High Recovery Rate of Adrenal Function After Successful Surgical Treatment of Cushing’s Syndrome

Posted on April 23, 2025 by MaryO

Abstract

Context

Successful first-line treatment of Cushing’s syndrome by resection of the underlying tumor is usually followed by adrenal insufficiency.

Purpose

The aims of this study were to determine the recovery rate and time to recovery of adrenal function after treatment for different forms of endogenous Cushing’s syndrome and to identify factors associated with recovery.

Methods

In this retrospective study of 174 consecutive patients with Cushing’s syndrome, the recovery rate and time to recovery of adrenal function after surgery were assessed.

Results

The 1-year, 2-year and 5-year recovery rates of patients with Cushing’s disease were 37.8, 70.1 and 81.1%, respectively. For patients with adrenal Cushing’s syndrome, the 1-year, 2-year and 5-year recovery rates were higher: 49.3, 86.9 and 91.3%, respectively. Median time to recovery for patients with Cushing’s disease and adrenal Cushing’s syndrome was 13.9 and 12.1 months, respectively. The median time to recovery of adrenal function in patients with Cushing’s disease with and without recurrence was 9.9 versus 14.4 months, respectively. Higher age was associated with a lower probability of recovery of adrenal function: HR 0.83 per decade of age (95% CI 0.70–0.98).

Conclusion

The recovery rate of adrenal function after successful surgery as first-line treatment in patients with Cushing’s syndrome is high. However, it may take several months to years before recovery of adrenal function occurs. In case of early recovery of adrenal function, clinicians should be aware of a possible recurrence of Cushing’s disease.

Introduction

Cushing’s syndrome (CS) is characterized by chronic exposure to an excess of glucocorticosteroids (1). Endogenous hypercortisolism is a rare disorder with an estimated incidence of 0.2–5 patients per million per year (1). CS can cause severe, disabling signs and symptoms and is associated with significantly increased morbidity and mortality. In approximately 70% cases, endogenous CS is caused by an ACTH-producing pituitary adenoma, also known as Cushing’s disease (CD). In 15–25% cases, an ACTH-independent form of CS is caused by a unilateral adrenal adenoma, adrenal carcinoma or bilateral micro- or macronodular hyperplasia (adrenal CS). An ACTH-producing ectopic tumor is a rare cause of CS. First-line treatment of CS is surgical removal of the pituitary, adrenal or ectopic tumor (1, 2).

Successful first-line treatment by resection of the underlying tumor is usually followed by adrenal insufficiency (AI) due to suppression of the hypothalamic–pituitary–adrenal axis after prolonged exposure to high concentrations of cortisol (3, 4, 5). Theoretically, one would expect that the hypothalamic–pituitary–adrenal axis recovers over time and that the substitution of glucocorticosteroids can slowly be reduced and stopped as long as there is no irreversible damage to the remaining adrenal or pituitary tissue. However, in clinical practice, AI is not always transient. In a subset of patients, this is caused by permanent AI due to perioperative damage to the pituitary gland or irreversible atrophy of the contralateral adrenal gland. In other cases, tapering the dosage of glucocorticosteroids is not possible because this causes worsening of symptoms. Despite the glucocorticoid replacement therapy, patients often experience symptoms resembling AI, such as fatigue, myalgia, arthralgia, depression, anxiety and decreased quality of life, also known as glucocorticoid withdrawal syndrome (GWS) (6). GWS is caused by dependence on supraphysiologic glucocorticoid concentrations after chronic exposure to high concentrations of glucocorticoids, which can complicate and delay the withdrawal of exogenous steroids. As a result, patients and physicians often struggle with a dilemma: on the one hand, lowering the cortisol substitution is necessary to enable functional recovery of the hypothalamic–pituitary–adrenal axis. On the other hand, lowering the substitution therapy often causes worsening of symptoms. In clinical practice, it is not always possible to completely taper the substitution of steroids due to GWS, even in spite of intensive guidance and support by the treating physician, specialized nurse and other healthcare professionals. Moreover, in patients remaining on glucocorticoid replacement, it is not always clear whether the failure to recover from AI is caused by the irreversible damage of the remaining pituitary or adrenal tissue or the failure to overcome the GWS. The time after which adrenal function recovers and substitution therapy can be tapered off varies largely between patients but may take several years (7).

A recent survey among patients with CS highlighted the need of patients for better information about the difficult post-surgical course (8). However, scientific data about this post-operative period, particularly regarding the recovery rate and time to recovery from AI are scarce (9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20). Because of the rarity of CS, most studies are hampered by a limited number of patients. The reported recovery rates of adrenal function after first-line treatment for CS vary widely, between 37 and 93% for CD (9, 10, 11, 12, 13) and between 38 and 93% for overt adrenal CS (10, 12, 14, 15, 16, 17).

The reported duration to recovery of the hypothalamic–pituitary–adrenal axis after CD and adrenal CS also varies widely, between 13 and 25 months after CD (9, 10, 11, 13, 19) and between 11 and 30 months in overt adrenal CS (10, 14, 15, 16, 18, 20).

Factors which influence the recovery rate and the duration to recovery of adrenal function are not entirely clear. A few studies reported a lower chance of recovery and a longer duration to recovery of adrenal function in patients who are younger, have more severe hypercortisolism, and longer duration of symptoms before diagnosis, whereas other studies could not confirm these findings (10, 13, 21). By contrast, other studies reported a higher chance of recovery in younger patients (21). Identification of these factors may help provide patients with more information about the expected post-surgical course.

Therefore, the aims of the present study were to assess the recovery rate and time to recovery of adrenal function after successful first-line treatment in the different subtypes of CS in a large series of consecutive patients treated at a tertiary referral center and to identify factors associated with recovery.

Methods

Patients

The medical records of adult and pediatric patients treated for CS at Radboud University Medical Center, Nijmegen, between 1968 and 2022 were examined retrospectively. This is a tertiary referral hospital where practically all cases of CS from the large surrounding geographic area are managed. All patients with CD, adrenal CS and ectopic CS who were in remission and developed AI after first-line surgical treatment were included. Exclusion criteria were bilateral adrenalectomy as first-line treatment, adrenocortical carcinoma, radiotherapy of the pituitary gland before surgery, pituitary carcinoma and the therapeutic use of corticosteroids for conditions other than AI. Data were collected on age, sex, body mass index (BMI), duration of CS symptoms, comorbidities, the use of medication, biochemical results at diagnosis and during follow-up, preoperative imaging, surgical treatment and histology.

