scholarly journals Increased Hypothalamic-Pituitary-Adrenal Axis Activity in Huntington’s Disease

Endocrinology ◽  
2009 ◽  
Vol 150 (3) ◽  
pp. 1558-1558
Author(s):  
N. Ahmad Aziz ◽  
Hanno Pijl ◽  
Marijke Frölich ◽  
A. W. Maurits van der Graaf ◽  
Ferdinand Roelfsema ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Huntington's Disease ◽  
Body Mass ◽  
Hpa Axis ◽  
Signs And Symptoms ◽  
Diurnal Variations ◽  
Cortisol Secretion ◽  
Hypothalamic Pituitary Adrenal ◽  
Total Cortisol ◽  
Cortisol Levels

Abstract Context: Huntington’s disease (HD) is a fatal hereditary neurodegenerative disorder characterized by motor, cognitive, and behavioral disturbances. Hypothalamic-pituitary-adrenal (HPA) axis dysfunction could contribute to a number of HD signs and symptoms; however, no data are available on cortisol diurnal variations and secretory dynamics in HD patients. Objective: The aim of the study was to perform a detailed analysis of HPA axis function in HD patients in relation to clinical signs and symptoms. Design, Setting, and Participants: Twenty-four-hour cortisol secretion was studied in eight early-stage, medication-free HD patients and eight age-, sex-, and body mass index-matched controls in a clinical research laboratory. Cortisol levels were measured every 10 min. Main Outcome Measures: Multiparameter autodeconvolution and cosinor regression were applied to quantify basal, pulsatile, and total cortisol secretion rates as well as diurnal variations in cortisol levels. Results: Total cortisol secretion rate and the amplitude of the diurnal cortisol profile were both significantly higher in HD patients compared with controls (3490 ± 320 vs. 2500 ± 220 nmol/liter/24 h, P = 0.023; and 111 ± 14 vs. 64 ± 8 nmol/liter, P = 0.012, respectively). Cortisol concentrations in patients were particularly increased in the morning and early afternoon period. In HD patients, mean 24-h cortisol levels significantly correlated with total motor score, total functional capacity, as well as body mass index. Conclusions: HPA axis hyperactivity is an early feature of HD and is likely to result from a disturbed central glucocorticoid feedback due to hypothalamic pathology. HPA axis dysfunction may contribute to some signs and symptoms in HD patients.

scholarly journals Combined Receptor Antagonist Stimulation of the Hypothalamic-Pituitary-Adrenal Axis Test Identifies Impaired Negative Feedback Sensitivity to Cortisol in Obese Men

2009 ◽  
Vol 94 (4) ◽  
pp. 1347-1352 ◽  
Author(s):  
Cecilia Mattsson ◽  
Rebecca M. Reynolds ◽  
Kotryna Simonyte ◽  
Tommy Olsson ◽  
Brian R. Walker
Keyword(s):  
Body Mass Index ◽  
Receptor Antagonist ◽  
Body Mass ◽  
Hpa Axis ◽  
Negative Feedback ◽  
Hypothalamic Pituitary Adrenal ◽  
The Metabolic Syndrome ◽  
Endogenous Cortisol ◽  
Cortisol Levels ◽  
Stimulation Of

Abstract Context: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie disorders including obesity, depression, cognitive decline, and the metabolic syndrome. Conventional tests of HPA axis negative feedback rely on glucocorticoid receptor (GR) agonists such as dexamethasone but do not test feedback by endogenous cortisol, potentially mediated by both GR and mineralocorticoid receptors (MR). Objective: The objective of the study was to use a combination of GR (RU38486, mifepristone) and MR (spironolactone) antagonists to explore the poorly understood activation of the HPA axis that occurs in obesity. Design: This was a double-blind, placebo-controlled, randomized, crossover study. Setting: The study was conducted at a clinical research facility. Participants: Participants included 15 lean (body mass index 22.0 ± 1.6 kg/m2) and 16 overweight/obese (body mass index 30.1 ± 3.5 kg/m2) men. Intervention: Subjects attended on four occasions for blood and saliva sampling every 30 min between 1800 and 2200 h. At 1100 and 1600 h before visits, subjects took 200 mg spironolactone, 400 mg RU38486, 200 mg spironolactone + 400 mg RU38486, or placebo orally. Main Outcome Measures: Serum cortisol levels after drug or placebo were measured. Results: Cortisol levels did not differ between lean and obese after placebo. Spironolactone and RU38486 alone had modest effects, increasing cortisol by less than 50% in both groups. However, combined spironolactone plus RU38486 elevated cortisol concentrations substantially, more so in lean than obese men [2.9- (0.3) vs. 2.2 (0.3)-fold elevation, P = 0.002]. Conclusions: Combined receptor antagonist stimulation of the HPA axis reveals redundancy of MR and GR in negative feedback in humans. Obese men have impaired responses to combined receptor antagonist stimulation, suggesting impaired negative feedback by endogenous cortisol. Such an approach may be useful to dissect abnormal HPA axis control in neuropsychiatric and other disorders.

