Abstract
This chapter reviews the normal physiology of the five major endocrine organs relevant to anesthesiology: the pituitary gland, parathyroid glands, thyroid gland, adrenal glands, and pancreas. Disturbances in endocrine hormone production from these glands lead to various endocrine disorders (such as thyroiditis, Cushing syndrome, and diabetes mellitus). The pathophysiology of the most common endocrine disorders and considerations for anesthetic management of patients with these disorders are discussed.
Keywords
pituitary disease, hyperthyroidism, hypothyroidism, diabetes, hyperparathyroidism
Chapter Outline
Endocrine physiology encompasses processes that range from master regulation by the pituitary gland to the much larger pancreas, which controls energy utilization processes of the body. This chapter reviews normal endocrine physiology and pathophysiology, as well as the basic anesthetic implications associated with the 5 major endocrine organs relevant to anesthesiologists: the pituitary gland, parathyroid glands, thyroid gland, adrenal glands, and the pancreas.
Pituitary Physiology
The pituitary gland controls the function of many other endocrine glands, often being referred to as the “master gland.” Despite its central role in the endocrine system, the pituitary is extremely small—about the size of a pea—and weighs only about 0.5 g. It is attached to the hypothalamus by the pituitary stalk (or infundibulum) and rests in the sella turcica, a small, bony cavity in the sphenoid bone at the base of the brain. The pituitary secretes at least 8 hormones that regulate organ function and are critical to survival.
Both functionally and anatomically, the pituitary can be divided into the anterior lobe (or adenohypophysis) and the posterior lobe (or neurohypophysis). The lobes are different enough from one another that they can be considered as entirely different glands. In fact, consistent with their distinct structure and function, the embryonic origin of each lobe is entirely different: the anterior pituitary arises from the oral ectoderm whereas the posterior pituitary arises from the neuroectoderm.
Anterior Pituitary
The anterior pituitary is a glandular secretory organ. The most important hormones produced by the anterior pituitary include adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), prolactin (PRL), and the two gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Melanocyte-stimulating hormone (MSH) is also produced by the anterior pituitary but is not required for homeostasis.
The anterior pituitary is composed of 3 cell types, as identified with traditional aniline dye stains: acidophils, basophils (often collectively referred to as chromophils ), and chromophobes. The chromophils are the principal secretory cell types whereas the chromophobes are not thought to have secretory function. Today, 5 cell types producing the 6 major hormones are best differentiated using immunohistochemical staining, as follows:
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Somatotrophs, which produce GH (acidophilic)
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Mammotrophs, which produce PRL (acidophilic)
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Corticotrophs, which produce ACTH, MSH, and various endorphins (basophilic)
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Thyrotrophs, which produce TSH (basophilic)
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Gonadotrophs, which produce FSH and LH (basophilic)
In general, the balance of releasing factors secreted by the hypothalamus and inhibiting factors secreted by each hormone’s target organ control the secretion of each hormone produced by the anterior pituitary. For example, TSH stimulates the thyroid to produce triiodothyronine (T 3 ) and tetraiodothyronine (T 4 ). The secretion of TSH by the anterior pituitary is stimulated by the secretion of thyrotropin-releasing hormone by the hypothalamus, but inhibited by both thyroid hormones (T 3 and T 4 ), creating a feedback loop. The releasing and inhibiting factors for each hormone are summarized in Table 35.1 . The exception to this principle is prolactin, which is under tonic-inhibition by dopamine secreted by the hypothalamus.
| Hormone | Acronym | Protein Structure | Releasing Factor (From Hypothalamus) | Inhibiting Factors | Anatomic Target | Effects |
|---|---|---|---|---|---|---|
| Adrenocorticotropic hormone | ACTH | Polypeptide | Corticotropin-releasing hormone | Glucocorticoids | Adrenal gland | Secretion of glucocorticoids |
| Thyroid-stimulating hormone | TSH | Glycoprotein | Thyrotropin-releasing hormone | T 3 and T 4 | Thyroid gland | Secretion of thyroid hormones |
| Growth hormone | GH | Polypeptide | Growth hormone-releasing hormone | Growth hormone, insulin-like growth factor 1 (IGF-1), somatostatin | Liver, adipose tissue | Growth, anabolic, promotes lipid and carbohydrate metabolism |
| Prolactin | PRL | Polypeptide | See text | Dopamine | Ovaries, mammary glands | Milk production, lipid and carbohydrate metabolism |
| Luteinizing hormone | LH | Glycoprotein | Gonadotropin-releasing hormone | Estrogen, testosterone | Gonads | Sex hormone production |
| Follicle-stimulating hormone | FSH | Glycoprotein | Gonadotropin-releasing hormone | Estrogen, testosterone | Gonads | Sex hormone production |
The action of releasing factors secreted by the hypothalamus is facilitated by the presence of a portal blood supply to the anterior pituitary. The hypothalamus secretes releasing factors into a primary capillary plexus from which they travel to a secondary capillary plexus in the anterior pituitary.
