Adrenocorticotropin Hormone Stimulation Research Articles

Multivariable Model to Predict an ACTH Stimulation Test to Diagnose Adrenal Insufficiency Using Previous Test Results.

The adrenocorticotropin hormone stimulation test (AST) is used to diagnose adrenal insufficiency, and is often repeated in patients when monitoring recovery of the hypothalamo-pituitary-adrenal axis. To develop and validate a prediction model that uses previous AST results with new baseline cortisol to predict the result of a new AST. This was a retrospective, longitudinal cohort study in patients who had undergone at least 2 ASTs, using polynomial regression with backwards variable selection, at a Tertiary UK adult endocrinology center. Model was developed from 258 paired ASTs over 5 years in 175 adults (mean age 52.4 years, SD 16.4), then validated on data from 111 patients over 1 year (51.8, 17.5) from the same center, data collected after model development. Candidate prediction variables included previous test baseline adrenocorticotropin hormone (ACTH), previous test baseline and 30-minute cortisol, days between tests, and new baseline ACTH and cortisol used with calculated cortisol/ACTH ratios to assess 8 candidate predictors. The main outcome measure was a new test cortisol measured 30 minutes after Synacthen administration. Using 258 sequential ASTs from 175 patients for model development and 111 patient tests for model validation, previous baseline cortisol, previous 30-minute cortisol and new baseline cortisol were superior at predicting new 30-minute cortisol (R2 = 0.71 [0.49-0.93], area under the curve [AUC] = 0.97 [0.94-1.0]) than new baseline cortisol alone (R2 = 0.53 [0.22-0.84], AUC = 0.88 [0.81-0.95]). Results of a previous AST can be objectively combined with new early-morning cortisol to predict the results of a new AST better than new early-morning cortisol alone. An online calculator is available at https://endocrinology.shinyapps.io/sheffield_sst_calculator/ for external validation.

Adrenal insufficiency updates in children.

The current article will review the newest diagnostic tools, genetic causes, and treatment of adrenal insufficiency in children. It is common practice to perform an adrenocorticotropin hormone (ACTH) stimulation test when adrenal insufficiency is suspected. The indications for use of a high-dose or low-dose of synthetic ACTH in children have been refined. In addition, newer studies propose adding 15 and 30-min serum or salivary cortisol levels to the low-dose ACTH stimulation test to correctly identify adrenal insufficiency. Recent identification of genetic mutations in children with non-classic steroidogenic acute regulatory protein and other mutations associated with primary and secondary adrenal insufficiency have expanded the cause and pathophysiology of monogenic adrenal insufficiency. In addition, newer hydrocortisone formulations and delivery methods and medications to use in combination with hydrocortisone are being explored to improve treatment for children with adrenal insufficiency. Improved diagnostic aids, detection of newer genetic mutations, and better treatment options and delivery systems will help correctly identify and manage children with adrenal insufficiency to improve health outcomes and quality of life. http://links.lww.com/COE/A21.

Favorable outcome of pheochromocytoma in a dog with atypical Cushing\u2019s syndrome and diabetes mellitus following medical treatment: a case report

BackgroundPheochromocytoma (PCC) has poor prognosis and adrenalectomy is hard to be performed, in case of caudal vena cava invasion. The long-term administration of phenoxybenzamine in PCC has not been reported in dogs.Case presentationA 14-year-old castrated male Poodle dog presented with an abdominal mass. On physical examination, hypertension, increased lens opacity, calcinosis cutis, generalized alopecia, and systolic murmur were observed. Serum chemistry and urinalysis profiles revealed hyperglycemia, hypercholesterolemia, elevated liver enzymes, and glucosuria. Abdominal ultrasonography showed a right adrenal mass with invasion of the caudal vena cava, which was cytologically diagnosed as suspected PCC. An adrenal mass (width × height × length, 28 × 26 × 48 mm3) was found on computed tomography and diagnosed as PCC with increased plasma metanephrines and normetanephrines. An adrenocorticotropin hormone stimulation test showed elevated adrenal hormones (androstenedione, estradiol, progesterone, and 17-OH progesterone) with normal cortisol, compatible with atypical Cushing’s syndrome. The dog was managed with trilostane, phenoxybenzamine, and insulin therapy. Glycosylated hemoglobin and fructosamine levels gradually decreased, and hypertension resolved. In the 10-month follow-up period, the liver enzymes levels gradually decreased, and the clinical signs of the dog were well-controlled without deterioration.ConclusionsThis case report describes long-term medical management without adrenalectomy of PCC complicated with atypical Cushing’s syndrome and DM.

