The fasting plasma glucose (FPG) level is assessed by a simple blood test after the person has not eaten for 8 hours. A normal FPG level is between 70 and 100 milligrams per deciliter (mg/dL).¹ A fasting glucose level between 100 and 125 mg/dL identifies a person who is prediabetic.¹ Even these individuals are at increased risk for complications of diabetes, such as coronary heart disease and stroke. A FPG level of 126 mg/dL (7 millimoles per liter [mmol/L]) or higher is diagnostic of diabetes (Table 32-1). In nonurgent settings, the test is repeated on another day to ensure that the result is accurate. After a meal, the concentration of glucose increases in the bloodstream. Recommended postprandial blood glucose levels should not exceed 180 mg/dL (10 mmol/L).¹

TABLE 32-1

BLOOD GLUCOSE LEVELS

PATIENT STATUS	FASTING BG (mg/dL)	FASTING BG (mmol/L)
Hypoglycemia	<70	< 3.9
Normal	70-100	>3.9-5.6
Prediabetes	100-125	5.6-6.9
Diabetes	≥126	≥7.0

BG, Blood glucose; mg/dL, milligram per deciliter; mmol/L, millimole per liter.

Data from American Diabetes Association. Standards of medical care in diabetes—2012, Diabetes Care. 2012;35(suppl 1):S11.

All critically ill patients must have their blood glucose levels monitored frequently while in the hospital. Clinical practice guidelines from the American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association (ADA) recommend instituting insulin therapy when the blood glucose is greater than 180 mg/dL in critical illness.³ A target blood glucose range of 140 to 180 mg/dL is recommended.³

When a continuous insulin infusion is administered, point-of-care blood glucose testing is performed hourly or according to hospital protocol by the critical care nurse to achieve and maintain the blood glucose within the target range.³

Hypoglycemia is defined as a blood glucose level below 70 mg/dL (3.9 mmol/L).1,3 A complication of intensive glucose control is that hypoglycemic episodes may occur more frequently both in the hospital and with self-management of glucose levels in diabetes.³

Before discharge to home, patients with diabetes should be taught to monitor their blood glucose levels.⁴ Maintaining blood glucose within the normal range is associated with fewer long-term diabetes related complications.⁴ Laboratory blood tests and point-of-care or self-monitoring of blood glucose represent the standard of care for management of diabetes. Unfortunately, home monitoring of blood glucose is not the norm despite research evidence that maintaining blood glucose levels as close to normal as possible prolongs life and reduces complications.

Urine Glucose

Testing the urine for glucose is not recommended for patients with diabetes because too much variation exists in the threshold for glucose when diabetes-related kidney damage has occurred. Urine glucose measurements are affected by variation in fluid intake, reflect an average glucose level, not a specific point in time, and are altered by some medications. Urine glucose testing does not offer any help in the identification of hypoglycemia. For all of these reasons, urine glucose testing is never to be used.

Glycated Hemoglobin

Blood testing of glucose is useful for daily management of diabetes. However, a different blood test is used to achieve an objective measure of blood glucose over an extended period. The glycated hemoglobin test, also known as glycosylated hemoglobin (HbA_1C or A_1C) provides information about the average amount of glucose that has been present in the patient’s bloodstream over the previous 3 to 4 months. During the 120-day life span of red blood cells (RBCs; erythrocytes), the hemoglobin within each cell binds to the available blood glucose through a process known as glycosylation. Typically, 4% to 6% of hemoglobin contains the glucose group A_1C. A normal A_1C value is less than 5.4%, with an acceptable target level for diabetic patients below 6.5%.1,2,5 The A_1C value correlates with specific blood glucose levels as shown in Table 32-2.^1,2 The American Diabetes Association recommends use of the A_1C value both during initial assessment of diabetes mellitus, and for follow-up to monitor treatment effectiveness.¹

TABLE 32-2

CORRELATION BETWEEN HEMOGLOBIN A_1c CONCENTRATION AND PLASMA GLUCOSE LEVEL

HbA_1c (%)	MEAN PLASMA GLUCOSE LEVEL (mg/dL)	MEAN PLASMA GLUCOSE LEVEL (mmol/L)
6	126	7.0
7	154	8.6
8	183	10.2
9	212	11.8
10	240	13.4
11	269	14.9
12	298	16.5

HbA_1c, Glycosylated hemoglobin; mg/dL, milligram per deciliter; mmol/L, millimole per liter.

