Effect of bariatric surgery on microvascular dysfunction associated to metabolic syndrome: a 12-month prospective study.

OBJECTIVE: To prospectively evaluate the effect of weight loss after bariatric surgery on microvascular function in morbidly obese patients with and without metabolic syndrome (MetS). METHODS: A cohort of morbidly obese patients with and without MetS was studied before surgery and after 12 months of surgery. Healthy lean controls were also examined. Microvascular function was assessed by postocclusive reactive hyperemia (PORH) at forearm skin evaluated by laser Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated from laser-Doppler skin blood flow and blood pressure. Regression analysis was performed to assess the contribution of different clinical, metabolic and biochemical parameters to microvascular function. RESULTS: Before surgery, 62 obese patients, 39 with MetS and 23 without MetS, and 30 lean control subjects were analyzed. The absolute area under the hyperemic curve (AUC(H)) CVC of PORH was significantly decreased in obese patients compared with lean control subjects. One year after surgery, AUC(H) CVC significantly increased in patients free of MetS, including patients that had MetS before surgery. In contrast, AUC(H) CVC did not significantly change in patients in whom MetS persisted after surgery. Stepwise multivariate regression analysis showed that only changes in HDL cholesterol (HDL-C) and oxidized LDL (oxLDL) independently predicted improvement of AUC(H) after surgery. These two variables together accounted for 40.9% of the variability of change in AUC(H) CVC after surgery. CONCLUSIONS: Bariatric surgery could significantly improve microvascular dysfunction in obese patients, but only in patients free of MetS after surgery. Improvement of microvascular dysfunction is strictly associated to postoperative increase in HDL-C levels and decrease in oxLDL levels.

A cellular and molecular basis for the selective desmopressin-induced ACTH release in Cushing disease patients: key role of AVPR1b receptor and potential therapeutic implications.

CONTEXT: Desmopressin is a synthetic agonist of vasopressin receptors (AVPRs). The desmopressin stimulation test is used in the diagnosis and postsurgery prognosis of Cushing disease (CD). However, the cellular and molecular mechanisms underlying the desmopressin-induced ACTH increase in patients with CD are poorly understood. OBJECTIVE: The objectives of this study were to determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release and to elucidate the cellular and molecular mechanisms involved in desmopressin-induced ACTH increase in CD. DESIGN: A total of 8 normal pituitaries (NPs), 23 corticotropinomas, 14 nonfunctioning pituitary adenomas, 17 somatotropinomas, and 3 prolactinomas were analyzed for AVPR expression by quantitative real-time RT-PCR. Primary cultures derived from corticotropinomas, nonfunctioning pituitary adenomas, somatotropinomas, prolactinomas, and NPs were treated with desmopressin, and ACTH secretion/expression, [Ca(2+)]i kinetics, and AVPR expression and/or proliferative response were evaluated. The relationship between AVPR expression and plasma adrenocorticotropin/cortisol levels obtained from desmopressin tests was assessed. RESULTS: Desmopressin affects all functional parameters evaluated in corticotropinoma cells but not in NPs or other pituitary adenomas cells. These effects might be due to the dramatic elevation of AVPR1b expression levels found in corticotropinomas. In line with this notion, the use of an AVPR1b antagonist completely blocked desmopressin stimulatory effects. Remarkably, only AVPR1b expression was positively correlated with elevated plasma adrenocorticotropin levels in corticotropinomas. CONCLUSIONS: The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and postsurgery prognosis of CD. Furthermore, our data indicate that AVPR1b is responsible for the direct/exclusive desmopressin stimulatory pituitary effects observed in CD, thus opening the possibility of exploring AVPR1b antagonists as potential therapeutic tools for CD treatment.

Self-limited acute hepatotoxicity caused by pegvisomant.

We present a case of acute severe hepatitis in a patient with acromegaly receiving combination therapy with somatostatin analogs and pegvisomant. Hepatitis resolved completely 18 weeks after diagnosis of hypertransaminasemia without discontinuation of therapy and with a close clinical and biochemical follow-up. In this case, despite the severity of the hepatitis, therapy could be continued as hypertransaminasemia was gradually decreasing after the maximum peak. We also review the literature on toxic hepatitis associated to pegvisomant therapy analyzing the etiology, clinical predisposing factors and natural evolution.

[Assessment of hypothalamo-pituitary axis in early phase of severe cranioencephalic brain injury]. / Valoración del eje hipotálamo-hipofisario en la fase precoz del traumatismo craneoencefálico grave.

