Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model.

Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.

Acute Kidney Injury After Thyroid Hormone Withdrawal in an Adolescent with Papillary Thyroid Carcinoma.

Objectives: We report a patient with papillary thyroid carcinoma (PTC) who developed acute kidney injury (AKI) and elevated creatine kinase (CK) after thyroid hormone withdrawal (THW) prior to radioiodine therapy. Case presentation: A 12-year-old female patient who had undergone total thyroidectomy for PTC one year ago presented with leg pain for the past 2 days. Following THW 3 weeks ago, the case had received 70 mCI radioiodine treatment 6 days ago. Serum creatinine (1.53 mg/dL, normal range [NR]: 0.3-1.1), aspartate aminotransferase (102 IU/L, NR: 0-40) and CK (3451 IU/L, NR: 26-174) levels were elevated. Thyrotropin level was elevated (>100 µIU/ml, NR: 0.51-4.3), and free T4 level was decreased (0.05 ng/dL, NR: 0.98-1.63). Serum creatinine and CK levels decreased after intravenous hydration and levothyroxine treatment. Conclusion: In PTC cases with thyroidectomy, kidney function and CK elevation should be assessed after THW and dehydration should be prevented.

Serum afamin and its implications in adult growth hormone deficiency: a prospective GH-withdrawal study.

Introduction: Adult growth hormone deficiency (AGHD) is associated with a high prevalence of metabolic syndrome (MS), which contributes to the unfavorable cardiovascular risk profile in these patients. Insulin like growth factor-1 (IGF-1) is a widely used biomarker, however it does not always reflect the cardiometabolic risk and has a poor relationship with clinical efficacy endpoints. Consequently, there is an unmet need for biomarkers to monitor responses to GH-replacement. Afamin is a hormone-like glycoprotein, expressed in the liver. Higher afamin levels are strongly associated with MS and insulin resistance (IR). Although both MS and IR are very common in AGHD, afamin has not been investigated in these patients. Purpose: To investigate afamin as a potential biomarker in patients with AGHD. Materials and methods: Participants included 20 AGHD patients (11 GH-substituted and 9 GH-unsubstituted) and 37 healthy controls. Subjects underwent routine laboratory examinations, anthropometric measurements, body composition analysis using multi-frequency bioelectrical impedance analysis (InBody720) and measurement of serum afamin concentrations. In GH-substituted subjects, GH-substitution was withdrawn for 2 months. Measurements were carried out right before GH-withdrawal, at the end of the 2-month withdrawal period, and 1 month after reinstituting GH-replacement therapy (GHRT). Results: GH-unsubstituted patients demonstrated higher afamin levels compared to controls (p=0.03). Afamin positively correlated with skeletal muscle mass, bone mineral content, total body water, extracellular- and intracellular water content, insulin (all, p<0.01), HOMA-IR (p=0.01) and C-peptide (p=0.03) levels in AGHD but not in healthy controls. In GH-substituted patients 2-month of GH-withdrawal caused significant changes in body composition, including decreased fat-free mass, skeletal muscle mass, total body water, and intracellular water content (all, p<0.01); but these changes almost fully recovered 1 month after reinstituting GHRT. Unexpectedly, afamin levels decreased after GH-withdrawal (p=0.03) and increased with reinstitution (p<0.01). Changes of afamin levels during GH-withdrawal positively correlated with changes of HOMA-IR (r=0.80; p<0.01) and changes of insulin (r=0.71; p=0.02). Conclusion: Higher afamin levels in unsubstituted AGHD patients might indicate severe metabolic dysregulation. Significant changes accompanying GH-withdrawal and reinstitution, along with strong correlations with measures of IR, suggest that afamin could be a promising biomarker to monitor GHRT-associated changes of insulin sensitivity.

