An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Excess (MACE) Due to Adrenal Adenomas in Postmenopausal Women
Phase: PHASE4
Conditions: Mild Autonomous Cortisol Excess
Sponsor: Icahn School of Medicine at Mount Sinai

An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Excess (MACE) Due to
Adrenal Adenomas in Postmenopausal Women
PI: Dr. Alice C. Levine
NCT05038878
Document Date: Aug 2, 2018

CONFIDENTIAL 
Template: Investigator Initiated Study Agreement – 02AUG2018 
40,022 
EXHIBIT A 
PROTOCOL 
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Section 
1.0 
 General Information 
1.1 
Study 
Title: 
Pilot study of Elagolix for the treatment of autonomous cortisol secretion (ACS) 
due to adrenal adenomas in postmenopausal women (SA- 002509, Protocol # 
A19-745) 
1.2 
1.2 
Institution 
Name: 
Icahn School of Medicine at Mount Sinai Hospital 
1.3 
Investigat
or Contact 
Informatio
n: 
Alice C. Levine, MD
Alice.levine@mountsinai.org 
(212) 241-3422 
Contact: Regina Belokovskaya, DO (regina.belokovskaya@mountsinai.org) 
2.0 
Background Information 
2.1 
Rationale 
& 
Backgroun
d 
Informatio
n 
The rationale specifies the reasons for conducting the research in light of current 
knowledge.  It should include a well-documented statement of the need/problem that is 
the basis of the project, the cause of this problem and its possible solutions.  It should 
answer the question of why and what: why the research needs to be done and what will 
be its relevance.  Selected literature references critical to the study design, dosage 
selection, or rationale for the study should be cited, as appropriate. 
Increasingly, patients are found to have incidentally found adrenal adenomas on 
imaging performed for other purposes. The most common secretory syndrome 
in adrenal nodules is autonomous cortisol secretion (ACS) where patients lack 
the typical clinical stigmata of overt hypercortisolism (1). 
Exposure to even low levels of excess cortisol can result in long term metabolic 
and cardiovascular effects which may not be completely reversible.  Subclinical 
hypercortisolism due to adrenal incidentalomas has been shown in multiple, 
large retrospective studies to be associated with an increased prevalence of 
hypertension and type 2 diabetes mellitus (T2DM) and cardiovascular risk (2, 3, 
4, 5). Morelli et al. reported that cardiovascular event prevalence was higher in 
patients with subclinical hypercortisolism, regardless of age and the presence of 
T2DM (6).  Most notably, a study by Di Dalmazi et al. demonstrated increased 
mortality due to cardiovascular disease in patients with even mild cortisol 
excess due to adrenal adenomas (2).  Mild, chronic cortisol excess is particularly 
toxic to bone resulting in increased bone demineralization and increased risk of 
vertebral fractures (7,8). There are limited studies regarding outcomes after 
unilateral adrenalectomy or medical management to treat this disorder.  
A recent publication demonstrated that adrenalectomy for patients with 
adenomas resulting in ACS reduces the risk of vertebral fractures (9).  
      Current options for medical treatment of Cushing syndrome include 
steroidogenesis enzyme inhibitors suitable for all causes of CS (ketoconazole, 
metyrapone, the glucocorticoid receptor antagonist, mifepristone), agents to 
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suppress ACTH in Cushing’s disease, such as dopamine agonists and pasireotide, 
and the adrenolytic and steroidogenic enzyme inhibitor mitotane for adrenal 
cortical carcinomas that secrete cortisol.   Mifepristone is currently the only FDA 
approved medication for Cushing’s syndrome with the specific indication for the 
treatment of elevated blood sugar in patients with Cushing’s syndrome and type 
2 diabetes mellitus (24).  We recently completed a pilot study that 
demonstrates that Mifepristone treatment of ACS is associated with a 
statistically significant decrease in fasting glucose and insulin resistance as 
measured by HOMA-IR scores (25).   With various insurance policies it is 
sometimes difficult to get these medications approved. Often time, 
ketoconazole, though not FDA approved, may be the first one covered by the 
insurance. However side effects are common, with the most limiting one being 
elevation in LFTs with ketoconazole.   
