Thyroid Medication Research Articles

Thyroid Hormone Status and Health-Related Quality of Life in the LifeLines Cohort Study

Thyroid disorders are prevalent in Western society, yet many subjects experience limited symptoms at diagnosis, especially in hypothyroidism. We hypothesize that health-related quality of life (HR-QOL) is more severely impaired in subjects with more abnormal thyroid hormone function tests. This is a cross-sectional study of Dutch adults participating in the LifeLines Cohort Study between December 2009 and August 2010. In 9491 Western European participants (median age 45 years; 3993 men and 5498 women), without current or former use of thyroid medication, we compared HR-QOL using the RAND 36-Item Health Survey between subjects with normal thyrotropin (TSH) values and subjects with disturbed thyroid hormone status (serum TSH, free thyroxine, and free triiodothyronine). The influence of possible confounders (age, smoking, co-morbidity) on HR-QOL was evaluated as well. Suppressed TSH values (TSH < 0.5 mU/L) were found in 114 (1.2%), while 8334 (88.8%) had TSH within the normal range, 973 participants (10.3%) had TSH between 4 and 10 mU/L, and 70 (0.7%) had TSH > 10 mU/L. Men had a higher HR-QOL than women (70-92 vs. 65-89; p < 0.001), except for the domain "general health" (72 vs. 72; p = 0.692). Men with suppressed or elevated TSH values did not score significantly lower than euthyroid men for any of nine domains of the RAND 36-Item Health Survey. Compared with euthyroid women, women with suppressed TSH scored significantly lower in the domains "physical functioning" (84 vs. 89, p = 0.013) and "general health" (67 vs. 72, p = 0.036). Women with markedly elevated TSH (> 10 mU/L) had a score in all HR-QOL domains that was similar to that of women with normal TSH values. There were no differences in the physical component score and the mental component score between any of the TSH groups. Physical component score and mental component score were mainly determined by smoking status, co-morbidity, and body mass index or waist circumference. In this population-based study, HR-QOL scores of subjects with suppressed TSH values or markedly elevated TSH values were generally not significantly lower than those of subjects with normal or mildly elevated TSH values.

Selenite supplementation in euthyroid subjects with thyroid peroxidase antibodies

Euthyroid thyroid peroxidase (TPO-Ab)-positive subjects are at risk for progression to subclinical and overt autoimmune hypothyroidism. Previous studies have shown a decrease in TPO-Ab and improvement of quality-of-life (QoL) in L-T4-treated hypothyroid patients upon selenium supplementation. To evaluate in euthyroid TPO-Ab-positive women without thyroid medication whether selenite decreases TPO-Ab and improves QoL. Randomized, placebo-controlled, double-blind study. Euthyroid (TSH 0·5-5·0 mU/l, FT4 10-23 pm) women with TPO-Ab ≥ 100 kU/l were randomized to receive 200 mcg sodium selenite daily (n = 30) or placebo (n = 31) for 6 months. TSH, FT4, TPO-Ab, selenium (Se), selenoprotein P (SePP) and QoL were measured at baseline, 3, 6 and 9 months. There were no differences in baseline characteristics between the Se group and the placebo group. During selenite supplementation, serum Se and SePP did not change in the placebo group, but increased in the Se group. TPO-Ab and TSH did not change significantly in any group. TPO-Ab in the Se group were 895 (130-6800) at baseline, 1360 (60-7050) kU/l at 6 months, in the placebo group 1090 (120-9200) and 1130 (80-9900) kU/l, respectively (median values with range). TSH in the Se group was 2·1 (0·5-4·3) at baseline, 1·7 (0·0-5·3) mU/l at 6 months, in the placebo group 2·4 (0·7-4·4) and 2·5 (0·2-4·3) mU/l, respectively. QoL was not different between the groups. Six months selenite supplementation increased markers of selenium status but had no effect on serum TPO-Ab, TSH or quality-of-life in euthyroid TPO-Ab-positive women.

Smoking reduces the risk of hypothyroidism and increases the risk of hyperthyroidism: evidence from 450 842 mothers giving birth in Denmark

Smoking may influence on the occurrence of thyroid disease, but studies have led to inconsistent results. In Denmark, information on maternal smoking during pregnancy is registered by midwives, and we investigated the association between maternal smoking as reported during pregnancy and the subsequent maternal risk of having hyper- or hypothyroidism diagnosed. Population-based cohort study. Using Danish nationwide registers, we identified mothers giving birth in Denmark, 1996-2008, and studied their first pregnancy in the study period. Information on maternal smoking during the pregnancy and maternal diagnosis of hyper- or hypothyroidism was obtained from the Danish National Hospital Register (DNHR) and prescription of thyroid medication from the Danish National Prescription Register (DNPR). Cox proportional hazards model was used to estimate hazard ratio (HR) with 95% confidence interval (95% CI) for onset of maternal hyper- or hypothyroidism after birth of the child in multivariate analyses adjusting for potential confounders. Among mothers included (n = 450 842), altogether 89,022 (19·7%) reported that they were smokers during the first pregnancy in the study period, and 8905 (2·0%) developed hyper (n = 3389)- or hypothyroidism (n = 5516) after birth of the child. Maternal smoking was associated with a subsequent decreased risk of developing hypothyroidism (adjusted HR 0·75 (95% CI 0·70-0·81)) and an increased risk of hyperthyroidism (1·38 (1·27-1·49)). Danish nationwide registration of maternal smoking during pregnancy adds further evidence to an association between smoking and thyroid dysfunction; smoking reduced the risk of hypothyroidism and increased the risk of hyperthyroidism.

