Journalist Handbook Special focus on Cushing’s...
Transcript of Journalist Handbook Special focus on Cushing’s...
Journalist HandbookSpecial focus on Cushing’s disease Provided by Novartis Oncology
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Contents
Note to JournalistsThe Internet has presented patients with the resources to understand their illness, and a majority of people today (68%) will first research their symptoms online to be better informed when speaking with their doctor1. Unfortunately, for people affected by a rare condition called Cushing’s disease, which is generally believed to be one to two people per million annually worldwide but estimates vary. Patients experience many signs and symptoms, including weight gain, depression, diabetes, fatigue and high blood pressure, which are also indicative of other illnesses2,3.
To help increase your understanding of this often over-looked and misdiagnosed disease, the following handbook has been developed by Novartis Oncology to provide you with background about Cushing’s disease.
The following provides essential information needed to better understand the clinical manifestations of the disease, the necessary steps to obtain a proper diagnosis and disease management.
This handbook also provides information that may assist in your reporting of Cushing’s disease and other medical topics, including a glossary of commonly used terms that are associated with Cushing’s disease and a listing of medical resources, including government and non-governmental organizations, and medical publications that provide scientifically accurate information about endocrine disorders
We hope you find the handbook useful as you consider reporting on Cushing’s disease in the near future.
We hope you find the handbook useful as you consider reporting on Cushing’s disease in the near future.
3 Cushing’s disease: A Rare Endocrine Disorder 4 Definition & Epidemiology5 Mechanism of Disease6 Clinical Manifestations6 Complications7 Diagnosing Cushing’s disease9 Disease Management
10 Selected Resources 10 Sources for Medical Reporting •MedicalJournals •MedicalConferences10 Medical Literature Databases 10 Clinical Trial Databases 10 Government Agencies and Resources 11 Professional Medical Organizations11 Patient and Disease-Related Organizations 11 Peer-Reviewed Journals
12 Commonly Used Terms 12 Statistical Terms12 Clinical Trial Terms
13 Cushing’s disease Glossary
14 References
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Cushing’s disease: A Rare Endocrine Disorder
As we begin our overview of Cushing’s disease – which is a rare endocrine disorder – it is important to provide a brief summary
of the endocrine system4. The endocrine system includes eight major glands through-out the body that produce hormones, which travel through the bloodstream to tissues or organs, affecting body processes from head to toe, such as growth and development, metabolism, sexual function, reproduction and mood. The endocrine system plays a critical role in many bodily functions and regulation of these processes contributes to a person’s overall health5.
Endocrine disorders occur when hormone levels are imbalanced. Hormone levels that are too high or too low may be caused by an endocrine disorder. An endocrine disorder may also occur if the body does not respond to hormones the way it is supposed to5.
There are many different endocrine disorders that impact various parts of the body5. Diabetes, the most common endo-crine disorder, was estimated to affect nearly 366 million people aged 20-79 worldwide in 2011 and is associated with long-term complications that affect almost every part of the body6,7. Cushing’s disease, a less well-known disorder of the endocrine system affects a much smaller portion of the global population but can also have endur-ing effects on the body2,8.
Cushing’s disease is caused by a tumor on the pituitary gland, an endo-crine gland positioned at the base of the brain8. Because this disease affects only a small portion of the global population and presents with a constellation of symptoms easily mistaken for other diseases when looked at individually and not taken as a whole, it can be difficult to recognize and often takes years for patients to receive a correct diagnosis9,10.
Hormone levels that are too high or too low may be caused by an endocrine disorder.
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What is Cushing’s disease?
To explain Cushing’s disease, we first have to explain Cushing’s syndrome. Cushing’s syndrome is an endocrine disorder caused by excessive cortisol (hypercortisolism), a vital hormone that regulates metabolism, maintains cardiovascular function and helps the body respond to stress5. Many people have Cushing’s syndrome because they are regularly exposed to medicine(s) that con-
tinually add too much cortisol to the body (referred to as an exogenous – outside the body – cause)11. Others have Cushing’s syn-drome due to an internal trigger that causes the adrenal glands to overproduce cortisol – (referred to as an endogenous – inside the body – cause)12.
Cushing’s disease is the most common form of endogenous Cushing’s syndrome, accounting for about 70% of all cases9,11. It is caused when excessive cortisol pro-duction is triggered by a non-cancerous adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma (tumor)8.
This rare and potentially debilitating endocrine disorder affects approximately one to two people per million per year with a current estimated prevalence of 39.1 cases per million2,14. Cushing’s disease most commonly affects adults from 20 to
50 years old and affects women as much as three times more often than men4,11.
To date, no known causes or risk factors have been identified for development of the non-cancerous tumors in the pituitary gland that cause Cushing’s disease11.
Cushing’s disease is a debilitat-ing endocrine disorder caused by excess cortisol in the body due to the presence of a non-cancerous pituitary tumor3,8.
