Synacthen

Human adrenocorticotrophin (ACTH), a peptide hormone consisting of 39 amino acid residues (Fig. 5.3a) was identified as an important factor of the hypothalamus-pituitary-adrenal system in the 1950s, and numerous studies have been conducted ever since to elucidate its struc-ture, plasma concentrations, structure-activity relationships, degradation products, and synthetic analogues.ACTH was shown to 

In contrast to Synacthen, ACTH yielded a significantly different product ion mass spectrum that is predominantly composed by b-ions (Fig. 5.4b). ACTH bears an extended and acidic C-terminus compared to Synacthen, which was suggested to provoke the location of charges 

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The short Synacthen (tetracosactide) test is the most commonly used test for assessing adrenal suppression. The potential of a simpler and more cost-effective procedure, the morning salivary cortisol concentration, as an out-patient screening tool to detect adrenal suppression in... 

Patel RS, Shaw SR, McIntyre HE, McGarry GW, Wallace AM. Morning salivary cortisol versus short Synacthen test as a test of adrenal suppression. Ann Chn Biochem 2004 41 408-10. 

Glass D, Nuki G, Daly JR. Development of antibodies during long-term therapy with corticotrophin in rheumatoid arthritis. II. Zinc tetracosactrin (Depot Synacthen). Ann Rheum Dis 1971 30(6) 593-6. 

The N-terminal tetracosapeptide of ACTH (Synacthen) finds therapeutic application in the treatment of arthrorheumatism, bronchial asthma, and nephroses. 

Diagnostic use as a test of the capacity of the adrenal cortex to produce cortisol with the short test, the plasma cortisol (hydrocortisone) concentration is measured before and after an i.m. injection of tetracosactride (Synacthen) a normal response is a rise of more than 200 nanomol/1 in the plasma concentration of hydrocortisone. Longer variants of the test in cases of difficulty involve use of the depot (sustained-release) formulation i.m. For example, 1 mg of the depot is injected daily for 3 days at 9.00 am, with a short tetracosactride test performed on day 3. 

Tetracosactride Zinc Injection (Synacthen Depot) in which the hormone is adsorbed on to zinc phosphate from which it is slowly released. This is the form used in the long tetracosactride test. 

Two patients, a 29-year-old woman and a 10-year-old girl, developed Cushingoid features after taking Shen Loon for 4 and 5 months respectively (138). Their morning plasma cortisol concentrations were increased and adrenal suppression was confirmed by a short Synacthen test. Both recovered after withdrawal of the remedy and treatment with prednisone. 

INHIBITORS may enhance sympathetic activity. Synacthen tetracosactrin. 

Protocol for the Rapid Adrenocorticotropic Hormone (ACTH) (Synacthen) Test... 

Procedure A baseline blood sample is drawn for determination of serum cortisol concentration then 250p,g of Synacthen (1-24 ACTH) is given intramuscularly or intravenously. Further samples for serum cortisol determination are drawn 30 and 60 minutes after injection. 

Procedure ACTH gel, 80U/day, is injected for 3 days. This is followed by a standard 8-hour infusion of ACTH (250 p.g of Synacthen over 8 hours). Urinary free cortisol and serum cortisol are measured daily. 

It is essential that a Synacthen test is performed in this patient to exclude or confirm the diagnosis of adrenal failure. As the patient has severe skeletal muscle pain the creatine kinase should be measured as the hyperkalaemia may be due to potassium released from damaged muscle. If rhabdomyolysis were detected, it would be important to monitor renal function and calcium status carefully. 

Administration of a synthetic ACTH preparation (Synacthen) stimulates the adrenal cortex. An impaired cortisol responscloSynaclhen is seen in Addison s disease (primary adrenal failure). 

The short Synacthen test indicates the ability of the adrenal cortex to respond to ACTH (Fig. 3). Synacthen. a synthetic... 

Normally, the resting value is within the reference range (280-720 nmol/l at 08.(X)-I0.IX) am). An acceptable basal concentration is >22.3 nmol/l. There should be an increment of more than 200 nmol/l after Synacthen and the final... 

A short Synacthen lest was perfomied and the semm cortisol was less than 60 nmol/l both before and after an intravenous injection of 0.25 mg of Synacthen. 

