Rare Pituitary Gland Tumor Found to Trigger Cushing’s: Case Study
Researchers note importance of recognizing plurihormonal tumors
A rare plurihormonal tumor in the brain’s pituitary gland — one that produced and released both adrenocorticotrophic hormone (ACTH) and growth hormone — caused Cushing’s disease in a woman in her 30s, a case study reported.
Given the rarity of tumors in which both types of hormones are produced, the researchers stressed the importance of recognizing them during the diagnostic process. They also noted a need for close follow-up and further treatment options for patients with these rare tumors.
“We aim to raise more awareness of this rare type of pituitary [tumor], shed light on the importance of recognising rare presentations and highlight the necessity of rigorous follow-up given morbidity and potentially higher mortality risk,” the team wrote.
The study, “Plurihormonal pituitary adenoma cosecreting ACTH and GH: a rare cause of Cushing’s disease,” was published in the journal BMJ Case Reports.
Investigating a rare pituitary gland tumor
Cushing’s syndrome includes a group of disorders marked by abnormally increased levels of the stress hormone cortisol. Cushing’s disease is a specific type of the syndrome in which high cortisol levels are caused by a tumor, usually benign, in the brain’s pituitary gland that releases ACTH.
A plurihormonal tumor is a unique type of pituitary gland tumor, characterized by the production and release of several hormones. The most common are those that secrete, or release, growth hormone and prolactin, a hormone involved in lactation. In rare cases, growth hormone is secreted along with ACTH. In such cases, very few patients develop Cushing’s disease.
Now a group of researchers in Canada reported a case of a woman with a recurrent plurihormonal pituitary tumor secreting both growth hormone and ACTH, who developed Cushing’s disease.
The woman first was treated at age 16 for weight gain, excessive hair growth (hirsutism), acne, and irregular periods. Given the symptoms, she was believed to have polycystic ovarian syndrome, in which the ovaries produce an abnormal amount of male hormones.
However, other symptoms developed in the following years, including memory decline, changes in school scores, lack of energy, and insomnia. Her face swelled up into a moon shape — a hallmark of Cushing’s —she had fat deposits in the neck, and developed thicker and darker skin patches (acanthosis).
A urine test revealed the presence of high levels of cortisol, at 544 nanomoles per day (nmol/day) — the normal range is 50–220 nmol/ day.
A dexamethasone suppression test, commonly used to diagnose Cushing’s, was performed. In this test, patients take the steroid medication dexamethasone at night and then have their blood cortisol levels measured the next morning. Dexamethasone normally blocks cortisol production. Cushing’s may be suspected when cortisol levels fail to drop in response to the medication.
There are two types of dexamethasone suppression tests: low- and a high-dose. The low-dose test is typically used to detect hypercortisolism, or excessive cortisol levels in the body, while the high-dose test normally pinpoints the source of excessive cortisol.
In this woman, poor cortisol suppression was observed in the lower dose test, consistent with the presence of Cushing’s. Adequate suppression, however, was seen in response to the higher dose test, also consistent with the presence of Cushing’s disease.
However, ACTH was not suppressed, showing a value of 15 picomoles per liter (pmol/L) (normal range: 0–18 pmol/L). Levels of prolactin and growth hormone were normal.
Bone density tests indicated that the woman had low bone density for her age. Imaging tests also showed a pituitary tumor, which was surgically removed. Tumor tissues were analyzed for the presence of ACTH, growth hormone, and prolactin using immunohistochemistry — a method that detects these hormones by staining tissue samples with highly selective antibodies.
The test confirmed the presence of the three hormones.
A new pituitary gland tumor
After surgery, the woman developed adrenal insufficiency, a condition that occurs when the adrenal glands, which sit atop the kidneys, do not make enough cortisol and other hormones. As such, she was placed on cortisol replacement therapy with cortisone acetate for one year. Her symptoms eased.
Nine years later, however, the woman returned to the hospital with complaints of headache, weight gain, face widening, worsening acne and hirsutism, and oily skin. She also reported anxiety, mood changes, and irregular periods. Given these symptoms, clinicians suspected Cushing’s had returned.
Cortisol levels were high in the urine (346 nmol/day; normal range 8–120 nmol/day) and saliva (13 nmol/L; normal range 0–7 nmol/L). However, ACTH levels were normal.
A dexamethasone suppression test again showed an adequate suppression of cortisol with high-dose dexamethasone, but a poor one with low-dose.
Imaging tests showed a lesion in the pituitary gland and a portion of residual pituitary tumor. According to researchers, such plurihormonal pituitary tumors “have been associated with higher risk of recurrence; particularly those cosecreting ACTH.”
She again was diagnosed with Cushing’s disease and with acromegaly, a hormonal condition that develops when the pituitary gland produces too much growth hormone during adulthood. In this case, this condition was secondary to the pituitary tumor. As such, she had surgery again to remove the tumor.
Immunohistochemistry tests performed in tumor tissue samples revealed the presence of both ACTH and growth hormone, as well as the transcription factors that regulate the levels of these hormones. Transcription factors are proteins able to control the activity of certain genes.
According to researchers, “diagnosis based solely on clinical findings and biochemistry [blood and urine tests] may pose a challenge given the variability of hormone secretion, thus immunohistochemistry plays an important role in diagnosis.”
Considering novel treatment options
Th patient was given cabergoline to reduce the secretion of ACTH and ketoconazole to lower cortisol levels, but no improvements were observed. She therefore underwent another surgery to remove both pituitary lesions.
After surgery, she again developed adrenal insufficiency, with cortisol levels dropping to 40 nmol/L (normal range 120–535 nmol/L). She underwent cortisol replacement therapy, this time with hydrocortisone, for five months. Overall, her symptoms eased.
Five years later, she remains stable and continues to be followed.
“Given the high recurrence rate and morbidity related to this rare type of PHAs [plurihormonal pituitary tumors], we emphasize the importance of maintaining close follow-up,” the researchers wrote.
However, despite these improvements and “given the nature of this rare disease, one cannot rule out the possibility of future recurrence. Thus, the search for different management options is crucial,” the team wrote.
One of the options proposed by researchers is treatment with Signifor (pasireotide), a therapy for patients with Cushing’s disease who are ineligible for surgery or whose tumor came back after surgery. However, they recognize that “future studies are needed to assess its long-term effect in this specific population.”
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