scholarly journals Cortisol-binding globulin is important in the interpretation of dynamic tests of the hypothalamic--pituitary--adrenal axis

2002 ◽  
pp. 231-235 ◽  
Author(s):  
WS Dhillo ◽  
WM Kong ◽  
CW Le Roux ◽  
J Alaghband-Zadeh ◽  
J Jones ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Objective Assessment ◽  
Dynamic Tests ◽  
Hypothalamic Pituitary Adrenal ◽  
Total Cortisol ◽  
Significant Difference ◽  
Synacthen Test ◽  
Cortisol Levels ◽  
Short Synacthen Test ◽  
Time Point

OBJECTIVE: Assessment of the hypothalamic--pituitary--adrenal (HPA) axis relies on the interpretation of serum (total) cortisol in response to dynamic tests of the HPA axis. Most cortisol is bound to cortisol-binding globulin (CBG) and serum total cortisol levels are significantly affected by variation in CBG. We hypothesised that CBG variation significantly affects interpretation of dynamic tests of the HPA axis. DESIGN: We investigated the effect of CBG variation on the outcome of the 250 microg short Synacthen test (SST) in 30 healthy adults. METHODS: Blood was sampled at time -30, 0 (at which point Synacthen was given) and +30 min. CBG and total cortisol were measured at each time-point. Integrity of the HPA axis was confirmed by measurement of urine cortisol. RESULTS: We found that CBG varied significantly within individuals, falling from 51+/-3.4 to 43 +/-3.2 microg/ml (P<0.0001) on changing from standing to lying. Total cortisol levels strongly correlated with CBG (r=0.88, P<0.0001). Thirteen subjects had a +30 min total cortisol <550 nmol/l. In these subjects, the CBG levels at each time-point were significantly lower compared with subjects who had a +30 min total cortisol of >550 nmol/l (P<0.05). To correct for variation in CBG we calculated the total cortisol:CBG ratio and found no significant difference in the +30 min ratio between these two groups. CONCLUSION: CBG varies significantly within and between individuals. This is accompanied by changes in serum total cortisol large enough to affect the outcome of an SST and, by implication, other tests of the HPA axis.

scholarly journals Factors Associated with Low Body Mass Index in Huntington's Disease: A Spanish Multicenter Study of the European Huntington's Disease Registry

2016 ◽  
Vol 3 (5) ◽  
pp. 452-459
Author(s):  
Esther Cubo ◽  
Jessica Rivadeneyra ◽  
Natividad Mariscal ◽  
Asunción Martinez ◽  
Diana Armesto ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Body Mass ◽  
Multicenter Study ◽  
Disease Registry ◽  
Factors Associated ◽  
Low Body Mass Index

Developmental changes in cortisol secretion in normal and at-risk youth

2001 ◽  
Vol 13 (3) ◽  
pp. 721-732 ◽  
Author(s):  
ELAINE F. WALKER ◽  
DEBORAH J. WALDER ◽  
FELICIA REYNOLDS
Keyword(s):  
Hpa Axis ◽  
Clinical Symptoms ◽  
Psychiatric Symptoms ◽  
Early Adulthood ◽  
At Risk Youth ◽  
Cortisol Secretion ◽  
Cross Sectional ◽  
Axis Ii ◽  
Schizotypal Personality ◽  
Cortisol Levels

Adolescence is associated with an increase in the rate of certain psychiatric symptoms, and it is typically the developmental period when prodromal features of the major psychiatric disorders emerge. This is especially true of schizophrenia, with the majority of patients showing a marked postpubertal rise in schizotypal signs that predates the onset of clinical symptoms in early adulthood. Cross-sectional studies of youth have revealed a positive correlation between age and saliva cortisol level, suggesting a normative maturational increase in activity of the hypothalamic–pituitary–adrenal (HPA) axis. It has been hypothesized that this increase may trigger the expression of symptoms in vulnerable individuals. The present longitudinal study measured cortisol secretion and its relation with symptom development in samples of youth with schizotypal personality disorder (SPD), other personality disorders, or no Axis II disorder. The findings indicate moderate stability in cortisol levels across a 2-year period, with a longitudinal increase in cortisol levels over time. Cortisol levels at the first and second assessments were correlated with the severity of SPD symptoms at follow-up. The results are consistent with the notion that the HPA axis undergoes a postpubertal maturational process that moderates the expression of psychiatric symptoms.

