The Combined Effect of Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors on Thyroid Function.

Background: Recent successes with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of solid malignancies have paved the way for a new era of combined therapy. A common side effect seen with each of these classes of treatment is thyroid dysfunction, with rates estimated at 30-40% for TKI and 10-20% for ICI. However, little is known about the effect of combined ICI+TKI therapy on thyroid function. Therefore, this study evaluated the incidence, clinical features, and risk factors for developing thyroid abnormalities during ICI+TKI therapy and the relationship to cancer outcomes. Methods: We conducted a retrospective cohort study of patients treated with combination ICI+TKI cancer therapy at City of Hope Comprehensive Cancer Center from 2017 to 2023 who had pretreatment normal thyrotropin (TSH) levels. Primary analyses assessed the frequency, timing, and severity of thyroid function test abnormalities during ICI+TKI cancer therapy, and the requirement for thyroid hormone replacement. Secondary analyses evaluated risk factors for the development of thyroid dysfunction, including sex and drug regimen, and the association with cancer progression-free survival or overall survival. Univariable and multivariable models were used. Results: There were 106 patients who received ICI+TKI therapy with a median age of 63.5 years and a median follow-up of 12.8 months (interquartile range [IQR] 5.9-20.9). Notably, 63.2% (67/106) developed thyroid function abnormalities during ICI+TKI therapy, including 11 (10.4%) with hyperthyroidism, 42 (39.6%) with subclinical hypothyroidism (SCHypo), and 14 (13.2%) with overt hypothyroidism. The onset of thyroid dysfunction occurred at a median of 7 weeks (IQR 3.1-9.0) after start of ICI+TKI treatment for hyperthyroidism, 8.0 weeks (IQR 3.0-19.0) for SCHypo, and 8.1 weeks (IQR 5.9-9.1) for overt or worsening hypothyroidism. Hyperthyroidism resolved to hypothyroidism or normal TSH without intervention in all subjects, suggesting thyroiditis, and hypothyroidism was readily treated with thyroid hormone replacement. Conclusions: Thyroid dysfunction is a frequent adverse event in individuals treated with combination ICI+TKI therapy, with our data suggesting a rapid onset and higher incidence than previously seen with ICI or TKI therapy alone. Therefore, close monitoring of thyroid function during initial therapy and multidisciplinary care with endocrinology are recommended to facilitate early detection and initiation of thyroid hormone replacement in these patients.

Computer-Assisted Levothyroxine Dose Selection for the Treatment of Postoperative Hypothyroidism.

Background: Thyroid hormone replacement with levothyroxine (LT4) is a recommended treatment for patients undergoing thyroidectomy. The starting LT4 dose is frequently calculated based on the patient's weight. However, the weight-based LT4 dosing performs poorly in clinical practice, with only ∼30% of patients achieving target thyrotropin (TSH) levels at the first thyroid function testing after treatment initiation. A better way to calculate the LT4 dose for patients with postoperative hypothyroidism is needed. Methods: In this retrospective cohort study we used demographic, clinical, and laboratory data for 951 patients after thyroidectomy and several regression and classification machine learning methods to develop an LT4 dose calculator for treating postoperative hypothyroidism targeting the desired TSH level. We compared the accuracy with the current standard-of-care practice and other published algorithms and evaluated generalizability with fivefold cross-validation and out-of-sample testing. Results: The retrospective clinical chart review showed that only 285/951 (30%) patients met their postoperative TSH goal. Obese patients were overtreated with LT4. An ordinary least squares regression based on weight, height, age, sex, calcium supplementation, and height:sex interaction predicted prescribed LT4 dose in 43.5% of all patients and 45.3% of patients with normal postoperative TSH (0.45-4.5 mIU/L). The ordinal logistic regression, artificial neural networks regression/classification, and random forest methods achieved comparable performance. LT4 calculator recommended lower LT4 doses to obese patients. Conclusions: The standard-of-care LT4 dosing does not achieve the target TSH in most thyroidectomy patients. Computer-assisted LT4 dose calculation performs better by considering multiple relevant patient characteristics and providing personalized and equitable care to patients with postoperative hypothyroidism. Prospective validation of LT4 calculator performance in patients with various TSH goals is needed.

