Reactivation of Pituitary Hormone Release and Metabolic Improvement by Infusion of Growth Hormone-Releasing Peptide and Thyrotropin-Releasing Hormone in Patients with Protracted Critical Illness1

1999 ◽  
Vol 84 (4) ◽  
pp. 1311-1323 ◽  
Author(s):  
Greet Van den Berghe ◽  
Pieter Wouters ◽  
Frank Weekers ◽  
Subburaman Mohan ◽  
Robert C. Baxter ◽  
...  
Keyword(s):  
Critical Illness ◽  
Protein Degradation ◽  
Biochemical Markers ◽  
Feedback Inhibition ◽  
Elevated Serum ◽  
Random Order ◽  
Serum Cortisol ◽  
Pituitary Hormone ◽  
Metabolic Markers ◽  
Deconvolution Analysis

Protracted critical illness is marked by protein wasting resistant to feeding, by accumulation of fat stores, and by suppressed pulsatile release of GH and TSH. We previously showed that the latter can be reactivated by brief infusion of GH-releasing peptide (GHRP-2) and TRH. Here, we studied combined GHRP-2 and TRH infusion for 5 days, which allowed a limited evaluation of the metabolic effectiveness of this novel trophic endocrine strategy. Fourteen patients (mean ± sd age, 68 ± 11 yr), critically ill for 40 ± 28 days, were compared to a matched group of community-living control subjects at baseline and subsequently received 5 days of placebo and 5 days of GHRP-2 plus TRH (1+1μ g/kg·h) infusion in random order. At baseline, impaired anabolism, as indicated by biochemical markers (osteocalcin and leptin), was linked to hyposomatotropism [reduced pulsatile GH secretion, as determined by deconvolution analysis, and low GH-dependent insulin-like growth factor and binding protein (IGFBP) levels]. Biochemical markers of accelerated catabolism (increased protein degradation and bone resorption) were related to tertiary hypothyroidism and the serum concentration of IGFBP-1, but not to hyposomatotropism. Metabolic markers were independent of elevated serum cortisol. After 5 days of GHRP-2 plus TRH infusion, osteocalcin concentrations increased 19% vs. −6% with placebo, and leptin had rose 32% vs. -15% with placebo. These anabolic effects were linked to increased IGF-I and GH-dependent IGFBP, which reached near-normal levels from day 2 onward. In addition, protein degradation was reduced, as indicated by a drop in the urea/creatinine ratio, an effect that was related to the correction of tertiary hypothyroidism, with near-normal thyroid hormone levels reached and maintained from day 2 onward. Concomitantly, a spontaneous tendency of IGFBP-1 to rise and of insulin to decrease was reversed. Cortisol concentrations were not detectably altered. In conclusion, 5-day infusion of GHRP-2 plus TRH in protracted critical illness reactivates blunted GH and TSH secretion, with preserved pulsatility, peripheral responsiveness, and feedback inhibition and without affecting serum cortisol, and induces a shift toward anabolic metabolism. This provides the first evidence of the metabolic effectiveness of short term GHRP-2 plus TRH agonism in this particular wasting condition.

scholarly journals CUSHING DISEASE MASQUERADING AS GLAUCOMA

2019 ◽  
Vol 5 (5) ◽  
pp. e290-e293
Author(s):  
Yumiko Tsushima ◽  
Lubna Bashir Munshi ◽  
Charit Taneja ◽  
Se-min Kim
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Case Reports ◽  
Elevated Serum ◽  
Serum Cortisol ◽  
Thyroid Stimulating Hormone ◽  
Pituitary Hormone ◽  
Cushing Disease ◽  
Corticosteroid Administration ◽  
Late Night ◽  
Stimulating Hormone

