Pathophysiology

Acute adrenocortical insufficiency, also known as adrenal crisis and Addisonian crisis, is a life-threatening condition that manifests as shock with profound, refractory hypotension. Severe sepsis with pituitary suppression and steroid withdrawal are the most common causes of acute adrenal insufficiency in critically ill patients. Adrenal crisis also results from acute exacerbation of chronic adrenocortical insufficiency in patients who become stressed by sepsis, surgery, adrenal hemorrhage (septicemia-induced Waterhouse-Friderickson syndrome from meningococcemia), and anticoagulation complications. There are approximately 50 total hormones produced by the adrenal glands, with cortisol and aldosterone being by far the most abundant.

The function of the adrenal cortex is dependent on the hypothalamic-pituitary axis. The normal relationship occurs as the hypothalamus secretes releasing factors, which:

If primary adrenal insufficiency is the cause of the crisis, the adrenal glands are the root cause of the problem. Addison disease manifests when the entire adrenal cortex is destroyed, which stops the production of glucocorticoids (cortisol) and mineralocorticoids (aldosterone). Glucocorticoids are essential hormones produced by the adrenal cortex that help maintain vascular tone and cardiac contractility, facilitate wound healing, and support immunity. Cortisol deficiency intensifies the clinical effects of hypovolemia by promoting a decrease in vascular tone, which is partially related to unopposed endothelial production of nitric oxide, and a decreased vascular response to the catecholamine hormones epinephrine and norepinephrine. Relative hypoglycemia may be present, as the breakdown of stored glycogen is not possible without cortisol. Mineralocorticoid hormones are primary regulators of fluid and electrolyte balance, and when unavailable, patients experience hyponatremia, hypovolemia, hyperkalemia, and metabolic acidosis. Large amounts of sodium and water are excreted in the urine. Severe hypotension, shock, and eventually death may occur without intravenous adrenocortical hormone and fluid replacement. In patients with chronic primary adrenocortical insufficiency or Addison disease, acute crises may be prevented by tripling hormone replacement doses during periods of stress.

Primary adrenal insufficiency is relatively rare, can be acute or chronic, and is most often caused by autoimmmune-mediated, idiopathic atrophy. Other causes include tuberculosis, fungal infection, hemorrhage, congenital adrenal hyperplasia, enzyme inhibitors (e.g., metyrapone), cytotoxic agents (e.g., mitotane), and other diseases infiltrating the adrenal glands.

Secondary adrenal insufficiency is relatively common and caused by a failure of either the pituitary gland or hypothalamic-pituitary axis to provide appropriate signals to the adrenal glands to secrete cortisol. Exogenous glucocorticoids (e.g., hydrocortisone) administered elevate the circulating level and the hypothalamic-pituitary-adrenal axis is no longer functional. The adrenal glands do not receive signals to produce endogenous cortisol because the circulating level remains high while the glucocorticoid therapy continues. When glucocorticoid therapy is abruptly discontinued, the adrenal gland cannot immediately respond and the patient experiences adrenal crisis. Secondary adrenocortical insufficiency also manifests when inflammatory mediators or trauma suppress or damage the hypothalamus or pituitary. Pituitary or other tumors may impair pituitary function or, in rarer cases, produce glucocorticoids, which suppress the hypothalamic-pituitary axis.

In patients with possible pituitary suppression from severe sepsis, glucocorticoid replacement for relative adrenal insufficiency remains controversial. Relative adrenal insufficiency is not readily identified by all practitioners. Patients with pituitary dysfunction generally do not require mineralocorticoid replacement because the release of aldosterone is dependent on release of angiotensin II rather than ACTH from the pituitary.

Endocrine assessment adrenals

Collaborative management

DIAGNOSIS AND MANAGEMENT OF CORTICOSTEROID INSUFFICIENCY IN CRITICALLY ILL PATIENTS

From Marik PE, Pastores SM, Annane D, et al: Crit Care Med 36(6):1937–1949, 2008.

Pathophysiology

Diabetes insipidus (DI) is a metabolic disorder that affects total body free water regulation, resulting in an abnormally high output of extremely dilute urine, increased fluid intake, and constant thirst. The volume of hypotonic urine excreted is 3-20L/day. Vasopressin (antidiuretic hormone [ADH]) is a key component in the regulation of fluid and electrolyte balance, through direct effects on renal water regulation. Vasopressin is produced in the hypothalamus, is stored in the posterior pituitary gland, and exerts action in the kidneys for water regulation. Three subtypes of receptors respond to the effects of vasopressin (Table 8-1).

When any aspect of water regulation fails, if free water is lost, the extracellular fluid volume rapidly decreases, causing plasma osmolality and serum sodium to rise. Plasma osmolality is the main determinant of vasopressin secretion from the posterior pituitary. The osmoregulatory systems for thirst and vasopressin secretion, and the actions of ADH on renal water excretion, maintain plasma osmolality between 284 and 295 mOsmol/kg. Thirst and drinking are key processes in the maintenance of fluid and electrolyte balance. Thirst perception and the regulation of water ingestion involve complex neural and neurohormonal pathways. Thirst occurs when plasma osmolality rises above 281 mOsm/kg, similar to the threshold for ADH release. The osmoreceptors regulating thirst are located in the hypothalamus. Situations that alter the balance between plasma osmolality and vasopressin concentration include:

There are four major subtypes of DI, based on which mechanism involved with concentrating urine has failed:

The most common presentation of DI is following head trauma or intracranial surgery. When a person cannot adequately respond to stimulation of the thirst center by drinking fluids, extracellular and intracellular dehydration may result. Electrolyte imbalance, primarily hypernatremia, may produce neurologic symptoms ranging from confusion, restlessness, and irritability to seizures and coma. DI sometimes occurs in brain-dead organ donors and must be managed to effectively preserve organs.

In normal individuals, a more concentrated circulating volume stimulates ADH release through activation of osmoreceptors that monitor serum osmolality. ADH is also released as part of the renin-angiotensin-aldosterone mechanism as a result of hypotension sensed by the juxtomedullary apparatus located outside the glomerulus of the kidney. A 5% to 10% decrease in arterial BP is necessary to increase circulating vasopressin concentrations. Progressive hypotension in healthy individuals results in an exponential increase in plasma ADH via baroreceptor stimulation, while osmoregulated ADH release in response to dehydration is more linear. If the hypothalamus is damaged, production of ADH may not be possible and both the ability to regulate circulating volume and vascular tone may be affected.

In addition to the pharmacologic use of vasopressin in managing DI, exogenous vasopressin also has a role in responding to changes in cardiovascular status and is used as an alternative to epinephrine in resuscitation following cardiac arrest. Exogenous vasopressin administration is used to manage vasodilated shock because ADH is also a potent vasopressor agent with actions mediated through receptors (V₁R) located in vascular smooth muscle cells. Although systemic effects on arterial BP are only seen at high concentrations, ADH is also important in maintaining BP in mild volume depletion.

