Adrenocorticotropic Hormone Gel Research Articles

ACTH Gel in Resistant Focal Segmental Glomerulosclerosis After Kidney Transplantation.

Treatment of focal segmental glomerular sclerosis (FSGS) after kidney transplantation is challenging with unpredictable outcomes. The objective was to investigate the use of adrenocorticotropic hormone (ACTH) analogue gel in kidney transplant recipients with de novo or recurrent FSGS resistant to therapeutic plasma exchange (TPE) and/or rituximab. We performed a retrospective review of cases of de novo or recurrent resistant FSGS at 2 large US transplant centers between April 2012 and December 2016. Proteinuria was measured by urine protein to creatinine ratio. We identified 20 cases of posttransplant recurrent and de novo FSGS resistant to conventional therapy with TPE and rituximab. Mean ± SD age was 49 ± 15.5 years, 14 (70%) were male, 13 (65%) were whites, and 8 (38%) had previous kidney transplants. Median (interquartile range) of recurrent and de novo FSGS was 3 (0.75-7.5) months posttransplant. The majority of patients, 15 (75%), received TPE as a treatment at the time of diagnosis and 10 (50%) received rituximab, which was started before the use of ACTH gel. There was a significant improvement of urine protein to creatinine ratio from a mean ± SD of 8.6 ± 7.6 g/g before ACTH gel to 3.3 ± 2.3 g/g after the use of ACTH gel (P = 0.004). Ten (50%) patients achieved complete or partial remission. Although, the response varied among the recipients, ACTH gel might be an effective therapy for posttransplant resistant FSGS cases that fail to respond to TPE and rituximab.

Adrenocorticotropic hormone analogue as novel treatment regimen in ocular cicatricial pemphigoid

PurposeTo report the clinical outcome of a patient with ocular cicatricial pemphigoid, treated with adrenocorticotropic hormone gel. ObservationsA 75-year-old female with a biopsy proven ocular cicatricial pemphigoid (OCP) presented with bilateral conjunctival inflammation, fornix shortening, subepithelial fibrosis and corneal scarring. The patient was previously treated with topical steroids, topical cyclosporine and lubricating drops, and had undergone several amniotic membrane transplants due to recurrent corneal erosions. Once OCP diagnosis was established, the patient was started on oral corticosteroids (60 mg daily). In order to wean the patient off from systemic steroids, other immunomodulatory agents had been tried, including mycophenolate mofetil (1000 mg twice daily) and methotrexate (up to 25 mg weekly). However, none of these agents adequately controlled the ocular surface inflammation, and the patient experienced bilateral progressive cicatrization and corneal decompensation, as well as the development of side effects from the systemic corticosteroids, methotrexate and mycophenolate mofetil therapies. Treatment with twice weekly subcutaneous adrenocorticotropic hormone (ACTH) gel was initiated, along with tapering of systemic corticosteroids. During the 19 months treatment period, the patient demonstrated significant improvement in the ocular surface inflammation, visual acuity was stable and no significant adverse effects were observed. Systemic corticosteroids dosage was successfully reduced from 10 mg/day to none at last follow up. Conclusions and importanceACTH gel has shown to be an effective and safe treatment option for chronic, refractory and progressive ocular inflammatory disease. To the best of our knowledge, this is the first case report of a patient with OCP, treated successfully with ACTH gel. This case report may encourage ophthalmologists to employ ACTH gel in the management of OCP.

Efficacy and safety of adrenocorticotropic hormone gel in refractory dermatomyositis and polymyositis

AimTo evaluate the efficacy, safety, tolerability and steroid-sparing effect of repository corticotropin injection (RCI), in an open-label clinical trial, in refractory adult polymyositis (PM) and dermatomyositis (DM).MethodsAdults with refractory PM...

Successful Treatment of an Unusual Case of Membranous Nephropathy With Adrenocorticotropic Hormone Gel in HIV Patient

Successful Treatment of an Unusual Case of Membranous Nephropathy With Adrenocorticotropic Hormone Gel in HIV Patient

Adrenocorticotropic hormone gel in the treatment of systemic lupus erythematosus: A retrospective study of patients.

