Long-term follow-up of RET Y791F carriers in Denmark 1994-2017: A National Cohort Study.

BACKGROUND AND OBJECTIVES: Recently, a comprehensive study presented evidence that a long-disputed REarranged during Transfection (RET) variant, RET Y791F, should be classified as nonpathogenic. In spite of this, several subsequently published papers, including the revised American Thyroid Association guidelines for medullary thyroid carcinoma, refer to the variant as pathogenic. This study presents data from a unique national Danish cohort of RET Y791F carriers who have been followed by watchful waiting instead of being subjected to early thyroidectomy, to determine if any carrier shows evidence of multiple endocrine neoplasia 2A (MEN2A) at long-term follow-up. METHODS: A national cohort of all patients tested for RET mutations in Denmark from September 1994 to October 2017 was searched for carriers of RET Y791F. Medical records and laboratory reports of carriers were reviewed for signs of MEN2A at latest follow-up (medullary thyroid carcinoma, primary hyperparathyroidism, pheochromocytoma, cutaneous lichen amyloidosis, or Hirschsprung's disease). RESULTS: In total, twenty RET Y791F-carriers were identified, none of whom showed any evidence of MEN2A, despite an age range from 7 to 87 years. CONCLUSIONS: Our national cohort study of all Danish RET Y791F carriers substantiates the claim that the RET Y791F variant is nonpathogenic.

Changes in quality of life 6 months after parathyroidectomy for primary hyperparathyroidism.

Objective: The extent of symptoms due to primary hyperparathyroidism (PHPT) depends on the population being studied. PHPT is mainly discovered incidentally through routine laboratory findings. Less is known about patient-experienced improvement following successful parathyroidectomy. The aim of our study was to assess the changes in the quality of life (QoL) after successful surgery using an SF-36 questionnaire. Design: This is a prospective cohort study based on questionnaires. Methods: Forty consecutive patients diagnosed with PHPT were prospectively administered an SF-36 questionnaire before and 6 months after successful parathyroidectomy. A subgroup of 18 patients answered the questionnaire at 1 and 3 months after surgery. Successful surgery was based on biochemistry and pathology reports as confirmed by an endocrinologist. Results of each SF-36 subcategory were compared to the results at baseline in order to detect changes in patient-reported QoL after successful surgery. Results: There were significant improvements in six of eight SF-36 subcategories: vitality (P = 0.0001), physical functioning (P = 0.04), general health perception (P = 0.004), physical role functioning (P = 0.04), social role functioning (P = 0.004), and mental health perception (P = 0.0001). Changes appeared within a month after surgery with no further significant changes at later time points. Conclusions: Parathyroidectomy significantly improves QoL as measured by a decrease in SF-36 scores as early as 1 month after successful parathyroidectomy. The SF-36 QoL questionnaire is suitable for monitoring changes in patient well-being after successful parathyroidectomy.

Spinal versus conventional fine needle for ultrasound-guided thyroid nodule biopsy: a protocol for a randomised clinical trial.

INTRODUCTION: Thyroid nodules are very common and constitute an increasing clinical challenge since improved imaging capabilities and utilisation have led to a higher number of incidental findings. Ultrasound-guided fine-needle aspiration biopsy (FNAB) is the standard diagnostic tool in the work-up of thyroid nodules suspected of malignancy. Non-diagnostic results remain common and require repeated FNAB, leading to increased costs and delayed treatment of thyroid diseases, including treatment of thyroid cancer. If cytological diagnoses cannot be achieved, surgery may be warranted, which may potentially lead to overtreatment. Optimisation of the FNAB procedure is therefore essential. Spinal needles with a stylet have been found to lead to fewer non-diagnostic results, but studies on the subject are few. METHODS: This is a multicentre, two-arm, randomised clinical trial. Adults with thyroid nodules suspected of malignancy will be included consecutively. A total of 350 patients will be assigned randomly 1:1 to have a FNAB with either a spinal (25G) or a conventional (25G) needle. The primary outcome is the rate of diagnostic cytological samples according to the Bethesda system. Secondary outcomes are patient-experienced pain, complication rate and sensitivity and specificity. CONCLUSIONS: This trial will explore whether FNAB from thyroid nodules employing spinal needles compared with conventional fine needles improves diagnostic results, thereby providing evidence-based recommendations for a future choice of the FNAB needle. Secondary outcomes are patient-experienced pain, complication rate and sensitivity and specificity. FUNDING: This trial received funding from Erik and Susanna Olesens Fond. The funding source had no influence on trial design, data collection, analysis or publication. CLINICALTRIALS: gov Identifier: NCT04879355. Registration date: 07032021; version: 29062022.

Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules.

Fine needle aspiration biopsy (FNAB) remains crucial in the evaluation of thyroid nodules with suspicious clinical findings or ultrasound (US) features suggestive of malignancy. The use of US-guidance for FNAB allows real-time visualization of the needle, but is also highly operator-dependent. Physicians from many specialties (endocrinologists, otolaryngologists/endocrine surgeons, nuclear medicine physicians, radiologists, and pathologists) are involved in the diagnostic workup of thyroid nodules and a standardized and meticulous technique for US-FNAB is essential for lowering the yield of nondiagnostic specimens and false-negative results. This video, therefore, demonstrates a well-proved technique and technical tips to increase the diagnostic results from US-FNAB.

Locating hyperfunctioning parathyroid glands using 11C-Choline PET/CT: an inter- and intra-observer variation study.

BACKGROUND: Use of 11C-Choline PET/CT is gaining ground in detecting hyperfunctioning parathyroid glands in primary hyperparathyroidism. The purpose of this study was to evaluate the robustness of 11C-Choline PET/CT by assessing intra- and inter-observer agreement to determine whether the method was reader sensitive and therefore should only be performed at highly specialised sites with a high number of cases. PET/CT images of 40 patients diagnosed with primary hyperparathyroidism were anonymised and evaluated three times by three readers: an expert reader and two non-experts (non-experts were experienced in PET/CT imaging, but not in 11C-Choline PET/CT in the setting of primary hyperparathyroidism). Number of hyperfunctioning parathyroid glands, location relative to the thyroid gland and confidence of each assessment (low, moderate or high) were noted, and intra- and inter-observer agreement calculated using Fleiss' kappa method. Sensitivities and specificities of the non-experts were calculated using the expert reader as gold standard. RESULTS: Intra-observer agreement was 'good' to 'near perfect' for all readers. Inter-observer agreement was good between non-experts and the expert, with kappa values ≥ 0.74. Sensitivities between non-experts and the expert were high, > 81%, when assessing which side and 75% when assessing thyroid quadrant. All specificities were > 94%. Reader certainties were 'high' in > 80% of cases for the expert and > 70% and > 65%, respectively for the two non-experts. CONCLUSION: 11C-Choline PET/CT is not reader sensitive for the localisation of hyperfunctioning parathyroid glands and may therefore be safely implemented at sites that have a moderate number of cases. Access to a cyclotron laboratory is, however, a necessity for the production of 11C-Choline. The study was conducted in accordance with the Helsinki 2 declaration and The International Council for Harmonisation Guideline for Good Clinical Practice (ICH_GCP) clinical trial, approved by the Research Ethics Committee of the Capital Region of Denmark (Journal-nr.:H-18012490, date of approval: 18 June 2018) and the Danish Medicines Agency (EudraCT no. 2018-000726-63, date of approval: 6 June 2018). The GCP unit in Eastern Denmark has carried out regular monitoring of the trial according to GCP (ID: 2018-1050).

Amplicon-Based NGS Panels for Actionable Cancer Target Identification in Follicular Cell-Derived Thyroid Neoplasia.