Thyroid Hormone Levels Within Reference Range Are Associated with Heart Rate, Cardiac Structure, and Function in Middle-Aged Men and Women

Triiodothyronine (T3) has many effects on the heart, and marked changes in cardiac function and structure occur in patients with (subclinical) thyroid disease. We investigated whether between-subject variation in thyroid hormone levels within the euthyroid range is also associated with heart rate and echocardiographic heart function and structure. Subjects were selected from the Asklepios study (n=2524), a population-representative random sample of patients aged between 35 and 55 years, free from overt cardiovascular disease at baseline. Analyses were restricted to 2078 subjects (1013 women and 1065 men), not using antihypertensive or thyroid medication nor having antithyroperoxidase antibody levels above clinical cut-off or thyrotropin (TSH) levels outside the reference range. All subjects were phenotyped in-depth and underwent comprehensive echocardiography, including diastolic evaluation. Thyroid function parameters were determined by automated electrochemiluminescence. Heart rate was robustly positively associated with (quartiles of) free T3 (FT3) and T3, both in subjects with TSH levels within reference (0.27-4.2 μU/L) and in narrow TSH range (0.5-2.5 μU/L; p<0.0001). FT3 and T3 were negatively associated with left ventricular (LV) end-diastolic volume but positively associated with relative wall thickness. Total T3 (TT3) was associated with enhanced ventricular contraction (as assessed by tissue Doppler imaging). Free thyroxine, FT3, and TT3 were positively associated with late ventricular filling, and TT3 was associated with early ventricular filling. We have demonstrated a strong positive association between thyroid hormone levels within the euthyroid range and heart rate, and more subtle effects on cardiac function and structure. More specifically, we suggest a smaller LV cavity size (with increased relative wall thickness), an enhanced atrial and ventricular contraction, and LV relaxation with higher circulating thyroid hormones. These results illustrate that variation in thyroid hormone levels, even within the reference range, exerts effects on the heart.

Subclinical Thyroid Dysfunction and Cardiovascular Outcomes among Prospective Cohort Studies

The association between subclinical thyroid dysfunction and cardiovascular outcomes has been recently clarified with the publication of three individual participant data (IPD) analyses from the Thyroid Studies Collaboration. We identified original cohort studies with a systematic review and pooled individual data from over 70'000 participants to obtain a more precise estimate of the risks of cardiovascular outcomes associated with subclinical thyroid dysfunction. Subclinical hypothyroidism and subclinical hyperthyroidism, defined as normal thyroxine (FT4) levels with increased or decreased Thyroid-Stimulating Hormones (TSH or thyrotropin) respectively, are associated with increased risk of cardiovascular outcomes compared to euthyroid state, particularly in those with a more pronounced thyroid dysfunction. Specifically, subclinical hypothyroidism is associated with an increased risk of coronary heart disease (CHD) events, CHD mortality and heart failure (HF) events in individuals with higher TSH levels, particularly in those with TSH levels ≥10.0 mIU/L. Conversely, subclinical hyperthyroidism is associated with an increased risk of total mortality, CHD mortality, HF and atrial fibrillation, particularly in those with suppressed TSH levels <0.10 mIU/L. Pending ongoing randomized controlled trials, these observational findings allow identifying potential TSH thresholds for thyroid medication initiation based on risk of clinical outcomes, although clinical decision based solely on observational data need caution. The impact of thyroid replacement among the elderly with subclinical hypothyroidism is currently studied in a multicenter international randomized controlled trial (Thyroid Hormone Replacement for Subclinical Hypothyroidism Trial, TRUST trial).