The study was assessed by the Committee for Research with Humans, Arnhem/Nijmegen Region and the need for written approval by individual patients was waived since this study did not fall within the remit of the Medical Research Involving Human Subjects Act (WMO). The study has been reviewed by the ethics committee on the basis of the Dutch Code of conduct for health research, the Dutch Code of conduct for responsible use, the Dutch Personal Data Protection Act and the Medical Treatment Agreement Act. The ethics committee has passed a positive judgment on the study. The procedures were conducted according to the principles of the Declaration of Helsinki.

Diagnostics and definitions

Patients were diagnosed with CS according to the guidelines available at the time, i.e., the presence of signs and symptoms of hypercortisolism in combination with confirmatory biochemical tests, including the 1 mg dexamethasone suppression test (DST), 24-h urine free cortisol (UFC), late-night salivary cortisol concentrations and/or hair cortisol. The cutoff value for adequate cortisol suppression after the DST was <50 nmol/L (22). For UFC, the times upper limit of normal was calculated because several assays with different reference values were used over time.

First-line treatment consisted of pituitary surgery in patients with CD and unilateral adrenalectomy in patients with ACS. In patients with bilateral macronodular hyperplasia, adrenalectomy of the largest adrenal was performed after carefully outweighing the risks and benefits of surgery together with the patient, taking into account factors such as age, severity of symptoms, comorbidities associated with hypercortisolism (e.g., diabetes mellitus type 2, cardiovascular disease, osteoporosis) and the severity of the hypercortisolism (2).

Peri- and postoperatively, all patients received glucocorticoid stress dosing, which was tapered off within a few days after surgery. Adrenal function was initially evaluated with a postoperative morning fasting cortisol concentration, measured at least 24 h after the last dose of hydrocortisone or cortisone acetate, within 7 days after surgery. If the postoperative morning fasting cortisol was <200 nmol/L, the patient was considered to have AI and glucocorticoid replacement therapy was continued. The starting dose was usually hydrocortisone 30 mg once daily (or an equivalent dose of cortisone acetate in the early years). For children, the dose was weight-based. Afterwards, the dose was slowly tapered off according to the symptoms/well-being of the patient and fasting cortisol values. During follow-up, the dose was usually divided into two or three doses a day.

Remission of CS after treatment was defined as either a morning cortisol of ≤50 nmol/L, adequate cortisol suppression after DST or a late-night salivary cortisol concentration within the reference range. Duration of AI was defined as the time between surgery and discontinuation of glucocorticoid replacement therapy. Complete recovery of adrenal function was assessed by spontaneous fasting cortisol concentration, an insulin tolerance test or a 250 μg ACTH stimulation test after discontinuation of glucocorticoid replacement therapy. In cases where fasting morning cortisol ≥520 nmol/L, adrenal function was considered as completely recovered. For the dynamic tests, assay-dependent cutoff values were used according to the guidelines available at the time. The dynamic tests were not performed routinely in all patients until 1999. In patients for whom no dynamic tests (results) were available, complete recovery of AI was defined as complete discontinuation of replacement therapy. Recurrence of CS was defined as the presence of signs and symptoms of hypercortisolism in combination with confirmatory biochemical tests, including the 1 mg DST, 24-h UFC, late-night salivary cortisol concentrations and/or hair cortisol.

Statistical analysis

Continuous data were expressed as mean ± SD or median + interquartile range (IQR), and categorical data were presented as frequency (n) and percentage (%). We produced Kaplan–Meier curves to determine the unadjusted probability of recovery of adrenal function over time. Patients that tapered off and completely stopped the glucocorticoid replacement therapy were assigned in the survival analyses as having an event (=recovery of adrenal function). The date of the last follow-up visit was assigned in the survival analyses as the last date and patients that were lost to follow-up or developed a recurrence before stopping the glucocorticoid replacement therapy were censored. In order to identify factors associated with recovery of adrenal function, we compared Kaplan Meier curves between several subgroups of patients: CD versus adrenal CS versus ectopic CS, age (at diagnosis) groups of ≤35 versus 36–55 versus ≥56 years old, patients with or without postoperative pituitary deficiencies, patients with or without recurrence of CS during follow-up, patients with or without preoperative medical treatment (PMT), patients operated before versus after 2010 and patients with a low versus slightly higher post-operative morning cortisol (<100 nmol/L versus 100–200 nmol/L), measured within 7 days after surgery. The Kaplan–Meier curves of the subgroups were compared using the two-sided log-rank test. The P-value ≤0.05 was considered statistically significant. The Kaplan–Meier curves provided the 1-year, 2-year and 5-year recovery rates and the median time to recovery of the adrenal gland. We used Cox proportional hazards models to calculate hazard ratios (HRs) with a 95% confidence interval (CI) of the probability of recovery of adrenal function over time in order to identify factors associated with recovery of adrenal function (univariate analyses). Cox proportional hazards models with multivariate analyses were performed to calculate the adjusted HRs with 95% CI. The model of multivariate analysis for the whole group included the variables: etiology of CS, age, sex, BMI, duration of symptoms before diagnosis, UFC and postoperative cortisol 0.10–0.20 versus <0.10 mcmol/L. The model of multivariate analysis for the patients with CD only included the variables: etiology of CD, age, sex, BMI, duration of symptoms before diagnosis, UFC, post-operative cortisol 0.10–0.20 versus <0.10 mcmol/L, PMT, hormonal deficiencies of the anterior pituitary gland other than AI and micro/macroadenoma. A 95% CI not including 1 was considered statistically significant.

All statistical analyses were performed using STATA version 11 (StataCorp, USA).

Results

In total, 174 patients were included in the analysis. The assessment of eligibility, the number of patients excluded from this study and the reasons for exclusion are shown in Fig. 1. The baseline characteristics are described in Table 1. The median follow-up was 6.8 years (IQR: 2.2–12.6). In 69.6% (94/135) of all patients who discontinued their glucocorticoid replacement therapy, the recovery of adrenal function was confirmed with a dynamic test or a morning cortisol concentration ≥520 nmol/L.

Figure 1View Full Size
Figure 1
Flowchart showing the assessment for eligibility, the number of patients excluded from the study and the reasons for exclusion.

Citation: Endocrine Connections 14, 5; 10.1530/EC-24-0612

Table 1Baseline characteristics.

