Common Endocrinologic Disorders

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CHAPTER 12 Common Endocrinologic Disorders

I. Diabetes Mellitus

Diabetes mellitus (DM) is a metabolic disorder characterized by glucose intolerance. People in the United States who are at the highest risk for diabetes are Latino Americans, African Americans, Native Americans, and Asian Americans. It is the leading cause of blindness in adults as well as a major cause of end-stage renal disease and amputations.

A. Classification

1. Type 1 diabetes is a failure of the pancreas to make enough insulin for the body to function. It was previously called insulin-dependent diabetes or juvenile-onset diabetes. It occurs more often in younger patients than older patients. Type 1 diabetes requires insulin therapy.
2. Type 2 diabetes refers to decreased insulin production from the pancreas, decreased sensitivity of cells to insulin, and decreased ability to get glucose into cells. It was previously called non–insulin dependent diabetes and adult-onset diabetes. It occurs more often in older patients than younger patients, although the incidence of type 2 diabetes is increasing in children in the United States. Patients may start with diet and exercise therapy. Most patients start with oral medications but may progress to requiring insulin therapy.
3. Gestational diabetes is diabetes that occurs during pregnancy. It does not mean the patient will have diabetes for the rest of her life, but she will have increased risk of developing type 2 diabetes. Patients typically use insulin therapy due to risk to the fetus when using oral antidiabetic medications. Gestational diabetes is usually detected through administration of an oral glucose tolerance test (OGTT) during pregnancy.
4. Prediabetes is the increased risk of developing DM.

a) Impaired fasting glucose (IFG): fasting glucose 100–125 mg/dL
b) Impaired glucose tolerance (IGT): Two-hour glucose 140–199 mg/dL during oral glucose tolerance test (OGTT)

B. Signs and symptoms

1. The 3 Ps: polyuria, polydipsia, polyphagia
2. Blurred vision
3. Fatigue
4. Dry, itchy skin
5. Slow wound healing
6. Weight loss (type 1 diabetes)

C. Diagnosis

1. Random plasma glucose > 200 mg/dL plus signs and symptoms of diabetes OR
2. Fasting plasma glucose > 126 mg/dL OR
3. Two-hour postprandial glucose > 200 mg/dL during OGTT
4. Confirm the above.
5. Hemoglobin A1c testing (HbA1c): HbA1c is not used to diagnose DM, but is used for long-term monitoring.

D. Goals of therapy

Goals of Therapy

Target Area Treatment Goals (for the patient with diabetes)
Preprandial plasma glucose (fasting) 90–130 mg/dL
Postprandial plasma glucose (after meals) <180 mg/dL
Glycosylated hemoglobin (HbA1c) <7%
Blood pressure <130/80 mmHg
Lipid levels

LDL cholesterol
HDL cholesterol
Triglycerides

<100 mg/dL
>40 mg/dL (men); >50 mg/dL (women)
<150 mg/dL

Based on the American Diabetes Association guidelines. Individual treatment goals may vary slightly from these guidelines based on personal medical history.

E. Treatment

1. Diet
2. Exercise
3. Type 1: insulin therapy, pramlintide (Symlin)
4. Type 2: oral agents and/or insulin, pramlintide (Symlin), exenatide (Byetta)

F. Insulin

1. Background

a) Insulin is produced in the beta cells of the pancreas. It is released at a basal rate of 0.5 to 1 U/h. Insulin response is increased in response to food.
b) The mechanism of action is not completely understood.

(1) Muscle: increase glucose transport into cell, glycogenesis, protein and triglyceride synthesis
(2) Liver: increase glucose transport into cell, glycogenesis, glucose utilization in Krebs cycle, protein synthesis
(3) Adipose: increase glucose transport into cell, glycogenesis, triglyceride synthesis
(4) Take home point: Insulin is necessary for the body to use glucose.

2. Types of insulin

a) Short-acting

(1) Used for mealtime control
(2) Administered 15–30 minutes before meal
(3) May also be used for sliding scale
(4) Examples

(a) Insulin aspart (NovoLog)
(b) Insulin lispro (Humalog)
(c) Insulin glulisine (Apidra)
(d) Regular (Humulin R)

b) Intermediate-acting

(1) Used for basal control
(2) Dosed twice daily for optimal control; may also be dosed once daily at bedtime for patients with type 2 diabetes who also take oral medications to suppress overnight hepatic gluconeogenesis
(3) Example

(a) Isophane insulin, NPH (Humulin N)

c) Long-acting

(1) Like intermediate-acting are used for basal control
(2) Usually dosed once daily
(3) Should not be mixed with any other insulin
(4) Examples

(a) Insulin glargine (Lantus)
(b) Insulin detemir (Levemir)

d) Combination products

(1) Humulin 70/30 (70% NPH, 30% regular)
(2) Humulin 50/50 (50% NPH, 50% regular)
(3) Humalog mix 50/50 (50% insulin lispro protamine suspension, 50% lispro)
(4) Humalog mix 75/25 (75% insulin lispro protamine suspension, 25% lispro)
(5) NovoLog mix 70/30 (70% insulin aspart protamine suspension, 30% aspart)