Achievements in Hypothyroidism Treatment with Herbal Medicine: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Hypothyroidism is a common endocrine disease in the world that causes morbidity and mortality due to its association with metabolic diseases, especially in old age, and longterm treatment with levothyroxine causes many side effects for patients. Treatment with herbal medicine can regulate thyroid hormones and prevent side effects. OBJECTIVE: The purpose of this systematic review is the evaluation of the effect of herbal medicine on the signs and symptoms of primary hypothyroidism. METHODS: PubMed, Embase, Google Scholar, Scopus, and Cochrane Central Register of Controlled Trials were searched until 4 May, 2021. We selected randomized clinical trials (RCTs) that have assessed the effect of herbal medicine on hypothyroidism. RESULTS: Out of 771 articles, 4 trials with 186 participants were included. In one study, Nigella sativa L. caused a significant decrease in weight (P=0.004) and body mass index (BMI) (P=0.002). TSH levels were reported to be decreased and T3 increased in the treatment group (P =0.03) (P=0.008), respectively. In another study on Nigella sativa L., results did not show a significant difference between the two groups (p=0.02). A significant decrease in total cholesterol (CHL) and fasting blood sugar (FBS) was reported in participants with negative anti-thyroid peroxidase (anti-TPO) antibodies. In patients with positive anti-TPO antibodies, a significant increase in total cholesterol and FBS was observed in the intervention group (p=0.02). In the third RCT, T3 in the ashwagandha group at 4 and 8 weeks significantly increased by 18.6% (p=0.012) and 41.5% (p < 0.001), respectively. A noticeable increase was found in the T4 level from baseline by 9.3% (p= 0.002) and 19.6% (p < 0.001) at 4 and 8 weeks, respectively. TSH levels fell remarkably in the intervention group compared to placebo at 4 weeks (p <0.001) and 8 weeks (p <0.001), respectively. In the last article selected, Mentha x Piperita L. showed no significant difference in fatigue scores between intervention and control groups at the midpoint (day 7), while fatigue scores improved in the intervention group in all subscales compared to the control group on day 14. CONCLUSION: Some herbal remedies, including Nigella sativa L., ashwagandha, and Mentha x Piperita L., can improve the signs and symptoms of primary hypothyroidism, but using a more extensive and advanced methodology will provide us with more complete results.

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.

Serum lipid profile in relation to free thyroxine and the effect of levothyroxine treatment on lipids in patients with isolated hypothyroxinemia during pregnancy: a single-center retrospective study.

BACKGROUND: Thyroid function is widely considered a lipid metabolism regulator. However, studies on lipid metabolism in pregnant women with low free thyroxine (FT4) levels are limited and inconclusive. Furthermore, the association between maternal FT4 deficiency and adverse lipid metabolic parameters is unknown. Therefore, we aimed to investigate this association and the effects of levothyroxine (L-T4) treatment on these metabolic indicators. METHODS: This retrospective study included 164 patients with isolated hypothyroidism (IH) (FT4 levels below the 5th percentile with normal thyroid stimulating hormone levels according to the gestational-specific reference range) and 407 euthyroidism patients (control group who had regular antenatal examinations at Zhejiang Provincial People's Hospital, Hangzhou, China) between January 1, 2019, and December 31, 2020. Patients with IH were divided into levothyroxine (L-treatment group, n = 77) and dietary iodine supplement treatment groups (dietary treatment group, n=87) according to the hospital's treatment policy and clinical experience. The intervention lasted for at least 8 weeks. Metabolic indicators, including thyroid function and lipid parameters, were collected at least twice before and after the intervention. Other data collected included maternal age, history of abortion, prepregnancy BMI, and gestational weight gain (Fig. 1). RESULTS: Compared with the control group, Patients with IH had a higher degree of dyslipidemia, reflected in elevated total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) levels. In IH patients, an inverse correlation was found between FT4 and TG levels, which remained after adjusting for prepregnancy BMI. The L-treatment group demonstrated a significantly slower rate of hypercholesterolemia progression during pregnancy than the dietary treatment group. In addition, there was a relationship between the therapeutic effect and the degree of disease, with the main factors being FT4, TSH and TG levels prior to starting treatment. CONCLUSIONS: Low FT4 levels were associated with elevated blood lipid levels. Serum FT4 and lipid levels in patients could be improved by medical intervention.

