Basal Thyroid-stimulating Hormone Research Articles

Thyroid-stimulating hormone levels are associated with estradiol levels and impact reproductive outcomes in preconceptionally euthyroid women undergoing their first IVF/ICSI cycles.

Controlled ovarian hyperstimulation (COH) has been reported to affect thyroid function; however, the impact of thyroid-stimulating hormone (TSH) levels during COH on embryo development and early reproductive outcomes has largely not been determined. Therefore, the aim of the present study was to investigate whether TSH levels are associated with COH and impact early reproductive outcomes in preconceptionally euthyroid women. This was a prospective cohort study. A total of 338 euthyroid women who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment using the gonadotropin releasing hormone agonist (GnRH-a) protocol were included. Samples were collected at different representative time points for TSH and estradiol measurements. TSH levels significantly increased with the administration of Gn and maintained this tendency until the trigger day. Basal TSH levels increased along with basal estradiol levels and remained stable when estradiol levels were higher than 150 pmol/L. On the trigger day, TSH levels changed with increasing estradiol levels in the high-normal basal TSH group but not in the low TSH group. TSH did not impact clinical pregnancy or early pregnancy loss after adjusting for age, stage or number of embryos. Serum TSH levels change significantly during COH and are associated with significant changes in estradiol levels. However, euthyroid women with high-normal TSH levels showed similar development potential for inseminated embryos and early reproductive outcomes compared to those with low TSH levels.

Thyroid function, glycemic control, and diabetic nephropathy in patients with type 2 diabetes over 24 months: prospective observational study

BackgroundThe higher prevalence of thyroid dysfunction in type 1 diabetes patients has been well established, whereas it is a matter of debate whether that is also observed in type 2 diabetes patients. This study was conducted to reveal whether higher prevalence of thyroid dysfunction is observed in patients with type 2 diabetes.MethodsWe examined thyroid functions and thyroid autoantibodies in 200 patients with type 2 diabetes and 225 controls, with 24 months follow up for those with type 2 diabetes.ResultsSerum free triiodothyronine (fT3) levels and fT3/free thyroxine (fT4) ratio were significantly lower, while fT4 levels were significantly higher in patients with type 2 diabetes. The number of patients with thyroid dysfunction or patients positive for thyroid autoantibodies were not different between the two groups. The fT3/fT4 ratio was positively and negatively correlated with serum c-peptide and HbA1c levels, respectively, suggesting that the difference can be attributable to insulin resistance and diabetic control. In the follow-up observation, we found no significant correlation between basal thyrotropin (TSH), fT3, fT4 or fT3/fT4 ratio with the amounts of changes of HbA1c levels at 12 or 24 months after the basal measurements. There was a negative relationship between TSH levels and eGFR at baseline measurements, but TSH levels did not seem to predict future decline of eGFR levels. No relationship was observed between urine albumin/ g‧cre levels and thyroid function.ConclusionThyroid dysfunction and thyroid autoantibodies were not different in prevalence between patients with type 2 diabetes and controls, although in patients with type 2 diabetes, the fT3/fT4 ratio was decreased. Basal thyroid function did not predict future diabetes control or renal function within 24 months of follow-up.

P-133 A study of the relationship between in vitro embryo development and maternal hypothyroidism

