1. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice
8 Critical Care 10 Endocrine Problems — 1
10 ENDOCRINE PROBLEMS
Robert H. Bartlett, M.D., and Preston B. Rich, M.D.
Patients scheduled for operation may be receiving treatment glucose levels should be carefully monitored in patients taking this
with insulin, oral hypoglycemics, corticosteroids, thyroid hor- medication who have experienced injury or undergone operation.
mone, or estrogen. The presence of any state calling for such
treatment must be taken into consideration in planning opera- Laboratory Studies
tive management and perioperative care. In addition, glucose The degree of control of diabetes can be assessed by recording
intolerance may develop in otherwise normal patients after oper- blood glucose measurements at frequent intervals during fasting
ation, and this possibility must be taken into account as well. In and at other times during the day and by determining what per-
what follows, we describe an approach to preventing and man- centage of total hemoglobin is combined with carbohydrate (i.e.,
aging common endocrine conditions that occur as complicating glycosylated). Normally, glycosylated hemoglobin (commonly
factors in the perioperative period. We do not, however, address called HbA1c) accounts for 4% to 7% of total hemoglobin. HbA1c
perioperative problems related to operations for primary levels increase when hyperglycemia occurs, and the increases are
endocrine disease. cumulative over time. The value of measuring HbA1c in a preop-
erative patient known to be diabetic is that it gives the attending
physicians some idea of how well hyperglycemic episodes are
Diabetes Mellitus being controlled by insulin or oral hypoglycemics. Monthly mea-
Diabetics have a 50% chance of undergoing a surgical proce- surements yield a good picture of the adequacy of glucose control
dure during their lifetime.1 In the past, operation in these over extended periods. HbA1c percentages higher than 10% to
patients was associated with a mortality of 4% to 13%,2 usually 20% indicate that the hyperglycemic aspect of diabetes has been
attributed to cardiovascular complications—clearly a significant poorly controlled. Chronic diabetic complications are reduced
operative risk. Any subsequent improvement in diabetes-related when good control of blood glucose is maintained; diabetic
operative mortality has probably been offset by the increasing patients are advised to measure their blood glucose levels fre-
age of patients with diabetes and the larger variety of procedures quently, which should result in normal HbA1c levels. HbA1c per-
they undergo. centages higher than 15% suggest that the diabetes is quite brit-
Perioperative management of diabetic patients [see Figure 1] is tle and that more frequent monitoring of blood glucose levels and
complicated both by the metabolic abnormalities of the disease closer control of insulin administration are indicated during and
and by the effects of any diabetic complications that may be pres- after operation. As long as the patient is carefully monitored,
ent. There is also an increased risk of postoperative surgical site there is no evidence that high levels of HbA1c are associated with
infection (SSI). any increased risk of impaired glucose control or complications
after operation.
EVALUATION OF THE DIABETIC PATIENT
The other important laboratory study in diabetic patients is
measurement of serum creatinine levels (or, perhaps, creatinine
History and Physical Examination clearance) as an indicator of renal function. Renal insufficiency
In taking a preoperative history from a diabetic patient, atten- is a common complication of diabetes that may not be recog-
tion should be directed to any recent fluctuation in blood glu- nized during normal preoperative testing.
cose level as well as to the type of therapy used to control the
PREOPERATIVE MANAGEMENT
condition. The timing and dosage of medication should be con-
sidered, especially if the patient is taking long-acting insulin or
an oral hypoglycemic.The extent to which diabetes is controlled Metabolic Monitoring and Medications
in the perioperative period, which has a significant impact on All diabetic patients who are candidates for elective surgical
postoperative recovery, may be affected by certain medications procedures should undergo careful preoperative assessment,
(e.g., antihypertensive agents). The presence of diabetic compli- including metabolic monitoring. Ideally, glycemic control is
cations (e.g., atherosclerotic disease, diabetic nephropathy, and achieved before a diabetic patient is admitted to the hospital.