Primary Care Physicians' Attitudes Regarding Collaborating with Home-Based Depression Care Management Providers

Symptom Checklist-20 [HSCL-20], PHQ-9), disability (World Health Organization Disability Assessment Schedule-II, WHODAS-II), and satisfaction. Results: No participants dropped out. Depression care specialists engaged in an average of 2.4 phone calls and 6.3 faxes per client to the contact person (e.g., receptionist, nurse) at each client’s primary care clinic. In these phone calls and faxes, depression care specialists made an average of 5.4 requests per client, and physicians responded to an average of 3 requests. Each client’s physician responded to at least one collaboration request (e.g., initiating or changing dosage of antidepressant medication; reducing sleep, anxiolytic, and antipsychotic medication; changing pain medication; initiating thyroid medication). Six clients achieved meaningful reductions in PHQ-9 scores at the end of active treatment (i.e., 50% reduction, 5/6 in full remission). In paired t-tests, HSCL-20 and WHODAS-II scores improved from baseline to end of active DCM and from baseline to three months after active DCM (p 0.025). Satisfaction ratings also were favorable. Conclusions: Results of this pilot study suggest that augmenting an existing DCM protocol with a collaboration intervention is feasible to implement by depression care specialists and can improve physician collaboration and client outcomes. Larger scale research is required to determine whether augmenting home-based DCM with the collaboration intervention is more effective than DCM alone. Such research could have implications for theories and models of collaboration across service systems.

New-Onset Atrial Fibrillation Is a Predictor of Subsequent Hyperthyroidism: A Nationwide Cohort Study

AimsTo examine the long-term risk of hyperthyroidism in patients admitted to hospital with new-onset AF. Hyperthyroidism is a well-known risk factor for atrial fibrillation (AF), but it is unknown whether new-onset AF predicts later-occurring hyperthyroidism.Methods and ResultsAll patients admitted with new-onset AF in Denmark from 1997–2009, and their present and subsequent use of anti-thyroid medication was identified by individual-level linkage of nationwide registries. Patients with previous thyroid diagnosis or thyroid medication use were excluded. Development of hyperthyroidism was assessed as initiation of methimazole or propylthiouracil up to a 13-year period. Risk of hyperthyroidism was analysed by Poisson regression models adjusted for important confounders such as amiodarone treatment. Non-AF individuals from the general population served as reference. A total of 145,623 patients with new-onset AF were included (mean age 66.4 years [SD ±13.2] and 55.3% males) of whom 3% (4,620 events; 62.2% women) developed hyperthyroidism in the post-hospitalization period compared to 1% (48,609 events; 82% women) in the general population (n = 3,866,889). In both women and men we found a significantly increased risk of hyperthyroidism associated with new-onset AF compared to individuals in the general population. The highest risk was found in middle-aged men and was consistently increased throughout the 13-year period of observation. The results were confirmed in a substudy analysis of 527,352 patients who had thyroid screening done.ConclusionNew-onset AF seems to be a predictor of hyperthyroidism. Increased focus on subsequent risk of hyperthyroidism in patients with new-onset AF is warranted.

Childhood Weight Gain and Thyroid Autoimmunity at Age 60–64 Years: The 1946 British Birth Cohort Study

Background:Complex bidirectional relationships have been described between body weight, thyroid function, and risk of thyroid disorders, including thyroid autoimmunity. We used a life-course approach to examine the potential association of childhood or adult body weight with the risk of thyroid autoimmunity and other thyroid disorders at age 60–64 years in a large population-based birth cohort study.Methods:In the UK Medical Research Council 1946 British Birth Cohort study, at age 60–64 years, 1277 women and 1185 men (78% of the target sample) responded to a postal questionnaire, which included questions on thyroid disease and thyroid medication. Circulating antithyroid peroxidase antibodies, free T4, and TSH concentrations were measured in 1057 women and 997 men at a subsequent clinic visit. Birth weight was recorded, and height and weight were measured at ages 2, 4, 6, 7, 11, 15 years and also repeatedly in adulthood.Results:At age 60–64 years, 10.9% of women (139 of 1277) and 2.3% of men (27 of 1185) reported they were taking T4, and 11.5% of women (122 of 1057) and 3.3% of men (33 of 997) had positive anti-TPO antibodies (>100 IU/mL), consistent with thyroid autoimmunity. Among women, both T4 use and positive anti-TPO antibodies at age 60–64 years were positively associated with childhood body weight, childhood overweight, and adult body mass index. Childhood weight gain between 0 and 14 years of age was positively associated with later T4 use (odds ratio 1.21, 95% confidence interval 1.03–1.42) and positive anti-TPO antibodies (1.21, 1.00–1.47). Women who were overweight or obese at age 14 years (127 of 972) had a higher risk of later positive anti-TPO antibodies (2.05, 1.12–3.76). In men and women without any thyroid disorders, serum free T4 concentrations were inversely associated with concurrent body mass index (P = .002).Conclusions:Childhood weight gain and childhood overweight conferred an increased susceptibility to later hypothyroidism and thyroid autoimmunity, particularly in women.