OBJECTIVE: To assess early pituitary function in a sequential cohort of critical care patients after severe traumatic brain injury (TBI). DESIGN: This was a prospective observational study. The pituitary function was always tested on the third day after TBI. SETTING: Neurocritical intensive care unit (ICU) in a University hospital. PATIENTS: A total of 136 adult patients with severe TBI (range, 16-65 years) enrolled over a 2 year and 9 month period having a stay in the ICU treated than 48 hours. INTERVENTION: None. MEASUREMENTS AND DATA COLLECTED: The following data were recorded within the first 72 hours after injury: demographic variables, injury severity, neuromonitoring data, systemic secondary brain insults, use of vasoactive drugs and type of TBI according to the computerized tomography (CT) scan findings. Pituitary function was evaluated by measurement of both the pituitary and target organ hormones, with the exception of the somatotrophic function, which was assessed by measurement of basal serum values of insulin-like growth factor-I (IGF-I). RESULTS: Pituitary dysfunction was observed in 101 patients (74.2%). Seventy-nine patients (58%) had impairment of only one pituitary axis, the axes being affected as follows: gonadotropic 63.7% (87 patients), thyrotropic 8.8% (12 patients) and corticotropic 0.7% (1 patient). Low IGF-1 plasmatic levels in accordance to the patient's age were observed in 90 patients (66.7%). However, only 26 of them had a value below 90 ng/ml. CONCLUSIONS: Our data show that pituitary dysfunction occurs early and with high frequency after severe TBI, but the real significance of these findings still needs to be elucidated.

Valoración del eje hipotálamo-hipofisario en la fase precoz del traumatismo craneoencefálico grave / Assessment of hypothalamo-pituitary axis in early phase of severe cranioencephalic brain injury

Objetivo. Analizar las características de la función hipofisaria en la fase inicial de pacientes críticos con traumatismo craneoencefálico grave (TCEG). Diseño. Estudio observacional, prospectivo. La función hipofisaria se evaluó siempre el tercer día tras el TCEG. Ámbito. Unidad de cuidados intensivos (UCI) neurotraumatológica de un hospital universitario. Pacientes. Se incluyó a 136 pacientes con TCEG (intervalo, 16-65 años), durante un período de 2 años y 9 meses y estancia en UCI mayor de 48 h. Intervención. Ninguna. Medidas y datos recopilados. Se recogieron durante las primeras 72 h tras el traumatismo: variables demográficas, severidad de la lesión, parámetros de neuromonitorización, lesiones cerebrales secundarias, uso de fármacos vasoactivos y el tipo de traumatismo craneoencefálico (TCE) acorde a los hallazgos encontrados en la tomografía computarizada (TC). La evaluación de la función hipofisaria se determinó por medición de hormonas hipofisarias y las de los órganos diana, con la excepción de la función somatotropa, que se evaluó midiendo las concentraciones séri- cas basales de insulin-like growth factor-1 (IGF-1). Resultados. Se observó disfunción hipofisaria en 101 (74,2%) pacientes; 79 (58%) pacientes tenían afectado solamente un eje hipofisario, la afectación de ejes es la siguiente: gonadotropo, el 63,7% (87 pacientes); tirotropo, el 8,8% (12 pacientes), y corticotropo, el 0,7% (1 paciente). Se observaron concentraciones plasmáticas bajas de IGF-1 acorde a la edad en 90 (66,7%) pacientes, aunque sólo 26 de ellos mostraron un valor menor de 90 ng/ml. Conclusiones. Nuestros datos muestran que la disfunción hipofisaria ocurre precozmente y con gran frecuencia tras un TCEG, aunque el significado real de estos hallazgos están aún por determinar

Objective. To assess early pituitary function in asequential cohort of critical care patients after severetraumatic brain injury (TBI).Design. This was a prospective observationalstudy. The pituitary function was always tested onthe third day after TBI.Setting. Neurocritical intensive care unit (ICU)in a University hospital.Patients. A total of 136 adult patients with severeTBI (range, 16-65 years) enrolled over a 2year and 9 month period having a stay in the ICUtreated than 48 hours.Intervention. None.Measurements and data collected. The followingdata were recorded within the first 72 hoursafter injury: demographic variables, injury severity,neuromonitoring data, systemic secondarybrain insults, use of vasoactive drugs and type ofTBI according to the computerized tomography (CT) scan findings. Pituitary function was evaluatedby measurement of both the pituitary and targetorgan hormones, with the exception of the somatotrophicfunction, which was assessed bymeasurement of basal serum values of insulinlikegrowth factor-I (IGF-I).Results. Pituitary dysfunction was observed in101 patients (74.2%). Seventy-nine patients (58%)had impairment of only one pituitary axis, the axesbeing affected as follows: gonadotropic 63.7%(87 patients), thyrotropic 8.8% (12 patients) andcorticotropic 0.7% (1 patient). Low IGF-1 plasmaticlevels in accordance to the patient’s age wereobserved in 90 patients (66.7%). However, only 26of them had a value below 90 ng/ml.Conclusions. Our data show that pituitary dysfunctionoccurs early and with high frequency aftersevere TBI, but the real significance of thesefindings still needs to be elucidated

