Relationship between clinical, 24-hour, average day-time and night-time blood pressure and measures of arterial stiffness in essential hypertension

Arterial wall stiffness is considered an independent cardiovascular risk factor. Aim of this study was to evaluate relationship between clinical, 24-hour, average day-time and night-time blood pressure (BP) and measures of arterial stiffness assessed by pulse wave velocity (PWV) (using SphygmoCor applanation tonometer) in essential hypertension (severe-resistant (RH, n=29) and moderate hypertension (EH, n=35)) and in normotensive control subjects (n-29) (NCS) matched by age. After multiple regression analysis, PWV remains significantly correlated mainly with night-time pulse pressure and to a lesser extent with age. PWV was significantly higher in RH compared to moderate EH and NCS.     

24-hour profiles of blood pressure and heart rate in Cushing's syndrome: relationship between cortisol and cardiovascular rhythmicities

We monitored the circadian profiles of cortisol, systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) in 33 matched normotensive subjects, 32 patients with essential hypertension and 16 patients with Cushing's Syndrome (8 pituitary adenomas, 6 adrenal adenomas and 2 adrenal carcinomas). Each subject underwent serial blood drawings at 4-hr intervals along the 24-hr cycle. BP and HR were automatically recorded every 30 min. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry). Both the control subjects and essential hypertensives showed a circadian profile of BP and HR characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: P less than 0.001). The rhythmicity of BP was disrupted in patients affected by Cushing's Syndrome, whereas the 24-hr oscillation of HR was preserved (P less than 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control.     

Twenty-Four hour blood pressure profile in subjects with different subtypes of primary aldosteronism

The aim of our study was to evaluate the potential differences in blood pressure (BP) profile in subjects with different forms of primary aldosteronism (PA). Simultaneously, we studied the effects of PA treatment on BP curve. We therefore monitored 24-hour ambulatory blood pressure values in 22 subjects with aldosterone-producing adenoma (APA), 22 subjects with idiopathic hyperaldosteronism (IHA) and 33 subjects with essential hypertension (EH) as controls. We found a significantly attenuated nighttime systolic BP decline in the APA group (P=0.02). Patients with IHA had lower nighttime systolic BP values (P=0.01) and also a diastolic BP decline (P=0.02) during the night in comparison with EH. We did not detect any significant differences in BP profile characteristics between APA and IHA. Specific treatment of primary aldosteronism (adrenalectomy, treatment with spironolactone) led to the normalization of the BP curve with a marked BP decline. Our study thus demonstrates a blunted diurnal BP variability in patients with primary aldosteronism the specific treatment of which normalized previously attenuated nocturnal BP fall.     

Blunting of circadian rhythms and increased acrophase variability in sleep-time hypertensive subjects

24 h and ultradian rhythms of blood pressure (BP) have been previously shown to be disorganized in nocturnal hypertensive subjects. The present study was undertaken to further analyze the ultradian and circadian BP rhythm structure in sleep-time hypertensive subjects with normal or elevated awake-time BP levels. Fourier analysis was used to fit 24, 12, 8, and 6 h curves to mean BP as well as heart rate (HR) time series data derived from 24 h ambulatory blood pressure monitoring. Awake and sleep periods were defined according to individual sleep diaries. Awake-time hypertension was defined as diurnal systolic (SBP) and/or diastolic BP (DBP) means ≥135/85 mmHg. Sleep-time hypertension was defined as nocturnal SBP and/or DBP means ≥120/70 mmHg. The sample included 240 awake-time normotensive subjects (180 sleep-time normotensives and 60 sleep-time hypertensives) and 138 untreated awake-time hypertensive subjects (31 sleep-time normotensives and 107 sleep-time hypertensives). The amplitude and integrity (i.e., percent rhythm) of the 24 and 12 h BP rhythms were lower in the sleep-time hypertensive subjects and higher in the awake-time hypertensive subjects. However, no differences were detected when the integrity and amplitude of the 6 and 8 h mean BP rhythms were analyzed. The sleep-time hypertensive group showed significantly higher 24 h BP rhythm acrophase variability. No differences could be found in any of the HR rhythm parameters. Altogether, the findings suggest a disorganization of the BP circadian rhythm in sleep-time hypertensives that results in reduced 24 h rhythm amplitude and integrity that could be related to cardiovascular risk.     

