Transcript M3lip-thyroid907

Thyroid Disorders and
Hyperlipidemia
Uzma Khan M.D.
Division of Endocrinology
HYPOTHYROIDISM
•Results from
inadequate thyroid
hormone
•Since thyroid hormone
is necessary for growth
and metabolism, the
manifestations are
diverse
Causes of Hypothyroidism:
Primary Hypothyroidism
Congenital:
Thyroid dysgenesis
Iodine deficiency
Acquired
Iatrogenic including
radioiodine and surgery
Hashimoto’s thyroiditis
Reidel’s thyroiditis
Infiltrative diseases
(amyloidosis)
Central Hypothyroidism
Pituitary lesions ( secondary
hypothyroidism)
Hypothalamic lesions( tertiary
hypothyroidism)
TSH
Subclinical
T4
N
T3
N
Mild
N or
N or
overt
Treatment of hypothyroidism
Levothyroxine (LT4) is used
TSH checked in 8-12 weeks after starting
LT4 to allow for stabilization of thyroid
hormone levels
Once TSH normalized, it should be
assessed every 6 to 12 months by an
appropriate physical exam and laboratory
tests.
Hyperthyroidism
Grave’s disease ( 80%)
Thyrotoxicosis factitia
Toxic multinodular goiter
Toxic adenoma
Thyroiditis
Hyperemesis gravidarum
Struma ovarii
Grave’s Disease
An autoimmune disease with a female to
male ratio of about 3.5:1.
specific manifestations include
– ophthalmopathy
– pretibial myxedema
– acropachy
TSH is suppressed, Free T4 is elevated
and specific Thyroid antibodies are
elevated
Grave’s Ophthalmopathy
•Photophobia, eye irritation and diplopia
•Periorbital edema and chemosis
•Proptosis with lid lag
•Impaired eye movements, especially convergence
Utility of Radioactive Iodine Uptake (RAIU)
RAIU
RAIU
Grave’s
Thyroiditis
Toxic MNG
Exogenous
Toxic adenoma Iodine
ingestion
Hyperemesis
Struma
gravidarum
ovarii
Trophoblastic Metastatic
tumor
thyroid Ca
Treatment
Thionamide drugs
• propylthiouracil and methimazole
• inhibit thyroid hormone synthesis
• Side effects include agranulocytosis
and hepatic dysfunction
Radioiodine Therapy
• Most commonly used treatment in the USA
• May lead to hypothyroidism
• “Radiation thyroiditis” is uncommon
• May exacerbate Grave’s opthalmopathy
Surgery
• Reserved for patients who refuse other options
• Have nodules suspicious for cancer
LIPIDS
The main lipids in human plasma are free cholestrol,
cholestrol ester, triglyceride and phospholipid
Nonpolar lipids are carried as lipoproteins in plasma
Lipoproteins:
-central core of cholesterol esters
And triglycerides
-surface monolayer of polar lipids;
-unesterified cholestrol
and phospholipids, and apoproteins
Apoproteins are proteins that help direct
the metabolism of lipids in the body
Unesterified
cholestrol
Cholestrol ester
triglycerides
apoprotein
phospholipids
Lipoprotein classes
There are seven classes of lipoproteins
–
–
–
–
–
–
–
Chylomicrons
Chylomicron remnants
VLDL
IDL
LDL
HDL
Lp(a)
CASE 1
38 year old man
Father died of MI at
age 53
Brother has PVD, and
had a stent placed
Lipid profile:
–
–
–
–
TC: 380 mg/dl
Trig: 315 mg/dl
HDL: 35 mg/dl
LDL : 58 mg/dl
Dysbetalipoproteinemia: (Type III)
High IDL due to abnormal Apo E on remnant
particles
Tuberous or tuboeruptive xanthomas on elbows,
knees and knuckles, and palmer xanthomas
high risk for premature atherosclerosis,
especially PVD
Responds very well to treatment, including diet
CASE 2
35 yo male, admitted
with an MI
Father died at age 50
of MI
Lipid profile:
–
–
–
–
TC: 380 mg/dl
Trig:135 mg/dl
LDL:280 mg/dl
HDL: 35 mg/dl
Familial Hypercholestrolemia: (Type IIa)
High LDL due to disrupted LDL receptor function
Hypercholesterolemia from birth, Total
cholesterol ranges from 300-600 mg/dl in
heterozygotes, LDL is > 250 mg/dl,
In homzygotes TC is 600-1000 mg/dl, LDL >500
– Rare, 1/ million---about 250 people in the US
Accelerated atherosclerosis, Can present with
myocardial infarctions in 30-40 years of age
