Pharmacotherapy

in
Endocrine System

dr. R. Setiadji, M.Sc

 2

Contents
Penyakit di SKDI dengan level kompetensi 3-4Slide 3
DMT 2, DMT1, Hipoglikemia, Ketoasidosis, hiperosmolar non
ketotikDM Type 2
Hyperthyroidisme
Obesitas
Dislipidemia
 3

1 Diabetes melitus tipe 1 4A

2 Diabetes melitus tipe 2 4A

3 Diabetes melitus tipe lain (intoleransi 3A

glukosa akibat penyakit lain atau obat-
obatan)
4 Ketoasidosis diabetikum 3B

5 Hiperglikemi hiperosmolar non ketotik 3B

 4

6 Hipoglikemia ringan 4A

7 Hipoglikemia berat 3B

8 Diabetes insipidus 1

9 Akromegali, gigantisme 1

10 Defisiensi hormon pertumbuhan 1

 5

11 Hiperparatiroid 1

12 Hipoparatiroid 3A

13 Hipertiroid 3A

14 Tirotoksikosis 3B

15 Hipotiroid 2
 6

16 Goiter 3A

17 Tiroiditis 2

18 Cushing's disease 3B

19 Krisis adrenal 3B

20 Addison's disease 1
 7

21 Pubertas prekoks 2
22 Hipogonadisme 2
23 Prolaktinemia 1
24 Adenoma tiroid 2
25 Karsinoma tiroid 2
 8

26 Malnutrisi energi-protein 4A
27 Defisiensi vitamin 4A
28 Defisiensi mineral 4A
29 Dislipidemia 4A
30 Porfiria 1
31 Hiperurisemia 4A
32 Obesitas 4A

Back
DM Type 2
 10

Key points
Diabetes mellitus type 2 is a chronic metabolic
disorder characterized by relative resistance to
insulin and dysfunction of the -cells in the
pancreatic islets of Langerhans
Onset is slow and insidious; the disease tends to
present in middle-aged and elderly adults but may
occur at any age
Patients can present with thirst, polyuria, and
lethargy; symptoms due to complications; or
incidental findings of glycosuria or elevated blood
glucose
 11

Key points
Ketosis can occur but is uncommon in patients with type 2
diabetes; it may occur late in the disease when significant
-cell depletion or exhaustion has occurred
Management always includes dietary modification and
regular exercise, usually in conjunction with oral
hypoglycemic drugs; insulin may be required for adequate
glucose control
The natural course of the disease is progressive
deterioration of glucose control with the development of
microvascular and macrovascular complications
 12

Diagnosis
Random plasma glucose level greater than or
equal to 200 mg/dL (11.1 mmol/L) with symptoms
of hyperglycemia
Fasting plasma glucose level greater than or equal
to 126 mg/dL (7.0 mmol/L)
Plasma glucose level greater than or equal to 200
mg/dL (11.1 mmol/L) 2 hours after a 75-g
anhydrous glucose load in an oral glucose
tolerance test
HbA1c greater than or equal to 6.5%
 13

Overall goals for the treatment of

diabetes mellitus
Alleviate symptoms
Enhance quality of life
Minimize the development of long-term
complications
Reduce early mortality
 14

To reduce the risk of complications and delay the

rate of progression of complications
Good glycemic control
Good control of blood pressure
Lipid lowering
Prevention and treatment of complications of
diabetes
Lifestyle changes, such as smoking cessation,
weight control, and dietary modification
 15

Immediate action
In patients with severely elevated serum glucose
levels or impending diabetic ketoacidosis or
nonketotic hyperosmolar state, initiate urgent
insulin and fluid therapy in an inpatient setting
Urgent admission to the hospital may be
required
 16

Immediate action
In patients with hypoglycemia who are receiving insulin or
sulfonylurea therapy:
Administer rapidly absorbed carbohydrate ( eg , glucose tablets, glucose drink,
orange juice, or cola) if the patient is alert and able to swallow without the risk of
aspiration
Administer glucagon, 1 mg subcutaneously, if the patient is obtunded or
unresponsive. This requires administration by a friend, relative, or emergency
personnel. It is important to note that glucagon will only increase blood glucose for
approximately 45 minutes, so additional treatment is needed
Consider administering 50% dextrose, 25 to 50 mL intravenously, for severe
hypoglycemia when the patient is under medical care and venous access can be
obtained
Monitor glucose level and patient status carefully following treatment in order to
prevent further hypoglycemia, and change the patient's diabetes treatment regimen
if warranted
Determine the cause of the hypoglycemic episode
Urgent admission to the hospital may be required
 17