24-Hour Profiles of Blood Pressure and Heart Rate in Cushing's Syndrome: Relationship Between Cortisol and Cardiovascular Rhythmicities

We monitored the circadian profiles of Cortisol, systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) in 33 matched normotensive subjects, 32 patients with essential hypertension and 16 patients with Cushing's Syndrome (8 pituitary adenomas, 6 adrenal adenomas and 2 adrenal carcinomas). Each subject underwent serial blood drawings at 4-hr intervals along the 24-hr cycle. BP and HR were automatically recorded every 30 min. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry). Both the control subjects and essential hypertensives showed a circadian profile of BP and HR characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: P< 0.001). The rhythmicity of BP was disrupted in patients affected by Cushing's Syndrome, whereas the 24-hr oscillation of HR was preserved (P < 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control.     

Repeated assessment of the endogenous 24-hour profile of blood pressure under constant routine

The impact of environmental and behavioral factors on the 24-h profile of blood pressure (BP) has been well established. Various attempts have been made to control these exogenous factors, in order to investigate a possible endogenous circadian variation of BP. Recently, we reported the results of the first environmentally and behaviorally controlled laboratory study with 24-h recordings of BP and heart rate (HR) during maintained wakefulness. In this constant-routine study, a pronounced endogenous circadian rhythm of HR was found, but circadian variation of BP was absent. This result suggested that the circadian rhythm of BP observed in earlier controlled studies, with sleep allowed, was evoked by the sleep-wake cycle as opposed to the endogenous circadian pacemaker. In order to verify our previous finding during maintained wakefulness, we repeated the experiment five times with six normotensive, healthy young subjects. Statistical analyses of the hourly measurements of BP and HR confirmed the replicable presence of an endogenous circadian rhythm of HR, as well as the consistent absence of an endogenous circadian variation of BP. Thus, this study provided additional evidence that the 24-h profile of BP—as observed under normal circumstances—is the sole result of environmental and behavioral factors such as the occurrence of sleep, and has no endogenous circadian component. (Chronobiology International, 18(1), 85-98, 2001)     

Changes in blood pressure, heart rate and blood constituents during heat exposure in men with elevated blood pressure

Although the vascular volume response of hypertensive men during exercise has been rather well characterized, the effect of resting heat exposure in this patient population has not been examined. This was done in the present report in seven men with high blood pressure (BP) (i.e., diastolic pressure greater than 12 kPa (90 mmHg) upon initial interview) and 5 normotensive control subjects. 50 min after each subject had consumed an amount of water equal to 1% of his body weight, he reclined on a cot. 10 min later the subject was carried into an environmental chamber equilibrated at Tdb = 45 degrees C, Twb = 28 degrees C. Free-flowing venous blood samples were obtained from a cubital vein, and BP and heart rate were measured, before the heat exposure and at 15 min intervals during the experiment. Within 30 min systolic, diastolic and mean BP of the high BP subjects had decreased to normal levels; no BP changes were detected in normotensive subjects. Accompanying this depressor response was an exaggerated elevation in plasma glucose concentration. No alterations were found with haematocrit, plasma osmolality or electrolytes, or total protein and albumin. The data suggest that heat exposure may have been more stressful for the subjects with high BP than for their controls. This finding implies that phasic depressor responses may be as important as phasic pressor episodes in the aetiology of established essential hypertension.     

