[Comparison of Different Doses of ACTH Used in ACTH Stimulation Test to Determine the Subtypes of Primary Aldosteronism]. / ä¸åŒå‰‚é‡ä¿ƒè‚¾ä¸Šè ºçš®è´¨æ¿€ç´ å ´å¥‹è¯•éªŒåœ¨åŽŸå‘æ€§é†›å›ºé ®å¢žå¤šç—‡åˆ†åž‹è¯Šæ–­ä¸­çš„æ¯”è¾ƒ.

Objective: To compare the diagnostic value of adrenocorticotropic hormone (ACTH) stimulation test (AST) with different doses of ACTH combined with midnight administration of 1 mg dexamethasone for the determination of the subtypes of primary hyperaldosteronism (PA). Methods: This is a prospective observational study. Patients diagnosed with PA in the Department of Endocrinology, the First Medical Center of of Chinese PLA General Hospital from January 1, 2020 to September 30, 2022 underwent AST with different doses of ACTH. All patients received 1 mg dexamethasone at midnight for inhibition. Then, the patients were randomly assigned to 25-unit and 50-unit ACTH treatment groups by a ratio of 1:2. Subtype classification and diagnosis of aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) was made on the basis of adrenal venous blood samples and/or postoperative pathology and clinical follow-up findings. Receiver operating characteristics (ROC) curves were plotted to examine the diagnostic efficacy and the difference of AST by varying doses of ACTH in distinguishing APA and IHA. Results: A total of 82 patients, including 49 patients with APA (59.8%) and 33 patients with IHA (40.2%), were enrolled. There were 29 patients in the 25-unit ACTH group (35.4%) and 53 patients in the 50-unit ACTH group (64.6%). There were no significant differences in age, sex, blood pressure, minimum serum potassium, and biochemical parameters between the 25-unit and 50-unit groups. After ACTH stimulation, plasma aldosterone concentration (PAC), cortisol (F), and PAC/F at different points of time showed no statistical difference between the two groups (P>0.05). The area under the curve (AUC) of PAC in the 25-unit group was higher than that of PAC/F. The AUC of PAC reached the maximum at 90 minutes (0.948, 95% confidence interval [CI]: 0870-1.000) and the optimal cutoff was 38.0 ng/dL, which had a sensitivity of 92.9% and a specificity of 86.7% for differentiating APA and IHA. Similar to the 25-unit group, the maximum AUC of PAC in the 50-unit group was greater than that of PAC/F. The AUC of PAC reached the maximum 90 minutes (0.930, 95% CI: 0.840-0.994) and the optimal cutoff was 39.6 ng/dL, which had a sensitivity of 91.2% and a specificity of 83.3%. The AUC of PAC at different points of time in the 25-unit ACTH group (0.862-0.948) was greater than that of 50-unit ACTH group (0.823-0.930), but the difference was not statistical significance. Conclusion: AST with 25-unit or 50-unit ACTH combined with small-dose dexamethasone can be used in PA subtype determination, ie, differentiation between APA and IHA. The optimal PAC cut-off values for 25-unit or 50-unit ACTH are similar, being 38.0 ng/dL and 39.6 ng/dL, respectively, and both cutoff values show higher sensitivity and specificity at 90 min. The AST with 25-unit ACTH has the smaller dose and the better safety. Therefore, it is recommended for the diagnosis of PA subtypes.

Adrenal gland response to adrenocorticotropic hormone is intact in patients with postural orthostatic tachycardia syndrome.