autonomic neuropathy) should be documented because these More realistically, however, admission may have to be scheduled
conditions may have serious effects during and after operation. for the day before the operation to allow time for optimizing
Medications used to control diabetes include the various forms metabolic control in all insulin-dependent patients as well as in
of insulin as well as oral hypoglycemic agents. The most com- non–insulin-dependent patients who have inadequate metabolic
monly used oral hypoglycemics are sulfonylurea, which acts by control. As a rule, target blood glucose levels before operation
stimulating insulin secretion, and metformin, which acts by should be less than 125 mg/dl (6.9 mmol/L) during fasting and
decreasing intestinal absorption. Patients should stop taking oral less than 180 mg/dl (10.0 mmol/L) postprandially. If emergency
hypoglycemics before major operations, and their blood glucose operation is required in patients with severe metabolic derange-
should be controlled with insulin if necessary. Because sudden ments (e.g., diabetic ketoacidosis or hyperosmolar nonketotic
discontinuance of sulfonylurea can lead to hypoglycemia, blood states), 6 to 8 hours of intensive treatment with insulin infusion

2. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice
8 Critical Car 10 Endocrine Problems — 2
Diabetic patient is undergoing Diabetic patient is scheduled mone) increase in nondiabetic as well as diabetic patients.
emergency procedure for elective procedure Increased secretion of these hormones in the setting of low
insulin levels stimulates hepatic production of glucose. In non-
Give insulin and glucose as Evaluate for cardiovascular and diabetic persons, major procedures are frequently associated
needed to control blood glucose, renal complications. with blood glucose levels of 150 to 200 mg/dl (8.3 to 11.1
ketoacidosis, and blood volume. Measure HbA1c to assess degree mmol/L). In diabetic persons, the metabolic abnormality varies
of glucose control (10%–20% according to the extent and duration of the surgical procedure
suggests poor control).
and the degree to which insulin secretion is impaired.
Give insulin and glucose as
needed to control blood glucose. A study in patients with stable type 1 (insulin-dependent) dia-
betes mellitus showed that blood glucose levels rose from about
180 mg/dl (10.0 mmol/L) to about 270 mg/dl (15.0 mmol/L)
postoperatively.3 Ketone body levels increased by about 100%,
as compared with levels in nondiabetic control subjects. Similar
During operation metabolic findings were reported even in patients with type 2
diabetes mellitus who underwent minor procedures that gener-
Monitor blood glucose. ated relatively little stress: blood glucose levels rose to 180 mg/dl
Give insulin and glucose as needed. (10.0 mmol/L), with higher than normal levels of ketone bodies
Consider potential effects of
and free fatty acids.4
diabetic complications.
Autonomic neuropathy can cause severe hypotension during
induction of anesthesia. Diabetic nephropathy complicates fluid
management and usually results in electrolyte abnormalities. All
diabetic patients are at high risk for postoperative myocardial
infarction, which is often asymptomatic. Poor nutrition and
After operation: diabetic patient After operation: nondiabetic impaired phagocytosis make diabetic patients more susceptible
patient with acquired glucose to infection and slower to heal.
Control blood glucose with intolerance
glucose and intermittent insulin. Insulin and Glucose Administration
If blood glucose is labile, give Suspect infection, the presence
insulin by continuous infusion. of necrotic tissue, or steroid use. Emergency procedures Diabetic patients may be more
If patient is on TPN, give no Control blood glucose with likely than nondiabetic patients to undergo emergency opera-
additional glucose. insulin. If patient is on TPN, give tion, which can cause rapid metabolic decompensation with
Consider possible postoperative no additional glucose.
dehydration, hyperglycemia, and ketoacidosis. In addition, a
SSI.
surgical emergency can precipitate uncontrolled diabetes in
Assess renal function, and
perform serial ECGs in patients
patients with no history of diabetes. Appropriate management
at risk for cardiac complications. depends, to a large extent, on the patient’s metabolic condition.
When one is faced with a so-called surgical abdomen, it is cru-
Figure 1 Shown is an algorithm outlining preoperative and cial to determine whether there is a metabolic abnormality that
postoperative management of the diabetic surgical patient. may be causing the condition. Given this possibility, it is sensi-
ble to manage the patient conservatively at first, with an empha-
sis on metabolic correction. If the underlying problem is in fact
and volume restoration usually improves their general condi- metabolic, it should resolve or improve in 3 to 4 hours; if the
tion. This brief period permits clarification of the diagnosis in problem is surgical, it should remain the same or worsen over
patients with acute abdominal pain, which may be the conse- this period.
quence of diabetic ketoacidosis rather than a so-called surgical
abdomen. Elective major procedures In a patient undergoing gen-
In preparing diabetic patients for operation, all long-acting eral anesthesia, regardless of the duration of the operation, infu-
insulins (i.e., Ultralente preparations) should be replaced with sion of insulin and glucose is recommended if the patient is tak-
intermediate-acting insulins (i.e., neutral protamine Hagedorn ing insulin for diabetes or is using drugs or diet therapy (or both)
[NPH] or Lente preparations). If the patient has type 2 (non– without achieving satisfactory control of type 2 diabetes mellitus.