Cognitive deterioration due to GH deficiency in patients with traumatic brain injury: a preliminary report.

PRIMARY OBJECTIVE: To determine whether cognitive and behavioural disorders observed in TBI patients are due to hormonal deficits or to the brain injury itself. RESEARCH DESIGN: Transversal, between-group design. METHODS AND PROCEDURES: Studied 22 severe TBI patients (GCS < 8): 11 had isolated GH deficiency and 11 did not. Prepared detailed clinical reports on patients and performed physical examinations, standard biochemical and full blood count analysis. Patients underwent neuropsychological assessment and hormonal evaluation 6 months after TBI diagnosis. RESULTS: TBI patients with GH deficiency show greater deficits in attention, executive functioning, memory and emotion than those without GH deficiency. CONCLUSIONS: Results show GH-related cognitive impairment in patients who develop GH deficiency after TBI and suggest that treatment of GH deficiency would improve cognition. The clinical importance of these findings should be established to better understand the nature, magnitude and meaning of GH-related cognitive impairment in patients who develop GH deficiency after TBI.

Long-term challenges in growth hormone treatment.

Growth hormone deficiency (GHD) is defined biochemically as a response to hypoglycaemia with a peak GH concentration of less than 5 microg/l. The 'GHD syndrome' is a range of psychological and physical symptoms that are associated with GHD, which include increased central adiposity, decreased bone mineral density, abnormal lipid profiles, decreased cardiovascular performance, reduced lean body mass (LBM), social isolation, depressed mood and increased anxiety. Importantly, the combination of physical and psychological problems can often result in a reduced quality of life. A number of trials have shown that GH replacement therapy can lead to a substantial improvement in GHD associated symptoms. Following up to 12 months of treatment with GH, LBM increased, left ventricular systolic function improved and the mean volume of adipose tissue fell. After only 4 months of treatment, a rise in exercise capacity was recorded, and after 2 years' treatment, isokinetic and isometric muscle strength had normalized in proximal muscle groups. Feelings of well-being and vitality also improved significantly. However, studies on the effects of treatment on insulin sensitivity in GH-deficient patients have had conflicting results. In this paper, we will discuss the long-term consequences of GHD and the effects of GH replacement therapy.

Variability in the presence of the metabolic syndrome in Type 2 diabetic patients attending a diabetes clinic. Influences of age and gender.

In this study, we have assessed age and gender-related influences on the presence of the metabolic syndrome (MS) and closely related variables in Type 2 diabetic patients attending a diabetes clinic. For this purpose, we have taken retrospective clinical and biochemical data from consecutive Type 2 diabetic patients (n = 291) and we have classified them by gender, age (with 55 and 70 years as cut-off levels) and having or not having the MS (using both the WHO and NCEP-ATP III MS definitions). A higher prevalence of adiposity and hypertension was present in the females. Males were characterized by higher uric acid and lower HDL-cholesterol and apoA(1) levels (two-way ANOVA considering jointly age and gender as main effects, P < 0.05 in every case). Overall the prevalence of NCEP-ATP III-defined MS was less frequent than WHO-defined MS (63.2% versus 81.1%, respectively). This difference was greater for males (42.1% versus 77.6%, respectively) than for females (75.5% versus 83.2% respectively). The kappa-coefficient for the concordance between both MS definitions was 0.46 for males and 0.72 for females in the first age band, 0.29 for males and 0.48 for females in the second age band and 0.24 for males and 0.51 for females in the third age band. Thus, this study reveals relevant differences in the application of WHO and NCEP-ATP III MS definitions in a clinic-based Type 2 diabetic population from Southern Spain. In addition, the data suggest that gender confers a specific influence upon some MS-associated features in Type 2 diabetic patients attending a diabetes clinic irrespective of age band.

