Incidentalomas during imaging for primary hyperparathyroidism--incidence and clinical outcomes.

BACKGROUND: Imaging for pre-operative localisation of parathyroid glands in primary hyperparathyroidism is now routine. This has led to the detection of incidental lesions (incidentalomas) in other organs, the nature of which is not well characterised. The aim of this study was to determine the incidence, characteristics and outcomes in patients who had incidental findings on parathyroid imaging. METHODS: Records of patients who underwent imaging for primary hyperparathyroidism over 2 years were reviewed to identify incidental lesions detected on parathyroid imaging. Patients with persistent or renal hyperparathyroidism were excluded. Details on the management of detected incidentalomas were obtained from patient records. RESULTS: Incidentalomas were identified in 17 of 170 patients (10%) undergoing parathyroid imaging. Incidentalomas included thyroid (n = 11), breast (n = 3), lateral compartment of the neck (n = 1), lung (n = 1) and clavicle (n = 1). However, no disease of clinical significance needing treatment was detected on further investigation. CONCLUSIONS: Although a significant proportion of patients undergoing parathyroid imaging had incidental lesions detected, these seem to be of little clinical significance. The morbidity and cost of further interventions on these incidentalomas need to be weighed against the benefits of routine imaging in improving outcomes of first-time surgery in patients with primary hyperparathyroidism.

Incidence and predictors of post-thyroidectomy hypocalcaemia in a tertiary endocrine surgical unit.

BACKGROUND: Post-thyroidectomy hypocalcaemia is a common complication with significant short and long term morbidity. The aim of this study was to determine the incidence and predictors of post-thyroidectomy hypocalcaemia (as defined by a corrected calcium <2.1 mmol/l) in a tertiary endocrine surgical unit. METHODS: A total of 238 consecutive patients who underwent completion or bilateral thyroid surgery between 2008 and 2011 were included in this retrospective study. Clinical and biochemical data were obtained from electronic and hard copy medical records. RESULTS: The incidence of post-thyroidectomy hypocalcaemia on first postoperative day (POD1) was 29.0%. There was variation in the incidence of hypocalcaemia depending on the timing of measurement on the first postoperative day. At six months following surgery, 5.5% of patients were on calcium and/or vitamin D supplementation. Factors associated with post-thyroidectomy hypocalcaemia were lower preoperative corrected calcium (p=0.005) and parathyroid gland (PTG) auto-transplant (p=0.001). Other clinical factors such as central lymph node dissection, inadvertent PTG excision, ethnicity, preoperative diagnosis and Lugol's iodine were not associated with post-thyroidectomy hypocalcaemia. CONCLUSION: The incidence of post-thyroidectomy hypocalcaemia was underestimated by 6% when only POD1 measurements were considered. The timing of measurement on POD1 has an impact on the incidence of post-thyroidectomy hypocalcaemia. Auto-transplantation and lower preoperative calcium were associated with post-thyroidectomy hypocalcaemia.

Primary hyperparathyroidism: an analysis of failure of parathyroidectomy.

BACKGROUND: Preoperative imaging in patients undergoing surgery for primary hyperparathyroidism (PHPT) is used primarily to facilitate targeted parathyroidectomy. Failure of preoperative localisation mandates a bilateral exploration. It is thought that the results of imaging may also predict the success of surgery. The aims of this study were to assess whether the findings on preoperative localisation influenced outcomes following parathyroidectomy for PHPT and to explore factors underlying failure to cure at surgery. METHODS: We analysed outcomes of all patients who underwent first-time surgery for PHPT in two centres over a 5-year period to determine an association with demographic characteristics and findings on preoperative imaging. Records of patients not cured by initial surgery were reviewed to explore factors underlying failure to cure. RESULTS: The failure rate (persistent disease) in the entire cohort was 5 % (25/541) (bilateral neck explorations, 5 %; unilateral exploration, 7 %; targeted approach, 4 %), while two patients developed recurrent disease. In patients who had undergone dual imaging with an ultrasound scan and (99m)Tc-sestamibi scintigraphy, failure rates with "lateralised and concordant" imaging, "nonconcordant" imaging, and "dual-negative" imaging were 2, 9, and 11 %, respectively (p = 0.01). Of the 25 patients with persistent disease, multigland disease (MGD) was present in 52 % (13/25) and ectopic adenoma in 24 % (6/12). CONCLUSIONS: Patients with PHPT who do not have lateralised and concordant dual imaging are at higher risk of persistent disease. A significant proportion of failures are due to the inability to recognise the presence and/or extent of MGD.