     The incidence of adrenal adenomas and ACS is higher in women than 
men with peak incidence at ages 50-70.  In addition, several case reports have 
demonstrated luteinizing hormone/human chorionic gonadotropin receptor 
(LH/HCG-R) expression in adrenal secretory tumors in postmenopausal and 
pregnant females .  A report by Teo et al. described a post-menopausal and 2 
pregnant women with aldosterone-producing adrenal adenomas, each of which 
harbored activating mutations of CTNNB1, the gene encoding β-catenin. The 
mutations stimulate Wnt activation and cause adrenocortical cells to de-
differentiate toward their common adrenal-gonadal precursor cell type 
including the expression of  LH/hCGR and GATA-4 [10].  
The adrenals and the gonads share a common lineage during embryogenesis 
(adrenogenital ridge).  Adrenal cortex arises from the coelomic mesoderm of 
the urogenital ridge, and the medulla arises from neural crest tissue. We have 
recently demonstrated that adrenal adenomas overexpress LH/HCG-R and Gata-
4 (gonadal differentiation factor) (11).  As such, there is strong evidence that 
adrenal tumor development is at least partially driven by LH in postmenopausal 
women.  We also will present data at The Endocrine Society 2019 
demonstrating expression of LH/HCG-R in 24/24 adrenal adenomas derived 
from postmenopausal women (12). Such findings have also been seen in 
primate species.  Lasley et al demonstrated the presence of luteinizing 
hormone/gonadal chorionic gonadotropin receptors in the adrenal cortex of 
ovarectomized female rhesus macaque (13). Further corroborating our data, 
Saxenda and Seely demonstrated a positive correlation between serum LH 
levels and urinary free cortisol levels in postmenopausal women (14).  
As such, there is strong evidence that adrenal tumor development is at least 
partially driven by LH in postmenopausal women.  Most recently, Doroszko et al 
studied the effects of the GnRH antagonist cetrorelix acetate (CTX) on 
adrenocortical tumor cells from mouse and human subjects in vitro and in 
transgenic mice in vivo, demonstrating that CTX decreased cell viability and 
proliferation in vitro and tumor size in vivo (15).  
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Thus, we hypothesize that LH/HCG-R is a viable target for the treatment of ACS 
due to adrenal adenomas in postmenopausal women.  In this study, we propose 
the use of elagolix, an oral GnRH antagonist recently approved for the 
treatment of endometriosis, to treat ACS in postmenopausal women with 
adrenal adenomas. 
3.0 
Core Protocol 
3.1 
Study 
Objectives 
and 
Purpose 
Objectives should be simple (no complex) and specific (no vague). After the statement 
of the primary objective, secondary objectives may be mentioned 
The goal of this pilot study is to determine if treatment of postmenopausal 
women with adrenal incidentaloma and ACS with elagolix for 6 months  leads to 
a decrease in adrenal adenoma size, reduction in hypercortisolism leading to 
improvement in metabolic, bone, mood and quality of life measures.   
3.2 
Study 
Design 
This section is a concise overview of the study design and should include the following: 
●
Type of experimental design (observational or interventional, randomized 
block, crossover, etc.); 
●
Whether the study is controlled (treatments other than the test product and/or 
placebo); 
●
Description of the type/design of the study to be conducted (e.g., open-label, 
single or double-blind); 
●
A specific statement of the primary endpoints and the secondary endpoints, if 
any, to be measured during the study; and, 
●
The number of the study centers (single or multi-center). 
The number of study centers (single or multi-center) and the total number of subjects 
included in the study and how they will be assigned to treatment groups must be 
indicated.  When appropriate, state if the subjects will be stratified. 
This is a pilot, open-label, interventional study.  Subjects will be recruited from 
The Mount Sinai Adrenal Center, Mount Sinai Internal Medicine Associates 
(IMA) and Faculty Practice Associates (FPA).  A total of 12 patients will be 
enrolled and all patients enrolled will receive study drug. This will be a change-
from-baseline approach. 
Primary Endpoints:  To determine the effects of elagolix treatment on 1) adrenal 
adenoma size 2) cortisol secretion 3) metabolic parameters and 4) bone 
turnover markers and vertebral fractures rates between baseline and 6 months 
treatment.
Secondary Endpoints:  To determine the effects of elagolix treatment on mood 
and quality of life. 
