The endocrine system is composed of many glands scattered throughout the body; these glands secrete unique and potent chemicals called hormones directly into the bloodstream (Figure 4-1). Most hormones direct their action to target glands or tissues at distant receptor sites, thereby regulating critical body functions, such as urinary output, cellular metabolic rate, and growth and development. Hormonal secretions typically are regulated by negative feedback; information about the hormone level or its effect is fed back to the gland, which then responds accordingly (Figure 4-2).

FIGURE 4–1 Major glands of the normal endocrine system.

Certain endocrine glands are stimulated to secrete hormones in response to other hormones. Hormones that stimulate secretion of other hormones are called tropic hormones. For example, in women the gonadotropins stimulate the synthesis of ovarian hormones. In diagnostic analysis, when excessive hormones are produced by an ectopic source (e.g., a malignant tumor), the tropic hormones are low. Other secreting cells that perform endocrine functions may be scattered in the tissue, such as in the digestive tract, where local hormones regulate the motility and secretions of other hormones.

Endocrine diseases result from an abnormal increase or decrease in the secretion of hormones. Symptoms of disease vary with the degree of increase or decrease in hormonal secretion and the age of the patient. This divergence from normal hormone quantities may be the result of hyperplasia, hypertrophy, or atrophy of an endocrine gland. Changes in gland size that affect the gland’s production and secretion of a hormone often result from an insult to the gland, such as infection, radiation, trauma, surgical intervention, and inflammation. Dysfunction of an endocrine gland is associated with many physical and mental symptoms. Some common symptoms are:

• Growth abnormalities

• Emotional disturbances or psychiatric problems

• Skin, hair, and nail changes

• Edema

• Hypertension or hypotension

• Arrhythmia

• Changes in urine output

• Muscle weakness and atrophy

• Menstrual irregularity or amenorrhea

• Impotence or changes in libido

• Sterility

• Sharp changes in energy level

To appreciate the effect of endocrine gland function on health and disease, review the main glands and their primary hormones (Table 4-1). The pituitary gland, intimately related to the hypothalamus, plays a central role in regulating most of the endocrine glands; it has a cascading effect on the glands it stimulates. The pituitary gland is divided into anterior and posterior lobes; the anterior lobe accounts for about 80% of the gland. The hypothalamus, a part of the brain that also has endocrine functions, controls many activities of the pituitary gland via neural and chemical stimuli. Pituitary dysfunction can affect some or all of the glands that are targets of pituitary hormones, thereby indirectly affecting body structure and function (Figure 4-3).