scholarly journals Relationship Between Salivary Cortisol, Self-Assessed Stress Levels, and Body Mass Index in High Achieving High School Adolescents

Elements ◽  
2018 ◽  
Vol 14 (1) ◽  
Author(s):  
Sara Samir
Keyword(s):  
Blood Pressure ◽  
Body Mass Index ◽  
Body Mass ◽  
Perceived Stress ◽  
Salivary Cortisol ◽  
The Body ◽  
Metabolism Regulation ◽  
Stress Levels ◽  
Cortisol Levels ◽  
High Achieving

Studies of stress and cortisol levels in adults indicate that keeping normal levels of cortisol is beneficial to subjects. The hormone cortisol has many functions including proper glucose metabolism, regulation of blood pressure, immune function, and inflammatory  response. When cortisol levels spike, as with stress, there can be a negative effect on the individual. Due to the hectic pace of modern life, the body’s stress response does not always have time to return to normal, leading to cortisol levels remaining too high. This can lead to suppressed thyroid function, blood sugar imbalances, higher blood pressure, lowered immunity, and increased abdominal fat. Stress plays a prominent role in the lives of millions of people all across the globe. This problem is not one that affects solely the adult population but also a multitude of adolescents and children. Oftentimes, stress can have both a physical and psychological effect on an individual. Many persons report an effect on food consumption when under stressful situations, causing one to either eat more or less than normal. In turn, these eating patterns can potentially influence the Body Mass Index (BMI) of an individual. While increased stress can lead to a higher or lower than normal cortisol level and BMI in adults, the role in adolescents is not entirely clear. This study investigated whether there is a relationship between stress and BMI in high-achieving adolescents, aged 14 to 18. The Perceived Stress Scale survey paired with additional questions that helped determine variables believed to impact stress levels were administered to determine overall stress levels in each subject. To determine cortisol levels, a competitive enzyme immunoassay was used.  This study indicates that there   are no significant correlations between perceived stress levels, salivary cortisol levels, and BMI in this group of individuals. However, a distinct difference in self-assessed stress levels was apparent between males and females. Somewhat unexpectedly, a negative relationship was found between BMI and salivary cortisol levels and perceived stress and salivary cortisol levels.

scholarly journals Response of the Hypothalamic-Pituitary-Adrenocortical Axis to High-Protein/Fat and High-Carbohydrate Meals in Women with Different Obesity Phenotypes

2002 ◽  
Vol 87 (8) ◽  
pp. 3984-3988 ◽  
Author(s):  
Valentina Vicennati ◽  
Luana Ceroni ◽  
Lorenza Gagliardi ◽  
Alessandra Gambineri ◽  
Renato Pasquali
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Body Fat ◽  
Hpa Axis ◽  
Abdominal Obesity ◽  
Area Under The Curve ◽  
Fat Distribution ◽  
Normal Weight ◽  
Body Fat Distribution ◽  
High Carbohydrate

Subjects with abdominal obesity are characterized by hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis. Food intake, particularly at noon, is a well-known inducer of HPA axis activation. Whether obese subjects present an abnormal response to meals containing different macronutrient proportions is at present unknown. Therefore, this study was carried out to investigate the effect of a high-lipid/protein meal (HLP-meal) and a high-carbohydrate meal (HCHO-meal) on the HPA axis activity in women with different obesity phenotypes. Nondepressed, noncomplicated obese (body mass index greater than 28 kg/m2) women with abdominal (A-BFD) (n = 10) and peripheral body fat distribution (P-BFD) (n = 9) and a group of 11 normal-weight controls were investigated in the follicular phase of the menstrual cycle. They were randomly given an 800-kcal HCHO-meal (containing 89% carbohydrates, 11% proteins, 0% lipids), and an 800-kcal HLP-meal (containing 53% lipids, 43% proteins, 4% carbohydrates), which were eaten within 15 min at noon, with an interval of 2 d between each meal. Blood samples for ACTH, cortisol, glucose, and insulin were obtained at 15-min intervals before and after each meal. Baseline hormone and glucose concentrations in the three groups were similar. After the HLP-meal, ACTH tended to similarly but insignificantly increase in all groups, whereas cortisol increased significantly (P &lt; 0.05) in the P-BFD group and insignificantly in the other groups. Conversely, both ACTH and cortisol significantly (P &lt; 0.05) increased only in the A-BFD group, without any significant changes in both controls and P-BFD women. The analysis of the interaction between meals and groups clearly indicated that the cortisol response to the HLP-meal and the HCHO-meal was significantly different (P &lt; 0.025) between the two obese groups, the A-BFD group being characterized by a significantly lower response to the HLP-meal and a significantly higher response to the HCHO-meal, compared with the P-BFD group. Considering all groups together and after adjusting for body mass index, a highly significant relationship was found between cortisol-area under the curve and ACTH-area under the curve after each meal test. However, no relationships were found between changes in ACTH and cortisol and those of glucose, insulin, and the glucose:insulin ratio after each meal. Therefore, our data demonstrate that the response of the HPA axis to meals containing different macronutrient proportions may depend on the pattern of body fat distribution. We also suggest that the activation of the HPA axis following the ingestion of large amounts of carbohydrates may have some pathophysiological relevance, specifically in women with the abdominal obesity phenotype.