BACKGROUND: Many patients with postural orthostatic tachycardia syndrome (POTS) are hypovolemic with plasma volume deficits of 10-30 %. Some also have low levels of aldosterone and diminished aldosterone-renin ratios despite elevations in angiotensin II, pointing to potential adrenal dysfunction. To assess adrenal gland responsiveness in POTS, we measured circulating levels of aldosterone and cortisol following adrenocorticotropin hormone (ACTH) stimulation. METHODS: While on a low Na+ diet (∼10 mEq/day), 8 female patients with POTS and 5 female healthy controls (HC) received a low dose (1 µg) ACTH bolus following a baseline blood sample. After 60 min, a high dose (249 µg) infusion of ACTH was administered to ensure maximal adrenal response. Venous aldosterone and cortisol levels were sampled every 30 min for 2 h. RESULTS: Aldosterone increased in both groups in response to ACTH but was not different between POTS vs. HC at 60 min (53.5 ng/dL [37.8-61.8 ng/dL] vs. 46.1 ng/dL [36.7-84.9 ng/dL]; P = 1.000) or maximally (56.4 ng/dL [49.2-67.1 ng/dL] vs. 49.5 ng/dL [39.1-82.8 ng/dL]; P = 0.524). Cortisol increased in both groups in response to ACTH but was not different in patients with POTS vs. HC at 60 min (39.9 µg/dL [36.1-47.7 µg/dL] vs. 39.3 µg/dL [35.4-46.6 µg/dL]; P = 0.724) or maximally (39.9 µg/dL [33.9-45.4 µg/dL] vs. 42.0 µg/dL [37.6-49.7 µg/dL]; P = 0.354). CONCLUSIONS: ACTH appropriately increased the aldosterone and cortisol levels in patients with POTS. These findings suggest that the response of the adrenal cortex to hormonal stimulation is intact in patients with POTS.

Immunological markers of drug resistant epilepsy and its response to immunomodulatory therapy with ACTH in children.

INTRODUCTION: Drug-resistant epilepsy in infancy and childhood is a devastating condition, frequently associated with neuropsychiatric comorbidities. West syndrome is one of the most severe epilepsy syndromes. Adrenocorticotropic hormone (ACTH) treatment is recommended in such cases, but its mechanism of action is still unknown. We prospectively observed levels of selected cytokines in order to identify biomarkers of response to ACTH and the potential mechanism of its antiseizure effect. MATERIAL AND METHODS: Fifty-three infants and young children with pharmacoresistant epilepsy receiving ACTH 1-24 were included. There were 2 control groups - children with epilepsy responding to the first medication and children with no history of epilepsy. Blood concentrations of IL-1b, IL-1Ra, IL-6, IL-8, IL-10, TNF-a, IFN-g, MCP-1 and MIP-1a were analyzed at three time points: T0 (before ACTH), T1 (after intensive ACTH treatment) and at T2 (at the end of ACTH withdrawal). The results were correlated with the response to treatment, dose of ACTH and concomitant medications. RESULTS: We found statistically significantly higher concentrations of IL-1, IL-8 and MIP-1a at baseline (T0) in the study group compared to the control groups. ACTH significantly lowered levels of IL-6, IFN-g and MCP from time T0 to T1. This effect was short lasting and no significant changes in cytokine levels were found between T2 and T0. We did not find any differences in immunological markers between the responders and non-responders to ACTH. Our research did not allow us to identify any reliable immunological marker of response to ACTH treatment. We did not observe a positive effect of higher ACTH doses on the response rate in the patients. Our study showed significantly lower concentrations of IL-10 and IFN in the group of patients receiving levetiracetam. The concentration of TNF was higher and the concentration of MIP was lower in the group receiving valproic acid. CONCLUSIONS: Our study indicates that increased levels of IL-1, IL-8 and MIP-1a are associated with drug-resistant epilepsy in infants and young children and might be considered immunological markers. IL-6, IFN-g and MCP-1 take part in the effect of ACTH. Immunological mechanisms seem also to be involved in the mechanism of action of classical antiseizure drugs.

Differences in thyroid function tests after administration of a single supraphysiological dose of ACTH or a high dose of a synthetic steroid.

