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INTRODUCTION

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The adrenal gland synthesizes steroid hormones in the cortex and catecholamines in the medulla. Adrenal insufficiency is deficiency of adrenal gland hormone production in the cortex. Primary adrenal insufficiency, or Addison's disease, is due to intrinsic adrenal gland dysfunction and results in decreased cortisol, aldosterone, and sex hormone production. The condition is rare, with prevalence ranging from 39 to 144 cases per million population.1

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Secondary adrenal insufficiency is due to hypothalamic-pituitary dysfunction with failure to secrete corticotropin-releasing hormone and/or adrenocorticotropic hormone. This disorder results in cortisol deficiency only.

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Adrenal crisis is a life-threatening exacerbation of adrenal insufficiency when an increased demand fails to increase hormone production.

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ADRENAL GLAND PHYSIOLOGY

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The adrenal gland is made up of the cortex and medulla producing steroid hormones and catecholamines, respectively. The adrenal cortex produces three categories of steroids: the glucocorticoids (cortisol), mineralocorticoids (aldosterone), and gonadocorticoids (sex hormones). Glucocorticoids are produced in the zona fasciculata, and mineralocorticoids and gonadocorticoids are produced in the zona glomerulosa and zona reticularis of the adrenal cortex. The adrenal medulla produces adrenaline, noradrenaline, and a small amount of dopamine in response to stimulation by sympathetic preganglionic neurons.

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Cortisol is secreted in response to direct stimulation by adrenocorticotropic hormone. Adrenocorticotropic hormone secretion is stimulated by corticotropin-releasing factor released from the hypothalamus. Secretion occurs in a diurnal rhythm, with higher levels secreted in the morning and lower levels in the evening. In normal circumstances, the daily cortisol equivalent is about 20 milligrams/d of hydrocortisone. Plasma cortisol suppresses the release of adrenocorticotropic hormone through negative feedback inhibition. Cortisol facilitates the stress response by affecting the heart, vascular bed, water excretion, electrolyte balance, potentiation of catecholamine action, and control of water distribution. It affects fat, protein, and carbohydrate metabolism by stimulating glycogenolysis and neoglycogenesis. It is involved in immunologic and inflammatory responses and affects calcium metabolism. It promotes growth and development but, in excess, interferes with the GI tract mucosa maintenance, leading to peptic ulcer.

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Aldosterone secretion is controlled primarily by the renin-angiotensin system and serum potassium concentration. The renin-angiotensin system controls aldosterone levels in response to changes in volume, posture, and sodium intake. Serum potassium (hyperkalemia) influences the adrenal cortex directly to increase aldosterone secretion. Aldosterone maintains sodium and potassium plasma concentrations. It regulates extracellular volume and controls sodium and water balance.

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Gonadocorticoids include androgen hormones and estrogen. Androgens produced include testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate, which are present in both men and women. In women, androgens are produced in the adrenal glands as well as the ovaries and promote the development of sex characteristics such as axillary and pubic hair and libido. In men, most androgens (testosterone) are produced in the testes. Androgens made by the adrenal glands are less important for normal sexual function.

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PRIMARY ADRENAL INSUFFICIENCY

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