  
M Ruggeri
Keyword(s):  
Fibrinolytic Activity ◽  
Normal Values ◽  
Common Finding ◽  
Factor Xii ◽  
Normal Range ◽  
Congenital Deficiency ◽  
Fibrin Plate ◽  
Sporadic Cases ◽  
Laboratory Investigations ◽  
Normal Controls

Sporadic cases of thromboembolic events have been reported in patients with congenital factor XII deficiency and a relationship with a reduced intrinsic fibrinolysis has been suggested.We report here the results of clinical and laboratory investigations in 10 new families comprising 15 homozygotes (age 16-72) and 14 heterozygotes (age 18-65).In homozygotes, kaolin-activated-PTT was indefinitely prolonged and F XII activity and antigen were undetectable, whereas functional assays . of high molecular weight kininogen ahd kallikrein yielded normal values. Intrinsic fibrinolytic activity - assayed on fibrin plate by measuring lysis zones determined i. by euglobulin fraction, obtained in presence of dextran sulphate and flufenamate (Blood activator inventory test, Kluft 1979) - was reduced in all homozygous pts. to about 50% of normal (range 15-70%; normal range 80-120%); normal values were observed in all heterozygotes. Basal extrinsic fibrinolytic activity (measured after addition of Cl-inhibitor) was absent or minimal as in normal controls. None of our patients showed evidence of thrombotic diathesis.In conclusion, our study demonstrates that a reduced intrinsic fibrinolysis, as assayed by blood activator inventory test, is a common finding in F XII deficiency. The absence of thrombotic diathesis in our cases suggests that, this defect is probably devoid of any clinical significance.

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