Abstract Study question Are there an association between the maternal thyroid condition and in vitro fertilization (IVF) outcomes? Summary answer Maternal hypothyroidism was found to be related to oocyte maturation and blastocyst development. What is known already Previous studies have shown that thyroid-stimulating hormone (TSH) levels affect ovarian stimulation in assisted reproductive technology (ART). In addition, changes in serum TSH levels have been linked to a sub-optimal environment for the implantation and development of the embryo. Thyroid-related receptors are present in granulosa cells, ovaries, and the endometrium. In addition, those receptors play a role in ovulation and folliculogenesis. This study aims to determine the association between maternal hypothyroidism and adverse implications for IVF outcomes in IVF/ICSI treated women. Study design, size, duration This retrospective study performed 333 cycles of 208 patients with TSH levels ranging from 0.043-16.627 µIU/mL, treated at the RMC National IVF Center between 2019 and 2022. The study population consisted of 1171 oocytes, which were divided into two groups based on their maternal basal TSH levels: normal TSH ≤ 2.5 µIU/mL (control group, n = 865, euthyroid) and higher TSH > 2.5 µIU/mL (case group, n = 306, hypothyroid). Participants/materials, setting, methods Maternal basal serum TSH levels were measured using Fluorescence Enzyme Immunoassay on the third day of the menstrual cycle. IVF outcome expressed oocyte maturation, fertilization, cleavage, and blastocyst formation rate. Oocytes were divided into mature (metaphase II) and immature (metaphase I and prophase I) groups. Blastocysts are graded by the Kato Ladies Clinic classification system and divided into high potential (A and B grades) and low potential (C, D, and E grades) groups. Main results and the role of chance In our study, there was no statistically significant difference in age and partner’s semen criteria between the two groups (p > 0.05). As regards oocyte maturation, MII oocytes retrieved significantly higher in the control group (82.2% vs. 75.8%). Logistic regression analysis found that TSH levels > 2.5 µIU/mL were related to statistically significantly increased risks of oocyte maturation stages like MI or GV (Age affect adjusted model: B = 0.456, p = 0.005; OR = 1.578, 95% CI = 1.146-2.175). The fertilization, cleavage, and blast formation rates have no differences between the groups. However, 91% (n = 324/356) of higher potential blastocysts in the control group were significantly higher than the case group (79.7%, n = 106/133). While, by the logistic regression analysis found that higher TSH levels ( > 2.5 µIU/mL) were related to statistically significantly increased risks of lower potential for implantation grades (B = 0.947, p = 0.001; OR = 2.579, 95%CI = 1.477-4.502). Limitations, reasons for caution The study relied on TSH as the primary indicator of thyroid function and excluded participants with abnormal prolactin levels. Other markers, such as FT4 and TSHR, should also be considered for a thorough evaluation of thyroid function. Wider implications of the findings Thyroid dysfunction can negatively impact IVF success, and screening and managing thyroid function in women undergoing IVF are essential. More research is needed to understand the mechanisms and develop strategies to improve oocyte and blastocyst quality. Trial registration number not applicable

Less basal thyrotropin levels predict antidepressant response in patients with major depression

IntroductionThe close association among thyroid metabolism, mood disorders and behavior has long been known. The role of basal thyroid axis in antidepressant treatment response is less known.ObjectivesThe aim of the present study was to study the association of basal serum thyrotropin (TSH) levels, with antidepressant treatment response in major depressive disorder.MethodsThirty-one depressed adult outpatients were included. Major depressive episode was diagnosed through the MINI (DSM-IV-TR) interview. Clinical symptomatology and blood samples were assessed at baseline, and at 4- and 8-weeks of either escitalopram or sertraline. Treatment response was defined by an improvement ≥50% in MADRS scores at 4-, and 8-weeks. Basal TSH levels were included in a linear regression model as predictor of treatment response.ResultsTwenty-seven patients finished 8-weeks of treatment. Response to treatment was of 74% at 4-weeks, and 63% at 8-weeks of antidepressant treatment. Basal median TSH levels were between normal ranges (M+SD=1.85+1,02 mlU/L). Basal TSH levels not correlated with basal MADRS scores, but with higher MADRS scores at week-4 (r=0,415, p=0,031) and at week-8 (r=0,392, p=0,043). Moreover, less baseline TSH levels trend to be a significant good predictor for treatment response at 4-weeks (R2=.116, p=.083); and a good predictor at 8-weeks treatment (R2=.147, p=.049).ConclusionsBaseline TSH levels even within the normal range may play a role in predicting antidepressant response.DisclosureNo significant relationships.

Thyroid Dysfunction after Gonadotropin-Releasing Hormone Agonist Administration in Women with Thyroid Autoimmunity.

