Exercise training associated with diet improves heart rate recovery and cardiac autonomic nervous system activity in obese children.

The purpose of this study was to test the hypotheses that in obese children: 1) hypocaloric diet (D) improves both heart rate recovery at 1 min (Δ HRR1) cfter an exercise test, and cardiac autonomic nervous system activity (CANSA) in obese children; 2) Diet and exercise training (DET) combined leads to greater improvement in both Δ HRR1 after an exercise test and in CANSA, than D alone. Moreover, we examined the relationships among Δ HRR1, CANSA, cardiorespiratory fitness and anthropometric variables (AV) in obese children submitted to D and to DET. 33 obese children (10 ± 0.2 years; body mass index (BMI) >95 (th) percentile) were divided into 2 groups: D (n=15; BMI=31 ± 1 kg/m²)) and DET (n=18; 29 ± 1 kg/m²). All children performed a maximal cardiopulmonary exercise test on a treadmill. The Δ HRR1 or LF/HF ratio (P>0.05). In contrast, the DET group showed increased peak VO2 ( P=0.01) and improved Δ HRR1 (Δ HRR1=37.3 ± 2.6; P=0.01) and LF/HF ratio ( P=0.001). The DET group demonstrated significant relationships among Δ HRR1, peak VO2 and CANSA (P<0.05). In conclusion, DET, in contrast to D, promoted improved ÄΔ HRR1 and CANSA in obese children, suggesting a positive influence of increased levels of cardiorespiratory fitness by exercise training on cardiac autonomic activity.

Weight loss associated with exercise training restores ventilatory efficiency in obese children.

The purpose of this study was to test the hypothesis that in obese children: 1) Ventilatory efficiency (VentE) is decreased during graded exercise; and 2) Weight loss through diet alone (D) improves VentE, and 3) diet associated with exercise training (DET) leads to greater improvement in VentE than by D. Thirty-eight obese children (10+/-0.2 years; BMI >95th percentile) were randomly divided into two study groups: D (n=17; BMI=30+/-1 kg/m (2)) and DET (n=21; 28+/-1 kg/m (2)). Ten lean children were included in a control group (10+/-0.3 years; 17+/-0.5 kg/m (2)). All children performed maximal treadmill testing with respiratory gas analysis (breath-by-breath) to determine the ventilatory anaerobic threshold (VAT) and peak oxygen consumption (VO (2) peak). VentE was determined by the VE/VCO (2) method at VAT. Obese children showed lower VO (2) peak and lower VentE than controls (p<0.05). After interventions, all obese children reduced body weight (p<0.05). D group did not improve in terms of VO (2) peak or VentE (p>0.05). In contrast, the DET group showed increased VO (2) peak (p=0.01) and improved VentE (DeltaVE/VCO (2)=-6.1+/-0.9; p=0.01). VentE is decreased in obese children, where weight loss by means of DET, but not D alone, improves VentE and cardiorespiratory fitness during graded exercise.

Effects of diet and exercise training on neurovascular control during mental stress in obese women.

Since neurovascular control is altered in obese subjects, we hypothesized that weight loss by diet (D) or diet plus exercise training (D + ET) would improve neurovascular control during mental stress in obese women. In a study with a dietary reduction of 600 kcal/day with or without exercise training for 4 months, 53 obese women were subdivided in D (N = 22, 33 +/- 1 years, BMI 34 +/- 1 kg/m2), D + ET (N = 22, 33 +/- 1 years, BMI 33 +/- 1 kg/m2), and nonadherent (NA, N = 9, 35 +/- 2 years, BMI 33 +/- 1 kg/m2) groups. Muscle sympathetic nerve activity (MSNA) was measured by microneurography and forearm blood flow by venous occlusion plethysmography. Mental stress was elicited by a 3-min Stroop color word test. Weight loss was similar between D and D + ET groups (87 +/- 2 vs 79 +/- 2 and 85 +/- 2 vs 76 +/- 2 kg, respectively, P < 0.05) with a significant reduction in MSNA during mental stress (58 +/- 2 vs 50 +/- 2, P = 0.0001, and 59 +/- 3 vs 50 +/- 2 bursts/100 beats, P = 0.0001, respectively), although the magnitude of the response was unchanged. Forearm vascular conductance during mental stress was significantly increased only in D + ET (2.74 +/- 0.22 vs 3.52 +/- 0.19 units, P = 0.02). Weight loss reduces MSNA during mental stress in obese women. The increase in forearm vascular conductance after weight loss provides convincing evidence for D + ET interventions as a nonpharmacologic therapy of human obesity.

