Recombinant Human Thyrotropin Research Articles

Enhancement of Human Thyrotropin Synthesis by Sodium Butyrate Addition to Serum-Free CHO Cell Culture

The influence of sodium butyrate (NaBu) on the synthesis of recombinant human thyrotropin (r-hTSH) by CHO cells was investigated for the first time. A volumetric productivity of ~10 μg hTSH/mL was repeatedly obtained, with a 3.3-fold increase over a control culture carried out in the absence of NaBu. Since NaBu can induce CHO cell apoptosis and cell growth arrest, the increase in specific productivity was even higher, i.e., ca. 5-fold. Analysis of the N-glycan composition of r-hTSH obtained with the addition of NaBu to the culture medium showed an approximately 12 % increase in the amount of sialic acid, as well as in total carbohydrate, partly due to the increase in the site occupancy from 2.77 to 2.93 glycans per mole of hTSH. The two hormone preparations were characterized by N-glycan structural analysis, which showed that NaBu increased the bi-antennary structures by ca. 13 % while decreasing the tri-antennary structures by approximately the same amount. The in vivo biological activity and pharmacokinetic behavior (clearance) were found to be similar for the two hormone preparations.

Absence of Bone Marrow Toxicity in Elderly Patients Treated With Recombinant Human Thyroid-stimulating Hormone and Empirically Dosed Radioiodine for Thyroid Cancer

The purpose of this paper is to evaluate the rate of clinically significant bone marrow toxicity in elderly patients after recombinant human thyroid-stimulating hormone (rhTSH) and empirically dosed radioiodine therapy for thyroid cancer. This is a retrospective review of 15 patients with differentiated thyroid cancer that were at least 70 years old at the time of their first radioiodine treatment at our institution administered by the authors under a protocol involving an empiric dose prescription and preparation with rhTSH rather than hypothyroidism. The median dose per administration was 203 mCi and the median total dose per patient was 234 mCi. One third of the patients had at least 1 positive posttreatment whole-body scan and the other two thirds all had negative posttreatment whole-body scans. The primary study endpoint was a red cell, white cell, or platelet count below the lower limit of the normal range that produced symptoms or resulted in a recommendation for treatment. Complete blood count follow-up was at least 1 year in all patients, with a median value of 4 years. There was no evidence of clinically important bone marrow toxicity from radioiodine therapy in the patients in this study. No patient required treatment for anemia, leucopenia, or thrombocytopenia. In patients with normal renal function, clinically significant bone marrow toxicity from radioiodine therapy is highly unlikely with rhTSH preparation and empiric dosing with <250 mCi per administration and total cumulative doses <350 mCi.

18-Fluorodeoxyglucose Positron Emission Tomography in the Early Diagnostic Workup of Differentiated Thyroid Cancer Patients with a Negative Post-Therapeutic Iodine Scan and Detectable Thyroglobulin

Surgery and high-dose radioactive iodine ((131)I) treatment are the cornerstones in the treatment of differentiated thyroid cancer. Patients without (131)I uptake on the post-therapeutic whole body scan (WBS), but with detectable thyroglobulin (Tg) during thyroxine withdrawal (Tg-off), are evaluated with an 18-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) for tumor localization within three months. The yield of (18)F-FDG-PET imaging and clinical usefulness of a Tg-off cutoff value to predict a positive scan were assessed. From 2002 to 2011, 52 patients with a negative WBS and concurrent detectable Tg-off were evaluated. Thirty-five PET scans were performed during initial treatment, 17 after recurrent disease. Thirty-two patients were on substitution therapy, 17 were evaluated with endogenous thyrotropin elevation, and 3 after recombinant human thyrotropin stimulation. To determine the Tg-off cutoff value, a receiver operating characteristic curve was used. Nine (17%) (18)F-FDG-PET scans were true positive, 3 (6%) false positive, 36 (69%) true negative, and 4 (8%) false negative (sensitivity 69%, specificity 92%). In 13%, a true-positive scan resulted in a change in the clinical management. The area under the receiver operating characteristic curve is 0.82 [CI 0.64-0.99] (p<0.01), and the Tg-off cutoff value is 38.00 ng/mL (sensitivity 67%, specificity 95%). Ninety percent of (18)F-FDG-PET true-positive patients had a Tg-off >2.00 ng/mL. An (18)F-FDG-PET within three months after a negative WBS with detectable Tg-off showed additional tumor localization in 17% of the patients, leading to a change in clinical management in 13%. A clinically useful Tg-off cutoff value was not found, but 90% of positive (18)F-FDG-PET scans occurred in patients with a Tg-off >2.00 ng/mL.

