Lingual thyroid in a 16-year-old girl.

Lingual thyroid is a rare congenital disorder displaying ectopic thyroid tissue at the base of the tongue. This is the most common location for ectopic thyroid tissue and is usually the only thyroid tissue present. This is a case report of a 16-year-old female who presented with nasal congestion. Fiberoptic laryngoscopy showed swelling at the base of the tongue and an ultrasound examination of the neck was without visible thyroid tissue. A 99mTc-pertechnetate scintigraphy confirmed the clinical diagnosis. As the patient was euthyroid and without symptoms active surveillance was planned.

Diagnosis of possible nasopharyngeal malignancy in adults with isolated serous otitis media; a systematic review and proposal of a management algorithm.

PURPOSE: The objective of this study was (1) to systematically review the evidence of routine post-nasal space blind biopsies and/or imaging of adults with isolated serous otitis media (SOM) of unknown cause for detection nasopharyngeal malignancy (NPM), and (2) to design a clinical management algorithm for these patients. METHODS: A systematic search was conducted in the databases PubMed, Embase and Cochrane Library guided by the study question "Should adults with isolated SOM of unknown cause undergo routine biopsies of the post-nasal space and/or diagnostic imaging for detection of NPM?". All retrieved studies were reviewed and quantitatively analyzed. RESULTS: The systematic literature search identified 552 publications accessible for title-abstract screening. This yielded 23 studies for full text assessment, of which 6 were found eligible for inclusion. All six studies dealt with nasopharyngeal blind biopsies, whereas no studies on cross-sectional imaging were identified. The derived summarized results of the included studies showed that 5.5% (31/568) of patients with isolated SOM of unknown cause were diagnosed with NPM. Of these, 6.5% (2/31) had normal nasopharyngeal endoscopy (i.e., malignancy was discovered by blind biopsies). Finally, 0.35% (2/568) of patients with isolated SOM of unknown cause diagnosed with NPM had normal nasopharyngeal endoscopy findings (i.e., nasopharyngeal endoscopy ruled-out malignancy in 99.65% of patients). CONCLUSIONS: We found no evidence supporting routine use of blind biopsies or cross-sectional imaging in adults with isolated serous otitis media of unknown cause. We propose a pragmatic management algorithm for workup of adults with persistent secretory otitis media.

Odontogenic myxoma involving the orbit in a 3-year-old boy: removal, reconstruction and review of the literature.

We present a rare case of a 3-year-old boy with an odontogenic myxoma (OM) involving the orbita. Including our case, only nine cases of OM have been reported to involve the eye in children.There is no gold standard for treatment of OM in children with orbital involvement. The recurrence rate of OM in children seems low, which advocates for less invasive surgery. A gentle resection of the OM was carried out. The floor and medial wall of the orbit was reconstructed immediately using a non-resorbable Medpor implant with passive adaptation. Reconstruction with a Medpor implant in children has rarely been reported in the literature. No clinical or radiological recurrence was observed 24 months after surgical removal, and the patient presented with symmetric appearance and normal vision.

Systemic oxidative stress to nucleic acids is unaltered following radioiodine therapy of patients with benign nodular goiter.

