Adrenal Referral Pattern: Management of Patients With an Adrenal Incidentaloma

Abstract

Introduction:

Adrenal incidentalomas (AIs) are found in 3%–4% of abdominal computed tomography scans. Timely evaluation of their functional status and malignant potential is necessary to guide nonoperative surveillance or surgery. This study aims to evaluate the adherence of referring service patterns to the American Association of Endocrine Surgeons and American Association of Clinical Endocrinologists guidelines for the biochemical workup of AIs at a tertiary surgical clinic.

Methods:

We conducted a retrospective study of 125 patients evaluated for AIs at the endocrine surgery clinic between 2017 and 2022. Information on patient demographics, referral source, and reasons for referral was collected. The appropriateness of the biochemical workup for AIs by referring physicians was assessed. Statistical analyses included chi-square and Kruskal–Wallis tests.

Results:

Referrals came from endocrinologists (44.8%), other subspecialists (31.2%), and primary care physicians (PCPs) (19.2%). Among 125 patients, diagnoses included benign adrenal masses (52.8%), aldosteronomas (10.4%), cortisol-secreting tumors (15.2%), pheochromocytomas (12.8%), and metastatic masses (4.0%). Endocrinologists were more likely to conduct a complete biochemical workup compared to other subspecialties and PCPs (P < 0.001). Eighty-three (66.4%) patients underwent adrenalectomy, with those referred by endocrinologists more likely to undergo surgery than those referred by other subspecialties and PCPs (P < 0.001). There was no significant difference in the time from the initial clinic visit to surgery by referral source (P > 0.05).

Conclusions:

Over half of AIs referrals to the endocrine surgery clinic came from subspecialists and PCPs rather than endocrinologists. Familiarizing all referring physicians with American Association of Endocrine Surgeons/Association of Clinical Endocrinologists guidelines may reduce undiagnosed functional AI cases and facilitate timely surgical management.

Introduction

Adrenal incidentaloma (AI) is the term given to an adrenal mass discovered incidentally, often during an imaging procedure. The incidence of AI has been rising sharply due to the increased use of radiographic imaging.¹ The prevalence of AIs in the general population is estimated to be 4.5%, based on computed tomography (CT) scans.^2,3 To help guide clinicians, the American Association of Endocrine Surgeons/American Association of Clinical Endocrinologists have developed consensus guidelines to provide recommendations on the imaging, functional evaluation, and follow-up of patients with AIs.^4,5 However, in daily clinical practice, adherence to these management guidelines appears to be inadequate, and a significant number of patients with adrenal masses do not receive the recommended hormonal workup or dedicated adrenal imaging studies.^6–11

Recognizing the significance of properly evaluating adrenal masses is crucial. More than 20% of AIs prove to be clinically significant, either due to their hormonal activity, such as pheochromocytoma, aldosteronoma, or cortisol-producing adenoma, or malignant potential, including primary adrenal malignancy or metastatic to the adrenal.¹² It has been shown previously that education and collaboration on the management of AIs in the primary care setting may provide an opportunity to improve patient care.¹³ However, literature regarding the referring physician’s impact and degree of adherence to the recommended guidelines for AIs workup is sparse and yet to be determined. Our study aims to evaluate the adherence of referring services including primary care physician (PCP), endocrinologist and other specialties to the American Association of Endocrine Surgeons/American Association of Clinical Endocrinologists guidelines for the biochemical workup of AIs at a single tertiary surgical clinic.

Methods

We conducted a retrospective analysis of patients referred to a tertiary endocrine surgery clinic for AIs between November 2017 and January 2022. Throughout this period, our practice group comprised of four endocrine surgeons, each holding clinics on the same day of the week. All referrals, whether internal (from University of Alabama at Birmingham) or external (from other medical centers), were centralized through a designated patient service coordinator. Internal referrals were processed electronically within the medical record system, while external referrals first contacted our coordinator by phone and sent medical records by fax. Referrals stating a preference for a specific surgeon were directed to that surgeon for the earliest available clinic date. In the absence of a specified preference, referrals were uniformly distributed among the available surgeons for the next clinic date.