OBJECTIVE: Although the suppressive action of synthetic steroids on the hypothalamus-pituitary-thyroid (HPT) axis is established, little is known regarding the effect of the administration of synthetic adrenocorticotropic hormone (ACTH). DESIGN: In the context of a randomized, open label, comparative study assessing the efficacy and safety of ACTH and betamethasone in the treatment of hospitalized patients with acute gout, we compared the effects of these agents on thyroid function tests. METHODS: Serum TSH, total T4 and T3 and cortisol were measured before and at 24 and 48 h after a single intramuscular dose of synthetic ACTH (1 mg) or betamethasone (6 mg), in 38 hospitalized patients with acute gout and normal thyroid function. RESULTS: The final analysis included 32 patients, due to missing data. The ACTH and betamethasone groups did not differ regarding the mean age, gender, severity of gout attack, and baseline thyroid parameters. In the ACTH group TSH and T4 were significantly decreased at 24 and at 48 h compared to baseline, while T3 was decreased at 24 but not at 48 h. In the betamethasone group T3 remained stable; TSH and T4 decreased significantly from baseline levels at 24 h; at 48 h, TSH had returned to and T4 showed a partial rebound towards pre-treatment values. CONCLUSIONS: A single IM administration of 1 mg of synthetic ACTH has more profound and prolonged effects on the HPT axis, lasting for at least 48 h, compared to a single IM dose of 6 mg betamethasone.

Repository Corticotropin Injection as an Alternative Treatment for Refractory Ocular Mucous Membrane Pemphigoid.

PURPOSE: The purpose of this study was to report the clinical course and outcome of patients with refractory ocular mucous membrane pemphigoid (MMP) treated by repository corticotropin injection (RCI). METHODS: Patients with biopsy-proven ocular MMP treated with RCI from 3 tertiary medical centers were evaluated. Medical records between January 2013 and January 2021 were reviewed and deidentified to retrieve relevant disease-related data. Primary outcome measures included conjunctival inflammatory activity, change in Foster clinical conjunctival scarring staging after RCI treatment, and the development of ocular and systemic complications. RESULTS: Included were 15 patients (10 women and 5 men; 36-95 yrs of age) with a mean follow-up of 4.5 years. Most of the patients (80%) had Foster stage 3 at presentation, and all patients had active MMP. Each patient had failed to respond to at least 1 immunomodulatory drug during the follow-up, and 9 (60%) patients had treatment failure of at least 2 other agents before the use of RCI. The mean duration of RCI treatment was 21 months (range, 3-54 mo). Foster stage did not change in any of the 15 patients at the last follow-up. Nine patients continued RCI therapy at the last follow-up, and in all of them, the disease activity of MMP was well controlled. No serious adverse events because of RCI were documented during the follow-up in any treated patient. CONCLUSIONS: RCI may serve as an alternative or an adjunctive treatment in patients with severe and refractory ocular MMP. Treatment with RCI seems to be safe and well-tolerated.

Comparison of Bolus and Continuous Infusion of Adrenocorticotropic Hormone During Adrenal Vein Sampling.

Background: Adrenocorticotropic hormone (ACTH) is widely used in adrenal vein sampling (AVS) and can be administered as a bolus injection or continuous infusion. The optimal administration method has not been determined. We aimed to compare the effects of ACTH bolus with infusion on cannulation success, lateralization assessment and adverse events (AEs). Methods: Retrospectively collected data from patients with primary aldosteronism who underwent AVS with ACTH at a tertiary hospital in China. Rate of successful cannulation, lateralization index (LI), complete biochemical remission and AEs related to AVS were analyzed. Results: The study included 80 patients receiving ACTH bolus and 94 receiving infusions. The rate of successful cannulation was comparable between bolus and infusion groups (75/80, 93.4% vs 88/94, 93.6%). In those with successful cannulation, the bolus group had a higher selectivity index than the infusion group, while LI [6.4(1.8-17.5) vs. 7.6(2.0-27.8), P=0.48] and rate of complete biochemical remission (43/44, 97.7% vs 53/53, 100%, P=0.45) did not significantly differ between the two groups. One in the bolus and one patient in the infusion group had adrenal vein rupture but they recovered with conservative treatment. The bolus group reported more transient AEs such as palpitation (52.9% vs 2.2%) and abdominal discomfort (40.0% vs 2.2%) than the infusion group. Conclusions: Due to their similar effects on cannulation success and lateralization, but a lower rate of transient AEs in the infusion group, the continuous infusion method should be recommended for ACTH stimulation in AVS.

