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10 - Endocrine Disorders |
267
not require pinching up of the skin. Although no
insulin pen devices are specifically promoted for
individuals who are visually impaired, patients
can be trained to use these devices successfully
if they are provided with appropriate opportuni-
ties to practice their use. A product called Count-
A-Dose attaches up to two vials of insulin and
uses a low-dose syringe (<50 units). The product
clicks with each unit of insulin withdrawn from the
vial and also allows for mixing different types of
insulin.
Adjunctive Medications
Other medications may be used as adjunctive
therapies, although they have not been well
studied in older adults. The primary goal of
adding these medications to existing regimens
is to control blood glucose with little or no hypo-
glycemia or other adverse effects.
16
Clinicians
should recognize that many older adults may
have a limited income; each additional medica-
tion should be evaluated for cost, ease of use,
adverse effects, and actual effects on glycemic
control.
Meglitinides, including repaglinide and
nateglinide, are similar to the sulfonylureas and
stimulate beta cells to increase insulin secre-
tion, although they bind to a different receptor.
These drugs have a shorter half-life than sulfo-
nylureas and should be dosed with meals.
22
The
primary benefit of the meglitinides is that the
risk of hypoglycemia is lower because patients
take the medication only if they are eating food
containing carbohydrates, and they may skip
doses if they are not eating.
10
Alpha-glucosidase inhibitors, such as acar-
bose and miglitol, slow polysaccharide absorp-
tion in the brush border of the small intestine.
Glucose absorption is delayed, thereby lowering
postprandial glucose concentrations; the HbA
1c
level is lowered by 0.5%. The medication should
be used cautiously in patients with serum creati-
nine >2 mg/dL even though <2% of the drug is
absorbed. The initial dosage of acarbose should
be 25 mg three times a day with the first bite of
each meal. If the patient forgets to take acarbose
with the first bite of the meal, he or she should
skip that dose. Increased gas and belching
occur in 25% to 45% of patients.
22
Patients who
become hypoglycemic while taking a combina-
tion of antidiabetic drugs that include acarbose
or miglitol should be advised to take glucose
tablets or skim milk, and not sucrose products
such as orange juice. This can be an important
counseling point in long-term care environments
where nursing protocols may include orange
juice as an intervention for hypoglycemia.
The GLP-1 agonists are produced by
the L-cells in the small intestine and enhance
glucose-stimulated insulin secretion. Exena-
tide and liraglutide are analogs of GLP-1 and
have a longer half-life than the naturally occur-
ring peptide.
21,32
Exenatide slows gastric motility
and suppresses the secretion of glucagon.
Although hypoglycemia does not occur, gastro-
intestinal symptoms such as nausea, vomiting,
and diarrhea may develop.
21,32
Patients taking
GLP-1 agonists may decrease their nausea
by ingesting smaller meals. The nausea from
GLP-1 agonists may also be due to previously
unrecognized diabetic gastroparesis. The initial
dosage of exenatide is 5 mcg injected subcu-
taneously twice daily and slowly titrated after a
month to a maximum of 10 mcg twice a day prior
to meals. The long-acting exenatide is dosed
2 mg once weekly and is dispensed in a recon-
stituted kit. This formulation requires multiple
steps and adequate hand strength to admin-
ister, which may be difficult in some older adults.
Although studies of exenatide have enrolled
older adults, its use in this patient group has not
been specifically evaluated. Liraglutide is dosed
0.6 mg subcutaneously once daily and may be
increased to 1.2 mg or 1.8 mg daily. The effects
of liraglutide on cardiovascular outcomes are
being evaluated in an ongoing trial.
33
The amylin agonist, pramlintide, is dosed
three times daily before meals in patients using
mealtime insulin. The drug inhibits glucose-
dependent glucagon secretion and slows
gastric emptying, ultimately lowering postpran-
dial glucose values.
21
Adverse effects include
nausea, anorexia, and weight loss. Severe
hypoglycemia may occur if the insulin dosage
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| Fundamentals of Geriatric Pharmacotherapy
is not halved when pramlintide is first started.
Pramlintide is usually dosed 60–120 mcg subcu-
taneously prior to meals in patients with type 2
diabetes.
The dipeptidyl peptidase-IV (DPP-IV)
enzyme rapidly breaks down GLP-1 and
glucose-dependent insulinotropic peptide (GIP).
Sitagliptin, saxagliptin, alogliptin, and linagliptin
are DPP-IV inhibitors which enhance the activity
of GLP and GIP.
21,34
Although well tolerated, the
HbA
1c
is only lowered by 0.6% to 0.9%. The
dosing of DPP-IV inhibitors in older adults is
the same as the usual adult dosing, although
alogliptin, sitagliptin, and saxagliptin require a
dosage reduction as the creatinine clearance
declines.