Referring providers were categorized based on their specialty, with the primary sources being endocrinologists, other subspecialists, and PCPs. A comparative analysis was conducted including patient demographics, referral reasons, rate of surgery following referrals, and the appropriateness of AI workups across these referral groups. Referral reasons and data on biochemical workups ordered by referring physicians for detected AIs were obtained from clinic notes provided by referring providers and patient records, while details of operative outcomes and pathology report were extracted from postoperative note and reports. Reasons for not undergoing surgery were obtained from endocrine surgery clinic notes.

The adherence to management guidelines was further investigated by querying both external and internal medical records of patients to determine the tests ordered by referring physicians at the time of AI detection or before referral, providing comprehensive insights into the diagnostic approaches employed by the referring physician. Hormonal assessment for functional tumors included plasma or urine metanephrines for pheochromocytomas, 24-h urine cortisol, midnight salivary cortisol or dexamethasone suppression test for cortisol-producing adenomas, and serum aldosterone-to-renin ratio in cases of hypertension for aldosteronomas.

Descriptive statistics, including means and standard deviations, were conducted for normally distributed continuous data. A univariate analysis was performed using Chi-Square tests to compare these variables, including patient demographics, reasons for referral, and evaluation outcomes among referring sources. For non-normally distributed variables, such as time from referral to clinic and time from referral to the operating room, median and interquartile range (IQR) were used for descriptive statistics. Statistical comparisons for these variables were conducted using the Kruskal–Wallis rank sum test. IBM SPSS version 28.0 software was used for data analysis. The University of Alabama at Birmingham Institutional Review Board approved this study with informed consent waiver.

Results

This study included 125 patients, with an average (standard deviation) age of 56 ± 15 y. Most of the patients were female (67.8%) and identified as White (77.5%). Endocrinologists referred the highest number of patients (n = 56, 44.8%), followed by other subspecialties (n = 39, 31.2%), and PCPs (n = 24, 19.2%). The primary reasons for referrals included adrenal mass (n = 91, 72.8%), functional tumors (n = 30, 24.0%), and adrenal metastasis (n = 4, 3.2%). The majority of patients in this study (n = 83, 66.4%) underwent surgery. The top two reasons for not undergoing surgery were a benign character on imaging (n = 20, 16.0%) and surveillance (n = 14, 11.2%). Forty-eight patients underwent adrenalectomy due to functional tumors, of which 13 (27.0%) had a final diagnosis of aldosteronoma, 19 (39.6%) had cortisol-secreting tumors, and 16 (33.3%) had pheochromocytoma (Table 1).

Table 1 –

Patient characteristics and referral pattern for AIs (n = 125).

Variable	n (%)
Age (y), mean ± SD	56 (±15)
Sex
Female	81 (64.8%)
Male	44 (35.2%)
Race
White	93 (77.5%)
Black	26 (21.7%)
Asian	1 (0.8%)
Unknown	5 (4.0%)
Ethnicity
Non-Hispanic	122 (97.6%)
Hispanic	3 (2.4%)
Referral source
Endocrinology	56 (44.8%)
PCP	24 (19.2%)
Other subspecialties	39 (31.2%)
Breast surgery	3 (2.4%)
Cardiology	7 (5.6%)
Colorectal	3 (2.4%)
CT surgery	1 (0.8%)
General surgery	1 (0.8%)
Genetics	1 (0.8%)
Heme/oncology	6 (4.8%)
Inpatient consult	2 (1.6%)
Liver transplant	4 (3.2%)
Neurology	2 (1.6%)
OB/GYN	2 (1.6%)
Radiation oncology	1 (0.8%)
Surgical oncology	4 (3.2%)
Trauma surgery	1 (0.8%)
Urology	1 (0.8%)
Self-referral	6 (4.8%)
Reason for referral
Adrenal mass	91 (72.8%)
Functional tumors	30 (24.0%)
Adrenal metastasis	4 (3.2%)
Did patient receive surgery (yes)	83 (66.4%)
Reason for not receiving the surgery
Benign characters on imaging	20 (16.0%)
Surveillance	14 (11.2%)
Labs suggested benign nodule	2 (1.6%)
Delay operation due to medical condition	1 (0.8%)
Lost to follow-up	2 (1.6%)
Deferred to medical management	1 (0.8%)
Final diagnosis of functional tumors	48 (38.4%)
Aldosteronoma	13 (27.0%)
Cortisol-secreting tumor	19 (39.6%)
Pheochromocytoma	16 (33.3%)