Establishing a new screening 17 hydroxyprogesterone cut-off value and evaluation of the reliability of the long intramuscular ACTH stimulation test in the diagnosis of nonclassical congenital adrenal hyperplasia.

OBJECTIVE: Nonclassical congenital adrenal hyperplasia (NCAH) is a common genetic transmitted endocrinological disease. The validity of screening by using a 17 hydroxyprogesterone (17 OH-P) cut-off level of 2 ng/ml is controversial due to the frequent overlap with the polycystic ovary syndrome (PCOS). The availability of the standard intravenous cosyntropin (ACTH) formula is a problem in many countries including our country and the diagnostic test is performed by using the intramuscular depot form. In this study, we aimed to determine our own cut-off value for screening and to test the reliability of long intramuscular ACTH stimulation test in our patients. PATIENTS AND METHODS: One hundred and seventy-five fertile age women whose basal follicular phase 17 OH-P level above 2 ng/ml were included in the study. All of the patients underwent an intramuscular long cosyntropin (ACTH) stimulation test. RESULTS: 17 OH-P levels were above 10 ng/ml in 16 of 175 (9.14%) patients who were compatible with the diagnosis of NCAH. There was no significant difference between NCAH, PCOS and idiopathic hyperandrogenism (IH) groups in terms of hirsutism and hyperandrogenemia. In ROC analysis, 3.19 ng/ml was found to be a reliable cut-off value (AUC: 0.698, 95% GA: 0.540-0.855, p <0.05). In the extended intramuscular ACTH stimulation test, sensitivity increased from 56.2% to 91.6% at 180th minute CONCLUSIONS: Our study gives a perspective about the detection of screening threshold value for the diagnosis of NCAH and the availability of the intramuscular long ACTH stimulation test.

[Spontaneous Hypoglycemia: A Diagnostic Challenge]. / Spontanhypoglykämien: Eine diagnostische Herausforderung.

HISTORY: A 59-year-old woman presented for an endocrinological evaluation of recurrent spontaneous hypoglycemia. The complaints always regressed after carbohydrate intake. Due to classic congenital adrenal hyperplasia, the patient received substitution therapy with hydrocortisone for decades. FINDINGS AND DIAGNOSIS: The patient was in good general condition and slightly overweight. The blood glucose at the time of admission was 87 mg/dl. The cortisol and adrenocorticotropic hormone (ACTH) under substitution with delayed-release hydrocortisone were unremarkable. The mixed-meal tolerance test (MMTT, standardized breakfast test) showed no reactive hypoglycemia. In the subsequent 72-hour fast, symptomatic hypoglycemia of 46 mg/dl was demonstrated after 36 hours. The insulin secretion was suppressed. The low cortisol as well as the high ACTH indicated an undersupply of hydrocortisone at this time. THERAPY AND COURSE: Initially, the morning dose of delayed-release hydrocortisone was increased. However, this had no effect on blood glucose. Therefore, hydrocortisone was also prescribed at night. CONCLUSION: In addition to endogenous hyperinsulinism, a disturbance of the contrainsulinergic hormones can also be responsible for spontaneous hypoglycemia.The MMTT and the 72-hour fast test should be used for diagnosis. It is important to ensure that hormone analysis is carried out immediately in hypoglycemia. The ratio of insulin, C-peptide and proinsulin to blood glucose and the constellation of counter-regulatory hormones such as cortisol, ACTH, growth hormone, Insulin-like growth factor 1 (IGF-1) and catecholamines can provide information about the etiology of hypoglycemia.

Effect of intramuscular ACTH versus oral prednisolone on the developmental trajectories of children with West syndrome over 24 months: A randomised control study.