Larger pharmacologic doses of vasopressin exert powerful vascular effects in the regulation of regional blood flow. The sensitivity of vascular smooth muscle to the vasoconstrictive effects of ADH varies with each vascular bed and within various parts of each bed. Vasoconstriction of splanchnic, hepatic, and renal vessels occurs at ADH concentrations close to the normal range. Selective actions within the kidney blood vessels lead to redistribution of blood flow from the renal medulla to the cortex. Baroregulated (pressure response) release of vasopressin is a key physiologic mediator in an integrated hemodynamic response to volume depletion.

Endocrine assessment: diabetes insipidus

Collaborative management

Additional nursing diagnoses

If patient has developed DI following a transphenoidal hypophysectomy, see Decreased intracranial adaptive capacity, Ineffective breathing pattern, Risk for infection, and Pain in Care of the Patient After Intracranial Surgery, p. 638; also see Hypernatremia and Hyponatremia in Fluid and Electrolyte Disturbances, p 37.)

Pathophysiology

Management of hyperglycemia (elevated blood glucose level) in hospitalized patients has been a key factor in collaborative care since late in 2001, when a landmark study by Van den Berghe and colleagues resulted in dramatic improvement in outcomes of postoperative cardiovascular surgical intensive care patients when glucose was maintained within normal range (80 to 110 mg/dl) using an IV insulin infusion. The practice of normalizing blood glucose was termed “tight glycemic control.” Values in excess of 110 mg/dl were regarded as hyperglycemia after the study, versus the previously accepted value of 126 mg/dl, the threshold fasting blood sugar level associated with a diagnosis of diabetes mellitus. A subset of patients without diabetes mellitus are hyperglycemic as a result of an exaggerated stress response. Prior to 2001, most care providers were prompted to manage hyperglycemia solely in patients with diabetes mellitus.

Patients in the Van den Berghe study who received tight glycemic control for new-onset hyperglycemia realized a much greater improvement in outcomes than did patients with diabetes mellitus, a particularly difficult concept for the medical community to accept. A subset of those with “new-onset” hyperglycemia were found to be undiagnosed diabetics, which prompted a recommendation that all patients undergo glycohemoglobin screening (hemoglobin A1c) performed on hospital admission. Assessment of glycemic control prior to hospitalization helps care providers anticipate whether patients will need insulin following hospitalization. Those with diabetes mellitus may be discharged on oral hypoglycemic agents or insulin. “Stress responders” without diabetes generally do not require insulin following hospitalization, because the stress of their illness or procedure resolves.

Care providers aware of the evolving research began practicing tight glycemic control. Organizations not traditionally focused on blood glucose control, including the Society of Critical Care Medicine, the American Association of Critical Care Nurses, and corresponding international societies, were challenged by the problem of hyperglycemia. Normalization of blood glucose was considered “best practice.” Numerous studies ensued to discern how glucose control was suddenly thrust into the forefront of management of hospitalized patients. Despite recommendations by numerous professional societies, to date, less than 10% of hospitals have implemented glycemic control programs for all patients.

Ongoing studies have yielded variable findings using tight glycemic control. Favorable results include a reduction in morbidity and mortality, decreased incidence of sepsis and wound infections, decreased need for blood transfusions, and lower incidence of acute renal failure requiring hemodialysis. Tight glycemic control has been shown in selected studies to reduce morbidity associated with stroke, acute coronary syndromes, vascular disease, community-acquired pneumonia, and other medical-surgical diagnoses. Without glucose control, many patients studied had longer length of hospital stay and increased morbidity and mortality compared with those with tight glycemic control.

There is no question that controlling glucose in hospitalized patients improves outcomes, but defining a safe target range has been challenging. The range of control has undergone rigorous debate, and has become the focal point of studies, without regard to the different IV insulin dosing regimens used for each study. Rather than focusing on how insulin should be dosed for differing patient populations, an ongoing debate ensued regarding whether 80 to 110 mg/dl was a safe goal for all critically ill patients, because along with positive results, many studies resulted in increased incidence of hypoglycemia. Exploring the efficacy of various insulin dosing regimens in controlling hyperglycemia while avoiding life-threatening hypoglycemia (less than 40 mg/dl) has not been a priority. Researchers have sought a universally accepted, safe range of blood glucose control that can be attained using all dosage protocols in all patient populations without adverse effects. To compound the difficulty of this monumental task, the definition of hypoglycemia has been inconsistent.

Physicians create insulin titration regimens, because no one method of insulin dosing has been universally accepted. Unlike the frequent titration of medications used to manage hypotension or hypertension, most dosage adjustments of IV insulin infusions are done hourly, because a continuous reading of glucose level is not possible. Dose responses are more difficult to assess. Few protocols individualize dosing based on insulin sensitivity or resistance. Individualization increases the complexity of care if nurses must perform mathematical calculations to make dosing adjustments.

Technology has evolved in response to research supporting tight glycemic control. Several computerized IV insulin dosing systems are available to lessen the burden of mathematical calculations being done by nurses. With the raging debate regarding safety of tight glycemic control in all patient populations, less than 5% of hospitals in the United States have been comfortable investing in the equipment.

In early 2009, the NICE SUGAR trial highlighted that the incidence of hypoglycemia was unacceptably high when tight control was used in many studies. The American Diabetes Association (ADA) and American Association of Clinical Endocrinologists (AACE) moved away from recommending tight glycemic control for hospitalized patients and created a less stringent guideline recommending that critically ill patients be controlled to blood glucose values of 140 to 180 mg/dl. For more stable hospitalized patients who are eating meals, the recommendation became for premeal blood glucose values to be less than 140 mg/dl. The change prompted confusion and controversy within hospitals with a low incidence of hypoglycemia using tight glycemic control. Centers that realized improved outcomes using tight control may not embrace the new guidelines, while others may compromise, using a target range such as 90 to 140 mg/dl.

Krinsley’s research revealed that extreme variations in glucose are associated with poorer outcomes. Insulin dosing regimens with little ability to be individualized have caused severe drops in glucose, prompting administration of 50% dextrose solution to recover patients. Patients with hyperglycemia due to an exaggerated stress response often respond to insulin differently than do patients with diabetes mellitus already receiving either insulin or oral hypoglycemic agents. Many insulin dosing protocols failed to consider patient condition and other care environment variables, and thus were more likely to result in hypoglycemia. A myriad of factors impact glucose control.

Varying methods are used by care providers who may lack the knowledge of how to appropriately monitor blood glucose when insulin is given. Some centers rely on laboratory glucose readings instead of POC testing. POC testing can be done more frequently, with timelier availability of results, affording a better opportunity for insulin dosage adjustments. Several studies have cast doubt on the accuracy of POC testing systems, because hemoglobin level has been shown to affect results. Those with higher hematocrit readings may have lower glucose readings.

