Keywords
Adrenal crisis - adrenal insufficiency - glucocorticoid replacement therapy - hydrocortisone
- prednisolone
Introduction
Adrenal insufficiency (AI) comprises a group of rare diseases, including primary AI,
secondary AI, and congenital adrenal hyperplasia.[[1]],[[2]] Glucocorticoid (GC) replacement is the cornerstone therapy in the management of
AI, intended to prevent life-threatening complications related to AI and improve the
well-being and quality of life in patients with AI.
Adrenal crisis is a grave complication of AI, occurring even in subjects on regular
GC replacement. The incidence of adrenal crisis is estimated at 5–10 per 100 patient-years,
with a mortality of 0.5 per 100 patient-years.[[3]] The primary trigger identified for the development of adrenal crisis is a delay
in increased GC dose in cases of infection.[[4]],[[5]] Patient education is essential to gain the skills needed to prevent acute impairment
of their AI disorder.[[6]],[[7]]
Furthermore, previous findings suggest that the treating physicians are the patients'
primary source of information regarding AI (89%). Professional healthcare workers
are essential for sharing knowledge and advice regarding the various aspects of managing
the disease.[[8]] However, a debate exists on whether physicians' knowledge regarding AI is sufficient,
in part due to the rareness of this endocrine disorder.[[9]],[[10]],[[11]],[[12]] Significant barriers to diagnosis and management of AI were identified in some
developing regions of the world with indicators of tiered healthcare that may expose
deficiencies in management.[[13]],[[14]] Therefore, we aimed to examine AI management's current knowledge and perceptions
among a sample of physicians from the Middle East and North Africa (MENA) region and
in various specialties. Our long-term goal is to identify critical deficiencies in
AI management by physicians in our region for better guidance of future educational
efforts in the realm of AI.
Materials and Methods
We aimed to determine the level of practical and clinically relevant knowledge of
physicians in the MENA region. A convenience sample of physicians from a wide range
of professional grades and experiences was surveyed. There is no single MEA regional
endocrine society with a unified membership list that can define a study population.
Therefore, the target population was identified from a list of electronic mails pooled
from continuous professional development delegates, speakers, authors, or members
of several medical groups in various parts of the MEA region. Consequently, six questions
were added to the survey to help define the profiles of the respondents and their
practices.[[15]],[[16]],[[17]],[[18]],[[19]],[[20]] Participants were asked to complete an electronic questionnaire sent via a commercial
survey software (Survey Monkey, USA) with various possible answers on the subject
of AI. The questions are analogous to a previously published study with similar objectives.[[9]] In brief, questions covered the daily cortisol production rate in healthy individuals,
various GC preparations used to treat AI, half-life time of hydrocortisone (HC), clinical
signs of GC under-and over-replacement, and potential therapeutic approaches with
AI [[Table 1]]. Data are presented in descriptive statistics.
Table 1: The survey questions and potential multiple-choice options
Results
Respondents' profiles
A total of 96 physicians from various medical disciplines in the MENA regions completed
the questionnaire [[Table 2]]. The majority (62.8%) were male. Half of the participants (50.0%) were consultant/attending
physicians, while 36.5% were senior specialists, and the remainder (13.5%) were junior
residents or interns. The predominantly represented single-specialty was adult endocrinology
(44.2%). This was followed by general internal medicine with a particular interest
in endocrinology (15.8%) and general internal medicine alone (11.6%). The majority
reported working in clinical, public health services (67.7%), followed by the clinical,
private sector services (20.8%). Nearly half of the respondents (49.0%) have treated
ten or fewer patients with AI. Only 17.7% reported treating over 50 AI patients thus
far.
Table 2: Demographic and professional profiles of participants, and workload and style of
communication for management of adrenal insufficiency
Glucocorticoid physiology and pharmacology
Respondents' knowledge of physiology and pharmacology of GC hormones were assessed
via two questions [[Table 3]]. Assessment of knowledge regarding normal daily rates of cortisol production in
healthy individuals revealed split responses. While the dominant answer given was
“10–20 mg” in 39.6% of respondents, near-equal responses were given for “5–10 mg”
(29.2%) and “20–30 mg” (30.2%). The majority (58.8%) listed “8 h” as the half-life
of HC, while only 22.3% identified “1 h” as the correct answer.
Table 3: The adrenal survey
Patterns in clinical practices
Physicians' patterns in prescribing and monitoring the adequacy of GC replacement
therapy were assessed via five questions [[Table 1]]. Results are presented in [[Table 3]]. The majority (81.3%) identified HC preparations for use in GC replacement therapy.
This was followed by prednisone/prednisolone reported by 46.9%, longer-acting formulations
of prednisolone in 13.5%, and Dexamethasone also reported in 13.5%.