Hyperpituitarism and Anterior Lobe Tumors
Essentially all cases of hyperpituitarism occur secondary to pituitary adenoma. These tumors are commonly encountered in clinical practice. They represent only 10% of diagnosed brain neoplasms; however, as many as 20% of people have a pituitary tumor on postmortem examination, suggesting that many pituitary adenomas are asymptomatic.
Although the majority of pituitary adenomas are asymptomatic, most tumors present in 3 discrete ways: (1) hormonal hypersecretion, (2) local mass effects (including pituitary hypofunction due to compression of the normal gland), or (3) incidental discovery during cranial imaging for an unrelated condition. Approximately 75% of pituitary tumors are “functioning” and produce a single predominant hormone; these patients typically present with the signs and symptoms of hormone excess. For example, patients with a TSH-secreting adenoma have pituitary hyperthyroidism and present with the signs and symptoms of hyperthyroidism. Patients with Cushing disease (secondary to an ACTH-secreting adenoma) and acromegaly (secondary to a growth hormone-secreting adenoma) merit special attention and are discussed later. The perioperative management of patients with pituitary tumors undergoing surgery has been extensively reviewed. Pituitary adenomas are often classified based on their size at the time of discovery. Tumors larger than 10 mm in any dimension are classified as macroadenomas ; tumors smaller than 10 mm are classified as microadenomas .
The mass effects produced by pituitary tumors can be extensive and problematic given the location of the pituitary gland within the brain. Patients can present with varying degrees of hypopituitarism secondary to compression of normal anterior pituitary tissue by the expanding intrasellar mass. Seventy percent to 90% of patients with nonfunctioning pituitary macroadenomas exhibit deficiencies in at least one pituitary hormone with formal testing. Thus, while it is easy to focus on the signs and symptoms of glucocorticoid excess in a patient with Cushing disease, for example, the patient with Cushing disease might also suffer from pituitary hypothyroidism. Furthermore, PRL is frequently elevated in patients with all varieties of pituitary tumors secondary to disruption in normal inhibitory tone from the hypothalamus. Regardless, posterior pituitary dysfunction is unusual, even among patients with very large tumors.
Gigantism and Acromegaly
The unregulated hypersecretion of growth hormone by the anterior pituitary leads to increased production of insulin-like growth factor 1 (IGF-1) by the liver. Children in whom the epiphyses have not closed experience gigantism. In contrast, acromegaly develops in adults. Cardiac disease, hypertension, and ventricular hypertrophy are the most important causes of morbidity and mortality in acromegalic patients. Patients with acromegaly have a characteristic facies as the soft tissues of the nose, mouth, tongue, and lips become thicker and contribute to the acromegalic appearance. Airway obstruction and obstructive sleep apnea (OSA) can affect up to 70% of acromegalic patients. A high risk of perioperative airway compromise has been well documented in acromegalic patients. Other manifestations of acromegaly are summarized in Fig. 35.1 .
Cushing Disease
Cushing disease specifically results from the unregulated hypersecretion of ACTH by a pituitary adenoma and consequent hypercortisolism. Systemic hypertension is among the most common manifestations. Increased endogenous corticosteroids have been shown to cause systemic hypertension by a variety of mechanisms. Secondary to hypertension, a high prevalence of left ventricular hypertrophy and concentric remodeling has been reported. Glucose intolerance occurs in at least 60% of patients, with overt diabetes mellitus (DM) present in up to one-third of all patients. Patients are typically obese, with characteristic “moon facies.” Although not as common as in acromegaly, patients frequently have OSA. Despite the association with OSA, endotracheal intubation is not usually more difficult. Other manifestations of Cushing disease are summarized in Fig. 35.1 . Cushing syndrome is also frequently encountered in clinical practice but, unlike Cushing disease, results from iatrogenic corticosteroid medications (e.g., for asthma, inflammatory conditions, and so forth) and not from a pituitary adenoma. The unique aspects of Cushing syndrome are discussed in detail later.
