Low Thyroxine Research Articles

Protein interference in thyroid assays: an in vitro study with in vivo consequences

Background Pathological concentration of plasma proteins may cause problems in immunoanalytics. The low triiodotyronine (T3) and thyroxine (T4) levels, frequently found in seriously ill patients, may be ascribed either to laboratory artifact due to the lower thyroid hormone binding capacity or to a compensatory response of the organism to the disease. Methods The authors performed an in vitro experiment, in which sera of seriously ill patients with either low immunoglobulin G (IgG), and/or low albumin levels were investigated for free thyroid hormones (fT3, fT4) following stepwise adjustment of the serum IgG and/or albumin. All two hormones were measured with two different automated immunoassays: the microparticle enzyme immunoassay (MEIA) with two steps (AxSym, Abbott, USA) and the electrochemiluminescence immunoassay (ECLIA). Results The bias of fT3 and fT4 exhibited positive correlations with serum IgG and albumin. The bias of fT3 was more pronounced than that of fT4 following the addition of albumin (40–150% and 10–40%, respectively) as well as following the addition of IgG (8–30% and 0–8%, respectively). The MEIA method was more sensitively affected in case of fT4, whereas the bias of fT3 was more influenced in the ECLIA assay. In MEIA assay, the influence of albumin on the bias of fT3 and fT4 was stronger if serum IgG levels were low. Conclusion The results confirm that pathological thyroid findings in seriously ill patients may largely be ascribed to some laboratory artifacts.

Are Maternal Thyroid Autoantibodies Generated by PCBs the Missing Link to Impaired Development of the Brain?

In her interesting review addressing endocrine disruption and the developing brain, Colborn (2004) asked rightly for special attention to the role of a disruption of thyroid hormones and thyroid hormone metabolism, which negatively influence early development of the fetal brain. As mechanisms of action, chemicals such as polychlorinated biphenyls (PCBs) were discussed in a dose-related way; the higher the exposure level of the mother, the more problems of brain development will be found in the baby (Colborn 2004). However, this is not always true. Patandin et al. (1999) found a four-point decline in IQ at 4 years of age in relation to maternal PCB levels in the Netherlands. In a follow-up study of Faroese children at 7 years of age, Grandjean et al. (1997) found no relation of PCBs with cognitive impairment; the levels of PCBs were almost 4 times higher in the Faroese population than in the Dutch population (Longnecker et al. 2003). One explanation of the missing link might be that effects of PCBs are not directly toxic but instead are toxic through immunomodulatory mechanisms in the mother. In a comment on the impact of maternal PCB and dioxin exposure on the neonate’s thyroid hormone status, Vulsma (2000) noted that PCBs affect the generation of autoantibodies against thyroid tissue [e.g., thyroid peroxidase antibodies (TPO-Ab)]. In a study in Slovakia, Langer et al. (1998) described an increase in TPO-Ab in relation to PCB exposure. These antibodies do pass through the placenta. An important risk factor for impaired infant development is a low free thyroxine (fT4) concentration in early pregnancy; particularly at risk are the mothers with low fT4 and high TPO-Ab titers. These anti-bodies are found in 10% of (euthyroid) women at 12 weeks’ gestation in the Netherlands (Pop et al. 1995, 1999). To my knowledge, none of the studies on effects of PCBs in human pregnancy have reported data on maternal TPO-Ab titers. If the findings reported by Colborn (2004) can be explained by autoimmune processes that cause low fT4 in the mother and negatively affect her developing baby, then it seems more logical that prenatal PCB exposure is related to developmental impairment instead of the amount of PCBs transferred by breast milk after birth. I agree with Colborn (2004) that all women who plan to become pregnant should be evaluated for thyroid hormone status.