Summary of therapies
Lifestyle modifications, including patient education
, dietary modification , and a physical activity
program , should be initiated immediately and
continued and/or intensified throughout therapy
Current guidelines now recommend that drug
therapy be initiated in all patients as soon as the
diagnosis of diabetes is established to prevent the
deterioration of glycemic control
 18

Summary of therapies

Guidelines of the American Association of Clinical

Endocrinologists aim for an HbA1c of up to 6.5%.
The American Diabetes Association, in concert
with the European Association for the Study of
Diabetes, has published guidelines that aim for an
HbA1c of up to 7.0%. Both guidelines include the
roles of newer therapies and address data from
recent trials
 19

ADAGuidelines
In addition to lifestyle modification, initiate metformin in all
patients immediately, provided there are no
contraindications, to achieve (in most patients) a target
HbA1c lower than 7.0%
If the HbA1c target is not achieved within 3 months,
consider two-drug therapy by adding to metformin one of
the following: a sulfonylurea , a thiazolidinedione , a
dipeptidyl peptidase4 (DPP-4) inhibitor , a glucagon-like
peptide-1 (GLP-1) receptor agonist , or an insulin (usually
basal)
 20

ADAGuidelines
If the HbA1c target is not achieved within an additional 3
months, consider three-drug therapy by adding one of the
following to the regimen: a sulfonylurea, a
thiazolidinedione, a DPP-4 inhibitor, a GLP-1 receptor
agonist or an insulin (usually basal)
If combination therapy that includes basal insulin fails to
achieve target levels of HbA1c after 3 to 6 months, proceed
to more complex insulin therapy ( eg , multiple daily doses)
with one or two non-insulin agents
Insulin is likely to be more effective than other agents as a
third-line therapy when HbA1c is >9%
Progression to complex insulin therapy from a two-drug
regimen may be justified in patients with HbA1c >10%
 21

Metformin
Metformin is used for initial treatment of diabetes
mellitus type 2
Dose information
Immediate-release formulation: 500 mg orally,
twice a day initially; increase by 500 mg/d at
weekly intervals
Maintenance: 500 to 850 mg orally two or three
times a day
Maximum: 2,000 mg/d
Slow release formulation can be given once daily
 22

Metformin Major contraindications

Diabetic ketoacidosis
Metabolic acidosis
Radiographic contrast administration
Renal disease
Renal failure
Renal impairment
 23

Metformin
Comments
Dose selection in the elderly should be cautious,
usually starting at the low end of the dosing range.
This reflects the greater frequency of decreased
hepatic, renal, or cardiac function and concomitant
diseases and medications
 24

Metformin Evidence
A systematic review of 29 trials involving over
5,000 patients compared metformin monotherapy
versus placebo and a variety of other agents and
found that metformin improved glycemic control,
weight, dyslipidemia, and diastolic blood pressure.
[10] Level of evidence: 1
 25

Metformin Evidence
Metformin has the clinical benefit of not producing
marked weight gain, but it is associated with some
harms, including the rare but serious effect of lactic
acidosis. However, a systematic review of 347
RCTs incorporating the experience of about
120,000 patients found no evidence from
prospective comparative trials or from
observational cohort studies that metformin is
associated with an increased risk of lactic acidosis
as compared to other oral hypoglycemic agents
evaluated in RCTs. [11] Level of evidence: 1
 26

Metformin Evidence
An RCT of 451 patients found that patients with
type 2 diabetes taking metformin regularly
experienced reductions in HbA1c versus those
receiving placebo. [12] Level of evidence: 1
Another RCT, this one including 96 patients, found
both acarbose and metformin equally effective in
comparison to placebo with respect to a reduction
in HbA1c. [13] Level of evidence: 3
Hypoglycemia
 28