Prolactinomas
Prolactinomas are the most frequently observed type of hyperfunctioning pituitary adenoma, representing 20% to 30% of all clinically recognized pituitary tumors and half of all functioning tumors. Despite their frequency, prolactinoma is not associated with significant mortality. In women, hyperprolactinemia causes amenorrhea, galactorrhea, loss of libido, and infertility. In men, symptoms of hyperprolactinemia are relatively nonspecific and include decreased libido, impotence, premature ejaculation, erectile dysfunction, and oligospermia.
Posterior Pituitary
Unlike the anterior pituitary, the posterior pituitary gland (neurohypophysis) is not a secretory gland but rather a collection of axon terminals arising from the supraoptic and paraventricular nuclei of the hypothalamus. The posterior pituitary is principally responsible for the secretion of oxytocin and vasopressin, also known as antidiuretic hormone (ADH).
ADH is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus. After initial synthesis, the precursor hormone is transported down the pituitary stalk into the posterior lobe of the pituitary where ADH undergoes final maturation to active hormone and is stored in vesicles for future release. Plasma osmolarity is the primary stimulus for ADH secretion; however, other factors—such as left atrial distention, circulating blood volume, exercise, and certain emotional states—can also alter ADH release. ADH is considerably more sensitive to small changes in osmolarity than to similar changes in blood volume. A 1% to 2% increase in osmolarity is sufficient to increase ADH secretion. ADH binds to vasopressin 2 (V 2 ) receptors on the renal collecting ducts, which increases their permeability to water. This results in a significant increase in water reabsorption. Additionally, ADH increases blood pressure by increasing systemic vascular resistance through interaction with V la receptors on blood vessels. The effect of ADH on blood pressure is mild in the healthy state, but becomes much more important in hypovolemic shock. It is used therapeutically as a vasopressor (see Chapter 25 ).
Diabetes Insipidus and Syndrome of Inappropriate Antidiuretic Hormone
The absence of ADH secretion results in pituitary diabetes insipidus (DI), whereas oversecretion or “inappropriately high” levels of ADH (or ADH-like hormones) results in the syndrome of inappropriate ADH (SIADH). DI is most commonly associated with pituitary surgery and is most often transient. Whereas 18% of 881 patients undergoing transsphenoidal surgery experienced early postoperative DI, only 2% had persistent DI 1 week after surgery. Its onset is heralded by the abrupt onset of polyuria, accompanied by thirst and polydipsia. SIADH is most commonly associated with central nervous system injury or trauma and certain cancers, especially lung cancer. Unlike DI, which typically presents with polyuria, SIADH typically presents with the signs and symptoms of hyponatremia. Characteristics of DI and SIADH are summarized in Table 35.2 .
| SIADH | DI | |
|---|---|---|
| Associated conditions |
|
|
| Presentation | Hyponatremia | Polyuria |
| Plasma volume (awake patients) | Euvolemic (or slightly hypervolemic) | Euvolemic (practically speaking) Hypovolemic if not allowed access to fluids or unconscious |
| Serum osmolarity | Hypotonic (< 275 mOsm/L) | Hypertonic (> 310 mOsm/L) |
| Serum Na + | Falling (< 135 mEq/L) | Rising (> 145 mEq/L) |
| Urine volume | Low (but not normally absent) | Voluminous (4–18 L/day) |
| Urine osmolarity | Relatively high (> 100 mOsm/L) | Relatively low (< 200 mOsm/L) |
| Urinary Na + | > 30 mEq/L | Normal (or variable) |
| Treatment |
|
|
Like ADH, oxytocin is also synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and transported down the pituitary stalk into the posterior pituitary for release. The principal physiologic functions of oxytocin are to stimulate cervical dilation and uterine contraction during labor and to allow milk to be let down into the subareolar sinuses during lactation. Oxytocin is one of the few hormones involved in a positive feedback loop. For example, uterine contractions stimulate oxytocin release from the posterior pituitary, which, in turn, increases uterine contractions.
Parathyroid Physiology
The parathyroid glands generally consist of 4 pea-sized glands located posterior to the thyroid gland in the neck; however, many variations in location, and even number, of the glands exist. The glands possess a rich vascular supply via the inferior thyroid artery and consist mainly of chief cells primarily responsible for secreting parathyroid hormone (PTH) in response to hypocalcemia.