Maternal Thyroid Autoantibodies: Colborn’s Response

Vol. 112, No. 15 PerspectivesOpen AccessMaternal Thyroid Autoantibodies: Colborn’s Responseis accompanied byAre Maternal Thyroid Autoantibodies Generated by PCBs the Missing Link to Impaired Development of the Brain? Theo Colborn Theo Colborn Search for more papers by this author Published:1 November 2004https://doi.org/10.1289/ehp.112-a862bCited by:2AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit I thank Koppe for raising the question of the significance of the presence of increased thyroid peroxidase antibodies (TPO-Ab) during neurodevelopment or even later in life. I have wondered for years why medical practitioners and laboratories do not routinely quantify TPO-Ab in blood screening for thyroid disorders. High priority should be given to learning more about the relationship between the combination of high TPO-Ab and low free thyroxine (fT4), and impaired IQ and psychomotor development and the possible role of foreign substances such as polychlorinated biphenyls (PCBs) in these changes. Although the value of routine antithyroglobin antibody (TG-Ab) testing is being questioned, in future epidemiologic studies looking at the role of PCBs in neurodevelopment perhaps TG-Ab should be included in the design as well. It might prove enlightening to also routinely test for TG-Ab at several research/medical institutions to continue to explore this immune connection with the thyroid economy. Also, perhaps it is time to explore the nutritional state (protein consumption, quality and quantity of serum proteins) of the mother and her unborn child during gestation, which might contribute to the conflicting findings among the various cohort studies about the role of PCBs in neurodevelopment. In the meantime, until more is understood about neurodevelopmental impairment, I would like to take this opportunity to reinforce the need to routinely test all pregnant women and those planning to become pregnant for fT4, free triiodothyronine, thyroid-stimulating hormone, and TPO-Ab. Information such as this would allow for intervention, if needed, to prevent irreversible brain damage.FiguresReferencesRelatedDetailsCited by Nicolson G, Gan R, Nicolson N and Haier J (2007) Evidence forMycoplasma ssp.,Chlamydia pneunomiae, and human herpes virus-6 coinfections in the blood of patients with autistic spectrum disorders, Journal of Neuroscience Research, 10.1002/jnr.21203, 85:5, (1143-1148), Online publication date: 1-Apr-2007. Bornman M, Pretorius E, Marx J, Smit E and van der Merwe C (2007) Ultrastructural effects of DDT, DDD, and DDE on neural cells of the chicken embryo model, Environmental Toxicology, 10.1002/tox.20261, 22:3, (328-336), Online publication date: 1-Jun-2007. Related articlesAre Maternal Thyroid Autoantibodies Generated by PCBs the Missing Link to Impaired Development of the Brain?1 November 2004Environmental Health Perspectives Vol. 112, No. 15 November 2004Metrics About Article Metrics Publication History Originally published1 November 2004Published in print1 November 2004 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Abnormal cognitive function in treated congenital hypopituitarism

Aims: To assess cognitive function in school age children with congenital pituitary hormone deficiency (PHD). Methods: Ten children with PHD (aged 6.0–15.6 years, mean 11.5 years) and sibling controls (aged...

Reciprocal interaction between seasonal testis and thyroid activity in Zembra Island wild rabbits (Oryctolagus cuniculus): effects of castration, thyroidectomy, temperature, and photoperiod.

The reproductive cycle of wild rabbits (Oryctolagus cuniculus) living in Zembra Island (North Tunisia) is dependent on an external factor, the photoperiod: the gonads are inhibited by long days and stimulated by short days or melatonin implants. Here we studied the role of an internal factor, thyroid hormones and the possible thyroid-gonadal interrelationships, in animals captured on Zembra Island and maintained in natural conditions of photoperiod and temperature. We determined the seasonal profile of the thyroid and testis cycles and investigated the effects of castration and thyroidectomy on the seasonal testosterone and thyroxine cycles. Plasma thyroxine and testosterone levels followed similar, parallel seasonal patterns, with a peak in autumn (October) and low values from January to August. In thyroidectomized animals, plasma testosterone levels, although significantly higher than those in controls (P < 0.001), remained low throughout the 13 mo of the experiment, and no testicular reactivation was observed in the fall. In castrated animals, despite the increase in thyroxine concentration in the 3 mo following castration (P < 0.01), plasma thyroxine levels remained low during the 2 yr of the study. We then investigated the combined effects of long days (16L:8D) and moderately high temperature (25 degrees C) on these two endocrine axes. In constant gonado-inhibiting conditions (16L:8D), whether the temperature was kept constantly high or allowed to fluctuate naturally, no reactivation of the thyroid and testicular axes was observed in the fall. In control animals, the peaks of testosterone and thyroxine concentrations observed in September were larger (P < 0.001) than those in animals subjected to the same natural photoperiod conditions but with constantly high temperature. The lower level of autumnal testis stimulation (P < 0.001) in animals maintained in conditions of constant high temperature (25 degrees C) may be attributed to the low thyroxine levels induced by high temperature. These results clearly confirm that the thyroid and testicular cycles display similar seasonal variations and show that the thyroid and gonadal axes are strictly interdependent. This study provides the first demonstration, for a given species, that the seasonal reactivation of gonad activity is controlled by the thyroid, and thyroid activity is controlled by the gonads.

