Basal Serum Thyroxine Level should Guide Initial Thyroxine Replacement Dose in Neonates with Congenital Hypothyroidism

Objective: Initial high-dose sodium levothyroxine (Na-LT4) (10-15 µg/kg/day) replacement for primary congenital hypothyroidism (CH) is recommended in guidelines. However, high-dose Na-LT4 risks iatrogenic hyperthyroidism. The aim of this study was to investigate the normalizing effect of varying initial doses of Na-LT4 on serum thyroid hormone levels. Methods: Fifty-two patients were analyzed retrospectively. The patients were classified into mild (27/51.9%), moderate (11/21.1%) and severe (14/26.9%) CH, based on initial free thyroxine (fT4) levels. Time taken to achieve target hormone levels was compared within groups. Results: Initial mean Na-LT4 doses for mild, moderate and severe disease were 6.9±3.3, 9.4±2.2 and 10.2±2 µg/kg/day. Serum fT4 levels reached the upper half of normal range (>1.32 ng/dL) in a median of 16, 13 and 16 days in patients with mild, moderate and severe CH with the mean time from initial treatment to first control visit of 14.8±6 days (range 1-36). There was no significant difference in terms of time to achieve target fT4 hormone levels according to disease severity (p=0.478). Seven (25.9%), eight (72.7%) and eight (57.1%) patients experienced hyperthyroxinemia (serum fT4 >1.94 ng/dL) in the mild, moderate, and severe CH groups at the first visit, respectively (p=0.016). Conclusion: Not all patients diagnosed with CH require high-dose Na-LT4. Initial dose of Na-LT4 may be selected on the basis of pre-treatment thyroid hormone levels. Some patients with moderate and severe CH, experienced iatrogenic hyperthyroxinemia even though the dose was close to the lower limit of the recommended range in guidelines. We suggest that lower initial doses may be appropriate with closer follow-up within the first week.

A systematic review of thyroid dysfunction in preterm neonates exposed to topical iodine.

OBJECTIVE: To determine whether maternal exposure to iodine or neonatal exposure to topical iodine-containing solutions increases the risk of transient thyroid dysfunction in neonates born <32 weeks' gestation or <1.5 kg. DESIGN: Systematic review. SEARCH STRATEGY: Electronic searches were conducted using Medline and the Cochrane Library. ELIGIBILITY CRITERIA: A study was eligible for review if it reported neonatal exposure to topical iodine or maternal iodine exposure. The key outcome measure was neonatal thyroid function. The search had no restrictions on date of publication, type of study or language. RESULTS: 794 papers were identified during the initial search; 15 studies were fully reviewed. The incidence of (transient) hypothyroidism/hyperthyrotropinaemia following exposure to topical iodine ranged from 12 to 33 per 100 infants; the incidence in non-exposed infants was 0. CONCLUSIONS: There is evidence that neonatal exposure to iodine-containing disinfectants causes thyroid dysfunction in infants born <32 weeks. None of the studies evaluated neurodevelopment. Larger scale studies are needed to determine definitively the nature of the relationship and the impact of exposure on neurodevelopment. In the meantime, it would seem prudent to restrict exposure of iodine-containing skin disinfectants in preterm infants; chlorhexidine might be a credible alternative.

Hipertiroxinemia con tirotropina detectable / No disponible

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[The specific features of thyrotoxicosis and euthyroid hyperthyroxinemia developed due to the use of cordarone]. / Osobennosti tireotoksikoza i eutireoidnoi gipertiroksinemii, razvivaiushchikhsia na fone priema kordarona.

Thyrotoxicosis (TT) is one of the thyroid (T) dysfunctions occurring with the use of cordarone. The clinical features of TT were studied in cordarone-treated patients living in Moscow and its regions (mild and moderate iodine deficiency regions). The patients were examined by using currently available procedures for measuring thyroid-stimulating hormone, free thyroxine, free triiodothyronine, antibodies to TH, TPO, interleukin-6 (IL-6), and C-reactive protein (CRP), and by employing T ultrasound study, Holter ECG monitoring. TT was ascertained to develop in the presence of both the pathologically altered (16/23, 69%) and intact T (7/23, 31%). Examining the course of cardiac arrhythmias (CA) in developed TT has established that this condition gives rise to their recurrence. As compared with the control group, the patients with TT were not found to have higher levels of IL-6 and CRP (p > 0.05; Mann-Whitney test). Therapy with thyrostatic agents alone or in combination with glucocorticosteroids normalizes the levels of thyroid hormonesfollowing, on the average, 2-3 months. Euthyroid hyperthyxinemia (EHT) is frequently recorded with the use of cordarone. Examination of 20 patients with EHT has revealed organic pathology in 13 (65%) patients and its absence in 7 (35%). Recurrences of prior CA have not been found in EHT (p < 0.05; McNemar test). The confidence interval for the difference of relative frequencies of signs did not include 0). Thus, TT is a condition that leads to the fact that cordarone loses its antiarrhythmic effects and TT requires compulsory treatment. If required, therapy should be performed during the continued administration of the drug. EHT is not thyrotoxicosis, which is to be followed up.

