HYPOTHYROIDIM Made Easy –Through Case Studies, Dr. Sharda jain

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HYPOTHYROIDIM Made Easy – Through Case Studies

DR. SHARDA JAINDr. Jyoti Agarwal Dr. Jyoti Bhasker

Dr. Dipti Nabh


DR. SHARDA JAINDr. Jyoti Agarwal Dr. Jyoti Bhasker

Dr. Dipti Nabh

Dr. Sharda Jain / Dr Jyoti Agarwal Life Care Centre has a over 200 ppt on shildeshare.net

For benefit of Medical fraternity. use it yourself & share among your friends

The thyroid gland is a butterfly-shaped endocrine gland that is normally located in the lower front of the neck

Thyroid Gland

Physiological Function of Thyroid Hormone

• AFFECT GROWTH– Increase in thyroid hormones increases the rate of growth and

vice versa– Promote the growth and development of the brain during

foetal life and infancy– Stimulate carbohydrate metabolism by increasing metabolic

enzyme synthesis– Stimulate fat metabolism by mobilising lipids from the fat

tissue, thereby decreasing the fat stores of the body– Cause increased requirement of vitamins because it increases

many enzymes that have vitamins as an essential

Guyton H. Textbook of Medical Physiology. 2007: 931-943.

Physiological Effects of Thyroid Hormones

• Basal metabolic rate• Body weight• Cardiovascular

system• Blood flow• Cardiac output• Heart rate• Strength of heart

muscle

• Respiration• Gastrointestinal

motility• Central nervous

system• Function of the

muscles• Sleep• Endocrine glands• Sexual functionGuyton H. Textbook of Medical Physiology. 2007: 931-943.

USP of Thyroid Gland

• "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.“

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Laboratory determinations of thyroid function are useful in distinguishing patients with euthyroidism

(normal thyroid gland function) from those with hyperthyroidism (increased function) or

hypothyroidism (decreased function)

Thyroid Function Test

Hypothyroidism Hyperthyroidism

Diseases of Thyroid Gland

Elevated TSH (>4.5 mU/Lhypothyroidism

Low TSH (<4.5 mU/Lhyperthyroidism

Normal range: 0.5 – 4.5mU/L

One of the best thyroid function screening test

TSH : Thyroid – Stimulation Hormone

Hypothyroidism• Decreased T4

Hyperthyroidism• Increased T4

Normal range: 65 – 150nmol/L

T4 : Serum Total Thyroxine

Hypothyroidism• Decreased T3

Hyperthyroidism• Increased T3

Normal range: 1.8 – 3nmol/L

T3: Serum Total Triiodothyronine

Patterns of thyroid function tests during assessment of thyroid function

Source: UpToDate.com.

Serum TSH Serum Free T4 Serum T3 Assessment

Normal hypothalamic-pituitary functionNormal Normal Normal Euthyroid

High Low Normal or low Primary hypothyroidismHigh Normal Normal Subclinical hypothyroidismLow High or normal High HyperthyroidismLow Normal Normal Subclinical hyperthyroidismAbnormal hypothalamic-pituitary function

Normal or high High High TSH-mediated hyperthyroidism

Normal or low* Low or low-normal Low or normal Central hypothyroidism

* In central hypothyroidism, serum TSH may be low, normal or slightly high.

Antithyroid peroxidase antibodies

Used to diagnose suspected Hashimoto’s thyroiditis in

hypothyroidism

Antithyroglobulin antibodies

Used to diagnose autoimmune thyroiditis or Graves’ disease in

hyperthyroidism

Thyroid Antibodies

ULTRASOUND

FNA’C

Radioactive Iodine Uptake

131I used to detect functional derangements of thyroid gland.

About 15 mci of 131I given intravenously

After a few hours, the patient is monitored at the neck region by movable gamma-ray counter, which will pick up

the radiation emitted by thyroid gland

RADIOACTIVE IODINE UPTAKE

Normal response

•About 25% uptake by thyroid within 2 hours•About 50% uptake by thyroid within 24 hours

Abnormal response

•Increased uptake in hyperthyroidism•Decreased uptake in hyporthyroidism

RADIOACTIVE IODINE UPTAKE

Hypothyroidism• 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.

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Cold intolerance, Bradycardia

Depression

Fatigue, Goiter Hyperlipidemia

Weight gain

Dry skin and dry hair,

Myxedema

Menstrual irregularities

Signs & Symptoms of Hypothyrodism

Case Presentation 1• During her routine visit to

doctor,Dr. Lakshmi Devi , an apparently healthy 63-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.