Data from American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35(suppl 1):S11.

Blood Ketones

Ketone bodies are a byproduct of rapid fat breakdown. Ketone blood levels rise in acute illness, fasting, and with sustained elevation of blood glucose in type 1 diabetes in the absence of insulin. In diabetic ketoacidosis (DKA), fat breakdown (lipolysis) occurs so rapidly that fat metabolism is incomplete, and the ketone bodies (acetone, beta-hydroxybutyric acid, and acetoacetic acid) accumulate in the blood (ketonemia) and are excreted in the urine (ketonuria). It is recommended that all patients with diabetes perform self-test, or have their blood or urine tested, for the presence of ketones during any alteration in level of consciousness or acute illness with an elevated blood glucose.⁶ A blood test that measures beta-hydroxybutyrate, the primary metabolite of ketoacidosis, provides the most accurate measurement.^6,7 Self-test meters to measure blood ketones from a fingerstick are now available.⁶

Elevated levels of ketones (ketonemia) may be detected by a fruity, sweet-smelling odor on the exhaled breath. This distinctive breath odor derives from the elimination of acetone as part of the compensatory response to maintain a normal pH.

Urine Ketones

Ketones are eliminated in the urine, and urine may be tested for ketones. Ketonuria is retrospective and indicates that blood ketones were or are elevated.6,7 Ketonuria may also occur in fasting and starvation states.

Pituitary Gland

The pituitary gland, recessed in the base of the cranium, is not accessible to physical assessment. The critical care nurse must, therefore, be aware of the systemic effects of a normally functioning pituitary to be able to identify dysfunction. One essential hormone formed in the hypothalamus but secreted through the posterior pituitary gland is antidiuretic hormone (ADH), also known as vasopressin.

Physical Assessment

ADH controls the amount of fluid lost and retained within the body. Acute dysfunction of the posterior pituitary or the hypothalamus may result in insufficient or excessive ADH production. The clinical signs of posterior pituitary dysfunction often manifest as fluid volume deficit (insufficient ADH production) or fluid volume excess (excessive ADH production).

Hydration Status

The nurse determines the effectiveness of ADH production by conducting a hydration assessment. A hydration assessment includes observations of skin integrity, skin turgor, and buccal membrane moisture. Moist, shiny buccal membranes indicate satisfactory fluid balance. Skin turgor that is resilient and returns to its original position in less than 3 seconds after being pinched or lifted indicates adequate skin elasticity. The skin over the forehead, clavicle, and sternum is the most reliable for testing tissue turgor because it is less affected by aging and more easily assessed for changes related to fluid balance. The skin in the groin and axilla is slightly moist to touch in a well-hydrated patient. In older patients, these typical assessment findings may be absent.

Other indicators that the patient’s hydration status is adequate for metabolic demands include a balanced intake and output and absence of thirst. Absence of thirst, however, is not a reliable indicator of dehydration in those with decreased thirst mechanisms such as the older or critically ill patients. Absence of abrupt changes in mental status may also indicate normal hydration. Other indicators of normal hydration include absence of edema, stable weight, and urine specific gravity that falls within the normal range (1.005 to 1.030).