Variable All patients CD Adrenal CS
Participants (n) 174 135 35
Female (%) 135/174 (77.6%) 102/135 (75.6%) 32/35 (91.4%)
Median age at diagnosis (y) 44 (35–55) 43 (32–55) 47 (36–54)
Median BMI at diagnosis (kg/m2) 28.3 (24.7–32.4) 28.6 (24.7–32.9) 28.0 (26.0–31.8)
Median duration of symptoms before diagnosis of CS (years) 3.0 (1.0–5.6) 3.0 (1.0–6.0) 3.5 (1.5–5.6)
Median times upper limit of normal UFC at diagnosis 3.7 (1.9–5.8) 3.9 (2.0–6.4) 2.4 (1.4–4.1)
Median cortisol after DST (nmol/L) 480 (320–630) 460 (290–620) 550 (330–710)
Median salivary cortisol at diagnosis (nmol/L) 8.6 (5.4–15.4) 10.1 (5.9–18.0) 6.1 (4.0–8.9)
Median follow up (years) 6.8 (2.2–12.6) 8.4 (3.0–13.5) 2.2 (1.2–4.7)
Preoperative medical therapy* (n) 120/174 (69%) 106/135 (78.5%) 10/35 (28.6%)
Pituitary microadenoma/macroadenoma/no adenoma detected on MRI scan (n) – 64/27/28** –
Bilateral disease (n) – – 7/35 (20.0%)

CD, Cushing’s disease; CS, Cushing’s syndrome; BMI, body mass index; UFC, 24-h urine free cortisol; DST, 1 mg dexamethasone suppression test. Continuous data are summarized as median and interquartile ranges. Categorical data are presented as frequencies and percentages.

*Cortisol-lowering medication, either metyrapone or ketoconazole.

**Missing data on MRI in 16 patients.

Recovery rates and recovery times of adrenal function

The probability of recovery of AI for CD, adrenal CS and ectopic CS are depicted in Fig. 2. The 1-year, 2-year and 5-year recovery rates of adrenal function for the entire cohort were 40.1, 73.4 and 83.3%, respectively. The median time to recovery of adrenal function was 13.9 months. The 1-year, 2-year and 5-year recovery rates of patients with CD were 37.8, 70.1 and 81.1%, respectively. The median recovery time was 13.9 months for patients with CD. For patients with adrenal CS, the 1-year, 2-year and 5-year recovery rates were higher: 49.3, 86.9 and 91.3%, respectively (two-sided log-rank test: P = 0.14). The median recovery time for patients with adrenal CS was 12.1 months. Seven out of the 35 patients with adrenal Cushing had bilateral disease. The median time to recovery in patients with bilateral disease was 17.5 versus 11.0 months in patients with unilateral disease.

Figure 2View Full Size
Figure 2
Cumulative probability of recovery of adrenal function in CD (n = 135), adrenal CS (n = 35) and ectopic Cushing (n = 4).

Citation: Endocrine Connections 14, 5; 10.1530/EC-24-0612

Of the 15 evaluated patients with ectopic CS, only four patients underwent successful resection of the ectopic tumor and were included in our study. All four patients had a neuroendocrine tumor of the lung and recovered from AI. The time to recovery of adrenal function was known in three patients: 5.7, 7.9 and 14.5 months.

Factors associated with recovery of adrenal function

Age at diagnosis

Figure 3 shows the Kaplan–Meier curves of three different age groups (group 1: 0–35 years old, group 2: 36–55 years old and group 3: 56–100 years old). The 1-year recovery rates of patients aged between 0–35, 36–55 and 56–100 years old were 54.6, 37.2 and 31.4%, respectively. The 2-year recovery rates were 79.3, 72.6 and 68.4%, respectively and the 5-years recovery rates were 89.6, 83.8 and 75.1%, respectively. The median times to recovery of adrenal function of patients aged between 0–35, 36–55 and 56–100 years old were 11.2, 13.4 and 17.6 months, respectively. The probability of recovery of AI was higher in young patients (0–35 years old) (two-sided log-rank test: P = 0.05).

Figure 3View Full Size
Figure 3
Cumulative probability of recovery of adrenal function by age groups.

Citation: Endocrine Connections 14, 5; 10.1530/EC-24-0612

Recurrence after primary treatment

In total, 17.8% patients with CD (24/135) had developed a recurrence during follow-up. Figure 4 shows the Kaplan–Meier curves with the probability of recovery of AI of the groups with and without recurrence during follow-up in patients with CD. The probability of recovery of AI was higher in patients with a recurrence (two-sided log-rank test: P-value = 0.02). In patients with a recurrence, the 1-, 2- and 5-year recovery rates of AI were 60.9, 78.3 and 87.0%, respectively. In patients without a recurrence, the 1-, 2- and 5-years recovery rates of AI were 32.6, 68.3 and 79.7%, respectively. The median time to recovery of adrenal function in patients with CD with and without recurrence was 9.9 versus 14.4 months, respectively.

Figure 4View Full Size
Figure 4
Cumulative probability of recovery of adrenal function by recurrence during follow-up in patients with CD.

Citation: Endocrine Connections 14, 5; 10.1530/EC-24-0612

There was only one patient with adrenal CS with a recurrence. This was a patient with bilateral macronodular hyperplasia. During the first surgery, the largest adrenal was removed. However, 3 years later, the contralateral adrenal was also removed because of the recurrence of CS.

Hypopituitarism after pituitary surgery

In patients with CD, we performed a sub-analysis based on the presence of anterior pituitary deficiencies after pituitary surgery for CD, besides AI. Antidiuretic hormone (ADH) deficiency was not included in this analysis. As expected after pituitary surgery and in line with the literature, temporary ADH deficiency occurred in a substantial part of the patients after surgery (23). Therefore, only central hypothyroidism, hypogonadotropic hypogonadism and growth hormone deficiency were taken into account (Fig. 5). The probability of recovery of AI was lower in patients with one or more pituitary deficiencies versus patients with intact pituitary function after surgery (two-sided log-rank test: P-value = 0.05). In patients with anterior pituitary deficiencies, the 1-, 2- and 5-years recovery rates of AI were 35.6, 60.4 and 67.6%, respectively. In patients without anterior pituitary deficiencies, the 1-, 2- and 5-years recovery rates of AI were 39.2, 76.0 and 89.1%, respectively. The median time to recovery of adrenal function in patients with CD with and without anterior pituitary deficiencies was 15.9 versus 13.4 months, respectively. Figure 6 shows the Kaplan–Meier curves by the number of hormonal deficiencies of the anterior pituitary gland, other than AI. Although statistical significance was not reached, there is a trend showing that the more postoperative hormonal deficiencies present, the lower the probability of recovery of AI is (two-sided log-rank test: P-value = 0.15).