REPEATED ASSESSMENT OF THE ENDOGENOUS 24-HOUR PROFILE OF BLOOD PRESSURE UNDER CONSTANT ROUTINE*

The impact of environmental and behavioral factors on the 24-h profile of blood pressure (BP) has been well established. Various attempts have been made to control these exogenous factors, in order to investigate a possible endogenous circadian variation of BP. Recently, we reported the results of the first environmentally and behaviorally controlled laboratory study with 24-h recordings of BP and heart rate (HR) during maintained wakefulness. In this constant-routine study, a pronounced endogenous circadian rhythm of HR was found, but circadian variation of BP was absent. This result suggested that the circadian rhythm of BP observed in earlier controlled studies, with sleep allowed, was evoked by the sleep–wake cycle as opposed to the endogenous circadian pacemaker. In order to verify our previous finding during maintained wakefulness, we repeated the experiment five times with six normotensive, healthy young subjects. Statistical analyses of the hourly measurements of BP and HR confirmed the replicable presence of an endogenous circadian rhythm of HR, as well as the consistent absence of an endogenous circadian variation of BP. Thus, this study provided additional evidence that the 24-h profile of BP—as observed under normal circumstances—is the sole result of environmental and behavioral factors such as the occurrence of sleep, and has no endogenous circadian component. (Chronobiology International, 18(1), 85–98, 2001)     

Modeling the circadian variability of ambulatorily monitored blood pressure by multiple-component analysis

The use of a set of new end points derived from ambulatory blood pressure monitoring (ABPM), in addition to the blood pressure (BP) values themselves, has been advocated to improve the sensitivity and specificity in diagnosing hypertension and to evaluate a person's response to treatment. An adequate estimation of rhythmic parameters depends, however, on the ability to describe properly the circadian pattern of BP variability. The purpose of this study was to identify a simple model that could characterize sufficiently well the circadian pattern of BP in normotensive healthy volunteers sampled by ambulatory monitoring. We studied 278 clinically healthy Spanish adults (184 men), 22.7±3.3 yr of age, without medical history of hypertension and mean BP from ambulatory profiles always below 135/85 mmHg for systolic/diastolic BP, who underwent sequential ABPM providing a total of 1115 series of BPs and heart rates (HRs), sampled on each occasion at 0.5h intervals for 48 h. Subjects were assessed while adhering to their usual diurnal activity and nocturnal sleep routine, without restrictions but avoiding the use of medication. The circadian rhythm in BP and HR for each subject was established by multiple-component analysis. A statistically significant 24h component is documented for 97% of the BP profiles, with a significant second (12h) harmonic documented in 65% of the profiles. Other ultradian harmonic components were significant in less than 20% of the profiles. A statistically significant increase in the coefficient of determination (percent of overall variability explained by the function fitted to the data) was only obtained after including the periods of 24 and 12 h for BP, and periods of 24, 12, and 6 h for HR in the model components. Although other ultradian components can be demonstrated as statistically significant in a small percent of subjects, a rather simple model including only the two first harmonics of the 24h period describes sufficiently well, at the specified sampling rate, the circadian pattern of BP in normotensive subjects. Departure from this model could characterize overt pathology, as recently demonstrated in the diagnosis of preeclampsia.     

AGT M235T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE Family Study

We investigated the association between angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) gene polymorphisms and exercise training responses of resting and exercise blood pressure (BP). BP at rest and during submaximal (50 watts) and maximal exercise tests was measured before and after 20 wk of endurance training in 476 sedentary normotensive Caucasian subjects from 99 families. AGT M235T and ACE insertion/deletion polymorphisms were typed with PCR-based methods. Men carrying the AGT MM and MT genotypes showed 3. 7 +/- 0.6 and 3.2 +/- 0.5 (SE) mmHg reductions, respectively, in diastolic BP at 50 watts (DBP(50)), whereas, in the TT homozygotes, the decrease was 0.4 +/- 1.0 mmHg (P = 0.016 for trend, adjusted for age, body mass index, and baseline DBP(50)). Men with the ACE DD genotype showed a slightly greater decrease in DBP(50) (4.4 +/- 0.6 mmHg) than the II and ID genotypes (2.8 +/- 0.7 and 2.4 +/- 0.5 mmHg, respectively, P = 0.050). Furthermore, a significant (P = 0.022) interaction effect between the AGT and ACE genes was noted for DBP(50); the AGT TT homozygotes carrying the ACE D allele showed no response to training. Men with the AGT TT genotype had greater (P = 0.007) diastolic BP (DBP) response to acute maximal exercise at baseline. However, the difference disappeared after the training period. No associations were found in women. These data suggest that, in men, the genetic variation in the AGT locus modifies the responsiveness of submaximal exercise DBP to endurance training, and interactions between the AGT and ACE loci can alter this response.     