The most frequent sign reported for GC under-replacement was “nausea” (84.4%), followed
by “weight loss” (81.3%), “headaches” (44.8%), and “sleep disturbances” (36.5%). Only
8.3% of respondents identified “weight gain” as a sign of GC under-replacement. The
most frequent sign reported for GC over-replacement was “high blood pressure” (91.6%),
followed closely by “weight gain” (90.5%) and “increased blood glucose” (86.3%). Only
6.3% and 3.2% of respondents identified “weight loss” and “low blood pressure” as
symptoms of GC over-replacement, respectively.
The situations most frequently identified as necessary for adjustments of GC dosages
were “acute severe disease” (92.7%) and “fever more than 38°C” (79.2%). The most-reported
adjustment in the GC regimen needed in the presence of acute severe disease was “increase
dose by 2–5-fold” by 77.1% of respondents. 6.3% of respondents reported “GC dose reduction
by 50%,” and similarly, 6.3% reported “omission of GC for 1–2 days” in response to
necessary GC adjustments in severe illness.
Prevention of adrenal crisis
Assessments of perceptions and practices for the prevention of adrenal crisis are
summarized in [[Table 3]] and [Table 4]. The majority of respondents (80.9%) identified the need for emergency,
standby medications for patients with AI. In addition, 94.7% reported the need to
issue an emergency card, and 80.9% reported the need for relative and friends' education
regarding AI. Only 1.1% stated that no specific measures were necessary for the prevention
of adrenal-related complications.
When traveling on holiday, the majority instructed patients to pack their GC preparations
(90.5%), pack an emergency card (89.5%), and pack their emergency medications (70.5%).
Finally, most physicians (90.6%) would educate their patients on all the above via
direct, personal dialogues. Fewer physicians would utilize written information (29.2%)
or Internet resources (6.3%).
Discussion
Lifesaving GC therapy was introduced over 60 years ago, but several advances in treatment
have taken place since then. For instance, little is known about short- and long-term
treatment effects and morbidity and mortality.[[21]] Data from systematic cohort and registry studies have demonstrated potential disadvantages
of unphysiological GC replacement. Hence, new modes of replacement that aim to mimic
normal GC physiology.[[21]] Furthermore, how best whatever limited information is used clinically is not clear.
A recent, single-institution study in Germany evaluated the knowledge and competence
of a group of physicians from various specialties regarding the management of AI.[[9]] The study identified significant deficiencies and knowledge gaps concerning AI
management amongst physicians despite the institution's specialized status.[[9]] Similar results of a needs assessment exercise showed that primary care physicians
both needed and desired professional development targeting AI diagnosis and management.[[10]] The study suggested a strong need to improve physicians' education on GC replacement
treatment in AI.[[22]] This is particularly relevant to clinical practice in developing regions of the
world, where more challenges have been observed.[[13]],[[14]] The German study came from a specialized endocrine department which limits the
generalizability. In contrast, our study included both endocrinologists and nonendocrinologists,
giving a more representative sample of doctors whom AI patients may face at the time
of stress. We refrained from making any subgroup analysis due to the small sample
size. Indeed, previous studies demonstrated that 45% of patients were diagnosed only
after hospitalization due to an adrenal crisis despite prior evident signs of AI.[[23]] Furthermore, it has been demonstrated that 68% of patients with AI had an incorrect
diagnosis at first.[[24]] However, in none of the studies, information was available on the physicians' education,
knowledge on GC replacement, or medical specialty. The findings of the present study
and the two previous studies[[9]],[[10]] fill this gap in various professional groups and support the idea to provide ongoing
education to physicians on AI, a rare but essential disorder since patients rely in
large parts on the information provided by their physicians.[[19]]
Besides, special attention is needed in several special situations in clinical practice
where the possibility of AI. Adrenal suppression may occur despite following recommended
GC tapering regimens and suspicion of GC-induced AI requires careful diagnostic workup
and quick introduction of a GC replacement treatment.[[11]] HIV-associated AI is commonly seen in Africa.[[13]] Deliberate manipulation of replacement therapy while observing Ramadan fasting
in people with AI may induce a state of under replacement and possibly precipitate
an adrenal crisis. Professional guidance and continuous monitoring of the management
of AI during Ramadan fasting are needed.[[25]],[[26]]
Conclusions
The present data demonstrate a suboptimal knowledge of the practical aspects of the
management of AI. The present study confirms the observations from the German study
in a larger sample and more realistically representative participants in a setting
with a potentially higher risk. The study supports the notion that there might be
a need for additional structured education and training on AI in local, national,
and regional conferences to improve physicians' knowledge and enhance their clinical
skills and confidence on the disease and thereby foster timely and optimal treatment.
Authors' contribution
Both authors contributed to the conception of the study. SAB adopted and managed the
survey. Both authors jointly drafted and revised the manuscript and approved its final
version.
Compliance with ethical principles
The study was approved by the Institutional Renew Board of the Dheikh Khalifa Medical
City, Abu Dhabi, UAE. All participants provided an informed consent prior to accessing
the survey.
Availability of data
The raw data will be available by reasonable requests to the corresponding author.