OBJECTIVE: To assess the developmental progression and compare the developmental attainments of children treated with two hormonal therapies for infantile spasms (IS) over two years (seizure and EEG outcomes of this RCT published previously). METHODS: Newly diagnosed infants with IS were randomised to receive adrenocorticotrophin (ACTH) or prednisolone for 14 days. All underwent Bayley III Infant and Toddler Assessments in cognitive (Cog), receptive (RC) and expressive (EC) communication, fine (FM) and gross (GM) motor developmental subsets at baseline (T0), one-year (T1) and two-years (T2). RESULTS: 95 infants randomised to prednisolone (n = 48) and ACTH (n = 47) groups were eligible for developmental assessments. Mean age at initial assessment was 8.75 months (SD = 6.37, range 1.46-34.4 months). 48 children presented for all three assessments. Mean composite scores of each developmental domain improved across the three time points; but the progression was significant only in relation to motor development (p = 0.04). When comparing the treatment outcomes at 2-years, mean composite scores of children treated with ACTH were significantly lower in motor domain (p = 0.023). As for developmental delay, the ACTH group (n = 32) showed significant delay in expressive communication (adjusted OR 5.46, 95% CI: 1.1, 28.57; p = 0.04) and fine motor (adjusted OR 9.4, 95% CI: 1.1, 83.3; p = 0.04) at T2 compared to the prednisolone (n = 30) in a regression analysis. CONCLUSION: The number of children with delay at the 2 year follow up were significantly higher in two domains in the ACTH group compared to the prednisolone group. Overall results do not show a significant advantage of ACTH over prednisolone for developmental outcomes at two years, but further comparative studies over longer periods are required for more definitive conclusions.

Epilepsy Outcome at Four Years in a Randomized Clinical Trial Comparing Oral Prednisolone and Intramuscular ACTH in West Syndrome.

BACKGROUND: This article explores the role of initial treatment on control of spasms and other epilepsies at four years in children previously treated for West syndrome. METHODS: The Sri Lanka Infantile Spasm Study is a prospective clinical trial evaluating response to intra-muscular adrenocorticotropic hormone (ACTH) versus oral prednisolone. A previous report documented response through age 12 months. This article provides four-year follow-up data. RESULTS: At age four years, 65 of the original 97 were available for follow-up; another 13 had died, and 19 moved and could not be contacted. Of the 65 children, 37 (57%) continued to have seizures and 28 were seizure free. In the 37 children with ongoing epilepsy, 32.4% continued to have spasms, either alone or in combination with other seizure types. The epilepsy types seen in these children were focal epilepsy (59.4%), mixed focal and generalized epilepsy (24%), generalized epilepsy only (10.8%), and uncertain (5%). The majority of those still having epilepsy (66.7%) were controlled on medication. There was no significant difference in the rate of epilepsy or spasms or their control by medication between those treated with ACTH or oral prednisolone. Spasm control at day 14 did not influence the four-year spasm or epilepsy outcome. CONCLUSIONS: A majority of children diagnosed with West syndrome continued to have seizures at age four years, although most were controlled on antiseizure medication. The long-term risk of developing epilepsy or its control was the same, regardless of whether ACTH or prednisolone was initially used as treatment.

Management of repository corticotropin injection therapy for non-infectious uveitis: a Delphi study.

PURPOSE: Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases. METHODS: The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). RESULTS: The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent. CONCLUSIONS: Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.

Encephalopathy related to status epilepticus during sleep due to a de novo KCNA1 variant in the Kv-specific Pro-Val-Pro motif: phenotypic description and remarkable electroclinical response to ACTH.

Although the classic phenotype of episodic ataxia type 1 (EA1) caused by variants in KCNA1 includes episodic ataxia and myokymia, further genotype-phenotype correlations are difficult to establish due to highly heterogeneous clinical presentations associated with KCNA1 pathogenic variants. De novo variants in the paralogous Pro-Val-Pro motif (PVP) of KCNA2, an essential region for channel gating, have been reported to be associated with severe epilepsy phenotypes, including developmental and epileptic encephalopathies (DEE). Here, we describe the first patient with a DEE who developed an encephalopathy related to status epilepticus during sleep (ESES) and cerebellar signs, harbouring a variant in the Kv-specific PVP motif of the KCNA1 gene. Interestingly, he showed a remarkable long-term electroclinical response to IM ACTH therapy. This report extends the range of phenotypes associated with KCNA1 variants to include that of ESES, and suggests that ACTH therapy is likely to have a positive effect in patients with these variants.

