Health care access of thyroid disease patients in Serbia during the COVID-19 pandemic.

PURPOSE: The aim of this study was to assess the impact of repurposing health care facilities in response to COVID-19 on the access of patients with thyroid disease to health care. METHODS: This study consisted of a web-based survey. The survey was anonymous and consisted of forty questions. RESULTS: This survey included 206 respondents. 91.3% of the respondents had health insurance through the Republic Fund of Health Insurance, 9.7% had private or both health insurances, and 3.4% did not have any health insurance. A significant proportion of respondents (60.4%) had to switch from public to private health care to reach a physician and 73.8% had to switch from public to private laboratories. For the 91.9%, this was perceived as a financial burden. Before the pandemic, 83.1% of respondents reported regular follow-up by physicians, which decreased to 44.9% during the pandemic (p < 0.01). 76.3% of the respondents regarded that their thyroid disease was managed optimally before the pandemic, while this figure declined to only 48% during the pandemic (p < 0.01). CONCLUSIONS: The COVID-19 pandemic disrupted the medical care of thyroid patients in Serbia. For the patients treated in the public health care system, access to general practice was hindered, while access to specialist care was disrupted. It led to a switch from public to private health care, which was perceived as a financial burden for almost all the respondents. However, private health care proved to be an important safety net when the public system was overwhelmed.

Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society.

PURPOSE: The standard treatment of hypothyroidism is levothyroxine (LT4), which is available as tablets or soft-gel capsules in Denmark. This study aimed to investigate Danish endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: An e-mail with an invitation to participate in an online survey investigating practices about substitution with thyroid hormones was sent to all members of the Danish Endocrine Society (DES). RESULTS: Out of 488 eligible DES members, a total of 152 (31.2%) respondents were included in the analysis. The majority (94.1%) of responding DES members use LT4 as the treatment of choice. Other treatment options for hypothyroidism are also used, as 58.6% prescribe combination therapy with liothyronine (LT3) + LT4 in their clinical practice. LT4 + LT3 combination is preferred in patients with persistent symptoms of hypothyroidism despite biochemical euthyroidism on LT4 treatment. Over half of the respondents answered that thyroid hormone therapy is never indicated for euthyroid patients, but 42.1% will consider it for euthyroid infertile women with high antibody levels. In various conditions that could interfere with the absorption of LT4, most responding Danish endocrinologists prefer tablets and do not expect a significant difference when switching from one type of tablet formulation to another. CONCLUSION: The treatment of choice for hypothyroidism is LT4. Combination therapy with LT4 + LT3 is considered for patients with persistent symptoms. Even in the presence of conditions affecting bioavailability, responding Danish endocrinologists prefer LT4 tablets rather than newer LT4 formulations, such as soft-gel capsules.

[Features of the use of synthetic analogues of thyroid hormones: а 2020 THESIS* questionnaire survey of members of the Belarusian Public Medical Association of Endocrinology and Metabolism].

BACKGROUND: The standard treatment for hypothyroidism is levothyroxine (LT4), which in the Republic of Belarus is available in tablet form whereas liothyronine (LT3) is not registered, but patients can purchase them on their own abroad. AIM: This study aimed to investigate Belarusian endocrinologists' attitude of thyroid hormones in hypothyroid and euthyroid patients. MATERIALS AND METHODS: An online survey was conducted, for which members of the Belarusian Medical Association of Endocrinology and Metabolism were invited by posting information in the group chat and by e-mail. The research period was from October 1 to December 26, 2020. 210 questionnaires were received, 146 of which were used. RESULTS: The majority of participants, 145 (99.3%), indicated that they were using LT4 as the first-choice drug for the treatment hypothyroidism. Sixty-one (41.8%) doctors answered that LT3 + LT4 combination likely can be used in patients with long-term untreated hypothyroidism and 15 (10.3%) - in patients with persistent symptoms of hypothyroidism, despite biochemical euthyroidism on therapy LT4. Over half of the respondents 84 (57.5%) answered that thyroid hormone therapy was never indicated for euthyroid patients, but 50 (34.2%) would consider it for female infertility with high level of thyroid antibodies and 36 (24.7%) for simple goiter growing over time. In various conditions that could interfere with absorption of LT4, most responding Belarusian endocrinologists do not expect a significant difference with different formulations (tablets+"I do not expect major changes in different forms" vs. "soft gel capsules"+"liquid solution"; p <0.001). Persistent symptoms of hypothyroidism on the background of LT4 replacement therapy with the achievement of the target TSH can mainly be caused by psychosocial factors, concomitant diseases, unrealistic patient expectations, chronic fatigue syndrome, and the burden of chronic disease. CONCLUSION: The method of choice of Belarusian endocrinologists in the treatment of hypothyroidism is LT4 replacement therapy, but the appointment of LT4 + LT3 combination therapy can be considered in certain clinical situations. As a rule, endocrinologists do not prescribe LT4 in patients with euthyroidism and do not expect a significant difference when using other forms of levothyroxine.