Modeling the circadian variability of ambulatorily monitored blood pressure by multiple-component analysis

The use of a set of new end points derived from ambulatory blood pressure monitoring (ABPM), in addition to the blood pressure (BP) values themselves, has been advocated to improve the sensitivity and specificity in diagnosing hypertension and to evaluate a person's response to treatment. An adequate estimation of rhythmic parameters depends, however, on the ability to describe properly the circadian pattern of BP variability. The purpose of this study was to identify a simple model that could characterize sufficiently well the circadian pattern of BP in normotensive healthy volunteers sampled by ambulatory monitoring. We studied 278 clinically healthy Spanish adults (184 men), 22.7±3.3 yr of age, without medical history of hypertension and mean BP from ambulatory profiles always below 135/85 mmHg for systolic/diastolic BP, who underwent sequential ABPM providing a total of 1115 series of BPs and heart rates (HRs), sampled on each occasion at 0.5h intervals for 48 h. Subjects were assessed while adhering to their usual diurnal activity and nocturnal sleep routine, without restrictions but avoiding the use of medication. The circadian rhythm in BP and HR for each subject was established by multiple-component analysis. A statistically significant 24h component is documented for 97% of the BP profiles, with a significant second (12h) harmonic documented in 65% of the profiles. Other ultradian harmonic components were significant in less than 20% of the profiles. A statistically significant increase in the coefficient of determination (percent of overall variability explained by the function fitted to the data) was only obtained after including the periods of 24 and 12 h for BP, and periods of 24, 12, and 6 h for HR in the model components. Although other ultradian components can be demonstrated as statistically significant in a small percent of subjects, a rather simple model including only the two first harmonics of the 24h period describes sufficiently well, at the specified sampling rate, the circadian pattern of BP in normotensive subjects. Departure from this model could characterize overt pathology, as recently demonstrated in the diagnosis of preeclampsia.     

Angiotensin receptor blockers shift the circadian rhythm of blood pressure by suppressing tubular sodium reabsorption

Recently, we found that an angiotensin II receptor blocker (ARB) restored the circadian rhythm of the blood pressure (BP) from a nondipper to a dipper pattern, similar to that achieved with sodium intake restriction and diuretics (Fukuda M, Yamanaka T, Mizuno M, Motokawa M, Shirasawa Y, Miyagi S, Nishio T, Yoshida A, Kimura G. J Hypertens 26: 583-588, 2008). ARB enhanced natriuresis during the day, while BP was markedly lower during the night, resulting in the dipper pattern. In the present study, we examined whether the suppression of tubular sodium reabsorption, similar to the action of diuretics, was the mechanism by which ARB normalized the circadian BP rhythm. BP and glomerulotubular balance were compared in 41 patients with chronic kidney disease before and during ARB treatment with olmesartan once a day in the morning for 8 wk. ARB increased natriuresis (sodium excretion rate; U(Na)V) during the day (4.5 ± 2.2 to 5.5 ± 2.1 mmol/h, P = 0.002), while it had no effect during the night (4.3 ± 2.0 to 3.8 ± 1.6 mmol/h, P = 0.1). The night/day ratios of both BP and U(Na)V were decreased. The decrease in the night/day ratio of BP correlated with the increase in the daytime U(Na)V (r = 0.42, P = 0.006). Throughout the whole day, the glomerular filtration rate (P = 0.0006) and tubular sodium reabsorption (P = 0.0005) were both reduced significantly by ARB, although U(Na)V remained constant (107 ± 45 vs. 118 ± 36 mmol/day, P = 0.07). These findings indicate that the suppression of tubular sodium reabsorption, showing a resemblance to the action of diuretics, is the primary mechanism by which ARB can shift the circadian BP rhythm into a dipper pattern.     