3. Cautions

a) Causes hypoglycemia at high doses
b) Lispro has more rapid onset than regular and should not be interchanged with it
c) Patients with type 1 DM should not use once-daily dosing of insulin initially
d) Changes in insulin should only be made under supervision of medical personnel
e) Caution is warranted when switching from animal (either pork or bovine) to purified porcine insulin or biosynthetic human insulin due to increased potentcy or bioavailability and increased risk of hypoglycemia.
f) Injection needles should not be reused
g) Insulin should not be used during hypoglycemia
h) Insulin should still be used when ill (may need more insulin when ill)
i) Use of lispro has not been studied in pregnancy, fetal abnormalities occurred in two infants
j) Contraindication: hypersensitivity to the medications
k) Insulin dosing and use requires constant patient education and monitoring

4. Interactions

a) Medications affecting glucose: may increase or decrease effect of insulin
b) Pork and human insulin should not be mixed or used together

5. Toxicity and side effects

a) Hypoglycemia
b) Lipodystrophy
c) Weight gain
d) Patients may develop resistance to insulin treatment
e) Patients may develop sensitivity to animal insulin

6. Remarks regarding insulin

a) Should always be dosed in “units” (e.g., 10 units subcutaneous [SC])
b) Regular insulin solution should be clear
c) Mixing*

(1) Semilente/lente/ultralente: can be mixed in any proportion
(2) Regular + lente: bind immediately, if mixed, must use immediately after mixing or inject separately
(3) Lente + phosphate-buffered insulin (NPH, NovoNordisk, Humulin BR): must never be mixed; lente will become immediate-acting instead of delayed
(4) NPH and regular insulin can be combined in the same syringe and refrigerated for a maximum of 21 days

7. Injection technique

a) Use abdomen, arm, leg, or buttocks
b) Clean the injection area first with alcohol
c) Examine bottle and roll gently in hands
d) Inject air into vial, draw up desired dose
e) Pinch the skin with one hand, and insert the needle at an angle of 45°–90°
f) Dispose of the syringe properly
g) Rotate the injection site

8. Adjusting insulin dose

a) Adjustments are made based on glucose monitoring and HbA1c as well as pattern of response
b) Adjust basic insulin dose 1–2 units at a time; 2–4 units or more for extreme cases
c) For every unit of rapid-acting insulin, glucose may be reduced by 25–50 mg/dL
d) Long-acting insulin should be adjusted based on fasting glucose

Insulin Calculations

Starting Insulin: Staged Diabetes Management Guideline (SDM)

From Staged Diabetes Management, ed 4 © 2005, International Diabetes Center at Park Nicollet, Minneapolis, MN. All rights reserved. Reprinted with permission (+1)800-637-2675; and Pearson J, Powers M: Systematically Initiating Insulin: The Staged Diabetes Management Approach, The Diabetes Educator 32(Suppl)(1):23s–25s, 2006.

Guideline for starting and titrating background insulin: Background insulin + oral agent(s) insulin glargine or insulin detemir

<70 mg/dL Decrease 1–2 U
140–250 mg/dL Increase 2–4 U
>250 mg/dL Increase 4–8 U

0.1 U/kg body weight if A1c levels are <9% (long acting insulin)

0.2 U/kg body weight if A1c levels are ≥9%

Adjustments are made weekly based on fasting blood glucose.

It is common to start insulin therapy by using only insulin glargine (Lantus) at bedtime in combination with oral agents. The use of background insulin with oral antidiabetic agents is a common approach to initiate insulin therapy. The average dose that was effective in the Treat-to-Target study was 0.4 to 0.5 U/kg at bedtime. Continue to escalate dose if goal is not reached. If the dose surpasses 0.7 U/kg, transition return to background insulin. Mealtime regimen is recommended for tighter control.

Guideline for starting and titrating premixed insulin: Premixed insulin Aspart 70/30 or Lispro premix 75/25

Blood Glucose Adjust Insulin*

Prebreakfast

<70 mg/dL Decrease pm 1–2 U
140–250 mg/dL Increase pm 1–2 U
>250 mg/dL Increase pm 2–4 U

Presupper

<70 mg/dL Decrease am 1–2 U
140–250 mg/dL Increase am 1–2 U
>250 mg/dL Increase am 2–4 U

Start

0.1 U/kg in morning and evening if A1c <9%

0.2 U/kg in morning and evening if A1c ≥9%

Total daily units

0.2–0.4 U/kg

Adjust weekly based on am or pm blood glucose

Guidelines for starting and titrating background/mealtime insulin: Long-acting insulin (insulin glargine or insulin detemir) + rapid-acting insulin with meals

Blood Glucose Adjust Insulin†
Prebreakfast Long-acting (detemir or glargine)
Prelunch am Rapid acting
Presupper lunch Rapid acting
Prebedtime supper Rapid acting
Start If A1c <9%:
• 0.1 U/kg long-acting insulin
• 0.1 U/kg rapid-acting insulin divided between meals

If A1c ≥9%:
• 0.2 U/kg long-acting insulin
• 0.2 U/kg rapid-acting insulin divided between meals

Total units 0.2–0.4 U/kg Adjust Minimum weekly

* Stop secretagogue; consider continuing insulin sensitizer(s).

† Adjust insulin by 1–2 U based on blood glucose pattern. Review insulin-to-carbohydrate ratios and activity. Stop secretagogue; consider continuing insulin sensitizer(s).

