ACTH Concentrations Research Articles

DHEAS and Differential Blood Counts as Indirect Signs of Glucocorticoid Excess in Adrenal Non-Producing Adenomas.

The majority of incidentally discovered adrenal tumors are later characterized as non-producing adrenocortical adenomas (NPA). We asked whether laboratory abnormalities in parameters that reflect glucocorticoid action can be found in patients with NPA despite their nature of being clinically unapparent. Since glucocorticoids are potent immunosuppressants we studied blood counts and differential blood counts along with corticotropin and dehydroepiandrostenedione sulfate (DHEAS) blood concentrations, as well as cortisol values before and after an overnight 1 mg dexamethasone suppression test. We compared the results of normal individuals, of patients with adrenal adenomas and normal hormone profiles and with subclinical autonomous glucocorticoid hypersecretion, as well as overt cortisol excess. We found that almost all indices of the blood counts were significantly different between the patients groups. In particular, patients with adrenal non-producing adenomas already showed signs of glucocorticoid excess, including relative lymphocytopenia, lowered DHEAS, and ACTH concentrations than control individuals. We also found that the extent of lymphocytopenia correlated with the concentrations of DHEAS and ACTH, and DHEAS correlated well with ACTH. We conclude that the basal ACTH and DHEAS values along with the differential blood counts give good information on the extent of glucocorticoid excess and that silent adrenal adenomas seem to oversecrete glucocorticoids at concentrations that already alter these parameters.

Therapeutic Riding Horses: using a hypothalamic-pituitary-adrenal axis measure to assess the physiological stress response to different riders

In this study, circulating β-endorphin, ACTH and cortisol concentrations were chosen as physiological markers of the hypothalamic-pituitary-adrenal (HPA) stress-related response in Therapeutic Riding Horses (TRHs). The aim of this research was to investigate HPA axis hormonal response in TRHs and check the effects of different kind of riders (mentally-impaired and able-minded riders). The main hypothesis was that, in TRHs, the HPA axis reaction would be less responsive to mentally-impaired than to able-minded riders, due to increasing levels of horse control by the able-minded riders. 6 TRHs were randomly ridden in the same setting by 2 groups of riders, adult mentally-impaired riders (Treatment Group A) and able-minded adult riders (Treatment Group B). Both groups consisted of inexperienced riders. Each rider rode 2 times a week for 6 consecutive weeks. The horses performed the same gaits and exercises at all sessions, with both Treatment Group A and Treatment Group B riders. All hormones’ concentrations were determined on a resting day (baseline, T0), before the session (T1), and at 5 min (T2) and 30 min (T3) after each session. Statistical analysis showed significant effects of the different Treatment Groups on the cortisol concentrations only, with lower cortisol concentrations both at T2 and at T3 in Treatment Group A than in Treatment Group B. Related to changes over the sampling time, ccortisol concentrations in horses were significantly higher at T1 than at T0 in Treatment Group A, and at T1, T2 and T3 than at T0, in Treatment Group B. ACTH concentrations were significantly higher at T1, T2 and T3 than at T0, only in Treatment Group B. β-endorphin concentrations at T3 were significantly higher than at T0, only in Treatment Group B. Results showed differences in the TRHs' stress levels between rider groups, with significantly lower cortisol concentrations in Treatment Group A than in Treatment Group B. Thus, although sessions’ workload stress was equivalent, the minor response of HPA axis could be related to different effects of horse-human interaction.

Circadian Rhythms of Oxidant-Antioxidant Agents, HPA Axis and Protein Carbonyl Content in Serum, Brain and Adrenal Gland Tissues

The aim of this experiment is to study the circadian rhythm of oxidant-antioxidant components in the body. A total of 20 adult male rabbits were divided into 2 groups (G1and G2)and kept in 2 different rooms. Serum was isolated after blood collection at 12 A.M or 12 P.M respectively from G1 and G2.The results reveal a significant elevation in serum GSH, MDA and SOD during night hours. The B-endorphin showed a value of 84.36±1.36 in rabbits serum during night compared with 53.23±1.12 during day hours. Serum ACTH and cortisone concentration during night hours expressed a value of 71.03±0.16 and 24.46±0.38 compared to 52.80±0.37 and 11.80±0.57 during day hours respectively. Protein carbonyl contents shows a regular variation between serum and tissues during day and night hours. It was concluded that the oxidant-antioxidant imbalance lead to such variation between day and night hours due to activities and metabolism. Extensive research is needed to minimize and overlap such stress.

Diagnostic Accuracy of Dehydroepiandrosterone Sulfate and Corticotropin in Autonomous Cortisol Secretion.