Hospitals also struggle with the logistics involved with safe blood glucose control. Staffing, skill level, movement of patients around the hospital for procedures, adjustments in diet, delivery of meal trays, medication delivery systems, ability to perform POC glucose testing, and other factors impact the ability to control hyperglycemia. Hyperglycemic and hypoglycemic emergencies result.

Although both quality organizations and insurers acknowledge the challenges of glycemic control, as of October 2009, the occurrences of hypoglycemia, diabetic ketoacidosis (DKA), and hyperglycemic hyperosmolar syndrome (HHS) have been considered “never events” for hospitalized patients. Hospital-acquired conditions that are considered preventable are termed “never events” for hospitalized patients. If patients are admitted with the conditions present, the hospital is paid if they recur, but if the same conditions occur in patients without a history, the events are considered preventable. Careful admission screening of all patients related to past experience with both hyperglycemia and hypoglycemia is of paramount importance to realize payment for treatment of the patients. Despite the difficulties, hospitals must prevent both hyperglycemic and hypoglycemic crises or risk not being paid for care associated with managing the crises and sequelae.

Pathophysiology

DKA is a life-threatening complication of diabetes mellitus characterized by hyperglycemic crisis, ketosis, acidosis, hypovolemic shock due to dehydration, and electrolyte imbalance involving potassium. Progressive hyperglycemia occurs due to inadequate circulating insulin, preventing cellular uptake of glucose and resulting in a state of starvation at the cellular level. Starvation prompts glucagon secretion from the pancreas and release of other stress hormones including catecholamines, cortisol, and growth hormone (GH), which facilitate glycogenolysis and gluconeogenesis, further raising plasma glucose. Proteolysis and lipolysis ensue, forming free fatty acids, which are converted to ketoacids (acetoacetate, beta-hydroxybutyrate, and acetone), due to lack of intracellular glucose required for normal metabolic conversion of the acids.

Accumulation of ketones creates a metabolic acidosis. The excessive glucose and ketones in the blood cause severe osmotic diuresis as intracellular fluids move into the vascular compartment to dilute the blood; however, the excess fluid is eliminated by the kidneys, which also lose the ability to effectively eliminate excess glucose. A vicious cycle of progressive metabolic disruption begins and will continue until hydration, insulin, and additional management of acidosis/fluid and electrolyte imbalance are provided. Osmotic diuresis causes loss of sodium, potassium, phosphorus, magnesium, and body water, which leads to dehydration and, possibly, hypovolemic shock. Increased blood viscosity and platelet aggregation can result in thromboembolism.

Despite significant loss of potassium in the urine, the patient may initially manifest normal or elevated plasma potassium because of the dramatic shift of potassium out of the cells secondary to insulin deficiency, acidosis, and tissue catabolism. Dehydration lowers BP and decreases tissue perfusion, and cells begin anaerobic metabolism. The resulting lactic acid waste products worsen acidosis. Low pH stimulates the respiratory center, producing deep, rapid, Kussmaul respirations. Abundant plasma ketones cause fruity or acetone breath. If not managed, elevated serum osmolality, acidosis, and dehydration depress consciousness to a coma state. Death can result.

The cause of death in patients with DKA and the other hyperglycemic emergency, HHS, rarely results from the metabolic complications of hyperglycemia or metabolic acidosis. Death is related to the underlying medical illness that caused the metabolic decompensation. Successful treatment depends on a prompt and careful evaluation for the precipitating cause(s). The clinical symptoms of DKA generally appear within 24 hours of failure to manage hyperglycemia.

Pathophysiology

HHS is a life-threatening emergency created by a relative insulin deficiency and significant insulin resistance, resulting in severe hyperglycemia, with profound osmotic diuresis leading to life-threatening dehydration and hyperosmolality. HHS is also known as hyperosmolar hyperglycemic state, hyperosmolar nonketotic syndrome (HONK), hyperosmolar nonketotic state (HNS), hyperglycemia hyperosmolar nonketotic syndrome (HHNS), and, traditionally, hyperosmolar hyperglycemic nonketotic coma (HHNK). HHNK, HHNS, HNS, and HONK are somewhat incorrect titles for the syndrome, as recent evidence reveals a mild degree of ketosis is often present with HHS, and true coma is uncommon. The mortality rate of HHS ranges from 10% to 50%, higher than that for DKA (1.2% to 9%). Mortality data are difficult to interpret because of the high incidence of coexisting diseases or comorbidities.

Historically, HHS and DKA were described as distinct syndromes, but one third of patients exhibit findings of both conditions. HHS and DKA may be at opposite ends of a range of decompensated diabetes, differing in time of onset, degree of dehydration, and severity of ketosis. HHS occurs most commonly in older people with type 2 diabetes, but with the recent obesity epidemic, occasionally obese children and teenagers with both diagnosed and undiagnosed type 2 diabetes manifest HHS. The cascade of events in HHS begins with osmotic diuresis. Glycosuria impairs the ability of the kidney to concentrate urine, which exacerbates the water loss. Normally, the kidneys eliminate glucose above a certain threshold and prevent a subsequent rise in blood glucose level. In HHS, the decreased intravascular volume or possible underlying renal disease decreases the glomerular filtration rate (GFR), causing the glucose level to increase. More water is lost than sodium, resulting in hyperosmolarity. Insulin is present, but not in adequate amounts to decrease blood glucose levels, and with type 2 diabetes, significant insulin resistance is present. DKA and HHS are compared in Table 8-3.

Table 8-3 COMPARISON OF DIABETIC KETOACIDOSIS (DKA) AND HYPERGLYCEMIC HYPEROSMOLAR SYNDROME (HHS)