Antithyroid drugs in Graves' hyperthyroidism: differences between "block and replace" and "titration" regimes in frequency of euthyroidism and Graves' orbitopathy during treatment.

PURPOSE: Whereas antithyroid drugs (ATD) are the preferred treatment modality for Graves' hyperthyroidism (GH), there is still controversy about the optimal regimen for delivering ATD. To evaluate whether 'Block and Replace' (B + R) and 'Titration' (T) regimes are equivalent in terms of frequency of euthyroidism and Graves' Orbitopathy (GO) during ATD therapy. METHODS: A prospective multicentre observational cohort study of 344 patients with GH but no GO at baseline. Patients were treated with ATD for 18 months according to B + R or T regimen in line with their institution's policy. RESULTS: Baseline characteristics were similar in both groups. In the treatment period between 6 and 18 months thyrotropin (TSH) slightly increased in both groups, but TSH was on average 0.59 mU/L (95% CI 0.27-0.85) lower in the B + R group at all time points (p = 0.026). Serum free thyroxine (FT4) remained stable during the same interval, with a tendency to higher values in the B + R group. The point-prevalence of euthyroidism (TSH and FT4 within their reference ranges) increased with longer duration of ATD in both groups; it was always higher in the T group than in the B + R group: 48 and 24%, respectively, at 6 months, 81 and 58% at 12 months, and 87 and 63% at 18 months (p < 0.002). There were no significant differences between the B + R and T regimens with respect to the fall in thyrotropin binding inhibiting immunoglobulins (TBII) or thyroid peroxidase antibodies (TPO-Ab). GO developed in 15.9% of all patients: 9.1 and 17.8% in B + R group and T group, respectively, (p = 0.096). GO was mild in 13% and moderate-to-severe in 2%. CONCLUSION: The prevalence of biochemical euthyroidism during treatment with antithyroid drugs is higher during T compared to B + R regimen. De novo development of GO did not differ significantly between the two regimens, although it tended to be higher in the T group. Whether one regimen is clinically more advantageous than the other remains unclear.

Asymmetry indicates more severe and active disease in Graves' orbitopathy: results from a prospective cross-sectional multicentre study.

PURPOSE: Patients with Graves' orbitopathy can present with asymmetric disease. The aim of this study was to identify clinical characteristics that distinguish asymmetric from unilateral and symmetric Graves' orbitopathy. METHODS: This was a multi-centre study of new referrals to 13 European Group on Graves' Orbitopathy (EUGOGO) tertiary centres. New patients presenting over a 4 month period with a diagnosis of Graves' orbitopathy were included. Patient demographics were collected and a clinical examination was performed based on a previously published protocol. Patients were categorized as having asymmetric, symmetric, and unilateral Graves' orbitopathy. The distribution of clinical characteristics among the three groups was documented. RESULTS: The asymmetric group (n = 83), was older than the symmetric (n = 157) group [mean age 50.9 years (SD 13.9) vs 45.8 (SD 13.5), p = 0.019], had a lower female to male ratio than the symmetric and unilateral (n = 29) groups (1.6 vs 5.0 vs 8.7, p < 0.001), had more active disease than the symmetric and unilateral groups [mean linical Activity Score 3.0 (SD 1.6) vs 1.7 (SD 1.7), p < 0.001 vs 1.3 (SD 1.4), p < 0.001] and significantly more severe disease than the symmetric and unilateral groups, as measured by the Total Eye Score [mean 8.8 (SD 6.6) vs 5.3 (SD 4.4), p < 0.001, vs 2.7 (SD 2.1), p < 0.001]. CONCLUSION: Older age, lower female to male ratio, more severe, and more active disease cluster around asymmetric Graves' orbitopathy. Asymmetry appears to be a marker of more severe and more active disease than other presentations. This simple clinical parameter present at first presentation to tertiary centres may be valuable to clinicians who manage such patients.