PTH plays a chief role in bone remodeling and Ca 2+ homeostasis. PTH stimulates bone resorption and consequently release of Ca 2+ into the bloodstream. In addition, PTH causes renal Ca 2+ reabsorption in the distal tubule and phosphate excretion in the proximal tubule. Note that while the majority of renal Ca 2+ reabsorption occurs in the proximal tubule, reabsorption at this site is not under hormonal control. PTH facilitates vitamin D conversion to its activated form such that it facilitates intestinal and renal absorption of Ca 2+ . Activated vitamin D also acts on bone to increase resorption, thus leading to further Ca 2+ release into the bloodstream. Primary control of the release of PTH comes via negative feedback inhibition once elevated vitamin D and plasma Ca 2+ levels are detected by a parathyroid Ca 2+ -sensing receptor. Other mechanisms also affect the release of PTH: (1) increased phosphate levels lead to increases in production and release of PTH; (2) hypomagnesemia, like hypocalcemia, causes release of PTH; and (3) adrenergic agonists, such as epinephrine, increase PTH release through β-adrenergic receptors on parathyroid cells. Indeed, this effect of adrenergic agonists is more pronounced at lower Ca 2+ levels while it is transient and very mild in the setting of hypercalcemia. In addition, β-adrenergic antagonists, such as propranolol, decrease PTH in normal patients but are less likely to cause secondary hyperparathyroidism. Calcitonin counteracts the effects of PTH, as it inhibits bone resorption and increases excretion of Ca 2+ through the kidneys.
The net result of the interactions of PTH, Ca 2+ , vitamin D, and calcitonin is maintenance of normal plasma Ca 2+ concentration, which, in turn, helps maintain normal cellular function, nerve transmission, membrane stability, bone integrity, coagulation, and intracellular signaling. Normal plasma Ca 2+ levels are 8.5 to 10.5 mg/dL (2.1–2.6 mM). The majority of Ca 2+ is stored in the bones and teeth. Only 1% is found in plasma in one of the following forms: ionized or unbound Ca 2+ (50%; normally 1.0–1.2 mM), protein-bound Ca 2+ (40%), and Ca 2+ bound to citrate and phosphate (10%). The ionized, or unbound, Ca 2+ is the form sensed by the Ca 2+ receptors in the parathyroid gland. Protein-bound Ca 2+ is primarily bound to albumin with implications for changes in blood pH. Acidosis causes a decrease in protein binding, thus leading to higher ionized Ca 2+ , whereas alkalosis results in higher protein binding, thus reducing the free Ca 2+ fraction in blood.
Primary Hyperparathyroidism
Primary hyperparathyroidism is excess PTH production and release most often due to parathyroid gland hyperplasia or tumor. The elevated PTH increases bone resorption and extracellular Ca 2+ . It occurs most commonly in patients aged 30 to 50 years and is more common in women than men. Clinically, patients exhibit increased intact PTH levels, hypercalcemia, hypercalciuria, hypophosphatemia, nephrolithiasis, osteoporosis, and neuromuscular changes, such as fatigue, weakness, and difficulties with cognition. Nausea, vomiting, constipation, and anorexia are common symptoms of hypercalcemia and patients may also complain of depression, confusion, and psychosis. Despite these manifestations, primary hyperparathyroidism is most often asymptomatic and detected incidentally on routine laboratory analysis as isolated hypercalcemia. Treatment of primary hyperparathyroidism centers on surgical excision of the parathyroid glands or tumor because there is increased risk of morbidity and cardiovascular mortality with long-standing hypercalcemia and untreated hyperparathyroidism.
Multiple Endocrine Neoplasia
Hyperparathyroidism may also present in concert with one of the multiple endocrine neoplasia (MEN) familial syndromes. MEN1 is a rare, autosomal-dominant syndrome in which tumors develop in the parathyroid glands, pancreas, and anterior pituitary gland of affected individuals. Most patients with MEN1 present with hyperparathyroidism. MEN2 is also an autosomal-dominant syndrome but has incomplete penetrance and variable expression. MEN2A is associated with medullary thyroid carcinoma (develops in essentially 100% of these patients), pheochromocytoma (50% incidence), and hyperparathyroidism (10%–30% incidence). Hyperparathyroidism is not a component of MEN2B. MEN4 is a rare familial endocrine syndrome associated with hyperparathyroidism and pituitary adenoma, which has only recently been described.