The effect of local injection of methylprednisolone acetate on the hypothalamic-pituitary-adrenal axis among patients with greater trochanteric pain syndrome.

Greater trochanteric pain syndrome (GTPS) is a common clinical entity for which the most effective treatment is local corticosteroid injection (LCI). There are no studies on the effect of LCI among patients with GTPS on the hypothalamic-pituitary-adrenal axis. The present study recruited nonselected patients diagnosed with GTPS. After consenting, participants received low dose (1μg) of adrenocorticotropin hormone (ACTH) stimulation test at 09:00. Immediately following the test, participants received a LCI of 80mg of methylprednisolone acetate at the greater trochanteric region. The ACTH stimulation test was repeated 1, 2, 4, and 6weeks following the LCI. Cortisol samples were obtained at just prior to (basal) and 30min (post-stimulation) following every ACTH stimulation test. Serum cortisol levels of <500μmol/l obtained 30min following the ACTH stimulation test were considered evidence of secondary adrenal insufficiency. The study enrolled 22 patients, 21 of whom completed participation. There were 19 female participants (~90%), and mean age of all the participants was 55.2±8.6years. Four participants showed evidence of secondary adrenal insufficiency, which was observed only at weeks 1 and 2 following the LCI. Mean serum cortisol level among these four participants 30min following the ACTH stimulation test was 354μmol/l, with a range of 268-430μmol/l. LCI of 80mg of methylprednisolone acetate in the greater trochanteric area among patients with GTPS was associated with transient secondary adrenal insufficiency in ~20% of the patients, mainly 1week following the injection.

The effects of smoked nicotine on measures of subjective states and hypothalamic-pituitary-adrenal axis hormones in women during the follicular and luteal phases of the menstrual cycle.

To determine the acute effects of cigarette smoking on hypothalamic-pituitary-adrenal (HPA) axis hormones and subjective states as a function of the menstrual cycle in nicotine-dependent women. Seventeen healthy nicotine-dependent women were studied during the follicular and/or luteal phase of the menstrual cycle. Because of observation of a possible bimodal distribution of progesterone levels within the luteal phase group, we performed a set of a posteriori analyses. Therefore, we divided the luteal group into a low progesterone and a high progesterone groups. Smoked nicotine activated HPA, measured by adrenocorticotropin hormone (ACTH), cortisol, and dehydroepiandrosterone (DHEA) response and affected subjective states in both follicular and luteal phases, with increased "High," "Rush," and decreased "Craving." The HPA stimulation revealed a blunting of ACTH response. There was only modest evidence for a blunting of subjective state responses in the luteal phase. However, upon post hoc analyses, the high progesterone luteal group showed a marked blunting of measures of subjective states and a blunted ACTH response. Examining the association between hormone and measures of subjective states revealed tentative associations of ACTH stimulation with increased "Rush" and "Craving," and DHEA stimulation with increased "Craving." This pilot study suggests that menstrual cycle phase differences in progesterone levels may attenuate nicotine's addictive effects via diminution of its reinforcing properties and augmentation of its aversive effects interfering with the pleasure associated with cigarette smoking.

Simultaneous Bilateral Knee Injection of Methylprednisolone Acetate and the Hypothalamic-Pituitary Adrenal Axis

ObjectiveThe objective of this study was to evaluate the effect of simultaneous bilateral intra-articular injection (IAI) of methylprednisolone acetate (MPA) on the hypothalamic-pituitary-adrenal axis in patients with knee osteoarthritis.MethodsNonselected patients...

