**3. Conclusion**

The importance of maternal thyroxine for the development of the fetus brain early in pregnancy has received increasing acceptance. It has more recently become evident that maternal hypothyroxinemia results in the birth of children with decreased mental and psychomotor development.

This project proved the usefulness of universal screening of thyroid disease in pregnancy. The occurrence of pathological results in laboratory tests was 679/3577. Determination of the specific reference intervals for TSH, FT4, and TPO Ab in pregnancy is one of the basic requirements when implementing the general examination. Cooperation with gynaecologists differed, the main stumbling block was the willingness of gynaecologists to inform pregnant women about the project.

Thyroid in Pregnancy 49

Goodwin, T.M.; Montoro, M.; Mestman, J.H.; Pekary, A.E. & Hershman, J.M. (1992) The role

Haddow, J.E.; Palomaki, G.E.; Allan, W.C.; Williams, J.R.; Knight, G.J.; Cagnon, J.; O'Heir,

Hollowell, J.G.; Staehling, N.W.; Flanders, S.; Hannon, W.H.; Gunter, E.Q.; Spencer, C.A. &

Jensen, E.A.; Petersen, P.H.; Blaabjerg, O.; Hansen, P.S.; Brix, T.H. & Hegedüs, L. (2006)

Klein, R.Z.; Sargent, J.D. & Larsen, P.R.; (2001) Relation of severity of maternal

Lazarus, J.H. (2002) Epidemiology and prevention of thyroid disease in pregnancy. *Thyroid,*

Lazarus, J.H. & Premawardhana, L.D. (2005) Screening for thyroid disease in pregnancy, *Journal of Clinical Pathology,* (May 2005), Vol. 58, No 5, pp. 449–452. ISSN 0021-9746 Morreale de Escobar, G.; Obregon, M.J. & Escobar del Rey, F. (2004) Role of thyroid

Mitchell, M.L. & Klein, R.Z. (2004) The sequelae of untreated maternal hypothyroidism.

Negro, R.; Formoso, G.; Mangieri, T.; Pezzarossa, A.; Dazzi, D. & Hassan, H. (2006)

Pop, V.J.; Brouwers, E.P.; Vader, H.L.; Vulsma, T.; van Baar, A.L. & de Vijlder, J.J. (2003)

1945-7197

75, No 5, pp. 1333–1337, ISSN 1945-7197

No 8, pp.549–555, ISSN 0028-4793

87, No 2, pp.489–99, ISSN 1945-7197

(2001), Vol. 8, No 1, pp. 18–20, ISSN 0969-1413

(October 2002), Vol. 12, No 10, pp.861–865, ISSN 1050-7256

(November 2004) Vol. 151, No 3, pp.U:25–37, ISSN: 0804-4643

pp.991-998, ISSN 1434-6621

ISSN: 0804-4643

pp.573–82, ISSN 1050-7256

pp. 282-288, ISSN 1365-2265

iodine deficiency during pregnancy: maternal and neonatal effects. *Journal of Clinical Endocrinology & Metabolism*, (January 1995), Vol. 80, No 1, pp. 258–269, ISSN

of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. *Journal of Clinical Endocrinology & Metabolism* (November 1992), Vol.

C.E.; Mitchel, M.L.; Hermos, R.J.; Waisbren SE, Faix JD & Klein RZ. (1999) Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. *New England Journal of Medicine,* (August 1999), Vol. 341,

Braverman, L.E. (2002) Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). *Journal of Clinical Endocrinology & Metabolism,* (February 2002), Vol.

Establishment of reference distributions and decision values for thyroid antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and the thyrotropin receptor (TRAb). *Clinical Chemistry and Laboratory Medicine,* (2006), Vol. 44, No 8,

hypothyroidism to cognitive development of offspring. *Journal of Medical Screening*

hormone during early brain development. *European Journal of Endocrinology* 

*European Journal of Endocrinology* (November 2004), Vol. 151, No 3, pp.U45–48.