9. Alternative methods of insulin administration

a) Pen

(1) Portable and convenient; an alternative to vial and syringe
(2) NovoPen 3, Flex Pen (NovoLog, NovoLog 70/30, Levemir)
(3) Humalog, Humalog mix 75/25, Humulin N, Humulin 70/30

b) Pump

(1) Continuous subcutaneous infusion

c) Inhaled insulin (Exubera)

(1) Withdrawn from the market due to lack of demand
(2) High cost
(3) Long-term pulmonary safety profile of concern

10. Somogyi effect and dawn phenomenon

a) Somogyi effect

(1) Rebound hyperglycemia due to insulin-induced hypoglycemia
(2) Treatment

(a) Adjust evening snack
(b) Decrease evening NPH or give at a later time
(c) Switch to a basal insulin

b) Dawn phenomenon

(1) Rise in blood glucose level upon waking during the early morning hours (usually between 4 am and 9 am)
(2) Treatment

(a) Limit or regulate evening snacks
(b) Possibly increase NPH dose or basal insulin

G. Synthetic amylin analog, pramlintide acetate (Symlin)

1. Mechanism of action: synthetic analog of human amylin

a) Amylin, like insulin, is located in pancreatic beta cells. It is secreted with insulin in response to food intake.
b) Reduces postprandial glucose
c) Slows gastric emptying
d) Decreases food intake
e) Increases satiety

2. Indications

a) Type 1 and type 2 diabetes as an adjunct to mealtime insulin

3. Usual adult dosage

a) Type 1 diabetes: initially, 15 mcg SC before meals; may titrate up at 15 mcg increments (without nausea for 3 days); maintenance: 30–60 mcg SC before meals
b) Type 2 diabetes: initially, 60 mcg SC before meals; may increase dose to 120 mcg SC before meals (without nausea for three days)

4. Adverse effects

a) Nausea
b) Hypoglycemia

5. Contraindications and considerations

a) Avoid in gastroparesis and hypoglycemia unawareness
b) Potential for drug interactions due to delayed gastric emptying
c) Reduce premeal insulin by 50% when initiating pramlintide

H. Incretin mimetic agent, exenatide (Byetta)

1. Mechanism of action

a) Stimulates the body’s ability to produce insulin in response to elevated concentrations of blood glucose
b) Inhibits the release of glucagon after meals
c) Slows the rate of gastric emptying
d) Reduces food intake

2. Indications

a) Treatment of type 2 diabetes (adjunct to metformin, sulfonylurea, or thiazolidinedione)

3. Usual adult dosage

a) Initially, 5 mcg SC bid given within 60 minutes before morning and evening meal
b) May increase dose to 10 mcg SC bid after one month
c) Available in prefilled pens (must refrigerate)

4. Adverse effects

a) Hypoglycemia (more likely when combined with a sulfonylurea)
b) Nausea

5. Contraindications and considerations

a) Hypersensitivity to exenatide
b) Potential for drug interactions due to delayed gastric emptying
c) Has not been studied for use with insulin
d) Pancreatitis

I. Oral agents for diabetes

1. Sulfonylureas

a) Mechanism of action

(1) Stimulates insulin release from pancreatic beta cells; increases peripheral sensitivity
(2) Inhibits hepatic glucose production; enhances glucose uptake in muscle
(3) Insulin secretagogues

b) First generation versus second generation-

(1) Fewer adverse effects with second generation agents (e.g., glyburide, glipizide), although patient is still at risk for hypoglycemia
(2) Second generation (e.g., glyburide, glipizide, glimepiride) more potent
(3) Comparable efficacy

c) Indications: management of type 2 diabetes as monotherapy; also combined with other antidiabetic medications if needed (e.g., metformin, insulin)
d) Usual adult dosage

Comparable Efficacy

  Generic (Brand) Adult Daily Dose Range
First generation Acetohexamide (Dymelor) 250–1500 mg
Tolbutamide (Orinase) 500–3000 mg
Tolazamide (Tolinase) 100–1000 mg
Chlorpropamide (Diabinese) 100–500 mg
Second generation Glipizide:

Glucotrol
Glucotrol XL

2.5–40 mg
2.5–20 mg

Glyburide:

Micronase, DiaBeta
Glynase

2.5–20 mg
1.5–12 mg
  Glimepiride (Amaryl) 1–4 mg
e) Adverse effects

(1) Hypoglycemia
(2) Nausea/vomiting
(3) Weight gain
(4) Rash
(5) Dyspepsia
(6) Hematologic reactions

f) Contraindications and considerations

(1) Hypersensitivity
(2) Type 1 diabetes
(3) Avoid alcohol

2. Biguanides: Metformin (Glucophage, Glucophage XR, Fortamet, Glumetza, Riomet)

a) Mechanism of action

(1) Inhibit gluconeogenesis and glycogenolysis
(2) Improve insulin sensitivity
(3) Does not stimulate insulin secretion; insulin sensitizers

b) Indications

(1) Management of type 2 diabetes as monotherapy or in combination with sulfonylurea

c) Usual adult dosage

(1) Initially, 500 mg daily for 7–10 days.
(2) Standard dose 500 mg bid with meals
(3) May increase at 1- or 2-week intervals by 500 mg if needed
(4) Maximum dose: 2550 mg/day for younger adults; pediatric and elderly patients should receive lower maximum daily doses.

d) Adverse effects

(1) Metallic taste
(2) Abdominal discomfort/cramping
(3) Diarrhea
(4) Nausea/vomiting
(5) Decrease vitamin B12 levels
(6) Lactic acidosis

e) Contraindications

(1) Avoid in patients with renal dysfunction (SCr >1.5 mg/dL for men and >1.4 for women)
(2) Hypersensitivity
(3) History of lactic acidosis
(4) Pharmacologically treated heart failure
(5) Radiologic contrast procedures (use of contrast increases risk for renal dysfunction and lactic acidosis). Discontinue metformin 48 hours before and after procedure.
(6) Alcoholism (especially frequent binge drinking)