Hypoglycemia
Hypoglycemia is defined as a serum glucose levels
below normal, typically <54mg/dL (<2.5mmol/L)
and concurrent with the patient's symptoms
Symptoms caused by hypoglycemia are
associated with increased autonomic nervous
system activity (adrenergic and cholinergic
symptoms), and include anxiety, tremulousness,
palpitation, sweating, nausea, and hunger
 29

Hypoglycemia
Severe hypoglycemia is commonly associated with
symptoms of compromised central nervous system
function because of brain glucose deprivation
(neuroglycopenic symptoms)
Neuroglycopenic symptoms include weakness,
fatigue, confusion, seizures, focal neurologic
deficit, and coma
 30

Hypoglycemia
Hypoglycemia occurs most frequently in patients
being treated for diabetes, but also occurs with
excessive alcohol intake, some medications,
excess insulin secretion, and a variety of metabolic
and hormonal abnormalities
Symptoms of hypoglycemia resolve rapidly after
restoration of normal serum glucose levels
 31

Immediate action
Administration of glucose, with the goal of attaining
a serum glucose level >54mg/dL (>2.5mmol/L)
If the patient has a normal level of consciousness,
oral glucose can usually be given.
In patients who are unable to take oral glucose due
to a decreased level of consciousness and/or
because of nausea, glucose can be given
intravenously
Glucagon may be administered by family members
of diabetic patients who develop hypoglycemia, but
it is not typically given in the healthcare setting
 32

Key points
Hypoglycemia may be due to disorders that cause excess
insulin production, decreased insulin clearance, or
decreased glucose production
The most common cause of hypoglycemia is iatrogenic
hypoglycemia due to therapy for diabetes
Treatment is with glucose administration as well as
management of the underlying cause of the
hypoglycemia
Treatment should not be delayed for diagnostic
studies, as severe hypoglycemia can progress to
stupor, coma, and death
 33

Diabetic Ketoacidosis and

Hyperosmolar Nonketotic Coma
34
 35

Description
Life-threatening complication of diabetes mellitus
Requires urgent inpatient treatment
Severe electrolyte imbalance with dehydration
Severe insulin shortage
May be the initial presenting feature of diabetes mellitus
Mainly occurs in patients with type 1 diabetes mellitus but
can occur in patients with type 2 diabetes mellitus
Look for underlying infections and other precipitating
factors
36
 37

Immediate action

the role of the primary care physician is to arrange

immediate and rapid transfer to a hospital
and not to initiate treatment, which is unsafe and
difficult to titrate without close biochemical
monitoring
 38

Immediate action

In remote areas where transfer times to units able

to monitor acid and electrolyte balance are
significant, fluid and insulin replacement may be
cautiously commenced in transit.
Careful monitoring for fluid overload is essential.
Physicians should be very familiar with the
management of patients with DKA
because there is a significant risk of rapid
electrolyte shifts and cerebral edema if fluids and
insulin are administered too rapidly
 39

Immediate action

Initial fluid replacement should be with 0.9%

normal saline.
In adults:
The usual rate of fluid infusion is 500 to
1,000 mL in the first hour followed by 300 to
500 mL/h until arrival at the hospital. Err on
the side of caution if in doubt
 40

Immediate action

Traditionally, the insulin infusion rate is a

bolus loading dose of 0.1 U/kg followed by a
constant infusion of 0.1 U/kg/h until arrival at
the hospital. However, recent data suggest
that a priming bolus dose is not required if
the initial infusion rate is 0.14 U/kg/h
 41

Immediate action
If continuous intravenous insulin
administration is not possible, subcutaneous
or intramuscular administration of a short-
acting or rapid-acting insulin analog ( eg ,
insulin lispro or insulin aspart) every 1 to 2
hours is safe and may be as effective as
intravenous insulin. Administer an initial
subcutaneous dose of 0.3 U/kg followed by
0.1 U/kg every hour until the serum glucose
level is <250 mg/dL; then administer half of
the initial subcutaneous insulin dose (0.05
U/kg) every hour until DKA has resolved
 42

Immediate action

Patients with severe DKA or DKA and

concomitant hypotension, anasarca, or
severe critical illness should be managed
with intravenous regular insulin in the ICU;
the subcutaneous insulin protocol should be
reserved for patients with mild DKA and
when there is a nursing protocol in place to
provide the frequent care required by such
protocols
 43

Immediate action

Potassium replacement is usually not

necessary during the first hour because of
potassium movement out of cells due to
metabolic acidosis
 44

