ENDOCRINE AND METABOLIC

DISORDERS
DIABETES
Type I Diabetes
- Due to autoimmune beta cell destruction, which results in zero insulin
produced
- Untreated, can lead to ketoacidosis
- Onset is not common after 30 years
- 5-10% of diabetes
Type 2 Diabetes
- Manifested as insulin resistance, along with some degree of insulin
deficiency.
- 90% of diabetic cases
- Prevalence is increasing
Gestational Diabetes
- Onset of glucose intolerance in pregnancy
RISK FACTORS
1. Drugs
o APs
o Beta-adrenergic antagonists
o Glucocorticoids
o Niacin
o Protease inhibitors
o Thiazide or loop diuretics
2. Overweight
3. Poor nutrition
4. Sedentary lifestyle
5. Age >40
6. Hypertension
7. High risk population

8. Family history
9. PCOS
10.Schizophrenia
Non-Pharm
- Minimum of 3 blood glucose measurements daily for those on insulin
regimens
- SMBG is not necessary for patient on oral metformin
- Physical activity improves CVS function, enhances insulin sensitivity and
lowers blood pressure and lipid levels
- Encourage aerobic exercise > or equal to 150 min per week, along with
resistance training 3 times per week
- BG levels will after mod exercise, but after intense activity (stress
response)
Monitoring
-

BP measures
Foot examinations annually
A1C measurements q 3 mo
Serum creatinine annually
Fasting lipid profile

PHARMACOLOGIC CHOICES
Type 1 Diabetes
Insulin
- Can be administered by syringe, pen, or continuous s/c insulin infusion
- Animal insulin has been replaced by human preparations, due to frequency
of adverse reactions
- Rapid-acting insulin analogues (insulin aspartame, insulin glulisine, insulin
lispro)
- The long acting insulin analogues (insulin detemir and insulin glargine)
appear to produce more predictable effects than intermediate-acting human
insulin (NPH), and may be associated with fewer episodes of hypoglycemia
(esp. nocturnal hypoglycemia)
- Regular insulin should be administered 20-30 min before eating meals

- Rapid acting insulin analogues can be given before or within 20 min of

starting a meal
Adverse Effects of Insulin Therapy
- Hypoglycemia
o Most commonly the result of either a missed meal or an unusual amount
of exercise
o Mild hypoglycemia is manifested by: sweating, tremors, tachycardia,
hunger, nausea
o Severe hypoglycemia: confusion, altered behavior, difficulty speaking,
disorientation
o Conscious patient: give oral glucose preparation of 20 g carbohydrate
o Unconscious patient: 1 mg of glucagon IM or SC temporarily blood
glucose.
DO NOT GIVE glucagon to malnourished patients or in alcoholinduced hypoglycemia.
Give IV 50 mL of 50% dextrose in these situations
- Localized fat hypertrophy
o Often result of frequent use of same injection site
o Causes low or unpredictable absorption of insulin from the site
TYPE 2 DM
- Patients with A1C < 9%
o Can initiate with just diet and exercise
o But medication must be started if glycemic targets are not met within 23 months
o 1st line: Monotherapy with metformin is usually recommended
- In patients with A1C > or equal to 9%
o Medication must be initiated immediately + diet and exercise
o Combination therapy with 2 medications from different classes is
recommended.
o A1C should be reached within 6-12 months
ANTIHYPERGLYCEMIC AGENTS
1. 2nd line: Insulin secretagogues (sulfonylureas and meglitinides)

Sulfonylureas:
a. 1st gen SU: Chlorpropamide and Tobutamide
i. Typically not used due to PK profile and risk of DI
b. 2nd gen SU: Gliclazide, glimepiride, glyburide
i. Glyburide is inexpensive, but associated w/ risk of hypoglycemia
ii. SUs are 2nd line in T2DM therapy, they are either add-on or monotx in
patients with CI to metformin
Meglitinides
o
o
o
o
o

Nateglinide and repaglinide insulin release

Meglitinides have a shorter duration of action than SUs
They need to be taken just before meals to post-prandial glucose
Should be omitted if meal is missed
Repaglinide A1C = to SU, but has risk of hypoglycemia

2. Drugs that hepatic glucose production and/or tissue sensitivity to insulin

(thiazolidinediones and metformin)
Metformin (1st line) :
a. 1st line for T2DM
b. is a biguanide
c. hepatic glucose production, may lower glucose absorption and
insulin-mediated glucose uptake
d. Can hypoglycemic effects of insulin and sulfonylureas
e. CI in patients with HF, renal or hepatic disease or hypoxemic states
f. No increase in the rate of lactic acidosis compared to other
antihyperglycemic agents
g. Hold metformin pre-operatively and when imaging contrast agents are
being given, to avoid possibilities of acute renal failure (which can
chances of lactic acidosis)
Thiazolidinediones (TZDs)
o Pioglitazone and rosiglitazone are agonists at PPAR gamma receptors
located in the cell nucleus
o They insulin sensitivity and glood glucose and circulating insulin
levels