TABLE 4–1

Major Endocrine Gland Secretions and Functions

ENDOCRINE GLAND	HORMONE	TARGET ACTION
Anterior pituitary	Growth hormone (GH)	Promotes bone and tissue growth
	Thyrotropin (thyroid-stimulating hormone [TSH])	Stimulates thyroid gland and production of thyroxine
	Corticotropin (adrenocorticotropic hormone [ACTH])	Stimulates adrenal cortex to produce glucocorticoids
	Gonadotropins
	Follicle-stimulating hormone (FSH)	Initiates growth of eggs in ovaries; stimulates spermatogenesis in testes
	Luteinizing hormone (LH)	Causes ovulation; stimulates ovaries to produce estrogen and progesterone; stimulates testosterone production
	Prolactin	Stimulates breast development and formation of milk during pregnancy and after delivery
	Melanocyte-stimulating hormone (MSH)	Regulates skin pigmentation
Posterior pituitary	Vasopressin (antidiuretic hormone [ADH])	Stimulates water resorption by renal tubules; has antidiuretic effect
	Oxytocin	Stimulates uterine contractions; stimulates ejection of milk in mammary glands; causes ejection of secretions in male prostate gland
Thyroid	Thyroxine (T₄) and triiodothyronine (T₃)—thyroid hormone (TH)	Regulates rate of cellular metabolism (catabolic phase)
	Calcitonin	Promotes retention of calcium and phosphorus in bone; opposes effect of parathyroid hormone
Parathyroid	Parathyroid hormone (parathormone, PTH)	Regulates metabolism of calcium; elevates serum calcium levels by drawing calcium from bones
Adrenal cortex	Mineralocorticoids (MC), primarily aldosterone	Promote retention of sodium by kidneys; regulate electrolyte and fluid homeostasis
	Glucocorticoids (GC): cortisol, corticosterone, cortisone	Regulate metabolism of carbohydrates, proteins, and fats in cells
	Gonadocorticoids: androgens, estrogens, progestins	Govern secondary sex characteristics and masculinization
Adrenal medulla	Catecholamines: epinephrine and norepinephrine	Produce quick-acting “fight or flight” response during stress; increase blood pressure, heart rate, and blood glucose level; dilate bronchioles
Pancreas	Insulin	Regulates metabolism of glucose in body cells; maintains proper blood glucose level
	Glucagon	Increases concentration of glucose in blood by causing conversion of glycogen to glucose
Ovaries	Estrogens	Cause development of female secondary sex characteristics
	Progesterone	Prepares and maintains endometrium for implantation and pregnancy
Testes	Testosterone	Stimulates and promotes growth of male secondary sex characteristics and is essential for erections
Thymus	Thymosin	Promotes development of immune cells (gland atrophies during adulthood)
Pineal gland	Melatonin	Regulates daily patterns of sleep and wakefulness. Inhibits hormones that affect ovaries; other functions unknown

Diagnosing endocrine disorders requires correctly matching the patient’s symptoms with a specific hormone dysfunction and obtaining laboratory confirmation of overproduction or underproduction of a particular hormone or hormones. Hormone levels usually are detected by blood tests done mostly now by radioimmunoassay (RIA) or occasionally by a 24-hour urine test. Scans, ultrasound, and magnetic resonance imaging (MRI) can help determine the type and location of a lesion. A biopsy is taken to determine whether a lesion is malignant.

After an endocrine problem is identified, treatment is initiated to replace the hormone deficit or reduce a lesion by surgical removal or radiation therapy. Newer medical therapies also inhibit the synthesis of hormones. However, therapeutic drugs may have substantial side effects.

Pituitary Gland Diseases

Hyperpituitarism

Hyperpituitarism, a chronic and progressive disease, is caused by excessive production and secretion of pituitary hormones, for example, human growth hormone (hGH). The excessive hGH produces one of two distinct conditions—gigantism or acromegaly—depending on the time of life at which the dysfunction begins.

Gigantism

Description

Gigantism describes an abnormal pattern of growth and stature.

ICD-9-CM Code 253.0

ICD-10-CM Code E22.0 (Acromegaly and pituitary gigantism)

Symptoms and Signs

When the hypersecretion of GH (growth hormone, somatotropin) occurs before puberty, the result is gigantism, a proportional overgrowth of all body tissue (Figure 4-4). The child experiences abnormal and accelerated growth, especially of the long bones, because epiphyseal closure has not begun. Typically an accelerated linear growth prompts an initial investigation in children. Sexual and mental developments are often retarded.

FIGURE 4–4 Effects of growth hormone. Comparison of (left to right) gigantism, normal, and dwarfism. (From Thibodeau GA: Anatomy and physiology, ed 6, St Louis, 2006, Mosby. Courtesy of Dr. Edmund Beard, Cleveland.)

Acromegaly

Description

Acromegaly is a chronic metabolic condition of adults caused by hypersecretion of growth hormone (GH) by the pituitary gland.