GnRH agonists (GnRHa) are a useful tool for pretreatment before artificial endometrial preparation for frozen-thawed embryo-transfer (FET). Their prolonged administration has been associated with thyroid dysfunction, both hyper and hypothyroidism. The aim of this study is to investigate the impact of GnRHa administration on thyroid function in women undergoing artificial endometrial preparation. Seventy-eight euthyroid women undergoing endometrial preparation with hormone replacement for FET were retrospectively reviewed. They were divided into two groups according to pretreatment with GnRHa (group A, 42 women) or with an oral contraceptive (group B, 36 women). Group A was subsequently divided into two subgroups according to thyroid autoimmunity presence. Thyroid function has been evaluated and compared among groups and subgroups. Our results did not show any statistically significant differences in age, body mass index, and basal thyroid stimulating hormone (TSH). Total estradiol dosage, duration of treatment, and endometrial thickness were comparable among groups. When TSH was measured 14 days after embryo transfer, no significant differences between the two groups were reported. Among women of group A, TSH was significantly higher only in women with thyroid autoimmunity. GnRHa seems to be associated with thyroid dysfunction in women with thyroid autoimmunity undergoing hormone replacement therapy for FET.

Long-Term Effects of Lithium Use on Children and Adolescents: A Retrospective Study from Turkey.

Background: The aim of this study was to evaluate the long-term effects of lithium treatment on white blood cell (WBC) count, serum creatinine, and thyroid-stimulating hormone (TSH) levels in children and adolescents with bipolar disorder (BD) and non-BD in a Turkish children and adolescent sample. Methods: The study is based on retrospective chart review. Children and adolescent patients with BD and non-BD prescribed lithium in a mental health and neurological disorders hospital between 2012 and 2017 were included in the study. Data were collected from the electronic medical files. Laboratory values for WBC count, serum creatinine, and TSH levels at baseline within the week before the onset of lithium, and at 1st, 3rd, 6th, and 12th month of treatment were recorded. Results: A total of 143 patients (82 females, 61 males; 100 BD, 43 non-BD) aged 9-18 were included. Non-BD diagnoses were psychotic and schizoaffective disorders, unipolar depression, attention-deficit/hyperactivity disorder, conduct disorder, severe mood dysregulation syndrome, borderline personality disorder, and autism. Mean age of the participants were 15.90 ± 1.16 years for the bipolar group and 14.88 ± 1.79 years for the nonbipolar group. Patients with BD reported more adverse effects. There was a statistically significant increase in WBC counts and TSH levels at any time point. A statistically significant elevation in serum creatinine was found at 3rd and 12th month of treatment. During the course of lithium treatment, WBC counts exceeded 13,000 in 14 (9.8%) patients, and TSH levels exceeded 5.5 mU/L in 41 patients (28.6%). Twenty-one (14.68%) patients were started on thyroxin replacement. Basal TSH levels and duration of the lithium treatment were higher in the participants with TSH levels exceeding 5.5 mU/L. Lithium maximum dose, lithium blood level, basal TSH level, and duration of treatment were higher in the participants receiving thyroxin replacement. No patients had serum creatinine levels exceeding the normal reference values. Conclusion: Our study suggests that lithium is a generally safe and tolerable agent for children and adolescents with BD and non-BD; however, close monitoring of thyroid functions particularly in patients with a higher basal TSH level and longer duration of lithium use is important.

Effect of Ramadan Fasting on Thyroid Hormone Levels in Patients on Levothyroxine Treatment.

To evaluate the changes in thyroid functions in Ramadan, and compare late evening and pre-seheri use of levothyroxine in patients with hypothyroidism. Cross-sectional study. Department of Endocrinology, Ankara Ataturk Education and Research Hospital and Ankara Yildirim Beyazit University, Turkey, from May to June 2018. Patients who were on levothyroxine treatment and having normal thyroid functions were recruited for the study in the last one week before Ramadan. Patients were offered to take levothyroxine at 22.30-23.00 pm before sleep or between 01:30-03:00 am at least 30 min pre-seheri. There were 53 (85.5%) female and 9 (14.5%) male patients. Basal thyrotrophin (TSH) was 2.02 μIU/mL (0.27-4.14) and insignificantly increased at the end of Ramadan [2.18 μIU/mL (0.04-19.69), p=0.167]. Free-triiodothyronine (fT3) decreased while free-thyroxine (fT4) increased (p<0.001 for both). Eighteen patients preferred to take levothyroxine in late evening and 44 preferred to take at pre-seheri. There were insignificant increases in TSH in both groups (p=0.401 and p=0.276, respectively). At the end of Ramadan, TSH increased in 39 (63.9%), decreased in 22 (36.1%), and did not change in one patient. Increase in TSH was not significant after Ramadan. While there was an insignificant increase in median TSH, about one-third of patients had lower TSH, indicating for the need to evaluate every patient individually and follow closely during Ramadan. Clinical studies with larger sample sizes will be helpful to determine the optimal time for levothyroxine use during Ramadan. Key Words: Thyroid functions, Ramadan fasting, Hypothyroidism, Levotyhroxine.

