Levothyroxine Liquid Solution Versus Tablet for Replacement Treatment in Hypothyroid Patients

BackgroundAlthough replacement treatment with L-thyroxine (LT4) seems easy to manage, about one-third of hypothyroid patients show thyroid-stimulating hormone (TSH) values outside the normal range.ObjectivesTo explore whether LT4 liquid formulation (monodose vials or drops) affects TSH stability values and to assess its ability to maintain TSH within the normal range compared to tablets.MethodsA total of 100 hypothyroid patients on replacement treatment with LT4 liquid solution were enrolled (Liquid Group) at a follow-up visit (revisit). The inclusion criteria were 1) treatment for surgical hypothyroidism for at least 2 years or autoimmune hypothyroidism for at least 5 years, 2) normal TSH at the previous visit 12 months before enrollment (baseline visit), and 3) maintenance of the same LT4 dosage during the time interval between the baseline and the follow-up visit. Using the same selection process, we also enrolled 100 hypothyroid patients on replacement treatment with LT4 tablets (Tablet Group).ResultsAt the follow-up visit, 19 patients of the Tablet Group and 8 patients of the Liquid Group had abnormal TSH values (P = .023). Weekly and daily LT4 dosage per kilogram were higher in Tablet Group (P = .016 and .006, respectively). The magnitude of TSH change from baseline to follow-up visit was greater in the Tablet Group (P < .001).ConclusionThe use of LT4 liquid formulation compared to tablet resulted in a significantly higher number of hypothyroid patients who maintained the euthyroid state in a 12-month follow-up period and a reduced variability in TSH values. (Endocr Pract. 2014;20:901-906)     

Frequency of Thyroid Hormone Replacement After Lobectomy for Differentiated Thyroid Cancer

ObjectiveTo determine the frequency of levothyroxine (LT4) supplementation after therapeutic lobectomy for low-risk differentiated thyroid cancer (DTC).MethodsThis retrospective cohort study enrolled adult patients with low-risk DTC confirmed using surgical pathology who underwent therapeutic lobectomy at a single institution from January 2016 through May 2020. The outcome measures were postoperative serum thyroid-stimulating hormone (TSH) levels and the initiation of LT4. The predictors of a postoperative TSH level of >2 mU/L and initiation of LT4 were evaluated using Cox proportional hazards models.ResultsPostoperative TSH levels were available for 115 patients (91%), of whom 97 (84%) had TSH levels >2 mU/L after thyroid lobectomy. Over a median follow-up of 2.6 years, a postoperative TSH level of >2 mU/L was associated with older age (median 52 vs 37 years; P = .01), higher preoperative TSH level (1.7 vs 0.85 mU/L; P < .001), and primary tumor size of <1 cm (38% vs 11%, P = .03). Multivariate analysis revealed that only preoperative TSH level was an independent predictor of a postoperative TSH level of >2 mU/L (hazard ratio [HR] 1.53, P = .003). Among patients with a postoperative TSH level of >2 mU/L, 66 (68%) were started on LT4 at a median of 74 days (interquartile range 41-126) after lobectomy, with 51 (77%) undergoing at least 1 subsequent dose adjustment to maintain compliance with current guidelines.ConclusionMore than 80% of the patients who underwent therapeutic lobectomy for DTC developed TSH levels that were elevated beyond the recommended range, and most of these patients were prescribed LT4 soon after the surgery.     

Tablet Levothyroxine (L-T4) Malabsorption Induced by Proton Pump Inhibitor; A Problem that was Solved by Switching to L-T4 in Soft Gel Capsule

