Module 3: Diagnosis and Management of Hypothyroidism

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CME module 3

Diagnosis and Management of Hypothyroidism

Dear Doctor,

Welcome to the online CME module 3 on Diagnosis and Management of Hypothyroidism.

This CME module will present diverse scientific information to promote better understanding of hypothyroidism.

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  • Introduction

    • Hypothyroidism

    • Symptoms

    • Prevalence

    • Subclinical hypothyroidism

  • Diagnosis

    • Thyroid stimulating hormone (TSH) test

    • Free thyroxine (FT4) in serum

  • Evaluation for Suspected Hypothyroidism

  • Treatment

    • Levothyroxine

    • Levothyroxine Dosing Guidelines for Hypothyroidism

  • American Thyroid Association Guidelines

In this module, we will be presenting clinical features, diagnostic and therapeutic considerations of hypothyroidism with focus on special treatment groups, and recent guideline recommendations.

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Hypothyroidism1

Hypothyroidism is a failure of the thyroid gland to produce sufficient thyroid hormone to meet the metabolic demands of the body.

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Causes of primary hypothyroidism2

  • Chronic autoimmune thyroiditis

  • Iodine deficiency or excess

  • Thyroidectomy

  • Therapy with radioactive iodine

  • External radiotherapy

  • Drugs

  • Thyroid agenesis or dysgenesis

Primary gland failure resulting in decreased synthesis and secretion of thyroid hormones can occur due to multiple causes. These include:

  • Chronic autoimmune thyroiditis

  • Iodine deficiency or excess

  • Thyroidectomy

  • Therapy with radioactive iodine

  • External radiotherapy

  • Drugs

  • Thyroid agenesis or dysgenesis

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Causes of secondary (Central) hypothyroidism2

PituitaryHypothalamus

Pituitary adenomas

Hypothalamic or suprasellar tumors

History of pituitary surgery or radiotherapy

History of hypothalamic surgery or radiotherapy

History of head trauma

History of pituitary apoplexy

Secondary or central causes of hypothyroidism occur due to disorders of the pituitary or the hypothalamus that reduce secretion of TSH and thyroid hormone secretion from the thyroid gland.

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Common Symptoms of hypothyroidism1

Hypothyroidism is characterized by non-specific symptoms such as weight gain, fatigue, poor concentration, depression, menstrual irregularities, constipation, cold

intolerance, dry skin, and

hair thinning or loss

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Hypothyroidism is prevalent in 11% of Indian population3 and 4-5% worldwide.4

Of which, 13.1% Indian patients are between the age of 46–54 years, while only 7.5% patients belong to the age group 18–35 years.3

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Subclinical hypothyroidism

Subclinical hypothyroidism is characterized by the general absence or minimal symptoms associated with hypothyroidism,2 but elevated serum TSH levels and normal levels of serum free thyroxine.

It is prevalent in 3-8% of population with thyroid disease.5

The prevalence is also higher in the elderly and women.5

Diagnosis of subclinical hypothyroidism is done solely on the basis of TSH measurement with a normal free thyroxine and the absence of clinical findings of hypothyroidism.2

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Diagnosis of hypothyroidism2

The most common laboratory examinations for diagnosis of hypothyroidism and for differential diagnosis between primary and secondary one are measurement of TSH and FT4

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The levels of TSH and FT4 help in classifying hypothyroidism.1,2

Primary hyperthyroidism presents with high TSH and low or normal FT4

Subclinical hypothyroidism occurs when TSH is increased and FT4 is normal.

When TSH is normal or low and FT4 is low, it is secondary hypothyroidism.

Guideline recommendations for Treatment of hypothyroidism6

Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid AssociationTask Force on Thyroid Hormone Replacement

Key objectives:

  • Review the goals of levothyroxine therapy

  • Optimal dosage of levothyroxine therapy

  • Sources of dissatisfaction with levothyroxine therapy Treatment alternatives

  • Relevant knowledge gaps

Guideline recommendations for Treatment of hypothyroidism

In 2014, American Thyroid Association (ATA) has proposed recommendations to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps.