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Mechanism of disease
In someone not affected by Cushing’s disease, the adrenal gland secretes the hor-mone cortisol, commonly known to prompt the “fight or flight” reaction, in response to stimulation by ACTH, which is produced by the pituitary gland15,16. ACTH is secreted in response to two other hormones, cor-ticotropin releasing hormone (CRH) and vasopressin, both of which are secreted from the hypothalamus (a part of the fore-brain). This mechanism is controlled by a negative feedback loop, with cortisol driving the cycle by influencing both CRH and vaso-pressin in the hypothalamus, and ACTH in the pituitary16.
In healthy individuals, cortisol is secreted in a circadian rhythm. Levels are highest in the morning (7:00-9:00 AM) and gradually decline throughout the day, beginning to rise again at approximately 3:00 AM.
The presence of ACTH-secreting pituitary tumors results in the loss of the negative feedback of cortisol to both the hypothala-mus and pituitary. This finally results in continuouscortisol secretion by the adrenal gland and subsequent loss of circadian rhythm12,18. This condition is clinically referred to as Cushing’s disease3.
The presence of ACTH-secreting pituitary tumors results in the loss of the negative feedback of cortisol to both the hypothalamus and pituitary.
The hypothalamus sends CRH to the pituitary, which responds by secreting ACTH. ACTH then causes the adrenals to release cortisol into the bloodstream4,16,17.
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Clinical manifestations
The clinical manifestations of Cushing’s disease caused by hypercortisolism are broad and diverse but can be grouped into three main categories that include, but are not limited to:
Physical• Weight gain3
• Central obesity (abdomen that sticks out with thin arms and legs)4
•Moon face (round, red and full)9
• Purple striae (stretch marks) on the abdomen, thighs and breasts4
• Buffalo hump (collection of fat on the back of the neck)4
•Acne or skin infections9
•Thin skin/bruising9
• Hirsutism (excessive and unusual hair growth in females)4
•Muscle weakness3
•Headache9
•Osteoporosis9
Hormonal/Psychiatric •Depression, anxiety4
•Mood swings, irritability4
• Impotence4
• Irregular or absent menstruation4
Metabolic/Cardiovascular •Cardiovascular disease19
•Severe fatigue3
•Metabolic disturbance4 • Increased thirst and urination4
Additional clinical manifestations include backaches, swelling, appetite changes, memory problems, sleeping problems, repeated infections, hair loss and slow wound healing. When viewed individu-ally, many of the signs and symptoms of Cushing’s disease can be caused by more common health conditions, so it is impor-tant for patients to accurately convey the entire constellation of symptoms they are experiencing to a healthcare professional12.
Complications
There are many serious health complica-tions associated with Cushing’s disease, including: osteoporosis and subsequently fractures, diabetes, high blood pressure (hypertension), hyperglycemia, cardiovascu-lar disease, lipid disorders, infections, high cholesterol, kidney stones and blood clotting disorders9,16,20. Some of these complications can lead to heart problems such as excess blood clotting and high cholesterol and triglycerides20. Cushing’s disease may also reduce thyroid function (hypothyroidism) and cause infertility8,20.
Many of the signs and symptoms of Cushing’s disease can be caused by more common health conditions…
High blood pressure(called hypertension)
Impaired glucosemetabolism/diabetes
Obesity
Infections
Heart disease
High cholesteroland triglycerides(called hyperlipidemia)
Stroke
Excess clotting of the blood(called hypercoagulability)
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Diagnosing cushing’s disease
Diagnosing Cushing’s disease is challenging for several reasons. The most difficult step is recognizing Cushing’s syndrome, which must be done first. Once Cushing’s syn-drome has been identified, doctors can run a number of tests to determine the cause of excess cortisol, which will determine if the patient’s Cushing’s syndrome is actually Cushing’s disease12.
As noted earlier, many of the signs and symptoms of excess cortisol are indistin-guishable from other health conditions when looked at individually. Because of this, healthcare professionals may delay testing for this rare disease in order to eliminate more common conditions such as depression or other psychiatric disorders, alcoholism, weight problems caused by improper diet and/or exercise, diabetes or polycystic ovarian syndrome12. Additionally, clinical manifestations of the disease do not present the same way in all people affected – people may have all or some of the symptoms at any given time9.
As a result, the process for diagnosing Cushing’s disease is often lengthy. The time to diagnosis for a patient is on average six
years from the time they notice symptoms. To accurately confirm a suspected diagnosis of Cushing’s disease, there are a variety of tests a doctor will employ10.
Diagnosis generally happens in three phases, with patients often visiting several medical specialists.
Phase 1: The first step to diagnose Cushing’s syndrome is for a patient to pro-vide the doctor with a complete medical history, including any known conditions and current medications12. Many medicines used
for allergies, respiratory problems and skin problems contain glucocorticoid medicines, which may cause similar signs and symptoms associated with exogenous Cushing’s syndrome11,20.