Maximal Bite Force and Its Association with Signs and Symptoms of TMD, Occlusion, and Body Mass Index in a Cohort of Young Adults

CRANIO® ◽  
2003 ◽  
Vol 21 (4) ◽  
pp. 248-252 ◽  
Author(s):  
Jari P. Ahlberg ◽  
Outi A. Kovero ◽  
Kirsti A. Hurmerinta ◽  
Inta Zepa ◽  
Maunu J. Nissinen ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Young Adults ◽  
Body Mass ◽  
Signs And Symptoms ◽  
Bite Force

scholarly journals Adrenal Sensitivity to Adrenocorticotropin 1–24 Is Reduced in Patients with Autoimmune Polyglandular Syndrome

2004 ◽  
Vol 89 (2) ◽  
pp. 675-680 ◽  
Author(s):  
R. Giordano ◽  
M. Pellegrino ◽  
S. Oleandri ◽  
M. Baldi ◽  
M. Balbo ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Autoimmune Diseases ◽  
Body Mass ◽  
Clinical Signs ◽  
Plasma Renin ◽  
Signs And Symptoms ◽  
Autoimmune Polyglandular Syndrome ◽  
Sequential Administration ◽  
Young Subjects ◽  
Clinical Signs And Symptoms

Autoimmune polyglandular syndromes are fairly common diseases that are classified into four constellations based on the clinical clustering of the various component diseases. In types 1, 2, and 4, primary adrenal insufficiency due to an autoimmune process is usually present, but its diagnosis is often delayed because it is difficult to detect in a subclinical phase. It is widely accepted that the classical dose of 250 μg ACTH1–24 is supramaximal, whereas 0.06 μg has been shown to be one of the lowest ACTH doses that is able to stimulate adrenal secretion in normal young subjects. The aim of this study was to clarify the sensitivity and maximal secretory response of the adrenal gland to ACTH in a group of patients with at least two autoimmune diseases, without clinical signs and symptoms of overt or subclinical hypocortisolism. Cortisol (F), aldosterone (A), and dehydroepiandrosterone (DHEA) responses to the sequential administration of very low and supramaximal ACTH1–24 doses [0.06 μg followed by 250 μg ACTH1–24 iv at 0 and +60 min] were studied in 18 patients with at least two autoimmune diseases (AP; age, 20–40 yr; body mass index, 22–26 kg/m2). The results in the patients were compared with the results recorded in 12 normal age-matched control subjects (CS; age, 22–34 yr; body mass index, 20–25 kg/m2). At baseline, ACTH levels in AP were within the normal range but higher (P &lt; 0.05) than in CS, whereas F, A, DHEA, urinary-free F, and plasma renin activity were similar in both groups. F, A, and DHEA responses to ACTH were dose dependent in both groups. However, in AP, F, A, and DHEA levels showed no response to the 0.06-μg ACTH dose, which, in turn, elicited clear responses (P &lt; 0.01) in CS. On the other hand, F, A, and DHEA responses to 250 μg ACTH in AP were not different from those in CS. In conclusion, patients with autoimmune diseases who displayed a normal basal adrenal function showed a loss of F, A, and DHEA response to the very low ACTH dose, although they were normal responders to the high ACTH dose. These data are likely to indicate that a reduced sensitivity to ACTH in all adrenal zones occurs in patients with different types of autoimmune disease.

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