3.3 
Inclusion 
Criteria 
Eligible post-menopausal women that have incidentally found adrenal 
adenomas with benign appearing characteristics on imaging (<4 cm, non-
contrast CT <10 HU and/or lipid rich and benign appearing on MRI), the absence 
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of anti-anabolic clinical features of overt Cushing’s signs (proximal muscle 
weakness, >three ecchymoses, hyperpigmented striaie)  and 2 of 3 of the 
following: 1) elevated 24 hr urine free cortisol (UFC) above the upper limit of 
normal (>50 mcg/24 hours) in at least two complete 24-hour tests and/or 2)  
late night salivary cortisol more than upper limit of normal in at least two tests 
and/or 3) an abnormal dexamethasone suppression defined as post 1mg 
dexamethasone suppression test serum cortisol concentration of >1.8 mcg/ml 
will be eligible for inclusion (2).    
Post-menopausal is defined as: clinic status of cessation of menses for 12 mo in 
a previously cycling woman and reflecting complete or nearly complete 
permanent cessation of ovarian function and fertility (26). 
Patients with osteoporosis can be included in the study. However, if they are 
receiving treatment with either antiresorptive medications (bisphosphonates, 
denosumab) or anabolic agents (teriparitide, abaloparatide or romosozumab) 
any bone related data will be excluded from their analysis. 
3.4 
Exclusion 
Criteria 
Subjects receiving medications for chronic medical problems that may interact 
with elagolix, untreated hypothyroidism or hypopituitarism, known pituitary 
disorder, dexamethasone or CRH in the week prior to testing, use of elagolix, 
ketoconazole, metyrapone or mifepristone for one month prior, or known 
allergy to elagolix. In addition patients will be excluded if they have poorly 
controlled hypertension (mean systolic BP >170 mm Hg or mean diastolic BP 
>110 mm Hg) at screening, poorly controlled diabetes mellitus (Hemoglobin A1C 
>12% at screening), abnormal liver test results (total bilirubin >1.5 x upper limit 
normal or elevated alanine aminotransferase or aspartate amino transferase 
>3X upper limit normal at baseline), severe renal insufficiency (GFR <= 29 
ml/min) at baseline.  Patients will be excluded if they use or plan to use 
somatostatin analogues (octreotide, lanreotide or pasireotide) or have used 
these drugs within 8 months prior to study start.  Patients with adrenal cortical 
carcinoma will also be excluded. Patients with a history of malabsorption will be 
excluded. Patients on HRT will be excluded. 
Elagolix is also a substrate of CYP3A and therefore should not be used 
concomitantly with drugs that are strong CYP3A inhibitors including: 
clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, 
atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, 
tipranavir. 
Drug interactions of note (not Exclusion Criteria): Elagolix is also a substrate of 
CYP3A and therefore should not be used concomitantly with drugs that are 
strong CYP3A inhibitors including: clarithromycin, telithromycin, nefazodone, 
itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, 
ritonavir, saquinavir, tipranavir. Elagolix is also a substrate of organic anion 
transporting polypeptide (OATP) therefore the concomitant use of strong OATP 
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1B1 inhibitors (e.g., cyclosporine and gemfibrozil) is contraindicated as they may 
increase plasma concentrations of elagolix. 
Elagolix is a weak to moderate inducer of cytochrome P450 (CYP) 3A. Co-
administration with Elagolix may decrease plasma concentrations of drugs that 
are substrates of CYP3A (i.e. amlodipine and atorvastatin). Elagolix is a weak 
inhibitor of CYP 2C19. Co-administration with Elagolix may increase plasma 
concentrations of drugs that are substrates of CYP2C19 (e.g., omeprazole) but 
this only requires attention if very high doses are used such as in Zollinger-
Ellison syndrome.
3.5 
Study 
Flowchart 
A study flow chart is highly recommended.  It should display all clinical and laboratory 
measurements and the time periods (e.g., hours, days, and/or weeks) at which data are 
to be collected. 
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3.6 
Study 
Procedure
s 
This section is a detailed explanation of the experimental design.  The use of 
subheadings, lists, tables, or outlines are recommended.  Describe the initial screening 
period(s), baseline period(s), treatments to be compared, study configuration (e.g., 
parallel, crossover, etc.), duration of the treatment period(s), control group(s), follow-up 
procedures, and length of time specified for washout intervals and safety follow-up. 