Autonomous cortisol secretion (ACS) affects up to 50% of patients with adrenal adenomas. Despite the limited evidence, clinical guidelines recommend measurement of serum concentrations of dehydroepiandrosterone-sulfate (DHEA-S) and corticotropin (ACTH) to aid in the diagnosis of ACS. Our objective was to determine the accuracy of serum concentrations of DHEA-S and ACTH in diagnosing ACS. We conducted a retrospective single center study of adults with adrenal adenoma evaluated between 2000−2020. Main outcome measure was diagnostic accuracy of DHEA-S and ACTH. ACS was defined as post-dexamethasone cortisol >1.8 mcg/dL. Of 468 patients, ACS was diagnosed in 256 (55%) patients with a median post-DST cortisol of 3.45 mcg/dL (range, 1.9–32.7). Patients with ACS demonstrated lower serum concentrations of DHEA-S (35 vs. 87.3 mcg/dL, p < 0.0001) and ACTH (8.3 vs. 16 pg/mL, p < 0.0001) compared to patients with non-functioning adrenal tumors (NFAT). Serum DHEA-S concentration <40 mcg/dL diagnosed ACS with 84% specificity and 81% PPV, while serum ACTH concentration <10 pg/mL diagnosed ACS with 75% specificity and 78% PPV. The combination of serum concentrations of DHEA-S <40 mcg/dL and ACTH <10 pg/mL diagnosed ACS with the highest accuracy with 92% specificity and 87% PPV. Serum concentrations of DHEA-S and ACTH provide additional value in diagnosing ACS.

Adrenal Gland Ultrasonographic Measurements and Plasma Hormone Concentrations in Clinically Healthy Newborn Thoroughbred and Standardbred Foals.

Simple SummaryThe hypothalamic–pituitary–adrenal axis regulates many physiologic and metabolic functions and plays a central role in the inflammatory response to illness. Clinically, hypothalamic–pituitary–adrenal axis function can be evaluated by combined assessment of adrenal hormones, adrenocorticotropin plasma concentrations and ultrasonographic examination of the adrenal glands in other species. Multiple individual variables have been demonstrated to affect ultrasonographic measurements of adrenal glands in several species. Ultrasonographic measurements of the adrenal glands and plasma concentration of adrenocorticotropin, cortisol, dehydroepiandrosterone, progesterone, aldosterone and adrenocorticotropin/adrenal hormone ratios were assessed and compared between Thoroughbred and Standardbred healthy neonatal foals. The effect of age, weight and sex on ultrasonographic measurements of the adrenal glands was also investigated. The width of whole adrenal glands and the medulla differed significantly between Thoroughbreds and Standardbreds. Cortisol and adrenocorticotropin were, respectively, higher and lower in Thoroughbreds than in Standardbreds. The cortisol/dehydroepiandrosterone ratio was higher in Thoroughbreds than in Standardbreds. The results of this study provide reference ranges for healthy neonatal Thoroughbred and Standardbred foals and suggest the presence of breed-related differences in ultrasonographic measurements, plasmatic cortisol and adrenocorticotropin concentrations. The higher cortisol/dehydroepiandrosterone ratio of Thoroughbred foals may suggest a different response to stress and environmental stimulation between the two breeds.Adrenal hormones, ACTH plasma concentrations and the ultrasonographic evaluation of the adrenal glands are considered complementary in clinical evaluations of the hypothalamic–pituitary–adrenal (HPA) axis function in several species. In dogs, age, size and weight have a significant effect on the ultrasonographic size of the adrenal glands. In neonatal foals, ultrasonographic evaluation and measurements of the adrenal glands have been demonstrated to be reliable; however, the effect of individual variables on ultrasonographic features has not been investigated, and the clinical usefulness of adrenal gland ultrasonography is still not known. The aims of this study were: (i) to provide and compare adrenal glands ultrasound measurements in healthy newborn Thoroughbred and Standardbred foals, and assess any effect of age, weight and sex on them; (ii) to assess and compare ACTH and steroid hormone concentrations in healthy neonatal foals of the two breeds. Venous blood samples and ultrasonographic images of the adrenal glands were collected from 10 healthy neonatal Thoroughbred and 10 healthy neonatal Standardbred foals. Ultrasonographic measurements of the adrenal glands were obtained and adrenocorticotropin (ACTH), cortisol, dehydroepiandrosterone (DHEA), progesterone (P4) and aldosterone plasma concentrations were assessed. The ACTH/cortisol, ACTH/progesterone, ACTH/aldosterone, ACTH/DHEA and cortisol/DHEA ratios were calculated. A significant positive correlation was found between the height of the right adrenal gland and the foal’s weight; the width of the right and left adrenal gland and the medulla was significantly lower in Thoroughbreds than in Standardbreds. Cortisol and ACTH plasma concentrations were significantly higher and lower, respectively, in Thoroughbreds compared with Standardbreds. The cortisol/DHEA ratio was significantly higher in Thoroughbreds. This study provides reference ranges for neonatal Thoroughbred and Standardbred foals, and suggests the presence of breed-related differences in ultrasonographic adrenal gland measurements, plasmatic cortisol and ACTH concentrations. The higher cortisol/DHEA ratio detected in Thoroughbred foals could suggest a different response to environmental stimulation in the two breeds.

Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?

PMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. There is very little known on the effect of impaired N-glycosylation on the hypothalamic-pituitary-adrenal axis function and whether CDG patients are at risk of secondary adrenal insufficiency and decreased adrenal cortisol production.Cortisol and ACTH concentrations were simultaneously measured between 7:44 am to 1 pm in forty-three subjects (20 female, median age 12.8 years, range 0.1 to 48.6 years) participating in an ongoing international, multi-center Natural History study for PMM2-CDG (ClinicalTrials.gov Identifier: NCT03173300). Of the 43 subjects, 11 (25.6%) had cortisol below 5 μg/dl and low to normal ACTH levels, suggestive of secondary adrenal insufficiency. Two of the 11 subjects have confirmed central adrenal insufficiency and are on hydrocortisone replacement and/or stress dosing during illness; 3 had normal and 1 had subnormal cortisol response to ACTH low-dose stimulation test but has not yet been started on therapy; the remaining 5 have upcoming stimulation testing planned.Our findings suggest that patients with PMM2-CDG may be at risk for adrenal insufficiency. Monitoring of morning cortisol and ACTH levels should be part of the standard care in patients with PMM2-CDG.

Relationship between endogenous plasma adrenocorticotropic hormone concentration and reproductive performance in Thoroughbred broodmares.

BackgroundPituitary pars intermedia dysfunction (PPID) is an endocrine disorder the clinical signs of which include infertility, but few reports have examined the relationship between PPID and reproductive performance in broodmares.Hypothesis/ObjectiveBroodmares with infertility of unknown etiology were screened for PPID using baseline endogenous plasma ACTH concentrations, and its relationship with subsequent reproductive performance was analyzed.AnimalsSixty‐seven Thoroughbred broodmares.MethodsAdrenocorticotropic hormone concentrations were measured in autumn. The broodmares were divided into 3 groups based on endogenous plasma ACTH concentration (low, <50 pg/mL; intermediate 50‐100 pg/mL; and high >100 pg/mL) as recommended by the Equine Endocrinology Group. We compared these results with those of other blood tests, clinical examinations, subsequent conception, and frequency of normal delivery.ResultsThe numbers of horses per group (percentage) were 22 (32.8%), 20 (29.9%), and 25 (37.3%). The mean ± SD ages (years) were 11.1 ± 3.4, 12.1 ± 4.5, and 13.0 ± 4.3, with no significant difference among groups. Mean ± SD plasma cortisol concentrations (μg/dL) were 4.0 ± 1.6, 7.1 ± 1.4, and 7.6 ± 1.9, with the intermediate and high ACTH groups having significantly higher results than the low ACTH group (P < .001). Conception rates were 77.3%, 89.5%, and 56.5% and normal delivery rates were 77.2%, 84.2%, and 43.5% with the percentage of each significantly lower in the high ACTH group (P = .02, P = .008, respectively).Conclusions and Clinical ImportanceThe study group of infertile broodmares may include horses with PPID. The reproductive performance of the high ACTH group was significantly lower than the other groups. Early diagnosis and treatment of infertile broodmares by screening plasma ACTH concentrations could help improve reproductive performance.

Relationship Between 24-Hour Serum LH and Testosterone Concentrations and Their Interrelationships With Other Pituitary Hormones in Healthy Older Men