Thyroid Hormone Withdrawal versus Recombinant Human TSH as Preparation for I-131 Therapy in Patients with Metastatic Thyroid Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Differentiated thyroid carcinoma (DTC) is characterized by an excellent prognosis with a 10-year survival rate > 90%. However, when DTC develops in a metastatic form, it has been shown to significantly impact patient survival and quality of life. Although I-131 has been shown to be an effective therapy in patients with metastatic DTC, whether its efficacy after recombinant human TSH (rhTSH) is comparable to endogenous TSH stimulation by thyroid hormone deprivation (THW) is still debated. Our present study was prompted to compare clinical results obtained in metastatic DTC by I-131 administered after rhTSH and THW stimulation protocols, respectively. METHODS: A systematic search on PubMed, Web of Science, and Scopus was performed from January to February 2023. Pooled risk ratios with 95% CI were determined for evaluating the initial response after to I-131 therapy after preparation with rhTSH or THW and the disease progression. To track the accumulation of evidence and reduce type I errors because of small data, a cumulative meta-analysis was performed. A sensitivity analysis was also performed to examine the impact of individual studies on overall prevalence results. RESULTS: Ten studies were included with a total of 1929 patients pre-treated with rhTSH (n = 953) and THW (n = 976), respectively. The cumulative data of our systematic review and meta-analysis showed an increase in the risk ratio over the years without any change in favour of a pre-treatment or the other on the effectiveness of I-131 therapy of metastatic DTC. CONCLUSIONS: Our data suggest that pretreatment with rhTSH or THW has no significant impact on the effectiveness of I-131 therapy for metastatic DTC. This implies that concerns about the use of one or the other pretreatment should be deferred to clinical evaluations made considering patient characteristics and reduction in side effects.

Recombinant or endogenous thyroid-stimulating hormone for radioactive iodine therapy in thyroid cancer: state of knowledge and current controversies.

For patients undergoing radioiodine therapy (RIT) of differentiated thyroid carcinoma (DTC), thyroid-stimulating hormone (TSH) stimulation prior to RIT can be achieved using thyroid hormone withdrawal (THW) or administration of recombinant human TSH (rhTSH). As THW can lead to nausea, headaches, vomiting, fatigue, and dizziness secondary to transient acute hypothyroidism, rhTSH could be a good alternative. Recombinant human TSH has been administered in patients in order to stimulate TSH for RIT since 2005. According to the Martinique criteria formulated by the leading professional societies involved in care of patients with DTC, rhTSH can be applied in 3 settings: for remnant ablation, adjuvant treatment, and treatment of known disease. Numerous studies have investigated the effects of rhTSH as a method of TSH stimulation on the thyroid cell, the systemic effects, biokinetics, and clinical outcomes; however, no consensus has been reached about many aspects of its potential use. Recombinant human TSH is able to stimulate sufficient TSH levels (>30 mIU L-1) and is hypothesized to decrease risks of tumor cell proliferation. As rhTSH-use avoids the transiently impaired renal function associated with THW, radioiodine excretion is faster with the former, leading to a lower iodine-131 uptake and a difference in fractional remnant uptake, effective half-life, mean residence time, and dose to the blood. Differences between rhTSH and THW were observed in radioiodine genotoxic effects and endothelial-dependent vasodilation and inflammation. For thyroid remnant ablation, THW and rhTSH lead to similar remnant ablation rates. For adjuvant therapy and treatment of known disease, insufficient trials have been conducted and future prospective studies are recommended. The current review provides a state-of-the-science overview on the issues and debates surrounding TSH stimulation through either rhTSH adminsitration orendogenous TSH production after levothyroxin withdrawal.

Recombinant human thyrotropin versus thyroid hormone withdrawal preparation for radioiodine ablation in differentiated thyroid cancer: Experience in a South Taiwanese medical center.