Serum TSH 10 mlU/L(0.3-5.5)

Serum free T4 1.3 ng/dL(0.7-2)

Serum total cholesterol 205mg/dL(150-200)

Serum HDL cholesterol 46 mg/dL(30-60)

Serum LDL cholesterol 150 mg/dl(80-150)

Thyroperoxidase antibodies Positive

• 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 10 mIU/L and 1.4 ng/dL, respectively.

• Diagnosis: Subclinical hypothyroidism (Hashimoto’s thyroiditis)

Serum TSH 10 mlU/L(0.3-5.5)

Serum free T4 1.3 ng/dL(0.7-2)

Serum total cholesterol 205mg/dL(150-200)

Serum HDL cholesterol 46 mg/dL(30-60)

Serum LDL cholesterol 150 mg/dl(80-150)

Thyroperoxidase antibodies Positive

Case Presentation 1

HYPOTHYROIDISM: OVERVIEW, MANIFESTATIONS AND TREATMENT

IN WOMEN

HypothyroidismThyroid gland

• 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

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.

http://www.nlm.nih.gov/medlineplus/ency/article/000353.htm

SECONDARY HYPOTHYROIDISM

• 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

27

1. Ladenson P. Cecil Medicine. 2008:1698-1713.

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.

Cold intolerance, Bradycardia

Depression

Fatigue, Goiter Hyperlipidemia

Weight gain

Dry skin and dry hair,

Myxedema

Menstrual irregularities

Signs & Symptoms of Hypothyroidism

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

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.

Symptoms1,2– Dyspnea– Hoarseness of voice– Hearing Impairment– Carpal tunnel

syndrome– Menorrhagia(miscarri

age)– Paresthesia

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

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.

Clinical Manifestations: Signs

• 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 therapyAACE 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.

• Desiccated thyroid hormone and T3+T4

mixture: Insufficient evidence and not recommended for replacement therapy by the AACE guidelines

Treatment Overview


SUBCLINICALHYPOTHYROIDISM

Subclinical Hypothyroidism: Dr. Lakshmi’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 ie.

I in 20 %• Most common cause: autoimmune

thyroiditis (Hashimoto’s disease)• Predisposing factors

– Advancing age– Greater iodine consumption

• Often asymptomatic • May represent early thyroid failure


Lifecare’s Experience• Infertility – 16%• Recurrent Abortion 18%• Women Population 11%

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

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.

http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf


Subclinical Hypothyroidism

• 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

Dr. Lakshmi's Case: Management

• Dr. Lakshmi was put on LT4 therapy based on the following findings:– Increased TSH – Positive antithyroid

antibodies– Dyslipidemia

• Dosage administered was 50 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


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 T 4 after 4-6 weeks

• Follow up after 6 months and thereafter annually, once TSH is in normal range


Levothyroxine: Dosing• Adjust doses as appropriate in case of

ABSORPTION VARIABILITY & DRUG INTERACTIONS

• Keep in mind that inappropriate dose adjustments can lead to increased costs due to additional patient visits and laboratory tests


Levothyroxine: Drug Interactions• Increase LT4 dose with

– Drugs that reduce thyroxine production: lithium, iodine-containing drugs, and amiodarone

– Drugs that reduce thyroxine absorption: ferrous sulfate, cholestyramine, 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 C1. 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 ActivityWhich of the following agents increase the absorption of LT4?

A. Calcium

B. Furosemide

C. Ferrous sulfate

D. Rifampin

CASE STUDYTHERAPY AND FOLLOW-UP

Dr. Lakshmi's Case: Therapy and FOLLOW-UP

– Serum TSH measurement was repeated after 4 , 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.

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CONCLUSIONS

Thyroid dysfunction is quite prevalent in India, particularly in females Women and men >35 years of age should be screened every 5 years Screening of hypothyroidism is recommended in women suffering from infertility The diagnosis of hypothyroidism must be considered in every patient with depression.All patients with elevated lipid levels should be screened for hypothyroidism .Screening should be done in peri-and post menopausal women to prevent complications of hypothyroidism.

Conclusion of HYPOTHYROIDISM in women

Diagnosis of hypothyroidism is important in adolescence because this condition retards Growth in height and development of secondary sexual characteristics and delayed onset of pubertyIn patients on treatment for both thyroid disorders and diabetes,Thyroid status should be kept in mind while titrating anti - diabetic therapy Increased TSH values are increasingly noted in the elderly population.

Screening should be done I peri -and menopausal women To prevent complications of hypothyroidism

Conclusion

• Maternal hypothyroidism should be avoided by early diagnosis at the first prenatal visit or

At diagnosis of pregnancy to avoid mental retardation to baby .

• Screening of hypothyroidism is recommended within first seven days of birth

Conclusion

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HYPOTHYROIDIM Made Easy –Through Case Studies, Dr. Sharda jain

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