Clinician’s Perspective to Hypothyroidism
Module 2
Copyright © 2011 Abbott India Limited. All rights reserved
"The thyroid gland regulates the metabolic functions of the body in virtually every cell,“ . "Everything from the brain to the skin is affected by the hormone made by the thyroid gland.“
Hypothyroidism "It slows you down,It makes you lethargic and fatigued Your hair becomes brittle, and your skin becomes dry. You become cold much easier than the average person.
2
Case Presentation 1
During her routine visit to doctor, Ayesha, an apparently healthy 70-year-old woman complained of mild fatigue, dry skin, and difficulty in losing weight since last 2 years.
The past medical and surgical history were uneventful.
There was no reported family history of DM/HTN/IHD.
Physical examination results were normal including a non- palpable thyroid gland.
ECG was normal. Fasting and postprandial blood sugar and CBC were within normal limits.
Serum TSH and FT4 tests were repeated 2 weeks after the first visit and were found to be 8.1 mIU/L and 1.4 ng/dL, respectively.
Diagnosis: Subclinical hypothyroidism (Hashimoto’s thyroiditis)
Serum TSH 8.0 mlU/L(0.3-5.5)
Serum free T4 1.3 ng/dL(0.7-2)
Serum total cholesterol220 mg/dL(150-200)
Serum HDL cholesterol46 mg/dL(30-60)
Serum LDL cholesterol 150 mg/dl(80-150)
Serum triglycerides 80 mg/dL(75-150)
Thyroperoxidase antibodies Positive
Hypothyroidism: Overview, Manifestations and Treatment
Hypothyroidism
Condition where there is a reduced production of thyroid hormone1
Categorized as primary and secondary on the basis of its cause
Primary hypothyroidism occurs due to improper functioning of the thyroid gland May be further classified as overt and subclinical
hypothyroidism2,3
Affects approximately 5% of individuals with elderly women being most commonly affected3
Secondary hypothyroidism occurs due to inadequate stimulation of thyroid gland by thyroid stimulating hormone (TSH)
May be due to congenital or acquired defects in the pituitary or hypothalamus
Rare and occurs in less than 1% of individuals3
Thyroid gland
1. Hypothyroidism, Medline Plus. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000353.htm; 2011:1-7.2. Roberts CGP. Lancet. 2004;363: 793-803.3. Ladenson P. Cecil Medicine. 2008:1698-1713.4. AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13
http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
Primary Hypothyroidism: Etiology
Thyroid dysfunction Autoimmune thyroiditis (Hashimoto’s thyroiditis)
Congenital absence or defect in the thyroid tissue
Thyroid removal by surgery
Radio ablation by radio active iodine or irradiation
Destruction of thyroid tissue caused by infiltrative disorders(amyloidosis,sarcoidosis)
Impaired synthesis of thyroid hormone Iodine deficiency----MOST COMMON CAUSE
Congenital enzymatic defects
Drug-mediated: thionamides, amiodarone, lithium, aminoglutethimide,carbemazole
Ladenson P, Kim M. Cecil Medicine. 2008:1698-1713.
Secondary Hypothyroidism: Etiology
Reduced secretion of TRH or TSH Hypothalamic disorders
– Tumor (lymphoma, germinoma, glioma)
– Infiltrative disorders (sarcoidosis, hemochromatosis, and histiocytosis)
Hypopituitarism
– Mass lesions
– Pituitary surgery
– Pituitary irradiation
– Hemorrhagic apoplexy (Sheehan’s syndrome)
– Lymphocytic hypophysitis
Ladenson P, Kim M. Cecil Medicine. 2008:1698-1713.
Clinical Manifestations: Symptoms
Symptoms1,2
Tiredness/ weakness Weight gain with poor appetite Dry skin Cold sensation Hair loss(diffuse alopecia) Nail growth is retarded Poor concentration/memory loss Constipation Dyspnea Hoarseness of voice Hearing Impairment Carpal tunnel syndrome Menorrhagia(miscarriage) Paresthesia1. Ladenson P and Kim M. Cecil Medicine. 2008:1698-1713.
