cosyntropin and Syndrome

To report a prospectively planned analysis of two randomised controlled trials with embedded comparisons of prednisolone versus tetracosactide depot for the treatment of infantile epileptic spasms syndrome (IESS).. Individual patient data from patients randomly allocated to prednisolone or tetracosactide depot were analysed from two trials (UKISS, ICISS). The comparison was embedded within trials in which some patients also received vigabatrin but only patients receiving monotherapy with randomly allocated hormonal treatments are included in this analysis. The main outcome was cessation of spasms (Days 13-14 after randomisation). Lead time to treatment and underlying aetiology were taken into account. Cessation of spasms on Days 14-42 inclusive, electroclinical response (EEG Day 14), plus developmental and epilepsy outcomes (at 14 months in UKISS and 18 months in ICISS) are also reported. Minimum treatment was prednisolone 40 mg per day for two weeks or tetracosactide depot 0·5 mg IM on alternate days for two weeks, all followed by a reducing dose of prednisolone over two weeks.. 126 infants were included in this study. On tetracosactide depot, 47 of 62 (76%) were free of spasms on Days 13-14 compared to 43 of 64 (67%) on prednisolone (difference 9%, 95% CI -7·2% to +25·2%, chi square 1·15, p = 0·28). For Day 14-42 cessation of spasms, on tetracosactide depot, 41 of 61 (67%) were free of spasms compared to 35 of 62 (56%) on prednisolone (difference 11%, 95% CI -6·4% to +28·4%, chi square 1·51, p = 0·22). There was no significant difference in mean VABS score between infants who received prednisolone compared with those who received tetracosactide depot (74·8 (SD 18·3) versus 78·0 (SD 20·2) t = -0·91 p = 0·36). The proportion with ongoing epilepsy at the time of developmental assessment was 20 of 61 (33%) in the tetracosactide group compared with 26 out of 63 (41%) in the prednisolone group (difference 8%, 95% CI -9·2% to +25·2%, Chi [2] 0·95, p = 0·33).. With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome.

Topics: Anticonvulsants; Cosyntropin; Epilepsy; Humans; Infant; Prednisolone; Randomized Controlled Trials as Topic; Spasm; Spasms, Infantile; Syndrome; Treatment Outcome; Vigabatrin

A 6 year-old Chinese boy with Kabuki syndrome presented with hypoglycemic seizure. He was diagnosed to have isolated adrenocorticotropin deficiency. To our knowledge, this is the first case of Kabuki syndrome with isolated adrenocorticotropin deficiency in the literature.

Topics: Abnormalities, Multiple; Adrenocorticotropic Hormone; Child; Corticotropin-Releasing Hormone; Cosyntropin; Dermatoglyphics; Fingers; Hormones; Humans; Hypoglycemia; Hyponatremia; Intellectual Disability; Male; Seizures; Syndrome; Water-Electrolyte Imbalance

Activating mutations of the ACTH receptor have not been previously described. We investigated a 69-year-old woman with normal blood cortisol but undetectable blood ACTH concentrations. The aim of this study was to evaluate her hypothalamo-pituitary-adrenal axis by measuring circadian variation in blood ACTH and cortisol, and by performing CRH and ACTH stimulation and dexamethasone suppression tests. We also examined biological activity of her circulating blood ACTH using bovine adrenocortical cell suspensions and ACTH receptor gene structure by Northern blotting analysis.. Random plasma cortisol concentrations ranged from 182 to 328 nmol/l, while ACTH concentrations were always undetectable. After an intravenous bolus injection of human CRH 100 micrograms, plasma ACTH rose slightly, while plasma cortisol increased appropriately. ACTH stimulation tests revealed that a small amount of ACTH (5 ng/kg b.w.) had the maximal cortisol stimulatory activity, and even smaller amounts of ACTH (0.5 and 0.05 ng/kg b.w.) produced significant increases in cortisol levels. ACTH bioassay of the patient's plasma demonstrated weak biological activity in the HPLC fractions which corresponded to the band of synthetic human ACTH 1-39. The ACTH receptor coding region was amplified by polymerase chain reaction using the leucocyte genomic DNA. There were two base mutations; cysteine 21-->arginine and serine 247-->glycine in the sequences coding for the first extramembranous N-terminal domain and the third extramembranous loop of the ACTH receptor.. This patient with normal blood cortisol but undetectable ACTH levels showed increased adrenocortical sensitivity to ACTH and two point mutations in the ACTH receptor gene. This study, therefore, reports a previously undescribed syndrome--ACTH hypersensitivity syndrome--and provides insights into the molecular mechanism of ACTH receptor action.

Topics: Adrenal Cortex Function Tests; Adrenocorticotropic Hormone; Aged; Aldosterone; Biomarkers; Corticotropin-Releasing Hormone; Cosyntropin; Dehydroepiandrosterone; Female; Glossitis; Humans; Hydrocortisone; Point Mutation; Polymerase Chain Reaction; Receptors, Corticotropin; Reference Values; Sequence Analysis, DNA; Stomatitis, Aphthous; Syndrome

In many animal species, the ICV injection of ACTH and of several shorter sequences of the ACTH molecule (melanocortin peptides) induces a peculiar behavioral syndrome mainly characterized by excessive grooming and by repeated acts of stretching and yawning. In adult males, spontaneous penile erections with ejaculation are also induced. We have studied the effect of NO synthase inhibition on this behavioral syndrome. The IP injection of the NO synthase inhibitor L-NG-nitroarginine methyl ester (NAME) significantly prevented--at the doses of 50 and 100 mg/kg--all the behavioral symptoms induced by the ICV administration of ACTH(1-24) (4 micrograms/rat). On the other hand, the ICV injection of NAME (up to 300 micrograms/rat) had no influence on the ACTH-induced excessive grooming and stretching, while significantly inhibited the display of yawnings and penile erections. These data indicate that brain NO synthase is involved in the mechanism of ACTH-induced yawning and penile erections, whereas peripheral NO synthase is involved in the induction of stretching and grooming.

Topics: Animals; Arginine; Behavior, Animal; Cosyntropin; Enzyme Inhibitors; Grooming; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Penile Erection; Rats; Rats, Wistar; Syndrome; Yawning

We report two children of a family with congenital adrenocortical unresponsiveness to ACTH. Repeated stimulation of the adrenal by Synthetic 1-24 ACTH (Synacthen) failed to increase cortisol secretion, but produced significant rises of serum aldosterone. This was, however, associated with increased plasma renin activity. Only when the renin-angiotensin effect was eliminated, by a converting enzyme blocker, did Synacthen fail to affect serum aldosterone. These data support the view that glucocorticoid deficiency in this disorder results from unresponsiveness to ACTH and that development of the zona glomerulosa and normal aldosterone secretion is achieved by action of the renin-angiotensin system.

Topics: Adrenal Cortex; Adrenal Cortex Diseases; Adrenal Cortex Function Tests; Aldosterone; Captopril; Cosyntropin; Glucocorticoids; Humans; Hydrocortisone; Infant; Infant, Newborn; Male; Renin; Syndrome