Subclinical Hypothyroidism: Will you initiate thyroid replacement therapy?

 

28 year old non pregnant female presents with symptoms of depression. On evaluation her thyroid-stimulating hormone (TSH) level is elevated with normal free thyroxine (T4) and normal free triiodothyronine (T3) levels.

 


This post will focus on following important clinical facts:

  1. Risk factors for high and low TSH level.

  2. USPSTF Screening Recommendation for thyroid dysfunction.

  3. When will you initiate thyroid replacement therapy in subclinical hypothyroidism?

  4. How to dose and time of levothyroxine?

  5. Which medications may result in hypothyroidism?

  6. Does levothyroxine replacement therapy for subclinical hypothyroidism result in improved survival or decreased cardiovascular morbidity?

 


(1) RISK FACTORS

 

(A) Risk factors for an elevated TSH level:

  • female sex

  • advancing age

  • white race

  • type 1 diabetes

  • Down syndrome

  • family history of thyroid disease

  • goiter

  • previous hyperthyroidism

  • external-beam radiation in the head and neck area

 

(B) Risk factors for a low TSH level:

  • female sex

  • advancing age

  • black race

  • low iodine intake

  • personal or family history of thyroid disease

  • ingestion of iodine-containing drugs, such as amiodarone

 

Source: Annals of Internal Medicine • Vol. 162 No. 9 • 5 May 2015.

 


(2) USPSTF Screening Recommendation for thyroid dysfunction

 

  • The primary screening test: serum TSH level

  • Note: Multiple tests over 3- 6 months should be performed to confirm or rule out abnormal findings.

  • Follow-up testing of serum thyroxine (T4) levels in persons with persistently abnormal TSH levels can differentiate between subclinical (normal T4 level) and “overt” (abnormal T4 level) thyroid dysfunction .

 


(3) When will you initiate thyroid replacement therapy in subclinical hypothyroidism?

 

(a) TSH >10: All patient’s should be treated irrespective of age and symptoms. 

 

(b) TSH >7 and <10: Recommended in age <65 years. No benefits noted in older (> 65 years) asymptomatic patients. 

 

(c) TSH <7: not indicated in asymptomatic patients. Treat only symptomatic patient with age <65 yr; AND patients with high titers of anti-TPO antibodies.

 

Source: 

  1. Thyroid. 2012;22(12):1200.
  2. Arch Intern Med. 2012;172(10):811.

 


(4) How to Dose and Time levothyroxine?

 

  • Average replacement dose in adults: 1.7 mcg/kg/day (100-125 mcg/day for 70 kg adult).

  • For patients >50 years or patients <50 years with underlying cardiac disease: initial starting dose of 25-50 mcg/day.

  • Recommended starting dose of levothyroxine sodium in elderly patients with cardiac disease: 12.5-25 mcg/day.

 

  • Timing of medication: preferably on an empty stomach, one-half to one hour before breakfast. Levothyroxine absorption is increased on an empty stomach.

 

Source: levothyroxine Package Insert.

 


 

(5) Which medications may result in hypothyroidism?

 

Mechanism

Medications

Decrease thyroid hormone secretion

    1. Lithium

    2. Aminoglutethimide

    3. Amiodarone

    4. Iodide (including iodine-containing radiographic contrast agents)

    5. Methimazole

    6. Propylthiouracil

    7. Sulfonamides

    8. Tolbutamide

Decrease T4 Absorption

    1. Ferrous Sulfate

    2. Orlistat

    3. Sucralfat

    4. Antacids

    • Aluminum & Magnesium Hydroxides

    • Simethicone Bile Acid Sequestrants

    • Cholestyramine

    • Colestipol Calcium Carbonate Cation Exchange Resins

 

  • Kayexalate

 


(6) Does levothyroxine replacement therapy for subclinical hypothyroidism result in improved survival or decreased cardiovascular morbidity?

 

The following Chocrane review will answer this question:-

 

Search strategy: The authors searched The Cochrane Library, Medline, Embase, and Lilacs. Ongoing trials databases, reference lists, and abstracts of congresses were scrutinized as well.

 

Selection criteria: All studies had to be randomized controlled trials comparing thyroid hormone replacement with placebo or no treatment in adults with subclinical hypothyroidism. Minimum duration of follow-up was one month.

 

Main results:

  • 12 trials of 6-14 months duration involving 350 people were included.

  • 11 trials investigated levothyroxine replacement with placebo and 1 study compared levothyroxine replacement with no treatment.

  • The authors did not identify any trial that assessed (cardiovascular) mortality or morbidity. Seven studies evaluated symptoms, mood, and quality of life with no statistically significant improvement.

  • 1 study showed a statistically significant improvement in cognitive function.

  • 6 studies assessed serum lipids, and there was a trend for reduction in some parameters following levothyroxine replacement.

  • Some echocardiographic parameters improved after levothyroxine replacement therapy, such as myocardial relaxation, as indicated by a significant prolongation of the isovolumic relaxation time, as well as diastolic dysfunction.

  • Only four studies reported adverse events with no statistically significant differences among groups.

 

Authors Conclusions: In current randomized controlled trials, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not demonstrate significant differences among intervention groups. Some evidence indicates that levothyroxine replacement improves some parameters of lipid profiles and left ventricular function.

 

Source

    1. Annals of Internal Medicine • Vol. 162 No. 9 • 5 May 2015
    2. Chocrane Review: http://www.cochrane.org/CD003419/ENDOC_thyroid-hormone-replacement-for-subclinical-hypothyroidism
    3. levothyroxine Package Insert.

 


Please do post your questions or comments below. 


Dr. Harvinder Singh, M.D. (Admin)


Enroll in our online course to have access to all important clinically relevant psychiatry topics in one place.


Related Articles