Follicular cell-derived thyroid cancers are heterogenous and morphological classification is a complex and highly specialized task. Hence, identification of somatic alterations could provide insights to tumor biology and serve as an add-on diagnostic tool. Furthermore, results from these add-on tools could point in the direction of a more personalized treatment strategy. In the present study we set out to identify and validate the somatic mutation profile in a sample-set of follicular cell-derived thyroid neoplasia. One-hundred-and-one archived formalin fixed paraffin embedded (FFPE) tissue samples from patients diagnosed with follicular cell-derived thyroid neoplasia were included, and upon DNA-extraction and qualitative measurements 99 samples were eligible for amplicon-based next-generation-sequencing. Libraries were generated using the TruSeq Amplicon Cancer Panel, followed by sequencing using a MiSeq. Upon data processing and variant filtering all variants were manually assessed to exclude false positive mutations in the final curated list. Moreover, hot-spot mutations were validated using an independent platform from Agilent. Each diagnostic group were correlated to mutation burden and individual mutations were classified according to recent guidelines for somatic mutation classification. Close to 100% of the archived FFPE samples were eligible for DNA-library preparation and amplicon sequencing based on DNA quality criterion. The distribution of mutations in the specific diagnostic groups resulted in a higher mutation frequency among the most dedifferentiated than in the groups with a more differentiated cell profile. Based on the distribution mutations across the samples and using hierarchical clustering, we generated four tentative mutational signatures; highly mutated tumors; tumors with mainly NRAS and TP53 mutations; BRAF mutated tumors and tumors with none or single sporadic mutations. Future studies including more samples and follow-up data may amend these signatures, however our results imply that morphological classification of follicular cell derived thyroid neoplasia could be supplemented with a somatic mutational signature. Taken together, broad screening of the somatic alterations in FFPE tissue of thyroid neoplasia is comprehensible and essential for future identification of possible treatment targets and personalized medicine.

11C-Choline PET/CT vs. 99mTc-MIBI/123Iodide Subtraction SPECT/CT for Preoperative Detection of Abnormal Parathyroid Glands in Primary Hyperparathyroidism: A Prospective, Single-Centre Clinical Trial in 60 Patients.

BACKGROUND: In patients with primary hyperparathyroidism (PHPT) locating hyperfunctioning glands (HPGs) is crucial when planning minimally invasive surgery. Dual-isotope subtraction scintigraphy with 99mTc-MIBI/123Iodide using SPECT/CT and planar pinhole imaging (Method A) has previously shown a sensitivity >93%. However, the method is costly and time consuming and entails a high radiation dose. 11C-Choline PET/CT (Method B) is an appealing candidate method unencumbered by these disadvantages. METHODS: Sixty patients with newly diagnosed PHPT participated and were scanned using both methods prior to parathyroidectomy. We investigated whether sensitivities of Method A and Method B are similar in a method-to-method comparison when using surgical findings as the true location. RESULTS: At the patient level, sensitivities were (A) 0.98 (95% CI: 0.90-1.00) and (B) 1.00 (95% CI: 0.93-1.00). At the gland level, sensitivities were (A) 0.88 (95% CI: 0.78-0.94) and (B) 0.87 (95% CI: 0.76-0.92). With a non-inferiority margin of ∆ = -0.1, we found a 1-sided p-value < 0.001. CONCLUSION: Our methods comparison study found that sensitivity of Method B was not inferior to Method A. We suggest that 11C-Choline PET/CT is a clinically relevant first-choice candidate for preoperative imaging of PHPT and that Method B can likely replace Method A in the near future.

[New criteria for malignancy risk stratification of the thyroid nodule based on ultrasound].

In this review, we propose implementation of the five-category Thyroid Imaging Reporting and Data System (TIRADS) risk scoring system in Denmark, to obtain a structured and standardised thyroid ultrasound reporting, and for better selection of nodules recommended for biopsy and follow-up. This is based on recent European guidelines. A major goal of ultrasound assessment of thyroid nodules is to depict those lesions, which should undergo fine needle aspiration biopsy in order to diagnose thyroid malignancy. As no single sonographic criterion is sufficiently accurate in this respect, the clinician is left with little guidance regarding a cost-effective approach for the workup of thyroid nodules.

Long-term outcome following laser therapy of benign cystic-solid thyroid nodules.

