Silvia Gutierrez

OVERT AND SUBCLINICAL HYPOTHYROIDISM COMPLICATING PREGNANCY

We studied the evolution of 150 pregnancies corresponding to 114 women (16-39 years old) with primary hypothyroidism. Fifty-one pregnancies (34%) were conceived under hypothyroidism: 16 overt (X +/- standard deviation [SD], thyroxine [T4]: 2.44 +/- 0.7 microg/dL; thyrotropin [TSH]: 33.4 +/- 8.82 mIU/L), and 35 subclinical hypothyroidism (T4: 6.93 +/- 1.88 microg/dL; TSH: 12.87 +/- 8.43 mIU/L); 99 pregnancies were conceived under euthyroidism while undergoing thyroid therapy. When treatment with levothyroxine was inadequate, the outcome of pregnancy was abortion in 60% of overtly hypothyroid patients and in 71.4% of subclinically hypothyroid patients, premature delivery in 20% and 7.2% respectively, and term delivery in 20% and 21.4%, respectively. When treatment was adequate, 100% of overtly hypothyroid patients and 90.5% of subclinically hypothyroid patients carried pregnancies to term; there were no abortions in any of the groups. Abortions, premature and term deliveries in patients who were euthyroid on levothyroxine at the time of conception were 4%, 11.1% and 84.9% respectively. Of the patients receiving levothyroxine therapy before conception, 69.5% had to increase the dose (mean increase 46.2 +/- 29.6 microg/d). Of 126 evaluated newborns, 110 were delivered at term while 16 were premature. Eight newborns, 4 were premature, had congenital malformations (6.3%), and 4 died. Our results show that the evolution of pregnancies did not depend on whether the hypothyroidism was overt or subclinical but mainly on the treatment received. The adequate treatment of hypothyroidism during gestation minimizes risks and generally, makes it possible for pregnancies to be carried to term without complications.

Subclinical hypothyroidism and thyroid autoimmunity in women with infertility

Objective. To determine the prevalence of different subclinical hypothyroidism (SH) grades and thyroid autoimmunity (TAI) in infertile women. Design. Retrospective study. Setting. Endocrinology division of a public hospital in Argentina. Patients. Group I comprised 244 women consulting on infertility (>1 year without pregnancy); Group C (controls) comprised 155 healthy women with confirmed fertility. Intervention. Thyroid-stimulating hormone and thyroid peroxidase antibodies were measured in all patients, and a thyrotropin-releasing hormone (TRH) stimulation test was performed in 71 patients to diagnose SH grade 1. The pregnancy rate in hypothyroid women on levothyroxine treatment was also evaluated. Results. SH was diagnosed in 13.9% of the patients in Group I and in 3.9% of Group C (p < 0.002). The TRH stimulation test was useful to detect SH grade 1 in 12.7% of the infertile patients. Patients with precocious ovarian failure, tubal disturbances and ovulatory dysfunction presented higher SH rates (40.0, 18.2 and 15.4%, respectively) than control patients (p < 0.0001, p < 0.002 and p < 0.003). No significant difference in TAI prevalence was shown in Group I relative to Group C. Pregnancy rate of 44.1% was achieved under levothyroxine treatment. Conclusions. We observed a higher prevalence of SH, but not of TAI, in patients with infertility. Our results support thyroid screening in women with reproductive failure.

The Relationship of Preconception Thyrotropin Levels to Requirements for Increasing the Levothyroxine Dose During Pregnancy in Women with Primary Hypothyroidism

BACKGROUND Most women with hypothyroidism require an increase in their dose of levothyroxine (LT4) after conception. To minimize fetal and maternal complications of maternal hypothyroidism, it is thought that women should be rapidly restored to the euthyroid state. The objectives of this study was to determine the percentage of hypothyroid women who would need to increase their dose of LT4 dose even if they had a preconception (pre-C) serum thyrotropin (TSH) of <2.5 mIU/L as recommended by the Endocrine Societys guidelines and to ascertain whether there was a relationship between the pre-C TSH value and the need to increase the LT4 dose during pregnancy. METHODS Fifty-three pregnant women with hypothyroidism on LT4 treatment in whom the pre-C serum TSH was <2.5 mIU/L, but which was within the normal range, within the 6 months before pregnancy were retrospectively studied. An additional selection criterion was that their LT4 dose at the time of their first prenatal visit was the same as that received pre-C. RESULTS Seventeen patients had to increase their LT4 dose during pregnancy, because their serum TSH was increased at the time of the first prenatal visit (Group 1); and 36 patients did not have to increase their dose of LT4 during pregnancy (Group 2). The pre-C TSH was significantly higher in Group 1 (1.55 ± 0.62 mIU/L) than in Group 2 (0.98 ± 0.67 mIU/L). When pre-C TSH range was 1.2-2.4 mIU/L, 50% of the patients required an increase in the LT4 dose during pregnancy. In contrast, when the pre-C TSH was <1.2 mIU/L, only 17.2% (p< 0.02) had to increase the LT4 dose during pregnancy. CONCLUSIONS We suggest that in women with hypothyroidism who are planning to become pregnant, serum TSH levels should be in the normal range but should not be greater than about 1.2 mIU/mL.