This retrospective study was designed to compare the treatment response of patients with differentiated thyroid cancer (DTC) prepared for radioiodine ablation (RIA) with thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH) stimulation. Patients with DTC were followed-up retrospectively between 2013 and 2018 in Kaohsiung Chang Gung Memorial Hospital, Taiwan. We compared the excellent response ratios between THW (49.9%) and rhTSH (50.1%) stimulation. Patients were then divided into subgroups, on the basis of age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage, for analysis. In all, 647 patients were followed-up after RIA. The ratios of THW or rhTSH use in the different subgroups were not statistically significant. In all the patients, the excellent response rate with THW and rhTSH was 80% and 76.5%, respectively, which was not statistically significant. The subgroup analysis, including age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage (low and high risk), showed similar results. Furthermore, the logistic regression analysis revealed no statistically significant differences among the subgroups. The multivariate analysis showed extrathyroidal extension, lymph node metastasis, and high I131 dose were the prognostic factors affecting the excellent response rate. In conclusion, the THW and rhTSH preparations for RIA were similar in terms of the excellent response rates and subgroup clinical outcomes.

Effect of recombinant human thyroid stimulating hormone on long-term salivary gland dysfunction in thyroid cancer patients treated with radioactive iodine. A systematic review.

Adjuvant radioactive iodine (RAI) is administered to thyroid cancer patients following thyroidectomy for remnant tissue ablation and metastatic disease management. Patients are prepared with thyroid hormone withdrawal (THW) or recombinant human thyroid stimulating hormone (rhTSH). Long-term salivary gland dysfunction (LT-SGD) is a common, dosage-dependent, RAI adverse effect. Although rhTSH preparation seems to reduce LT-SGD, this effect could be due to lower RAI activity generally used in rhTSH-prepared patients. Therefore, this meta-analysis investigated the effect of preparation type on LT-SGD development. Literature search (PubMed, Medline, EmBase, Cochrane, Web of Science, LILACS, Google Scholar) was performed four times (January-November 2022) and studies reporting LT-SGD incidence ≥1 year after RAI in patients prepared with rhTSH/THW were identified. The LT-SGD risk ratio (RR) was estimated with various models considered for sensitivity analysis (fixed-effect, random-effects, study-quality adjusted, publication-bias adjusted, individual-patient-data meta-analysis adjusted for RAI). Subgroup analysis according to RAI activity (<3.7/≥3.7 GBq) also was performed. Literature search resulted in five studies (321 rhTSH, 632 THW patients). The pooled RRs according to various models were 0.65 (95% confidence interval -95CI, 0.49-0.86; fixed-effect); 0.62 (95CI, 0.38-1.02; random-effects); 0.72 (95CI, 0.54-0.96; quality adjusted); 0.76 (95CI, 0.58-0.99; publication-bias adjusted); 0.0.80 (95CI, 0.55-1.14; individual-patient-data meta-analysis). The pooled RRs stratified for RAI activity were 0.26 (95CI, 0.05-1.30) for <3.7 GBq; 0.75 (95CI, 0.57-0.98) for ≥3.7 GBq. The number of patients needed to be prepared with rhTSH to prevent one case of LT-SGD ranged between seven and thirty-seven. There is moderate-quality scientific evidence that rhTSH preparation may consistently protect salivary gland function.

Randomized Clinical Trial: Probiotics Alleviated Oral-Gut Microbiota Dysbiosis and Thyroid Hormone Withdrawal-Related Complications in Thyroid Cancer Patients Before Radioiodine Therapy Following Thyroidectomy.