Peptide ACTH4-7-PGP: Effects on Various Types of Pain and Pain-Induced Behavior in Rats after Systemic and Central Administration.

The effects of peptide ACTH4-7-PGP (Semax) were studied in 12 min after its intraperitoneal (in doses of 5, 15, 50, 150, and 450 µg/kg) or intracerebroventricular (in doses of 16, 40, and 400 pg) administration to rats with different types of pain and pain-induced behavior. It was found that the peptide increased pain sensitivity and induced avoidance behavior during thermal stimulation ("hot plate" test), but had an analgesic effect (more pronounced after central administration) and weakened emotional-affective behavior in electrocutaneous stimulation of the paws (foot-shock model) and tail in rats. It was shown that changes in activity of supraspinal brain structures were of primary importance in the mechanism of action on the nociceptive process and the formation of behavior.

Fulminant vigabatrin toxicity during combination therapy with adrenocorticotropic hormone for infantile spasms: Three cases and review of the literature.

Vigabatrin (VGB), adrenocorticotropic hormone (ACTH), and prednisone are first-line treatments for infantile spasms (IS). A recent study reported benefits from the use of combination VGB and hormonal therapy over hormonal treatment alone in IS. We describe three patients with IS who developed acute encephalopathy with extrapyramidal symptoms, vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM), and death in one patient shortly after initiation of therapy with VGB and ACTH. A literature review supports increased risk of fulminant, symptomatic VABAM in patients receiving VGB in association with hormonal therapy, raising concerns regarding its safety in IS.

ACTH Treatment of Infantile Spasms: Low-Moderate- Versus High-Dose, Natural Versus Synthetic ACTH-A Retrospective Cohort Study.

BACKGROUND: High dosages of natural adrenocorticotropic hormone are used in many centers in the United States for the treatment of infantile spasms. However, lower dosages of synthetic adrenocorticotropic hormone (tetracosactide) might be equally efficient as high dosages. We analyzed the treatment options for infantile spasms, especially regarding the adrenocorticotropic hormone dosage and the formulation (natural versus synthetic) and evaluated which options were more effective in a retrospective cohort from 1960 to 1976. METHODS: We compared the short-term response rates of patients treated with high dosages of natural adrenocorticotropic hormone (120 IU/day) (N = 31) (Group1) with those of patients treated with low-moderate dosages of natural adrenocorticotropic hormone (40 IU/day) (N = 52) (Group2). We also compared the short-term response rates of patients treated with natural adrenocorticotropic hormone (N = 83) with those of patients treated with synthetic adrenocorticotropic hormone, (N = 23) (Group3). The responses were evaluated clinically and by electroencephalography at two to three weeks after the onset of therapy. RESULTS: A response was seen in 24 of 31 children treated with high dosages and in 43 of 52 children treated with low-moderate dosages of natural adrenocorticotropic hormone (P = 0.56). All children with an unknown etiology responded to both high and low-moderate dosages of natural adrenocorticotropic hormone. The proportion of children with a good early response to synthetic adrenocorticotropic hormone (16 of 23) did not differ from the proportion of children with a good early response treated with natural adrenocorticotropic hormone (67 of 83) (P = 0.25). CONCLUSIONS: High dosages of adrenocorticotropic hormone are not more effective than low-moderate dosages in the short term for treating infantile spasms. Synthetic adrenocorticotropic hormone is equally effective as natural adrenocorticotropic hormone.

Evaluating the Low-Dose ACTH Stimulation Test in Neonates: Ideal Times for Cortisol Measurement.

