An unusual case of shortness of breath.

Myopathy is a well-known complication of hypercortisolism and commonly involves proximal lower-limb girdle. We report a rare case of Cushing's syndrome in a 60-year-old female presenting with significant respiratory muscle weakness and respiratory failure. She had history of rheumatoid arthritis, primary biliary cirrhosis and primary hypothyroidism and presented with weight gain and increasing shortness of breath. Investigations confirmed a restrictive defect with impaired gas transfer but with no significant parenchymatous pulmonary disease. Respiratory muscle test confirmed weakness of respiratory muscles and diaphragm. Biochemical and radiological investigations confirmed hypercortisolaemia secondary to a left adrenal tumour. Following adrenalectomy her respiratory symptoms improved along with an objective improvement in the respiratory muscle strength, diaphragmatic movement and pulmonary function test. LEARNING POINTS: Cushing's syndrome can present in many ways, a high index of suspicion is required for its diagnosis, as often patients present with only few of the pathognomonic symptoms and signs of the syndrome.Proximal lower-limb girdle myopathy is common in Cushing's syndrome. Less often long-term exposure of excess glucocorticoid production can also affect other muscles including respiratory muscle and the diaphragm leading to progressive shortness of breath and even acute respiratory failure.Treatment of Cushing's myopathy involves treating the underlying cause that is hypercortisolism. Various medications have been suggested to hinder the development of GC-induced myopathy, but their effects are poorly analysed.

Hypervitaminosis-D, an uncommon reality!

Vitamin D deficiency is highly prevalent in India. This has set off a trend among medical practitioners to prescribe vitamin D supplements empirically. Whilst this approach is generally safe, in predisposed individuals it may lead to hypervitaminosis D. Here we present a case where empirical use of high dose vitamin D supplementation had serious consequences highlighting the need to use vitamin D therapy judiciously and to remain vigilant for side-effects in high-risk individuals.

Sphenoid mucocele: an uncommon complication of a rare condition.

A 58-year-old white woman presented with sudden onset of diplopia, headache and vomiting with a history of tiredness and lethargy over the past four to six months. She had smooth, pale, hairless skin and on examination she was found to have left-sided third and sixth nerve palsy. Laboratory tests confirmed pan-anterior hypopituitarism. Computerized tomography scan of head and magnetic resonance imaging appearances were consistent with those of a sphenoid sinus mucocoele. Following adequate replacement with hydrocortisone and thyroxine she underwent sphenoid mucocoele drainage and endoscopic left sphenoethmoidectomy. Her symptoms were relieved over the next few days and she had a near-total recovery of ophthalmoplegia over the following three months. Pituitary function tests showed partial resolution of hypopituitarism with recovery of hypothalamic-pituitary-adrenal axis and hydrocortisone therapy was withdrawn, but she continued to require thyroxine.

The norepinephrine transporter gene is a candidate gene for panic disorder.

Panic disorder (PD) is an anxiety disorder characterized by recurrent panic attacks with a lifetime prevalence of 4.7%. Genetic factors are known to contribute to the development of the disorder. Several lines of evidence point towards a major role of the norepinephrine system in the pathogenesis of PD. The SLC6A2 gene is located on chromosome 16q12.2 and encodes the norepinephrine transporter (NET), responsible for the reuptake of norepinephrine into presynaptic nerve terminals. The aim of the present study was to analyze genetic variants located within the NET gene for association with PD. The case-control sample consisted of 449 patients with PD and 279 ethnically matched controls. All cases fulfilled the ICD-10 diagnostic criteria for PD. Genotyping was performed using the Sequenom platform (Sequenom, Inc, San Diego, USA). To test for allelic and haplotypic association, the PLINK software was used, and COMBASSOC was applied to test for gene-wise association. After quality control 29 single nucleotide polymorphisms (SNPs) spanning the gene-region were successfully analyzed. Seven SNPs located within the 5' end of the gene were significantly associated with PD. Furthermore, the NET gene showed overall evidence for association with the disease (P = 0.000035). In conclusion, the present study indicates that NET could be a susceptibility gene for PD.

The effectiveness of a hospital diabetes outreach service in supporting care for acutely admitted patients with diabetes.