ObjectiveTo report a patient in whom the impaired absorption of tablet levothyroxine (L-T4) due to a proton pump inhibitor (PPI) use was corrected by switching the patient to the soft gel capsule.MethodsA woman with Hashimoto’s thyroiditis-associated hypothyroidism (serum thyroid-stimulating hormone [TSH] 6.8-9.6 mU/L) had been treated with tablet L-T4 (100 μg/day). Because she used to take pantoprazole just before L-T4 in the morning, TSH failed to normalize (4.4-6.5 mU/L). Thus, the daily dose had been progressively increased to 125 and 150 μg/day, with serum TSH levels of 2.4 and 0.6 mU/L, respectively.ResultsWhile maintaining pantoprazole, we switched the tablet L-T4 (150 g/day) to a soft gel capsule (125 μg/ day; Tirosint® capsule, IBSA, Lugano, Switzerland) and after 2 months, to 100 μg/day. Serum TSH was lower than under the equivalent regimens with the tablet: 0.5 versus 2.4 mU/L (125 μg/day) and 2.4 versus 4.4 to 6.5 mU/L (100 μg/day). Upon switching back to the tablet (100 μg/day), serum TSH increased to 3.2 and 4.7 mU/L and then dropped to 2.7-3.0 mU/L when the dose was increased to 125 μg/day. We also acutely evaluated the intestinal absorption of L-T4 by administering 600 μg LT4 as a tablet or soft gel capsule while maintaining pantoprazole. Pharmacokinetic indices showed better and faster absorption for the soft gel capsule versus tablet (area under the curve [AUC]_0-4h = 16,240 vs. 10,960 nmol/L × 4 hours, maximum absorption [C_max] = 108 vs. 73 nmol/L, and time of maximum absorption [T_max] = 120 minutes vs. 180 minutes).ConclusionConfirming in vitro studies conducted by other authors, the soft gel capsule L-T4 is negligibly affected by changes in gastric pH compared to tablet L-T4. (Endocr Pract. 2014;20:e38-e41)     

Italian Association of Clinical Endocrinologists Statement–Replacement Therapy for Primary Hypothyroidism: A Brief Guide for Clinical Practice

Objective: Hypothyroidism requires life-long thyroid hormone replacement therapy in most patients. Oral levothyroxine (LT4) is an established safe and effective treatment for hypothyroidism, but some issues remain unsettled.Methods: The Italian Association of Clinical Endocrinologists appointed a panel of experts to provide an updated statement for appropriate use of thyroid hormone formulations for hypothyroidism replacement therapy. The American Association of Clinical Endocrinologists' protocol for standardized production of clinical practice guidelines was followed.Results: LT4 is the first choice in replacement therapy. Thyroid-stimulating hormone (TSH) should be maintained between 1.0 and 3.0 mIU/L in young subjects and at the upper normal limit in elderly or fragile patients. Achievement of biochemical targets, patient well-being, and adherence to treatment should be addressed. In patients with unstable serum TSH, a search for interfering factors and patient compliance is warranted. Liquid or gel formulations may be considered in subjects with hampered LT4 absorption or who do not allow sufficient time before or after meals and LT4 replacement. Replacement therapy with LT4 and L-triiodothyronine (LT3) combination is generally not recommended. A trial may be considered in patients with normal values of serum TSH who continue to complain of symptoms of hypothyroidism only after co-existent nonthyroid problems have been excluded or optimally managed. LT3 should be administered in small (LT4:LT3 ratio, 10:1 to 20:1) divided daily doses. Combined therapy should be avoided in elderly patients or those with cardiac risk factors and in pregnancy.Conclusion: LT4 therapy should be aimed at resolution of symptoms of hypothyroidism, normalization of serum TSH, and improvement of quality of life. In selected cases, the use of liquid LT4 formulations or combined LT4/LT3 treatment may be considered to improve adherence to treatment or patient well-being.Abbreviations:AACE = American Association of Clinical EndocrinologistsFT3 = free triiodothyronineFT4 = free thyroxineLT3 = levotriiodothyronineLT4 = levothyroxineMeSH = medicine medical subject headingsQoL = quality of lifeTSH = thyroid-stimulating hormone     

Iodine Status of Preterm Infants Born in an Area of Iodine Sufficiency: Are They at Risk of Iodine Deficiency?