Secondary Hyperparathyroidism
Secondary hyperparathyroidism is a complication most commonly due to chronic renal failure but can result from any disease that causes chronic hypocalcemia. Early in the course of renal failure, decreased vitamin D and ionized Ca 2+ levels cause increased production and release of PTH. The kidneys are also unable to excrete the phosphate load, which contributes to low serum Ca 2+ . Over time, the parathyroid glands become more resistant to the negative feedback mechanism of vitamin D and Ca 2+ on PTH release, such that an increase in Ca 2+ results in less efficient inhibition of PTH release. Hyperphosphatemia also further results in uremia-induced parathyroid gland hyperplasia, and PTH production and release. Goals of treatment of secondary hyperparathyroidism include maintaining Ca 2+ and phosphate levels close to normal, reducing PTH secretion, and treating preexisting bone disease. These treatments focus on dietary phosphate restriction, maintaining daily Ca 2+ intake greater than or equal to 1500 mg, administration of phosphate binder agents, and vitamin D replacement.
Anesthetic considerations for patients with hyperparathyroidism (whether primary or secondary) focus on the effects of hypercalcemia. Preoperative evaluation should focus on eliciting the cause of the hyperparathyroidism and the degree of hypercalcemia. If hypercalcemia is mild to moderate and patients are without severe cardiovascular or renal complications, most surgery can proceed without further evaluation. Patients can have polydipsia and polyuria, and may present for surgery to remove renal calculi, as nephrolithiasis is common. Commonly observed electrocardiographic (ECG) changes in hypercalcemia include shortened PR interval, shortened QT interval, and cardiac arrhythmias. Patients with hyperparathyroidism can be hypertensive, and severe hypercalcemia can cause significant hypovolemia such that volume resuscitation is required. Severe hypercalcemia should be treated preoperatively. Aggressive volume resuscitation with subsequent diuretic administration can be used to acutely lower serum Ca 2+ levels. Loop diuretics, such as furosemide, decrease the reabsorption of Ca 2+ from the proximal tubules. For patients with renal dysfunction or failure, hemodialysis is immediately effective to reduce Ca 2+ levels. Medications such as mithramycin and calcitonin can also be used but have significant side-effect profiles and should be administered with caution.
Induction and maintenance of anesthesia should proceed carefully but there are no specific requirements as to choice of agent. Most anesthetic concerns for parathyroid surgery focus on emergence and postoperative care. After surgery of the thyroid and parathyroid glands, recurrent laryngeal nerve damage, airway swelling, and hematoma formation are serious potential complications with severe implications. The recurrent laryngeal nerves innervate all muscles of the larynx with the exception of the cricothyroid, which is supplied by the external laryngeal nerve. If the recurrent laryngeal nerve is completely paralyzed, the vocal cord will be abducted, resulting in stridor and hoarseness. If the recurrent laryngeal nerve is partially paralyzed, the vocal cord will be adducted. Thus, a partial lesion is more concerning for airway obstruction and a complete lesion more concerning for possible aspiration risk. Hypocalcemia can occur quickly after parathyroid removal; therefore, patients should be monitored with serial Ca 2+ , Mg 2+ , phosphate, and PTH levels. Hypocalcemia can also present with rapid onset of weakness and airway compromise.
Hypoparathyroidism
Hypoparathyroidism is associated with other endocrine disorders and neoplasias or may result from surgical removal of the parathyroid glands. Hypocalcemia is the major acute result of inadvertent removal of the parathyroid glands. Hypocalcemic tetany can manifest as painful spasms of the facial muscles and extremities and laryngeal muscle spasm with upper airway obstruction. ECG changes associated with hypocalcemia include prolonged QT interval and possible heart block. Pseudohypoparathyroidism is not due to reduced PTH levels, but instead to reduced target sensitivity to PTH due to a receptor defect. Patients exhibit low plasma Ca 2+ levels, high phosphate levels, and high PTH levels. Depending on the type of receptor defect, patients with pseudohypoparathyroidism demonstrate either complete, systemic resistance to PTH (and present with short stature and skeletal abnormalities) or simply manifest renal resistance to PTH.
There are few anesthetic considerations for the patient with a history of hypoparathyroidism presenting for surgery. The patient should have baseline Ca 2+ , phosphate, and Mg 2+ levels and an ECG to determine QT interval. Hypocalcemia can be treated with calcium gluconate or calcium chloride in order to maintain serum Ca 2+ levels.