Sentinel node biopsy in papillary thyroid cancer--what is the potential?

PURPOSE: Sentinel node biopsy (SNB) may identify lymph node metastases in patients with papillary thyroid cancer (PTC), enabling selective application of central node dissection (CND). The aim of this study was to assess the feasibility of implementing SNB in patients undergoing thyroidectomy for a cytologically indeterminate/suspicious/malignant thyroid nodule and to determine the potential improvement in clinical outcomes and the costs associated with the SNB technique. METHODS: The treatment strategies and clinical and pathological outcomes of two retrospective cohorts of patients who underwent preoperative thyroid FNA over a 5-year period in two different centres were studied. The potential for implementing the SNB technique and the benefits and costs associated with implementation were estimated. RESULTS: In centre 1, in 819 adult patients who had thyroid fine-needle aspiration cytology, the final cytology was indeterminate, suspicious and diagnostic of malignancy in 113, 29 and 28 patients, respectively. One hundred eight patients were 'suitable' for SNB. Twenty-three of these patients had PTC, six of whom underwent CND. Of these six patients, node metastasis was absent in five--the cohort in whom prophylactic CND may have been avoided consequent to a negative 'sentinel node' biopsy. Morbidity attributable to CND may have been avoided in up to four patients over a 5-year period. Costs associated with implementation of SNB outweighed any potential savings. Analysis of 491 patients in centre 2 confirmed that the benefit of SNB in PTC was similarly limited; morbidity attributable to CND may have been avoided in up to seven patients over a 5-year period. CONCLUSIONS: Even under ideal conditions (assuming 100 % node identification rate and 0 % false negative rate), the potential short- to medium-term benefit of sentinel node biopsy in patients with thyroid cancer in centres implementing a policy of selective or routine prophylactic CND is low.

Systematic review of intravenous methylene blue in parathyroid surgery.

BACKGROUND: Methylene blue is an intraoperative adjunct for localization of enlarged parathyroid glands. The availability of preoperative and other intraoperative localization methods, and the reported adverse effects of methylene blue make its routine use debatable. The aim of this study was to perform a systematic review of the use of methylene blue in parathyroidectomy. METHODS: A systematic review of English-language literature in MEDLINE and Scopus databases on the use of intravenous methylene blue in parathyroid surgery was carried out. RESULTS: There were no randomized clinical trials. Thirty-nine observational studies were identified, of which 33 did not have a control arm. The overall median staining rate for abnormal parathyroid glands was 100 per cent. The median cure rates in the methylene blue and no-methylene blue arms were 100 and 98 per cent respectively. Neurotoxicity was reported in 25 patients, all of whom were taking serotonergic medication. CONCLUSION: Observational evidence suggests that methylene blue is efficacious in identifying enlarged parathyroid glands. Toxicity appears to be mild in the absence of concomitant use of serotonin reuptake inhibitors. The effectiveness of methylene blue in the context of currently used preoperative and intraoperative localization techniques has yet to be shown.

Systematic review and meta-analysis of sentinel node biopsy in thyroid cancer.

BACKGROUND: Sentinel node biopsy (SNB) is employed as standard treatment in some solid organ cancers to assess lymph node spread and enable targeted treatment. Several studies have investigated the role of SNB in thyroid cancer. This is a systematic review and meta-analysis of the role of SNB in the management of thyroid cancer. METHODS: A systematic search was performed in the PubMed database to identify all original articles on the role of SNB in thyroid cancer. Data on methodologies used, short-term outcomes and adverse effects were summarized, and used to address relevant clinical questions related to the application of the SNB technique in thyroid cancer. RESULTS: Twenty-four studies were included. The overall sentinel node (SN) detection rates for the blue dye, radioisotope and combined techniques were 83·7, 98·4 and 96 per cent respectively. A positive SN was seen in 42·9 per cent of patients with papillary thyroid cancer with an identified SN. The overall false-negative rates for the blue dye, radioisotope and combined techniques were 7·7, 16 and 0 per cent respectively. A negative frozen-section examination of the SN was unreliable in 12·0 per cent of patients. Immunohistochemical assessment of the SN showed evidence of nodal metastases in an additional 15 per cent of patients (7 of 47 sentinel nodes). CONCLUSION: SNB in thyroid cancer is a promising technique that has the potential to avoid prophylactic lymph node surgery in up to 57 per cent of patients with clinically node-negative thyroid cancer.

