Rare Blood Clot Disorder Follows Pituitary Gland Surgery in Teen

A 14-year-old girl with aggressive Cushing’s disease developed cavernous sinus thrombosis — a rare condition that causes blood clots to form in a cavity at the base of the brain — after an initial surgery to remove a benign tumor in the pituitary gland.

Her case highlights that cavernous sinus thrombosis is an unusual but possible complication of Cushing’s disease, and one requiring prolonged treatment.

The case study, “Recurrent cavernous sinus thrombosis: a rare complication of Cushing disease” was published in the journal BMJ Case Reports.

The girl arrived at the hospital in Malaysia in September 2017 with a headache and a drooping right upper eyelid.

She had missed her menstrual cycle for the previous eight months, during which she had a weight gain of 30 kg (around 66 lbs), leading to her being diagnosed as obese.

The girl’s blood pressure was elevated, requiring treatment with an antihypertensive, and she showed mild hirsutism (excessive hair growth), and problems with the oculomotor nerve of her right eye. This nerve controls eye and eyelid movements, as well as the pupil and lens inside the eye.

MRI scans revealed a large benign tumor, called a macroadenoma, in the brain’s pituitary gland, consistent with a diagnosis of Cushing’s disease.

Clinicians then conducted a short synacthen test, which measures blood cortisol levels before and after the administration of a lab made cortisol-controlling adrenocorticotropic hormone (ACTH), to evaluate her pituitary and adrenal glands. Test results were normal.

Although her initial hormonal profile did not support a Cushing’s diagnosis, the presence of a macroadenoma along with some of her symptoms — obesity and high blood pressure — led physicians to diagnose the girl with this disease.

Surgeons removed the tumor in October. Six months later, in 2018, the girl returned to the hospital with severe headaches, but no fever or signs of an infection.

Computed tomography (CT) brain scans revealed the presence of cavernous sinus thrombosis — a rare, life-threatening condition that causes blood clots to form within the cavernous sinus, a cavity at the base of the brain through which deoxygenated blood from the brain is brought back to the heart.

She was started on an anticoagulant and again underwent screening tests for Cushing’s disease. This time, tests showed higher than normal levels of ACTH and cortisol.

Her blood cortisol levels also failed to drop after an overnight, low-dose dexamethasone suppression test, confirming the diagnosis. This test measures blood cortisol levels in the morning that follows a patient taking a tablet of dexamethasone, a corticosteroid that normally blocks its production.

Two months later (eight months post-surgery), she again experienced severe headaches with complete right upper eyelid droopiness. This was accompanied by impaired function of six cranial nerves — a set of nerves that arise in the brain and are responsible for controlling sensations, movements, and reflexes in different parts of the head and neck.

CT scans showed features of cavernous sinus thrombosis affecting the right side of her brain, along with residual signs of the condition on the left side.

Her treatment was switched to enoxaparin, another anticoagulant (sold as Lovenox, among other brand names). But severe headaches again returned six months later, along with upper eyelid droopiness on her left eye.

MRI scans revealed the recurrence of a mass in the left side of her pituitary gland, and she underwent another surgery to remove it. On a surveillance MRI scan five months later, a mass was detected on the right side of her pituitary gland, accompanied by right cavernous sinus thrombosis. This mass was deemed inoperable.

The girl was then started on radiotherapy. After 30 completed cycles, a follow-up MRI scans showed a shrinking in the tumor’s mass. Cavernous sinus thrombosis was no longer evident.

At the latest follow-up, she was still showing typical signs of Cushing’s disease, with high ACTH levels and a failure to respond to the dexamethasone suppression test.

The patient was waiting to begin treatment with Signifor (pasireotide), an approved therapy for people with Cushing’s disease for whom surgery has failed, at the report’s close. While waiting, she began treatment with cabergoline, a medication that lowers the secretion, or release, of ACTH by the pituitary gland.

According to the researchers, this case of a “ young girl with aggressive [Cushing’s disease] complicated with recurrent [cavernous sinus thrombosis]” highlighted the importance of repeating lab tests for Cushing’s whenever there is clinical suspicion for the disease, and considering cavernous sinus thrombosis as a possible complication.

They also noted that in children with Cushing’s disease, a  “multidisciplinary team approach is important.”