ICD-9-CM Code 253.0

ICD-10-CM Code E22.0 (Acromegaly and pituitary gigantism)

Symptoms and Signs

When the hypersecretion of GH occurs after puberty, acromegaly (an overgrowth of the bones of the face, hands, and feet) occurs, with an excessive overgrowth of soft tissue because there is already epiphyseal closure (Figure 4-6). It is often seen in people 30 to 40 years old after they experience years of excess growth hormone. The patient notices that he or she must wear larger gloves, shoes, or both. The jaw grows, causing larger spaces between the teeth. He or she may experience joint pain resulting from osteoarthritis and a host of other clinical features in the body systems.

FIGURE 4–6 Clinical features of acromegaly. (From Bennett JC, Plum F: Cecil textbook of medicine, ed 20, vol 2, Philadelphia, 1996, Saunders.)

The clinical picture of abnormal thickening of the bones of the face, hands, and feet leads the physician to perform diagnostic tests. Levels of GH are elevated. In conjunction another reliable test is a glucose tolerance test because increased glucose levels fail to suppress GH levels. As with gigantism, magnetic resonance imaging (MRI) of the pituitary and computed tomography (CT) can detect the presence of a pituitary lesion.

Treatment

The object of treatment is to reverse or prevent tumor mass effects and reduce the amount of GH secreted. Correcting the disorder prevents further disfigurement and reduces the mortality that results from production of excess growth hormone. This is performed ideally by surgery (transsphenoidal approach) with or without the addition of radiation to the pituitary gland to reduce its size (see Figure 4-5). The success of medical therapies depends on the response of tumor cells to the intervention.

Offer visual aids, including videos when available, that explain the anatomy and function of the pituitary gland and its hormones. Reinforce the physician’s explanation of the cause and treatment of acromegaly. Explain the purpose of the required diagnostic tests. Describe the surgical procedures if appropriate. Explain the medication dosage schedule and the possible adverse effects to report. Encourage the patient to express concerns and questions about changes in body image.

Hypopituitarism

Description

Hypopituitarism is a condition caused by a deficiency or absence of any of the pituitary hormones, especially those produced by the anterior pituitary lobe.

ICD-9-CM Code 253.2

ICD-10-CM Code E23.0 (Hypopituitarism)

(E23.0-E23.7 = 6 codes of specificity)

Symptoms and Signs

Because the anterior pituitary secretes several major hormones, the syndrome can be complex and marked by metabolic dysfunction, sexual immaturity, or growth retardation. Physical findings vary with the specific hormone deficiency. A deficiency of pituitary hormones that stimulate other endocrine glands can result in the atrophy of those glands. When thyrotropin (thyroid-stimulating hormone [TSH]) secretion is reduced, the functioning of the thyroid gland is affected and the patient experiences symptoms of hypothyroidism. When the secretion of corticotropin (adrenocorticotropic hormone [ACTH]) dwindles, salt balance and nutrient metabolism are affected. Gonadotropin deficiency impairs sexual functions, including sexual development, menstruation, and libido.

Hypopituitarism produces growth retardation in children. Headache and blindness are signs of tumor infringement on the optic nerve.

Patient Screening

Symptoms of the complex syndromes associated with this disorder usually have an insidious onset. Schedule a complete medical evaluation and follow office policy for referral to an endocrinologist.

Etiology

The cause of hypopituitarism may be a pituitary tumor or a tumor of the hypothalamus. Some causes are congenital deficiencies and some are acquired. In some instances, hypopituitarism results from damage to the pituitary gland caused by radiation or surgical removal or from ischemia of the gland caused by infarct, tumor, or basilar skull fracture. If the ischemia is severe and not reversed, permanent destruction of glandular tissue begins. Destruction of the entire anterior lobe is termed panhypopituitarism, and none of the important anterior pituitary hormones are secreted. The condition is most common in women, and sometimes the cause is unknown.

Diagnosis

When the patient has the clinical symptoms of hyposecretion of any of the anterior pituitary hormones, a complete medical evaluation is necessary to detect partial or selective hormone deficiencies and pinpoint the diagnosis. A history of head trauma, previous radiation, or a surgical procedure to the gland or nearby tissue contributes to the diagnosis. Plasma levels of all or some of the pituitary hormones are low. Radiographic films of the skull, cranial CT, and MRI scans are used to identify tumors. The clinical investigation must rule out disease of the target glands themselves.