Background: With ageing, LH levels rise while T levels decline in men, although this decline in T levels could also be caused by a change in health status, including body composition, inflammation, and comorbidities. Not only levels of LH and T change with age, but levels of other pituitary hormones also change concomitantly with age. It could be hypothesized that these hormonal changes are synchronized with each other.Objective: In this study, we aimed to determine the relationship between 24-h serum LH and T concentrations in healthy older men. Besides, we aimed to determine which health factors, including body composition, metabolic and inflammatory markers, and LH-T related markers are associated with the strength of this LH-T relationship. Furthermore, we explored the interrelationships between LH and T with 24-h serum concentrations of GH, TSH, cortisol, and ACTH.Design: Hormones were measured in serum samples collected every 10 min during 24 h from 20 healthy men, comprising 10 offspring of long-lived families and 10 control subjects, with a mean (SD) age of 65.6 (5.3) years. We performed cross-correlation analyses to assess the relative strength between two 24-h hormone concentration series for all possible time shifts.Results: A mean (95% confidence interval) maximal correlation coefficient of 0.21 (0.10 – 0.31) at lag time 60 min was found between LH and total T concentrations. Results were comparable for calculated free, bioavailable, or secretion rates of T. Men with strong LH-T cross-correlations had, compared to men with no LH-T relationship, lower fat mass (18.5 (14.9 – 19.7) vs. 22.3 (18.4 – 29.4) kg), waist circumference (93.6 (5.7) vs. 103.1 (12.0) cm), hsCRP levels (0.7 (0.4 – 1.3) vs. 1.8 (0.8 – 12.3) mg/L), IL-6 levels (0.8 (0.6 – 1.0) vs. 1.2 (0.9 – 3.0) pg/mL), and 24-h mean LH levels (4.3 (2.0) vs. 6.1 (1.5) U/L), and stronger LH-T feedforward synchrony (1.5 (0.3) vs. 1.9 (0.2)). Furthermore, T was positively cross-correlated with TSH (0.32 (0.21 – 0.43)), cortisol (0.26 (0.19 – 0.33)), and ACTH concentrations (0.26 (0.19 – 0.32)).Conclusions: LH concentrations were followed by T concentrations/secretion with a delay of 60 min in healthy older men, which is in line with literature. Men with a strong LH-T relationship had more favorable body composition, inflammatory markers, 24-h mean LH levels, and LH-T feedforward synchrony. In contrast, chronological age and 24-h mean T levels were not associated with the strength of the LH-T relationship. This observation could indicate that LH and health markers play a bigger role in determining the strength of LH-T cross-correlations than T and chronological age. Furthermore, we observed positive correlations between T and TSH, cortisol, and ACTH concentrations. These exploratory analyses could indicate that T and other hormones are driven by a common regulator or that there is crosstalk between these hormones.

Testing of Adrenal Axis Function in Patients With Combined Pituitary Hormone Deficiency Caused by PROP1 Mutation

Background: The mechanism of adrenal axis deterioration in PROP1 mutation remains uncertain and challenging. Aim: The aim of the project was to investigate the adrenal axis function in patients with combined pituitary function deficiency and PROP1 mutation. Methods: We performed the corticotrophin (CRH) stimulation test in 15 patients ((8W/7M) with confirmed CPHD due to the PROP1 mutation. 9/15 were familial cases from four families. Time of observation (ToO) was calculated since the first pituitary axis/ACTH insufficiency has occurred. The results were reported in the group with confirmed Adrenal Insufficiency (AI) and without AI defined as cortisol >18 ug/dl at any point during CRH test. ACTH is reported in pg/ml and cortisol in ug/dl, time of test is given in minutes (0‘, 15’,30’,45’,60’,120’). Results: The mean age of the group was 40,6 ± 12,1 years with mean 34,7 ± 10,3 years of CPHD observation (range 18 – 54 years). The In 5/15 the cortisol response met the criteria excluding AI. Among siblings there were patients both with/without AI. Both subgroups had similar ToO (without AI 35,6 ± 10,0 years vs 34,2 ± 10,3 years with AI). Mean time of AI duration was 15,0 ± 9,3 years. In the group of 5 patients without AI the mean morning cortisol was 12,48 ± 4,31 and ACTH was 31,26 ± 5,43. The mean maximal concentration of cortisol and ACTH were 24,94 ± 3,6 and 123,6 ± 39,9 respectively; Mean increase of cortisol was 12,46 ±4,04 and 92,34±34,48 for ACTH. In 10 patients with AI the mean morning cortisol was 3,33±1,39 and ACTH 22,71±6,75. The mean maximal concentration of cortisol and ACTH were 10,15±4,47 and 97,05 ± 59,15 respectively; Mean increase of cortisol was 6,83 ± 3,41 and 74,35 ± 53,72 for ACTH. For two patients high ACTH increase from 36,7 to 260 and from 28,65 to 112,0 was observed. Analysis of cortisol and ACTH response in both groups revealed that in group without AI the time of peak of ACTH was observed in 15’ (2/5) and 30’ (3/5) vs. in 15’(3/10), 30’(6/10) and 45’ in group with AI. The peak cortisol was observed in 30’, 45’ and 60’ (3/5) in group without AI vs 60’(6/10) or 120’ (4/10) in AI group. The mean maximal increase of ACTH was by 4,09±1,46 and 4,12±1,58 in AI group vs no AI group respectively. Conclusions: In patients with PROP1 mutation the adrenal axis can deteriorate long after other axis insufficiencies, however there are patients with no adrenal insufficiency even during lifelong observation. There is no specific order of deterioration even among affected siblings. In the vast majority of patients independently of cortisol increase there is ACTH response after CRH. Further studies on the pituitary function deterioration in patients with PROP1 mutation should be carried out to understand better the underlying mechanism and to set up the diagnostic timing and procedures.