This section should also include subject withdrawal criteria (e.g, terminating 
investigational product treatment/trial treatment) and procedures specifying: 
a)
When and not to withdraw subjects from the trial/investigational product 
treatment; 
b)
The type and timing of the data to be collected for withdrawn subjects; 
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c)
Whether and how subjects are to be replaced; 
d)
The follow-up for subjects withdrawn from investigational product 
treatment/trial treatment. 
The study will be submitted for IRB approval by the Mount Sinai Institutional 
Review Board and registered with the clinical trials office. A determination will 
be made regarding eligibility of this study for an Investigational New Drug (IND) 
exemption.  
The following parameters will be measured: 
Adenoma Size:  All patients will have baseline imaging (CT or MRI) within 6 
months to start of treatment and then will have repeat imaging with CT 
abdomen without contrast at 6 months to determine the effect of elagolix 
treatment on adrenal adenoma size and imaging characteristics. The images will 
be reviewed by a dedicated adrenal radiologist for consistency. 
Clinical Exam and parameters:  At baseline, one month, 3 months and 6 months 
patient will have full physical exam include measurement of vital signs.  Body 
weight and waist circumference will be measured.  Weight will be measured 
without overcoat and shoes and with only light clothing.  Waist circumference 
measurements will be obtained to the nearest 0.5 cm following removal of 
clothing from the waistline. Waist circumference will be measured in 
centimeters (cm) in the horizontal plane midway between the lowest ribs and 
the iliac crest (16). 
     In addition at baseline, three month and 6 month study visits patients will 
have a measurement of proximal muscle strength utilizing the sit to stand test.
The test evaluates the ability of patients to go from standing to sitting in a chair 
and then getting up again with/without the use of their arms or other aids.  
Patients seated in a chair will be asked to fold their arms across their chests and 
to stand up from the seated position once.  If they are able to successfully rise 
from the chair, they will be asked to sit down again and then stand up and sit 
down, a total of 5 times as quickly as possible.  Study staff will use a stopwatch 
to measure the total time it takes for the patient to stand up and sit down five 
times.  Start time is in the seated position and stop time is in the final standing 
position.  The total time of the test is measured.  
Cortisol Secretion and Metabolic Parameters:  At the baseline, 3 and 6 month 
study visits, patients will undergo a history and physical examination, including 
measurement of weight, blood pressure and waist circumference.   Fasting 8AM 
laboratory testing will be obtained, including a comprehensive metabolic panel, 
cortisol, ACTH, DHEAS, hemoglobin A1c, preserved glucose and insulin levels, 2 
hour oral glucose tolerance test, lipid profile, LH and estradiol. Fasting glucose 
and insulin level will be used to calculate HOMA-IR (Homeostatic Model 
Assessment for Insulin Resistance).  Results of oral glucose tolerance testing 
and C-peptide values to calculate a Matsuda index, oral disposition index, 
and HOMA IR (all measures of insulin resistance). Dexamethasone 
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suppression test will be performed at baseline and completion of the study. In 
addition, 24 hour urine free cortisol measurements will be done at time 0, 3 and 
6 months.   
Bone turnover markers and vertebral fracture rate:  At the baseline and 6 
months determination of serum c-telopeptide (CTX), a marker of osteoclastic 
activity and osteocalcin (a marker of osteoblastic activity) will be determined.  
Previous studies have demonstrated a suppressive effect of high cortisol on 
osteocalcin with return to normal levels after treatment (17). Fragility, or low 
traumatic fractures, which are fractures associated with either minimal or no 
discernible trauma, is a common complication of endogenous Cushing’s 
syndrome (1). Mild hypercortisolism has also been shown to increase vertebral 
fracture rates and a recent study demonstrated that surgical adrenalectomy for 
SH due to adrenal adenomas reduces vertebral fractures.  Interestingly, bone 
density measurements may underestimate the deleterious effects of 
glucocorticoids on bone quality (9).   Accordingly, baseline and 6 month 
vertebral fractures rates will be assessed by lateral X-rays of thoracic and 
lumbar spine. 
Study subjects are allowed to take Calcium and Vitamin D. 