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A Thesis* Questionnaire Survey of Romanian Physicians *Thesis: Treatment of Hypothyroidism in Europe by Specialists: an International Survey.

OBJECTIVE: Romania has no national guidelines for hypothyroidism treatment, nor are there any recommendations from national societies to adhere to international guidelines. Our aim was to identify the attitudes of Romanian physicians relating to hypothyroidism treatment focusing on available formulations of levothyroxine (LT4). METHODS: All 748 members of the Romanian Society of Endocrinology were invited to participate in a web-based survey. A total of 316 (42.24%) members responded, of whom 222 (70.2%) completed all questions. RESULTS: Half of the respondents recommended LT4 treatment in euthyroid patients, from 3.6% in euthyroid patients with obesity to 36.4% in euthyroid females with infertility associated with high levels of thyroid antibodies. LT4 was considered the preferred treatment for hypothyroidism (compared to combination treatment of LT4 with LT3 or LT3 alone) by 98.6% of respondents. LT4 in liquid solution was preferred over tablets if malabsorption is suspected (56.5% vs. 27.3%), for patients with unexplained poor biochemical control (52.5% vs. 22.9%) and for patients not able to adhere to ingesting LT4 fasted (74.0% vs. 9.8%). The most and least probable explanations for persistent symptoms in patients with hypothyroidism who achieve a normal TSH under medication were "psychosocial factors" and "burden of having to take medication", respectively. CONCLUSION: A significant proportion of Romanian physicians would use LT4 in some groups of euthyroid patients, contrary to current evidence. The preferred treatment for hypothyroidism was LT4. Alternative LT4 formulations (liquid solution) are considered in specific clinical conditions. Diversification of available thyroid hormone formulations was readily incorporated into everyday practice.

Graves' orbitopathy as a rare disease in Europe: a European Group on Graves' Orbitopathy (EUGOGO) position statement.

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682). The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves' hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves' Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02-1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00-5.00/10,000; unilateral GO 0.50-1.50/10,000. CONCLUSION: GO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.

Management of thyroid eye disease in the United Kingdom: A multi-centre thyroid eye disease audit.

This article aims to provide baseline data and highlight any major deficiencies in the current level of care provided for adult patients with thyroid eye disease (TED). We undertook a prospective, nonrandomized cross-sectional multicenter observational study. During a 3-month period June-August 2014, consecutive adult patients with TED who presented to nominated specialist eye clinics in the United Kingdom, completed a standardized questionnaire. Main outcome measures were: demographics, time from diagnosis to referral to tertiary centre, time from referral to review in specialist eye clinic, management of thyroid dysfunction, radioiodine and provision of steroid prophylaxis, smoking, and TED classification. 91 patients (mean age 47.88 years) were included. Female-to-male ratio was 6:1. Mean time since first symptoms of TED = 27.92 (73.71) months; from first visit to any doctor with symptoms to diagnosis = 9.37 (26.03) months; from hyperthyroidism diagnosis to euthyroidism 12.45 (16.81) months. First, 13% had received radioiodine. All those with active TED received prophylactic steroids. Seven patients who received radioiodine and did not have TED at the time went on to develop it. Then, 60% patients were current or ex-smokers. 63% current smokers had been offered smoking cessation advice. 65% patients had active TED; 4% had sight-threatening TED. A large proportion of patients (54%) were unaware of their thyroid status. Not enough patients are being provided with smoking cessation advice and information on the impact of smoking on TED and control of thyroid function.

Does early response to intravenous glucocorticoids predict the final outcome in patients with moderate-to-severe and active Graves' orbitopathy?

