A new digital health tool for the telemonitoring of patients with scleroderma during iloprost administration: a feasibility and acceptability study.

OBJECTIVE: To assess the feasibility of a new device for telemonitoring vital parameters during iloprost infusion. MATERIALS AND METHODS: In a pilot study, patients with systemic sclerosis received iloprost infusion while being telemonitored with Umana T1 Heart Monitor, within the hospital, under the supervision of family/community nurses and rheumatologists. Patients were administered a questionnaire to obtain information on satisfaction, practicability, and compliance with the new monitoring device. RESULTS: Data recorded by the device for blood pressure, heart rate, and oximetry were concordant with those registered directly by nurses. Most patients found the device useful and thought it could be used at home, even while working. CONCLUSIONS: Umana Heart Monitor T1 could be a valuable aid in at-home iloprost therapy in patients with systemic sclerosis.

Mycophenolic acid in rheumatology: mechanisms of action and severe adverse events.

Mycophenolic acid (MPA) is an immunosuppressive agent, more and more extensively used in transplantation, rheumatology and nephrology. In this review, we will analyze the molecular mechanisms of its action, including the newest insights, in particular the inhibition of lymphocytes and the induction of tolerogenic dendritic cells (DCs) and its direct effects on non-immune cells (fibroblasts and myofibroblasts, mesangial cells, vascular smooth muscle cells [VSMC], endothelial cells). The latters suggest new therapeutic indications, specifically fibrosis (i.e. glomerulosclerosis and interstitial lung diseases), vascular damage and pulmonary hypertension, which represent key pathogenic features in connective tissue diseases. Given the differences in sensitivity to MPA among the various cell types and the great inter-individual variability in MPA pharmacokinetics, adequate daily doses and therapeutic drug monitoring may be decisive to ensure those MPA concentrations needed to switch off inflammation and restore peripheral tolerance in autoimmune disease (AID) patients. A warning on the severe adverse events strictly linked to immune suppression (i.e. progressive multifocal leukoencephalopathy [PML]) will be stressed.

Are subjects with erectile dysfunction aware of their condition? Results from a retrospective study based on an Italian free-call information service.

The aim of the study was to analyse the socio-demographic and epidemiological characteristics of the Italian male population affected by sexual disturbances. Men complaining of erectile dysfunction (ED) who called the Pfizer program "Man and Woman in Health" between April 18th 2001 and May 27th 2002 and asked for information about their medical condition, were interviewed by trained doctors using a computer-assisted questionnaire. 16007 out of 25018 calls were considered for statistical analysis. Mean age of callers was 48.8+/-14.2 yr, reporting ED in 83% of cases. In the majority of men ED was severe (58%) and lasting more than 3 yr (25%). Multivariate analysis revealed that diabetes, depression, prostate surgery, heart disease, neurological disorders, liver and renal diseases were all significant and independent contributors to the degree of erectile impairment adjusted for age (p<0.001). The principal concomitant medications were anti-hypertensive (23%), antidiabetic (9%) and cardiovascular agents (6%). Cigarette smoking was present in 24%. On directed questioning of the caller, anxiety and distress were perceived as the most frequent causes of ED (42%) across all age groups, followed by the presence of concomitant disease/s (26%) especially in aging men. Also, a large number of men (41 %) with severe ED waited for more than 3 yr before looking for medical referral. Interestingly, only 19% had ever tried any specific medication for ED. These data indicate that 5 yr after worldwide approval and release of sildenafil, ED is still largely undiagnosed and under-treated, possibly because it is still perceived as a condition mainly due to distress or advancing age and therefore not deserving medical referral. Effective prevention of ED commences with better awareness of the pathological causes by the population and modification of risk factors by the doctors.

Did men with erectile dysfunction discuss their condition with partner and physicians? A survey of men attending a free call information service.