Figure 5View Full Size
Figure 5
Kaplan–Meier curve by the presence/absence of hormonal deficiencies of the anterior pituitary gland (other than AI) after surgery in patients with CD.

Citation: Endocrine Connections 14, 5; 10.1530/EC-24-0612

Figure 6View Full Size
Figure 6
Kaplan–Meier curve by the number of hormonal deficiencies of the anterior pituitary gland after surgery in patients with CD.

Citation: Endocrine Connections 14, 5; 10.1530/EC-24-0612

Preoperative cortisol-lowering medical therapy, year of surgery and fasting cortisol concentration at the initial postoperative evaluation

Sub-analyses regarding patients who received PMT versus patients without PMT did not show any difference in the probability of recovery. In patients without PMT, the 1-, 2- and 5-years recovery rates of AI were 42.6, 77.6 and 85.2%, respectively. In patients with PMT, the 1-, 2- and 5-years recovery rates of AI were 41.6, 73.7 and 82.3%, respectively. The median time to recovery of adrenal function in patients without PMT and with PMT was 14.1 versus 13.5 months, respectively.

Sub-analyses regarding patients operated on before versus after 2010, regarding the results of the 1 mg dexamethasone suppression test at diagnosis and regarding patients with a low versus slightly higher postoperative morning cortisol within 7 days after surgery (<100 versus 100–200 nmol/L) also did not show any difference in the probability of recovery of adrenal function.

Table 2 shows HRs of univariate and multivariate Cox regression analyses. Adrenal CS and ectopic CS were associated with a higher probability of recovery of AI in comparison with patients with CS. Higher age was associated with a lower probability of recovery of AI.

Table 2Uni- and multivariate Cox regression analyses.

Variable Univariate Cox regression Multivariate Cox regression
HR 95% CI P value HR 95% CI P value
Etiology of CS (CD/adrenal CS/ectopic) 1.44 1.00–2.08 0.05 1.76 1.11–2.80 0.02
Etiology of CS (CD/adrenal CS) 1.42 0.91–2.22 0.12
Age (decades) 0.81 0.71–0.93 0.002 0.83 0.70–0.98 0.03
Sex (male/female) 1.02 0.68–1.55 0.92 0.74 0.46–1.20 0.22
BMI (kg/m2) 1.00 0.97–1.02 0.81 1.01 0.97–1.05 0.61
Duration of symptoms before diagnosis (years) 0.95 0.90–1.01 0.08 0.95 0.89–1.01 0.09
UFC (ULN) 1.03 0.99–1.07 0.15 1.01 0.97–1.05 0.57
Post-operative cortisol 0.10–0.20 versus <0.10 mcmol/L 0.92 0.56–1.50 0.73 1.16 0.58–2.30 0.67
In patients with CD only
PMT (no/yes) 1.23 0.75–2.02 0.40 1.26 0.53–3.02 0.60
Hormonal deficiencies of the anterior pituitary gland, other than AI (no/yes) 0.65 0.43–0.99 0.05 0.67 0.40–1.11 0.12
Micro/macroadenoma 1.13 0.70–1.83 0.62 1.42 0.79–2.52 0.24

PMT, preoperative medical treatment; HR, hazard ratio; CI, confidence interval; CS, Cushing’s syndrome; CD, Cushing’s disease; BMI, body mass index; UFC (ULN), times upper limit 24-h urine free cortisol; AI, adrenal insufficiency. The model of multivariate analysis for the whole group included the variables: etiology of CD, age, sex, BMI, duration of symptoms before diagnosis, UFC and postoperative cortisol 0.10–0.20 versus <0.10 mcmol/L. The model of multivariate analysis for the patients with CD only included the variables: etiology of CD, age, sex, BMI, duration of symptoms before diagnosis, UFC, postoperative cortisol 0.10–0.20 versus <0.10 mcmol/L, preoperative medical treatment, hormonal deficiencies of the anterior pituitary gland other than AI and micro/macroadenoma.

Discussion

In this study, we investigated the recovery rate of adrenal function and time to recovery after first-line treatment in patients with CS. The main finding is that the recovery rates of adrenal function are high. However, it may take several months to years before recovery of adrenal function occurs.

Patients with adrenal CS had higher recovery rates than patients with CD. This can be explained by the fact that the cortisol excess is generally less severe in adrenal CS and the fact that one adrenal gland remains completely intact after unilateral adrenalectomy. By contrast, patients who undergo pituitary surgery are at risk of developing new pituitary hormone deficiencies, including corticotrope deficiency, due to permanent structural damage to the pituitary gland. Our finding that patients with additional pituitary deficiencies after surgery for CD had lower recovery rates of adrenal function supports this hypothesis.

The recovery rates of adrenal function in CD, as well as in adrenal CS, are higher than what was reported in some previous studies (10, 11, 12), but are similar to other reports (13, 15, 17, 18). As shown in Table 3, it is difficult to compare previous studies because they all differ in design, study population and inclusion and exclusion criteria. For example, Berr et al. and Klose et al. used a different cutoff value of postoperative cortisol (<100 nmol/L) than we did (<200 nmol/L) to define initial AI shortly after surgery. However, only 25 patients in our cohort had a postoperative morning cortisol between 100 and 200 nmol/L and sub-analysis of patients with a morning cortisol <100 nmol/L versus patients with a morning cortisol between 100 and 200 nmol/L did not show any difference in recovery rate or time. Another difference between studies is the strategy for tapering off and stopping glucocorticoids in the postoperative period. In our study, patients started with 30 mg hydrocortisone per day after surgery. One might expect that a higher dose of hydrocortisone leads to a longer time to recovery of adrenal function. However, there are no data or evidence-based guidelines regarding the best strategy for tapering off and stopping glucocorticoids in the postoperative period.

Table 3Overview of previous studies regarding recovery of adrenal function after surgery in patients with CS.