Background: Thyroid hormone withdrawal (THW) in postoperative thyroid cancer patients who need always accompanied by complications (e.g., dyslipidemia and constipation). At present, there are no effective and safe means to alleviate these complications. Purpose: We aimed to assess the oral-gut microbiota profiles in THW patients then investigate whether probiotics could alleviating alleviate THW related complications and investigate whether these therapeutic effects were associated with the oral-gut microbiota state. Methods: Fifty eligible thyroid carcinoma patients undergoing thyroidectomy were randomly assigned to receive probiotics or placebo during THW. Complications were assessed through validated questionnaires and plasma lipid indicators. The complex probiotics preparation was composed of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus. Results: Probiotics alleviated lack of energy, constipation, weight gain, and dry mouth and decreased the levels of fecal/serum LPS and plasma lipid indicators (total cholesterol, triglycerides, low-density lipoprotein, and apolipoprotein A) (P < 0.05). Gut and oral microbial diversity were significantly decreased after THW, while an increased microbial dysbiosis index (MDI) was observed. Probiotics distinctly restored the gut and oral microbial diversity. Increased Holdemanella, Enterococcus, and Coprococcus_2, while decreased Fusobacterium, Eubacterium_ruminantium_group, Ruminococcus_1, and Parasutterella in the gut were found after probiotics intervention. Lack of energy, constipation, weight gain, and dyslipidemia were seen to be related to the above microbiota. In addition, probiotics reduced oral Prevotella_9, Haemophilus, Fusobacterium, and Lautropia, which were positively correlated with the occurrence of dry mouth. Conclusion: Probiotics reduce the incidence of complications in patients after THW, which may be related to modifying the oral and gut microbiota. Clinical Trial Registration: [https://clinicaltrials.gov/], identifier America Clinical Trial Registry NCT03574051.

Metastatic Differentiated Thyroid Cancer Survival Is Unaffected by Mode of Preparation for 131I Administration.

Context: Recombinant human thyrotropin (rhTSH) is currently not Food and Drug Administration approved for the treatment of high-risk patients with differentiated thyroid cancer (DTC). Objective: The goal of our study was to compare the outcomes in higher-risk patients with metastatic DTC prepared for radioiodine (RAI) therapy with rhTSH vs thyroid hormone withdrawal (THW). Methods: A retrospective chart review was performed of patients with metastatic DTC in follow-up at MedStar Washington Hospital Center and MedStar Georgetown University Hospital from 2009 to 2017. Patients were divided according to their preparation for RAI therapy, with assessment of progression-free survival (PFS) and overall survival (OS). Results: Fifty-five patients with distant metastases (16 men, 39 women) were prepared for RAI therapy exclusively either with rhTSH (n = 27) or with THW (n = 28). There were no statistically significant differences between the groups regarding clinicopathological features and history of RAI therapies. The median follow-up time for patients with rhTSH-aided therapies was 4.2 years (range, 3.3-5.5 years) and for patients with THW-aided therapies was 6.8 years (range, 4.2-11.6 years) (P = .002). Multivariate analysis showed that the method of thyrotropin stimulation was not associated with a difference in PFS or OS. Conclusion: As has been shown previously for low-risk DTC, this study indicates that the mode of preparation for RAI therapy does not appear to influence the outcomes of patients with metastatic DTC. PFS and OS were similar for patients with THW-aided or rhTSH-aided RAI therapies.

Feasibility of Recombinant Human TSH as a Preparation for Radioiodine Therapy in Patients with Distant Metastases from Papillary Thyroid Cancer: Comparison of Long-Term Survival Outcomes with Thyroid Hormone Withdrawal.

BACKGROUND: this study was designed to compare the long-term survival outcomes of patients prepared for radioiodine (RAI) therapy using either thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH) stimulation, by specifically focusing on cases with distant metastases from papillary thyroid cancer (PTC). METHODS: A retrospective analysis was performed on 88 patients with distant metastases from PTC. Fifty-one and thirty-seven patients were prepared for RAI treatment by either THW or rhTSH stimulation, respectively. The primary endpoints were progression-free survival (PFS) and disease-specific survival (DSS). RESULTS: The 10-year DSS rates of patients prepared for RAI therapy using either THW or rhTSH stimulation were 62.2% and 73.3%, respectively. Using multivariate analysis, RAI-avid metastases (p = 0.025) and preparation with rhTSH (p = 0.041) were identified as independent prognostic factors for PFS. Notably, PFS in the group of patients with RAI-avid metastases and preparation with rhTSH was significantly better than that in the other groups (p = 0.025). CONCLUSIONS: Preparation for RAI therapy using rhTSH stimulation is not inferior to THW preparation in terms of long-term survival outcomes experienced by patients with PTC and distant metastasis. Patients with RAI-avid metastases and preparation with rhTSH had the most favorable PFS.