Clinical observation of Hashimoto thyroiditis in patients with chronic hepatitis C undergoing pegylated-interferon alpha-2a and ribavirin combination therapy

To investigate the relation of thyroid function with hashimoto thyroiditis (HT, an autoimmune disease of unknown etiology also known as chronic lymphocytic thyroiditis) in patients with chronic hepatitis C (CHC) receiving treatment with pegylated-interferon-alpha (Peg-IFNa) based on the observation that HT is common among individuals undergoing IFN-based therapy. One-hundred-and-seven patients with chronic hepatitis C were enrolled for study between January 2008 and December 2010. Thyroid function was assessed by electrochemiluminescence assays to detect serum levels of anti-thyroid peroxidase (A-TPO) antibodies, thyroid stimulating hormone (TSH), and free thyroxine (FT4) prior to initiation of the IFN-based therapy. The treatment strategies (drugs, doses, schedules) were designed according to HT status (CHC with HT, or CHC without HT). Patients were monitored during the 24 weeks of treatment (including measuring serum alanine aminotransferase (ALT), TSH, and FT4 every two to four weeks, and HCV RNA every four weeks) so that the IFNa dose could be adjusted and thyroid medications (levothyroxine sodium or methimazole) added as necessary. The response rate at end of treatment (week 24) was assessed. Twenty-one of the CHC patients were diagnosed with HT, and the incidence of thyroid dysfunction among the CHC patients with HT was 71.4% (15/21); among the CHC patients with no HT, the incidence of thyroid dysfunction was significantly lower (30.2% (26/86), X2 = 12.1995, P less than 0.01). In the CHC patients with HT, 90.5% (19/21) had serum levels of A-TPO antibodies that were more than or equal to 2-times higher than the normal value at the end of treatment. Of the 15 CHC patients with HT and thyroid dysfunction, 73.3% (11/15) continued to show thyroid dysfunction at the end of treatment. Hypothyroidism was the most common form of thyroid dysfunction observed (4/11), and all of those patients responded to levothyroxine sodium treatment. The virological response rates of the two groups (CHC with HT and CHC without HT) were not significantly different at any time point examined (treatment week 4, 12, and 24, P more than 0.05). The incidence of thyroid dysfunction is significantly higher among CHC patients with HT than among CHC patients without HT. If suspected, these patients should be carefully monitored because the clinical symptoms of thyroid dysfunction are not obvious and the drug therapy should be carefully adjusted to minimize the thyroid dysfunction while maximizing the antiviral effect.

Should Infertile Women with Normal TSH Levels (

IS, MB, AK: nothing to disclose, JCP: consultant Interlace Medical. For hypothyroid women attempting pregnancy the optimal preconception TSH level is considered to be <2.5mIU/L, however controversy exists in regards to the upper limit of the TSH euthyroid range in women undergoing fertility treatments. To compare the outcome of OI/IUI cycles with a preconception TSH level <2.5mIU/L to that of cycles with TSH ≥2.5mIU/L (but <5.0mIU/L). Design: Retrospective study. Setting: Academic fertility center. Patients: Women with a TSH<5.0mIU/L undergoing OI with either clomiphene citrate (CC) or gonadotropins (FSH). Interventions: Data from 4542 OI cycles (28% CC/IUI, 72% FSH/IUI) were reviewed and stratified by the preconception TSH level (<2.5 vs ≥2.5mIU/L, groups 1 and 2 respectively). Primary outcome measures: clinical pregnancy, spontaneous abortion, multiple pregnancy rates per cycle (CPR, SABR, MPR respectively). Secondary outcome measures: total dose of gonadotropins, estradiol (E2) the day prior to and the day of HCG trigger (available in FSH/IUI cycles only); HCG trigger day, number of preovulatory follicles (≥13 mm), and endometrial thickness (available in all cycles). Statistics: t-test and x2 used as appropriate. In 3357 (74%) cycles the TSH was <2.5mIU/L, and in 1185 (26%) it was ≥2.5mIU/L. 368 (8.1%) patients were euthyroid, albeit on thyroid medication. 175 (14.7%) group 2 patients had a TSH ≥4.0mIU/L. Age and basal FSH were comparable among groups. Total dose of gonadotropins, peak E2 levels, pre-ovulatory follicle count, HCG trigger day, and endometrial thickness were comparable among groups. Overall, clinical pregnancy and multiple pregnancy rates did not differ among groups, however an unexpected significantly higher SAB rate was noted in women with a TSH<2.5mIU/L (Table 2). The difference was noted in FSH/IUI cycles but not in CC/IUI ones (SABR: 22.8% vs 12.1%, P<0.01, and 15.9% vs 9.7%, P:0.56, respectively). Results did not change after excluding patients with PCOS and women on thyroid medication (SABR: 22.9% vs 9.6%, P<0.01 for group 1 vs 2, respectively). Furthermore, the difference persisted despite the FSH/IUI sub-groups being comparable in age, BMI, and baseline FSH (35.8±4.4 vs 35.7±4.4 years, 24.4±4.7 vs 24.6±4.9 kg/m2, 7.9±3.5 vs 8.1±3.3 IU/L, P>0.05 for all comparisons). The application of a stricter TSH cut-off value (<2.5mIU/L) among women undergoing OI/IUI with a euthyroid TSH <5.0mIU/L does not seem to improve the outcome of the cycle. When comparing FSH/IUI cycles with a TSH<2.5mIU/L to those with a TSH≥2.5mIU/L, an unexpected higher SAB rate was noted in the former and persisted even after considering possible confounders.