Acthar Gel is a long-acting formulation of adrenocorticotropic hormone (ACTH) with anti-inflammatory effects thought to be mediated in part through melanocortin receptor activation. This study was initiated to understand the role of Acthar Gel in SLE treatment in rheumatology practices. This is a retrospective case series of nine adult female patients treated with Acthar Gel for at least six months at five academic centers. Treating physicians completed a one-page questionnaire on lupus medications, disease activity, and outcomes. Clinical response was defined using SLEDAI 2K and improvement in the clinical manifestation(s) being treated. The most common clinical SLE manifestations/indications requiring therapy with Acthar Gel were arthritis, rash, and inability to taper corticosteroids. The mean SLEDAI 2K score at baseline was 5.8 ± 5.0 (range 0-16). Six patients were concomitantly treated with corticosteroids (mean dose 18.3mg/day). All patients were on background SLE medications including immunosuppressives. Seven of nine patients had an overall improvement, with a decrease in SLEDAI 2K from 5.8 ± 5.0 at baseline to 3.5 ± 2.7 (range 0-8); four of five patients had improvement or resolution in arthritis, and one of two patients had resolution of inflammatory rash. Four patients discontinued corticosteroids and one patient tapered below 50% of the initial dose by 3 months of treatment with Acthar Gel. No adverse events were reported. This study suggests a role for Acthar Gel as an alternative to corticosteroids in the treatment of SLE. Acthar Gel appears to be safe and well-tolerated after 6 months of treatment, with a significant reduction in disease activity.

Adrenocorticotropic hormone gel in the treatment of systemic lupus erythematosus: A retrospective study of patients.

Objectives: Acthar Gel is a long-acting formulation of adrenocorticotropic hormone (ACTH) with anti-inflammatory effects thought to be mediated in part through melanocortin receptor activation. This study was initiated to understand the role of Acthar Gel in SLE treatment in rheumatology practices. Methods: This is a retrospective case series of nine adult female patients treated with Acthar Gel for at least six months at five academic centers. Treating physicians completed a one-page questionnaire on lupus medications, disease activity, and outcomes. Clinical response was defined using SLEDAI 2K and improvement in the clinical manifestation(s) being treated. Results: The most common clinical SLE manifestations/indications requiring therapy with Acthar Gel were arthritis, rash, and inability to taper corticosteroids. The mean SLEDAI 2K score at baseline was 5.8 ± 5.0 (range 0-16). Six patients were concomitantly treated with corticosteroids (mean dose 18.3mg/day). All patients were on background SLE medications including immunosuppressives. Seven of nine patients had an overall improvement, with a decrease in SLEDAI 2K from 5.8 ± 5.0 at baseline to 3.5 ± 2.7 (range 0-8); four of five patients had improvement or resolution in arthritis, and one of two patients had resolution of inflammatory rash. Four patients discontinued corticosteroids and one patient tapered below 50% of the initial dose by 3 months of treatment with Acthar Gel. No adverse events were reported. Conclusions: This study suggests a role for Acthar Gel as an alternative to corticosteroids in the treatment of SLE. Acthar Gel appears to be safe and well-tolerated after 6 months of treatment, with a significant reduction in disease activity.

Adrenocorticotropic hormone gel in patients with refractory rheumatoid arthritis: a case series

While many patients with rheumatoid arthritis respond to treatment with disease-modifying antirheumatic drugs, some patients have refractory disease. The mechanism of action of adrenocorticotropic hormone (ACTH) gel and its direct action on melanocortin receptors is thought to result in steroid-independent anti-inflammatory and immunomodulatory effects, in addition to steroidogenic effects. ACTH gel may provide efficacy for patients who previously failed treatment with prednisone or disease-modifying antirheumatic drugs. In this case series, we report five patients with refractory rheumatoid arthritis on ACTH gel who have failed up to five previous treatments. In these patients, ACTH gel provided improvements in inflammatory markers and/or patient-reported symptoms in each case.