3. Thiazolidinediones, pioglitazone (Actos), rosiglitazone (Avandia)

a) Mechanism of action

(1) Increases peripheral glucose utilization
(2) Decreases hepatic glucose production
(3) Insulin sensitizer and consequently reduces insulin secretion

b) Indications

(1) Management of type 2 diabetes as monotherapy or in combination with sulfonylurea, metformin, or insulin

c) Usual adult dosage

(1) Pioglitazone: initially, 15 or 30 mg daily; may increase at 8- or 12-week intervals; maximum 45 mg daily
(2) Rosiglitazone: initially, 4 mg daily or in divided doses; may increase at 8- or 12-week intervals; maximum 8 mg daily

d) Adverse effects

(1) Edema
(2) Weight gain
(3) Anemia
(4) Cardiovascular event (e.g., heart failure, heart attack risk may be increased with rosiglitazone)
(5) Hepatic events (liver damage)

(a) Monitor LFT

(6) Potential increased fracture risk (hands, feet) in women with long-term use

e) Contraindications and considerations

(1) Avoid in patients with congestive heart failure (CHF) or liver disease

4. Meglitinides, repaglinide (Prandin), nateglinide (Starlix)

a) Mechanism of action

(1) Similar to sulfonylureas
(2) Stimulates insulin release from beta cells in a glucose-dependent manner
(3) Insulin secretagogues

b) Indications

(1) Management of type 2 diabetes as monotherapy or in combination with metformin or thiazolidinedione

c) Usual adult dosage

(1) Repaglinide: If patients have HbA1c <8% or are naïve: 0.5 mg before meals. If they have been previously treated with HbA1c >8%, 1–2 mg before meals may be used. Maximum dose 16 mg daily
(2) Nateglinide: Initially, 120 mg tid before meals; maintenance 120 mg tid before meals; patients near goal HbA1c may use 60 mg tid
(3) For both: Doses should be skipped if a meal is skipped

d) Adverse effects

(1) Hypoglycemia
(2) GI upset
(3) Headache
(4) Weight gain
(5) Flu-like symptoms

e) Contraindications and considerations

(1) Type 1 diabetes or for the treatment of diabetic ketoacidosis (DKA)

5. Alpha glucosidase inhibitors, acarbose (Precose), miglitol (Glyset)

a) Mechanism of action

(1) Competitive inhibition of disaccharidases and pancreatic enzymes
(2) Delays intestinal absorption of carbohydrates (starch blockers)

b) Indications

(1) Management of type 2 diabetes as monotherapy or in combination with sulfonylurea, metformin, or insulin

c) Usual adult dosage

(1) Initially, 25 mg daily with the first bite of main meal
(2) May titrate up at 2-week intervals
(3) Maximum 100 mg TID with main meals
(4) For both: Dose should be skipped if meal is skipped

d) Adverse effects

(1) Flatulence
(2) Abdominal cramps
(3) Diarrhea
(4) Borborygmus (stomach rumbling sounds)

e) Contraindications

(1) Inflammatory bowel disease (IBD)
(2) Intestinal obstruction

6. Dipeptidyl peptidase-4 (DPP-4) inhibitors: sitagliptin phosphate (Januvia)

a) Mechanism of action

(1) Blocks dipeptidyl peptidase IV (DPP-4), results in increased insulin release after meals and when glucose levels are high

b) Indications

(1) Monotherapy or in combination with other hypoglycemic agents for type 2 diabetes

c) Usual adult dosage

(1) 100 mg once daily with or without food

d) Adverse effects

(1) Nasopharyngitis
(2) Upper respiratory tract infection
(3) Headache

e) Contraindications and considerations

(1) Type 1 diabetes or for the treatment of diabetic ketoacidosis (DKA)

J. Complications of diabetes

1. Acute

a) Hyperglycemia
b) Hypoglycemia
c) Diabetic ketoacidosis (DKA)

(1) Characterized by high levels of ketones in the blood
(2) Signs and symptoms

(a) Loss of appetite
(b) Nausea
(c) Vomiting
(d) Fever
(e) Stomach pain
(f) A sweet, fruity smell on the breath, especially if the blood sugar level has been consistently greater than 250 mg/dL

(3) More common in type 1 diabetes than type 2
(4) Treated with insulin therapy (typically therapy is begun as an insulin infusion in intensive care setting) and intravenous fluids

2. Microvascular complications

a) Diabetic neuropathy (nerve damage caused by prolonged hyperglycemia, often occurring in feet and legs)

(1) Peripheral neuropathy
(2) Autonomic neuropathy

b) Diabetic retinopathy (a leading cause of blindness in the United States)
c) Diabetic nephropathy (kidney damage, nephrons lose filtering capacity, may lead to kidney failure and need for dialysis or transplant

3. Macrovascular complications

a) Hyperlipidemia
b) Hypertension
c) Cardiovascular disease, atherosclerosis
d) Stroke

4. Other complications

a) Increased risk for skin and skin structure infection (e.g., diabetic foot ulcer)
b) Gum disease; oral health complications

K. Patient education

1. Diet
2. Exercise
3. Home blood glucose monitoring
4. Action plan for hypo- and hyperglycemia
5. Insulin administration; administration and timing of other antidiabetic medications
6. Complications and prevention of diabetes
7. Eye care
8. Dental care
9. Foot care

II. Thyroid Disorders

Thyroid disorders are among the most common medical endocrine conditions but, because their symptoms often appear gradually over time, they are commonly misdiagnosed. There are two main types of thyroid disease: hyperthyroidism, or too much thyroid hormone, and hypothyroidism, or too little thyroid hormone.