2. Jameson JL, et al. Harrison's Principles of Internal Medicine. 2008: 2224-2247.
Clinical Manifestations: Signs
Signs1,2
Cold peripheral extremities Dry, coarse and yellow skin Puffiness of face, hands and feet Pre tibial non pitting edema Hair loss and brittle nails Bradycardia/ diastolic hypertension Slow relaxation of tendon reflex (woltmans sign) Serous cavity effusions Normal/enlarged/atrophied thyroid gland
Hypothyroidism in children Delayed growth in children and delayed appearance of permanent teeth Delayed or precocious puberty Pseudohypertrophy of muscles
1. Ladenson P and Kim M. Cecil Medicine. 2008:1698-1713.2. Jameson JL et al. Harrison's Principles of Internal Medicine. 2008: 2224-2247.
Laboratory Diagnosis
TSH assay: Primary test to establish the diagnosis
Additional tests: Estimation of free T3 and T4
Test for thyroid autoantibodies
Thyroid scan/ultrasonography
Serum cholesterol- in hypothyroidism
T3/T4
Subclinical hypothyroidism
Overt hypothyroidism
TSH
TSH
AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
T3/T4
Treatment Overview
Goal: To mimic normal, physiological levels and alleviate signs, symptoms, and biochemical abnormalities
Treatment should be tailored to individual needs
Treatment of choice:Levothyroxine (LT4) replacement therapy
Desiccated thyroid hormone and T3+T4
mixture: Insufficient evidence and not recommended for replacement therapy by the AACE guidelines
AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
Subclinical Hypothyroidism
Subclinical Hypothyroidism: Ayesha’s Case
Criteria defining subclinical hyperthyroidism:
Slightly elevated serum TSH levels
FT4 and T3 levels within the reference range
Affects 1-10% of adults, with greater prevalence in women
Most common cause: autoimmune thyroiditis (Hashimoto’s disease)
Predisposing factors
Advancing age
Greater iodine consumption
Often asymptomatic
May represent early thyroid failure
AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
Subclinical Hypothyroidism: Management Algorithm
1. Col NF, et al. JAMA 2004; 291:239-243. 2. Surks MI, et al. JAMA 2004;291:228-238.
Algorithm for the management of subclinical hypothyroidism (T4 = thyroxine: TSH = thyrotropin-stimulating hormone)
Serum TSH >4.5 mU/L
Repeat Serum TSH Measurement with FT4
Measurement 2 to 12 Weeks Later
Serum TSH Level within Reference Range
(0.45 to 4.5 mlU/L)?
Serum TSH Level 4.5 to 10mlU/L
Monitor Every 6 to 12 mo for Several Years
Serum TSH Level > 10mlU/L
Signs or Symptoms Consistent with
Hypothyroidism?
FT4 Level Decreased
(<0.8 ng/dL)?
Treat with Levothyroxine*
Pregnant or Contemplating
Pregnancy?
Consider Levothyroxine Treatment with Periodic
MonitoringMonitor Serum TSH
Every 6 to 12 mo
FT4 Level Decreased
(<0.8 ng/dL)?
Treat with Levothyroxine*
Pregnant or Contemplating
Pregnancy?
Consider Levothyroxine Treatment in Appropriate
Clinical Settings
Yes No Yes No
Yes NoNoYes
Yes No
No Yes
1. TSH: Thyroid stimulating hormone2. FT4: Free Thyroxine3. Mo: Months
Rule out hypopituitarism
Subclinical Hypothyroidism Dosing and Monitoring1,2
Always start with a small dose to prevent risk of Atrial Fibrillation Dose of LT4: 25-50 mcg/day (reduced dose in elderly and in patients with
heart disease) Adjustment in dosage is made in 12.5-25µg inc or dec Serum TSH levels to be measured 6-8 weeks after starting treatment or
after a change in the dosage Target TSH levels: 0.3-3.0 µIU/mL Annual examination after achieving stable TSH levels
Progression to overt hypothyroidism1
Occurs in 3-20% patients Patients with goiter and thyroid antibodies at higher risk for progression
Associated risks1
Progression to overt hypothyroidism Cardiovascular effects Hyperlipidemia Neuropsychiatric effects
1. AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13. \http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.2. Shah SN, Joshi SR. Journal of the Association of Physicians of India. 2011;59(Supplement):1-68.