21,34
For example, sitagliptin is dosed
100 mg once daily, but if creatinine clearance
is between 30 to 50 mL/min, dosage should be
50 mg daily and <30 mL/min at 25 mg daily.
Hypoglycemia was three times lower in older
adults treated with DPP-IV inhibitors compared
to those receiving conventional oral antihypergly-
cemic agents.
35
Although not preferred drugs, colesevelam
and bromocriptine have a labeled indication
lowering blood glucose in type 2 diabetes. The
use of colesevelam in older adults may improve
lipid and glucose concentrations and with good
adherence might reduce the risk of acute MI
and stroke.
36,37
The most common adverse effect
of colesevelam is constipation, which can be
a concern in the elderly.
38
Bromocriptine may
reduce HbA
1c
by 0.5%.
38
Although the mecha-
nism of action is unknown, bromocriptine may
affect the circadian rhythm, subsequently helping
to reduce obesity and insulin resistance.
38
Older
adults should use the drug cautiously because
of potential drug interactions, symptomatic
hypertension, and an unknown effect of impaired
kidney function.
39
Sodium-glucose cotransporter 2 (SGLT2)
inhibitors such as canagliflozin work by inhib-
iting the reabsorption of glucose in the proximal
renal tubules. This lowers the renal threshold for
glucose, resulting in increased urinary excretion.
Canagliflozin is dosed 100 mg daily prior to the
first meal of the day and may be increased to
300 mg if the creatinine clearance is >60 mL/
min. Patients with renal impairment of 45 mL/
min to <60 mL/min should take a maximum of
100 mg daily; in the presence of a creatinine
clearance <45 mL/min, the drug should not be
used. Although well tolerated in some studies,
older adults are at higher risk of hypotension,
dizziness, urinary tract infection, and dehydra-
tion due to intravascular volume depletion from
canagliflozin.
40
Special Considerations in Older
Adults
Team Approach
Patients with diabetes should be managed
using an individualized team-based approach
that includes physicians, pharmacists, nurses,
and dietitians, among others. All patients
need education about their disease as well as
problem-solving skills to manage their diabetes
on a day-to-day basis. A patient’s age, activity
level, eating patterns and preferences, dental
issues, cultural and social factors, personality,
financial situation, eyesight, and other medical
conditions should be considered in developing
an individualized care plan. Collaboration
between the patient, family or other caregivers,
and health professionals is essential for optimal
care.
Comprehensive Care
Older adults with diabetes are a heterogeneous
group. Although some may have had diabetes
for several years with mild-to-severe microvas-
cular and macrovascular complications already
present, other individuals may have just been
diagnosed with diabetes and have no complica-
tions. According to the ADA
16
and the American
Geriatrics Society
6
clinical practice guidelines,
frail patients and patients who have complica-
tions that lead to shortened life expectancy
should have a less intensive HbA
1c
goal. Even
if the therapeutic plan does not include tight
control of blood glucose, other conditions should
be assessed independently from this deci-
sion. For example, aggressive treatment with
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10 - Endocrine Disorders |
269
moderate- to high-intensity statins in diabetes
patients age 40 to 75, or anticoagulation in atrial
fibrillation, may be appropriate even if the HbA
1c
target for a patient is 8%.
41
Another example is
control of hypertension, which has demonstrated
benefit in healthy older adults with diabetes. In
the Systolic Hypertension in the Elderly Program
trial, older persons with diabetes and isolated
systolic hypertension treated with antihyperten-
sive therapy had a significantly decreased risk of
coronary events compared to their nondiabetic
counterparts.
42
In addition, older persons often
have more disability because of their diabetic
complications, which may lead to depression in
patients over 55 with diabetes. Their depression
should be managed aggressively.
43
In managing diabetes in older adults,
the effect of concomitant diseases and drug
therapy, vision and hearing problems, poor
nutritional intake, and financial issues related to
medications and other diabetic supplies should
be carefully considered as well as cognitive
problems and depression. A frail older adult with
unrecognized cognitive impairment who is living
alone will have difficulty adhering to compli-
cated lifestyle interventions and complex drug
regimens. Also, adults age 18–44 with diabetes
have a 15% prevalence of blindness, whereas
27% of adults 75 and older with diabetes are
blind.
9
The management of diabetes requires
patients to have adequate vision and dexterity
to use devices such as an insulin syringe and a
glucometer for self-monitoring of blood glucose
concentrations. Drawing up insulin from a vial
requires adequate vision to accurately read the
markings on the syringe. Dexterity is also impor-
tant for insulin administration and blood glucose
monitoring, which requires fine motor skills and
dexterity to get test strips out of storage vials.
