Measurement of cortisol and testosterone in hair of obese and non-obese human subjects.

OBJECTIVE: Hair analysis has been demonstrated to accurately reflect exposure to drug abuse, environmental toxins and exogenous hormones. We tested the feasibility of measuring cortisol and testosterone in hair of healthy and obese subjects. MEASUREMENTS: A modified immunoassay (ELISA) originally developed for saliva was used. Hair, urine and blood samples were collected from young non-obese and obese patients. Perceived stress (PSS) was measured using a validated questionnaire. RESULTS: There was no difference in PSS between non-obese and obese subjects. Hair cortisol levels were significantly correlated with weight (r = 0.27, p < 0.05) and systolic blood pressure (r = 0.28, p < 0.05), while the correlation with BMI did not reach statistical significance (p = 0.063). Hair cortisol levels did not correlate with age or urinary cortisol. There was a negative correlation between hair testosterone and age (r = -0.47, p < 0.05) and BMI (r = -0.40, p < 0.05). The correlation between hair testosterone and free androgen index (FAI) did not reach statistical significance (p = 0.098). The ratio of hair cortisol over hair testosterone (C/T) was higher in the obese group than in the young non-obese group. The C/T ratio correlated positively with age (r = 0.56, p < 0.01), waist circumference (r = 0.63, p < 0.01) and BMI (r = 0.62, p < 0.01), while the correlation between C/T ratio and FAI did not reach statistical significance. CONCLUSION: Hair cortisol levels increase, while hair testosterone levels decrease with obesity. The hair C/T ratio was significantly correlated with age, BMI and waist circumference better than hair cortisol or testosterone alone. As hair collection is non-invasive and is not influenced by moment-to-moment variations, the measurement of hormones in hair is a useful tool in research and possibly clinical practice.

Oral opioids for chronic non-cancer pain: higher prevalence of hypogonadism in men than in women.

The effect of chronic oral opioids on hypothalamus-pituitary-gonadal axis in women, and on bone mineral density (BMD) in men and women is not known. The objective of this cross-sectional study was to determine the effect of long-term oral opioids on gonadal status and BMD in male and female patients with chronic non-cancer pain (CNCP). We included 26 community-dwelling CNCP patients, 12 men and 14 premenopausal women, treated with oral opioids for at least one year. We obtained Visual Analogue Scale for pain score, BMD and plasma LH and FSH in all patients; menstrual history and estradiol in women; free androgen index and total and free testosterone in men. Men were older then women (p<0.05) and had used opioids for a longer period (7.2+/-3.8 and 4.1+/-1.8 years, respectively; p<0.05), but there was no difference in opioid dose or pain score between sexes. The prevalence of hypogonadism was high in men (75%), while only 21% of the women reported oligo- or amenorrhea indicating hypogonadism (P<0.01, between sexes). Osteopenia was found in 50% of men and 21% of women (p=NS). We conclude that in CNCP patients receiving chronic opioid therapy there is a much higher prevalence of hypogonadism in men then in women. This needs to be considered clinical practice.

Thyroid hormone-induced overexpression of functional ryanodine receptors in the rabbit heart.

Modifications in the Ca(2+)-uptake and -release functions of the sarcoplasmic reticulum (SR) may be a major component of the mechanisms underlying thyroid state-dependent alterations in heart rate, myocardial contractility, and metabolism. We investigated the influence of hyperthyroid state on the expression and functional properties of the ryanodine receptor (RyR), a major protein in the junctional SR (JSR), which mediates Ca(2+) release to trigger muscle contraction. Experiments were performed using homogenates and JSR vesicles derived from ventricular myocardium of euthyroid and hyperthyroid rabbits. Hyperthyroidism, with attendant cardiac hypertrophy, was induced by the injection of L-thyroxine (200 microg/kg body wt) daily for 7 days. Western blotting analysis using cardiac RyR-specific antibody revealed a significant increase (>50%) in the relative amount of RyR in the hyperthyroid compared with euthyroid rabbits. Ca(2+)-dependent, high-affinity [(3)H]ryanodine binding was also significantly greater ( approximately 40%) in JSR from hyperthyroid rabbits. The Ca(2+ )sensitivity of [(3)H]ryanodine binding and the dissociation constant for [(3)H]ryanodine did not differ significantly between euthyroid and hyperthyroid hearts. Measurement of Ca(2+)-release rates from passively Ca(2+)-preloaded JSR vesicles and assessment of the effect of RyR-Ca(2+)-release channel (CRC) blockade on active Ca(2+)-uptake rates revealed significantly enhanced (>2-fold) CRC activity in the hyperthyroid, compared with euthyroid, JSR. These results demonstrate overexpression of functional RyR in thyroid hormone-induced cardiac hypertrophy. Relative abundance of RyR may be responsible, in part, for the changes in SR Ca(2+) release, cytosolic Ca(2+) transient, and cardiac systolic function associated with thyroid hormone-induced cardiac hypertrophy.