Learning Activity
Learning Activity
All of the following statements related to subclinical hypothyroidism are true, EXCEPT:
A. The most common cause of subclinical hypothyroidism is Hashimoto’s disease.
B. Subclinical hypothyroidism is more common in women.
C. Subclinical hypothyroidism is characterized by elevated levels of TSH and free T4.
D. Subclinical hypothyroidism may represent early thyroid failure.
Case Study
Ayesha's Case: Management
Ayesha was put on LT4 therapy based on the following findings: Increased TSH Positive antithyroid
antibodies Dyslipidemia
Dosage administered was
30 mcg/day. She was asked to visit
again for follow-up after 8 weeks
Levothyroxine
Levothyroxine
Synthetic T4 identical to that produced in the human thyroid gland
Indications: Hypothyroidism: All types Pituitary TSH suppression
– Euthyroid goiters– Thyroid nodules– Subacute or chronic lymphocytic
thyroiditis (Hashimoto’s thyroiditis)
– Adjunct to surgery and radioiodine therapy in the management of thyroid cancer
Synthroid PI,Abbott. 2008
Levothyroxine: Important Facts
Levothyroxine sodium has a narrow therapeutic range
Regardless of indication of use, careful dose titration is necessary to avoid consequences of over- or under- treatment
Even small changes in the dose of LT4 can shift a patient from a euthyroid to a hyperthyroid or hypothyroid state.
The AACE recommends the use of a high-quality brand preparation of levothyroxine
Same brand of LT4 should be received throughout treatment
AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
Levothyroxine: Dosing
Recommended mean daily dose of LT4 therapy: 1.6 mcg/kg of body weight
Initiate with 12.5 mcg daily to a full replacement dose of LT4 depending on age, weight, and cardiac status
Reassess TSH and/or free T4 after 6 weeks Follow up after 6 months and thereafter annually, once
TSH is in normal range Adjust doses as appropriate in case of absorption
variability and drug interactions Keep in mind that inappropriate dose adjustments can
lead to increased costs due to additional patient visits and laboratory tests
AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
Levothyroxine: Drug Interactions
Increase LT4 dose with Drugs that reduce thyroxine production: lithium, iodine-containing
drugs, and amiodarone
Drugs that reduce thyroxine absorption: sucralfate, ferrous sulfate, cholestyramine, colestipol, aluminum-containing antacids, and calcium supplements
Drugs that increase thyroxine metabolism: rifampin, phenobarbital, carbamazepine, warfarin, and oral hypoglycemic agents
Decrease LT4 dose with Drugs that displace thyroxine from binding proteins: furosemide,
mefenamic acid, salicylates, vitamin C
1. Hueston WJ. Treatment of Hypothyroidism. American family physician. 64(10): 1717-1724.2. AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13
http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
Learning Activity
Learning Activity
Which of the following agents increase the absorption of LT4?
A. Calcium
B. Furosemide
C. Ferrous sulfate
D. Rifampin
Case Study 1
Ayesha's Case: Therapy and Follow-up
Follow-up
Serum TSH measurement was repeated after 8 weeks of commencing the treatment. They had fallen to 1.2 mIU/mL and remained within the range of 1 to 1.5 mIU/mL on consecutive visits.
She was asked to stay on the treatment and follow up after1 year.
After 1 year of treatment, she had lost weight and was asymptomatic. On investigation, her serum cholesterol and low-density lipoprotein (LDL) cholesterol levels were 190 and 100 mg/dL, respectively.
Case Study 2
Case Presentation: 2
Patient Shobha, a 32-week pregnant 30-year-old woman
presents premature labor Inappropriate weight gain for gestational age Cold intolerance during past few months
Past medical history She was diagnosed with hypothyroidism at the
age of 20 She was on LT4 therapy Last dose modification was 2 years back after which
she continued on same dose.
Case Presentation: 2 (Continued)
Physical Examination Weight : 100 kg Pulse Rate: 68 per minute BP: 140/90 mm Hg Facial puffiness Skin: Cold, Dry Deep tendon reflexes,: Slow relaxation
Thyroid Function Tests Serum TSH: 11 mIU/L Free T4: 1.2 pmol/L
Fetal Examination Fetal distress in labour
Outcome of Pregnancy She delivered a preterm low birth weight male.
