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Journal ListAACE Clin Case Repv.5(5); Sep-Oct 2019PMC6876956

Logo of aaceccr
AACE Clin Case Rep. 2019 Sep-Oct; 5(5): e302–e306.
Published online 2019 Jun 7. doi: 10.4158/ACCR-2019-0128
PMCID: PMC6876956
PMID: 31967058
A RARE CASE OF ACROMEGALY AND AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE:
CASE REPORT AND BRIEF REVIEW OF LITERATURE
Swayamsidha Mangaraj, MBBS, MD, DM,corresponding author Debasish Patro, MBBS, MD, Arun
Kumar Choudhury, MBBS, MD, DM, and Anoj Kumar Baliarsinha, MBBS, MD, DM
Author information Article notes Copyright and License information Disclaimer
Go to:
Abstract
Objective:
Acromegaly is a classic endocrine disorder caused by a growth hormone (GH)–secreting pituitary
adenoma in an overwhelming majority of patients. The diagnosis may be delayed by several years
due to the slow growing and insidious nature of the disease. Autosomal dominant polycystic kidney
disease (ADPKD) is an inherited disorder characterized by multiple renal cysts and various other
systemic manifestations. The purpose of this article is to report a rare case of acromegaly with
coexistent ADPKD.
Methods:
We report a case of 42-year-old female with acromegaly and ADPKD along with a brief review of
literature.
Results:
The patient was referred to us for evaluation of progressive acral enlargement and coarsening of
facial features. Endocrine evaluation confirmed the diagnosis of acromegaly due to an underlying
GH–secreting pituitary macroadenoma. She was also found to have ADPKD. We discuss the clinical
features and management of the patient.
Conclusion:
The association of pituitary adenomas and ADPKD is very rare and interesting. All affected
individuals with pituitary adenomas and ADPKD in the literature are women. Furthermore, all
reported pituitary adenomas in these individuals (including ours) are functional GH–secreting ones.
These findings argue against a mere chance association between the two diseases.
Go to:
INTRODUCTION
Acromegaly is a relatively rare endocrine disorder. In a vast majority of patients, the underlying cause
is a growth hormone (GH)–secreting pituitary tumor. The classic somatic manifestations of
acromegaly are due to the effects of elevated levels of GH and insulin-like growth factor 1 (IGF-1).
Due to its multisystemic involvement, the disease can lead to significant morbidity and mortality. On
the other hand, autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder
caused by mutations in the PKD1 and PKD2 genes resulting in classical renal and extrarenal
manifestations (1,2). The association of ADPKD with acromegaly is very rare and to the best of our
knowledge only 4 such cases have been reported in the literature (3–6). We report a case of a
42-year-old woman with acromegaly and ADPKD with a brief review of literature.
Go to:
CASE REPORT
A 42-year-old female presented with progressive enlargement of hands and feet along with
coarsening of her facial features for last 5 years. There was no history of similar complaints in any of
her family members. She also complained of headache, excessive sweating, and multiple joint pains
for the past year. She was hypertensive for last 5 years and was taking tablet amlodipine 5 mg once
daily. She had no history of diabetes mellitus. There was no history of early morning facial puffiness,
pedal edema, or decreased urination in past. She had no history of renal disease and therefore no
comprehensive renal assessment was previously undertaken. However, she revealed that two of her
brothers had some renal cyst-like problems. But they could not be evaluated due to their
unavailability. She had normal menstrual cycles in the past and has two children. However, she had
undergone a hysterectomy 15 years back due to uterine prolapse. Clinical examination revealed
classical somatic stigmata of hypersomatotropism in the form of acral enlargement with warm and
moist hands, fleshy lips, macroglossia, and prognathism. She had a body mass index of 23.31 kg/m2.