Severe Resistance to Thyroid Hormone Beta in a Patient with Athyreosis.

We report a patient with congenital hypothyroidism due to athyreosis complicated by a heterozygous thyroid hormone receptor beta (THRß) gene mutation (R320L), resulting in a severe resistance to thyroid hormone beta phenotype. The proband inherited the mutant allele from his father, presenting a very mild phenotype. While the precise reason for this discrepancy remains unknown, we postulate the possibility of de novo mutation and mosaicism in the father. Correlating thyrotropin (TSH) with free thyroxine (fT4) allowed us to predict the amount of fT4 required to normalize the proband's TSH, which supported the treatment with high dose of levothyroxine.

Efficacy and safety of Barg-e-Sahajna (Moringa oleifera Lam.) in primary hypothyroidism.

OBJECTIVES: Hypothyroidism is the most common disorder arising from hormone deficiency. It frequently affects women than men. The prevalence of overall hypothyroidism has been reported to be 4.8-11%. Levothyroxine is the treatment of choice for all types of hypothyroidism. The purpose of this pilot study was to evaluate the efficacy and safety of Barg-e-Sahajna (Leaves of Moringa oleifera Lam.) among diagnosed patients of primary hypothyroidism. METHODS: This study was an open observational study. A total of 22 patients were screened, out of which 10 were excluded (did not meet inclusion criteria) and 2 refused to consent to be part of the study, rest 10 participants were enrolled after obtaining written informed consent finally 8 subjects completed the study and 2 are dropout in last follow up. The drug was given in the form of decoction at the dose of 5 g fresh leaves twice a day after meal for 45 days. RESULTS: The study effects on objective parameter thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were found extremely significant when compared before (16.62 ± 11.49, 132 ± 19.32, 9.28 ± 1.46) and after (4.75 ± 3.12, 150.37 ± 20.68, 11.84 ± 3.81) treatment with a significant decrease in serum TSH level (p<0.0246) and an increase in serum T3 (p<0.0005) and T4 (p<0.0438) levels. The results were analyzed using paired "t" test. CONCLUSIONS: The improvements in thyroid profiles (TSH, T3 and T4) after consuming 'Barg-e-Sahajna' show that the test drug is effective in primary hypothyroidism and the relief was considerable. No significant effect on safety parameters (serum-glutamic-oxaloacetic-transaminase [SGOT], serum glutamic-pyruvic transaminase [SGPT], blood urea, and serum creatinine) was observed. Therefore, it may be concluded that the Barg-e-Sahajna is preliminarily safe and effective in the management of primary hypothyroidism.

Hyperthyroidism treatment by alternative therapies based on cupping and dietary-herbal supplementation: a case report.

OBJECTIVES: Hyperthyroidism is characterized by increasing production of thyroid hormone (TH) and decreasing of thyroid stimulation hormone (TSH) secretion. The treatment of hyperthyroidism includes such as anti-thyroid drugs, radioiodine, and thyroidectomy have many side effects without complete curing results. We described a successful treatment of hyperthyroidism patient with dietary-herbal supplementation with wet cupping without any medicine. CASE PRESENTATION: A 29-years female, blood analysis showed that she had low TSH (0.012 mlU/mL), and normal levels of T3 and T4. After completing 16 weeks on Carbimazole, TSH value still low (0.024 mlU/mL) and urticaria was appeared. She decided to stop Carbimazole and try alternative therapy choices. She received wet cupping and dietary-herbal supplementations (including royal jelly, green barley grass and Taraxaf®) for two months. Notably, TSH values was increased during-after intervention and urticaria was disappeared. CONCLUSIONS: Alternative therapy could be a beneficial choice for hyperthyroidism treatment without any side effects or complications under physician supervision.