We present data collected among men attending a free call service on information on erectile dysfunction (ED) activated in Italy during the period 1997-1999. Their attitudes towards discussion with their partner and physician about the condition are considered. Each subject, was asked if he was affected by ED (defined as inability to achieve and maintain an erection sufficient for satisfactory sexual performance). In the case of a positive answer, the subject was asked if he had ever discussed his condition with partner or a physician. A total of 12 761 subjects with ED called the service: 7265 (56.9%) reported to have discussed their condition with their partner. The proportion tended to increase with duration of ED, being 47.9% in subjects reporting ED lasting <6 months and 59.9% in those reporting ED lasting >3 y (w(2)(1) trend <0.05). Likewise, the proportion of subjects reporting to have discussed ED with a physician was 50.3% (6416 subjects), being 33.6% in subjects with ED lasting <6 months and 57.9% of those with ED lasting >3 y (w(2)(1) trend, P<0.01).

Acute estradiol and progesterone administration reduced cardiovascular and catecholamine responses to mental stress in menopausal women.

Steroid hormones are involved in the regulation of sympathoadrenal activity. Since the effect of sex steroids on the cardiovascular system and catecholamine secretion could also be exerted through an acute, nongenomic mechanism, we have studied the response to mental stress (color word test, CWT) in a group of 15 menopausal women during estrogen (100 microg of estradiol by patch), progesterone (100 mg i.m.) or placebo administration. Systolic blood pressure (SBP) increased during CWT in the three sessions (F = 11.0, p < 0.001) but the area under the curve of SBP was higher during placebo (2,855 +/- 131 mm Hg x min) than during estradiol (2,585 +/- 139 mm Hg x min) and progesterone (2,553 +/- 179 mm Hg x min, p < 0.05 for both). Plasma epinephrine increased during CWT in the three sessions (F = 31.1, p < 0.001) and the plasma epinephrine response to mental stress was higher during placebo than during estradiol administration (F = 4.3, p < 0.01). The area under the curve of epinephrine was 10,342 +/- 1,348 pmol/min x 1 during placebo and 7,280 +/- 818 pmol/min x 1 during estradiol (p < 0.03). The plasma glycerol levels at the end of CWT were higher during placebo (0.26 +/- 0.04 nmol/l) than during estradiol (0.19 +/- 0.03 mmol/l) and progesterone (0.17 +/- 0.04 mmol/l) administration (p < 0.05 for both). No significant differences were found in the responses of diastolic blood pressure, heart rate, norepinephrine and cortisol to mental stress during placebo and estradiol or progesterone administration. This study demonstrates that acute steroid administration is able to modify the cardiovascular and catecholamine response to mental stress in menopausal women.

Alpha-2 adrenergic activity in perimenopausal women.

Lipid alterations and increased blood pressure may occur during perimenopause. No data are available in perimenopausal women on the alpha-2 adrenergic activity which affects norepinephrine secretion. We studied cardiovascular and catecholamine responses to clonidine (300 mg per os) in a group of 15 perimenopausal women (PeriMW) and in a control group of 13 premenopausal women (PreMW). Nine of the perimenopausal women were also studied after 4-month percutaneous estrogen replacement therapy (PeriMWE). Systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma norepinephrine (NE) and epinephrine (E) were evaluated before and at 120 min, 130 min, 140 min after clonidine administration. Basal values of SBP, DBP and HR were not different (F = 0.7, p = NS; F = 0.2, p = NS and F = 0.1, p = NS respectively) between PeriMW both before and after therapy and PreMW. Resting levels of E were similar in PreMW and in PeriMW before and during estrogen therapy (F = 0.8, p = NS); PeriMW showed higher basal NE levels both before and during estrogen therapy than PreMW (F = 12; p < 0.001). Clonidine administration decreased SBP, DBP and NE levels in PreMW, in PeriMW and in PeriMWE without any difference between the groups (F = 1.2, p = NS; F = 0.5, p = NS and F = 1.3, P = NS respectively). HR decreased significantly after clonidine in PreMW (F = 5.4, p < 0.03) but not in PeriMW before (F = 1.0, p = NS) and during estrogen therapy (F = 0.5, p = NS). Clonidine did not affect plasma E in the three groups studied (F = 2.8, p = NS; F = 2.2, P = NS and F = 0.1, p = NS). The present study demonstrates that increased basal plasma NE levels are present in PeriMW. The cardiovascular and catecholamine response to clonidine in PeriMW both before and during estrogen therapy are similar to those observed in PreMW, suggesting a normal inhibitory alpha-2 receptor pathway.