BACKGROUND: Little is known about the whole body oxidative stress burden following radioactive iodine ((131)I) therapy of thyroid diseases. METHODS: We studied 17 patients with benign nodular goiter treated with (131)I therapy. The targeted thyroid dose was 50 Gy in 11 patients pretreated with 0.1 mg of recombinant human TSH (rhTSH). In 6 patients, the applied thyroid dose was 100 Gy without rhTSH prestimulation. Well-established biomarkers of oxidative stress to RNA (8-oxo-7,8-dihydroguanosine; 8-oxoGuo) and DNA (8-oxo-7,8-dihydro-2'-deoxyguanosine; 8-oxodG) were measured in freshly voided morning urine (normalized against the creatinine concentration) at baseline, and 7 and 21 days after rhTSH (not followed by (131)I), and 7 and 21 days after (131)I therapy, respectively. RESULTS: The baseline urinary excretions of 8-oxoGuo and 8-oxodG were 2.20 ± 0.84 and 1.63 ± 0.70 nmol/mmol creatinine, respectively. We found no significant changes in the excretion of any of the metabolites, neither after rhTSH stimulation alone nor after (131)I therapy. Also, no significant differences were found between the rhTSH group (low dose, median (131)I: 152 MBq) and the non-rhTSH group (high dose, median (131)I: 419 MBq; 8-oxoGuo: p = 0.66, 8-oxodG: p = 0.71). CONCLUSION: Systemic oxidative stress, as detected by nucleic acids metabolites in the urine, is not increased after thyroid stimulation with 0.1 mg of rhTSH, or after (131)I therapy. Our method cannot quantify the oxidative stress induced locally in the thyroid gland, but the study supports that (131)I therapy of benign nodular goiter carries no or only a minute risk of developing subsequent malignancies. It remains to be explored whether our findings also apply to hyperthyroid disorders.

[Odontogenic myxoma of the maxilla in a three-year-old boy].

A three-year-old boy presented with a painless mass in the nasolabial fold and ipsilateral increased tearing. A diagnosis of odontogenic myxoma (OM) was established by biopsy, and the tumour was excised using a combined oral and transconjuctival approach. In small children OM occurs almost exclusively in the maxilla. Orbital involvement is very rare, and to our knowledge reconstruction with a Medpore sheet has not previously been reported. At post-operative follow-up normal eye function and an excellent cosmetic result was observed. OM should be considered in a midfacial mass.

The role of radioiodine therapy in benign nodular goitre.

For treatment of benign nodular goitre the choice usually stands between surgery and (131)I therapy. (131)I therapy, used for 30 years for this condition, leads to a goitre volume reduction of 35-50% within 1-2 years. However, this treatment has limited efficacy if the thyroid (131)I uptake is low or if the goitre is large. Recombinant human TSH (rhTSH)-stimulated (131)I therapy significantly improves goitre reduction, as compared with conventional (131)I therapy without pre-stimulation, and adverse effects are few with rhTSH doses of 0.1 mg or lower. RhTSH-stimulated (131)I therapy reduces the need for additional therapy due to insufficient goitre reduction, but the price is a higher rate of hypothyroidism. Another approach with rhTSH-stimulation is to reduce the administered (131)I activity by a factor that equals the increase in the thyroid (131)I uptake. Using this approach, radiation exposure is considerably reduced while the goitre reduction is similar to that obtained with conventional (131)I therapy.

Substantial interobserver variation of thyroid volume and function by visual evaluation of thyroid (99m)Tc scintigraphy.

INTRODUCTION: (99m)Tc-pertechnetate scintigraphy is much used in the evaluation of patients with nodular goitre. We investigated the ability of experienced observers to estimate the thyroid 24-h (131)I uptake (RAIU) and the thyroid volume by visual evaluation of the scintigram. MATERIAL AND METHODS: Two endocrinologists and two nuclear medicine specialists visually evaluated thyroid scintigrams from 171 patients with nodular goitre. The variables were assessed in a blinded fashion according to predefined categories and then compared with the true values. The assessments were repeated after four weeks. Kappa (κ ω) statistics were used. RESULTS: There was a low probability (range 6-22%) for the observers to assess the thyroid RAIU correctly. The probability of assessing the thyroid volume correctly was in the 14-22% range. Endocrinologists tended to underestimate the thyroid RAIU, mostly in patients with a RAIU > 30%. All observers significantly underestimated the thyroid volume if this was > 80 ml. There was a low interobserver agreement for the thyroid RAIU assessment (κ ω-values: 0.03-0.43) as well as for the thyroid volume assessment (κ ω-values: 0.19-0.48). The corresponding κ ω-values for the intraobserver agreement were 0.34-0.68 and 0.37-0.62, respectively. Nuclear medicine specialists achieved a significantly higher agreement than endocrinologists in their evaluation of both thyroid parameters. CONCLUSION: Thyroid (99m)Tc scintigraphy has poor interobserver agreement and is inaccurate for assessment of quantitative thyroid parameters, even when performed by experienced specialists. FUNDING: This study was supported by grants from the Danish Agency for Science, Technology and Innovation. TRIAL REGISTRATION: not relevant.

Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: results from a multicenter, international, randomized, placebo-controlled, dose-selection study.

BACKGROUND: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ((131)I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with (131)I therapy. METHODS: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2 ± 9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 mL; range 31.9-242.2 mL) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30), or 0.03 mg MRrhTSH (n=33) 24 hours before a calculated (131)I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively. RESULTS: At six months, TV reduction was enhanced in the 0.03 mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01 mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44 ± 12.7% (SD) in the placebo group, 41 ± 21.0% in the 0.01 mg MRrhTSH group, and 53 ± 18.6% in the 0.03 mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH group, the subset of patients with basal (131)I uptake <20% had a 24% greater TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03 mg MRrhTSH group (13.4 ± 23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01 mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01 mg, and 0.03 mg MRrhTSH groups respectively. The overall safety profile of the study was favorable. CONCLUSIONS: When used as adjuvant to (131)I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤ 0.03 mg, indicating that the lower threshold for efficacy is around this level.

Prestimulation with recombinant human thyrotropin (rhTSH) improves the long-term outcome of radioiodine therapy for multinodular nontoxic goiter.

OBJECTIVE: The objective of the study was to evaluate the long-term outcome of recombinant human TSH (rhTSH)-augmented radioiodine ((131)I) therapy for benign multinodular nontoxic goiter. PATIENTS AND METHODS: Between 2002 and 2005, 86 patients with a multinodular nontoxic goiter were treated with (131)I in two randomized, double-blind, placebo-controlled trials. (131)I-therapy was preceded by 0.3 mg rhTSH (n = 42) or placebo (n = 44). In 2009, 80 patients completed a follow-up (FU) visit, including determination of thyroid volume, thyroid function, and patient satisfaction by a visual analog scale. RESULTS: In both groups, thyroid volume was further reduced from 1 yr to final FU (71 months). The mean goiter volume reductions obtained at 1 yr and final FU [59.2 ± 2.4% (sem) and 69.7 ± 3.1%, respectively] in the rhTSH group were significantly greater than those obtained in the (131)I-alone group (43.2 ± 3.7 and 56.2 ± 3.6%, respectively, P = 0.001 and P = 0.006), corresponding to a gain of 24% at final FU. At last FU the mean reduction in compression visual analog scale score was significantly greater in patients receiving rhTSH (P = 0.049). Additional therapy (thyroid surgery or (131)I) was required more often in the placebo group (nine of 44) compared with the rhTSH group (two of 42) (P = 0.05). The prevalence of hypothyroidism at 1 yr [9 and 43% in the placebo and rhTSH groups, respectively (P < 0.0001)] increased to 16 and 52%, respectively, at final FU (P = 0.001). CONCLUSION: Enhanced goiter volume reduction with rhTSH-augmented (131)I therapy improves the long-term reduction in goiter-related symptoms and reduces the need for additional therapy compared with plain (131)I therapy. Overall patient satisfaction is benefited, despite a higher rate of permanent hypothyroidism.

[Icatibant is a new treatment option in life-threatening angioedema triggered by angiotensin-converting enzyme inhibitor]. / Icatibant er en ny behandlingsmulighed ved livstruende angiotensinkonverterende enzym-inhibitor-udløst angioødem.

