scholarly journals GDF15 Is Elevated in Conditions of Glucocorticoid Deficiency and Is Modulated by Glucocorticoid Replacement

2019 ◽  
Vol 105 (5) ◽  
pp. 1427-1434
Author(s):  
Audrey Melvin ◽  
Dimitrios Chantzichristos ◽  
Catriona J Kyle ◽  
Scott D Mackenzie ◽  
Brian R Walker ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Addison’S Disease ◽  
Neural Circuitry ◽  
Addison's Disease ◽  
Primary Adrenal Insufficiency ◽  
Site Of Action ◽  
Glucocorticoid Deficiency ◽  
The Impact ◽  
Dose Dependent ◽  
Cortisol Deficiency

Abstract Context GDF15 is a stress-induced hormone acting in the hindbrain that activates neural circuitry involved in establishing aversive responses and reducing food intake and body weight in animal models. Anorexia, weight loss, nausea and vomiting are common manifestations of glucocorticoid deficiency, and we hypothesized that glucocorticoid deficiency may be associated with elevated levels of GDF15. Objective To determine the impact of primary adrenal insufficiency (PAI) and glucocorticoid replacement on circulating GDF15 levels. Methods and Results We measured circulating concentrations of GDF15 in a cohort of healthy volunteers and Addison’s disease patients following steroid withdrawal. Significantly higher GDF15 (mean ± standard deviation [SD]) was observed in the Addison’s cohort, 739.1 ± 225.8 pg/mL compared to healthy controls, 497.9 ± 167.7 pg/mL (P = 0.01). The effect of hydrocortisone replacement on GDF15 was assessed in 3 independent PAI cohorts with classical congenital adrenal hyperplasia or Addison’s disease; intravenous hydrocortisone replacement reduced GDF15 in all groups. We examined the response of GDF15 to increasing doses of glucocorticoid replacement in healthy volunteers with pharmacologically mediated cortisol deficiency. A dose-dependent difference in GDF15 (mean ± SD) was observed between the groups with values of 491.0 ± 157.7 pg/mL, 427.0 ± 152.1 pg/mL and 360 ± 143.1 pg/mL, in the low, medium and high glucocorticoid replacement groups, respectively, P < .0001. Conclusions GDF15 is increased in states of glucocorticoid deficiency and restored by glucocorticoid replacement. Given the site of action of GDF15 in the hindbrain and its effects on appetite, further study is required to determine the effect of GDF15 in mediating the anorexia and nausea that is a common feature of glucocorticoid deficiency.

Cognitive function in patients with primary adrenal insufficiency (Addison's disease)

2015 ◽  
Vol 55 ◽  
pp. 1-7 ◽  
Author(s):  
Katharina Schultebraucks ◽  
Katja Wingenfeld ◽  
Jana Heimes ◽  
Marcus Quinkler ◽  
Christian Otte
Keyword(s):  
Cognitive Function ◽  
Adrenal Insufficiency ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Primary Adrenal Insufficiency

Osmoregulation of arginine-8-vasopressin secretion in primary hypothyroidism and in Addison's disease

1987 ◽  
Vol 114 (3) ◽  
pp. 389-395 ◽  
Author(s):  
F. Laczi ◽  
T. Janáky ◽  
T. Iványi ◽  
J. Julesz ◽  
F. A. László
Keyword(s):  
Healthy Volunteers ◽  
Plasma Osmolality ◽  
Addison’S Disease ◽  
Primary Hypothyroidism ◽  
Addison's Disease ◽  
Water Metabolism ◽  
Positive Correlation ◽  
Vasopressin Secretion ◽  
Impaired Water ◽  
Hypothyroid Patients