ObjectiveTo the assess the iodine status of preterm infants born in an area of iodine sufficiency using the urinary iodine concentration (UIC) and thyroid-stimulating hormone (TSH) levels and compare these values across different feeding practices during the first 7 days of life.MethodsIn this cross-sectional study, 88 preterm infants born at 30 to 34 weeks of gestation and admitted to the neonatal intensive care unit of a referral hospital in Tehran (Iran) were included. The infant UIC and TSH levels and breast milk iodine concentration in mothers who were exclusively breastfeeding were measured.ResultsMedian (interquartile range [IQR]) UIC and TSH levels in the study population were 81 (39-189) μg/L and 1.60 (0.80-2.85) mIU/L, respectively. When preterm infants were stratified by the type of feeding, the median (IQR) UICs were 64 (42-126) μg/L in parenteral nutrition, 125 (41-195) μg/L in exclusively breastfeeding, 57 (28-123) μg/L in formula feeding, and 45 (35-132) μg/L in mixed feeding, with no statistically significant difference between the groups (P = .31). The median (IQR) breast milk iodine concentration was 271 (177-521) μg/L in preterm infants exclusively fed their mothers’ own milk. There was no significant difference in the proportion of the TSH levels of >5 mIU/L between preterm infants who received enteral and parenteral nutrition (P = .27).ConclusionPreterm infants are at risk of iodine deficiency even in an area where the general population has adequate iodine. Only the preterm infants who received exclusively their mothers’ own milk had marginally adequate iodine status. Further studies are warranted to determine the necessity of iodine supplementation for this vulnerable group.     

Trace elements in bipolar disorder

IntroductionTrace elements may play an important role in bipolar disorders. The objective of this study is to determine serum copper and zinc, blood lead and cadmium and urine lead, cadmium and thallium concentrations in patients diagnosed with bipolar disorders and to compare these levels with those of a healthy control group.Materials and methodsA total of 25 patients diagnosed with bipolar disorder and 29 healthy subjects participated in this study. Serum copper and zinc concentrations were measured using flame atomic absorption spectrometry; the blood lead and cadmium concentrations were measured by electrothermal atomization atomic absorption spectrometry with Zeeman background correction; urine lead, cadmium and thallium concentrations were measured by inductively coupled plasma mass spectrometry.ResultsMedian blood and urine lead and cadmium levels were significantly higher among the bipolar patients than among the control group: Blood lead (μg/dL): patient median: 3.00 (IQR: 1.40–4.20); control median (μg/dL): 2.20 (IQR: 0.90–3.00) p = 0.040. Blood cadmium (μg/L): patient median: 0.39 (IQR: 0.10–1.15); control median: 0.10 (IQR: 0.10–0.17) p < 0.001. The median of cadmium (μg/L) in patients who smoked (1.20 IQR: 0.44–2.30) was higher than that in non-smokers (0.12 IQR: 0.10–0.34) p < 0.001. There was a statistically significant increase (p = 0.001) in zinc levels among patients in the manic phase (mean 111.28, SD: 33.36 μg/dL) with respect to the control group (mean 86.07, SD: 12.39 μg/dL).ConclusionsThe results suggest that there could be higher levels of some toxic trace elements in the group of patients with bipolar disorder than in the healthy control group.     

Gonadotropin Therapy Once a Week for Spermatogenesis in Hypogonadotropic Hypogonadism

ObjectiveHypogonadotropic hypogonadism (HH) can be caused by congenital HH (CHH), pituitary stalk interruption syndrome (PSIS), and pituitary injury (acquired HH). Gonadotropin therapy, typically administered every other day or twice a week, is commonly used to promote spermatogenesis. The aim of this retrospective study was to evaluate the efficacy of weekly gonadotropin therapy on spermatogenesis in patients with HH (n = 160).MethodsThe patients’ diagnoses include Kallmann syndrome (KS) (n = 61), normosmic CHH (nCHH) (n = 34), PSIS (n = 48), and acquired HH (n = 17). The rate of successful spermatogenesis and median time to achieve spermatogenesis among these 4 subgroups were compared as well as between a weekly group (n = 95) and a twice-a-week group (n = 223) of CHH patients.ResultsOnce-a-week gonadotropin therapy resulted in 74% (119/160) of HH patients achieving spermatogenesis with significantly increased testicular volume and total testosterone levels (P < .001). The median period of spermatogenesis was 13 (interquartile range[IQR] 11.4-14.6) months. Larger basal testicular volume (P = .0142) was an independent predictor for earlier sperm appearance. Six spontaneous pregnancies occurred. Compared with the twice-a-week regimen for spermatogenesis, the weekly injection group had a similar median time of sperm appearance (14 [IQR, 11.6-16.4] vs 15 [IQR, 13.5-16.5] months), success rate (78% [74/95] vs 64% [143/223]), sperm concentration (20.9 [IQR, 5.0-46.3] vs 11.7 [IQR, 2.1-24.4] million/mL), and progressive sperm motility (40.8 ± 27.3% vs 36.9% ± 20.2%).ConclusionWeekly gonadotropin therapy is effective in inducing spermatogenesis, similar to that of twice-a-week therapy. A larger basal testicular size was a favorable indicator for earlier spermatogenesis.     