Even the simple act of recording blood glucose
concentrations in a logbook requires dexterity,
vision, adequate cognition, and other steps to
successfully accomplish the task.
A pharmacist can provide patient coun-
seling or assessment of self-administration abili-
ties as well as support caregivers who provide
insulin administration assistance. In the long-
term care setting, the consultant pharmacist’s
observance of an “insulin pass” by the nursing
staff is one way of providing ongoing quality
assurance regarding administration procedures.
Blood Glucose Monitoring
Self-monitoring of blood glucose is recommended
for all patients who have been prescribed an inten-
sive insulin regimen consisting of multiple injec-
tions per day.
16
In other patients, self-monitoring
of blood glucose is an important tool in managing
the disease. Although improved glycemic control
has not been consistently demonstrated in
studies, blood glucose monitoring in the older
adult might help to improve long-term outcomes
and prevent hypoglycemic reactions.
The preferred frequency and timing of
blood glucose measurements in older adults
is not known, so individual patients should be
assessed to evaluate their interest and abili-
ties. As the diabetes therapy intensifies, blood
glucose monitoring should also be increased,
either by the patient or a qualified caregiver.
Fasting blood glucose at pre-lunch, pre-dinner,
and pre-bedtime intervals can be checked. If a
patient is able to adhere to, or cooperate with, an
intensive monitoring schedule, this provides the
safest oversight of therapy outcomes. However,
depending on the situation there are many
instances in which more intensive monitoring is
not feasible. For instance, in the care of individ-
uals with dementia, finger stick monitoring can
be a source of significant agitation and distress.
In any circumstance where medication or insulin
management is deemed medically necessary
but a reduction in monitoring intensity is desired,
a pattern management approach is one strategy
that can achieve this while still yielding good
information about glucose control over time. For
example, once a reasonably predictable pattern
of blood glucose control is established using a
regimen of four assessments per day, this can be
divided in half by testing twice daily for 3 days in
the morning and pre-dinner, and then twice daily
for another 3 days before lunch and at bedtime.
Those patients with Medicare will be able to
obtain diabetes test strips if they are diagnosed
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270
| Fundamentals of Geriatric Pharmacotherapy
with diabetes. The amount that Medicare covers
will vary depending on whether the patient is on
insulin. Many third-party payers will only cover
300 test strips and lancets every 3 months for
patients who use insulin; noninsulin-dependent
patients can get 100 test strips and lancets every
3 months. Patients who are taking medications
that increase insulin secretion, such as sulfonyl-
ureas, meglitinides, or insulin, may require more
testing than patients receiving other therapies.
Frail older adults are at an increased risk of
severe hypoglycemia, and blood glucose moni-
toring by caregivers may reduce this risk.
44
Blood glucose monitors help to improve
a patient’s autonomy in his or her diabetes
management. All patients should be shown how
to use their glucose monitors and have routine
follow-up to ensure proper technique.
16
However,
the use of glucose monitors can be difficult for
patients who have cognitive or visual impair-
ment or dexterity problems. Blood glucose
monitors vary in size, amount of blood needed
for obtaining sample, visual acuity required to
perform the test, dexterity required to handle
test strips and supplies, and cognitive ability
required to accomplish a successful test. Some
glucose monitors are able to “talk” to patients to
assist them in testing their blood glucose (e.g.,
Prodigy
®
, GLUCOCARD Expression). Other
systems also help patients maintain indepen-
dence in their diabetes self-care.
For older patients with good vision, but
dexterity problems, several glucose meters can
be used. Test strips for glucose meters are small
and removing them from the vial to insert into the
meter can be difficult if the patient has arthritis
of the hands. Some glucose monitors have
cartridge or drum systems that contain several
test strips in a disk and allows for multiple tests to
be done (i.e., Accu-Chek Compact
®
). Coding the
meter, code keys, and setting meters can also be
difficult. Several meters do not require changing
codes or code keys, which allows patients to test
their blood glucose with fewer steps.
Ongoing self-management of diabetes is a
key component in the successful treatment of the
disease. Many older adults with diabetes, either
newly diagnosed or those with long-standing
disease, will have challenges in managing their
diabetes. Health professionals, particularly phar-
macists, must be aware of these barriers and be
able to offer potential strategies for overcoming
the specific challenges.
Prevention of Diabetes-Related
Complications
A primary goal in treating diabetes is to prevent
the long-term complications of cardiovascular
disease, nephropathy, retinopathy, neuropathy,
impaired wound healing, and dental disease.
The long-term complications may or may not
be relevant to a newly diagnosed older adult
with diabetes, given the patient’s predicted
life expectancy. Few large placebo-controlled
prospective studies of diabetes have enrolled
older adults. The United Kingdom Prospective
Diabetes Study (UKPDS) examined the effect of
different treatments on the chronic complications
from type 2 diabetes mellitus in patients 25 to 65
years old.