Mood and Quality of Life Measures:   Patients will also complete several 
validated surveys at baseline and 6 months’ treatment, including Cushing QOL 
(18), Nottingham Health Profile (19), Beck’s Depression Scale (20), State Trait 
Anxiety Inventory (STAI) (21) and a visual analogue scale assessing hunger, 
fullness, and satiety (22). The surveys will be scored based on validated scoring 
system.
Safety Monitoring and Subject Withdrawal Criteria: Patients will be assessed at 
baseline, one month, three months and six months including history, physical, 
and laboratory testing (comprehensive metabolic panel and complete blood 
count with differential).  Study drug will be discontinued for any adverse 
reactions including nausea, vomiting, and/or diarrhea, a single episode 
occurring within 6-8 hours after administration of Elagolix.  Drug will also be 
discontinued for elevations greater than 3-4x normal in liver function tests, any 
abnormalities in electrolytes (above or below normal range) or kidney function 
(elevation of BUN and/or creatinine above normal range) and any abnormalities 
in hematologic parameters. 
Procedures for Reporting a Serious Adverse Event (SAE):  Any SAE occurring 
from the time of signing of the informed consent form (ICF) and for at least 30 
days after the last dose of study drug must be reported within 24 hours to the 
designated safety contact and recorded on the SAE form.  The investigator will 
supply the sponsor and the IRB/IEC with any additional requested information.
Adverse Event Follow-up:  All adverse events will be followed until resolution, 
until deemed stable by the Principal Investigator, or until the patient is deemed 
by the Principal Investigator to be lost to follow-up.  
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3.7 
Statistical 
Analysis 
and 
Sample 
Size 
Justificatio
n 
The statistical methods proposed to be used for the analysis of data should be clearly 
outlined, including reasons for the sample size selected, power of the study, level of 
significance to be sued, procedures for accounting for any missing or spurious data, etc.  
For projects involving qualitative approaches, specify in sufficient detail how the data 
will be analyzed. 
State who will be responsible for analyzing the study data (e.g., investigator, contract 
CRO, etc.). 
Investigator will be responsible for analyzing the study data. The significance of 
the effect of elagolix treatment on different outcome measures will be assessed 
with the Wilcoxon matched-pairs signed rank test to generate a two-tailed p-
value. Calculations will be performed with Prism 6 (Graphpad Software, Inc.). 
Sample Size Justification: No hypothesis testing, pilot study. 
3.8 
Specific 
Drug 
Supply 
Requirem
ents 
The investigator is responsible for keeping accurate records of the clinical supplies, the 
amount dispensed to and returned by the subjects, and the disposition at the end of the 
study.   
Clinical supplies must be received by a designated person at the study site, handled and 
stored safely and properly, and kept in a secured location to which only the investigator 
and designated assistants have access.  Clinical supplies are dispensed in accordance 
with the protocol.   
The investigator will be responsible for the destruction of the supplies at the study 
center pursuant to the ICH/GCP Guidelines, local regulations, and the investigator’s 
institutional policies.   
Elagolix 200 mg BID has an acceptable safety profile and results in rapid 
suppression of LH (23).  We selected this dose because it has been deemed to 
be safe and we are aiming for maximal efficacy.  Once screened and with 
informed consent, patients will be administered elagolix 200 mg orally twice 
daily for a total of 6 months.
3.9 
Safety 
Reporting 
In addition to compliance with all FDA reporting requirements pursuant to 21 CFR 312, 
the Principal Investigator shall: 
a)
Report to AbbVie all serious adverse events (SAEs) experienced by a study 
subject receiving an AbbVie product within 24 hours of learning of the event 
regardless of the relationship of the event to the AbbVie product.  Principal 
Investigator shall make available to AbbVie promptly such records as may be 
necessary and pertinent to investigate any such event, if specifically requested 
by AbbVie, and, 
b)
Copy AbbVie on the submission to the FDA of events meeting the definition of 
IND safety reports at the time of submission to the Agency; and, 
c)
Notify AbbVie upon any subjects receiving an AbbVie Product whose pregnancy 
has resulted in a negative outcome or untoward event during the course of 
pregnancy or upon delivery. 