Her pulse rate (80/min) and blood pressure (132/80 mm Hg without significant postural drop) were
normal at present. A grade 1 diffuse goiter was palpable. She had extensive acanthosis nigricans with
multiple skin tags. There were no neurocutaneous markers. Fundus examination was normal. Visual
perimetry assessment showed presence of superior quadrantanopia in the left eye. Examination of
chest and cardiovascular system were normal. Complete blood count was normal except for the
presence of mild hypochromic microcytic anemia. Evaluation of glycemic status revealed a fasting
plasma glucose level of 95 mg/dL and a postprandial plasma glucose level of 145 mg/dL. Her
glycosylated hemoglobin level was 6.1% (43 mmol/mol; normal, <6.5% [<48 mmol/mol]). Hepatic
function tests and renal function tests revealed no abnormality. Estimation of serum electrolytes
including sodium, potassium, calcium, and phosphorous were within normal limits. Hormonal
evaluation showed raised serum IGF-1 (644 ng/mL; normal, 101 to 267 ng/mL) and prolactin (39.77
ng/mL; normal, 5.18 to 26.5 ng/mL) levels. The 2-hour post glucose GH suppression test showed
elevated GH levels (34.3 ng/mL; normal, <1 ng/mL), which was suggestive of a GH excess state. Her
thyroid-stimulating hormone (0.77 mIU/mL; normal, 0.45 to 4.5 mIU/mL), free thyroxine (1.14 ng/dL;
normal, 0.8 to 1.8 ng/dL), and free triiodothyronine (3.31 pg/ml; normal, 1.4 to 4.4 pg/mL) levels were
normal. Similarly, estimation of other pituitary hormones revealed a serum cortisol (8:00 AM) level of
12.95 mcg/dL (normal, 5 to 25 mcg/dL), a luteinizing hormone level of 2.2 mIU/mL (normal, 2 to 12
mIU/mL), and follicle-stimulating hormone (FSH) level of 1.5 mIU/mL (normal, 1 to 8 mIU/mL).
Magnetic resonance imaging (MRI) of the brain and pituitary revealed a pituitary macroadenoma
(size, 16 mm × 20 mm × 21 mm) with suprasellar and parasellar extension (Fig. 1). The
two-dimensional echocardiography revealed the presence of concentric left ventricular hypertrophy
with diastolic dysfunction. Ultrasonography of the abdomen and pelvis revealed multiple renal,
hepatic, and pancreatic cysts of varying sizes. Contrast enhanced computerized tomography of the
abdomen and pelvis revealed multiple cysts of varying sizes in the liver and kidneys which was
compatible with findings seen in ADPKD (Fig. 2). Based on the above findings, the patient was
diagnosed with acromegaly due to a GH–secreting pituitary macroadenoma and ADPKD. However,
no genetic test was done. The patient underwent transsphenoidal surgery for resection of pituitary
adenoma. A reassessment of disease status after surgery showed persistence of disease as revealed
by raised IGF-1 (462 ng/mL; normal, 101 to 267 ng/mL) and random GH levels (7.52 ng/mL; normal, <1
ng/mL). The two-hour post-glucose GH suppression test showed elevated GH levels (6.3 ng/mL;
normal, <1 ng/mL). She was started on octreotide long-acting release 20 mg monthly depot therapy.
A repeat MRI of the brain and pituitary revealed persistence of the pituitary macroadenoma. She was
offered radiotherapy for management of the residual tumor.
An external file that holds a picture, illustration, etc.

Object name is i2376-0605-5-5-e302-f01.jpg
Fig. 1.
Magnetic resonance imaging of pituitary showing a pituitary macroadenoma of size 16 mm × 20 mm
× 21 mm with suprasellar and parasellar extension.

Fig. 2.
Contrast enhanced computerized tomography of abdomen and pelvis showing multiple cysts in liver
and kidneys.
Go to:
DISCUSSION
ADPKD is an inherited kidney disease which represents an important cause of end-stage renal
disease (1). It is characterized by the relentless development and growth of cysts causing progressive
kidney enlargement associated with hypertension, abdominal fullness, pain, episodes of cyst
hemorrhage, gross hematuria, nephrolithiasis, and cyst infections (2,7). The disease is caused by
mutations in PKD1 or PKD2 genes, with allele frequencies of 1:500 to 1:1,000 (1). Mutations in PKD1
comprise 85% of the cases. PKD1 encodes polycystin-1 and a large integral membrane protein (8).