Levothyroxine Treatment in Euthyroid Pregnant Women with Autoimmune Thyroid Disease: Effects on Obstetrical Complications. *Journal of Clinical Endocrinology & Metabolism,* (July 2006), Vol.91, No 7, pp. 2587-91, ISSN 1945-7197 Nicholson, W.K.; Robinson, K.A. & Smallridge, R.C.(2006), Prevalence of postpartum

thyroid dysfunction: a quantitative review. *Thyroid* (Juny 2006), Vol. 16, No 6,

Maternal hypothyroxinemia during pregnancy and subsequent child development : a 3 year follow – up study. *Clinical Endocrinology* (September 2003), Vol. 59, No 3,

In Czech Republic, case finding screening is able to disclose less than 20% of asymptomatic mild or deep hypothyroidism or women with positive TPO Ab in pregnancy. Investigation of combination of TSH and TPO Ab is necessary. Maternal hypothyroxinemia appears to be a much more frequent cause of deficits in the progeny than congenital hypothyroidism, for which we have successful neonatal thyroid screening programs. This study maybe will help define the impact of universal screening (TSH, FT4, TPO Ab) on the health care system. The introduction of general screening of thyroid failure in pregnancy needs to be emphasized in public education; moreover, interdisciplinary cooperation of gynaecologist, endocrinologist and general practitioner, not to mention midwives should be improved. The other analysis would be more clearly identify the causal relationships between mild thyroid hormone deficiency and thyroid autoimmunity, on the one hand, and fetal neurological development on the other. In the meantime, physicians and obstetricians must use their own judgment about the optimal management for their individual patients.

#### **4. Acknowledgment**

The authors are grateful to the General Insurance Company of the Czech Republic for founging of the pilot project. The special thank belongs to all coopreating laboratories for help with blood sampling and perfekt resolving all administrative problems. Last but not least thank technicians from the Institute of Clinical Biochemistry and Laboratory Diagnostics Charles University, Prague, Czech Republic for their support in setting of reference intervals for pregnancy.

#### **5. References**


In Czech Republic, case finding screening is able to disclose less than 20% of asymptomatic mild or deep hypothyroidism or women with positive TPO Ab in pregnancy. Investigation of combination of TSH and TPO Ab is necessary. Maternal hypothyroxinemia appears to be a much more frequent cause of deficits in the progeny than congenital hypothyroidism, for which we have successful neonatal thyroid screening programs. This study maybe will help define the impact of universal screening (TSH, FT4, TPO Ab) on the health care system. The introduction of general screening of thyroid failure in pregnancy needs to be emphasized in public education; moreover, interdisciplinary cooperation of gynaecologist, endocrinologist and general practitioner, not to mention midwives should be improved. The other analysis would be more clearly identify the causal relationships between mild thyroid hormone deficiency and thyroid autoimmunity, on the one hand, and fetal neurological development on the other. In the meantime, physicians and obstetricians must use their own

The authors are grateful to the General Insurance Company of the Czech Republic for founging of the pilot project. The special thank belongs to all coopreating laboratories for help with blood sampling and perfekt resolving all administrative problems. Last but not least thank technicians from the Institute of Clinical Biochemistry and Laboratory Diagnostics Charles University, Prague, Czech Republic for their support in setting of

Abalovich, M.; Amino, N.; Barbour, L.A.; Cobin, R.H.; De Groot, L.J.; Glinoer, D.; Mandel,

Casey, B.M.; Dashe, J.S.; Wells, C.E.; McIntire, D.D.; Leveno, K.J. & Cunningham, F.G. (2006)

Dashe, J.S.; Casey, B.M.; Wells, C.E.; McIntire, D.D.; Byrd, E.W.; Leveno, K.J. & Cunnigham,

Dayan, C.M. ; Saravanan, P. & Bayly, G. (2002) Whose normal thyroid function is better-

Demers, L.M. & Spencer, C.A. (2003) Laboratory medicine practice guidelines: laboratory

Dosiou, C.; Sanders, G.D; Araki, S.S. & Crapo, L.M. (2008) Screening pregnant women for

*Endocrinology* (Juny 2008), Vol. 158, No 6, pp. 841-51, ISSN: 0804-4643 Glinoer, D.; De Nayer, P.; Delange, F.; Lemone, M.; Toppet, V.; Spehl, M.; Grün, J.P.;

(February 2006), Vol.107, No 2, pp. 337-341. ISSN 0029-7844

(October 2005), Vol. 106, No 4, pp.753–757. ISSN 0029-7844

(February 2003) Vol. 58, No 2, pp. 138-40, ISSN 1365-2265

yours or mine? *Lancet* (August 2002) Vol. 360, No 3, pp. 353–354.

