Combining growth hormone releasing hormone-arginine and synacthen testing diminishes the cortisol response.

OBJECTIVES: The GHRH/arginine test and short synacthen test (SST) have been validated as safe alternatives to the insulin tolerance test for the assessment of the GH reserve and hypothalamic-pituitary-adrenal axis integrity, respectively. However, these two tests are usually performed separately. The objective was to see whether the synacthen and GHRH/arginine tests could be combined to save time and blood samples and minimize inconvenience to patients. PATIENTS/METHODS: Twenty-four consecutive patients with adult onset pituitary disease requiring pituitary function testing were randomized to receive sequentially and in random order a SST, a GHRH/arginine test, and a combined SST and GHRH/arginine test on three different visits separated by at least 1 wk. RESULTS: There was no difference in basal cortisol or ACTH values for the SST done alone or during the combined test. However, when GHRH/arginine was given with synacthen, patients had a lower peak cortisol response with a mean difference of 116 nmol/liter (95% confidence interval, 52.54 to 179.37; P < 0.001), and one patient with a normal response on the SST had a subnormal cortisol response in the combined test. Similar lower peak cortisol responses were observed in males and females with combined test. The difference between the peak cortisol responses showed no significant correlation with age (r = 0.123; P = 0.58) or with the body mass index (r = -0.376; P = 0.09). There was no difference in GH measurements between the GHRH/arginine test done alone or in combination with the SST. CONCLUSIONS: Combining the SST and GHRH/arginine test results in a lower cortisol response to synacthen. For this reason, the combined test cannot be recommended to assess the integrity of cortisol and GH reserve using current diagnostic criteria.

Circadian hydrocortisone infusions in patients with adrenal insufficiency and congenital adrenal hyperplasia.

OBJECTIVE: Conventional hydrocortisone therapy in adrenal insufficiency cannot provide physiological replacement. We have explored the potential of circadian delivery of hydrocortisone as proof of concept for such therapy delivered in modified-release tablet formulation. METHODS: We investigated whether the circadian intravenous infusion of hydrocortisone could improve control of ACTH and androgen levels. Two healthy subjects, two patients with Addison's disease and two patients with congenital adrenal hyperplasia (CAH) were studied. RESULTS: In patients on thrice daily oral hydrocortisone, peak serum cortisol levels were higher than in normal subjects and overnight levels were very low. Patients had very high plasma ACTH levels before their morning dose of hydrocortisone, both at the beginning and at the end of their conventional oral therapy: mean +/- SEM 311.8 +/- 123.2 and 311.2 +/- 85.4 ng/l, respectively. In the patients with CAH, serum 17-hydroxyprogesterone levels were also elevated: 550 and 642 nmol/l at the beginning and 550 and 777 nmol/l at the end of conventional treatment, respectively. The overall 24-h mean cortisol levels were similar for conventional oral hydrocortisone and the circadian infusion. At 0700 h, ACTH levels were much higher on conventional treatment than after circadian infusion: mean +/- SEM 311.2 +/- 85.4 vs. 70.5 +/- 45.0 ng/l, respectively (P < 0.05). The same pattern was observed in 17-hydroxyprogesterone levels, which were 550 and 777 nmol/l after conventional treatment and 3 and 64 nmol/l after circadian infusion. CONCLUSIONS: In patients with poor biochemical control of Addison's disease and CAH, a 24-h circadian infusion of hydrocortisone can decrease morning ACTH and 17-hydroxyprogesterone levels to near normal.

An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen.

Little is known of the underlying biology of estrogen receptor-negative, progesterone receptor-negative (ER(-)/PR(-)) breast cancer (BC), and few targeted therapies are available. Clinical heterogeneity of ER(-)/PR(-) tumors suggests that molecular subsets exist. We performed genome-wide expression analysis of 99 primary BC samples and eight BC cell lines in an effort to reveal distinct subsets, provide insight into their biology and potentially identify new therapeutic targets. We identified a subset of ER(-)/PR(-) tumors with paradoxical expression of genes known to be either direct targets of ER, responsive to estrogen, or typically expressed in ER(+) BC. Differentially expressed genes included SPDEF, FOXA1, XBP1, CYB5, TFF3, NAT1, APOD, ALCAM and AR (P<0.001). A classification model based on the expression signature of this tumor class identified molecularly similar BCs in an independent human BC data set and among BC cell lines (MDA-MB-453). This cell line demonstrated a proliferative response to androgen in an androgen receptor-dependent and ER-independent manner. In addition, the androgen-induced transcriptional program of MDA-MB-453 significantly overlapped the molecular signature of the unique ER(-)/PR(-) subclass of human tumors. This subset of BCs, characterized by a hormonally regulated transcriptional program and response to androgen, suggests the potential for therapeutic strategies targeting the androgen signaling pathway.

Hypopituitary patients prefer a touch-screen to paper quality of life questionnaire.

UNLABELLED: Health Related Quality of Life questionnaires are frequently used for research, however only recently has their use been recommended in the routine clinical management of pituitary patients. Questionnaires frequently have complex scoring systems, and may be cumbersome, limiting widespread application. Touch-screen technology can overcome these limitations. We have developed a touch-screen 'Questions on Life Satisfaction-Hypopituitarism' QLS-H (Flash 5 Action script, program design by IG) questionnaire and compared its use and accuracy with a paper version questionnaire in 50 pituitary patients who were attending routine clinics. The HRQoL Z-score for the patient group was lower than the average for the normal UK population, as might be predicted for this patient group. There was no statistically significant difference between scores obtained by the touch-screen and paper questionnaires; mean (SD) Z score was -1.33 (1.4) for touch-screen and -1.26 (1.5) for paper. The touch-screen was preferred by 80% of patients, and quicker to complete (<5min). Additionally, there were significant errors in 14 (28%) of manually scored paper questionnaires. IN CONCLUSION: Touch-screen QLS-H questionnaires have advantages over the paper version for the routine clinical assessment of patients with hypopituitarism.

Prevalence of astroviruses in a children's hospital.

An enzyme immunoassay for astrovirus was used to screen 357 stool samples from 267 symptomatic inpatients at a tertiary-care children's hospital. Thirty stool samples from 26 patients contained astrovirus antigen, while rotavirus was found in 34 samples and Clostridium difficile toxin was found in 40. Half of the astrovirus infections were nosocomial. Additional pathogens were identified in six of the astrovirus antigen-positive stool samples. Most (80%) of the astroviruses recovered were of serotype 1. Astrovirus infections were significantly more common than rotavirus or C. difficile infections in very young infants and in those with surgical short-bowel syndrome.