Similarly, PKD2 encodes polycystin-2 and a transient receptor potential calcium ion channel (8).
Together, these proteins function as a mechanosensory ion channel complex. Acromegaly is a
relatively uncommon endocrine disorder with an annual incidence of around 3 to 4 cases per million
(9). The disease is characterized by elevated levels of GH and IGF-1, which result in classical signs and
symptoms of hypersomatotropism. In the overwhelming majority (over 90% of patients), acromegaly
is caused by a GH–secreting pituitary adenoma (9). The association of acromegaly with ADPKD is
very rare and to the best of our knowledge only 4 such cases have been described previously (3–6). In
all of these reported cases, pituitary tumors in ADPKD patients were functional GH–secreting ones.
Furthermore, all of the affected individuals (including our case) were females. The above described
findings argue against a mere chance association between the two diseases.
The first case describing the association of acromegaly and ADPKD was reported by Fajfr et al (3) in
2002. The authors described the case of a woman with ADPKD who was incidentally found to have a
pituitary adenoma while undergoing evaluation of cerebral aneurysm. Later on, hormonal evaluation
of the pituitary adenoma confirmed it to be a GH–secreting adenoma. The results showed elevated
IGF-1 (569 ng/mL; normal, 230 to 546 ng/mL) and nonsuppressed GH levels after an oral glucose
tolerance test (5.7 ng/mL; normal, <1 ng/mL). In 2005, Kannabiran et al (4) reported the second case
of a 50-year-old woman with ADPKD and pituitary macroadenoma. She had elevated levels of GH,
IGF-1, and prolactin hormones. Interestingly, Ruggeneti et al (5) described a woman with ADPKD and
acromegaly in whom the renal cysts showed no appreciable change after 2 years of long-acting
somatostatin analogue treatment used to control GH excess. Hence, the authors suspected a
potentially beneficial effect of octreotide on progression of renal cyst size in ADPKD patients. Lastly,
Syro et al (6) reported the case of a 39-year-old female suffering from acromegaly due to
GH–secreting pituitary macroadenoma and ADPKD. The authors had done extensive hormonal,
molecular, and histologic work-up of this particular case. They found that the patient harbored a
sparsely granulated GH cell adenoma. On genetic analysis, the most commonly harbored PKD1
mutation (5014_5015delAG) was found. Furthermore, analysis of the entire SSTR5 gene disclosed the
variant c.143C>A (p.L48M, rs4988483) change in the heterozygous state (6). It is interesting to note
that the PKD1 and the SSTR5 genes are both located in chromosome 16. The PKD1 gene is located
on the short (p) arm of chromosome 16 at position 13.3, whereas the SSTR5 gene is located 1 million
base pairs (approximately 1 centimorgan) from the PKD1 gene on the same chromosome (6). After
extensive molecular analysis of both these genes in their reported case, Syro et al (6) concluded that
the most likely explanation for a GH–secreting adenoma occurring in ADPKD is due to two
independent gene alterations in the patient underlying the two phenotypes.
GH and IGF-1 play critical roles as regulators of renal development, growth, and function. It has been
suggested that IGF-1 plays a potential role in mediating tubular cell proliferation in the cystic kidney.
These data come from few animal studies where renal IGF-1 content was shown to correlate with the
severity of polycystic kidney disease (10,11). Another interesting study which looked at the potential
role of IGF-1 in cystic kidney disease, reported that polycystin-1 deficiency was associated with
increased sensitivity to IGF-1 along with a permissive effect of cAMP on cell growth (10,12). These
experimental findings in part may explain the potential association of ADPKD and acromegaly. An
excellent review summarizing the implications of GH and IGF-1 in renal physiology and
pathophysiology has been published by Kamenický et al (10). Growth retardation is commonly seen
in children suffering from ARPKD. These children with ARPKD who receive GH therapy for short
stature, offer an interesting avenue to study the effect of GH/IGF-1 on cystic kidney disease.