BACKGROUND: Patients with diabetes have increased frequency of hospital admissions and longer lengths of stay compared to patients without diabetes. Our specialist diabetes inpatient service was reconfigured to deliver a proactive diabetes outreach service to improve the overall care of this population. AIMS: To ascertain the effect of a structured diabetes outreach service to acutely admitted patients with diabetes on avoidable admissions, delayed discharges and appropriate diabetes related follow-up plans. METHODS: Audits were carried out before and 4 months after the introduction of a diabetes outreach service. The proportion of patients under care of the diabetes team, avoidable admissions, delayed discharges and existence of effective follow-up plans were compared pre- and post-implementation of this outreach service. RESULTS: The number of inpatients with diabetes fell by 35% (83 on a typical day pre-outreach vs. 53 post-outreach) despite a similar number of total medical admissions in that month (1449 vs.1459). This was due to a reduction in those admitted with diabetes related (13 vs. 5) and general medical (29 vs. 10) problems whilst numbers requiring other specialist care (41 vs. 39) remained unchanged. The proportion of patients under the care of diabetes team rose (23% vs. 73%) while those with avoidable admissions (18% vs. 7%), delayed discharges (17% vs. 2%) and inappropriate discharge plans (65% vs. 11%) all fell. CONCLUSION: This reformatted service was associated with a marked improvement in a number of parameters relevant to inpatient care.

Adrenal incidentaloma: evaluation and management.

Adrenal incidentalomas are adrenal masses discovered incidental to imaging studies performed for reasons unrelated to adrenal pathology. Although most adrenal incidentalomas are non-functioning benign adenomas, their increasing prevalence presents diagnostic and therapeutic challenges. The assessment of adrenal incidentalomas is aimed at deciding whether or not the tumour should be surgically removed. Adrenalectomy is indicated for phaeochromocytoma, other symptomatic hormone-secreting tumours and those with a high risk of malignancy. Biochemical screening for tumour hypersecretion is mandatory in all adrenal incidentalomas, since hormone secreting tumours may be clinically silent. The diagnosis of phaeochromocytoma is of paramount importance because of its life-threatening complications. Non-functioning adrenal incidentalomas need assessment for risk of malignancy, and this is based on the size of the tumour and its imaging characteristics. An observational policy with periodic radiological and biochemical reassessment is pursued in patients with non-functioning incidentalomas with low malignancy risk. The duration and frequency of reassessment remains unclear, as the natural history of adrenal incidentalomas has yet to be clearly defined, and there is a lack of controlled studies comparing surgical intervention with observation. However, the possibility of acquiring autonomous hypersecretion or conversion to malignancy in an incidentaloma diagnosed to be a benign non-functioning lesion is very low, and most patients may be safely discharged after an initial follow-up period of 2 years.

An assessment of the coverage of a district-wide diabetic retinopathy screening service.

AIMS: To assess the coverage of the diabetes retinopathy screening service (DRSS) in North Staffordshire, to identify patient characteristies associated with non-attendance and to assess the proportion of patients with diabetic retinopathy who achieved glycaemic and blood pressure (BP) control targets. METHODS: Data for all patients who underwent annual retinal screening between 1 May 2000 and 30 April 2001 were obtained from the North Staffordshire Diabetes Register. Age, gender, ethnicity, socio-economic status, type and duration of diabetes were compared between patients who underwent eye screening and those who did not. Frequencies of patients who achieved glycaemic and BP targets in these groups of patients were compared to the remaining patients. RESULTS: 5646 of the 11682 (48%) patients on the diabetes register underwent retinal screening during the year. Patients with Type 2 diabetes, older patients, patients belonging to ethnic minorities and those wholly managed in primary care were less likely to attend for eye screening (P < 0.05 for all groups) with ethnic minority or primary care management demonstrating independent influence (P < 0.001). The percentage of patients with retinopathy achieving HbA1c and systolic BP targets was significantly lower than in their unaffected counterparts (chi2 = 63, P < 0.001 and chi2 = 71, P < 0.001 respectively). CONCLUSIONS: The efficacy of the DRSS in North Staffordshire is low and might be improved by targeting specific patient groups. Glycaemic control and systolic BP control needs to be improved in patients with diabetic retinopathy.

Prediction of recurrence of nonfunctioning pituitary tumours by loss of heterozygosity analysis.

BACKGROUND: Postsurgical regrowth or recurrence of nonfunctioning pituitary adenomas (NFAs) is not uncommon and often requires further surgery or radiotherapy (DXT). Routine postoperative DXT increases the incidence of hypopituitarism, which is associated with increased morbidity and mortality. Identification of genetic abnormalities in the tumour tissue, which can predict recurrence, may allow targeting DXT to the most appropriate patients. DESIGN AND METHODS: We have performed loss of heterozygosity (LOH) analysis on 96 NFAs of which 43 (45%) were recurrent and 53 (55%) were nonrecurrent tumours. Analysis of all tumours was performed on the surgical specimen obtained at the time of first surgery. All tumours underwent allelotyping across nine highly informative microsatellite markers selected on the basis of high LOH frequency in an earlier study involving genome-wide allelotyping. LOH frequency across all microsatellite markers as well as across individual markers was compared between the two cohorts of tumours. RESULTS: LOH frequency in tumours that subsequently recurred was significantly higher across all microsatellite markers as compared to tumours that did not recur (P < 0.05). Allelic loss across one or more microsatellite marker was significantly higher in recurrent tumours (30/43) as compared to their nonrecurrent counterparts (17/53) (P < 0.01). On Poisson regression analysis, the higher LOH frequency in recurrent tumours was independent of the invasiveness of tumours determined radiologically. In addition, LOH at the microsatellite markers D1S215 and D1S459 was significantly higher in tumours that recurred as compared to tumours that did not (32%vs. 3% and 27%vs. 2%, respectively; P < 0.01 for both). No significant difference in LOH frequency between the two tumour groups was evident at the other markers. No association could be demonstrated between the frequency and pattern of LOH and the time to manifest recurrence. CONCLUSIONS: We have shown that it may be possible to predict recurrence of NFAs by LOH analysis of the initial tumour specimen at predefined microsatellite markers, especially on chromosome 1q. This merits further prospective study.