Consumptive hypothyroidism in an Egyptian baby with benign neonatal hemangiomatosis: a case report

IntroductionBenign neonatal hemangiomatosis is a condition in which multiple cutaneous hemangiomas appear at birth or shortly thereafter; visceral complications are absent. Here, we report a case of a consumption hypothyroidism in an Egyptian baby with benign neonatal hemangiomatosis.Case presentationAn 8-month-old Egyptian boy with benign neonatal hemangiomatosis was referred to our institution for evaluation of developmental delay. Initial examination revealed a quiet baby who was able to sit only with support. He had hypotonia, a large anterior fontanelle, puffy eyes, cold extremities, hypothermia, bradycardia, and abdominal distension. An examination of his skin revealed more than 100 dome-shaped red-purple cutaneous hemangiomas that varied in size from 5 to 10mm on the back, the abdomen and the extremities without mucus membrane involvement. He had low serum free thyroxine concentration and triiodothyronine levels and high thyroid-stimulating hormone and reverse-triiodothyronine levels. A work-up that involved appropriate imaging ruled out visceral involvement. Based on the above mentioned data, a diagnosis of consumptive hypothyroidism due to benign neonatal hemangiomatosis was made. He was started on oral thyroid medication which was gradually increased to 90μg L-thyroxine daily (15μg/kg/day). After three months of treatment, he was able to sit alone without support and he had normal levels of thyroid-stimulating hormone and serum free thyroxine.ConclusionThyroid function should be assessed periodically in babies with benign neonatal hemangiomatosis, especially if symptoms of hypothyroidism appear or the size and number of hemangiomatosis increase rapidly. Moreover, high doses of L-thyroxine may be needed to achieve euthyroidism during the infancy.

Rectus muscle resection in Graves' ophthalmopathy

In the treatment of Graves' ophthalmopathy, rectus muscle resections generally are avoided because of the concern of reaggravating inflammation and creating excessive extraocular muscle restriction. In patients with large-angle strabismus and in patients with residual strabismus after maximal recession surgery, however, rectus muscle resection may be considered. We report a series of 8 patients with Graves' ophthalmopathy who underwent rectus muscle resections. The records of 270 patients with Graves' ophthalmopathy who had undergone strabismus surgery were retrospectively reviewed. Data from subjects who had undergone rectus muscle resections were collected, including age at surgery, duration of disease, duration of diplopia, previous eye or strabismus surgeries, history of radioactive iodine or corticosteroid treatment, current thyroid medications, current use of corticosteroids, tobacco use, and signs and symptoms used to diagnose Graves' ophthalmopathy. Eight patients (5 females) were identified (mean age, 51.1±17.6 years). Preoperatively, 4 patients had a horizontal deviation and 4 patients had both horizontal and vertical deviations in primary gaze. Mean preoperative horizontal deviation was 27.9(Δ) ± 15.2(Δ) and mean vertical deviation was 6.3(Δ) ± 5.4(Δ). At final follow-up examination, 7 patients were orthotropic in primary gaze; 1 patient had a larger deviation from slippage as the result of a broken suture within the first postoperative week. None of the patients were overcorrected or developed atypical inflammation. In this series, patients with Graves' ophthalmology were successfully treated with the use of rectus muscle resections as part of the surgical plan. Careful ocular motility assessment and patient selection is critical if this option is contemplated.

How good is the levothyroxine replacement in primary hypothyroidism patients in Brazil? Data of a multicentre study.

Studies from every continent have shown that only around 50% of the patients subjected to thyroid hormone replacement have TSH in the normal range. However, to date, there are no consistent data about Brazil. To evaluate levothyroxine (LT4) replacement treatment in patients with primary hypothyroidism followed in referral centers in Brazil. Patients with primary hypothyroidism followed in referral centers (University Hospitals from Universidade Federal do Rio de Janeiro - UFRJ, Unicamp, Universidade Federal do Paraná - UFPR and Universidade Federal do Ceará-UFC) answered a questionnaire that inquired about clinical and biochemical conditions, social- economic status, life quality and clinicians' orientations as well as their understanding about the information given. Serum TSH was checked close to the interview. 2292 consecutive patients met the inclusion criteria. Mean age 51.2 yr and TSH values between 0.4 and 4.0 mUI/l were considered to be within the reference range. Among all patients taking thyroid medication, 42.7% had an abnormal serum TSH (28.3% were undertreated and 14.4% were overtreated). Approximately all patients (99%) took LT4 in the morning but less than 30 min before breakfast (85.4%). Regarding the clinicians' orientations: 97.5% of the patients were instructed to take the medication daily, and 92.6% to take 30 min before breakfast (92.6%). However, only 52.1% were told not to take LT4 along with other medication. Our study found that a significant number of patients taking thyroid hormones were not in the therapeutic range. Clinicians should, therefore, consider monitoring patients on thyroid replacement more frequently and being more precise on giving recommendations about the correct use of LT4.