Impact of Ramadan Fasting on Thyroid Status and Quality of Life in Patients with Primary Hypothyroidism: a Prospective Cohort Study from karachi,pakistan

Objective: Ramadan is the ninth month in the lunar calendar, during which Muslims fast from predawn to sunset and major changes occur in their dietary, sleep, and physical activity patterns. Most patients with hypothyroidism are unable to comply with the proper timings of levothyroxine (LT4) administration. The objective of the study was to determine the change in thyroid-stimulating hormone (TSH) level and quality of life (QOL) before and after Ramadan in patients with primary hypothyroidism.Methods: This prospective cohort study included adult patients on stable doses of LT4 who fasted for at least 20 days during the month of Ramadan in the Islamic year 1437 Hijri (June/July 2016). Baseline characteristics and TSH levels were recorded on all consenting patients within 6 weeks prior to Ramadan. Post-Ramadan TSH was tested within 1 to 2 weeks after Eid-ul-Fitr.Results: During the study period, 64 patients with hypothyroidism were enrolled, of which 58 were female. The mean age of participants was 44.2 ± 13.2 years. Average daily dose of LT4 was 95.3 ± 35.4 μg. On average, patients fasted for 26.5 days and missed a dose of LT4 on 1.27 days. Mean TSH pre-Ramadan was 2.37 ± 1.35 mIU/L, and post-Ramadan, it was 4.69 ± 3.87 mIU/L. Mean difference between TSH pre- and post-Ramadan was 2.32 ± 3.80 mIU/L (P<.001). However, the difference in TSH was not significantly different between those who were compliant with meals and LT4 interval versus those who were not (compliant, 2.04 mIU/L; noncompliant, 3.15 mIU/L; P = .30). Overall, an increase in QOL scores in the domains of physical health, psychological health, and social relationships was observed after Ramadan.Conclusion: We observed statistically significant changes in TSH concentrations after the month of Ramadan in hypothyroid patients who fasted. The change in TSH was not affected by timing of LT4 intake and interval from meal.Abbreviations: AKUH = Aga Khan University Hospital; LT4 = levothyroxine; QOL = quality of life; TSH = thyroid-stimulating hormone     

Alterations of urinary perchlorate levels in euthyroid postpubertal children with autism spectrum disorder

BackgroundPerchlorates ClO₄(⁻) are known environmental and food contaminants that act as inhibitors of iodine uptake by the thyroid gland; however, information concerning their possible association with the development of autism spectrum disorder (ASD) is still missing. The current study is first presenting the alterations in perchlorate urine levels in euthyroid children with ASD.ObjectivesTo examine urinary perchlorates and iodides in euthyroid children diagnosed with ASD, compared to age-, and BMI-matched neurotypical controls, and to verify the association between these two ions in ASD.MethodsIons were determined in 24 h urine samples determined by ion chromatography–conductivity cell detection (IC-CD) and ion chromatography–pulsed amperometric detection (IC-PAD) techniques, respectively, in a total of 130 postpubertal euthyroid children with normal BMI (the mean age 14.46 years, SD = 1.32; the mean BMI 20.6, SD = 1.37), divided into age- and BMI-matched groups of ASD patients and neurotypical, healthy children (control).ResultsThe ASD group presented with significantly higher perchlorate urine levels than the controls (median = 1.05 μg/L, interquartile range(IQR) = 1.5 versus median = 0.09 μg/L, IQR = 0.097, respectively), as well as lower iodide urine levels (median = 100.2 μg/L, IQR = 37 versus median = 156.95 μg/L, IQR = 26.11, respectively). The ASD group presented significantly lower TSH and higher free thyroid hormone (fT4, fT3) levels than the controls. In regression analyses, perchlorate urine levels showed significant positive relationships with normal BMI values and serum TSH, and inverse relationships with serum fT4. Urinary iodide levels showed significant inverse relationships with BMI values. The absence of ASD was associated with decreased odds of perchlorate urine levels (OR = 0.012, 95 % confidence interval [CI] 0.0002−0.76), and increased odds of iodide urine levels (OR = 1.15, 95 %CI 1.05–1.27).ConclusionsASD may have an independent and significant impact on perchlorate as well as iodide levels in urine of euthyroid lean postpubertal children. Perchlorate levels do not appear to be directly associated with iodide levels in euthyroid children.     