o They peripheral glucose uptake, enhance fat cell sensitivity to insulin

and hepatic glucose output
o Low risk of hypoglycemia; can be compounded w/ insulin and SU
o Associated w/ weight gain, fluid retention and edema (which risk of
HF)
o risk of fractures of wrist and hip
o Health Canada requires that new Rx for rosiglitazone includes patient
informed consent to ensure risks and benefits are understood by patient
nd
3. 2 line: Drugs that mimic or enhance incretin hormones (dipeptidyl
peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists
DPP-4 inhibitors:
o Augment actions of GLP-1, an endogenous incretin hormone.
o GLP-1 is secreted in response to food ingestion by endocrine cells found
in the GI tract
o GLP-1 insulin secretion, suppresses glucagon secretion during
postprandial period, slows gastric emptying, and satiety
o DPP-4 breaks down GLP-1
o DPP-4 inhibitors Saxagliptin and Sitagliptin are currently approved for
use in Canada, given po
Lack of long term safety, high cost make them 2nd line
GLP-1 Analogues
o GLP-1 agonists mimic actions of GLP-1, GLP-1 action by 5 times
o Appear to lower A1C to a greater extent than DPP-4 inhibitors
o Can cause more initial nausea than DPP-4 inhibitors initially
o Only available via S/C injections
o Exenatide is approved for use in Canada, but not marketed
4. 3rd line: Drugs that delay or prevent the digestion or complex carbohydrates
(alpha-glucosidase inhibitor acarbose)
a. Acarbose inhibits intestinal alpha-glucosidases
b. This delays digestion of starches and disaccharides, which postprandial
glucose levels
c. They do not significantly inhibit intestinal lactase
d. Does not cause hypoglycemia
e. Can risk of HG when combined with insulin or insulin secretagogues

f. Causes GI effects
g. Hypoglycemia in these patients should be treated by glucose, rather than
sucrose, as acarbose prevents digestion of sucrose
INSULIN FOR T2DM
- Due to progressive nature of T2DM, oral antihyperglycemic agents
gradually lose effectiveness over time
- Insulin is best at A1C
- Appropriate to use insulin when:
o Max dose or maximally tolerated dose of oral agents is reached, yet
A1C is > 7%
o End organ damage (such as kidney failure), which renders oral agents
inappropriate
o Initial diagnosis, when A1C > 9%
o Metabolic decompensation
o Preconception and pregnancy
- Insulin is often delayed because:
o Self-injection is seen as complex
o Associated with weight gain, risk of hypoglycemia
o Requires self-monitoring
- Commonly used insulin regimes:
o Insulin is added to existed oral therapy
Daily HS injection of basal insulin at 0.1-0.2 units/kg of insulin
NPH or long-acting analogue
Or, empiric dose of 5-10 U of NPH or LA insulin (glargine or
detemir). Dose is then adjusted (approx. 2 units q 3 days) until < 7
mmol/L is reached
Oral antihyperglycemic agents other than metformin may need to be
discontinued
o If glycemic targets are not met with bedtime insulin + daytime oral
AHG agent, then mealtime insulin injections may have to be given
Generally oral AHG agents are d/c when meal time insulin is started,
except metformin
o If glycemic values are v. high upon initial presentation, then intensive
insulin has to be started immediately

 Start with 40% of total daily dose (0.5 units/kg divided over 24
hours) given as basal insulin (NPH or long acting analogue)
20% of daily dose given before meals 3 times daily
Dose is then adjusted to reach glucose <7 mmol/L and 2 hour post
prandial glucose < 10 mmol
Insulin may be given BID injections of premixed insulin with 2/3rd
of daily dose (0.5 units/kg) given before breakfast and remaining
1/3rd of dose given before evening meal
Flexible regimen, allows for correction of abnormal results
PREGNANCY AND BREASTFEEDING
PREGNANCY
- Gestational DM develops during pregnancy, primarily due to insulin
resistance that results from high levels of gestational hormones
- Pre-existing diabetes (T1DM or T2DM) risk of miscarriage, perinatal
mortality, fetal macrosomia, congenital malformations
- GDM risk of fetal hyperinsuliemia, higher birth weight, neonatal
hypoglycemia
- Target A1C of <7% should be achieved before conception.
- Should avoid hypoglycemia and avoid oral AHG agents
- Folic acid supplementation should begin at least 3 months prior to
conception. Initial dose is 5mg daily, continued into pregnancy. After 3
months gestation, dose is reduced to 0.4-1 mg daily, continued throughout
pregnancy, and for a minimum of 6 months postpartum or until
breastfeeding is done
- Eye exam is important, as retinopathy can be accelerated due to poor
glycemic control
- Switch to an insulin regimen from oral hypoglycemic agents
- Can use glyburide in pregnant women
BREASTFEEDING
- Insulin goes into breast milk, but no risk as hormone is degraded in GI tract
before reaching systemic circulation

- BG should be monitored, as insulin regimens can change as more calories

are burned during BF
- GDM usually leaves 24 hours postpartum
- Glyburide and metformin can be used in women who were diabetic
before/after pregnancy.