Maternal Hypothyroidism
32
Maternal Hypothyroidism
One of the most common endocrine disorders in pregnancy1
Overt hypothyroidism found in 1.3 per 1000 pregnant women and subclinical hypothyroidism in 23 per 1000 pregnant women1
Most common cause: endemic iodine deficiency2
Women with hypothyroidism carry an increased risk of infertility, miscarriage, and obstetric complications1
Foetal complications: premature birth, low-birth weight (LBW), fetal distress in labor, fetal death, perinatal death, and congenital hypothyroidism1
Even an untreated subclinical hypothyroidism during pregnancy can lead to cognitive impairment in the offspring.3
1. Sahu MT, et al. Arch.Gynaecol. Obstet. 2010;218:215-220.2. Lazaras JH. British Medical Bulletin. 2010;1-12.3. AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13
http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
Thyroid Physiology in Pregnancy
Decreased TSHDecreased TSH
PlacentaPlacenta hCGhCG
Increased TH degradation
Increased TH degradation
Thyroid stimulation for increased TH
Production
Thyroid stimulation for increased TH
Production
EstrogenEstrogen
Increased serum TBG
Increased serum TBG
Increased hepatic production of TBGIncreased hepatic production of TBG
Increased half life of TBG
Increased half life of TBG
Type 3 deiodinaseType 3 deiodinase
Stimulates TSH receptorStimulates TSH receptor
Decreased free THDecreased free TH
Stimulation of hypothalamic pituitary axis
Stimulation of hypothalamic pituitary axisIncreased serum THIncreased serum TH
hCG: Human chorionic gonadotropinTSH: Thyroid stimulating hormoneTH: Thyroid hormoneTBG: Thyroxine-binding globulin
Increased oestrogen in pregnancy
Two- to threefold
increase in TBG
Decrease Free T3 and T4
Similar structure of hCG and TSH
hCG stimulates
release of T3 and T4
Transient TSH decrease in
weeks 8 to 14
Increased peripheral
metabolism of T3 and T4
Decrease Free T3 and T4
Thyroid Physiology in Pregnancy
1. Jameson JL. Harrison's Principles of Internal Medicine. 2008:2224-2247.2. Lazarus JH. Br Med Bull.2010;1-12.3. Galofre JC, Davies TF. J Womens Health (Larchmt). 2009;18(11):1847-1856..
0
50
75
100
125
150
0
0.5
1.5
2.5
3.5
4.5
40 8 12 16 20 24 28 32 36 40
TS
H (
mU
/L)
hC
G (
IU/m
L
hCG
TSH
Weeks of gestation
0
1.5
2.0
2.5
3.0
3.5
0
5
10
15
20
25
40 8 12 16 20 24 28 32 36 40
TT
4 (m
cg/d
L)
TB
G (
mg
/dL
)
TBG
Total T4
Weeks of gestation
0.2
0.6
1.0
1.4
1.8
160
220
280
340
400
40 8 12 16 20 24 28 32 36 40
FT
3 (p
g/d
L)
FT
4 (n
g/d
L)
Free T4
Free T3
Weeks of gestation
A
B CTBG: Thyroxine- binding globulinTSH: Thyroid stimulating hormoneHCG: Human chorionic gonadotropinTT4: Total thyroxineFT3: Free triiodothyronineFT4: Free thyroxine
Thyroid Function Tests in Pregnancy
FT4, Free thyroxine; FT3, Free triiodothyronine; TSH, Thyroid stimulating hormone
Referral Values for TFT in Pregnant Indian Women1,2
Thyroid Hormone
Normal Values in Nonpregnant
Trimester Range (5th-95th Percentile)
FT33.7-7.2 pM/L(240.26-467.53
pg/dL)
I 1.92-5.86 pM/L (124.68-380.51 pg/dL)
II 3.2-5.73 pM/L (207.8-372 pg/dL)
III 3.3-5.18 pM/L (214.3-336.36 pg/dL)
FT412-23 pM/L (0.93-1.79
ng/dL)
I 12-19.45 pM/L (0.93-1.51 ng/dL)
II 9.48-19.58 pM/L (0.74-1.521 ng/dL)
III 11.32-17.7 pM/L (0.88-1.38 ng/dL)