Author n, etiology Recovery rate AI Time to recovery, years Follow up years Definition of AI/remission Substitution therapy (start doses) Recurrence rate (CD)
Alexandraki, 2013 (8) 131 CD 49/81 (60.5%) during follow up Median 1.5 years Minimum 6 years, mean 15.9 ± 6 years Postoperative cortisol ≤50 nmol/L Prednisolone 5 + 2 mg or HC 20 mg in divided doses 22.7% (microadenoma) 33.3% macroadenoma
Berr, 2015 (9) 5-year: Median: Mean 8.2 years Morning cortisol ≤100 nmol/L HC 40–50 mg/day
54 CD CD: 58% CD: 1.4 years CD: 7.0 years
26 ACS ACS: 38% ACS: 2.5 years ACS: 8.5 years
11 ECS ECS: 82% ECS: 0.6 years ECS: 13.5 years
Serban, 2019 (12) 61 CD 5-year: Median 1.6 years Minimum 3 years, median 6 years Morning cortisol ❤ μg/dL or cortisol after 250 μg synacthen test <18 μg/dL Cortisone acetate 25 mg, divided in 2–3 doses 16.4%
Persistent remission: 55.8% 2.1 years
Recurrence: 100% 1.0 years
Ciric 2012 (10) 86 CD 59.3% during follow up Mean 1.1 years Minimum 0.5 years, mean 5.7 years Drop in immediate postoperative cortisol, range <0.5–5.3 µg/dL and symptoms No specific unified algorithm 9.7%
Klose, 2004 (11) 2-year: Median: Post-operative cortisol <100 nmol/L and/or UFC <50 nmoL/24h Hydrocortisone 20–30 mg/day
18 CD CD: 67% CD: 2 years CD: 22.2%
14 ACS ACS: 79% ACS: 2 years ACS: 0%
Prete, 2017 (18) Median: Minimum 2 years Postoperative morning serum cortisol <5 μg/dL/138 nmol/L Hydrocortisone 20–30 mg/day in divided in 2–3 doses Patients with recurrence were excluded
15 CD CD: 1.3 years CD: median 5.8 years
31 ACS ACS: 0.8 years ACS: Median 4.0 years
 14 overt ACS Overt ACS: 1.5 years
 17 subclinical ACS Subclinical ACS: 0.5 years
Hurtado, 2018 (14) 81 ACS 87.8% during follow up Median ACS: 0.4 years Median ACS: 1.2 years Postoperative morning (day 1) serum cortisol <10 μg/dL/276 nmol/L or hemodynamic instability or received perioperative GC due to anticipated AI after unilateral adrenalectomy Prednisone or hydrocortisone, median hydrocortisone-equivalent dose 40 mg/day
 27 severe CS Severe: 1.0 years Severe: 1.0 years
 24 moderate CS Moderate: 0.2 years Moderate: 1.0 years
 30 MACE MACE: 0.2 years MACE: 1.5 years
Dalmazi, 2014 review on adrenal function after adrenalectomy for subclinical CS, 28 studies (17) ACS: 376 overt ACS 141 subclinical ACS Overt ACS: 93.4% subclinical ACS: 97.9% Mean overt ACS: 0.9 years subclinical ACS 0.5 years

CD, Cushing’s disease; ACS, adrenal Cushing’s syndrome; ECS, ectopic Cushing’s syndrome; AI, adrenal insufficiency; Subclin: subclinical; MACE, mild autonomous cortisol excess.

One might also hypothesize that the studies reporting high recurrence rates are related to higher recovery rates in CD patients. In our study, the recurrence rate was 17.8%, which is in line with previous studies (9, 13, 24). The establishment of recovery of adrenal function in patients with a recurrence later on is a difficult matter: despite the exclusion of patients with immediate obvious persistent disease in our study, recovery of glucocorticoid secretion in patients who developed a recurrence later on could be an early manifestation of recurrence instead of true recovery of physiological adrenal function. A striking finding in this study, in line with the aforementioned hypothesis, was the considerably higher 1-year recovery rate and the shorter time to recovery of patients with a recurrence in comparison to patients without a recurrence. Recovery of adrenal function is more rapid in patients with recurrences (13, 25). These findings imply that in case of an early recovery of adrenal function, clinicians should be aware of a possible recurrence of CD.

Another difference between studies is the inclusion or exclusion of patients with mild autonomous cortisol secretion (MACS), formerly known as subclinical CS. Previous studies have shown that patients with subclinical CS have a higher probability of recovery and a shorter duration of AI (14, 15, 16, 18). In our study, only two patients were diagnosed with subclinical CS (in this study characterized as inadequate suppression after DST in combination with values of UFC within the reference range) and therefore subgroup analysis was not possible.

In the present study, a rather high number of patients received PMT in comparison to other studies. In our institution, it was common practice to start PMT 3 months before pituitary surgery in patients with CD with the aim to improve hemostasis and other Cushing-related comorbidities, although the benefit of PMT has not yet been well established by randomized controlled trials. At the liberty of the treating physician, the dose of ketoconazole or metyrapone was titrated with the aim to normalize the 24-h UFC excretion. The doses needed to achieve normal 24-h UFC and the time to normalization of 24-h UFC varied between patients.

One could hypothesize that lowering cortisol levels during the weeks to months before surgery may result in a faster recovery of adrenal function. However, this was not the case in this study.

Overall, the present study shows a high recovery rate of adrenal function after treatment for CS. The time until recovery is partly dependent on the strategy and success of tapering off of glucocorticoids replacement and therefore may be very long because of GWS. These are meaningful findings. Tapering glucocorticoid substitution in parallel with the recovery of cortisol secretion after surgery for CS is often a challenging and lengthy trajectory for both patients and physicians. The lack of standardization of the follow-up and of the tapering protocols, the need for constant shared decision-making and personalized support for patients, particularly of those who are also confronted with severe associated comorbidities and unpredictable withdrawal symptoms, may discourage patients and physicians from proceeding in this endeavor. Given the rarity of the disease, knowledge on this topic is scarce. Previous, mainly smaller studies reported a wide range of recovery rates of adrenal function after first-line treatment for CS (varying between 37 and 93% for CD, and for overt adrenal CS between 38 and 93%) (10, 11, 12, 13, 15, 17, 18). The rather low percentages of recovery of adrenal function in some of these previous studies could discourage patients and physicians to persevere the attempt to taper off hydrocortisone. Our findings in a large cohort of patients with CS, including a sizable subgroup of patients with CD, allow us to deepen the multivariate analysis to uncover factors that are associated with a better chance of recovery. The data indicate that in this real-life setting, despite the long time to achieve recovery, the recovery rates are high and while this occurs for most of the patients within 1–2 years after treatment, recovery is still possible even after a longer follow-up. Moreover, this study showed that the recovery rate is higher in patients with adrenal CS versus CD, in younger patients and in patients with CD with preserved pituitary function after pituitary surgery. These findings are very important for clinical practice. They highlight the importance of continuing to taper off the glucocorticoids, if necessary slowly and steadily, in the years after surgery. They also help us better inform the patients beforehand and to improve the management and the expectations of both patients and physicians to motivate them to persevere in tapering of the glucocorticosteroids while considering the factors such as those identified to influence the chance of recovery during their personalized counseling and guidance of the patients in this often very difficult and lengthy period.