Daytime blood pressure elevation after nocturnal hypoxia.

The purpose of this study was to investigate whether nocturnal hypoxia causes daytime blood pressure (BP) elevation. We hypothesized that overnight exposure to hypoxia leads the next morning to elevation in BP that outlasts the hypoxia stimulus. We studied the effect on BP of two consecutive night exposures to hypobaric hypoxia in 10 healthy normotensive subjects. During the hypoxia nights, subjects slept for 8 h in a hypobaric chamber at a simulated altitude of 4,000 m (barometric pressure = 462 mmHg). Arterial O(2) saturation and electrocardiogram were monitored throughout the night. For 30 min before the nocturnal simulated ascent and for 4 h after return to baseline altitude the next morning, BP was measured every 5 min while the subject was awake. The same measurements were made before and after 2 normoxic nights of sleep in the hypobaric chamber at ambient barometric pressure (745 mmHg). Principal components analysis was applied to evaluate patterns of BP response after the second night of hypoxia and normoxia. A distinct pattern of diastolic BP (DBP) elevation was observed after the hypoxia night in 9 of the 10 subjects but in none after the normoxia night. This pattern showed a mean increase of 4 mmHg in DBP compared with the presleep-awake baseline in the first 60 min and a return to baseline by 90 min. We conclude that nocturnal hypoxia leads to a carryover elevation of daytime DBP.     

Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension.

Angiotensin I-converting enzyme (ACE) is responsible for production of angiotensin II and breakdown of kinins, leading to increased blood pressure (BP). Furthermore, ACE inhibitors are effective antihypertensive agents. A 287 bp insertion/deletion polymorphism in intron 16 of the ACE gene (ACE) was examined by PCR in a cross-sectional study of 80 hypertensive (HT) and 93 normotensive (NT) subjects whose parents had a similar BP status at age greater than or equal to 50. The frequency of the insertion allele was 0.56 in HTs and 0.41 in NTs, and the difference between observed alleles in all subjects in each group was significant (chi 2 = 7.6, P less than 0.01). The data thus provide evidence in favour of an association of HT with a polymorphism at the ACE locus (17q23), so implicating this locus, and possibly a genetic variant of ACE itself, in human essential hypertension.     

Effects of one-year swimming training on blood pressure and insulin sensitivity in mild hypertensive young patients

Swimming is a lifestyle intervention recommended by many clinicians in the prevention and treatment of hypertension. Yet, not all studies have agreed that swimming training can reduce blood pressure (BP). Inclusion of normotensive subjects could be a confounder for discrepancies among studies. In this one-year longitudinal study, long-term effects of swimming training on BP were investigated in 7 mild hypertensive patients (systolic BP (SBP) > 140 mmHg) and 16 normotensive controls. At baseline, these subjects (aged 21.5 +/- 0.1 years) did not participate in any form of sport training activity for the previous 3 months before enrollment into the training program. The training distance progressed from 0 (baseline) to 7 kilometers per week. BP and the homeostasis model assessment for insulin resistance (HOMA-IR) were determined under fasted condition at baseline and 48 h after the last swimming bout. The hypertensive patients displayed significantly greater HOMA-IR than age-matched normotensive controls. When data of all subjects were pooled, plasma glucose concentration was only slightly lowered after training, but weight, height, body mass index, SBP, diastolic BP (DBP) and HOMA-IR values were not significantly altered. However, when observation was restricted to the hypertensive patients, swimming training significantly lowered SBP by approximately 17 mmHg, concurrent with 41% reduction in HOMA-IR. Intriguingly, SBP in the normotensive subjects was elevated by approximately 6 mmHg after training. CONCLUSIONS: The present study found normalization rather than universal reduction effect of swimming training on BP. Furthermore, the BP-lowering effect of training in hypertensive patients appears to be associated with improvement in insulin sensitivity.     

