Acute care handbook for physical therapists (fourth edition) chapter 10 endocrine system

Acute care handbook for physical therapists (fourth edition) chapter 10 endocrine system Acute care handbook for physical therapists (fourth edition) chapter 10 endocrine system Acute care handbook for physical therapists (fourth edition) chapter 10 endocrine system Acute care handbook for physical therapists (fourth edition) chapter 10 endocrine system Acute care handbook for physical therapists (fourth edition) chapter 10 endocrine system

CHAPTER OBJECTIVES

The objectives of this chapter are the following:

1 Provide an understanding of normal functions of the endocrine system, including the thyroid, pituitary, adrenal, and parathyroid glands, as well as the pancreas

2 Describe the clinical evaluation of these endocrine organs

3 Describe the health conditions associated with endocrine system dysfunction and subsequent medical management

4 Provide physical therapy guidelines for working with patients who have endocrine system dysfunction

PREFERRED PRACTICE PATTERNS

The most relevant practice patterns for the diagnoses discussed in this chapter, based on the

American Physical Therapy Association’s Guide to Physical Therapist Practice, second edition,

are as follows:

• Primary Prevention/Risk Reduction for Skeletal Demineralization: 4A

• Impaired Aerobic Capacity/Endurance Associated with Deconditioning: 6B

• Primary Prevention/Risk Reduction for Integumentary Disorders: 7APlease refer to Appendix A for a complete list of the preferred practice patterns, as individual patient conditions are highly variable and other practice patterns may be applicable

The endocrine system consists of endocrine glands, which secrete hormones into the stream, and target cells for those hormones Target cells are the principal sites of action for the endocrine glands Figure 10-1 displays the location of the primary endocrine glands.The endocrine system has direct effects on cellular function and metabolism throughout the entire body, with symptoms of endocrine dysfunction, metabolic dysfunction, or both often mimicking those of muscle weakness.1 Therefore it is important for the physical therapist to carefully distinguish the source (endocrine versus musculoskeletal) of these symptoms to opti-mally care for the patient For example, complaints of weakness and muscle cramps can both result from hypothyroidism or inappropriate exercise intensity If the therapist is aware of the patient’s current endocrine system status, then inquiring about a recent medication adjustment may be more appropriate than adjusting the patient’s exercise parameters

blood-As a group, the prevalence of endocrine and metabolic disorders is approximately 5% of the U.S population.2 An estimated deficit in endocrinologists to meet the demands of the population is projected through the year 2020.2 According to the Centers for Disease Control and Prevention (CDC), approximately 1.7% of the diagnoses of patients admitted to the emergency room were classified as endocrine disorders,3 4.9% of ambulatory care visits are a result of endocrine or metabolic disorders,4 and 5.3% of hospital discharges had endocrine or metabolic disorders listed as a primary diagnosis.5

General Evaluation of Endocrine FunctionMeasurement of endocrine function can be performed by examining (1) the endocrine gland itself, using imaging techniques, or (2) levels of hormones or hormone-related substances in the bloodstream or urine When reviewing the medical record, it is important for the physical therapist to know that high or low levels of endocrine substances can indicate endocrine

Body Structure and Function

Adrenal and Metabolic Tests

dysfunction A common method for assessing levels of hormone

is radioimmunoassay (RIA).6 RIA is an immunologic technique

for comparing levels of radiolabeled hormone with unlabeled

hormone, which compete for binding sites on a given

antibody

Another method of evaluation, referred to as provocative

testing, can be classified into suppression or stimulation tests

Stimulation tests are used for testing endocrine hypofunction;

suppression tests are useful for evaluating endocrine

hyperfunc-tion.7 The most commonly used endocrine tests are discussed

in this chapter Clinicians should refer to their particular

insti-tution’s laboratory values (generally located in the lab result

section of the clinical record) for normal ranges of hormone or

hormone-related substances referenced in their setting

referred to as the thyroid hormones (Table 10-1) Thyroxine and triiodothyronine require the presence of adequate amounts of iodine to be properly synthesized Therefore dietary deficiencies

of iodine can hinder thyroid hormone production The tion and secretion of thyroid hormones are regulated by thyro-tropin (also called thyroid-stimulating hormone [TSH]), which

produc-is secreted from the anterior pituitary gland TSH levels are directly influenced by T4 levels through a negative feedback loop Thyrotropin is further regulated by thyrotropin-releasing hormone, which is secreted from the hypothalamus.8-10

Thyroid Tests

Thyroid hormones T4 and T3 circulate throughout the stream bound to proteins or unbound, in which case they are metabolically active by themselves Thyroxine-binding globu-lin (TBG) is one of the major thyroid transport proteins.9Serum levels of T4 and T3 are usually measured by RIA Table10-2 describes the tests used to measure thyroid hormones, and Table 10-3 summarizes other tests used to measure thyroid function

blood-FIGURE 10-1

Schematic representation of the primary endocrine glands in women and

men (Courtesy Marybeth Cuaycong.)