Abstract. The osmoregulation of arginine-8-vasopressin (AVP) was investigated in 14 patients with primary hypothyroidism and in 6 with Addison's disease. Plasma AVP was measured by radioimmunoassay. Patients with primary hypothyroidism were classified into subgroups with elevated (6.81 ± 1.12 pmol/l) or normal (3.92 ± 0.96 pmol/l) basal levels of plasma AVP. Following the infusion of 2.5% saline, a positive correlation was established between plasma AVP and plasma osmolality. A decreased osmotic threshold was found in hypothyroid patients with augmented basal AVP levels (pAVP = 0.37 (pOs-265), r = 0.71, P < 0.01) as compared with that in hypothyroid patients with a normal AVP level (pAVP = 0.42 (pOs-280), r = 0.93, P < 0.001). A relationship was demonstrated between the alteration in the AVP osmoregulation and the severity of the thyroid insufficiency. Patients with Addison's disease exhibited an increased basal level of plasma AVP (9.59 ± 1.25 pmol/l) and a decreased osmotic threshold (pAVP = 0.42 (pOs-261), r = 0.63, P < 0.01) contrasted to that of healthy volunteers (pAVP = 0.41 (pOs-280), r = 0.83, P < 0.001). The osmoregulation disturbance of the AVP secretion may play a major role in the impaired water metabolism in primary hypothyroidism and in Addison's disease.

No inhibition of corticotrophin (ACTH)-hypersecretion in adrenal insufficiency by somatostatin

1980 ◽  
Vol 95 (1) ◽  
pp. 71-74 ◽  
Author(s):  
A. Jara-Albarrán ◽  
J. Bayort ◽  
A. Caballero ◽  
R. Eusebio ◽  
P. García-Peris ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Primary Adrenal Insufficiency ◽  
No Inhibition ◽  
Infusion Period

Abstract. Somatostatin (250 μg as a bolus iv and 250 μg as a I h infusion) was administered to 6 patients with primary adrenal insufficiency (Addison's disease). The fall in plasma ACTH during the infusion period ranged between 0–30% with a mean reduction of 11.2 ± 11.6%. These findings suggest that with the method employed, somatostatin is not an inhibitor of ACTH secretion in a condition in which glucocorticoids are lacking.

Mineralocorticoid Before Glucocorticoid Deficiency in a Dog with Primary Hypoadrenocorticism and Hypothyroidism

2013 ◽  
Vol 49 (1) ◽  
pp. 54-57 ◽  
Author(s):  
Kathryn M. McGonigle ◽  
John F. Randolph ◽  
Sharon A. Center ◽  
Richard E. Goldstein
Keyword(s):  
Clinical Signs ◽  
Addison’S Disease ◽  
Serum Cortisol ◽  
Primary Hypothyroidism ◽  
Addison's Disease ◽  
Acth Stimulation Test ◽  
Acth Stimulation ◽  
Clinical Illness ◽  
Glucocorticoid Deficiency ◽  
Electrolyte Abnormalities

A dog with an unexpected presentation of primary hypoadrenocorticism was evaluated for clinical signs and electrolyte abnormalities characteristic of Addison’s disease. Although the initial adrenocorticotropic hormone (ACTH) stimulation test documented serum cortisol concentrations within the reference range, subsequent assessments confirmed hypoaldosteronism. Mineralocorticoid replacement promptly normalized electrolytes and transiently improved clinical illness. Six weeks after initial ACTH stimulation testing, the dog became glucocorticoid deficient. Concurrent primary hypothyroidism was also documented. Hypoaldosteronism preceding hypocortisolemia is a unique presentation of canine Addison’s disease.

scholarly journals A Patient with a Sudden Onset of Oral Pigmentation

2020 ◽  
pp. 60-65
Author(s):  
Jack Botros ◽  
Firoozeh Samim
Keyword(s):  
Weight Loss ◽  
Case Report ◽  
Skin Pigmentation ◽  
Addison’S Disease ◽  
Sudden Onset ◽  
Addison's Disease ◽  
Primary Adrenal Insufficiency ◽  
Endocrine Disease ◽  
Oral Mucous Membrane ◽  
Early Diagnostic

Addison's disease or primary adrenal insufficiency (hypoadrenocorticism) is an endocrine disease characterized by a deficiency in the production of the adrenal cortex hormones, particularly cortisol and aldosterone. Patients affected by Addison's disease develop anorexia, weight loss, hypoglycemia, fatigue, nausea, vomiting, skin, and mucosal pigmentation. Skin pigmentation is considered a commonly encountered manifestation of the disease; however, oral mucous membrane pigmentation is rarely noticed early enough for diagnosis. This case report demonstrates a case where oral pigmentation was an early diagnostic sign of Addison's disease.

