Failure of MC2R to activate in response to ACTH causes familial glucocorticoid deficiency (FGD), a rare autosomal recessive disorder characterized by severe cortisol deficiency with high plasma ACTH levels and normal mineralocorticoid levels (see "Causes and clinical manifestations of primary adrenal insufficiency in children", section on 'Familial glucocorticoid deficiency (FGD)' ). MC2R mutations resulting in effective loss of the receptor function are responsible for FGD type 1, which accounts for up to 25 percent of all FGD cases [ 4 ]. The melanocortin receptor accessory protein (MRAP) and its paralogue MRAP2 are small single-pass transmembrane proteins; MRAP is a key accessory factor for the functional expression of the MC2R /ACTH receptor. The clinical observation that 20 percent of FGD cases are due to inactivating MRAP mutations highlights the importance of MRAP in adrenal gland physiology [ 5 ].
Steroid isolation , depending on context, is the isolation of chemical matter required for chemical structure elucidation, derivitzation or degradation chemistry, biological testing, and other research needs (generally milligrams to grams, but often more  or the isolation of "analytical quantities" of the substance of interest (where the focus is on identifying and quantifying the substance (for example, in biological tissue or fluid). The amount isolated depends on the analytical method, but is generally less than one microgram.  [ page needed ] The methods of isolation to achieve the two scales of product are distinct, but include extraction , precipitation, adsorption , chromatography , and crystallization . In both cases, the isolated substance is purified to chemical homogeneity; combined separation and analytical methods, such as LC-MS , are chosen to be "orthogonal"—achieving their separations based on distinct modes of interaction between substance and isolating matrix—to detect a single species in the pure sample. Structure determination refers to the methods to determine the chemical structure of an isolated pure steroid, using an evolving array of chemical and physical methods which have included NMR and small-molecule crystallography .  :10–19 Methods of analysis overlap both of the above areas, emphasizing analytical methods to determining if a steroid is present in a mixture and determining its quantity.