Abnormal serum free thyroid hormone levels due to heparin administration.

Fractionated or unfractionated heparin may produce artefactual elevation in measured concentrations of free thyroid hormones. Although the specific cause is unknown, it may be a consequence of displacement of thyroid hormones from their binding sites by free fatty acids liberated in vitro. We describe four cases of heparin-induced abnormalities in free thyroid hormone measurements where some diagnostic confusion was generated. Increasing physician awareness of this poorly appreciated entity may avert diagnostic confusion and unnecessary investigation.

Transient elevation of serum thyroid hormone levels following lithium discontinuation.

UNLABELLED: Lithium therapy has been associated with altered thyroid function and even goiter in as many as half of chronically treated patients. We describe the case of a 16-year-old boy who developed transient hyperthyroxinemia after discontinuation of chronic lithium therapy. The lack of clinical hyperthyroidism and the gradual resolution of the biochemical abnormalities in this patient pointed to the benign character of his condition known as "euthyroid hyperthyroxinemia". CONCLUSION: Euthyroid hyperthyroxinemia may be a benign, transient complication of lithium-therapy discontinuation and should be considered in the diagnostic evaluation of lithium-related thyroid abnormalities.

[The effect of antioxidants on lipid metabolism in myocardium in experimental hyperthyroxinemic conditions]. / Wplyw antyutleniaczy na metabolizm lipidowy miesnia sercowego w warunkach doswiadczalnej hipertyroksynemii.

This experiment was conducted on 38 white Wistar-strain rats subdivided into five experimental groups. Group I were control animals which receiving intraperitoneal 0.5 ml injections of the sodium chloride physiological solution everyday during the whole experimental period of 26 days. Rats from Group II were injected intraperitoneally L-thyroxine (600 micrograms per kg of body weight) five times a week. The animals from Groups III, IV, and V, in addition to thyroxine injected in the same way as in Group II, were additionally administered one of such antioxidants as allopurinol, desferal, or vitamin C. The purpose of this research was to find an answer to the question whether the application of the above-mentioned antioxidants modifies the non-beneficial hyperthyroxinemic impact on the lipid metabolism of the cardiac muscle. It was found that the thyroxine influenced the change of the triglyceride and phospholipid contents in the cardiac muscle. All the applied antioxidants partly modified the thyroxine influence on the lipid balance in the cardiac muscle, especially in the area of triglycerides.

Excessive thyroid hormone replacement therapy.

BACKGROUND: Excessive thyroid hormone replacement carries the potential for serious long-term metabolic complications (e.g., accelerated osteoporosis). The increased bioavailability of commercially available products, along with improved laboratory assays for measuring thyrotropin (TSH), has led to an increased chance of actual or detected iatrogenic hyperthyroxinemia. The purpose of this study was to determine the frequency of excessive prescribing and to examine the impact of changes in potency of replacement thyroid hormone formulations and sensitivity of thyroid function tests on its incidence. METHODS: A retrospective chart review was done of patients requiring thyroid hormone replacement therapy treated at a university-based, family medicine residency training program. The following information was extracted from each chart: specific thyroid medication (including dose and date of onset of therapy) and thyroid laboratory tests results (including serum thyroxine [T4] and TSH). This information from two different time periods (1975 to 1981 and 1982 to 1989) was compared using one-way analysis of variance. RESULTS: Serum T4 levels were not significantly different between the two time periods, 1975 to 1981 and 1982 to 1989 (8.06 +/- 2.93 micrograms/dl versus 9.0 +/- 03.69 micrograms/dl; NS), despite significant changes in TS serum levels (23.6 +/- 38.9 mIU/mL versus 7.44 +/- 18.7 mIU/ml; P = 0.009) and levothyroxine dosage (184 +/- 59.6 micrograms/d versus 145 +/- 64.1 micrograms/d; P = 0.002). Significantly more patients had low (supersuppressed) TSH levels between 1982 and 1990 than between 1975 and 1981 (33 percent versus 10 percent; P = 0.02.) CONCLUSIONS: Excessive thyroid hormone replacement with iatrogenic hyperthyroxinemia is a common occurrence. Clinicians need to be aware of this problem and implement measures (e.g., periodic monitoring of TSH) to minimize the occurrence of overdosing and the potential for long-term complications.

