Childhood Cushing’s Patients May Experience Long-Term Hormonal Deficits, Mood Disorders

People diagnosed with Cushing’s disease during childhood may experience lowered pituitary hormones long after receiving surgery, as well as mood and cognitive disorders, a long-term follow-up study shows.

The study, “Long-Term Outcome in Patients After Treatment for Cushing’s Disease in Childhood,” was published in the journal PLoS ONE.

Cushing’s disease (CD) is caused by a benign tumor (an adenoma) in the pituitary gland that secretes too much adrenocorticotropic hormone (ACTH). High ACTH levels cause the adrenal glands, which sit above the kidneys, to produce too much cortisol.

The condition is extremely rare in children and usually is treated by surgically removing the tumor. Although the short-term effects of this surgery are known, how these patients fare in the long run is much less clear.

To address this issue, physicians at the Children’s Memorial Health Institute (CMHI) in Poland performed a retrospective analysis of 29 patients (15 girls and 14 boys) diagnosed with Cushing’s disease at an average age of 13.5 years and followed up for an average of 10.2 years after the surgery.

At the last follow-up appointment, 23 patients (86%) had long-term disease remission, including 18 patients (62%) who received a single surgery to remove the pituitary tumor, two patients (6.9%) who required two pituitary surgeries, one patient (3.4%) who received pituitary surgery plus radiotherapy, and three patients (10.3%) who also underwent surgical removal of both adrenal glands in addition to the pituitary surgery.

One patient (3.4%) died after the second operation due to complications, one patient (3.4%) had persistent disease, and in one patient (3.4%) the long-term follow-up was not possible.

Despite remission in most patients, 17 patients (63%) needed to take levothyroxine a medicine used to treat hypothyroidism (low thyroid hormone) continuously, 16 patients (59%) required hydrocortisone treatment, 10 patients (37%) needed sex hormone replacement and four patients (15%) were on antidiuretic hormone.

According to the research team, these relatively high rates of hormone deficiencies may be explained by two factors: first, the pituitary surgeries were extensive, resulting in high remission rates, but at the cost of removing parts of the gland needed to produce other hormones; second, they were performed a long time ago, “when imaging, accessibility of diagnostic methods and surgical technique were not ideal.”

Two patients reported being depressed and under constant psychiatric care six and 16 years after surgery, but they did not require anti-depressant therapy. Neither of these two patients had psychiatric problems before the pituitary surgery.

Thirty-eight percent of 18 surveyed adults reported low mood, 33% depressive states, 44% memory problems, 50% emotional lability, 39% problems with concentration, 61% mood swings, and 67% irritability.

Other findings revealed that 62% of the initial 29 patients developed diabetes insipidus, one patient had delayed puberty. However, all five patients with high blood pressure at the time of diagnosis saw this condition resolve. One patient developed high blood pressure during follow-up.

Recurrence occurred in four of 28 patients (14%), 3.6 years on average after definitive treatment. One patient (3.4%) developed Nelson’s syndrome — a disorder characterized by abnormal hormone secretion, enlargement of the pituitary gland, and the development of large and invasive growths known as adenomas–  after removal of both adrenal glands.

Two patients (6.9%) were suspected of relapse at the latest follow-up.

“CD recurrence can occur even a long time after effective treatment,” the team concluded. “Long-term observation of patients after CD treatment in childhood indicates the presence of a large number of patients with hormonal pituitary deficits, as well as a significant problem of mood and cognitive disorders that may be the result of [excess cortisol] in the past.”