A 78 year-old woman with life-threatening angiotensin-converting enzyme inhibitor (ACE-i) induced angioedema was unresponsive to conventional treatment with corticosteroids, antihistamines and epinephrine. She was successfully treated with icatibant licensed for treatment of hereditary angioedema knowing that both conditions involve bradykinin induced activation of bradykinin B2 receptors. Randomised, controlled trials are warranted to document the efficacy of icatibant in ACE-i angioedema.

Non-surgical approach to the benign nodular goiter: new opportunities by recombinant human TSH-stimulated 131I-therapy.

The optimal treatment strategy in a goiter patient depends--among other factors--on goiter size, the degree of cosmetic or compressive symptoms, the age of the patient, the impact on the upper airways, the wish to maintain normal thyroid function, the ability of the thyroid gland to take up (131)I, and the possibility of thyroid malignancy. When treatment is warranted in a patient with benign goiter, the choice usually stands between surgery and (131)I-therapy. Focal destructive treatment, by ethanol sclerotherapy or interstitial laser photocoagulation, may be considered in patients with a solitary benign nodule. If thyroid hyperfunction due to nodular autonomy is the dominant problem, life-long anti-thyroid drug treatment may be relevant in elderly individuals. With the advent of recombinant human TSH (rhTSH) stimulation the goiter reduction following (131)I-therapy is significantly enhanced and this treatment is of particular benefit, as compared with conventional (131)I-therapy, in patients with a low baseline thyroid (131)I uptake and a large goiter. If the rhTSH dose does not exceed 0.1 mg the risk of temporary hyperthyroidism and acute thyroid swelling is low. Since patient satisfaction seemingly is not improved by the greater goiter reduction obtained by rhTSH-stimulated (131)I-therapy, and permanent hypothyroidism is more frequent, it may be more relevant to reduce the administered radioactivity equivalent to the rhTSH-induced increase in the thyroid (131)I uptake. Future large-scale well-controlled studies should explore this strategy, with focus on cost-benefit and quality of life. A major hindrance of widespread and routine use of rhTSH-stimulated (131)I-therapy is its present status as an off-label treatment.

Recombinant human thyrotropin-stimulated radioiodine therapy of nodular goiter allows major reduction of the radiation burden with retained efficacy.

CONTEXT AND OBJECTIVE: Stimulation with recombinant human TSH (rhTSH) before radioiodine (131I) therapy augments goiter volume reduction (GVR). Observations indicate that rhTSH has a preconditioning effect beyond increasing thyroid (131)I uptake. We test the hypothesis that an equivalent GVR might be obtained by an absorbed thyroid dose well below what has been used previously. PATIENTS AND DESIGN: In a double-blinded setup, 90 patients (78 women; median age, 52 yr; range, 22-83) with a nontoxic nodular goiter (median size, 63 ml; range, 25-379 ml) were randomized to either 0.1 mg rhTSH (n=60) followed by a thyroid dose of 50 Gy or placebo followed by 100 Gy (n=30). RESULTS: At 12 months, the mean relative GVR in the placebo and the rhTSH group was identical (35+/-3%; P=0.81). The median administered 131I-activity was 170 MBq (45-1269) in the rhTSH group and 559 MBq (245-3530) in the placebo group (70% reduction, P<0.0001). According to the official radiation regulation, hospitalization was required in 14 patients in the placebo group vs. one patient in the rhTSH group (P<0.0001). In both groups, goiter-related symptoms were effectively relieved in the majority of patients. The prevalence of myxedema (10%) did not differ among groups. CONCLUSIONS: This is the first study to demonstrate that rhTSH not only increases the thyroid 131I uptake, but per se potentiates the effect of 131I-therapy, allowing a major reduction of the 131I-activity without compromising efficacy. This approach is attractive in terms of minimizing posttherapeutic restrictions and in reducing the potential risk of radiation-induced malignancy.

Dose-dependent acute effects of recombinant human TSH (rhTSH) on thyroid size and function: comparison of 0.1, 0.3 and 0.9 mg of rhTSH.