Long-Term Corticotroph Function Following Cure of Cushing’s Syndrome

Introduction: Hyper- and hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis in Cushing’s syndrome (CS) and Addison’s disease (AD) is associated with disturbances of classical feedback mechanisms. Time to recovery of adrenal function after CS remission depends on the etiology of CS and is longest after adrenal CS. To date there are no data on the recovery of corticotroph function following CS remission, and the synacthen test is recommended for testing adrenal function in patients with hypopituitarism. Aim Here we aim to test corticotroph function after long-term cure of Cushing’s syndrome following bilateral adrenalectomy (BADx), compared to patients with primary glucocorticoid deficiency due the presence of 21-hydroxylase antibodies or adrenoleucodystrophy, a pathophysiological model of glucocorticoid and mineralocorticoid deficiency. Methods: We retrospectively evaluated data from patients with CS and AD attending our endocrine department between 2000 and 2020, using the following inclusion criteria: BADx performed for pituitary/ectopic/adrenal or occult CS or primary adrenal insufficiency confirmed either by the presence of 21-hydroxylase antibodies or genetically in adrenoleucodystrophy. Results: Full data were available for 93 patients: 43 patients with BADx due to CS (18 patients with pituitary CS, 14 patients with adrenal CS and 11 patients with ectopic/occult CS, F:M 29:14, mean age at BADx 45.4 years age range 13-74 years) and 50 patients with AD (47 cases with positive 21-hydroxylase antibodies, 3 cases with adrenoleucodystrophy, F:M ratio 27:23, mean age at diagnosis 35 years, age range 6-57 years). The observation period was 537.5 patient-years after BADx (mean 12.5 years, range 1-38 years) and 647 patient-years following AD diagnosis (mean 14.2 years, range 1-46 years). At the last visit, there were no differences between the hormone substitution regimes between the groups. ACTH concentrations during the whole observation period and also at the last visit were lowest in patients with adrenal CS (56.5 pg/ml) when compared to patients with AD (487 pg/ml, p<0.001), or with patients with pituitary CS (377.5 pg/mL, p=0.011). ACTH values in patients with AD in long-term follow-up were significantly higher when compared to all patients with CS (141 pg/mL, p<0.001). Conclusion: These data highlight a long-term defective corticotroph function in patients with CS following BADx. Low ACTH concentrations long term after BADx for adrenal CS corroborate that corticotroph function fails to recover after CS cure. In the light of these findings, the utility of the synacthen test for excluding secondary/tertiary adrenal insufficiency following CS remission is disputable and remains to be evaluated in future studies dedicated to CS cohorts.

Influence of endocrine disease on l-lactate concentrations in blood of ponies.

BackgroundBlood l‐lactate concentrations are higher in people with developing or established diabetes mellitus and insulin resistance.ObjectivesTo investigate whether blood l‐lactate concentrations are positively correlated with measures of insulin dysregulation (ID) or increased autumnal ACTH concentrations in ponies.AnimalsSystemically healthy client‐owned ponies (n = 101).MethodsProspective case‐control study. Blood samples were obtained from 101 clinically healthy ponies. Breed, weight, height, and subjective and objective measures of body condition were recorded. Blood l‐lactate, glucose, triglyceride, total adiponectin, and ACTH concentrations were measured and an oral sugar test (OST) was carried out. Correlations between blood l‐lactate and variables of endocrine health were determined.ResultsUsing a seasonal cutoff point of ACTH concentrations ≥47 pg/mL, 55 ponies had increased autumnal ACTH concentrations and 45 did not. Using a basal insulin concentration of >50 μiU/mL, 42 ponies were diagnosed with ID and 58 were not. Using a 60 minutes after OST cutoff point of >45 μiU/mL, 57 ponies had ID and 37 did not. Blood l‐lactate concentrations were significantly lower in obese (average body condition score ≥ 7/9) compared to nonobese ponies (0.6 mmol/L; range, 0.0‐1.9 mmol/L vs 0.8 mmol/L; range, 0.3‐2.7 mmol/L; P = .01). No other significant correlations were detected. No differences were detected between ponies with and without increased autumnal ACTH concentrations (0.7 mmol/L; range, 0.0‐2.7 mmol/L vs 0.7 mmol/L; range, 0.3‐1.8 mmol/L; P = .84) and with and without ID (0.7 mmol/L; range, 0.3‐2.7 mmol/L vs 0.8 mmol/L; range, 0.0‐1.6 mmol/L; P = .63).Conclusions and Clinical ImportanceResults do not support an effect of endocrine status on l‐lactate concentrations in blood of ponies.

Stereotactic radiosurgery before bilateral adrenalectomy is associated with lowered risk of Nelson's syndrome in refractory Cushing's disease patients.