Increased cardiovascular response to caffeine in perimenopausal women before and during estrogen therapy.

Perimenopause and menopause may be associated with an increased risk of cardiovascular disease, so we have investigated the cardiovascular and catecholamine response to caffeine in perimenopausal women compared to young cycling premenopausal subjects. Caffeine (250 mg per os) was administered to nine perimenopausal women and nine premenopausal women. The perimenopausal women repeated the test after 4 months of percutaneous estrogen replacement therapy. Systolic and diastolic blood pressure, pulse rate, plasma norepinephrine, epinephrine, glucose, insulin and free fatty acids were determined at 0, 15, 30, 45, 60, 90 and 120 min after caffeine administration. No differences were found in the basal values of systolic blood pressure, diastolic blood pressure, pulse rate, norepinephrine, epinephrine, insulin, glucose and free fatty acids between perimenopausal women, both before and after therapy, and premenopausal women. Caffeine induced a higher increase of systolic (F = 4.9; p < 0.05) and diastolic blood pressure (F = 4.7; p < 0.05) in perimenopausal women before and during estrogen therapy as compared with premenopausal women. Pulse rate increased significantly only in perimenopausal women before therapy (F = 6.5; p < 0.03). These data show that perimenopause either before or during short-term estrogen therapy is associated with enhanced cardiovascular reactivity to caffeine. This phenomenon is not due to increased adrenergic and metabolic responses.

The effects of clonidine on blood pressure, catecholamine and growth hormone release in hypogonadal men is preserved and not influenced by testosterone replacement therapy.

It has been demonstrated that castration impairs the hypotensive effect of clonidine in rat as well as its GH-releasing activity while testosterone replacement restores to normal the effects of alpha-2 adrenoceptor activation. Thus, these data point to main role of the gonadal steroid testosterone in modulating the effects of alpha-2 adrenergic activation on blood pressure, catecholamine and GH release in animal. Aim of the present study was to verify the activity of clonidine on blood pressure, catecholamine and GH release in human male hypogonadism before and after testosterone replacement. To this goal, 14 hypogonadal men (HP, age 33.8 +/- 2.9 yr; BMI < 25 kg/m2; 8 with hypergonadotropic and 6 with hypogonadotropic hypogonadism) received clonidine administration (CLON, 300 micrograms po at 0 min) before and after 3 months of testosterone replacement (testosterone propionate depot, 250 mg i.m. every 21 days). Ten normal adult volunteers (NS, age 31.5 +/- 1.9 yr; BMI < 25 kg/m2) were studied as control group. In all subjects, before and after clonidine administration, systolic and diastolic blood pressure (SBP and DBP), pulse rate (PR), norepinephrine (NE), epinephrine (E) and GH levels were recorded. In HP basal testosterone levels were lower than those in NS (1.25 +/- 0.3 vs 7.34 +/- 1.5 ng/ml, p < 0.05) and were restored to normal by hormonal replacement (6.91 +/- 1.3 ng/mL) in HP, both SBP and DBP as well as PR were normal in basal conditions and were not modified by testosterone replacement. Both before and during testosterone CLON lowered SBP, DBP and PR in HP to the same extent observed in NS. In HP, basal NE levels were lower than those in NS (0.85 +/- 0.15 vs 1.28 +/- 0.19 nmol/l, p < 0.05) and were restored to normal during testosterone replacement (1.25 +/- 0.13 nmol/l). On the other hand, basal E levels in HP were similar to those in NS (179 +/- 42 vs 197 +/- 38 pmol/l) and were not modified by testosterone therapy (167 +/- 28 pmol/l). In HP, both before and during testosterone replacement, CLON reduced NE (0.44 +/- 0.10 and 0.58 +/- 0.07 nmol/l) levels to the same levels recorded in NS (0.68 +/- 0.08 nmol/l). Basal GH and IGF-I levels in HP (1.15 +/- 0.5 and 234 +/- 42 micrograms/l, respectively) were similar to those in NS (1.18 +/- 0.4 and 221 +/- 38 micrograms/l, respectively) and were not modified by testosterone (1.35 +/- 0.6 and 256 +/- 32 micrograms/l, respectively). CLON administration induced a clear GH response in HP (F = 37; p < 0.001) which overlapped with that recorded in NS and was not modified by testosterone (F = 1.7; P = NS). Our present findings demonstrate that, differently from in animal, in man testosterone has no role in modulating the effects of alpha-2 adrenergic activation by clonidine on blood pressure, catecholamine and GH release. On the other hand, our data suggest the existence in male hypogonadism of a reduced basal noradrenergic activity which is restored by testosterone replacement.