Mechanisms underlying the neuroendocrine response to physical exercise.

Exercise initiates a coordinated series of physiological responses, including hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system activation, that, in combination, lead to the appropriate selection and utilization of metabolic substrates. Physical activity acts as a powerful stimulus for the hypothalamic-pituitary axis, leading to the liberation of several neuroendocrine hormones. The nature of this stimulation varies according to the kind of exercise (intensity, duration, aerobic, strength) and subject characteristics (gender, previous training), as well as depending on the time of the day and meal ingestion. As a whole, the neuroendocrine responses to exercise represent an accurate regulator of fuels (glucose, free fatty acids) homeostasis in a special situation characterized by a drastic increase of the energy requirements at muscle level. In this article the current knowledge about this topic is reviewed.

Diagnóstico del déficit de hormona del crecimiento en pacientes adultos / Diagnosis of growth hormone deficiency in adults

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Influence of cortisol status on leptin secretion.

The discovery of the adipocyte-produced hormone leptin has changed the field of obesity research and our understanding of energy homeostasis. It is now accepted that leptin is the afferent loop informing the hypothalamus about the states of fat stores, with hypothalamic efferents regulating appetite and energy expenditure. I addition, leptin has a role as a metabolic adaptator in overweight and fasting states. New and previously unsuspected neuroendocrine roles have emerged for leptin. Leptin participates in the expression of CRH in the hypothalamus, interacts at the adrenal level with ACTH, and is regulated by glucocorticoids. Since leptin and cortisol show an inverse circadian rhythm, it has suggested that a regulatory feedback is present. However glucocorticoids appears to play a modulatory, but not essential roles in generating leptin diurnal rhythm. Glucocortiocids act directly on the adipose tissue and increase leptin synthesis and secretion in humans. Leptin levels are markedly increased in Cushing's syndrome patients and in other pseudo-Cushing's syndrome states. Glucocorticoids appears to act as a key modulator of body weight and food intake, promoting leptin secretion by adipocytes, limiting central leptin induced effects and favoring those of the NPY. Furthermore the modulatory role of glucocorticoids could be altered in obesity, but the precise mode of action remains to be established. The relevance of this finding merits further studies.

Estudio analítico cromatográfico de los metabolitos urinarios del cortisol / Analytical chromatography study of urinary cortisol metabolites

El objetivo de nuestro trabajo ha consistido en estudiar el cortisol y sus metabolitos urinarios. El conocimiento de estos compuestos, así como de la actividad enzimática 11Beta-hidroxiesteroide-deshidrogenasa tiene gran interés clínico porque nos proporciona información sobre el estado de la función adrenal. Se han descrito diferentes métodos, todos ellos relacionados con la cromatografía líquida de alta resolución (HPLC) usando el radioinmunoensayo o la espectometría de masas para la cuantificación final. Nosotros hemos analizado estos metabolitos urinarios en 25 sujetos clínicamente sanos realizando la valoración final en el propio sistema de HPLC mediante un detector ultravioleta-visible (UV-VIS). LA metodología empleada presenta la ventaja de su rapidez y economía, y los resultados obtenidos pueden ser utilizados en la práctica clínica (AU)

The growth hormone (GH)-releasing hormone-GH-insulin-like growth factor-1 axis in patients with fibromyalgia syndrome.

Fibromyalgia (FM) is a painful syndrome of nonarticular origin, characterized by fatigue and widespread musculoskeletal pain, tiredness, and sleep disturbances, without any other objective findings on examination. Interestingly, some of the clinical features of FM resemble the ones described in the adult GH-deficiency syndrome. Furthermore, insulin-like growth factor (IGF)-1 levels are frequently reduced in patients with FM. To gain further insight into the mechanisms leading to dysregulation of the GH-IGF-1 axis in these patients, we assessed 24-h spontaneous GH secretion, GH responses to GHRH, and IGF-1 and IGF binding protein (BP)-3 levels before and after 4 days treatment with human (h)GH. We found that, in comparison with controls, patients with FM exhibited a marked decrease in spontaneous GH secretion as assessed by mean GH secretion (2.5 +/- 0.4 microg/L in controls vs. 1.2 +/- 0.1 microg/L in FM, P < 0.05), pulse height (4.7 +/- 0.8 microg/L in controls vs. 2.5 +/- 0.3 microg/L in FM, P < 0.05), and pulse area (4.7 +/- 1 min/mg x L in controls vs. 2.3 +/- 0.3 min/mg x L in FM, P < 0.05). In contrast, GH responses to GHRH (100 microg, i.v.) were similar in controls (mean peak, 13.5 +/- 2.5 microg/L) and in patients with FM (12.2 +/- 3 microg/L). Finally, treatment with hGH (2 IU, s.c. daily), over 4 days, led to a clear-cut increase in plasma IGF-1 and IGFBP-3 levels in patients with FM. In conclusion, our data show that patients with FM exhibited a marked decrease in spontaneous GH secretion, but normal pituitary responsiveness to exogenously administered GHRH, thus suggesting the existence of an alteration at the hypothalamic level in the neuroendocrine control of GH in these patients. Furthermore, our finding of increased IGF-1 and IGFBP-3 levels after GH treatment, over 4 days, opens up the possibility of testing the therapeutic potential of hGH in patients with FM.