OBJECTIVE: Laser therapy (LT) is considered a safe and effective procedure for inducing thyroid nodule necrosis, fibrosis and shrinkage. Little is known about long-term efficacy of LT in benign complex thyroid nodules, which we report here. DESIGN AND METHODS: One hundred and ten euthyroid outpatients (28 men and 82 women; median age 48 years (range 17-82)) with a recurrent cytologically benign cystic (≥2 mL cyst volume) thyroid nodule causing local discomfort were assigned to LT. LT was performed after complete cyst aspiration and under continuous ultrasound (US) guidance. Nineteen patients (17 within 6 months) had surgery after LT. The median follow-up for the remaining 91 patients was 45 months (range: 12-134). RESULTS: The overall median nodule volume in the 110 patients decreased from 9.0 mL (range: 2.0-158.0) to 1.2 mL (range: 0.0-85.0) (P < 0.001) at the final evaluation, corresponding to a median reduction of 85% (range: -49 to 100%). Remission of the cystic part (volume ≤1 mL) was obtained in 82 of 110 (75%) patients after LT. The median cyst volume decreased from 6.3 mL (range: 2.0-158.0) to 0.0 mL (range: 0.0-85.0) (P < 000.1), corresponding to a median reduction of 100% (range: -49 to 100%). These results correlated with a significant decrease in pressure as well as cosmetic complaints. Side effects were restricted to mild local pain. CONCLUSION: US-guided aspiration and subsequent LT of benign recurrent cystic thyroid nodules results in a satisfactory long-term clinical response in the majority of patients. LT constitutes a clinically relevant alternative to surgery in such patients.

Randomized prospective study comparing a single radioiodine dose and a single laser therapy session in autonomously functioning thyroid nodules.

OBJECTIVE: To compare the efficacy of interstitial laser photocoagulation (ILP) with radioiodine in hot thyroid nodules. DESIGN: Thirty consecutive outpatients with subclinical or mild hyperthyroidism and a scintigraphically solitary hot nodule with extraglandular suppression were randomized to either one ILP session or one radioiodine ((131)I) dose. METHODS: ILP was performed under continuous ultrasound-guidance and with an output power of 2.5-3.5 W. (131)I was given as a single dose based on thyroid volume and a 24-h thyroid (131)I uptake. Thyroid function and nodule volume were evaluated at inclusion and at 1, 3 and 6 months after treatment. RESULTS: Normalization of serum TSH was achieved in 7 out of 14 patients in the ILP group and in all 15 patients in the (131)I group (P=0.0025). In the ILP group, mean thyroid nodule volume reduction was 44+/-5% (s.e.m.; P<0.001), and in the (131)I group 47+/-8% (P<0.001), within 6 months, without between-group difference (P=0.73). The mean reduction of total thyroid volume was 7+/-5% in the ILP group (P=0.20) and 26+/-8% (P=0.006) in the (131)I group (P=0.06 between-group). Two patients in the (131)I group developed hypothyroidism but no major side effects were seen. CONCLUSIONS: This first randomized study, comparing ILP with standard therapy, demonstrates that ILP and (131)I therapy approximately halves thyroid nodule volume within 6 months; but in contrast to (131)I, extranodular thyroid volume is unaffected by ILP and no patient developed hypothyroidism. Using the present design, ILP seems inferior to (131)I therapy in normalization of serum TSH. The potential value of ILP as a non-surgical alternative to (131)I needs further investigation.

Continuous methimazole therapy and its effect on the cure rate of hyperthyroidism using radioactive iodine: an evaluation by a randomized trial.

BACKGROUND: A randomized clinical trial was performed to clarify whether continuous use of methimazole (MTZ) during radioiodine ((131)I) therapy influences the final outcome of this therapy. DESIGN: Consecutive patients with Graves' disease (n = 30) or a toxic nodular goiter (n = 45) were rendered euthyroid by MTZ and randomized to stop MTZ 8 d before (131)I (-MTZ; n = 36) or to continue MTZ until 4 wk after (131)I (+MTZ; n = 39). Calculation of the (131)I activity included an assessment of the (131)I half-life and the thyroid volume. RESULTS: The 24-h thyroid (131)I uptake was lower in the +MTZ group than in the -MTZ group (44.8 +/- 15.6% vs. 62.1 +/- 9.9%, respectively; P < 0.001). At 3 wk after therapy, no significant change in serum free T(4) index was observed in the +MTZ group (109 +/- 106 vs. 83 +/- 28 nmol/liter at baseline; P = 0.26), contrasting an increase in the -MTZ group (180 +/- 110 vs. 82 +/- 26 nmol/liter; P < 0.001). The number of cured patients was 17 (44%) and 22 (61%) in the +MTZ and -MTZ groups, respectively (P = 0.17). Cured patients tended to have a lower 24-h thyroid (131)I uptake (50.1 +/- 13.8% vs. 56.4 +/- 17.1%; P = 0.09). By adjusting for a possible interfactorial relationship through a regression analysis (variables: randomization, 24- and 96-h thyroid (131)I uptake, type and duration of disease, age, gender, presence of antithyroid peroxidase antibodies, thyroid volume, dose of MTZ), only the continuous use of MTZ correlated with treatment failure (P = 0.006), whereas a low 24-h thyroid (131)I uptake predicted a better outcome (P = 0.006). CONCLUSION: Continuous use of MTZ hinders an excessive increase of the thyroid hormones during (131)I therapy of hyperthyroid diseases. However, such a strategy seems to reduce the final cure rate, although this adverse effect paradoxically is attenuated by the concomitant reduction of the thyroid (131)I uptake.

