Adrenal function following ACTH therapy for infantile spasms: A retrospective study.

OBJECTIVE: To determine if treatment with ACTH for infantile spasms (IS) is associated with secondary adrenal insufficiency. PATIENTS AND METHODS: This is a retrospective study of patients diagnosed with infantile spasms and treated with ACTH between 2007 and 2018 at Soroka University Medical Center (SUMC). We reviewed the records of patients who had a post-hormonal laboratory assessment of their adrenal function; either a low dose ACTH test or a random morning cortisol level and looked for laboratory or clinical signs of adrenal insufficiency. RESULTS: Between the years 2007 and 2018, 45 children were diagnosed with IS at our Pediatric Neurology Unit, 20 patients were treated with ACTH, of them 14 children met the inclusion criteria and had a post-treatment laboratory assessment of adrenal function by low dose ACTH test or morning cortisol level. Five children had a normal low dose ACTH test, two had normal morning cortisol level, five were not conclusive, and two had subnormal levels of cortisol. None of the children showed clinical signs of adrenal insufficiency. CONCLUSION: Our study adds to the limited literature on this topic and in contrast to previous publications suggests that adrenal suppression should not occur after ACTH treatment.

Evaluation of the effectiveness and tolerance of tetracosactide in the treatment of post-dural puncture headaches (ESYBRECHE): a study protocol for a randomised controlled trial.

BACKGROUND: Post-dural puncture headache (PDPH) is one of the most common complications of neuraxial anaesthesia. It limits patients' general activity and increases the length of hospital stays and the use of care. It is particularly disabling during the postpartum period, when mothers have to take care of their child. Epidural blood patch is the standard treatment for PDPH. However, it is an invasive procedure that may result in rare but serious complications. Recent evidence has suggested that adrenocorticotropic hormone (ACTH) is effective in the management of PDPH. The aim of this study is to assess the efficacy and safety of tetracosactide (Synacthen®), a synthetic analogue of ACTH, for PDPH treatment in patients who receive neuraxial anaesthesia during labour. METHODS: This randomised, double-blind, placebo-controlled, parallel-arm trial, is performed in two French university hospitals. Eligible patients are those suffering from postpartum PDPH, who are randomised to receive either 1 mg of tetracosactide intravenously over 20 min or to 0.9% saline (placebo). The primary endpoint is the rate of epidural blood patch within a 15-day follow-up period. Headache duration, pain intensity, reduction of general activity, increase in length of hospital stay, adverse events, analgesic use (type and duration) and number of blood patches per patient in each group are recorded. DISCUSSION: We expect a decrease in the use of epidural blood patch in those receiving tetracosactide, thus indicating a decrease in PDPH symptoms in these patients. This will define the therapeutic success of tetracosactide and the possibility to use this treatment as a non-invasive alternative to blood patch for PDPH treatment. TRIAL REGISTRATION: Primary Registry ClinicalTrials.gov Protocol Registration and Results System Date of Registration 24 June 2016 Unique Protocol ID 69HCL15_0429 Secondary IDs EudraCT Number 2015-003357-17 ClinicalTrials.gov ID NCT02813655 ANSM 160214A-31 Protocol version V4 28/09/2018.

Use of synthetic adrenocorticotropic hormone in patients with IgA nephropathy.

BACKGROUND: Synthetic adrenocorticotropic hormone (ACTH) has been demonstrated to be effective in patients with membranous nephropathy, minimal change disease and some histological subtypes of focal segmental glomerulosclerosis. Its clinical impact in patients with IgA nephropathy is currently unclear. CASE PRESENTATION: In this report, we describe the clinical use of ACTH in patients with IgA nephropathy. Three female patients (24-44 years) with overt proteinuria received intramuscular (IM) ACTH for varying time periods (8-14 months). Pre-treatment urine protein varied from 2.9 g/d to 4.3 g/d. CONCLUSIONS: There was complete remission in one patient on ACTH monotherapy and in the other two when prescribed as a steroid-sparing agent in combination with cyclophosphamide. All three had resolution in proteinuria to less than 1 g/d and maintained their GFR to baseline values. There were no reported side effects at a once a week dose. This study illustrates that ACTH is an effective agent that is well tolerated with minimal side effects and can be used as an alternative to prednisone in patients with IgA nephropathy.

