Cushing’s Patients’ Thyroid Hormone Levels Eventually Normalize Following Transsphenoidal Surgery, Study Finds

Most Cushing’s disease patients who achieve remission experience overproduction of thyroid hormones, followed by a return to normal levels,  within 12 months after surgery to remove a pituitary tumor, according to new research.

The findings also showed that changes in thyroid hormones are associated with serum levels of cortisol.

The research, “A Study of Thyroid Functions in Patients With Cushing`s Syndrome: A Single-Center Experience,” was published in the journal

Although previous studies in Cushing’s syndrome patients reported abnormal levels of thyroid hormones after remission, these patients still may be misdiagnosed with hypothyroidism (insufficient thyroid hormone production) or hyperthyroidism (excessive thyroid hormone production), due to scarce information about the condition.

A team at Fudan University, in China, attempted to bridge this knowledge gap by analyzing thyroid function of patients with Cushing’s syndrome and assessing the clinical course of variations in thyroid hormones levels in Cushing’s disease patients pre- and post-operatively.

The study included 118 patients, 102 with Cushing’s disease, 10 with adrenal Cushing’s syndrome, and six with ectopic adrenocorticotropic syndrome (when the source of adrenocorticotropic hormone, or ACTH, is a tumor outside the pituitary gland). They were hospitalized at Huashan Hospital between January 2013 and April 2016.

The researchers measured the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free T3 (FT3), free T4 (FT4), and serum cortisol at diagnosis in all patients. Among those with Cushing’s disease, levels also were measured three months after transsphenoidal pituitary tumor removal.

Nine patients who achieved Cushing’s disease remission further underwent hormonal measurements at intervals of one day, two weeks, one month, and two months after surgery. Also, hormone and anti-thyroid antibody evaluations were conducted in 28 Cushing’s disease patients achieving remission before and three, six and 12 months after surgery.

Of note, remission was defined as having morning serum cortisol levels lower than 5.0 μg/dL within seven days of tumor removal. Replacement treatment with cortisone began after remission.

The results showed that, at diagnosis, levels of thyroid hormones were below the reference range in 31% (TSH), 69% (T3), 44% (FT3), 11% (T4) and 19% (FT4) of the Cushing’s disease patients. Thirty-three patients (28%) showed low levels of TSH and T3 or T4.

Serum cortisol levels were higher in ectopic adrenocorticotropic syndrome patients compared to those with adrenal Cushing’s syndrome or Cushing’s disease. The ectopic group also had significantly lower FT3 and FT4 levels compared to patients with Cushing’s disease.

A total of 81 Cushing’s disease patients achieved remission within three months after surgery, 20 of whom did not need cortisone thereafter. Compared to values before surgery, remitted patients had significantly higher post-surgery levels of TSH, T3, FT3, and T4.

Levels of TSH (nine patients), T3 (four patients) and FT3 (14 patients) were above the reference range at three months in the remission group. In contrast, FT4 slightly decreased post-surgery.

The data further showed that TSH, T3, and FT3 were higher in patients on remission than in the remaining 21 participants with Cushing’s disease. The opposite result was seen with FT4 levels.

Statistical analyses found that, before surgery, higher serum cortisol levels correlated with lower values of thyroid hormones, including TSH, T3, and FT3. Also, higher body mass index was associated with higher levels of T3 and FT3, while older age correlated with lower FT3 and FT4 amounts.

As for the nine Cushing’s disease patients closely monitored over three months, TSH increased from the first day after surgery, while the levels of T3 and FT3 increased markedly after a transient reduction, which the scientists attributed to surgery stress.

Cortisol levels dropped significantly after surgery among the 28 patients on a 12-month follow-up. The proportion of patients receiving cortisone replacement lowered from 85.7% the day after surgery, to 14.3% at 12 months. Levels of TSH, T3 and FT3 steadily increased postoperatively, although, at the end of follow-up, TSH levels above the reference range were seen in only three patients, and only one participant had a similar increase in FT3.

“After remission of CD, TSH, T3, and FT3 increased significantly, even above the reference range, but returned to normal one year after surgery in most cases,” the team wrote.