Effects of diet and exercise training on neurovascular control during mental stress in obese women

Since neurovascular control is altered in obese subjects, we hypothesized that weight loss by diet (D) or diet plus exercise training (D + ET) would improve neurovascular control during mental stress in obese women. In a study with a dietary reduction of 600 kcal/day with or without exercise training for 4 months, 53 obese women were subdivided in D (N = 22, 33 ± 1 years, BMI 34 ± 1 kg/m²), D + ET (N = 22, 33 ± 1 years, BMI 33 ± 1 kg/m²), and nonadherent (NA, N = 9, 35 ± 2 years, BMI 33 ± 1 kg/m²) groups. Muscle sympathetic nerve activity (MSNA) was measured by microneurography and forearm blood flow by venous occlusion plethysmography. Mental stress was elicited by a 3-min Stroop color word test. Weight loss was similar between D and D + ET groups (87 ± 2 vs 79 ± 2 and 85 ± 2 vs 76 ± 2 kg, respectively, P < 0.05) with a significant reduction in MSNA during mental stress (58 ± 2 vs 50 ± 2, P = 0.0001, and 59 ± 3 vs 50 ± 2 bursts/100 beats, P = 0.0001, respectively), although the magnitude of the response was unchanged. Forearm vascular conductance during mental stress was significantly increased only in D + ET (2.74 ± 0.22 vs 3.52 ± 0.19 units, P = 0.02). Weight loss reduces MSNA during mental stress in obese women. The increase in forearm vascular conductance after weight loss provides convincing evidence for D + ET interventions as a nonpharmacologic therapy of human obesity.

Alpha2B-adrenergic receptor deletion polymorphism and cardiac autonomic nervous system responses to exercise in obese women.

OBJECTIVE: To investigate the association of short form (Glu9/Glu9) of the 12Glu9 deletion polymorphism of the alpha2B-adrenergic receptor (alpha2B-AR) gene polymorphism with the cardiac autonomic responsiveness during sustained isometric handgrip exercise. DESIGN: Cross-sectional clinical study. SUBJECTS: In all, 97 normotensive obese women (body mass index (BMI) = 33.2 kg/m2). Of these, 78 (80.41%) were genotyped as Glu12/Glu12, 13 (13.40%) as Glu12/Glu9 and six (6.19%) as Glu9/Glu9 form. MEASUREMENTS: The sympathovagal balance was assessed by means of power spectral analysis of heart rate variability at rest and during sustained isometric handgrip exercise at 30% of maximal voluntary handgrip contraction for 3 min. Two spectral components were analysed: low-frequency component reflecting sympathetic efferent activity and high-frequency power (HFnu) reflecting parasympathetic modulation. In addition, a normalized low-frequency power (LFnu) and HFnu were analysed. Genotypes were determined by polymerase chain reaction followed by agarose gel electrophoresis. RESULTS: There were no differences in baseline measurements among groups. The absolute level of LFnu throughout handgrip exercise was significantly lower in Glu9/Glu9 subjects compared with other genotypes, while the decline of absolute HFnu was significantly smaller compared with Glu12/Glu12 genotype. CONCLUSION: These findings suggest that 12Glu9 deletion polymorphism of the alpha2B-AR gene (Glu9/Glu9 genotype) might result in reduced autonomic responsiveness by altering cardiac sympathetic and vagal function during sustained handgrip exercise in normotensive obese women.

Muscle metaboreflex control is diminished in normotensive obese women.