Delusional parasitosis with hyperthyroidism in an elderly woman: a case report

IntroductionDelusional parasitosis is a rare, monosymptomatic psychosis involving a delusion of being infested with parasites. It is commonly observed among female patients over the age of 50. It is classified as a ‘delusional disorder’ according to the 10th revision of the International Classification of Diseases and as a ‘delusional disorder - somatic type’ according to the Diagnostic and Statistical Manual, Fourth Edition. Delusional parasitosis was reported to be associated with physical disorders such as hypoparathyroidism, Huntington’s chorea and Alzheimer’s disease, among others. Other than vitamin deficiencies however, a causal relationship has not to date been identified. We present this case due to the rarity of Turkish patients with this condition, its duration of follow-up, and its temporal pattern of symptoms paralleling thyroid function tests.Case presentationOur patient was a 70-year-old white Anatolian Turkish woman with primary school education who had been living alone for the past five years. She presented to our psychiatry department complaining of ‘feeling large worms moving in her body’. The complaints started after she was diagnosed with hyperthyroidism, increased when she did not use her thyroid medications and remitted when she was compliant with treatment. She was treated with pimozide 2mg/day for 20 months and followed-up without any antipsychotic treatment for an additional nine months. At her last examination, she was euthyroid, not receiving antipsychotics and was not having any delusions.ConclusionAlthough endocrine disorders, including hyperthyroidism, are listed among the etiological factors contributing to secondary delusional parasitosis, as far as we are aware this is the first case demonstrating a temporal pattern of thyroid hyperfunction and delusions through a protracted period of follow-up. It may be that the treatment of delusional parasitosis depends on clarifying the etiology and that atypical antipsychotics may help in the management of primary delusional parasitosis. Further studies on the relationship between thyroid hormones and dopaminergic neurotransmission may be warranted.

Effects of 5HT2c Blockade of Dibenzodiazepines on Thyroid Levels in Patients with Schizophrenia or Schizoaffective Disorder

Drug-induced hypothyroidism has been often observed with the use of lithium in patients with mental disorders. However, atypical antipsychotic medications, especially those with serotonin 2c (5HT2c) blockade like dibenzodiazepines have not been examined for their association with the occurrence of subclinical hypothyroidism. Atypical antipsychotic medications are commonly used in patients with psychiatric disorders, specifically in schizophrenia and schizoaffective disorders. The objective of this retrospective case analysis is to examine the thyroid function of patients with schizophrenia or schizoaffective disorder receiving dibenzodiazepines. This study includes patients that are on one or more of these atypical anti-psychotic agents: clozapine, olanzapine, quetiapine. Clinical outcome measured includes the effect on dibenzodiazepines on thyroid function (e.g. TSH, Free T4, and T4). A total of 42 charts of the patients were included in the study. Out of the 42 patients, 13 had normal thyroid labs, 11 had abnormal thyroid labs, and 18 patients had a diagnosis of hypothyroidism, and currently on a thyroid medication. Therefore, 31% of these patients were found to have normal thyroid levels, while 69% of these patients were found to have either slightly abnormal thyroid indices (subclinical hypothyroidism), or an impairment of thyroid function. The results of our study show that in patients with schizophrenia or schizoaffective disorder that are on clozapine, olanzapine, quetiapine, or any combination of the four, a higher percentage of them exhibited abnormal thyroid function with subclinical hypothyroidism, or on thyroid supplements. Future studies may be warranted to further evaluate the effect of antipsychotics with 5HT2c blockade on thyroid function.

High prevalence of subclinical hypothyroidism during first trimester of pregnancy in North India

Background:Thyroid dysfunction is a common occurrence in pregnancy and affects both maternal and fetal outcomes. There are limited data on prevalence of hypothyroidism during pregnancy from India. Therefore, this study was designed to evaluate the prevalence of thyroid dysfunction especially hypothyroidism during first trimester in a large public hospital in North India.Materials and Methods:All the consecutive first trimester pregnant women attending Lok Nayak and Kasturba Hospitals were enrolled in the study after institutional ethics approval and consent from the study subjects. The pregnant women with diagnosed thyroid disease and on thyroid medications were excluded from the study. Morning samples of study participants were analyzed for thyroid hormone profile which included free T3, free T4, TSH, and TPO Ab. In addition, all study participants were tested for CBC, LFT, KFT, and lipid profile.Results:A total of 1000 women were enrolled for this prospective observational study. The mean (SD) age of study subjects was 25.6 (11.1) years, and mean (SD) gestational age was 10.3 (3.4) weeks. One hundred and forty-three (14.3%) subjects had TSH values more than 4.5 mIU/L above the cutoff used for definition of hypothyroidism. Out of these, 135 had normal free T4 and therefore labeled as subclinical hypothyroidism and 7 had low free T4 suggestive of overt hypothyroidism. TPO Ab was positive in 68 (6.82%) of total, 25 (18.5%) of subclinical and 5 (71%) of overt hypothyroid patients.Conclusion:Hypothyroidism, especially subclinical, is common in North Indian women during first trimester. Further countrywide studies are needed to evaluate the prevalence and etiology of hypothyroidism to prevent maternal and fetal adverse effects of hypothyroidism in India.

