CATS II Long-term Anthropometric and Metabolic Effects of Maternal Sub-optimal Thyroid Function in Offspring and Mothers.

CONTEXT AND OBJECTIVES: The Controlled Antenatal Thyroid Screening Study I (CATS-I) was a randomized controlled trial investigating the effects of levothyroxine therapy for suboptimal gestational thyroid function (SGTF), comparing outcomes in children of treated (SGTF-T) with untreated (SGTF-U) women during pregnancy. This follow-up study, CATS-II, reports the long-term effects on anthropometric, bone, and cardiometabolic outcomes in mothers and offspring and includes a group with normal gestational thyroid function (NGTF). DESIGN & PARTICIPANTS: 332 mothers (197 NGTF, 56 SGTF-U, 79 SGTF-T) aged 41.2±5.3 years (mean±SD) and 326 paired children assessed 9.3±1.0 years after birth for (i) body mass index (BMI); (ii) lean, fat, and bone mass by dual-energy X-ray absorptiometry; (iii) blood pressure, augmentation index, and aortic pulse-wave-velocity; and (iv) thyroid function, lipids, insulin, and adiponectin. The difference between group means was compared using linear regression. RESULTS: Offspring's measurements were similar between groups. Although maternal BMI was similar between groups at CATS-I, after 9 years (at CATS-II) SGTF-U mothers showed higher BMI (median [interquartile ratio] 28.3 [24.6-32.6] kg/m2) compared with NGTF (25.8 [22.9-30.0] kg/m2; P = 0.029), driven by fat mass increase. At CATS-II SGTF-U mothers also had higher thyroid-stimulating hormone (TSH) values (2.45 [1.43-3.50] mU/L) than NGTF (1.54 [1.12-2.07] mU/L; P = 0.015), since 64% had never received levothyroxine. At CATS-II, SGTF-T mothers had BMI (25.8 [23.1-29.8] kg/m2, P = 0.672) and TSH (1.68 [0.89-2.96] mU/L; P = 0.474) values similar to NGTF mothers. CONCLUSIONS: Levothyroxine supplementation of women with SGTF did not affect long-term offspring anthropometric, bone, and cardiometabolic measurements. However, absence of treatment was associated with sustained long-term increase in BMI and fat mass in women with SGTF.

The Relationship Between Thyroid Antibodies and Vitamin D Level in Primary Hypothyroidism.

INTRODUCTION: Vitamin D deficiency is a global health problem. Its deficiency has been reported to be associated with different autoimmune diseases. AIM: The aim of this study was to evaluate the relationship between vitamin D level and thyroid antibodies in autoimmune hypothyroidism. METHODS: A total number of 150 individuals were enrolled in this study. They were divided into the fallowing groups: group I included 50 patients with autoimmune thyroid disease (AITD), group II included 50 patients without autoimmune thyroid disease. Group III included 50 apparently healthy participants representing a control group. All participants underwent a detailed clinical examination and laboratory tests including, 25 (OH) vitamin D, thyroid-stimulating hormone (TSH) and thyroid autoantibodies assessment, including anti-thyroid peroxidase antibodies (anti-TPO) and anti-thyroglobulin antibodies (anti-TG). RESULTS: Serum levels of 25 (OH) vitamin D recorded a highly significant difference between the studies groups (20,76±6,31 ng/ml in group I vs. 24,37±9,05ng/ml in group II vs. 24,57±6,45ng/ml in group III, p<0,01). Moreover, there was a highly significant difference between patients with AITD and patients without AITD (20,76±6,31ng/ml vs. 24,37±9,05ng/ml, respectively; p<0,01). The concentration of anti-TPO and anti-TG antibodies were statistically significant higher in patients with vitamin D deficiency (p< 0,001). Serum TSH were significantly higher in group I (p< 0,001). CONCLUSION: Significantly low levels of vitamin D were documented in patients with AITD that were related to the presence of anti-thyroid antibodies and higher level thyroid-stimulation hormone (TSH), suggesting the involvement of vitamin D in the pathogenesis of AITD and the advisability of supplementation.

Controlled Antenatal Thyroid Screening II: Effect of Treating Maternal Suboptimal Thyroid Function on Child Behavior.