There is no information about the muscle metaboreflex control in obese individuals. In 40 normotensive obese women (OW; body mass index 33.5 +/- 0.4 kg/m2, age 32.4 +/- 1.1 yr) and 15 age-matched, normotensive lean women (LW; body mass index 22.7 +/- 0.8 kg/m2, age 34.4 +/- 1.4 yr), we measured muscle sympathetic nerve activity (MSNA) and forearm blood flow (FBF) in the nonexercising forearm during static exercise at 10 and 30% of maximal voluntary contraction (MVC). Baseline MSNA (38 +/- 2 vs. 31 +/- 1 bursts/min, P = 0.001) and mean blood pressure were significantly higher in OW compared with LW. FBF was significantly lower, whereas forearm vascular resistance was significantly higher in OW. During 10% MVC, MSNA increased similarly in both groups, but during 30% MVC, MSNA was higher in LW. FBF and forearm vascular resistance responses during both 10 and 30% MVC were similar between groups. During posthandgrip circulatory arrest, MSNA remained significantly elevated compared with baseline in both groups, but this increase was significantly lower in OW (3.8 +/- 0.82 vs. 9.4 +/- 1.03 bursts/min, P = 0.002). In conclusion, muscle metaboreflex control of MSNA is blunted in OW. MSNA responses are not augmented during selective activation of central command/mechanoreceptors and metaboreceptors, despite increased MSNA levels in OW. Muscle vasodilatory response during graded handgrip isometric exercise is preserved in OW.

Muscle sympathetic nerve activity and hemodynamic alterations in middle-aged obese women.

To study the relationship between the sympathetic nerve activity and hemodynamic alterations in obesity, we simultaneously measured muscle sympathetic nerve activity (MSNA), blood pressure, and forearm blood flow (FBF) in obese and lean individuals. Fifteen normotensive obese women (BMI = 32.5 +/- 0.5 kg/m2) and 11 age-matched normotensive lean women (BMI = 22.7 +/- 1.0 kg/m2) were studied. MSNA was evaluated directly from the peroneal nerve by microneurography, FBF was measured by venous occlusion plethysmography, and blood pressure was measured noninvasively by an autonomic blood pressure cuff. MSNA was significantly increased in obese women when compared with lean control women. Forearm vascular resistance and blood pressure were significantly higher in obese women than in lean women. FBF was significantly lower in obese women. BMI was directly and significantly correlated with MSNA, blood pressure, and forearm vascular resistance levels, but inversely and significantly correlated with FBF levels. Obesity increases sympathetic nerve activity and muscle vascular resistance, and reduces muscle blood flow. These alterations, taken together, may explain the higher blood pressure levels in obese women when compared with lean age-matched women.

Muscle sympathetic nerve activity and hemodynamic alterations in middle-aged obese women

To study the relationship between the sympathetic nerve activity and hemodynamic alterations in obesity, we simultaneously measured muscle sympathetic nerve activity (MSNA), blood pressure, and forearm blood flow (FBF) in obese and lean individuals. Fifteen normotensive obese women (BMI = 32.5 + or - 0.5 kg/m²) and 11 age-matched normotensive lean women (BMI = 22.7 + or - 1.0 kg/m²) were studied. MSNA was evaluated directly from the peroneal nerve by microneurography, FBF was measured by venous occlusion plethysmography, and blood pressure was measured noninvasively by an autonomic blood pressure cuff. MSNA was significantly increased in obese women when compared with lean control women. Forearm vascular resistance and blood pressure were significantly higher in obese women than in lean women. FBF was significantly lower in obese women. BMI was directly and significantly correlated with MSNA, blood pressure, and forearm vascular resistance levels, but inversely and significantly correlated with FBF levels. Obesity increases sympathetic nerve activity and muscle vascular resistance, and reduces muscle blood flow. These alterations, taken together, may explain the higher blood pressure levels in obese women when compared with lean age-matched women

Activating mutation of the stimulatory G protein (gsp) as a putative cause of ovarian and testicular human stromal Leydig cell tumors.