Effect of testosterone replacement therapy on the somatotrope responsiveness to GHRH alone or combined with pyridostigmine and on sympathoadrenal activity in patients with hypogonadism.

There is evidence suggesting that androgens influence GH secretion in man. Our aim was to verify whether the GH releasable pool is preserved and influenced by testosterone replacement in male hypogonadism. To this goal, in eight male hypogonadal patients (HP, age 32.2 +/- 5.0 yr; Body Mass Index 23.9 +/- 1.1 kg/m2) before and after 3 months testosterone therapy, we studied the GH response to GHRH (1 microgram/kg iv) alone and combined with pyridostigmine (PD, 120 mg po), a cholinesterase inhibitor which likely inhibits hypothalamic somatostatin release allowing exploration of the maximal somatotrope secretory pool. Sixteen normal subjects (NS, age 30.1 +/- 3.5 yr; Body Mass Index 22.5 +/- 1.8 kg/m2) were studied as controls. The GH response to GHRH in HP was similar to that in NS (AUC, mean +/- SE: 1238 +/- 362 vs 1018 +/- 182 micrograms/L/h). PD potentiated to the same extent the GH response to GHRH in both groups (2092 +/- 807 and 2840 +/- 356 micrograms/L/h). After three month testosterone therapy, in HP the GH responses to GHRH alone (1352 +/- 612 micrograms/L/h) and combined with PD (1948 +/- 616 microgram/L/h) were unchanged. Also IGF-I levels in HP were similar to those in NS (222 +/- 42 vs 210.6 +/- 55.8 micrograms/L) and were unchanged during testosterone replacement (280 +/- 31 micrograms/L). As androgens have been reported to modulate sympathoadrenal activity in the rat, both before and during testosterone replacement, we also measured plasma catecholamine levels. Basal NE (p < 0.05) but not E levels were lower in HP than in NS; testosterone restored basal NE levels to normal without affecting basal E. delta absolute increase of NE and E (p < 0.05 and 0.01 vs baseline, respectively) after PD in HP were similar to those in NS and were unchanged during testosterone replacement. In conclusion, these results demonstrate that the GH releasable pool is preserved in male hypogonadism. As in this condition a reduction of spontaneous GH secretion has been reported, it could be due to neurosecretory dysfunction but not to pituitary impairment. Subtle alterations of sympathoadrenal activity seem to be present in male hypogonadism and reversed by testosterone replacement.

Cardiovascular and catecholamine response to clonidine in obese subjects.