Falsely Undetectable TSH in a Cohort of South Asian Euthyroid Patients

An index case of a clinically euthyroid woman of South Asian descent was identified with discordant TSH results: undetectable TSH on our routine assay and normal TSH on an alternate assay. Low TSH concentrations due to functionally compromising TSH mutations have been reported. Here we describe a new phenomenon of functional TSH that is undetectable by 4 widely used US Food and Drug Administration (FDA)-approved TSH immunoassays marketed by a single vendor. The purpose of this study was to identify additional cases and investigate the cause of the falsely undetectable TSH. All samples with TSH results of <0.01 μIU/mL were retested with a second TSH assay. Discordant samples were evaluated on up to 8 FDA-approved TSH immunoassays and the TSHβ gene was sequenced. Retrospectively, thyroid function tests, diagnoses, and medications from 1.6 million individuals were analyzed. Out of approximately 2 million individuals, we have identified a cohort of 20 hypothyroid and euthyroid patients of shared ethnicity with falsely undetectable TSH (<0.01 μIU/mL) in 4 of 8 commercially available TSH assays. Half of these individuals were initially treated based on repeated falsely undetectable TSH values (7 euthyroid patients were treated with methimazole and 2 hypothyroid patients had doses of levothyroxine decreased). In all cases, a retrospective chart review revealed that clinical assessments and free T4 and total T3 results were inconsistent with the undetectable TSH results. Specific antibodies failing to detect TSH in these cases were identified in the 4 affected assays. A novel TSHβ point mutation was identified. Our data suggest that these individuals have a previously unrecognized, functionally normal, TSH variant to which some monoclonal antibodies fail to bind. To assure appropriate patient management, clinicians and laboratorians need to be aware that certain TSH variants may be undetectable in some hyperselective TSH assays.

General Error Analysis in the Relationship between Free Thyroxine and Thyrotropin and Its Clinical Relevance

Background. This treatise investigates error sources in measurements applicable to the hypothalamus-pituitary-thyroid (HPT) system of analysis for homeostatic set point computation. The hypothalamus-pituitary transfer characteristic (HP curve) describes the relationship between plasma free thyroxine [FT4] and thyrotropin [TSH]. Objective. We define the origin, types, causes, and effects of errors that are commonly encountered in TFT measurements and examine how we can interpret these to construct a reliable HP function for set point establishment. Design and Methods. The error sources in the clinical measurement procedures are identified and analyzed in relation to the constructed HP model. Results. The main sources of measurement and interpretation uncertainties are (1) diurnal variations in [TSH], (2) TFT measurement variations influenced by timing of thyroid medications, (3) error sensitivity in ranges of [TSH] and [FT4] (laboratory assay dependent), (4) rounding/truncation of decimals in [FT4] which in turn amplify curve fitting errors in the [TSH] domain in the lower [FT4] range, (5) memory effects (rate-independent hysteresis effect). Conclusions. When the main uncertainties in thyroid function tests (TFT) are identified and analyzed, we can find the most acceptable model space with which we can construct the best HP function and the related set point area.

A retrospective cohort analysis of the relationship between thyroid hormone level and herpes simplex virus-1 activation

A number of physiological factors have been suggested to participate in the Herpes Simplex Virus Type-1 (HSV-1) reactivation. Of particular interest is the effect of hormonal aberration on gene expression and activation. Thyroid hormone (TH) was shown to play a role in HSV-1 gene expression and replication in cell culture and animal models. We hypothesize that TH participates in the control of HSV latency and reactivation in humans by regulating viral gene expression and replication. Prior to implementing a full-scale population-based inquiry into this hypothesis, a pilot study using a pharmacy claims data base and a case-controlled, retrospective cohort preliminary investigation was conducted to develop further the hypothetical link between TH and HSV-1 reactivation. Using prescriptions for treating thyroid disorders and HSV-1 infections as proxies for biologic functions, we queried a prescription data base to construct two patient cohorts: Cohort 1 was comprised of patients receiving prescription drugs for thyroid disorders over a three-month period, and Cohort 2 was composed of patients not receiving thyroid medications during this period. HSV-1 medications were recorded for each cohort and the difference in the frequency of HSV-1 prescription drug utilization was examined for statistical significance. Using a 2 × 2 contingency table, a chi-square of 10.12 was calculated that was significant at p = 0.0015, confirming that a significant difference was found in HSV-1 utilization between these two cohorts, suggesting that patients who receive thyroid drugs have a greater chance of receiving antiviral drugs for HSV-1 infection/reactivation. Since this pilot study has inherent limitations in the data set, this finding is descriptive, not explanatory, and further research involving more detailed patient records in a larger patient population will be implemented to explore the relationship more robustly.

