Adrenalectomy Cuts Fracture Risk in Adults With MACS

Adrenalectomy significantly reduced the risk for vertebral fractures compared with conservative care in adults with mild autonomous cortisol secretion (MACS), according to data from a recent study.

Previous research suggested that MACS occurs in approximately half of the patients with adrenal incidentalomas and may promote cardiometabolic conditions, but recovery from MACS may reduce this risk, wrote Valentina Morelli, MD, of IRCCS Istituto Auxologico Italiano, Milan, Italy, and colleagues.

“Among the other possible complications correlated with MACS is skeletal fragility, and in particular, some studies have shown that patients with MACS have an increased prevalence and incidence of vertebral fractures compared to patients with nonfunctioning tumors,” said co-author Vittoria Favero, MD, of the University of Milan, Milan, Italy, in an interview. However, intervention studies on the possible effect of the recovery from MACS on bone fragility are lacking, she said.

The European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas developed in collaboration with the European Network for the Study of Adrenal Tumors (ESE-ENSAT guidelines of 2src23) regarded the link between MACS and osteoporosis as not well established. The current study sought to address the effect of treating MACS on bone health, specifically the risk for vertebral fractures, Favero told Medscape Medical News.

The researchers performed separate analyses of two cohorts of patients with MACS, one through a retrospective study and the other via a prospective study. Their findings were published in The Journal of Clinical Endocrinology & Metabolism.

In the retrospective study, 53 adult outpatients with MACS were followed for approximately 35 months after undergoing adrenalectomy or conservative care to evaluate the incidence of vertebral fractures.

In the prospective study, 51 adult outpatients with MACS were randomized to adrenalectomy or conservative care and followed for 24 months to evaluate the effect of adrenalectomy on outcomes potentially associated with hypercortisolism, including vertebral fractures, body weight, blood pressure, bone mineral density (BMD), and glucometabolic control.

In the retrospective study, the percentage of women was 74.2% in the surgical group and 45.5% in the conservative care group; the average ages were 63 and 64 years, respectively.

For the prospective study, women accounted for 67% of the surgical group and 78% of the conservative care group, with average ages of 63 and 69 years at baseline, respectively.

All patients were assessed at baseline and follow-up for calcium-phosphorus metabolism and BMD at the lumbar spine, total hip, and femoral neck.

In the retrospective study, patients in the surgery group had a significantly lower incidence of vertebral fractures than those in the conservative care group (9.7% vs 5src%; P <.srcsrc5). BMD at all three locations was similar between the groups.

In the prospective study, patients in the surgery group had a significantly lower incidence of vertebral fractures than those in the conservative care group (4.8% vs 25%; P =.src4). Patients in the surgery group also showed an increase in calcium and phosphorous levels at 6 months, 12 months, and the end of the follow-up period compared with baseline. BMD was stable and similar in both groups.

The dramatic impact of recovery from mild cortisol excess on vertebral fracture risk reflects data from similar studies, the researchers wrote in their discussion. Considering data from both studies, adrenalectomy was associated with a 6.5-fold reduced risk for vertebral fractures in patients with MACS, they said.

“The randomized study confirms that the conservatively treated patients with MACS are exposed to an increased risk of vertebral fractures, similarly to what has already been suggested from retrospective data,” the researchers added.

The findings were limited by several factors including the lack of trabecular bone score, the potential for confounding variables in the retrospective study, the longer observation period in the surgery patients, and the lack of blinding of the radiologists who reviewed the results, the researchers noted.

Additional larger studies are needed to better identify patients with MACS at a greater risk for incident vertebral fractures; meanwhile, the current data suggest clinicians consider the increased risk for vertebral fractures in patients who do not undergo surgery, they concluded.

“The key message for clinical practice is that adrenalectomy significantly reduces the risk of vertebral fractures in patients with adrenal incidentalomas and MACS,” Favero told Medscape Medical News. The finding that fragility fractures occurred mainly at vertebral sites aligns with data from previous studies on subclinical hypercortisolism and MACS showing the sensitivity of trabecular bone to glucocorticoid excess, she added.

“The inadequate response to bisphosphonates in some patients was also an expected finding, as it is consistent with the understanding that MACS increases the risk of fragility fractures beyond what is typically seen in postmenopausal osteoporosis,” said Favero.

The results suggest that clinicians consider bone fragility when determining the most appropriate treatment strategy for these patients, she noted.

Looking ahead, further research is needed to identify tools beyond BMD evaluation to better identify patients with MACS at a higher risk for fractures, Favero said.

Data Define the Benefits of Surgery

Although cortisol excess is known to have detrimental effects on bone health, the degree to which lower levels of cortisol excess, as is seen in MACS, affects bone health is not as well understood, said Trenton Foster, MD, assistant professor of surgery at the Mayo Clinic, Rochester, Minnesota, in an interview.

The current study is important for better quantifying the benefits of adrenalectomy, and the findings were not unexpected, said Foster, who was not involved in the study. “Many studies in recent years have shown that MACS is a clinically relevant condition with a detrimental impact on health if left untreated, and definitive treatment with adrenalectomy results in improved outcomes for these patients,” he noted.

“There are many reasons to consider adrenalectomy for treatment of MACS,” said Foster. “This paper shows reducing fracture risk is another reason to do so.”

Personalized Risk-Benefit Discussions Needed

Most studies on adrenalectomy for MACS have been retrospective and observational; the current study includes one of the few prospective randomized clinical trials, said Feibi Zheng, MD, an endocrine surgeon and assistant professor of surgery at Baylor College of Medicine, Houston, in an interview.

In a recent meta-analysis looking at MACS-associated comorbidity improvement after adrenalectomy, differences in BMD and fracture rate were among the strongest findings favoring adrenalectomy over conservative management, said Zheng, who was not involved in the study.

“Patients with MACS should not be monitored; they should be referred for surgical evaluation,” Zheng told Medscape Medical News. “Not every patient with MACS needs or should have adrenalectomy, but every patient should have an opportunity to meet an endocrine surgeon and have a personalized discussion of risks and benefits of surgery,” she said.

Further research is needed to examine other MACS-associated comorbidities such as hypertension and glycemic control, she added.

The study was supported by the Italian Ministry of Health. The researchers had no financial conflicts to disclose. Foster