OBJECTIVE: To investigate central alpha-2 adrenergic activity, one of the main inhibitory factors affecting norepinephrine secretion, in human obesity. DESIGN: Cardiovascular and catecholamine responses to clonidine (300 micrograms per os) were evaluated in a group of obese subjects. SUBJECTS: 10 obese men (OM) and 14 obese women (OW). MEASUREMENTS: Mean arterial pressure, pulse rate, plasma norepinephrine (NE) and epinephrine (E) before and 120', 130', 140' after clonidine (CL) administration. RESULTS: The mean arterial pressure decreased after CL administration in obese patients (from 92 +/- 12 to 79 +/- 2 mmHg; P < 0.001) with no significant differences between OM and OW. The values of pulse rate were reduced in obese patients after clonidine (60 +/- 1 b/min vs 65 +/- 1 b/min before clonidine; P < 0.01) with no differences between OM and OW. Plasma E was not affected by the administration of clonidine and no sex related differences were found in the basal (OM: 0.23 +/- 0.03 vs OW: 0.15 +/- 0.03 nmol/L; P = NS) and in the post-CL E levels (OM: 0.22 +/- 0.02 vs OW: 0.14 +/- 0.03 nmol/L; P = NS). Basal plasma NE values were not different between OM (1.32 +/- 0.15 nmol/L) and OW (1.03 +/- 0.11 nmol/L; P = NS). Plasma NE decreased after CL in obese patients (from 1.20 +/- 0.10 to 0.59 +/- 0.08 nmol/L; P < 0.001) and a significant difference was found in the post-CL values between OM and OW (0.74 +/- 0.11 vs 0.40 +/- 0.06 nmol/L respectively; P < 0.01). The decrease in plasma NE was strongly correlated with the basal value of NE (r = 0.70; P < 0.001). The sex-related differences in plasma NE responses to clonidine in obese subjects did not differ with those previously observed in control subjects (P = NS). CONCLUSION: The cardiovascular and catecholamine response to CL in obese patients were similar to that previously observed in normal subjects, indicating a normal alpha-2 adrenergic activity. The sex related difference in the NE response to CL, previously reported in normal subjects, was maintained in obese patients.

Effect of estradiol on the sympathoadrenal response to mental stress in normal men.

It has been shown that steroid hormones are able to influence the sympathoadrenal system activity. Therefore, we have investigated in a double blind cross-over study the effect of percutaneous estradiol administration (100 micrograms) on the sympathoadrenal and cardiovascular responses to mental arithmetic stress in 20 normal young males. The plasma estradiol level was 154 +/- 14 pmol/L during the estrogen session (ES) and 44 +/- 7 pmol/L during the placebo session (PL; P < 0.001). The mental stress induced a significant increase in systolic blood pressure during both the PL (F = 7.2; P < 0.001) and the ES (F = 4.8; P < 0.01); the peak obtained during PL was, however, higher than that during ES (128 +/- 2 vs. 122 +/- 3 mm Hg; P < 0.02). A significant increase in pulse rate was observed during PL (F = 4.2; P < 0.002), but not during ES (F = 2.6; P = 0.47), with the peak pulse rate being higher during mental stress in the PL than the ES (78 +/- 2 vs. 74 +/- 2 beats/min; P < 0.03). In response to the mental stress, plasma epinephrine increased significantly during PL (F = 3.2; P < 0.03), but not during ES (F = 1.1; P = 0.3). The stress-induced peak in plasma epinephrine during PL was higher than that during ES when expressed as the absolute value or the incremental peak (513 +/- 103 vs. 125 +/- 32 pmol/L; P < 0.005). The incremental peak in plasma norepinephrine obtained during PL was higher than that during ES (0.78 +/- 0.1 vs. 0.27 +/- 0.07 nmol/L; P < 0.02). Plasma free fatty acid, acetoacetate, and 3-hydroxybutyrate increased significantly from basal values during PL, but not during ES. These data show that mildly elevated levels of estradiol are able to influence the response of the adrenal medulla to mental stress in men.

[Invasive pulmonary aspergillosis in oncological hematology: its pathogenesis and correlated radiographic picture]. / L'aspergillosi polmonare invasiva nell'oncoematologia: patogenesi e quadri radiografici correlati.