Vital Signs

Changes in heart rate, blood pressure, and central venous pressure (when available) are useful to determine fluid volume status. Blood pressure and pulse are monitored frequently. Decreased blood pressure with increased pulse is characteristic of hypovolemia, whereas elevated blood pressure and a rapid, bounding pulse may indicate hypervolemia. Orthostatic hypotension, which occurs when intravascular fluid volume decreases, is identified by a drop in systolic blood pressure of 20 mm Hg or a drop in diastolic blood pressure of 10 mm Hg when the patient changes position from lying to standing.

Weight Changes and Intake and Output

Daily weight changes coincide with fluid retention and fluid loss. Sudden changes in weight can result from a change in fluid balance; 1 L of fluid lost or retained is equal to approximately 2.2 pounds (lb), or 1 kilogram (kg), of weight gained or lost. To use weight as a true determinant of the fluid balance, all extraneous variables are eliminated, and the same scale is used at the same time each day. Precise measurement and notation of intake and output are used as criteria for fluid replacement therapy.

Laboratory Assessment

No single diagnostic test identifies dysfunction of the posterior pituitary gland. Diagnosis usually is made through the patient’s clinical presentation and history. Although serum measurement of ADH is available, it is rarely obtained in critical illness.

Serum Antidiuretic Hormone

The normal serum ADH range is 1 to 5 picogram per milliliter (pg/mL). Prior to ADH measurement, all medications that may alter the release of ADH are withheld for a minimum of 8 hours. Common medications that affect ADH levels include morphine sulfate, lithium carbonate, chlorothiazide, carbamazepine, oxytocin, and selective serotonin reuptake inhibitors (SSRIs). Nicotine, alcohol, positive-pressure and negative-pressure ventilation, and emotional stress also influence ADH.

Serum ADH levels are then compared with the blood and urine osmolality to differentiate syndrome of inappropriate antidiuretic hormone (SIADH) from central diabetes insipidus (DI). Increased ADH levels in the bloodstream compared with a low serum osmolality and elevated urine osmolality confirms the diagnosis of SIADH. Reduced levels of serum ADH in a patient with high serum osmolality, hypernatremia, and reduced urine concentration signal central DI. Chapter 33 provides more information about SIADH and DI.

Serum and Urine Osmolality

Values for serum osmolality in the bloodstream range from 275 to 295 milliosmole per kilogram of water (mOsm/kg H₂O). Osmolality measurements determine the concentration of dissolved particles in a solution. In a healthy person, a change in the concentration of solutes triggers a chain of events to maintain adequate serum dilution. The most accurate measures of the body’s fluid balance are obtained when urine and blood samples are collected simultaneously.

Increased serum osmolality stimulates the release of ADH, which reduces the amount of water lost through the kidney. Body fluid is thus retained at the kidney tubules and collecting ducts to dilute the particle concentration in the bloodstream.

Decreased serum osmolality inhibits the release of ADH. The kidney tubules increase their permeability, and fluid is eliminated from the body in an attempt to regain normal concentration of particles in the bloodstream. Urine osmolality in the person with normal kidneys depends on fluid intake. With high fluid intake, particle dilution is low but will increase if fluids are restricted. The expected range for urine osmolality is, therefore, wide, ranging from 50 to 1400 mOsm/kg.

Antidiuretic Hormone Test

The ADH test is used to differentiate neurogenic DI (central) from nephrogenic (kidney) DI. The patient is challenged with 0.05 to 1.0 mL of intranasally administered ADH in the form of desmopressin (1-deamino-8-D-arginine vasopressin, commonly abbreviated as DDAVP). An intravenous line is inserted before ADH administration, and urine volume and osmolality are measured every 30 minutes for 2 hours before and after the ADH challenge. The patient with normal posterior pituitary function responds to the exogenous ADH by resorbing water at the kidney tubule and raising the urine osmolality slightly. In cases of severe central DI, in which the pituitary is affected, the urine osmolality shows a significant increase (becomes more concentrated), which indicates that the cell receptor sites on the kidney tubules are responsive to vasopressin. Test results in which urine osmolality remains unchanged indicate nephrogenic DI, suggesting kidney dysfunction because the kidneys are no longer responsive to ADH. This test is rarely performed in the critical care unit because of the unstable hemodynamic and volume status of most patients.