Adequate Levothyroxine Doses for the Treatment of Hypothyroidism Newly Discovered During Pregnancy

BACKGROUND Recent guidelines recommend thyrotropin (TSH) target levels of ≤2.5 mIU/L for the first trimester and ≤3 mIU/L for the subsequent trimesters. Euthyroidism should be attained as soon as possible, but there are no precise indications about the initial levothyrorine (LT4) dose. The aim of our study was to determine the appropriate LT4 doses in order to normalize TSH levels in patients with newly discovered subclinical hypothyroidism (SCH) during pregnancy, and to correlate them with basal TSH levels. The adequate LT4 doses for women with SCH were also compared to those required in pregnant women with overt hypothyroidism (OH). METHODS Seventy-seven patients with newly diagnosed hypothyroidism during pregnancy were retrospectively analyzed. Patients were assigned to group 1 (n = 64) with SCH or group 2 (n = 13) with OH. SCH patients were subdivided into two groups: group 1a serum TSH >2.5 (1st trimester) or >3 (2nd or 3rd trimester) to 4.2 mIU/L; and group 1b TSH level > 4.21-10 mIU/L. All patients were treated with LT4 as soon as hypothyroidism was diagnosed. The dose that allowed a TSH of ≤2.5 mIU/L to be reached in the first trimester or one that allowed a TSH of ≤3 mIU/L to be reached during the second and third trimesters was considered the appropriate one. RESULTS A significant difference (p < 0.0001) in the appropriate LT4 dose (mean ± SD, μg/kg/day) was observed between group 1 and group 2: 1.31 ± 0.36 versus 2.33 ± 0.59. Patients in group 1a required a significantly lower LT4 dose (p < 0.014) than group1b: 1.20 ± 0.39 versus 1.42 ± 0.31 μg/kg/day. In 57 of the 64 (89.06%) women with SCH and in 10/13 (76.92%) women with OH, the appropriate LT4 dose coincided with the initial dose. Only 11% and 23% respectively required additional adjustments. Once the appropriate dose of LT4 was prescribed, the time at which euthyroidism (mean ± SD, weeks) was confirmed was similar in patients with SCH (6.06 ± 3.3) and OH (5.3 ± 1.8). There were no miscarriages or premature deliveries. CONCLUSIONS When hypothyroidism is newly discovered during pregnancy, we suggest initiating the treatment with the following LT4 doses: 1.20 μg/kg/day for SCH with TSH ≤ 4.2  mIU/L, 1.42 μg/kg/day with TSH > 4.2-10, and 2.33 μg/kg/day for OH. By taking this approach, patients will promptly attain the euthyroid state avoiding additional increments and, probably, obstetric risks.

An International Survey of Screening and Management of Hypothyroidism during Pregnancy in Latin America

OBJECTIVE To determine how endocrinologists in Latin America deal with clinical case scenarios related to hypothyroidism and pregnancy. MATERIALS AND METHODS In January 2013, we sent an electronic questionnaire on current practice relating to management of hypothyroidism in pregnancy to 856 members of the Latin American Thyroid Society (LATS) who manage pregnant patients with thyroid disease. Subsequently, we have analyzed responses from physician members. RESULTS Two hundred and ninety-three responders represent clinicians from 13 countries. All were directly involved in the management of maternal hypothyroidism and 90.7% were endocrinologists. The recommendation of a starting dose of L-thyoxine for a woman diagnosed with overt hypothyroidism in pregnancy, preconception management of euthyroid women with known thyroid autoimmunity and approach related to ovarian hyperstimulation in women with thyroid peroxidase antibodies were widely variable. For women with known hypothyroidism, 34.6% of responders would increase L-thyroxine dose by 30-50% as soon as pregnancy is confirmed. With regard to screening, 42.7% of responders perform universal evaluation and 70% recommend TSH < 2.5 mUI/L in the first trimester and TSH < 3 mUI/L in the second and third trimester as target results in known hypothyroid pregnant women. CONCLUSION Deficiencies in diagnosis and management of hypothyroidism during pregnancy were observed in our survey, highlighting the need for improvement of specialist education and quality of care offered to patients with thyroid disease during pregnancy in Latin America.