Tumour epidermal growth factor receptor, erbB-2 and cathepsin D in node-negative invasive breast cancer: their impact on the selection of patients for systemic adjuvant therapy.

OBJECTIVE: To determine the feasibility and the economic impact of tumour EGFR, erbB-2 and cathepsin-D measurements in women with node-negative breast cancer. DESIGN: Consecutive tumour samples received at a regional steroid receptor laboratory from patients with node-negative breast cancer were evaluated with commercially available kits to determine EGFR, erbB-2 and cathepsin-D levels. SETTING: All node-negative patients whose tumours were submitted to the steroid receptor laboratory from November 1992 to March 1994 were included (n = 142). A control group of concurrent node-negative breast cancer patients from the London Regional Cancer Centre (LRCC) database were also evaluated to determine the representativeness of our sample. MAIN OUTCOME MEASURE: To determine the proportion of patients who were positive for the 3 newer prognostic factors relative to their risk of relapse. RESULTS: We found 75 positive values in 69 patients (48.6%). We demonstrated that each factor identified a different high-risk subgroup. Epidermal growth factor receptor (EGFR) positivity (> 10 fmol/mg protein) was found in 16.3% of patients, with 19.9% of patients positive for erbB-2 (> 250 units/mg protein) and 17.3% positive for cathepsin D (> 70 pmol/mg protein). Between 10% and 23.2% more node-negative patients currently seen in a regional cancer centre could be offered systemic adjuvant chemotherapy based on a single positive new factor. CONCLUSIONS: These tumour evaluations are straightforward using material already available in a regional steroid receptor laboratory or on tumour tissue available to pathologists. The economic impact is minimal; the 1995 cost of performing all 3 evaluations is Can$425-616 (US$304-440) per patient treated depending on the number of assays per run. Prospective clinical trials incorporating tumour EGFR, erbB-2 and cathepsin D are feasible and economically viable.

Exaggerated TSH responses to TRH in depressed patients with "normal" baseline TSH.

BACKGROUND: Subclinical hypothyroidism (elevated thyroid-stimulating hormone [TSH] with normal thyroid hormone levels) can present with depression. This may be confirmed by an exaggerated TSH response to thyrotropin-releasing hormone (TRH) on the TRH stimulation test (TRH-ST). The objective of this study was to determine the prevalence of exaggerated TRH-ST results in a sample of depressed patients with "high-normal" screening TSH levels. METHOD: Depressed patients with TSH levels of 3.00-5.50 mIU/L underwent a TRH-ST. After baseline TSH was drawn, TRH 400 micrograms was injected intravenously, and TSH samples were drawn at +20 min, +30 min, and +40 min postinjection. A rise in TSH after TRH (peak value minus baseline) of > 25 mIU/L represented an exaggerated TSH response. RESULTS: Twenty-three (38%) of 60 patients had an exaggerated TSH response to TRH. The 38% prevalence is significantly (Chi 2 = 59.65, df = 1, p < .001) greater than the 6% prevalence of positive TRH-ST results reported in the euthyroid general population. The prevalence of positive TRH-ST results was not attributable to differential patterns of psychotropic or thyroid hormone treatment. Unexpected observations were a lack of correlation in TSH levels week to week (r = .17, N.S.) and a lack of correlation between screening TSH value and subsequent TRH-ST results (r = .28, N.S.). CONCLUSION: Subtle thyroid underfunction may be contributing to depression in some patients with TSH in the upper half of the range usually considered normal. If so, then the TRH-ST may be more sensitive in identifying this than measurement of TSH alone.

Quantification of osteopontin in human plasma with an ELISA: basal levels in pre- and postmenopausal women.

OBJECTIVES: To develop an immunoassay for osteopontin (OPN), a secreted phosphoglycoprotein that is implicated in a number of human diseases, and establish basal plasma OPN levels in healthy women. DESIGN AND METHODS: An antigen-capture ELISA was developed to quantity OPN in plasma using a combination of mouse monoclonal and rabbit polyclonal antibodies. Basal OPN levels were determined in blood plasma of 21 pre- and 14 postmenopausal women obtained at 7-day intervals over a 4-week period. RESULTS: A group of 35 healthy women had a median OPN level of 31 micrograms/L (range = 14-64 micrograms/L). Comparison between pre- and postmenopausal women showed that their 4-week average OPN levels did not differ significantly (p > 0.16, Mann-Whitney test), and that levels in each premenopausal individual remained constant during the menstrual cycle, unaffected by cyclical levels of leuteinizing hormone and progesterone. CONCLUSION: Systematic quantification of plasma OPN can now be done by ELISA, which was used to establish basal plasma OPN levels in a group of healthy women. Levels in pre- and postmenopausal women appeared relatively stable over a 4-week period.