45
As a result, the findings from UKPDS
are difficult to apply to frail individuals in their 80s
or older.
The Action to Control Cardiovascular Risk
in Diabetes (ACCORD) trial randomized patients
between the ages of 40 and 79 into either inten-
sive glucose control (targeting HbA
1c
<6%) or
standard treatment (HbA
1c
7% to 7.9%).
17
The
mean age of participants was 62. The primary
and secondary outcomes of the ACCORD trial
were nonfatal MI, nonfatal stroke, death from
cardiovascular causes, or death from any cause.
Overall, the primary and secondary outcomes
were increased in patients receiving intensive
treatment compared to the group receiving stan-
dard therapy. The worst outcomes in the inten-
sive group may have been due to the rapidity
of the decrease in blood glucose concentra-
tions early in therapy.
17
Hypoglycemia requiring
medical assistance was three times higher in
the group receiving intensive versus standard
therapy.
17
A significant weight gain of 10 kilo-
grams occurred twice as frequently in the group
receiving intensive therapy.
17
Although older
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10 - Endocrine Disorders |
271
adults were enrolled in this study, few partici-
pants had common concomitant diseases, such
as heart failure, or were otherwise frail.
Participants in the Action in Diabetes and
Vascular Disease: Preterax and Diamicron in
Controlled Evaluation (ADVANCE) trial had a
mean age of 66 years and only included patients
over 55.
18
This study evaluated whether intensive
management of blood glucose versus standard
treatment decreased microvascular or macro-
vascular outcomes. Primary outcomes were
composites of macrovascular and microvas-
cular events, and secondary outcomes included
death from any cause, death from cardiovas-
cular causes, and major coronary events. The
outcome was not influenced by age.
Diabetic nephropathy is the leading cause
of end-stage kidney disease and is increased in
patients who have microalbuminuria. Several
trials have demonstrated the benefit of reducing
nephropathy in patients with type 2 diabetes.
46
The ADVANCE trial showed a 21% relative risk
reduction of nephropathy in patients intensively
managed using sulfonylureas and other medica-
tions; the average age of participants was 66.
18
The presence of microalbuminuria should be
tested in all patients at the time of diagnosis of
type 2 diabetes and annually thereafter.
6
An estimated 60% of patients with type
2 diabetes and proteinuria will also have reti-
nopathy. Patients with newly diagnosed type 2
diabetes should have a dilated eye exam imme-
diately and annually thereafter.
16
Older adults
with diabetes and nephropathy are also likely
to have dental disease and peripheral neurop-
athy. Appropriate dental care for older adults
with diabetes should include brushing teeth
twice daily and flossing every day. Patients with
diabetes should visit their dentist every 6 months
for routine scaling and check-up.
16
Note that
many older adults will not have insurance for
dental care, and in the nursing home setting,
appropriate dental monitoring may be difficult to
obtain.
Complications from neuropathies are
common in older adults and are often under-
treated.
6
Older adults should be assessed at
diabetes diagnosis and periodically thereafter.
They should be asked about pain, as well as
descriptive words to help assess the patient.
Some cultures may not use words such as pain,
but rather discomfort or “aching in legs.” Postural
hypotension from autonomic neuropathies and
weakness secondary to peripheral neuropa-
thies can lead to falls in older adults.
47
Although
low-dose tricyclic antidepressants, anticonvul-
sants, and other medications treat peripheral
neuropathies, adverse effects commonly occur
in older adults. Adverse effects may include
fatigue, urinary retention, dizziness, constipa-
tion, delirium, and confusion.
48
Treatment options
for peripheral neuropathy are discussed more
fully in Chapter 13.
Hypoglycemia
Hypoglycemia is a potentially dangerous
adverse effect in any patient with diabetes.
Although hypoglycemia is usually mild and
includes symptoms of shakiness, nervousness,
dizziness, sweating, weakness, and confusion, a
loss of consciousness may occur. Older adults
may lose the ability to feel certain symptoms of
hypoglycemia; they can be educated to recog-
nize symptoms such as sweating, weakness,
and fatigue. They or their caregivers should be
encouraged to test their blood glucose when
feeling these symptoms. Patients should also be
encouraged to wear medical identification and
carry glucose tablets or other 15-gram carbohy-
drate sources.
Cognitive impairment often prevents an indi-
vidual from being able to articulate symptoms of
hypoglycemia. In long-term care settings, regular
blood glucose monitoring should be coupled
with monitoring of dietary intake patterns. Facility
protocols should include orders for hypogly-
cemia interventions, including parameters
instructing the nursing staff when to react.
