Mark P. Trolice, M.D.

Perhaps the most confusing endocrine organ involved in reproduction, the thyroid gland has become increasingly complex in its integration with pregnancy. Recent evidence now links thyroid dysfunction, specifically subclinical hypothyroidism, as a risk factor in impaired neurologic fetal development and compromised cognitive function in newborns. Additionally, there is new insight into recurrent miscarriage and antibodies to the thyroid that may improve outcome in this challenging population of patients. As a result, this article will review the latest information on the thyroid gland as it pertains to reproduction.

Epidemiology
Thyroid disorders affect approximately 5% of the general population, with two thirds women. Subclinical hypothyroidism is diagnosed in 4.3% of patients, and subclinical hyperthyroidism in 0.7%. In pregnancy, subclinical dyfunction affects 3.6% of women; overt hypothyroidism 2.5%; and overt hyperthyroidism 0.2%.

Fertility
Hypo- or Hyperthyroidism has well established effects on the menstrual cycle including ovulatory dysfunction and abnormal uterine bleeding. This is not completely understood buy may be contributed by elevated prolactin. Given the acceptance of TRH (Thyrotropin Releasing Hormone) as a Prolactin-stimulating factor, all patients with elevated prolactin levels should be evaluated, and treated if necessary, for hypothyroidism. Once the thyroid dysfunction is resolved, a persistent prolactin elevation should then be managed appropriately.

Regarding miscarriage, there has long been an association with antimicrosomal antibodies (TPO). A recent article in the Journal of Clinical Endocrinology & Metabolism suggested a lower miscarriage rate when low dose thyroxine was used in patients with recurrent miscarriage, TPO but normal thyroid testing.

Pregnancy and subclinical hypothyroidism (SH)
Several studies have demonstrated an association between SH and lower IQ scores in the offspring. No clear data are available on the benefit of thyroid replacement to improve congntive development but two large studies are presently underway. Recommendations are that pregnant woman and those desiring fertility should be treated with thryoxine replacement when they are found to have subclinical hypothyroidism but there is no census on when and whom should be screened. There may also be a link with placental abruption and preterm delivery.

Postpartum thyroiditis (PPT)
Occurring in 5-10% of women, PPT is unexplained though probably autoimmune related. The clinical course is usually hyperthyroid for the first four months, then hypothyroid for the next four months, followed by resolution within 12-18 months postpartum. However, approximately 20% of patients remain hypothyroid and 20% will have a recurrence in the subsequent pregnancy. Risk factors include autoimmune thyroid disease (thyroid antibodies) and type 1 diabetes mellitus.

Key Points

1. In an otherwise healthy reproductive aged woman, the management of Primary Hypothyroidism requires the replacement of thyroxine based on patient weight using 1.6 – 1.7 mcg/kg/day.
2. TSH is the most sensitive indicator of disease. Since thyroxine has a long half-life (seven days), monitoring serum TSH following initiating or adjustment of thyroid replacement should be in approximately four – six weeks.
3. Never provide thyroid replacement without being assured of normal adrenal function since an increase in metabolism by thyroxine can result in adrenal crisis.
4. hCG, TSH, FSH, LH, all have identical alpha subunits. During the first trimester, TSH may be low to low normal due to cross reactivity with hCG that is rising until 12 weeks. The following are pathophysiologic examples:
   • Hyperthyroidism from excessively high hCG levels in Gestational Trophoblastic Disease activating the TSH receptors on the thyroid to produce thyroxine;
   • Primary Hypothyroidism in childhood resulting in feedback stimulation of TSH with consequential cross reactivity of ovarian FSH receptors to produce estradiol.

Know these signs and symptoms of thyroid dysfunction

Consequences of untreated thyroid dysfunction are significant

Risk factors for hypothyroidism include other autoimmune disorders

REFERENCES
1. What you need to know about thyroid disorders in pregnancy. OBG Management. 2007;19:27-41.