We will now present key recommendations of the 2014 Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement

Levothyroxine monotherapy is considered the standard of care for hypothyroidism6

Recommended choice for the treatment of hypothyroidism due to:

  • Efficacy in resolving the symptoms of hypothyroidism

  • Long-term experience of its benefits

  • Favorable side effect profile

  • Ease of administration

  • Good intestinal absorption

  • Long serum halflife

  • Low cost

Levothyroxine is recommended as the preparation of choice for the treatment of hypothyroidism due to its efficacy in resolving the symptoms of hypothyroidism, long-term experience of its benefits, favorable side effect profile, ease of administration, good intestinal absorption, long serum halflife, and low cost.

What is the best approach to initiating and adjusting levothyroxine therapy?6

Initial dose: 1.6 µg per kg per day in the morning, 60 minutes before eating

Maintenance dose: Increased to 12.5-25 µg every 4 to 6 weeks

What is the best approach to initiating and adjusting levothyroxine therapy?

Levothyroxine is given at an initial dose of 1.6 µg per kg per day in the morning, 60 minutes before eating.

Adjust the dose of levothyroxine to 12.5-25 µg increments every 4 to 6 weeks, based on results of the TSH test.

How should levothyroxine administration be timed with respect to meals and beverages?6

Levothyroxine must be consistently taken either:

  • 60 minutes before breakfast or

  • At bedtime (3 or more hours after the evening meal)

How should levothyroxine administration be timed with respect to meals and beverages

in order to maintain maximum, consistent absorption?

Because co-administration of food and levothyroxine is likely to impair levothyroxine absorption, we recommend that, if possible, levothyroxine be consistently taken either 60 minutes before breakfast or at bedtime (3 or more hours after the evening meal) for optimal, consistent absorption.

What factors determine the levothyroxinedose required by a hypothyroid patientfor reaching the appropriate serum TSH goal?6

Factors to be considered include:

  • Patient’s weight

  • Lean body mass

  • Pregnancy status

  • Etiology of hypothyroidism

  • Degree of thyrotropin elevation

  • Age

  • General clinical context, including the presence of cardiac disease

What factors determine the levothyroxinedose required by a hypothyroid patientfor reaching the appropriate serum TSH goal?

When deciding on a starting dose of levothyroxine, the patient’s weight, lean body mass, pregnancy status, etiology of hypothyroidism, degree of thyrotropin elevation, age, and general clinical context, including the presence of cardiac disease, should all be considered.

Levothyroxine Dosing Guidelines for Hypothyroidism in special populations1

How should levothyroxine therapy be managed in the elderly with hypothyroidism?

  • Normal serum thyrotropin (TSH) ranges are higher in older populations

  • Higher serum TSH targets may be appropriate

How should levothyroxine therapy be managed in the elderly with hypothyroidism?

It should be recognized that normal serum thyrotropin ranges are higher in older populations (such as those over 65 years), and that higher serum thyrotropin targets may be appropriate.6

Levothyroxine Dosing Guidelines for Hypothyroidism in special populations1

Subclinical hypothyroidism

Levothyroxine in recommended in following conditions:

  • Initial TSH levels greater than 10 mIU/L

  • Patients with significantly elevated thyroid peroxidase antibody titers

  • Patients with symptoms suggestive of hypothyroidism

  • Patients who are pregnant or are attempting to conceive

Recommended dosage

  • TSH < 10 mIU per L: 50 mcg daily, increase by 25 mcg daily every six weeks until TSH = 0.35 to 5.5 mIU per L

  • TSH ≥ 10 mIU per L: 1.6 mcg per kg per day

It is recommended to treat subclinical hypothyroidism with levothyroxine in following conditions:

  • When initial TSH levels are greater than 10 mIU/L

  • Patients with significantly elevated thyroid peroxidase antibody titers

  • Patients with symptoms suggestive of hypothyroidism

  • Patients who are pregnant or are attempting to conceive

When TSH level is <10 mIU per L, it is recommended to administer 50 mcg daily and then increase by 25 mcg daily every six weeks until TSH level reaches 0.35 to 5.5 mIU per L.