Interestingly, GH treatment has been shown to be effective and safe in these children as evidenced
by good growth response without a detrimental effect on kidney function or kidney cyst dimensions
(13).
Both ADPKD and acromegaly are associated with various cardiovascular abnormalities. Cardiac
manifestations including early-onset hypertension, left ventricular hypertrophy, pericardial effusion,
and cardiac valvular abnormalities occur in a high percentage of ADPKD patients. Hypertension is
very common in patients with ADPKD, occurring in upwards of 60% of patients even before renal
dysfunction is observed (14). Activation of the renin-angiotensin-aldosterone system (RAAS) occurs
as a result of cyst expansion and local renal ischemia in ADPKD. This plays an important role in the
subsequent development of hypertension (14). Hence, RAAS blockade represents a preferred
first-line treatment in such individuals. The reported cardiovascular abnormalities in acromegaly
include left ventricular hypertrophy, asymmetric septal hypertrophy, cardiomyopathy, hypertension,
and congestive heart failure (9). Hence, individuals suffering from both ADPKD and acromegaly may
be at significantly higher risk for adverse cardiovascular events.
Somatostatin analogues play a major role in medical management of acromegaly. With respect to
somatostatin analogues use in ADPKD, 3 placebo-controlled randomized controlled trials have
suggested a beneficial renal effect. However, these trials were of short duration and included a
relatively small number of patients (5,15–17). A randomized double-blinded placebo-controlled trial
evaluating the use of long-acting octreotide in patients with ADPKD showed that octreotide use led
to significant reduction in liver cyst volume (approximately 5%) and maintained renal cyst stability
when compared with placebo over a 1-year period (17). Another small-scale study with 3 years of
follow-up also suggested similar beneficial effects with somatostatin analogues (18). Despite these
data, an executive summary from a Kidney Disease: Improving Global Outcomes conference
recommends that somatostatin analogues should not be prescribed for renoprotection outside of a
research study until the results of larger trials become available (19). In addition to its potential
beneficial effects on renal cysts, the use of somatostatin analogues has also resulted in significant
reduction of liver cyst volume with continued use over a 1-year period (17). However, in the second
year of treatment no further reduction in liver cyst volume was noted in patients who were treated
for 2 years (20).
Go to:
CONCLUSION
The association of ADPKD and pituitary adenomas is very rare. Interestingly, all reported individuals
in the literature with this unique association are women harboring GH–secreting pituitary adenomas.
These individuals offer a rare avenue to study the influence of a GH excess state on the natural course
of ADPKD. The therapeutic utility of long-acting somatostatin analogues in addressing the
progression of renal cysts in ADPKD also remains to be seen in future studies.
Go to:
ACKNOWLEDGMENT
The authors thank the patient and her family members for their cooperation. Written informed
consent was obtained from the patient for publication of this case report and any accompanying
images.
Go to:
Abbreviations
ADPKD autosomal dominant polycystic kidney disease
GH growth hormone
IGF-1 insulin-like growth factor 1
Go to:
Footnotes
DISCLOSURE
The authors have no multiplicity of interest to disclose.
Go to:
REFERENCES
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16. Caroli A, Antiga L, Cafaro M et al. Reducing polycystic liver volume in ADPKD: effects of
somatostatin analogue octreotide. Clin J Am Soc Nephrol. 2010;5:783–789. [PMC free article]
17. Hogan MC, Masyuk TV, Page LJ et al. Randomized clinical trial of long-acting somatostatin for
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Review Autosomal dominant polycystic kidney disease.
[Lancet. 2007]
Volume progression in polycystic kidney disease.
[N Engl J Med. 2006]
[Hypophyseal incidentaloma in a patient with autosomal dominant polycystic kidney disease].