The endocrinology of hypothalamic hamartoma surgery for intractable epilepsy

ABSTRACT Intractable epilepsy has replaced central precocious puberty (CPP) as the main indication for surgery in patients with hypothalamic hamartoma (HH). However, concern about endocrine complications and the paucity of published endocrine data may dissuade clinicians from recommending HH surgery. We report the preoperative endocrine status and postoperative endocrine findings of patients undergoing HH surgery at our centre. Twenty‐nine patients aged 4‐23 years (mean 10 years) underwent detailed clinical assessment and biochemical testing of the hypothalamic‐pituitary axis before and after transcallosal resection of their HH. The perioperative evaluation included comprehensive evaluation of pubertal status, growth, weight, thyroid and adrenal function, and osmoregulation. Forty‐five percent of patients had CPP at presentation and this was not altered by HH surgery. Asymptomatic deficiencies in thyroid hormone, growth hormone and cortisol response were identified in several patients prior to surgery, and biochemical CPP was present in four, clinically prepubertal children. Free thyroxine fell after surgery in the majority, and to clinically significant levels prompting treatment in 5 patients. Low growth hormone was present in 5/8 patients who had had previous HH surgery and in 6/29 following transcallosal surgery at our centre; short stature did not result during the period of follow‐up. Hypernatraemia developed in most patients postoperatively with sodium &gt; 150 mmol/L seen in 16 (55%) patients; however, this was asymptomatic, not often associated with polyuria, and transient; no patient required ongoing antidiuretic hormone replacement. Appetite stimulation and early postoperative weight gain occurred in 45% patients, but resolved in half. Disturbance of endocrine function may be clinically silent and should be routinely evaluated prior to HH surgery for intractable epilepsy. Following surgery, hypernatraemia, low thyroxine, low growth hormone, and weight gain are the main endocrine problems encountered. Prior, unsuccessful surgery may be a risk factor for endocrinopathy. Except for weight gain in some patients, these postoperative endocrine disturbances appear to be transient, mild or asymptomatic, and easily treated where necessary. Long term follow‐up of growth and sexual development in a large series of patients is required.

Matching the heart to heat-induced circulatory load: heat-acclimatory responses.

Heat acclimation enhances cardiac efficiency by increasing stroke volume and decreasing heart rate. These adaptations involve biochemical changes in the contractile apparatus, switched on by altered expression of genes coding contractile and calcium-regulatory proteins and partially mediated by persistent low thyroxine. Heat acclimation also produces cross-tolerance to oxygen deprivation, thus reinforcing cardiac adaptation to oxygen demand/supply mismatching via energy-sparing pathways.

Relationship of circulating C-reactive protein levels to thyroid status and cardiovascular risk in hyperlipidemic euthyroid subjects: low free thyroxine is associated with elevated hsCRP