When TSH level is ≥10 mIU per L, it is recommended to administer 1.6 mcg per kg per day

How should levothyroxine therapy be managedin pregnant women with hypothyroidism?6

  • Levothyroxine replacement therapy with the dose titrated to achieve a thyrotropin concentration within the trimester specific reference range

  • Assess the serial serum thyrotropin levels every 4 weeks during the first half of pregnancy

  • Reassess serum thyrotropin during the second half of pregnancy

  • Initiate two additional doses per week of the current levothyroxine dose, given as one extra dose twice weekly in women already taking levothyroxine

How should levothyroxine therapy be managedin pregnant women with hypothyroidism?

Women with overt hypothyroidism should receive levothyroxine replacement therapy with the dose titrated to achieve a thyrotropin concentration within the trimesterspecific reference range. Serial serum thyrotropin levels should be assessed every 4 weeks during the first half of pregnancy in order to adjust levothyroxine dosing to maintain thyrotropin within the trimester specific range. Serum thyrotropin should also be reassessed during the second half of pregnancy. For women already taking levothyroxine, two additional doses per week of the current levothyroxine dose, given as one extra dose twice weekly with several days separation, may be started as soon as pregnancy is confirmed.

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Levothyroxine Dosing Guidelines for Hypothyroidism in special populations1

Patients with persistent symptoms

Alternative Causes of Persistent Hypothyroid Symptoms

  • Adrenal insufficiency (rare)

  • Anemia

    • B12deficiency

    • Iron deficiency

  • Chronic kidney disease

  • Depression, anxiety disorder, and/or somatoform disorders

  • Liver disease

  • Obstructive sleep apnea

  • Viral infection (e.g., mononucleosis, Lyme disease, human immunodeficiency virus/AIDS)

  • Vitamin D deficiency

Recommended dosage

Combination T4/T3 (liothyronine)therapy, in the form of desiccated thyroid hormonepreparations (e.g., thyroid USP, Armour thyroid), or levothyroxine plus liothyronine

In some patients, symptoms persist, despite being treated with an adequate dose of levothyroxine.

This may occur due to several causes including adrenal insufficiency (rare), anemia, chronic kidney disease, depression, anxiety disorder, and/or somatoform disorders, liver disease, obstructive sleep apnea, viral infection (e.g., mononucleosis, Lyme disease, human immunodeficiency virus/AIDS), or vitamin D deficiency

For patients who continue to have persistent symptoms following correction of any underlying problems or issues, it administering combination T4/liothyronine (T3) therapy, in the form of desiccated thyroid hormone preparations (e.g., thyroid USP, Armour thyroid) or levothyroxine plus liothyronine is a reasonable therapeutic intervention

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Summary

  • Hypothyroidism is a commonly encountered clinical disorder

  • Prevalent in India as well as globally and its prevalence increases with age

  • Laboratory assessment: Serum TSH and FT4 measurement

  • Management of hypothyroidism: oral administration of levothyroxine

  • Hypothyroidism is a commonly encountered clinical disorder.

  • Hypothyroidism is prevalent India as well as globallyand its prevalence increases with age.

  • The best laboratory assessment of thyroid function is serum TSH and FT4measurement.

  • Alleviation of symptoms can be accomplished with oral administration of levothyroxine.