Increased nitro-oxidative stress toxicity as a major determinant of increased blood pressure in mood disorders

BackgroundHypertension, atherogenicity and insulin resistance are major risk factors of cardiovascular disorder (CVD), which shows a strong comorbidity with major depression (MDD) and bipolar disorder (BD). Activated oxidative and nitrosative stress (O&NS), inflammatory pathways, and increased atherogenicity are shared pathways underpinning CVD and mood disorders. MethodsThe current study examined the effects of lipid hydroperoxides (LOOH), superoxide dismutase (SOD), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), and malondialdehyde (MDA) on systolic (SBP) and diastolic (DBP) blood pressure in 96 mood disordered patients and 60 healthy controls. ResultsA large part of the variance in SBP (31.6%) was explained by the regression on a z unit-weighted composite score (based on LOOH, AOPP, SOD, NOx) reflecting nitro-oxidative stress toxicity (NOSTOX), coupled with highly sensitive C-reactive protein, body weight and use of antihypertensives. Increased DBP was best predicted (23.8%) by body mass index and NOSTOX. The most important O&NS biomarkers predicting an increased SBP were in descending order of significance: LOOH, AOPP and SOD. Higher levels of the atherogenic index of plasma, HOMA2 insulin resistance index and basal thyroid-stimulating hormone also contributed to increased SBP independently from NOSTOX. Although there were no significant changes in SBP/DBP in mood disorders, the associations between NOSTOX and blood pressure were significant in patients with mood disorders but not in healthy controls. ConclusionsActivated O&NS pathways including increased lipid peroxidation and protein oxidation, which indicates hypochlorous stress, are the most important predictors of an increased BP, especially in patients with mood disorders.

TRH stimulation test in patients with repeatedly elevated TSH and normal FT4

ABSTRACT Subclinical hypothyroidism (SCH) is defined by elevated thyroid-stimulating hormone (TSH) with normal free thyroxine (FT4). We aimed to evaluate the thyrotropin-releasing hormone (TRH) stimulation test in patients with repeatedly elevated TSH (up to 10 mIU/l) and normal FT4, but without apparent thyroid disease. Women with TSH > 4.5 and ≤ 10 mIU/l (in two measurements) and normal FT4 were selected. Women with a known non-thyroid cause of TSH elevation, those treated with anti-thyroid drugs, amiodarone, lithium, and those with a history of thyroidectomy, neck radiotherapy and 131I treatment were excluded. Seventy women had negative antithyroperoxidase antibodies. Ultrasonography revealed a eutopic thyroid, usual echogenicity, and a volume ≤ 15 ml, and they underwent the TRH stimulation test during initial evaluation. After stimulation with TRH, TSH > 30 mIU/l was observed in 38 women (expected response), while 32 women had TSH < 20 mIU/l (inadequate response). Age, basal TSH or thyroid volume did not differ between both groups, but FT4 concentrations were significantly lower in the first group. Follow-up was available for 66/70 women. Seven women developed a need for levothyroxine, all of them in the group with an adequate response to TRH [7/36 (19.4%) versus 0/30]. The results suggest that some cases of TSH elevation (even persistent) do not represent the early stage of thyroid insufficiency.

Thyroid Therapy or Dysfunction in Athletes: Is it Time to Revisit the Clinical Practice Guidelines?