How is adrenocortical cancer being managed in the UK?

INTRODUCTION: Adrenocortical carcinomas are rare. This case series is reported to give an overview of how adrenocortical carcinoma is currently managed in the UK. PATIENTS AND METHODS: A retrospective review was made of case notes from patients with adrenocortical carcinomas presenting to the authors (TWJL, RDB, BJH, and DS-C) over the past 10 years in Newcastle, Sheffield and Cardiff. RESULTS: Newcastle treated twelve, Sheffield eleven and Cardiff seven cases. The median follow-up was 25.5 months (range, 1-102 months). All tumours were greater than 5 cm in diameter. The majority presented with symptoms of hormone excess. Adrenalectomy was performed in 83% - this was radical in 30% and followed by excision of recurrence in 13%. Adjuvant mitotane was given in 64% of patients, in combination with cytotoxic chemotherapy in 20%. One-third of patients did not receive any adjuvant therapy. There was no significant difference in survival between the three centres. The majority of patients (57%) died during the period of follow-up of this study. The median survival was 37 months (range, 2-102 months). CONCLUSIONS: The size of tumour, stage and mode of presentation, age and overall survival of patients in this study are comparable to published series of adrenocortical carcinomas from major endocrine surgical centres world-wide. Despite controversies about benefits, adjuvant mitotane was used in the majority of cases, whereas cytotoxic chemotherapy was only used in the minority. The exact role of adjuvant therapy in the management of adrenocortical carcinoma is not as well established as for other more common malignancies. Establishing a database for adrenocortical carcinomas in the UK would contribute to our understanding of the management of this disease.

Environmental risk factors for the development of psoriatic arthritis: results from a case-control study.

OBJECTIVE: To identify potential risk factors for the onset of inflammatory arthritis (IA) in a large cohort of patients with psoriatic arthritis (PsA) of recent onset. METHODS: We recruited cases with psoriasis and an onset of IA within the past 5 years. Controls were patients who had psoriasis but no arthritis. We assessed potential factors associated with the development of IA using a detailed postal questionnaire. An unmatched analysis adjusted for age and gender was performed. Exposure was censored in the controls at a "dummy-date" assigned randomly in proportion to the percentage of cases developing IA in any given year. RESULTS: We studied 98 cases and 163 controls. Exposures showing a positive association before the onset of IA in patients with psoriasis were: rubella vaccination (OR (95% CI) = 12.4 (1.2 to 122)), injury sufficient to require a medical consultation (2.53 (1.1 to 6.0)), recurrent oral ulcers (4.2 (2.0 to 9.0)) and moving house (2.3 (1.2 to 4.4)). Cases were also more likely to have experienced a fractured bone requiring hospital admission (50% vs 9%, p = 0.040). CONCLUSIONS: We found a number of environmental exposures associated with the onset of IA in subjects with psoriasis. The strongest associations were with trauma thereby adding to the hypothesis of a "deep Koebner phenomenon" in PsA. Our data also suggest that exposure of the immune system to certain infection-related triggers may also be of relevance. Further studies are needed to verify these observations and to examine potential immunological mechanisms that underlie them.

Percutaneous biopsy of adrenal and extra-adrenal retroperitoneal lesions: beware of catecholamine secreting tumours!