CONTEXT & OBJECTIVES: The Controlled Antenatal Thyroid Screening (CATS) study was the first randomized controlled trial to investigate effects of treating suboptimal gestational thyroid function (SGTF) on child cognition. Since observational studies indicated that SGTF may also increase symptoms of autism and attention-deficit/hyperactivity disorder (ADHD), the CATS cohort was used to investigate whether treatment of mothers affected their children's behavior. DESIGN & PARTICIPANTS: Mothers (N = 475) completed 3 questionnaires: the Strengths and Difficulties Questionnaire (SDQ), the Child ADHD Questionnaire, and the Social Communication Questionnaire (SCQ, used as a screen for autism spectrum disorder [ASD]), about their children (mean age 9.5 years). Group comparisons of total scores, numbers of children above clinical thresholds, and association between high maternal free thyroxine (FT4) (> 97.5th percentile of the UK cohort, "overtreated") and child neurodevelopment were reported. RESULTS: There were no differences in total scores between normal gestational thyroid function (GTF) (n = 246), treated (n = 125), and untreated (n = 104) SGTF groups. More children of treated mothers scored above clinical thresholds, particularly the overtreated. Scores were above thresholds in SDQ conduct (22% vs 7%), SCQ total scores (7% vs 1%), and ADHD hyperactivity (17% vs 5%) when comparing overtreated (n = 40) and untreated (N = 100), respectively. We identified significantly higher mean scores for SDQ conduct (adjusted mean difference [AMD] 0.74; 95% confidence interval [CI], 0.021-1.431; P = 0.040, effect size 0.018) and ADHD hyperactivity (AMD 1.60, 95% CI, 0.361-2.633; P = 0.003, effect size 0.028) comparing overtreated with normal-GTF children. CONCLUSIONS: There was no overall association between SGTF and offspring ADHD, ASD, or behavior questionnaire scores. However, children of "overtreated" mothers displayed significantly more ADHD symptoms and behavioral difficulties than those of normal-GTF mothers. Thyroxine supplementation during pregnancy requires monitoring to avoid overtreatment.

Lack of association between hypothyroxinemia of prematurity and transient thyroid abnormalities with adverse long term neurodevelopmental outcome in very low birth weight infants.

INTRODUCTION: The association between hypothyroxinemia of prematurity with neurodevelopment was controversial. OBJECTIVES: To compare 5 year neurodevelopmental outcomes of very low birth weight (VLBW) infants with hypothyroxinemia of prematurity against those without. METHODS: Retrospective cohort study in a single tertiary neonatal centre of VLBW infants born between the year 2008 to 2011. Comparisons were made between all abnormal and normal thyroid function controls using cord thyroid function tests, thyroid function tests during admission and pre-discharge thyroid function test done at term equivalent age. At 2 years corrected age, Bayley scales of infant and toddler development-third edition and Vineland II adaptive behaviour scales (VABS) were collected. At 5 years, Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), Bracken School Readiness Assessment, VABS and Beery Test of Visual-Motor Integration were collected. RESULTS: 110 subjects were studied at 2 years corrected age and 80 subjects at 5 years old. 29 infants had abnormal thyroid function test (10 infants with hypothyroxinemia of prematurity and 19 infants with transient thyroid abnormalities). There were no significant difference in the 2 years and 5 years developmental outcome between infants with and without hypothyroxinemia of prematurity (p-value>0.05); and between infants with and without transient thyroid abnormalities (p-value>0.05). There were no significant difference in neurological, visual and hearing impairment between infants with or without hypothyroxinemia of prematurity (p-value>0.05). CONCLUSIONS: Hypothyroxinemia of prematurity or transient thyroid abnormalities in VLBW infants were not associated with poorer neurodevelopment and did not support the need for levothyroxine supplementation.

The effect of Hordeum vulgare on the monoaminergic system modulating neural-thyroid dysfunction in hypothyroid female rats.