Synthetic ACTH in High Risk Patients with Idiopathic Membranous Nephropathy: A Prospective, Open Label Cohort Study.

New therapeutic agents are warranted in idiopathic membranous nephropathy. Synthetic ACTH may be advantageous with reported remission rates up to 85% and few side effects. We conducted a prospective open label cohort study from 2008 till 2010 (NCT00694863). We prospectively selected patients with idiopathic membranous nephropathy and high risk for progression (defined as ßeta-2-microglobulin (ß2m) excretion of >500 ng/min). For comparison, we selected matched historical controls treated with cyclophosphamide. The prospectively selected patients received intramuscular injections of synthetic ACTH during 9 months (maximal dose 1 mg twice a week). The primary endpoints concerned the feasibility and incidence of remissions as a primary event. Secondary endpoints included side effects of treatment and the incidence of remissions and relapses at long-term follow-up. Twenty patients (15 men) were included (age 54±14 years, serum creatinine 104 µmol/l [IQR 90­113], urine protein:creatinine ratio 8.7 g/10 mmol creatinine [IQR 4.3­11.1]). Seventeen patients (85%) completed treatment. 97% of injections were administered correctly. Cumulative remission rate was 55% (complete remission in 4 patients, partial remission 7 patients). In a group of historical controls treated with cyclophosphamide and steroids, 19 of 20 patients (95%) developed a remission (complete remission in 13 patients, partial remission in 6 patients) (p<0.01). The main limitation of our study is its small size and the use of a historical control group. We show that treatment with intramuscular injections of synthetic ACTH is feasible. Our data suggest that synthetic ACTH is less effective than cyclophosphamide in inducing a remission in high risk patients with idiopathic membranous nephropathy. The use of synthetic ACTH was also associated with many adverse events. Therefore, we advise against synthetic ACTH as standard treatment in membranous nephropathy.

Risk of catecholaminergic crisis following glucocorticoid administration in patients with an adrenal mass: a literature review.

BACKGROUND: Glucocorticoids as diagnostic or therapeutic agents have been reported to carry an increased risk of catecholaminergic crisis (CC) in patients with pheochromocytoma or paraganglioma (PPGL). METHODS: We searched literature databases using the following terms: pheochromocytoma, paraganglioma, adrenal incidentaloma, steroids, glucocorticoids, dexamethasone suppression test (DST), hypertensive crisis, cosyntropin and CRH. From all published case reports (1962-2013), we reviewed medical history, presenting symptoms, dose and route of steroid administration, location and size of adrenal mass, biochemical phenotype and outcome. RESULTS: Twenty-five case reports describing a CC were identified. Three patients with an adrenal incidentaloma suffered a CC following high-dose DST, and in one case, this was fatal. In two of these patients, biochemical testing missed the diagnosis, and in the third, a DST was done despite elevated urinary metanephrines. No CC has been reported for patients undergoing a low-dose DST. Three of 16 patients who received therapeutic glucocorticoids and four of six patients following cosyntropin testing died. No specific biochemical phenotype was related to adverse events. CONCLUSIONS: Although a causal relationship cannot be established from this review, it seems prudent to exclude a PPGL in patients with a large incidentaloma or when high-dose DST is considered in a patient with an incidentaloma of any size. Our literature review does not support the need for biochemical testing for PPGL prior to a low-dose (1 mg) DST. Finally, before starting therapeutic glucocorticoids, any clinical signs or symptoms of a potential PPGL should prompt reliable biochemical testing to rule out a PPGL.

Paradoxical Results after Inadvertent Use of Cosyntropin [Adrenocorticotropin Hormone (1-24)] Rather than Acthrel (Ovine Corticotropin Releasing Hormone) during Inferior Petrosal Sinus Sampling.