BACKGROUND: Many patients undergo abdominal imaging for non-specific symptoms. An increasing number of these patients are discovered to have incidental adrenal or retroperitoneal tumours. Approximately 5% of all incidentally detected adrenal lesions are phaeochromocytomas and 25% of phaeochromocytomas are discovered during imaging studies for unrelated disorders. 10% of phaeochromocytomas are extra-adrenal. METHODS: Retrospective case notes review of three patients with adrenal/retroperitoneal lesions who had percutaneous biopsy before biochemical testing and tertiary referral. FINDINGS: Adrenal/retroperitoneal lesions are still being biopsied without prior biochemical testing. One patient with phaeochromocytoma had a critical event. The others were found to have a phaeochromocytoma and a ganglioneuroma. CONCLUSIONS: The possibility of a catecholamine secreting tumour should be considered in adrenal and extra-adrenal retroperitoneal lesions. If a biopsy is planned, rarely required in adrenal lesions, phaeochromocytoma must be excluded by biochemical testing prior to the biopsy to avoid potential life threatening complications.

Overexpression of type 2 iodothyronine deiodinase in follicular carcinoma as a cause of low circulating free thyroxine levels.

Thyroid function is normally undisturbed in patients with thyroid carcinoma. We have identified three patients with large or widely metastatic follicular thyroid carcinoma who had a persistently increased ratio of serum T(3) to T(4) in the absence of autonomous production of T(3) by the tumor. To investigate the possibility of tumor-mediated T(4) to T(3) conversion, we assayed types 1 and 2 iodothyronine selenodeiodinase (D1 and D2) activity in a 965-g follicular thyroid carcinoma resected from one of these patients. The V(max) for D2 was 8-fold higher than in normal human thyroid tissue. Resection of this tumor, leaving the left thyroid lobe intact, normalized the serum T(3) to T(4) ratio. In two other patients, treatment with sufficient levothyroxine to suppress TSH was associated with a high normal T(3) and a subnormal free T(4) index. In one, concomitant administration of the D1 inhibitors, propylthiouracil and propranolol, did not decrease the elevated serum T(3) to T(4) ratio. These data illustrate that increased T(4) to T(3) conversion in follicular thyroid carcinomas, probably by D2, can cause a significant perturbation in peripheral thyroid hormone concentrations.

Assessing periarticular bone mineral density in patients with early psoriatic arthritis or rheumatoid arthritis.

BACKGROUND: Periarticular osteoporosis is an early finding in the hands of patients with rheumatoid arthritis (RA), due to release of bone resorbing cytokines from the inflamed synovium. There has been disagreement as to whether periarticular bone loss occurs in psoriatic arthritis (PsA). Bone mineral density (BMD) can now be measured accurately using dual energy x ray absorptiometry (DEXA). Recently, DEXA has been used to measure periarticular BMD at predefined regions of interest (ROIs) around the joints. OBJECTIVES: Firstly, to compare periarticular BMD around the finger joints of patients with early RA or PsA. Secondly, to determine whether periarticular bone loss is related to joint inflammation and radiological erosions in RA and PsA. METHODS: Seventeen patients with RA and 15 with PsA were recruited, all with disease duration of less than five years. All finger joints were examined by one person for swelling, or tenderness, or both. Hand radiographs were scored for the presence of erosions. Periarticular BMD was measured at 10 predetermined ROIs using a Hologic QDA-4500A fan-beam densitometer. RESULTS: Patients with PsA were less likely to be positive for rheumatoid factor (RF) (13% v 94%) and more likely to be men (60% v 23%) than patients with RA. There were no other clinical differences between patients with RA or PsA. Patients with RA had significantly lower BMD at each of the ROIs than those with PsA (p<0.05). However, these differences disappeared after adjusting for age and sex. Among patients with RA, those with a higher total number of swollen and/or tender hand joints had significantly lower periarticular BMD at the metocarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. No such association was found for patients with PsA. CONCLUSIONS: In early disease, periarticular bone loss occurred both in patients with RA and those with PsA. Among patients with RA, periarticular osteoporosis was related to measures of joint inflammation. There was no association between joint inflammation and periarticular bone loss in patients with PsA, which lends support to the hypothesis that the primary site of inflammation in PsA is extrasynovial.

The incidence of thyroid abnormalities in adults irradiated for lymphoma.