The thyroid produces hormones, called thyroxine (T4) and triiodothyronine (T3), which affect the body’s metabolism and energy level. T3 is the short-acting and more potent of the two hormones. Thyroid hormone is also produced in response to thyroid stimulating hormone (TSH, also known as thyrotropin) secreted by the pituitary gland.

A. Hypothyroidism occurs when the thyroid gland does not produce enough thyroid hormone.

1. Hashimoto thyroiditis

a) Most common type
b) Inflammation of thyroid gland (not caused by infection)
c) Occurs when the individual’s immune system attacks the thyroid gland, causing low levels of thyroid hormone
d) Exhibits low plasma free T4 and elevated TSH levels

2. Signs and symptoms

a) Cold intolerance
b) Fatigue
c) Somnolence
d) Constipation
e) Menorrhagia
f) Myalgia
g) Hoarseness
h) Gland enlargement
i) Bradycardia
j) Edema
k) Dry skin
l) Weight gain

3. Treatment

a) Thyroid replacement hormones

(1) Levothyroxine (T4) (Synthroid, Levothroid, Levoxyl, others)

(a) Typical adult maintenance dose after titration: 100–120 mcg PO daily as a single dose 30 minutes before breakfast, given with plenty of plain water

(i) Adjust dose in the elderly and in patients with coronary artery disease
(ii) Initial dose in elderly 25 mcg per day versus the initial dose for younger adults, which is typically 50 mcg per day
(iii) Those with cardiac disease also start at 25 mcg daily

(b) Highly protein bound
(c) Precautions

(i) Long-term use has been associated with increased bone reabsorption and decreased bone density

(d) Drug interactions

(i) Antacids, calcium, or iron supplements should not be taken within four hours of levothyroxine dose; may decrease T4 absorption
(ii) Warfarin effects are enhanced by levothyroxine
(iii) Digoxin levels may be reduced by levothyroxine

(2) Liothyronine (T3) (Cytomel, Triostat)

(a) Adult dose: 25 mcg PO qd

(3) Liotrix (T4 and T3, 4:1 ratio) (Thyrolar)

(a) Adult dose: 60–120 mg PO qd

(4) Desiccated thyroid, variable T4 and T3 content due to animal gland sourcing (Armour Thyroid, Naturethroid, Westhyroid)

(a) Adult dose: 60–120 mg PO qd

B. Hyperthyroidism (thyrotoxicosis): occurs when the thyroid gland produces too much thyroxine. As a result, the individual’s metabolism increases dramatically, leading to weight loss and irregular heartbeat.

1. Graves disease

a) Most common cause
b) Malfunction in the body’s immune system releases abnormal antibodies that mimic thyroid-stimulating hormone (TSH)
c) Thyroid hormone factories work overtime and produce an excess of thyroid hormone
d) Exhibits elevated T4 and subnormal TSH levels
e) Can lead to thyroid storm: a life-threatening and sudden exacerbation of symptoms of thyrotoxicosis

(1) Characterized by fever, tachycardia, frank diarrhea, delirium, and coma
(2) Treatment: antipyretic (not aspirin); antithyroid drug plus Lugol solution 1 hour later; beta blockers

2. Signs and symptoms

a) Sudden and unexplained weight loss
b) Increased or irregular heartbeat
c) Nervousness
d) Irritability
e) Tremors (especially in the hands)
f) Increased sweating
g) Abnormal menstruation
h) Increased sensitivity to warmth
i) More frequent bowel movements
j) Enlarged thyroid gland (goiter)
k) Fatigue
l) Difficulty sleeping
m) Muscle weakness
n) Inability to close the eyelid (eyelid retraction)

3. Treatment

a) Antithyroid drugs

(1) Methimazole (Tapazole)

(a) Adult dose: 5–40 mg QD
(b) Favored over propylthiouracil (PTU) due to longer half-life, which allows for once a day dosing
(c) More potent than PTU

(2) Propylthiouracil (PTU)

(a) Adult dose: Initially, 300 mg QD, then usually 100–150 mg daily
(b) Although both drugs cross the placenta, the drug of choice in pregnant patient is PTU because it crosses less

(3) Strong iodine solution (Lugol’s solution)

(a) Adult dose: 0.1–0.3 mL (3–5 gtts) PO TID

(4) Saturated solution of potassium iodide (SSKI)

(a) Usual adult dose: 1–5 gtts PO TID in water or juice

b) Surgery
c) Radioactive iodine

(1) Sodium iodide-131 (131I), the agent of choice for Graves disease
(2) Most will require thyroid hormone supplementation after radioactive iodine treatment

PATIENT PROFILE

Patient Initials: CC
Sex: Female
Age: 22 years
Height: 5′ 4′′
Weight: 68 kg
Race: Latin American
Allergies: No known drug allergies (NKDA)
Chief Complaint:
CC is a 22-year-old woman with a history of gestational diabetes; she has one child, now 2 years old. She presents to the pharmacist clinic service for the first time because her family doctor has just told her that she now has type 2 diabetes. “My blood sugars were high on two tests,” she explains, “but I feel great, and I am young. Why do I have to take medications? Can’t I just exercise and lose some weight?”
Social History:
Tobacco use: None
Alcohol use: A few glasses of wine per week, usually with dinner
Exercise: Began walking program last week with her mother, who also has type 2 diabetes and is overweight
Medications:
Multivitamin once daily
New prescription: Metformin 500 mg PO twice daily
Other: Wears eyeglasses for reading
Laboratory:
Blood glucose: 220 mg/dL, nonfasting
Blood glucose: 140 mg/dL, fasting
Hemoglobin A1c (HbA1c): 8.6%