Criterion	DKA	HHS
Diabetes type	Type 1	Type 2; rarely, Type 1
Typical age group	More common in young children and adolescents than adults	57-69 yrs, with average age 60 yrs
Signs and symptoms	Polyuria, polydipsia, polyphagia, weakness, orthostatic hypotension, lethargy, changes in LOC, fatigue, nausea, vomiting, abdominal pain	Same as DKA, but slower onset Also, very commonly, neurologic symptoms predominate
Physical assessment	Dry and flushed skin, poor skin turgor, dry mucous membranes, decreased BP, tachycardia, altered LOC (irritability, lethargy, coma), Kussmaul respirations, fruity odor to the breath	Same as DKA, but no Kussmaul respirations or fruity odor to the breath; instead, occurrence of tachypnea with shallow respirations
History and risk factors	Recent stressors such as surgery, trauma, infection, MI; insufficient exogenous insulin; undiagnosed type 1 diabetes mellitus	Undiagnosed type 2 diabetes mellitus; recent stressors such as surgery, trauma, pancreatitis, MI, infection; high-calorie enteral or parenteral feedings in a compromised patient; use of diabetogenic drugs (e.g., phenytoin, thiazide diuretics, thyroid preparations, mannitol, corticosteroids, sympathomimetics)
Monitoring parameters	ECG: Dysrhythmias associated with hyperkalemia: peaked T waves, widened QRS complex, prolonged PR interval, flattened or absent P wave. Hypokalemia (K+ <3 mEq/L), which may produce depressed ST segments, flat or inverted T waves, or increased ventricular dysrhythmias	ECG evidence of hypokalemia as listed with DKA Hemodynamic measurements: CVP >3 mm Hg below patient’s baseline; PADP and PAWP >4 mm Hg below patient’s baseline
Diagnostic tests	Serum glucose: Greater than 250 mg/dl	Greater than 600 mg/dl
	Serum ketones: Large presence	Usually absent to mild presence due to dehydration
	Urine glucose: Positive	Positive
	Urine acetone: “Large”	Usually Negative
	Serum osmolality: Greater than 290 mOsm/L	Greater than 320 mOsm/L
	Bicarbonate: Less than 15 mEq/L	Greater than 15 mEq/L
	Serum pH: <7.2	Normal or mildly acidotic (pH < 7.4)
	Anion Gap: Elevated greater than 13	Normal
	Serum potassium: normal or elevated >5.0 mEq/L initially and then decreased	Normal or <3.5 mEq/L
	Serum sodium: elevated, normal, or low	Elevated, normal, or low
	Serum Hct: elevated because of osmotic diuresis with hemoconcentration	Elevated because of hemoconcentration
	BUN: elevated >20 mg/dl	Elevated
	Serum creatinine: >1.5 mg/dl	Elevated
	Serum phosphorus, magnesium, chloride: decreased	Elevated
	WBC: elevated, even in the absence of infection	Normal unless infection present
Onset	A few days	Days to weeks
Mortality	1-10%	14%–58% because of age group and complications such as stroke, thrombosis, renal failure

BP, Blood pressure; BUN, blood urea nitrogen; CVP, central venous pressure; DKA, diabetic ketoacidosis; ECG, electrocardiogram; Hct, hematocrit; HHS, hyperglycemic hyperosmolar syndrome; LOC, level of consciousness; MI, myocardial infarction; PADP, pulmonary artery diastolic pressure; PAWP, pulmonary artery wedge pressure; WBC, white blood cell count.

Primary causes of HHS include infections, noncompliance with a diabetes management regimen, undiagnosed diabetes, medications, substance abuse, and coexisting diseases. Infections are the leading cause (57% of patients); pneumonia (often gram negative) is the most common, followed by UTI and sepsis. Lack of compliance with diabetic medications or other aspects of diabetes management may be a frequent cause (21%). Undiagnosed diabetes prompts a failure to recognize early symptoms of the complications of unmanaged hyperglycemia. Acute coronary syndrome (MI), stroke, pulmonary embolus, and mesenteric thrombosis have caused HHS. In urban populations, at least one study revealed the three leading causes to be lack of compliance with medications, drinking alcohol, and use of cocaine. Chronic use of steroids and gastroenteritis are commonly associated with HHS in children.

The blood glucose level is higher with HHS than with DKA. A global electrolyte loss is present. Sodium and potassium levels vary at diagnosis, but deficiencies of both are present. Magnesium, calcium, phosphate, and chloride deficiencies evolve. Patients may lose from 15% to 25% of total body water or approximately 100 to 200 ml/kg. Fluids are drawn from cells to dilute the concentrated bloodstream. Significant intracellular dehydration results. Neurologic deficits occur in response to severe dehydration and hyperosmolality. The blood is highly viscous, and flow slows, increasing risk for the formation of thromboemboli. Increased cardiac workload and decreased renal and cerebral blood flow may result in MI, renal failure, and stroke.

Unlike DKA, wherein acidosis produces severe symptoms, HHS develops slowly, and frequently symptoms are nonspecific. Polyuria and polydipsia occur but may be ignored. Neurologic deficits may be mistaken for senility. Similarity of symptoms to other disease processes in older adults may delay diagnosis and treatment, allowing the process to progress.

Metabolic assessment: hyperglycemia

Goal of metabolic assessment

Evaluate for degree of hyperglycemia and its effects on overall hemodynamics, respiratory rate/pattern, and mental status. Hyperglycemia may be asymptomatic or, with DKA, result in hypotension causing decreased perfusion, increased work of breathing with Kussmaul respirations, ineffective breathing patterns, abdominal pain, and neurologic deficits including coma and/or strokelike symptoms. HHS findings are similar but are more likely to result in neurologic changes, cause abdominal pain less often, and almost never cause compensatory Kussmaul respirations, because acidosis is mild, if present at all. Dehydration, hyperglycemia, and acidosis must be managed immediately. Associated electrolyte imbalances may be managed as the patient’s glucose level normalizes and hydration is provided.

History and risk factors

Hyperglycemia manifests more commonly in hospitalized patients with diabetes mellitus or impaired glucose tolerance than in normal patients with an exaggerated response to stress. Obese patients are more likely to have insulin resistance associated with metabolic syndrome, impaired tolerance for glucose, or undiagnosed type 2 diabetes mellitus. Type 2 diabetic patients generally manifest HHS when hyperglycemia is ineffectively managed. Rarely, a type 2 patient will manifest DKA. The majority of patients with DKA have type 1 diabetes mellitus. The type 1 patient will die without adequate insulin administration.

Recent stressors that prompt dka in patients with diabetes mellitus include:

• Infection (20% to 55%): May be overestimated because DKA may prompt leukocytosis and vasodilation, which mimic sepsis.

• Inadequate insulin/noncompliance (15% to 40% ): Teenagers may be at higher risk for noncompliance; all illnesses increase stress, which increases the need for insulin. Type 1 patients are totally reliant on administration of exogenous insulin to control hyperglycemia, because without functional beta islet cells in the pancreas, they have no ability to produce insulin.

• Undiagnosed diabetes (10% to 25%): Onset of type 1 diabetes is generally preceded by a significant illness—often a viral infection or childhood disease.

• Other medical illness (10% to 15%): Pneumonia, urinary tract infection, ischemic bowel, pregnancy, hypothyroidism, pancreatitis, pulmonary embolism, surgery, and new medications (notably corticosteroids, sympathomimetics, alpha and beta blockers, fluoroquinolone antibiotics [Levaquin], and diuretics)

• Cardiovascular disease (3% to 10%): Significant cardiovascular disease may be the result of diabetes mellitus, and subsequently, unstable patients may experience variable stress levels making control of hyperglycemia difficult. Vascular events such as MI, cerebrovascular accident (CVA), or ischemic bowel may precipitate or worsen DKA.