Clinical features of migraine with onset prior to or during start of combined hormonal contraception: a prospective cohort study.

Many studies have described the features of menstrually related migraines but there is a lack of knowledge regarding the features of migraine in combined hormonal contraceptive users (CHC). Hormone-withdrawal migraines in the pill-free period could differ from those in the natural cycle. Gynaecologic comorbidities, like dysmenorrhea and endometriosis, but also depression or a family history might modify the course of migraine. A better understanding of migraine features linked to special hormonal situations could improve treatment. For this prospective cohort study, we conducted telephone interviews with women using a CHC and reporting withdrawal migraine to collect information on migraine frequency, intensity, triggers, symptoms, pain medication, gynaecologic history and comorbidities (n = 48). A subset of women agreed to also document their migraines in prospective diaries. The mean number of migraine days per cycle was 4.2 (± 2.7). Around 50% of these migraines occurred during the hormone-free interval. Migraine frequency was significantly higher in women who suffered from migraine before CHC start (5.0 ± 3.1) (n = 22) in comparison to those with migraine onset after CHC start (3.5 ± 2.1) (n = 26). Menstrually related attacks were described as more painful (57.5%), especially in women with migraine onset before CHC use (72%) (p < 0.02). Comorbidities were rare, except dysmenorrhea. The majority of migraine attacks in CHC users occur during the hormone-free interval. Similar as in the natural cycle, hormone-withdrawal migraines in CHC users are very intense and the response to acute medication is less good, especially in those women, who developed migraine before CHC use.

Recombinant human thyrotropin versus thyroid hormone withdrawal in differentiated thyroid carcinoma follow-up: a single center experience.

Introduction: Our goal was to evaluate and compare the diagnostic utility of thyroid hormone withdrawal (THW) and recombinant thyroid-stimulating hormone (rhTSH) methods in detecting recurrence/persistence (R/PD) of differentiated thyroid carcinoma (DTC). Methods: The study included 413 patients with DTC who underwent total thyroidectomy and had remnant ablation. DxWBS, s-Tg levels, R/PD were evaluated retrospectively. A s-Tg level≥2 ng/mL was considered as "positive s-Tg". Results: DxWBS and s-Tg levels were evaluated with rhTSH in 116 and THW in 297 subjects, respectively. The sensitivity and specificity of "positive s-Tg" for R/PD in THW group were 77.3% and 92.7%, with 90.3% accuracy, respectively. The sensitivity and specificity of "positive s-Tg" for R/PD in rhTSH group were 58.8% and 100% with 93.9 % accuracy, respectively. An uptake outside thyroid bed at WBS showed a sensitivity of 17.1%, specificity of 100% for R/PD with 89.4% accuracy in THW group. An uptake outside thyroid bed at WBS showed a sensitivity of 7.7%, specificity of 100% for R/PD with 88.8% accuracy in rhTSH group. Conclusion: Method of TSH stimulation did not influence the reliability of DxWBS. The "positive s-Tg level" had a higher sensitivity with THW when compared to rhTSH in detecting R/PD.

Pooled analysis of bleeding profile, efficacy and safety of oral oestradiol valerate/dienogest in women aged 25 and under.