Lack of relationship between genotype and virulence in Candida species

BackgroundThe virulence of isolates among different Candida species causing candidemia may play a role in the prognosis of the patients. Furthermore, the potential relationship between genotype and virulence is still unclear and need to be further studied.AimsWe aim to assess the relationship between genotype and virulence in Candida species using a Galleria mellonella larvae infection model.MethodsOne hundred and ninety-four isolates from 68 clusters (Candida albicans, 114/41; Candida parapsilosis, 74/24; Candida tropicalis, 6/3) were compared against the same number of each species singleton genotypes in terms of survival of G. mellonella larvae.ResultsThe median of survival and the IQR ranges of clusters and singleton were as follows: C. albicans (2 days, IQR 1.5–2 vs. 2 days, IQR 1–2.25), C. parapsilosis (2 days, IQR 1.5–2.6 vs. 2 days, IQR 2–3.3), and C. tropicalis (1 day, IQR 1–3.5 vs. 2 days, IQR 2–3.5; p < 0.05). High intra-cluster variability in terms of median of survival was found regardless the species.ConclusionsNo relationship between genotype and virulence in Candida was observed with the G. mellonella model.     

Blood lead in children and associations with trace elements and sociodemographic factors

BackgroundNo safe blood lead concentration in children has been identified. Lead can affect nearly every system in the body and is especially harmful to the developing central nervous system of children.The aim of this study is to analyze blood lead in a population of children and its association with sociodemographic variables, biochemical parameters, copper, iron, selenium and zinc.MethodsWe recruited 155 children (86 boys and 69 girls) with a mean age of 7.3 (SD:4.1). Blood lead and serum selenium concentrations were measured by electrothermal atomic absorption spectrometry. Serum copper and zinc concentrations were measured by flame atomic absorption spectrometry. Serum iron levels were determined by colorimetric assay. A risk exposure questionnaire for lead was administered to the participants.ResultsThe median blood lead level was 1.1 (IQR 0.7–1.6) μg/dL. Regarding risk exposure factors, the youngest children (<2 years) who played outdoors presented a median blood lead concentration of 1.1 μg/dL IQR: 0.48–1.48, compared to the median of 0.3 μg/dL IQR:0.2-0.48 in the children who stated they played at home (p = 0.024). Significant differences were also found when taking into account those parents who smoked (median 1.3 IQR 0.8–1.9 μg/dL vs 0.9 IQR 0.5–1.4 μg/dL of non-smokers, p = 0.002). Children who drank tap water had higher blood lead levels (median 1.2 IQR 0.7–1.6 μg/dL) than those who drank bottled water (median 0.7 IQR 0.2–1.3 μg/dL p = 0.014). In addition, children whose mothers had not finished school had higher blood lead levels (median 1.7 IQR 1.2–2.3 μg/dL) than those whose mothers had finished school (median 1.2 IQR 0.7–1.7 μg/dL) and those whose mothers had gone to university (median 0.9 IQR 0.5–1.4 μg/dL) p = 0.034. In the multivariate lineal regression analysis we continue to observe the association between mother’s higher level of education and lower blood levels (p = 0.04) and the interaction between age and outdoor play (p = 0.0145).ConclusionsIn spite of the decline in blood lead concentrations, associated risk factors continue to exist in vulnerable populations such as children.     