After evaluating this information, doctors may test for hypercortisolism if any of the following characteristics and/or symptoms are present:•Moon face9
•Purple striae4
•Easy bruising9
•Central obesity4
•Diabetes4
• Adrenal tumor found during an ultrasound or similar procedure12
Test for Cushing’s disease20
ACTH MeasurementPha
se 3
Imaging TestsCorticotropin-releasing hormone
(CRH) stimulation test
Patients Medical History12,20
Known ConditionsPha
se 1
Current medications
Key signs/symptoms: Moon face, purple striae, easy bruising,
central obesity, diabetes, hirutism, adrenal tumor
Pha
se 2 Test for Cushing’s Syndrome4,12
Urinary-free cortisol (UFC) test
Late-night salivary cortisol test
Late-night plasma cortisol test
Dexamethasone suppression test (DST) (Overnight or 48-hour)
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Phase 2: To confirm a diagnosis of Cushing’s syndrome, a doctor can employ several types of tests to measure the level of cortisol in the body. These tests should only be done when exogenous hypercortisolism is ruled out12.
Specifically, there are four tests that are used to identify Cushing’s syndrome. These tests measure the amount of cortisol in samples of urine, blood, or saliva to determine how much cortisol is circulating in the body. If the tests show that the level of cortisol is too high, a diagnosis of Cushing’s syndrome can be confirmed12.
Tests for Cushing’s syndrome
Urinary-free cortisol (UFC) test
What it measures: Cortisol in urine20
Why it’s used: Almost all people with Cushing’s syndrome have high urine corti-sol levels. This test only measures the type of cortisol that causes Cushing’s syndrome, called, “circulating, free cortisol”12
How it’s done: Urine samples are collected at every opportunity throughout a 24-hour period and provided to a lab for testing12
Late-night salivary cortisol test
What it measures: Cortisol in saliva20
Why it’s used: Cushing’s syndrome will cause elevated levels of cortisol in saliva at night, when levels are usually lowest12
How it’s done: A saliva sample is obtained between 11:00 PM and 12:00 AM on two different nights and provided to a lab for testing18
The timing of the collection should be adjusted to the time of sleep-ing if a person’s bedtime is usually long after midnight33
Late-night plasma cortisol test
What it measures: Cortisol in the blood20
Why it’s used: Cushing’s syndrome will cause elevated levels of cortisol in the blood at night, when levels are usually lowest20
How it’s done: A blood sample is obtained at night while the patient is sleeping in a hospital and provided to a lab for testing20
Dexamethasone suppression test (DST)
What it measures: Cortisol in the blood20
Why it’s used: Normally, low doses of the corticosteroid dexamethasone will reduce cortisol levels but in a person with Cushing’s syndrome, these doses will not have an effect11
How it’s done: There are two DST test options; overnight and 48-hour. Once a sample is collected, a lab test is done to determine if cortisol levels were reduced11
Overnight DST (short test): A 1-mg dose of dexamethasone is taken between 11:00 PM and 12:00 AM. The next morning a blood sample is taken between 8:00 AM and 9:00 AM11,20
48-hour DST (long test): A 0.5-mg dose of dexamethasone is taken every 6 hours for 48 hours. Six hours following the last dose, a blood sample is taken at the doctor’s office11,20
To confirm a diagnosis of Cushing’s syndrome, a doctor can employ several types of tests to measure the level of cortisol in the body.
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Phase 3: If a diagnosis of Cushing’s syn-drome is confirmed, additional tests will be conducted to determine why the patient’s body is producing too much cortisol and confirm if it’s due to a pituitary tumor (Cushing’s disease) or a different form of Cushing’s syndrome11.
Disease management guidelines
The first line and most common manage-ment approach for Cushing’s disease is surgical removal of the tumor, known as selective adenomectomy, usually performed via transsphenoidal route4. Using a micro-scope and small instruments, a surgeon approaches the pituitary gland through
a nostril or an opening made below the upper lip. The reported initial success rate for pituitary surgery for Cushing’s disease varies between 60% and 86%, however up to 25% of patients suffer from recurrence even after apparent remission34.
If surgery is not appropriate or effec-tive, other management options include radiation to the pituitary gland, stereotactic radiosurgery or gamma knife radiation, and in extreme cases full removal of the adrenal glands, called an adrenalectomy4. Patients undergoing adrenalectomies will require lifelong mineralocorticoid and glucocorticoid replacement35. For radiation treatment alone, it may take several months or years before patients experience improvement in their symptoms; therefore, cortisol-inhibiting drugs can be required4. While there is no cure, treatments are available that may help3.