Body Structure and Function

The thyroid gland secretes three hormones: thyroxine (T4),

tri-iodothyronine (T), and calcitonin, with T and T commonly

Gland Hormones

Hormone(s) Target Site(s) Actions

Thyroxine (T 4 ) and triiodothyronine (T 3 )

Systemic Increases metabolic rate;

stimulates growth, and development of all cells, particularly of the nervous system; and enhances the effects of catecholamines Thyrocalcitonin Bone Inhibits bone resorption

Lowers blood levels of calcium Data from Brashers VL, Jones RE: Mechanisms of hormonal regulation In McCance KL, Huether SE, Brashers VL et al, editors: Pathophysiology: the biologic basis for disease in adults and children, ed 6, St Louis, 2010, Mosby,

pp 697-726; Hall S: Prescribing in thyroid disease, Nurse Prescribing

8(8):382-387, 2010.

CLINICAL TIP

Low levels of thyroid hormones T3 or T4 may result in weakness, muscle aching, and stiffness Based on this information, the physical therapist may decide to alter treatment parameters by decreasing the treatment intensity to optimize activity toler-ance, minimize patient discomfort, or both Radionuclide testing may also affect a patient’s mobility: patients may be on bed rest or precautions after radionuclide studies The physical therapist should refer to the physician’s orders after testing to clarify the patient’s mobility status

Thyroid Disorders

Disorders of the thyroid gland result from a variety of causes and can be classified as hyperthyroidism or hypothyroidism

TABLE 10-2 Thyroid Hormone Tests

Hormone Test Description Normal Value (adults)

Serum thyroxine (T 4 ) Radioimmunoassay (RIA) measurement 4-12 mcg/dl

Serum triiodothyronine (T 3 ) RIA measurement 40-204 ng/dl

Free thyroxine index Direct RIA measurement or indirect calculated

Thyroid-stimulating hormone (TSH) Radioisotope and chemical labeling

Thyrotropin-releasing hormone (TRH) Intravenous administration of TRH to patients.

TRH augments the function of TSH in patients with hypothyroidism.

Only performed in difficult diagnostic cases.

The expected response is a rise in TSH levels.

Normal rise in men and women is 6 µU/ml above baseline TSH levels.

Normal rise in men older than 40 years is

2 µU/ml above baseline.

Hypothyroidism is indicated by increased response to TRH.

Hyperthyroidism is indicated by no response to TRH.

Data from Sacher RA, McPherson RA, Campos JM, editors: Widman’s clinical interpretation of laboratory tests, ed 11, Philadelphia, 2000, FA Davis, pp 741-823; Cohee L: Endocrinology In Johns Hopkins Hospital, Arcara K, Tschudy M, editors: The Harriet Lane handbook, ed 19, St Louis, 2011, Mosby.

Test Description

Triiodothyronine resin uptake

(RT 3 U) RT3disorders from true thyroid disease Thyroid hormone uptake is high with hyperthyroidism and low U qualifies levels of bound versus unbound T4 and T3 and helps to distinguish protein-binding

with hypothyroidism.

Thyroidal 24-hour radioactive

iodine uptake (RAIU) Used to determine metabolic activity of the thyroid gland Radioactive iodine is administered, and the percentage of total administered radioactive iodine taken up by the thyroid in 24 hours is then

calculated.

Normal radioactive iodine uptake is 10% to 25%.

Hypothyroidism results in reduced uptake.

Thyroid imaging or scan Intravenous administration of radionuclides allows imaging or scanning of particular areas of the

thyroid gland.

Increased or decreased uptake of the radionuclide can help diagnose dysfunction.

Ultrasound Nodules of the thyroid gland that are palpable or detected by other imaging modalities are indications

for ultrasound to help diagnose possible malignancy.

Needle biopsy Fine-needle aspiration of thyroid cells may help diagnose a suspected neoplasm.

Data from Sacher RA, McPherson RA, Campos JM, editors: Widman’s clinical interpretation of laboratory tests, ed 11, Philadelphia, 2000, FA Davis, pp 786-793; Bastin S, Bolland MJ, Croxson MS: Role of ultrasound in the assessment of nodular thyroid disease, J Med Imaging Radiat Oncol 53;177-187, 2009; McDermott M: Endocrine secrets, ed 5, St Louis, 2009, Mosby, pp 279-282.

Hyperthyroidism

Hyperthyroidism, or thyrotoxicosis, is primarily characterized

by excessive sympathomimetic and catabolic activity resulting

from overexposure of tissues to thyroid hormones In addition,

it has been reported that hyperthyroidism results in both an

increased sympathetic activity with concurrent decreased vagal

(parasympathetic) tone.11 Spectral analysis of heart rate

vari-ability has been shown to detect these changes and is helpful in

determining the severity of hyperthyroidism.11 Heart rate

vari-ability is discussed further in Chapter 3 Patients may also

present with subclinical hyperthyroidism, which may or may not

lead to overt hyperthyroidism Subclinical hyperthyroidism is

defined by low TSH levels and normal T3 and T4 levels.12

The most common causes of hyperthyroidism are outlined in

• Fatigue, weakness, increased reflexes

• Palpitations, atrial fibrillation, tachycardia

• Moist and warm skin, or smooth and velvety skin

• Increased perspiration, heat intolerance

• Diarrhea, thirst, weight loss despite increased appetite

• Reduced menstruation

• Lid lag, retraction, or both

• Finger nails that grow away from the nail bed, thinning or loss of hair

• Thyroid bruit, presence of goiter

• Patients may also present with subclinical hyperthyroidism

• Delayed deep tendon reflexes

• Cold intolerance

• Weakness, muscle cramps, and aching and stiffness

• Slow speech, decreased hearing

• Paresthesia

• Nonpitting edema of eyelids, hands, and feet

• Bradycardia with elevated systolic and diastolic blood pressure

• Cardiac failure, pericardial effusion

• Coma and respiratory failure in severe casesAdditional laboratory findings that are associated with hypo-thyroidism include the following16:

• Low glucose and serum sodium levels

• Anemia

• Elevated levels of cholesterol, creatinine phosphokinase MM), serum myoglobin, lactate dehydrogenase, liver enzymes, homocysteine, and prolactin

(CK-• ProteinuriaManagement of hypothyroidism typically includes lifelong thyroid hormone replacement, primarily consisting of generic and brand-name variations of levothyroxine.10,13 A complete list

of medications is provided in Chapter 19, Table 19-42

Management of hyperthyroidism primarily includes

phar-macologic therapy, which is summarized in Chapter 19, Table

19-42 Surgical management is indicated for patients with large

goiters, large “hot” nodules or where other options have been

ruled out.14 Surgical options include six different procedures

that remove portions or all of the thyroid gland.15

Hypothyroidism

Hypothyroidism is the insufficient exposure of peripheral tissues

to thyroid hormones It affects growth and development, as well

as many cellular processes Primary hypothyroidism is caused by

decreased thyroid hormone production by the thyroid gland and

accounts for the majority of thyroid disease Secondary

hypothy-roidism is caused by either pituitary or hypothalamic disease

resulting in reduced TSH levels.13

The following are the causes of primary and secondary

hypothyroidism13,14:

• Congenital maldevelopment, hypoplasia, or aplasia of the

thyroid gland

• Hashimoto’s thyroiditis (autoimmune inflammation)

• Hypopituitarism or hypothalamic disease

• Severe iodine deficiency

• Thyroid ablation from surgery, radiation of cervical

neo-plasms, or radioiodine therapy for hyperthyroidism

• Drug toxicity (from amiodarone or lithium)

General signs and symptoms of hypothyroidism vary

accord-ing to the degree of thyroid deficiency Signs and symptoms

include the following8,10,13:

• Lethargy, somnolence, and reduced cognitive function

• Constipation and ileus (decreased motility)

• Rough, scaly, dry, and cool skin, decreased perspiration,

yel-lowish complexion

CLINICAL TIP

Properly managed hyperthyroidism or hypothyroidism should not affect physical therapy intervention or activity tolerance If the signs or symptoms just mentioned are present during physi-cal therapy evaluation, treatment, or both, then consultation with the medical team is indicated to help differentiate the etiol-ogy of the physical findings

Cause Description

Graves’ disease A familial, autoimmune disorder responsible for approximately 80% to 90% of hyperthyroid

cases Occurs more commonly in women than men.

Distinguishing features include diffuse thyroid enlargement, ophthalmopathy (double vision and sensitivity to light), exophthalmos (excessive prominence of the eyes), pretibial myxedema (thickening, redness, and puckering of skin in the front of the tibia), atrial fibrillation, fine hand tremors, and weakness of the quadriceps muscle.

Thyroiditis Inflammation of the thyroid gland can result from an acute bacterial infection, a subacute

viral infection, or chronic inflammation with unknown etiology.

Pain may or may not be present on palpation of the gland.

Toxic nodular and multinodular goiter Areas of the enlarged thyroid gland (goiter) become autonomous and produce excessive

amounts of thyroid hormones.

Thyroid adenoma Solitary, benign follicular adenomas that function autonomously result in hyperthyroidism if

the adenoma nodule is larger than 4 cm in diameter.

May present as a painless lump in the throat.

Thyroid carcinoma Four types of malignancies in the thyroid gland: papillary carcinoma (most common),

follicular carcinoma, anaplastic carcinoma, and medullary carcinoma.

Exogenous hyperthyroidism Ingestion of excessive amounts of thyroid hormone or iodine preparation.

Can be classified as iatrogenic hyperthyroidism, factitious hyperthyroidism, or iodine-induced hyperthyroidism.

Data from Woolf N, editor: Pathology, basic and systemic, London, 1998, Saunders, pp 863-873; Mitrou P, Raptis SA, Dimitriadis G: Thyroid disease in older people, Maturitas 70:5-9, 2011.

Pituitary Gland

Body Structure and Function

Hormones secreted by the pituitary gland are responsible for a

variety of functions that are summarized in Table 10-5

Secre-tions of hormones from the pituitary gland are closely regulated

by the hypothalamus and by negative feedback from the

hor-mones that are secreted from the pituitary gland.8

Pituitary Tests

Individual pituitary hormone levels can be measured (1) by

random blood samples; (2) by blood samples before and after

the administration of specific releasing substances, such as

serum TSH, during a thyrotropin-releasing hormone test (see

Table 10-2); or (3) by blood samples before and after the

admin-istration of specific stimuli acting directly on the pituitary

or via the hypothalamus, such as serum growth hormone

(GH), serum cortisol, and plasma adrenocorticotropic hormone

(ACTH) Table 10-6 describes common tests of pituitary

function

Pituitary function can also be evaluated by (1) thyroid

func-tion tests, which are an indirect assessment of TSH secrefunc-tion

from the pituitary, and (2) plain x-rays or computed

tomogra-phy with contrast to highlight a pituitary tumor.17

Pituitary Disorders

Dysfunction of the pituitary-hypothalamic system generally

results from hypersecretion or hyposecretion of tropic hormones

Hypersecretion of pituitary hormones (hyperpituitarism) is

most commonly due to adenoma in the anterior lobe (benign

tumors).18 Hyposecretion of pituitary hormones (pituitary

insufficiency) can result from pituitary disease, diseases affecting

the hypothalamus or surrounding structures, or disturbance of

blood flow around the hypothalamus and pituitary.19,20

Hormone(s) Target Site(s) Action(s)