Objective: Glaucoma is a well-recognized side effect of corticosteroids. However, steroid-induced glaucoma typically refers to that caused by exogenous corticosteroid administration. Glaucoma secondary to endogenous overproduction of corticosteroids has only been reported in a few case reports. We aim to bring attention to glaucoma as a rare but important manifestation of endogenous hypercortisolism. Methods: Patient history, physical exam, laboratory results, and imaging studies were reviewed. Results: We report a case of glaucoma as the initial presentation of Cushing disease (CD). The patient was diagnosed with glaucoma 16 months prior to his endocrinology evaluation. At our initial encounter, the patient had a cushingoid appearance. Levels of 24-hour urinary cortisol and late-night salivary cortisol were elevated. Serum cortisol was not suppressed by 1 mg of dexamethasone overnight, but it was suppressed by 8 mg of dexamethasone. Adrenocorticotropic hormone was also elevated. All other pituitary hormone axes were unremarkable (thyroid-stimulating hormone, free thyroxine, follicle-stimulating hormone, luteinizing hormone, growth hormone, prolactin, and insulin-like growth factor). Pituitary magnetic resonance imaging suggested a small adenoma (2 to 3 mm); therefore, the patient underwent inferior petrosal sinus sampling. The results were consistent with CD. Transsphenoidal resection was performed and final pathology confirmed an adrenocorticotropic hormone-positive adenoma. Hypercortisolism and intraocular pressures improved after the surgery. Conclusion: Glaucoma can lead to irreversible blindness if left untreated or uncontrolled. However, endogenous hypercortisolism-induced glaucoma can be reversed with treatment of the underlying CD. Thus, heightened awareness of extraocular manifestations of secondary causes of glaucoma such as endogenous hypercortisolism is necessary in order to promote prompt evaluation and treatment.

scholarly journals Novel insights into the neuroendocrinology of critical illness

2000 ◽  
pp. 1-13 ◽  
Author(s):  
G Van den Berghe
Keyword(s):  
Stress Response ◽  
Critical Illness ◽  
Acute Stress ◽  
Feedback Inhibition ◽  
Chronic Phase ◽  
Pituitary Hormone ◽  
Reverse T3 ◽  
Pulsatile Secretion ◽  
Target Organs ◽  
Releasing Factors

An unexplained hallmark of prolonged critical illness is the fact that food does not prevent or reverse protein wasting, while fat is paradoxically accrued. This 'wasting syndrome' often persists after the underlying disease has been resolved and thus perpetuates intensive care dependency. Although the crucial role of an intact hypothalamus-pituitary axis for homeostasis during stress is well recognized, the differences between the neuroendocrine changes observed in acute and prolonged critical illness were only recently described. Novel insights in this area are reviewed here. The initial endocrine stress response consists primarily of a peripheral inactivation of anabolic pathways while pituitary activity is essentially amplified or maintained. These responses presumably provide the metabolic substrates and host defense required for survival and to delay anabolism, and thus should be considered as adaptive and beneficial. Persistence of this acute stress response throughout the course of critical illness was hitherto assumed. This assumption has now been invalidated, since a uniformly reduced pulsatile secretion of ACTH, TSH, LH, prolactin (PRL) and GH has been observed in protracted critical illness, causing diminished stimulation of several target organs. Impaired pulsatile secretion of anterior pituitary hormones in the chronic phase of critical illness seems to have a hypothalamic rather than a pituitary origin, as administration of relevant releasing factors evoked immediate and pronounced pituitary hormone release. A reduced availability of TRH, one of the endogenous ligands of the GH-releasing peptide (GHRP) receptor (such as the recently discovered ghrelin) and, in very long-stay critically ill men, also of GHRH, appear to be involved. This hypothesis was further explored by investigating the effects of continuous i.v. infusion of GHRH, GHRP, TRH and their combinations for several days. Pulsatile secretion of GH, TSH and PRL was re-amplified by relevant combinations of releasing factors which also substantially increased circulating levels of IGF-I, GH-dependent binding proteins, thyroxine and tri-iodothyronine (T3) while avoiding a rise in reverse T3. Active feedback-inhibition loops prevented overstimulation of target organs and metabolic improvement was noted with the combined infusion of GHRP and TRH. Whether this novel endocrine strategy will also enhance clinical recovery from critical illness remains to be explored.

scholarly journals Hepatic Steatosis Is Associated with Elevated Serum Iron in Patients with Obesity and Improves after Laparoscopic Sleeve Gastrectomy

Obesity Facts ◽  
2020 ◽  
pp. 1-8
Author(s):  
Bingwei Ma ◽  
Hang Sun ◽  
Bing Zhu ◽  
Shilin Wang ◽  
Lei Du ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Laparoscopic Sleeve Gastrectomy ◽  
Hepatic Steatosis ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Postprandial Blood Glucose ◽  
Iron Level ◽  
Metabolic Markers ◽  
Alcoholic Fatty Liver ◽  
Negatively Associated

