Phase 1: Open-ended Patient Survey
Ninety-one patients submitted a complete survey response, 78 (85.7%) of whom were female and 9 (9.9%) of whom were male; the remaining 4 respondents' sex identity was unknown. Most had CD (63/91; 69.2%), whereas 30.8% (28/91) had a primary adrenal cause of CS. No patient indicated an ectopic source of ACTH as an etiology. No patient underwent bilateral adrenalectomy.
Of the 91 patients, 25 (27.5%) were taking CRM at the time of the survey. Subjects who had discontinued CRM estimated that they received treatment for a median of 10.5 months (IQR, 6–18; range, 0–108; n = 54).
Although all survey respondents self-reported being in surgical remission, not all patients considered themselves recovered. Forty-two respondents (46.2%) indicated they had not yet recovered at the time of the survey. Patients who did consider themselves recovered reported a median recovery time of 22 months (IQR, 12–27; range, 0–50; n = 48).
The most frequently cited challenge in recovery reported in an open-ended question was the long duration of recovery (37/91; 40.7%; 95% CI, 31.1–51.0), followed by pain (29/91; 31.9%; 95% CI, 23.2–42.0) and fatigue (22/91; 24.2%; 95% CI, 16.6–33.9). Fourteen patients reported neuropsychiatric impairment (15.4%; 95% CI, 9.4–24.2), an aggregate category that included responses about memory loss, inability to focus, depression, anxiety, and mood changes. Seven patients (7.7%; 95% CI, 3.8–15.0) reported nausea or loss of appetite during the recovery period.
Patients were asked what they found helpful in coping with the recovery process in an open-ended question (Table 4). The most helpful coping mechanisms described by respondents in the phase 1 survey were family and friends (38.5%), support groups (23.1%), rest (16.5%), and exercise (16.5%).
Phase 2: Surveys of Patients and Endocrinologists
Respondent Characteristics. Most patient respondents identified as female (312/341, 91.5%), 25 identified as male (7.3%), and 4 did not choose either option (male or female). Respondents reported a median age of 43 years (IQR, 33–53; range, 12–76; n = 337). The majority had CD (234/338, 69.2%), whereas 26.9% had a primary adrenal cause of CS (91/338) and 3.8% reported unknown or other etiologies (13/338). Patients with CD underwent significantly more surgeries than patients with an adrenal cause of CS (mean, 1.5 vs 1.1; P = 0.0258).
The median time since last surgery for CS was 34 months (IQR, 17–74; range, 0.5–405; n = 162), though this information was only available for 47.5% of respondents. Whether the patient was in the upper or lower 50th percentile of time since last surgery did not affect their responses to questions about perception of recovery, coping mechanisms used during recovery, primary source of information on recovery, CRM management, or return to employment, nor were there differences in sex or CS etiology between the 2 groups.
Of the 54 physician responses, 15 were from women (27.8%). Most respondents were aged 40 to 49 (17/52, 32.7%) or 50 to 59 (18/52, 34.6%). Most were hospital-based (42/53, 79.3%), whereas a few worked either in a medical office (6/53, 11.3%) or an academic setting (4/53, 7.6%). Respondents practiced in the United States (n = 10), the United Kingdom (n = 3), Italy (n = 3), or elsewhere (n = 10) including Argentina, Australia, Brazil, Canada, Germany, Mexico, Netherlands, New Zealand, Portugal, and Spain (response rate, 48.1%). Over the course of their careers, endocrinologists reported seeing a median of 100 surgically treated CS patients (IQR, 42.5–200; range, 10–400; n = 53). There was no correlation between age of physician and number of surgically treated CS patients seen.
Type, Duration, and Management of Cortisol Replacement Medication
Endocrinologists and patients reported a similar duration of CRM following surgery (P = 0.95), with physicians reporting a median of 9 months (IQR, 6–12 months; range, 3–15; n = 48) and patients reporting a median of 8 months (IQR, 5–14; range, 0–82; n = 172; response rate, 50.4%). Among patients, reported CRM duration differed by CS etiology. Patients with CD reported a median CRM duration of 6 months (IQR, 4–12; range, 0–40; n = 113), whereas patients with adrenal etiologies reported a median duration of 12 months (IQR, 6–18; range, 2–82; n = 57), a significantly longer timeframe (P = 0.0025).