Thyroid hormones regulate the development and maturation of the brain by maintaining levels of neurotransmitters and their related metabolites. The present work emphasizes the neural dysfunction in the brain caused by hypothyroidism and the potential role of Hordeum vulgare (water soluble barley, (B)) in ameliorating these effects. The study was conducted on euothyroid and hypothyroid adult female rats. The induction of hypothyroidism was conducted by oral-administration of neo-mercazole (5.0 mg.kg-1) daily for thirty days prior the study and terminated at the end of the study. The groups were assigned as; euthyroid (EU) and hypothyroid (H) groups and other two groups were treated with 100 mg.kg-1 water soluble barley; daily for one month and assigned as (EU+B) and (H+B) groups. Compared with EU and EU+B groups, a reduction in fT4, and ERK1/2 levels and elevation in TSH in brain tissue, Moreover, a  significant elevation in 8-OH deoxyguanosine and caspase-3 levels, confirmed with increase percentage DNA-damage in the brain and thyroid tissues in hypothyroid control rats. Furthermore, a significant decrease in all monoamines levels in different brain areas and downregulation of dopamine and 5-hydroxytreptamin receptors transcription, with a significant increase in excitatory amino acids and no significant change in the levels inhibitory amino acids were recorded in control hypothyroid group. Treatment of hypothyroid group with Hordeum vulgare improved the above-mentioned adverse impact by ameliorating the thyroid hormone levels with depleting the DNA-degradation and elaborating the levels of neurotransmitters with related receptors and amino acids in brain areas.  Water soluble Hordeum vulgare as a phytonutrient, is safe and efficient agent in ameliorating the neural dysfunction resulting from hypothyroidism status in adult female rats.

Aframomum melegueta prevents the ejaculatory complications of propylthiouracil-induced hypothyroidism in sexually experienced male rats: Evidence from intravaginal and fictive ejaculations.

OBJECTIVE: Hypothyroidism has been claimed to generate sexual dysfunctions such as ejaculatory disorders. Aframomum melegueta is an aphrodisiac plant with pro-ejaculatory properties. We investigated the protective effects of aqueous extract (AE) and methanolic extract (ME) of A. melegueta on the ejaculatory function of hypothyroid male rats. METHODS: Forty sexually experienced male rats were partitioned into 8 groups (5 rats per group) and treated for 28 d as follows: Group 1, Control; Group 2, propylthiouracil (PTU, 10 mg/kg) + distilled water (DW, 10 mL/kg); Group 3, PTU + 5% Tween 80 (10 mL/kg); Group 4, PTU + bromocriptine (6 mg/kg); Group 5, PTU + AE (20 mg/kg); Group 6, PTU + AE (100 mg/kg); Group 7, PTU + ME (20 mg/kg), and Group 8, PTU + ME (100 mg/kg). On days 0, 7, 14 and 28 of treatment, each male rat was paired with primed receptive female for measurement of ejaculatory latency time (ELT) and post-ejaculatory interval (PEI) for 1.5 h. On day 29, each male rat was urethane-anesthetized and the spinal cord was transected. Thereafter, following urethral/penile stimulations and intravenous injection of dopamine, contractions of the bulbospongiosus muscles and the intraseminal pressure were registered. After these recordings, blood was collected through the catheterization of abdominal artery and plasma was used for thyroid-stimulating hormone (TSH), prolactin and testosterone assays. RESULTS: PTU-induced hypothyroidism was characterized by a significant elevation (P < 0.001) of plasmatic TSH and prolactin levels, but a decline (P < 0.001) in plasmatic testosterone, compared to untreated group. ELT, PEI, contractions of the bulbospongiosus muscles and the intraseminal pressure were also altered by PTU treatment. On the contrary, A. melegueta extracts elevated testosterone (AE, 100 mg/kg, P < 0.01; ME, 100 mg/kg, P < 0.05) and decreased prolactin (AE, 100 mg/kg, P < 0.05; ME, 20 mg/kg, P < 0.05) levels, compared to corresponding controls. With regard to DW + PTU group, prolactin concentration was lowered (P < 0.05) in rats administered with bromocriptine. Treatment with A. melegueta extracts significantly prevented the lengthening of ELT (P < 0.05) and PEI (P < 0.001). Hypothyroid state also altered the fictive ejaculation by increasing the latency and decreasing the number and frequency of bulbospongiosus muscle contractions. There was also a decrease in the intraseminal pressure. These alterations were significantly (P < 0.05) alleviated in plant extract-treated groups. CONCLUSION: This study highlighted the ejaculatory disturbance of hypothyroidism in male rats and its prevention with A. melegueta extracts.

