Thyreopathy in pregnancy and in newborns

Thyreopathy or thyroid gland disorder affect a significant proportion of women of childbearing potential. Untreated thyroid disorders can cause infertility, complications in pregnancy (abortions, premature births, etc.) and can contribute to the delay of the child's psychomotor development. Therefore, early detection and treatment of thyroid disorders in pregnancy is necessary. According to the recommendations of the Czech Society of Endocrinology from 2018, thyroid stimulating hormone (TSH), free thyroxine (fT4) and antibodies against thyroid peroxidase (TPOAb) should also be taken during the first blood collection during pregnancy (i.e. usually in weeks 9-11). According to some international professional associations, this examination is not necessary for women without risk factors (see below). Iodine supplementation (150-200 ug of elemental iodine per day over and above normal dietary intake) is recommended for all pregnant and lactating women (except those with hyperthyroidism).


 * Risk factors for thyreopathies in pregnancy
 * Tyreopathy in personal or family anamnesis;
 * Symptoms of thyroid dysfunction or goiter;
 * Type 1 diabetes mellitus or other autoimmune diseases;
 * Miscarriage or premature birth in the anamenesis;
 * Positive TPOAb;
 * History of head and/or neck irradiation;
 * Obesity with BMI ≥40 kg / m2;
 * Use of amiodarone, lithium, use of cytokines, recent use of iodine X-ray contrast agent;
 * Infertility;
 * Living in an area with moderate or severe iodine deficiency.

The most common endocrine disease in women is autoimmune thyroid disease – especially chronic lymphocytic thyroiditis (CLT) a Graves' disease (GB).

Physiology (effect of pregnancy on the thyroid gland)

 * during pregnancy, the volume of plasma increases along with the plasma pool of thyroxine (T4) and triiodothyronine (T3);
 * the renal clearance of iodine increases and part of the iodine passes through the placenta into the fetal circulation;
 * acceleration of metabolic inactivation of T4 and T3 by deiodination on the inner ring by the enzyme deiodase 3, which is overexpressed in the placenta (quantitatively the most important factor);
 * the above changes result in an overall increased need for iodine and thyroid hormones in pregnancy - women with normal iodine stores in the thyroid gland and with normal gland function easily adapt to these changes with increased synthesis of T4 and T3;


 * at the beginning of pregnancy the concentration of thyroxine-binding globulin (TBG), which is the main binding protein for T4 and T3, increases due to the increase in estrogens → therefore the free fraction of T4 and T3 is temporarily decreased → after the synthesis increase, FT4 normalizes and bound (therefore the overall) T4 remains increased;


 * at the beginning of pregnancy, chorionic gonadotropin (hCG) rises sharply, which, among other things, stimulates the thyroid gland (similar to TSH - together they share a large part of the molecule - alpha chain) → T4 and T3 secretion increases (FT4 and FT3) and by negative feedback the secretion of TSH is partially or even completely suppressed, especially in conditions with high hCG (eg twins) - a transient and clinically insignificant condition.

The synthesis of thyroxine (T4) and triiodothyronine (T3) is dependent on iodine supply. These hormones are necessary both for the preconception period and for fertilization and throughout the pregnancy up to several months after birth. In hypothyroidism, increased prolactin levels cause fertility problems. The fetus is completely dependent on the mother's production of thyroxine, especially until the 12th to 16th week, after which the fetal thyrocytes begin their own synthesis of T4, but the mother's supply of T4 is important throughout the whole pregnancy.

Hypothyroidism

 * the most common causes: autoimmune thyroiditis, failure to increase the replacement dose in times of increased demands, and relative iodine deficiency; central hypothyroidism (decreased serum FT4) is rare;
 * treatment: levothyroxine substitution (target TSH values are <2.5 mIU / l) and iodine supplementation.


 * Manifested hypothyroidism: Elevation of TSH and decreased FT4 or TSH elevation> 10 mIU / l and normal FT4 - indicated for treatment with levothyroxine;
 * Subclinical hypothyroidism: Elevation of TSH ≤10 mIU / l and normal FT4 - indicated for levothyroxine treatment;
 * Isolated positive antibodies: Positive TPOAb and normal TSH and FT4 - consider treatment with levothyroxine (especially in women with abortions, premature births, infertility, decreased FT4, etc.);
 * Isolated hypothyroxinemia: Decreased FT4 and normal TSH and negative TPOAb - consider levothyroxine treatment if no improvement is made after iodine supplementation.