THYROID DISORDERS
HYPOTHYROIDISM
- Clinical syndrome that results from a deficiency of thyroid hormone
- Rarely, can be due to resistance to thyroid hormone
- Thyroid-stimulating hormone (TSH) measurement is sensitive indicator of
hypothyroidism, but can be low or normal in pituitary or hypothalamic
disease
- Subclinical hypothyroidism is defined as an TSH with normal thyroid
hormone levels.
o If confirmed, consider treatment, esp. in patients with TSH > 10 mU/L
(normally 0.3-6 mU/L), abnormal lipid profile, symptoms of
hypothyroidism, in patients who are antithyroid peroxidase (anti-TPO) +
or those planning a pregnancy
Symptoms:
-

Fatigue
Weight gain
Impaired memory
Constipation
Cold intolerance
Appearance: coarse features, dry skin, hair
Hypertension, bradycardia

PHARMACOLOGIC CHOICES
1. LEVOTHYROXINE (L-T4)
o Goal of L-T4 therapy is to normalize the TSH level
o Dosage adjustment is made every 4-6 weeks as needed
o Generally it takes 6 weeks to attain a new steady state after dosage
adjustments

2. LIOTHYRONINE (Triiodothyronine, T3)

o T3 is used for short-term management of patients with thyroid cancer
undergoing withdrawal of L-T4
o Little to no benefit for coming T3 and L-T4
PREGNANCY
- Hypothyroidism can cause infertility and miscarriage
- Can cause lower IQ scores in children of women who had elevated TSH at
the time of conception
- Women on thyroid hormone replacement or at risk of hypothyroidism should
have preconception TSH measurement
- 1st trimester TSH levels are low due to beta HCG levels
- If TSH is not low in 1st trimester, this means under-treatment with thyroxine
or new diagnosis of hypothyroidism
- Follow with repeat TSH or adjust dose of thyroxine
MANAGEMENT
- Women already taking thyroid hormone replacement prior to pregnancy
should their thyroid hormone dose by 2 extra tabs per week, immediately
following a positive pregnancy test
- Further dose adjustment should be based on TSH levels
- Thyroid binding globulins during pregnancy, so requirements for L-T4
(levothyroxine) may up to 50% during pregnancy to maintain TSH at
around 1-3 mU/L
- Throughout pregnancy, women should check TSH level every 8-6 weeks
following dose adjustment
- TSH level is low in 1st trimester normal, dont fix this if free T4 and free
T3 levels are ok!
- Postpartum, thyroid hormone requirements stabilize
- Iron absorption of thyroxine, separate by 6 hours
BREASTFEEDING
- Manage just as in non-breastfeeding women
- Thyroid hormone therapy is safe in pregnancy and BF
TT

- Myxedema coma is treated with levothyroxine 300-500 ug IV initially,

followed by 100 ug IV daily. Also treat with corticosteroids, such as
hydrocortisone 100 mg q8h IV.
HYPERTHYROIDSIM
- Syndrome of excessive thyroid hormone production
- Subclinical hyperthyroidism is common, can be RF for atrial fibrillation
- In subclinical hyperthyroidism, TSH is suppressed while thyroid hormone
levels are normal
- Treatment is indicated if patient is frail and/or elderly, has RF for atrial
fibrillation, or has Sx of hyperthyroidism
Lab Tests
- TSH, fT3, fT4
- Thyroid scan
- Radioactive iodine uptake (RAIU)
NonPharm
- Thyroid surgery in patients with thyroid nodules
- Large goitre
Pharmacologic Choices
1. Radioactive iodine (131I) to destroy thyroid tissue in patients with Graves
disease, toxic autonomous nodules and toxic multinodular goitres
a. Main risk is inducing hypothyroidism
b. CI in pregnancy
c. Caution in patients with significant ophthalmopathy, or in patients on
corticosteroids
2. Methimazole (MMI)
a. production of thyroid hormones
b. Should stop 5 days prior to thyroid scan, RAIU, or treatment with
radioactive iodine
c. S/E: allergy, rash, agranulocytosis. Rare: hepatoxicity, nephrotoxicity
3. Propylthiouracil (PTU)
a. Blocks conversion of T4 to T3
b. production of thyroid hormones

c. Should stop 5 days prior to thyroid scan, RAIU, or treatment with

radioactive iodine
d. S/E: allergy, rash, agranulocytosis. Rare: hepatoxicity, nephrotoxicity
e. PTU may make thyroid resistant to radioactive iodine
f. If possible avoid PTU in children in favor of methimazole due to
concerns about heptatoxicity
4. Beta-adrenergic blockers
a. Block symptoms of adrenergic excess
b. Used adjunctively in management of Graves disease or toxic nodules
c. Nonselective agents can conversion of T4 to T3.
d. Caution in patients with asthma and obstructive respiratory disorders
5. Iodine
a. Oral Lugols solution
b. IV sodium iodide
c. Blocks thyroid hormone production
d. Can be used to acutely manage severe hyperthyroidism