Immediate action
Potassium replacement is later titrated against
serum potassium. If this is not possible during
very prolonged transfer times from rural areas,
potassium replacement may be started when
there is no electrocardiographic evidence of
hyperkalemia (tall-peaked T waves,
decreased or absent P waves, short QT
interval, widened QRS complex), and urine
output is established. In patients with normal
renal function, potassium chloride, 20 to 40
mEq/L, may be added to the intravenous
fluids
 45

Immediate action

Bicarbonate is not routinely used because it

can worsen hypokalemia and intracellular
acidosis and cause cerebral edema. Its use
is confined to the ICU in instances in which
the pH is very low ( ie , <6.9)
 46

Immediate action

Although patients with DKA are phosphate

depleted, phosphate repletion is not
generally recommended, based on the
results of randomized, controlled trials.
Phosphate repletion should be reserved for
patients with extreme phosphate deficiency
(levels <1.0 mg/dL) and/or significant
cardiac or respiratory compromise. In this
situation, phosphate can be repleted with
the addition of sodium phosphate to the
replacement fluids
Hyperthyroidism

R. Setiadji
 48

Key points

Hyperthyroidism, the presence of excessive thyroid hormone produced

by the thyroid gland, is usually caused by Graves disease, toxic
multinodular goiter, toxic uninodular goiter, and thyroiditis
Diagnosis involves testing to assess levels of thyroid-stimulating
hormone (TSH) and thyroid function
Treatment is aimed at relieving symptoms and restoring metabolic
function
Take immediate action in patients with thyroid storm, a life-threatening
condition characterized by exaggerated signs and symptoms of
hyperthyroidism, including fever, arrhythmia, and altered mental status.
It is usually precipitated by concurrent illness or injury but also occurs
following withdrawal of antithyroid medications
 49

Description
Hyperthyroidism refers to conditions caused by excessive thyroid
hormone produced by thyroid gland
Most common causes of hyperthyroidism are Graves disease, toxic
multinodular goiter, toxic uninodular goiter, and thyroiditis
Less common causes of hyperthyroidism are thyroid-stimulating
hormone (TSH)-producing tumors, pituitary resistance to thyroid
hormone, trophoblastic disease, and iodine ingestion
Signs and symptoms generally result from stimulation of adrenergic
nervous system
Overt hyperthyroidism is defined as low serum TSH with elevated
peripheral thyroid hormone values (free T3and/or free T4), while
subclinical hyperthyroidism is defined as low serum TSH with normal
peripheral thyroid hormone values
 50

Common causes:
Toxic diffuse goiter or Graves disease (most
common cause): an autoimmune disease in which
thyroid gland is being stimulated by thyrotropin
receptor antibodies, also known as thyroid-
stimulating immunoglobulin
Toxic multinodular goiter: multiple areas in thyroid
gland overproduce thyroid hormone independently
of TSH
Toxic uninodular goiter (adenoma): solitary nodule
in thyroid gland overproducing thyroid hormone
independently of TSH
 51

Common causes:
Subacute thyroiditis : usually idiopathic but sometimes can
be result of virally mediated inflammation and destruction of
thyroid gland. Consequently, stored thyroid hormones are
released into circulation, causing transient thyrotoxic state
and thyroid pain
Postpartum or sporadic thyroiditis: painless autoimmune
inflammation of thyroid gland, in which stored thyroid
hormones are released into circulation, causing a transient
thyrotoxic state
Amiodarone-induced (types I and II): Type I is iodine-
induced, while Type II is type of thyroiditis
Iatrogenic or factitious thyrotoxicosis: due to intentional or
inadvertent ingestion of exogenous thyroid hormone
 52

Risk factors
Positive family history of hyperthyroid condition
Gender: females predisposed to hyperthyroid
condition
Other autoimmune disorders
Iodide repletion after deprivation
 53

Symptoms

Nervousness Increase in appetite

Sweating Increased frequency of
Sensitivity to heat bowel movement, or
diarrhea
Fatigue
Oligomenorrhea or
Eye irritation amenorrhea
Palpitations Swelling in legs
Dyspnea
 54