Purpose: To evaluate differences in key outcomes between younger and older women receiving the oral contraceptive oestradiol valerate/dienogest (E2V/DNG).Methods: We conducted a pooled post hoc analysis of primary data from 12 studies of E2V/DNG, stratified by age (≤25 [n = 1309] and >25 [n = 2132] years). Outcomes included safety, efficacy, bleeding profile and hormone-withdrawal-associated symptoms (HWAS). Bleeding and HWAS analyses are also presented for women aged ≤20 years (n = 362). Discontinuations were considered a proxy for patient satisfaction.Results: Results were generally similar for younger and older women. The percentage of women aged ≤25 and >25 years experiencing intracyclic bleeding did not differ between groups (13.4% and 12.8% at cycle 12, respectively), with similar results in women aged ≤20 years (12.7%, cycle 12). Rates of withdrawal bleeding were very similar in women aged ≤25 and >25 years (78.5% and 78.9%, respectively, cycle 12). We also found a similar adjusted Pearl index in the two age groups (0.45 vs 0.57, respectively), similar rates of AEs and HWAS and no difference in discontinuations.Conclusions: Women aged ≤25 and >25 years have a similar experience with an E2V/DNV oral contraceptive, supporting this as an appropriate contraceptive option in younger and older women.

Pharmacokinetics of L-Triiodothyronine in Patients Undergoing Thyroid Hormone Therapy Withdrawal.

Background: L-triiodothyronine (LT3) is a substitute for levothyroxine (LT4) for thyroid cancer (TC) patients during the preparation for nuclear medicine procedures, and it is used in combination with LT4 in patients who do not respond to the standard treatment for hypothyroidism. This therapy is commonly done by using fixed doses, potentially resulting in supraphysiologic levels of triiodothyronine (T3). A good understanding of the LT3 pharmacokinetics (PK) is necessary to design combination treatment schemes that are able to maintain serum T3 levels within the reference range, but data on the PK of LT3 are conflicting. Here, we present a study designed to characterize the PK of LT3 in patients devoid of endogenous thyroid hormone production, and not receiving LT4 therapy. Methods: We performed an open-label, PK study in patients undergoing thyroid hormone withdrawal in preparation for nuclear medicine procedures for the evaluation and treatment of follicular-derived TC. LT3 was substituted for LT4 at a 1:3 mcg/mcg dosage ratio thrice daily for at least 30 days. PK of the last LT3 dose while at steady state and terminal elimination was assessed over 11 days. Thereafter, a PK study was performed following the nuclear medicine procedure in patients who volunteered for a second study. Results: Fourteen patients age 48.5 ± 16.0 years completed the last dose study and five completed the second PK study. PK analysis indicates a time to maximum serum concentration of 1.8 ± 0.32 hours and two distinct phases of linear elimination, with a fast distribution phase and slow elimination phases with half-lives of 2.3 ± 0.11 hours and 22.9 ± 7.7 hours, supporting a two-compartment model. PK modeling predicts that a twice-daily administration of low-dose LT3 (0.07 mcg/kg twice daily) in combination with LT4 can predictably increase the serum T3 concentration without significant peaks above the reference range. Conclusions: The PK of LT3 is well described by a two-compartment model that assumes elimination only from the sampling compartment, with a rapid distribution phase and a slow elimination phase. This information will contribute to design therapeutic strategies for LT3/LT4 combination therapies directed to maintain stable T3 serum levels.

Long-term outcomes of renal function after radioactive iodine therapy for thyroid cancer according to preparation method: thyroid hormone withdrawal vs. recombinant human thyrotropin.