In thyroxine-replaced hypothyroid postmenopausal women under simultaneous calcium supplementation, switch to oral liquid or softgel capsule L-thyroxine ensures lower serum TSH levels and favorable effects on blood pressure, total cholesterolemia and glycemia.

PURPOSE: In postmenopausal women under L-T4 therapy, which was subsequently accompanied by calcium carbonate (CC) supplementation taken 6-8 h after tablet L-T4, TSH levels were greater than prior to adding CC. Total cholesterolemia [CHOL], fasting glycemia [FG], systolic and diastolic blood pressure [SBP, DBP] were also greater than baseline. Our aim was to explore the effects of either liquid or softgel capsule L-T4, while maintaining CC ingestion 6-8 h, later on TSH levels, CHOL, FG, SBP, and DBP. METHODS: We proposed to 50 hypothyroid postmenopausal women under tablet L-T4 therapy, to switch to either liquid or softgel capsule L-T4 at the same daily dose while maintaining CC ingestion 6-8 h later. Sixteen women accepted [group I; liquid (n = 9), capsule (n = 7)], while 34 continued tablet L-T4 [group II, (n = 34)]. RESULTS: After 3 months, in group I, TSH decreased significantly (1.23 ± 0.49 vs. 1.80 ± 0.37 mU/L, P < 0.01), as did FG (80.7 ± 7.9 vs. 83.4 ± 6.3 mg/dL, P < 0.05); CHOL, SBP, and DBP decreased, though insignificantly. In contrast, in group II, TSH, FG, CHOL, SBP increased insignificantly, and DBP increased borderline significantly (69.7 ± 9 vs. 66.3 ± 6.5, P < 0.10). Compared to baseline (before adding CC), in group I, TSH was significantly lower (P < 0.01) and the other indices similar; in group II, TSH, FG, and SBP were significantly higher (P < 0.05), DBP borderline significantly higher (P < 0.10) and CHOL insignificantly higher. Performance of liquid L-T4 and capsule L-T4 was similar. CONCLUSION: Delaying CC ingestion even by 6-8 h after taking tablet L-T4 is not entirely satisfactory, unlike liquid or softgel L-T4.

Subclinical-Hypothyroidism: A Pathology in Evolution.

Subclinical-hypothyroidism is identified as suboptimal thyroid hormonal production associated with mild TSH (thyroid stimulating hormone) elevation. Though several non-thyroidal illness in the later stages, medications and dietary supplements may resemble SCH (subclinical-hypothyroidism), but mild persistent subnormal thyroidal pathologies are usually termed as SCH. This review briefly describes the various cardiovascular risk associations with subclinicalhypothyroidism and attempts to provide an insight into the risk and benefit association, which a patient faces once treated for SCH.

L-thyroxine malabsorption due to calcium carbonate impairs blood pressure, total cholesterolemia, and fasting glycemia.

PURPOSE: Calcium carbonate was previously shown to interfere with L-thyroxine absorption. To estimate the magnitude of tablet L-thyroxine malabsorption caused by calcium carbonate, with resulting increase in serum thyrotropin (TSH), we performed a cohort study in a referral care center. METHODS: Fifty postmenopausal hypothyroid L-thyroxine-treated women (age 71.7 ± 5.1 years) who added calcium supplementation (600-1000 mg/day) were considered. They were taking L-thyroxine 45-60 min before breakfast (setting 1). After 4.4 ± 2.0 years from initiation of L-thyroxine therapy, they took calcium supplemaentation within 2 h after L-thyroxine taking (setting 2) for 2.3 ± 1.1 years. Hence, we recommended postponing calcium intake 6-8 h after L-thyroxine (setting 3). We evaluated TSH levels, the prevalence of women with elevated TSH (>4.12 mU/L), total cholesterolemia, fasting glycemia, blood pressure, and the prevalence of hypercholesterolemia, hyperglycemia, and hypertension. RESULTS: TSH levels were 3.33 ± 1.93 mU/L versus 1.93 ± 0.51 or 2.16 ± 0.54 comparing setting 2 with setting 1 or 3 (P < 0.001, both). In setting 2, 18% women had elevated TSH versus none in setting 1 or 3 (P < 0.01). Total cholesterolemia, fasting glycemia, systolic, and diastolic blood pressure were also significantly higher in setting 2 compared to settings 1 and 3. For every 1.0 mU/L increase within the TSH range of 0.85-6.9 mU/L, total cholesterolemia, glycemia, systolic, and diastolic blood pressure increased by 12.1, 3.12 mg/dL, 2.31, and 2.0 mmHg, respectively. CONCLUSIONS: Monitoring of hypothyroid patients who ingest medications that decrease L-thyroxine absorption should not be restricted to solely measuring serum TSH.