Recent media have highlighted the controversy surrounding treatment of elite athletes for hypothyroidism. The World Anti-Doping Agency denied a request by the United States Anti-Doping Agency to ban the use of thyroid medication. At present, there is no scientific evidence that thyroid medication has the potential to enhance performance. Clinical practice guidelines are not definitive in regard to what classifies a patient as having hypothyroidism. Thyroid-stimulating hormone and free T4 are recommended to screen for thyroid disease; however, the thyrotropin-releasing hormone stimulation test is still advocated by some for detecting the earliest stages of hypothyroidism. Hypothyroidism has been demonstrated to reduce cardiopulmonary function and result in musculoskeletal symptoms, such as fatigue and muscle stiffness. Symptoms of hypothyroidism, including depression, fatigue, and impaired sleep, are similar to those reported in overtraining. These patients may have hypothalamic-pituitary dysfunction that may complicate interpretation of basal thyroid-stimulating hormone and free T4. To date, no association has been identified between training state and hypothyroidism. Research to more clearly define hypothyroidism using provocative testing, evaluate the potential for thyroid medication to enhance performance, and examine whether training may induce hypothyroidism in athletes is desirable.

Effects of controlled ovarian stimulation on thyroid stimulating hormone in infertile women

ObjectiveTo study the effects of long-acting gonadotropin-releasing hormone agonist (GnRH-a) on thyroid function in euthyroid patients of in vitro fertilization (IVF)/ intracytoplasmic sperm injection of embryo transfer (ICSI-ET) and to investigate the timing and alteration of thyroid stimulating hormone (TSH) during controlled ovarian stimulation(COS). Materials and methodsEuthyroid patients scheduled for IVF/ICSI were enrolled. Euthyroidism was defined as having no history of hypothyroidism with normal TSH before IVF. Long GnRH-a protocol was chosen as COS protocol. 207 patients were divided into two groups based on basal serum TSH level: group A with 0.35mIU/L＜TSH＜2.5mIU/L (n = 137) and group B with 2.5mIU/L ≤ TSH＜4.5mIU/L (n = 70). Serum TSH was tested on 6 time points: before COS (2–5days in menstrual cycle, before GnRH-a injection), Gn injection day 1, Gn injection day 5, human chorionic gonadotropin (HCG) day, 14 and 28 days after transplantation. The serum TSH, clinical pregnancy and abortion rate were investigated. ResultThe serum TSH value was significantly (P < 0.05) increased after injection of long-acting GnRH-a in all patients. Both groups had significant (P < 0.05) increases in serum TSH level after long-acting GnRH-a injection. The TSH level was increased in 131(63.3%) patients after GnRH-a injection, of which twenty (9.7%) had subclinical hypothyroidism with TSH level over 4.5 mIU/L. The other 76 (36.7%) patients had decreased TSH. In group A, 79 (57.7%) patients showed an increase of TSH, including three patients (2.2%) with simultaneous rise of TPOAb and four (2.9%) diagnosed of subclinical hypothyroidism with TSH level over 4.5 mIU/L, and the rest fifty-eight (42.3%) patients had decreased TSH with one patient with elevated TPOAb who was diagnosed with subclinical hyperthyroidism. In group B, fifty-two (74.3%) patients showed an increase of TSH, including thirteen (18.6%) patients with elevated TPOAb and sixteen (22.9%) patients diagnosed of subclinical hypothyroidism with TSH level over 4.5 mIU/L, and the rest eighteen (25.7%) patients had decreased TSH with one patient diagnosed with subclinical hyperthyroidism. Group B had a significant higher proportion of patients with elevated serum TSH than group A (P ＜ 0.05). Compared to the baseline level, serum TSH ascended distinctly and reached peak level on HCG day in all patients. Group A and B had similar trends of alteration. Patients in group A had significantly (P＜0.05) higher clinical pregnancy rate than in group B. No significant (P＞0.05) difference in abortion rate were observed between the two groups. ConclusionGnRH-a can significantly increase serum TSH levels with possible development of subclinical thyroid dysfunction. Infertile patients with serum TSH > 2.5 mIU/L are more susceptible to GnRH-a while patients with basal TSH less than 2.5 mIU/L may get a higher clinical pregnancy rate when receiving IVF/ICSI.