Diagnostic Procedures

In addition to laboratory tests, radiographic examination, computed tomography (CT), and magnetic resonance imaging (MRI) are used to diagnose structural lesions such as cranial bone fractures, tumors, or blood clots in the region of the pituitary. Although these procedures do not diagnose DI or SIADH, they are useful in uncovering the likely underlying cause.

Radiographic Examination

A basic radiographic examination of the inferior skull views the sella turcica and surrounding bone formation. Bone fractures or tissue swelling at the base of the brain, which are apparent on a radiograph, suggest interference with the vascular supply and nerve impulses to the hypothalamic–pituitary system. Dysfunction may occur if the hypothalamus, infundibular stalk, or pituitary gland is impaired.

Computed Tomography

CT of the base of the skull identifies pituitary tumors, blood clots, cysts, nodules, or other soft tissue masses. This rapid procedure causes no discomfort except that it requires the patient to lie perfectly still. CT studies can be performed with radiopaque contrast or without contrast. The contrast dye is given intravenously to highlight the hypothalamus, infundibular stalk, and pituitary gland. This dye may cause allergic reactions in iodine-sensitive persons, and the patient must be carefully questioned about iodine allergy before the test. The size and shape of the sella turcica and the position of the hypothalamus, infundibular stalk, and pituitary are identified.⁸

Magnetic Resonance Imaging

MRI enables the radiologist to visualize internal organs and cellular characteristics of specific tissues. MRI uses a magnetic field rather than radiation to produce high-resolution, cross-sectional images. The soft brain tissue and surrounding cerebrospinal fluid (CSF) make the brain especially suited to MRI especially in cases of DI or SIADH.⁸

Thyroid Gland

Clinical Assessment

History

The history of a patient in the critical care unit should be as detailed as possible. Information regarding the clinical manifestations of hypothyroidism or hyperthyroidism must be obtained from the patient, family, or others with knowledge about the patient. Sample questions considered pertinent to detection of thyroid disease are provided in Box 32-2.

Box 32-2 Data Collection

Thyrotoxicosis (Hyperthyroidism) and Myxedema (Hypothyroidism)

The patient is the best source for the following information. If the patient is unable to respond, the following questions can be directed to family, friends, a significant other, or those involved in admission of the patient to the critical care unit.

• Have you ever been diagnosed with overactive thyroid, increased metabolism, or hyperthyroidism? What about underactive thyroid, slowed metabolism, or hypothyroidism?

• Have you ever been treated for hyperthyroidism or hypothyroidism?

• Have you ever had an operation for thyroid disease?

• Have you ever received radioactive iodine for thyroid disease?

• Were you taking any medicine for thyroid disease? If so, what is the name of the medicine, and what is the prescribed dose and frequency?

• When did you first notice the constant restlessness or extreme fatigue?

• Has your weight been the same or changed over the past year?

• Has your appetite changed over the past 6 months?

• Have you lost weight even though your appetite has increased (may indicate hyperthyroidism)?

• Have you gained weight or stayed at the same weight even though you have not felt like eating over the past 6 months (may indicate hypothyroidism)?

• Do you always feel warm (may indicate hyperthyroidism)?

• Do you open windows in house, even in winter months?

• Do you wear lightweight clothing, even when others are wearing layers of heavier clothing?

• Do you always feel cold (may indicate hypothyroidism)?

• Do you wear multiple layers of clothing despite warm weather or the use of a heater or furnace?

• Do you use several blankets and keep windows closed, even in warm weather?

• Do you complain about never being able to “warm up”?

• Over the past 6 months to 1 year, have you developed any of the following?