<b><i>Background:</i></b> Iron is closely related to metabolism. However, the relationship between iron and hepatic steatosis has not been fully elucidated. <b><i>Objective:</i></b> We aimed to investigate the triangular relationship between iron and hepatic steatosis and laparoscopic sleeve gastrectomy (LSG) in patients with obesity. <b><i>Methods:</i></b> A total of 297 patients with obesity and 43 healthy individuals with a normal BMI were enrolled. Eighty-two patients underwent LSG. Anthropometrics, glucose-lipid metabolic markers, and hepatic steatosis assessed by FibroScan (CAP value and E value) were measured at baseline, and again at follow-up time intervals of 6 months and 1 year after surgery. <b><i>Results:</i></b> (1) Iron was significantly higher in patients with obesity or overweight than in the individuals with normal BMI (8.18 ± 1.47 vs. 7.46 ± 0.99 mmol/L, <i>p</i> = 0.002). Iron was also higher in subjects with high blood pressure, dyslipidemia, and hyperuricemia than non-corresponding disorders (all <i>p</i> &#x3c; 0.05). Moreover, iron was significantly higher in the severe than mild or moderate non-alcoholic fatty liver disease (NAFLD) group (<i>p</i> = 0.046 and 0.018). (2) Iron was positively associated with body weight, BMI, waist-to-hip ratio, uric acid, liver enzymes, postprandial blood glucose, fasting insulin, HOMA-IR, triglycerides, free fatty acid, and hepatic steatosis (CAP value), and negatively associated with high-density lipoprotein cholesterol (all <i>p</i> &#x3c; 0.05). Iron was also positively associated with the visceral adipose area in patients with obesity and negatively associated with the subcutaneous adipose area in patients with overweight (all <i>p</i> &#x3c; 0.05). (3) Iron levels and CAP values were decreased gradually 6 months and 1 year after surgery (all <i>p</i> &#x3c; 0.05). <b><i>Conclusions:</i></b> Overall, our results indicated that iron is associated with hepatic steatosis in obesity. The iron level was significantly higher in patients with severe NAFLD than with mild or moderate NAFLD. LSG may reduce iron levels while improving fat deposition in the liver.

Abstract 530: Impact of a Single Mixed Mediterranean-Type Meal Compared with a High-Saturated Fat Meal on Postprandial Endothelial Function and Metabolic Markers

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Sebastien Lacroix ◽  
Christine Des Rosiers ◽  
Mathieu Gayda ◽  
Anil Nigam
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Saturated Fat ◽  
Random Order ◽  
Flow Mediated Dilation ◽  
Omega 3 ◽  
Metabolic Markers ◽  
Endothelial Impairment ◽  
Artery Flow ◽  
Fat Meal

Background: Endothelial dysfunction is considered a precursor of atherosclerosis and is an independent predictor of cardiovascular events. A high-saturated fat meal (HFM) has been shown to induce postprandial endothelial dysfunction. However, no studies have evaluated the acute endothelial effect of a single mixed Mediterranean-type meal (MMM). Our objective was to evaluate postprandial endothelial and metabolic function in response to a MMM in comparison to an isocaloric HFM. Methods: In this ongoing crossover study, 26 of 28 healthy non-smoking males have completed the research protocol. In random order on two separate days during a 1-week interval, subjects were fed two isocaloric meals after an overnight fast. The MMM (885 kcal) consisted of fresh salmon, almonds and vegetables baked in olive oil providing 51% of total calories from fat (7.87g SFA and 2.29g of omega-3, 2:1 DHA:EPA). The HFM consisted of a McDonald’s sausage, egg and cheese McMuffin and three hashbrowns (858 kcal) providing 58% of total energy from fat (14.78g SFA and no omega-3). Endothelial function was evaluated by measuring brachial artery flow-mediated dilation (%FMD) at baseline and at two (T2) and four (T4) hours postprandial. Results: Mean postprandial %FMD tends to be less impaired following the MMM than the HFM (variation at T4 -0.15±3.6% vs -2.83±3.3% respectively, p<0.1). Postprandial variations of TG and TG/HDL at T4 were also less severe with the MMM than the HFM (p≤0.05) and did not correlate to %FMD variations. When subdividing the population on the basis of the median fasting TG levels (0.90 mmol/L), the HFM led to significant endothelial impairment in the subjects with higher-TG while it had no effect in the low-TG group. Conclusion: Our data suggest that a single MMM exerts less of a deleterious effect on postprandial endothelial function and metabolic markers than does a HFM. A single MMM could thus be less atherogenic than a HFM. Moreover, subjects with higher fasting TG levels (avg. 1.54±0.59 mmol/L, well bellow hypertriglyceridemia threshold) could be at higher risk of endothelial injury following a single HFM. Data on all 28 subjects will be available in April 2012.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: New concepts to further unravel adrenal insufficiency during critical illness