Activating mutations of the G protein genes have been associated with the development of several endocrine neoplasms. Such activating mutations, gip2, affecting the alpha-subunit of the G alpha i2 protein were previously described by a single group in 30% of ovarian sex cord stromal tumors. Other activating mutations of the alpha-subunit of the Gs (gsp) have been identified in GH-secreting and nonfunctioning pituitary tumors, autonomous thyroid adenomas, and all affected McCune-Albright tissues, but not in sex cord stromal tumors. In the present study, we investigated the presence of gip2 and gsp mutations in 14 human sex cord stromal tumors. Six Leydig cell tumors (4 ovaries and 2 testes), 2 thecomas, 2 granulosa cell tumors, 3 androblastomas, and 1 gonadoblastoma (sex cord and germ cell) were included in this study. Genomic DNA was obtained from either fresh-frozen tumor tissues or paraffin-embedded sections and in some cases from blood samples. Using PCR, denaturing gradient gel electrophoresis, and direct sequencing, we detected 4 tumors (66.6%) with the gsp mutation (R201C) in our series of ovarian and testicular Leydig cell tumors. In contrast, no gip2 mutations were found in any of the sex cord stromal tumors studied. In conclusion, our findings suggest that the putative oncogene gsp may play a significant role in the molecular mechanism of these tumors.

Growth hormone receptor messenger ribonucleic acid in normal and pathologic human adrenocortical tissues--an analysis by quantitative polymerase chain reaction technique.

GH receptor (GHR) has been reported to express in both normal rat and human adrenals. However, no study examined GHR expression in diseased human adrenal cortex. We quantitated, with RT-PCR, GHR messenger RNA (mRNA) in both normal and diseased human adrenal cortex with the following results: GHR mRNA levels in four histologically normal, not steroid-stimulated, control adrenal cortices was 1.5-11 x 10(4) molecules/microgram total RNA; in three diffusely hyperplastic adrenals (DH): 6.7-17.7 x 10(4); in two nonfunctioning tumors (NF): 0.84-1.9 x 10(4); in five androgen-producing neoplasms (AP): 4.6-34 x 10(4); and in five glucocorticoid-producing neoplasms (GP): 6.7-87 x 10(4). GHR transcript levels among adrenal cortices, DH, NF, AP, and GP reached statistically significant difference (P < 0.03). The GP group exhibited higher GHR mRNA levels than controls (P < 0.006). NF, as well as GP and AP, tumors had less GHR mRNA than their histologically normal adjacent cortex (P < 0.05). A positive correlation between urinary cortisol and GHR messenger RNA (mRNA) levels from GP and DH was observed (r = 0.93, P < 0.003). Our data suggest that GHR is expressed in both normal and diseased adrenal cortex and that GHR mRNA accumulation is less efficient in adrenocortical neoplasm than their adjacent nonneoplastic cortex. GHR expression in adrenal cortex provides an evidence of direct GH action in this tissue.

Effect of glycemic control on growth hormone and IGFBP-1 secretion in patients with type I diabetes mellitus.

Growth hormone (GH) secretion disorders have been reported in poorly controlled type I diabetes mellitus patients. Our work was aimed to evaluate GH secretion in 9 type I young diabetes mellitus patients as well as the low molecular weight IGF-binding protein secretion (IGFBP-1) in 5 of them. The patients did not show any signs of malnutrition or neurovascular complications, neither were they on any medication except for insulin. The study protocol included blood samples collection during a 24-h period for measurement of glucose, glycated hemoglobin, GH IGF-I and IGFBP-1 levels under two situations: on poor glycemic control and after 2-3 months on better control through systematic diet, low in carbohydrates and increase in insulin dosage. GH secretion data were analyzed by Cluster algorithm for pulsatility parameters; for rhythm assessment Cosinor method was used. The first study (poor control) reported significant increase of GH maximal and incremental amplitude and duration pulse values, when compared to the second study (better control). Mean 24-h secretion values as well mean GH for interpulse intervals (valleys) decreased, although not statistically significant. The fraction of pulsatile GH/24 h GH did not change significantly with better glycemic control. No changes in pulse frequency were observed. Mean IGF-I concentrations were significantly higher when patients were on better glycemic control. An ultradian variation for GH secretion was noticed in the first study (poor control) and a circadian variation in the second one (better control). IGFBP-1 analysis showed significant decrease of the mean 24-h values under better glycemic control. Linear regression analysis demonstrated a correlation between IGFBP-1 levels and fasting glucose levels. A circadian variation was present in IGFBP-1 secretion, irrespective of glycemic control. Therefore, we concluded that for type I diabetic patients: 1. GH secretion is increased on poor control, through maximal, incremental amplitude and pulse duration values; 2. IGFBP-1 values were significantly reduced and IGF-1 levels significantly higher after better glycemic control; 4. GH ultradian secretion is reported on poor control, and circadian on the better one, 5. IGFBP-1 circadian secretion occurred irrespective of glycemic control.