insulin-dependent) diabetes mellitus, use of long-acting sulfony- Several methods of insulin administration may be used dur-
lureas (e.g., chlorpropamide and glyburide) should be stopped ing the perioperative period. Most of the protocols include I.V.
because of the risk of hypoglycemia; a short-acting preparation administration of short-acting insulin and 5% to 10% glucose.
should be substituted. Use of metformin should be stopped In some, glucose and insulin are administered together in a sin-
because of the risk of lactic acidosis when renal function is gle infusion.The advantage of this approach is that if the glucose
impaired, as it may be during any procedure requiring anesthe- infusion is accidentally disconnected or obstructed, the insulin
sia. Chronically hyperglycemic patients are frequently dehydrat- infusion is disconnected or obstructed as well, so that the risk of
ed, and this condition should be corrected before operation. hypoglycemia is eliminated. The disadvantage of this method is
that it is impossible to change the delivery rate of one agent
INTRAOPERATIVE MANAGEMENT
without changing the delivery rate of the other. Administration
of insulin and glucose in separate bags allows either infusion rate
Metabolic Effects of Operation and Anesthesia
to be adjusted without the other being affected.The insulin infu-
During anesthesia and operation, endogenous insulin secre- sion rate is progressively increased and the glucose infusion rate
tion is suppressed, but the plasma levels of counterregulatory progressively decreased in accordance with the capillary blood
hormones (glucagon, epinephrine, cortisol, and growth hor- glucose levels, measured hourly [see Table 1]. With this protocol,

3. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice
8 Critical Care 10 Endocrine Problems — 3
daily is recommended during the first 24 to 48 hours after cessa-
Table 1—Representative Protocol for tion of the insulin and glucose infusions and before resumption
of the patient’s usual insulin regimen.
Insulin-Glucose Infusion during Total parenteral nutrition (TPN) [see 8:22 Nutritional
the Perioperative Period Support], often required during the postoperative period, can
cause serious metabolic derangements in diabetic patients. For a
1. Infuse 5% dextrose in water (D5W) I.V. via pump.
diabetic patient receiving TPN, a variable insulin infusion sched-
2. Make insulin solution with 0.5 U/ml of short-acting insulin (i.e., ule [see Table 2] is recommended, with hourly determinations of
250 U of regular insulin in 500 ml of normal saline). Administer
in piggyback fashion via infusion pump into D5W infusion or blood glucose; however, additional glucose is not needed,
through a separate I.V. site. because it is included in the TPN solution. Initially, the insulin
3. After initiating glucose-insulin infusion, stop all subcutaneous should be given as a continuous infusion separate from the TPN
insulin therapy. solution. Once a stable dose of insulin is reached (usually within
4. Measure capillary blood glucose levels every hour. 24 to 48 hours), the total amount of insulin required over a 24-
hour period can be added to the TPN bag. This amount may be
5. On the basis of hourly blood glucose levels, adjust each infusion
according to the following schedule: high—often more than 100 units. At this point, capillary blood
glucose levels can be measured every 2 to 4 hours.
Insulin Infusion Hypoglycemia can be difficult to detect in critically ill
Blood Glucose D5W Infusion
(mg/dl) (ml/hr)
patients, in whom blood glucose levels are often elevated for any
(ml/hr) (U/hr) of a number of reasons. Accordingly, it has been common prac-
tice to accept blood glucose levels ranging from 150 to 200
< 70* 1.0 0.5 150
mg/dl in these patients. This practice, however, was called into
71–100 2.0 1.0 125
question by a 2001 randomized study of 1,548 ICU patients in
101–150 3.0 1.5 100
which liberal glucose control (blood glucose level, 180 to 200
151–200 4.0 2.0 100 mg/dl) was compared with tight control (blood glucose level, 80
201–250 6.0 3.0 100 to 110 mg/dl).5 ICU survival was significantly better in the tight
251–300 8.0 4.0 75 control group (95.4%) than in the liberal control group (92%).
> 300 12.0 6.0 50 In addition, the tight control group had a lower incidence of sys-
*Give 10 ml D5W I.V. and repeat blood glucose measurement 15 min later.
temic infection, had less need of antibiotic therapy, required
fewer transfusions, and were less subject to hypobilirubinemia.