Tests for Cushing’s disease
ACTH Measurement
What it measures: ACTH in the blood20
Why it’s used: To determine tumor location. Normal to high ACTH levels may be indicative of a tumor in the pitu-itary gland, and would confirm a diagnosis of Cushing’s disease9,20
How it’s done: A blood sample is collected and provided to a lab for testing20
Imaging Tests
What it measures: Location/presence of a tumor20
How it’s done: If ACTH levels are high, a magnetic resonance imaging (MRI) or computerized tomography (CT) test will be conducted to confirm the location and presence of a tumor in the pituitary gland20 However sometimes the tumor will be too small to be detected by imaging4
Corticotropin-releasing hormone (CRH) stimulation test
What it measures: How CRH changes ACTH and cortisol levels20
Why it’s used: To confirm the presence of a pituitary tumor if ACTH measurement or imaging tests are inconclusive4
How it’s done: Blood tests are used to measure ACTH and cortisol levels, then a CRH intravenous injection is given, after which blood tests are repeated several times to recheck ACTH levels. If these levels have increased, this helps to confirm the presence of a pituitary tumor and therefore a diagnosis of Cushing’s disease20
Inferior Petrosal Sinus Sampling
What it measures: ACTH in the blood from the inferior petrosal sinuses21
Why it’s used: To confirm the presence of a pituitary tumor if ACTH measurement or imaging tests are inconclusive21
How it’s done: Tests are used to measure ACTH levels in blood taken from the inferior petrosal sinus, which collects venous drainage from the pituitary gland21
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Selected Resources
This section provides an overview on where
to obtain credible information regarding
Cushing’s disease.
Sources for medical reporting
Medical JournalsArticles published in peer-reviewed medical
journals provide the primary source for
credible medical news. In peer review jour-
nals, independent experts screen submitted
scientific papers to ensure that they meet
the accepted standards of their discipline.
Medical journals such as The Lancet,
the British Medical Journal, The New England
Journal of Medicine (NEJM) and the Journal
of the American Medical Association (JAMA)
encapsulate many different aspects of
medicine and appeal to a wide variety of
healthcare professionals. Specialty medi-
cal journals that focus on endocrinology
include European Journal of Endocrinology,
Clinical Endocrinology, Journal of Clinical
Endocrinology & Metabolism, Endocrine
Reviews, Neuroendocrinology and Endocrine
Pathology.
Medical ConferencesResearchers share preliminary and updated
results of their work at medical confer-
ences23. Typical formats for presentation of
information at medical conferences include:
• Presentation abstract: a synopsis of the
study submitted for presentation at a
medical conference. The sponsoring orga-
nization will publish the accepted abstracts
prior to or during the conference, in an
abstract book and often online, and may
make them available to reporters23.
• Oral presentation: research that has been
selected for presentation by means of a
live lecture during the conference (usually
with slides)24
• Poster presentation: the study is sum-
marized on a large paper poster board,
illustrating the research methods and
outcomes in text and graphics. Typically,
a poster presentation allows viewers to
discuss the study with one or more of the
researchers24.
Caution: Check with individual journals and
conference sponsors for their embargo policies.
Tip: Sign up with journals and conference
sponsors to receive email alerts of upcoming
publications and meetings.
Medical literature databases
• Thompson Reuters: http://science.thom-
sonreuters.com/mjl/
•PubMed (US): www.pubmed.gov
Clinical trial databases
• International Clinical Trials Registry
Platform (WHO): www.who.int/ictrp
• Clinical Trials (USA): www.clinicaltrials.gov/
Government agencies and resources
• European Medicines Agency (EU):
www.ema.europa.eu
• National Endocrine and Metabolic Disease
Information Service (USA): http://www.
endocrine.niddk.nih.gov/
• US Food and Drug Administration (USA):
www.fda.gov
• World Health Organization: www.who.int
Special focus on Cushing’s disease | 11
Professional medical organizations
• Addison & Cushing International
Federation: www.nvacp.nl
• American Association of Clinical
Endocrinologists: https://www.aace.com/
• European Neuroendocrine Association:
http://www.eneassoc.org/
• European Organisation for Rare Diseases:
http://www.eurordis.org/
• European Register on Cushing’s Syndrome:
http://www.lohmann-birkner.de/ercusyn/
• European Society for Immunodeficiencies:
http://www.esid.org
• European Society of Endocrinology:
http://www.euro-endo.org/
• Instituto de Investigatión de Enfermedades
Raras: http://iier.isciii.es/er/
• The Endocrine Society:
http://www.endo-society.org/
Patient and disease-related organizations
• Canadian Organization for Rare Disorders
(CA): http://raredisorders.ca/
• Cushing’s Help and Support (USA):
http://www.cushings-help.com/
• Cushing’s Support and Research
Foundation (USA): http://www.csrf.net/
• Cushing’s Understanding Support & Help
Organization (USA): http://www.cush.org/
• Hormone Health Network (USA):
http://www.hormone.org/
• Magic Foundation (USA):
http://www.magicfoundation.org
• National Adrenal Diseases Foundation
(USA): http://www.nadf.us/
• National Organization for Rare Disorders
(USA): http://www.rarediseases.org/
• Netzwerk Hypophysen–und
Nebennierenerkrankungen e.V. (German
Pituitary and Adrenal Network) (DE):
www.glandula-online.de
• Pituitary Network Association (USA):
http://www.pituitary.org
• The Pituitary Foundation (UK): www.pitu-
itary.org.uk
Peer-reviewed medical journals
Novartis does not endorse and is not
responsible for the content of any of the
listed resources. Please note that this is not
an exhaustive list of resources.