Hashimoto's thyroiditis – chronic autoimmune thyroiditis

 * one of the most common autoimmune diseases, affects about 5% of women of reproductive age;
 * arises partly from a genetic basis;
 * it develops very slowly as chronic lymphocytic inflammation, mediated mainly by cellular immunity directed against follicular cells of the gland;
 * it is also manifested by the production of circulating autoantibodies against glandular structures, of which antibodies against thyroperoxidase (TPOAb) are of the greatest importance for diagnosis;
 * limits the gland's secretory reserve - functional impairment varies in severity;
 * the functional impairment of the gland can be assessed by the rise of TSH and, in more severe disorders and/or iodine deficiency, also by the drop in free T4;
 * ultrasonographic image: coarse structure (dispersive → diffuse), hypoechogenic and hypervascularized.

Hyperthyroidism

 * physiological pregnancy can mimic hyperthyroidism clinically and laboratory (increased cardiac output, peripheral vasodilation, increase in total and partially free thyroxine, mild goiter, physiological TSH suppression due to chorionic gonadotropin);
 * however, the prevalence of true peripheral hyperthyroidism in pregnancy is up to 10 times lower than in the general population;
 * the most common cause is Graves's disease (in 85% of cases), other causes are rare (hyperfunctional phase of autoimmune thyroiditis, iodine excess, thyroid hormone overdose, toxic adenoma, polynodose toxic reconstruction / goiter);
 * untreated or inadequately treated hyperthyroidism in pregnancy increases the risk of preterm birth and miscarriage;
 * overdose of thyrostatics in pregnancy leads to fetal hypothyroidism with negative consequences for CNS development and fetal goiter;
 * thyrostatic treatment - in the 1st trimester propylthiouracyl (increased incidence of VVV after methimazole and carbimazole), from the 2nd trimester change to methimazole (higher incidence of hepatopathies after propylthiouracyl), during breastfeeding methimazole;
 * The most serious side effects of thyrostatics: agranulocytosis and hepatopathy (monitoring of liver enzymes is indicated).


 * Manifested hyperthyroidism: Reduced TSH, increased FT4 and confirmed thyroid etiology (by TSH receptor antibody (TRAK) testing and ultrasound), significant clinical signs - indicated for treatment with thyrostatics (propylthiouracil in the 1st and methimazole in the 2nd and 3rd trimester), not iodine supplementation indicated;
 * Subclinical hyperthyroidism: Decreased TSH, normal FT4 and confirmed thyroid etiology, minimal or no clinical signs - not indicated for thyrostatic treatment or iodine supplementation;
 * Transient gestational suppression of TSH: Decreased TSH and normal FT4 of non-thyroid etiology - not indicated for thyrostatic treatment but is indicated for iodine supplementation;
 * Isolated hyperthyroxinemia: Elevated FT4, normal TSH and negative TPOAb - not indicated for thyrostatic therapy but is indicated for iodine supplementation.


 * Newly diagnosed node by palpation or by ultrasound (> 1 cm) - endocrinological examination indicated.

Consequences of untreated thyropathies in pregnancy

 * Abortions;
 * Pregnancy arterial hypertension;
 * Preeclampsia/eclampsia;
 * Placental abruption;
 * Premature births;
 * Higher caesarean section rates;
 * Low birth weight;
 * Disorders of the development of the embryo, fetus, newborn and child - mainly in the area of ​​the central nervous system;
 * Postpartum thyroid dysfunction (postpartum thyroiditis).

Postpartum thyroiditis

 * a variant of autoimmune thyroiditis that occurs in the first year after delivery (even after abortion);
 * cause: "rebound" phenomenon of immunotolerance, induced in pregnancy by the presence of an antigenically different fetus in the mother's body;
 * risk factors: positive TPOAb, type 1 diabetes mellitus and other autoimmune diseases;
 * in women with TPOAb and type 1 DM positive, TSH screening is recommended 3 and 6 months after delivery;
 * clinical manifestation:
 * hyperfunction with a transition to hypofunction (about 1/3 of cases),,
 * hyperfunction followed by permanent normalization (about 1/3) - hyperfunction is caused by the destruction of thyroid follicles and the release of thyroid hormones into the circulation, so that thyrostatics are not effective; resolves spontaneously in 4-6 weeks,
 * hypofunction (about 1/3) - levothyroxine substitution and iodine supplementation during breastfeeding.