OBJECTIVE: The use of ovine corticotropin releasing hormone (oCRH) maximizes the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in patients with adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome (CS). oCRH is marketed as ACTHrel and, understandably, may be confused with cosyntropin [ACTH (1-24)]. The inadvertent substitution of synthetic ACTH(1-24) for oCRH (ACTHrel) during IPSS may cause unexpected and misleading results. The aim of this report is to raise awareness of the potential confounding results created when synthetic ACTH(1-24) is mistakenly used during IPSS. METHODS: We present 3 patients treated at 3 different centers with ACTH-dependent CS in whom ACTH(1-24) was mistakenly substituted for oCRH (ACTHrel) during IPSS. RESULTS: In all patients, there was an abrupt and unexpected decrease in plasma ACTH in the inferior petrosal sinus (IPS) samples after presumptive stimulation with oCRH. Re-evaluation of the patients' pharmacy records confirmed that synthetic ACTH(1-24) had been used rather than oCRH during each procedure. Because "sandwich" immunometric assays for ACTH measure the entire pool of endogenous ACTH, the administration of synthetic ACTH(1-24) artifactually decreases the endogenous plasma ACTH(1-39) measurement by binding only to the N-terminal antibody raised against ACTH(1-17) and not to the C-terminal antibody raised against ACTH(34-39). This results in a lack of a detectable sandwich complex and explains the apparent reduction in ACTH concentration. CONCLUSION: An abrupt decrease in ACTH during IPSS suggests that synthetic ACTH(1-24) rather than oCRH (ACTHrel) has been administered. The labeling of oCRH as ACTHrel poses a potential patient safety problem about which endocrinologists, interventional radiologists, and pharmacists should be aware.

[Adrenal hemorrhage acutised by adrenocorticotropin hormone]. / Hématomes surrénaliens potentialisés par le Synacthène (HSS).

OBJECTIVE: Many spontaneous adrenal hematomas have been observed in patients being treated by Synacthène. The purpose of this study is to define how to take those patients in charge on a short-, mid- and long-term. PATIENTS AND METHODS: From January 2000 to December 2008, five patients (four males and one female), mean age 47, were taken in charge in our service for spontaneous adrenal hematomas. All those patients had been treated with Synacthène for a mid-sciatic pain for 72 hours. We associated a clinical, endocrine and radiologic staging to treat those patients. RESULTS: Four patients underwent a watchful waiting, only one patient needed surgery. No adrenal tumor was ever found during the mean two years follow-up (one to four). Two patients suffered of the condition of the antiphospholipid syndrome. CONCLUSION: Spontaneous adrenal hematomas are a most uncommon pathology. The clinical attitude has thus to be defined clearly. The patient must be under close clinical evaluation. Biological and morphological parameters have to be often repeated. An adrenal tumor has to be excluded by the evaluation, as that tumor could be secreting or could not be secreting. Antiphospholipid syndrome must also be excluded.

Bilateral whirlbone necrosis in a young multiple sclerosis patient.

A case of avascular necrosis of whirlbone in a young man affected by multiple sclerosis and treated with high doses of corticosteroids is described. The authors discuss the causes of this collateral effect underlining the risks of underevaluating the symptoms.

Therapeutic efficacy and adverse effects of adrenocorticotropic hormone therapy in west syndrome: differences in dosage of adrenocorticotropic hormone, onset of age, and cause.