The mechanism(s) by which low circulating levels of thyroid hormones may lead to development of premature atherosclerosis remain to be established. These mechanisms include indirect effects of thyroid hormones on cardiovascular risk factors such as plasma lipoproteins, homocysteine and fibrinogen. High-sensitivity C-reactive protein (hsCRP) has been identified as an independent predictor of cardiovascular events. We presently investigated the relationship between hsCRP and free thyroxine (FT4) levels in a large population of euthyroid hyperlipidemic patients ( n=429, mean age: 47.1 years, 28% of current smokers). None of these subjects presented a recent history of infection or inflammatory disease and those taking drugs known to influence thyroid or hsCRP were excluded. Serum FT4 levels were measured by radioimmunoassay and CRP, by a high-sensitivity immunoassay. In the population of non-smokers, plasma FT4 levels were negatively and significantly correlated with those of hsCRP ( r=−0.13, P=0.02). Significant correlations between FT4 levels and age ( r=−0.16, P=0.003), glycemia ( r=−0.14, P=0.01), and fibrinogen ( r=−0.18, P=0.001) were equally observed. Upon division of the population on the basis of FT4 tertiles, the mean level of hsCRP was significantly higher in non-smoker patients with the lowest FT4 tertile as compared to those displaying the highest FT4 level (3.04 mg/l versus 1.77 mg/l, respectively, P<0.05). No correlation between FT4 levels and CRP was found in smokers. In conclusion, we demonstrate that hsC-reactive protein is significantly negatively correlated with free thyroxine levels in non-smoker hyperlipidemic patients, suggesting that low thyroxine levels in euthyroid hyperlipidemic subjects constitute a new biomarker of elevated cardiovascular risk.

Developmental toxicity of in ovo exposure to polychlorinated biphenyls: II. Effects of maternal or paternal exposure on second-generation nestling american kestrels.

The development of second-generation nestling American kestrels (Falco sparverius) was altered by in ovo exposure of only one parent to polychlorinated biphenyls (PCBs). Polychlorinated biphenyls appear to alter nestling development through both maternally and paternally mediated effects. In 1998, F0 parent kestrels consumed approximately 5 to 7 microg total PCBs/g bird/d (Aroclors 1248:1254: 1260) for approximately 100 d prior to eggs hatching; these eggs, containing total PCB concentrations of 34.1 microg/g, produced 13 F1 offspring, which were then paired in 1999 with unexposed kestrels to examine developmental effects of maternal or paternal in ovo PCB exposure. Using a toxicokinetics model, eggs from the maternally exposed group had predicted PCB levels of 0.03 to 0.34 microg/g, with enriched higher chlorinated congeners. Polychlorinated biphenyl concentrations in eggs of all generations have recently been found in eggs and nestlings of free-ranging eagles. Consistent with the first generation, maternally exposed F2 females generally were larger, had altered growth rates, and delayed maximal growth and fledging compared with control females. Maternally exposed F2 males were heavier but had shorter bones, grew more quickly and earlier, and fledged 2 d later than control males. In the maternally exposed group, concentrations of plasma triiodothyronine were elevated in F2 females but suppressed in F2 males. Paternally exposed F2 hatchlings of both sexes were comparable in size to controls with the exception of having longer tarsi bones, but subsequently showed slower, delayed growth (both sexes) and fledging (females) and lower thyroxine concentrations (males). The alterations in thyroid hormones in the F2 generation are discussed in light of the enrichment of higher chlorinated PCB congeners and hydroxylated PCB congeners. The developmental changes in the kestrel nestlings are likely a function of several possible mechanisms involving maternal PCB deposition, parental behavior, and neurobehavioral and endocrine-thyroid function in nestlings.

Biologic Limits of Viability

After completing this article, readers should be able to: 1. Define the gestational range for extremely preterm birth. 2. Explain the difference between possibility and probability in reference to survival following extremely preterm birth. 3. Describe the key lung development required for adequacy of gas exchange. 4. Describe the renal functional limitations for water, sodium, and creatinine homeostasis in the first postnatal week of the extremely preterm infant. 5. List at least one structural and/or functional limitation of at least five organ systems that increases mortality risks for the extremely preterm infant. With the advent of neonatal intensive care in the 1960s, preterm infants born at progressively lower gestational ages began to survive. The progression of the decrement did not follow a recognizable relationship; rather, it was erratic as the knowledge base of neonatal physiology and pathology expanded and new technical capabilities for life support were developed. The most dramatic increase in survival of extremely preterm birth (<26 completed weeks’ gestation) came with the introduction of surfactant replacement therapy in the late 1980s. The increased use of maternal antenatal corticosteroid therapy for induction of lung maturation with threatened preterm delivery following the National Institute of Child Health and Human Development Consensus Conference recommendations in 1994 also contributed to improved survival. Since that time, the survival of infants of gestational ages as low as 22 weeks’ has been reported. The purpose of this article is to review the current understanding of the biologic factors limiting survival potential, particularly as they inform clinical decision-making. Viability or survival potential, when used in reference to a fetus, frequently is used to indicate the possibility for a fetus to be live born and capable of living to a specified endpoint of either a designated time, reaching a certain age or a landmark event, admission to a neonatal intensive care unit, …

Low serum total thyroxine and free triiodothyronine in patients with hepatic encephalopathy due to non-alcoholic cirrhosis.