Anterior Lobe

Growth hormone Systemic Stimulates body growth, lipolysis, inhibits insulin action on

carbohydrates and lipids Thyrotropin (thyroid-stimulating hormone) Thyroid Stimulates production of thyroid hormones

Adrenocorticotropic hormone (ACTH) Adrenal cortex Stimulates production of androgens and glucocorticoids by adrenal

cortex Follicle-stimulating hormone Ovaries Development of follicles and secretion of estrogen

Testes Development of seminiferous tubules and spermatogenesis Luteinizing or interstitial cell–stimulating

hormone OvariesTestes Ovulation, formation of corpus luteum, and secretion of progesteroneSecretion of testosterone Prolactin or lactogenic hormone Mammary glands Stimulates milk production and secretion

Posterior Lobe

Antidiuretic hormone * (also called

vasopressin) Kidney Controls rate of water excretion into the urineFluid and electrolyte balance

Breast Expression of milk

*Actually produced in the hypothalamus but stored in the pituitary gland.

From Hall JE: Pituitary hormones and their control by the hypothalamus In Guyton and Hall textbook of medical physiology, ed 12, St Louis, 2010, Saunders Elsevier, pp 895-906.

HyperpituitarismThe overproduction of the pituitary hormones GH, ACTH, and antidiuretic hormone (ADH) is discussed next

Growth Hormone Overproduction Excessive GH

secre-tion is referred to as acromegaly in adults or gigantism in children Excessive GH secretion has been linked primarily to anterior pituitary adenomas and not necessarily to excessive hypothalamic stimulation of the pituitary.20

Clinical manifestations for children with gigantism are acterized by disproportionately long limbs.18

char-Signs and symptoms of adults with acromegaly include the following20,21:

• Enlargement of hands and feet, coarse facial features with furrowed brows

• Oligomenorrhea or amenorrhea in women

• Paresthesia of hands, carpal tunnel syndrome

of choice in both Europe and the United States) and gery for macroadenomas.22 Medical therapy consists of GH

CLINICAL TIP

ity progression should proceed cautiously, with a focus on energy conservation, joint protection techniques, and fall-prevention strategies

Given the multisystem effects in patients with acromegaly, activ-TABLE 10-6 Pituitary Hormone Tests

Hormone(s) Test Description

Growth hormone (GH) Serum level measurement by radioimmunoassay (RIA); normal values for men are 0 to 5 ng/ml; normal values

for women are 0 to 10 ng/ml.

Growth hormone–stimulation test (arginine test or insulin tolerance test) A baseline level of GH is established,

then arginine or insulin is administered to the patient, and serial blood draws are performed to measure

GH levels GH should normally rise Failure of GH levels to rise significantly may indicate growth hormone deficiency.

Growth hormone suppression test (glucose load test) A baseline level of GH is established, followed by patient

ingestion of a glucose solution Levels of GH are redrawn at timed intervals Normally, glucose inhibits the secretion of GH If GH levels remain high despite the glucose load, then the likelihood of gigantism

or acromegaly is increased.

Adrenocorticotropic

hormone (ACTH) Plasma ACTH levels are measured by RIA Normal values are 25-100 pg/ml in the morning and 0-50 pg/ml in the evening.

ACTH-stimulation test (Cortrosyn stimulating test) Indicated for evaluating primary or secondary adrenal

insufficiency Cosyntropin (Cortrosyn, a synthetic form of ACTH) is administered to the patient after a baseline level of cortisol is measured ACTH acts to increase cortisol secretion from the adrenal gland Normal results show an increased plasma cortisol level to >20 pg/dl after 30-60 minutes.

ACTH-suppression test (dexamethasone suppression test) Dexamethasone is administered to the patient to

determine ACTH response, which should be a reduction in ACTH levels in non-obese individuals May be used in the diagnosis of Cushing’s syndrome.

Water deprivation test (dehydration test or concentration test) Indicated to aid in the diagnosis of diabetes

insipidus (DI), either central or nephrogenic DI, or primary polydipsia.

Water loading test Indicated to aid in the diagnosis of syndrome of inappropriate antidiuretic hormone

(SIADH) During the test, the patient ingests 20 to 25 ml/kg of fluid, with hourly serum and urine osmolality levels being measured for 4 hours.

Data from Malarkey LM, McMorrow ME, editors: Nurse’s manual of laboratory tests and diagnostic procedures, Philadelphia, 2000, Saunders, pp 580-584, 552-555, 613-614, 616-619; and Wilson G, Mooradian A, Alexandraki I, Samrai G: Endocrinology In Rakel RE, Rakel DP, editors: Textbook of family medicine, ed 8, Phila- delphia, 2011, Elsevier Saunders, pp 756-784.