• Cause unknown (5% to 35%): Any physiologically stressing illness or event has the potential to cause the condition. Certain women are more likely to go into DKA at the time of menstruation. Severe emotional stress is associated with onset of DKA.

Recent stressors that prompt hhs in patients with diabetes mellitus:

• Diabetes: First symptomatic presentation of undiagnosed hyperglycemia; poor control of hyperglycemia (noncompliance, inadequate resources, abuse or neglect of patient by caregivers or self-inflicted, accidental omission of medication, or ingestion of excessive carbohydrates)

• Associated medical conditions

1. Infection: urinary tract, pneumonia, cellulitis, sepsis, dental infection/abscess

2. MI or other acute coronary syndromes

3. Stroke or intracranial hemorrhage

4. Temperature alteration: hyperthermia or hypothermia

5. Mesenteric ischemia: intestinal/bowel ischemia or bowel infarction

6. Pancreatitis

7. Pulmonary embolism

8. Acute abdomen

9. Acute renal failure or decompensated chronic renal failure (“acute on chronic”)

10. Burns

11. Hyperthyroidism

12. GI bleeding

13. Cushing syndrome or other ACTH-secreting tumor

• Medication related

14. Beta blockers (metoprolol, atenolol, inderal)

15. Carbonic anhydrase inhibitors (diazoxide)

16. Calcium channel blockers (diltiazem, verapamil)

17. Chlorpromazine or other antipsychotics (olanzepine)

18. Diuretics (loop: furosemide, bumetanide; thiazide: HCTZ)

19. Glucose-containing fluids (total parenteral nutrition, tube feedings, dialysis solutions)

20. Glucocorticoid/steroids (cortisone, hydrocortisone, prednisone)

21. H₂-receptor antagonists (ranitidine, cimetidine)

22. Phenytoin or other anticonvulsants

23. Substance abuse: alcohol, amphetamines, cocaine, MDMA (“ecstasy”)

Vital signs

• Findings vary significantly, depending on patient’s situation.

• Hyperglycemia alone may have no effect on vital signs.

• Tachycardia and tachypnea are present if a hyperglycemic crisis (DKA, HHS) is present.

• Hypotension is present with DKA and HHS.

• Hypovolemia alone may prompt tachycardia.

Observation

• Hyperglycemia alone may not cause overt physical assessment changes.

• Skin should be examined for lesions, rashes, cellulitis, and other signs of possible infection.

• If patient presents to the emergency department, observe for signs of recent alcohol consumption.

• With DKA: Kussmaul respirations (rapid, deep) are present to exhale CO₂ as a compensatory response to relieve metabolic acidosis; may appear fatigued, with or without diaphoresis from Kussmaul breathing

• With DKA and HHS:

1. Significant abdominal pain is present in at least 40% of patients; paralytic ileus or gastroparesis may be present, but will resolve when hyperglycemia and dehydration are managed.

2. Ashen, pale or gray/blue facial color, lip color, or nail beds from severe hypotension and hypoperfusion due to dehydration

3. Signs of dehydration: poor skin turgor, dry mouth/lips, sunken eyes, slow capillary refill

4. Generalized weakness, possible exhaustion, nausea and vomiting, impaired vision and leg cramps may be present; patients may become unable to get out of bed.

5. Cranial nerve examination may be abnormal, with nerve palsies present.

6. Altered LOC (confusion, disorientation, agitation) is more common with older adults; strokelike symptoms may be present; coma is present in about 10% of patients presenting with HHS; seizures are present in 25% of HHS patients.

7. If severe shock has ensued, agitation is more commonly associated with hypoxemia, while somnolence is associated with hypercarbia (elevated carbon dioxide level) and acidosis.

8. Associated findings: patient may manifest symptoms of heart failure, pneumonia, and other risk factors if hyperglycemic crisis is present.

Auscultation

• Hyperglycemia does not change baseline physical assessment unless it has progressed to crisis level (DKA, HHS).

• Clear breath sounds with DKA and HHS because dehydration is present.

• Bowel sounds may be absent if paralytic ileus and gastroparesis are present with DKA and HHS.

• Heart sounds may reflect heart failure with DKA and HHS.

Palpation

• For DKA: Abdomen may be palpated if abdominal pain is present.

Percussion

• For DKA and HHS: Lung percussion may reveal presence of consolidation or fluid (dullness) indicative of a pulmonary infection.

Screening labwork

• POC capillary blood glucose (bedside glucose monitoring)

• If POC glucose is elevated, a plasma glucose sample should be drawn.

• In addition, if DKA or HHS is suspected:

1. ABG analysis: Done promptly to evaluate for acidosis, hypoxemia, and hypercapnia

2. CBC: Evaluates for elevated WBCs indicative of infection

3. Sputum and urine culture and sensitivity: Identifies infecting organism

4. Blood culture and sensitivity: If positive, indicates organism has migrated into the bloodstream to cause a systemic infection