An assessment of care of paediatric and adolescent patients with diabetes in a large district general hospital.

AIMS: To assess the process of clinical care and outcomes of young patients with diabetes attending clinics at a large district general hospital. METHODS: Retrospective analysis of data obtained from 106 case notes of patients aged 12-22 years attending the paediatric, combined adolescent or adult diabetes clinics between 1998 and 2000. The frequency of follow-up, rate of admission, glycaemic control, systolic blood pressure, weight change and screening for complications were assessed. RESULTS: The mean attendance rate was 78%. The admission rate was 91 admissions per 1000 patient years. Overall, the mean HbA1c was 9.1% with only 15% of paediatric and adolescent patients having mean HbA1c

Genome-wide amplification and allelotyping of sporadic pituitary adenomas identify novel regions of genetic loss.

Through the use of a candidate gene approach, several previous studies have identified loss of heterozygosity (LOH) at putative tumor-suppressor gene (TSG) loci in sporadic pituitary tumors. This study reports a genome-wide allelotyping by use of 122 microsatellite markers in a large cohort of tumors, consisting of somatotrophinomas and non-functioning adenomas. Samples were first subject to prior whole genome amplification by primer extension pre-amplification (PEP) to circumvent limitations imposed by insufficient DNA for whole-genome analysis with this number of microsatellite markers. The overall mean frequency of loss in invasive tumors was significantly higher than that in their non-invasive counterparts (7 vs. 3% somatotrophinomas; 6 vs. 3% non-functioning adenomas, respectively). Analysis of the mean frequency of LOH, across all markers to individual chromosomal arms, identified 13 chromosomal arms in somatotrophinomas and 10 in non-functioning tumors, with LOH greater than the 99% upper confidence interval calculated for the rate of overall random allelic loss. In the majority of cases, these losses were more frequent in invasive tumors than in their non-invasive counterparts, suggesting these to be markers of tumor progression. Other regions showed similar frequencies of LOH in both invasive and non-invasive tumors, implying these to be early changes in pituitary tumorigenesis. This genome-wide study also revealed chromosomal regions where losses were frequently associated with an individual marker, for example, chromosome arm 1q (LOH > 30%). In some cases, these losses were subtype-specific and were found at a higher frequency in invasive tumors than in their non-invasive counterparts. Identification of these regions of loss provides the first preliminary evidence for the location of novel putative TSGs involved in pituitary tumorigenesis that are, in some cases, subtype-specific. This investigation provides an unbiased estimate of global aberrations in sporadic pituitary tumors as assessed by LOH analysis. The identification of multiple "hotspots" throughout the genome may be a reflection of an unstable chromatin structure that is susceptible to a deletion or epigenetic-mediated gene-silencing events.

Combination of insulin and thiazolidinedione therapy in massively obese patients with Type 2 diabetes.

AIMS: To evaluate the influence of addition of rosiglitazone to insulin therapy over a 24-week period in massively obese patients with poorly controlled Type 2 diabetes taking large doses of insulin. METHODS: Eight massively obese patients (median body mass index (BMI) 42 kg/m2) with Type 2 diabetes who were on large doses of insulin (median daily dose of 204 U) and/or had poor glycaemic control (median HbA1c of 8.1% (upper limit for normal 5.5%)) were treated over a 24-week period with the combination of insulin and maximum doses of rosiglitazone. Outcomes monitored were changes in weight, BMI, HbA1c, dose of insulin and development of side-effects. RESULTS: At the end of 24 weeks there was a median weight gain of 3 kg (P < 0.01), a fall in median HbA1c from 8.1% to 6.7% (16% reduction from baseline) (P < 0.01) and a reduction in median insulin dose from 204 U/day to 159 U/day (P < 0.01) (23% reduction from baseline). Peripheral oedema was the only significant side-effect and was seen in five patients. CONCLUSIONS: Combination of insulin and rosiglitazone is effective in massively obese patients with Type 2 diabetes, though there is a high incidence of peripheral oedema.