CLINICAL TIP

Blood pressure changes during activity should be monitored, given the possibility of hypertension Caution should also be taken to avoid bruising during mobility Refer to the Diabetes Mellitus section for further activity considerations

suppression with somatostatin receptor ligands (SRLs),

dopa-mine agonists (DAs), and GH receptor antagonists (GHRA)

Radiation therapy is considered third-line treatment.23

Adrenocorticotropic Hormone Overproduction An

increase in ACTH production by the pituitary gland results in

increased levels of serum cortisol, which is a glucocorticoid

secreted by the adrenal glands Glucocorticoids are involved

with carbohydrate, protein, and fat metabolism; therefore excess

cortisol levels affect these cellular processes Cushing’s

syn-drome results from glucocorticoid excess (hypercortisolism)

Cushing’s disease, however, is specific to ACTH-producing

microadenomas in the pituitary gland.24 Pituitary

hypersecre-tion of ACTH occurs in approximately 70% of patients with

Cushing’s syndrome The hypersecretion of ACTH may

origi-nate either from a tumor in the pituitary gland or from ectopic

neuroendocrine tumors elsewhere in the body.8,25

Signs and symptoms of Cushing’s syndrome include the

following8,17,20,25:

• Truncal obesity with thin extremities (loss of type II muscle

fibers)18

• Redness and rounding of the face (moon face)

• Easy bruising, thinning of the skin, and presence of striae

and darker pigmentation

• Hirsutism, oligomenorrhea, or amenorrhea

• Hypertension

• Osteoporosis (radiographically confirmed)

• Peripheral muscle wasting

Management of weakness, pain, edema, and osteoporosis should be the focus of physical therapy intervention and should be complementary to the medical management of the patient

• Decreased libido, impotence with loss of pubic and axillary hair in men

• Amenorrhea and infertility in women

• Pallor

• Short stature (in children)

• Hypothyroidism

• HypoadrenalismManagement of panhypopituitarism may include the follow-ing: replacement therapy or pituitary hormones, such as thyrox-ine, glucocorticoids, and GH for children; desmopressin for DI; androgen therapy for men; or estrogen therapy for women younger than 50 years of age Management of other clinical sequelae of hypopituitarism is specific to the involved areas.17,33Diabetes Insipidus

DI involves the excretion of a large volume (i.e., greater than

50 ml/kg per day) of dilute urine (hypotonic polyuria) DI may result from an absence of vasopressin or an inadequate response to vasopressin Four categories of DI exist: primary polydipsia, central (hypothalamic) DI, gestational DI, and nephrogenic DI.34

Signs and symptoms of DI may be transient or permanent, and include the following28,33,35,36:

• Polyuria, nocturia with resultant hypernatremia (increased sodium)

• Thirst (especially for cold or iced drinks), polydipsia

• Dehydration

• Weight loss

• Dry skin with decreased turgor

• Central nervous system manifestations (e.g., irritability, mental dullness, ataxia, hyperthermia, and coma) if access to water is interrupted

Management of DI may include pharmacologic treatment, such as the following: deamino-8-d-arginine vasopressin (des-mopressin), chlorpropamide (Diabinase), clofibrate (Atromid-S), carbamazepine (Tegretol), and thiazide diuretics in combination with a sodium-restricted diet.37

Adrenal Gland

Body Structure and Function

The adrenal gland has two distinct areas, the outer cortex and the inner medulla, that differ in their function and embryologic origin.8Table 10-7 summarizes the target sites and actions of the adrenal gland hormones

Adrenal and Metabolic Tests

Adrenal TestsEvaluation of the adrenal cortical (glucocorticoids, androgens, and mineralocorticoids) and medullary (epinephrine and norepi-nephrine) hormones is typically performed by measuring plasma and/or urinary levels of the hormone in question Reference values for adults for each hormone are listed in Table 10-7 The primary method for evaluating adrenal activity is by measuring plasma cortisol levels Levels are usually drawn at 8 am and then

Antidiuretic Hormone Overproduction The syndrome of

inappropriate ADH (SIADH) secretion is a condition of fluid

and electrolyte imbalance resulting in hyponatremia (reduced

sodium levels) from excessive water reabsorption In this

condi-tion, ADH is secreted from the posterior pituitary gland when

it should be inhibited Hyponatremia is fairly common in

hos-pitalized patients and can result in significant morbidity and

mortality.26 Numerous etiologies of SIADH exist, with the most

frequent cause being small cell or oat cell carcinomas of the

lung Other etiologies include the following27,28:

• Bacterial pneumonias, chronic obstructive pulmonary

disease, tuberculosis, lung abscesses

• Malignancies of the pancreas, duodenum, colon, lymphoid

tissue, and thymus

• Medication side effects from antipsychotics,

sedative-hypnotics, antidepressants, diuretics, antihypertensives,

analgesics, cardiac drugs, nonsteroidal antiinflammatory

drugs, and antibiotics29

• Head trauma, central nervous system neoplasms

Mild SIADH is usually asymptomatic More severe cases,

however, can result in fluid and electrolyte imbalances, resulting

in interstitial edema from a lack of serum sodium Many systems

will be affected by this edema, with the nervous system being

most severely involved Manifestations may include the

follow-ing: headaches, nausea, confusion, gait disturbances, falls, and

cerebral edema that leads to seizures and coma (in severe

cases).18,26,27

Management of SIADH may include the following:

treat-ment of the underlying cause, fluid restriction, or

administra-tion of select agents such as demeclocycline, lithium, and urea

Intravenous administration of sodium chloride (saline) solution,

or administration of diuretics (furosemide) may also be used as

initial therapies but not for long-term management.26,27,29

The developing use of vaptans or vasopressin-2 receptor

antagonists for mild to moderate cases of SIADH has resulted

in good outcomes.26,30

Hypopituitarism

Decreased secretion of pituitary hormones can result from either

pituitary or hypothalamic dysfunction Complete anterior

pitu-itary hormone deficiency is referred to as panhypopituitarism.31

Most cases of pituitary hypofunction arise from destructive

pro-cesses involving the anterior pituitary, such as ischemic necrosis

occurring during the late stages of pregnancy (Sheehan’s

syn-drome) Additional causes may include pituitary adenomas,

traumatic brain injury, pituitary surgery, or radiation.31

Symptoms and physical findings depend on the extent of the

disorder and the specific hormone (GH, TSH, or ACTH) and

target cells involved, such as32:

Glucose Tolerance Test One of the criteria of the National

Diabetes Data Group is to have a glucose tolerance test (GTT) result that presents with normal fasting blood glucose and a peak GTT and a 2-hour value of greater than 200 mg/dl on more than one occasion.39 To perform the test, a 75-g or 100-g glucose load is given to the subject in the morning after a 12-hour fast Blood glucose levels are then measured at variable time periods, ranging from every half hour to every hour for the next 2 to 4 hours after the glucose administration The subject must remain inactive and refrain from smoking throughout the duration of the test Normally, the blood glucose levels should fall back to baseline values in a 2-hour period Normal glucose value for a fasting blood sugar (BS) is less than approximately

110 mg/dl After 1 hour of ingesting the glucose load, expected levels of glucose are less than 200 mg/dl and 70 to 115 mg/dl after 4 hours.39

Adrenal Disorders

Adrenal HyperfunctionIncreased secretion of glucocorticoids (hypercortisolism) results

in Cushing’s syndrome, which is discussed in detail earlier in this chapter

4 pm to evaluate whether there is any deviation from the

expected diurnal variation Cortisol levels peak in the morning

and taper during the rest of the day Increased levels indicate

Cushing’s syndrome, decreased levels suggest Addison’s disease

Normal serum levels are 5 to 23 mcg/dl (8 to 10 am) and 3 to

13 mcg/dl (4 to 6 pm).38,39

Analysis of urine over a 24-hour period is used to determine

the urinary levels of free cortisol Normal levels are less than

100 mcg/dl for a 24-hour period.38,39 ACTH levels are usually

examined concomitantly with cortisol levels, as ACTH

secre-tion from the pituitary gland is necessary for cortisol secresecre-tion

from the adrenal glands Refer to Table 10-6 for details on

ACTH measurement

Anatomic investigation of the adrenal glands may also be

performed to diagnose possible adrenal dysfunction Common

methods to accomplish this are computed tomography scan (to

identify adrenal tumors), radioisotope scan using

selenocholes-terol, ultrasound, arteriogram, adrenal venogram (allows

mea-surements of hormone levels), and intravenous pyelogram (see

the Diagnostic Tests section in Chapter 9).38

Metabolic Tests

Metabolic tests are described in this section, as glucocorticoids

(cortisol) affect carbohydrate, protein, and fat metabolism

Hormone(s) Target Site(s) Action(s) Reference Values*

Cortex

Mineralocorticoids

(aldosterone) Kidney Reabsorption of sodium and waterElimination of potassium Upright position5-30 ng/dl (females)†:

6-22 ng/dl (males) Urine:

2-26 mcg/24 hr Glucocorticoids (cortisol) Systemic Metabolism of carbohydrate,

protein, and fat Response to stress Suppresses immune responses Anti-inflammation

5 to 23 mcg/dl (8 to 10 am)

3 to 13 mcg/dl (4 to 6 pm) 39

Urine:

<100 mcg/dl in 24 hours Sex hormones (androgens,

progesterone, and

estrogen)

Systemic Preadolescent growth spurt, affects

secondary sex characteristics Testosterone:280-180 ng/dl (males)

<70 ng/dl (females) Estrogen:

10-50 pg/ml (males) 20-750 pg/ml (females, menstrual phase dependent)

<20 pg/ml (postmenopausal female) Medulla

Epinephrine Cardiac and smooth

muscle, glands Emergency functionsStimulates the action of the

sympathetic system

Epinephrine: 1.7-22.4 mcg/24 hr

Norepinephrine Organs innervated by

sympathetic nervous system

Chemical transmitter substance Increases peripheral resistance Norepinephrine: 12.1 to 85.5 mcg per 24 hours

*Blood levels unless otherwise specified.

†Aldosterone levels vary from supine to upright positions.

