Adrenocorticotropic Hormone Group Research Articles

Multicenter long‐term follow‐up of children with idiopathic West syndrome: ACTH versus vigabatrin

Long-term follow-up of children with idiopathic West syndrome (WS) treated with adrenocorticotropic hormone (ACTH) or vigabatrin. Records of 28 normal magnetic resonance imaging (MRI) WS cases were reviewed for seizure development and cognitive outcome in relation to treatment type and lag. Average age at disease onset was 5.5 months, and average lag time to treatment was 25 days. Fourteen patients were treated with ACTH (eight early and six late), and 14 with vigabatrin (without delay). Response rates were 88% for ACTH and 80% for vigabatrin. Short-term outcomes for seizure cessation and electroencephalography normalization were identical between the groups. In the long-term, early ACTH treatment was better than the rest combined. Average follow-up time was 9 years. A normal cognitive outcome was achieved in 100% of the early-ACTH group, 67% of the late-ACTH group and 54% of the vigabatrin group (P = 0.03). Seizures subsequently developed in 54% of the vigabatrin group, in 33% of the late ACTH group, and 0% of the early ACTH group (P < 0.05). Idiopathic WS with normal MRI is associated with a good cognitive outcome. Early ACTH treatment, administered within 1 month, yields a better cognitive and seizure outcome than vigabatrin or late ACTH.

Effects of continuous elevated cortisol concentrations during oestrus on concentrations and patterns of progesterone, oestradiol and LH in the sow

This study investigated the effect of continuous elevated cortisol concentrations during standing oestrus on time of ovulation and patterns of progesterone, oestradiol and luteinising hormone (LH) in sows. The elevation of cortisol concentrations was achieved through repeated intravenous injections of synthetic adrenocorticotropic hormone (ACTH) every 2 h for approximately 48 h, from the onset of the second standing oestrus after weaning. Treatment was terminated when ovulation was detected (monitored by transrectal ultrasonography every 4 h) or when the sow had received a maximum of 24 injections. The dose of ACTH (2.5 μg/kg) was chosen to mimic the cortisol concentrations seen during mixing of unfamiliar sows. The sows ( n = 14) were surgically fitted with jugular vein catheters and randomly divided into a control (C group where only NaCl solution were injected) or an ACTH group. Blood samples were collected every 2 h. In parallel with the blood sampling, saliva samples for cortisol analyses were taken from eight sows before onset of treatment and from four of the sows during treatment. There was no difference in time from onset of standing oestrus to ovulation between the two groups. The interval between the peaks of oestradiol and LH to ovulation was prolonged in the ACTH group compared to the C group ( p < 0.05), with a tendency towards an earlier decline of oestradiol in the ACTH group. Cortisol and progesterone concentrations were significantly elevated during treatment in the ACTH group ( p < 0.001), with cortisol peak concentrations occurring between 40 and 80 min after each ACTH injection. Cortisol concentrations in saliva and plasma were highly correlated ( p < 0.001). In conclusion, elevated cortisol concentrations from the onset of standing oestrus increase progesterone concentrations and prolong the interval between oestradiol and LH peaks to ovulation, the latter possible due to an early decline in oestradiol concentrations and a change of the LH peak outline. The effect these hormonal changes have on reproductive performance need to be further investigated. Saliva samples might be a useful and non-invasive method to assess cortisol concentrations in sows.

Comparative effects of Nitrazepam and ACTH on the treatment of infantile spasm.

