Sub-clinical Cushing's syndrome in patients with adrenal gland incidentalomas. Pitfalls in diagnosis and management

Widespread use of contemporary imaging techniques (ultrasound, computerized axial tomography, and magnetic resonance imaging scans) have led to the incidental discovery of asymptomatic adrenal neoplasms with increasing frequency. Patients with such adrenal "incidentalomas" typically have no clinical manifestations of adrenal cortical hyperfunction at the time of discovery. We have studied 122 patients with asymptomatic adrenal masses ranging in size from 2 to 7 cm in diameter from 1978 to 1988. Selected patients, after adrenal metastases, pheochromocytoma, myelolipomas, and cysts were ruled out, were further evaluated for adrenal cortical hyperfunction by measuring urinary 17-hydroxysteroids, 17-ketosteroids, and free cortisol, serum A.M., P.M. cortisol, and plasma ACTH levels. These values were also measured before and after dexamethasone suppression. NP-59 adrenal scintiscans were performed on all patients. Six patients were identified with sub-clinical Cushing's syndrome. Baseline cortisol levels were normal in each of these patients. Loss of diurnal rhythm appeared to be the most sensitive indicator of abnormal adrenal cortical function. When adrenalectomy is performed in such patients, especially when contralateral adrenal gland suppression is evidenced by NP-59 scanning or other biochemical assessment, perioperative steroids should be administered in a manner similar to that used for patients with symptomatic Cushing's syndrome. Unilateral adrenalectomy in a patient with an asymptomatic adrenal adenoma, insufficiently studied, may result in Addisonian crisis.     

The New Zealand Socioeconomic Index: developing and validating an occupationally-derived indicator of socio-economic status

OBJECTIVE: Following revision of the international standard classification (ISCO88), to update and validate on health data an occupationally derived indicator of socio-economic status (SES) adapted to changing occupational and demographic conditions. METHOD: The development of the New Zealand Socioeconomic Index (NZSEI) is based on a 'returns to human capital' model of the stratification process and uses data from the 1991 New Zealand Census (n = 1,051, 926) to generate scores for 97 occupational groups. The construct validation of the scale is carried out on data from the 1992-93 nationwide Household Health Survey (n = 3,000) using three health indicators (self-assessed health, cigarette smoking, general practitioner visits). RESULTS: In general, the results are consistent with expected socio-economic patterns drawn from the literature for the three indicators. CONCLUSIONS: While further work is required on a number of methodological and conceptual issues, the NZSEI provides a robust, standardised and internationally comparable occupational scale of SES for both males and females in either full- or part-time employment. IMPLICATIONS: The NZSEI can be used on routinely collected occupational data. It has a clear conceptual rationale, updates existing SES scales, and provides a link to international standards in SES and occupational classification.     

Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic

OBJECTIVE: To assess whether central corneal thickness (CCT) is a confounding factor in the classification of patients attending for glaucoma assessment in a district general hospital. DESIGN: Cross-sectional study by a single observer. PARTICIPANTS: Patients attending a general ophthalmic clinic: 235 clinically normal eyes, 52 eyes with normal-tension glaucoma (NTG), 335 eyes with primary open-angle glaucoma (POAG), 12 eyes with pseudoexfoliative glaucoma (PXE), 42 eyes with chronic angle closure glaucoma (CACG), and 232 glaucoma suspect (GS) eyes. INTERVENTION: Central corneal thickness was measured using ultrasonic pachymetry. MAIN OUTCOME MEASURE: Correlation of CCT and diagnosis. RESULTS: Mean CCT was 553.9 microm (95% confidence intervals [CI] for the mean, 549.0-558.8 microm) in the clinically normal eyes, 550.1 microm (95% CI, 546.6-553.7 microm) in the POAG eyes, 514.0 microm (95% CI, 504.8-523.3 microm) in the NTG eyes, 530.7 microm (95% CI, 511.2-550.1 microm) in the PXE eyes, 559.9 microm (95% CI, 546.8-573.0 microm) in the CACG eyes, and 579.5 microm (95% CI, 574.8-584.1 microm) in the GS eyes. The differences of mean CCT between the groups were highly significant (P< 0.001 analysis of variance). Eighty-five percent of eyes with NTG and only 36% of eyes with POAG had a mean CCT of 540 microm or less. Thirteen percent of eyes with POAG and 42% of GS eyes had a mean CCT greater than 585 microm. CONCLUSIONS: The CCT measurement is desirable in patients attending for glaucoma assessment in a district general hospital to avoid misclassification resulting from the relationship between CCT and tonometric pressure. Central corneal thickness alone is not an accurate predictor for the clinical diagnosis in this group of eyes. However, many eyes diagnosed as having NTG have thin corneas, which would tend to lower the tonometrically recorded intraocular pressure (IOP), so the finding of a less-than-normal thickness cornea introduces some doubt as to the diagnosis of NTG. For the GS eyes, most eyes had thick corneas, which would tend to increase the tonometrically recorded IOP. Thus, GS eyes with modest elevation of IOP and a thick cornea may be at low risk of progressing to POAG. Thus, many patients with "high IOPs" and a thick CCT do not necessarily have high IOPs and may not need to be followed as GS eyes.     