Evaluation of serum concentrations of cortisol and thyroxine in bitches with early-stage mammary carcinoma

ABSTRACT: In view of the fact that cancer is considered a chronic disease that can interfere with hormonal homeostasis by means of cytokines, we hypothesized that, even at early stages, mammary carcinoma is able to alter the balance of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes. To test this hypothesis, the serum concentrations of basal cortisol, thyroxine (T4), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were evaluated in 20 unspayed bitches that had a histopathological diagnosis of grade 1 mammary carcinoma at clinical stage I according to the World Health Organization (WHO) classification (T1N0M0). The control animals comprised 10 unspayed bitches in perfect health conditions that were matched with those with mammary carcinoma by age. No significant differences regarding the concentrations of basal cortisol, TSH, t4, and fT4 were found between the bitches carrying early stage mammary carcinoma when compared to the control group. This suggests that, even if malignant, early-stage mammary carcinomas do not exhibit the ability to alter the concentrations of hormones produced by the hypothalamic-pituitary-adrenal or hypothalamic-pituitary-thyroid axes.

Mutations in IRS4 are associated with central hypothyroidism

BackgroundFour genetic causes of isolated congenital central hypothyroidism (CeH) have been identified, but many cases remain unexplained. We hypothesised the existence of other genetic causes of CeH with a Mendelian...

Lowered quality of life in mood disorders is associated with increased neuro-oxidative stress and basal thyroid-stimulating hormone levels and use of anticonvulsant mood stabilizers.

Major affective disorders including bipolar disorder (BD) and major depressive disorder (MDD) are associated with impaired health-related quality of life (HRQoL). Oxidative stress and subtle thyroid abnormalities may play a pathophysiological role in both disorders. Thus, the current study was performed to examine whether neuro-oxidative biomarkers and thyroid-stimulating hormone (TSH) levels could predict HRQoL in BD and MDD. This cross-sectional study enrolled 68 BD and 37 MDD patients and 66 healthy controls. The World Health Organization (WHO) QoL-BREF scale was used to assess 4 QoL subdomains. Peripheral blood malondialdehyde (MDA), advanced oxidation protein products, paraoxonaxe/CMPAase activity, a composite index of nitro-oxidative stress, and basal TSH were measured. In the total WHOQoL score, 17.3% of the variance was explained by increased advanced oxidation protein products and TSH levels and lowered CMPAase activity and male gender. Physical HRQoL (14.4%) was associated with increased MDA and TSH levels and lowered CMPAase activity. Social relations HRQoL (17.4%) was predicted by higher nitro-oxidative index and TSH values, while mental and environment HRQoL were independently predicted by CMPAase activity. Finally, 73.0% of the variance in total HRQoL was explained by severity of depressive symptoms, use of anticonvulsants, lower income, early lifetime emotional neglect, MDA levels, the presence of mood disorders, and suicidal ideation. These data show that lowered HRQoL in major affective disorders could at least in part result from the effects of lipid peroxidation, protein oxidation, lowered antioxidant enzyme activities, and higher levels of TSH.

Outcome of in vitro fertilization in women with subclinical hypothyroidism

BackgroundPrevious studies examining associations between subclinical hypothyroidism (SCH) with in vitro fertilization (IVF) outcome indicate some benefits of levothyroxine (LT4) treatment. But IVF outcomes in treated SCH women whose serum Thyroid Stimulating Hormone (TSH) concentration did and did not exceed 2.5 mIU/L before the IVF cycle has not been studied thoroughly.MethodsIn this study, we performed a prospective cohort study with 270 treated subclinical hypothyroidism patients undergoing their first IVF retrieval cycle at a single cite.ResultsSCH in women receiving LT4 replacement with a basal TSH level between 0.2-2.5mIU/L displayed a similar rate of clinical pregnancy (47.4% vs 38.7%, P = .436), miscarriage (7.4% vs 16.7%, P = .379) and live birth (43.9% vs 32.3%, P = .288) compared to women with a basal TSH level between 2.5-4.2 mIU/L.ConclusionStrictly controlled TSH (less than 2.5 mIU/L) before IVF may have no effect on the pregnancy rate in LT4 treated SCH women.

Hypothyroidism following allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia

BackgroundHypothyroidism may complicate allogeneic hematopoietic stem cell transplantation (allo-HSCT); we therefore analyzed risk factors in this study. Patients and methodsWe studied 229 patients with acute myeloid leukemia (AML) who underwent an allo-HSCT between 2003 and 2013 with different conditioning regimens (myeloablative, reduced-intensity, chemotherapy-based, or total body irradiation-based). Thyroid-stimulating hormone (TSH) and free thyroxine levels (fT4) were available in 104 patients before and after allo-HSCT. ResultsThe median age at transplantation (n=104) was 47 (IQR 40–59)], 37 (35.6%) patients were female, and the overall mortality was 34.6% (n=36). After a median follow-up period of 47 (IQR 25–84) months, overt hypothyroidism (basal TSH>4.49mIU/l, FT4<11.6pmol/l) was observed in 4 patients (3.8%) and subclinical hypothyroidism (basal TSH>4.49mIU/l, normal fT4) was observed in 20 patients (19.2%). Positive thyroperoxidase (TPO) antibodies were found in 5 (4.8%) patients. A total of 13 patients (12.5%) were treated with thyroid hormone replacement. Acute graft-versus-host disease (aGvHD) ≥grade 2 occurred in 55 (52.9%) and chronic GvHD (cGvHD) in 74 (71.2%) of the patients. The risk of developing hypothyroidism was higher in the patients with repeated allo-HSCTs (P=0.024) and with positive TPO antibodies (P=0.045). Furthermore, the development of overt hypothyroidism was inversely proportional to age (P=0.043). No correlation was found with GvHD, HLA-mismatch, total body irradiation, and gender. ConclusionAfter allo-HSCT, a significant number of patients experience thyroid dysfunction, including subclinical and overt hypothyroidism. Long-term and continuous follow-up for thyroid function after HSCT is important to provide timely and appropriate treatment.

A Worthy Finding: Decrease in Total Cholesterol and Low-Density Lipoprotein Cholesterol in Treated Mild Subclinical Hypothyroidism.

Mild subclinical hypothyroidism (SCH) affects a large number of people and is known to be a risk factor for dyslipidemia. However, whether mild SCH patients should be treated with L-thyroxine to improve lipid profiles remains controversial. In addition, it is also unclear whether all mild SCH patients can benefit from L-thyroxine treatment, regardless of basal thyrotropin or lipid levels. This study aimed to assess the effects of L-thyroxine replacement therapy on the lipid profiles of mild SCH patients. This open-label randomized controlled trial was performed in Ningyang County, Shandong Province, China. A total of 378 mild SCH patients with diagnoses confirmed by two thyroid function tests were randomly assigned to either the intervention group (L-thyroxine replacement therapy) or the control group (no treatment). The primary outcome was a change in serum total cholesterol (TC) concentration. In all, 369 participants completed the 15-month follow-up period. Reduced TC concentrations were more prominent in the intervention group than they were in the control group (-0.41 mmol/L vs. -0.17 mmol/L; p = 0.012), and changes in low-density lipoprotein cholesterol levels exhibited the same trend. Subgroup analyses were performed to assess the effects of L-thyroxine in patients with different thyrotropin or TC levels. When the study population was stratified according to basal thyrotropin concentration, all patients who had received L-thyroxine showed reduced TC levels (p < 0.001). The treatment was similarly beneficial for all patients, regardless of basal TC level. Even for subjects with TC levels <5.18 mmol/L, serum TC concentrations remained unchanged in the intervention group (p = 0.936) but increased by 0.35 mmol/L in the control group (p = 0.004). The findings suggest that mild SCH patients could benefit from L-thyroxine treatment to improve lipid profiles, regardless of basal thyrotropin or TC concentrations.