2016 ◽  
Vol 175 (1) ◽  
pp. R1-R9 ◽  
Author(s):  
Eva Boonen ◽  
Greet Van den Berghe
Keyword(s):  
Critical Illness ◽  
Adrenal Insufficiency ◽  
Feedback Inhibition ◽  
High Plasma ◽  
Future Research ◽  
Relative Adrenal Insufficiency ◽  
New Concepts ◽  
High Incidence ◽  
Circulating Levels ◽  
New Framework

The concept of ‘relative’ adrenal insufficiency during critical illness remains a highly debated disease entity. Several studies have addressed how to diagnose or treat this condition but have often yielded conflicting results, which further fuelled the controversy. The main reason for the controversy is the fact that the pathophysiology is not completely understood. Recently, new insights in the pathophysiology of the hypothalamic–pituitary–adrenal axis response to critical illness were generated. It was revealed that high circulating levels of cortisol during critical illness are explained more by reduced cortisol breakdown than by elevated cortisol production. Cortisol production rate during critical illness is less than doubled during the day but lower than in healthy subjects during the night. High plasma cortisol concentrations due to reduced breakdown in turn reduce plasma ACTH concentrations via feedback inhibition, which with time may lead to an understimulation and hereby a dysfunction of the adrenal cortex. This could explain the high incidence of adrenal insufficiency in the prolonged phase of critical illness. These novel insights have created a new framework for the diagnosis and treatment of adrenal failure during critical illness that has redirected future research.

Serum Cortisol Abnormalities after Craniocerebral Trauma

Neurosurgery ◽  
1979 ◽  
Vol 5 (5) ◽  
pp. 559-565 ◽  
Author(s):  
Paul Steinbok ◽  
Gordon Thompson
Keyword(s):  
Head Injury ◽  
Cortisol Level ◽  
Diurnal Rhythm ◽  
Elevated Serum ◽  
Craniocerebral Trauma ◽  
Serum Cortisol ◽  
Feedback Mechanism ◽  
Serum Cortisol Level ◽  
Skull Fractures ◽  
Middle Fossa

Abstract Serial estimations of serum cortisol were performed in 49 patients with craniocerebral trauma. Abnormalities of serum cortisol, including alterations in diurnal rhythm and elevations of serum cortisol level, occurred in 21 patients. The frequency and severity of the abnormalities correlated with the severity of the head injury, and there was a trend suggesting that middle fossa basal skull fractures predisposed to cortisol abnormalities. A further 6 patients were studied to assess the effects of exogenous dexamethasone, and in all patients there was suppression of elevated serum cortisol levels by the dexamethasone. The findings suggest that hypercortisolemia after head injury is related to an alteration rather than an abolition of the normal feedback mechanism.

Acute effects of cortisone acetate on growth hormone response to growth hormone-releasing hormone in normal adult subjects

1990 ◽  
Vol 122 (2) ◽  
pp. 206-210 ◽  
Author(s):  
Andrea Giustina ◽  
Mauro Doga ◽  
Corrado Bodini ◽  
Angela Girelli ◽  
Fabio Legati ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Random Order ◽  
Serum Cortisol ◽  
Cortisone Acetate ◽  
Acute Administration ◽  
Acute Effects ◽  
Gh Secretion ◽  
Normal Man ◽  
The Relationship ◽  
Dose Dependent

Abstract Glucocorticoids have been shown to inhibit GH secretion in normal man when administered in large amounts for several days. The aim of our study was 1. to investigate the acute effects of a single dose of glucocorticoids on GH secretion in normal man; 2. to look at the relationship between the increase in serum cortisol concentration and GH response to the stimuli. Six healthy volunteers received on three occasions in random order an iv injection of GHRH (1–29) NH2, 100 μg, alone or 60 min after oral administration of either 25 or 50 mg of cortisone acetate. Mean stimulated GH levels, GH peak and integrated GH concentration were significantly lower after GHRH plus cortisone 25 mg than after GHRH alone. Mean GH levels at 15 and 30 min after GHRH injection and the peak GH level showed a further decrease after GHRH plus cortisone 50 mg. We conclude that acute administration of pharmacological doses of glucocorticoids is able to inhibit GH response to GHRH, probably through enhancement of endogenous somatostatin release. Moreover, this pharmacological effect of glucocorticoids seems to be dose-dependent and thus directly related to serum cortisol concentrations.