Physicians' most commonly reported CRM was a hydrocortisone taper (35/54; 64.8%; 95% CI, 51.5–76.1), which they most frequently discontinued at a daily dose of 5 mg (11/35; 31.4%; 95% CI, 18.6–48.0) or 10 mg (13/35; 37.1%; 95% CI, 23.2–53.7). Prednisone (11/54; 20.4%; 95% CI, 11.8–32.9) and cortisone acetate (5/54; 9.3%; 95% CI, 4.0–19.9) also were reported. Less experienced endocrinologists, defined as those who had seen fewer than 100 patients with CS in their careers, were more likely to prescribe hydrocortisone alone for recovery (21/26; 80.8%) than those who had seen 100 patients or more (13/27; 48.1%) by 32.6% (95% CI, 6.8–53.1; P = 0.0133). Neither physician age nor sex had an effect on likelihood of prescribing solely hydrocortisone.
The majority of patients reported that their physician decided when to stop or reduce their CRM (173/320; 54.1%; 95% CI, 48.6–59.4). However, 10.3% (33/320; 95% CI, 7.4–14.1) of patient respondents indicated they unilaterally made these decisions, and 35.3% (113/320; 95% CI, 30.3–40.7) said they worked in conjunction with their physician. There was no difference in these management decisions between male and female patients, and there was no relationship between management strategy and whether respondents described their recovery as positive, negative, or mixed.
Time to Complete Recovery
Endocrinologists reported a median time to complete recovery of 12 months (IQR, 9–18; range, 1–36; n = 34; response rate, 63.0%) following surgery. Patients who considered themselves recovered reported a median recovery time of 18 months (IQR, 12–24; range, 2–96; n = 112), a significantly longer duration than physicians described (P = 0.0104). Whether the patient was in the upper or lower 50th percentile of recovery time did not impact their responses to questions about perception of recovery, coping mechanisms used during recovery, primary source of information on recovery, CRM management, or return to employment, nor did reported recovery time differ by CS etiology or sex. Notably, among patients who considered themselves recovered and provided CRM duration, time to complete recovery was significantly longer than CRM duration (18 months vs 8 months, P < 0.0001, n = 73). This was also true for physicians who provided responses for both questions (12 vs 8 months, P = 0.0001, n = 33).
Patients returned to work a median of 3 months (IQR, 2–6; range, 0–120; n = 132; response rate, 38.7%) after their last surgical treatment. After surgery, 40.0% (113/284; 95% CI, 34.3–45.6) of patients went back to working full time, 38.0% (108/284; 95% CI, 32.6–43.8) worked part time, and 16.5% (47/284; 95% CI, 12.7–21.3) were unemployed; 5.6% (16/284; 95% CI, 3.5–9.0) described their return to work differently, such as working full time as a parent.
The Experience of Recovery
Most physicians and patients characterized the recovery experience as mixed (ie, having both positive and negative elements; physicians: 16/27; 59.3%; 95% CI, 40.7–75.5 vs patients: 188/336; 56.0%; 95% CI, 50.6–61.2). A similar proportion of physicians and patients considered the experience to be primarily positive (physicians: 5/27; 18.5%; 95% CI, 8.2–36.7 vs patients: 90/336; 26.8%; 95% CI, 22.3–31.8) or negative (physicians: 6/27; 22.2%; 95% CI, 10.6–40.8 vs patients: 53/336; 15.8%; 95% CI, 12.3–20.1). The physician response rate to this question was 50.0%. Physicians' level of experience with CS patients had no association with their perception of patients' recovery. Among patients, the description of recovery was not associated with sex.
A total of 90.8% of patients responding to a question about whether they experienced "mental exhaustion during recovery" responded affirmatively (216/238; 95% CI, 86.4–93.8; response rate, 70.0%). A range of neuropsychiatric disturbances including memory loss, confusion, word-finding difficulties, difficulty concentrating, difficulties in social functioning, anxiety, and depression were reported in this answer. There was no statistical difference between the proportions of men and women endorsing mental exhaustion, nor between patients with CD and those with adrenal causes of CS.