The use of exercise interventions to overcome adverse effects of androgen deprivation therapy.

Androgen deprivation therapy (ADT) induces severe hypogonadism and is associated with several adverse effects that negatively affect health and quality of life in patients with prostate cancer. ADT changes body composition characterized by an increase in fat mass and a reduction in muscle mass and strength. Insulin sensitivity is also diminished and population-based studies indicate an increased risk of diabetes mellitus and cardiovascular disease in men receiving ADT. Particularly the first 6 months of treatment seem to hold an additional risk of new cardiovascular events for patients with already existing cardiovascular disease. In this initial phase of ADT, metabolic changes are also most prominent. In addition, ADT increases the rate of bone loss and fracture risk. Currently available evidence supports the use of exercise interventions to improve physical function and mitigate ADT-induced fatigue. Some studies also indicate that exercise might moderate ADT-related changes in body composition. However, beneficial effects of exercise interventions on other ADT-related conditions have not been conclusively proven. Trials investigating the effects of ADT on fracture risk and development of diabetes mellitus and cardiovascular disease are still warranted. Furthermore, studies investigating safety and effects of physical activity in men with bone metastases are lacking.

Effect of ultrasound-guided interstitial laser photocoagulation on benign solitary solid cold thyroid nodules - a randomised study.

AIM: To evaluate the efficacy of ultrasound (US)-guided interstitial laser photocoagulation (ILP) on thyroid function, nodule size and patient satisfaction in benign solitary solid cold thyroid nodules by comparing one ILP session with no treatment in a prospective randomised study. MATERIALS AND METHODS: Thirty euthyroid outpatients with a benign solitary solid and a scintigraphically cold thyroid nodule causing local discomfort were assigned to one session of ILP (n = 15) or observation (n = 15) and followed for 6 months. Thyroid nodule volume and total thyroid volume were assessed by US and thyroid function was determined by routine assays before and during follow-up. Pressure and cosmetic complaints before and at 6 months were evaluated on a visual analogue scale. ILP was performed under US guidance and with an output power of 2.5-3.5 W. RESULTS: In the ILP group, the nodule volume decreased from 8.2 ml (6.1; 11.9) (median; quartiles) to 4.8 ml (3.0; 6.6) after 6 months (P = 0.001). The overall median reduction was 44% (37; 52), which correlated with a significant decrease in pressure symptoms as well as cosmetic complaints. In the control group, a non-significant increase in median nodule volume of 7% (0; 34) after 6 months was seen. No major side-effects were seen in the ILP group. There was no correlation between thermal energy deposition and nodule volume reduction. Thyroid function was unaltered throughout. CONCLUSION: US-guided ILP, given as a single treatment, resulted in a satisfactory clinical response in the majority of patients with a benign solitary solid cold thyroid nodule, and may become a clinically relevant alternative to surgery in selected patients.

[The value of ultrasound in the follow-up of thyroid cancer]. / Ultralydskanning ved recidivmonitorering for thyroideacancer.

The commonly used tumour-node-metastasis (TNM) staging system is designed to predict death and not recurrence. Based on this, patients with thyroid cancer are grouped into risk categories at the time of initial treatment. However, recent guidelines proposed a novel staging system focusing on microscopic invasion into the perithyroidal tissues, neck lymph node involvement and 131I uptake outside the thyroid bed following treatment. This risk re-assessment improves the prediction of recurrent/persistent disease. The cornerstone in the follow-up is measurement of plasma-thyroglobulin concentration and ultrasound of the neck focusing on the thyroid bed and classification of lymph nodes according to their location and high risk signs.