Signs
Tachycardia
Fever
Weight loss (although weight gain can occur in up
to one third of patients due to increased appetite)
Warm, moist skin
Tremor and hyperreflexia
Eye signs (erythema, lid retraction, stare)
Exophthalmos (Graves disease)
 55

Signs
Goiter
Bruit over thyroid (Graves disease)
Tenderness of thyroid gland (subacute thyroiditis)
Gynecomastia
Splenomegaly
Gynecomastia
Thyroid acropachy (Graves disease)
 56

Examination
Note appearance of toxicity or confusion. Consider thyroid
storm
Assess vital signs, including weight. Patients will usually be
tachycardic at rest, and there may be orthostasis
secondary to decreased intravascular volume
Examine hands for warmth and fine tremor
Check eyes for erythema, stare, lid lag, and proptosis.
Comparison of a photograph from the past with patient's
current appearance can bring out subtle changes in
proptosis
 57

Examination
Inspect neck for goiter, thyroid nodules, lymphadenopathy,
asymmetry, and thyroid bruit
Perform cardiac exam to check for arrhythmia and for
cardiac bruit, which may have resulted from long-standing
hyperthyroidism and high-output failure
Inspect muscle strength and reflexes, especially proximal
muscle weakness. Have patient squat; usually he/she has
difficulty standing back up
Patients will have brisk reflexes with rapid relaxation phase
and may even exhibit clonus
 58

Diagnostic testing

High-sensitivity thyroid-stimulating hormone (TSH) is the best single

screen for hyperthyroidism. Normal test rules out all sources of
thyrotoxicosis except those from excess TSH
Peripheral thyroid function tests : Free T4is preferred as lead thyroid
function test after TSH. Regular T4and T3resin uptake are alternatives
to assess level of circulating T4levels. Useful to assess severity and
follow therapy
T3radioimmunoassay or free T3: Occasionally a thyroid gland will
produce excess of T3rather than T4. Useful if T4is normal but patient is
clinically hyperthyroid. May also be useful in assessing severity and
monitoring therapy
Radioiodine uptake measures avidity with which thyroid gland is
absorbing iodine. High or normal in cases of hyperthyroidism from
Graves disease or toxic nodular goiter but low or absent in thyroiditis
 59

Diagnostic testing

Thyroid scan can be done with either 123-iodine or 99-technetium and

identifies areas in thyroid gland that are taking up iodine. Useful in
evaluating palpable nodules in thyroid gland to tell if they are
functioning and in differentiating Graves disease from toxic nodular
goiter
Thyroperoxidase antibodies are usually elevated in Graves disease and
often in autoimmune thyroiditis and may help to differentiate between
autoimmune and non-autoimmune causes of hyperthyroidism
Testing for thyrotropin receptor autoantibodies is useful in the pregnant
Graves patient to assess likelihood that newborn will have
hyperthyroidism
Erythrocyte sedimentation rate (ESR) is elevated in subacute thyroiditis
 60

Immediate action
Thyroid storm is a life-threatening condition which
can be precipitated by general anesthesia or
serious infection and needs swift attention and
aggressive therapy.
Treat any concurrent illness, but also start several
measures to control thyroid dysfunction
Thyroid storm is treated with a regimen that
includes -blocker, thioureylene, glucocorticoids,
and iodine solution
 61

Treatment

Goals for treatment are to alleviate signs and

symptoms, return metabolism to normal state, and
prevent long-term complications
 62

Treatment
Radioactive 131-iodine is very effective at ablating
hyperthyroidism. Frequently used except in
children and pregnant women. Achieves
permanent cure of hyperthyroidism and has lower
costs and complications when compared to
surgery. However, there is risk of permanent
hypothyroidism and thyroiditis, as well as usual
risks associated with radiation
 63

Treatment

Thioureylenes are antithyroid medications that

inhibit thyroid hormone biosynthesis. They offer
patients a chance of permanent remission;
advantages include low cost and no risk of
permanent hypothyroidism. May be used as
monotherapy in patients with mild disease or to
treat symptoms before patients are treated with
radioactive iodine or surgery. Remember that both
thioureylenes and 131-iodine are effective only in
patients producing excess thyroid hormone ( eg ,
Graves disease) but not in those with thyroiditis
 64