INDICATORS FOR HYPOTHYROIDISM	INDICATORS FOR HYPERTHYROIDISM
Loss of coarse, dry scalp hair and outer edge of eyebrow	Hair thinning Swelling (face, eyes, legs)
Sleepiness, lethargy, depression	Insomnia, nervousness, anxiety
Weight gain despite decreased appetite	Weight loss despite increased appetite
Severe constipation	Diarrhea
Muscle and joint pain (hands, wrists, feet)	Muscle weakness or wasting; tremors
Dry, itchy skin	Warm, moist skin
Increased sensitivity to cold	Heat intolerance, sweating
Bradycardia	Tachycardia, atrial fibrillation
Menstruation changes; impaired fertility	Menstruation changes; impaired fertility

Physical Examination

The thyroid is palpated for tenderness, nodules, and enlargement and is auscultated for bruits. The normal-size thyroid gland usually is neither visible nor palpable in the anterior neck.⁹ Palpation may be done from an anterior or posterior approach. Auscultation of the thyroid is accomplished by use of the bell portion of the stethoscope to identify a bruit or blowing noise from the circulation through the thyroid gland. The presence of a bruit indicates enlargement of the thyroid, as evidenced by increased blood flow through the glandular tissue.

Laboratory Studies

Controversy exists about routine measurement of thyroid function in adults without clinical symptoms. The American Thyroid Association recommends thyroid function measurement in all adults beginning at age 35 years and every 5 years thereafter; more frequent screening is recommended for high-risk or symptomatic individuals. The U.S. Preventive Services Task Force (USPSTF) found the research evidence insufficient to either recommend or recommend against routine screening for thyroid disease in asymptomatic adults.¹⁰ No specific recommendations have been made with regard to thyroid function screening for critically ill patients.

Thyroid hormone blood tests measure the levels of circulating thyroid hormone and assess the integrity of the hormonal negative feedback response within the hypothalamic–pituitary axis. An inverse, linear relationship exists between TSH and T₄.¹¹ When the hypothalamic–pituitary axis is normal, TSH production is inhibited by the presence of normal thyroid hormone and the TSH value will be normal.¹¹ Laboratory diagnosis of hyperthyroidism and hypothyroidism usually is based on the simultaneous measurement of thyroid-stimulating hormone (TSH) and free thyroxine (T₄).¹²

• Hypothyroidism: high TSH and low serum T₄

• Hyperthyroidism (thyrotoxicosis): very low TSH, high serum T₄, and an increased T₃:T₄ ratio ¹³

Thyroid Stimulating Hormone

Over the past decade, laboratory tests developed to analyze TSH have become much more sensitive, allowing more accurate measurement of low levels of thyroid hormone. Thyroid hormone reference ranges in adults are listed in Table 32-3.¹⁴ Because serum values vary slightly among laboratory methods, it is imperative to know the normal reference values used by the hospital laboratory.

TABLE 32-3

THYROID TESTS

NAME OF TEST	ABBREVIATION	REFERENCE VALUE*	REFERENCE VALUE*
Total serum thyroxine	TT₄	58-160 nmol/L	4.5-12.6 mcg/dL
Free thyroxine	T₄	9-23 pmol/L	0.7-1.8 ng/dL
Total serum triiodothyronine	TT₃	1.2-2.7 nmol/L	80-180 ng/dL
Free triiodothyronine	T₃	3.5-7.7 pmol/L	0.2-0.5 ng/dL
Thyroid-stimulating hormone (thyrotropin)	TSH	0.4-4.0 mIU/L
Thyroglobulin^†	Tg	3.0-40 mcg/L

mcg/L, Microgram per liter; mIU/L, milli-international unit per liter; nmol/L, nanomole per liter; pmol/L, picomole per liter.

^*Some tests are reported with more than one reference value because different laboratories report results using several reference scales.

^†Thyroglobulin (Tg) reference values should be determined locally because serum Tg concentrations are influenced by iodide intake.

Reference values from Demers LM, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003;13(1):3.

