Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect.

OBJECTIVES--To assess whether early treatment of congenital hypothyroidism fully prevents intellectual impairment. DESIGN--A national register of children with congenital hypothyroidism who were compared with unaffected children from the same school classes and matched for age, sex, social class, and first language. SETTING--First three years (1982-4) of a neonatal screening programme in England, Wales, and Northern Ireland. SUBJECTS--361 children with congenital hypothyroidism given early treatment and 315 control children. MAIN OUTCOME MEASURES--Intelligence quotient (IQ) measured at school entry at 5 years of age with the Wechsler preschool and primary scale of intelligence. RESULTS--There was a discontinuous relation between IQ and plasma thyroxine concentration at diagnosis, with a threshold at 42.8 nmol/l (95% confidence interval 35.2 to 47.1 nmol/l). Hypothyroid children with thyroxine values below 42.8 nmol/l had a mean IQ 10.3 points (6.9 to 13.7 points) lower than those with higher values and than controls. None of the measures of quality of treatment (age at start of treatment (range 1-173 days), average thyroxine dose (12-76 micrograms in the first year), average thyroxine concentration during treatment (79-234 nmol/l in the first year), and thyroxine concentration less than 103 nmol/l at least once during the first year) influenced IQ at age 5. CONCLUSIONS--Despite early treatment in congenital hypothyroidism the disease severity has a threshold effect on brain development, probably determined prenatally. The 55% of infants with more severe disease continue to show clinically significant intellectual impairment; infants with milder disease show no such impairment. The findings predict that 10% of early treated infants with severe hypothyroidism, compared with around 40% of those who presented with symptoms in the period before screening began, are likely to require special education.     

Dissociated response of thyrotropin and prolactin to dopamine receptor blockade with domperidone in hypothyroid subjects.

To investigate the hypothesis of an altered hypothalamic dopaminergic activity in primary hypothyroidism, eight patients with hypothyroidism and seven normal subjects, all female, were studied. All of them were submitted to two tests: TRH stimulation and after the administration of dopamine receptor-blocking drug, Domperidone. The hypothyroid patients with basal TSH values less than or equal to 60 mU/L (4 cases--group 1) had lower PRL levels than the remaining 4 subjects with TSH greater than 60 mU/L (group 2) (p less than 0.001), despite all patients presenting the PRL levels within the normal range. A significant increase occurred for both TSH and PRL after the administration of TRH and Domperidone in normal as well as in the hypothyroid subjects, except for TSH in group 1 after the administration of Domperidone. The area under the curve for PRL response to THR was not different between the normal subjects and both hypothyroid groups, while that under the curve for TSH was greater in the hypothyroidism as a whole than in the normal subjects (p = 0.006) and between the hypothyroid groups, being greater in group 2 than in 1 (p less than 0.009). In relation to Domperidone, the area under the curve for TSH was significantly higher in group 2 when compared to the normal controls (p less than 0.001), while for PRL it was not different between hypothyroid groups in relation to normal controls and when groups I and II were compared. These results suggest that the hypothalamic dopamine activity is not altered in primary hypothyroidism and favor the small relevance of dopamine on the control of TSH secretion.     

Executive Function and IQ Predict Mathematical and Attention Problems in Very Preterm Children