These findings support the view that tight regulation of glucose
and insulin to maintain normal blood glucose levels is desirable
a blood glucose level in the range of 125 to 200 mg/dl (6.9 to in critically ill patients.
11.1 mmol/L) can easily be maintained throughout the periop-
erative period. Close observation of blood glucose levels and Cardiovascular and Renal Assessment
prompt adjustment of insulin and glucose delivery are mandato- Serial postoperative electrocardiograms are recommended for
ry for achieving a stable blood glucose level. Electrolyte supple- older diabetic patients, those with long-standing type 1 diabetes
mentation is administered via a separate infusion. mellitus, and those with known heart disease. Postoperative
myocardial infarction, which may be silent, is associated with a
Minor procedures Diabetic patients who fast before minor high mortality. Careful monitoring of blood urea nitrogen and
operations (e.g., endoscopic procedures and operations per- serum creatinine levels facilitates the detection of acute renal
formed with the patient under local anesthesia) should omit the
morning dose of insulin or oral hypoglycemic agent, and their
capillary blood glucose level should be measured every 2 to 4
hours. Supplemental subcutaneous short-acting insulin can be Table 2—Management of Diabetes in Patients
administered according to a variable insulin schedule, and the Undergoing Minor Surgical Procedures30
usual insulin or oral agent can be taken after the procedure [see
Table 2].This method of administration, which is associated with If patient fasted
unpredictable absorption and variable plasma insulin levels, is
1. Withhold morning dose of insulin or oral agent.
restricted to surgical patients undergoing minor procedures and
2. Measure capillary blood glucose level before procedure
should not be used in those undergoing major operations. and every 2–4 hr thereafter.
POSTOPERATIVE MANAGEMENT 3. Give short-acting insulin every 2–4 hr, as follows:
Insulin and Glucose Administration Blood Glucose (mg/dl) Short-Acting Insulin (U)
After minor procedures, diabetic patients should receive I.V.
< 150 0
glucose and insulin until their metabolic condition is stable and
151–200 2
oral feeding can be tolerated. To prevent ketosis, the insulin and
glucose infusions should be continued for at least 1 hour after the 201–250 3
administration of subcutaneous short-acting insulin. After major 251–300 5
procedures, patients should receive I.V. glucose and in- > 300 6
sulin until they are able to take solid food without difficulty. A
regimen consisting of multiple subcutaneous injections of short- 4. After procedure, give usual dose of insulin or oral agent.
acting insulin before meals and intermediate-acting insulin twice

4. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice
8 Critical Care 10 Endocrine Problems — 4
Adrenal Insufficiency
failure [see 8:6 Renal Failure]. If a contrast agent is used, the
patient should be well hydrated before and after the procedure. The anti-inflammatory properties of the glucocorticoid
steroids [see Table 3] are commonly exploited to treat disease.
Infection Patients are often treated for long periods with large pharmaco-
SSI is common in diabetic patients with poor metabolic con- logic doses of steroids (commonly, prednisone by mouth) for
trol. Impaired granulocyte function resulting from hyper- inflammatory or autoimmune diseases such as arthritis, systemic
glycemia may predispose to bacterial infections. Autonomic neu- lupus erythematosus, inflammatory bowel disease, and bronchial
ropathy, if present, may lead to difficulty in postoperative void- asthma. Primary failure of the hypothalamic-pituitary-adrenal
ing, which increases the risk of urinary tract infection. Poor (HPA) axis (as in Addison disease, Sheehan syndrome, and pan-
circulation as a result of macroangiopathy or microangiopathy hypopituitarism) is rare, but when it does occur, it must be treat-
can also contribute to the likelihood of postoperative infection. ed with long-term administration of physiologic doses of corti-
Tight metabolic control during the perioperative period can costeroids. It is not uncommon for patients who are receiving
decrease the risk of postoperative infection.When SSIs do occur such corticosteroid therapy to require operations, and this surgi-
in the diabetic population, they are usually caused by mixed cal population presents a unique perioperative management
flora, including aerobic and anaerobic organisms such as challenge [see Figure 2]. It is axiomatic that any patient treated
Escherichia coli, Enterobacteriaceae, various streptococci, with exogenous steroids may eventually manifest adrenal atro-
Staphylococcus aureus, and Bacteroides fragilis. Necrotizing infec- phy as a result of suppressed endogenous production of adreno-
tions (e.g., fasciitis, gangrene, and Fournier gangrene) are more corticotropic hormone (ACTH). Actual or relative adrenal
common and spread more readily in diabetic patients. insufficiency may occur during or after a major operation, result-
Surgical debridement and drainage, if needed, should be per- ing in a syndrome whose manifestations can range from nausea,
formed early. Cultures should be obtained during drainage pro- vomiting, fever, abdominal pain, and electrolyte abnormalities to
cedures. Ideally, antibiotic therapy awaits and is based on culture complete circulatory collapse.