Treatment is with high dose statins, often in
combination with bile acid binding resins and
niacin
CASE 3
45 yo male admitted with
abdominal pain
History of pancreatitis,
and “borderline diabetes”
Lipid Profile today:
– TC:310 mg/dl
– Trig:1200 mg/dl
But 2 months ago:
–
–
–
–
TC: 275 mg/dl
TG: 480 mg/dl
LDL:----HDL:24 mg/dl
Hypertriglyceridemia (Type 1)
High Triglycerides ( usually > 1000 mg/dl)
– Familial Lipoprotein Lipase Deficiency
– Familial Apo C-II deficiency( Type I)
Recurrent episodes of abdominal pain,
pancreatitis, hepatosplenomegaly,
malabsorption and diabetes mellitus
After overnight refrigeration a milky white layer is
visible
Treatment: low fat diet, Fibric acid derivatives
Prevent exacerbation by avoiding alcohol, oral
estrogen, diuretics and beta blockers, and
controlling Diabetes
Secondary Dyslipidemias
cholesterol
triglyceride
HDL
Alcohol
High
High
Diabetes, type 2
High
Low
High
low
Hypothyroidism
High
Nephrotic syndrome High
Thiazides
High
What about low HDL
Secondary Causes of low HDL:
–
–
–
–
–
–
–
Elevated triglycerides
Obesity
Physical inactivity
Type 2 diabetes
Cigarette smoking
Very high carbohydrate intake ( > 60% energy)
Certain drugs: b-blockers, anabolic steroids,
progestational agents, thiazides
Case 4: What does he
have ?
61 years old white obese male,
smoker, hypertensive wants your
advise about abnormal labs
father died at age 62 of his second Myocardial
Infarction
Lab results:
Fasting glucose is 130 mg/dl
Fasting Lipid profile shows: cholesterol 240 mg/dl,
LDL 141 mg/dl, HDL 33 mg/dl and triglycerides of
271 mg/dl
Familial combined hyperlipidemia
(type IIb and III)
Common polygenic dyslipidemic disorder
Associated with increased risk of cardiovascular
disease
Cholesterol is usually > 250 mg/dl and
triglycerides > 175 mg /dl
Patients may have different lipoprotein
phenotypes at different times which may be
related to diet, exercise or medications
How will you decide his treatment?
– Lab results:
Fasting glucose is 130 mg/dl
Fasting Lipid profile shows: cholesterol 223 mg/dl, LDL
148 mg/dl, HDL 33 mg/dl and triglycerides of 209 mg/dl
Given his lipid profile, the first step is :
–
–
–
–
–
Lower LDL
Lower HDL
Lower triglycerides
Reduce non-HDL
Recheck in 3 months
ATP III
Non-HDL goal:
LDL goals:
–CHD or CHD Eq <100
–Non-HDL=TC – HDL
–2 + Risk factors < 130
–For patients with Trig > 200, LDL is the
primary goal, non-HDL is the secondary
goal
–< 2 risk factors
–Goal non-HDL= LDL goal + 30
70 –optional
– ? Low limit of LDL
–50-70 mg/dl
< 160
HDL:
–If > 60---negative risk factor
–< 40 in men, < 50 in women—consider Tx
New medications
-Ezetimibe (Zetia) is a new class of drugs that decreases
absorption of cholesterol and causes significant decreases in lDL
-Can be used in combination with statins
Action of Statins
Mean ({+/-}SE) Intima-Media Thickness of the Carotid Artery during 24 Months of Therapy
Kastelein J et al. N Engl J Med 2008;358:1431-1443
Estimated Cumulative Risk of Myopathy Associated with Taking 80 mg of Simvastatin Daily,
According to SLCO1B1 rs4149056 Genotype
The SEARCH Collaborative Group. N Engl J Med 2008;359:789-799
Three months later-----– Lab results:
Fasting glucose is 136 mg/dl
Fasting Lipid profile shows: cholesterol 185 mg/dl, LDL 92
mg/dl, HDL 33 mg/dl and triglycerides of 230 mg/dl
Given his lipid profile, the first step is :
–
–
–
–
–
Lower LDL
Lower HDL
Lower triglycerides
Reduce non-HDL
Recheck in 3 months
New medications
-Omega-3- acid (Lovaza) :lowers triglycerides, as much as 45
% -especially in people with TG > 500 mg/dl
-Can be used in combination with statins
So you advise him:
-lose weight,
-walk 30 minutes daily
-quit smoking
-Check him out for
diabetes
-Treat the dyslipidemia
-Continue follow up and
education
-Remember his family!!!