Role of Acupuncture and Fire Cupping in Reducing the Thyroxine Dose and Improving the Thyroid Function in Hypothyroidism Patients: A Case Series.

Hypothyroidism is one of the most common endocrine disorders linked to various systemic diseases ranging from obesity to cancers. The present line of management is insufficient as reports suggest that there is persistence of symptoms and poor adherence that makes the management of said disease challenging. Acupuncture and other Traditional Chinese Medicine (TCM) therapies are proven to alleviate endocrine dysfunctions. However, reports on acupuncture and cupping therapy on hypothyroidism are very scarce. Here, we report 5 cases of hypothyroid patients aged between 38-44 yrs who were treated with acupuncture and fire cupping for a period of three months. At the baseline, the patients presented with either a weak, wiry or vacuum pulse which represents spleen Qi deficiency. Further, they presented with elevated levels of Thyroid Stimulating Hormone (TSH), and higher Body Mass Index (BMI). Acupuncture treatment at ST36, LI4, SP6, and BL20 was given bilaterally whilst CV4, LR3, LR4, SP9, ST40, SP10, GV4, KI3, ST12, and SI17 were punctured unilaterally. At the end of the time period of three months, patients progressed to normal levels of TSH, reduction in BMI and had succeeded in tapering their medication doses. Supplementing this, the patients reported marked improvement in other symptoms like fatigue, hair loss, and cold feet post-treatment. The effects were consistent even during the three month follow-up period post-interventions. The results encourage the utilization of acupuncture and fire cupping in the management of hypothyroidism. However, large scale studies are warranted to strengthen this recommendation.

No difference in the outcome of metastatic thyroid cancer patients when using recombinant or endogenous TSH.

OBJECTIVE: At present, recombinant TSH cannot be used for the treatment of metastatic differentiated thyroid cancer patients. The aim of this study was to evaluate if the type of TSH stimulation, recombinant or endogenous, had an impact on the outcome of these patients. DESIGN AND METHODS: We compared the outcome of two propensity score-matched groups of metastatic patients, stimulated by either only recombinant TSH (n = 43) or only endogenous TSH (n = 34). RESULTS: As expected from the matching procedure, the clinical-pathological features and the cumulative 131-I activities administered to the two groups were very similar. After 4 years of follow-up, 4% of patients were cured, 3% had biochemical disease and 93% had structural disease. However, 91% of patients obtained a clinical benefit from this therapy in terms of stabilization of the disease or complete remission or partial response. When considering the two groups separately, we did not find any difference in their outcome. When considering the response to 131-I therapy of the single type of metastases, 8% of lymph node metastases and 8% of lung metastases disappeared but none of the bone metastases. The response to 131-I therapy of the single type of metastases was similar when we looked at the two groups separately. CONCLUSIONS: This study shows (i) an overall clinical benefit of the 131-I therapy, since the majority of patients remained affected but with a stable disease, and (ii) that the preparation with either recombinant or endogenous TSH has no impact on the 131-I therapy efficacy and the outcome of our two groups of patients.

The Role of Hormones and Trophic Factors as Components of Preservation Solutions in Protection of Renal Function before Transplantation: A Review of the Literature.