The upper limit of normal for some of these values is under scrutiny. A U.S. national survey found the average level of TSH in the population in all ages to be only 1.49 milli-international unit per liter (mIU/L), considerably lower than most cited laboratory norms.¹¹ The serum level of TSH increases as people grow older, which may signal declining thyroid function as more stimulation of the thyroid gland is required.¹¹ The average TSH level varies by age:¹⁴

1.60 mIU/L after age 50 years

1.79 mIU/L after age 60 years

1.98 mIU/L after age 70 years

2.08 mIU/L for those older than 80 years

Because this age-adjusted increase is predictable, it is not recommended that laboratories use age-adjusted reference values when assessing thyroid function.¹¹ Most asymptomatic people with a normal thyroid gland have a TSH level between 0.4 and 2.5 mIU/L.¹⁵

Thyroid Tests in the Critically Ill

Thyroid hormone testing in patients with nonthyroidal critical illness may be inconclusive because of the hormonal disruption caused by the illness.¹⁶ In critical illness, measurement of TSH is usually the first thyroid-related laboratory test that is obtained.

Medications and Thyroid Testing

Additional measurement difficulties involve concomitant use of certain medications that interfere with thyroid function and lower serum levels.¹⁷

TSH secretion is affected by several medications routinely administered in critical care units. Glucocorticoids in large doses may lower the serum level of T₃ and inhibit TSH secretion.¹¹ Dopamine infusions at greater than 1 mcg/kg/min directly blocks TSH release.¹⁷ Amiodarone, an antidysrhythmic medication is an iodine-rich compound that is structurally similar to T₃ and T₄. At usual doses, amiodarone contains 35 to 140 times the iodine recommended daily allowance (RDA) of 150 mcg per day.¹⁸

Several medications increase the serum level of T₄ by displacing protein-bound T₄.¹⁷ Medications that displace T₄, including unfractionated and low-molecular-weight heparins, cause an increase in serum T₄ levels.¹⁷ Salicylates (aspirin) and furosemide (Lasix) raise T₄ serum levels by the same mechanism.¹⁷ A more complete list of medications that alter thyroid hormone serum levels is provided in Table 32-4. It is not clear whether it is necessary to adjust management of the critically ill patient in response to these laboratory findings.

TABLE 32-4

MEDICATIONS THAT INFLUENCE DIAGNOSTIC THYROID LEVELS

Triiodothyronine (T₃)
*Increase*	*Decrease*
Methadone	Anabolic steroid
Estrogens	Androgens
Progestins	Salicylates
Amiodarone	Phenytoin
	Lithium
	Reserpine
	Propranolol
	Sulfonamides
	Propylthiouracil
	Methylthiouracil
Thyroxine (T₄)
*Increase*	*Decrease*
Oral contraceptives	Phenytoin
Heparin	Steroids
Aspirin	Diphenylhydantoin
Furosemide	Chlorpromazine
Clofibrate	Lithium
Phenylbutazone	Sulfonylurea
Some nonsteroidal anti-inflammatory drugs (NSAIDs)	Sulfonamides Reserpine
Propranolol	Chlordiazepoxide
Corticosteroids
Amiodarone
Thyroid-Stimulating Hormone (TSH)
*Increase TSH*	*Decrease TSH and TSH Response to TRH*
Metoclopramide	Glucocorticoids
Iodides	Dopamine
Lithium	Heparin
Potassium iodide	Aspirin
Morphine sulfate	Carbamazepine
Thyroxine-Binding Globulin (TBG)
*Increase*	*Decrease*
Opiates	Androgen therapy
Oral contraceptives	l-Asparaginase
Estrogens
Clofibrate
5-Fluorouracil (5-FU)
Perphenazine

TRH, Thyrotropin-releasing hormone.

Diagnostic Procedures

Diagnostic tests often begin with ultrasonography to visualize a nodule or tumor.19,20 To diagnose hypothyroidism, a nuclear medicine scan using an oral iodine radioactive isotope may be requested.²¹ The thyroid-scanning procedure may also detect the presence of ectopic thyroid tissue, thyroid carcinomas, and the amount of viable thyroid glandular tissue after therapeutic irradiation.