Characterization of recombinant human and bovine thyroid-stimulating hormone preparations by mass spectrometry and determination of their endotoxin content

BackgroundThe TSH stimulation test to confirm canine hypothyroidism is commonly performed using a recombinant human TSH (rhTSH), as up to date, canine TSH is not yet commercially available. Limiting factors for the use of rhTSH are its high costs and occasional difficulties in product availability. Less expensive bovine TSH preparations (bTSH) purified from bovine pituitary glands are readily commercially available. The aim of this study was to evaluate two different bTSH products as alternative to rhTSH using mass spectrometry.ResultsMore than 50 proteins, including other pituitary hormones, bovine albumin, hemoglobin, and tissue proteins were identified in the bTSH preparations. In contrast, rhTSH proved to be a highly pure product. Significantly higher endotoxin levels could be detected in all bTSH products compared to the rhTSH.ConclusionsBoth bTSH products are crude mixtures and therefore not an acceptable alternative to rhTSH. Their use should be discouraged to prevent unintended side effects.

Salivary and Lacrimal Gland Dysfunction After Remnant Ablation with Radioactive Iodine in Patients with Differentiated Thyroid Carcinoma Prepared with Recombinant Human Thyrotropin

One of the adverse effects of radioactive iodine (¹³¹I) treatment in patients with thyroid cancer is damage to the salivary and lacrimal glands. In almost all studies evaluating salivary and lacrimal gland dysfunction, the patients received ¹³¹I after levothyroxine (L-T4) withdrawal. Since the biokinetics of ¹³¹I after recombinant human thyrotropin (rhTSH) is not the same as in hypothyroidism, studies need to evaluate ¹³¹I-induced salivary and lacrimal toxicity after preparation with rhTSH. This prospective study investigated the occurrence of salivary and lacrimal damage after ablation with ¹³¹I using this preparation. One hundred forty-eight patients who had a total thyroidectomy were included in the study. The subjects were evaluated after thyroidectomy during L-T4 use to exclude those who already showed symptoms or had a history of ocular or oral disease. Symptoms were investigated 12 and 18 months after ablation. In patients who had persistent symptoms, specific tests were performed to confirm glandular dysfunction and to rule out other causes. Twelve months after ablation, symptoms of salivary or lacrimal dysfunction were observed in 10 (6.7%) patients, including oral symptoms in 8 (5.4%) and ocular symptoms in 6 (4%). Eighteen months after ¹³¹I, symptoms persisted in eight (5.4%) patients, including oral symptoms in seven (4.7%) and ocular symptoms in five (3.4%). In all of the patients, glandular dysfunction was confirmed by specific tests and other causes were ruled out. No symptoms were seen in the patients who received a low ¹³¹I dose (30 mCi). In the patients who received high ¹³¹I doses (100 or 150 mCi), symptoms were noted 12 months after ¹³¹I in 10 patients (9.2%), and 18 months after ¹³¹I in 8 patients (7.4%). Apparently, the rates of salivary and lacrimal damage were lower than those reported in prospective studies that used similar ¹³¹I activities, but these studies were performed in patients who were hypothyroid at the time of ¹³¹I ablation. Further studies are needed to compare radiotoxicity between patients prepared for ¹³¹I ablation with rhTSH and those prepared for ¹³¹I ablation with L-T4 withdrawal.