We evaluated serum thyroid hormone levels in non-alcoholic cirrhotic patients with and without hepatic encephalopathy. 15 consecutive patients with hepatic encephalopathy secondary to non-alcoholic cirrhosis (8 males and 7 females, age 37-75 years) and 33 non-alcoholic cirrhotic patients without encephalopathy (22 males and 11 females, age 36-74 years) were investigated. A control group consisted of 20 healthy subjects (10 men and 10 women aged 26-69 years). The levels of serum triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), free T3 (FT3) and free T4 (FT4) were studied in serum samples drawn in the morning. Thyroid function tests were set in relation to the severity of hepatic dysfunction and to the presence or absence of hepatic encephalopathy. Serum levels of FT3 and total T4 (but not total T3 and FT4) were significantly lower in patients with hepatic encephalopathy compared to decompensated cirrhotic patients without encephalopathy (p = 0.006 for T4, P <0.05 for FT3). Prothrombin-time also differed significantly between decompensated cirrhotic patients (Child C) with and without encephalopathy groups (p = 0.002). These results suggest that patients with hepatic encephalopathy secondary to decompensated non-alcoholic cirrhosis are typified by low FT3 and low total T4, as well as by a prolonged prothrombin time. Low FT3 does not obviously put patients at risk for hepatic encephalopathy, and thyroid parameters are secondary and late events.

Low serum total thyroxine and free triiodothyronine in patients with hepatic encephalopathy due to non-alcoholic cirrhosis.

We evaluated serum thyroid hormone levels in non-alcoholic cirrhotic patients with and without hepatic encephalopathy. 15 consecutive patients with hepatic encephalopathy secondary to non-alcoholic cirrhosis (8 males and 7 females, age 37-75 years) and 33 non-alcoholic cirrhotic patients without encephalopathy (22 males and 11 females, age 36-74 years) were investigated. A control group consisted of 20 healthy subjects (10 men and 10 women aged 26-69 years). The levels of serum triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), free T3 (FT3) and free T4 (FT4) were studied in serum samples drawn in the morning. Thyroid function tests were set in relation to the severity of hepatic dysfunction and to the presence or absence of hepatic encephalopathy. Serum levels of FT3 and total T4 (but not total T3 and FT4) were significantly lower in patients with hepatic encephalopathy compared to decompensated cirrhotic patients without encephalopathy (p = 0.006 for T4, P <0.05 for FT3). Prothrombin-time also differed significantly between decompensated cirrhotic patients (Child C) with and without encephalopathy groups (p = 0.002). These results suggest that patients with hepatic encephalopathy secondary to decompensated non-alcoholic cirrhosis are typified by low FT3 and low total T4, as well as by a prolonged prothrombin time. Low FT3 does not obviously put patients at risk for hepatic encephalopathy, and thyroid parameters are secondary and late events.

Thyroid hormones in HIV-infected patients in the highly active antiretroviral therapy era: evidence of an interrelation between the thyroid axis and the immune system.

In a total of 372 determinations of thyroid hormones in HIV-infected patients we found a correlation between free thyroxine and CD4 cell counts, which was maintained after stratification by CD4 cell count and therapeutic groups, and was confirmed by multivariate analysis. Patients with normal free thyroxine had higher CD4 cell counts than those with low free thyroxine. Anti-retroviral drugs did not influence free thyroxine levels. Our results support an interrelationship between the thyroid axis and the immune system.

Beta-Adrenergic signaling and thyroid hormones affect HSP72 expression during heat acclimation.