CONTEXT: Low-dose adrenocorticotropic hormone stimulation testing (LDST) can be used to diagnose central adrenal insufficiency. However, uncertainty remains over optimal times to draw serum cortisol levels. OBJECTIVE: To determine optimal times to draw serum cortisol levels for the LDST in neonates. DESIGN: A retrospective chart review of LDSTs performed on neonates from January 1, 2009 to September 30, 2017. SETTING: Children's Hospital of Eastern Ontario (CHEO), a tertiary-care outborn pediatric center. PATIENTS: Forty-nine patients were included: 23 (46.9%) born at term, 12 (24.5%) born very preterm to late preterm, and 14 (28.6%) born extremely preterm. INTERVENTION: Cortisol levels were drawn at baseline and 15, 30, and 60 minutes following administration of Cortrosyn 1 mcg/kg (maximum dose 1 mcg). MAIN OUTCOME MEASURE: Timing of peak cortisol level and marginal value of drawing a second and third cortisol sample at 15, 30, or 60 minutes was determined. RESULTS: Cortisol peaked at 15-, 30-, and 60-minute sampling times for 4%, 27%, and 69% of patients, respectively. The probability that a failed LDST changes to a pass by adding a 15- or 30-minute sample to the superior 60 minute sample is 5.6% (1% to 25.8%) and 11% (3.1% to 32.6%), respectively, for a cortisol pass threshold of 18.1mcg/dL (500 nmol/L). CONCLUSIONS: In contrast to studies of older children, we found that the majority of neonatal LDST cortisol peaks occurred at the 60-minute sampling time with the addition of a 30-minute sample providing substantial benefit. It is questionable if a 15-minute sample provides any benefit, making a case to revise LDST protocols to sample cortisol later for neonates.

Diagnostic contribution of individual components of adrenal function tests to diagnose canine hyperadrenocorticism.

There is limited information regarding the value of constitutive components of the ACTH stimulation test (ACTHST) and low-dose dexamethasone suppression test (LDDST) including serum baseline cortisol (BC), difference between post-ACTH stimulation cortisol (PC) and BC (ΔACTHC), cortisol concentration 4h after dexamethasone administration (4HC), difference between 4HC and BC (Δ4C), and the difference between cortisol concentration 8h after dexamethasone administration and 4HC (Δ8C). Therefore, the objective of this study was to determine if these components can predict hyperadrenocorticism, pituitary-dependent hyperadrenocorticism (PDH), or functional adrenocortical tumor (FAT) in dogs. Cortisol concentrations were normalized, as fold change (FC), to the PC reference interval upper limit. A total of 1267 dogs were included, with hyperadrenocorticism diagnosed in 537 (PDH, n=356; FAT, n=28; undetermined, n=153) and excluded in 730. The area under the receiver operating curves for BC, ΔACTHC, 4HC, Δ4C, and Δ8C to predict hyperadrenocorticism were 0.76 (95% confidence interval (CI), 0.73-0.79), 0.91 (95% CI, 0.89-0.93), 0.83 (95% CI, 0.80-0.87), 0.55 (95% CI, 0.50-0.60), and 0.67 (95% CI, 0.62-0.72), respectively. A diagnostic limit of ≥0.78 FC for ΔACTHC had excellent sensitivity (1.00; 95% CI, 0.74-1.00), but poor specificity (0.67; 95% CI, 0.64-0.71), to predict FAT in dogs with a positive ACTHST. A diagnostic limit of ≥-0.26 FC for Δ4C had excellent sensitivity (1.00; 95% CI, 0.79-1.00), but poor specificity (0.21; 95% CI, 0.18-0.26), to predict FAT in dogs with a positive LDDST. In hyperadrenocorticoid dogs that have positive ACTHST or LDDST results, ΔACTHC or Δ4C, respectively, could be used to exclude FAT.

Use of Adrenocorticotropic Hormone in Ophthalmology.

The ability of the adrenocorticotropic hormone (ACTH) to induce steroidogenesis and upregulate anti-inflammatory processes has long been known. More recently, however, extrasteroidal mechanisms, through which ACTH exerts anti-inflammatory processes, have been described. This has renewed hope that ACTH can combat inflammatory conditions even when resistant to steroids. This review article summarizes the literature on the use of ACTH in ocular disease. Unfortunately, much of the data regarding the clinical utility of ACTH are outdated, with many studies published in the 1950s and 1960s. Many of these older studies are inconsistent or incomplete with their reporting, making it difficult to ascertain the meaning of the outcomes. Despite the limitations, 2 important trends are evident. First, when used to treat an inflammatory disease, ACTH can be effective at decreasing or eliminating ocular inflammation, even in a refractory disease resistant to multiple treatment modalities. Second, adverse effects of ACTH are rare and are most likely to be reported with relatively high doses of ACTH therapy. Taken as a whole, these studies offer initial promising data that ACTH may be a safe and effective alternative in refractory ocular inflammatory disease. However, they highlight an important lack of prospective data to more rigorously understand the true safety and efficacy of this therapy.