PATIENT PROFILE QUESTIONS

1. After discussion with the patient, it is clear that CC has little understanding of her new diagnosis and will need extensive diabetic education. When discussing blood sugar and HbA1c tests, which of the following would a pharmacist state as CC’s HbA1c treatment goal?

a. <6.5%
b. <8%
c. <7.5%
d. <7%

Answer: d. Based on well-known studies such as the Diabetes Control and Complications Trial (DCCT), a goal HbA1c of less than 7% reduces the risk of microvascular complications, such as diabetes-related nephropathy and retinopathy. Higher HbA1c levels increase the risk of chronic complications of diabetes. Some organizations recommend more aggressive goals (e.g., HbA1c <6.5%), but aggressive goals expose a patient to a greater risk of severe hypoglycemia.

2. The pharmacist encourages CC’s new exercise routine and weight loss goals. These plans are endorsed by her family doctor. Exercise may improve insulin sensitivity, promote weight reduction, and improve overall health. Weight reduction can lower the need for medications in some patients. In addition to exercise, what other preventative options should be recommended for CC at this time?

I. Checking with her doctor regarding her cholesterol levels
II. Taking a “baby aspirin” (aspirin 81 mg) daily to prevent heart disease
III. Performing daily foot self-examinations
IV. Keeping regularly scheduled ophthalmic exams
a. I and II
b. III and IV
c. I, III, and IV
d. All of the above

Answer: c. All patients with diabetes should be screened for lipid disorders because early management can help prevent macrovascular complications, such as myocardial infarction (MI). Current evidence suggests that aspirin is ONLY recommended for patients with diabetes with known heart disease and as primary prevention ONLY in patients with diabetes older than 30 years old with heart disease risk factors. CC is 22 years of age and is in an age bracket where insufficient benefit and risk information is available regarding preventative aspirin therapy. Daily self-examinations of the feet for cracks, callus formation, ulcers, and other issues will help avoid serious foot problems. Routine eye exams are recommended for any patient with diabetes with known visual difficulty; how often they are performed depends on age and known visual problems. Annual eye exams are recommended for those older than 30 years of age without any current visual difficulties. Younger patients should have routine exams at least every 5 years or more frequently if they already have visual impairment or changes.

3. CC will begin the metformin prescription as prescribed. During discussion with CC, the pharmacist should include which of the following in the counseling about the new prescription?

I. Metformin is often a drug of choice when type 2 diabetes is first diagnosed. It is effective at lowering blood sugar, does not cause weight gain, and does not cause low blood sugar when used alone.
II. Common side effects that usually decrease in a few weeks include nausea or reduced appetite.
III. CC should avoid binge drinking of alcohol to avoid lactic acidosis, a serious but rare side effect that can harm the kidneys.
IV. If CC follows her recommended diet and exercise plan, maintains a recommended body weight, and takes the metformin as prescribed, she can expect her HbA1c to drop about 1.5% with the medication.
a. I only
b. II only
c. I, II, and III
d. All of the above

Answer: d. Diabetes treatment guidelines place metformin monotherapy as first-line treatment for healthy, adults newly diagnosed with type 2 diabetes who have no other contraindications to metformin use. Common side effects are nausea, diarrhea, reduced appetite, and sometimes a metallic-like taste. These usually go away in a few weeks. Binge drinking of alcohol can be a risk factor for lactic acidosis and is often an important counseling point in a young patient with an active social life. Metformin will reduce HbA1c, will not cause weight gain, and can help CC reach her optimal health goals. If she is educated and adherent, she may avoid the need for additional medications.

REVIEW QUESTIONS

(Answers and Rationales on page 356.)

1. Lipohypertrophy in patients with diabetes is due to which of the following?

a. Repeated injections into the same site
b. Injections into fat-rich tissue
c. Too-rapid insulin injection
d. Hypersensitivity to insulin
e. Hypersensitivity to insulin vehicle

2. Which of the following is true of insulin?

a. It is secreted by pancreatic alpha cells
b. It promotes peripheral glucose uptake and utilization
c. It inhibits hepatic gluconeogenesis
d. a and b
e. b and c

3. Which of the following insulin preparations is available as a recombinant human analog?

a. Insulin lispro
b. Lente insulin
c. Regular insulin
d. None of the above
e. All of the above

4. Which of the following steroids have the longest duration of action?

I. Betamethasone
II. Dexamethasone
II. Hydrocortisone
a. I only
b. III only
c. I and II
d. II and III
e. I, II, and III

5. Which of the following conditions increases the risk of amputations in diabetics?

a. Peripheral Neuropathy
b. Peripheral Vascular Disease
c. Erythema
d. All of the above
e. None of the above

6. Which of the following is used for treatment of thyroid storm:

I. levothyroxine
II. hydrocortisone
III. propylthiouracil
a. I only
b. III only
c. I and II
d. II and III
e. I, II, and III

7. Which of the following classes of drugs requires periodic monitoring of liver function?

a. Thiazolidinedione
b. Biguanide
c. Meglitinide
d. Sulfonylurea
e. None of these drugs requires monitoring of liver function