Heat acclimation upregulates 72-kDa heat shock protein (HSP72) and predisposes to faster activation of the heat shock response (HSR). This study investigates the role played by beta-adrenergic signaling and/or plasma thyroxine level in eliciting these features by using rats undergoing 1) heat acclimation (AC; 34 degrees C, 2 and 30 days); 2) AC with beta-adrenergic blockade; 3) AC-maintained euthyroid; 4) hypothyroid; 5) hyperthyroid; and 6) controls. The hsp72 mRNA (RT-PCR) and HSP72 levels (Western blot) were measured before and after heat stress (2 h, 41 degrees C, rectal temperature monitored). beta-Adrenergic blockade during AC abolished HSP72 accumulation, without disrupting HSR. Low thyroxine blunted the HSR at posttranscriptional level, whereas thyroxine administration in hyperthyroid and AC-maintained euthyroid rats arrested heat stress-evoked hsp72 transcription. We conclude that beta-adrenergic signaling contributes to the high HSP72 level characterizing the AC state. Thyroxine has two opposing effects: 1) direct repressive on rapid hsp72 transcription after heat stress; and 2) indirect stimulatory via beta-adrenergic signaling. Low thyroxine could account for diminished HSP72 synthesis via lower heat production and thermoregulatory set point.

Type 1 iodothyronine deiodinase in the house musk shrew ( Suncus murinus, Insectivora: Soricidae): cloning and characterization of complementary DNA, unique tissue distribution and regulation by T 3

The house musk shrew Suncus murinus (Insectivora: Soricidae) has been reported as having low thyroxine to 3,3 ′5-triiodothyronine (T 3) converting activity in liver and kidney homogenates and was assumed to be type 1 iodothyronine deiodinase (D1)-deficient. To study whether this is due to structural abnormality of shrew D1, we cloned the cDNA and characterized the enzyme. The deduced amino acid sequence of shrew D1 was found to be highly homologous to other known D1s and the enzyme itself to have similar catalytic activity. However, unlike in other species, the D1 activity was detected only in liver. Moreover, the D1 activity in liver of the shrew was less than half of that in rat liver and its expression was not up-regulated by T 3. In contrast, a very high activity of D2 was demonstrated in brain and brown adipose tissue. The present study also revealed that the serum level of T 3 in the shrew was in the same range as these in other mammals. These results suggest that D2 contributes to the production and maintenance of T 3 levels in the house musk shrew.

Hypothyroidism in patients with multiple myeloma following treatment with thalidomide

Thalidomide is used for the management of several diseases, including the treatment of patients with multiple myeloma who have relapsed(1–3). As the number of patients receiving thalidomide for longer periods of time increases, several previously unrecognized adverse events have been observed (4–6). We observed symptomatic hypothyroidism, characterized by a high serum thyroid-stimulating hormone (TSH) level and low thyroxine level, in a patient with multiple myeloma during therapy with thalidomide. Indeed, known adverse effects of thalidomide, such as bradycardia, lethargy, and constipation, are potential manifestation of hypothyroidism. This led us to evaluate thyroid function tests, when available, in multiple myeloma patients who had received thalidomide in our clinical trials.

Validation of a novel high-sensitivity radioimmunoassay procedure for measurement of total thyroxine concentration in psittacine birds and snakes.

To validate a novel high-sensitivity radioimmunoassay (RIA) procedure developed to accurately measure the relatively low serum total thyroxine (T4) concentrations of birds and reptiles and to establish initial reference ranges forT4 concentration in selected species of psittacine birds and snakes. 56 healthy nonmolting adult psittacine birds representing 6 species and 42 captive snakes representing 4 species. A solid-phase RIA designed to measure free T4 concentrations in dialysates of human serum samples was used without dialysis to evaluate total T4 concentration in treated samples obtained from birds and reptiles. Serum T4 binding components were removed to allow assay of undialyzed samples. Assay validation was assessed by determining recovery of expected amounts of T4 in treated samples that were serially diluted or to which T4 was added. Intra- and interassay coefficient of variation (CV) was determined. Mean recovery of T4 added at 4 concentrations ranged from 84.9 to 115.0% and 95.8 to 119.4% in snakes and birds, respectively. Intra- and interassay CV was 3.8 and 11.3%, respectively. Serum total T4 concentrations for 5 species of birds ranged from 2.02 to 768 nmol/L but ranged from 3.17 to 142 nmol/L for blue-fronted Amazon parrots; concentrations ranged from 0.21 to 6.06 nmol/L for the 4 species of snakes. This new RIA method provides a commercially available, accurate, and sensitive method for measurement of the relatively low serum T4 concentrations of birds and snakes. Initial ranges for the species evaluated were established.