Diagnostic Tests for Hyperglycemia and Hyperglycemic Emergencies

Test	Purpose	Abnormal Findings
Hemoglobin A1c (HbA1c) or glycosylated hemoglobin Performing this test more frequently than every 6–8 weeks does not yield useful information about blood glucose control	Assesses for control of blood glucose for the 6 to 8 weeks preceding the test. Recommended screening for all hospitalized patients so poorly controlled blood glucose readings can be addressed immediately to avoid development of DKA (diabetic ketoacidosis) or HHS (hyperglycemia hyperosmolar syndrome)	HbA1c >7 reflects poor control. AACE and ADA guidelines have varied; stricter guidelines recommend patients with HbA1c >6 have inadequate control. If a patient with diabetes mellitus who has been managing at home presents with an elevated value, home management and medications should be adjusted. If a patient without diabetes has an elevated value, the patient should undergo a full evaluation for presence of undiagnosed diabetes.
Fasting blood glucose (FBG) Test is performed in the morning after fasting all night and prior to consuming breakfast	Evaluates the effectiveness of basal insulin dosage by assessing for presence of hyperglycemia or hypoglycemia; used for daily screening of blood glucose control during hospitalization	<40 mg/dl: Severe hypoglycemia 41–69 mg/dl: Hypoglycemia 70–110mg/dl: Normoglycemia 111–125mg/dl: Borderline hyperglycemia 126–180mg/dl: Hyperglycemia 181–220mg/dl: Significant hyperglycemia >220 mg/dl: Possible impending DKA or HHNS if glucose is not managed
Mealtime blood glucose Generally, a point-of-care (POC) reading is done either 15 to 30 minutes prior to a meal, or as the meal begins.	Assesses blood glucose control with existing hyperglycemia management program	If reading is <140 mg/dl (2009 AACE and ADA recommendation), no mealtime, short acting, subcutaneous insulin is needed. The recommendations have not been universally accepted. Thresholds for supplemental insulin vary with each hospital and sometimes, each physician.
Postprandial blood glucose May be done 1 or 2 hours following meals using serum glucose or point of care capillary glucose readings	Evaluates ability of glucose to normalize following a meal. Readings may be done 1 or 2 hours following the meal.	>180 mg/dl: If glucose is >180 at 1 hour following a meal, the patient is unable to produce enough insulin, or has not received enough mealtime insulin, or may be insulin resistant, or may require initiation of mealtime insulin. >140 mg/dl: If glucose is >140 at 2 hours following a meal, the patient is unable to produce enough insulin or may be insulin resistant.
Oral glucose tolerance test (OGTT) Following at least 8 hours of fasting, oral glucose is consumed by the patient to determine how quickly it is cleared from the blood.	Used to test for diabetes, insulin resistance, and reactive hypoglycemia. Fasting blood glucose (FBG) is used at the beginning of the test. Additional readings are done 2 hours later. Fasting readings are compared to 2 hours post glucose ingestion to determine extent of glucose intolerance.	FBG >126 mg/dl with 2-hour reading >200 mg/dl: Confirms diagnosis of diabetes mellitus (DM) FBG 111–125 mg/dl with 2-hour reading >140 mg/dl: Patient has impaired glucose tolerance (IGT) FBG 111–125mg/dl with 2-hour reading <140 mg/dl: Patient has impaired fasting glucose (IFT)
Arterial blood gas analysis (ABG) Done promptly, following confirmation of hyperglycemia to assess for DKA and HHS.	Assess for abnormal gas exchange or compensation for metabolic derangements in patients in hyperglycemic crisis; profound acidosis can indicate DKA is present, since HHS typically presents with minimal to mild acidosis unless prolonged, severe hypovolemic shock is present.	pH changes: With DKA, may be 6.8–7.2; acidosis results from ketosis or lactic acidosis Carbon dioxide: With DKA, decreased CO2 reflects tachypnea and Kussmaul respirations Hypoxemia: With DKA or HHS, PaO2 <80 mm Hg may indicate pneumonia precipitated the crisis Oxygen saturation: If pneumonia or heart failure is present, SaO2 may be <92% Bicarbonate: HHS: HCO3− 15-22 mEq/L; DKA: HCO3– may be <15 mEq/L Base deficit: HHS <−2; with DKA, <−10
Complete blood count (CBC)	Evaluates for presence of infection	Increased WBC count: >11,000/mm3 is seen with bacterial pneumonias, urinary tract infections and other infections.
Sputum Gram stain, culture and sensitivity	Screens for pneumonia, a common underlying cause of hyperglycemic crisis; identifies infecting organism	Gram stain positive: Indicates organism is present; Culture: Identifies organism Sensitivity: Reflects effectiveness of drugs on identified organism.
Blood culture and sensitivity	Screens for sepsis, a common underlying cause of hyperglycemic crisis Identifies whether an organism has become systemic	Secondary bacteremia: a frequent finding; patients with bacteremia are at higher risk for developing respiratory failure.
Blood chemistry	Screens for electrolyte imbalances; potassium imbalances may create potentially dangerous dysrhythmias	DKA and HHS: Hypernatremia is present: BUN, creatinine, and K+ may be elevated, normal, or low. Anion gap DKA: >13 Anion gap HHS: 10–12
Plasma osmolality	Screens for elevated osmolality associated with severe hyperglycemia	Osmolality is increased more with HHS than with DKA. DKA: 290–320 mmol/L HHS: >320 mmol/L
Urine ketones	Screens for the presence of ketones to confirm diagnosis of DKA; HHS does not cause ketonuria.	DKA: Ketones strongly positive HHS: Ketones negative, or mildly positive
12-Lead ECG	Used to rule out myocardial infarction as the cause of HHS or DKA	Tall, peaked T waves if ↑K+ is present prior to management of hyperglycemia, hypovolemia and acidosis; VPCs/ventricular irritability is seen with ↓K+ seen as insulin normalizes glucose.
Chest radiograph	Screens for pneumonia and acute respiratory distress syndrome, which may prompt DKA and HHS	“Fluffy whiteness” may not initially be present due to dehydration, but may appear as patient is rehydrated revealing pneumonia or ARDS
Computed tomography (CT) brain scan	Screens for ischemic and hemorrhagic stroke, which may prompt DKA and HHS	Generally not done until patient has had at least 1 hour of rehydration and insulin therapy to see if symptoms resolve spontaneously.

Collaborative management

When approaching how to manage hyperglycemia in hospitalized patients, the following key elements should be considered when evaluating current management blood glucose control strategies:

Additional nursing diagnoses

See also nursing diagnoses and interventions in Hyperkalemia, Hypokalemia, and Hypovolemia in Fluid and Electrolyte Disturbances, p 37; Alterations in Consciousness, p 24; Prolonged Immobility (p. 149); and Emotional and Spiritual Support of the Patient and Significant Others (p. 200).

Pathophysiology

Myxedema coma is a life-threatening condition that occurs when hypothyroidism is untreated or when a stressor such as infection affects an individual with known/unknown hypothyroidism. The clinical picture of myxedema coma includes exaggerated hypothyroidism, with decreased mental status or coma, hypoventilation, hypothermia, hypotension, seizures, and shock. Myxedema coma usually develops slowly, has a greater than 50% mortality rate, and requires prompt, aggressive treatment. Even with early diagnosis and treatment, mortality is nearly 45%.

Hypothyroidism is a common endocrine disorder reflecting inadequacy of production or uptake of the thyroid hormone. Localized disease of the thyroid gland that results in decreased thyroid hormone production is the most common cause of hypothyroidism. Normally, the thyroid gland releases 100 to 125 nmol of thyroxine (T₄) daily and only small amounts of triiodothyronine (T₃). T₄ is a prohormone functioning as a reservoir for the more metabolically active form of the thyroid hormone, T₃. Primary conversion occurs in the peripheral tissues via 5′-deiodination. Decreased production of T₄ and failure of deiodinization to T₃ causes an increase in the secretion of thyroid-stimulating hormone (TSH) by the functional pituitary gland. TSH stimulates hypertrophy and hyperplasia of the thyroid gland and an increase in thyroid T₄–5′-deiodinase activity. Early in the disease process, compensatory mechanisms maintain T₃ levels; however, this compensatory mechanism may be short lived.

Individuals who are acutely or critically ill may have an extreme disruption of the normal hypothalamic–anterior pituitary–thyroid axis, particularly related to the nocturnal surge that is normally seen with thyrotropin. These patients will have a low T₃ level even after the TSH is restored to normal and are commonly referred to as presenting with low T₃ syndrome. Patients with poor heart function or more intense inflammatory reaction show more pronounced downregulation of the thyroid system. During sepsis, the pituitary gland is activated via blood-borne proinflammatory cytokines and through a complex interaction between the autonomic nervous system and the immune cells. Sepsis elicits a pattern of pituitary hormone dysfunction which may cause a significant decrease in the secretion of TSH.

