D r . H i s h a m A b i d A l d a b a g h

I n t e r n a l M e d i c i n e S p e c i a l i s t

Hypothyroidism

Update Evidence-Based Guideline

Recommendations

Kingdom of Saudi Arabia

Ministry of Health

General Directorate of Health

Affairs in Gurayat

General Gurayat Hospital

Learning Objectives

Be able to practice procedures concerning the following topics about Hypothyroidism(according to evidence-based guideline recommendations):

1- Diagnosis.

2- Screening.

3- Treating.

4- Monitor treatment.

5-Follow up.

Hypothyroidism may occur as a result of primary gland failure or insufficient thyroid gland stimulation by the hypothalamus or pituitary gland.

Autoimmune thyroid disease is the most common etiology of hypothyroidism in the United States.

The prevalence increases with age, and is higher in females than in males.

About one in 300 persons in the United States has hypothyroidism.

Clinical symptoms of hypothyroidism are nonspecific and may be subtle, especially in older persons.

The best laboratory assessment of thyroid function is a serum thyroid-stimulating hormone test (TSH).

There is no evidence that screening asymptomatic adults improves outcomes.

Untreated hypothyroidism can contribute to hypertension, dyslipidemia, infertility, cognitive impairment, and neuromuscular dysfunction.

In the majority of patients, alleviation of symptoms can be accomplished through oral administration of synthetic levothyroxine, and most patients will require lifelong therapy.

Thyroid hormone requirements increase during pregnancy.

Subclinical Hypothyroidism(SH)

Subclinical hypothyroidism is a biochemical diagnosis defined by a normal-range free T4 level and an elevated TSH level. Patients may or may not have symptoms attributable to hypothyroidism.

Evidence-Based Guideline Recommendation

1- How to make the diagnosis of hypothyroidism?

By measuring TSH. normal range values (0.45-4.5 mIU/L). Grade A.

Higher cutoff TSH levels must be considered for elderly patients. Grade A.

Patients with physical signs suspected of hypothyroidism, require a diagnostic workup that includes thyroid hormone assays. Grade B.

If the patient has clinical findings or a high probability of overt hypothyroidism, the measurement of both TSH and free T4 are required. Grade D.

To rule out SH, an initial TSH determination is suggested. If elevated, a repeat test adding free T4 should be performed 2-3 months later to confirm the diagnosis. Grade D.

The progression to OH in patients with SH depends on the presence of thyroid antibodies and TSH baseline levels. Measurement of TPOAb and thyroid US in patients with SH is useful to help predict a higher risk of progression to overt hypothyroidism. Grade A.

2- Who should be screened for hypothyroidism?

Women of fertile age and upwards, especially older than 60 years. Grade A.

Risk groups population including persons with previous radiation treatment of the thyroid gland, previous thyroid surgery, or thyroid dysfunction, TPOAb positivity, use of certain drugs such as amiodarone. Grade A or lithium, T1DM, Sjogren’ssyndrome, systemic lupus erythematosus, rheumatoid arthritis, vitiligo, Down’s syndrome, Turner syndrome, heart failure, dyslipemia, hyperprolactinemia and anemia. Grade B.

In the presence of goiter and clinical features of hypothyroidism. Grade D.

In patients with a family history of AITD. Grade A.

3- When should anti-thyroid antibodies be measured?

Anti-thyroid peroxidase antibody (TPOAb) measurements should be considered when evaluating patients with subclinical hypothyroidism.Grade B.

To confirm the presence of thyroid autoimmunity in primary hypothyroidism. Grade C.

When evaluating patients with recurrent miscarriage, with or without infertility. Grade A.

If autoimmunity is suspected as the cause of hypothyroidism. Grade B.

For diagnosis of AITD. Grade B.

In the risk groups for AITD. Grade B.

4- What are the preferred thyroid hormone measurements in addition to TSH in the assessment of patients with hypothyroidism?

Apart from pregnancy, assessment of serum free T4 should be done instead of total T4 in the evaluation of hypothyroidism. Grade A.

Assessment of serum free T4, in addition to TSH, should be considered when monitoring L-thyroxine therapy.Grade B.

In pregnancy, the measurement of total T4 or a free T4 index, in addition to TSH, should be done to assess thyroid status. Grade B.

Serum total T3 or assessment of serum free T3 should not be done to diagnose hypothyroidism. Grade A.

TSH measurements in hospitalized patients should be done only if there is an index of suspicion for thyroid dysfunction. Grade A.

5- When should thyroid ultrasonography be performed?

Routine thyroid US is not recommended in patients with either clinical or subclinical hypothyroidism. However, it should be considered for patients with negative thyroid antibodies to identify patients with autoimmune thyroiditis. Grade A.

Thyroid US can also be considered for those patients with subclinical hypothyroidism to help in the evaluation of the risk of progression to overt hypothyroidism. Grade A.

Thyroid US should be performed for patients with hypothyroidism and abnormal thyroid palpation. Grade D.

6- Is there an association between heart failure and subclinical hypothyroidism?

Data concerning the effects of subclinical hypothyroidism on the cardiac function and structure are conflicting.