CONTEXT: Recombinant human TSH (rhTSH) is used to augment the effect of radioiodine therapy for nontoxic multinodular goitre. Reports of acute thyroid swelling and hyperthyroidism warrant safety studies evaluating whether these side-effects are dose dependent. OBJECTIVE: To determine the effects on thyroid size and function of various doses of rhTSH. DESIGN: In nine healthy male volunteers, the effect of placebo, 0.1, 0.3 and 0.9 mg of rhTSH was examined in a paired design including four consecutive study rounds. MAIN OUTCOME MEASURES: Main outcome measures were evaluated at baseline, 24 h, 48 h, 96 h, 7 days and 28 days after rhTSH and included: Thyroid volume (TV) estimation by planimetric ultrasound, and thyroid function by serum TSH, free T3, free T4 and Tg levels. RESULTS: Following placebo or 0.1 mg rhTSH, the TV did not change significantly from baseline at any time. At 24 and 48 h after administration of 0.3 mg rhTSH, the TV increased by 37.4 +/- 12.3% (SEM) (P = 0.03) and 45.3 +/- 16.1% (P = 0.05) respectively. After 0.9 mg rhTSH, the TV increased by 23.3 +/- 5.8% (P = 0.008) and 35.5 +/- 18.4% (P = 0.02) respectively. The increase in serum FT3, FT4 and thyroglobulin (Tg) was greater when administering 0.3 mg compared with 0.1 mg (P = 0.02) and when administering 0.9 mg compared with 0.3 mg (P = 0.02). After 0.1 mg rhTSH, the increase in FT3 and Tg was not significantly different from placebo whereas the FT4 increase was significantly higher (P = 0.02 compared with placebo). CONCLUSIONS: In healthy individuals, rhTSH-induced thyroid swelling and hyperthyroidism is rapid and dose dependent. If valid for patients with goitre, our results suggest that these adverse effects are unlikely to be of clinical significance, following doses of rhTSH of 0.1 mg or less.

Optimizing 131I uptake after rhTSH stimulation in patients with nontoxic multinodular goiter: evidence from a prospective, randomized, double-blind study.

UNLABELLED: Prestimulation with recombinant human thyroid-stimulating hormone (rhTSH) augments radioiodine (131)I therapy for benign nontoxic multinodular goiter. The purpose of this study was to determine the optimal time interval between rhTSH and (131)I administration to enhance thyroid radioactive iodine uptake (RAIU). METHODS: Patients were randomized, in a 2-factorial design, to receive either a 0.1-mg dose of rhTSH (n = 60) or placebo (n = 30) and to a time interval of 24, 48, or 72 h before (131)I administration. The rhTSH- or placebo-stimulated RAIU study was performed at 4 wk after a baseline RAIU assessment in a tertiary referral center at a university hospital. A total of 90 patients (78 women; median age, 52 y; range, 22-83 y) referred to (131)I therapy for symptomatic nontoxic goiter (median goiter volume, 63 mL; range, 25-464 mL) were included in the study. Change in thyroid RAIU was determined at 24 and 96 h after (131)I tracer administration. RESULTS: In the placebo subgroups, RAIU did not change significantly from baseline. The mean (+/-SE) 24-h RAIU increased from 33.8% +/- 2.3% to 66.0% +/- 1.8% (111.2% increase) with a 24-h interval, from 36.8% +/- 2.1% to 64.6% +/- 2.7% (83.3% increase) with a 48-h interval, and from 33.0% +/- 2.7% to 49.6% +/- 2.5% (62.4% increase) with a 72-h interval. All within-group changes were highly significant (P < 0.001). The effect was negatively correlated with initial RAIU (r = -0.703, P < 0.001). The increase in 24- and 96-h RAIU was significantly higher in the rhTSH/24-h group than it was in the rhTSH/72-h group (P = 0.023 and 0.012, respectively) and insignificantly higher than in the rhTSH/48-h group (P = 0.37 and 0.26, respectively). CONCLUSION: The effect of rhTSH on thyroid RAIU is most pronounced when administered 24 h before (131)I administration and declines with longer time intervals. Whether there is a similar time dependency for goiter reduction after rhTSH-stimulated (131)I-therapy remains to be clarified.