American Journal of Physiology:
Endocrinology and Metabolism:
Publishes original, mechanistic studies on
the physiology of endocrine and metabolic
systems. (http://ajpendo.physiology.org/)
Clinical Endocrinology: Publishes papers
and reviews, which focus on the clinical
aspects of endocrinology, including the
clinical application of molecular endocrinol-
ogy. (http://www.wiley.com/bw/journal.
asp?ref=0300-0664)
Endocrine Practice: Official journal of
the American College of Endocrinology
and the American Association of Clinical
Endocrinologists. Published to enhance
the healthcare of patients with endocrine
diseases through continuing education
of practicing endocrinologists. (http://aace.
metapress.com/home/main.mpx)
Endocrine Reviews: Publishes comprehen-
sive, authoritative, and timely review articles
balancing both experimental and clinical
endocrinology themes and crystallizing
the most significant clinical experience
and current research in endocrinology and
related areas. (http://edrv.endojournals.org/)
Endocrinology: Publishes biomedical
research ranging from subcellular mecha-
nisms to whole animal physiology. Topics
include bone and mineral, growth factors;
reproductive/steroids, neuroendocrinology/
signal transduction, thyroid, and physiology.
(http://endo.endojournals.org/)
European Journal of Endocrinology:
Publishes original clinical and translational
research papers, reviews and commentaries
in pediatric and adult endocrinology.
(http://www.eje-online.org/)
Growth Hormone & IGF Research:
Publishes research on the regulation of
growth and metabolism in humans, ani-
mals, tissues and cells. (www.sciencedirect.
com/science/journal/aip/10966374)
Journal of Clinical Endocrinology &
Metabolism: Publishes endocrine clinical
research and clinical practice reviews to
provide in-depth coverage of new develop-
ments of the diagnosis and treatment of
endocrine and metabolic disorders. Regular
features of special interest include clini-
cal trials, clinical reviews, clinical practice
guidelines, case seminars and controver-
sies in clinical endocrinology, as well as
original reports of endocrine and metabolic
research. (http://jcem.endojournals.org/)
Molecular and Cellular Endocrinology:
Publishes full-length original research papers,
invited reviews and book reviews related
to biochemical and molecular aspects of
endocrine research and cell regulation.
(http://www.elsevier.com/locate/mce)
The Journal of the American Medical
Association: Publishes articles on a diverse
range of medical topics. (www.jama.ama-
assn.org)
The Lancet: Publishes medical news, origi-
nal research, and reviews on all aspects of
clinical medicine and public health. (http://
www.thelancet.com/)
The Lancet Diabetes & Endocrinology:
Focuses upon timely news, views, research
and reviews in diabetes, endocrinology
and metabolism. The new journal, which is
launching August 2013, will cover a wide
breadth and diversity of topics of interest
to clinicians, specialists and researchers,
including adrenal disorders, neuroendo-
crinology, pediatric endocrinology and
pituitary disorders. (www.thelancet.com/
diabetes-endocrinology)
The New England Journal of Medicine:
Publishes new medical research findings,
review articles, and editorial opinion on
a wide variety of topics of importance to
biomedical science and clinical practice.
Material is published with an emphasis
on internal medicine and specialty areas
including allergy/immunology, cardiology,
endocrinology, gastroenterology, hematol-
ogy, kidney disease, oncology, pulmonary
disease, rheumatology, HIV, and infectious
diseases. (www.nejm.org)
12 | Journalist Handbook
Commonly used terms
The following terms frequently appear
in journal articles and conference
presentations:
Statistical terms
Confidence interval (CI): describes how pre-
cise a particular result is and suggests how
reliable it may be beyond the specific study.
In a clinical trial, the CI indicates the limits
within which the difference between two
treatments is likely to lie. CIs are reported
as a range of values above and below the
study finding; the more narrow the range,
the more precise the result. For example, a
disease that is present in 25% of a popula-
tion with a CI of plus or minus 5% means
that the actual value can lie anywhere
between 20% and 30%25.
Mean: the sum of a set of numbers divided
by how many numbers are in the set. In a
clinical study, there will always be patients
who will fall above or below the mean26.
Median: the middle value in a set of
measurements26.
P-value (probability value): a measure of
probability that a difference between groups
during an experiment happened by chance.
For example, a p-value of .01 (p = 0.01)
means there is a 1 in 100 (1%) chance
the result occurred by chance. In a clinical
trial, the lower the p-value, the more likely
it is that the difference between groups was
caused by the treatment being studied25.
Statistical significance: results that are
statistically significant are unlikely to be
due to chance. A p-value less than 0.05
(meaning that the result would have arisen
by chance on less than one occasion in 20)
is generally considered statistically signifi-
cant. In clinical trials, the level of statistical
significance depends on the number of
participants studied and the observations
made, as well as the magnitude of differ-
ences observed27,28.
Clinical trial terms
Blinded trial: a study in which the patients
(single-blinded) or the patients and their
doctors (double-blinded) do not know
which drug or treatment is being given;
the opposite of an open label study29.