In our institution, it is common practice to counsel and provide guidance intensively to patients in this difficult period, both by the treating physician and a specialized nurse, as we consider this coordinated guidance of utmost importance. Moreover, all patients are provided with contact details so that they can reach to us for advice 24 h a day, either by phone or by secure email throughout this process. When indicated, patients are referred to other healthcare professionals such as psychologists, physical therapists, social workers and other specialists.

One important strength of our study is the large size of our single-center cohort, considering the rarity of the disease. This has also allowed us to do subgroup analyses and assess factors associated with recovery from postoperative AI. The limitations include the retrospective character of this study and the fact that patients were included over a long period of time (1968 to 2022) during which diagnostic tools and management protocols for CS have somewhat changed over this period of time. We have tried to mitigate the limitations that are inevitable with a retrospective study by being thorough and extensive in the quality and amount of data that we were able to collect. In addition to that, the diagnostic assessment and the treatment of the patients followed very strict and uniform protocols in conformity with the internationally recognized clinical guidelines available at the time. On the other hand, the fact that this represents a real-life study renders the results more relatable for clinical practitioners and strengthens its impact.

We collected data from medical records regarding the duration of CS-related signs and symptoms before diagnosis, as mentioned by the patient during history taking. We are well aware that these data are rather subjective and dependent on the accuracy of the recollection of the patient. However, this is the only way to assess the duration of symptoms before diagnosis. In our opinion, these data still could be very valuable.

In conclusion, our study shows that the large majority of patients with CS recover their adrenal function after first-line surgical treatment, even though the time to recovery may take several months to years. Informing patients beforehand and providing support, encouragement and guidance in this process is therefore paramount. Herewith, one could consider factors such as the age of the patient, the etiology of CS and the presence of additional pituitary deficiencies after pituitary surgery. In case of an early recovery of adrenal function, clinicians should be aware of a possible recurrence of CD. Future studies should establish the optimal postoperative management for CS to improve the chance for success of recovery of adrenal function.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the work reported.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

References

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Insights on Diagnosing and Managing Cushing’s Syndrome

Posted on August 18, 2024 by MaryO

Cushing’s syndrome, or endogenous hypercortisolemia, is a rare condition that both general practice clinicians and endocrinologists should be prepared to diagnose and treat. Including both the pituitary and adrenal forms of the disease, the Endocrine Society estimates that the disorder affects 10 to 15 people per million every year in the United States. It is more common in women and occurs most often in people between the ages of 20 and 50.

Even though Cushing’s remains a rare disease, cortisol recently made waves at the American Diabetes Association 84th Scientific Session. A highlight of the meeting was the initial presentation of data from the CATALYST trial, which assessed the prevalence of hypercortisolism in patients with difficult-to-control type 2 diabetes (A1c 7.5+).

CATALYST is a prospective, Phase 4 study with two parts. In the prevalence phase, 24% of 1,055 enrolled patients had hypercortisolism, defined as an overnight dexamethasone suppression test (ODST) value greater than 1.8 µg/dL and dexamethasone levels greater than 140 µg/dL. Results of CATALYST’s randomized treatment phase are expected in late 2024.

Elena Christofides, MD, FACE, founder of Endocrinology Associates, Inc., in Columbus, OH, believes the CATALYST results will be a wake-up call for both physicians and patients seeking to advocate for their own health. “This means that nearly 1 in 4 patients with type 2 diabetes have some other underlying hormonal/endocrine dysfunction as the reason for their diabetes, or significant contribution to their diabetes, and they should all be screened,” she said. “All providers need to get comfortable with diagnosing and treating hypercortisolemia, and you need to do it quickly because patients are going to pay attention as well.”

In Dr. Christofides’ experience, patients who suspect they have a hormonal issue may start with their primary care provider or they may self-refer to an endocrinologist. “A lot of Cushing’s patients are getting diagnosed and treated in primary care, which is completely appropriate. But I’ve also met endocrinologists who are uncomfortable diagnosing and managing Cushing’s because it is so rare,” she said. “The important thing is that the physician is comfortable with Cushing’s or is willing to put in the work get comfortable with it.”

According to Dr. Christofides, the widespread popular belief that “adrenal fatigue” is causing millions of Americans to feel sick, tired, and debilitated may be creating barriers to care for people who may actually have Cushing’s. “As physicians, we know that adrenal fatigue doesn’t exist, but we should still be receptive to seeing patients who raise that as a concern,” said Dr. Christofides. “We need to acknowledsalige their lived experience as being very real and it can be any number of diseases causing very real symptoms. If we don’t see these patients, real cases of hypercortisolemia could be left undiagnosed and untreated.”

Dr. Christofides, who also serves as a MedCentral Editor-at-Large, said she reminds colleagues that overnight dexamethasone suppression test (ODST) should always be the first test when you suspect Cushing’s. “While technically a screening test, the ODST can almost be considered diagnostic, depending on how abnormal the result is,” she noted. “But I always recommend that you do the ODST, the ACTH, a.m. cortisol, and the DHEAS levels at the same time because it allows you to differentiate more quickly between pituitary and adrenal problems.”

Dr. Christofides does see a place for 24-hour urine collection and salivary cortisol testing at times when diagnosing and monitoring patients with Cushing’s. “The 24-hour urine is only positive in ACTH-driven Cushing’s, so an abnormal result can help you identify the source, but too many physicians erroneously believe you can’t have Cushing’s if the 24-hour urine is normal,” she explained. “Surgeons tend to want this test before they operate and it’s a good benchmark for resolution of pituitary disease.” She reserves salivary cortisol testing for cases when the patient’s ODST is negative, but she suspects Cushing’s may be either nascent or cyclical.

Surgical resection has long been considered first-line treatment in both the pituitary and adrenal forms of Cushing’s. For example, data shared from Massachusetts General Hospital showed that nearly 90% of patients with microadenomas did not relapse within a 30-year period. A recent study found an overall recurrence rate of about 25% within a 10-year period. When reoperation is necessary, remission is achieved in up to 80% of patients.

As new medications for Cushing’s syndrome have become available, Dr. Christofides said she favors medical intervention prior to surgery. “The best part about medical therapy is you can easily stop it if you’re wrong,” she noted. “I would argue that every patient with confirmed Cushing’s deserves nonsurgical medical management prior to a consideration of surgery to improve their comorbidities and surgical risk management, and give time to have a proper informed consent discussion.”