SD = standard deviation; CT = computed tomography.

There were no statistical differences in age, gender, race, and referral reasons among patients when stratified by different referring providers. Patients referred by endocrinologists underwent surgery more frequently than those referred by other specialists and PCPs (80.4% versus 58.9% versus 54.1% respectively, P < 0.001). However, for patients who underwent adrenalectomy, there was no significant difference observed in the duration (in d) from referral date to the initial clinic visit and the time of surgery when referred to a tertiary care hospital by different referring providers (P > 0.05) (Table 2).

Table 2 –

Baseline characteristics of the study population stratified by referring service (n = 125).

Variables	Self-referral (n = 6)	PCP (n = 24)	Other subspecialties (n = 39)	Endocrinologist (n = 56)	P value
Age (y), mean ± SD	64 (19.0)	53 (15.0)	54 (13.0)	56 (15.0)	0.432
Gender					0.343
Female	3 (50.0%)	14 (58.3%)	23 (59.0%)	41 (73.2%)
Male	3 (50.0%)	10 (41.7%)	16 (41.0%)	15 (26.8%)
Race					0.383
White	5 (100.0%)	19 (90.5%)	27 (71.1%)	42 (75.0%)
Black	0 (0.0%)	2 (9.5%)	10 (26.3%)	14 (25.0%)
Asian	0 (0.0%)	0 (0.0%)	1 (2.6%)	0 (0.0%)
Ethnicity					0.011
Hispanic	1 (16.7%)	2 (8.3%)	0 (0.0%)	0 (0.0%)
Non-Hispanic	5 (83.3%)	22 (91.7%)	39 (100.0%)	56 (100.0%)
Reason for referral					0.221
Adrenal mass	3 (50.0%)	21 (87.5%)	28 (71.8%)	39 (69.6%)
Functional adrenal tumor	1 (16.7%)	0 (0.0%)	2 (5.1%)	1 (1.8%)
Adrenal metastases	2 (33.3%)	3 (12.5%)	9 (23.1%)	16 (28.6%)
Did the patient receive surgery? (yes)	2 (33.3%)	13 (54.2%)	23 (58.9%)	45 (80.4%)	<0.001
Time from referral to clinic, (d), median (IQR)	10 (3–14)	12 (7–20)	14 (9–20)	15 (8– 21)	0.315
Time from referral to OR, (d), median (IQR)	14 (4–12)	39 (20–75)	46 (34–74)	48 (26–73)	0.521
Time from clinic to OR, (d), median (IQR)	6 (3– 9)	22 (15–58)	29 (24– 67)	27 (12–43)	0.167
Reason for not receiving the surgery					0.620
Benign characters on imaging	1 (25.0%)	7 (63.6%)	8 (50.0%)	4 (36.4%)
Surveillance	3 (75.0%)	3 (27.3%)	5 (31.2%)	3 (27.3%)
Patient deferred operation	0 (0.0%)	0 (0.0%)	1 (6.2%)	1 (9.1%)
Labs suggested benign nodule	0 (0.0%)	0 (0.0%)	0 (0.0%)	2 (18.2%)
Delay operation due to medical condition	0 (0.0%)	0 (0.0%)	1 (6.2%)	0 (0.0%)
Lost to follow-up	0 (0.0%)	1 (9.1%)	0 (0.0%)	1 (9.1%)
Deferred to medical management	0 (0.0%)	0 (0.0%)	1 (6.2%)	0 (0.0%)
Final diagnosis of functional tumor					0.07
Aldosteronoma	0 (0.0%)	4 (50.0%)	1 (10.0%)	8 (26.6%)
Cortisol-secreting tumor	0 (0.0%)	0 (0.0%)	2 (20.0%)	17 (56.6%)
Pheochromocytoma	0 (0.0%)	4 (50.0%)	7 (70.0%)	5 (16.6%)
Biochemical evaluation of AIs
Aldosteronoma	0 (0.0%)	3 (12.5%)	13 (33.3%)	48 (85.7%)	<0.001
Cortisol-secreting tumor	0 (0.0%)	4 (16.7%)	11 (28.2%)	45 (80.4%)	<0.001
Pheochromocytoma	0 (0.0%)	4 (16.7%)	16 (41.0%)	48 (85.7%)	<0.001