Differential effects of hypo- and hyperthyroidism on remodeling of contacts between neurons expressing the neuropeptide EI and tyrosine hydroxylase in hypothalamic areas of the male rat.

The Neuropeptide EI (NEI, glutamic acid- isoleucine amide) participates in neuroendocrine function. Previously we demonstrated that NEI concentration is regulated by thyroid hormones in discrete hypothalamic areas in rats. We observed that the thyroid status affects the dopaminergic regulation of the pituitary hormones. In this study we explored possible interactions between NEI and tyrosine hydroxylase (TH) containing elements in selected hypothalamic areas of male rats. Neuronal somas, terminals and boutons were assessed by confocal microscopy, in hypo- and hyperthyroid animals. We observed a remodeling of the contacts between the TH and NEI immunoreactive elements in the incerto-hypothalamic area (IHy, also known as rostromedial zona incerta) according to thyroid function. However, in the dorsolateral zone of the peduncular part of the lateral hypothalamus (DL-PLH) the thyroid hormones affect the dendritic trees of the neurons without perturbing the overall NEI/TH contacts. Also, we demonstrated that TRH Receptor 1 (TRH-R1) is colocalized in NEI immunoreactive neurons in the peduncular part of the lateral hypothalamus (PLH) and NEI precursor mRNA expression increased by hypothyroidism indicating that NEI neurons are responsive to the feedback mechanisms of the Hypothalamic Pituitary-Thyroid Axis (HPT). In conclusion, the hypothyroid status seems to increase the interactions between the NEI neurons and the dopaminergic pathways while hyperthyroidism either decreases or displays no effects. Altogether these observations support the participation of the IHy and PLH NEI as a modulating component of the HPT suggesting that altered neuroendocrine, behavioral and cognitive dysfunctions induced by dysthyroidism could be in part mediated by NEI.

The influence of thyroid disorders on bone density and biochemical markers of bone metabolism.

Background Thyroid dysfunction, predominantly hyperthyroidism, has been previously linked to impaired bone mass density (BMD) and increased risk of fractures. On the other hand, data in the field of hypothyroidism (HT) are missing. The purpose of the present study was to investigate the impact of thyroid disorders on bone density serum and urine calcium (Ca) and phosphate (P) as well as serum osteocalcin and alkaline phosphatase and urine hydroxyproline in a series of post-menopausal women. Materials and methods The study was conducted in the Reproductive Endocrinology Outpatient Clinic of our hospital. A consecutive series of post-menopausal women was included, after excluding patients under hormone treatment (including levothyroxine supplementation) and those who received raloxifene, tamoxifen or tibolone during the study period as well as those who received treatment during the previous 12 months were excluded from the present study. Results Overall, 188 women were included in the present study. Among them, 143 women had normal thyroid function, 32 women had hyperthyroidism and 13 women had HT. Correlation of thyroid function indices with osteoporosis indices revealed statistically significant correlations between thyroxine (T4) and free triiodothyronine (T3) with T-, Z-scores and BMD. Logistic regression analysis concerning the impact of HT and hyperthyroidism on T-score, Z-score and bone mass density revealed that both pathological entities negatively affect bone health (p < 0.05). Conclusion The findings of our study suggest that not only hyperthyroidism, but also HT negatively affects BMD. Future studies should investigate this association and corroborate our findings.

Is Parenteral Levothyroxine Therapy Safe in Intractable Hypothyroidism?