Hypothyroidism results in inadequate amount of circulating thyroid hormone, causing a decrease in metabolic rate that affects all body systems.

Primary hypothyroidism, the most common presenting form of thyroidal disorders, is caused by thyroid suppression for any direct reason (i.e., cancer, radiation, autoimmune dysfunction).

Secondary hypothyroidism results from inadequate secretion of TSH from the anterior pituitary gland. The cause of the deficiency is not always clear but is often associated with surgery, trauma, or radiation therapy. If TSH level is inadequate, the thyroid lacks the proper stimulus to produce T₄.

Tertiary hypothyroidism is related to hypothalamic dysfunction and is diagnosed by the release of thyrotropin-releasing hormone (TRH). Other causes are listed in Box 8-2.

Because all metabolically active cells require thyroid hormone, the effects of hormone deficiency vary. Systemic effects are due to either derangements in metabolic processes or direct effects by myxedematous infiltration in the tissues. The patient’s presentation may vary from asymptomatic to, rarely, coma with multisystem organ failure (myxedema coma). Hypothyroidism is eight times more likely to occur in women than in men, and it frequently presents in the later years of life; older women are the most likely candidates to present with myxedema.

ESS should be considered when TSH and/or T₄ are normal, T₃ is low, and the patient presents with symptoms that suggest hypothyroidism.

Endocrine assessment: myxedema coma

Goal of system assessment

Evaluate for end-organ effects of hypothyroidism, including altered mental status, hypothermia, hypoglycemia, hypotension, bradycardia, and hypoventilation. Not all patients have noticeable myxedema (polysaccharide accumulation).

History and risk factors

Signs and symptoms may be life-threatening in a patient with history of hypothyroidism who has experienced a recent stressful event. Undiagnosed patients may report early fatigue, weight gain, anorexia, lethargy, cold intolerance, menstrual irregularities, constipation, depression, and muscle cramps. Family may report depression, psychosis, cognitive dysfunction, or poor memory.

A change in mental status may be the most compelling sign to assist in making the diagnosis.

Vital signs

Cardinal signs and symptoms of myxedema coma include hypothermia (may be less than 80°F), hypoventilation, hypotension, and bradycardia, as well as hyponatremia and hypoglycemia. The presentation of any three of these signs and symptoms together should be considered in differential diagnosis as signs of acute hypothyroidism until proven otherwise.

The presence of a normal temperature in a patient who appears to present with acute hypothyroid dysfunction is abnormal and should be considered an indicator of infection.

Observation

Cardiac: Nonspecific ECG changes, prolonged conduction times, prolonged QT syndrome. Cardiac enlargement, possible effusion. If hypotensive, may be refractory to volume and vasopressors until thyroid hormone given.

Respiratory: Respiratory depression from reduced hypoxic drive and decreased ventilatory response and increasing CO₂. The increase in CO₂ is a major factor in the induction of coma. May also have edema of the conducting airways.

Gastrointestinal: Anorexia, nausea, abdominal pain, and constipation. Quiet abdomen, ileus, and megacolon not uncommon.

Hypothyroidism

• Possible presence of obesity and/or weight gain from fluid retention

• The skin may be dry, cool, and coarse, and the hair may be thin, coarse, and brittle. The tongue may be enlarged (macroglossia), and the reflexes may be slowed. Periorbital edema may be noted.

• There may be a surgical scar or a goiter when evaluating the neck. Nodules may be palpated.

• The patient may have muscle weakness, memory and mental impairment, and constipation.

• Polysaccharide substances may be deposited beneath the skin (myxedema), which may prompt hypovolemia.

A change in mental status may be the most important sign. It is commonly noted first to be lethargy, then stupor, and ultimately coma.

Screening labwork

Blood studies may reveal the presence of thyroid dysfunction. Expected abnormalities include (see also Figure 8-2):

• TSH increased or normal (chronic thyroiditis)

• T₄ decreased

• Hypercholesterolemia

• Elevated serum lactate

• Hypoglycemia

• Hyponatremia

• Hypoxemia

• Hypercapnia

Figure 8-2 Diagnosing hypothyroidism.

Common Diagnostic Tests for Hypothyroid Crisis: Myxedema Coma

Test	Purpose	Abnormal Findings
Blood Studies
Thyroid-stimulating hormone (TSH) Standard normal: 0.4–4.5 mIU/L Revised normal: 0.4–2.5 mIU/L TSH >2.5 mIU/L from the NAHAMES III study indicated hypothyroidism.	Measures TSH output from the anterior pituitary. Completes a negative feedback loop with the thyroid. When thyroid hormone level decreases, TSH level should increase.	Elevated unless hypothyroidism is longstanding or severe. When TSH is higher than 2.5 mIU/L in the presence of clinical symptoms, the diagnosis of hypothyroidism will be considered positive until proved otherwise. Always beneficial to also evaluate T4 at the same time. If TSH is higher than 4.5, the diagnosis of hypothyroidism is considered positive.
Thyroperoxidase antibodies	Assesses for thyroid antibodies	Positive test signals chronic autoimmune thyroiditis.
Free T4 or free thyroxine index (FTI) Normal: 60–170 nmol/L	Measures the level of primary thyroid hormone May be unreliable in the face of critical illness	Decreased. When levels are below normal, diagnosis of hypothyroidism is made. If the TSH is high, diagnosis would be a primary hypothyroidism, If TSH is normal or low and T4 is low, the problem is in the hypothalamic- pituitary response to elevated circulating thyroid levels (secondary hypothyroidism). However if the T3 is also low, this may signify euthyroid sick syndrome.
T3 (triiodothyronine) Normal: 0.8–2.7 nmol/L	Measures the more metabolically active form of the thyroid hormone.	Controversial regarding value of treatment of low levels, since it has a higher frequency of adverse cardiac events and is generally reserved for patients who are not improving clinically on LT4.
Thyroid-binding globulin (TBG)	To measure the level of the protein that binds with circulating thyroid hormones. Abnormal T4 or T3 measurements are often due to binding protein abnormalities rather than abnormal thyroid function.	Total T4 or T3 must be evaluated with a measure of thyroid hormone binding such as T3 resin uptake or assay of thyroid-binding globulin. These methods are known as free T4 or free T3 even though they do not measure free hormone directly.
Electrolytes Potassium (K+) Magnesium (Mg2+) Calcium (Ca2+) Sodium (Na+)	Assess for possible abnormalities	Frequently, abnormalities of calcium are related to parathyroid disorders exist concurrently with thyroid dysfunction.
Radiology/Imaging
Thyroid scan with radioactive iodine uptake123| or 99mTc pertechnetate	To identify thyroid nodules	Not beneficial in hypothyroidism as uptake of radioactive iodine may not occur
Thyroid scan 131I and radioactive iodine uptake	To identify thyroid nodules	In primary hypothyroidism, will be less than 10% in a 24-hour period. In secondary hypothyroidism, uptake increases with administration of exogenous TSH.
Chest radiograph	Assess size of heart, and presence of pericardial or pleural effusion	Cardiac enlargement or fluid around the heart is common with myxedema
Ultrasound	Assess size and presence of nodules and goiter	Abnormal thyroid is unusual in Hashimoto disease.
Fine needle biopsy	Evaluate suspicious nodes	Cancerous cells indicate thyroid cancer