PURPOSE: Intravenous glucocorticoids (ivGCs) given as 12-weekly infusions are the first-line treatment for moderate-to-severe and active Graves' orbitopathy (GO), but they are not always effective. In this study, we evaluated whether response at 6 weeks correlated with outcomes at 12 (end of intervention) and 24 (follow-up) weeks, particularly in patients initially unresponsive. METHODS: Our database (Bartalena et al. J Clin Endocrinol Metab 97:4454-4463, 10), comprising 159 patients given three different cumulative doses of methylprednisolone (2.25, 4.98, 7.47 g) was analyzed, pooling data for analyses. Responses at 6 weeks were compared with those at 12 and 24 weeks using three outcomes: overall ophthalmic involvement [composite index (CI)]; quality of life (QoL); Clinical Activity Score (CAS). Responses were classified as "Improved", "Unchanged", "Deteriorated", compared to baseline. RESULTS: Deteriorated patients at 6 weeks for CI (n = 8) remained in the same category at 12 weeks and 7/8 at 24 weeks. Improved patients at 6 weeks for CI (n = 51) remained in the same category in 63% and 53% of cases at 12 and 24 weeks, respectively. Unchanged patients at 6 weeks (n = 100) eventually improved in 28% of cases (CI), 58% (CAS), 32% (QoL). There was no glucocorticoid dose-dependent difference in the influence of early response on later outcomes. CONCLUSIONS: Patients who deteriorate at 6 weeks after ivGCs are unlikely to benefit from continuing ivGCs. Patients unresponsive at 6 weeks still have a significant possibility of improvement later. Accordingly, they may continue ivGC treatment, or, alternatively, possibly stop ivGCs and be switched to a second-line treatment.

Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides recommendations on the management of thyroid cancer in adults and is based on the 2014 British Thyroid Association guidelines. Recommendations • Ultrasound scanning (USS) of the nodule or goitre is a crucial investigation in guiding the need for fine needle aspiration cytology (FNAC). (R) • FNAC should be considered for all nodules with suspicious ultrasound features (U3-U5). If a nodule is smaller than 10 mm in diameter, USS guided FNAC is not recommended unless clinically suspicious lymph nodes on USS are also present. (R) • Cytological analysis and categorisation should be reported according to the current British Thyroid Association Guidance. (R) • Ultrasound scanning assessment of cervical nodes should be done in FNAC-proven cancer. (R) • Magnetic resonance imaging (MRI) or computed tomography (CT) should be done in suspected cases of retrosternal extension, fixed tumours (local invasion with or without vocal cord paralysis) or when haemoptysis is reported. When CT with contrast is used pre-operatively, there should be a two-month delay between the use of iodinated contrast media and subsequent radioactive iodine (I131) therapy. (R) • Fluoro-deoxy-glucose positron emission tomography imaging is not recommended for routine evaluation. (G) • In patients with thyroid cancer, assessment of extrathyroidal extension and lymph node disease in the central and lateral neck compartments should be undertaken pre-operatively by USS and cross-sectional imaging (CT or MRI) if indicated. (R) • For patients with Thy 3f or Thy 4 FNAC a diagnostic hemithyroidectomy is recommended. (R) • Total thyroidectomy is recommended for patients with tumours greater than 4 cm in diameter or tumours of any size in association with any of the following characteristics: multifocal disease, bilateral disease, extrathyroidal spread (pT3 and pT4a), familial disease and those with clinically or radiologically involved nodes and/or distant metastases. (R) • Subtotal thyroidectomy should not be used in the management of thyroid cancer. (G) • Central compartment neck dissection is not routinely recommended for patients with papillary thyroid cancer without clinical or radiological evidence of lymph node involvement, provided they meet all of the following criteria: classical type papillary thyroid cancer, patient less than 45 years old, unifocal tumour, less than 4 cm, no extrathyroidal extension on ultrasound. (R) • Patients with metastases in the lateral compartment should undergo therapeutic lateral and central compartment neck dissection. (R) • Patients with follicular cancer with greater than 4 cm tumours should be treated with total thyroidectomy. (R) • I131 ablation should be carried out only in centres with appropriate facilities. (R) • Serum thyroglobulin (Tg) should be checked in all post-operative patients with differentiated thyroid cancer (DTC), but not sooner than six weeks after surgery. (R) • Patients who have undergone total or near total thyroidectomy should be started on levothyroxine 2 µg per kg or liothyronine 20 mcg tds after surgery. (R) • The majority of patients with a tumour more than 1 cm in diameter, who have undergone total or near-total thyroidectomy, should have I131 ablation. (R) • A post-ablation scan should be performed 3-10 days after I131 ablation. (R) • Post-therapy dynamic risk stratification at 9-12 months is used to guide further management. (G) • Potentially resectable recurrent or persistent disease should be managed with surgery whenever possible. (R) • Distant metastases and sites not amenable to surgery which are iodine avid should be treated with I131 therapy. (R) • Long-term follow-up for patients with differentiated thyroid cancer (DTC) is recommended. (G) • Follow-up should be based on clinical examination, serum Tg and thyroid-stimulating hormone assessments. (R) • Patients with suspected medullary thyroid cancer (MTC) should be investigated with calcitonin and carcino-embryonic antigen levels (CEA), 24 hour catecholamine and nor metanephrine urine estimation (or plasma free nor metanephrine estimation), serum calcium and parathyroid hormone. (R) • Relevant imaging studies are advisable to guide the extent of surgery. (R) • RET (Proto-oncogene tyrosine-protein kinase receptor) proto-oncogene analysis should be performed after surgery. (R) • All patients with known or suspected MTC should have serum calcitonin and biochemical screening for phaeochromocytoma pre-operatively. (R) • All patients with proven MTC greater than 5 mm should undergo total thyroidectomy and central compartment neck dissection. (R) • Patients with MTC with lateral nodal involvement should undergo selective neck dissection (IIa-Vb). (R) • Patients with MTC with central node metastases should undergo ipsilateral prophylactic lateral node dissection. (R) • Prophylactic thyroidectomy should be offered to RET-positive family members. (R) • All patients with proven MTC should have genetic screening. (R) • Radiotherapy may be useful in controlling local symptoms in patients with inoperable disease. (R) • Chemotherapy with tyrosine kinase inhibitors may help in controlling local symptoms. (R) • For individuals with anaplastic thyroid carcinoma, initial assessment should focus on identifying the small proportion of patients with localised disease and good performance status, which may benefit from surgical resection and other adjuvant therapies. (G) • The surgical intent should be gross tumour resection and not merely an attempt at debulking. (G).