Treatment

Subtotal or total thyroidectomy is rarely treatment of first

choice. May be recommended in young children, pregnant
women who have had adverse reaction to
pharmacotherapy, patients with compressive symptoms,
those in whom there is concern about possibility of thyroid
cancer, and when rapid control of hyperthyroidism is
needed or avoidance of exacerbation of symptoms is
required ( ie , cardiac patients). Like radioactive iodine,
there is risk of permanent hypothyroidism and severe
adverse effects; cost may also be an issue with surgery.
Surgery may be more effective in treating Graves
ophthalmopathy than other treatment modalities
 65

Treatment

Treatment with alternative agents, such as lithium,

potassium perchlorate, iodine ipodate and
cholestyramine may be considered in certain
circumstances as adjunctive treatment or in
patients intolerant to thioureylenes but are not
commonly used
 66

Treatment

-blockers are used to reduce adrenergic

manifestations of hyperthyroidism and may be
used concomitantly with antithyroid therapies.
Propranolol is often considered -blocker of choice
since it is thought to have additional benefit of
blocking peripheral conversion of T4to T3. Atenolol
is also sometimes used
 67

Treatment

Calcium-channel blockers are rarely used (unless

-blockers are contraindicated) as they do not
have any antiadrenergic properties. Diltiazem may
be useful for rate control in patients intolerant to
propranolol
 68

Treatment

Hyperthyroid patients should be educated about

relevant lifestyle matters, such as avoidance of
tobacco, especially in the setting of Graves
disease, as there is some correlation between
smoking and worsening eye disease
There is no evidence that moderating amount of
iodine in diet will have any clinical effect in
hyperthyroid patients
 69

Graves disease
Graves disease may remit in up to 40% of cases
and can be treated with thioureylenes for 6 to 18
months
If no remission is achieved, patient can receive
radioactive 131-iodine or thyroidectomy
There is some evidence to suggest that Graves
ophthalmopathy improves after thyroid surgery but
not after radioactive iodine ablation. Rituximab has
been used to treat Graves ophthalmopathy
Active Graves ophthalmopathy may benefit from
various means of eye protection, such as
 70

Graves disease
Active Graves ophthalmopathy may benefit from
various means of eye protection, such as
sunglasses, artificial tears, elevation of head of
bed, and eye protection at night
Steroids, surgical decompression, or external
radiation may be required in patients with severe
ophthalmopathy
 71

Goiter

Patients with toxic uninodular and multinodular

goiter do not go into remission and require surgery
or radioactive 131-iodine. Thioureylenes and/or -
blockers may be given prior to definitive therapies
 72

Thyrostatic
Treatment of hyperthyroidism
Dose information
Methimazole :
Adult: 15 to 60 mg/d by mouth given in divided
doses every 8 hours
Pediatric: 0.4 mg/kg/d by mouth given in divided
doses every 8 hours
 73

Thyrostatic
Propylthiouracil :
Adult: 300 to 450 mg/d initially by mouth given in
divided doses every 8 hours; usual maintenance
dose is 100 to 150 mg/d, given in divided doses
every 8 hours to a maximum of 1200 mg/d
Pediatric: 5 to 7 mg/kg/d by mouth given in divided
doses every 8 hours
Major contraindications
Breastfeeding (methimazole)
 74

Thyrostatic
Comments
Safety and efficacy of propylthiouracil in patients
younger than 6 years of age have not been
established
Propylthiouracil is considered second-line agent in
pediatric patients due to case reports of fulminant
hepatic failure associated with its use in children
Use caution in patients with bone marrow
suppression
 75

Thyrostatic Evidence
A small randomized trial that compared a single
daily dose of methimazole versus a single daily
dose of propylthiouracil for 12 weeks in 71 patients
with newly diagnosed Graves disease found that
methimazole (15 mg/d) was more effective than
propylthiouracil in promoting euthyroidism. [1]
Level of evidence: 2
 76

Thyrostatic Evidence
A randomized trial compared radioactive iodine
(with or without subsequent corticosteroids for 3
months) versus 18 months of methimazole in 443
patients with hyperthyroidism. It found that
radioactive iodine treatment was more frequently
associated with appearance or worsening of
ophthalmopathy compared with treatment with
methimazole. However, this effect was often
transient and could be prevented by administration
of prednisone. [2] Level of evidence: 2
 77