Chemotherapy for desmoid tumours in association with familial adenomatous polyposis: a report of three cases

Objective

To determine the efficacy of chemotherapy for inoperable desmoid tumours associated with familial adenomatous polyposis.

Design

A review of three cases of unresectable desmoid tumours and of the literature on the subject.

Setting

The Steven Atanas Stavro Polyposis Registry at Mount Sinai Hospital in Toronto.

Patients

Three patients with symptomatic, unresectable desmoid tumours associated with familial adenomatous polyposis and unresponsive to conventional hormone therapy.

Intervention

A chemotherapy regimen of seven cycles of doxorubicin (dose ranging from 60 to 90 mg/m²) and dacarbazine (1000 mg/m²), followed by carboplatin (400 mg/m²) and dacarbazine.

Outcome Measures

Clinical improvement and tumour regression demonstrated by computed tomography.

Results

In each of the three cases significant tumour regression was seen clinically and radiologically.

Conclusions

Cytotoxic chemotherapy is an effective treatment for desmoid tumours associated with familial adenomatous polyposis. The chemotherapy should be started early in cases of symptomatic desmoid tumour unresponsive to conventional medical therapy.     

Caloric vs. pharmacologic effects of ethanol consumption on activity anorexia in rats

Food restriction, combined with access to a running wheel, produces "activity anorexia" (self-starvation) in rats. The relative effects of ethanol and propylene glycol on activity-maintained self-starvation were examined. Young male rats were provided with access to a running wheel while on a 22.5-h food deprivation schedule. One-third were concurrently provided with a 7% solution of ethanol, one-third with a (pharmacologically weak) 7% solution of propylene glycol, and one-third with water. Results indicated that neither survival rate nor running activity were affected significantly by ethanol consumption, relative to water-drinking controls. However, increased survival rates and decreased activity were observed for those animals which consumed propylene glycol. Antagonistic effects of ethanol on energy metabolism, stress responses, and the preservation of body weight are considered in light of these findings.     

Controlled trial of a home and ambulatory program for asthmatic children

Care of asthmatic children is often episodic and more therapeutic than preventive. A 2-year randomized, controlled trial involving 95 children measured the impact of a comprehensive home and ambulatory program for pediatric asthma management using objective outcome measures. Interventions for the study group during the first year included 3-month clinic visits, education, and home visits by a specially trained research nurse. Control subjects continued to receive regular care from a family physician or pediatrician. Eight-nine subjects (93%) completed the study. Study subjects had less school absenteeism than control subjects (10.7 vs. 16.0 days, P = .04) and showed significantly better small airway function after 1 year. Asthma severity improved in 13 study subjects and worsened in 5. The reverse was true for control subjects. Study subjects exhibited better metered aerosol technique than control subjects (P = .0005). Fewer days were spent in hospital by the study subjects admitted compared with control subjects (3.67 vs 11.2 days, P = .02). After 1 year, more study than control families (72.1% vs 33.1%, P = .006) reported that their asthmatic child took responsibility for the asthma management. The intervention failed to reduce exposure to secondhand smoke or to household pets. There were no significant differences in medical visits, theophylline levels, or records of asthma symptoms. One year after discontinuing the intervention, a marked "washout" effect was observed. Comprehensive ambulatory programs of childhood asthma management can improve objective measures of illness severity but must be sustained.     

Cure rates of oral contraceptive users and non-users when treated for vulvovaginal candidiasis (moniliasis) with miconazole nitrate 2% vaginal cream

Analysis of the data from a carefully conducted multi-investigator study utilizing 261 subjects with a diagnosis of vulvovaginal candidiasis determined the cure rates in oral contraceptive users as compared to the cure rates in oral contraceptive non-users when treated with miconazole nitrate 2% Vaginal Cream (MONISTAT¹). The criteria for a cure required that subjects have a negative KOH smear, negative NICKERSON'S Medium culture for $\text{Candida}$ species, and complete absence of the signs and symptoms of vulvovaginal candidiasis 30 or more days following the course of therapy. There was no significant difference in the cure rates of the oral contraceptive users when compared to the oral contraceptive non-users. It is concluded that there is no justification for routinely discontinuing oral contraceptive therapy during treatment for vulvovaginal candidiasis with miconazole nitrate 2% Vaginal Cream (MONISTAT).     

The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective.

Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches, to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (P450) probe substrates, inhibitors and inducers and for the development of classification systems to improve the communication of risk to health care providers and to patients. While existing guidances cover mainly P450-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently, and should also be addressed. This article was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers.