Adrenocortical Function

Prenatal diagnosis and fetal therapy of affected female fetuses may be desirable since corrective surgery of external genitalia is not always optimal. Oral administration of a synthetic glucocorticoid (dexamethasone, which crosses the placenta) to the mother during pregnancy can limit the virilization of a female fetus. Dexamethasone is used instead of cortisol because cortisol does not readily cross the placental barrier. 

Deficiency of 17a-hydroxylase (CYP17), the enzyme required for formation of cortisol and androgens, also causes congenital adrenal hyperplasia. The genetic defect also affects the gonads, which consequently cannot synthesize androgens or estrogens. Thus, the anterior pituitary increases its output of ACTH, LH, and FSH. 

Steroidogenic pathways in ITa-hydroxylase (CYP17) deficiency. Synthesis of steroids within the boxed area is diminished as a result of deficiency in the enzyme. Production of those steroids will increase outside the boxed area. 

Steroidgenic pathways in 1 lj8-hydroxylase CYPBl and CYPB2 deficiency. A CYPl IB 1 defect causes a deficiency of cortisol and the disorder congential adrenal hyperplasia (CAH). A CYPl 1B2 defect causes an aldosterone deficiency. Synthesis of steroids within the boxed areas is decreased and steroids outside the boxed area increased, respectively, for each enzyme deficiency. 

Excess Inappropriately large amounts of aldosterone or cortisol result from a disturbance at the level of the adrenals (primary) or of the regulation of adrenal function (secondary). 

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Neuromedin U is a neuropeptide which is widely distributed in the gut and central nervous system. Peripheral activities of neuromedin U include stimulation of smooth muscle, increase in blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. The actions of neuromedin U are mediated by G-protein coupled receptors (NMU1, NMU2) which are coupled tO Gq/11. 

Corticotropin is used for diagnostic testing of adrenocortical function. This drug may also be used for the management of acute exacerbations of multiple sclerosis, nonsuppurative thyroiditis, and hypercalcemia associated with cancer. It is also used as an anti-inflammatory and immunosuppressant drug when conventional glucocorticoid therapy lias not been effective (see Display 50-1). 

Schimmer, B. (1980). Cyclic nucleotides in adrenocortical function. Adv. Cyclic Nucleotide Res. 13, 181-214. 

F20. Fukata, J., Imura, H and Nakao, K Cytokines as mediators in the regulation of the hypothalamic-pituitary-adrenocortical function. / Endocrinol. Invest. 16, 141-155 (1993). 

A5. Anonymous, Pantothenic acid and adrenocortical function. Nutrition Revs. 18, 3-4 (1960). 

Tetracosactide (tetracosactrin) is an analogue of corticotrophin (ACTH) and is used to test adrenocortical function. It is administered by intramuscular injection. Side-effects are very similar to those with corticosteroids. 

In conventional doses, thiopentone has no effect on hepatic, renal or adrenocortical function. Adverse effects... 

Onset of unconsciousness is rapid but it is associated with a high incidence of excitatory effects, comparable to methohexitone, but these can be reduced by prior administration of an opioid. Analogous to the barbiturates, etomidate decreases CMR02, CBF and ICP but the haemodynamic stability of the drug will maintain CPP. Its well-known inhibition of adrenocortical function limits its clinical usefulness for long-term control of elevated ICP. While etomidate can produce convulsion-like EEC potentials in the absence of apparent convulsions, it has been used to terminate status epilepticus. 

Aqueous nasal triamcinolone spray 220 or 440 micrograms od for the treatment of allergic rhinitis reportedly had no measurable adverse effects on adrenocortical function in 80 children (aged 6-12 years) in a placebo-controlled, double-blind study (442). Plasma triamcinolone concentrations measured over 6 hours fell rapidly and there was little or no accumulation during 6 weeks. 

Nayak AS, Ellis MH, Gross GN, Mendelson LM, Schenkel EJ, Lanier BQ, Simpson B, Mullin ME, Smith JA. The effects of triamcinolone acetonide aqueous nasal spray on adrenocortical function in children with allergic rhinitis. J Allergy Clin Immunol 1998 101(2 Part l) 157-62. 

Adrenocortical function has been assessed in a randomized trial after intravenous etomidate in 30 patients who required rapid-sequence induction and tracheal intubation (402). The controls received midazolam. Etomidate caused adrenocortical dysfunction, which resolved after 12 hours. 