Nelson's syndrome is a rare but challenging sequelae of Cushing's disease (CD) after bilateral adrenalectomy (BLA). We sought to determine if stereotactic radiosurgery (SRS) of residual pituitary adenoma performed before BLA can decrease the risk of Nelson's syndrome. Consecutive patients with CD who underwent BLA after non-curative resection of ACTH secreting pituitary adenoma and had at least one follow-up visit after BLA were studied. Nelson's syndrome was diagnosed based on the combination of rising ACTH levels, increasing volume of the pituitary adenoma and/or hyperpigmentation. Fifty patients underwent BLA for refractory CD, and 43 patients (7 men and 36 women) had at least one follow-up visit after BAL. Median endocrine, imaging, and clinical follow-up were 66 months, 69 months, and 80 months, respectively. Nine patients (22%) were diagnosed with the Nelson's syndrome at median time after BLA at 24 months (range: 0.6-119.4 months). SRS before BLA was associated with reduced risk of the Nelson's syndrome (HR = 0.126; 95%CI [0.022-0.714], p=0.019), while elevated ACTH level within 6 months after BLA was associated with increased risk for the Nelson's syndrome (HR = 9.053; 95%CI [2.076-39.472], p=0.003). SRS before BLA can reduce the risk for the Nelson's syndrome in refractory CD patients requiring BLA and should be considered before proceeding to BLA. Elevated ACTH concentration within 6 months after BLA is associated with greater risk of the Nelsons' syndrome. When no prior SRS is administered, those with a high ACTH level shortly after BLA may benefit from early SRS.

The association between insulin-like growth factor 1 levels within reference range and early postoperative remission rate in patients with Cushing’s disease

ABSTRACT Introduction The relationship between growth hormone (GH)/insulin-like growth factor 1 (IGF-1) and glucocorticoids (GC) was examined in various studies. Long-term GC treatment was shown to decrease GH concentration and, interestingly, to increase IGF-1 concentration. We performed a retrospective study in order to examine how preoperative IGF-1 concentrations vary within the reference range and if tertiles of age- and sex-adjusted normal IGF-1 are predictive for early postoperative remission in the patients with Cushing’s Disease (CD). Patients and Methods Patients diagnosed with CD were retrospectively evaluated. After the exclusion of 67 patients, a final cohort of 250 CD patients were included. Age- and sex-adjusted normal IGF-1 levels were divided into tertiles (T1, T2 and T3). Early postoperative remission was defined as a nadir morning cortisol concentration measured within the first 3 consecutive days following surgery of less than 5 µg/dL (138 nmol/L). Results Early postoperative remission rate was the lowest in T1 and highest in T3; 49.1% (n = 28) versus 77.3% (n = 75), p = .001, respectively. Binary logistic regression analysis showed the remission rate in T3 was three times higher than that in T1 (p = .003). Cortisol and ACTH concentration were significantly higher and GH concentrations were significantly lower in T1 compared to those in the other two tertiles. Conclusions As the first study evaluating the correlation between early postoperative remission rate in patients with CD and the tertiles of normal age- and sex-adjusted IGF-1 levels, we have shown that higher IGF-1 levels could predict better outcome in CD.

Glucagon, insulin, adrenocorticotropic hormone, and cortisol in response to carbohydrates and fasting in healthy neonatal foals.

BackgroundThe endocrine pancreas and hypothalamic‐pituitary‐adrenal axis (HPAA) are central to energy homeostasis, but information on their dynamics in response to energy challenges in healthy newborn foals is lacking.ObjectivesTo evaluate glucagon, insulin, ACTH, and cortisol response to fasting and carbohydrate administration in healthy foals.AnimalsTwenty‐two healthy Standardbred foals ≤4 days of age.MethodsFoals were assigned to fasted (n = 6), IV glucose (IVGT; n = 5), PO glucose (OGT; n = 5), and PO lactose (OLT; n = 6) test groups. Blood samples were collected frequently for 210 minutes. Nursing was allowed from 180 to 210 minutes. Plasma glucagon, ACTH, serum insulin, and cortisol concentrations were measured using immunoassays.ResultsPlasma glucagon concentration decreased relative to baseline at 45, 90, and 180 minutes during the OLT (P = .03), but no differences occurred in other test groups. Nursing stimulated marked increases in plasma glucagon, serum insulin, and glucose concentrations in all test groups (P < .001). Plasma ACTH concentration increased relative to baseline at 180 minutes (P < .05) during fasting and OLT, but no differences occurred in other test groups. Serum cortisol concentration increased relative to baseline during OLT at 180 minutes (P = .04), but no differences occurred in other test groups. Nursing resulted in decreased plasma ACTH and serum cortisol concentrations in all test groups (P < .01).Conclusions and Clinical ImportanceThe endocrine response to enterally and parenterally administered carbohydrates, including the major endocrine response to nursing, suggests that factors in milk other than carbohydrates are strong stimulators (directly or indirectly) of the endocrine pancreas and HPAA.

