Ectopic ACTH-secreting pituitary adenomas (EAPAs), a rare cause of Cushing’s disease, are more commonly found in women, who also have a poorer prognosis than men with the same condition, a study suggests.
Titled “Long-term follow-up for ectopic ACTH-secreting pituitary adenoma in a single tertiary medical center and a literature review” and published in the journal Pituitary, the study also highlights diagnostic challenges in identifying these ectopic ACTH-secreting pituitary adenomas, which are tumors made up of pituitary cells that grow outside the pituitary gland.
The most common cause of Cushing’s syndrome is a tumor on the pituitary gland that causes it to secrete too much adrenocorticotropic hormone (ACTH), which, in turn, increases cortisol levels and leads to the symptoms of Cushing’s.
Tumors outside the pituitary gland can also secrete ACTH and cause Cushing’s syndrome in rare instances, such as with ectopic ACTH-secreting pituitary adenomas. These tumors are made of pituitary cells, but they aren’t located on the pituitary gland itself. Rather, they are located in structures surrounding the pituitary and often arise from residual pituitary cells left behind during embryonic development.
This phenomenon can provide diagnostic challenges, and prognosis and best treatment strategies aren’t fully understood.
Researchers conducted a retrospective analysis on six patients (four female, two male) with EAPA-related Cushing’s syndrome who were treated at the Peking Union Medical College Hospital between 2000 and 2019. All had symptoms indicative of Cushing’s, including central obesity and elevated levels of ACTH in the blood.
Diagnosing these individuals with EAPA was a challenge. Four patients underwent inferior petrosal sinus sampling (IPSS), a diagnostic technique that measures ACTH levels in the veins by draining the pituitary to determine the source of excess ACTH in circulation.
Three of these patients had results suggestive of an ACTH-secreting pituitary tumor, but none had pituitary tumors. Additional careful magnetic resonance imaging (MRI) analysis was used to identify the EAPAs. One of the cases required multiple MRIs after an initial result proved to be a false-positive after exploratory surgery.
“Because of the biochemical similarity between EAPA and intrasellar pituitary corticotrophin adenoma, it is difficult to distinguish them by the use of common tests only, including IPSS,” the researchers said. The term “intrasellar” refers to being within the compartment of the skull housing the pituitary gland.
All six tumors were eventually removed. After surgery, two patients were in full remission, one was in partial remission, and three required additional treatment such as radiotherapy.
Following the analysis of patients treated at their clinic, the researchers conducted a review of the available scientific literature to better understand the prognosis for EAPAs. They identified data for a total of 54 individuals. Most (77.8%) were female, and the average age was 38.
This literature review revealed that some of the diagnostic challenges, such as misleading IPSS results, have been reported before. Of the 24 people who underwent IPSS, 83.3% had a result generally considered indicative of a tumor in the pituitary.
The actual location of the EAPAs was most commonly in regions of the skull close to the pituitary, but in separate spaces, including the cavernous sinus, sphenoid sinus, and suprasellar region. There were no significant differences in terms of prognosis (chance of remission or recurrence) or diagnosis (IPSS results) among tumors at these locations.
Remission rates were significantly higher among males (100%) than females (68.4%). Other clinical and demographic factors were not significantly associated with the likelihood of remission. The most common treatment strategy was surgery.
These findings emphasize diagnostic challenges presented by EAPAs, and provide insight into the medical management of these tumors.
“Given the severity of the disease, for patients with negative intrasellar findings, a careful review of imaging examinations should be considered due to the possibility of this uncommon situation,” the researchers wrote. “Once the disease is highly suspected, tumor resection should be performed as the first choice of treatment by an experienced surgeon.”