References

  • Gaitonde DY, Rowley KD, Sweeney LB. Hypothyroidism: an update. Am Fam Physician. 2012;86:244-51. PMID: 22962987
  • Kostoglou-Athanassiou I, Ntalles K. Hypothyroidism-new aspects of an old disease. Hippokratia. 201014:82-7.PMID: 20596261
  • Bagcchi S. Hypothyroidism in India: more to be done. Lancet Diabetes & Endocrinol. 2014;2:778.PMID: 25282085
  • Unnikrishnan AG, Kalra S, Sahay RK, et al. Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India. Indian J Endocrinol Metab. 2013;17:647-52.PMID: 23961480
  • Fatourechi V. Subclinical hypothyroidism: an update for primary care physicians. Mayo Clin Proc. 2009;84:65-71. PMID: 19121255
  • Jonklaas J, Bianco AC, Bauer AJ, et al. American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24:1670-751. PMID: 25266247

MCQs

Which of the following is the most common cause of hypothyroidism

A.Acute thyroiditis

B.Hashimoto disease

C.Radioactive iodine exposure

D.Thyroidectomy

Hashimoto disease (chronic lymphocytic thyroiditis) is the most common cause of hypothyroidism. Hypothyroidism also can occur as a result of acute thyroiditis, a viral infection of the thyroid gland. Treatments for Graves’ disease, such as thyroidectomy and administration of radioactive iodine, also frequently cause the expected side effect of hypothyroidism

 

A patient has a high serum thyrotropin (TSH) level, but a normal thyroxine (T4) level. What is the most appropriate diagnosis?

A.Subclinical hypothyroidism

B.Hypothalamic dysfunction

C.Pituitary dysfunction

D.Primary hypothyroidism

Subclinical hypothyroidism (SCH), also called mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within normal reference laboratory range but serum thyroid-stimulating hormone (TSH) levels are mildly elevated.

 

Which of the following is the preferred initial hormone replacement therapy for hypothyroidism?

A.Desiccated thyroid

B.Levothyroxine

C.Liothyronine

D.Levothyroxine and liothyronine

Levothyroxine (T4) is the preferred initial therapy for hypothyroidism. Liothyronine can cause abrupt increases in serum triiodothyronine (T3). A more stable, uniform level of T3 is achieved by administering levothyroxine due to regulated T4 to T3 conversion. Desiccated thyroid and combination agents containing both levothyroxine and liothyronine may increase T3 levels and thus may have adverse effects similar to those of liothyronine.

 

What is the recommended initial daily dosage of levothyroxine in elderly adults with primary hypothyroidism?

A.Initial dose of 25 µg daily

B.Initial dose of 50 µg daily

C.Initial dose of 75 µg daily

D.Initial dose of 100 µg daily

In the stable elderly patient, it is recommended to begin therapy at a low synthetic T4 dose of 25 µg daily and increase the dose by 25- to 50-µg increments every 4 to 6 weeks, based on results of the TSH test.

Which of the following is NOT a common clinical symptom of hypothyroidism?

A.Cold intolerance

B.Depression

C.Diarrhea

D.Muscle cramps

E.Weight gain

Patients with hypothyroidism present with constipation, whereas patients with hyperthyroidism can have diarrhea. Hypothyroidism slows down the body’s systems and can cause cold intolerance, weight gain, muscle cramps, and depression

Hypothyroidism caused by Hashimoto's thyroiditis is much more common in women than in men.

A.True

B.False

This condition is 7 times more likely to occur in women than in men. One of the major risk factors for hypothyroidism include being female.

Although the symptoms of hypothyroidism may be difficult to detect, if hypothyroidism is suspected, the condition can best be diagnosed with:

A.An MRI scan

B.An ultrasound

C.A thyroid stimulating hormone test (TSH)

D.A hemoglobin test or hematocrit test

Hypothyroidism can be detected by a thyroid stimulating hormone (TSH) test, a blood test that checks for the hormone made by the pituitary gland that stimulates the thyroid.

A person with untreated hypothyroidism may also suffer from:

A.High cholesterol

B.Low blood pressure

C.Low blood sugar

D.None of the above

People with untreated hypothyroidism also have high total and LDL ("bad") cholesterol levels

In women, hypothyroidism can affect pregnancy by:

A.Reducing the chance of getting pregnant

B.Boosting the chance of getting pregnant

C.Making miscarriage more likely

D.Making labor and delivery more difficult

An underactive thyroid can also cause changes to a woman's menstrual cycle, from irregular, heavy periods to a loss of periods.