[Familial dysalbuminemic hyperthyroxinemia in long-term amiodarone treated patients]. / Familiäres dysalbuminämisches Hyperthyroxinämie-syndrom unter Amiodaron-Langzeitbehandlung.

A serum sample of an outpatient, under long-term amiodarone (AM) treatment was submitted for routine checkup of thyroid function parameters. It revealed the pattern of euthyroid dysalbuminemic hyperthyroxinemia. Since no results have been published so far covering the influence of amiodarone on the specific thyroxine binding proteins, we undertook a prospective study to investigate 28 amiodarone patients, comparing these with a series of age and sex matched euthyroid subjects. Not one amiodarone patient showed changed radio-T4 distribution against the normal group. Yet, in 3 relatives of the propositus, familial screening revealed the typical pattern of thyroid function tests and of T4 distribution in radio immune ice gel electrophoresis, respectively, proving familial dysalbuminemic hyperthyroxinemia syndrome. Thus, it is most likely that this syndrome has been prevalent already prior to the amiodarone administration and consequently amiodarone was of no influence on thyroxine transport protein patterns.

Effects of thyroxine excess on peripheral organs.

Aim of this paper is to review the effects of T4 excess due to exogenous thyroid hormone administration on target organs, with particular regard to heart, bone, liver and pituitary. Therapy with TSH-suppressive doses of T4 has been shown in a cross sectional echocardiographic study to increase left ventricular contractility and to induce mild myocardial hypertrophy. Whether the latter represents a risk for the patients remains a matter of debate. Clinically it does not seem to be important. The long-term evaluation of T4-therapy has provided controversial results. Some have reported that T4-treated patients under the age of 65 have an increased risk of ischemic heart disease, whereas others were unable to find any change in morbidity, mortality and quality of life, including cardiovascular events. Thyroid hormones enhance both osteoblastic and osteoclastic activities in cortical and trabecular bone. Overt hyperthyroidism is well known to represent a risk factor for osteoporosis. Studies in the late eighties have suggested a reduced bone density in T4-treated patients, with a particular risk for cortical bone in postmenopausal women. More recent studies have failed to show any substantial T4-related change in bone mass. Taken together the evidence of the literature suggests that TSH-suppressive therapy with T4 is, if well controlled, probably not associated with significant loss of bone mass at least in premenopausal women. A mild elevation of the activity of hepatic enzymes (glutathione-S-transferase, gamma glutamyltransferase, alanine amino-transferase, angiotensin-converting enzyme) has been observed in patients under T4 treatment in TSH-suppressive doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperthyroxinemia in patients receiving thyroid replacement therapy.

Eleven patients, with a history of hypothyroidism, who had hyperthyroxinemia and an elevated free thyroxine index but normal serum triiodothyronine concentrations on levothyroxine replacement underwent levothyroxine dose reduction at three-month intervals until the free thyroxine index fell into the normal range. All were clinically euthyroid throughout. Normalization of the thyrotropin response to thyrotropin-releasing hormone occurred concomitantly, indicating correction of subtle hyperthyroidism. The mean thyroxine dose decreased from 161 micrograms/d (2.06 micrograms/kg) to 120 micrograms/d (1.51 micrograms/kg). The resting heart rate fell in eight of 11 patients (P less than .02). The left ventricular ejection fraction decreased in eight of 11 patients, although the decrease was not statistically significant. Considering the sensitivity of pituitary, cardiac, and bone tissue to even a small excess of thyroxine over time, hyperthyroxinemia associated with an elevated free thyroxine index should be corrected even in patients taking levothyroxine replacement who are clinically euthyroid and whose serum triiodothyronine concentrations are within normal limits.