Case Report Points to Subclinical Cushing’s Syndrome as Possible Diagnosis in Pregnancy with Preeclampsia

Cushing’s syndrome can occur during pregnancy without obvious signs and symptoms specific to the condition, a new case report shows, suggesting the disease should be considered as a diagnosis in cases of high blood pressure during early pregnancy.

The case report, “A case of subclinical Cushing’s syndrome in pregnancy with superimposed preeclampsia,” was published in Clinical Case Reports.

Cushing’s syndrome is caused by elevated levels of the hormone cortisol, which lead to the typical symptoms of the condition. Sometimes — particularly in instances of Cushing’s caused by an adrenal tumor — cortisol levels can be elevated, but without causing obvious symptoms. This is called subclinical Cushing’s syndrome.

The new case report details the case of a 34-year-old woman who was pregnant after having given birth twice before. There had been no abnormal blood pressure readings in either previous pregnancy, but 12 weeks into this third pregnancy, the woman’s blood pressure suddenly increased to 170/91 mm Hg. (Normal values would typically be under 120/80 mm Hg.)

Such a spike in blood pressure during pregnancy might be indicative of preeclampsia, a condition that occurs in pregnancy and typically characterized by high blood pressure and protein in urine, among other symptoms.

However, 12 weeks would be quite early for preeclampsia to develop. (It typically begins after 20 weeks.) Additionally, “the patient showed no sign of preeclampsia [apart from the high blood pressure] at this time,” the researchers wrote.

Because of this, it was suspected that the patient had a pre-pregnancy condition that was causing elevated blood pressure.

A hormonal profile at this stage revealed cortisol levels to be somewhat high (15.5 μg/dL), though still within the range of what is considered normal (4.5‐21.1 μg/dL). However, levels of adrenocorticotropic hormone (ACTH), which helps regulate cortisol levels and is often involved in Cushing’s, were abnormally low (less than 1.5 pg/mL; the normal range is 7.2‐63.3 pg/mL).

From these results, a diagnosis of subclinical Cushing’s syndrome was suspected.

By 28 weeks of pregnancy, the patient had developed HELLP syndrome, which is characterized by the breakdown of blood cells, low numbers of platelets, and high levels of certain liver enzymes. At that time, the infant was delivered by cesarean section.

Following delivery, additional tests — including a dexamethasone suppression test and various imaging scans — revealed that the patient had an adrenal tumor causing abnormal ACTH/cortisol levels, confirming the diagnosis of subclinical Cushing’s syndrome. The patient is expected to undergo surgical removal of the tumor.

It is noteworthy that Cushing’s during pregnancy has been associated with numerous complications, both for the pregnant person and the fetus. However, whether subclinical Cushing’s during pregnancy has such effects isn’t clear. This is further complicated by the fact that normal physiological changes during pregnancy can themselves influence cortisol levels, making it even less likely for the condition to be diagnosed.

“There is no consensus on the management of SCS [subclinical Cushing’s syndrome] during pregnancy due to the rarity of this condition,” the team noted.

Nonetheless, as of the publication of the case report, “No neurodevelopmental difficulties have been identified in the infant.” Whether or not this is a typical outcome of subclinical Cushing’s in pregnancy will require more research.

This case report advises that subclinical Cushing’s is a diagnosis to consider when there is an elevation in blood pressure detected during early pregnancy, without an obvious cause: “When we see preexistent hypertension in pregnancy, subclinical Cushing’s syndrome should be considered in the differential diagnosis,” the researchers wrote.