[Praxis (Bern 1994). 2002]
Review Autosomal dominant polycystic kidney disease.
[Lancet. 2007]
Volume progression in polycystic kidney disease.
Kidney volume and functional outcomes in autosomal dominant polycystic kidney disease.
[Clin J Am Soc Nephrol. 2012]
Review Extra-renal manifestations of autosomal dominant polycystic kidney disease (ADPKD):
considerations for routine screening and management.
[Nephrol Dial Transplant. 2014]
Review Medical progress: Acromegaly.
[Praxis (Bern 1994). 2002]
[Praxis (Bern 1994). 2002]
Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney
disease.
[Kidney Int. 2005]
Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney
disease: SSTR5 polymorphism and PKD1 mutation.
[Pituitary. 2012]
Review Growth hormone, insulin-like growth factor-1, and the kidney: pathophysiological and clinical
implications.
[Endocr Rev. 2014]
Increased endothelin and endothelin receptor mRNA expression in polycystic kidneys of cpk mice.
[J Am Soc Nephrol. 1993]
Hyperproliferation of PKD1 cystic cells is induced by insulin-like growth factor-1 activation of the
Ras/Raf signalling system.
[Kidney Int. 2007]
Recombinant human growth hormone therapy in autosomal recessive polycystic kidney disease.
[Pediatr Nephrol. 2003]
Review Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease.
[Nat Rev Nephrol. 2009]
Review Medical progress: Acromegaly.
Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney
disease.
[Kidney Int. 2005]
Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled
trial.
[Gastroenterology. 2009]
Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and
liver disease.
[J Am Soc Nephrol. 2010]
Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant
polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial.
[Lancet. 2013]
Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease:
Improving Global Outcomes (KDIGO) Controversies Conference.
[Kidney Int. 2015]
Somatostatin analog therapy for severe polycystic liver disease: results after 2 years.
[Nephrol Dial Transplant. 2012]
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Journal ListAACE Clin Case Repv.5(5); Sep-Oct 2019PMC6876962

Logo of aaceccr
AACE Clin Case Rep. 2019 Sep-Oct; 5(5): e307–e310.
Published online 2019 Aug 28. doi: 10.4158/ACCR-2019-0239
PMCID: PMC6876962
PMID: 31967059
ELECTROCARDIOGRAM CHANGES IN ADDISON DISEASE: POTENTIAL CLINICAL MARKER FOR
ADRENAL CRISIS
Pedro E. Perez, BS, Wilson Sze, MD, and Joshua Miller, MD, MPHcorresponding author
Author information Article notes Copyright and License information Disclaimer
Go to:
Abstract
Objective:
To present a unique phenomenon of a patient in addisonian crisis with electrocardiogram (ECG)
anomalies that resolved following glucocorticoid therapy.
Methods:
We present the case report followed by discussion with literature review.
Results:
A 25-year-old male with Addison disease (AD) presented with a 1-week history of lightheadedness,
shortness of breath, chest pain, abdominal pain, postural hypotension, and tachycardia. The patient
was diagnosed with addisonian crisis and started on intravenous, high-dose glucocorticoids. An ECG
showed right-heart axis deviation and T-wave inversions. In the context of ongoing chest pain, there
was concern for myocardial ischemic attack and the patient underwent an extensive cardiac
evaluation. Cardiac workup was negative and an echocardiogram showed an ejection fraction of 50
to 55%. The ECG abnormalities resolved 1 day into his hospital admission and his other symptoms
resolved 2 days following treatment with steroids.
Conclusion:
AD is a rare, potentially lethal, and commonly misdiagnosed disease often first encountered clinically
amidst an incident episode of adrenal crisis. Our AD patient was undergoing an adrenal crisis with
ECG changes positive for probable cardiac ischemia. Glucocorticoid deficiency has been previously
linked with decreased cardiac function and myocardial ischemia, though the underlying mechanisms
are not fully clear. This patient recovered within 2 days after receiving corticosteroid
supplementation. There have been similar cases previously reported. In each of these, patients
underwent extensive and costly workup to evaluate cardiac function, yet all patients fully recovered
with corticosteroids. Understanding the physiology and clinical presentation of adrenal crisis will be
useful in establishing an earlier diagnosis, thus preventing mortality and avoiding unnecessary,
expensive evaluations.