Clinical trial: a research study that tests
the effectiveness and safety of medications,
devices, and/or treatment paradigms in
humans27.
• Phase I clinical trial: initial studies con-
ducted with a small number of volunteers
with or without the disease (can be fewer
than 80) to assess the safety and various
dose ranges for an experimental treat-
ment28.
• Phase II clinical trial: mid-stage studies
(which occur after a Phase I trial) typically
involving a larger number of patient
volunteers to further assess safety
and effectiveness of an experimental
treatment28.
• Phase III clinical trial: large trials (which
occur after Phase II) carried out to con-
firm the effectiveness of an experimental
treatment, and identify adverse events.
Phase III trials are conducted to compare
an experimental treatment to commonly
used treatments, and collect informa-
tion to evaluate the overall risk/benefit
ratio. Phase III trials provide the basis for
applications with regulatory agencies for
authorization to market a new drug28.
• Endpoint: an overall measurable outcome
that the study is designed to evaluate.
The primary endpoint(s) measure out-
comes related to the main objective of the
study and secondary endpoints evaluate
measures for other related questions in
the study27,30.
Non-inferiority trial: a study intended to
show that the effect of a treatment is not
worse than that of an active control, by no
more than a specified range31.
Open-label trial: a study in which both the
patients and the doctors know which treat-
ment is being given; opposite of a blinded
study31.
Post-hoc analysis: an examination of data,
after a clinical trial has concluded, for
analyses that were not specified previously32.
Prospective trial: a study or clinical trial in
which participants are identified and then
followed forward in time25.
Randomized trial: a study in which the
participants are assigned by chance to
separate groups that compare different
treatments. Large, randomized, double-
blind, controlled prospective clinical trials
are considered to provide the highest qual-
ity of scientific evidence25,30.
Retrospective study: a study that compares
patients with the disease or condition under
study (cases) and a similar group of people
who do not have the disease or condition
(controls). Researchers study the medical
and lifestyle histories of the people in
each group to learn what factors may be
associated with the disease or condition.
A retrospective study is also called a
case-control study27.
Sub-analysis study: a study that examines
data from a subset of patients from a
clinical trial27.
Special focus on Cushing’s disease | 13
Glossary
Key terms for use in interpreting information
and developing stories on Cushing’s disease.
Adenoma: a non-cancerous tumor of a glan-
dular structure or of glandular origin23.
Adenomectomy: is the surgical removal of
the tumor by a surgeon who approaches the
pituitary gland through a nostril or an opening
made below the upper lip. This process is the
first line and most common disease manage-
ment approach for Cushing’s disease4.
Adrenalectomy: is the surgical removal of
the adrenal glands, which may occur if sur-
gery or other disease management options
are not appropriate or effective. It is also
known as a bilateral adrenalectomy4.
Adrenal glands: either of a pair of com-
plex endocrine organs near the anterior
medial border of the kidney consisting of
a mesodermal cortex that produces gluco-
corticoid, mineralocorticoid and androgenic
hormones, and an ectodermal medulla that
produces epinephrine and norepinephrine23.
Adrenocorticotropic hormone (ACTH): a
protein hormone of the anterior lobe of
the pituitary gland that stimulates the
adrenal cortex23.
Cardiovascular: of, relating to, or involving
the heart and blood vessels23.
Cholesterol: a steroid alcohol present in
animal cells and body fluids that regu-
lates membrane fluidity, functions as a
precursor molecule in various metabolic
pathways; as a constituent of LDL, it may
cause arteriosclerosis23.
Corticotropin-releasing hormone (CRH): a
substance secreted by the median eminence
of the hypothalamus that regulates the
release of ACTH by the anterior lobe of the
pituitary gland23.
Cortisol: a glucocorticoid produced by the
adrenal cortex upon stimulation by ACTH
that mediates various metabolic processes
(such as gluconeogenesis), has anti-inflam-
matory and immunosuppressive properties,
and whose levels in the blood may become
elevated in response to physical or psycho-
logical stress23.
CT (CAT) scan: a sectional view of the body
constructed by computed tomography23.
Cushing’s disease: Cushing’s syndrome
caused by excessive cortisol production trig-
gered by a non-cancerous ACTH-secreting
pituitary tumor23.
Cushing syndrome: is an endocrine disorder
caused by excessive cortisol, a vital hor-
mone that regulates metabolism, maintains
cardiovascular function and helps the body
respond to stress5.
Dexamethasone: a synthetic glucocorti-
coid also used in the form of an acetate or
sodium phosphate, especially as an anti-
inflammatory and antiallergic agent23.
Diabetes: A chronic, progressive disease in
which the body does not produce or prop-
erly use insulin5.
Ectopic: occurring in an abnormal position23.
Endocrinologist: a medical professional
who studies the glands and hormones of the
body and their related disorders23.
Endogenous: caused by factors within
the body or mind or arising from internal
structural or functional causes. Cushing’s
disease is an endogenous disease caused
by a tumor on the pituitary gland23.