The Effect of Intra-articular Injection of Betamethasone Acetate/Betamethasone Sodium Phosphate at the Knee Joint on the Hypothalamic-Pituitary-Adrenal Axis

BackgroundIntra-articular corticosteroid injection (IACI) of betamethasone depot preparation is a popular procedure at the knee joint. Intra-articular corticosteroid injection in general could be associated with systemic effects including suppression of...

Adrenal reserve function after unilateral adrenalectomy in patients with primary aldosteronism

After unilateral adrenalectomy (uADX) in patients with a unilateral aldosterone-producing adenoma (APA), the remaining contralateral adrenal gland is generally considered sufficient to support life. However, few studies have compared adrenal reserve function before and after uADX. Therefore, we closely evaluated adrenal cortisol secretory function before and after uADX in patients with unilateral APA. Patients who were diagnosed with APA and underwent uADX for unilateral APA were initially included in this study. Patients with subclinical Cushing's syndrome (SCS) or Cushing's syndrome were excluded on suspicion of autonomous cortisol secretion. Fourteen patients were finally evaluated. Morning basal serum cortisol and plasma adrenocorticotropin hormone (ACTH) levels were measured, and ACTH stimulation tests under 1-mg dexamethasone suppression (dex-ACTH test) were performed before and after uADX. No patient developed clinical adrenal insufficiency. Basal cortisol levels were not significantly different before and after uADX. However, basal ACTH levels were significantly elevated after uADX. In addition, peak cortisol levels on the dex-ACTH test decreased in all patients after uADX. The peak cortisol level after uADX was 86.6 (81.4-92.4)% of the level before uADX. The adrenal cortisol secretory response to ACTH stimulation is mildly reduced after uADX in patients with unilateral APA without SCS or Cushing's syndrome, although their basal cortisol level is sustained by elevated ACTH. These data will be important as a point of discussion when patients with unilateral APA consider either uADX or specific pharmacotherapy as treatment options.

Intra-articular methylprednisolone acetate injection at the knee joint and the hypothalamic–pituitary–adrenal axis: a randomized controlled study

The objective of this study was to evaluate the effect of intra-articular corticosteroid injection (IACI) of methylprednisolone acetate (MPA) on the hypothalamic-pituitary-adrenal (HPA) axis in patients with osteoarthritis of the knee. Patients with symptomatic osteoarthritis of the knee who failed to respond to nonsteroidal anti-inflammatory medications and physical therapy were randomized between group 1 and group 2. Group 1 patients had an IACI of 80mg of MPA at the knee joint and group 2 patients had an intra-articular injection (IAI) of 6ml (60mg) of sodium hyaluronate (control group). Immediately prior to the IAI and on weeks 1, 2, 3, 4, and 8 following IAI, patients from both groups underwent a low-dose (1μg) adrenocorticotropin hormone (ACTH) stimulation test. Demographic, clinical, laboratory, and radiologic variables were documented in all patients. Both criteria of <7μg/dl increase in the serum cortisol level and absolute levels of <18μg/dl 30min following the ACTH stimulation test were used to define secondary adrenal insufficiency (SAI). Twenty patients were randomized in each group. In group 1, 25% of patients had SAI vs. none in group 2 (p = 0.0471). The earliest SAI was observed at week 2, and latest SAI was observed at week 4. SAI was observed at one time point, two consecutive time points, or two separate time points in the same patient. There was no correlation between SAI and any of the demographic, clinical, or laboratory variables. An IACI of 80mg MPA at the knee joint induced a transient SAI in 25% of the patients, an effect that was observed between week 2 and week 4 following the IACI.