Altered microstructural pattern of white matter in Cushing’s disease identified by automated fiber quantification

A growing body of evidence suggests that altered brain structure plays a crucial role in the pathogenesis of neuropsychological abnormalities induced by hypercortisolism in patients with Cushing’s disease. While most studies mainly focus on gray matter, white matter structure has been largely overlooked. In the current study, we conducted a cross-sectional diffusion tensor imaging study on 58 patients with Cushing’s disease and 54 matched healthy individuals to profile the microstructural pattern using automated fiber quantification and investigate its association with neuroendocrine and neuropsychological deficits. The study revealed that microstructural pattern showed a widespread mean diffusivity, radial diffusivity increase, fractional anisotropy decrease and partial axial diffusivity increase among tracts notably in corpus callosum forceps, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, uncinate fasciculus and arcuate fasciculus, while within the same tract abnormalities localized to specific positions. Moreover, compromised microstructural pattern of white matter in specific tracts and locations along the trajectory were associated with ACTH and cortisol concentration and cognitive decline in patients with Cushing’s disease. Collectively, our study elucidates the form of white matter pathology induced by hypercortisolism and its association with cognitive decline which may provide further targets for early identification and intervention of Cushing’s disease.

Функциональная активность звеньев стресс-реализующей и стресс-лимитирующей систем в условиях светового десинхроноза

The secretion of most hormones obeys biological cyclicity and, if it is violated, approaches to the level, that determines the development of pathological processes. To prevent them, it is important to take into account not only the effects of the stress-implementing system, but also the state of the components of the stress-limiting system. The lack of specificity about endocrine shifts under conditions of light desynchronosis determined the expediency of an experimental study of the hormonal status of stress systems. Research methods. The experiment was carried out on 48 white male rats, which was divided into 4 equal groups: control and three experimental. The 1st, 2nd and 3rd experimental groups of animals were under round-the-clock artificial lighting during 1, 10 and 21 days respectively. Animals of the control group (4th) were kept in natural light conditions. The activity of stress-limiting and stress-realizing systems was assessed by blood serum ELISA for the concentration of ACTH, melatonin, and beta-endorphin. In blood smears, the number of catecholamine granules per 100 erythrocytes was counted in 10 fields of view. Research results. On the 1st day of the experiment, there was an increase of catecholamines and ACTH, a decrease of beta-endorphin in comparison with the control values. The corticotropin of the 2nd and 3rd experimental groups underwent only slight fluctuations. The 10th day is also characterized by a statistically significant increase in the content of catecholamines in comparison with individuals of the control group. When assessing changes after 21 days of dark deprivation, a significant sharp increase in the concentration of catecholamines and a drop in the level of melatonin were noted. The discussion of the results. In the experiment, a phased development of hormonal changes in stress systems is observed, which corresponds to the stages of OSA, which is due to a violation of melatonin rhythms. The use of the L / L lighting model has a pronounced negative effect on the state of the body as a whole and leads to a breakdown of the mechanisms of the stress-limiting system. The results of the experiment allow us to conclude that light desynchronosis is a risk factor for pathologies of the neuroendocrine system, which necessitates a more detailed study of this topic in order to develop measures to prevent the development of stress and associated diseases of adaptation.

Clinical implications of using adrenocorticotropic hormone diagnostic cutoffs or reference intervals to diagnose pituitary pars intermedia dysfunction in mature horses.

BackgroundDiagnosis of pituitary pars intermedia dysfunction (PPID) is problematic because of large variations in ACTH concentrations.Hypothesis/ObjectivesCompare the test characteristics of baseline and post–thyrotropin‐releasing hormone (TRH) stimulation plasma ACTH concentrations in horses using diagnostic cutoff values (DCOVs) and reference intervals (RIs) and determine the clinical consequences of using each method.AnimalsOne hundred six mature horses: 72 control cases and 34 PPID cases.MethodsProspective case‐controlled study. Horses underwent monthly TRH stimulation tests. Diagnostic cutoff values were determined monthly by receiver operating characteristic curves using the Youden index. Reference intervals were determined monthly by a robust method. For each case age, sex and body condition score (BCS) were recorded.ResultsBaseline ACTH concentrations varied by month (P < .001) with significant “month × age” (P = .003), “month × sex” (P = .003), and “month × BCS” (P = .007) effects. Baseline ACTH concentrations were accurate to diagnose PPID (0.91 ± 0.06) with DCOVs increasing the test sensitivity (0.61 ± 0.21 to 0.87 ± 0.05, P = .002) and RI increasing test specificity (0.85 ± 0.12 to 0.98 ± 0.01, P = .01). Thyrotropin‐releasing hormone stimulation improved test accuracy (0.91 ± 0.06 to 0.97 ± 0.03, P = .004).Conclusions and Clinical ImportanceACTH concentrations follow a circannual rhythm and vary with physiological factors. As using DCOVs increases the ability to detect mild cases and using RI decreases the risk of unnecessary treatments, ACTH concentrations should be interpreted within a specific clinical context. The TRH stimulation test improves the diagnosis of PPID.