The role of colonoscopic screening in acromegaly revisited: review of current literature and practice guidelines.

INTRODUCTION: Acromegaly is a chronic, debilitating and disfiguring condition with a significantly increased morbidity and mortality due to cardiovascular, as well as respiratory complications. Patients with acromegaly are usually diagnosed at the age of 40, however, the duration of symptoms can vary from 5 to 10 years before the formal diagnosis is confirmed. Recent advances in the field of acromegaly have improved survival significantly. A strong association between acromegaly and premalignant colonic lesions and colon cancer has been highlighted. Furthermore, patients with acromegaly have a greater lifetime risk of malignant transformation and a far worse overall prognosis from colorectal cancer, which is now considered a major disease related complication. MATERIALS AND METHODS: A comprehensive search strategy was applied for the Medline/PubMed electronic database from its inception until April 2014. We considered all human research articles published in English, not classified as case report, editorial, comment, letter, or news. CONCLUSION: Specific recommendations for large bowel endoscopic screening in patients with acromegaly have been proposed. In this comprehensive review we discuss the current state of knowledge and evidence on colonoscopic screening in patients with acromegaly illustrated by a case of aggressive colorectal cancer presenting late in a young woman with difficult to control acromegaly.

Pilot of BRAF mutation analysis in indeterminate, suspicious and malignant thyroid FNA cytology.