Objective of this study was to examine the impact of executive function (EF) on mathematical and attention problems in very preterm (gestational age ≤ 30 weeks) children. Participants were 200 very preterm (mean age 8.2 ± 2.5 years) and 230 term children (mean age 8.3 ± 2.3 years) without severe disabilities, born between 1996 and 2004. EFs assessed included verbal fluency, verbal working memory, visuospatial span, planning, and impulse control. Mathematics was assessed with the Dutch Pupil Monitoring System and parents and teachers rated attention problems using standardized behavior questionnaires. The impact of EF was calculated over and above processing speed indices and IQ. Interactions with group (very preterm versus term birth status) were examined. Analyses were conducted separately for two subsamples: children in preschool and children in primary school. Very preterm children performed poorer on tests for mathematics and had more parent and teacher rated attention problems than term controls (ß_s>.11, P_s<.01). IQ contributed unique variance to mathematics in preschool and in primary school (ß_s>.16, P_s<.007). A significant interaction of group with IQ (ß = −. 24, P = .02) showed that IQ contributed unique variance to attention problems as rated by teachers, but that effects were stronger for very preterm than for term infants. Over and above IQ, EF contributed unique variance to mathematics in primary school (ß = .13, P<.001), to parent rated inattention in preschool and in primary school (ß_s>−.16, P_s<.04), and to teacher rated inattention in primary school (ß = −.19; ß = .19, P_s<.009). In conclusion, impaired EF is, over and above impaired IQ, an important predictor for poor mathematics and attention problems following very preterm birth.     

Undetectable levels of tumor necrosis factor-alpha,nitric oxide and inadequate expression of inducible nitric oxide synthase in congenital hypothyroidism

OBJECTIVE: To analyse the production of TNF-alpha and NO in euthyroid and hypothyroid newborns. PATIENTS: A cross-sectional study was conducted involving 10 newborns diagnosed with primary congenital hypothyroidism (CH; group A) and 10 euthyroid children (group B). RESULTS: There were undetectable plasma levels of TNF-alpha and NO in the hypothyroid children, however plasma levels of TNF-alpha (5.5 0.5 pg/ml) and NO (5.6 1.7 microM) were detected at normal levels in all euthyroid children. Moreover, expression of iNOS mRNA in PBMC, determined by RT-PCR, was negative in both groups of infants. CONCLUSION: TNF-alpha and NO production are both impaired in hypothyroid newborns. We report for the first time evidence of undetectable levels of TNF-alpha and NO in infants with CH.     

Pre-academic and early academic achievement in children with velocardiofacial syndrome (del22q11.2) of borderline or normal intelligence

School-aged children with del22q11.2 tend to show a typical learning and neuropsychological profile, which is characterised by a VIQ-PIQ discrepancy (in favour of the VIQ) and significantly better scores for reading (decoding) and spelling compared to mathematics. To the best of our knowledge, there exists no systematic research on the pre-academic and early academic skills that might underpin these learning difficulties. The purpose of the current study was to investigate more systematically these pre-academic and early academic skills in borderline to normal intelligent (FSIQ > 70) children with del22q11.2 in the last year of kindergarten and first grade of primary school in Flanders. In the kindergarten group, meta-linguistic awareness and counting skills were examined. In the group of first graders, children were tested on reading, spelling and mathematics. Thirteen children (mean age: 6 years 4 months (SD = 0.84); 9 boys, 4 girls) participated in this study. In the present study, there were no differences in intelligence and academic outcomes between boys and girls, and no differences in IQ and academic achievement between children with cardiac defects or severe velopharyngeal insufficiency (VPI) and children without these deficits. With regard to pre-academic achievement in general, a characteristic profile with clearly better results for meta-linguistic awareness in comparison to counting skills was found, but this difference is not statistically significant. Concerning early academic achievement, children with del22q11.2, as a group, perform (despite their somewhat lower general intelligence) on average compared with their age-related peers. However, at an individual level--especially within the domain of counting skills and mathematics--there is a wide variability, with some children showing remarkable learning difficulties already at an early age.     