Treatment

The age of the patient, the severity and type of deficiency, and the underlying cause of hypopituitarism determine the course of treatment. When neoplasia is the cause, removal of the tumor eases the symptoms. Replacement therapy with hormonal supplements, including thyroxine, cortisone, sex hormones, or somatrem or somatropin (hGH), is usually effective. Hormone levels must be continually monitored during hormone replacement therapy.

Give the patient visual aids depicting the pituitary gland, and describe the features of the major pituitary hormones. Explain the diagnostic procedures and any planned surgical intervention. Emphasize the importance of following any instructions given by the endocrinologist regarding hormone replacement therapy, and list warning signs of overreplacement. Emphasize the importance of follow-up visits to monitor the results of therapy and adjust the dosage.

Dwarfism

Description

Dwarfism is the abnormal underdevelopment of the body, or hypopituitarism, occurring in children.

ICD-9-CM Code 253.3

ICD-10-CM Code E23.0 (Hypopituitarism)

Symptoms and Signs

Hyposecretion of the pituitary gland hormones, especially GH, results in growth retardation. As a result, the child is extremely short, with a body that is small in proportion (see Figure 4-4). The prepubescent child does not develop secondary sex characteristics. The condition may be linked to other defects and a varying degree of mental retardation.

Patient Screening

Children deficient in growth hormone require regular follow-up appointments during therapy. Follow office policy for referral to an endocrinologist.

Etiology

Dwarfism can be congenital or the result of a cranial hemorrhage after the birth process. Occasionally, there is no identifiable cause. A deficiency of the growth-hormone-releasing hormone (GH-RH) produced by the hypothalamus is termed secondary hypopituitarism and results from head trauma, tumor, or infection.

Diagnosis

Physical examination shows that the child fails to grow at a normal rate and is short in stature. The child’s general health appears to be good. However, secondary tooth eruption is delayed, and fat deposits may be noted in the lower trunk area. Persistently low serum GH levels are found. A CT scan may confirm the presence of a cranial tumor.

Treatment

Somatotropin (hGH) is administered until the child reaches a height of 5 feet. These children also may need replacement of thyroid and adrenal hormones when multiple hormone deficiencies are found to exist. As they approach puberty, sex hormones are administered if necessary.

Prognosis

Clinical manifestations of GH deficiencies depend on the time of onset and the degree of hormone deficiency. Growth hormone replacement is effective in children with well-documented GH deficiency. Treatment is essential to help reach final adult height. Safety for long-term GH administration indicates negligible adverse effects.

Prevention

Known causes are not preventable, except that common precautions may be taken against head trauma and infection.

Patient Teaching

Give the patient and family visual aids, using e-learning media when available, to familiarize them with the pituitary gland and the hormones that affect growth and maturation. Explain the regimen of GH treatment, which may include frequent injections, and emphasize the importance of patient compliance to achieve the desired therapeutic goal.

Diabetes Insipidus

Description

Diabetes insipidus is a disturbance of water metabolism resulting in extreme thirst and excessive secretion of dilute urine.

ICD-9-CM Code 253.5

ICD-10-CM Code E23.2 (Diabetes insipidus)

Symptoms and Signs

Diabetes insipidus is a deficiency in the release of vasopressin (antidiuretic hormone [ADH]) by the posterior pituitary gland, resulting in the excretion of copious amounts of colorless and dilute urine (polyuria). The patient experiences excessive thirst (polydipsia), fatigue, and symptoms of dehydration, including dry mucous membranes, hypotension, dizziness, and poor skin turgor. The onset of symptoms may be abrupt.

Patient Screening

An abrupt onset of excessive thirst and excessive urination together with the symptoms of dehydration merits prompt medical attention.

