Adrenal Cushing’s syndrome during pregnancy

Abstract

Cushing syndrome (CS) during pregnancy is a rare condition with only a few cases reported in the literature. Misdiagnosis of CS is common because of overlapping features like fatigue, weight gain, striae and emotional changes that can occur during normal pregnancy. Changes in maternal hormones and their binding proteins complicate assessment of glucocorticoid hormone levels during gestation. CS during pregnancy is most frequently due to an adrenal adenoma and to a lesser degree to adrenocorticotropic hormone (ACTH) hypersecretion by a pituitary adenoma. Furthermore, aberrant expression of luteinizing hormone (LH) receptors in the adrenal cortex has been suggested to be involved in the pathogenesis of adrenal CS during pregnancy. We report three pregnant women with ACTH-independent Cushing's syndrome and an adrenal tumor. After uncomplicated delivery, patient 1 underwent testing for aberrant hormone receptor expression by the adenoma. Cortisol responses were found after administration of luteinizing hormone-releasing hormone (LHRH), human chorionic gonadotropin (hCG), glucagon, vasopressin and a standard mixed meal. All patients were treated with laparoscopic adrenalectomy. Adrenal tumor tissue of two patients showed positive immunohistochemical staining of LH receptors. Considering the cortisol responses to LHRH and hCG, and the development of CS during pregnancy in these patients, it is likely that ACTH-independent hypercortisolism was induced by the pregnancy-associated rise in hCG levels that activated aberrantly expressed LH receptors in the adrenal adenoma. Remarkably, adrenal adenomas may simultaneously express multiple aberrant receptors and individual ligands may play a role in the regulation of cortisol production in CS during pregnancy.

MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing’s syndrome during pregnancy: solved and unsolved questions

“…Patients with active CS in pregnancy-induced CS, experienced more problems in pregnancy and had the worst fetal prognosis in comparison to other causes (7). Andreescu et al (28) recently reported the rare cases of 3 patients with hypercortisolism and adrenal adenoma during pregnancy: 1 of them showed in vivo response of cortisol production to HCG, LHRH, glucagon, vasopressin and a standard mixed meal. In these 3 patients, pregnancy led to overt hypercortisolism.…”

“…The outcome in such patients is difficult to predict: autonomous cortisol secretion can happen only during pregnancy or can be maintained, usually at lower levels of cortisol, after delivery (28).…”

Cushing syndrome in pregnancy, diagnosed after delivery

“…Second, the clinical signs of hypercortisolism (weight gain, fatigue, hypertension, and hyperglycemia) overlap with the physiological changes that characterize pregnancy [2,5]. Therefore, CS is often not diagnosed until the second trimester [6]. However, although many of the symptoms overlap, the occurrence of pathological fracture should provoke a CS work-up [7].…”

Pregnancy-induced Cushing’s syndrome with an adrenocortical adenoma overexpressing LH/hCG receptors: a case report

“…If surgery is contraindicated or must be delayed, treatment with steroidogenesis inhibitors, usually with metyrapone, can be an alternative [22]. Metyrapone has been shown to control hypercortisolism effectively in most instances [23], despite its adverse effects including hypertension, worsening of preeclampsia and the risk of affecting fetal adrenal steroid synthesis since it can cross the placenta [24]. In our case, the patient was managed conservatively by controlling Cushingoid comorbidities and achieved satisfactory management of blood pressure and blood glucose, given that the adrenal mass was determined by MRI late in the third trimester.…”