Hair analysis provides a historical record of cortisol levels in Cushing's syndrome.

The severity of Cushing's Syndrome (CS) depends on the duration and extent of the exposure to excess glucocorticoids. Current measurements of cortisol in serum, saliva and urine reflect systemic cortisol levels at the time of sample collection, but cannot assess past cortisol levels. Hair cortisol levels may be increased in patients with CS, and, as hair grows about 1 cm/month, measurement of hair cortisol may provide historical information on the development of hypercortisolism. We attempted to measure cortisol in hair in relation to clinical course in six female patients with CS and in 32 healthy volunteers in 1 cm hair sections. Hair cortisol content was measured using a commercially available salivary cortisol immune assay with a protocol modified for use with hair. Hair cortisol levels were higher in patients with CS than in controls, the medians (ranges) were 679 (279-2500) and 116 (26-204) ng/g respectively (P<0.001). Segmental hair analysis provided information for up to 18 months before time of sampling. Hair cortisol concentrations appeared to vary in accordance with the clinical course. Based on these data, we suggest that hair cortisol measurement is a novel method for assessing dynamic systemic cortisol exposure and provides unique historical information on variation in cortisol, and that more research is required to fully understand the utility and limits of this technique.

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.

Elevated content of cortisol in hair of patients with severe chronic pain: a novel biomarker for stress.

Hair analysis has been used to reflect long-term systemic exposure to exogenous drugs and toxins. Several studies have demonstrated the feasibility of measuring endogenous steroid hormones, e.g. cortisol, in hair. Recently, a study in macaques showed a significant increase in hair cortisol levels induced by stress. We explored whether hair cortisol levels may be used as a biomarker for long-term stress in humans. Patients with severe chronic pain, aged 18 years or older, receiving opioid treatment for at least one year were recruited. Controls were non-obese (body mass index, BMI < 30 mg/kg(2)) adults. The Perceived Stress Scale (PSS) questionnaire was used to assess perceived stress over the last 4 weeks. A hair sample was obtained from the vertex posterior. Cortisol was measured using an enzyme-linked immunosorbent assay. We included fifteen patients (nine females and six males) and 39 non-obese control subjects (20 females, 19 males). PSS scores (median and range) were significantly higher in chronic pain patients (24: 12-28) than in controls (12: 3-31)(P < 0.001). Hair cortisol contents (median and range) were significantly greater in chronic pain patients (83.1: 33.0-205 g/mg) than in controls (46.1: 27.2-200 pg/mg) (P < 0.01). We conclude that hair cortisol contents are increased in patients with major chronic stress. Measurement of cortisol levels in hair constitutes a novel biomarker of prolonged stress.

[No response to antihypertensive therapy: consider non-adherence]. / Geen reactie op antihypertensieve therapie: denk aan therapieontrouw.

In 3 patients, 2 men aged 62 and 43 years, respectively, and 1 woman aged 53 years, the medication prescribed to reduce blood pressure was insufficiently effective. Drug adherence was questioned. The first patient was afraid of the side effects mentioned in the medication information leaflet. The second patient had insufficient plasma levels of the medication but would not discuss the subject. The blood pressure of the third patient was uncontrolled despite treatment with three antihypertensive drugs. During a short hospital stay, her blood pressure responded favourably to treatment with only one of the three drugs. Subsequent repeated instruction did not improve her situation. Drug adherence is an important issue in daily clinical practice. In patients with asymptomatic conditions like hypertension, adherence is expected to be poor and worsen over time. Adherence is very difficult to measure. Risk factors for poor adherence include complex medication schedules, multiple dosing times, depression and real or suspected side effects. Measures to improve drug adherence include simplifying the medication schedule, discussing the schedule during check-ups, using automated blood pressure measuring devices at home, maintaining e-mail contact with the patient and involving a specialised nurse. Increased awareness of poor adherence is an important step toward improving hypertension treatment.

Dehydroepiandrosterone administration in humans: evidence based?