Etiology

In diabetes insipidus, the posterior pituitary gland releases reduced amounts of vasopressin. The condition may be hereditary, or it may be the result of an insult to the hypothalamus or to the pituitary gland resulting from head trauma, cerebral edema, or an intracranial lesion. Nephrogenic diabetes insipidus results from renal tubular resistance to the action of vasopressin. More common in men than women, this disease may occur in childhood or early adulthood. In many cases, the cause is unknown. When the amount of vasopressin is insufficient, the distal tubules of the nephron do not reabsorb water from the filtrate back into the bloodstream; consequently, the volume of urine is excessive.

Diagnosis

The presence of polyuria and polydipsia leads the clinician to investigate the composition of the urine through laboratory tests. Urinalysis that reveals almost colorless urine that has a low specific gravity (less than 1.005) suggests diabetes insipidus as a diagnosis. To confirm the diagnosis of diabetes insipidus, the patient is given a water-restriction test, during which the kidneys exhibit the inability to concentrate urine when the patient is deprived of fluid intake for several hours. When the urine concentration (osmolality) is stable on consecutive measurement or the blood osmolality is above normal, vasopressin (antidiuretic hormone [ADH]) is administered. Urine volume is compared with specific gravity. Reduced output and increased specific gravity of urine after the administration of vasopressin indicate diabetes insipidus.

Treatment

Treatment consists of vasopressin injections, nasal spray, or oral desmopressin acetate (DDAVP). In nephrogenic diabetes insipidus, thiazide diuretics block the ability of the kidneys to excrete free water by inhibiting reabsorption of sodium and chloride and increasing the excretion of sodium, chloride, and water. Any underlying cause should be identified and treated. When the excessive diuresis is the result of trauma to the pituitary gland, the symptoms begin to subside as the insult resolves.

Give the patient guidelines for monitoring fluid intake and output to ensure adequate water replacement. Instruct the patient to notify the physician of any increase in symptoms, including weight loss or gain. Demonstrate the procedure of checking the specific gravity of urine. Discuss the side effects or toxic effects of prescribed medications. Encourage the patient to wear a Medic Alert bracelet (Figure 4-7).

Thyroid Gland Diseases

Thyroid diseases present as functional disturbances that produce excessive or reduced secretions of thyroid hormones thyroxine (T₄) and triiodothyronine (T₃), and mass lesions of the thyroid. Table 4-2 lists types of thyroid diseases with their signs and symptoms. Fortunately, diseases of the thyroid gland may be resolved through medical and surgical intervention.

TABLE 4-2

Comparison of Hypothyroid and Hyperthyroid Disorders

	HYPOFUNCTION OF THYROID	HYPERFUNCTION OF THYROID
Names or types	Congenital, untreated can become cretinism or thyroid dwarfism	Hyperthyroidism
	Myxedema	Thyrotoxicosis
	Hashimoto’s thyroiditis	Graves’ disease—autoimmune with or without exophthalmos
	Iodine deficiency—simple goiter	Toxic nodular hyperplasia
	Idiopathic hypothyroidism	Toxic adenoma, thyroid tumors
Symptoms and signs	Decreased activity, sleepiness, lethargy	Restlessness, irritability, easy fatigability, nervousness
	Reduced mental alertness, easy fatigability	Tremors
	Dry skin and hair, decreased sweating	Moist skin, increased sweating
	Cold intolerance	Heat intolerance
	Bradycardia	Tachycardia and palpitations
	Constipation	Diarrhea
	Weight gain	Weight loss, increased appetite
	Edema, bloated face, puffy eyelids	Polydipsia
	Poor circulation, extremity edema	Loss or thinning of hair
	TSH levels increased	TSH levels decreased
	T₃, T₄ levels decreased	T₃, T₄ levels increased
	I¹³¹ uptake decreased	I¹³¹ uptake increased