Invasive pulmonary aspergillosis (IPA) in the presence of hematologic malignancies is an increasingly common condition characterized by high morbidity and mortality. Plain chest films are a valuable tool for diagnosis but the radiologist must be familiar with the morphological features of the disease to interpret radiographic abnormalities and to differentiate IPA from opportunistic pneumonia. The chest films of 16 leukemia and IPA patients performed from January 1987 to September 1993 were reviewed. The natural course of infection from its early stage (nodular lesions) to the subsequent phases when eventual medullary recovery plays a critical role was thus traced. Our major finding was related to the histogenesis of primary pulmonary lesions: the most common features we observed--i.e., the spherical rather than triangular shape of necrosis areas, with no relationship to the pleura or scissural delimitation suggest that supposed ischemia from vascular infiltration cannot be the only pathogenetic factor of pulmonary injury, in spite of the well-known angioinvasivity of the fungus Aspergillus.

Plasma catecholamines after thyrotropin-releasing hormone administration in hypothyroid patients before and during therapy.

In order to investigate sympathoadrenal activity in hypothyroidism we studied the cardiovascular and catecholamine responses to thyrotropin-releasing hormone (TRH) infusion in nine hypothyroid patients before and during adequate therapy and in seven healthy subjects. We evaluated mean arterial pressure, heart rate, plasma epinephrine and norepinephrine levels after TRH administration (200 micrograms iv) in the three groups. Mean arterial pressure, heart rate and plasma epinephrine levels were not different in the three groups and did not change after TRH administration. Hypothyroid subjects showed increased plasma norepinephrine levels (1.48 +/- 0.15 nmol/l), which were reduced after euthyroidism was reached (0.84 +/- 0.11 nmol/l) (p < 0.01). An exaggerated response of norepinephrine to TRH was observed in hypothyroid patients before therapy (incremental peak (IP) = 0.59 +/- 0.13 nmol/l) but not in hypothyroid patients during therapy (IP = 0.19 +/- 0.02 nmol/l p < 0.02) or in the control group (IP = 0.15 +/- 0.04 nmol/l; p < 0.05). This study indicated that TRH administration is able to influence the sympathetic activity during hypothyroidism in humans.

Alpha 2-adrenergic activity is normal in patients with thyroid disease.

OBJECTIVE: Several studies indicate an inverse relationship between the sympathetic nervous system activity and thyroid function. Altered adrenoceptor sensitivity, particularly alpha 1 and beta, have been described in hypothyroid and hyperthyroid patients. No information in patients with thyroid disease is available on the main mechanism regulating sympathetic nervous system outflow, i.e. the alpha 2-adrenoceptor pathway. In our study we evaluated alpha 2-adrenergic activity in patients with thyroid disease by the assessment of cardiovascular and catecholamine response to clonidine, a central alpha 2 adrenergic agonist. PATIENTS: Ten patients with hypothyroidism, six patients with hyperthyroidism before and during adequate therapy, and ten healthy subjects. MEASUREMENTS: After three blood samples for the basal determination of noradrenaline and adrenaline, the subjects swallowed 4 micrograms/kg body weight of clonidine. Blood pressure and pulse rate were measured 30, 60, 90, 120, 130 and 140 minutes after clonidine administration; blood samples for determination of catecholamines were drawn at 120, 130 and 140 minutes. RESULTS: At presentation the decrease in plasma noradrenaline after clonidine in the patients was similar to that of the control group (hypothyroids: 1.07 +/- 0.23 nmol/l mean +/- SEM; hyperthyroids: 0.54 +/- 0.06 nmol/l; controls; 0.36 +/- 0.10 nmol/l; F = 1.2, P = NS). No differences were detected in the fall in adrenaline and mean arterial pressure (MAP) after clonidine. The adequate therapy induced in hypothyroid patients a decrease in the basal levels of noradrenaline (1.88 +/- 0.28 vs 0.67 +/- 0.10 nmol/l; P < 0.05) and a lesser fall in mean arterial pressure after clonidine (delta MAP 20.4 +/- 2.0 vs 9.7 +/- 2.8 mmHg; P < 0.05). No variations were detected in hyperthyroid patients after therapy either in basal hormones levels or in the magnitude of decrement in MAP and noradrenaline induced by clonidine. CONCLUSIONS: We conclude that in spite of the previously reported abnormalities in alpha 1 and beta-adrenergic receptor activity, the inhibitory alpha 2-receptor pathway is normal in patients with altered thyroid function.

