Primary Renal Carcinoid - A Case Report.

Carcinoid tumours in the abdomen are uncommon, but typically occur in the gastrointestinal tract. Primary renal carcinoid is an extremely rare tumour, poorly described in the literature. We describe an unusual case where an atypical renal mass on imaging led to a preoperative diagnosis of renal carcinoid on imaging guiding biopsy.

Spontaneous resolution of avascular necrosis of femoral heads following cure of Cushing's syndrome.

UNLABELLED: Avascular necrosis (AVN) is a rare presenting feature of endogenous hypercortisolism. If left untreated, complete collapse of the femoral head may ensue, necessitating hip replacement in up to 70% of patients. The majority of the described patients with AVN due to endogenous hypercortisolaemia required surgical intervention. A 36-year-old female, investigated for right leg pain, reported rapid weight gain, bruising and secondary amenorrhoea. She had abdominal adiposity with violaceous striae, facial plethora and hirsutism, atrophic skin, ecchymosis and proximal myopathy. Investigations confirmed cortisol excess (cortisol following low-dose 48h dexamethasone suppression test 807nmol/L; 24h urinary free cortisol 1443nmol (normal<290nmol)). Adrenocorticotrophic hormone (ACTH) was <5.0pg/mL. CT demonstrated subtle left adrenal gland hypertrophy. Hypercortisolaemia persisted after left adrenalectomy. Histology revealed primary pigmented micronodular adrenal disease. Post-operatively, right leg pain worsened and left leg pain developed, affecting mobility. MRI showed bilateral femoral head AVN. She underwent right adrenalectomy and steroid replacement was commenced. Four months after surgery, leg pain had resolved and mobility was normal. Repeat MRI showed marked improvement of radiological abnormalities in both femoral heads, consistent with spontaneous healing of AVN. We report a case of Cushing's syndrome due to primary pigmented nodular adrenocortical disease, presenting with symptomatic AVN of both hips. This was managed conservatively from an orthopaedic perspective. Following cure of hypercortisolaemia, the patient experienced excellent recovery and remains symptom free 4 years after adrenalectomy. This is the first report of a favourable outcome over long-term follow-up of a patient with bilateral AVN of the hip, which reversed with treatment of endogenous hypercortisolaemia. LEARNING POINTS: AVN of femoral head can be a presenting feature of hypercortisolism, both endogenous and exogenous.Rarely, treatment of hypercortisolaemia can reverse AVN without the need for orthopaedic intervention.Primary pigmented nodular adrenal disease is a rare cause of ACTH-independent Cushing's syndrome.

Role of age stratification for colposcopy referral following initial diagnosis of mild dyskaryosis.

INTRODUCTION: Referral to colposcopy following a single mildly dyskaryotic smear is becoming more widely recommended in the developed world. This has workload and cost implications. AIM: To investigate if stratification of mildly dyskaryotic smears by age group might allow selection of populations that could be followed by repeat cytology initially. METHODS: The study set was of all women with a diagnosis of dyskaryosis between July 2004 and June 2005 in an opportunistic screening programme. The dyskaryosis was divided into high grade (moderate and severe) and low grade and ratios of high to low grade were calculated for age groups. The age intervals were under 20 years, and every 5 years from 20 to 54 years. RESULTS: In the study period, a total of 34 180 cervical smears were examined. Of these, 2326 women were diagnosed with dyskaryosis, (1566 (67%) low grade, 760 (33%) high grade) in the given age groups. This gave an overall ratio of high grade to low grade of 1:2. Ratios of high-grade dyskaryosis to low-grade dyskaryosis stayed relatively constant throughout the age intervals from 20 to 54 years of age, Pearson correlation coefficient 0.91, p = 0.0014. CONCLUSION: The ratios of incidences of grades of dyskaryosis remained constant throughout the age intervals suggesting that selective patterns of referral to colposcopy based on patient's age at diagnosis of mild dyskaryosis are not applicable.

Current treatment of asthma--focus on leukotrienes.

Since their identification in 1979, the cysteinyl leukotrienes (cysLTs) have been shown to be prominent in many inflammatory conditions, including asthma, allergic rhinitis, rheumatoid arthritis, psoriasis, cystic fibrosis and inflammatory bowel disease. They are potent pro-inflammatory agents, as well as causing bronchoconstriction, and undoubtedly have a role in asthma. The cysLTs are products of arachidonic acid metabolism and have been shown to have effects via a cysteinyl leukotriene receptor (CysLTR1) on vascular permeability, mucus production, chemotaxis and bronchial smooth muscle. Their detection in certain body fluids in allergic, aspirin-sensitive and exercise-induced asthma is well documented and potential roles in pathogenesis, proposed. The development of agents affecting production or action offers an exciting new approach to the treatment of asthma. Two approaches to antileukotriene therapy have been developed: blocking their production by inhibiting the action of 5-lipoxygenase enzyme or blocking the CysLTR1. Both approaches have been tried in studies in asthma and overall the results are encouraging, with a decrease in both daytime and nocturnal symptoms, a decrease in additional beta 2 agonist usage and improvement in lung function. The changes, however, are small in some studies. This may be a reflection of disease severity in the study subjects, but of note is a heterogeneity of response to these treatments that may be genetically determined. Antileukotriene therapy has been shown to have an effect in specific types of asthma where the role of cysLTs seems well established--aspirin-sensitive/intolerant asthma and exercise-induced asthma. Longer term studies are needed in other areas such as severe asthma and chronic persistent asthma in both children and adults to provide evidence for the appropriate placement of antileukotriene treatment in current asthma guidelines, in comparison with other established treatments.