In general, medications to treat Cushing’s disease rely on either cortisol production blockade or receptor blockade, said Dr. Christofides. Medications that directly limit cortisol production include ketoconazole, osilodrostat (Isturisa), mitotane (Lysodren), levoketoconazole (Recorlev), and metyrapone (Metopirone). Mifepristone (Korlym, Mifeprex) is approved for people with Cushing’s who also have type 2 diabetes to block the effects of cortisol. Mifepristone does not lower the amount of cortisol the body makes but limits its effects. Pasireotide (Signifor) lowers the amount of ACTH from the tumor. Cabergoline is sometimes used off-label in the US for the same purpose.

Following surgery, people with Cushing’s need replacement steroids until their adrenal function resumes, when replacement steroids must be tapered. But Dr. Christofides said she believes that all physicians who prescribe steroids should have a clear understanding of when and how to taper patients off steroids.

“Steroid dosing for therapeutic purposes is cumulative in terms of body exposure and the risk of needing to taper. A single 2-week dose of steroids in a year does not require a taper,” she said. “It’s patients who are getting repeated doses of more than 10 mg of prednisone equivalent per day for 2 or more weeks multiple times per year who are at risk of adrenal failure without tapering.”

Physicians often underestimate how long a safe, comfortable taper can take, per Dr. Christofides. “It takes 6 to 9 months for the adrenals to wake up so if you’re using high-dose steroids more frequently, that will cause the patient to need more steroids more frequently,” she explained. “If you’re treating an illness that responds to steroids and you stop them without tapering, the patient’s disease will flare, and then a month from then to 6 weeks from then you’ll be giving them steroids again, engendering a dependence on steroids by doing so.”

When developing a steroid taper plan for postoperative individuals with Cushing’s (and others), Dr. Christofides suggests basing it on the fact that 5 mg of prednisone or its equivalent is the physiologic dose. “Reduce the dose by 5 mg per month until you get to the last 5 mg, and then you’re going to reduce it by 1 mg monthly until done,” she said. “If a patient has difficulty during that last phase, consider a switch to hydrocortisone because a 1 mg reduction of hydrocortisone at a time may be easier to tolerate.”

Prednisone, hydrocortisone, and the other steroids have different half-lives, so you’ll need to plan accordingly, adds Dr. Christofides. “If you do a slower taper using hydrocortisone, the patient might feel worse than with prednisone unless you prescribe it BID.” She suggests thinking of the daily prednisone equivalent of hydrocortisone as 30 mg to allow for divided dosing, rather than the straight 20 mg/day conversion often used.

What happens after a patient’s Cushing’s has been successfully treated? Cushing’s is a chronic disease, even in remission, Dr. Christofides emphasized. “Once you have achieved remission, my general follow-up is to schedule visits every 6 months to a year with scans and labs, always with the instruction if the patient feels symptomatic, they should come in sooner,” she said.

More on Cushing’s diagnosis and therapies.

https://www.medcentral.com/endocrinology/cushings-syndrome-a-clinical-update

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Day 24: Cushing’s Awareness Challenge

Posted on April 24, 2024 by MaryO

Over the years, we went on several Windjammer Barefoot Cruises.  We liked them because they were small, casual and were fairly easy on the wallet.

They sailed around the Caribbean to a variety of islands, although they sometimes changed itineraries depending on weather, crew, whatever.  One trip we were supposed to go to Saba but couldn’t make port.  A lot of people got off at the next port and flew home.

The captains were prone to “Bedtime Stories” which were often more fiction than true but they added to the appeal of the trip.  We didn’t care if we missed islands or not – we were just there to sail over the waves and enjoy the ride.

The last trip we took with them was about two years before I started having Cushing’s problems.  (You wondered how I was going to tie this together, right?)

The cruise was uneventful, other than the usual mishaps like hitting docks, missing islands and so on.  Until it was a particularly rough sea one day.  I was walking somewhere on deck and suddenly a wave came up over the deck making it very slippery.  I fell and cracked the back of my head on the curved edge of a table in the dining area.  I had the next-to-the-worse headache I have ever had, the worst being after my pituitary surgery. At least after the surgery, I got some morphine.

We asked several doctors later if that hit could have contributed to my Cushing’s but doctors didn’t want to get involved in that at all.

The Windjammer folks didn’t fare much better, either. In October 1998, Hurricane Mitch was responsible for the loss of the s/v Fantome (the last one we were on). All 31 crew members aboard perished; passengers and other crew members had earlier been offloaded in Belize.

 

The story was recorded in the book The Ship and the Storm: Hurricane Mitch and the Loss of the Fantome by Jim Carrier.  The ship, which was sailing in the center of the hurricane, experienced up to 50-foot (15 m) waves and over 100 mph (160 km/h) winds, causing the Fantome to founder off the coast of Honduras.

“In October 1998, the majestic schooner Fantome came face-to-face with one of the most savage storms in Atlantic history. The last days of the Fantome are reconstructed in vivid and heartbreaking detail through Jim Carrier’s extensive research and hundreds of personal interviews. What emerges is a story of courage, hubris, the agony of command, the weight of lives versus wealth, and the advances of science versus the terrible power and unpredictability of nature.”

This event was similar to the Perfect Storm in that the weather people were more interested in watching the hurricane change directions than they were in people who were dealing with its effects.

I read this book and I was really moved by the plight of those crew members.

I’ll never know if that hit on my head contributed to my Cushing’s but I have seen several people mention on the message boards that they had a traumatic head injury of some type in their earlier lives.

 

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Day 19, Cushing’s Awareness Challenge

Posted on April 19, 2024 by MaryO

In case you haven’t guessed it, my cause seems to be Cushing’s Awareness.  I never really decided to devote a good portion of my life to Cushing’s, it just fell into my lap, so to speak – or my laptop.

I had been going along, raising my son, keeping the home-fires burning,  trying to forget all about Cushing’s.  My surgery had been a success, I was in remission, some of the symptoms were still with me but they were more of an annoyance than anything.

I started being a little active online, especially on AOL.  At this time, I started going through real-menopause, not the fake one I had gone through with Cushing’s.  Surprisingly, AOL had a group for Cushing’s people but it wasn’t very active.

What was active, though, was a group called Power Surge (as in I’m not having a hot flash, I’m having a Power Surge).  I became more and more active in that group, helping out where I could, posting a few links here and there.

Around this time I decided to go back to college to get a degree in computer programming but I also wanted a basic website for my piano studio.  I filled out a form on Power Surge to request a quote for building one.  I was very surprised when Power Surge founder/webmaster Alice (AKA Dearest) called me.  I was so nervous.  I’m not a good phone person under the best of circumstances and here she was, calling me!