scholarly journals The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients

2014 ◽  
Vol 171 (5) ◽  
pp. 571-579 ◽  
Author(s):  
Oskar Ragnarsson ◽  
Anders F Mattsson ◽  
John P Monson ◽  
Helena Filipsson Nyström ◽  
Ann-Charlotte Åkerblad ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Primary Adrenal Insufficiency ◽  
Main Hypothesis ◽  
Gh Replacement ◽  
Significant Difference ◽  
Patients Experience ◽  
The Impact ◽  
The Relationship ◽  
Dose Dependent

ObjectiveQuality of life (QoL) is impaired in hypopituitary patients and patients with primary adrenal insufficiency. The aim of this study was to analyse the impact of glucocorticoid (GC) replacement on QoL. The main hypothesis was that ACTH-insufficient patients experience a dose-dependent deterioration in QoL.Design, patients and methodsThis was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Data from 2737 adult GH-deficient (GHD) hypopituitary patients were eligible for analysis. Thirty-six per cent were ACTH sufficient and 64% ACTH insufficient receiving a mean±s.d. hydrocortisone equivalent (HCeq) dose of 22.3±8.7 mg (median 20.0). QoL at baseline and 1 year after commencement of GH replacement was assessed by the QoL-assessment of GHD in adults.ResultsAt baseline, no significant difference in QoL was observed between ACTH-sufficient and -insufficient patients. Increasing HCeq dose was associated with worse QoL. Patients on HCeq ≤10 mg had the best and patients receiving ≥25 mg demonstrated the poorest QoL. At 1 year of GH replacement, the improvement in QoL did not differ between ACTH-sufficient and -insufficient patients, and no association was observed between HCeq dose and QoL improvement.ConclusionAdult hypopituitary patients with untreated GHD receiving GC replacement have similar QoL as ACTH-sufficient patients. Among ACTH-insufficient patients, there is a dose-dependent association between increasing dose and impaired QoL. This association may be explained by supraphysiological GC exposure although it remains plausible that clinicians may have increased GC doses in order to address otherwise unexplained QoL deficits.

scholarly journals Premature Mortality in Patients with Addison’s Disease: A Population-Based Study

2006 ◽  
Vol 91 (12) ◽  
pp. 4849-4853 ◽  
Author(s):  
Ragnhildur Bergthorsdottir ◽  
Maria Leonsson-Zachrisson ◽  
Anders Odén ◽  
Gudmundur Johannsson
Keyword(s):  
Survival Rate ◽  
Confidence Interval ◽  
Infectious Diseases ◽  
Adrenal Insufficiency ◽  
Addison’S Disease ◽  
Population Based ◽  
Addison's Disease ◽  
Primary Adrenal Insufficiency ◽  
Background Population

Abstract Background: The survival rate of patients with primary adrenal insufficiency (Addison’s disease) undergoing currently accepted replacement therapy is not known, although well-informed patients are considered to have a normal survival rate. In this study, we evaluated the mortality of patients with Addison’s disease in Sweden. Methods: A population-based, retrospective, observational study was performed, using the National Swedish Hospital and Cause of Death Registers, covering the period from 1987–2001. After a diagnosis of Addison’s disease, each patient was followed until the end of follow-up or death. Mortality was compared with that of the Swedish background population. Findings: We identified 1675 patients (995 women and 680 men) diagnosed with primary adrenal insufficiency. The average follow-up from initial diagnosis was 6.5 yr. Five hundred seven patients died during the study period compared with an expected 199. The risk ratio for all-cause mortality was 2.19 (confidence interval 1.91–2.51) for men and 2.86 (confidence interval 2.54–3.20) for women. The excess mortality in both men and women was attributed to cardiovascular, malignant, and infectious diseases. Concomitant diabetes mellitus was observed in 12% of the patients, but only contributed to the increased mortality to a minor extent. Interpretation: Compared with the background population, we observed that the risk ratio for death was more than 2-fold higher in patients with Addison’s disease. Cardiovascular, malignant, and infectious diseases were responsible for the higher mortality rate.

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