PURPOSE: Long-term effects of iatrogenic hypothyroidism on renal function from thyroid hormone withdrawal during radioactive iodine therapy (RAIT) have not been studied, especially in subjects with mildly impaired renal function. We compared renal function in thyroid cancer subjects according to preparation method of either thyroid hormone withdrawal (THW) or injection of recombinant human thyrotropin (rhTSH). METHODS: This retrospective study enrolled 241 thyroidectomized patients (rhTSH group, n = 87 and THW group, n = 154). Changes in glomerular filtration rate (GFR) were measured prior to surgery, at the time of RAIT, and during a regular follow-up at least one year after RAIT. RESULTS: Baseline renal function was comparable between the rhTSH group and the THW group (91.4 mL/min/1.73 m2 vs. 92.4 mL/min/1.73 m2). At the time of RAIT, GFR was significantly decreased in the THW group (70.6 mL/min/1.73 m2, -23.6%), whereas renal function was preserved in the rhTSH group (85.4 mL/min/1.73 m2, -6.6%). In the THW group, renal function was fully recovered within 6 months after RAIT and was maintained up to 24 months, even in subjects with baseline GFR less than 90 mL/min/1.73 m2. CONCLUSIONS: THW for RAIT preparation induced considerable reduction in renal function, but this change was transient. In contrast, injection of rhTSH did not decrease renal function, making it a good option for RAIT preparation for subjects with renal dysfunction.

Does the use of recombinant TSH in preparation for I-131 scintigraphy scan affect hearing function?

OBJECTIVE: The objective of this study was to examine the effect of hypothyroidism on hearing function in patients surgically treated for differentiated thyroid cancer and subsequently experienced hypothyroidism during preparation for follow up I-131 scintigraphy scan by either recombinant human thyroid stimulating hormone (rhTSH) treatment or thyroid hormone withdrawal (THW). METHODS: A total of 55 patients undergoing I-131 scintigraphy scan following surgeries for differentiated thyroid cancer were included in the study, including 25 patients prepared by administration of recombinant TSH (rhTSH Group) and 30 patients by thyroid hormone withdrawal (THW Group). RESULTS: Air conduction thresholds at 1, 2 and 4 kHz for both ears were higher during hypothyroid period than during euthyroid period for patients in the THW group (p < 0.05) but not for patients in the rhTSH group. CONCLUSION: Sensorineural hearing loss was detected, especially at low frequencies, in patients with DTC after surgical treatment whose hormone replacement therapy was withdrawn but not in those receiving rhTSH. It is therefore preferred to use rhTSH when preparing for I-131 scintigraphy scan in patients at risk for hearing loss.

The inconvenience due to women's monthly bleeding (ISY) survey: a study of premenstrual symptoms among 5728 women in Europe.

OBJECTIVES: The aim of the ISY study was to investigate the prevalence of menstrual-related symptoms prior to and/or during menstrual or withdrawal bleeding among women from 12 European countries. METHODS: A 15-min quantitative online survey was conducted in two waves from February to September 2015 among 5728 women aged between 18 and 45 years, with an equal distribution of women using a combined hormonal contraceptive, including regular combined oral contraceptives (COCs) (CHC group, n = 2739) and women using a non-hormonal contraceptive or no contraceptive (non-HC group, n = 2989). RESULTS: The prevalence of at least one menstrual-related symptom was high in CHC users (93%) and in non-HC users (95%) (p < .0001) and the average number of symptoms reported was 5.3 vs. 5.9, respectively, (p < .0001). Pelvic pain, bloating/swelling, irritability and mood swing were reported in more than half of the women in both groups. Although generally modest, symptom severity was higher in non-HC users, except for headache. Overall, during the last four cycles, 60-75% of women did not require a treatment for most symptoms but headaches and pelvic pain. Mood swings/irritability, water retention/weight gain, lack of energy/mood swings and lack of energy/irritability were common symptoms that frequently co-occurred. No associations were reported between symptoms and age, educational qualifications or women's desire to reduce the frequency of menstruation. CONCLUSIONS: Premenstrual and menstrual symptomatology was less frequent, less numerous and less severe (except for headache) in women using CHCs; however, it remains a common concern. Reducing the frequency of menstrual periods could reduce withdrawal-related symptoms.

Improvement of migraine with change from combined hormonal contraceptives to progestin-only contraception with desogestrel: How strong is the effect of taking women off combined contraceptives?