A prospective study of correlation between hormonal profile and acne vulgaris in adult patients

Introduction: Although various studies has been conducted regarding pathogenesis of acne vulgaris and proved it to be multi factorial, but there is strong association between acne vulgaris and hormone profile of patients. Present study has been designed to document and access the correlation between hormone profile and acne vulgeris, with a primary aim to know the hormonal profile of acne vulgaris patient and correlate the hormone level with acne vulgaris patients. Materials and Methods: This study is prospective randomized case control study conducted in the dept. of dermatology venereology and leprology Konaseema institute of medical science Amalapuram Andhra Pradesh from August 2015 to April 2018. In present study 80 clinically diagnosed, acne vulgeris patients were randomly selected for this study based on inclusion and exclusion criteria. Another 80 age and sex matched healthy volunteers were taken as control group who are free from acne. Result: Mean serum concentration of testosterone was 83.54+28.31ng/dl in cases, but in control group mean serum concentration was 48.89+38.79 ng/dl, with P value 0.00001. Mean of serum DHEAS concentration was 265.79+53.48, mcg/dl in patients but in healthy volunteers it was 211.48+36.11 mcg/dl, with P value 0.00012. Serum insulin level in acne patients were (mean+SD) 7.163+ 1.843, mIU/L but in control group it was 5.48 +1.24 mIU/L with P value 0.0019. Mean concentration of serum glucocorticoid was 14.63+3.24mcg/dl in cases but in control it was 13.42+4.94 mcg/dl having P value 0.89. Serum IGF-1 mean value was 272.62+62.32 ng/ml in cases, and 246.76+70.32ng/ml in control with P value 0.074. Serum ACTH concentration was 39.66+ 4.24pg/ml in cases (mean +SD) but in control 33.60+ 9.92pg/ml with P value 0.0035. Discussion and Conclusion: Serum concentration of testosterone, DHEAS, ACTH and IGF-1 level was higher in acne vulgeris cases then control which indicate a correlation between these hormone and acne vulgeris. Increase in ser

Physiological effects of transport duration on stress biomarkers and meat quality of medium-growing Yellow broiler chickens

Pre-slaughter transport exerts negative effects on broilers’ welfare, meat yield, and meat quality, but little is known about the effect of transport on medium-growing broiler chickens. This study aimed at evaluating the effects of different durations of transport (0, 0.5, 1, 2, and 3h) on stress biomarkers and meat quality of medium-growing Yellow-feathered broiler chickens. One hundred and eighty Chinese Yellow-feathered broilers aged 75days (marketing age), of 2.02kg average BW, were allotted into five groups; each group contained six replicates (six birds/replicate (crate)). Each crate with dimensions 74×55×27cm (length × width × height) was loaded with six birds, that is, 30kg live BW/m2 crate. The tested transport durations increased BW loss (linear, P<0.01), plasma concentrations of ACTH (linear, P<0.10), cortisol and corticosterone (quadratic, P<0.05), and activity of glutathione peroxidase (linear, P<0.05), whereas plasma glucose was not affected. In breast muscle, contents of glycogen, lactic acid, malondialdehyde, and reduced glutathione were not affected (P>0.05), but total antioxidant capacity decreased (linear, P<0.01). The drip loss of breast muscle increased (linear, P<0.01), whereas shear force, pH at 24h postmortem, and breast meat color lightness (L*), redness (a*), and yellowness (b*) scores were not affected. In conclusion, the tested transport durations (from 0.5 to 3h) increased BW loss and some plasma stress biomarkers in 75-day-old Yellow-feathered broiler chickens, but the effect on meat quality attributes was minor.

Age over 25 years, but not plasma adrenocorticotropic hormone con-cen-tration above the seasonally adjusted reference range is predictive for radio-graphically assessed changes of chronic laminitis in elderly horses.

Endocrinopathic laminitis occurs as a consequence of hormonal derangements like pituitary pars intermedia dysfunction (PPID). The objective of the present study was to assess the occurrence of radiographic changes associated with chronic laminitis in elderly, clinically sound horses. Fifty-one horses were included in the study. Horses were assigned to different age groups, in groups according to their BCS and CNS as well as to groups with different ACTH concentrations in order to assess their risk of chronic laminitis (reported as odds ratios (OR) and confidence intervals (CI)). Horses assigned to an older age group (26-32 years) were significantly more likely to have radiographically assessed changes of chronic laminitis than horses in a younger age group (15-25 years) (OR 3.33; CI 1.05-10.59). The other variables (body condition score, cresty neck score, ACTH concentration) were not associated with an increased risk of having laminitic changes in these horses.