Deferasirox Is Associated with Reduced Mortality Risk in a Medicare Population with Myelodysplastic Syndromes

AbstractAbstract 426 Background:While there is extensive evidence of the impact of iron chelation therapy (ICT) on clinical outcomes in thalassemia patients (pts), there is a paucity of data relevant to myelodysplastic syndromes (MDS). In this study, we examined the association between oral deferasirox (DFX) therapy and conditions potentially associated with iron overload [congestive heart failure (CHF) and endocrine disease (diabetes or thyroid)], drug side effects (renal disease), and overall mortality, among MDS pts in a U.S. Medicare cohort. Methods:MDS pts from 2005–2008 were identified using ICD-9 CM codes (1 inpatient or 2 outpatient) from the 100% Medicare claims database. Pts meeting a minimum transfusion threshold of 20 units packed RBC were considered “eligible” for ICT. The study cohort consisted of ICT-eligible pts enrolled in Medicare Part D, under which oral drug prescriptions are reimbursed. The observation period began the week (wk) after the RBC threshold was met and ended at incident diagnosis of a condition of interest, death, or end of study. Patients receiving parenteral ICT (deferoxamine) during the observation period were excluded. Patients with a history of the specific condition (CHF, endocrine disease, renal disease) were excluded from the outcome-specific sample, but were included in overall survival analysis. Onset of CHF or renal disease was based on the presence of 1 inpatient or 2 outpatient Medicare claims with ICD-9-CM diagnoses of each condition. Onset of diabetes or thyroid disease was measured based on new use of oral anti-diabetic or thyroid medications, respectively. Covariates in the outcome models included demographics (age, sex, race), ICD-9 coded MDS risk category at diagnosis, baseline indicators for co-morbid conditions, and time-varying exposure to RBC, erythropoiesis-stimulating agents (ESA), lenalidomide and hypomethylating agents (HMA). Marginal structural models (MSM) estimated the effects of cumulative DFX, controlling for anemia management and patient characteristics. The analysis adjusted for effects of time-varying health status on the probability of receiving DFX. Results:The cohort of 4,226 beneficiaries with MDS was 54% female, 90% white, with mean age of 77.7 years. MDS risk status was 16% lower/del5q, 5% higher, & 79% not otherwise specified. Common baseline comorbidities included CHF (46%), diabetes (18%), thyroid disease (21%), and renal disease (29%). Drug exposures prior to cohort entry included ESA (84%), HMA (19%) and lenalidomide (7%). Prior ICT was noted for 4.5% of patients. Patients were observed for a median of 35 weeks. Death occurred in 2496 (59%) of the cohort. DFX was used during the observation period by 544 (12%) patients, with mean duration of 29.2 weeks (median 20.5). Estimates from MSM indicate that each incremental week of DFX was associated with a decreased risk of death [hazard ratio (HR) 0.987; 95%CI 0.981–0.993]. The magnitude of risk reduction increased from HR 0.77 (95%CI 0.536–1.02) for patients receiving 14–26 weeks of DFX to HR 0.342 (95%CI 0.179–0.651) for patients with 53 or more weeks. Cumulative RBC units were associated with increased risk of death (HR 1.01, 95%CI 1.007–1.013 per unit), as were a baseline solid tumor diagnosis, renal and cardiac disease, and poor predicted performance status. After controlling for time-varying incidence of sepsis, bleeds, and cytopenias in MSM treatment propensity model, DFX use was not found to be associated with altered risk of CHF, endocrine or renal disease. Conclusions:This is the first large population-based Medicare study evaluating the association between DFX use in older MDS patients and sequelae of iron overload and mortality. The decrease in risk of death was proportional to the duration of therapy. Application of MSM addresses the role of observed time-varying confounders between treatment and outcomes, while permitting us to assess the duration-outcome relationships. The MSM analysis cannot address potential confounding by unobserved factors that may influence physician selection of patients for ICT. Nonetheless, this retrospective analysis controls for bias associated with observed patient health status, and lends significant support to a positive association of oral iron chelation therapy with decreased mortality in MDS patients with a minimum transfusion threshold, and ongoing transfusion needs. Disclosures:Gore:Celgene Corporation: Consultancy, Research Funding. Baer:Novartis, Inc.: Research Funding; Celgene, Inc.: Research Funding. Sasane:Novartis Pharmaceuticals: Employment. Paley:Novartis: Employment. Davidoff:GlaskoSmithKline: Research Funding; National Institutes of Health: Research Funding; Celgene: Research Funding; Novartis: Research Funding.