results; however, in practice, it is often preferable to initiate The adrenal cortex is central to the maintenance of homeo-
empirical therapy for the most likely organisms before the results stasis both at rest and during stress.10 Cortisol, the predomi-
are available. Swarming of Proteus organisms may obscure other nant glucocorticoid hormone, is produced by the fascicular and
pathogens on culture plates. Unless the patient is clearly mani- reticular zones of the adrenal cortex. It is under the strict regula-
festing a septic response, aminoglycosides should be avoided tory control of both the hypothalamus (via corticotropin-releasing
because of their nephrotoxicity and the likelihood that diabetic hormone) and the anterior pituitary gland (via ACTH). Cortisol
patients may have underlying renal disease. If severe infections itself participates in its own regulation, imparting a potent nega-
do not respond to antibiotic therapy, the presence of Candida or tive feedback signal to both the hypothalamus and the ACTH-
other fungal species should be suspected. producing basophilic cells within the adenohypophysis of the pitu-
Many factors play a role in the increased susceptibility of dia- itary.Together, these components, which constitute the HPA axis,
betics to infection, including macroangiopathy, microangiopa- form a finely regulated feedback loop for cortisol secretion.
thy, neuropathy, impaired neutrophil and lymphocyte function, Under unstressed physiologic conditions, the adrenal cortex
increased capillary permeability, and impaired granulation and constitutively produces approximately 20 to 25 mg of cortisol
healing.6 An obvious example of this interaction of multiple con- daily.11 Cortisol secretion normally occurs in diurnal surges;
tributing factors is a chronically infected nonhealing ulcer on a consequently, simple measurements of serum cortisol levels in
neuropathic foot. A less obvious but more serious example is the isolation generally do not suffice for accurate evaluation of the
failure of host defenses against peritonitis, soft tissue infection, status of the HPA axis. Much of the daily variability in cortisol
and bacteremia that develops in diabetic patients. Chemotaxis, secretion can be tracked with 24-hour urinary measurements of
adherence, phagocytosis,7 bacterial killing, and production of the hydroxysteroid metabolites; however, there can be significant
cytokines and complement are all impaired in patients with type
1 diabetes mellitus. The greater prominence of such abnormali-
ties in patients with type 1 diabetes mellitus suggests that the Table 3 Selected Corticosteroid Preparations
most likely cause is related to chronic and irreversible glycosyla-
tion of many proteins, which limits the function of intracellular
Preparation Equivalent Glucocorticoid Mineralocorticoid
and intercellular messengers. The implication of this theory is Doses (mg) Activity* Activity*
that tight short- and long-term control of blood glucose should
allow better control of infection.5 Short-acting (8–12 hr)
The impaired wound healing seen in diabetic patients clearly is Hydrocortisone 20 1 1
related in part to increased susceptibility to infection; however, it Cortisone 25 0.80 0.80
is also observed with sterile wounds. Many animal studies have Intermediate-acting
corroborated the clinical observation that skin, fascia, and bone (12–36 hr)
all heal more slowly and with less strength in diabetic patients. Prednisone 5 4 0.80
Such studies have generally found that this impaired healing is Prednisolone 5 4 0.80
partially mitigated by insulin control, which suggests that glyco- Methylprednisolone 4 5 0
sylation of proteins is an important factor. A 1999 study indicat- Triamcinolone 4 5 0
ed that the impaired healing is significantly mediated by endoge- Long-acting (36–54 hr)
nous corticosteroids.8 Local application of inflammatory sub- Betamethasone 0.60 25 0
stances or growth factors (e.g., platelet-derived growth factor, Dexamethasone 0.75 30 0
Mineralocorticoid
tissue growth factor, bacterial by-products, growth hormone,
Fludrocortisone — 10 125
and hyperosmotic sugar) has been shown to stimulate healing in
diabetic animals.6,9 *Ranked on a scale rating hydrocortisone as 1.

5. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice
8 Critical Care 10 Endocrine Problems — 5
Patient with history of steroid therapy is undergoing operation
Perform history and physical examination, with particular attention to previous
adrenal insufficiency or hypopituitarism.
Determine extent of current or previous steroid use.
Reduce steroid dose to lowest possible level before elective procedure.
Patient is currently taking Patient previously received
exogenous steroids steroid therapy
Dosage < 10 mg/day Dosage ≥ 10 mg/day Steroid use < 3 mo ago Steroid use ≥ 3 mo ago
Continue current dosage; Treat as if patient is currently Assume HPA axis function
additional steroids are taking exogenous steroids is normal; additional
unnecessary. (left). steroids are unnecessary.
Procedure is minor Procedure is of moderate magnitude Procedure is major
Give scheduled dose plus 25 mg of Give scheduled dose plus 25 mg of Give scheduled dose plus 25 mg of
hydrocortisone before induction. hydrocortisone before induction, then hydrocortisone before induction, then
100 mg over next 24 hr. 100 mg/day for next 2–3 days.
After operation
Consider potential complications of long-term steroid use
(immunosuppression, poor wound healing, hypoglycemia).
Figure 2 Shown is an algorithm
Consider administering vitamin A if risk of SSI is significant.
outlining preoperative and postoper-
Consider possibility of previously unidentified cause of adrenal
ative care of the surgical patient at
insufficiency in ICU (e.g., emergency operation, trauma).
risk for adrenal insufficiency.
overlap between normal patients and those with clinical adrenal ulated cortisol levels above which the HPA axis can be assumed
insufficiency.12 Provocative testing of the HPA axis is based on to be intact, it has been suggested that a value higher than 600
the normal physiologic response of the adrenal gland to release mol/L at 30 minutes should be a sufficiently sensitive confirma-
cortisol in a receptor-mediated G-protein–coupled response to tion of an intact HPA axis.
circulating ACTH. Adrenal glucocorticoids are important modulators of the
Although there is some controversy regarding which laborato- stress response: they play a complex role in the metabolic path-
ry evaluation is the best predictor of adequate adrenal response ways for carbohydrates, fats, and proteins; modulate gluconeo-
to a surgical stress, it is clear that ACTH stimulatory testing is genesis and lipolysis; mediate insulin resistance; and exert a host
more sensitive and specific than unprovoked steroid measure- of well-documented effects on inflammation and wound healing.
ment alone. Hypoglycemia-induced release of ACTH in It is clear that physiologic stresses (e.g., burns, trauma, and iatro-
response to exogenous insulin infusion (the insulin tolerance genic tissue damage occurring during operations) result in an
test, or ITT) has long been considered the gold standard for ACTH-induced surge in the adrenal steroid response.16,17
determination of relative adrenal insufficiency, but various com- Serum measurements reveal that this response can produce cor-
plications, including discomfort, seizures, and even death, limit tisol elevations several times greater than those produced under
its clinical usefulness as a routinely applied test.13 In several stud- basal conditions. It is becoming apparent that although this
ies, strong correlations have been observed between the ITT and exaggerated adrenal stress response may have conferred a certain
adrenal stimulation with a synthetic corticotropin construct.14,15 evolutionary benefit, prolonged exposure to high doses of
In this test, the plasma cortisol response is measured 0, 30, and steroids may nonetheless have deleterious consequences. The
60 minutes after infusion of 250 µg of the ACTH analogue. potential complications of long-term or high-dose administra-
Although there is no unanimously accepted cutoff value for stim- tion of glucocorticoids are well described: they include hyper-

6. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice
8 Critical Care 10 Endocrine Problems — 6
tension, cataracts, myopathy (especially when glucocorticoids such as occur during surgery. Complete or even relative adrenal
are used in conjunction with nondepolarizing paralytic drugs), insufficiency is preventable; when it does occur, it can have disas-
osteonecrosis (particularly on the femoral head), impaired trous consequences if not recognized and appropriately treated.
wound healing, and immunosuppression.18 Exogenous administration of steroids in sufficient doses is gener-
It was the observed (and presumably physiologic) magnitude ally adequate to prevent the syndrome of adrenal insufficiency.
of the cortisol response to stress that led to the long-held—albeit The decision to administer supplemental perioperative steroids
never corroborated—assumption that supraphysiologic levels of should be based on the specific details of the history of steroid use
steroids were required to maintain homeostasis in the stressed as well as on the magnitude of the proposed operation.