Effect of 131 iodine therapy on the course of Graves' ophthalmopathy: a quantitative analysis of extraocular muscle volumes using orbital magnetic resonance imaging.

There remains uncertainty as to the effect of radioactive iodine (131I) therapy on the associated ophthalmopathy (GO). Twenty newly diagnosed patients with Graves' hyperthyroidism treated with 131I (median dose, 15.5 mCi) were followed with ophthalmologic evaluations (OE) and magnetic resonance imaging (MRI) at baseline, 2, and 6 months, and with OE alone at 3 years. For MRI, the superior, inferior, and medial rectus muscle volumes and total muscle volumes (TMV) were measured. Replacement levothyroxine was initiated as low thyroxine (T4) levels were noted. At baseline, 10 patients (50%) showed evidence of mild GO by OE and/or MRI. There was a significant difference in TMV between the 20 patients with Graves' hyperthyroidism and 10 controls (mean +/- standard error [SE]; 2,652 +/- 118 vs. 2,046 +/- 96 mm3; P = 0.002) and between the 10 patients with and 10 without GO (3,006 +/- 96 vs. 2,298 +/- 61 mm3; P = 0.001). TMV correlated with the Hertel score (r = 0.56, P = 0.01). TMV showed no significant change at 2 or 6 months posttreatment. The inferior rectus volume increased slightly at 2 months posttreatment (P = 0.03) but remained stable at 6 months. Furthermore, no significant changes occurred in Hertel scores or in clinical assessments up to 3 years posttreatment and none showed worsening or new development of GO. In conclusion, our results show no significant risk for radioiodine-induced initiation or progression of mild GO.

Growth-restricted premature infants are at increased risk for low thyroxine.

To evaluate, in extremely premature infants, the relationship between growth restriction and early total thyroxine levels, and to determine how maternal, prenatal, perinatal and neonatal variables influence the relationship. 719 infants born at four medical centers in Massachusetts, New York and New Jersey between 1991 and 1993 were studied. Entry criteria included: gestational age 23--30 weeks, birth weight 500--1500 g, and a serum thyroxine level obtained in the first week of life. Infants born to mothers with a history of thyroid disease were excluded. Birth weight and total thyroxine level are expressed as z-scores (standard deviation units) to adjust for their relationship to gestational age. In linear regression analysis, there was a 0.18 decrease in the total thyroxine z-score for each 1.0 (1 standard deviation unit) decrease in birth weight z-score (p=0.0001). Adjustment for multiple potential maternal, prenatal, perinatal and neonatal confounders failed to identify a factor or factors that could account for the observed association. The early total thyroxine level in extremely preterm infants was significantly associated with birth weight z-score. This relationship persisted even after adjustment for maternal, prenatal, perinatal and neonatal confounders suggesting antenatal influences. Of clinical importance, growth-restricted infants are at increased risk for early hypothyroxinemia and, possibly, to its related morbidities.

Alphafetoprotein in screening for congenital hypothyroidism

This study was conducted on 500 full-term neonates and 25 older patients with congenital hypothyroidism (CH), newly or previously diagnosed. Alphafetoprotein (AFP) was elevated in two neonates. In one, persistent elevation of AFP and thyroid stimulating hormone (TSH) with low thyroxine (T4) were found (congenital hypothyroidism). In the other, AFP, TSH and T4 levels normalized (transient hypothyroidism). The mean AFP level in new CH patients was significantly higher than in previously diagnosed patients, and was higher in CH patients than in controls. Significant relationships were found between AFP and T4, AFP and TSH, and AFP and age. AFP is a sensitive indicator of thyroid status and can be used as a screening test for hypothyroidism from the first day of life and in follow-up of CH patients.