Exogenous: caused by factors (such as food
or a traumatic factor) or an agent (such as
a disease-producing organism) from outside
the organism or system23.
Glucocorticoid: any of a group of corticoste-
roids (such as cortisol or dexamethasone)
that are involved in carbohydrate, protein
and fat metabolism; that tend to increase
liver glycogen and blood sugar by increasing
gluconeogenesis; and that are used widely
in medicine (such as in the alleviation of the
symptoms of rheumatoid arthritis)23.
High blood pressure: means that the body’s
blood flow is causing too much pressure
against artery walls23.
Hirsutism: excessive growth of facial/body
hair of normal or abnormal distribution23.
Hormone: product of living cells that circu-
lates in body fluids (such as blood) or sap
and produces a specific, often stimulatory,
effect on the activity of cells usually remote
from a hormone’s point of origin23.
Hypercortisolism: a state of overproduction of
cortisol in the body, often a result of tumor(s)
in the adrenal or pituitary glands23.
Hypothyroidism: deficient activity of the
thyroid gland; also, a resultant bodily con-
dition characterized by lowered metabolic
rate and general loss of vigor 23.
Infertility: not fertile; incapable of or
unsuccessful in achieving pregnancy over a
considerable period of time (such as a year)
in spite of determined attempts by hetero-
sexual intercourse without contraception23.
Magnetic resonance imaging (MRI): a non-
invasive diagnostic technique that produces
computerized images of internal body tis-
sues and is based on nuclear magnetic
resonance of atoms within the body induced
by the application of radio waves23.
Malignant: tending to produce death or
deterioration; especially tending to infiltrate,
metastasize, and terminate fatally23.
Metabolic disturbance: a combination
of problems that includes excess weight
around the waist, high blood pressure,
abnormal levels of cholesterol and triglycer-
ides in the blood and insulin resistance3.
Obesity: a high body mass index (that is,
the amount of fat in the body). Central obe-
sity is when high BMI occurs in the middle
part of the body (around the abdominal
area), while arms and legs remain thin20.
Osteoporosis: a condition that especially
affects older women and is characterized
by decrease in bone mass with decreased
density and enlargement of bone spaces,
producing porosity and brittleness23.
Pituitary gland: a small, vascular endocrine
organ that is attached to the brainstem.
The pituitary gland has several parts associ-
ated with various hormones that directly or
indirectly affect most basic bodily functions
and include substances that exert a control-
ling and regulating influence on other
endocrine organs by controlling growth and
development or modifying the contraction of
smooth muscle, renal function and repro-
duction26.
Steroid hormone: any of numerous hor-
mones (such as estrogen, testosterone,
cortisone and aldosterone) having the
characteristic ring structure of steroids and
formed in the body from cholesterol 26.
Triglycerides: any of a group of fats that
are formed from one molecule of glycerol
and three molecules of one or more fatty
acids; they are widespread in fat tissue26.
Tumor: an abnormal non-cancerous or
malignant new growth of tissue that pos-
sesses no physiologic function and arises
from uncontrolled usually rapid cellular
proliferation26.
Urinary-free cortisol: these measurements
are used in the diagnosis of hypercorti-
solism caused by Cushing’s syndrome or
Cushing’s disease4.
14 | Journalist Handbook
References
1. Consumers Trek Online to Take Charge
of Their Health. Adweek. 5 Oct. 2010.
Available at http://www.adweek.
com/news/advertising-branding/
consumers-trek-online-take-charge-their-
health-107855. Accessed January 2012.
2. Lindholm, J. et. al. Incidence and late
prognosis of cushing’s syndrome:a
population-based study. J Clin Endocrinol
Metab. 2001 Jan;86(1):117-23.
3. Pedroncelli, Alberto. Medical Treatment of
Cushing’s Disease: Somatostatin Analogues
and Pasireotide. Neuroendocrinology.
2010;92(Suppl. 1): 120-124.
4. National Institutes of Health. Cushing’s
syndrome. Bethesda, MD: National
Institutes of Health; 2008.
5. National Institutes of Health. Endocrine
Diseases. Available at http://www.nlm.
nih.gov/medlineplus/endocrinediseases.
html. Accessed January 2012.
6. International Diabetes Atlas. Fifth
Edition. Available at http://www.idf.org/
diabetesatlas/5e/the-global-burden.
Accessed January 2012.
7. International Diabetes Federation. About
Diabetes. Available at http://www.idf.org/
about-diabetes. Accessed January 2012.
8. PubMed Health. Cushing’s Disease. 23
November 2009. Available at http://
www.ncbi.nlm.nih.gov/pubmedhealth/
PMH0001388/. Accessed January 2012.
9. Nieman LK, Ilias I. Evaluation and treat-
ment of Cushing’s syndrome. Am J
Med. 2005;118:1340-1346.
10. Psaras, M. et. al. Demographic Factors
and the Presence of Comorbidities do
not Promote Early Detection of Cushing’s
Disease and Acromegaly. Exp Clin
Endocrinol Diabetes. 2011;119(1): 21-25.