Most studies of diabetes and hypoglycemia
have excluded older adults. In one trial, severe
hypoglycemia requiring hospitalization was eval-
uated in patients over 80 with type 2 diabetes.
49
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| Fundamentals of Geriatric Pharmacotherapy
Most patients had several comorbid conditions
and the HbA
1c
averaged 5.1%, indicating very
tight control. Almost 75% of patients had been
prescribed glyburide, and only a few were regu-
larly self-monitoring blood glucose concentra-
tions. This study indicated that older adults who
are aggressively managed are likely to experi-
ence severe hypoglycemia requiring hospitaliza-
tion. Older patients who are taking medications
that can cause hypoglycemia should be closely
monitored and have their medication dosages
adjusted when the HbA
1c
is within target range.
49
Another trial examined the risk of sulfonyl-
ureas and insulin in causing severe hypogly-
cemia in older adults. Combining both treatment
groups, the incidence of severe hypoglycemia
was 2 per 100 person-years, which would indi-
cate a certain safety in treating older adults with
hypoglycemic agents. The patients who were
at a higher risk of developing severe hypogly-
cemia were the very elderly, patients who were
frequently admitted to the hospital, and those
patients with multiple medications.
50
If a patient
is likely to have hypoglycemia, he or she should
have a less stringent HbA
1c
goal of <8%.
Hyperosmolar Hyperglycemic
Nonketotic Syndrome
In contrast to diabetic ketoacidosis, which is more
common in type 1 diabetes, hyperosmolar hyper-
glycemic nonketotic syndrome (HHNS) is more
common in adults with type 2 diabetes and has
a peak incidence in the seventh decade of life.
Patients who develop HHNS have severe hyper-
glycemia and dehydration as well as increased
serum osmolality. Individuals who have dementia
are at the highest risk of developing HHNS.
51
Older patients presenting with HHNS often have
other acute conditions such as pneumonia,
pancreatitis, and cardiovascular events. They
may have had a severe osmotic diuresis, and
their dehydration is due to both extracellular and
intracellular water loss.
51
Fluid replacement can
be initiated with 0.9% NaCl until vital signs have
stabilized, and then switched to 0.45% NaCl. A
regular insulin bolus of 10–15 units followed by
continuous infusion of 0.1 unit/kg/hr should be
also initiated. Frequently patients who present
with HHNS may be managed on oral agents
when they are discharged from the hospital.
51
O
The prevalence of obesity in older adults has
been increasing, and data from 2007–2008 indi-
cate that 37.1% of men and 33.6% of women
60 and older were obese.
52
Body weight usually
peaks in middle age, stabilizes around ages 65
to 70, and then may decline slightly after age 70
until the end of life.
53,54
Age-related increases
in body fat may be due to a decrease in total
energy expenditure.
53,55
In addition, older adults
may experience a decrease in lean body mass,
some loss of height due to skeletal disorders,
and a decrease in total body water.
54
Although
BMI is used to indicate whether an individual
is overweight or obese, waist circumference
may be a better indicator of obesity in this age
group.
53,54
Benets of Weight Loss
Obesity is associated with poor quality of life,
chronic illness, functional disability, and loss of
independence.
53,54
Older adults who are obese
are at a greater risk of morbidity as well as osteo-
arthritis, obstructive sleep apnea, and cardiovas-
cular disease; also, frailty may be worsened.
53
Weight loss has the potential to improve these
conditions, lessen depression, and increase
quality of life.
54
The onset of type 2 diabetes in
obese individuals with impaired glucose toler-
ance may be delayed or prevented by weight
loss.
54,56
The Diabetes Prevention Program has
indicated that simply a 5% weight loss may
decrease the 5-year risk of developing diabetes
by more than 50%.
56
Weight loss is recom-
mended by the American Society for Nutrition
and the Obesity Society for older adults who are
obese and have risk factors such as functional
impairment and/or medical complications.
53
Longevity and quality of life for an individual
older adult should be considered when making
this decision.
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273
Risks of Weight Loss
Risks associated with weight loss include
decreased bone mineral density and increased
risk of osteoporosis and fractures. Increased
mortality, frailty, decreased muscle mass, and
vitamin deficiencies may also result.
52-54
Conse-
quently, older adults should discuss their weight
with a healthcare professional to create an appro-
priate weight-loss plan. In addition, concomitant
diseases and medications may have contributed
to obesity and should be assessed. For example,
patients taking insulin or sulfonylureas for type 2
diabetes may gain weight.
54
Uncontrolled or undi-
agnosed hypothyroidism may increase weight,
which may be treated with thyroid hormone,
although thyroid hormone would be an inappro-
priate obesity treatment in euthyroid patients.
57
KEY POINT:
Before beginning a
weight-loss program, older adults should
carefully consider the risks and benets.
Nonpharmacologic Options
A combination of caloric reduction (also called
energy restriction), exercise, and behavioral
therapy are best for safe and effective weight
loss in older adults. Behavioral therapy includes
self-monitoring, goal-setting, social support, and
stimulus control.
53
Although behavioral therapy
involves minimal risk and is effective for weight
loss, it remains underused. The 2003 U.S.
Preventive Services Task Force guidelines state
that all adults should be screened for obesity
and offered weight-loss counseling if obese. Yet
only 44.5% of adults ages 60–69 and 32.4% of
adults ages 70 and older who are obese reported
receiving weight-loss counseling.
52
Regular exercise has many potential
benefits. Flexibility and range of motion can be
improved, as well as concentration and ability
to manage stress. Independence may be main-
tained or increased, and endurance and func-
tional capacity may be improved.
55
A review of
14 randomized, controlled trials evaluated the
effects of energy restriction, energy restriction
plus aerobic training, energy restriction plus
resistance training, or energy restriction plus a
combination of aerobic training and resistance
training on body mass and body composition.
55
The trials ranged from 3 to 12 months in dura-
tion. The age range of participants was 51–70
years, and BMI range was 30.9–37 kg/m
2
. Some
studies showed positive results for cardiorespi-
ratory fitness and muscle strength, in addition to
decreases in body mass. The 12-month study
demonstrated that energy restriction decreased
body mass by 7.1 kg, and energy restriction plus
exercise decreased it by 8.9 kg. Energy restric-
tion was not found to prevent the age-related
decrease in lean body mass.
55
Bariatric surgery is an effective proce-
dural option, although the long-term benefits in
older adults are unclear. A review of random-
ized, controlled trials with adults 60 years and
older with a BMI of 30 kg/m
2
or greater found
that bariatric surgery was lacking evidence
of effectiveness.
52
The best candidates for
bariatric surgery include those individuals who
are morbidly obese (BMI 35.0–39.9 kg/m
2
) and
have at least one medical complication associ-
ated with obesity, such as heart failure, hyper-
tension, type 2 diabetes, or sleep apnea. In
addition, individuals with a BMI of 40 kg/m
2
and
a low probability of success with other weight-
loss options may be candidates.
53
Standard Adult erapy
Three medications have a labelled indication for
weight loss. These drugs include orlistat, lorca-
serin, and combination phentermine and topira-
mate. At present, the evidence supporting the
use of these drugs to treat obesity in older adults
is limited.
52,53
Orlistat is a reversible inhibitor of gastroin-
testinal lipase and is used in combination with
a reduced-calorie diet. Individuals taking orli-
stat are advised to reduce their fat intake to
30% or less of their total caloric intake. Most
studies of orlistat excluded older adults or did
not analyze results by age group if older adults
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| Fundamentals of Geriatric Pharmacotherapy
were included.
52
Orlistat may reduce the ability to
absorb fat-soluble vitamins. In addition, the drug
may cause fecal incontinence, for which many
older adults are already at risk because of age-
related changes in sphincter function.
53
Lorcaserin is a serotonin 2C receptor
agonist that is used as an adjunct to a reduced-
calorie diet and increased exercise. Unlike older
nonselective drugs in this class, lorcaserin has
not demonstrated valvular heart disease after
2 years of use.
56
Lorcaserin is indicated for
patients with a BMI of 30–45 kg/m
2
or a BMI
27–29.9 kg/m
2
with hypertension, dyslipidemia,
cardiovascular disease, impaired glucose toler-
ance, or sleep apnea. Data on its use in individ-
uals over 65 years are not available.
56
The effi-
cacy and safety of lorcaserin has been studied
in patients who have type 2 diabetes versus
placebo.
58
The average patient included was
52.7 years, female, white, had a BMI of 36 kg/
m
2
, and is taking metformin and a sulfonylurea.
Lorcaserin reduced body weight up to 5.5%, and
decreased HbA
1c
up to 1.9%.
58
Phentermine and topiramate extended
release is an adjunct to a reduced-calorie diet
and increased exercise. The combination has
been studied in patients age 18–70, although
<10% of patients were 65 or older and no patient
was older than 70.
59,60
Patients had a BMI of
27–45 kg/m
2
and two or more comorbid condi-
tions.
60
On average, patients were 51 years old,
female, white, with an average baseline weight
of 102 kg, a BMI of 36 kg/m
2
, an HbA
1c
of 5.9%,
and a history of hypertension and/or metabolic
syndrome.