Impact of Renal Function and Demographic/Anthropomorphic Variables on Peak Thyrotropin After Recombinant Human Thyrotropin Stimulation: A Stepwise Forward Multiple-Regression Analysis

When applying the recommended standard doses of recombinant human thyrotropin (rhTSH) in the diagnostic/therapeutic management of patients with differentiated thyroid cancer (DTC), the resulting peak TSH levels vary extensively. Previous studies applying multivariate statistics identified patient-inherent variables influencing the rhTSH/peak TSH relation. However, those results were inconclusive and partly conflicting. Notably, no independent role of renal function was substantiated, despite the fact that the kidneys are known to play a prominent role in TSH clearance from blood. Therefore, the study's aim was to investigate the impact of renal function on the peak TSH concentration after the standard administration of rhTSH used in the management of thyroid cancer. The second objective was to calculate a ranking regarding the effect sizes of the selected variables on the peak TSH. There were 286 patients with DTC included in the study. Univariate and multivariate analyses were performed, testing the correlation of serum creatinine and glomerular filtration rate (GFR) as surrogate parameters of renal function, age, sex, weight, height, and body surface area (BSA) with the peak TSH level. In six additional patients, the subsequent TSH pharmacokinetics after the TSH peak were measured and qualitatively compared. By univariate analyses, TSH correlated negatively with BSA, GFR, weight, and height, and positively with age, female sex, and serum creatinine (p<0.001). On the multivariate analysis, the stepwise forward multiple linear regression revealed BSA and renal function as the two most influential independent variables, followed by age, sex, and height. The pharmacokinetic datasets indicated that these identified parameters also influence the TSH decline over time. Identifying those patients with a favorable combination of parameters predicting a high-peak TSH is the first step toward an individualization of rhTSH dosing. Additionally, the subsequent TSH decrease over time needs to be taken into account. A complete understanding of the interrelation of the identified key parameters and both the TSH peak and subsequent TSH pharmacokinetics might allow for a more personalized rhTSH dosage strategy to achieve sufficient TSH levels instead of the fixed dosing procedure used at present.

The influence of single dose recombinant human thyroid-stimulating hormone on the efficacy of radioiodine therapy in patients with non toxic nodular goitre with low RAIU

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Site-Specific PEGylation of Human Thyroid Stimulating Hormone to Prolong Duration of Action

Recombinant human thyroid stimulating hormone (rhTSH or Thyrogen) has been approved for thyroid cancer diagnostics and treatment under a multidose regimen due to its short circulating half-life. To reduce dosing frequency, PEGylation strategies were explored to increase the duration of action of rhTSH. Lysine and N-terminal PEGylation resulted in heterogeneous product profiles with 40% or lower reaction yields of monoPEGylated products. Eleven cysteine mutants were designed based on a structure model of the TSH-TSH receptor (TSHR) complex to create unique conjugation sites on both α and β subunits for site-specific conjugation. Sequential screening of mutant expression level, oligomerization tendency, and conjugation efficiency resulted in the identification of the αG22C rhTSH mutant for stable expression and scale-up PEGylation. The introduced cysteine in the αG22C rhTSH mutant was partially blocked when isolated from conditioned media and could only be effectively PEGylated after mild reduction with cysteine. This produced a higher reaction yield, ~85%, for the monoPEGylated product. Although the mutation had no effect on receptor binding, PEGylation of αG22C rhTSH led to a PEG size-dependent decrease in receptor binding. Nevertheless, the 40 kDa PEG αG22C rhTSH showed a prolonged duration of action compared to rhTSH in a rat pharmacodynamics model. Reverse-phase HPLC and N-terminal sequencing experiments confirmed site-specific modification at the engineered Cys 22 position on the α-subunit. This work is another demonstration of successful PEGylation of a cysteine-knot protein by an engineered cysteine mutation.