Adrenal Gland

Primary Adrenal Disorders

Admission to the critical care unit with a primary adrenal disorder is rare. The term primary indicates that the principal problem lies within the adrenal gland. Secondary adrenal dysfunction is caused by dysfunction in another gland or by a clinical condition such as sepsis.

The adrenal gland is actually two glands in one, as described in Chapter 31, and this may make the history and presentation complex. The adrenal cortex (outer layer) secretes two classes of hormones, and if deficient or released in excess, they may cause clinical symptoms. Two hormones relevant to care of the critically ill are: 1) the glucocorticoid hormone cortisol and 2) the mineralocorticoid hormone aldosterone. Cortisol is secreted in response to physiologic stress as a result of infection, trauma, and hypoglycemia. Aldosterone is secreted in response to intravascular hypovolemia. It is the final step in renin–angiotensin–aldosterone system (RAAS) pathway.

The adrenal medulla (inner layer) also secretes two hormones that cause clinical symptoms if they are deficient or released in excess. They are epinephrine (also known as adrenalin), and norepinephrine (noradrenalin), and both are secreted from the adrenal gland in response to stress.

Clinical Assessment

History

A detailed history may help to identify conditions or medications that may affect adrenal gland function. Primary endocrine disorders are rare, but a history of uncontrolled hypertension despite three or more oral medications may indicate whether endocrine-related hypertension should be investigated. The medication history may help determine whether the patient takes glucocorticoid tablets, and the patient or family should be asked about using steroid creams for dermatologic conditions and about using steroid-based inhalers for chronic obstructive lung disease (COPD).

Physical Examination

The physical examination is related to the effects of adrenal dysfunction, and the signs depend on the hormone involved and whether the problem is related to excess or deficiency. This means that the signs and symptoms are very diverse. A methodic approach to assessing all signs and symptoms is important because adrenal disease is often missed or misdiagnosed.

Adrenal Cortex

Primary Cushing Syndrome.

Cushing syndrome is caused by the excess release of the glucocorticoid hormone cortisol. Excess cortisol produces the classic signs and symptoms listed in Box 32-3. Primary Cushing disease is rare, but if a patient is not taking exogenous steroids, it becomes a diagnosis of exclusion when the relevant constellation of signs and symptoms are present.²²

Box 32-3 Causes of Cushing Syndrome

Primary Cushing Syndrome

Cushing syndrome is divided into adrenocorticotropin-dependent and adrenocorticotropin-independent types. Adrenocorticotropin is also known as adrenocorticotropic hormone (ACTH) or corticotropin.

ACTH-Dependent Cushing Syndrome

Most cases (80%) result from a pituitary adenoma that causes the pituitary gland to produce excess ACTH. Excess secretion of ACTH stimulates the adrenal cortex to release supraphysiologic amounts of cortisol into the bloodstream, circumventing the normal inhibitory feedback loop.

The other 20% of cases are caused by ectopic ACTH secretion from small-cell cancers of the lung, metastases, and endocrine tumors.

ACTH-Independent Cushing Syndrome

It is usually caused by a unilateral adrenal tumor: adrenal adenoma (60%) or adrenal carcinoma (40%).

Secondary or Iatrogenic Cushing Syndrome

The patient takes pharmacologic doses of glucocorticoids, which may be prescribed to prevent rejection after solid organ transplantation or for the treatment of chronic inflammatory conditions.

Clinical Signs and Symptoms of Cushing Syndrome

• Emotional lability (can range from depression to psychosis)

• Hyperglycemia and poorly controlled type 2 diabetes

• Obesity or weight gain in abdomen

• Rounded face

• Acne

• Thin skin, bruises easily, poor wound healing

• Hypertension

• Hirsutism (excess hair growth)

• Dorsocervical fat pad (“buffalo hump”)

• Decreased libido

• Fatigue, weakness

Secondary Cushing Syndrome.