11. Newell-Price J, Bertagna X, Grossman
AB, Nieman LK. Cushing’s syndrome.
Lancet. 2006;367:1605-1617.
12. Nieman LK, Biller BMK, Findling JW,
et al. The diagnosis of Cushing’s syn-
drome: an Endocrine Society Clinical
Practice Guideline. J Clin Endocrinol
Metab. 2008;93:1526-1540.
13. De Bruin, C. et. al. Coexpression of
Dopamine and Somatostatin Receptor
Subtypes in Corticotroph Adenomas.
J Clin Endocrinol Metab. 2009:
94(4):1118-1124.
14. Extabe, J., Vazquez, J.A., Morbidity
and mortality in Cushing’s disease:
an epidemiological approach. Clinical
Endocrinology 1994;40;479-484.
15. A.D.A.M. Medline Plus Encyclopedia.
Available at http://www.nlm.nih.
gov/medlineplus/encyclopedia.html.
Accessed January 2012.
16. Stratakis, Constantine A., Chrousos,
George P. Neuroendocrinology and
Pathology of the Stress System. Annals
of the New York Academy of Sciences.
2005;771;1-18.
17. Smooke Praw, Stephanie, Heaney, Anthony
P. Medical Treatment of Cushing’s Disease:
Overview and Recent Findings. Int J Gen
Med. 2009; 2: 209-217.
18. Newell-Price, John et. al. The Diagnosis
and Differential Diagnosis of Cushing’s
Syndrome and Pseudo-Cushing’s States.
Endocrine Reviews. 1998; 19(5):647-672.
19. Colao, Annamaria et. al. Persistence of
Increased Cardiovascular Risk in Patients
with Cushing’s Disease after Five Years
of Successful Cure. J Clin Endocrinol
Metab. 1999; 84: 2664-2672.
20. Arnaldi G, Angeli A, Atkinson AB, et
al. Diagnosis and complications of
Cushing’s syndrome: a consensus
statement. J Clin Endocrinol Metab.
2003;88:5593-5602.
21. Javorsky, Bradley R., Findling, James
W. Inferior Petrosal Sampling for
the Differential Diagnosis of ACTH-
Dependent Cushing’s Syndrome.
Contemporary Endocrinology. 2011;
105-119.
22. Patil, Chirag G. et. al. Late Recurrences of
Cushing’s Disease after Initial Successful
Transsphenoidal Surgery. J Clin
Endocrinol Metab. 2008:93(2):358-362.
23. Kelly, J. A. Scientific Meeting Abstracts:
Significance, Access, and Trends. Bull
Medical Library Association. 1998
January: 86(1):68-76.
24. Descriptions of Session Types.
ASCO 2011 Annual Meeting.
Available at http://chicago2011.
asco.org/AbouttheMeeting/
DescriptionsofSessionTypes.aspx.
Accessed March 2012.
25. Health Statistics Glossary. NICHSR.
Available at http://www.nlm.nih.
gov/nichsr/hta101/ta101014.html.
Accessed March 2012. Merriam-Webster
Dictionary. Available at
http://www.merriam-webster.com.
Accessed January 2012.
26. Merriam-Webster Dictionary. Available
at http://www.merriam-webster.com.
Accessed January 2012.
27. Clinical Trials Portal Glossary. IFPMA.
Available at http://clinicaltrials.ifpma.
org/clinicaltrials/en/tips/glossary/
index.htm. Accessed March 2012.
28. Understanding Clinical Trials. National
Institutes of Health. Available at http://
clinicaltrials.gov/ct2/info/understand.
Accessed March 2012.
29. Dictionary of Cancer Terms. National
Cancer Institute. Available at http://
www.cancer.gov/dictionary/. Accessed
March 2012.
30. Glossary of Clinical Trials Terms.
National Institutes of Health. Available
at http://www.clinicaltrials.gov/ct2/
info/glossary. Accessed March 2012.
31. Snapinn, Steven M. Noninferiority Trials.
Curr Control Trials Cardiovasc Med.
2000: 1:19-21.
32. Rui Wang, M.S. Statistics in Medicine
– Reporting of Subgroup Analyses in
Clinical Trials. New England Journal of
Medicine. 2008: 358;1199-1200.
33. The Endocrine Society and The
Hormone Foundation. Patient Guide to
the Diagnosis of Cushing’s Disease. May
2008. Available at http://www.hormone.
org/Resources/Patient_Guides/upload/
mgmt-cushings-syndrome-070609.pdf.
Accessed October 2012.
34. Alwani, R et. al. Biochemical Predictors
of Outcome of Pituitary Surgery for
Cushing’s Disease. Neuroendocrinology
2010;91:169–178.
35. Liu, J.et. al Treatment Options for
Cushing Disease After Unsuccessful
Transsphenoidal Surgery. Neurosurgical
Focus. 2007:23(3):E8.
Special focus on Cushing’s disease | 15
*Note: This handbook is intended for use by ex-US journalists to assist
with reporting on Cushing’s disease.