Use of recombinant human thyroid-stimulating hormone for evaluation of thyroid function in guinea pigs (Cavia porcellus)

To evaluate the effects of administration of recombinant human (rh) thyroid-stimulating hormone (TSH) for evaluation of thyroid function in euthyroid guinea pigs (Cavia porcellus). Prospective, experimental study. 10 healthy, sexually intact, pet guinea pigs (approx 1 year of age). Guinea pigs were given rhTSH (100 μg, IM); plasma thyroxine concentrations were determined prior to and 3 and 4 hours after rhTSH injection. The animals were housed in 2 groups on the basis of sex and fed different commercial maintenance diets according to their husbandry. There was no significant difference in thyroxine concentrations between males and females before or after rhTSH injection. There was also no difference between thyroxine concentrations at 3 versus 4 hours after rhTSH injection. There was a significant difference between thyroxine concentrations before (median, 9.05 nmol/L [0.70 μg/dL]; 10% to 90% range, 7.39 to 16.99 nmol/L [0.57 to 1.32 μg/dL]) and after (mean ± SD, 23.95 ± 4.2 nmol/L) rhTSH injection. Euthyroid guinea pigs had plasma thyroxine concentrations of at least 7.30 nmol/L (0.57 μg/dL) and an increase of at least 2.6 times prestimulation thyroxine concentrations at 3 or 4 hours after stimulation. The results suggested that rhTSH administered IM can be used for the TSH stimulation testing in guinea pigs. We suggest thyroxine concentration in a euthyroid guinea pig should at least double 3 to 4 hours after rhTSH injection.

Long-Term Results after Treatment of Very Low-, Low-, and High-Risk Thyroid Cancers in a Combined Setting of Thyroidectomy and Radio Ablation Therapy in Euthyroidism

Introduction. Differentiated thyroid cancer treatment usually consists of thyroidectomy and radio ablation in hypothyroidism 4-6 weeks after surgery. Replacing hypothyroidism by recombinant human thyroid stimulating hormone can facilitate radio ablation in euthyroidism within one week after surgery. The outcome of this approach was investigated. Methods. This is a prospective randomized trial to compare thyroidectomy and radio ablation within a few days after preconditioning with recombinant human thyroid stimulating hormone versus thyroidectomy and radio ablation separated by four weeks of L-T4 withdrawal. Tumors were graded into very low-, low- , or high-risk tumors. Recurrence-free survival was confirmed at follow-up controls by neck ultrasound and serum thyroglobulin. Suspected tumor recurrence was treated by additional radio ablation or surgery. Quality-of-life questionnaires with additional evaluation of job performance and sick-leave time were used in all patients. Results. Radio ablation in euthyroidism in quick succession after thyroidectomy did not lead to higher tumor recurrence rates of differentiated thyroid cancers in any risk category and was significantly advantageous with respect to quality-of-life (P < 0.001), sick-leave time (P < 0.001), and job performance (P = 0.002). Conclusion. Recombinant human thyroid stimulating hormone can be used safely and with good efficacy to allow radio ablation under sustained euthyroidism within one week after thyroidectomy.

Recombinant Human Thyroid-Stimulating Hormone To Stimulate 131-1 Uptake For Remnant Ablation And Adjuvant Therapy

To review the current literature with regard to the use of recombinant human thyroid stimulating hormone (rhTSH) as an adjunct to radioactive iodine (RAI) remnant ablation and adjuvant therapy. Literature review of clinical studies examining rhTSH and/or thyroid hormone withdrawal preparations for RAI remnant ablation. The primary endpoints evaluated were (1) effectiveness at ablating the thyroid bed as demonstrated by the lack of significant uptake in the thyroid bed on follow-up diagnostic imaging and (2) effectiveness in facilitating the adjuvant therapy function of RAI ablation as manifested by follow-up thyroid stimulating hormone (TSH)-stimulated serum thyroglobulin levels and clinical outcomes (recurrence rates, likelihood of having no evidence of disease at final follow-up). RAI remnant ablation can be successfully achieved using either traditional thyroid hormone withdrawal or recombinant human TSH preparation. While initial studies included primarily thyroid cancer patients at low risk of recurrence, more recent studies suggest that rhTSH can also be effectively used as preparation for RAI ablation in patients with an intermediate or high risk of recurrence. Furthermore, while early studies focused primarily on the endpoint of thyroid bed remnant ablation, more recent retrospective studies suggest that final clinical outcomes (recurrence rates, likelihood of achieving no evidence of disease status at final follow-up) over 5-10 years of follow-up are very similar with either method of preparation. rhTSH is an effective alternative to thyroid hormone withdrawal in preparation for RAI remnant ablation in patients without evidence of distant metastases who are at low, intermediate, or high risk of recurrence.

