Prolonged hypercortisolism can manifest as diabetes mellitus. Due to glucocorticoid-induced immune system suppression, patients become more susceptible to infection. Glucocorticoids' mineralocorticoid activities, along with a possible increase in aldosterone secretion, result in salt and water retention, leading to hypertension. Excessive androgen secretion in women can cause hirsutism, male pattern baldness, and clitoral enlargement (adrenogenital syndrome).

Blockage of any enzyme that reduces cortisol synthesis will increase ACTH secretion and cause adrenal hyperplasia. The most common form of congenital adrenal hyperplasia is due to a deficiency of the enzyme 21-hydroxylase (CYP21). Individuals with this condition cannot produce normal quantities of cortisol, deoxycortisol, DOC, corticosterone, or aldosterone. Impaired cortisol production and elevated ACTH levels stimulate steroidogenesis, increasing the synthesis of products "upstream" of the missing enzyme, as well as products of the zona reticularis. Since the latter includes the adrenal androgens, females may experience virilization.

The adrenal gland consists of a cortex derived from mesoderm and a medulla derived from neuroectoderm. The cortex synthesizes steroid hormones, while the medulla produces catecholamines.

The rate-limiting enzymes in medullary catecholamine synthesis are tyrosine hydroxylase and dopamine β-hydroxylase, which are induced by sympathetic stimulation, and phenylethanolamine-N-methyltransferase, induced by cortisol.

Catecholamines increase serum glucose and fatty acid levels. They stimulate gluconeogenesis, glycogenolysis, and lipolysis. Catecholamines enhance cardiac output but have specific effects on blood flow to various organs.

Pheochromocytoma is a tumor of chromaffin tissue that overproduces catecholamines. Symptoms of pheochromocytoma are often sporadic and include hypertension, headaches, sweating, anxiety, palpitations, chest pain, and orthostatic hypotension.

The adrenal cortex exhibits clear structural and functional zonation: the zona glomerulosa produces the mineralocorticoid aldosterone, the zona fasciculata produces the glucocorticoid cortisol, and the zona reticularis produces the weak androgens DHEA and DHEAS.

Cortisol binds to the glucocorticoid receptor. During stress, cortisol increases blood glucose levels by promoting gluconeogenesis in the liver and breaking down muscle protein for gluconeogenic precursors. Cortisol also reduces glucose uptake by muscle and adipose tissue and has permissive effects on glucagon and catecholamines. Additionally, cortisol has multiple effects on other tissues, with its most significant pharmacological effect being immunosuppression/anti-inflammatory action.
Fig.43.10 ).Prolongedhypercortisolismcanleadtomanifestationsofdiabetesmellitus.Becauseofsuppressionoftheimmunesystemcausedbyglucocorticoids,patientsaremoresusceptibletoinfection.Themineralocorticoidactivitiesofglucocorticoidsandthepossibleincreaseinaldosteronesecretionproducesaltretentionandsubsequentwaterretentionthatresultinhypertension.Excessiveandrogensecretioninwomencanproducehirsutism,malepatternbaldness,andclitoralenlargement(adrenogenitalsyndrome).
AnyenzymeblockagethatdecreasescortisolsynthesiswillincreaseACTHsecretionandproduceadrenalhyperplasia.Themostcommonformofcongenitaladrenalhyperplasiaisduetodeficiencyoftheenzyme21-hydroxylase (CYP21). Theseindividualscannotproducenormalquantitiesofcortisol,deoxycortisol, DOC,corticosterone,oraldosterone(see
Figs.
43.8 43.10C ).BecauseofimpairedcortisolproductionandresultantelevatedACTHlevels,steroidogenesisisstimulated,therebyincreasingthesynthesisproducts“upstream”ofthemissingenzyme,aswellasproductsofthezonareticularis.Becausethelatterincludetheadrenalandrogens,afemale 1.
The adrenal gland is composed of a cortex that is of mesodermal origin and a medulla that is of neuroectodermal origin. The cortex produces steroid hormones, and the medulla produces catecholamines.
2.
The rate-limiting enzymes in medullary catecholamine synthesis are tyrosine hydroxylase and dopamine β-hydroxylase, which are induced by sympathetic stimulation, and phenylethanolamine-Nmethyltransferase, which is induced by cortisol.
3.
Catecholamines increase serum glucose and fatty acid levels. They stimulate gluconeogenesis, glycogenolysis, and lipolysis. Catecholamines increase cardiac output but have selective effects on blood flow to different organs.
4.
Pheochromocytoma is a tumor of chromaffin tissue that produces excessive quantities of catecholamines. Symptoms of pheochromocytoma are often sporadic and include hypertension, headaches, sweating, anxiety, palpitations, chest pain, and orthostatic hypotension.
5.
The adrenal cortex displays clear structural and functional zonation: the zona glomerulosa produces the mineralocorticoid aldosterone, the zona fasciculata produces the glucocorticoid cortisol, and the zona reticularis produces the weak androgens DHEA and DHEAS.
6.
Cortisol binds to the glucocorticoid receptor. During stress, cortisol increases blood glucose by increasing gluconeogenesis in the liver and breaking muscle protein down to supply gluconeogenic precursors. Cortisol also decreases glucose uptake by muscle and adipose tissue and has permissive actions on glucagon and catecholamines. Cortisol has multiple effects on other tissue. From a pharmacological point of view, the most important is the immunosuppressive/ antiinflammatory effect.
7.