Time to reconsider nonsurgical therapy of benign non-toxic multinodular goitre: focus on recombinant human TSH augmented radioiodine therapy.

The treatment of benign multinodular goitre (MNG) is controversial, but surgery is recommended in large compressive goitres. While some patients decline surgery others may have contraindications due to comorbidity, since MNG is prevalent in the elderly. Therefore, non-surgical treatment alternatives are needed. Until recently, levothyroxine therapy was the preferred non-surgical alternative, but due to low efficacy and potential side-effects, it is not recommended for routine use in recent international guidelines. Conventional radioiodine ((131)I) therapy has been used for two decades as an effective and safe alternative to surgery in the treatment of symptomatic non-toxic MNG. Since much higher activities of (131)I are employed when treating non-toxic rather than toxic MNG, there has been reluctance in many countries to use this treatment modality. Frequently, the (131)I -uptake in a non-toxic MNG is low, which makes (131)I therapy less feasible. Another challenge is the negative correlation between the initial goitre size and goitre volume reduction (GVR). With its ability to more than double the thyroid (131)I-uptake, recombinant human TSH (rhTSH) increases the absorbed radiation dose and thus enhances the GVR by 35-56% at the expense of up to fivefold higher rate of permanent hypothyroidism. An alternative strategy is to reduce the administered (131)I-activity with a factor corresponding to the rhTSH induced increase in (131)I-uptake. Hereby, the extrathyroidal irradiation can be reduced without compromising efficacy. Thus, although in its infancy, and still experimental, rhTSH-augmented (131)I therapy may profoundly alter the non-surgical treatment of benign non-toxic MNG.

The majority of Danish nontoxic goitre patients are ineligible for Levothyroxine suppressive therapy.

OBJECTIVE: Levothyroxine suppressive therapy (LT4-therapy), aimed at shrinking thyroid nodules is controversial. Despite evidence of limited effect and long-term side-effects, questionnaire surveys indicate widespread use. Our aim was to determine, in consecutive nontoxic goitre patients, the proportion ineligible for LT4-therapy. Exclusion criteria were set up in agreement with recent guidelines. SETTING: Secondary/tertiary referral centre at University Clinic. SUBJECTS AND METHODS: During 1997-2001, 822 patients were referred to our endocrine unit on suspicion of nontoxic goitre. Patients were evaluated clinically including fine needle aspiration biopsy, thyroid scintigraphy and ultrasound. Seven-hundred and forty-five patients (627 women and 118 men; median age 47 years, range 11-90) were potential candidates for LT4-therapy. Based on guidelines we defined conditions where LT4-therapy is contraindicated. Exclusion criteria included (1) Serum TSH < 1.0 mIU/l, (2) Post-menopausal status, or males older than 60 years, (3) Thyroid volume above 100 ml, (4) Intrathoracic goitre, (5) Clinical suspicion of malignancy, (6) Dominant thyroid cyst, (7) Nondiagnostic FNA, (8) Previous ineffective LT4-therapy, (9) Elevated serum calcitonin, (10) Osteoporosis or cardiovascular disease. RESULTS: Of patients 84% were ineligible for LT4-therapy. In diffuse goitre (n = 35) 63%, in uninodular goitre (n = 320) 77% and in multinodular goitre (n = 390) 91% were ineligible. Main ineligibility reasons were a low serum TSH, post-menopausal status, a large goitre or clinical suspicion of malignancy. CONCLUSION: The vast majority of consecutive Danish nontoxic goitre patients (84%) were ineligible for LT4-therapy. Due to low efficacy and potential long-term adverse effects on the skeleton and cardiovascular system we strongly advocate against LT4-therapy for nontoxic goitre.