Recombinant Human Thyrotropin-Aided Radioiodine Therapy in Tracheal Obstruction by an Invading Well-Differentiated Thyroid Carcinoma

Papillary thyroid carcinomas (PTCs) usually extend to lymph nodes in the neck and mediastinum. Rarely, they invade the neighboring upper airway anatomical structures. We report a 56-year-old woman who presented with symptoms of upper airway obstruction. Imaging studies revealed a lesion derived from the thyroid which invaded and obstructed the trachea, which appeared to be a highly differentiated PTC. Total thyroidectomy was performed, with removal of the endotracheal part of the mass along with the corresponding anterior tracheal rings. Two months later, a whole body I131 scan after recombinant human thyroid-stimulating hormone (rh-TSH) administration was performed and revealed a residual mass in upper left thyroid lobe. Subsequently, 150 mCi I131 were given following rh-TSH administration. Nine months later, there was no sign of residual tumor. This case is the first one reported in the literature regarding rh-TSH administration prior to RAI ablation in a PTC obstructing the trachea.

Improved follow-up of patients with differentiated thyroid carcinoma

SummaryAim: Physicians typically are unaware of the radioiodine uptake (RIU) detection limit (LoD) on scintigrams of differentiated thyroid carcinoma (DTC) patients. We evaluated a novel method to determine LoD as a quantitative upper limit for RIU in negative scans and as a value to contextualize faint visible uptake. Patients, methods: To test whether LoD is related to physicians’ ratings, RIU and LoD were calculated from scintigraphic count statistics for 120 static planar neck scans and were compared with the ratings of five nuclear medicine specialists blinded to patient/ scan characteristics regarding visible cervical uptake. Scans were acquired on days 1 (d1) and 2 (d2) post-administration of 298 ± 30 MBq iodine-131 in 60 consecutive DTC patients after recombinant human thyrotropin (rhTSH) or thyroid hormone withdrawal (THW) (n = 30 each). Results: Indicating good inter-observer agreement, ≥ 4 readers concurred regarding 56 (93.3%) [54 (90.0%)] d1[d2] scans. Seventeen scans from 12 patients received ≥ 3 positive votes; in 15 (88.2%), RIU exceeded LoD. RIU assessed from regions-of-interest over former thyroid beds in scans with ≤ 2 positive votes was typically below the LoD (99/103 scans, 96.1%). In 48 patients with ≤ 2 positive votes in both scans, LoD was a median 0.0094% (0.0050%) in d1(d2) images and was significantly lower (p &lt; 0.01) on early or late scans in 22 euthyroid rhTSH patients versus 26 hypo thyroid THW patients. Conclusion: LoD data obtained by the proposed method closely reflect nuclear medicine specialists’ scan ratings and provide comparators in serial scintigrams, improving diagnostic 131I imaging accuracy in differentiated thyroid carcinoma.