Pulsatile release and circadian rhythms of thyrotropin and prolactin in children with growth hormone deficiency.

We have measured mean concentrations and have appraised the pulsatile nature of thyrotropin (TSH) and prolactin (PRL) release in children with classical GH deficiency (GHD; n = 4) and neurosecretory GH dysfunction (NSD; n = 4) and have compared the results with those obtained in children with constitutional delay (control; n = 4). Blood samples were obtained at 20-min intervals for 24 h. Pulse analysis of TSH and PRL was undertaken using the Cluster pulse detection algorithm. Circadian rhythmicity of TSH and PRL was assessed using cosinor analysis. The mean 24-h concentration of GH in the control subjects was significantly higher than that obtained in the GHD and NSD groups. With regard to TSH, the mean serum concentration in the GHD and NSD group were higher than that of the control subjects. This augmentation reflects TSH pulses of large amplitude and area, and a higher interpulse valley mean rather than a difference in peak number or peak duration. No differences in mean PRL concentration or characteristics of PRL pulses were found between the control and GHD and NSD subjects. When the 24 h data sets were divided into day (0800-2000 h) and night (2000-0800 h), the mean nighttime TSH concentration was higher than the daytime concentration in the control, GHD, and NSD groups. Although there were no day versus night differences in TSH pulse frequency in either group, peak amplitude, area, and interpulse valley means were increased during the night in the control group, and peak area, duration, and amplitude mean in the NSD group. The nighttime mean PRL concentrations in the control, GHD, and NSD subjects were higher than those found during the day. This increase was accounted for by increases in PRL peak amplitude, area in the control group, and peak area, amplitude, and interpulse valley mean in the GHD and NSD groups. Cosinor analysis of the 24-h TSH and PRL data revealed clear circadian rhythmicity in all groups of subjects. These data suggest that GHD and NSD are associated with an increase in pulsatile TSH secretion due to an increase in pulse amplitude and interpulse valley mean.

Quantitative analysis by polymerase chain reaction of growth hormone receptor gene expression in human liver and muscle.

A single form of GH receptor (GHR) messenger RNA (mRNA) of 4.5 kilobases, encoding the full-length GHR, has been found in man. To measure the absolute number of mRNA molecules encoding the GHR in human tissues, we developed a quantitative polymerase chain reaction assay. An internal control RNA was constructed by inserting a 50-basepair fragment of the rat PRL receptor complementary DNA into a portion of the human GHR complementary DNA. The internal control RNA and the target mRNA were amplified together with the same set of primers. Twenty-four cycles of amplification were used to satisfy an exponential phase of amplification. It was possible to detect as few as 500 molecules of target mRNA/micrograms total RNA. In 3 liver samples obtained from normal donors at the time of transplant, the amount of GHR mRNA ranged from 0.5 +/- 0.1 to 1.4 +/- 0.4 x 10(6) molecules/micrograms total RNA. These results were confirmed by slot blot analysis of the same samples. The number of receptor transcripts did not appear to be correlated with the receptor-binding capacity found in the 3 liver samples. In 7 muscle biopsies, GH receptor mRNA varied between 4.0 +/- 0.4 and 34.6 +/- 1.4 x 10(4) molecules/micrograms total RNA. This technique allows direct measurement of GHR gene expression in human tissues and represents a valuable tool, particularly for tissues such as muscle, in which the receptor protein cannot be measured using conventional binding assays.

Reduced food intake is the main cause of low growth hormone receptor expression in uremic rats.

