Pregnancy and Cushing’s Syndrome

Emre KÖLE* & Merve KÖLE

Bilecik State Hospital Department of Obstetrics, Gynecology Bilecik, Turkey

*Correspondence to: Dr. Emre KÖLE, Bilecik State Hospital Department of Obstetrics, Gynecology Bilecik, Turkey.

Copyright © 2018 Dr. Emre KÖLE, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction
During normal pregnancy, serum cortisol levels gradually increase in the second trimester while maintaining the circadian rhythm. The increase of serum, urine and salivary cortisol contributes to the increase of estrogen and cortisol binding protein (CBG). During pregnancy the plasma concentration of ACTH is usually normal. In the last trimester, a gradual increase can be seen at ACTH level [1]. Cushing’s Syndrome is rare during pregnancy, because hypercortisolism is associated with anovulation and infertility. Compared to nonpregnant women, the incidence of ACTH-independent cases is increased in pregnant individuals. Of the 136 cases reported, approximately 60% had ACTH independent Cushing´s Syndrome: 44% adenoma, 11% carcinoma and remainder a mix of primary pigmented nodular adrenal disease, ACTH independent hyperplasia and ectopic ACTH secretion. Untreated cases of Cushing’s Syndrome (CS) has been associated with abortion (25%), premature delivery (50%), hypertension (70%), gestational diabetes (25%) and preeclampsia [2].

Discussion

Cushing’s Syndrome is often described as a state of glucocorticoid excess. This clinical condition, irrespective of the reason, can be caused by endogenous production of cortisol from the adrenal gland (endogenous CS) or by exogenous synthetic glucocorticoids (iatrogenic CS) administered in the treatment of any diseases. Adrenal diseases are rarely anticipated in pregnancy. Adrenal diseases such as Cushing’s Syndrome, Addison’s disease, pheochromocytoma, primary hyperaldosteronism and congenital adrenal hyperplasia can cause maternal and fetal serious morbidity and mortality in pregnancy. Since symptoms associated with pregnancy are also seen in adrenal diseases, the diagnosis of adrenal disorders in pregnancy is difficult to make. There are no clear recommendations in international guidelines for gynecologic diagnosis and treatment of many adrenal disorders. Since Cushing’s Syndrome (CS) is associated with infertility, it is rarely seen during pregnancy. High levels of cortisol in pregnancy can cause difficulties in interpreting diagnostic tests. Elevation of twenty-four-hour urinary free cortisol (UFC) to 2-3 times and deterioration of diurnal rhythm helps with the differential diagnosis. In diagnosis, ACTH-dependent Cushing’s syndrome highdose dexamethasone suppression test (HDDS) or CRH stimulation test can be performed on patients. MRI of the Pituitary Gland is helpful in radiological imaging. Because of the fetal and maternal complications, CS must be treated fully in pregnancy. If adenoma is confirmed, surgery must be performed in the second trimester of pregnancy. Metyrapone can be used in medical treatment, but there is a risk of hypertension, preeclampsia, intrauterine growth retardation (IUGR), fetal hypoadrenalism and coarctation of the aorta. Due to potential antiandrogen effects, ketoconazole use can be recommended as second line therapy [3-7].

Conclusion

Although Cushing’s Syndrome is rare and its diagnosis is difficult because of the reduced fertility, early diagnosis and decisive treatment are important because of both maternal and fetal morbidity and mortality.

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