CME INDIA Case Presentation by Dr. Sunetha, Gynaecologist, Coimbatore.

CME INDIA Case Study

Question asked in CME INDIA Group

• 29 year-old-female in early pregnancy, weight-72 kg
• On Thyroxine 75,
• TSH 9.8,
• Anti-TPO >1000
• Are steroids needed?

CME INDIA Discussion

Dr. Murugananth, Coimbatore:

• Is it new onset hypothyroidism or pre-existent Madam?

Dr. Sunetha, S DGO, Coimbatore:

• Pre-Existing.

Dr Vivek Ranjan Gupta, Surat:

• Anti-TPO antibody is the autoimmunity marker. It determines whether there is autoimmune thyroiditis in the thyroid gland; this is important in pregnancy. In pregnancy if there is subclinical hypothyroidism, and TSH is in the range of 5–9miU/L, but the TPO antibody is positive, treatment is required. In pregnancy if TPO is positive and there is a slight elevation of TSH (more than 4mIU/L), treatment is required.
• Increase dose of thyroxine to 125 to maintain TSH below 2.5 (Remember for pregnancy normal is not less than 5 but it should be less than 2.5 in first trimester).
• Anti tpo antibody comes positive in both hypo and hyperthyroidism.
• So, if the presentation is thyroiditis or sub-acute thyroiditis then we can think of steroids and other options. But in this case, it is hypothyroidism.

Dr. N. K. Singh:

• ATS 2019 is most commonly followed.
• Treatment of subclinical hypothyroidism is recommended for TPO (thyroid peroxidase)- positive women with thyrotropin levels greater than the pregnancy-specific range and TPO-negative women with thyrotropin levels greater than 10 mIU/L and can be considered for women with lower thyrotropin.

Dr. Om Lakhani, DNB Endo, Ahmedabad:

• No indication for steroids.
• Increase dose of LT4 to 125 mcg… make sure the timing and compliance of medications is correct.
• Repeat thyroid function after 1 month.
• Anti-TPO is a widely-misused test.
• It has very limited indications and it’s use in clinical decision making is declining.
• For example, in this patient there is no indication for Anti TPO since the patient is already having established hypothyroidism. Anti-TPO is not going to change the management in this case. So, the test was not indicated.
• See these experts from https://endocrinology.co.in/FOR+DOCTORS/THYROID/Thyroid+disorders+in+Pregnancy/2.+Hypothyroidism+in+pregnancy

Dr. S. K. Gupta, MBBS MD (Med) CFM (France), Senior Consultant Physician, Delhi:

• In pregnancy:
  • Treat in first TM (Trimester)treat if TSH is more than 4.
  • I remember TSH values as 1.5 for First Tm.
• 2.5 for Second TM.
• 3.5 for Third TM.
• (Though actual values are slightly different).
• If TSH value is between 2.5 and 4 than only Anti TPO should be advised if positive these patients may need treatment with low dose thyroxin.
• Steroids not to be used in this case.
• Anti TPO is non-specific marker which can present in number of conditions.

Dr. Ronak Shah, Senior Physician, Anand:

• Also, avoid iron & calcium supplements at the same time with thyroxine.
• TPO is useful in decision making for treatment of subclinical hypothyroidism.
• How TPO is useful in decision making.
• If TPO is significantly high and TSH between 4.5 to 10, we may start treatment.
• If TPO is negative, we may wait.
• This is for the most common cause of primary hypothyroidism i.e. Hashimoto’s thyroiditis.

Dr. Om Lakhani, DNB Endo, Ahmedabad:

• While this is true and accepted notion for a while this concept is now being challenged in the endocrine community.
• For people age less than 70 with TSH between 5 to 7 – Anti TPO can be used for decision making on whether to treat or not
• For people age less than 70 with TSH between 7 to 10 – Anti TPO is not required and treatment must be given since data has suggested that treatment in this group is associated with reduced CV disease.
• But always remember to repeat the thyroid function in non-pregnant individual with subclinical hypothyroidism before taking a decision, it is not uncommon to see lab errors with regards to TSH very commonly.
• A patient is established to have SCH only if she/he has elevated TSH on repeated measurements.

CME INDIA Learning Points

• Antithyroid antibodies, which include thyroid-stimulating hormone receptor antibodies (TRAbs), thyroid peroxidase antibodies (TPOAbs), and thyroid globulin antibodies (TgAbs), are widely known for their tight association with thyroid autoimmune diseases.
• The variation in all three kinds of antibodies also showed different trends during and after pregnancy
• Autoimmunity increases with age and is often commonly evaluated in women of the reproductive age group. Prevalence of thyroid antibodies is common even in euthyroid pregnant women
• Assays for anti–thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies may be helpful in determining the etiology of hypothyroidism or in predicting future hypothyroidism.
•  However, once a patient has been found to be antibody positive, repeated antibody testing adds little to the clinical picture and thus is not recommended.
• Assays for anti–thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies may be helpful in determining the etiology of hypothyroidism or in predicting future hypothyroidism.
• Anti-TPO antibodies have been associated with increased risk of infertility and miscarriage; whether levothyroxine (LT4) treatment can lower this risk is controversial.

CME INDIA Tail Piece

• Thyroid peroxidase (TPO), a membrane-bound enzyme, catalyzes the oxidation of iodide and the iodination of the tyrosyl residues of thyroglobulin.
• TPOAbs can bind to TPO and then damage the thyrocytes and cause hypothyroidism.
• Among the three kinds of antibodies, the TgAb is the earliest-discovered and it is mainly composed of IgG. It mainly attacks different antigenic determinants of thyroglobulin, which is located in the colloid of thyroid follicles.
• TPOAb and TgAb are frequently present in the same individual.

The variation in TPOAbs before, during, and after pregnancy. The curve is a set of data from one patient. The patient suffered from Hashimoto’s thyroiditis. (Courtsey: C.Lie et al.The Clinical Value and Variation of Antithyroid Antibodies during Pregnancy Volume 2020 |Article ID 8871951 | https://doi.org/10.1155/2020/8871951)

• Both the American Thyroid Association (ATA) and American Association of Clinical Endocrinology (AACE) recommend starting levothyroxine therapy under the following scenarios:
  • TSH is >10 mIU/l or;
  • Presence of hypothyroid symptoms or;
  • Presence of cardiovascular risk factors or;
  • Positive TPO antibody.

References:

1. Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception.
2. N Engl J Med.  2019; 380(14):1316-1325 (ISSN: 1533-4406)
3. https://pro.aace.com/sites/default/files/2021-01/AACE%20TRC%20Interpretation%20of%20TFTs%20Part%203-FINAL.pdf
4. https://endocrinology.co.in/FOR+DOCTORS/THYROID/Thyroid+disorders+in+Pregnancy/2.+Hypothyroidism+in+pregnancy
5. C.Lie et al.The Clinical Value and Variation of Antithyroid Antibodies during Pregnancy Volume 2020 |Article ID 8871951 | https://doi.org/10.1155/2020/8871951

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