Chapter 34: Endocrine Disorders

GENERAL CONCEPTS

The classic biology concept that endocrine effects are the result of substances secreted into the blood which act on distant target cells has been updated to account for additional ways in which hormonal effects occur. Specifically, paracrine systems involve the stimulation or inhibition of metabolic processes in neighboring cells (eg, within the pancreatic islets or cartilage). Autocrine hormone effects reflect the action of hormones on the same cells that produced them. The discoveries of local production of ghrelin, somatostatin, cholecystokinin, incretins, and many other hormones in the brain and gut support the concept of paracrine and autocrine processes in these tissues.

Another significant discovery in endocrine physiology was an appreciation of the role of specific hormone receptors in target tissues, without which the hormonal effects cannot occur. For example, in nephrogenic diabetes insipidus (DI), affected children have defective vasopressin or receptor function, and show the metabolic effects of DI despite more-than-adequate vasopressin secretion. Alternatively, ligand-independent activation of a hormone receptor leads to inappropriate effect without inappropriate hormone secretion. Examples of this phenomenon include McCune-Albright syndrome (precocious puberty and hyperthyroidism), testotoxicosis (familial male precocious puberty), and hypercalciuric hypocalcemia.

HORMONE TYPES

Hormones typically fall into one of three classes of compounds based on chemistry: peptides and proteins, steroids, and amines. The peptide hormones include the releasing factors secreted by the hypothalamus; the hormones of the anterior and posterior pituitary gland; pancreatic islet cells; parathyroid glands, lung (angiotensin II), heart, and brain (atrial and brain natriuretic hormones); and local growth factors such as insulin-like growth factor 1 (IGF-1). Steroid hormones are secreted primarily by the adrenal cortex, gonads, and kidney (active vitamin D [1,25(OH)₂ D3]). The amine hormones are secreted by the adrenal medulla (epinephrine) and the thyroid gland (triiodothyronine [T₃] and thyroxine [T₄]).

Peptide hormones and epinephrine act through cell surface receptors. The metabolic effects of these hormones are usually stimulation or inhibition of the activity of preexisting enzymes or transport proteins (posttranslational effects). The steroid hormones, thyroid hormone, and active vitamin D, in contrast, act more slowly and bind to cytoplasmic receptors inside the target cell and subsequently to specific regions on nuclear DNA. Their metabolic effects are generally caused by stimulating or inhibiting the synthesis of new enzymes or transport proteins (transcriptional effects).

Metabolic processes that require rapid response, such as blood glucose or calcium homeostasis, are usually controlled by peptide hormones and epinephrine, while processes that respond more slowly, such as pubertal development and metabolic rate, are controlled by steroid hormones and thyroid hormone. The control of electrolyte homeostasis is intermediate and is regulated by a combination of peptide and steroid hormones (Table 34–1).