Adrenocorticotropic hormone gel in the treatment of systemic lupus erythematosus: A retrospective study of patients.

Objectives: Acthar Gel is a long-acting formulation of adrenocorticotropic hormone (ACTH) with anti-inflammatory effects thought to be mediated in part through melanocortin receptor activation. This study was initiated to understand the role of Acthar Gel in SLE treatment in rheumatology practices.Methods: This is a retrospective case series of nine adult female patients treated with Acthar Gel for at least six months at five academic centers. Treating physicians completed a one-page questionnaire on lupus medications, disease activity, and outcomes. Clinical response was defined using SLEDAI 2K and improvement in the clinical manifestation(s) being treated.Results: The most common clinical SLE manifestations/indications requiring therapy with Acthar Gel were arthritis, rash, and inability to taper corticosteroids. The mean SLEDAI 2K score at baseline was 5.8 (range 0-16). Six patients were concomitantly treated with corticosteroids (mean dose 18.3mg/day). All patients were on background SLE medications including immunosuppressives. Seven of nine patients had an overall improvement, with a decrease in SLEDAI 2K to 3.5; four of five patients had improvement or resolution in arthritis, and one of two patients had resolution of inflammatory rash. Four patients discontinued corticosteroids and one patient tapered below 50% of the initial dose by 3 months of treatment with Acthar Gel. No adverse events were reported.Conclusions: This study suggests a role for Acthar Gel as an alternative to corticosteroids in the treatment of SLE. Acthar Gel appears to be safe and well-tolerated after 6 months of treatment, with a significant reduction in disease activity.

Complete Remission of Post-transplantation Recurrence of Focal Segmental Glomerulosclerosis With the Use of Adrenocorticotrophic Hormone Gel: Case Report

BackgroundPost-transplantation recurrence of primary focal and segmental glomerulosclerosis (FSGS) is estimated to occur in 30%–50% of cases and doubles the risk of allograft failure. Treatment of recurrent FSGS is challenging because specific pathogenic targets are unknown and available therapeutic options have limited efficacy. Case ReportWe report a case of recurrent FSGS with nephrotic-range proteinuria (urine protein creatinine ratio [UPCR], >50) and debilitating edema that was resistant to rituximab and plasmapheresis. The patient had a remarkable response to adrenocorticotropic hormone (ACTH) gel and achieved complete remission (UPCR, 0.5; serum albumin, 4.1 g/dL; serum creatinine, 1.0 mg/dL) which was maintained over 10 months on this treatment. ConclusionsWe conclude that ACTH gel is a potential therapeutic option for post-transplantation recurrence of FSGS and warrants further evaluation.

Treatment of Idiopathic FSGS with Adrenocorticotropic Hormone Gel

Adrenocorticotropic hormone (ACTH) has shown efficacy as primary and secondary therapy for nephrotic syndrome due to membranous nephropathy. The data on using ACTH to treat idiopathic FSGS are limited. This report describes our experience using ACTH for nephrotic syndrome due to idiopathic FSGS in the United States. Twenty-four patients with nephrotic syndrome from idiopathic FSGS were treated with ACTH gel at two academic medical centers between 2009 and 2012, either as part of investigator-initiated pilot studies (n=16) or by prescription for treatment-resistant FSGS (n=8). The primary outcome was remission of proteinuria. The median dose of ACTH was 80 units injected subcutaneously twice weekly. Treatment durations were not uniform. Twenty-two patients had received immunosuppression (mean, 2.2 medications) before ACTH therapy. Six patients had steroid-dependent and 15 had steroid-resistant FSGS. At the time of ACTH initiation, the median serum creatinine (interquartile range) was 2.0 (1.1-2.7) mg/dl, estimated GFR was 36 (28-78) ml/min per 1.73 m(2), and urine protein-to-creatinine ratio was 4595 (2200-8020) mg/g. At the end of ACTH therapy, 7 of 24 patients (29%) experienced remission (n=2 complete remissions, n=5 partial remissions). All remitters had steroid-resistant (n=5) or steroid-dependent (n=2) FSGS. Two responders relapsed during the follow-up period (mean ± SD, 70±31 weeks). Adverse events occurred in 21 of 24 patients, including one episode of new-onset diabetes that resolved after stopping ACTH and two episodes of AKI. Response to ACTH treatment among steroid-resistant or steroid-dependent patients with FSGS is low, but ACTH gel may be a viable treatment option for some patients with resistant nephrotic syndrome due to idiopathic FSGS. Further research is necessary to determine which patients will respond to therapy.

Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms

Adrenocorticotropic hormone (ACTH) has a renoprotective effect in chronic kidney disease; however, its effect on acute kidney injury (AKI) remains unknown. In a rat model of tumor necrosis factor (TNF)–induced AKI, we found that ACTH gel prevented kidney injury, corrected acute renal dysfunction, and improved survival. Morphologically, ACTH gel ameliorated TNF-induced acute tubular necrosis, associated with a reduction in tubular apoptosis. While the steroidogenic response to ACTH gel plateaued, the kidney-protective effect continued to increase at even higher doses, suggesting steroid-independent mechanisms. Of note, ACTH also acts as a key agonist of the melanocortin system, with its cognate melanocortin 1 receptor (MC1R) abundantly expressed in renal tubules. In TNF-injured tubular epithelial cells in vitro, ACTH reinstated cellular viability and eliminated apoptosis. This beneficial effect was blunted in MC1R-silenced cells, suggesting that this receptor mediates the anti-apoptotic signaling of ACTH. Moreover, ACTH gel protected mice against cecal ligation puncture–induced septic AKI better than α-melanocyte-stimulating hormone: a protein equal in biological activity to ACTH except for steroidogenesis. Thus, ACTH has additive renoprotective actions achieved by both steroid-dependent mechanisms and MC1R-directed anti-apoptosis. ACTH may represent a novel therapeutic strategy to prevent or treat AKI.

Advanced diabetic nephropathy with nephrotic range proteinuria: a pilot study of the long-term efficacy of subcutaneous ACTH gel on proteinuria, progression of CKD, and urinary levels of VEGF and MCP-1.

Background and Objective. Adrenocorticotropic hormone (ACTH) is able to reduce proteinuria in nondiabetic glomerulopathies through activation of melanocortin receptors (MCR) expressed in the podocyte. To determine the efficacy of ACTH, we conducted a randomized, open-label pilot trial of ACTH gel in patients with advanced diabetic nephropathy. Study Design. Twenty-three (23) patients with diabetic nephropathy were randomized to daily subcutaneous (SQ) injections of 16 or 32 units of ACTH gel for six months. Outcome. The primary endpoint was the percentage of patients achieving a complete remission (<300 mg/24 hours) within 6 months. Exploratory endpoints included the percentage of partial (50% reduction) remissions, changes in Cr, and urinary cytokine markers. Results. After 6 months of ACTH gel therapy, 8 of 14 (57%) patients achieved a complete (n = 1) or partial (n = 7) remission. In the low-dose ACTH gel group (16 units), urinary protein fell from 6709 + 953 to 2224 + 489 mg/24 hrs (P < 0.001). In contrast, 2 of 6 patients in the 32-unit group achieved partial remission, but aggregate proteinuria (5324 + 751 to 5154 + 853 mg/24 hours) did not change. Urinary VEGF increased from 388 to 1346 pg/mg urinary creatinine (P < 0.02) in the low-dose group but remained unchanged in the high-dose group. Conclusion. ACTH gel stabilizes renal function and reduces urinary protein for up to 6 months after treatment. The ClinTrials.gov identifier is NCT01028287.

Treatment of acute relapses in multiple sclerosis.