Transplantation is currently a routine method for treating end-stage organ failure. In recent years, there has been some progress in the development of an optimal composition of organ preservation solutions, improving the vital functions of the organ and allowing to extend its storage period until implantation into the recipient. Optimizations are mostly based on commercial solutions, routinely used to store grafts intended for transplantation. The paper reviews hormones with a potential nephroprotective effect, which were used to modify the composition of renal perfusion and preservation solutions. Their effectiveness as ingredients of preservation solutions was analysed based on a literature review. Hormones and trophic factors are innovative preservation solution supplements. They have a pleiotropic effect and affect normal renal function. The expression of receptors for melatonin, prolactin, thyrotropin, corticotropin, prostaglandin E1 and trophic factors was confirmed in the kidneys, which suggests that they are a promising therapeutic target for renal IR (ischemia-reperfusion) injury. They can have anti-inflammatory, antioxidant and anti-apoptotic effects, limiting IR injury.

Thyroid Uptake and Effective Half-Life of Radioiodine in Thyroid Cancer Patients at Radioiodine Therapy and Follow-Up Whole-Body Scintigraphy Either in Hypothyroidism or Under rhTSH.

Adjuvant radioiodine therapy (RITh) for differentiated thyroid carcinoma is performed either with thyroid hormone withdrawal or with administration of recombinant human thyroid-stimulating hormone (rhTSH). Heterogeneous results have been obtained on the impact of the method of patient preparation on thyroid uptake and whole-body effective half-life. A higher radiation exposure using thyroid hormone withdrawal for several weeks compared with rhTSH was reported in prior studies. It was the aim to examine whether these findings are reproducible in a modern protocol with a short interval between surgery and RITh. Methods: A retrospective study was performed on patients admitted for adjuvant RITh for differentiated thyroid carcinoma at the University Hospital of Cologne over a 5-y period from 2010. Dose rate measurements were analyzed for 366 patients, and subgroup analyses were performed for papillary thyroid cancer (n = 341) and follicular thyroid cancer (n = 25) patients, sex, length of hypothyroidism, and normal versus decreased glomerular filtration rate (GFR). Results: The median interval between surgery and RITh was 18 d for thyroid hormone withdrawal and 25 d for rhTSH (P < 0.01). The mean thyroid uptake was 4.2% ± 1.8% for the 300 hypothyroid patients versus 3.8% ± 1.6% (P = 0.12) for the 66 rhTSH patients. Whole-body half-life in the hypothyroid group was significantly longer at 19.3 ± 7.7 h versus 16.4 ± 4.6 h in the rhTSH group (P < 0.01). Results were predominantly influenced by data from the largest subgroup, that is, female papillary thyroid cancer patients. Within this group, whole-body half-life was significantly shorter in the rhTSH treatment arm. Duration of hypothyroidism and a decrease in GFR less than 60 mL/min/1.73 m2 significantly influenced results, with an increased whole-body half-life occurring in the hypothyroid group. When patients returned for whole-body scintigraphy, thyroid, half-life, and whole-body half-life were significantly shorter in the rhTSH groups, resulting in a low thyroid and remaining-body dose. Conclusion: With a shortening of the time between surgery and adjuvant RITh, thyroid uptake is not significantly changed but whole-body half-life becomes longer in the hypothyroid group. Radiation exposure for most patients is not significantly different. However, patients with a hypothyroid phase of more than 4 wk, and in particular those with a decreased GFR, experience higher radiation exposure.

Selected Controversies of Radioiodine Imaging and Therapy in Differentiated Thyroid Cancer.

This article discusses the more controversial areas of the management of differentiated thyroid cancer, namely, the utility of pretherapy staging radioiodine scans; the prescribed activity for iodine-131 remnant ablation, adjuvant treatment, and distant metastases; preparation with thyroid hormone withdrawal versus recombinant human thyroid-stimulating hormone; and the classification of radioiodine refractory differentiated thyroid cancer. The author reviews various aspects of the controversies, such as the recommendations of the 2015 guidelines of the American Thyroid Association, arguments for and against the various controversies, and selected references.

Differentiated Thyroid Cancer-Treatment: State of the Art.