CASE: A 32-year old woman was admitted to the hospital due to intractable hypothyroidism refractory to high dose of oral l-thyroxine therapy. She underwent total thyroidectomy and radioactive iodine therapy due to papillary thyroid cancer. After excluding poor adherence to therapy and malabsorption, levothyroxine absorption test was performed. No response was detected. Transient neurologic symptoms developed during the test. She developed 3 attacks consisting of neurologic symptoms during high dose administration. The patient was considered a case of isolated l-thyroxine malabsorption. She became euthyroid after intramuscular twice weekly l-thyroxine therapy. DISCUSSION: There are a few case reports regarding isolated l-thyroxine. We report successful long term results of twice weekly administered intramuscular l-thyroxine therapy. We also draw attention to neurologic side effects of high dose l-thyroxine therapy.

Constant iodine intake through the diet could improve hypothyroidism treatment: a case report.

Currently, hypothyroidism is usually treated only with drugs; patients are never told that they could regulate their levels of iodine with dietary recommendations in a complementary way. The objective of this work was to explore the effect of a constant iodine intake through the diet in a postmenopausal woman with subclinical grade II hypothyroidism, who also had mild hypercholesterolemia and obesity. Baseline anthropometric nutritional, pharmacological, and habit data were obtained, then the woman was scheduled for 1 month a diet in which she was provided food naturally containing iodine, so that the recommended requirements (iodine 150 µg/day) were met. All the information about which foods contain this mineral was supplied and explained to the patient. This diet was also designed to help her to gradually lose weight, and was more balanced and closer to the nutritional recommendations. The results obtained in this work were satisfactory, having achieved improved blood levels of thyroid-stimulating hormone (1.78 µIU/mL) and reduced total cholesterol levels (198 mg/dL). Statement of hypercholesterolemia was demoted. In addition, a significant improvement in relation to weight and body volume was reached (body mass index fell from 30.13 to 28.5 kg/m2), an important fact since it has impacted the overall well-being of the patient. In conclusion, it was demonstrated that a constant iodine intake through the diet for this patient with grade II hypothyroidism was very effective, and therefore, this aspect should be also considered during hypothyroidism treatment.

Discovery of GnIH and Its Role in Hypothyroidism-Induced Delayed Puberty.

It is known that hypothyroidism delays puberty in mammals. Interaction between the hypothalamo-pituitary-thyroid (HPT) and hypothalamo-pituitary-gonadal (HPG) axes may be important processes in delayed puberty. Gonadotropin-inhibitory hormone (GnIH) is a newly discovered hypothalamic neuropeptide that inhibits gonadotropin synthesis and release in quail. It now appears that GnIH is conserved across various mammals and primates, including humans, and inhibits reproduction. We have further demonstrated that GnIH is involved in pubertal delay induced by thyroid dysfunction in female mice. Hypothyroidism delays pubertal onset with the increase in hypothalamic GnIH expression and the decrease in circulating gonadotropin and estradiol levels. Thyroid status regulates GnIH expression by epigenetic modification of the GnIH promoter region. Furthermore, knockout of GnIH gene abolishes the effect of hypothyroidism on delayed pubertal onset. Accordingly, it is considered that GnIH is a mediator of pubertal disorder induced by thyroid dysfunction. This is a novel function of GnIH that interacts between the HPT-HPG axes in pubertal onset delay. This mini-review summarizes the structure, expression, and function of GnIH and highlights the action of GnIH in pubertal disorder induced by thyroid dysfunction.

Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats.

Individuals who consume a diet deficient in zinc (Zn-deficient) develop alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low metabolic rate and cold insensitivity. Although those disturbances are related to primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an increased thyrotropin (TSH) concentration, but unchanged thyroid hormone (TH) levels and decreased body weight. This does not support the view that the hypothyroidism develops due to a low Zn intake. In addition, intrauterine or postnatal Zn-deficiency in weaned and adult rats reduces the activity of pyroglutamyl aminopeptidase II (PPII) in the medial-basal hypothalamus (MBH). PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH). This hypothalamic peptide stimulates its receptor in adenohypophysis, thereby increasing TSH release. We analyzed whether earlier low TH is responsible for the high TSH levels reported in adults, or if TRH release is enhanced by Zn deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from one week prior to gestation and up to three weeks after delivery. We found a high release of hypothalamic TRH, which along with reduced MBH PPII activity, increased TSH levels in Zn-deficient pups independently of changes in TH concentration. We found that primary hypothyroidism did not develop in intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency enhances TSH levels since early-life, favoring subclinical hypothyroidism development which remains into adulthood.