Selective airway responsiveness in asthma.

Hyperresponsiveness of airway smooth muscle accounts for the susceptibility of asthmatic subjects to diverse bronchoconstrictor agents. It is widely presumed that hyperresponsiveness is not spasmogen selective. Hence, inhalation of methacholine is used routinely for clinical assessment of asthma and for evaluation of anti-asthma drugs. Comparative studies employing multiple spasmogens have revealed hyperresponsiveness to be markedly spasmogen selective. Because of this pronounced heterogeneity of hyperresponsiveness, sensitivity to methacholine cannot provide a reliable index of responsiveness. Development of exceptional hyperresponsiveness to bradykinin and to peptidoleukotrienes during allergic and other reactions could warrant the development of specific antagonists for asthma therapy. These issues are discussed here by Brian O'Connor, Simon Crowther, John Costello and John Morley.

Sympathomimetic enantiomers and asthma.

Airways of asthma patients can become hyperresponsive to airway spasmogens following regular use of isoprenaline or beta 2-selective sympathomimetics. Hyper-reactivity that results from acute exposure of animals to these drugs is pre-empted by vagal section (a procedure which does not influence spasmolytic efficacy of sympathomimetics), is not diminished by antagonism of beta 2-adrenoceptors and is not associated with loss of responsivity of beta 2-adrenoceptors in the airways. Since activation, modulation, or blockade of beta 2-adrenoceptors does not determine this form of hyperreactivity, the possibility that distomers may induce hyperreactivity must be considered. Ocular and vascular responses to distomers of sympathomimetics have long been recognised and, more recently, comparable observations have been made for the airways. Thus, reactivity of guinea-pig airways to spasmogens was increased following exposure to S-isoprenaline, S-salbutamol, or S-terbutaline and exposure to S-isoprenaline or S-salbutamol can intensify symptoms in asthmatics. Regular exposure to the racemate, especially during or following an allergic reaction, predisposes to expression of hyper-reactivity, which is nullified, acutely, by the eutomer. These observations imply that biological effects of sympathomimetic distomers may contribute to morbidity and mortality in asthma patients.

Hypothyroidism, an important cause of reversible hyperlipidemia.

Primary hypothyroidism was found to be the cause of hyperlipidemia in 22 patients. The mean age was 46 years, 59% were males, 27% had vascular disease, 14% had xanthomas and 86% had thyroid antibodies. Familial involvement was shown in 3 propositi. All patients were treated with L-thyroxine, 0.05--0.2 mg/day for a mean of 16 months. Combined hyperlipidemia was common (77%), and lipoprotein phenotyping revealed types IIB hyperlipopro-teinemia in 11, IIA in 5, III in 3 and IV in 3 patients. With treatment, normal plasma cholesterol (less than 265 mg/dl) and triglycerides (less than 200 mg/dl) were obtained in 91% and 86%, respectively. The mean maintenance L-thyroxine dose was 0.15 mg/day, but smaller doses often showed marked hypolipidemic effect. The mean +/- S. D. pretreatment fasting plasma cholesterol and triglycerides were 387 +/- 120 and 328 +/-247 mg/dl and on thyroid treatment the mean minimum levels were 205 +/- 46 and 133 +/- 65 mg/dl, respectively (both p values less than 0.005). Hypothyroidism has proved to be a common reversible form of hyperlipidemia. One cardiac patient died and three others had to have their L-thyroxine titrated to prevent angina. Family screening has been of use in case finding for auto-immune disease in 3 families.

A longitudinal assessment of lipid ratios in the diagnosis of type III hyperlipoproteinaemia.

Type III hyperlipoproteinaemia (HLP) has been overdiagnosed in the past, but still may go undiagnosed because of technical difficulties. This longitudinal study of 19 ultracentrifugally proven cases of Type III HLP shows that 2 lipid ratios can be used to supplement the findings of a floating beta band. These patients have been followed for 3 months to 2.5 years whilst on dietary and/or drug treatment. A group composed of more than 100 Type IIB, Type IV and Type IIB-IV hyperlipoproteinaemic patients has been used for comparison purposes. From a total of 310 ultracentrifugal analyses, it was found that the following 2 ratios have more than a 90 percent predictability for Type III HLP: supernatant cholesterol/supernatant triglyceride greater than or equal to 0.35 (Ratio 2); supernatant cholesterol/whole plasma triglyceride greater than or equal to 0.25 (Ratio 3). These ratios are particularly valuable in Type III HLP when the plasma is grossly hyperlipaemic or when the lipid levels are low because of successful treatment.