59,60
Both studies demonstrated statis-
tically significant differences in the percentage of
patients who achieved a 5% and a 10% reduc-
tion in weight after 1 and 2 years of use.
59,60
Renal
dosing is used for patients with CrCl <50 mL/
min. Common adverse effects include insomnia
and paresthesias. A dose-related increase in
resting heart rate has been observed (>20 beats
per minute), although its clinical significance is
unclear.
KEY POINT:
Evidence for ecacy and
safety of weight-loss drugs in older adults
is limited. All agents should be used with
lifestyle changes to achieve the best results.
Evidence for Pharmacologic erapy
in Older Adults
Clinically significant changes in body weight
have been demonstrated in adults with drug
therapy used as an adjunct to lifestyle changes.
However, the newer drugs have not been exten-
sively studied in older adults. The long-term
effects of lorcaserin, as well as combination
phentermine and topiramate extended release
on cardiovascular morbidity and mortality are
unknown. Neither medication has been studied
in patients using concomitant insulin. Older
adults at high risk for cardiovascular morbidity
and mortality who have tried lifestyle changes
alone and were unable to achieve at least a 5%
reduction in weight loss may benefit from behav-
ioral therapy.
T D
Individuals with thyroid disease, including
hypothyroidism, hyperthyroidism, and thyroid-
itis, comprise about 7.35% of the population.
10
Thyroid diseases are common in older adults,
especially women. Despite their frequency,
thyroid diseases may be a challenge because
their presentation may differ from that in young
or middle-aged adults. The symptoms of hyper-
thyroidism and hypothyroidism in older adults
are easily misinterpreted as part of the aging
process and usually develop slowly over time.
Clinicians should routinely consider thyroid
diseases as a potential diagnosis in older adults.
For example, a patient with new-onset atrial fibril-
lation due to a thyroid disorder has no symptoms
from the arrhythmia, nor does the patient have
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10 - Endocrine Disorders |
275
other signs or symptoms of thyroid disease. In
addition, thyroid function tests may be altered
by nonthyroidal diseases in older adults. Finally,
recent NHANES III data demonstrated that the
97.5th percentile of serum TSH increases by
0.3 milli-international units per liter every 10
years after age 39. This increase is independent
of body weight, antithyroid antibody, and urinary
iodine excretion.
57
Etiology, Epidemiology, and
Clinical Presentation in Older
Adults
Hyperthyroidism
In the United States, the most common causes
of hyperthyroidism are Graves’ disease, uni- or
multinodular goiters, and toxic adenomas.
61-63
An estimated 10% to 15% of patients over 60
have hyperthyroidism.
61
Between 50% to 80%
of patients with hyperthyroidism have Graves’
disease caused by thyroid-stimulating anti-
bodies.
62
The peak incidence of hyperthyroidism
is in the second to fourth decade of life, although
hyperthyroidism including Graves’ disease
occurs in older adults as well. The prevalence of
multinodular goiter and toxic nodules as a cause
of hyperthyroidism is increased in older adults.
64
Women are at higher risk of Graves’ disease than
are men; however, older men have the highest
risk of severe ophthalmopathy from Graves’
disease.
63
Although some older adults will have the
classic symptoms of hyperthyroidism, such as
tremor, nervousness, increased appetite, heat
intolerance, and diarrhea, many will lack these
presenting complaints. Palpitations, angina,
and especially atrial fibrillation with a slow
ventricular response may be more common
presenting cardiovascular symptoms in older
adults.
62,63
Muscle wasting, especially of the
quadriceps muscle in the thigh, may be present
and increases the risk of falling in older adults.
64
One form of Graves’ disease, apathetic hyper-
thyroidism, is more common in older adults and
may actually present with symptoms of apathy,
weakness, lethargy, and severe depression,
which can make the diagnosis of thyroid storm
very difficult.
65
One report identified the presence
of apathy, tachycardia, or weight loss as strong
predictors of thyrotoxicosis in older adults.
65
Hypothyroidism
The incidence of hypothyroidism increases with
advancing age and is more common in women
than in men. An estimated 10% of women and
2% of men over 60 have hypothyroidism.
61
Hypo-
thyroidism is divided into primary (in which the
thyroid gland is unable to respond to stimula-
tion by thyroid-stimulating hormone [TSH]) or
secondary (due to a pituitary or hypothalamic
cause). The latter type is rare in older adults.
Hypothyroidism in older adults is frequently due
to autoimmune disease such as Hashimoto’s
thyroiditis or chronic autoimmune thyroiditis.
57,63,66
Hypothyroidism may also result from the treat-
ment of Graves’ disease, especially following
the use of radioactive iodine or thyroidectomy.