Soy isoflavones inducing overt hypothyroidism in a patient with chronic lymphocytic thyroiditis: a case report.

BACKGROUND: Many people have thyroid conditions that make them susceptible to hypothyroidism. If the foods they eat may interfere with the production of thyroid hormone, which can lead to development of serious hypothyroidism. The danger of health drinks should always be noted. CASE PRESENTATION: A 72-year-old Japanese woman was previously diagnosed with chronic lymphocytic thyroiditis caused by a goiter and had an elevated thyroid-stimulating hormone level (6.56 µIU/ml), a high anti-thyroid peroxidase antibody level (>600 IU/ml), and a high antithyroglobulin level (> 4000 IU/ml) but normal levels of free triiodothyronine (3.08 pg/ml) and thyroxine (1.18 ng/ml). She presented to our hospital with sudden-onset general malaise, edema, and hoarseness with an elevated thyroid-stimulating hormone (373.3 µIU/ml) level and very low triiodothyronine (< 0.26 pg/ml) and thyroxine (0.10 ng/ml) levels. It was determined that for 6 months she had been consuming a processed, solved health drink ("barley young leaf") in amounts of 9 g/day, which included soybean and kale powder extract. Hypothyroidism might be affected by ingredients of health drinks. She discontinued consumption of the health drink immediately and began taking 12.5 µg of levothyroxine. The amount of levothyroxine was gradually increased every 3 days up to 100 µg. At day 61, her thyroid-stimulating hormone level had decreased (6.12 µIU/ml), her free triiodothyronine (2.69 pg/ml) and thyroxine (1.56 ng/ml) levels had increased, and her general condition was improved. Among risky foods lowering thyroid function, some experimental studies have revealed that isoflavones reduce thyroid function. Therefore, we measured the presence of isoflavones in the patient's frozen serum with thin-layer chromatography. After she discontinued consumption of the health drink, two components quickly disappeared, and the other three components gradually decreased. On the basis of developing solvent composition and a positive ferric chloride reaction in thin-layer chromatography experiment, the five ingredients that disappeared or decreased were highly suspected to be soy isoflavones. CONCLUSIONS: This case emphasizes that consuming health drinks that include soy isoflavone powder extracts can lead to severe hypothyroidism.

Central hypothyroidism - a neglected thyroid disorder.

Central hypothyroidism is a rare and heterogeneous disorder that is characterized by a defect in thyroid hormone secretion in an otherwise normal thyroid gland due to insufficient stimulation by TSH. The disease results from the abnormal function of the pituitary gland, the hypothalamus, or both. Moreover, central hypothyroidism can be isolated or combined with other pituitary hormone deficiencies, which are mostly acquired and are rarely congenital. The clinical manifestations of central hypothyroidism are usually milder than those observed in primary hypothyroidism. Obtaining a positive diagnosis for central hypothyroidism can be difficult from both a clinical and a biochemical perspective. The diagnosis of central hypothyroidism is based on low circulating levels of free T4 in the presence of low to normal TSH concentrations. The correct diagnosis of both acquired (also termed sporadic) and congenital (also termed genetic) central hypothyroidism can be hindered by methodological interference in free T4 or TSH measurements; routine utilization of total T4 or T3 measurements; concurrent systemic illness that is characterized by low levels of free T4 and normal TSH concentrations; the use of the sole TSH-reflex strategy, which is the measurement of the sole level of TSH, without free T4, if levels of TSH are in the normal range; and the diagnosis of congenital hypothyroidism based on TSH analysis without the concomitant measurement of serum levels of T4. In this Review, we discuss current knowledge of the causes of central hypothyroidism, emphasizing possible pitfalls in the diagnosis and treatment of this disorder.

Protease inhibitor-associated bone mineral density loss is related to hypothyroidism and related bone turnover acceleration.