To examine the respective effects of reduced food intake and of uremia on the growth defect in uremic rats, we have studied the expression of GH receptors in three groups of male rats: Group 1, rats fed ad libitum; Group 2, food-restricted to be pair-fed with uremic rats; Group 3, uremic rats. Animals were studied for a time period of 9 days starting 1 week after surgery (sham operation in rats of Groups 1 and 2, 5/6 nephrectomy in rats of Group 3). The gain in body length and weight of pair-fed controls and of uremic rats was comparable and significantly lower than that of rats fed ad libitum. IGF-1 plasma levels were low in rats of groups 2 and 3. Low food intake (50% that of rats fed ad libitum) resulted in a reduced number of GH receptors in liver membranes and a low plasma level of GH-binding protein (GHBP); GH receptor gene expression in the liver, as analyzed by Northern blots, was not significantly lower in normal food-restricted animals. In uremic rats, the low level of GH binding to liver membranes was comparable to that found in pair-fed controls; but the level of GHBP activity was normal, not different from the values found in rats fed ad libitum. However, expression of the liver GHBP mRNA was reduced in uremic rats. In uremia, the GH receptor dysfunction is not only at a transcriptional level but also at a post-transcriptional level. These findings suggest that uremia, as such, is not primarily responsible for the growth failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium and prolactin secretion in humans: effects of the channel blocker, verapamil, in the spontaneous and drug-induced hyperprolactinemia.

The effects of the intravenous administration of a calcium channel blocker, verapamil (0.0833 mg/min for 2-3 h after a 5 mg bolus) on prolactin (PRL) and thyrotropin (TSH) circulating levels were assessed in 7 normal subjects and in 17 patients with hyperprolactinemia (11 with prolactinoma and 6 sulpriride-induced). In the normal group a non-significant increase in PRL levels occurred (mean +/- SEM = 11.7 +/- 2.9 micrograms/l verapamil vs. 8.5 +/- 1.4 micrograms/l saline). In this control group the peak response of PRL and TSH to TRH (thyrotrophin releasing hormone) during verapamil or saline was also determined: PRL = 112.0 +/- 27.0 micrograms/l on verapamil vs. 53.6 micrograms/l on saline, p = 0.02; TSH 7.1 +/- 0.7 microU/l on verapamil vs. 9.0 +/- 0.6 mU/l on saline, p = 0.01. In the hyperprolactinemic subjects verapamil induced opposite effects on PRL levels, the prolactinoma group exhibiting an increase in the mean values (168.5 +/- 22.3 micrograms/l vs. 150.8 +/- 23.6 micrograms/l on saline, p = 0.04) whereas in the sulpiride-induced there was a reduction in the mean PRL levels (61.1 +/- 13.8 micrograms/l vs. 78.5 +/- 19.3 micrograms/l on saline, p = 0.002). In both groups of hyperprolactinemic patients no effects on TSH levels were observed. The authors discuss the possibility that the divergent effects of verapamil in hyperprolactinemia of different etiologies could be related to the balance between dopamine and calcium channel effects on hypothalamus and/or pituitary.

Calcium-dependent protein kinase-C activity in human adrenocortical neoplasms, hyperplastic adrenals, and normal adrenocortical tissue.

The calcium- and phospholipid-dependent protein kinase-C (PKC) is a critical enzyme of cellular signal transduction. In this report we studied calcium-dependent total PKC activity in eight adrenocortical carcinomas (group 1), nine adrenocortical adenomas (group 2), six hyperplasias (group 3), and five human normal adrenal tissues (group 4). The PKC activity assay was based on phosphorylation of a specific synthetic peptide from myelin basic protein. The specificity of the assay was confirmed by using an inhibitor peptide common to alpha-, beta-, and gamma-isoenzymes of PKC. The median value in group 1 was 1.15 pmol 32P/min.micrograms protein (range, 0.55-2.19), that in group 2 was 1.2 (range, 0.74-2.7), that in group 3 was 0.915 (range, 0.6-1.7), and that in group 4 was 1.22 (range, 0.6-3.95). The calcium-dependent total PKC activity was similar in the four groups studied. We did not find any correlation between urinary total cortisol, serum cortisol, testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, aldosterone, and estradiol concentrations and PKC activity. These findings suggest that the calcium-dependent PKC activity is not elevated in adrenocortical tumors and is not a useful marker of adrenocortical malignancy.