Objective Infantile spasms (IS) or West syndrome is a convulsive disease characterized by brief, symmetric axial muscle contractions (neck, trunk, and/or extremities). The therapy universally recognized as most effective in the treatment of IS, is treatment with the adrenocorticotropic hormone (ACTH) or oral corticosteroids. This therapy however has important side effects. Many studies have sought to find alternative therapies with fewer side effects. Nitrazepam, it has been proven, can be as effective as ACTH in controlling infantile spasms. The aim of this study was to evaluate and compare the efficacy of Nitrazepam and ACTH on the treatment of infantile spasms. Materials & Methods This randomized controlled clinical trial, enrolled sixty patients with newly diagnosed and previously untreated IS; diagnosis was made based on the criteria of The International Classification of Epilepsies of the International League Against Epilepsy (ILAE). Prior to treatment, all patients underwent Electro encephalo graphs (EEGs) and CT scans. Patients were randomized to receive 0.5-1 mg/kg Nitrazpam (NZP) in three daily doses or 40 IU Depot ACTH in a single morning dose. Complete cessation of spasms was considered to be as optimal response. Results Of the sixty patients studied, 24 (40%) were girls and 36(60%) were boys. All patients in the both groups were matched for age and sex.There were no differences between the both groups regarding age and sex (non-significant). Following treatments, at the end of the 6-week duration therapy, optimal response (Cessation of spasms) was obtained in 19 (63%) patients of NZP group and 9 (30%) patients of ACTH group, (P 0.05). Conclusion This study supports the belief that NZP offers an effective and possibly safer therapy than ACTH, for the management of IS and that the therapeutic response, if imminent, can be detected within 4-6 weeks of treatment. Clinicians should consider using NZP as a first-line therapy for IS.

A high dose of vitamin E inhibits adrenal corticosterone synthesis in chickens treated with ACTH.

The present experiment was conducted to study the effects of dietary vitamin E on plasma corticosterone (CTC) concentration and adrenal steroid syntheses in chickens treated with adrenocorticotropic hormone (ACTH). Chickens were divided into ACTH(-) and ACTH(+) groups, and each group was further divided into three subgroups administered with vitamin E (500 or 5,000 mg/kg diet) and without the vitamin. Vitamin E (DL-alpha-tocopheryl acetate) was mixed with the basal diet at levels of 500 and 5,000 mg/kg and fed for 6 d. ACTH (20 IU/kg body weight) was given daily by intraperitoneal injection for 5 d. alpha-Tocopherol levels in the plasma and adrenal gland were markedly elevated by vitamin E feeding, and the level of adrenal free cholesterol (CHOL), which is used for steroid synthesis, was significantly decreased by vitamin E feeding in a dose-dependent manner. However, the level of adrenal CHOL ester was unchanged by any treatment. The elevations of pregnenolone, progesterone and CTC levels in the adrenal gland of chickens with ACTH treatment were decreased by vitamin E administration. The elevation of plasma CTC concentration in the ACTH(+) group was dramatically decreased by vitamin E administration, while that concentration was not influenced by the vitamin administration in the ACTH(-) group. These findings indicate that vitamin E suppresses the elevation of the plasma CTC concentration due to ACTH in chickens, possibly by inhibiting the conversion of CHOL ester to free CHOL in the adrenal gland.

Liposteroid (Dexamethasone Palmitate) Therapy for West Syndrome: A Comparative Study With ACTH Therapy

Dexamethasone palmitate (liposteroid) was used for the treatment of West syndrome and compared with adrenocorticotropic hormone (ACTH) therapy. A single intravenous injection of liposteroid (0.25 mg/kg) was administered seven times in 3 months (total dosage = 1.75 mg/kg) to five symptomatic patients with West syndrome, aged 4-11 months. ACTH (0.025 mg/kg/day) was administered intramuscularly for 6 weeks according to the conventional therapy in Japan (total dosage = 0.625 mg/kg) to five symptomatic patients with West syndrome, aged 6-10 months. Nodding spasm and hypsarrhythmia on EEG disappeared in all patients in the liposteroid therapy group within four doses; however, partial seizures and focal spikes on EEG reappeared in three patients 2 months after the end of liposteroid therapy. In the ACTH therapy group, nodding spasm and hypsarrhythmia on EEG similarly disappeared during treatment in all patients, but nodding spasm reappeared 2 months after therapy in two patients and partial seizures reappeared in one patient 3 months after therapy. No notable adverse reactions occurred in the liposteroid group, but transient dysfunction of the thyroid and anterior pituitary gland and increased levels of serum cortisol were experienced in the ACTH group. These results suggest that glucocorticoid incorporated in a lipid emulsion is useful for the treatment of West syndrome.