Current and Future Perspectives in Thyroid Carcinoma Treatment

Thyroid nodules are a common clinical problem and evaluation with neck and thyroid ultrasound and fine-needle aspiration biopsy are the most accurate methods for evaluating and identifying those that require surgical resection. The surgical treatment of differentiated thyroid carcinoma is the most common and recommended approach. Postoperative131I remnant ablation is used to eliminate the postsurgical thyroid remnant and may facilitate the early detection of recurrence. The conclusion of two important recent studies is that the use of recombinant human thyrotropin and low131I dose, 30 mCi, for postoperative ablation may be sufficient for the management of low-risk thyroid cancer. Recently, multitargeted kinase inhibitors have emerged as promising treatments for metastatic differentiated thyroid cancers based on mutation detection in samples from thyroid cancer. Motesanib, sorafenib, vandetanib, sunitinib, lenvatinib, imatinib, and cabozantinib are multikinase inhibitors that have the ability of inhibiting the rearranged during transection (RET) and vascular endothelial growth factor receptor (VEGFR), and other kinases, and have been used in advanced differentiated thyroid carcinoma. By contrast, axitinib and pazopanib seem to act only as anti-angiogenic agents. Anaplastic thyroid carcinoma is often advanced and metastatic at diagnosis. Patients with localized disease not amenable to surgical resection can be treated with adjuvant chemoradiotherapy.

Potential Use of Recombinant Human Thyrotropin in the Treatment of Distant Metastases in Patients with Differentiated Thyroid Cancer

In order to effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum TSH levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The goal of this review is to present current data on the relative efficacy and side effects profile of rhTSH-aided versus THW-aided RAI therapy for the treatment of patients with distant metastases of DTC. We have searched the PubMed database for articles including the keywords "rhTSH", "thyroid cancer", and "distant metastases" published between January 1, 1996 and January 7, 2012. As references, we used clinical case series, case reports, review articles, and practical guidelines. Exogenous stimulation of TSH is associated with better quality of life because it obviates signs and symptoms of hypothyroidism resulting from endogenous TSH stimulation. The rate of neurological complications after rhTSH and THW-aided RAI therapy for brain and spine metastases is similar. The rate of leukopenia, thrombocytopenia, xerostomia, and pulmonary fibrosis is similar after preparation for RAI treatment with rhTSH and THW. There is currently a controversy regarding RAI uptake in metastatic lesions after preparation with rhTSH versus THW, with some studies suggesting equal and some superior uptake after preparation with THW. Analysis of available retrospective studies comparing survival rates, progression free survival, and biochemical and structural response to a dosimetrically-determined dose of RAI shows similar efficacy after preparation for therapy with rhTSH and THW. The rhTSH stimulation is not presently approved by the FDA as a method of preparation for adjunctive therapy with RAI in patients with metastatic DTC. Data on rhTSH compassionate use suggest that rhTSH stimulation is as equally effective as THW as a method of preparation for dosimetry-based RAI treatment in patients with RAI-avid metastatic DTC.

Effect of 1110 MBq Radioiodine in Reducing Thyroid Volume in Multinodular Goiter: A New Protocol

BackgroundThere is no consensus on the optimal treatment of multinodular goiter (MNG), but in the past few years, the use of radioiodine has increased. This study’s objective was to evaluate adjuvant methimazole (MMI) therapy to increase and standardize radioiodine uptake (RAIU) with a fixed therapeutic 131I dose of 1110 MBq (30 mCi).MethodsOur study included 5 women with MNG treated with MMI, 10 - 15 mg/day for 2 to 4 months, prior to the administration of 1110 MBq 131I (30 mCi); none of the patients developed hypothyroidism during MMI therapy and had average basal TSH levels of 0.32 ± 0.39 mIU/L that increased to 2.6 ± 0.9 mIU/L (P = 0.07).ResultsRAIU increased from 25.6 ± 8.7% to 49.2 ± 8.3% (P = 0.003). All patients were followed for 12 months: median thyroid volume (TV) decreased from 77.2 mL (32.9 - 124.2) to 48.8 ml (12.4 - 68.9) with an average decrease of 46.4 ± 14.8% (P = 0.01). All patients developed hypothyroidism during the first 6 months after radioiodine therapy.ConclusionsThis new therapeutic protocol using MMI as adjuvant therapy is effective in increasing RAIU as well as the deleterious effects of 131I, without increasing the required dose, but leading to thyroid volume decreases similar to those reported with the use of recombinant human thyrotropin (rhTSH) or higher radioiodine doses.