Familial short stature with very high levels of growth hormone binding protein.

We report a familial syndrome of short stature associated with partial GH resistance and very high levels of GH binding protein (GHBP). In three individuals of the same family, presenting with growth failure, high circulating GH levels, both basal and stimulated, were found. Insulin-like growth factor-1 plasma levels were either normal or in the low normal range. GH binding activity was extremely elevated in the plasma of the three subjects, with very high maximum binding capacity (30- to 110-fold higher than that of normal adult plasma) and normal binding affinity (5-7.4 x 10(8) M-1). The cause and the exact consequences of the very high level of plasma GHBP, resulting in a low proportion of free circulating GH, remain to be clarified. The short stature and the partial GH resistance are probably related to high GHBP levels.

[Cushing syndrome due to ectopic ACTH secretion]. / Síndrome de Cushing por secreção ectópica de corticotrofina (ACTH).

The authors studied 8 patients (4 males and 4 females) with Cushing's syndrome due to ectopic ACTH secretion. Chronological age ranged from 15 to 45 years and duration of the disease ranged from 3 to 48 months. All patients presented typical signs of Cushing's syndrome, blood hypertension, and four of them had hyperpigmentation of the skin. Five patients had fasting hyperglycemia and all patients but one had serum hypokalemia (serum K = 2.2 to 3.9mEq/l). The circadian rhythm of cortisol was absent in all patients and basal cortisol levels were elevated in all patients but one. Basal ACTH levels evaluated in 7 patients were elevated in 6 (29 to 1050 pg/ml-MRC). One patient presented normal depression of urinary 17-OH after two days of dexamethasone and normal increase of urinary 17-OH and serum 11-dexycortisol after methyrapone. Four patients had carcinoid tumor (3 thymic and 1 bronchial), two had pancreatic islets cell tumors, one had bilateral pheochromocytoma and medular carcinoma of the thyroid, and one had oat cell carcinoma of the lung and medular carcinoma of the thyroid. Thoracic X-rays identified the ectopic ACTH secretion tumor in four cases, all confirmed by CT scan. Abdominal CT showed a difuse enlargement of the adrenals in seven cases and bilateral nodules in one case (pheochromocytomas). Six patients died within 3 years of the diagnosis. The authors concluded that clinical and hormonal findings could mislead the findings of ACTH ectopic secretion and Cushing's disease, and suggest that thoracic X-rays and CT scans of the skull, thorax, and abdome should be done in all cases of Cushing's syndrome.

Estimulaçäo alfa-adranérgica na secreçäo de hormônio de crescimento: comparaçäo da clonidina com guanabenz / Cepha adrenergic stimulation in growth hormone secretion: comparison between clonidine and guanabenz

Avaliamos o efeito da administraçäo aguda de clonidina e de guanabenz na secreçäo de hormônio de crescimento (GH0 em nove pacientes com deficiência isolada idiopática de GH (DGH), seis do sexo masculino e três do feminino, e em 15 indivíduos de baixa estatura sem deficiência de GH (CN), 11 do sexo masculino e quatro do feminino. Nesses últimos sob hipoglicemia induzida o pico de GH foi de 11,34 ñ 4,48ng/ml e no teste seqüencial exercício L-DOP o pico foi de 12,97 ñ 3,94ng/ml (Mñep). Sob a a çäo da clonidina e do guanabenz os CN apresentaram picos de GH de 22,07 ñ 3,2 e 19,24 ñ 2,26ng/ml respectivamente. Esses resultados näo foram estatisticamente diferentes daqueles obtidos com os testes clássicos de liberaçäo de GH. Os pacientes com DGH näo respoderam a nenhum dos testes de liberaçäo utilizados. Nossos dados sugerem que ambos agonistas alfa-adrenérgicos säo potentes liberadores de GH, podendo ser utilizados na avaliaçäo da reserva hipofisária