Migraine is a disabling headache disorder, which affects up to 17% of the female population. Oestrogen withdrawal during the menstrual cycle or the hormone-free interval in users of combined hormonal contraceptives (CHC) plays a pivotal role. Two diary-based studies demonstrated a positive impact of the progestin-only pill (POP) desogestrel 75 µg on the frequency of the migraine attacks and pain intensity. In both studies, CHC users as well as nonusers were included, which makes it difficult to distinguish between the effect of taking women off the CHC and the benefit of the POP itself. With the present study, we compared the therapeutic effect of the POP desogestrel 75 µg on migraine in current CHC users and nonusers. We found a positive influence of desogestrel on migraine not only in women who switched from CHCs to desogestrel, but also in those who had not used hormones over 6 months before starting it. Our findings need to be confirmed in prospectively conducted studies with larger sample size.

Effects of thyroid hormone withdrawal on metabolic and cardiovascular parameters during radioactive iodine therapy in differentiated thyroid cancer.

Objective To investigate the cardiometabolic effects of a severe hypothyroid state induced by withdrawal of thyroid hormone replacement before radioactive iodine therapy. Methods Patients with thyroid cancer who were scheduled to receive radioactive iodine ablation were enrolled. Cardiometabolic parameters were measured using blood samples taken immediately before levothyroxine withdrawal, 4 weeks following withdrawal (on radiotherapy day), and 4 weeks following reinstitution of levothyroxine. Results Out of 48 patients (age 49.4 ± 10.5 years; 77.1% [37/48] female), the severe hypothyroid state induced by levothyroxine withdrawal significantly aggravated the majority of lipid parameters, particularly in patients with a greater number of metabolic syndrome components. Fasting plasma glucose levels and homeostatic model assessment values for insulin resistance and ß-cell function significantly decreased following levothyroxine withdrawal. Serum high-sensitivity C-reactive protein, fibrinogen and cystatin C levels significantly decreased, and homocysteine levels increased during the severe hypothyroid state. All of these changes were reversed by levothyroxine reinstitution. Conclusions Severe hypothyroid state induced pronounced changes in cardiometabolic parameters. Further studies should identify the long-term effects of changes in these parameters on cardiovascular morbidity and mortality in relation to thyroid disease.

Cytogenetic and dosimetric effects of (131)I in patients with differentiated thyroid carcinoma: comparison between stimulation with rhTSH and thyroid hormone withdrawal treatments.

A study directed to the cytogenetic and dosimetric aspects of radionuclides of medical interest is very valuable, both for an accurate evaluation of the dose received by the patients, and consequently of the genetic damage, and for the optimization of therapeutic strategies. Cytogenetic and dosimetric effects of (131)I in lymphocytes of thyroidectomized differentiated thyroid cancer (DTC) patients were evaluated through chromosome aberration (CA) technique: Euthyroid patients submitted to recombinant human thyroid-stimulating hormone (rhTSH) therapy (group A) were compared with hypothyroid patients left without levothyroxine treatment (group B). CA analysis was carried out prior to and 24 h, 1 week, 1 month and 1 year after radioiodine administration (4995-7030 MBq) in both groups. An activity-response curve of (131)I (0.074-0.740 MBq/mL) was elaborated, comparing dicentric chromosomes in vivo and in vitro in order to estimate the absorbed dose through Monte Carlo simulations. In general, radioiodine therapy induced a higher total CA rate in hypothyroid patients as compared to euthyroid patients. The frequencies of dicentrics obtained in DTC patients 24 h after treatment were equivalent to those induced in vitro (0.2903 ± 0.1005 MBq/mL in group A and 0.2391 ± 0.1019 MBq/mL in group B), corresponding to absorbed doses of 0.65 ± 0.23 Gy and 0.53 ± 0.23 Gy, respectively. The effect on lymphocytes of internal radiation induced by (131)I therapy is minimal when based on the frequencies of CA 1 year after the treatment, maintaining a higher quality of life for DTC patients receiving rhTSH-aided therapy.