Cushing’s May Return in the First Weeks After Childbirth: Case Report

Researchers said case was first to describe dormant Cushing’s disease at pregnancy that became symptomatic after delivery

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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The hormonal changes that occur during pregnancy and at childbirth may trigger the reappearance of Cushing’s disease in the mother following birth, a recent case report indicated.

This is the first reported case of a woman with dormant Cushing’s disease during pregnancy who became symptomatic following delivery, according to its authors, who noted that testing for Cushing’s during and after childbirth would help “determine when [Cushing’s disease] occurred in relation to pregnancy, so that we can further understand the link between pregnancy and [Cushing’s disease] occurrence, recurrence, and/or persistence.”

The report, “Persistent vs Recurrent Cushing’s Disease Diagnosed Four Weeks Postpartum,” was published in Case Reports in Endocrinology.

Cushing’s syndrome is marked by unusually high levels of a hormone called cortisol. In most cases, it’s caused by abnormally high levels of another hormone called adrenocorticotropic hormone (ACTH) due to a tumor in the brain’s pituitary gland. In these cases, the condition is known as Cushing’s disease.

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Despite being rarely seen in pregnancy, Cushing’s disease can be triggered by an increase of the corticotropin-releasing hormone (CRH) released by the placenta. CRH promotes the release of ACTH by the pituitary gland, which leads to elevated cortisol levels.

Most cases of Cushing’s disease during pregnancy occur during the peripartum period — the time immediately before, during, and shortly after birth.

Researchers at the Icahn School of Medicine at Mount Sinai, New York described the case of a woman with dormant Cushing’s disease during pregnancy that returned and caused her to become symptomatic after delivering a baby.

The 30-year-old woman, who had a miscarriage 10 months earlier, presented with a plethora of symptoms, including prediabetes, weight gain, dorsal hump, abdominal stretch marks, depression, weakness in her feet, and oligomenorrhea (infrequent menstrual periods).

Laboratory tests were consistent with hypercortisolism, or excessive cortisol levels, and an MRI scan identified a lesion on her pituitary gland.

She underwent transsphenoidal surgery (TSS), a minimally invasive surgery to remove tumors from the pituitary gland. Three days after surgery, her cortisol levels dropped to under normal levels and she received hydrocortisone to maintain them within a normal range.

Tissue analysis of the pituitary lesion failed to confirm its tumorigenicity, that is, whether it was benign or malignant. She was tapered off hydrocortisone six weeks after surgery.

The woman’s symptoms gradually eased and she became more energized and her mood improved. Her stretch marks resolved and her menstrual periods became regular. Lab tests found no signs of Cushing’s recurrence and no pituitary adenoma — a tumor of the pituitary gland — was seen on MRI scans.

She became pregnant, unexpectedly, three months after surgery. Her glucose (blood sugar) levels were normal by week 20 of gestation and she showed no other signs of Cushing’s disease.

Every eight weeks, her cortisol levels were checked. Despite having a higher cortisol level in the urine by week 17 — 93 mcg per 24 hours — it was lower than the range typically seen in Cushing’s disease.

By the end of the second trimester, she reported severe fatigue. Her cortisol levels were low and she restarted hydrocortisone treatment.

She underwent a cesarean section at 40 weeks due to oligohydramnios, a condition wherein there is too little amniotic fluid — the liquid that surrounds the fetus — and delivered a healthy baby boy. Hydrocortisone was discontinued immediately after delivery.

Within four weeks, however, she developed symptoms consistent with Cushing’s disease. Cortisol levels were abnormally high when measured in saliva at midnight — a diagnostic test known as midnight salivary cortisol test — and in a 24-hour urine test.

An MRI of the pituitary gland confirmed the presence of a small pituitary adenoma, which was consistent with her clinical history and was considered to be a recurrent tumor.

The tumor was removed by TSS. Following surgery, her cortisol levels dropped and within a month she was tapered off hydrocortisone.

She continued to have weight gain, muscle weakness, and fatigue, however. Three months after surgery, cortisol levels were once again elevated. Another MRI revealed a tumor in the pituitary gland.

The woman began treatment with metyrapone, a cortisol-lowering medication marketed under the brand name Metopirone. No significant improvements were seen and she decided to have a bilateral adrenalectomy, surgery to remove both adrenal glands, after talking to her medical team.

“We describe the first report of recurrent [Cushing’s disease] that was quiescent [dormant] during pregnancy and diagnosed in the immediate postpartum period,” the researchers wrote. “Understanding the risk and mechanisms of [Cushing’s disease] recurrence in pregnancy allows us to counsel these otherwise healthy, reproductive-age women in the context of additional family planning.”