Data from Fuller BF: Anatomy and physiology of the endocrine system In Hudak CM, Gallo BM, editors: Critical care nursing: a holistic approach, ed 6, phia, 1994, Lippincott, p 875; Corbett JV, editor: Laboratory tests and diagnostic procedures with nursing diagnoses, ed 5, Upper Saddle River, NJ, 2000, Prentice Hall Health, p 391; Pagana KD, Pagana TJ: Mosby’s diagnostic and laboratory test reference, ed 9, St Louis, 2009, Mosby.

Philadel-Adrenal Insufficiency

Autoimmune dysfunction can lead to destruction of the adrenal

cortex (i.e., primary adrenal insufficiency or Addison’s disease)

Additionally, ACTH deficiency from the pituitary gland can

lead to atrophy of the adrenal cortex (secondary adrenal

insuf-ficiency) The net result is an impaired adrenal system with

decreased levels of glucocorticoids (cortisols),

mineralocorti-coids (aldosterone), and androgens Given the systemic

func-tions of these hormones, Addison’s disease can have severe

consequences if left untreated Fortunately, the incidence of

Addison’s disease is rare.40

Cortisol deficiency results in decreased gluconeogenesis

(glucose production), which in turn alters cellular

metabo-lism Decreased gluconeogenesis also results in hypoglycemia

and decreased ability to respond to stress Aldosterone

deficiency causes fluid and electrolyte imbalance, primarily

as a result of increased water excretion that leads to

dehydration.41,42

Symptoms and physical findings common to adrenal

insuf-ficiency include the following40,43:

• Weakness, fatigue

• Weight loss, nausea, vomiting, vague abdominal pain

• Muscle and joint pain

• Salt craving in fewer than 20% of patients

• Hyperpigmentation

• Hypotension

Management of adrenal insufficiency typically includes

phar-macologic intervention with any of the following steroids:

hydrocortisone, prednisone, dexamethasone fludrocortisone, or

cortisone.36,40

Pheochromocytoma

Pheochromocytoma is a rare adrenomedullary disorder caused

by a tumor of the chromaffin cells in the adrenal medulla, which

results in excess secretion of the catecholamines, epinephrine,

and norepinephrine Disease presentation can occur either in

childhood or early adulthood with sporadic

pheochromocyto-mas occurring between 40 and 50 years of age.44 Given the rare

occurrence of this tumor, it often goes undiagnosed Proper

diagnosis is essential, as the sustained release of catecholamines

can be life threatening.43,45,46

Signs and symptoms of pheochromocytoma include the

following41,43,45,46:

• Classic triad of palpitations, headaches, and sweating lasting

minutes to hours

• Flushing, nausea, tiredness, or weight loss

• Abdominal pain, constipation, or chest pain

• Elevated blood glucose levels and glucosuria

Management of pheochromocytoma generally includes

sur-gical excision of the tumor with preoperative pharmacologic

management to block the effects of circulating catecholamine

in all patients with catecholamine-producing tumors with

alpha-adrenergic blockers and/or calcium channel blockers:

nifedipine, diltiazem, phenoxybenzamine, or doxazosin

Low-dose beta-blockade with metoprolol, bisoprolol, or atenolol may

also be implemented preoperatively.46

Pancreatic Disorders

Insulin Resistance

Insulin resistance is an important link to the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, and possibly some cancers Patients who are overweight or obese are more likely to develop insulin resistance over time; however, patients who are not obese may also have insulin resistance Patients who have insulin resistance also present with compen-satory hyperinsulinemia and hyperglycemia Furthermore, insulin resistance in the absence of metabolic syndrome criteria (see the next section) has also been shown to be independently related to developing cardiovascular disease Insulin resistance has been detected 10 to 20 years before developing diabetes in individuals who are offspring of patients with type 2 diabetes.47-50

Metabolic Syndrome

According to an international, multiassociation statement,

“metabolic syndrome is a complex of interrelated risk factors for cardiovascular disease (CVD) and diabetes mellitus Patients with the metabolic syndrome have twice the risk of developing CVD over the next 5 to 10 years as compared to individuals without the syndrome Additionally, metabolic syndrome confers a fivefold increase in risk for developing type 2 diabetes mellitus.”51

Metabolic syndrome is defined as the cluster of clinical festations that are present just before the onset of type 2 diabe-tes.52 Patients with metabolic syndrome have a high likelihood

mani-of having concurrent insulin resistance However, the difference between metabolic syndrome and insulin resistance syndrome

is that metabolic syndrome focuses on establishing a diagnosis for patients who are at higher risk for type 2 diabetes and car-diovascular disease and prescribing timely intervention to offset the development of these diseases and their complications Cur-rently, there are no defined diagnostic criteria for insulin resis-tance syndrome.47,53

The diagnosis of metabolic syndrome is established when patients have at least three of the criteria outlined in Table 10-8.The cornerstone of management of this syndrome is weight loss, with a modest reduction in initial weight of 7% to 10% demonstrating significant reduction in the development of dia-betes and cardiovascular disease.52 In addition to this therapeu-tic lifestyle change, participation in an exercise program has

CLINICAL TIP

In the acute care setting, physical therapists unfortunately will not have a significant role in exercise prescription to create the long-term changes necessary to modify metabolic syndrome However, if working with patients who have metabolic syn-drome, physical therapists should either ensure that patients can continue with a current exercise program or strongly recom-mend follow-up services for patients to begin an exercise program

on the classification of diabetes, the current terminology for diabetes uses type 1 and type 2 diabetes to distinguish between the two primary types.54,56 Other forms of glucose intolerance disorders exist but are not discussed in this book.