The effect of epidural methylprednisolone acetate injection on the hypothalamic-pituitary-adrenal axis

Study ObjectiveTo evaluate the effect of an epidural corticosteroid injection of 80 mg and 40 mg of methylprednisolone acetate on the hypothalamic-pituitary-adrenal axis and on back pain. DesignRandomized, single-blinded prospective study. SettingOperating room of a university-affiliated hospital. Patients42 patients with low back pain due to radiculopathy. InterventionsGroup 1 received an epidural corticosteroid injection of 80 mg of methylprednisolone acetate, and Group 2 received an epidural corticosteroid injection of 40 mg of methylprednisolone acetate. All study patients underwent a stimulation test of one μg of adrenocorticotropin hormone (ACTH), and their pain levels were graded just prior to and following the epidural corticosteroid injection on weeks one, 3, and 4. MeasurementsSerum cortisol of the ACTH stimulation tests and back pain levels were rated using a visual analog scale (VAS). Serum cortisol levels lower than 18 ng/mL 30 minutes following the ACTH stimulation test were considered to be secondary adrenal insufficiency. Main Results21 patients were enrolled in each group. The rate of secondary adrenal insufficiency in Group 1 was ~86%, ~ 22%, and ~17% of patients versus ~53% (P = 0.024), 15% (P = 0.874), and ~12% (P = 0.715) of Group 2 patients at weeks one, 3, and 4, respectively. About 62%, 56%, and 39% of Group 1 patients had a favorable clinical response as opposed to ~47% (P = 0362), 35% (P = 0.21), and ~6% (P = 0.049) of Group 2 patients at weeks one, 3, and 4, respectively. ConclusionsEpidural corticosteroid injection of methylprednisolone acetate in both groups was associated with very high rates of secondary adrenal insufficiency, but significantly more so in Group 1 at week one. This suppression was transient, with recovery of the gland in most patients noted over the ensuing weeks. An epidural corticosteroid injection of 80 mg had higher rates of favorable clinical response than a 40 mg injection, but significantly more so at week 4 only. This favorable response waned over a few weeks in both groups.

Hyponatraemia in older people as a sign of adrenal insufficiency: a case–control study

Hyponatraemia is a common cause of hospitalisation in older adults. Adrenal insufficiency (AI) can result in hyponatraemia. The aim of our study was to determine the frequency and characteristics of AI in elderly patients with hyponatraemia. Thirty patients ≥65 years with Na(+) ≤130 mmol/L and 30 age-matched control subjects, all hospitalised, were included in the study. Plasma cortisol levels were determined before and after intravenous administration of 1 µg synthetic adrenocorticotropin hormone. A peak cortisol >550 nmol/L was considered to exclude AI. Sodium levels were 125 ± 5 and 139.8 ± 2 mmol/L in the hyponatremic and control groups respectively. Baseline cortisol <550 nmol/L was found in a half of hyponatremic patients. However, stimulated cortisol levels were compatible with AI in only one case (3%) and none of the controls. The mean cortisol levels were significantly higher in hyponatremic compared with control subjects, both in the basal state (585 ± 215 and 381 ± 135 nmol/L, respectively, P < 0.001) and after stimulation (933 ± 254 and 781 ± 160 nmol/L, P < 0.05). However, the incremental increase in cortisol levels after stimulation was similar in the two groups (361 ± 196 and 403 ± 155 nmol/L) CONCLUSIONS: AI is an uncommon cause of hyponatraemia in older age. Based on this small cohort, AI may be present in 3% of elderly patients with hyponatraemia. AI cannot be excluded by baseline cortisol in a significant minority of hyponatremic patients and further testing with adrenocorticotropin hormone stimulation is needed.

ACTH receptor (MC2R) promoter variants associated with infantile spasms modulate MC2R expression and responsiveness to ACTH