The aim of the study was to investigate the incidence of thyroid abnormalities in neck irradiated lymphoma patients. Of the 298 patients who had irradiation to the neck for lymphoma between 1966-1988, 174 were found to be alive and free of disease. These patients were invited to participate in the study. From the 174, 93 were able to participate (group 1). Two control groups were recruited; both were sex and aged matched. One group (group 2) consisted of lymphoma patients who were treated with chemotherapy (n=39) or irradiation to areas other than the neck (n=16). The other group (group 3) consisting of healthy volunteers (n=35) recruited from hospital staff and minor surgery attendees, had never had lymphoma or radiotherapy. All participants were required to complete a past medical history and thyroid symptom questionnaire, had blood taken for assays of thyroid stimulating hormone (TSH), thyroglobulin antibodies, thyroid peroxidase antibodies, sodium iodide symporter antibodies and TSH receptor antibodies and underwent ultrasound and clinical examination of the neck. A significant percentage of patients who had been irradiated in the neck had abnormalities on ultrasound, compared to groups 2 and 3 (77% vs 42% vs 24%). Abnormal TSH levels were found to be significantly more common in neck irradiated patients compared to the other groups (50% vs 9% vs 5%). There is a clear difference between neck irradiated patients and control groups. The importance of screening irradiated patients for thyroid abnormalities is re-emphasised.

Carolyn Farb: first lady of philanthropy.

From cancer and medical research, children's and women's issues, to arts, education, and culture, Carolyn Farb's skill as a volunteer fund raiser has been fine-tuned to equal that of the best professional fund raisers in the country. She has made chairing successful charitable events an art form and unselfish life's occupation.

Male breast neoplasia in association with selective serotonin re-uptake inhibitor therapy: a report of three cases.

Male breast cancer is a rare condition with very poorly understood risk factors. We report three cases of men with malignant and pre-malignant breast disease who had all been prescribed selective serotonin re-uptake inhibitors (SSRIs) for depression. Concerns about an association between this group of drugs and breast cancer in women have been previously raised and experimental evidence has suggested that these drugs could influence regulation of cellular proliferation acting through internal cellular messengers. Risk factors for the development of breast cancer are likely to be multifactorial, possibly more so in women given the complex physiological changes that occur in the female breast. Whilst the cases we report are anecdotal and other risk factors may be present, we suggest that assessment of any possible contribution that SSRI therapy may make to the development of breast neoplasia may be more easily assessed in a male population.

The association of cigarette smoking with disease outcome in patients with early inflammatory polyarthritis.

OBJECTIVE: Cigarette smoking is known to increase rheumatoid factor (RF) and nodule formation in patients with rheumatoid arthritis (RA). In this study, we examined the influence of smoking on disease outcome at 3 years among patients newly presenting with inflammatory polyarthritis (IP). METHODS: We studied 486 patients with IP who were referred to the Norfolk Arthritis Register, of whom 323 (67%) satisfied the American College of Rheumatology 1987 criteria for RA. Smoking status was assessed at baseline. Disease outcome was assessed at 3 years, using measures of joint inflammation, functional disability, and radiologic damage. The influence of smoking on disease outcome was explored using logistic regression techniques, with patients who had never smoked as the referent group. Results are expressed as odds ratios (ORs), with their 95% confidence intervals (95% CIs). RESULTS: Current smokers were significantly more likely to be RF positive at baseline (47%) than were ex-smokers (34%) and never smokers (31%). After 3 years, rheumatoid nodules were significantly more common in smokers (13%) compared with ex-smokers/never smokers (4%), a relationship which persisted after adjusting for age and sex (OR 4.07, 95% CI 1.38-12). In contrast, after adjusting for age and sex, current smokers had significantly fewer swollen joints (OR 0.61, 95% CI 0.37-0.98). However, smoking status had no influence on the development of erosions or functional disability. CONCLUSION: Despite smokers being more likely to develop nodules and to be RF positive, current smokers did not have higher levels of radiologic damage, and had fewer swollen joints. We hypothesize that this could be due to either the effect of cigarette smoking on the inflammatory response or other factors (e.g., reduced physical activity in smokers) which may limit joint inflammation and damage.