TSH 0.27-4.2 µIU/mL
I 0.6-5.0 µIU/mL
II 0.44-5.78 µIU/mL
III 0.74-5.7 µIU/mL
1. Marwaha RK. BJOG. 2008;115(5):602-606.2. SI Units for Clinical Data. University of North Carolina.
Maternal Hypothyroidism
AACE recommendations
Carry out TSH assay routinely before pregnancy or during the first trimester to rule out thyroid disorder
Avoid complications by administering thyroid hormone replacement therapy
Both mild as well as overt hypothyroidism are managed by administering levothyroxine therapy which can be safely administered during pregnancy
Assess TSH levels every 6 weeks during pregnancy for appropriate dose adjustments
Increase the dose of thyroid hormone in pregnant women with moderate to severe hypothyroidism
AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
Maternal Hypothyroidism
Preconception: Optimize therapy in patients with preexisting disease
Pregnancy confirmed: Increase dose by 30-50% of preconception dose
Target levels
TSH<2.5 mIU/L in the first trimester
TSH<3 mIU/L in later pregnancy
After delivery, reduce dose to preconception dose
Assess thyroid function at 6 weeks postpartum
Post-ablative and post-surgical hypothyroidism require higher dose
Lazaras JH. British Medical Bulletin. 2010;1-12.
Learning Activity
Women with hypothyroidism carry an increased risk of ______.
A. Infertility
B. Miscarriage/spontaneous abortion
C. Maternal hypertension
D. All of the above
Case Presentation II: Congenital Hypothyroidism
The baby delivered by Shobha was apparently normal.
Findings on neonatal examination are within normal limits
Neonatal screening for congenital hypothyroidism on the 3rd day by cord blood
TSH: 38 mIU/L
Serum free T4: 0.5 ng/dL
Diagnosis: Congenital Hypothyroidism
Congenital Hypothyroidism
41
Congenital Hypothyroidism
Abnormality in the development of thyroid gland (dysgenesis or agenesis) and defect in the biosynthesis of thyroid hormones
Prevalence rate 1 in 4000 newborn infants in regions of sufficient daily iodine intake
2:1 incidence in females compared with males
Causes: Endemic iodine deficiency, genetic mutation, and hemangiomas
Routine thyroid function screening in neonates is recommended since no apparent clinical manifestation
Untreated congenital hypothyroidism results in development of cretinism
Do not delay diagnosis of congenital hypothyroidism until physical manifestations are seen Mental retardation
Deafness
Short stature
Characteristic facial deformities
Roberts CGP et al. Lancet. 2004;363: 793-803.
Congenital Hypothyroidism: Clinical Features
Roberts CGP et al. Lancet. 2004;363: 793-803.
Infants Children and Adolescents
Hypothermia Growth failure
Poor feeding Markedly delayed bone maturation
Bradycardia Delayed eruption of permanent teeth
Jaundice Muscle pseudohypertrophy
Enlarged posterior fontanel Delayed or precocious puberty
Umbilical hernia Pituitary enlargement
Galactorrhoea
Rastogi and LaFranchi. Orphanet Journal of Rare Diseases 2010,5:17;1-22.
DIAGNOSTIC ALGORITHM
Screen the newborn for hypothyroidism:Initial T4 <10%, TSH ↑
Or Initial TSH ↑Clinical suspicion of hypothyroidism
Measure serum TSH andfree T4 (or T4 and T3 resin uptake)
TSH ↑(>9 mU/L)Free T4 ↓ (<0.6 ng/dL)
Diagnosis primary CH confirmed
TSH ↓ or normal (<9 mU/L)Free T4 ↓ (<0.6 ng/dL)
Diagnosis likely secondary(central) hypothyroidism
Other diagnostic tests todetermine etiology (optional):•Radionuclide uptake and scan•Ultrasonography•Serum thyroglobulin•Maternal antithyroid antibodies•Urinary iodine
• Isolated: TSHβ gene analysis• Evaluate for other pituitary hormone
deficiencies• MRI of brain• Eye exam to check for optic nerve
hypoplasia
Diagnosis Of Congenital Hypothyroidism
TSH: Thyroid stimulating hormoneT4: ThyroxineT3: TriiodothyronineFree T4: Free thyroxineTSHβ: Thyroid stimulating hormone beta
Congenital Hypothyroidism Case: Follow Up
Initial work-up for Shobha’s child
The baby was referred to pediatric endocrinologist
Thyroid ultrasonography showed a normal thyroid gland.
Management
The baby was started on LT4 at an initial daily dose of 50 mcg
The serum T4 normalized in 3 days
TSH normalized by end of 2 weeks
The mother was asked to follow-up with the baby on monthly basis.