BACKGROUND: Clinical and experiments evidence indicate that protease inhibitors (PI) can cause bone mineral density (BMD) loss. However, the mechanism of such loss remains obscure. METHODS: This single-center, cross-sectional study included 184 HIV-infected patients treated with PI who underwent dual-energy X-ray absorptiometry scan. Serum phosphorus, percentage of tubular reabsorption of phosphate (%TRP), thyroid and parathyroid function (iPTH), vitamin D, osteocalcin (OC), urinary deoxypyridinoline (DPD), and urinary cross-linked N-telopeptide of type I collagen (u-NTx) were measured. RESULTS: The rate of hypothyroidism in PI-users [32/117 (27%)] was double that in non-PI users [8/67 (12%), p = 0.016] and was significantly associated with PI use in multivariate analysis [odds ratio (OR) 11.37, 95% confidence interval (CI) 1.358-95.17, p = 0.025]. Spine BMD was significantly lower in hypothyroid patients than euthyroid, for both total population (-1.37 vs. -1.00, p = 0.041) and PI users (-1.56 vs. -1.13, p = 0.029). Multivariate regression analysis identified inverse correlation between hypothyroidism and spine BMD [estimate -0.437, 95% CI -0.858 to -0.024, p = 0.042]. OC, DPD and u-NTx were significantly higher in PI users than in non-PI users (p = 0.01, 0.05, and 0.01, respectively). CONCLUSIONS: PI use is associated with hypothyroidism as well as bone turnover acceleration, which worsens PI-associated BMD loss. In PI-treated patients, thyroid function tests are warranted to prevent further progression of PI-associated BMD loss.

Thyroid dysfunction in patients with Down syndrome: Results from a multi-institutional registry study.

The goals of this undertaking were to assess the outcomes of thyroid screening tests and adherence to thyroid screening guidelines across five Down syndrome (DS) specialty clinics in various states. Data related to thyroid screening were collected for 663 individuals across five clinics specializing in the comprehensive care of individuals with DS for a period of 1 year. Of the 663 participants, 47.7% of participants had a TSH and free T4 ordered at their DS specialty clinic visit. Approximately 19.0% (60/316) had a new thyroid disorder diagnosis made. We conclude that a sizable proportion of the patients with DS are not up-to-date on current guidelines when they present to a DS specialty clinic, while adherence to thyroid screening guidelines helps facilitate early diagnoses. Hypothyroidism is prevalent in the population, consistent with reported literature. DS specialty clinics can help patients stay current on screening guidelines.

Role of levothyroxine and vitamin E supplementation in the treatment of oxidative stress-induced injury and apoptosis of myocardial cells in hypothyroid rats.

OBJECTIVE: To explore the underlying mechanism and treatment of myocardial injury caused by hypothyroidism, we evaluated oxidative stress in serum and myocardial tissue of hypothyroid rats. The effect of levothyroxine (LT4) replacement therapy and vitamin E (VitE) supplementation on oxidative stress-induced injury and apoptosis of myocardial tissue is examined. METHODS: Male Sprague-Dawley rats were divided into five groups: normal control group, propylthiouracil group (PTU group), LT4 treatment group (PTU + LT4 group), vitamin E treatment group (PTU + VitE group), and combined treatment group (PTU + LT4 + VitE group). Superoxide dismutase (SOD) activity and malondialdehyde (MDA) expression in serum and myocardium were determined. Myocardial apoptosis index (AI) in each group was determined by TUNEL assay. RESULTS: SOD levels in serum were significantly increased in PTU + VitE and PTU + LT4 + Vit E groups, as compared to that in PTU and PTU + LT4 groups (P < 0.05). MDA levels in serum and myocardial tissue were significantly lower in PTU + LT4, PTU + VitE, and PTU + LT4 + VitE groups, as compared to that in the PTU group (P < 0.05). Myocardial apoptosis was significantly increased in PTU and PTU + VitE groups as compared to that in the normal control group (P < 0.05), while it was significantly lower in PTU + LT4 and PTU + LT4 + VitE groups, as compared to that in the PTU group (P < 0.05). CONCLUSION: In this study, levothyroxine replacement therapy and vitamin E supplementation appeared to ameliorate myocardial apoptosis in hypothyroid rats, the mechanism of which appears to be related to improved thyroid function and reduced oxidative stress.