Comparison of parenteral adrenocorticotropic hormone with oral indomethacin in the treatment of acute gout

One hundred male patients who presented with acute gouty arthritis were alternately assigned to 2 treatment groups. Seventy-six patients completed the study protocol, in which each gout attack during a 1-year period was treated. For each gout episode, 36 patients received a single intramuscular injection of 40 IU of adrenocorticotropic hormone (ACTH), and 40 patients received oral indomethacin, 50 mg 4 times daily with meals, until the pain abated. The time interval until the pain was relieved, as well as any untoward effects, were recorded for each gout attack treated. Both groups were of similar age, and had similar values for intercritical serum uric acid, 24-hour urinary uric acid, and creatinine clearance (1 month after entry into the study). The mean interval (+/- SD) to relief of pain was significantly shorter for the ACTH group (3 +/- 1 hours) than for the indomethacin group (24 +/- 10 hours). No side effects were noted in the ACTH group. However, of the 40 patients receiving indomethacin, 22 had abdominal discomfort of dyspepsia, 15 had headaches, and 12 had difficulty with mentation. Single-dose parenteral ACTH appeared to be effective more rapidly and was associated with fewer side effects than oral indomethacin in the treatment of acute gout.

Antibody and gland studies in cortisone and ACTH-injected birds

Chicks were injected intramuscularly with 2.5 or 7.5 mg cortisone acetate (CA) two times a day for the first 5 days after hatching or i.m. injected once a day for the same period with 4 or 8 USP units of adrenocorticotropic hormone (ACTH). Body and bursa weights were significantly reduced 12 hr after the last injection of CA or ACTH. The mean weight of the spleen was significantly reduced in the CA-treated birds. The number of splenic germinal centers was reduced in the 7.5-mg CA birds. Adrenal weight and adrenal cholesterol were significantly increased and decreased, respectively, 12 hr after the last injection of ACTH. The bursa and thymus of approximately 3- and 6-week-old chicks from the CA and ACTH groups appeared, on histologic examination, to have recovered from the regressive influence of these hormones. The antibody response to BSA was significantly reduced in 4 ½ to 5-week-old birds from the 7.5 mg CA group while the mean antibody titer of the birds from the 2.5-mg CA and ACTH groups were similar to their respective controls. On the other hand, a primary injection of BSA into 8-week-old birds from the 7.5-mg CA group produced precipitin levels comparable to the antibody titer of control birds. The delay in normal antibody response of birds in the 7.5 mg CA group may, in part, be explained by an interference with normal bursa development.

Antibody and Gland Studies in Cortisone and ACTH-Injected Birds

Summary Chicks were injected intramuscularly with 2.5 or 7.5 mg cortisone acetate (CA) two times a day for the first 5 days after hatching or i.m. injected once a day for the same period with 4 or 8 USP units of adrenocorticotropic hormone (ACTH). Body and bursa weights were significantly reduced 12 hr after the last injection of CA or ACTH. The mean weight of the spleen was significantly reduced in the CA-treated birds. The number of splenic germinal centers was reduced in the 7.5-mg CA birds. Adrenal weight and adrenal cholesterol were significantly increased and decreased, respectively, 12 hr after the last injection of ACTH. The bursa and thymus of approximately 3- and 6-week-old chicks from the CA and ACTH groups appeared, on histologic examination, to have recovered from the regressive influence of these hormones. The antibody response to BSA was significantly reduced in 4 ½ to 5-week-old birds from the 7.5 mg CA group while the mean antibody titer of the birds from the 2.5-mg CA and ACTH groups were similar to their respective controls. On the other hand, a primary injection of BSA into 8-week-old birds from the 7.5-mg CA group produced precipitin levels comparable to the antibody titer of control birds. The delay in normal antibody response of birds in the 7.5 mg CA group may, in part, be explained by an interference with normal bursa development.