Plasma melatonin concentrations in hypertensive patients with the dipping and non-dipping blood pressure profile

Some patients with hypertension exhibit disturbed circadian organization in the cardiovascular system. Hormone melatonin can synchronize circadian rhythms and its repeated administration can improve synchronization of rhythmicity in blood pressure (BP). In our study we measured endogenous melatonin production in patients with essential hypertension exhibiting a dipping and non-dipping BP profile. Blood pressure was monitored for at least 24-hr with an automatic ambulatory BP monitor and patients with no decline in BP were classified as non-dippers. Plasma melatonin was measured in the middle of the daytime and night-time by radioimmunoassay. As expected night-time systolic (P <0.05), diastolic (P <0.001) and mean arterial (P <0.001) BP was higher in non-dippers than in dippers. No significant difference was found between both groups in BP during the day. Mean melatonin concentrations were higher during the night than during the day in both dippers and non-dippers. When patients were divided into dippers and non-dippers on the basis of mean arterial or diastolic BP a lower ratio of night/day concentration was determined in non-dippers than in dippers. Our study showed a blunted night/day difference in plasma melatonin concentrations in hypertensive patients with the non-dipping profile in diastolic BP indicating disturbances in the circadian system of these patients.     

Association of cholesteryl ester transfer protein (TaqIB) and apolipoprotein E (HhaI) gene variants with obesity

Background The pathophysiology of obesity is known to be influenced by alterations in lipid levels. We aimed to evaluate association of cholesteryl ester transfer protein (CETP) and apolipoprotein (APO) E gene variants with asymptomatic obesity. Methods A total of 437 subjects, 159 asymptomatic obese (BMI = 29.29 +/- 3.76) and 278 non-obese (BMI = 23.38 +/- 1.71) individuals, were included in this case-control study. Lipid levels were estimated using standard protocols. Analysis of CETP (TaqIB) and APOE (HhaI) gene polymorphisms was done using PCR-RFLP. Results We found significant difference in blood pressure (systolic, P < 0.0001 and diastolic, P < 0.0001), total cholesterol (P < 0.0001), LDL-cholesterol (P < 0.0001), and HDL-cholesterol (P < 0.0001) in obese as compared to non-obese group. Homozygous APO E4E4 genotype was only observed in 5.7% of obese individuals and none in non-obese group. APO E4 allele carriers were also susceptible for obesity (P = 0.016, OR = 1.73; 95% CI = 1.12-2.68) than non-carriers. Higher blood pressure (Systolic, P = 0.001 and Diastolic, P = 0.004) and triglyceride levels (P = 0.029) were observed in obese subjects with APO E4 allele than individuals without APO E4. However, CETP B1 variant allele carriers did not show alteration in blood pressure and lipid profile in asymptomatic obese subjects. Conclusions APO E4 genotype and allele were found to be associated with asymptomatic obesity, whereas CETP Taq1B polymorphism showed no such association in North Indian subjects.     

Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up.