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’s contact for reporting serious adverse drug experiences, pregnancy experiences, and 
communications of FDA submissions of IND safety reports shall be 
PPDINDPharmacovigilance@abbvie.com
t Complaints:  In addition to compliance with all FDA requirements pursuant to 21 CFR 
211 and 21 CFR 820, Principal Investigator will report to AbbVie within 24 hours any 
suspected quality defect in an AbbVie Product or its AbbVie-provided packaging, 
labeling, or medical device component (collectively, “Product Complaint”).  Principal 
Investigator will report Product Complaints that involve an AbbVie Product, whether 
AbbVie has supplied the AbbVie Product used in the Study or not.  AbbVie’s contact for 
reporting Product Complaints shall be RD_PQC_QS@abbvie.com
ollection of non-serious adverse events may be added per product-specific requirements. 
The events to be collected and the timing of this reporting should be included in this 
section as required.> 
Patients will be evaluated and questioned to identify AEs during the study. 
Collection of AEs will start immediately following the signing of the informed 
consent forms. Illnesses present before the patient signs the consent are 
considered pre-existing conditions and are documented on the medical history. 
Adverse events that occur after the start of the study drug and up to and 
including 30 days after administration of the last dose of study drug will be 
considered treatment emergent adverse events. Any adverse events reported 
more than 30 days after the last dose of study drug will be considered post 
treatment AEs.  
Any AEs/SAEs occurring from the time of signing the ICF and for at least 30 days 
after the last dose of study drug will be reported within 24 hours to the 
designated safety contact and recorded on the SAE form. All patients with an 
SAE will be followed and the outcomes will be reported. All AEs will be followed 
until resolution or until deemed stable by the Principal Investigator or until the 
patient is deemed to be lost to follow-up.  
SAEs will be reported in accordance to FDA requirements and AbbVie will be 
informed on these cases.
3.10 
Reference
s 
All literature references cited in the protocol should be listed accordingly in the 
reference section. 
1.
Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart 
PM, et al. The diagnosis of Cushing's syndrome: an Endocrine Society 
Clinical Practice Guideline. The Journal of clinical endocrinology and 
metabolism. 2008;93(5):1526-40. 
2.
Di Dalmazi G, Vicennati V, Garelli S, Casadio E, Rinaldi E, Giampalma E, 
et al. Cardiovascular events and mortality in patients with adrenal 
incidentalomas that are either non-secreting or associated with 
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intermediate phenotype or subclinical Cushing's syndrome: a 15-year 
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2014;2(5):396-405. 
3.
Androulakis, II, Kaltsas GA, Kollias GE, Markou AC, Gouli AK, Thomas DA, 
et al. Patients with apparently nonfunctioning adrenal incidentalomas 
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4.
Debono M, Bradburn M, Bull M, Harrison B, Ross RJ, Newell-Price J. 
Cortisol as a marker for increased mortality in patients with incidental 
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5.
Di Dalmazi G. Update on the risks of benign adrenocortical 
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6.
Morelli V, Eller-Vainicher C, Salcuni AS, Coletti F, Iorio L, Muscogiuri G, 
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7.
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8.
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9.
Salcuni AS, Morelli V, Eller Vainicher C, Palmieri S, Cairoli E, Spada A, et 
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The New England journal of medicine 373 (15):1429-1436.  
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12. Belokovskaya, R., Yao, S., Kirschenbaum, A. and Levine, 
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Chorionic Gonadotropin Receptor (LH/hCG Receptor) in Adrenal 
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Adenomas of Postmenopausal Women. 101st Annual Meeting of the 
Endocrine Society, New Orleans, LA, March 2019. 
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15. Doroszko, Milena, et al. "GnRH antagonist treatment of malignant 
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17. Guo W, Li F, Zhu C, Wang B, Wang K, Dai C. Effect of hypercortisolism on 
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19. Wiklund I. The Nottingham Health Profile--a measure of health-related 
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20. Whisman MA, Perez JE, Ramel W. Factor structure of the Beck 
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23. Struthers, R. Scott, et al. Suppression of gonadotropins and estradiol in 
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Clinical Endocrinology & Metabolism 94.2 (2009): 545-551. 
24. Feelders, RA, Newell-Price J, Pivonello R, Nieman LK, Hofland LJ,and 
LaCroix, A. Advances in the medical treatment of Cushing’s syndrome. 
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