OBJECTIVES: To determine the dosage and factors influencing efficacy of adrenocorticotropic hormone (ACTH) for West syndrome. STUDY DESIGN: A retrospective study of 135 patients receiving ACTH therapy with a synthetic analogue for initial effect, seizure outcome 1 year after therapy, and adverse effects. Efficacy and adverse effects were compared among the groups divided by clinical factors: dosage, treatment lag, onset age, and cause. RESULTS: One hundred thirteen patients had seizure control with ACTH. For more than 1 year after ACTH, 59 remained seizure free. Adverse effects were observed in 57, and ACTH therapy was discontinued in 23. The lowest dosage group (0.0125 mg/kg/d) had fewer episodes of discontinuation (P<.05), whereas differences in efficacy between different dosages were insignificant. None of the clinical factors correlated with initial effect. The earlier-onset group (<4 months) showed unfavorable seizure outcome 1 year after ACTH (P<.01). The cryptogenic patients showed better seizure outcome (P<.05) compared with the symptomatic. CONCLUSION: Synthetic ACTH therapy at a lower dosage is as effective as natural ACTH therapy at a higher dosage. Considering the adverse effects and the benefits for seizure control, the ACTH dosage of 0.0125 mg/kg/d (synthetic analogue) is more favorable than larger dosage.

The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial.

BACKGROUND: Infantile spasms, which comprise a severe infantile seizure disorder, have a high morbidity and are difficult to treat. Hormonal treatments (adrenocorticotropic hormone and prednisolone) have been the main therapy for decades, although little evidence supports their use. Vigabatrin has been recorded to have a beneficial effect in this disorder. We aimed to compare the effects of vigabatrin with those of prednisolone and tetracosactide in the treatment of infantile spasms. METHODS: The United Kingdom Infantile Spasms Study assessed these treatments in a multicentre, randomised controlled trial in 150 hospitals in the UK. The primary outcome was cessation of spasms on days 13 and 14. Minimum doses were vigabatrin 100 mg/kg per day, oral prednisolone 40 mg per day, or intramuscular tetracosactide depot 0.5 mg (40 IU) on alternate days. Analysis was by intention to treat. FINDINGS: Of 208 infants screened and assessed, 107 were randomly assigned to vigabatrin (n=52) or hormonal treatments (prednisolone n=30, tetracosactide n=25). None was lost to follow-up. Proportions with no spasms on days 13 and 14 were: 40 (73%) of 55 infants assigned hormonal treatments (prednisolone 21/30 [70%], tetracosactide 19/25 [76%]) and 28 (54%) of 52 infants assigned vigabatrin (difference 19%, 95% CI 1%-36%, p=0.043). Two infants allocated tetracosactide and one allocated vigabatrin received prednisolone. Adverse events were reported in 30 (55%) of 55 infants on hormonal treatments and 28 (54%) of 52 infants on vigabatrin. No deaths were recorded. INTERPRETATION: Cessation of spasms was more likely in infants given hormonal treatments than those given vigabatrin. Adverse events were common with both treatments.

Morning salivary cortisol versus short Synacthen test as a test of adrenal suppression.

BACKGROUND: The short Synacthen test (SST) is the most commonly used test for the assessment of adrenal suppression. We investigated the potential of a simpler and more cost-effective procedure [morning salivary cortisol (MSC)] as an outpatient screening tool to detect adrenal suppression in patients using topical intranasal corticosteroids for rhinosinusitis. METHOD: Forty-eight patients who were using topical corticosteroids underwent adrenal function assessment by way of SST and MSC measurement. RESULTS: Sixteen of the 48 patients had impaired MSCs. Of these 16 patients, 15 had an impaired SST (sensitivity 100%) and one had a normal SST. All patients with normal MSCs also had normal SSTs (specificity 97%). CONCLUSION: The morning salivary cortisol measurement is a useful screening tool for adrenal suppression in this setting.

[Inaugural unilateral adrenal hematoma of an antiphospholipid syndrome]. / Hématome surrénalien unilatéral inaugural d'un syndrome des antiphospholipides.