OBJECTIVE: To investigate the contribution of neuroleptic drugs to cognitive decline in dementia. DESIGN: Two year prospective, longitudinal study consisting of interviews every four months, with necropsy follow up. SETTING: Community settings in Oxfordshire. SUBJECTS: 71 subjects with dementia, initially living at home with informant. MAIN OUTCOME MEASURES: Cognitive function (score from expanded minimental state examination); behavioural problems (physical aggression, hallucinations, persecutory ideas, and disturbance of diurnal rhythm); and postmortem neuropathological assessment (cortical Lewy body pathology). RESULTS: The mean (SE) decline in cognitive score in the 16 patients who took neuroleptics was twice that in the patients who did not (20.7 (2.9) v 9.3 (1.3), P = 0.002). An increased rate of decline was also associated with aggression, disturbed diurnal rhythm, and persecutory ideas. However, only use of neuroleptics and severity of persecutory ideas were independently associated with more rapid cognitive decline when all other variables were adjusted for. The start of neuroleptic treatment coincided with more rapid cognitive decline: median rate of decline was 5 (interquartile range 8.5) points per year before treatment and 11 (12) points per year after treatment (P = 0.02). Cortical Lewy body pathology did not account for association between neuroleptic use and more rapid decline. CONCLUSIONS: Neuroleptic drugs that are sometimes used to treat behavioural complications of dementia may worsen already poor cognitive function. Randomised controlled trials are needed to confirm a causal relation.     

Effects of Capsaicin and Isoflavone on Blood Pressure and Serum Levels of Insulin-Like Growth Factor-I in Normotensive and Hypertensive Volunteers with Alopecia

Insulin-like growth factor-I (IGF-I) reduces arterial blood pressure. Since administration of capsaicin and isoflavone increases serum levels of IGF-I by sensory neuron stimulation in subjects with alopecia, it is possible that administration of capsaicin and isoflavone reduces arterial blood pressure in patients with hypertension. Systolic and diastolic blood pressure (BP) and serum levels of IGF-I were determined before and at 1, 3, and 5 months after administration of capsaicin and isoflavone in 42 volunteers with alopecia, 29 normotensive and 13 hypertensive volunteers. Neither systolic nor diastolic BP changed in the normotensive volunteers after combined administration of capsaicin and isoflavone. In contrast, systolic and diastolic BP was significantly reduced in hypertensive volunteers after administration of capsaicin and isoflavone. Serum levels of IGF-I significantly increased in both normotensive and hypertensive volunteers after administration of capsaicin and isoflavone. These observations suggest that administration of capsaicin and isoflavone might reduce BP in hypertensive, but not in normotensive subjects, probably by increasing serum levels of IGF-I.     

Association of Pheochromocytoma and Ganglioneuroma: Unusual Finding in Neurofibromatosis Type 1

ObjectiveTo report a rare case of association of pheochromocytoma and ganglioneuroma in an asymptomatic patient with neurofibromatosis type 1 (NF1) and to discuss the importance of annual biochemical and imaging studies.MethodsWe present the clinical, laboratory, and pathology findings in a 41-year-old woman with NF1 and review the pertinent literature.ResultsA 41-year-old woman with NF1 presented for a routine gynecologic examination, at which time a right adrenal mass (4 by 3 cm) was discovered by abdominal ultrasonography and confirmed by abdominal computed tomographic scans and magnetic resonance imaging. The patient was normotensive and complained only of discrete essential tremors. Biochemical studies showed a serum epinephrine level of 195 pg/mL (normal,<100) and a 24-hour urine epinephrine excretion of 55 μg (normal,<20), findings consistent with pheochromocytoma. Metaiodobenzylguanidine scintigraphy revealed uptake in the right adrenal gland, with no evidence of metastatic lesions. Before surgical treatment, the patient received an α-adrenergic antagonist for 30 days. Laparoscopic excision of the right adrenal gland yielded excellent postoperative results. Surgical pathology revealed a multinodular mass composed of pheochromocytoma and ganglioneuroma. In patients with NF1 (von Recklinghausen’s disease), a tumor consisting of pheochromocytoma and ganglioneuroma is rare and may be more aggressive than pheochromocytoma alone. An asymptomatic catecholamine-producing tumor may cause substantial morbidity and mortality, especially in patients who are undergoing surgical intervention or are under other stressors.ConclusionThe current guidelines for managing patients with NF1 are an annual history and physical examination. Because of the increased prevalence of pheochromocytoma and ganglioneuroma in patients with NF1, and the potential associated adverse effects, we emphasize the importance of periodic clinical evaluation with biochemical testing and imaging studies. (Endocr Pract. 2007;13:647-651)