Differentiated thyroid cancer (DTC) is a rare malignant disease, although its incidence has increased over the last few decades. It derives from follicular thyroid cells. Generally speaking, the prognosis is excellent. If treatment according to the current guidelines is given, cases of recurrence or persistence are rare. DTC requires special expertise by the treating physician. In recent years, new therapeutic options for these patients have become available. For this article we performed a systematic literature review with special focus on the guidelines of the American Thyroid Association, the European Association of Nuclear Medicine, and the German Society of Nuclear Medicine. For DTC, surgery and radioiodine therapy followed by levothyroxine substitution remain the established therapeutic procedures. Even metastasized tumors can be cured this way. However, in rare cases of radioiodine-refractory tumors, additional options are to be discussed. These include strict suppression of thyroid-stimulating hormone (also known as thyrotropin, TSH) and external local radiotherapy. Systemic cytostatic chemotherapy does not play a significant role. Recently, multikinase or tyrosine kinase inhibitors have been approved for the treatment of radioiodine-refractory DTC. Although a benefit for overall survival has not been shown yet, these new drugs can slow down tumor progression. However, they are frequently associated with severe side effects and should be reserved for patients with threatening symptoms only.

Efficacy of Low-dose and High-dose Radioactive Iodine Ablation With rhTSH in Korean Patients With Differentiated Thyroid Carcinoma: The First Report in Nonwestern Countries.

OBJECTIVE: The aim of this study was to confirm the equivalent efficacy of recombinant human TSH (rhTSH) and thyroid hormone withdrawal (THW) as used in the preparation for low-dose and high-dose radioactive iodine (RAI) ablation in Korean patients with differentiated thyroid carcinoma. SUBJECTS AND METHODS: This retrospective study was designed to compare the efficacy of rhTSH and THW when used before ablation with low-dose (30 mCi) and high-dose (100 mCi) RAI, respectively. The study group included 570 patients with DTC with tumors staged T1 to T3, N0 to N1, and M0. Before RAI ablation, 190 patients used rhTSH and 380 patients matched by age, sex, T-stage, and N-stage used THW. The success of ablation was evaluated in each group based on 4 criteria: (1) stimulated thyroglobulin (sTg) <2 ng/mL, (2) sTg<2 ng/mL and negative diagnostic whole-body scan (DxWBS), (3) sTg<1 ng/mL, and (4) sTg<1 ng/mL and negative DxWBS. RESULTS: When both sTg<2 ng/mL and negative DxWBS were selected as criteria for success in patients treated with low-dose RAI, the success rates were 80.5% and 77.0% with rhTSH and THW, respectively (95% confidence interval, 5.9-12.8). Using both sTg<1 ng/mL and negative DxWBS as criteria, success rates were 78.2% and 71.8% with rhTSH and THW, respectively (95% confidence interval, 3.6-16.2). Using any criteria for success, low-dose RAI ablation with rhTSH was as effective as THW. Similar results were found for high-dose RAI ablation in patients using either rhTSH or THW. CONCLUSIONS: Low-dose and high-dose RAI ablation were equally effective using either rhTSH or THW before ablation in Korean patients with DTC, respectively.

Recombinant human thyrotropin preparation for adjuvant radioiodine treatment in children and adolescents with differentiated thyroid cancer.