Thyrostatic Evidence
A meta-analysis of 12 trials involving different
regimens concluded that optimal duration of
treatment with antithyroid drugs in Graves disease
is 12 to 18 months. [3] Level of evidence: 2
 78

Propranolol
Propranolol is indicated to reduce adrenergic
manifestations of hyperthyroidism
This is an off-label indication
Dose information
Adult: 10 to 40 mg orally every 6 hours
Pediatric: 2 mg/kg/d orally, given in equally divided
doses every 6 to 8 hours
 79

Propranolol
Major contraindications
Asthma
AV block
Bradycardia
Cardiogenic shock
Sick sinus syndrome
 80

Propranolol
Comments
Safety and efficacy in pediatric patients have not been
established
Doses should be gradually reduced before ceasing therapy.
Do not stop treatment abruptly, risk of withdrawal syndrome
Use caution in patients with diabetes (may mask signs of
hypoglycemia), severe peripheral vascular disease,
hyperthyroidism, pheochromocytoma, vasospastic angina,
coronary artery disease, bronchospastic disease,
myocardial infarction, cardiac failure, and those patients
preparing for surgery
 81

Propranolol
Evidence
A small, double-blind, crossover, placebo-
controlled trial compared propranolol (40 mg/d)
with placebo as adjunctive treatment (with
carbimazole) for hyperthyroid tremor and
tachycardia in seven patients. All patients showed
improvement, but propranolol group showed
greater improvement than placebo group. [4] Level
of evidence: 2
 82

Patient Education
Adequate diet high in protein, vitamins, and
calories
Avoidance of physical exertion
Smoking cessation may slow deterioration in
Graves orbitopathy
Monitor patient's weight and tobacco consumption
at each visit
Dyslipidemia
 84

Description
Hyperlipidemia is a heterogeneous group of disorders
characterized by an excess of lipids in the bloodstream.
These lipids include cholesterol, cholesterol esters,
phospholipids, and triglycerides. Lipids are transported in
the blood as large 'lipoproteins'
Lipoproteins are divided into five major classes, based on
density: chylomicrons, very low-density lipoproteins (VLDL),
intermediate-density lipoproteins (IDL), low-density
lipoproteins (LDL), and high-density lipoproteins (HDL).
Most triglyceride is transported in chylomicrons or VLDL,
and most cholesterol is carried in LDL and HDL
 85

Description
Primary hyperlipidemias are probably genetically based,
but the genetic defects are known for only a minority of
patients
Secondary hyperlipidemia may result from diseases such
as diabetes, thyroid disease, renal disorders, liver
disorders, and Cushing's syndrome, as well as obesity,
alcohol consumption, estrogen administration, and other
drug-associated changes in lipid metabolism
Hyperlipidemia is a major, modifiable risk factor for
atherosclerosis and cardiovascular disease, including
coronary heart disease; this is true both of disorders
involving hypercholesterolemia and hypertriglyceridemia
 86

Immediate action
It has been shown that risk of recurrent
cardiovascular events is significantly lowered with
intensive statin therapy in patients at high risk.
Intensive statin therapy should be considered as
part of initial therapy in any patient admitted with
an acute coronary syndrome or myocardial
infarction .
 87

Urgent action

Patients with documented, stable coronary artery

disease and/or diabetes mellitus should have their
lipid levels measured and be started on
appropriate lipid management, including lifestyle
modifications.
 88

Hypercholesterolemia
Hypercholesterolemia, regardless of cause, is a major
modifiable risk factor for coronary artery disease
Hyperlipidemia is usually asymptomatic until serum lipid
levels are severely elevated, and well beyond the range at
which cardiovascular morbidity and mortality are increased
Identification of patients who would benefit from lipid-
lowering therapy, therefore, depends on screening of adults
and certain children for high serum lipid levels, as well as
obtaining a careful history to detect risk factors that suggest
the patient would benefit from lipid-lowering therapy, even if
serum lipid levels are 'normal
 89

Hypercholesterolemia
Effective and well-tolerated therapy for lowering LDL
cholesterol (LDL-C) is now available, and should receive
widespread application
Epidemiologic studies predict that for each 1% reduction in
the level of LDL-C, there is a 1% to 1.5% reduction in the
risk of major cardiovascular events
Treatment goals for lipid-lowering therapy depend on risk
stratification of the patient to identify appropriate lipid level
'targets'
Lifestyle modifications, such as weight loss, exercise, and
dietary changes, are also key in long-term management
 90