Xanthomas of the Achilles tendon: report of a bilateral case and review of the literature.

We report a case of bilateral Achilles tendon xanthoma as the first clinical manifestation of familial hypercholesterolemia. We review the literature and stress the need for orthopaedic surgeons to be familiar with this disease. An early diagnosis of this metabolic disorder is important to institute medical therapy and to alter the course of the disease before the onset of coronary artery disease.

Serum leptin levels in male marathon athletes before and after the marathon run.

Leptin is a hormone produced by the adipocytes to regulate food intake and energy expenditure at the hypothalamic level. It is commonly accepted that the main determinants of leptin secretion are the net amount of body fat and the mean size of adipocytes. On the contrary, important vectors of energy flux in the organism, such as food intake and energy expended on exercise, are not thought to be regulators of that secretion. To understand whether leptin is regulated by an acute energy expenditure such as strenuous exercise, 29 male athletes who had trained for marathon running were studied before and after a marathon run and compared with 22 nonobese, age-, sex-, and body mass index (BMI)-matched sedentary controls. Controls and marathon athletes showed no differences in BMI or fat-free mass. Marathon runners showed a strong reduction in total fat mass (6.2 +/- 0.4 kg; 9.1 +/- 0.5% of body fat) compared with controls (12.3 +/- 0.5 kg; 16.1 +/- 0.5% of body fat; P < 0.05). This difference in body composition was paralleled by a mean serum leptin level that in marathonians (2.9 +/- 0.2 micrograms/L) was significantly (P < 0.05) reduced compared with that in controls (5.1 +/- 0.6 micrograms/L). It is remarkable that the ratio of leptin per kg body fat, showed a very good agreement between the two groups, 0.40 +/- 0.04 microgram/L.kg for controls and 0.46 +/- 0.03 microgram/L.kg for marathonians. In the two groups, leptin was correlated with both body weight, BMI, and fat mass (P < 0.001). The marathon trajectory was the standard 42.195 km accomplished in an average time of 3 h, 17 min, 7 s, with a calculated energy expenditure of over 2800 Cal. After the marathon run, a water imbalance occurred, with a significant decrease in body weight and an increase in serum albumin. A significant (P < 0.05) reduction in leptin values was observed after the run (2.6 +/- 0.2 micrograms/L) compared with before (2.9 +/- 0.2 micrograms/L), which was more relevant considering the relative hemoconcentration. In conclusion, 1) compared with sedentary subjects, leptin levels are reduced in male marathon runners in parallel with the relevant reduction in total body fat; 2) expressed as a ratio of leptin per kg body fat, no differences were observed between marathonians and controls; and 3) after an energy expenditure of 2800 Cal in the marathon run, a reduction in leptin levels occurred. Strong changes in energy expenditure may regulate serum leptin levels in man.

Enhanced growth hormone (GH) responsiveness to GH-releasing hormone after dietary restriction in patients with Cushing's syndrome.