BACKGROUND: BRAF V600E mutation has been reported to show a high specificity for papillary thyroid carcinoma (PTC). Using this marker to upgrade 'indeterminate' or 'suspicious' thyroid fine needle aspiration (FNA) cytology to 'malignant' could potentially allow one-stage therapeutic total thyroidectomy. METHODS: For a 14-month period, FNA cytology specimens in the Thy3-5 categories, which are the UK equivalents of indeterminate (Thy3a, atypical; Thy3f, follicular), suspicious for malignancy (Thy4) and malignant (Thy5) in the Bethesda System, underwent BRAF mutation testing by melt curve analysis. The results were correlated with histology. RESULTS: We tested 123 cytology specimens of which 12 (9.8%) failed. The BRAF mutation rate in the remainder was 16.2% (18/111), with 93 showing the wild-type. Seventeen mutations were V600E and one was non-V600E. The rate of mutation increased significantly (P < 0.0001 if Thy3a and Thy3f were combined) with the cytology category: 1/42 Thy3a (2.4%), 1/36 Thy3f (2.8%), 4/15 Thy4 (26.7%), 12/18 Thy5 (66.7%). All BRAF mutations correlated with PTC on histology, except for one recurrent PTC without histology. One mutation-positive case with Thy3a cytology showed the target lesion to be a 10-mm follicular adenoma on histology with an immediately adjacent 4-mm micro-PTC, in a patient who did not require total thyroidectomy. CONCLUSION: BRAF mutational analysis by melt curve analysis is feasible in routine thyroid cytology, and in our series had a 100% specificity for PTC in subsequent histology. The application of BRAF analysis could be useful for indeterminate cytology, but we suggest that it would be most appropriate and cost-effective for Thy4/suspicious cases, for which it could enable one-stage therapeutic surgery in the context of multidisciplinary discussion. In contrast, the sensitivity is low and there is no role for avoiding diagnostic thyroid surgery if wild-type BRAF is found.

An unusual presenting symptom of graves' disease: myalgia.

A 50-year-old female patient presented with severe myalgia involving her proximal muscles for 3-4 weeks. She also reported mild thyrotoxic symptoms over the same time period. Examination revealed mild thyrotoxicosis, a moderate diffuse goiter and no eye signs. The clinical picture was dominated by muscle pain and tenderness involving mainly her proximal arms and legs, her calves and her fingers, requiring opiate analgesia. Muscle power and tendon reflexes were normal. Laboratory evaluation revealed undetectable serum thyroid stimulating hormone (TSH) with raised FT4, FT3 and positive TSH receptor antibodies. Treatment with carbimazole was started. Additional laboratory investigations were negative (inflammatory markers, creatine kinase and antibodies to antinuclear antibodies, gastric parietal cell, smooth muscle, mitochondrial, dsDNA, centromere, extractable nuclear antigen (ENA) ribonucleoprotein, ENA Sm, ENA Ro, ENA Anti-La, ENA Scl70, ENA Jo-1, anti-CCP and rheumatoid factor). Further assessment in the rheumatology clinic confirmed there was no small joint tenderness or loss of range of movement of her limbs, but widespread and profound muscle tenderness of the common extensors of the forearms, biceps, trapezius, calves and thighs. She was treated symptomatically with analgesic medication and continued on carbimazole. A month later she was euthyroid and her myalgia had resolved. Hyperthyroidism has a profound effect on skeletal muscle and often leads to myopathy. Severe myalgia in association with Graves' disease is rare and resolves with the restoration of euthyroidism.

Orbital decompression for Graves' orbitopathy in England.

AIMS: The purpose of this study was to obtain data on orbital decompression procedures performed in England, classed by hospital and locality, to evaluate regional variation in care. METHODS: Data on orbital decompression taking place in England over a 2-year period between 2007 and 2009 were derived from CHKS Ltd and analysed by the hospital and primary care trust. RESULTS AND CONCLUSIONS: In all, 44% of these operations took place in hospitals with an annual workload of 10 or fewer procedures. Analysis of the same data by primary care trust suggests an almost 30-fold variance in the rates of decompression performed per unit population. Expertise available to patients with Graves' orbitopathy and rates of referral for specialist care in England appears to vary significantly by geographic location. These data, along with other outcome measures, will provide a baseline by which progress can be judged.

Is Recombinant Human TSH a Trigger for Graves' Orbitopathy?

The pathogenesis of Graves' orbitopathy (GO) remains unknown. The hypothesis of a causal relationship between autoimmunity against the TSH receptor (TSHR) and GO is supported by clinical studies. Radioiodine treatment is associated with worsening or new onset of GO, possibly via antigen shedding or by inducing hypothyroidism. The coexistence of thyroid cancer with Graves' disease (GD) and GO is rare. Here we report 3 cases of reactivation of GO in patients who underwent treatment with recombinant human TSH (rhTSH) and radioiodine ablation. In each case, a thyroidectomy was performed to treat the GD, and an incidental thyroid cancer was discovered. In all 3 cases, reactivation of GO was observed 3-6 weeks after administration of rhTSH, despite maintaining euthyroidism, which was unaccompanied by a rise in serum TSHR antibodies after radioiodine and despite steroids in 1 of the 3 patients. These observations suggest that binding of either TSH or TSHR antibodies to the TSHR, independently of thyroid status, may be causally related to deterioration of GO. Clinicians should be aware of a possible association between rhTSH administration and reactivation of GO, which should be taken into account before prescribing rhTSH in patients with GO. Prophylactic steroids may need to be considered for patients at high risk of exacerbation of GO.