SD = standard deviation.

Notably, patients referred by endocrinologists were more likely to undergo a complete screening biochemical workup for AIs compared to those referred by other subspecialties and PCPs (P < 0.001) (Fig.). Almost half of the patients (n = 23, 47.9%) with functional tumors were referred to the endocrine surgery clinic without having undergone the full recommended biochemical workup for AIs. A total of 19 patients were referred to the endocrine surgery clinic with an adrenal mass as their primary complaint and hypertension as a secondary concern. Out of these 19 patients, 11 (57%) did not receive the recommended workup for aldosteronism. These 11 patients were referred by other subspecialties (n = 5, 45.4%), PCPs (n = 4, 36.4%), an endocrinologist (n = 1, 9.0%), and through self-referral (n = 1, 9.0%).

Fig –

Bar chart illustrating hormonal assessment of AIs by referring specialties at a tertiary care hospital between 2017 and 2022. Hormonal assessment methods used for diagnosing functional tumors: plasma or urine metanephrines for pheochromocytomas, 24-h urine cortisol, midnight salivary cortisol or dexamethasone suppression test for cortisol-secreting tumors, and serum aldosterone-to-renin ratio (PAC: PRA) in cases of hypertension for aldosteronomas.

Discussion

AIs are common endocrine diagnosis affecting 4.5% of the general population.^12,14 Our study showed that over 50% of patients referred to the endocrine surgery clinic did not undergo a comprehensive biochemical diagnostic assessment for AIs at the time of detection. The outcomes of our study align with findings from other research studies that examined the appropriateness of diagnostic assessment of adrenal masses upon their detection.^{9–11,13,15–20} Romy et al. reported limited rates of both biochemical and image assessments in a cohort of 1112 patients with AIs, with only 10.5% undergoing biochemical screening and 8.09% undergoing both biochemical and imaging workup.⁸ Similarly, Taye et al. reported that among 969 patients with AIs, only four individuals underwent comprehensive evaluation involving all three tests: 1 mg Dexamethasone suppression test, plasma aldosterone concentration to plasma renin activity ratio, and plasma or urine metanephrines within 12 mo of detection.¹⁷ In a comprehensive 2022 systematic review by Feeney et al., encompassing 31 studies, findings revealed that a minority of patients with AIs receive initial follow-up imaging (median 34%, IQR 20%–50%) or biochemical testing (median 18%, IQR 15%–28%)¹⁰ Similarly, Makris et al., reported low rates of evaluations for pheochromocytoma, autonomous cortisol production, and primary aldosteronism (8.4%, 2.4%, and 5.3%, respectively). Additionally, not a single patient underwent all indicated biochemical testing.¹⁸ A significant number of patients with AIs do not undergo assessments for autonomous hormone production or receive follow-up imaging upon detection, potentially resulting in the under-recognition of treatable conditions. An effective solution to this issue could involve promptly referring patients to an endocrine surgery clinic. Our study findings indicate that within tertiary care systems, the absence of preoperative hormonal evaluation by referring providers does not result in delays in surgery for patients with AIs. Prompt referrals to endocrine surgery can enhance patient outcomes while mitigating the impact of delays on their health, especially in the context of prolonged wait times for endocrinology consultations. Our research underscores the importance of establishing streamlined and clinically efficient systems to enhance patient care.