Influence of nutritional state on lipoprotein lipase activities in the hypothyroid rat

We have investigated the effects of nutritional state on the lipoprotein lipase activities of the experimentally hypothyroid rat. Both short-term effects (i.e., those of a 24 h fast with and without re-feeding) and long-term effects (due to decreased food intake in hypothyroidism) have been studied. The hypothyroid rats had significantly higher lipoprotein lipase activities of adipose tissue and heart muscle. The effect of hypothyroidism on adipose tissue lipoprotein lipase activities was modified by the nutritional state. In rats studied after 24 h fasting, the hypothyroid group had significantly higher lipoprotein lipase activities than weight-matched, age-matched and pair-fed (i.e., semi-starved) control groups. In rats studied in the re-fed state, the effects of hypothyroidism as such were less evident, since the pair-fed group also demonstrated significantly higher enzyme activities than did the other control groups. We have also studied the lipoprotein lipase activities of different enzyme preparations from adipose tissue. The effects of hypothyroidism were most clearly reflected in an increase of heparin-elutable enzyme activity from adipose tissue, whereas adipocyte lipoprotein lipase activity and the lipoprotein lipase secretion rate from adipocytes were affected to a lesser extent. We conclude that alterations in food intake strongly influence the lipoprotein lipase activities in the hypothyroidism. Our data also imply that the increased lipoprotein lipase activity in the hypothyroid state is due to a decreased degradation of the enzyme, both intra- and extracellularly.     

Effects of Mathematics Anxiety and Mathematical Metacognition on Word Problem Solving in Children with and without Mathematical Learning Difficulties

Mathematics is one of the most objective, logical, and practical academic disciplines. Yet, in addition to cognitive skills, mathematical problem solving also involves affective factors. In the current study, we first investigated effects of mathematics anxiety (MA) and mathematical metacognition on word problem solving (WPS). We tested 224 children (116 boys, M = 10.15 years old, SD = 0.56) with the Mathematics Anxiety Scale for Children, the Chinese Revised-edition Questionnaire of Pupil’s Metacognitive Ability in Mathematics, and WPS tasks. The results indicated that mathematical metacognition mediated the effect of MA on WPS after controlling for IQ. Second, we divided the children into four mathematics achievement groups including high achieving (HA), typical achieving (TA), low achieving (LA), and mathematical learning difficulty (MLD). Because mathematical metacognition and MA predicted mathematics achievement, we compared group differences in metacognition and MA with IQ partialled out. The results showed that children with MLD scored lower in self-image and higher in learning mathematics anxiety (LMA) than the TA and HA children, but not in mathematical evaluation anxiety (MEA). MLD children’s LMA was also higher than that of their LA counterparts. These results provide insight into factors that may mediate poor WPS performance which emerges under pressure in mathematics. These results also suggest that the anxiety during learning mathematics should be taken into account in mathematical learning difficulty interventions.     

Effects of thyroidectomy, T4, and DITPA replacement on brain blood vessel density in adult rats

In hypothyroid patients, altered microvascular structure and function may affect mood and cognitive function. We hypothesized that adult male hypothyroid rats will have significantly lower forebrain blood vessel densities (BVD) than euthyroid rats and that treatment with 3,5-diiothyroprionic acid (DITPA) (a thyroid hormone analog) or thyroxine (T(4)) will normalize BVDs. The euthyroid group received no thyroidectomy or treatment. The other three groups received thyroidectomies and pellets. The hypothyroid group received a placebo pellet, the DITPA group received an 80-mg DITPA-containing pellet, and the T(4) group received a 5.2-mg T(4) slow-release pellet for 6 wk. Body weights, cardiac function, and body temperatures were measured. A monoclonal antiplatelet endothelial cell adhesion antibody was used to visualize blood vessels. The euthyroid group averaged body weights of 548 +/- 54 g, while the hypothyroid group averaged a body weight of 332 +/- 19 g (P value < 0.001). Relative to the euthyroid group, the DITPA-treated group was significantly lighter (P value < 0.05), while the T(4)-treated group was comparable in body weight to the euthyroid group. The same trends were seen with body temperature and cardiac function with the largest difference between the euthyroid and hypothyroid groups. BVD in the euthyroid group was 147 +/- 12 blood vessels/mm(2) and in hypothyroid group 69 +/- 5 blood vessels/mm(2) (P = 0.013) but similar among the euthyroid, DITPA, and T(4) groups. These results show that hypothyroidism decreased BVD in adult rat forebrain regions. Moreover, DITPA and T(4) were efficacious in preventing effects of hypothyroidism on cardiac function and BVD.     