Vanacker B, Wiebalck A, Van Aken H, Sermeus L, Bouillon R, Amery A. Induktionsqualitat und Nebennierenrindenfunktion. Ein klinischer Vergleich von Etomidat-Lipuro und Hypnomidate. [Quality of induction and adrenocortical function. A clinical comparison of Etomidate-Lipuro and Hypnomidate.] Anaesthesist 1993 42(2) 81-9. 

Mitotane. Although the exact mechanism of this drug is unknown, mitotane (Lysodren) selectively inhibits adrenocortical function. This agent is used exclusively to treat carcinoma of the adrenal cortex. 

Corticotropin (corticotrophin adrenocorticotrophin ACTH) is a straight-chain polypeptide with39 amino acid residues, and its function is to control the activity of the adrenal cortex, particularly the production of corticosteroids. Secretion of the hormone is controlled by corticotropin-releasing hormone (CRH) from the hypothalamus. ACTH was formerly used as an alternative to corticosteroid therapy in rheumatoid arthritis, but its value was limited by variable therapeutic response. ACTH may be used to test adrenocortical function. It has mainly been replaced for this purpose by the synthetic analoguetetracosactide (tetracosactrin) (Figure 7.10), which contains the first 24 amino acid residues of ACTH, and is preferred because of its shorter duration of action and lower allergenicity. 

Al. Anderson, J., Brewis, E. G., and Taylor, W., Adrenocortical function in hyper-calcaemia of infancy. Arch. Disease Childhood 32, 114-119 (1957). 

Fuller RW. Serotonin receptors involved in regulation of pituitary-adrenocortical function in rats. Behav Brain Res 1996 73 215-219. 

Definitive diagnosis is achieved by the measurement of VLCFA in plasma. The results of this analysis are abnormal in nearly all males with X-ALD. The specific analyses that are included are the concentration of C26 0, the ratio of C24 0/C22 0, and the ratio of C26 0/C22 0, all of which are elevated in most cases. Increased concentration of VLCFA in plasma and/or cultured skin fibroblasts also is present in approximately 85% of female carriers, although identification of carriers is now available using molecular methods which are more reliable. Testing of at-risk family members is recommended and can identify affected males who may be candidates for therapy (see Therapy). In addition, it facilitates assessment of adrenocortical function in biochemically affected males, permitting treatment of those with adrenal insufficiency. This testing is accomplished byACTH stimulation. 

Both forms of PEM are associated with hy-percortisolemia.The level of cortisol in kwashiorkor is lower, however, than in marasmus, likely due to decreased adrenocortical function caused by low protein intake (and not adrenal failure). If a sufficiently high level of cortisol is not maintained, then adequate muscle protein is not mobilized to sustain hepatic protein synthesis. Indeed, hypoproteinemia, evident by the decreased serum albumin and transferrin levels, is more acute in kwashiorkor than marasmus. 

In the safety pharmacology protocol, the interaction of multiple endocrine systems in test animals is addressed. As discussed by Harvey (1996) and by Harvey and Everett (2003), effects on adrenocortical function are frequently found in toxicology studies, sometimes related to enzyme induction and effects on steroid biosynthesis (Loose et al. 1983, Nebert and Russell 2002, Weber et al. 1993). Test procedures in animals are required when there is a reason for concern. Frequently however the effects observed are due to stress rather than specific interaction with the target organ, and may involve effects on catecholamine release from the adrenal medulla (Tucker 1996). Recently, much new evidence has been accumulated from the testing of industrial chemicals with effects on adrenal steroid biosynthesis (Harvey and Johnson 2002). 

American Journal of Veterinary Research 59 1039-1043 Rush B R, Worster A A, Flaminio M J et al 1998c Alteration in adrenocortical function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. American Journal of Veterinary Research 59 1044-1047... 

Agrawal R, Chansouria JPN. 1989. Chronic effects of mercuric chloride ingestion on rat adrenocortical function. Bull Environ Contam Toxicol 43(3) 481-484. 

Davies CTM, Few JD. Effects of exercise on adrenocortical function. J Appl Physiol 1972 35 887-91. 

Watterberg KL. Adrenocortical function and dysfunction in the fetus and neonate. Semin Neonatol 2004 9 ... 

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