OBJECTIVE: In patients with Cushing's syndrome, decreased growth hormone (GH) secretion is observed although the basic mechanism is not yet understood. A short-term hypocaloric diet is known to increase both spontaneous and GHRH-stimulated GH secretion in normal subjects. In order to gain further insight into the altered GH secretion in patients with Cushing's syndrome, we assessed the effect of a short-term hypocaloric diet on GH responses to GHRH in these patients. DESIGN: Two GHRH tests (1 microgram/kg i.v.) were performed, the first under basal conditions (normocaloric diet) and the second after a 3-day hypocaloric diet (650 cal/day). PATIENTS: Six female patients with untreated Cushing's disease. MEASUREMENTS: Plasma GH levels were measured by immunoradiometric assay. RESULTS: GHRH-induced GH release was impaired in patients with Cushing's disease on a normal diet (mean peak 12.4 +/- 6.4 mU/l, area under the curve (AUC) 744 +/- 332 mU/l/120 min). Following a hypocaloric diet, GH responses to GHRH were markedly enhanced in the same group of patients (mean peak 46.2 +/- 14.8 mU/l, AUC 3142 +/- 1032 mU/l/120 min, P < 0.05). CONCLUSIONS: This study demonstrates that in patients with Cushing's disease the somatotroph hyporesponsiveness to growth hormone releasing home is improved after a short-term hypocaloric diet. Therefore, blunted growth-hormone secretion in chronic hypercortisolism is a potentially reversible state and the secretory capacity of the somatotroph appears not to be severely compromised in patients with Cushing's disease.

Neuropharmacological assessment of growth hormone secretion.

The biochemical diagnosis of individuals who are either deficient in growth hormone (GH) or who have alterations in the normal pattern of GH secretion is difficult. The uncertainty surrounding diagnosis reflects the lack of a thorough understanding of the physiology of GH secretion and of the hypothalamic hormones involved. At least three hormones are implicated: GH-releasing hormone (GHRH), somatostatin and the endogenous ligand of the GH secretagogue receptor, although the role that each plays in the release of GH is not clear from the available experimental evidence. In such a situation, most of the dynamic tests of GH secretory capacity in humans need to undergo a 'trial and error' process before being validated. The search for the 'gold standard' test of GH secretion is ongoing, and the combination of GHRH plus GH secretagogues will probably play an important role in future clinical diagnosis.

Acute pharmacological reduction of plasma free fatty acids enhances the growth hormone (GH)-releasing hormone-mediated GH secretion in patients with Cushing's syndrome.

In Cushing's syndrome, GH secretion is blocked with all the stimuli tested. It has been reported that the acute pharmacological reduction of free fatty acids (FFA) leads to an enhancement of GH secretion in normal subjects and in pathological conditions associated with reduced GH secretion. To understand if the elevated FFA levels of hypercortisolism may be responsible for the altered GH secretion, 14 patients with active Cushing's syndrome underwent 2 paired tests with 100 micrograms i.v. of GHRH on 2 different occasions. In one test, they were pretreated with placebo and in the other one, with acipimox 250 mg p.o. 4 h before, and 250 mg p.o. 1 h before GHRH. The basal FFA levels (799 +/- 57 mmol/L) were reduced by acipimox throughout the whole test (values under 240 +/- 28 mmol/L). In the placebo pretreated group, GHRH-induced GH secretion was severely impeded, with a mean GH peak of 1.8 +/- 0.3 micrograms/L and area under the curve of 121.3 +/- 21.6 micrograms/L-120 min. All the patients showed a GHRH-mediated GH peak under 4 micrograms/L. Acute reduction of FFA by acipimox enhanced the GHRH action, with a mean GH peak of 11.1 +/- 1.8 micrograms/L and area under the curve of 652.9 +/- 110.3 micrograms/L-120 min (both P < 0.005). Individually analyzed after acipimox, all 14 subjects presented an enhancement in the GHRH-mediated GH peak, and 8 patients showed a response over 10 micrograms/L. In conclusion, acute FFA reduction by acipimox increased the GH secretion elicited by GHRH in chronic hypercortisolism. Elevated FFA may be a contributing factor to the deranged GH secretion observed in Cushing's syndrome.

Serum immunoreactive-leptin levels are increased in patients with Cushing's syndrome.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Cushing's syndrome is a disease state usually associated with weight gain due to the accumulation of adipose tissue. In order to study the effect of chronic glucocorticoid excess upon serum leptin levels; in the present work, four patients with recently diagnosed Cushing's syndrome and a group of control subjects matched for age, sex and body mass index (BMI) were studied. Serum leptin concentrations, measured by radioimmunoassay, were assessed in samples taken every 60 minutes over a 24 hour period. Assessment of leptin concentrations over 24 hours, by means of the area under curve showed a twofold increase in serum leptin levels in patients with Cushing's syndrome (mean+/-SEM 54.3+/-14) in comparison to control subjects (29.3+/-4.4; p<0.05). In conclusion, our data show that leptin levels are markedly increased in Cushing's syndrome patients. The relevance of this finding to the increased body fat present in patients with Cushing's syndrome merits further studies.