environment. In the 1950s, two case reports were published that
described perioperative deaths thought to result from untreated
and unrecognized adrenal insufficiency.19,20 Thereafter, it Hormone Replacement
became common practice to supply supraphysiologic doses of Many surgical patients are receiving thyroid or ovarian hor-
exogenous steroids (i.e., doses two to three times that expected mone replacement therapy. In addition, the use of growth hor-
under basal conditions) to patients believed to be at risk for mone, growth hormone precursors, and anabolic steroids has
adrenal suppression and therefore unable to mount the expect- become more common in general practice. The effects of these
ed cortisol surge during operation. Subsequently, this practice hormone medications must be taken into account in any patient
came under scrutiny. Primary studies suggested that although undergoing an elective or emergency operation. Because all of
HPA suppression could occur as a result of long-term steroid these substances have long half-lives, replacement is not neces-
use, normal physiologic replacement doses were sufficient to sary for the first 2 weeks after operation; however, if the illness or
maintain perioperative homeostasis; supraphysiologic doses were the operation itself prevents oral intake for more than 2 weeks,
unnecessary.21 The concept that significantly lower doses of the possibility of hypothyroidism or estrogen depletion should be
steroids are required to maintain homeostasis and normotension considered. Postoperative weakness, lack of energy, depression,
in the perioperative period than was once believed has been sup- and sleeping disorders can all be caused by the lack of long-term
ported by prospective clinical studies in humans.22 hormone supplements.
It is clear that ACTH is not only stimulatory but also trophic Some patients exhibit decreased endogenous thyroid function
for the adrenal cortex. There is evidence that if the adrenal cor- after operation, either because their thyroid-stimulating hor-
tex is not exposed to ACTH, it is subject to hyposecretion and mone (TSH) levels are depressed as a consequence of long-term
anatomic atrophy. It was once thought that exposure to even low thyroid medication or because they experience complications
doses of steroids (< 10 mg of prednisone equivalent) was suffi- and become critically ill. Critical illness typically leads to
cient to suppress the endogenous release of ACTH and thus to reduced blood levels of triiodothyronine (T3) and thyroxine
result in a state of adrenal insufficiency. This belief led to the (T4). In addition, glucocorticoids, radiopaque dyes, propranolol,
common practice of administering so-called stress-dose steroids and amiodarone all lower plasma T4 levels,27 and dopamine
to surgical patients who had received exogenous steroids even in decreases TSH secretion directly.28 Most critically ill patients,
small doses or as long ago as 1 year before operation. Provocative however, do not exhibit metabolic or hemodynamic changes
studies on patients previously exposed to steroids demonstrated indicative of hypothyroidism. Measurement of TSH is helpful for
that the HPA axis usually remains intact despite either ongoing determining the significance of thyroid function in critically ill
exposure to small doses of exogenous steroids (< 10 mg of pred- patients. If the serum TSH level is lower than 5 µU/ml and the
nisone equivalent daily) or earlier steroid use (if the time since patient is not on high-dose dopamine therapy, thyroid function
discontinuance was longer than 2 to 3 months).23-26 is considered adequate regardless of other plasma markers. If the
In summary, the glucocorticoids are essential components of TSH level is higher than 20 µU/ml, replacement with thyroxine
human homeostasis both at rest and under stressful conditions is indicated.29
References
1. Root HF: Preoperative medical care of the dia- dence for a reaction between glucose and opso- assays: guidelines for the provision of clinical
betic patient. Postgrad Med 40:439, 1966 nizing proteins. J Clin Pathol 37:783, 1984 biochemistry service. Ann Clin Biochem 22:435,
2. Galloway JA, Shuman CR: Diabetes and 8. Bitar MS, Farook T, Wahid S, et al: Gluco- 1985
surgery: a study of 667 cases. Am J Med 34:177, corticoid dependent impairment of wound heal- 13. Jacobs HS, Nabarro JDN: Tests of hypothalam-
1963 ing in experimental diabetes: amelioration by ic-pituitary-adrenal function in man. Q J Med
3. Walts LF, Miller J, Davidson MB, et al: Peri- adrenalectomy and RU486. J Surg Res 82:234, 38:475, 1969
operative management of diabetes mellitus. 1999 14. Kehlet H, Binder C: Value of an ACTH test in
Anesthesiology 55:104, 1981 9. Qiu JG, Chang TH, Steinberg JJ, et al: Single assessing hypothalamic-pituitary-adrenocortical
4. Thompson J, Husband DJ, Thai AC, et al: Met- local installation of Staphylococcus aureus pepti- function in glucocorticoid-treated patients. BMJ
abolic changes in the non-insulin-dependent doglycan prevents diabetes impaired wound 2:147, 1973
diabetic undergoing minor surgery: effect of glu- healing. Wound Repair Regen 6:449, 1998 15. Clayton RN: Short Synacthen test versus insulin
cose-insulin-potassium infusion. Br J Surg 10. Orth DN, Kovacs WJ: The adrenal cortex. Wil- stress test for assessment of the hypothalamo-
73:301, 1986 liams Textbook of Endocrinology, 9th ed. Wil- pituitary-adrenal axis: controversy revisited. Clin
5. van den Berghe G, Wouters P, Weekers F, et al: son JD, Foster DW, Kronenberg HM, et al, Eds. Endocrinol 44:147, 1996
Intensive insulin therapy in critically ill patients. WB Saunders Co, Philadelphia, 1998, p 517 16. Chernow B, Alexander R, Smallridge RC, et al:
N Engl J Med 345:1359, 2001 11. White PC, Pescovitz OH, Cutler GB: Synthesis Hormonal responses to graded surgical stress.