Low-grade Cortisol Cosecretion Has Limited Impact on ACTH-stimulated AVS Parameters in Primary Aldosteronism.

CONTEXT: In primary aldosteronism, cosecretion of cortisol may alter cortisol-derived adrenal venous sampling indices. OBJECTIVE: To identify whether cortisol cosecretion in primary aldosteronism alters adrenal venous sampling parameters and interpretation. DESIGN: Retrospective case-control study. SETTING: A tertiary referral center. PATIENTS: 144 adult patients with primary aldosteronism who had undergone both adrenocorticotropic hormone-stimulated adrenal venous sampling and dexamethasone suppression testing between 2004 and 2018. MAIN OUTCOME MEASURES: Adrenal venous sampling indices including adrenal vein aldosterone/cortisol ratios and the selectivity, lateralization, and contralateral suppression indices. RESULTS: 21 (14.6%) patients had evidence of cortisol cosecretion (defined as a failure to suppress cortisol to ≤50 nmol/L post dexamethasone). Patients with evidence of cortisol cosecretion had a higher inferior vena cava cortisol concentration (P = .01) than those without. No difference was observed between the groups in terms of selectivity index, lateralization index, lateralization of aldosterone excess, or adrenal vein cannulation rate. CONCLUSIONS: Cortisol cosecretion alters some parameters in adrenocorticotrophic hormone-stimulated adrenal venous sampling but does not result in alterations in patient management.

Steroid Screening Tools Differentiating Nonclassical Congenital Adrenal Hyperplasia and Polycystic Ovary Syndrome.

PURPOSE: To analyze the performance of basal 17OH-progesterone (17OHP) levels versus the basal 17OHP/cortisol ratio in nonclassical congenital adrenal hyperplasia (NCAH) and polycystic ovary syndrome (PCOS) differential diagnosis. Basal 17OHP levels >10 ng/mL have been used to confirm NCAH diagnosis without the adrenocorticotropic hormone (ACTH) test; however, the optimal cutoff value is a matter of debate. METHODS: A cross-sectional study was performed at the endocrinology and gynecological endocrinology outpatient clinics of a tertiary hospital. A total of 361 patients with PCOS (age 25.0 ± 5.3 years) and 113 (age 19.0 ± 13.6 years) patients with NCAH were enrolled. Basal and ACTH-17OHP levels were measured by radioimmunoassay, and CYP21A2 molecular analysis was performed to confirm hormonal NCAH diagnosis. Receiver operating characteristic curve analysis compared basal 17OHP levels and the 17OHP/cortisol ratio between NCAH and PCOS patients. RESULTS: Basal 17OHP levels were higher in NCAH patients than in those with PCOS (8.85 [4.20-17.30] vs 1.00 [0.70-1.50] ng/mL; P < 0.0001), along with 17OHP/cortisol ratio (0.86 [0.47-1.5]) vs 0.12 [0.07-0.19]; P < 0.0001, respectively). Basal 17OHP levels and the 17OHP/cortisol ratio were strongly correlated in both groups (rho = 0.82; P < 0.0001). Areas under the curves for basal 17OHP levels (0.9528) and the 17OHP/cortisol ratio (0.9455) were not different to discriminate NCAH and PCOS (P > 0.05). Basal 17OHP level >5.4 ng/mL and 17OHP/cortisol ratio >2.90 had 100% specificity to identify NCAH. MAIN CONCLUSIONS: Basal 17OHP levels >5.4 ng/mL can be used to perform differential diagnoses between NCAH and PCOS, dismissing the ACTH test. The basal 17OHP/cortisol ratio was not superior to basal 17OHP levels in this scenario.