Thyroid Physiology
The thyroid gland is an acinar gland positioned in the neck, just anterior to the trachea with a rich vascular supply from the superior and inferior thyroid arteries. Weighing up to 25 g, the thyroid gland has a right and left lobe connected by the thyroid isthmus. Table 35.3 reviews the various cell types found within the thyroid gland and their corresponding functions. Other structures close to the thyroid gland include the trachea and esophagus as well as the recurrent laryngeal nerves and superior laryngeal nerve.
| Cell Type | Function |
|---|---|
| Follicular cells | Thyroid hormone (T 3 and T 4 ) synthesis |
| Endothelial cells | Line capillaries Provide blood supply to follicles |
| Parafollicular cells (also called C cells) | Produce and secrete calcitonin |
| Fibroblasts, lymphocytes, and adipose tissue | Structural support for the thyroid |
Thyrotropin-releasing hormone (TRH) is produced in the hypothalamus and released in response to decreased free circulating thyroid hormone. TRH binds to a G protein–coupled receptor in the anterior pituitary, causing an increase in intracellular Ca 2+ . Increased intracellular Ca 2+ then causes release of TSH into the bloodstream, which stimulates the thyroid gland to increase the synthesis and release of T 4 and T 3 into the systemic circulation. T 4 and T 3 inhibit further secretion of TSH by inhibiting secretion of TRH. Thus, thyroid hormone production and secretion are regulated via negative feedback by the hypothalamic-pituitary-adrenal (HPA) axis. Other mediators that inhibit TSH release include dopamine, somatostatin, and glucocorticoids.
Iodide is required for thyroid hormone synthesis. The body readily absorbs the necessary iodine from dietary sources, which is converted to iodide before being absorbed by the thyroid gland. In the follicle of the thyroid, thyroglobulin, a glycoprotein possessing several tyrosine residues, is iodinated, yielding mono-iodinated tyrosine (MIT) and di-iodinated tyrosine (DIT) residues. MIT and DIT ultimately are synthesized to T 3 and T 4 via thyroid peroxidase. The thyroid gland releases more T 4 than T 3 , and T 4 is converted to T 3 , primarily in the liver, as a result of the deiodination of T 4 . T 4 is less active than T 3 in that it has decreased affinity for the thyroid hormone receptor, but both T 3 and T 4 are stored in the thyroid gland for a 2- to 3-month supply. Thyroid hormones circulate in the bloodstream bound to proteins, mainly to thyroid-binding globulin but also to albumin. A small amount of each hormone circulates in an unbound, free form ready to enter the cell and bind to the thyroid hormone receptor. T 4 binds more avidly to plasma proteins and thus has a longer half-life of 7 days compared to T 3 , which has a half-life of only 1 day. Thyroid hormone metabolism involves the sequential removal of iodine. Thus, T 4 , a relatively inactive thyroid hormone, is deiodinated to T 3 , the active thyroid hormone. Removal of an additional iodine molecule to T 2 yields a completely inactive product. In addition, thyroid hormones can be conjugated in the liver to increase solubility and allow for biliary excretion.
Thyroid hormone receptors are found in virtually all tissues. Thyroid hormones play a chief role in cellular energy metabolism and are involved in the following :
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Transcription of cell membrane sodium-potassium adenosine triphosphatase (ATPase), leading to increase in oxygen consumption
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Transcription of uncoupling protein (UCP)
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Fatty acid oxidation and heat generation with production of ATP
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Protein synthesis and breakdown
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Epinephrine-induced glycogenolysis and gluconeogenesis with effects on insulin-induced glycogen synthesis and glucose utilization
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Cholesterol synthesis and lipoprotein receptor regulation
Thyroid hormone plays a major role in normal growth and development. Specific systems to note include the skeletal system, in which thyroid hormone is essential for bone growth, and the cardiovascular system, in which thyroid hormone has inotropic and chronotropic effects. These effects are evidenced by increased cardiac output and effects on blood volume and systemic vascular resistance. Thyroid hormone differentiates adipose tissue and regulates triglyceride and cholesterol metabolism in the liver. Thyroid hormone also regulates production of pituitary hormones and expression of genes involved in central nervous system myelination, cell differentiation, migration, and signaling.
Thyroid disease and dysfunction occurs as a result of alterations in thyroid hormone levels, impaired metabolism of thyroid hormones, or resistance to effects of thyroid hormones. The thyroid gland can undergo changes that contribute to altered thyroid function. Thyroid hyperplasia or enlargement occurs in Graves disease and thyroid destruction occurs in Hashimoto thyroiditis. Table 35.4 differentiates hypothyroidism from hyperthyroidism based on laboratory values and clinical manifestations.
