Cortisol production

O Signs and symptoms of adrenal insufficiency reflect the disturbance of normal physiologic carbohydrate, fat, and protein homeostasis caused by inadequate cortisol production and inadequate cortisol action. 

Adrenal hormone production is controlled by the hypothalamus and pituitary gland. Corticotropin-releasing hormone (CRH) is secreted by the hypothalamus and stimulates secretion of adrenocorticotropic hormone (ACTH), also known as corticotropin from the anterior pituitary. ACTH, in turn, stimulates the adrenal cortex to produce cortisol. When sufficient or excessive cortisol levels are reached, a negative feedback is exerted on the secretion of CRH and ACTH, thereby decreasing overall cortisol production. The control of adrenal androgen synthesis also follows a similar negative-feedback mechanism. 

The unstimulated serum cortisol and rapid ACTH stimulation tests are useful in the diagnosis of adrenal crisis (Table 42-2). The insulin tolerance test is contraindicated owing to preexisting hypoglycemia. The metyrapone test is also contraindicated because metyrapone inhibits cortisol production. 

IL-6 (21-28) Monocyte/macrophage, T cell endothelium, fibroblast, keratinocyte Induction of fever and the hepatic acute phase response. Stimulates cortisol production. Decreases IL-1 and TNF production. Participates in activation of B and T cells, facilitates Ig production by B cells. Induction of granulocyte-macrophage colony-stimulating factor, stimulation of hematopoietic progenitors. 

Hydrocortisone, cortisone, and prednisone are the glucocorticoids of choice, administered twice daily at the lowest effective dose while mimicking the normal diurnal rhythm of cortisol production. 

Effect of glucocorticoid administration on adrenocortical cortisol production (A). Release of cortisol depends on stimulation by hypophyseal ACTH, which in turn is controlled by hypothalamic corticotropin-releasing hormone (CRH). In both the hypophysis and hypothalamus there are cortisol receptors through which cortisol can exert a feedback inhibition of ACTH or CRH release. 

Decrease in cortisol production with cortisol dose < daily production... 

A rhythmic variation has been observed in levels of plasma hydroxy-corticosteroids (A9, B13, D9) and in the excretion of 17-ketosteroids (P7). As shown in Table 5, urinary excretions of potassium, sodium, chloride, 17-hydroxycorticosteroids and water have been reported to be greatest between 10 am to noon and lowest between 4 am and 6 am (S21). In this study it was shown that within 5 weeks subjects could acclimate to similar patterns for a 21-hour, rather than a 24-hour, day. Heilman and his associates reported that about half of the day s cortisol production is achieved in the early morning hours during sleep and that production is minimal between noon and 10 pm (H7). In one study the plasma cortisol in normal men was 24.6 5.5 /xg/100 ml at 7 am 13.1 3.4 fig/100 ml at 9 am 11.8 fig/100 ml at noon 9.1 2.3 jag/100 ml at 7 PM and 6.3 /ig/100 ml at 10 pm (A9). 

Metyrapone is a competitive inhibitor of 11 beta hydroxylation in the adrenal cortex, and effectively inhibits cortisol production. It is used in low doses, titrated to achieve plasma cortisol levels as close as possible to normal day-time values. Occasionally it is used in higher doses combined with replacement corticosteroid treatment. Its main side effects relate to overdosage and resulting hypoadrenalism, but it can also cause hirsutism and hypertension, due to accumulation of precursor steroids. Ketoconazole is also sometimes used to suppress adrenal steroid production, but its potential for hepatotoxicity limits its... 

A 27-year-old female is diagnosed with hypercortisolism. To determine whether cortisol production Is Independent of the pituitary gland, you decide to suppress ACTH production by giving a high-potency glucocorticoid. Which glucocorticoid is the best for this indication ... 

Infants with salt-losing crisis and adrenal insufficiency in infancy may have adrenal hypoplasia congenita. This can be of two types recessive, for which the cause has not been defined and which affects mostly the fetal zone, and X-linked, which is caused by mutations in the DAX-1 gene, which (with steroidogenic factor-1) controls definitive zone development and steroidogenesis [71]. GC-MS analysis of patients with the disorder show variant patterns from absence of neonatal A5 steroids, appropriate for the recessive form [81], to extremely low cortisol production and transient 11/Lhy-droxylase deficiency, as evidenced through increased THS excretion (Malunowicz, personal communication). 

FIGURE 29-3 Circadian rhythm of cortisol production in humans. Peak plasma cortisol levels normally occur approximately at the time an individual awakens (6 to 8 am). (Adapted from Katzung BG. Basic and Clinical Pharmacology. 2nd ed. Lange Medical Publications New York 1984 454 after Liddle, 1966. Reproduced with permission of the McGraw-Hill Companies.)... 

Enyeart JJ. Biochemical and ionic signaling mechanisms for ACTH-stimulated cortisol production. 

Kraan, P., Dullaart, R., Pratt, J., Wolthers, B., Drayer, N., and De-Bruin, R., The daily cortisol production reinvestigated in healthy men. The serum and urinary cortisol production rates are not significantly different, Journal of Clinical Endocrinoloqy and Metabolism, Vol. 83, No. 4, 1998, pp. 1247-1252. 

Other, more rare, forms of congenital adrenal hyperplasia are the result of deficiencies of other steroidogenic enzymes, particularlyl7-hydroxylase (P450cl7) and 11 (3-hydroxylase (Bondy, 1985 White and Speiser, 2000). As with P450c21 deficiency, impaired activity of either of these other enzymes also results in decreased cortisol production, enhanced ACTH secretion, and thus increased tropic drive to the adrenal. Deficiency of ll 3-hydroxylase is characterized by increased production of adrenal mineralocorticoids (e.g., corticosterone, aldosterone), resulting in sodium retention, potassium excretion, and increased blood pressure. In addition, adrenal androgens are produced in... 

Q10 Cortisol secretion is normally suppressed by exogenous glucocortocoids. In a normal subject, administration of the synthetic steroid dexamethasone produces a rapid feedback inhibition of CRF and ACTH, which in turn suppresses or diminishes cortisol production to a low level. In Cushing s disease little or no suppression will occur. 

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