Multiple sclerosis (MS) is a chronic progressive inflammatory demyelinating disease affecting the central nervous system. The most common clinical type of MS tends to follow a relapsing course, affecting the vast majority of patients living with this disease. Relapses are a hallmark of MS, and are often associated with significant functional impairment and decreased quality of life. Although usually followed by a period of remission, residual symptoms after MS relapses may persist and lead to sustained disability. Adequate management of MS relapses is important, as it may help to shorten and lessen the disability associated with their course. Historically, treatment of MS relapse was the first approach (and for a period of time, the only approach) to MS treatment in general. Systemic corticosteroids and adrenocorticotropic hormone (ACTH) have broad regulatory approval and remain the most established and validated treatment options for MS relapse. Therapeutic mechanisms of ACTH were previously associated (perhaps mistakenly) with only corticotropic actions; however, recently the direct anti-inflammatory effects and immunomodulatory activity of ACTH gel acting through melanocortin pathways have been shown. Second-line treatments of steroid-unresponsive MS relapses and a possible algorithm for MS relapse management are also reviewed in this article.

Treatment of Resistant Glomerular Diseases with Adrenocorticotropic Hormone Gel: A Prospective Trial

Background: Adrenocorticotropic hormone (ACTH) has shown promising results in glomerular diseases resistant to conventional therapies, but the reported data have solely been from retrospective, observational studies. Methods: In this prospective, open-label study (NCT01129284), 15 subjects with resistant glomerular diseases were treated with ACTH gel (80 units subcutaneously twice weekly) for 6 months. Resistant membranous nephropathy (MN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS) were defined as failure to achieve sustained remission of proteinuria off immunosuppressive therapy with at least 2 treatment regimens; resistant IgA nephropathy was defined as >1 g/g urine protein:creatinine ratio despite maximally tolerated RAAS blockade. Remission was defined as stable or improved renal function with ≥50% reduction in proteinuria to <0.5 g/g (complete remission) or 0.5–3.5 g/g (partial remission). Results: The study included 5 subjects with resistant idiopathic MN, 5 subjects with resistant MCD (n = 2)/FSGS (n = 3), and 5 subjects with resistant IgA nephropathy. Two resistant MN subjects achieved partial remission on ACTH therapy, although 3 achieved immunologic remission of disease (PLA₂R antibody disappeared by 4 months of therapy). One subject with resistant FSGS achieved complete remission on ACTH; one subject with resistant MCD achieved partial remission but relapsed within 4 weeks of stopping ACTH. Two subjects with resistant IgA nephropathy demonstrated >50% reductions in proteinuria while on ACTH, with proteinuria consistently <1 g/g by 6 months. Three of 15 subjects reported significant steroid-like adverse effects with ACTH, including weight gain and hyperglycemia, prompting early termination of therapy without any clinical response. Conclusions: ACTH gel is a promising treatment for resistant glomerular diseases and should be studied further in controlled trials against currently available therapies for resistant disease.

Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case series

BackgroundEffective and tolerable treatment options for patients with dermatomyositis and polymyositis are limited. This retrospective case review describes treatment with adrenocorticotropic hormone (ACTH) gel in five patients who experienced a disease exacerbation and either failed or were unable to tolerate the side effects of previous therapy with steroids, intravenous immunoglobulins, and steroid-sparing drugs.MethodsPatients received ACTH gel subcutaneous injections of 80 U (1 mL) twice weekly (four patients) or once weekly (one patient) over the course of 12 weeks for short-term treatment of symptom exacerbations. Manual muscle testing using the Medical Research Council scale was assessed at baseline and at 3 months.ResultsImprovement was seen in all patients, including improved muscle strength, decreased pain, and resolution of skin involvement. All patients tolerated the treatment well, and no significant side effects occurred.ConclusionThe treatment of dermatomyositis and polymyositis is an approved use for ACTH gel, and these anecdotal reports would suggest consideration of ACTH gel as a therapeutic option. Further investigation is warranted.