High prevalence of TPO-Abs and subclinical hypothyroidism in iodine-sufficient pregnant women in Northern Algeria

BackgroundIodine is a trace element whose adequate intakes are essential during gestation to promote the correct growth and development of the fetus. Historically, endemic goiter and cretinism affected northern regions of Algeria, and iodized salt was introduced in 1990. However, there has been no national study of iodine nutrition in Algeria since 1994. The aim of this study was to assess the iodine status and thyroid function of women of reproductive age (WRA) and pregnant women (PW) in northern Algeria.MethodsHealthy WRA and PW were recruited from an urban area (Algiers) and healthy WRA from a rural area (Tizi-Ouzou). Spot urine and venous blood samples were collected to assess iodine status (urinary iodine concentration, UIC) and serum thyroid hormones (TSH, FT4), thyroglobulin (Tg), and anti-thyroid peroxidase antibodies (TPO-Ab) concentrations.ResultsThe median UIC in WRA was 256 μg/L (IQR: 166−354 μg/L; n = 151) in Algiers and 253 μg/L (167−341 μg/L; n = 150) in Tizi-Ouzou. The median UIC for the PW in Algiers was 233 μg/L (IQR: 157−326 μg/L; n = 173).Thirty-five percent of WRA and 30% of PW had an UIC > 300 μg/L. Median TSH, FT4 and Tg concentrations were within reference ranges in all groups of women. Among PW, 72.7%, 75.4% and 75.5% in the first, second and third trimester were TPO-Ab+. Among TPO-Ab + PW in the first, second and third trimesters, 18.7%, 13% and 10.3% had subclinical hypothyroidism.ConclusionIn northern Algeria, median UICs in PW indicate iodine sufficiency, and in WRA indicate more than adequate intakes. About 75% of PW are TPO-Ab + and the prevalence of subclinical hypothyroidism is high. Monitoring and surveillance of iodine fortification programs is vital to avoid both iodine deficiency and excess. There is an urgent need for a comprehensive national iodine status survey including school-age children and other vulnerable population groups in Algeria.     

The Clinical Utility of Free Thyroxine in Oral Levothyroxine Absorption Testing

ObjectiveOriginal absorption studies for levothyroxine (LT₄) were validated using total thyroxine (TT₄) measurements. Free thyroxine (FT₄) has largely supplanted TT₄ in clinical practice. The objective of our study was to assess the clinical utility of FT₄ in oral LT₄ absorption testing.MethodsIn this retrospective electronic health record analysis, we recorded data of patients who underwent LT₄ oral absorption testing between November 2010 and January 2012 because of persistent hypothyroidism despite a greater than anticipated weight-based dose of LT₄. Patients included had primary hypothyroidism and an absorption test with assessment of both TT₄ and FT₄ measured at times 0, 30, 60, 90, 120, 180, 240, 300, and 360 minutes. The test was conducted with 1 mg (five 200-μg tablets) of Synthroid® after an overnight fast by a standard nonisotopic method.ResultsA total of 10 patients (3 men/7 women) underwent absorption testing. Prior to testing, the median daily LT₄ dose was 250 μg (range, 150 to 350 μg). Three patients were also on liothyronine (10, 20, or 50 μg daily). Based on the calculated amount absorbed, 1 patient demonstrated subnormal absorption, and 9 patients were normal. Median body mass index was 33 kg/m² (range, 21 to 50 kg/m²). Median calculated absorption was 105% (range, 3.7 to 195.6%). The correlation comparing FT₄ and TT₄ was 0.88 (95% confidence interval, 0.56 to 0.97, P < .001), a significant correlation.ConclusionFT₄ and TT₄ correlated highly, even in patients who were severely hypothyroid; FT₄ may be used interchangeably with TT₄ as a qualitative assessment of suspected malabsorption using an oral LT₄ absorption test. (Endocr Pract. 2014;20:925-929)     

Management of Hypothyroidism and Hypothyroxinemia During Pregnancy

ObjectiveTo review the diagnosis and management of hypothyroidism during pregnancy, in the preconception period, and in the postpartum period.MethodsA literature review of English-language papers published between 1982 and 2022, focusing on the most recent literature.ResultsDuring pregnancy, thyroid function laboratory tests need to be interpreted with regard to gestational age. Overt hypothyroidism, regardless of the thyroid-stimulating hormone (TSH) level, should always be promptly treated when it is diagnosed before conception or during pregnancy or lactation. Most women with pre-existing treated hypothyroidism require an increase in levothyroxine (LT4) dosing to maintain euthyroidism during gestation. LT4-treated pregnant patients need close monitoring of their serum TSH levels to avoid overtreatment or undertreatment. There is no consensus about whether to initiate LT4 in women with mild forms of gestational thyroid hypofunction. However, in light of current evidence, it is reasonable to treat women with subclinical hypothyroidism with LT4, particularly if the TSH level is >10 mIU/L or thyroperoxidase antibodies are present. Women who are not treated need to be followed up to ensure that treatment is initiated promptly if thyroid failure progresses. Additional studies are needed to better understand the effects of the initiation of LT4 in early gestation in women with subclinical hypothyroidism and hypothyroxinemia and determine optimal strategies for thyroid function screening in the preconception period and during pregnancy.ConclusionThe diagnosis and management of hypothyroidism in the peripregnancy period present specific challenges. While making management decisions, it is essential to weigh the risks and benefits of treatments for not just the mother but also the fetus.     

