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KEY POINTS

KEY POINTS

  1. The immune-neuroendocrine response of critical illness (CI) is marked by hypercatabolism and diminished hypothalamic-pituitary-end-organ function.

  2. Despite low circulating growth hormone (GH) levels in CI, the administration of exogenous GH is detrimental.

  3. Central adrenal insufficiency typically results from overly rapid tapering of corticosteroid dosing or increased stress in a patient who was recently tapered off of corticosteroids.

  4. CI or relative adrenal insufficiency, though real and relevant, is still the subject of great interest among intensivists and changes in definitions and management are likely to change in the near future.

  5. Diabetic ketoacidosis typically occurs in patients with type 1 diabetes that are newly diagnosed, acutely ill, or resulting from missed scheduled insulin doses.

INTRODUCTION

The endocrine system of extracellular hormone signaling maintains homeostasis via regulation of metabolic pathways and cellular function in multicellular organisms, including humans. During critical illness (CI), the extreme systemic inflammatory response disrupts normal physiology and alters hormone signaling. The immune-neuroendocrine response of CI is marked by hypercatabolism and diminished hypothalamic-pituitary-end-organ function. In some cases, disorders of the endocrine system directly lead to CI. This chapter reviews the endocrine and metabolic physiology and sequelae of CI as well as specific conditions of the endocrine system that can lead to CI.

PITUITARY FUNCTION AND CRITICAL ILLNESS

The pituitary gland, or hypophysis, is located within the sella turcica, inferior to the optic chiasm and is connected to the hypothalamus via the infundibulum. The pituitary is divided functionally and anatomically into anterior and posterior sections. Although much of its function is controlled by the hypothalamus, the pituitary is considered the “master gland” for its role in regulating many of the other endocrine glands.

The anterior pituitary secretes 6 major peptide hormones: growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH), and follicle stimulating hormone (FSH). The secretion of each of these hormones is pulsatile and follows a circadian rhythm. PRL synthesis is primarily regulated by inhibitory dopaminergic neurons of the hypothalamus. The other peptide hormones of the pituitary are synthesized primarily in response to stimulatory hypothalamic hormones.

Hypothalamic and anterior pituitary function are greatly reduced in CI as a result of high levels of circulating inflammatory cytokines (Table 44–1).1 In early CI, circulating GH, LH, and FSH levels diminish to negligible levels. TSH production initially rises sharply, but within 6 to 18 hours of CI, TSH secretion is also impaired as part of the nonthyroidal illness phenomenon. ACTH levels also initially increase as part of a generalized stress response of acute CI, but typically decline to below normal levels on day 3 of CI.2 Cortisol levels generally remain elevated, even as ACTH levels decline after day 3, suggesting an independent mechanism governing the release of cortisol as patient progress into the prolonged phase of CI.2,3...

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