67
TSH should be measured every 6–12 months in
individuals treated with radioactive iodine as the
risk for hypothyroidism after its use remains 2%
to 3% per year after the first year. Drugs such
as amiodarone, lithium, interferon, propylthio-
uracil, and methimazole may also cause hypo-
thyroidism.
Many signs and symptoms of hypothy-
roidism are easily attributed to the aging process.
Older adults may present less frequently with
weight gain, cold intolerance, muscle cramps,
and paresthesias than younger adults with
hypothyroidism. Hypertension, hyperlipidemia,
bradycardia, as well as both pitting and nonpit-
ting edema may be attributed to comorbid
diseases and drug therapies. Most importantly,
neuropsychiatric symptoms, including depres-
sion and impaired cognition, may be present in
older adults with hypothyroidism. A recent cohort
study from the Framingham study indicated that
women who had TSH concentrations <1.0 milli-
international units per liter (lowest tertile) and
over 2.1 milli-international units per liter (highest
tertile) were at increased risk of Alzheimer
disease.
68
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276
| Fundamentals of Geriatric Pharmacotherapy
KEY POINT:
A TSH concentration
should be obtained to rule out potentially
reversible causes of dementia in older adults.
Subclinical Hypothyroidism
Subclinical hypothyroidism is a common thyroid
disorder with a prevalence of over 15% among
older women.
57,69
The serum TSH concentration
is elevated, although the free thyroxine (T4)
concentrations are within the normal range.
Individuals may have antithyroid antibodies,
suggesting an autoimmune basis for the condi-
tion. Patients may have a history of Graves’
disease and/or the prior use of lithium or an
iodine-containing medication such as amio-
darone. The likelihood of developing hypothy-
roidism may be 4% per year for women with
positive antibodies and elevated TSH based on
data from the Whickham survey.
57,69
Screening
for the development of clinical hypothyroidism is
recommended every 5 years. In general, if the
serum TSH concentration is >10 milli-units per
liter, levothyroxine is initiated whether or not the
patient is symptomatic.
69
For individuals who are
asymptomatic and who have serum TSH concen-
trations between 4 and 10 milliunits/L, monitoring
is generally recommended.
69
Although subclin-
ical hypothyroidism may be treated based on
symptoms and TSH concentrations, evidence is
lacking to support an association between mild
cognitive impairment and subclinical hypothy-
roidism in older adults.
KEY POINT:
Initiation and dosage
adjustment of levothyroxine should
be made based on assessment of T4
and TSH, rather than TSH alone, to
avoid inappropriate treatment.
Euthyroid Sick Syndrome
The euthyroid sick syndrome (ESS) has been
described as abnormal thyroid function tests
in patients with serious nonthyroidal diseases
such as gastrointestinal, pulmonary, renal, or
cardiovascular illnesses.
61,70
These patients
lack a prior history of hypothalamic, pituitary, or
thyroid disease. In general, serum T3 concen-
trations are low and the reverse T3 uptake is
elevated. Serum concentrations of T4 are usually
in the normal range and TSH may be slightly
decreased. In severe nonthyroidal illnesses
such as sepsis, concentrations of T3, T4, and
TSH may be reduced, with an elevated reverse
T3 uptake. Patients with ESS often have elevated
cortisol concentrations.
61
After recovering from
the illness, thyroid function tests return to base-
line values. Whether the nonthyroidal disease is
causing an artificial effect on the thyroid func-
tion tests or whether it reflects a true change
in thyroid functioning is unknown. Although
advancing age is not necessarily a risk factor for
ESS, older adults have an increased prevalence
due to the greater risk of having multiple chronic
diseases. The primary treatment is focused on
managing the underlying illness and monitoring
thyroid function tests during and after recovery.
Summary of Standard Treatment
The recommended treatment for hyperthy-
roidism consists of the use of antithyroid drugs,
radioactive iodine (I-131), or thyroidectomy.
63,71
The antithyroid drugs, propylthiouracil and
methimazole, inhibit thyroid peroxidase and the
resulting synthesis of thyroid hormone. Propyl-
thiouracil also inhibits the peripheral conversion
of thyroxine (T4) to triiodothyronine (T3), so that
symptoms may resolve more quickly.
71
Methima-
zole has a longer half-life that permits once-daily
dosing of the drug compared to propylthio-
uracil, which requires multiple daily doses. In a
comparative study of once-daily methimazole
and once-daily propylthiouracil, methimazole
induced euthyroidism more quickly than propyl-
thiouracil.
67
Therapy with antithyroid drugs is
continued for 6 to 18 months.
71
The use of I-131
results in radiation-induced destruction of the
thyroid gland, while thyroidectomy removes all
or part of the thyroid gland. Adjunctive therapy
includes beta-adrenergic blockers to control
the tachycardia, tremor, and other symptoms of
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