2009 American Thyroid Association guidelines on thyroid nodules.

The American Thyroid Association guidelines on thyroid nodules and differentiated thyroid cancer, published in 2009, provide valuable recommendations based on current evidence. Inevitably, controversies and uncertainties will continue to challenge clinicians and patients. On topics where evidence is not clear-cut, judgement may be coloured by pre-existing practises and the structure of the health service in each country, so one has to be aware of the pitfalls of transferring recommendations to one's own practise.

Metachronous testicular teratoma, testicular seminoma and papillary thyroid carcinoma occurring in a single individual: a report of two unrelated cases.

We describe two unrelated men who both developed teratomas in one testis followed by seminomas in the contralateral testis followed by papillary thyroid carcinomas. Neither man had a family history of cancers. Although random occurrence is possible, genetic predisposition and/or environmental influence would seem a likely explanation for this previously unreported combination of tumours.

SDHB-associated renal oncocytoma suggests a broadening of the renal phenotype in hereditary paragangliomatosis.

Mutations in SDHB are one of the causes of hereditary paraganglioma syndrome. Germline mutations in SDHB predispose to the development of head and neck paragangliomas and phaeochromocytomas. Renal tumours are also increasingly being reported as component tumours in hereditary paragangliomatosis associated with mutations in SDHB. We present the first reported case of a family in whom an individual shown to carry a mutation in SDHB developed a renal oncocytoma. We review other reports of renal tumours associated with SDHB-associated hereditary paragangliomatosis and suggest that various histological subtypes of renal tumours are part of this condition. This observation indicates that SDHB-associated hereditary paragangliomatosis is unlike most tumour predisposition syndromes associated with the development of renal tumours which are usually associated with specific histological sub-types. The increasing recognition of the involvement of renal tumours in SDHB mutation carriers suggests that renal screening is likely to be valuable for these patients. SDHB mutations should also be considered in the context of genetic testing when renal tumours, regardless of histopathology, present in families with other tumours consistent hereditary paraganglioma syndrome.

Psychological implications of Graves' orbitopathy.

Patients with thyroid eye disease, Graves' orbitopathy (GO), often appear distressed and it is likely that features of the condition such as disturbances in visual function, orbital discomfort and alterations in facial appearance can impart significant psychological morbidity upon the patient, which in turn can be detrimental to their quality of life. When considering the psychological impact of GO, two elements of the disease are important. The disfiguring changes to the eyes and face can have a direct effect upon psychological health, while physical aspects of the disease such as altered visual acuity, diplopia, orbital pain and lacrimation may influence psychological function as a secondary phenomenon, due to interference with daily living. Evidence appears to confirm the anecdotal impression of many clinicians dealing with GO patients that the prevalence of psychological morbidity in this patient group is high. A 'biopsychosocial' approach to care that addresses biological and psychosocial functioning as major determinants of health is an appropriate strategy when treating patients with GO.

Plasma endothelin response to acute hypoglycaemia in adults with Type 1 diabetes.

AIMS: To determine whether acute insulin-induced hypoglycaemia provokes a detectable alteration in peripheral plasma endothelin (ET) concentrations in humans with Type 1 diabetes. METHODS: Serial plasma concentrations of ET were measured in 20 patients with Type 1 diabetes during controlled hypoglycaemia induced by intravenous infusion of soluble insulin. RESULTS: A significant increase was observed in plasma ET concentrations, from 3.80 +/- 0.31 pg/ml at baseline to 6.72 +/- 1.47 pg/ml at 60 min after the onset of the hypoglycaemic reaction (P < 0.05). CONCLUSIONS: Acute insulin-induced hypoglycaemia induces a rise in plasma endothelin concentrations in people with Type 1 diabetes. This finding is consistent with a putative role for ET in the mediation of hypoglycaemia-induced vasoconstriction, and the possible precipitation of macrovascular or microvascular events.