Infusion of β-endorphin has no suppressive effect on the releasing hormone-stimulated pituitary-adrenal-axis of normal human subjects

1990 ◽  
Vol 123 (5) ◽  
pp. 526-530 ◽  
Author(s):  
Heinrich M. Schulte ◽  
Bruno Allolio
Keyword(s):  
Plasma Levels ◽  
Feedback Inhibition ◽  
Human Subjects ◽  
Serum Cortisol ◽  
Suppressive Effect ◽  
Pituitary Hormones ◽  
Releasing Hormone ◽  
Constant Rate ◽  
Loop Feedback ◽  
Normal Human

Abstract. The existence of a short-loop feedback inhibition of pituitary ACTH release by administration of β-endorphin was postulated. However, data on the effect of peripherally administered β-endorphin in humans are highly controversial. We infused human synthetic β-endorphin at a constant rate of 1 μg · kg−1 · min−1 or normal saline to 7 normal volunteers for 90 min. Thirty min after starting the β-endorphin or placebo infusion, releasing hormones were injected as a bolus iv (oCRH and GHRH 1 μg/kg, GnRH 100 μg, TRH 200 μg) and blood was drawn for measurements of β-endorphin immunoreactivity, all other pituitary hormones, and cortisol. Infusion of β-endorphin resulted in high β-endorphin plasma levels with a rapid decrease after the infusion was stopped. During the control infusion, β-endorphin plasma levels rose in response to CRH. Plasma ACTH and serum cortisol levels in response to the releasing hormone were not different in subjects infused with β-endorphin or placebo. The PRL response to TRH was significantly higher after β-endorphin than after placebo (area under the stimulation curve 1209±183 vs 834±104 μg · 1−1 · h). There was no difference in the response of all other hormones measured. Our data on ACTH and cortisol secretion do not support the concept of a shortloop negative feedback of β-endorphin acting at the site of the pituitary.

scholarly journals Serum Cortisol and DHEA-S Levels in Schizophrenic Patients with Different Response to Antipsychotic Therapy: Association with Psychopathology / Серумски Концентрации На Кортизол И DHEA-S Кал Пациенти Со Шизофренша Со Различен Одговор На Антипсихотичната Терапша Асоци.1Аци.1А Со Психопатологшата

PRILOZI ◽  
2015 ◽  
Vol 36 (1) ◽  
pp. 175-182 ◽  
Author(s):  
Zoja Babinkostova ◽  
Branislav Stefanovski ◽  
Danijela Janicevic-Ivanovska ◽  
Valentina Samardziska ◽  
Lila Stojanovska
Keyword(s):  
Elevated Serum ◽  
Serum Cortisol ◽  
Control Group ◽  
Antipsychotic Treatment ◽  
Healthy Controls ◽  
Symptom Scale ◽  
Antipsychotic Therapy ◽  
Schizophrenic Patients ◽  
Different Response ◽  
Age And Sex

Abstract Background: Previous studies suggested that alterations in serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia. Imbalance in serum cortisol and DHEA-S levels may be related to responsivity to antipsychotic treatment. Aim: To compare serum cortisol and DHEA-S levels between patients with schizophrenia and healthy controls and to evaluate their association with psychopathology in schizophrenic patients with different response to antipsychotic treatment. Material and Methods: This clinical prospective study included 60 patients with schizophrenia and 40 healthy age and sex matched controls. All patients experienced an acute exacerbation of the illness (PANSS: P1 and P3 ≥ 4). Clinical evaluation of patients was performed using the Positive and Negative Symptom Scale. A questionnaire for socio-demographic and clinical data collection was used. For the purposes of the study, the examined group was divided in two subgroups: responders and nonresponders. Serum cortisol and DHEA-S levels were measuredat baseline in all participants and after 3 and 6 weeks of the antipsychotic treatment in patients with schizophrenia. Results: Patients with schizophrenia had significantly higher serum cortisol and DHEA-S levels comparedwith control group. Responders had significantly higher serum cortisol and DHEA-S levels compared with nonresponders. Responders group had significant correlation between serum cortisol and PANSS positive scale score as well as between hostility and serum DHEA-S. Conclusion: Elevated serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia. Serum cortisol and DHEA-S are associated with psychopathology in schizophrenic patients with different response to antipsychotic therapy.

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