S.J. & Stagnaro-Green, A. (2007) Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline. *Journal of Clinical Endocrinology & Metabolism,* (August 2007), Vol.92, No 8, pp.S1 –

Subclinical Hyperthyroidism and Pregnancy Outcomes. *Obstetrics and Gynecology,*

F.G. (2005) Thyroid-stimulating hormone in singleton and twin pregnancy: importance of gestational age-specific reference ranges. *Obstetrics and Gynecology,*

support for the diagnosis and monitoring of thyroid disease. *Clinical Endocrinology*

autoimmune thyroid disease: a cost-effectiveness analysis. *European Journal of* 

Kinthaert, J. & Lejeune, B. (1995) A randomized trial for the treatment of mild

judgment about the optimal management for their individual patients.

**4. Acknowledgment** 

**5. References** 

reference intervals for pregnancy.

S47, ISSN 1945-7197

iodine deficiency during pregnancy: maternal and neonatal effects. *Journal of Clinical Endocrinology & Metabolism*, (January 1995), Vol. 80, No 1, pp. 258–269, ISSN 1945-7197


**3** 

*Spain* 

**Adrenal Disease and Pregnancy** 

During pregnancy, maternal-endocrine regulation, as well as all their physiology, undergoes profound adaptive changes in the framework of a functional organization structured in three interrelated compartments: the mother, placenta and fetus. Many of these changes are initially induced by estradiol and progesterone produced by the corpus luteum, combined with chorionic gonadotropin. As the pregnancy progresses, steroid and peptide hormones produced by the fetoplacental unit, took over. As a result of these adaptive phenomena is achieved adequate nutritional support of the fetus, uterine quiescence is maintained during

During normal pregnancy, serum cortisol increase gradually from the second quarter, keeping the circadian rhythm. Part of the increase in serum cortisol is due to increased estrógens and secondarily to increased cortisol binding protein (CBG), although serum free cortisol, urine and saliva can be elevated up to 2-3 times. The plasma concentration of ACTH is usually normal, although during pregnancy can be reduced or increased. There is a gradual increase in late pregnancy and during delivery (Lindsay & Nieman, 2005). The placenta during gestation can produce CRH which is released into the maternal circulation, although this may have implications in the regulation of ACTH and cortisol secretion are

Cushing`s syndrome is uncommon during pregnancy, because hypercortisolism produces

The frecuency of ACTH-independent cases is increased in pregnant as compared to non pregnant individuals. Of the approximately 136 reported cases, approximately 60% had ACTH independent Cushing´s Syndrome: 44% adenoma y 11% carcinoma and the remainder a mix of primary pigmented nodular adrenal disease, ACTH independent hyperplasia and ectopic ACTH secretion. Five pregnant women with the ectopic ACTH

The fetus is partially protected from the hypercortisolemia because placental 11 betahydroxysteroid dehydrogenase converts 85% of maternal cortisol to biologically inactive cortisone. However, untreated Cushing´s syndrome has been associated with spontaneous abortion (25%), premature delivery (50%) and rarely, neonatal adrenal insufficiency (Aron et

childbirth, and breastfeeding is finally possible (Schindler, 2005).

anovulation and infertility by altering androgenos and gonadotropin.

syndrome have been reported (Guilhaume et al., 1992).

**1. Introduction** 

**2. Cushing´s syndrome**

not well known.

al., 1990).

Guadalupe Guijarro de Armas *University Hospital of Getafe (Madrid)* 