Treatment of recurrent thyroid cysts with ethanol: a randomized double-blind controlled trial.

Thyroid nodules are prevalent; when evaluated by ultrasonography (US), 15-25% of solitary thyroid nodules are cystic or predominantly cystic, and most are benign. Simple aspiration is the treatment of choice, but the recurrence rate is 10-80% depending on the number of aspirations and the cyst volume. The aim of this study was to evaluate the effect on recurrence rate of benign recurrent thyroid cysts in a double-blind randomized study comparing ethanol instillation with instillation of isotonic saline and subsequent complete emptying. Sixty-six consecutive patients with recurrent and benign (based on US-guided biopsy) thyroid cysts (>or=2 ml) were randomly assigned to either subtotal cyst aspiration, flushing with 99% ethanol, and subsequent complete fluid aspiration (n = 33), or to subtotal cyst aspiration, flushing with isotonic saline, and subsequent complete fluid aspiration (n = 33). In case of recurrence (defined as cyst volume >1 ml) at the monthly evaluations, the treatment was repeated but limited to a maximum of three treatments. Procedures were US-guided, and patients were followed for 6 months. Age, sex, number of previous aspirations, pretreatment cyst volume, and serum TSH did not differ in the two groups. Cure (defined as a cyst volume

Genetic and environmental causes of individual differences in thyroid size: a study of healthy Danish twins.

Factors such as iodine intake, serum TSH concentration, gender, age, body mass index, parity, and cigarette smoking are thought to influence thyroid size. The purpose of our study was to determine the relative roles of these environmental and physiological factors compared with genetic factors in euthyroid subjects with a clinically normal thyroid gland. A representative sample of self-reported healthy twin pairs was identified through the Danish Twin Registry. A total of 520 individuals divided into 104 monozygotic (MZ), 107 dizygotic same sex (DZ), and 49 opposite sex twin pairs were investigated. After adjustment for age, gender, and other covariates, intraclass correlations were calculated. To elucidate the relative importance of genetic and environmental factors to the variation of ultrasonically determined thyroid volume, quantitative genetic modeling was used. Regression analysis suggested that serum TSH, serum free T(4), gender, age, smoking, and body mass index each played a small, but significant, role for variation in thyroid volume. The intraclass correlations for thyroid volume were consistently higher for MZ than for DZ twin pairs (r(MZ) = 0.71; r(DZ) = 0.18; P < 0.001). Using quantitative genetic modeling, it was calculated that genetic factors (with 95% confidence intervals) accounted for 71% (61-78%) of the individual differences in thyroid volume. Genetic influences are important in the regulation of normal thyroid size. This fits the observation that goiter may be seen also in the absence of evident environmental goitrogens such as iodine deficiency and that not all individuals develop goiter even in iodine-deficient areas.

Ultrasound-guided interstitial laser photocoagulation of an autonomous thyroid nodule: the introduction of a novel alternative.

Radioiodine ((131)I) and surgery are the standard therapeutic options for the solitary autonomous thyroid nodule (AFTN). Percutaneous ethanol injection (PEI) has proven to be an effective technique and possible alternative to the conventional treatment options. However, PEI is not devoid of side effects and often necessitates multiple treatment sessions. We present a case of a 17-year-old female successfully treated with ultrasound (US)-guided percutaneous interstitial laser photocoagulation (ILP) for an AFTN. Initially, she had a serum thyrotropin (TSH) of 0.01 mU/L and normal peripheral thyroid hormone levels. Scintigraphically it was a hot nodule with suppression of extranodular uptake, and ultrasonographically it was a solitary solid 8.2-mL nodule. One treatment session (3 W for 650 seconds [1950 J]) normalized serum thyrotropin (TSH) level within 2 months and decreased the nodule volume to 4.9 mL (40% reduction) without further alterations during an additional 9 months of follow-up. Side effects were transient thyrotoxicosis and local pain as seen with PEI. To our knowledge, this is the first reported case of ILP used in a patient with a pretoxic thyroid nodule. US-guided thermic tissue coagulation with ILP could become a useful alternative for the AFTN in patients who cannot or will not undergo surgery or treatment with (131)I.