6. Kamal K, Powell RJ, Sumpio BE: The pathobi- and metabolism of corticosteroids. Principles Arch Intern Med 147:1273, 1987
ology of diabetes mellitus: implications for sur- and Practice of Endocrinology and Metabolism, 17. Hume DM, Bell CC, Bartter F: Direct measure-
geons. J Am Coll Surg 183:271, 1996 2nd ed. Becker KL, Ed. JB Lippincott Co, Phil- ment of adrenal secretion during operative trau-
adelphia, 1995, p 647 ma and convalescence. Surgery 52:174, 1962
7. Davidson NJ, Snowden JM, Fletcher J: Defective
phagocytosis in insulin controlled diabetics: evi- 12. Moore A, Aitken R, Burke C, et al: Cortisol 18. Dujovne CA, Azarnoff DL: Clinical complica-

7. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice
8 Critical Care 10 Endocrine Problems — 7
tions of corticosteroid therapy: a selected review. steroid-treated patients undergoing major sur- receiving low-dose prednisone. Am J Med 95:
Med Clin North Am 57:1331, 1973 gery. Br J Anesth 53:949, 1981 258, 1993
19. Fraser CG, Preuss FS, Bigford WD: Adrenal 23. Bromberg JS, Baliga P, Cofer JB, et al: Stress 27. Wartofsky L, Burman KD: Alterations in thyroid
atrophy and irreversible shock associated with steroids are not required for patients receiving a function in patients with systemic illness: “the
cortisone therapy. JAMA 149:1542, 1952 renal allograft and undergoing operation. J Am euthyroid sick syndrome.” Endocr Rev 3:164,
20. Lewis L, Robinson RF,Yee J, et al: Fatal adrenal Coll Surg 180:532, 1995 1982
cortical insufficiency precipitated by surgery 24. Bromberg JS, Alfrey EJ, Barker CF, et al: Adrenal 28. Kaptein EM, Spencer CA, Kamiel MD, et al:
during prolonged continuous cortisone treat- suppression and steroid supplementation in renal Prolonged dopamine administration and thyroid
ment. Ann Intern Med 39:116, 1953 transplant recipients.Transplantation 51:385, 1991 hormone economy in normal and critically ill
21. Udelsman R, Ramp J, Gallucci WT, et al: 25. Livanou T, Ferriman D, James VHT: Recovery of subjects. J Clin Endocrinol Metab 51:387, 1980
Adaptation during surgical stress: a re-evaluation hypothalamo-pituitary adrenal function after 29. Burman KD: Thyroid hormones. Pharmacologic
of the role of glucocorticoids. J Clin Invest corticosteroid therapy. Lancet 2:856, 1967 Approach to the Critically Ill Patient. Chernow B,
77:1377, 1986 26. LaRochelle G, LaRochelle AG, Ratner RE, et al: Ed. Williams & Wilkins, Baltimore, 1983, chap 30
22. Symreng T, Karlberg BE, Kagedal B, et al: Recovery of the hypothalamic-pituitary-adrenal 30. Surgery: practical guidelines for diabetes man-
Physiological cortisol substitution of long-term (HPA) axis in patients with rheumatic diseases agement. Clin Diabetes 5:49, 1987