Adrenocorticotropin hormone (ACTH) has been the standard treatment to infantile spasms (IS). However, the mechanism of ACTH therapy is still unclear. ACTH exerts the function via melanocortin 2 receptor (MC2R). Our previous study showed a common 4-single nucleotide polymorphism (SNP) haplotype TCCT at the MC2R promoter was strongly associated with responsiveness to ACTH therapy, where these 4 SNPs [rs1893219, rs1893220, rs2186944, and a novel SNP (T>C)] were mapped at position -853, -759, -7, and -2 bp based on the transcription start site of the MC2R gene. In this study, we further elucidated functional significances of the TCCT haplotype. To evaluate whether the TCCT haplotype influences MC2R transcription levels, the luciferase reporter vector was used by a transient transfection. Expression of rat MC2R cDNA driven by the TCCT-carrying or TCCC-carrying promoter was detected by the real-time quantitative reverse transcription-PCR. These assays were performed on cell lines cultured in absence or presence of ACTH. In the baseline, the light intensity of the luciferase reporter assay driven by the TCCT promoter was four times higher than that by the TCCC promoter. The intensity was dramatically increased in the pGL3-TCCT after ACTH stimulation, compared to that in the pGL3-TCCC. MC2R expression assay showed a 5-fold increase in the TCCT promoter in presence of ACTH, compared with that in absence of ACTH. The results showed that the haplotype TCCT in MC2R promoter significantly led to increased MC2R expression and strong responses to ACTH, providing evidence of the molecular mechanism of ACTH therapy in IS.

Initial transference of wild birds to captivity alters stress physiology

Maintaining wild animals in captivity has long been used for conservation and research. While often suggested that captivity causes chronic stress, impacts on the underlying stress physiology are poorly understood. We used wild-caught chukar (Alectoris chukar) as a model avian species to assess how the initial 10 days of captivity alters the corticosterone (CORT) secretory pathway. In the first few days of captivity, birds lost weight, had lower hematocrit and demonstrated changes in CORT concentrations. Both baseline and restraint-stress-induced CORT concentrations decreased by days 3–5 of captivity and remained significantly lower throughout the 10 days although stress-induced concentrations began to recover by day 9. To delineate potential mechanisms underlying these CORT changes, we evaluated alterations to the hypothalamic–pituitary–adrenal (HPA) axis. Although chukar appear to be resistant to arginine vasotocin’s (AVT) effects on CORT release, adrenocorticotropin hormone (ACTH) stimulated CORT release; however, ACTH stimulation did not differ during the 10 days of captivity. In contrast, negative feedback axis sensitivity, as determined by both dexamethasone suppression as well as endogenous negative feedback, decreased by day 5 but was regained by day 9. In addition, the combined stressors of capture and long distance transport eliminated the animals’ ability to mount an acute CORT response on the day following the move. Therefore, introduction into captivity appeared to shift the chukar into a temporary state of chronic stress that began to recover within 9 days. The duration of these alterations likely varies due to differences in capture techniques, transport distance, and species studied.

The effect of otic vehicle and concentration of dexamethasone on liver enzyme activities and adrenal function in small breed healthy dogs

Dexamethasone 0.1% in propylene glycol vehicle has been shown to cause adrenal suppression and increased liver enzyme concentrations in normal dogs. The objectives of this study were to determine if these effects are concentration or vehicle dependent and to evaluate a dexamethasone 0.01% solution. Twenty-one privately owned normal dogs were included in this double-blinded study. Chemistry panels and adrenocorticotropin hormone (ACTH) stimulation tests were performed on day 0 and 15. Dogs were randomly assigned treatment with dexamethasone 0.01% in saline, 0.1% in saline, or 0.1% in a commercial preparation (Tresaderm: Merial, Duluth, GA, USA) in each ear twice daily for 2 weeks. Nineteen dogs completed the study. After 2 weeks of treatment, all dogs receiving dexamethasone 0.01% in saline had normal ACTH stimulation tests and liver enzyme values. In contrast, four of seven dogs (57.14%) receiving dexamethasone 0.1% in saline experienced adrenal suppression, and four of six dogs (66.67%) receiving Tresaderm experienced adrenal suppression with three of those dogs (50%) experiencing marked adrenal suppression. No dogs receiving dexamethasone 0.1% in saline had increased liver enzyme concentration, while one of six dogs (16.67%) experienced a slight elevation in alkaline phosphatase. In conclusion, it appears that adrenal suppression caused by otic dexamethasone is concentration and perhaps vehicle dependent. Veterinarians who formulate dexamethasone 0.1% otic solutions should be cognizant of potential adrenal suppression similar to that seen with Tresaderm although not to the same degree. Dexamethasone at 0.01% did not cause adrenal suppression or liver enzyme alterations after 2 weeks of treatment.