Dehydroepiandrosterone (DHEA) and its ester dehydroepiandrosterone sulphate (DHEAS) are produced by the adrenal glands. These hormones are inactive precursors that are transformed into active sex steroids in peripheral target tissues. After a peak in early adulthood, there is a marked decrease in plasma concentrations throughout adult life. These hormones are thought to affect mood and well-being, have neurosteroid effects and may influence the immune system. Animal experiments suggest that DHEA has many other effects, including anticancer, immune-enhancing, neurotropic and general antiageing effects, but information based on studies in humans is limited. In female patients with adrenal insufficiency, treatment with DHEA replacement doses of 20 to 50 mg results in improvements in mood, quality of life and libido. These studies usually lasted only a few months, so the effect of chronic DHEA treatment or its effectiveness in male patients is not known. Some studies suggest a favourable effect of pharmacological doses of DHEA in the treatment of depression. DHEA may have a very limited effect on cognitive function in elderly people, and some studies suggest a beneficial immunomodulatory effect of DHEA in patients with autoimmune diseases, but further studies are warranted before introducing DHEA for these indications in clinical practice.

Massive reduction of tumour load and normalisation of hyperprolactinaemia after high dose cabergoline in metastasised prolactinoma causing thoracic syringomyelia.

In 1970 a 20 year old woman presented with a pituitary chromophobe adenoma for which she underwent transfrontal pituitary surgery. In 1978 she had to be reoperated on because of local tumour recurrence, resulting in hypopituitarism. Bromocriptine (5 mg/day) was given for 15 years, but the plasma prolactin levels remained elevated. In 2000 the patient presented with signs and symptoms suggestive of a spinal cord lesion at the mid-thoracic level. A magnetic resonance imaging (MRI) scan showed an extensive leptomeningeal mass extending from the brainstem to L5, with a thoracic syringomyelia at the T7-T8 level. The plasma prolactin level was very high (5114 microg/l). A biopsy showed the presence of a metastasised prolactinoma. On administration of high dose cabergoline, 0.5 mg twice a day orally, the plasma prolactin levels decreased within one month and then normalised within 26 months. Tumour load reduced considerably but unfortunately, her signs and symptoms did not improve. This case illustrates that a high dose dopamine agonist might be an important therapeutic option in patients with a metastasised prolactinoma.

Short-term cortisol infusion in the brachial artery, with and without inhibiting 11 beta-hydroxysteroid dehydrogenase, does not alter forearm vascular resistance in normotensive and hypertensive subjects.

BACKGROUND: Vascular tone is increased in primary hypertension, and glucocorticoids affect vascular tone. Local cortisol availability is modulated by activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). As this activity may be decreased in patients with primary hypertension, vascular sensitivity to cortisol may be increased in these patients. We studied the acute effect of cortisol on forearm vascular resistance (FVR) by infusing cortisol directly into the brachial artery, both with and without inhibition of 11 beta-HSD, in normotensive and hypertensive subjects. DESIGN: Twenty normotensive volunteers and 20 patients with primary hypertension participated in the study. After a 10-min infusion of vehicle (glucose 5%), cortisol was infused into the brachial artery in three stepwise increasing doses (3.5, 10.5 and 35 microg per 100 mL of forearm volume), each for 10 min. Next, the participants received placebo or 500 mg glycyrrhetinic acid (GA) orally, and 150 min later the same infusion schedule was repeated. Forearm vascular resistance was measured during the last 5 min of the infused vehicle and of each dose. Arterial and forearm venous plasma samples for measurement of cortisol and cortisone were taken at the end of the infusions of glucose 5% and the highest cortisol dose. RESULTS: In both normotensive and hypertensive subjects, neither the infusion of cortisol nor the administration of GA changed FVR. Also 2 h after the cortisol infusion there remained no change in FVR in both the normotensive and hypertensive groups who received placebo. Following the infusion of the highest cortisol dose, total plasma cortisone levels in the venous plasma were decreased compared with levels in the arterial plasma (36 +/- 3 and 49 +/- 4 nmol L-1, respectively, P < 0.05). The protein-bound venous cortisone was 37.1 +/- 4.8 nmol L-1 during the vehicle compared with 23.9 +/- 3.7 nmol L-1 during the cortisol infusion (P < 0.01), whereas the free cortisone level was not altered by the cortisol infusion. CONCLUSIONS: In both normotensive and hypertensive subjects, high-dose cortisol infusion both with and without 11 beta-HSD inhibition did not change FVR either immediately or after 2 h. We could not demonstrate in vivo 11 beta-HSD activity in the forearm vascular tissues. When binding of cortisone to CBG is changed, e.g. during cortisol infusion, arterio-venous changes in cortisone cannot reliably be used to assess (alterations in) local 11 beta-HSD activity.