Levothyroxine Monotherapy: What Works Better for the Individual With Hypothyroidism?

ObjectiveI explore objective data not supporting the addition of liothyronine (medication) (LT3) to levothyroxine (medication) (LT4) in patients with hypothyroidism. Accurate identification of patients with symptomatic (almost exclusively overt) hypothyroidism is important in evaluating clinical outcomes of therapies. Recent studies have documented that nearly a third of individuals who are offered thyroid hormone are euthyroid at the time of initiation. Additionally, others are clinically diagnosed without biochemical confirmation, so a sizable proportion of those started on LT4 are not hypothyroid. The assumption that nonhypothyroid symptoms will resolve with LT4 is problematic. The true underlying cause of these symptoms remains unidentified and untreated.MethodsIn a narrative fashion I will review the positive predictive value of and correlation of symptoms consistent with hypothyroidism and confirmed hypothyroidism likely to favorably respond to thyroid hormone replacement.ResultsFollowing a review of the reliability of thyroid-stimulating hormone (TSH) in predicting a euthyroid state, the correlation of circulating triiodothyronine (serum measurement) (T3) levels with symptoms and predictive value of T3 to forecast the outcome of adding LT3 to LT4 will be reviewed. The utility of striving for high, middle, or low TSH set points within the expected range to predict changes in clinical quality of life and the ability of blinded patients to sense subtle differences along this spectrum will be documented. In addition, the clinical impact of single nucleotide polymorphisms in the type 2 deiodinase gene will be reviewed. Finally, the overall satisfaction of selected patients with their thyroid hormone treatments will be outlined and preferences for T3-containing treatments from blinded studies will be summarized.ConclusionBasing thyroid hormone treatment decisions on patient symptoms likely results in missed diagnoses We should encourage primary care physicians to assess a differential diagnosis, exclude other diagnoses, and not assume a thyroid etiology when TSH is normal. Modifying treatment to a particular TSH target or adjusting based on a low T3 level does not seem to enhance patient outcomes. Finally, pending further trials of “symptomatic” participants, using sustained release LT3 to mimic normal physiology, and including monocarboxylate 10 transporter and Type 2 deiodinase polymorphisms and objective outcomes, I will continue to depend on therapy with LT4 monotherapy and seek alternative explanations for my patients’ nonspecific symptoms.     

Age as a major factor associated with zinc and copper deficiencies in pediatric thalassemia

BackgroundPatients with thalassemia encounter increased consumption of zinc (Zn) and copper (Cu) from chronic hemolysis and increased excretion from iron chelation. Iron-enriched diet restriction may result in low Zn and Cu intakes. Recent data on Zn and Cu status among Thai pediatric patients with thalassemia are lacking. This study aimed to identify frequencies and determine risk factors of Zn and Cu deficiencies among patients with thalassemia.MethodsPatients with transfusion-dependent thalassemia (TDT) receiving iron chelation ≥12 months and nonTDT (NTDT) aged 2–20 years were recruited. Serum Zn and Cu were measured. Dietary intakes were ascertained by interviews.ResultsA total of 209 patients (TDT = 126, NTDT = 83) were enrolled. Zn deficiency seemed to be associated with disease severity as median (IQR) Zn level of TDT was lower than that of NTDT [77 (69−85) vs. 80 (72−88) mcg/dL, p = 0.05], while higher frequency of Zn deficiency was identified in the former (24 % vs. 14 %). In TDT, Zn deficiency was associated with patients >10 years (OR 4.6; 95 %CI 1.1–6.4, p = 0.03), which likely resulted from combined low dietary Zn intake, prolonged exposures to hemolysis and iron chelators. Frequencies of Cu deficiency were similarly low in TDT and NTDT (8% and 7%) with comparable median (IQR) Cu levels of 103 (90−124) and 110 (92−132) mcg/dL, respectively (p = 0.13). Cu levels were inversely associated with age (r=-0.65 and r=-0.62 in TDT and NTDT, respectively; p < 0.001).ConclusionCompared with younger patients, Zn and Cu deficiencies were more common among patients with thalassemia >10 years. Age was a major factor associated with both Zn and Cu deficiencies.     