From integrative signalling to metabolic disorders

The adrenal cortex undergoes constant dynamic structural changes, a key element in ensuring integrative functionality of the gland. Studies have shown that the cellular environment can modulate cell functions such as proliferation and steroid secretion. For example, 3-day treatment with angiotensin II promotes protein synthesis with a concomitant decrease in proliferation of glomerulosa cells, when cultured on fibronectin, but not on collagen IV or laminin. These effects involve close interaction between cytoskeleton-associated proteins and activation of p42/p44 mapk and p38 MAPK pathways. On the other hand, adrenocorticotropin hormone (ACTH), which is clearly the most potent stimulus of fasciculata cells, induces specific modulation of targeted proteins, when cells are cultured on collagen IV, but not on fibronectin or laminin. In particular, ACTH treatment leads to increased expression of Seladin-1 and induces the relocalization of Seladin-1 from the cytoplasm to the nucleus, both in vivo and in culture conditions, in adult rats and in human fetal adrenal glands. As a whole, these results indicate that Seladin-1, together with collagen IV, is able to modulate ACTH responsiveness. Hence, Seladin-1 may participate in the regulation of steroidogenesis when localized in the cytoplasm, while conversely protecting cells against oxidative stress generated by intense ACTH stimulation when massively localized in the nucleus.

Adrenal function in sepsis: The retrospective Corticus cohort study

To refine the value of baseline and adrenocorticotropin hormone (ACTH)-stimulated cortisol levels in relation to mortality from severe sepsis or septic shock. Retrospective multicenter cohort study. Twenty European intensive care units. Patients included 477 patients with severe sepsis and septic shock who had undergone an ACTH stimulation test on the day of the onset of severe sepsis. None. Compared with survivors, nonsurvivors had higher baseline cortisol levels (29.5 +/- 33.5 vs. 24.3 +/- 16.5 microg/dL, p = .03) but similar peak cortisol values (37.6 +/- 40.2 vs. 35.2 +/- 22.9 microg/dL, p = .42). Thus, nonsurvivors had lower Deltamax (i.e., peak cortisol minus baseline cortisol) (6.4 +/- 22.6 vs. 10.9 +/- 12.9 microg/dL, p = .006). Patients with either baseline cortisol levels <15 microg/dL or a Deltamax <or=9 microg/dL had a likelihood ratio of dying of 1.26 (95% confidence interval, 1.11-1.44), a longer duration of shock, and a shorter survival time. Patients with a Deltamax <or=9 microg/dL but any baseline cortisol value had a likelihood ratio of dying of 1.38 (95% confidence interval, 1.18-1.61). Although delta cortisol and not basal cortisol level was associated with clinical outcome, further studies are still needed to optimize the diagnosis of adrenal insufficiency in critical illness. Etomidate influenced ACTH test results and was associated with a worse outcome.

Suspected relative adrenal insufficiency in a critically ill cat

AbstractObjective: To describe a case of likely relative adrenal insufficiency (RAI) in a cat with critical illness.Case summary: A cat recovering from polytrauma developed hypotension unresponsive to intravenous fluid support and vasopressor therapy. An adrenocorticotropin hormone stimulation test documented insufficient adrenal function. Treatment with exogenous low‐dose glucocorticoids in addition to standard therapies resulted in rapid hemodynamic and clinical improvement. The cat ultimately recovered and was weaned from supplemental glucocorticoids.New or unique information provided: This is the first report of changes consistent with acquired RAI in a cat with critical illness.