Collaborative management

Pathophysiology

Syndrome of inappropriate antidiuretic hormone (SIADH) or syndrome of inappropriate antidiuresis (SIAD) is a condition of abnormal release of antidiuretic hormone (ADH, vasopressin) in response to changes in plasma osmolality that results in hyponatremia. Hyponatremia is defined as an excess of water in relation to the amount of sodium in the extracellular fluid. SIADH is the most frequent cause of hyponatremia, the most common electrolyte imbalance in hospitalized patients. Mild hyponatremia (serum sodium, less than 135 mEq/L) occurs in 15% to 22% of hospitalized patients and 7% of ambulatory patients, while moderate hyponatremia (serum sodium, less than 130 mEq/L) occurs in 1% to 7% of hospitalized patients. Hyponatremia is often caused by extracellular fluid volume depletion associated with many diuretics, which cause a significant loss of sodium along with water. Hyponatremia is important to manage because of potential morbidity and should be recognized as an indicator of underlying disease.

ADH (vasopressin) is produced in the hypothalamus and stored in the posterior pituitary and regulates free water volume in the kidney. Hyponatremia resulting from chronic SIADH is not always caused by reduced water excretion or volume overload. Plasma ADH level may not be high and measurement is often not helpful in establishing the diagnosis. Findings may reflect dilute (hypo-osmolar) plasma and hyponatremia with a normal circulating blood volume. Morbidity and mortality of hyponatremia associated with SIAD stem from cerebral edema and abnormal nerve function. Values of serum sodium 100 mEq/L or less are life-threatening. Four patterns of abnormal vasopressin secretion have been identified in Table 8-4. The disorders and medications associated with SIAD are listed in Table 8-5.

Table 8-4 SYNDROME OF INAPPROPRIATE ANTIDIURESIS (SIAD): FOUR TYPES

Table 8-5 MEDICATIONS AND DISEASES ASSOCIATED WITH SIADH AND HYPONATREMIA

ADH is a key component in the regulation of fluid and electrolyte balance, through direct effects on renal water regulation. Water is reabsorbed in the distal nephron, where the kidney both concentrates and dilutes urine in response to the ADH level. Vasopressin (VP) stimulates the nephron to produce aquaporin (AQP), a specific water channel protein, on the surface of the interstitial cells lining the collecting duct. The presence of AQP in the wall of the distal nephron allows resorption of water from the duct lumen according to the osmotic gradient, and excretion of concentrated urine.

Hyponatremia resulting in SIAD is often drug induced, reflecting either direct stimulation of ADH/VP release from the hypothalamus, indirect stimulation of ADH action on the hypothalamus, or abnormal resetting of the hypothalamic osmotic threshold that governs release of ADH. The prevalence of hyponatremia in patients taking high-dose dopamine antagonists is greater than 25% and is associated with more than one class of these drugs. Hyponatremia secondary to antidepressants is common, occurring with most selective serotonin reuptake inhibitors (SSRIs). Patients receiving concurrent diuretic therapy are at high risk, indicating that hypovolemia contributes to the hyponatremia. Loop diuretics promote both sodium and water loss. Anticonvulsants commonly cause hyponatremia, which prompts SIAD. Patients treated with carbamazepine have a 5% to 40% incidence of SIAD.

Endocrine assessment: syndrome of inappropriate antidiuresis

Collaborative management

Additional nursing diagnoses

See also Hyponatremia in Fluid and Electrolyte Imbalances (p. 46).

Pathophysiology

Thyroid storm is a medical emergency caused by uncontrolled hyperthyroidism. Patients occasionally present with cardiovascular collapse and shock. Hyperthyroidism or thyrotoxicosis is a condition of increased circulating thyroid hormone. The crisis results from a surge of thyroid hormones into the bloodstream, which results in profound stimulation of the sympathetic nervous system, with marked increases in body metabolism. The hypothalamus, anterior pituitary, and thyroid normally work together to balance the level of circulating thyroid hormone. Hyperthyroidism may be caused by an increased synthesis and secretion of thyroid hormones (thyroxine [T₄] and triiodothyronine [T₃]) from the thyroid or from increased secretion of TSH from the anterior pituitary, possibly by an increase in TRH from the hypothalamus or by autonomous thyroid hyperfunction. Symptoms of hyperthyroidism can also result from excessive release of thyroid hormone from the thyroid without increased synthesis. Such release is commonly caused by the destructive changes of various types of thyroiditis. Thyrotoxicosis crisis may also follow subtotal thyroidectomy because of manipulation of the gland during surgery. Various clinical syndromes also produce hyperthyroidism, but thyroid storm is most often associated with Graves’ disease, also known as diffuse toxic goiter. Causes of acute hyperthyroid states are listed in Box 8-3. Not all conditions listed are associated with thyroid storm.

Abnormal laboratory analysis of thyroid function provides a relatively definitive diagnosis. Initial serum measurements should include a free T₄ and TSH, but concerns regarding thyroidal dysfunction should be referred to an endocrinology specialist for a more thorough and evaluative diagnostic panel. Calcium regulation may also be affected by thyroid disease if there is a problem with the level of thyrocalcitonin, a third thyroid hormone that is stimulated by increased calcium levels to help lower the calcium level. Recent diagnostic tests have isolated a long-acting thyroid stimulator, suggesting the disease is an autoimmune response. An acute decrease in thyroxine-binding globulin (inactivating or binding thyroid hormone) facilitates high levels of free and metabolically active hormone. The increased circulating levels of active thyroid hormone increase the response of beta adrenergic receptors (sympathetic stimulation increase) and also increase the system responsiveness to catecholamines.

Endocrine assessment: hyperthyroidism

Collaborative management

Additional nursing diagnoses

See Compromised Family Coping, in Oncologic Emergencies, p. 893; Nutritional Support, p. 117; Alterations in Consciousness, p. 24; Emotional and Spiritual Support of the Patient and Significant Others, p. 200; Dysrhythmias and Conduction Disturbances, p. 492; Heart Failure, p. 421.