AIM: Although recombinant human thyrotropin (rhTSH) is widely used in treating differentiated thyroid cancer (DTC), almost all clinical investigation has been in adults. The aim of our retrospective study was to evaluate outcomes of adjuvant, rhTSH-aided radioiodine treatment in children/adolescents with DTC and to compare them to (131)I therapy during l-thyroxin withdrawal (THW). METHODS: Patients with the diagnosis of DTC who were ≤18 years of age and had no signs of persistent disease at the time of (131)I treatment were included; 48 patients were treated after rhTSH (rhTSH group) and 82 after THW group. The median time of follow-up after therapy was 67 months and was longer in the THW group (99 vs 43 months, P<0.05). RESULTS: On the day of (131)I administration, all but one patient had TSH levels above 25 µIU/ml. Peak TSH concentration was significantly higher in the rhTSH group (152 µIU/ml vs 91 µIU/ml). Similarly, the thyroglobulin concentration was higher in the rhTSH group (9.7 ng/ml vs 1.8 ng/ml). No side effects requiring medical intervention were recorded after rhTSH administration. The evaluation of disease outcomes during TSH stimulation (6-18 months after (131)I treatment) revealed equal rates of thyroid ablation (71%) in both groups. During subsequent follow-up, five patients showed recurrence (P>0.05). CONCLUSIONS: In children/adolescents, rhTSH-aided adjuvant radioiodine treatment is associated with rates of remnant ablation and short-term recurrence similar to THW. As this preparation has several advantages over THW, rhTSH may become the preferred method of TSH stimulation once studies of long-term outcomes show non-inferiority to THW in this age group.

Effects of Thyroid Hormone Withdrawal and Recombinant Human Thyrotropin on Glomerular Filtration Rate During Radioiodine Therapy for Well-Differentiated Thyroid Cancer.

BACKGROUND: Renal function is related to thyroid hormonal status, and glomerular filtration rate (GFR) seems to be impaired in patients with hypothyroidism. The aim of this work was to evaluate quantitatively the effect of hypothyroidism on GFR using a (51)Cr-EDTA radioisotope assay. METHODS: Twenty-eight patients without known renal disease or dysfunction who had been referred for radioiodine therapy (RIT) after total thyroidectomy were enrolled in this study and divided into two groups. Group A underwent thyroid hormone withdrawal (THW) resulting in hypothyroidism, while group B underwent recombinant human thyrotropin (rhTSH) stimulation and hence remained euthyroid. GFR was assessed by (51)Cr-EDTA before and after THW or rhTSH. RESULTS: No clinical differences were observed between the two groups. The mean ± SD GFRs were 94 ± 19 mL/min/1.73 m(2) before THW and 76 ± 16 mL/min/1.73 m(2) after THW for group A (p = 0.009), and 91 ± 18 mL/min/1.73 m(2) before rhTSH and 93 ± 15 mL/min/1.73 m(2) after rhTSH for group B (p = 0.613). The percent decrease in GFR during hypothyroidism is approximately 18-22%. CONCLUSION: GFR decreases in patients with normal kidney function during THW for RIT, and rhTSH preserves GFR in these patients. This GFR impairment following thyroidectomy is related to hypothyroidism due to a significant reduction in thyroid hormone levels and is not due to a rise in the TSH level.

Avoiding the prenatal programming effects of glucocorticoids: are there alternative treatments for the induction of antenatal lung maturation?

BACKGROUND: The long-term outcomes of antenatal glucocorticoids (GCs) vary between reports, and have generated controversy in terms of repeated and single-course events, causing irreversible effects on endocrine set points. AIM: This study aimed to assess the effects of alternative therapeutic agents other than synthetic glucocorticoid GC administration for fetal lung maturation. METHODS: A review of literature from PubMed, EMBASE, Cochrane Library, and Google Scholar was conducted to assess the use of alternative therapies to synthetic GCs using recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). End points included the rates of respiratory distress syndrome (RDS), mRNA expression for pneumocyte type II, concentration of surfactant proteins in alveolar lavage, morphological differences, histological proof of lung maturation, and angiogenesis or quantification of the surfactant pool. RESULTS: In all 41 studies examined, we found that ambroxol showed positive effects on lung maturation, but it has yet to be analyzed with sufficient significance in humans. Interleukins and TNF-alpha produce accelerated lung maturation, but have only been evaluated in basic research/experimental studies. Growth factors promote structural and functional growth in all phases of lung maturation, but little is known about their reciprocal effects and exact mechanisms as therapeutics. Thyroid releasing hormone or vitamin A cause detrimental side effects or were less effective for lung maturation. CONCLUSIONS: The efficacy and safety of these alternative agents are differentiated and none up to now can be recommended as an alternative to GCs.