Recent studies indicate a bidirectional association between diabetes and depression with increased risk among individuals who are being treated for type 2 diabetes.57-59 Routine screening for depression should be considered if clinicians note increased risk of elevated symptoms in those with diabetes If patient is found to be at risk for depression, referral may be appropriate.57-59Outcome measure tools that are useful to assess depression include the Center for Epidemiologic Studies Depression Scale (CES-D), Mini Mental State Exam (MMSE), and Patient Health Questionaire.59-61

Type 1 DiabetesType 1 diabetes is an autoimmune disorder with a genetic-environmental etiology that leads to the selective destruction of beta cells in the pancreas This destruction results in decreased

or absent insulin secretion Type 1 diabetes represents 5% to 10% of the population with diabetes and generally occurs in individuals under the age of 40 years.54,56,62-64 Other etiologies for type 1 diabetes exist but are not discussed in this book.Classic signs and symptoms of type 1 diabetes are described

in the previous section with the diagnostic criteria for diabetes.62

Management of type 1 diabetes may include the following63-65:

• Close self- or medical monitoring of blood glucose levels (Table 10-9)

• Insulin administration through oral medications, cular injection, or continuous subcutaneous insulin infusion (CSII) pump CSII therapy has been shown to be as effective

intramus-as multiple daily injections of insulin, while also providing the ability to mimic a more natural glycemic response in fasting and postprandial states (Table 10-10) A medication summary is provided in Chapter 19, Table 19-39

• New options for insulin routes of administration have been

in various stages of investigation and development, ing oral spray, insulin pill, insulin patch, artificial pancreas, and inhaled insulin.66 These routes of administration are further described later, after the type 2 diabetes section

includ-• Diet modification based on caloric content, proportion of basic nutrients and optimal sources, and distribution of nutrients in daily meals

• Meal planning

• Exercise on a regular basis

Research directed at curing type 1 diabetes is aimed at specifically identifying the causative genes, permanent replace-ment of lost beta-cell function (which could involve islet cell transplantation), regeneration of beta cells, or development of

an immortalized insulin-secreting cell line.54 These therapies are administered directly after diagnosis to increase beta-cell function Currently stem cells from donor bone marrow and

a patient’s own umbilical cord blood are being investigated Drug studies are also being investigated in an attempt

to prevent this autoimmune attack by reeducating the immune system.67,68

been shown to either delay or prevent the development of type

2 diabetes as well as improve the cardiovascular risk profile of

patients by increasing HDL levels and lowering blood

pressure.53

Diabetes Mellitus

Diabetes mellitus is a syndrome with metabolic, vascular, and

neural components that originates from glucose intolerance,

which in turn leads to hyperglycemic states (increased plasma

glucose levels) Hyperglycemia can result from insufficient

insulin production, insulin action, or both Insulin promotes

storage of glucose as glycogen in muscle tissue and the liver

Deficiency of insulin leads to increased levels of plasma

glucose.54,55

The diagnosis of diabetes is based on the presence of any one

of the following four factors8,56:

1 Presence of polyuria, polydipsia, weight loss, blurred vision,

and random plasma glucose (regardless of last meal) ≥

200 mg/dl (11.1 mmol/L)

2 Fasting plasma glucose (FPG) ≥ 126 mg/dl (7.0 mmol/L)

Fasting involves no caloric intake for at least 8 hours

3 Two-hour postload glucose ≥ 200 mg/dl, during an oral

glucose tolerance test (OGTT) using a 75-g oral glucose

load dissolved in water, as described by the World Health

Organization

4 A1C ≥ 6.5%, measured with a standardized assay A1C is a

widely used marker for chronic glycemia and glycemic

management

The diagnosis is confirmed when one of the listed factors is also

found on a subsequent day or in situations when hyperglycemia

is unclear.8,55,56

The two primary types of diabetes mellitus are type 1

(insulin-dependent or juvenile-onset diabetes) and type 2 (non–

insulin-dependent or adult-onset diabetes) After much debate

TABLE 10-8 Criteria for Diagnosis of Metabolic

Elevated triglycerides # ≥150 mg/dl (1.7 mmol/L)

Reduced HDL-C †# <40 mg/dl (1.0 mmol/L) in males

<50 mg/dl (1.3 mmol/L) in females Elevated blood pressure # Systolic ≥ 130 and/or diastolic

85 mm Hg Elevated fasting glucose # ≥100 mg/dl

*Waist circumferences vary depending on specific country definitions.

†HDL-C indicates high-density lipoprotein cholesterol.

#If values are not available, then presence of drug therapy is an alternate

indicator.

Data from Alberti KGMM et al: Harmonizing the metabolic syndrome: a joint

interim statement of the International Diabetes Federation Task Force on

Epi-demiology and Prevention; National Heart, Lung, and Blood Institute;

Ameri-can Heart Association; World Heart Federation; International Atherosclerosis

Society; and International Association for the Study of Obesity, Circulation

120:1640-1645, 2009.