The influence of hypothyroidism on the adrenergic stimulation of glycogenolysis in perfused rat liver

The ability of noradrenaline (1 microM), phenylephrine (10 microM), and isoproterenol (1 microM) to stimulate glycogenolysis in euthyroid and hypothyroid perfused rat livers was investigated. It was found that hypothyroidism severely impaired alpha-receptor-mediated (noradrenaline, phenylephrine) glucose release. The initial Ca2+ efflux and K+ influx induced by these agonists in the euthyroid control group were almost totally absent in the hypothyroid group, while glycogen phosphorylase a activity in the hypothyroid rat livers was markedly lower than in the controls after infusing noradrenaline for 1 min. Diminished CA2+ efflux (and possibly diminished K+ influx) is likely to play a role in the large impairment in the action of noradrenaline or phenylephrine on glycogenolysis in the perfused hypothyroid rat liver. After prolonged stimulation (15 min) with noradrenaline, however, the phosphorylase a activity in the hypothyroid and euthyroid groups did not differ significantly. This was accompanied by Ca2+ influx in the hypothyroid livers, probably facilitated by a beta-adrenergic effect of noradrenaline in this group. Hypothyroidism potentiated the effect of isoproterenol on glycogenolysis. The glucose 6-phosphate content in the hypothyroid rat livers was markedly higher than in the euthyroid group after stimulation by noradrenaline or isoproterenol.     

Lack of An Association between BMI and TSH in Treated Hypothyroid Patients and Euthyroid Controls

Objective: The standard treatment for primary hypothyroidism is replacement with levothyroxine to achieve a thyroid-stimulating hormone (TSH) level within the normal range, (0.45–4.5 mIU/L), which is known to prevent complications including weight gain. While the normal TSH range includes the 95% confidence intervals, it is not known if there is an association between weight and TSH within this interval in treated hypothyroid patients.Methods: We conducted a retrospective analysis of patients treated within the Cooper Health System from January 1 to August 31, 2014. A sample of 245 treated hypothyroid patients and 162 euthyroid controls were studied. Data collected included age, sex, race/ethnicity, height, weight, levothyroxine dose, and diabetes and smoking history.Results: Hypothyroid and control groups were similar in height, weight, body mass index (BMI), and the number of patients with diabetes. There were more females, Caucasians, and nonsmokers in the hypothyroid group. The average TSH was slightly higher in the treated hypothyroid patients versus nonhypothyroid controls (median 1.87 vs. 1.55, P<.01). There was no significant relationship between TSH and BMI in the treated hypothyroid patients or the euthyroid controls.Conclusion: Since no significant relationship was found between BMI and TSH in treated hypothyroidism, there may be no weight reduction benefit gained by adjusting TSH to the lower end of normal range. Patients should be counseled that properly treated hypothyroidism is unlikely to contribute to weight gain. Other treatments such as nutrition and exercise counseling should be offered instead.Abbreviations:BMI = body mass indexTSH = thyroid stimulating hormone     

复杂性热性惊厥脑电图特征与癫痫发生的相关性

目的：探讨复杂性热性惊厥脑电图特征与癫痫发生的相关性。方法：2012年3 月到2014 年5 月选择在我院诊治为复杂性热 性惊厥的呼吸道感染患儿86 例作为观察组,同期选择在我院诊治的非热性惊厥的呼吸道感染患儿86 例作为对照组,两组都进 行脑电图监测与认知功能判定,对癫痫发生情况进行判定与分析。结果：观察组的言语智商、行为智商与总智商评分都明显低于 对照组(P<0.05)。观察组的癫痫发生率为9.3 %,脑电图异常率为8.1 %;而对照组的癫痫发生率为1.2 %,脑电图异常率为2.3 %, 对比差异都有统计学意义(P<0.05)。在观察组患儿中,Spearman 相关性分析显示脑电图异常与癫痫发生存在明显正向相关性(r=0. 349,P<0.05)。结论：复杂性热性惊厥伴随有脑电图异常,与癫痫发生存在明显正向相关性,损害患儿的认知功能。     