The Synacthen test Is used in diagnosis of primary adrenocortical failure. 

Cosyntropin. a -u-Conicotropin "-corticotro -pin tetracosactide tetraeosactrin Actholain Cortrosinta Cortrosyn Synacthen, mol wt 2,933.57, C... 

Finally in our initial trial of Synacthen, 107 asthmatics nonallergic to ACTH, received )5-l,24-corticotrophin, for 21 patients in its ordinary form, and for 86 in depot form. A total of 10 incidents were observed, 7 difficult to interpret, while 3 were likely to be allergic accidents. The new synthetic jS-l,24-corticotrophin causes a very low number of allergic incidents. However, we have to keep in mind the possibility of these incidents and one should ask every patient have you had any incident before, from Synacthen , especially if intravenous infusion of j8-l,24-cor-ticotrophin is planned. 

The diagnosis is not difficult. The one problem is not to forget to ask the patient have you experienced any incident after your previous injections of Synacthen It is often more difficult, as we have just stated, to appreciate the nature of the accident direct histamine release or type I allergy Skin tests, if properly used, give very interesting information. If they are positive with 1 100 or 1 1,000 dilutions, they confirm that the patient is sensitive to J -l,24-corticotrophin (Fig. 3) but this can be due either to allergy or to histamine release by the mast cells of the skin. 

Placebo-controlled studies Prolonged-release melatonin 2 mg at night (Circadin ) has been compared with placebo in a 6-month study of 791 adults with primary insomnia, of whom 534 took melatonin in the extension phase [45. The incidence and type of adverse events with melatonin and placebo were similar. Melatonin had no effect on vital signs, physical examination, electrocardiography, or laboratory tests, including prolactin, ACTH, T3, free T4, TSH, LH, FSH, estradiol in women, free and total testosterone in men, and cortisol before and after a Synacthen test. One patient taking melatonin had bouts of palpitation. There were no withdrawal effects after withdrawal of long-term melatonin. 

The N-terminal 24 amino acids which are essential for biological activity have been synthesized (Synacthen) and are used extensively in diagnosis and treatment. 

Low plasma cortisol levels and high levels of ACTH are found. One of the essential findings is that the patient does not respond in the Synacthen stimulation test. Other biochemical findings are hypoglycaemia and hyponatraemia. 

The synacthen stimulation test illustrates the principle behind these tests. In normal persons, administration of synacthen (a synthetic form of ACTH) results in stimulation of the adrenal cortex and a subsequent rise in the plasma cortisol level. When there is adrenocortical hypofunction, as in Addison s disease, the rise in the plasma cortisol level doe not occur or is markedly reduced. 

Synacthen (tetracosactrin) is a synthetic peptide having ACTH activity. It is used in the diagnosis of adrenocortical hypo-function. Injection of synacthen should normally result in an increase in plasma cortisol levels after 30 minutes as a result of stimulation of the adrenal gland. An impaired response suggests adrenocortical hypofunction. A further test may then be performed in order to distinguish between primary adrenocortical hypofunction (Addison s disease) and secondary adrenocortical hypofunction. This consists of three injections of synacthen on successive days. An improvement in cortisol production indicates secondary adrenocortical hypofunction. No improvement occurs if there is primary adrenocortical insufficiency. 

The incidence of h3q)othalamic-pituitary-adrenal axis suppression caused by concomitant administration of itraconazole and inhaled fluticasone was assessed by synacthen tests in 12 patients with cystic fibrosis receiving both medica-hons versus 12 patients on fluticasone alone [2 ]. The concomitant use of the above medications caused moderate to severe axis suppression in 5/12 patients. In contrast, fluticasone alone, only caused mild suppression in 2/12 controls. Neither itraconazole levels nor fluticasone dose appeared to be correlated with the degree of adrenal suppression. 

Depot Synacthen-tetracosactidc zinc phosphate DFP-dyflos... 

Thevis, M., BredehOft, M., Geyer, H., Kamber, M., Delahaut, R, and Schanzer, W. (2006) Determination of Synacthen in human plasma using immunoaffinity purification and liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry, 20, 3551-3556. 

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