There are consistent evidence regarding the association of subclinical hypothyroidism with congestive heart failure in elderly patients, particularly for TSH level > 10 mIU/L, Grade A, but not for younger patients.

There is no evidence concerning the role of levothyroxine treatment in reducing the incidence or progression of congestive heart failure on SH patients.

7- Is subclinical hypothyroidism associated to cardiovascular risk?

There is available evidence suggesting an association between subclinical hypothyroidism and CHD events and mortality, particularly for subjects younger than 65. Grade A.

TSH concentrations ≥10 mIU/L were consistently associated with increased risk of CHD events and CHD mortality. Grade A.

All patients with TSH level persistently > 10 mIU/L should be treated, because at this TSH level, patients have an increased likelihood of progression to overt disease Grade A, and a higher risk of congestive heart failure, cardiovascular disease and mortality. Grade A.

For patients with mildly increased serum TSH levels (4.5-10 mIU/L), treatment should be considered for those patients younger than 65 with increased cardiovascular risk , particularly when TSH level is persistently > 7 mIU/L. Grade A.

8- Should elderly patients be considered for treatment?

Routine treatment is not recommended for elderly (> 65 yr) and very-elderly (> 80 yr) patients with subclinical hypothyroidism at TSH levels < 10 mIU/L. Grade A.

Also treatment is not recommended for SH if the aim is to improve cognitive function in elderly people Grade A. However in > 65 years old, treatment can be considered on an individual basis. Grade D.

9- How should patients with hypothyroidism be treated?

Levothyroxine is the drug of choice to treat hypothyroidism. Grade A.

Routine use of combined therapy with levothyroxine and triiodothyronine for hypothyroid patients is not recommended. Grade A.

Levothyroxine therapy could be considered also for symptomatic middle-aged patients for a short period of time. If a clear beneficial effect is observed, levothyroxine therapy could be maintained. Grade D.

Treatment could be considered for patients with persistently mildly increased TSH levels with positive TPOAb and thyroid sonographic findings typical of autoimmune thyroiditis. Grade B.

10- How should levothyroxine be used?

Levothyroxine should be administered at least after 2 hours fast, 30 minutes before food intake Grade A. As an alternative, it could be administered in the evening. Grade B.

In clinical hypothyroidism, an initial levothyroxine daily dose of 1.6-1.8 μg/kg ideal body weight is recommended. Grade B.

In subclinical disease, an initial daily dose of 1.1-1.2 μg/kg. Grade D.

Individual adjustment of levothyroxine therapy should be considered. Grade D.

11- How to initiate and adjust doses in elderly and in patients with cardiopathy?

In elderly patients (> 60 years) and also in those with ischemic cardiac disease or heart failure, start levothyroxine therapy at lower doses (12.5-25 μg/day) Grade D, especially in subclinical hypothyroid patients. Grade B.

12- How should levothyroxine therapy be monitored?

Patients being treated for established hypothyroidism should have serum TSH measurements done at 4–8 weeks after initiating treatment or after a change in dose. Once an adequate replacement dose has been determined, periodic TSH measurements should be done after 6 months and then at 12-month intervals, or more frequently if the clinical situation dictates otherwise. Grade B.

13- In patients with hypothyroidism being treated with L-thyroxine who are pregnant, what should the target TSH ranges be?

The following upper-normal reference ranges are recommended: first trimester, 2.5 mIU/L; second trimester, 3.0 mIU/L; and third trimester, 3.5 mIU/L. Grade C.

14- How to approach hypothyroid patients with persistently high levels of TSH despite high levothyroxine dose?

After poor compliance and incorrect ingestion have been ruled out, consider possible food and drug interactions. Grade B, and also malabsorptionsyndromes that can alter levothyroxine absorption and metabolism. Grade D.

15- How to approach patients with persistent hypothyroid symptoms?

If hypothyroid symptoms persist despite adequate treatment, other comorbidities should be discarded. Grade C.

Increased levothyroxine dose or combination therapy with triiodotironine are not recommended. Grade B.

Key Concepts

TSH is the corner stone in approaching patients with hypothyroidism.

Levothyroxine is the drug of choice to treat hypothyroidism.

Thyroid hormone requirements increase during pregnancy.

TPOAb should be considered in approaching AITD.

Most Hypothyroidism patients require life long treatment.

References

American Thyroid Association Guideline Recommendations, 2012

ABE&M todos os direitos reservados. 290 Arq Bras Endocrinol Metab. 2013;57/4 Guidelines of hypothyroidism

DAVID Y. GAITONDE, MD; KEVIN D. ROWLEY, DO; and LORI B. SWEENEY, MD, Dwight D. Am FamPhysician. 2012 Aug 1;86(3):244-251.

Gabriela Brenta1, Mario Vaisman2, José Augusto Sgarbi3, Liliana Maria Bergoglio4, Nathalia Carvalho de Andrada5, Pedro Pineda Bravo6, Ana Maria Orlandi7, Hans Graf8, Latin American Thyroid Society (LATS), 2013.

Topics for Research

Prevalence and Etiology of Hypothyroidism in Al Gurayat Province.

Efficacy of Iodine Supplement Procedures Upon Thyroid Disorders.

Effectiveness of Treatment of Thyroid Disorders.

Thanks for your attention