Sex differences in catecholamine response to clonidine.

Sex-related differences both in the basal secretion of catecholamines and in the adrenergic reactivity to various stimuli have been described. We studied the responses of catecholamines and arterial blood pressure to clonidine (0.3 mg per os) in 31 normotensive subjects (10 men (M), aged 18-42 years, and 21 women (W), aged 20-48 years). Plasma catecholamines were determined by HPLC at -30, -15, 0, 120, 130, 140 min after clonidine. The basal levels of plasma norepinephrine were similar in men and in women (M = 1.16 +/- 0.26 vs. W = 0.87 +/- 0.07 nmol/l). Basal plasma epinephrine levels were not different in the two sexes (M = 0.21 +/- 0.03 vs. W = 0.14 +/- 0.03 nmol/l). The mean arterial pressure decrease after clonidine was similar in the two groups (M = 13 +/- 3 vs. W = 15 +/- 2 mmHg). The decrease in plasma epinephrine after clonidine was similar in men and women (M = 0.06 +/- 0.04 vs. W = 0.09 +/- 0.02 nmol/l). In contrast, the plasma levels of norepinephrine after clonidine were reduced more in women than in men either when expressed as absolute values (W = 0.63 +/- 0.07 vs. M = 0.3 +/- 0.1 nmol/l; F = 7.6, P < 0.02) or as percentage change (W = 71 +/- 3 vs. M = 34 +/- 8; P < 0.002). The present study demonstrates that an elevated alpha 2-adrenergic activity in women may be responsible for the sexual dimorphism in catecholamine secretion.

Daily variations in catecholamine excretion are not influenced by very low calorie diet in obese women.

The increase in metabolic efficiency during energy restriction seems to be an established phenomenon in obese patients. The sympathoadrenal system is involved in the control of energy expenditure and the catecholamine responses to stimuli vary during the day. We therefore studied the circadian pattern of urinary catecholamine excretion during 4-h collections for two consecutive days in a group of 20 obese female patients during and after a very low calorie diet (500 kcal/die). The diet period induced a significant weight loss in all the patients studied (99.1 +/- 3.7 vs 92.5 +/- 4.1 Kg; p < 0.01). The mean daily excretion of epinephrine did not change after 24 days of diet restriction when compared with the value obtained at the 4th day (12.0 +/- 2.5 vs 10.3 +/- 2.2 nmol/4 h respectively; p = NS) while a slight decrease was observed in the mean daily excretion of norepinephrine (52.5 +/- 8.7 vs 66.6 +/- 9.3 nmol/4 h respectively; p = NS). A circadian rhythm was detected for epinephrine and norepinephrine excretion both during and after very low calorie diet. No significant changes were found in the chronobiological characteristics of epinephrine and norepinephrine with the peak of excretion in the afternoon both during (epinephrine: 16:30 h; norepinephrine: 16:45 h) and after the diet (epinephrine: 17:35 h; norepinephrine: 18:00 h). It seems doubtful that alterations in the chronobiological pattern of catecholamines play a role in the metabolic adaptation occurring during very low calorie diet in obese females.

Effects of thyroid hormone status on the growth hormone responses to clonidine.

It has been shown that thyroid hormones are positive regulators of GH synthesis and secretion. The serum GH response to stimuli seems to be influenced either by sex or by spontaneous hypothalamic rhythm. The growth hormone responses to clonidine administration (4 micrograms/kg) have been therefore studied in a group of female patients with thyroid disease (seven hyperthyroid and five hypothyroid) before and after the achievement of the euthyroid state. In hyperthyroid patients both basal and clonidine-stimulated GH levels were similar to normal subjects; the achievement of euthyroidism did not modify the GH response to clonidine. Serum GH peaks after clonidine were lower in hypothyroids patients than in hyperthyroids and normal subjects; the GH response to alpha 2-agonist administration did not change during thyroid replacement therapy. The GH response to clonidine was not influenced by the GH secretory status in the preceding hour.