Symptoms identical to those of primary Cushing syndrome (see Box 32-3) occur in patients with the secondary form who chronically take pharmacologic doses of glucocorticoids, for example, transplant recipients who take steroids to prevent solid organ rejection; patients with COPD, or those with chronic inflammatory conditions. When patients are admitted to the critical care unit, it is important to ascertain whether they are steroid dependent to avoid the deleterious effects of abrupt steroid withdrawal.

Primary Aldosteronism

In patients with primary aldosteronism, the adrenal cortex secretes excess mineralocorticoid (aldosterone) unrelated to the renin–angiotensin system.²³ Several subtypes of this rare condition exist, but all may cause the patient to present emergently with severe hypertension and critically low serum level of potassium (hypokalemia), which can be lethal if not identified and effectively treated.

Addison Disease

Addison disease is a rare disorder of the adrenal cortex that involves hyposecretion of glucocorticoids (cortisol), sometimes occurring with hyposecretion of mineralocorticoids (aldosterone). Physiologically, it may be envisioned as the opposite of the disorders described previously, and the signs and symptoms are the inverse of the conditions with excess hormone secretion. An addisonian crisis is a life-threatening condition in which the adrenal gland is almost nonfunctional, usually because of destruction of adrenal tissue. The patient presents acutely with critical hypotension, an elevated serum potassium level (hyperkalemia), a low serum sodium level (hyponatremia), and hypoglycemia.

Critical Illness-Related Corticosteroid Insufficiency

The adrenal gland is designed to respond to acute physiologic stress. However, evidence suggests that the adrenal gland may become exhausted and no longer secrete adequate amounts of stress hormones in prolonged critical illness and in septic shock. The Society of Critical Care Medicine (SCCM) recommends that this condition be called critical illness–related corticosteroid insufficiency (CIRCI).²⁴ Differentiating the signs and symptoms of adrenal insufficiency caused by shock from other causes by clinical examination alone is almost impossible in the critically ill, and CIRCI was probably an overlooked diagnosis in the past. The routine use of the corticotropin stimulation test in the presence of refractory vasopressor-dependent hypotension helps to make this diagnosis.²⁴

Adrenal Medulla

Pheochromocytoma.

Pheochromocytomas are rare tumors that arise from the catecholamine-producing chromaffin cells of the adrenal medulla.25,26 Most produce norepinephrine, but some produce both norepinephrine and epinephrine.²⁶ These tumors produce a far greater quantity of catechols than normal adrenal medullary tissue. The concentrations of catecholamines are so high within the tumor that it has have been likened to a volcano that can erupt at any time.²⁶ When huge amounts of norepinephrine or epinephrine are released into the bloodstream, it creates a catecholamine storm that could be life threatening. The body responds as if to a severe fight-or-flight threat by hypertension, tachycardia, increased respiratory rate, and hyperglycemia. The patient may describe symptoms of headache, dizziness, palpitations, chest pain, anxiety, nervousness, and fatigue (Box 32-4).^25,26 Because the body perceives the catecholamine onslaught to be a signal for the person to be ready to escape a threatening situation, it slows down the GI tract, and constipation is another symptom. Most pheochromocytomas are detected on autopsy rather than during life.²⁷ The patients at greatest risk are those who are admitted to a critical care unit for another reason or are admitted in shock with an undiagnosed adrenal tumor.

Box 32-4 Pheochromocytoma

Signs and Symptoms

SIGNS*	SYMPTOMS*
Hypertension	Headaches
Tachycardia	Dizziness or faintness
Tachypnea	Palpitations, chest pain
Pallor or flushing	Anxiety and nervousness
Hyperglycemia or poorly controlled type 2 diabetes	Excessive sweating
Decreased gastrointestinal motility	Weakness, fatigue
	Weight loss
	Constipation