INTRODUCTION: A primary antiphospholipid syndrome is a very rare cause of adrenal haemorrhage. OBSERVATION: A 51 year-old man presented with a unilateral adrenal haemorrhage, enhanced by the prescription of Synacthène during the 4 days that preceded. There was no adrenal deficiency but the immunological control revealed the presence of anti-phospholipid antibodies. After 2 years of follow-up, adrenal controls have not shown any underlying tumour or endocrine insufficiency. COMMENTS: Adrenal involvement is described in the anti-phospholipid syndrome and may present in the form of adrenal deficiency in the case of occasionally only microscopic bilateral haemorrhages. Furthermore, Synacthène is known to induce adrenal haemorrhages although this complication remains rare. Moreover, any unilateral adrenal haemorrhage requires subsequent follow-up for several months or even years in order to eliminate any underlying tumour and to control the absence of any adrenal deficiency if the involvement is bilateral.

Elevated intraocular pressure associated with steroid treatment for infantile spasms.

PURPOSE: To evaluate the ocular changes and medical and surgical therapy after high-dose systemic steroid treatment in babies with infantile spasm and hypsarrhythmia. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: In 5 of the 9 (55%) babies with infantile spasm exposed to systemic corticosteroid treatment, an increase in intraocular pressure (IOP) and optic disc cupping was observed. INTERVENTION: Ophthalmic examination under mild sedation was conducted 3 to 4 weeks after initiation of systemic therapy. Antiglaucoma treatment was given to the patients found to have high IOPs and cup-to-disc ratio changes. Routine follow-up was continued until systemic therapy was completed. MAIN OUTCOME MEASURES: Controlled IOP with a decrease in cupping damage after antiglaucoma therapy. RESULTS: Five patients required antiglaucoma treatment; one also underwent augmented trabeculectomy. Mean IOP decreased in this subgroup from 30.1 +/- 9.5 mmHg to 15.4 +/- 4.2 mmHg in the right eye (P = 0.043) and from 32.6 +/- 7.4 mmHg to 15.2 +/- 1.8 mmHg in the left eye (P = 0.043). Mean cup-to-disc ratio improved from 0.53 +/- 0.2 to 0.37 +/- 0.04 in the right eye (P = 0.06) and from 0.57 +/- 0.12 to 0.35 +/- 0.05 in the left eye (P = 0.042). CONCLUSIONS: The rapid onset of IOP and cup-to-disc ratio changes in patients with infantile spasm and hypsarrhythmia treated by high-dose corticosteroids necessitates early and intensive monitoring to prevent anatomic ocular damage and visual impairment in the future.

Low-dose ACTH therapy for West syndrome: initial effects and long-term outcome.

BACKGROUND: Most Japanese pediatric neurologists attempt other treatments before using adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS), and even then, they use only a low-dose synthetic ACTH to avoid serious adverse effects. In this multi-institutional study, the authors analyzed the initial effects, adverse effects, and long-term outcome in patients treated with low-dose synthetic ACTH in Japan. METHODS: The medical records of 138 patients with WS, who were treated with low-dose synthetic ACTH therapy for the first time at the authors' institutions between 1989 and 1998, were analyzed. RESULTS: At the end of ACTH therapy, excellent effect on seizures was noted in 106 of 138 (76%) patients, good effect in 23 (17%), and poor effect in 9 (7%). Initial effects on EEG were excellent in 53 of 138 (38%) patients, good in 76 (55%), and poor in 9 (7%). As for seizure prognosis at the time of follow-up, 51 of 99 (52%) patients were seizure-free, whereas 48 (48%) patients had seizures. Mental outcome was normal in 6 of 98 (6%) patients, mild mental retardation in 16 (16%), moderate mental retardation in 26 (27%), and severe mental retardation in 50 (51%). The initial effects of ACTH on seizures and long-term outcome were not dose dependent (daily dosage 0.005 to 0.032 mg/kg, 0.2 to 1.28 IU/kg; total dosage 0.1 to 0.87 mg/kg, 4 to 34.8 IU/kg). The severity of adverse effects correlated with total dosage of ACTH, and the severity of brain volume loss due to ACTH correlated well with the daily dosage and total dosage of ACTH. CONCLUSION: Low-dose synthetic ACTH therapy is as effective for the treatment of WS as the higher doses used in previous studies. The dosage of synthetic ACTH used in the treatment of WS can be decreased as much as possible to avoid serious adverse effects.