Effect of thyroxine on munc-18 and syntaxin-1 expression in dorsal hippocampus of adult-onset hypothyroid rats

Adult-onset hypothyroidism induces a variety of impairments on hippocampus-dependent neurocognitive functioningin which many synaptic proteins in hippocampus neurons are involved. Here, we observed the effect of adult-onset hypothyroidism on the expression of syntaxin-1 and munc-18 in the dorsal hippocampus and whether the altered proteins could be restored by levothyroxine (T4) treatment. All rats were separated into 4 groups randomly: hypothyroid group, 5 μg T4/100 g body weight (BW) treated group, 20 μg T4/100g BW treated group and control group. The radioimmunoassay kits were applied to assay the levels of serum T3 and T4, and the levels of syntaxin-1 and munc-18 in hippocampus were assessed by immunohistochemistry and Western blot. Both analysis corroborated that syntaxin-1 in the hypothyroid group was significantly higher. Munc-18 was lower in four layers of CA3 and dentate gyrus by immunohistochemistry. After two weeks of treatment with 5 μg T4/100g BW for hypothyroidism, syntaxin-1 levels were completely restored, whereas the recovery of munc-18 only located in two of the four impaired layers. Twenty μg T4/100g BW treatment normalized munc-18 levels. These data suggested that adult-onset hypothyroidism induced increment of syntaxin-1 and decrement of munc-18 in the dorsal hippocampus, which could be restored by T4 treatment. Larger dosage of T4 caused more effective restorations.     

Incidence of congenital hypothyroidism: retrospective study of neonatal laboratory screening versus clinical symptoms as indicators leading to diagnosis.

Filter paper blood samples taken routinely from 100 239 newborn infants were radioimmunoassayed five years later for plasma thyrotrophin concentrations. In 32 cases (0.03%) these were found to be raised. Thirty one of these children were traced and subjected to follow up examination by a paediatrician and a psychologist. Of the 31 children, 15 were found to have been receiving treatment for congenital hypothyroidism since a median of 5 months of age (diagnosed group). Of the 16 others, seven children were found to have raised serum thyrotrophin concentrations and were classified as hypothyroid (undiagnosed group). The remaining nine children were euthyroid. Children in the diagnosed group had a mean Griffiths developmental quotient of 87 (control value 103; p less than 0.01), and five out of 13 showed impaired neurological development. Of the remainder, those in the undiagnosed group had a mean developmental quotient of 100 and those in the euthyroid group a mean developmental quotient of 107. In this study achieving a detection rate of congenital hypothyroidism of one in 3000 in a neonatal screening programme resulted in overdiagnosis of about a quarter of patients considered to have true positive findings. This was outweighed, however, by the early identification of all infants with the disease.     

The growth of IQ among Estonian schoolchildren from ages 7 to 19

The Standard Progressive Matrices test was standardized in Estonia on a representative sample of 4874 schoolchildren aged from 7 to 19 years. When the IQ of Estonian children was expressed in relation to British and Icelandic norms, both demonstrated a similar sigmoid relationship. The youngest Estonian group scored higher than the British and Icelandic norms: after first grade, the score fell below 100 and remained lower until age 12, and after that age it increased above the mean level of these two comparison countries. The difference between the junior school children and the secondary school children may be due to schooling, sampling error or different trajectories of intellectual maturation in different populations. Systematic differences in the growth pattern suggest that the development of intellectual capacities proceeds at different rates and the maturation process can take longer in some populations than in others.     