Hypertriglyceridemia
Drug therapy for elevated triglycerides is presently
available, and new drugs are being developed
Contrary to widespread belief, hypertriglyceridemia
is also a modifiable risk factor for cardiovascular
disease
 91

Common causes
Familial combined hypercholesterolemia is the
most common primary lipid disorder, characterized
by moderate elevation of plasma triglycerides and
cholesterol and reduced plasma HDL-C
Familial hypertriglyceridemia
Obesity
 93

Obesity in Adult
Obesity is a complex and multifactorial condition
characterized by an excess of body fat that can present in
isolation, with no symptoms, or in association with
considerable comorbidities ( eg , cancer, coronary artery
disease, diabetes, hypertension, gout, obstructive sleep
apnea, and osteoarthritis)
More than 300 million people worldwide are estimated to be
obese. Approximately 66% of the U.S. population is
classified as overweight, with an additional 33% classified
as obese. The economic and human consequences of
obesity in terms of the monetary cost of treatment and the
psychological impact on patients constitute a substantial
burden to contemporary society
 94

Obesity in Adult
The definitive test to establish the diagnosis of
obesity remains the calculation of body mass index
(BMI) or mass divided by height squared. Obesity
is defined in practice as a BMI 30 kg/m2
Other easily obtainable measurements to establish
obesity include waist-to-hip ratio and waist
circumference. Central or abdominal obesity has a
stronger association with obesity-related
comorbidities than peripheral obesity, so waist
circumference >102 cm (40 in) in men and >88 cm
(35 in) in women may be a better indicator of the
risk of obesity-related comorbidities than BMI
 95

Obesity in Adult
Management of obese patients includes both
pharmacologic and nonpharmacologic treatment
modalities; however, the overall efficacy and
durability of these interventions are poor. Surgical
management is an option for some obese patients
( eg , BMI 40 kg/m2or BMI 35 kg/m2with
significant comorbidities)
 96

Differential diagnosis
Hypothyroidism
Cushing syndrome
Polycystic ovary syndrome affects 4 to 5 million
women in the U.S.
Hypothalamic abnormalities
 97

Orlistat
Orlistat is approved by the FDA for long-term
treatment of obesity (including weight loss and
weight maintenance) in conjunction with a
reduced-calorie diet and appropriate exercise
Dose information
In patients aged 12 years and older: 120 mg orally
three times daily with each meal, taken during the
meal or up to an hour after the meal
 98

Orlistat
Major contraindications
Cholestasis
Malabsorption syndrome
 99

Orlistat
Comments
Has been shown to result in a 5% to 10% loss of
original weight and maintenance of weight loss
after 2 years; use has resulted in an average
weight loss of 3 kg
Supplementation of fat-soluble vitamins should be
considered in selected patients
 100

Rimonabant
Rimonabant is not approved by the FDA for the treatment
of obesity
Dose information
20 mg orally once daily
Comments
Depression, anxiety, diarrhea, and nausea are potential
adverse effects, and, thus, rimonabant should not be used
in patients with these conditions
Has been shown to result in a weight loss of 4 to 6 kg over
6 to 12 months
 101

Rimonabant
Evidence
A meta-analysis of four double-blind RCTs
comparing rimonabant, 20 mg, versus placebo in
4,105 patients found that patients receiving
rimonabant lost 4.7 kg more weight than those
receiving placebo but were more likely to
experience adverse effects (odds ratio, 1.4;
number needed to harm, 25 patients). [1] Level of
evidence: 1
 102

Phentermine
Phentermine is approved by the FDA for short-
term (approximately 12 weeks) treatment of
obesity in combination with exercise, diet, and
behavioral modification
Dose information
8 mg orally three times daily 30 minutes before
meals or 1 to 2 hours after mealsor
15 to 37.5 mg orally once daily in a single dose
before or 2 hours after breakfast
 103

Phentermine
Major contraindications
Arteriosclerosis
Cardiac disease
Glaucoma
Hypertension
Hyperthyroidism
Substance abuse
 104

Phentermine
Comments
Typically prescribed for patients who are at
increased medical risk because of their weight