Substantial variability exists among clinicians and institutions in the precision of biochemical evaluations, appropriate imaging, and the length of patient follow-up for AIs. In our investigation, more than 50% of the patients were referred by other subspecialists and primary care providers, as opposed to endocrinologists. Nevertheless, patients referred by endocrinologists demonstrated a higher likelihood of undergoing a comprehensive screening biochemical analysis for AIs upon detection, in comparison to those referred by other subspecialties and primary care providers (P < 0.001). Limited data exist regarding the adherence of other subspecialists and PCPs to AI evaluation guidelines. A study conducted by Zafar et al. found that primary care providers tend to employ inconsistent strategies in assessing AI, influenced by their own perceptions of the clinical significance of such findings.²¹ Another study indicated that the majority of primary care providers believed that hormonal evaluation (71%) or follow-up imaging (72%) were unnecessary for most asymptomatic patients.^13,22 Similarly, a study by Bujawanse et al. reported that over 50% of scans were requested by surgical specialties, yet these specialties were less likely to conduct thorough investigations and follow-ups for AIs.^7,23 In 2022, Hanna et al.’s study revealed that only 394 out of 4097 patients (9.6%) had a documented endocrinology referral code within 90 d, with medical specialties (11.8%) exhibiting a higher likelihood of referral compared to surgical specialties (7.2%).² Our research study emphasizes the potential of a multidisciplinary approach, which involves endocrinologists, surgeons, other subspecialists, and primary care providers (PCPs), to enhance and expedite patient care through collaborative efforts in referring and evaluating AIs.

Evaluating the functional status and malignant potential of AIs in a timely manner is necessary, as lesions can range from being benign to hormonally active and aggressive malignant lesions that require urgent surgical intervention.^17,24–26 However, unnecessary referrals may contribute to the inefficient use of already stretched and under-pressure health services and may lead to delayed treatment for patients. The results of our study suggest that patients referred by endocrinologists are more likely to receive surgery than those referred by other specialists and PCPs (81.8% versus 57.9% versus 52.0%, P < 0.001). Almost half of the patients referred by other subspecialists and PCPs didn’t require surgery due to benign nature of the lesions, prompting referral to endocrinologists for further monitoring. This discrepancy may arise from the thorough workup performed by endocrinologists before referral, coupled with their diligent follow-up care, ensuring surgical referral is reserved only for cases necessitating it. Conversely, PCPs and other subspecialists referred patients to endocrine surgery clinics without proper assessment of AI, leading to unnecessary referrals of patients to surgery clinics who didn’t require it. Our study highlights the need to redirect patients to endocrinologists by PCPs and other subspecialists for comprehensive evaluation before referral to surgical clinics. This consideration could help streamline the referral process, sparing patients unwarranted visits to the endocrine surgery clinic. By addressing the current gap in the implementation of evaluation protocols, we can achieve more accurate and timely diagnoses, and better utilization of existing resources, ultimately leading to improved patient care.

There were several limitations to this study. We had limited patient data from one single tertiary care center hospital, potentially limiting its universal representativeness. Furthermore, we could have included more factors that may have influenced physicians’ reporting or referral practices. Additionally, due to the retrospective nature of the study, there were limited long-term laboratory data and follow-up information. Moreover, we were unable to review imaging data in this study to determine the necessity for pheochromocytoma evaluation and the wait time for endocrinology consultations due to limited accessibility of patient records.

Conclusions

Our study revealed that over half of the patients referred to the endocrine surgery clinic for AIs were by other subspecialists and PCPs. However significant variability was observed in adherence to AI guidelines among these referring physicians. Enhanced collaboration and strict guideline adherence among referring physicians are crucial for timely AI evaluation and resource optimization.