Impact of Lifestyle Changes During Ramadan on Thyroid Function Tests in Hypothyroid Patients Taking Levothyroxine

Objective: The holy month of Ramadan poses a challenge for levothyroxine-treated patients due to altered eating habits and time restrictions. The aim of this study was to examine the impact of lifestyle changes during Ramadan on thyroid function tests in hypothyroid patients taking levothyroxine in the United Arab Emirates.Methods: Retrospective design whereby levothyroxine-treated hypothyroid patients who had thyroid function tests within 3 months pre-Ramadan and within 2 months post-Ramadan were included. We looked at adherence to levothyroxine, eating pattern, and levothyroxine administration in relation to meal times during Ramadan. Pre- and post-Ramadan thyroid function tests and the potential impact of independent variables using a random-intercept mixed effects linear model were examined.Results: A total of 112 patients (89 females) were recruited in the study, with a mean age ± standard error (SE) of 44.70 ± 1.36 years (range, 19.0 to 79.0 years). The mean thyroid-stimulating hormone (TSH) within 3 months before Ramadan was 1.809 ± 0.094 mIU/L (median, 41.5 days; interquartile range &lsqb;IQR], 25.0 to 73.0 days), while the mean TSH within 2 months post-Ramadan was higher at 3.072 ± 0.312 mIU/L (median, 27.5 days; IQR, 14.0 to 42.0 days). Post-Ramadan, 36 out of 112 patients had a plasma TSH outside of the normal reference range. The independent variable outcomes model showed that older patients and males were more likely to have an increased plasma TSH post-Ramadan. There was no relationship between the time of levothyroxine administration and change in TSH level.Conclusion: Levothyroxine-treated hypothyroid patients showed a significant increase in plasma TSH post-Ramadan, amounting to 2.525 standard deviations, with older patients and males more likely to be affected.Abbreviations: IQR = interquartile range; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Controlled Release Matrix Tablets of Olanzapine: Influence of Polymers on the <Emphasis Type="Italic">In Vitro</Emphasis> Release and Bioavailability

Controlled-release (CR) tablet formulation of olanzapine was developed using a binary mixture of Methocel® K100 LV-CR and Ethocel® standard 7FP premium by the dry granulation slugging method. Drug release kinetics of CR tablet formulations F1, F2, and F3, each one suitably compressed for 9-, 12-, and 15-kg hardness, were determined in a dissolution media of 0.1 N HCl (pH 1.5) and phosphate buffer (pH 6.8) using type II dissolution apparatus with paddles run at 50 rpm. Ethocel® was found to be distinctly controlling drug release, whereas the hardness of tablets and pH of the dissolution media did not significantly affect release kinetics. The CR test tablets containing 30% Methocel® and 60% Ethocel® (F3) with 12-kg hardness exhibited pH-independent zero-order release kinetics for 24 h. In vivo performance of the CR test tablet and conventional reference tablet were determined in rabbit serum using high-performance liquid chromatography coupled with electrochemical detector. Bioavailability parameters including C_max, T_max, and AUC_0–48 h of both tablets were compared. The CR test tablets produced optimized C_max and extended T_max (P < 0.05). A good correlation of drug absorption in vivo and drug release in vitro (R² = 0.9082) was observed. Relative bioavailability of the test tablet was calculated as 94%. The manufacturing process employed was reproducible and the CR test tablets were stable for 6 months at 40 ± 2°C/75 ± 5% relative humidity. It was concluded that the CR test tablet formulation successfully developed may improve tolerability and patient adherence by reducing adverse effects.Key words: bioavailability, controlled release, Ethocel®, olanzapine