Human Biochemistry, Volume 2 - Murray R. 1993

Biochemistry of Intracellular and Intercellular Communications
Adrenal Cortical Hormones
Pathophysiology of the Adrenal Cortex

Disorders Associated with Glucocorticoid Hormones

Primary adrenal insufficiency (Addison's disease) leads to hypoglycemia, extreme Insulin sensitivity, stress intolerance, anorexia, weight loss, nausea, and profound weakness. Patients with Addison's disease exhibit low Blood pressure, as well as a reduced Glomerular Filtration rate and a diminished capacity to handle a Water load. A craving for salt is frequently observed. Plasma Na⁺ levels in these patients are decreased, while K⁺ levels are elevated; the lymphocyte count in the blood is also increased. These patients often show enhanced pigmentation of the Skin and mucous membranes, resulting from the compensatorily elevated secretion of ACTH and related POMC Gene products. Secondary adrenal insufficiency is caused by ACTH deficiency, which in turn arises from a tumor, infarction, or infection. This condition presents the same metabolic syndromes as primary adrenal insufficiency, but without hyperpigmentation.

Conditions associated with glucocorticoid excess are generally referred to as Cushing's syndrome. As a rule, this disorder results from the pharmacological use of Steroids, but it may also be caused by an ACTH-secreting pituitary adenoma, an Adrenal Adenoma or carcinoma, or ectopic ACTH secretion by tumor Cells. In Cushing's syndrome, patients lose the characteristic diurnal rhythm of ACTH/cortisol secretion. Furthermore, hyperglycemia and/or glucose intolerance occur due to accelerated Gluconeogenesis. Directly related to this is a dramatic increase in Protein Catabolism, leading to skin thinning, Muscle wasting, Osteoporosis, pronounced involution of lymphoid tissue, and an overall negative nitrogen balance. A characteristic redistribution of fat deposits also occurs, specifically truncal obesity. Resistance to infections and inflammatory responses are impaired, and wound healing is delayed. A range of symptoms, including hypernatremia, hypokalemia, alkalosis, edema, and Hypertension, are attributed to the mineralocorticoid effects of cortisol.

Disorders Associated with Mineralocorticoid Hormones

Small adenomas of the zona glomerulosa cause primary aldosteronism (Conn's syndrome), the classic manifestations of which include hypertension, hypernatremia, and alkalosis. Patients with primary aldosteronism do not exhibit an excess of glucocorticoid hormones in the blood, and their renin and angiotensin II levels are depressed.

In renal artery stenosis accompanied by a decrease in perfusion pressure, hyperplasia and Hyperfunction of the juxtaglomerular cells may occur, leading to increased production of renin and angiotensin II. Ultimately, this results in secondary aldosteronism, which differs from the primary form only by elevated levels of renin and angiotensin II.

Congenital Adrenal Hyperplasia

Deficiencies in steroidogenic Enzymes lead to a shortage of end products, the accumulation of steroidogenesis intermediates, and the activation of alternative steroid synthesis pathways. A common feature of most of these syndromes, which develop during the Embryonic period, is inadequate cortisol production against a backdrop of ACTH overproduction and adrenal hyperplasia—hence the name of these syndromes, congenital adrenal hyperplasia. A second common feature is the overproduction of androgen. Excess androgens lead to accelerated body growth, virilization, and abnormal Development of the external genitalia; hence another name for these conditions is the "adrenogenital syndrome." The cause of virilization in congenital adrenal hyperplasia will become clear from the Structure/133.html">Discussion of sexual differentiation in Chapter 49. Other symptoms depend on whether aldosterone production is increased or decreased, resulting in hypertension or salt wasting, respectively.

More than 90% of congenital adrenal hyperplasia cases are caused by Two Types of 21-hydroxylase deficiency: partial (simple virilizing) or complete (salt-wasting); the remaining cases are primarily associated with 11ß-hydroxylase deficiency. Only isolated cases of deficiencies in Other Enzymes have been described: 3ß-hydroxysteroid dehydrogenase, 17α-hydroxylase, Cholesterol desmolase, 18-hydroxylase, and 18-dehydrogenase. Deficiencies in 18-hydroxylase and 18-dehydrogenase affect only aldosterone Biosynthesis and do not cause adrenal hyperplasia. Cholesterol desmolase deficiency blocks The biosynthesis of all steroids and is therefore incompatible with postnatal life.

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