Effect of short-term hypothyroidism on reproduction in the bitch

Hypothyroidism in bitches has been reported to cause a variable interestrus interval, infertility, abortion, and stillbirth. The objective of this study was to evaluate the effect of experimentally induced hypothyroidism in bitches on fertility, pregnancy, parturition, and neonatal health. Eighteen healthy multiparous bitches were used; hypothyroidism was induced (by radioiodine administration) in nine bitches and the remaining nine served as untreated controls. After breeding, bitches were evaluated for pregnancy, fetal resorption, gestation length, litter size, duration and strength of uterine contractions (during parturition), interval between delivery of pups, viability of pups at birth, periparturient survival, and weight of pups at birth through 4 weeks of age. Bitches were bred a median of 19 weeks after induction of hypothyroidism. All bitches became pregnant and delivered term litters. There was no difference in the interestrus interval, litter size, or gestation length between hypothyroid and control bitches. Duration of uterine contractions was longer, but contraction strength was weaker in hypothyroid than control bitches; however, the interval between delivery of pups was not affected. Periparturient puppy mortality was significantly higher in litters from hypothyroid bitches. Viability scores and weight at birth were significantly lower in pups from hypothyroid bitches than controls. There was no difference between groups in pup weight gain during the first 4 weeks, in the interval from birth to the eyes opened, or to the onset of walking. Although hypothyroidism of relatively short duration did not affect fertility, it prolonged parturition and reduced pup survival in the periparturient period.     

Hepatic lipase and the clearing reaction: studies in euthyroid and hypothyroid subjects

Eight patients with primary hypothyroidism were compared to eleven euthyroid subjects with regard to the effects of a single i.v. dose of heparin on plasma lipoprotein concentrations (the "clearing reaction"). The hypothyroid patients were moderately hypercholesterolemic but had normal plasma triglyceride levels. Maximal activities of hepatic lipase (HL) and lipoprotein lipase (LPL) were lower in the hypothyroid than in the normal subjects. The hypothyroid patients demonstrated a significant decrease in total plasma cholesterol levels after heparin injection (from 8.36 +/- 0.70 mmol/l to 7.55 +/- 0.62 mmol/l, P less than 0.02). The maximal activity of HL after heparin was significantly correlated to the decrease in plasma cholesterol levels (P less than 0.05) and in LDL-cholesterol levels (P less than 0.01). The euthyroid subjects demonstrated a smaller decrease in total plasma cholesterol concentrations (from 5.53 +/- 0.31 to 5.08 +/- 0.28 mmol/l, P less than 0.05). In this group, the fall in cholesterol levels was not correlated to maximal HL activity. The reduction in plasma triglyceride levels after heparin was similar and significant (P less than 0.01) in both groups. These data support the view that decreased activity of HL contributes to the dyslipoproteinemia seen in hypothyroidism. They are also in accordance with the notion that HL is involved in the elimination of cholesterol from plasma.     

Role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice

Postmenopausal women frequently develop hypothyroidism. Estrogen depletion is accompanied by an increase of IL-6, accelerating bone turnover. The influence of hypothyroidism on bone metabolism in postmenopausal women is poorly understood. The aim of the study was an attempt to clarify the role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice. The study was performed on 56, 12-13 weeks old, female mice: C57BL/6J (wild-type; WT) and C57BL/6JIL6-/-Kopf (IL-6 knock-out; IL6KO). The mice were randomly divided into 8 groups with 7 mice in each one: 1/ WT controls, 2/ IL6KO controls, 3/ WT hypothyroid mice, 4/ IL6KO hypothyroid mice, 5/ WT ovariectomized, 6/ IL6KO ovariectomized, 7/ WT ovariectomized hypothyroid mice and 8/ IL6KO ovariectomized hypothyroid mice. Experimental model of menopause was produced by bilateral ovariectomy carried out in 8-9 weeks old mice. Experimental model of hypothyroidism was induced by propylthiouracyl administration in driking water. The serum levels of TRACP 5b, osteocalcin, OPG and RANKL were determined by ELISA. Serum RANKL concentrations were elevated significantly in all groups of ovariectomized mice as compared to respective controls, but in a minor degree in IL6KO hypothyroid mice as compared to wild-type animals. Moreover sRANKL values were significantly lower in IL6KO as compared to WT controls and IL6KO PTU injected mice. Osteoprotegerin serum levels were decreased in all IL-6 deficient mice and in a highest degree in sham-operated hypothyroid mice. To sum up, the results of the present study suggest that estrogens deficit is a strong stimulus for RANKL-RANK/OPG pathway that breaks an inhibitory influence of hypothyroidism even in IL-6 deficient mice.     