The Long-Term Impact Of Controlled Ovarian Hyperstimulation On Thyroid Function

Evidence on the long-term impact of controlled ovarian hyperstimulation (COH) on thyroid function is scarce. To investigate this, we report on serum thyroid-stimulating hormone (TSH) modifications in euthyroid and hypothyroid women during COH and 3 months after the end of the stimulation cycle. Women who underwent in vitro fertilization (IVF) and who did not become pregnant were eligible. Cases were women with treated hypothyroidism and basal serum TSH <2.5 mIU/L. Controls were euthyroid women matched to cases by age and basal serum TSH. Women could be included if serum TSH was available at 4 time points: prior to initiating COH (time 1); at the time of human chorionic gonadotropin (hCG) administration (time 2); 16 days after hCG administration (time 3); and 3 months after the end of the IVF cycle (time 4). Thirty-seven case-control pairs were included. Serum TSH at times 1, 2, 3, and 4 was 1.7 ± 0.6, 3.1 ± 1.4, 3.1 ± 1.3, and 2.7 ± 1.7 mIU/L, and 1.7 ± 0.6, 2.9 ± 1.0, 2.7 ± 1.0, and 1.9 ± 0.7 mIU/L among cases and controls, respectively. A statistically significant difference emerged at time 4 (P<.001). In both groups, serum TSH was higher at time 4 compared to time 1. Serum TSH exceeded the recommended threshold of 2.5 mIU/L at time 4 in 51% of cases (95% confidence interval [CI], 35 to 68%) and in 16% of controls (95% CI, 4 to 28%) (P = .003). COH seems to have a long-term impact on TSH levels. The magnitude of this effect is particularly pronounced in hypothyroid women.

The Role of Thyrotropin-Releasing Hormone Stimulation Test in Management of Hyperthyrotropinemia in Infants.

Objective:Hyperthyrotropinemia, which can be either a permanent or a transient state, is an asymptomatic condition and there is a controversy in management and long-term consequences. The aim of this study was to evaluate the results of thyrotropin-releasing hormone (TRH) test in infants with hyperthyrotropinemia.Methods:Data of the patients who underwent a TRH test for mildly elevated thyroid-stimulating hormone (TSH) levels between 2004 and 2011 in a single academic pediatric endocrinology unit were retrospectively reviewed from the case files.Results:Twenty infants (13 female, 7 male) with the median (range) age of 33 days (25-50) were enrolled into the study. The median basal TSH was 7.0 mIU/L (4.9-8.9) and free thyroxine level was 1.4 ng/mL (1.2-1.6) at the time of the TRH test. Thyroid ultrasonography was performed to 10 of the cases, and one of them had thyroid hypoplasia. TRH test revealed normal results in four infants, while sixteen infants had exaggerated response suggestive of primary hypothyroidism. The median follow-up period was 3.5 years (2.3-3.7). Therapy was discontinued in seven cases (2 had normal TRH response, 5 had exaggerated response) with the median age of 3.2 years (2.5-4). Of these seven infants, three had an elevated TSH on follow-up and L-thyroxine was restarted. All of the infants, in whom therapy was restarted, had exaggerated response to TRH.Conclusion:TRH test response could be a useful diagnostic test to evaluate the persistence of the disease during the infantile age period.

Comparison of conventional L-thyroxine withdrawal and moderate hypothyroidism in preparation for whole-body 131-I scan and thyroglobulin testing.

After thyroidectomy for thyroid cancer, patients often withdraw L-T4 for diagnostic or therapeutic purposes, showing signs and symptoms of hypothyroidism. A slighter hypothyroidism (reducing L-T4 to one-half) has been proposed to limit these inconveniences. We evaluated half-dose L-T4 protocol, in comparison to conventional L-T4 withdrawal, in terms of effectiveness and improvement of clinical and biochemical disorders. We randomized 55 thyroid cancer patients into two groups: 29 patients underwent 5 weeks of half-dose of previous L-T4 treatment (HD group); 26 patients replaced L-T4 with L-T3 for 3 weeks followed by 2 weeks of withdrawal (TW group). Clinical features (Zulewsky clinical score) and biochemical parameters (lipids, liver, and muscle enzymes) were evaluated in all patients at baseline and after 5 weeks. Total cholesterol, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase increased at 5 weeks in both groups, but significantly more in TW, but no difference was found by clinical score. Patients who achieved the thyroid-stimulating hormone (TSH) target value (25 µU/ml) were 92.3% in TW group and 48.3% in HD group (p < 0.001). In the HD group, only basal TSH statistically correlated with the achievement of the TSH target. Receiver operating characteristic curves indicated that a basal TSH ≥0.52 μU/ml is required to reach an adequate TSH level. Half-dose L-T4 protocol, compared to conventional L-T4 withdrawal, is associated with less biochemical disorders but no significant clinical advantage. Therefore, the half-dose protocol reaches an adequate TSH target in 48.3% of patients and is not effective unless basal serum TSH is ≥0.52 μU/ml.