I had to go to my computer class but I said I’d call when I got back.  Alice showed me how to do some basic web stuff and I was off.  As these things go, the O’Connor Music Studio page grew and grew…  And so did the friendship between Alice and me.  Alice turned out to be the sister I never had, most likely better than any sister I could have had.

In July of 2000, Alice and I were wondering why there weren’t many support groups online (OR off!) for Cushing’s. This thought percolated through my mind for a few hours and I realized that maybe this was my calling. Maybe I should be the one to start a network of support for other “Cushies” to help them empower themselves.

I wanted to educate others about the awful disease that took doctors years of my life to diagnose and treat – even after I gave them the information to diagnose me. I didn’t want anyone else to suffer for years like I did. I wanted doctors to pay more attention to Cushing’s disease.

The first website (http://www.cushings-help.com) went “live” July 21, 2000. It was just a single page of information. The message boards began September 30, 2000 with a simple message board which then led to a larger one, and a larger. Today, in 2012, we have over 8 thousand members. Some “rare disease”!

This was on the intro page of Cushing’s Help until 2013…

I would like to give abundant thanks Alice Lotto Stamm, founder of Power Surge, premier site for midlife women, for giving me the idea to start this site, encouraging me to learn HTML and web design, giving us the use of our first spiffy chatroom, as well as giving me the confidence that I could do this. Alice has helped so many women with Power Surge. I hope that I can emulate her to a smaller degree with this site.

Thanks so much for all your help and support, Alice!

In August 2013 my friend died.  In typical fashion, I started another website…

I look around the house and see things that remind me of Alice.  Gifts, print outs, silly stuff, memories, the entire AOL message boards on floppy disks…

Alice, I love you and will miss you always…

MaryOOneRose

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Day 13, Cushing’s Awareness Challenge

Posted on April 13, 2024 by MaryO

UVA 2004
Cushing’s Conventions have always been special times for me – we learn a lot, get to meet other Cushies, even get referrals to endos!

As early as 2001 (or before) my pituitary function was dropping.  My former endo tested annually but did nothing to help me with the symptoms.

In the fall of 2002 my endo refused to discuss my fatigue or anything at all with me until I lost 10 pounds. He said I wasn’t worth treating in my overweight condition and that I was setting myself up for a heart attack. He gave me 3 months to lose this weight. Those 3 months included Thanksgiving, Christmas and New Years.  Needless to say, I left his office in tears, again.

Fast forward 2 years to 2004.  I had tried for a while to get my records from this endo. He wouldn’t send them, even at doctors’ or my requests.

I wanted to go see Dr. Vance at UVa but I had no records so she wouldn’t see me until I could get them.

Finally, my husband went to the former endo’s office and threatened him with a court order. The office manager managed to come up with about 13 pages of records. For going to him from 1986 to 2001 including weeks and weeks at NIH and pituitary surgery, that didn’t seem like enough records to me.

In April of 2004, many of us from the message boards went to the UVa Pituitary Days Convention. That’s where the picture above comes in.  Other pictures from that convention are here.

By chance, we met a wonderful woman named Barbara Craven. She sat at our table for lunch on the last day and, after we learned that she was a dietitian who had had Cushing’s, one of us jokingly asked her if she’d do a guest chat for us. I didn’t follow through on this until she emailed me later. In the email, she asked how I was doing. Usually I say “fine” or “ok” but for some reason, I told her exactly how awful I was feeling.

Barbara emailed me back and said I should see a doctor at Johns Hopkins. I said I didn’t think I could get a recommendation to there, so SHE referred me. The doctor got right back to me, set up an appointment. Between his vacation and mine, that first appointment turned out to be Tuesday, Sept 14, 2004.

Just getting through the maze at Johns Hopkins was amazing. They have the whole system down to a science, moving from one place to another to sign in, then go here, then window 6, then… But it was very efficient.

My new doctor was wonderful. Understanding, knowledgeable. He never once said that I was “too fat” or “depressed” or that all this was my own fault. I feel so validated, finally.

He looked through my records, especially at my 2 previous Insulin Tolerance Tests (ITT). From those, he determined that my growth hormone has been low since at least August 2001 and I’ve been adrenal insufficient since at least Fall, 1999 – possibly as much as 17 years! I was amazed to hear all this, and astounded that my former endo not only didn’t tell me any of this, he did nothing. He had known both of these things – they were in the past records that I took with me. Perhaps that was why he had been so reluctant to share copies of those records. He had given me Cortef in the fall of 1999 to take just in case I had “stress” and that was it.

The new endo took a lot of blood (no urine!) for cortisol and thyroid stuff. I went back on Sept. 28, 2004 for arginine, cortrosyn and IGF testing.

He said that I would end up on daily cortisone – a “sprinkling” – and some form of GH, based on the testing the 28th.

For those who are interested, my new endo is Roberto Salvatori, M.D.
Assistant Professor of Medicine at Johns Hopkins

Medical School: Catholic University School of Medicine, Rome, Italy
Residency: Montefiore Medical Center
Fellowship: Cornell University, Johns Hopkins University
Board Certification: Endocrinology and Metabolism, Internal Medicine

Clinical Interests: Neuroendocrinology, pituitary disorders, adrenal disorders

Research Interests: Control of growth hormone secretion, genetic causes of growth hormone deficiency, consequences of growth hormone deficiency.

Although I have this wonderful doctor, a specialist in growth hormone deficiency at Johns Hopkins, in November, 2004, my insurance company saw fit to over-ride his opinions and his test results based on my past pharmaceutical history! Hello??? How could I have a history of taking GH when I’ve never taken it before?

Of course, I found out late on a Friday afternoon. By then it was too late to call my case worker at the drug company, so we had to appeal on Monday. My local insurance person also worked on an appeal, but the whole thing was  just another long ordeal of finding paperwork, calling people, FedExing stuff, too much work when I just wanted to start feeling better by Thanksgiving.

As it turned out the insurance company rejected the brand of hGH that was prescribed for me. They gave me the ok for a growth hormone was just FDA-approved for adults on 11/4/04. The day this medication was approved for adults was the day after my insurance said that’s what is preferred for me. In the past, this form of hGH was only approved for children with height issues. Was I going to be a ginuea pig again?

The new GH company assigned a rep for me, submitted info to pharmacy, and waited for insurance approval, again.

I finally started the Growth Hormone December 7, 2004.

Was the hassle and 3 year wait worth it?

Stay tuned for April 15, 2016 when all will be revealed.

Read

Read Dr. Barbara Craven’s Guest Chat, October 27, 2004

Thanks for reading 🙂

MaryO

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