Relationship between resting metabolism and hepatic metabolism: effect of hypothyroidism and 24 hours fasting.

In this paper, we have examined the relationship between the changes in the resting metabolic rate (RMR) and the changes in hepatic metabolism induced by hypothyroidism and 24 h fasting. The results show that hypothyroidism induces a significant decrease in RMR, while 24 h fasting reduces RMR in euthyroid but not in hypothyroid rats. We have also measured oxygen consumption in isolated hepatocytes from euthyroid and hypothyroid rats, fed or fasted for 24 h. The results show that hypothyroidism is characterized by reduced hepatic oxygen consumption. On the other hand, 24 h fasting induces an increase in oxygen consumption in both euthyroid and hypothyroid rat liver cells, although the respiratory rates of hypothyroid rats were lower than those of euthyroid rats. The above findings, as a whole, show that hypothyroidism and 24 h fasting have similar effects on RMR but opposite effects on hepatic metabolism. In addition, a normal thyroid state does not appear to be necessary for the observed changes in hepatic metabolism due to 24 h fasting.     

Association of primary autoimmune hypothyroidism with Addison's anemia]

Intestinal absorption of vitamin B12 as measured by the Schillin test was studied in 50 patients with primary hypothyroidism of autoimmune origin. The impaired absorption of vitamin B12 was found in 24% of the patients studied, and in 6% a clinically evident form of pernicious anemia was diagnosed. The patients with hypothyroidism and simultaneous defect in absorption of vitamin B12 were characterized by more frequent occurrence of the high titer of antithyroid microsomal antibodies, higher blood serum concentration of TSH and lower blood content of hemoglobin as compared with hypothyroid patients having normal intestinal absorption of vitamin B12.     

Na-K-dependent ATPase in red cells and thyroid status

The Relationship between ouabain-sensitive ATPase (Na-K ATPase) activity in erythrocytes and the thyroid status was studied in 36 patients with Graves' disease and 58 patients receiving L-thyroxine (T4) replacement therapy. Forty normal children served as control. Total ATPase activity in 4 untreated hypothyroid patients was significantly reduced (11.0 +/- 4.6 vs 17.3 +/- 4.1 micrograms-P/h/mg-protein, P less than 0.01), and Na-K ATPase was undetectable, both of which were normalized after 4 weeks of L-T4 therapy. Na-K ATPase in hyperthyroid patients was also decreased (0.9 +/- 0.8 vs. 4.0 +/- 2.7, P less than 0.01), but was gradually normalized after 3 months of euthyroid state. Clinically euthyroid children treated with L-T4 were divided into 2 groups with regard to Na-K ATPase activity, normal and low. Analysis of the possible factors producing this difference revealed that, in primary hypothyroidism, the factor appeared to be the endogenous T4 level, while in patients with dwarfism, the secretory capacity of TSH or TSH-releasing hormone (TRH) was contributory. Thus Na-K ATPase activity in red cells remains within the normal range after L-T4 replacement in the presence of a severe degree of primary hypothyroidism or in association with secondary or tertiary hypothyroidism. Other factors such as the L-T4 dose, duration of the therapy, serum T4 and T3 concentrations, were not significantly different in the two groups. These results indicate that (1) Na-K ATPase in red cells is decreased in hyper- or hypothyroid state, (2) restoration of normal activity requires 1-3 months of euthyroid period, and (3) it is a sensitive index of peripheral thyroid status over the preceding few months.