Radioiodine ablation with 1,850 MBq in association with rhTSH in patients with differentiated thyroid cancer.

PURPOSE: The aim of this study was to evaluate the efficacy of post-operative radioiodine ablation with 1,850 MBq after recombinant human thyrotropin (rhTSH) administration in patients with differentiated thyroid carcinoma (DTC). We also aimed to assess the prognostic role of several patient features on the outcome of ablation. METHODS: We retrospectively analyzed data from a total of 125 patients with DTC who underwent post-operative radioiodine ablation with 1,850 MBq of ¹³¹I after preparation with rhTSH. One injection of 0.9 mg rhTSH was administered on each of two consecutive days; ¹³¹I therapy was delivered 24 h after the last injection, followed by a post-therapy whole-body scan. Successful ablation was assessed 6-12 months later and defined as an rhTSH-stimulated serum thyroglobulin (Tg) level ≤1.0 ng/ml and a normal neck ultrasound. RESULTS: Patients were stratified according to the American Thyroid Association (ATA) Management Guidelines for Differentiated Thyroid Cancer. Successful ablation was achieved in 82.4 % of patients, with an ablation rate of 95.1 % in low-risk patients and 76.2 % in intermediate-risk patients. Analyzing the correlation between ablation outcome and patient characteristics, we found a statistically significant association between failure to ablate and class of risk based on ATA guidelines (p = 0.025) and a stimulated Tg value at ablation of above 5 ng/ml (p < 0.001). CONCLUSION: The use of 1,850 MBq post-operative radioiodine thyroid remnant ablation in association with rhTSH is effective for low- and intermediate-risk patients. Moreover, in our study, we found a statistical correlation between failure to ablate and class of risk based on ATA guidelines for DTC and a stimulated Tg value at ablation.

Long-term outcome after radioiodine therapy with adjuvant rhTSH treatment: comparison between patients with non-toxic and pre-toxic large multinodular goitre.

In multinodular goitre (MNG), low radioiodine (RAI) activity after recombinant human (rh) TSH is able to reduce thyroid volume (TV) and improve symptoms. Our aim was to evaluate the long-term outcome of RAI after rhTSH treatment in patients who were divided according to their baseline TSH levels. Eighteen patients (69.2 ± 6.1 year) presented non-toxic (TSH >0.3 mIU/l) MNG (TV: 61.0 ± 3.8 ml; group 1), while 13 patients (74.1 ± 7.9 year) had non-autoimmune pre-toxic (TSH <0.3 mIU/l) MNG (TV: 82.6 ± 14.4 ml; group 2). TSH, thyroid hormones, TV (by ultrasonography), body mass index (BMI), symptoms and quality of life (QoL) were evaluated. Treatment induced short-term thyrotoxicosis in both groups, but this was slightly more marked in group 2 than in group 1. The number and severity of adverse events were similar. The follow-up period was 55.3 ± 4.1 months in group 1 and 57.2 ± 5.1 months in group 2. The final TV reduction was similar in groups 1 (63.4 ± 3.6%) and 2 (57.2 ± 4.6%) and TV reduction positively correlated only with initial TV. At the last examination, 14 group-1 subjects were on L-T4 therapy, while 2 group-2 subjects were on methimazole. An increase in BMI was noted only in group 2. MNG-related symptoms were significantly reduced in both groups. Symptoms related to sub-clinical hyperthyroidism improved in group 2, while no significant changes in QoL were noted in either group. This study confirms the effectiveness of rhTSH adjuvant treatment in reducing TV after low RAI activities, irrespective of baseline thyroid status. TSH levels <0.3 mIU/l proved to be predictive of a more severe thyrotoxic phase after rhTSH and RAI, while initial TSH levels >0.3 mIU/l were more frequently followed by a need for L-T4 therapy. Compressive symptoms improved in the majority of subjects.