Erratum

Erratum Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case series. Drug Des Devel Ther. 2012;6:133–139. The journal should have included the submitted complete disclosure statement in the published article. The correct text is as follows:AcknowledgmentsThe author would like to thank Lynanne McGuire, PhD, of MedVal Scientific Information Services, LLC, for providing medical writing and editorial assistance. This manuscript was prepared according to the International Society for Medical Publication Professionals’ Good Publication Practice for Communicating Company-Sponsored Medical Research: The GPP2 Guidelines.DisclosureDr Levine is a consultant for Questcor Pharmaceuticals, Inc. Funding to support the preparation of this manuscript was provided by Questcor Pharmaceuticals, Inc.

Monthly Pulse Adrenocorticotropic Hormone (ACTH) or Methylprednisolone Therapy for Long-Term Treatment of Multiple Sclerosis as an Add-On Therapy to beta-Interferons: Current Status of the Pilot Study (P04.147)

Objective: This pilot study is designed to evaluate the efficacy and safety of monthly adrenocorticotropic hormone (ACTH) treatment added to beta-interferon in breakthrough multiple sclerosis (MS) compared with monthly methylprednisolone (MP), the most commonly used therapy. Background ACTH gel is approved for treatment of MS relapses. There is mounting evidence that ACTH may have a variety of immune-modulating mechanisms relevant to the MS disease course. However, no clinical studies have evaluated ACTH pulse therapy for MS. Design/Methods: This single-center, examiner-blinded study enrolled MS patients receiving ongoing beta-interferon treatment with Expanded Disability Status Scale (EDSS) scores of 3.0-6.5 and ≥1 relapse or new T2 or Gadolinium-enhanced lesion within the previous year. Patients were randomly assigned to open-label ACTH (80 units intramuscularly once/day x 3 consecutive days) or MP (1 gram IV x 1 dose) monthly for 12 months, with assessments every 3 months. Outcomes include relapse rate (primary); EDSS, MS Functional Composite, and MS Quality of Life scores; MRI; bone density; and side effects. We report the current status of the study. Results: Of 26 patients enrolled (ACTH: n=14, mean±SD EDSS 4.4±1.4; MP: n=12, mean EDSS 4.7±1.4), 18 have ≥6 months of data (ACTH: n=10, MP: n=8). During 6 months of pulse therapy, there were 0 relapses in the ACTH group and 4 relapses (in 2 patients) in the MP group. Mean EDSS score at month 3 was 3.9±2.0 (p=0.028; n=12) for ACTH and 3.9±1.6 (p=0.058; n=10) for MP. EDSS at month 6 was 4.4±1.8 (p=0.075) for ACTH and 4.2±2.0 (p=0.401) for MP. Seventeen side effects were reported from 9 patients in the ACTH group and 13 side effects were reported by 6 patients in the MP group. Conclusions: These data suggest a potential role for ACTH pulse therapy in treating breakthrough MS. Supported by: Questcor Pharmaceuticals, Inc. Disclosure: Dr. Berkovich has received personal compensation for activities with Acorda Therapeutics, Bayer Pharmaceuticals Corporation, Biogen Idec, Teva Neuroscience and Questcor Inc. as a speaker. Dr. Berkovich has received research support from Questcor Inc. Dr. Amezcua has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Teva Neuroscience, and Serono/Pfizer Inc. Dr. Fernandez has nothing to disclose. Dr. Subhani has nothing to disclose. Dr. Kravtsova has nothing to disclose.

Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel

Purpose:A synthetic adrenocorticotropin (ACTH) analog has shown efficacy in Europe as primary and secondary therapy for nephrotic syndrome, but there is no published experience using the natural, highly purified ACTH gel formulation, available in the United States, for nephrotic syndrome. We therefore investigated the use of ACTH gel for nephrotic syndrome in the United States.Patients and methods:Twenty-one patients with nephrotic syndrome treated with ACTH gel outside of research settings in the United States, with initiation of therapy by December 31, 2009, allowing a minimum 6 months follow-up. We defined complete remission as stable renal function with proteinuria falling to <500 mg/day, and partial remission as stable renal function with >50% reduction in proteinuria from 500 to 3500 mg/day.Results:Twenty-one patients with nephrotic syndrome were treated: 11 with idiopathic membranous nephropathy (iMN), 4 with membranoproliferative glomerulonephritis (MPGN), 1 with focal segmental glomerulosclerosis (FSGS), 1 with minimal change disease (MCD), 1 with immunoglobulin A (IgA) nephropathy, 1 with class V systemic lupus erythematosus (SLE) glomerulonephritis, 1 with monoclonal diffuse proliferative glomerulonephritis, and 1 with unbiopsied nephrotic syndrome. ACTH was used as primary therapy for 3 patients; the remaining patients had previously failed a mean 2.3 immunosuppressive regimens. Eleven patients achieved a complete or partial remission, with 4 (19%) in complete remission. Of the 11 patients who achieved remission, 9 had iMN, 1 had FSGS, and 1 had IgA nephropathy. Of the 11 patients with iMN, 3 (27%) achieved complete remission and 6 (55%) achieved partial remission despite having previously failed a mean 2.4 therapies. Five patients reported steroid-like adverse effects, but there were no severe infections. The limitations were retrospective data analysis with short-term follow-up.Conclusion:ACTH gel may be a viable treatment option for resistant nephrotic syndrome due to membranous nephropathy. Short-term data suggest that remission rates may approach 80%.

Positive gallium scan in the syndrome of opsoclonus—myoclonus treated with adrenocorticotropic hormone

The syndrome of opsoclonus and myoclonus may be the first presenting symptom of neuroblastoma. The disorder is often controlled by treatment with adrenocorticotropic hormone (ACTH). A child with this disorder and treated with ACTH gel had abnormal uptake of 67Ga in both adrenal glands during studies to attempt to detect an occult neuroblastoma. Repeat 67Ga scans proved to be normal once the ACTH was discontinued and the patient was treated with prednisone. It is concluded that ACTH stimulation of normal adrenal tissue was responsible for these abnormal findings.

Regulation of aldosterone biosynthesis during sodium deficiency. Evidence for an essential role of the pituitary gland.

The aldosterone response to adrenocorticotropic hormone (ACTH) and angiotensin II (AII) was evaluated in patients with pituitary insufficiency before and after dietary sodium restriction (10 mEq Na+/day for 12 days). On normal sodium intake, plasma aldosterone concentration and plasma cortisol concentration failed to change from control levels in response to a single injection of ACTH or to a continuous 1-hour infusion of AII in patients with pituitary insufficiency. In response to dietary sodium restriction for 12 days, plasma renin activity (PRA) increased fivefold in patients with pituitary insufficiency, while plasma aldosterone concentration failed to increase significantly, averaging 11.0 +/- 3.1 before and 12.3 +/- 3.7 ng/dl (ns, p greater than 0.05) after sodium deficiency. Although aldosterone secretion failed to increase during sodium deficiency, the patients came into balance at 10 mEq without a significant change in arterial blood pressure (BP). In sharp contrast to the lack of aldosterone response to ACTH before sodium deficiency, plasma aldosterone concentration increased markedly from 12.9 +/- 3.3 to 156 +/- 17.3 ng/dl (p less than 0.001) in response to ACTH after sodium deficiency. Although the adrenal glomerulosa cells were markedly sensitive to ACTH during sodium deficiency, they remained almost totally refractory to AII since aldosterone secretion failed to increase significantly in response to continuous infusion of a pressor dose of AII for 1 hour. Replacement therapy with ACTH gel for 3 months in patients with pituitary insufficiency failed to restore a normal aldosterone response to either ACTH or AII. These data demonstrate that some non-ACTH pituitary factor(s) is essential for a normal aldosterone response to ACTH, AII, and sodium deficiency.