The Role of Recombinant Human Thyrotropin for Diagnostic Monitoring of Patients with Differentiated Thyroid Cancer

The Role of Recombinant Human Thyrotropin for Diagnostic Monitoring of Patients with Differentiated Thyroid Cancer

Effect of Recombinant Human Thyrotropin on the Uptake of Radioactive Iodine (123I) in Dogs with Thyroid Tumors

In humans, recombinant human thyrotropin (rhTSH) enhances radioactive iodine uptake (RAIU) in patients with differentiated thyroid cancer. No studies have been performed in veterinary medicine to optimize radioiodine treatment of thyroid cancer. The aim of this study was to evaluate the effect of rhTSH on the uptake of radioiodine-123 (123I) in dogs with thyroid tumors. Nine dogs with thyroid neoplasia were included in this prospective cross-over study. The dogs were divided in 2 groups. In one group, 123I was administered for a baseline RAIU determination in week 1. In week 2 (after a washout period of 2 weeks), these dogs received rhTSH (100 μg IV) 24 h before 123I injection. In the other group the order of the protocol was reversed. For each scan, the dogs received 37 MBq (1 mCi) of 123I intravenously (IV) and planar scintigraphy was performed after 8 and 24 h for tumor RAIU calculation. Overall, rhTSH administration caused no statistically significant change on thyroid tumor RAIU at 8 h (p = 0.89) or at 24 h (p = 0.98). A significant positive correlation was found between the effect of rhTSH on tumor 8h-RAIU and rhTSH serum concentrations at 6 h (τ = 0.68; p = 0.03), at 12 h (τ = 0.68; p = 0.03) and at 24 h (τ = 0.78; p = 0.02) after rhTSH injection. This study suggests that IV administration of 100 μg rhTSH 24 h before 123I has an inconsistent effect on thyroid tumor RAIU. Further studies are necessary to determine the best protocol of rhTSH administration to optimize thyroid tumor RAIU.

Is recombinant human TSH as effective as thyroid hormone withdrawal in the detection and treatment of metastatic differentiated thyroid cancer?

Evaluation of: Van Nostr D, Khorjekav GR, O’Neil J et al. Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal in the identification of metastasis in differentiated thyroid cancer with 131I planar whole body imaging and 124I PET. J. Nucl. Med 53(3), 359–362 (2012).In a recent article, Van Nostrand et al. compared two methods of patient preparation, that is, recombinant human thyroid-stimulating hormone and thyroid hormone withdrawal, for the detection of metastasis in patients previously treated for differentiated thyroid cancer, using both 131I whole-body imaging and 124I positron emission tomography. The major finding of this prospective study was that the number of patients and the number of foci for patient positive at 131I whole-body imaging and 124I PET performed after thyroid hormone withdrawal was significantly higher when compared with that related to patients prepared with recombinant human thyroid-stimulating hormone.

Harnessing the skin-thyroid connection for wound healing: a prospective controlled trial in guinea pigs

Different elements of the hypothalamic-pituitary-thyroid axis have been found to be implicated in the normal physiology of the human skin. Their effects on wound healing and hair growth in rats have been described previously. There is close homology between the thyroid hormone receptors in humans and guinea pigs. To assess the effect of different doses of topical 3,3',5-triiodo-L-thyronine (T3) and recombinant human thyroid-stimulating hormone (TSH) on wound healing in guinea pigs. Wounds were dressed every other day for 7 days, during which clinical measurements of the wounded areas were performed. Histological examination was performed at the end of the study. Application of high and low concentrations of topical T3 but not TSH demonstrated a significant dose-dependent reduction in the wound surface area through a process of contraction. The main significant histological result was an increase in the hair-follicle count. Topical T3 enhances wound healing in guinea pigs, primarily by wound contraction. As this is a critical stage in healing of chronic ulcers, topical T3 could be a useful treatment for wounds.