Management of Congenital Hypothyroidism
Goal: To normalize T4 within 2 weeks and TSH within 1 month
Assess permanence of congenital hypothyroidism If initial thyroid scan shows ectopic/absent gland, congenital
hypothyroidism is permanent
If initial TSH is <50 mIU/L and there is no increase in TSH after newborn period, off- therapy period is recommended at 3 years of age
If TSH increases during the off-therapy period, consider the condition as permanent congenital hypothyroidism
Medications: LT4: 10-15 g/kg by mouth once-daily
Monitoring: Recheck T4 and TSH At 2-4 weeks after initiation of LT4 treatment
Every 1-2 months in the first 6 months
Every 3-4 months between 6 months and 3 years of age
Every 6-12 months from 3 years of age to end of growth
Rose SR and Brown RS. Pediatrics. 2006;117(6):2290-2303.
Learning Activity
All of the following signs represent congenital hypothyroidism, EXCEPT
A.Tachycardia
B.Jaundice
C.Enlarged posterior fontanel
D.Umbilical hernia
Comorbid Conditions
48
Comorbid Conditions
1. AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
2. Duntas LH, Biondi B. Semin Thromb Hemost. 2011;37(1):27-34.
Comorbid Conditions (Contd.)
Diabetes mellitus Hashimoto’s thyroiditis may be associated with 10% patients of type
1 diabetes mellitus Approximately one-fourth of female patients with type 1 diabetes
mellitus develop postpartum thyroiditis AACE recommendations for patients with diabetes mellitus
Examine for goiter Assess TSH levels regularly especially in the presence of a goiter or
other autoimmune disorders
Infertility Hypothyroidism due to chronic thyroiditis may cause infertility,
miscarriage, and menstrual irregularities Treatment with LT4 replacement therapy restores normal menstrual
cycle and fertility
AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
Comorbid Conditions (Contd.)
Depression
In every patient with depression, diagnosis of overt or subclinical hypothyroidism should be considered
Periodic evaluation for thyroid function should be performed in patients receiving lithium therapy
Treatment is with LT4 replacement therapy
LT4 is indicated occasionally in combination with antidepressants in euthyroid patients with depression
AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.
Comorbid Conditions (Contd.)
Dyslipidemia and cardiovascular sequelae comorbid with overt hypothyroidism Overt hypothyroidism with dyslipidemia is characterized by
Increased levels of total cholesterol Increased LDL cholesterol
Mechanisms for dyslipidemia Impaired production of TC and Decreased expression of the LDL receptors
Severe cardiovascular disease and premature atherosclerosis, if untreated, lead to
Pericardial effusion Congestive heart failure Coronary artery disease
Duntas LH, Biondi B. Semin Thromb Hemost. 2011;37(1):27-34
Comorbid Conditions (Contd.)
Cardiovascular sequelae comorbid with subclinical hypothyroidismSubclinical hypothyroidism is associated with
– Impaired diastolic function and depressed left ventricular systolic function in middle-aged patients
– Increased risks of atherosclerosis and myocardial infarction
– Mortality in patients less than 65 years of age due to cardiovascular events
– Proatherogenic mechanisms that leads to low-grade inflammation and may suggest CVD
– Hypercoagulable stateLT4 therapy for subclinical hypothyroidism
– Reverses cardiovascular alterations – Reduces cardiovascular risk factors– Improves dyslipidaemia– Minimizes neurobehavioral changes
Duntas LH, Biondi B. Semin Thromb Hemost. 2011;37(1):27-34
The Cycle of Disease
SubclinicalHypothyroidism
Emerging Risk
Factors CVD
Endothelial Dysfunction
Cardiac Alterations
Blood Pressure
Hyperlipidemia
Hemostatic Balance
Obesity
CVD: Cardiovascular disease
Learning Activity
Learning Activity
Which of the following statements are TRUE regarding LT4 therapy in hypothyroidism? (Select all that apply.)
A.Congenital hypothyroidism is treated with LT4 at a dose of 50-100 mcg/kg orally once-daily.
B.LT4 therapy for subclinical hypothyroidism reverses cardiovascular alterations.
C.LT4 is contraindicated in combination with antidepressants in euthyroid patients with depression.
D.Both mild as well as overt hypothyroidism are managed by administering levothyroxine therapy.
Thank You
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