[The value of ultrasound in the follow-up of thyroid cancer].

The commonly used tumour-node-metastasis (TNM) staging system is designed to predict death and not recurrence. Based on this, patients with thyroid cancer are grouped into risk categories at the time of initial treatment. However, recent guidelines proposed a novel staging system focusing on microscopic invasion into the perithyroidal tissues, neck lymph node involvement and ¹³¹I uptake outside the thyroid bed following treatment. This risk re-assessment improves the prediction of recurrent/persistent disease. The cornerstone in the follow-up is measurement of plasma-thyroglobulin concentration and ultrasound of the neck focusing on the thyroid bed and classification of lymph nodes according to their location and high risk signs.

Interstitial laser photocoagulation (ILP) of benign cystic thyroid nodules--a prospective randomized trial.

CONTEXT: Recurrence rate, after aspiration, in cystic thyroid nodules is very high. Interstitial laser photocoagulation (ILP) is a minimally invasive procedure that reduces the need for surgery in patients with a benign solid thyroid nodule. OBJECTIVE: The aim of the study was to evaluate the efficacy of ILP on remission rates in recurrent, predominantly cystic thyroid nodules. DESIGN AND METHODS: Forty-four consecutive outpatients with a symptomatic, recurrent, and cytologically benign cystic (cyst volume ≥ 2 mL) thyroid nodule were randomized to a single aspiration with (n = 22) or without (n = 22) subsequent ILP and followed up after 1, 3, and 6 months. RESULTS: Successful outcome (cyst volume ≤ 1 mL) was obtained in 15 of 22 (68%) patients in the ILP group, compared to 4 of 22 (18%) in the aspiration group (P = .002). In the ILP group, the solid part of the nodule was reduced from a median of 1.8 to 1.0 mL (P = .02). In the aspiration-alone group, neither the cyst volume nor the solid nodule volume was significantly reduced. The reduction in median visual analog score (0-10 cm) for pressure symptoms was significantly higher in the ILP group (from 3.0 to 0.0 cm) than in the aspiration-alone group (from 4.0 to 3.5 cm) (P = .006, between groups). No major side effects occurred, and thyroid function was unaffected throughout. CONCLUSIONS: US-guided aspiration and subsequent ILP of benign recurrent predominantly cystic thyroid nodules is safe. It significantly reduces recurrence rate, the volume of the solid nodule component, and pressure symptoms. ILP constitutes an important alternative to surgery in such patients.

A placebo-controlled, blinded and randomised study on the effects of recombinant human thyrotropin on quality of life in the treatment of thyroid cancer.

BACKGROUND: It is well known that thyroid hormone withdrawal (THW) in thyroid cancer patients can induce a decrease in quality of life (QOL). Recombinant human thyrotropin (rh-TSH) has been used to avoid this; however, no blinded studies have ever documented the effect. OBJECTIVE: To compare QOL in patients with differentiated thyroid cancer (DTC) treated with either rh-TSH or liothyronine (L-T3) THW for 10 days. STUDY DESIGN: Double-blind, randomised cross-over. PATIENTS: Fifty-six patients with DTC treated by total thyroidectomy and indication for postsurgery radioiodine (RI) ablation therapy. INTERVENTION: Randomisation to either L-T3 and rh-TSH prior to the first RI course and following this to ingest placebo tablets and receive placebo injections before a second RI uptake measurement 4-6 months later, or to receive placebo before the primary RI ablation and active therapy 4-6 months later. MAIN OUTCOME MEASURES: QOL was measured by SF-36 and 2 visual analogue scale (VAS) scores at baseline and during RI therapy or RI uptake. RESULTS: A significant difference in QOL was seen in 2 of 4 predefined SF-36 domains (7.2 and 6.6%) and 2 VAS scales (10 and 14%), favouring rh-TSH therapy. CONCLUSION: This is the first blinded randomised clinical trial describing the effect of rh-TSH compared to L-T3 THW on QOL in DTC patients. A significant difference was demonstrated, though smaller than described in previous non-blinded studies.