Patients and physicians described different factors helpful to recovery (Table 4). Patient respondents reported family and friends (83.4%), rest (74.7%), physicians (48.4%), and support groups (44.5%) as the most helpful in their recovery. Physicians cited family and friends (87.8%), exercise (77.6%), activities (75.5%), and work (65.3%) as most helpful in patients' recovery. In contrast, a significantly smaller proportion of patients reported work (26.9% vs 65.3%, P < 0.0001), exercise (40.9% vs 77.6%, P = 0.0001), and activities (44.8% vs 75.5%, P = 0.0016) as helpful. Significantly fewer physicians reported religion (8.2% vs 42.9%, P = 0.0002), massage (2.0% vs 23.7%, P = 0.0172), and entertainment (12.2% vs 37.7%, P = 0.0117) as helpful coping mechanisms than did patients.
Information on Recovery
Most patients reported receiving information about the recovery experience from a physician: either their endocrinologist alone (100/293; 34.1%; 95% CI, 28.9–39.7), their surgeon alone (22/293; 7.5%; 95% CI, 5.0–11.1), or both (76/293; 25.9%; 95% CI, 21.3–31.3). However, 32.4% of patients reported they did not receive information from either (95/293; 95% CI, 27.3–38.0). Many of these patients reported receiving information primarily from other sources, including through support groups and other patients (19/293; 6.5%; 95% CI 4.2–9.9) or their own online research (13/293; 4.4%; 95% CI, 2.6–7.5). There was no statistical association between patients' reported experience of recovery (ie, positive, negative, or mixed) and where they received information on recovery.
All physician respondents reported giving information about the recovery process to patients in some way; 98.0% (49/50; 95% CI, 89.5–99.7) endorsed having a discussion about recovery and 38.0% (19/50; 95% CI, 25.9–51.9) endorsed giving written information. Sixty-two percent of respondents to this question indicated they rely solely on discussion, whereas 36.0% routinely use both discussion and written forms of information; 1 respondent endorsed using written information alone.
Endocrinologists also were asked whether the neurosurgeon operating on their patients routinely provides information about the recovery experience; of the 44 responses to this question, 14 (31.8%; 95% CI, 20.0–26.6) said yes, 21 (47.7%; 95% CI, 33.8–62.1) said no, and 9 (20.5%; 95% CI, 11.2–34.5) were unsure. Endocrinologists who did not believe or were unsure whether their neurosurgeons provided information on recovery were no more likely to offer multiple modalities of information (ie, both oral and written information) to patients than their counterparts who believed their neurosurgeon provided recovery information to patients. Few physicians (14.8%, 8/54) responded to a question asking whether they routinely include family members in their education process; of these, half said they did (4/8) and half said they did not (4/8).
Open-ended Question on Recovery
One question on the survey asked patients if they had any other thoughts about their recovery experiences and if there was anything that could have improved their experience. This was an open-ended question, but certain topics appeared frequently in responses (Table 5). Notably, 82.1% (280/341) of patients responded to this question; of these, 32.9% reported that they would have liked more information on what to expect going into their recovery or that they felt unprepared going into recovery, 16.1% felt as though not enough medical professionals were familiar with the symptoms of CS, 14.3% had difficulty with weight loss and/or suffered from persistent body image issues, and 12.1% reiterated the importance of support groups in their recovery.
Patients also described symptoms they experienced during recovery in this open-ended question (Table 5). A total of 18.6% complained of musculoskeletal pain, an aggregate category including any complaints of pain in joint, muscle, bone, back, knees, hips or body, and other comments such as "inability to stand for long periods," "shoulders froze and knees gave out," and "afraid the stress of standing would surely break my shins." A total of 16.1% of respondents mentioned fatigue (statements referring to being tired, exhausted, weak, lack of energy/stamina, and lethargy) and 11.0% explicitly reported experiencing depression. Overall, 68.6% (234/341; 95% CI, 63.5–73.3) of patients surveyed reported experiencing at least 1 of musculoskeletal pain, fatigue, depression, or mental exhaustion in either a fixed-answer question or this open-ended question.
Additional selected quotations in response to this open-ended question that illustrate the anguish and pain felt during recovery are listed in Table 6.
J Endo Soc. 2021;5(8) © 2021 Endocrine Society