Congenital hypothyroidism

 * most common congenital endocrine disease (prevalence 1:3000–4000);
 * thyroid hormones play a key role in brain development, especially up to 8 months of age (a little less then up to 3 years of age);
 * without replacement treatment, irreversible brain damage occurs – at the time of clinical diagnosis, the brain is already irreversibly damaged;
 * since 1985, nationwide newborn screening has been introduced - determination of the TSH level;
 * etiopathogenesis: in 75-80% of cases dysgenesis of the thyroid gland (agenesis, aplasia, hypoplasia, hemithyroid, cystic malformation, ectopia) or dyshormonogenesis (disruption of any level of synthesis or secretion of hormones; neonatal goiter ), or rare isolated congenital central hypothyroidism' (congenital TSH defect - cannot be detected by newborn screening);
 * clinical picture without treatment: initially only prolonged neonatal icterus (due to transplacental transfer of thyroid hormones from the mother), later (in the first 2-3 months of life) failure to thrive, delayed growth rate and bone maturation - late fontanel closure, delayed eruption baby teeth, macroglossia, muscle hypotonia, omphalocele, constipation, hoarse cry, thermoregulation disorders, anemia; still later growth disorder, psychomotor retardation, sensorineural hearing disorder;
 * neonatal goiter or normal-sized thyroid gland;
 * 2-5 times increased risk of combined congenital malformations compared to the rest of the population → ultrasound examination of the heart, kidneys and CNS is recommended;
 * laboratory findings: ↑TSH, ↓fT4; (for the central form ↓TSH and fT4);
 * therapy: lifelong levothyroxine replacement therapy (started as soon as possible); Intestinal absorption of L-thyroxine is worsened by concomitant consumption of fiber, soy milk, calcium or iron supplements, and malabsorption as such.

Transient hypothyroidism

 * causes:
 * in newborns of some mothers with autoimmune thyroid disease, TSH receptor-inhibiting maternal antibodies may be present on the basis of transplacentally transferred maternal antibodies;
 * maternal iodine deficiency;
 * excess of iodides in the perinatal period.

Congenital hyperthyroidism

 * a rare disorder that can endanger the life of a newborn;
 * etiopathogenesis: transplacental transfer of maternal antibodies of the IgG class stimulating the TSH receptor (aTSHR, TRAK, TRAb) in maternal thyrotoxicosis of the Graves-Basedow type but also after thyroidectomy or radioiodine treatment, as the antibodies may persist ("autoimmune neonatal thyrotoxicosis");
 * clinical picture in the fetus: tachycardia, arrhythmia, growth retardation (IUGR), goiter;
 * clinical picture in a newborn: goiter, increased irritability, tachycardia, more frequent loose stools, failure to thrive despite normal or increased appetite, insomnia, hypertension, hyperthermia, exophthalmos, hepatomegaly and/or splenomegaly, smaller large fontanelle, accelerated bone maturation;
 * risk of metabolic disruption and heart failure;
 * in newborns with a risk of transplacental transfer of TRAb, the recommended examination of the thyroid profile (T4, TSH, fT3) and TRAb already from the umbilical cord blood and then again during the first and second week of life
 * laboratory findings: ↑fT4;
 * therapy: antithyroid treatment (thiamazole) until the maternal antibodies disappear, i.e. in a decreasing dose for 2-3 months; beta blockers may be needed to affect tachycardia and adrenergic stimulation; long-term dispensary is necessary after the end of treatment.

Peripheral resistance to thyroid hormones

 * resistance of peripheral tissues to thyroid hormones → significant elevation of total and free T4 and T3, while the TSH level is slightly elevated or normal;
 * most common cause: genetically determined defect of the β subunit of the nuclear receptor for thyroid hormones;
 * clinical manifestations very variable: only biochemical abnormalities, picture of hypothyroidism or hyperthyroidism;
 * can be detected by newborn screening (elevation of TSH); otherwise, goitre, tachycardia and hyperactivity are the reasons for examination.

Iodine deficiency

 * our natural diet has a low iodine content → iodization of table salt since the 1950s (now with potassium iodate), supplementation of pregnant and lactating women, fortification of infant and toddler food products;
 * mild iodine deficiency → reduced thyroid hormone production → ↑TSH → iodopenic goiter → discrete cognitive impairments → poorer school performance;
 * the most severe form: endemic cretinism – eradicated (severe iodine deficiency in pregnant and lactating women → reduced production of thyroid hormones in the fetus and then in the newborn with serious consequences for CNS development).

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