8. Which of the following should be monitored in patients with diabetes treated with ACE inhibitors?

a. Serum creatinine, blood urea nitrogen, potassium, and sodium
b. Serum creatinine and blood urea nitrogen
c. Urine protein and sodium
d. Urine protein, sodium, and glucose
e. Urine protein, sodium, glucose, and potassium

9. Of the following patients, which is most likely to experience an adverse drug reaction?

a. 30-year-old man taking chlorpropamide and atenolol
b. 40-year-old woman taking pioglitazone with a serum BUN of 17 mg/dL
c. 30-year-old woman taking acarbose with an ALT of 80 IU/L and AST of 90 IU/L
d. 40-year-old man taking lisinopril and pioglitazone
e. 40-year-old woman taking lisinopril with an ALT of 30 IU/L and AST of 30 IU/L

10. Androgens are associated with which of the following adverse effects?

a. Priapism
d. Jaundice
c. Gynecomastia
d. Urinary retention
e. All of the above

11. Sulfonylureas are associated with which of the following adverse effects?

a. Jaundice
b. Photosensitivity
c. Nausea
d. a and b
e. a, b, and c

12. Which of the following statements about insulin is true?

a. It is secreted by pancreatic alpha cells,
b. It promotes peripheral glucose uptake and utilization,
c. It inhibits hepatic gluconeogenesis,
d. a and b
e. b and c

13. Which of the following is a useful feature to differentiate cholinestase inhibitor overdose with myasthenia gravis exacerbation?

a. Sweating
b. Weakness
c. Fasciculations
d. Salivation
e. All of the above

14. Which of the following agents can cause the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)?

a. Fluoxetine
b. Vincristine
d. MDMA
d. Risperidone
e. All of the above

15. Which of the following is TRUE about sulfonylureas?

a. Tolazamide is a second generation agent
b. Chlorpropamide is a first generation agent
c. Safe to use during pregnancy
d. a and b
e. b and c

16. What is the standard daily dose of glyburide?

a. 1.25–20 mg/day
b. 20–80 mg/day
c. 100–400 mg/day
d. 200–800 mg/day
e. 500–2000 mg/day

17. Patients taking chlorpropamide should be counseled to avoid which of the following?

a. Cheese
b. Vitamin K
c. Milk
d. Alcohol
e. Acetaminophen

18. Which of the following are responsible for inhibiting insulin release?

a. Secretin
b. Gastrin
c. Somatostatin
d. Cholecystokinin
e. All of the above

19. Which of the following drugs increase pancreatic insulin secretion?

a. Glipizide
b. Metformin
c. Acarbose
d. All of the above
e. None of the above

20. Oral medications to treat type 2 diabetes do which of the following?

I. Reduce insulin resistance
II. Stimulate endogenous insulin
III. Delay carbohydrate absorption
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III

21. Which of the following is/are the active ingredient(s) of Avandamet?

a. Rosiglitazone
b. Glipizide
c. Metformin
d. a and b
e. a and c

22. CO is a taking Precose (acarbose) 100 mg PO tid. Which of the following should be monitored?

a. AST
b. CK
c. PT
d. INR
e. CK

23. Glyset is a drug that inhibits:

a. alpha glucosidase
b. angiotensin-converting enzyme (ACE)
c. protease
d. acetylcholinesterase
e. topoisomerase

24. Which of the following is NOT an appropriate treatment for hyperthyroidism?

a. Propranolol
b. Corticosteroids
c. Bromocriptine
d. Propylthiouracil
e. Lugol solution

25. Which of the following is a side effect of biosynthetic growth hormone?

a. Hepatitis B
b. Antibody formation
c. Creutzfeldt-Jakob disease
d. HIV transmission
e. Hypoglycemia

26. Which of the following statements about insulin is true?

a. It is reabsorbed in the renal tubules.
b. It is metabolized in the liver.
c. It has a half-life of less than 10 minutes.
d. a and b
e. a, b, and c

27. Which of the following causes increased insulin activity after glucose consumption?

a. Gastrin
b. Secretin
c. Gastric inhibitory polypeptide (GIP)
d. a and b
e. a, b, and c

28. Which of the following is an effect of insulin?

a. Inhibition of hormone sensitive lipase
b. Increased glycogenolysis
c. Increased CNS glucose uptake
d. a and b
e. a and c

29. Insulin ultralente:

a. has an onset of action in 1–2 hours.
b. has peak activity at 4–6 hours.
c. has a duration of action of 18–24 hours.
d. All of the above
e. None of the above

30. Which of the following is NOT a side effect of chlorpropamide?

a. Hypoglycemia
b. Rash
c. Lactic acidosis
d. Syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH)
e. Disulfiram-type reaction

31. Which of the following is an effect of sulfonylureas?

a. Decreased hepatic gluconeogenesis
b. Increased peripheral tissue insulin sensitivity
c. Increased insulin-receptor binding
d. a and b
e. a, b, and c

32. Which of the following may cause SIADH?

a. Acetohexamide
b. Chlorpropamide
c. Glipizide
d. Tolazamide

33. Which of the following statements about oral hypoglycemic agents is true?

a. Second-generation agents have less affinity for albumin.
b. First-generation agents are more potent due to larger R substituents.
c. First- and second-generation hypoglycemic agents are sulfonylureas.
d. a and b
e. a and c

34. Which of the following is NOT a mechanism of oral sulfonylureas?

a. Regeneration of pancreatic beta cells
b. Correction of post receptor defects
c. Increased tissue insulin sensitivity
d. Decreased hepatic gluconeogenesis
e. All of the above are mechanisms of sulfonylureas

35. Which of the following is the correct insulin: onset of action pair?

a. Insulin Lispro: 1–3 hrs
b. Regular: 10–15 min
c. Insulin glargine: 0.5–1 hr
d. All of the above.
e. None of the above.