Adrenocortical function in hospitalised patients with active pulmonary tuberculosis receiving a rifampicin-based regimen—a pilot study

To assess whether adrenocortical function was compromised in patients with active tuberculosis (TB) during the first 5 days of therapy with either a rifampicin-based or ciprofloxacin-based regimen. Patients were randomised into two groups of 10 each. Adrenocortical function was compared in both groups by the measurement of biochemical indices, electrolytes, osmolality and pituitary-adrenocortical hormones. Adrenal reserve was assessed by intravenous 250 mug adrenocorticotropin hormone (ACTH) stimulation tests. Department of Medicine, Johannesburg Hospital. Twenty hospitalised patients who were diagnosed with TB. Respiratory rate, pulse rate and blood pressure were recorded, and urinary sodium and osmolality were measured. Serum ACTH, cortisol, dehydroepiandrosterone- sulphate (DHEA-S) and aldosterone were assayed. None of the patients demonstrated biochemical evidence of overt adrenal insufficiency. There were no significant differences between the two groups before or during therapy for any biochemical indices, electrolytes, hormones or calculated osmolality. Mean basal cortisol concentrations were substantially elevated and DHEA-S levels were consistently subnormal, resulting in a high cortisol/ DHEA-S ratio. In the ciprofloxacin group, cortisol responses to ACTH stimulation on day 1 were not significantly lower than on day 5. In the rifampicin group, cortisol concentrations decreased at each time point on day 5 compared with day 1 (p = 0.001). However, a significantly higher mean incremental rise from the basal cortisol concentration was measured on day 5 at 60 minutes (p = 0.04). In the entire cohort of 20 patients, 40% demonstrated an incremental cortisol rise of < 250 nmol/l after ACTH stimulation on day 1. Rifampicin did not additionally impair adrenocortical function during the initial period of therapy. The high cortisol/DHEA-S ratio might be of clinical relevance.

The Endocrine System during Sepsis

Endocrinopathy during sepsis can manifest as hyperglycemia and insulin resistance or as insufficient production of either adrenal corticosteroids or vasopressin. The results of a recent large clinical trial have demonstrated that tight glycemic control with insulin can confer survival benefit to selected intensive care unit patients. Relative impairment of adrenocortical reserve has been suggested to be an important contributor to the pathogenesis of shock in sepsis. Replacement doses of glucocorticoids and mineralocorticoids have been associated with improved survival in the subset of patients with blunted results on adrenocorticotropin hormone stimulation tests. Posterior pituitary production of vasopressin is diminished in septic shock while sensitivity to its vasopressor effects is enhanced. Clinical trials are underway to determine whether administration of vasopressin can improve outcomes in patients with septic shock. Whether the euthyroid sick syndrome represents an adaptive or a maladaptive response to severe illness remains unclear.

Relative adrenal insufficiency in critical illness

AbstractObjective: To review the effects of critical illness on hypothalamic–pituitary–adrenal (HPA) function in human and veterinary medicine.Data sources: Data from human and veterinary literature was reviewed.Human data synthesis: Relative adrenal insufficiency (RAI) appears to be common in critically ill human patients with sepsis or septic shock. Hypotension that is refractory to fluid therapy and requires vasopressors is the most common presentation of RAI in the human intensive care unit (ICU). Many investigators now advocate the use of a low‐dose adrenocorticotropin hormone stimulation test to diagnose RAI. It is important to evaluate for the presence of adrenal dysfunction, because current data suggest that treatment with ‘stress’ or low doses of glucocorticoids (200–300 mg hydrocortisone daily) may improve patient outcome in humans.Veterinary data synthesis: There is a paucity of controlled studies in the veterinary literature regarding the effects of critical illness on HPA function. The results of these studies are varied. However, research models of sepsis and hemorrhagic shock suggest the existence of RAI in animals. Prospective clinical studies are needed to further examine pituitary–adrenal response to severe illness in veterinary patients, and to determine if there are therapeutic options, including glucocorticoid administration, which will improve patient outcome in animals.Conclusions: RAI is well documented in critically ill human patients, yet little is known about adrenal dysfunction in veterinary critically ill patients. A small number of studies suggest that RAI may exist in certain subpopulations of veterinary patients. The syndrome of RAI could be considered as a differential diagnosis in seriously ill veterinary patients that fail to respond to appropriate therapy, especially when hypotension refractory to fluid and vasopressor therapy is encountered. This disorder may represent a previously unidentified syndrome in critically ill veterinary patients with important therapeutic implications.