36. Effects of insulin include:

a. increased glycogenolysis.
b. increased glycosuria.
c. increased conversion of protein to glucose.
d. increased transport of glucose into the central nervous system.
e. inhibition of hormone sensitive lipase.

37. Which of the following statements is correct?

a. Lente insulin has an initial onset of 1–2 hours, a peak at 6–14 hours, and a duration of 24 or more hours.
b. Regular insulin has an initial onset of 30 minutes to 1 hour, a peak at 2–4 hours, and a duration of 5–7 hours.
c. NPH insulin has an initial onset at 10–15 minutes, a peak at 2–4 hours, and a duration of 3–5 hours.
d. a and b
e. a and c

38. Which of the following may occur with methimazole?

a. Pruritus
b. Neutropenia
c. Decreases peroxidase activity
d. a and c
e. a, b, and c

39. What is the standard recommended dose range of glyburide?

a. 0.5–2 mg/day
b. 1.25–20 mg/day
c. 50–100 mg/day
d. 200 mg/day
e. 200–1000 mg/day

40. Patients taking chlorpropamide should avoid products containing:

a. acetaminophen.
b. ethanol.
c. vitamin A.
d. penicillins.
e. milk products.

41. Which of the following pregnant patients does NOT need to undergo a 50 g glucose screening test during weeks 24–28 of pregnancy?

a. 30-year-old Latin woman with a negative screen at 15 weeks
b. 30-year-old Pacific Island woman who has a body mass index of 30 and no family history of diabetes
c. 20-year-old African American woman with a body mass index of 22 and no family history of diabetes
d. 20-year-old Caucasian woman with normal body weight
e. 20-year-old Latin woman with a body mass index of 30 and no family history of diabetes

42. A 22-year-old patient is admitted to the hospital with diabetic ketoacidosis (DKA). What is the most appropriate treatment to decrease cerebral edema in this patient?

a. Sodium bicarbonate
b. Insulin
c. Methylprednisolone
d. Mannitol
e. None of the above

43. Normal blood glucose for a fasting patient is between:

a. 20–40 mg/dl
b. 60–80 mg/dl
c. 80–120 mg/dl
d. 180–200 mg/dl
e. 220–240 mg/dl

Read the following case study and answer the questions that follow.

A 55-year-old man goes to the physician for his annual check-up. He has a medical history significant for obesity, hypertension, gout, and hypercholesterolemia. He reports that 1 week earlier, he attended a free health clinic at his place of work where his random blood glucose was found to be 220 mg/dL. On examination, he has decreased hair growth over the lower legs, decreased sensation over the feet and ankles, and flame hemorrhages on opthalmoscopic examination. Laboratory diagnosis on a fasting blood sample shows a blood glucose of 175 mg/dL. His physician diagnoses DM.

44. Which of the following is NOT a risk factor for DM type 2?

a. Poor diet
b. Obesity
c. High fiber intake
d. Family history
e. Sedentary lifestyle

45. Which of the following is the most appropriate dosage and medication for the initial treatment of DM type 2?

a. Pioglitazone, 500 mg once per day
b. Metformin, 500 mg twice per day
c. Insulin glargine, 15 units once per day
d. Glipizide, 5 mg once per day
e. Repaglinide, 5 mg before each meal

46. Metformin:

a. may cause diarrhea.
b. is safe to use in diabetic ketoacidosis.
c. decreases gluconeogenesis.
d. a and b
e. a and c

47. Glipizide:

a. enhances insulin release.
b. enhances peripheral insulin sensitivity.
c. inhibits hepatic glucose production.
d. a and b
e. a, b, and c

48. True or False: Pioglitazone does not require dose adjustments for renal impairment.

a. True
b. False

49. Pioglitazone:

a. may cause myalgia.
b. should be taken on an empty stomach.
c. is poorly protein bound in circulation.
d. is excreted predominately (>90%) in the urine.
e. All of the above

50. Hemoglobin A1c (HbA1c):

I. Represents the average blood glucose for 3 months
II. Helps determine glycemic control
III. Should be more than 6%
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III

51. Diabinese (chlorpropamide):

I. Is a sulfonylurea
II. Has a prolonged duration of action
III. May cause disulfiram-like reactions
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III

52. Avandia:

I. Improves insulin secretion
II. Improves insulin sensitivity
III. Inhibits hepatic glucose production
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III

53. Humalog:

a. Has a rapid onset of action
b. Should be administered subcutaneously
c. Should be given within 15 minutes of a meal
d. Is insulin Lispro
e. All of the above

54. Which of the following is a rare but serious side effect of Glucophage?

a. Pulmonary fibrosis
b. Neurotoxicity
c. Lactic acidosis
d. Pulmonary embolism
e. Infertility

55. Which of the following insulin preparations has a prolonged duration of action?

a. Lantus
b. Humalog
c. Humulin R
d. NovoLog
e. All of the above

* When mixing regular and NPH, regular should be drawn up first or the protamine in NPH will cause the regular insulin in the vial to become cloudy (the same applies to mixing regular with any other insulin).

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