Go to:
INTRODUCTION
Primary adrenal insufficiency, also known as Addison disease (AD), is a potentially lethal disorder
defined by decreased synthesis of glucocorticoids and mineralocorticoids in the adrenal cortex with
concomitant elevation in adrenocorticotropic hormone. Misdiagnosis and delay in treatment of AD is
common due to a generalized, nondescript cluster of symptoms and signs. Developing a clearer
understanding of the different clinical presentations of AD will be highly beneficial to clinicians and
patients for earlier diagnosis. Electrocardiogram (ECG) abnormalities in patients with addisonian
(adrenal) crisis have been scarcely mentioned in the published literature. We report here a patient
presenting with addisonian crisis and prominent T-wave inversions on ECG of unknown etiology.
Go to:
CASE REPORT
A 25-year-old, Caucasian male with a medical history of previously diagnosed AD presented to the
emergency department with lightheadedness, shortness of breath, chest pain, chills, and bilateral
radiating pain in the lateral aspects of the abdomen. His symptoms had begun 7 days prior with mild,
non-exertional dyspnea. He then began to experience worsening generalized fatigue and
lightheadedness upon standing. Two days prior to presentation, the patient developed moderate,
left-sided chest pain, characterized as pressure-like, and radiating to the left shoulder. One day prior
to presentation, he reported bilateral abdominal pain and had 3 episodes of nausea with non-bilious,
non-bloody vomiting.
Due to the persistence of his symptoms and inability to tolerate oral intake, he came to the
emergency department for evaluation. The patient had reported a similar episode at age 14, whereby
he was diagnosed with primary adrenal insufficiency. He has been on a stable dose of prednisone and
fludrocortisone medications since. For 3 days prior to this presentation, he had tripled his outpatient
steroid regimen. The patient denied any recent history of weight loss, changes in bowel movements,
travel, illness, trauma, or any deviation from his regular routine.
The patient had an initial blood pressure of 100/67 mm Hg, heart rate of 98 beats per minute,
maximum temperature of 36.8°C, and O2 saturation of 98% on room air. He exhibited symptomatic
orthostatic hypotension. On physical exam, his chest pain was reproducible upon palpation and there
was mild tenderness with deep palpation of the abdominal left lower quadrant. His exam was
otherwise unremarkable.
Laboratory testing revealed a mildly elevated thyroid-stimulating hormone of 4.4 mIU/L,

leukocytosis with a count of 11.27 × 103/μL, and prominent neutrophil count of 8.19 × 103/μL. Lab
findings were otherwise within normal ranges with sodium at 136 mmol/L, potassium at 4.9 mmol/L,
chloride at 100 mmol/L, bicarbonate at 25 mmol/L, plasma glucose at 91 mg/dL, calcium at 9.7
mg/dL, and a blood urea nitrogen to creatinine ratio of 16:1.14. Liver function tests were within
normal limits. Additional lab analysis for cardiac dysfunction revealed 3 negative cardiac troponins
(<0.01 ng/mL) and B-type natriuretic peptide (<0.5 pg/mL).
A 12-lead ECG showed rightward heart axis deviation, prominent T-wave inversions in leads II and
aVF, and T-wave abnormalities in leads V3 to V6 concerning for inferolateral ischemia (Fig. 1).
Posteroanterior, anteroposterior, and lateral chest X-rays showed no acute cardiopulmonary process.
Given his history and presentation, the patient was diagnosed with addisonian crisis and
subsequently received fluid resuscitation with 2 liters of lactated Ringer solution and 100 mg of
hydrocortisone given intravenously.

Fig. 1.
Twelve-lead electrocardiogram of the patient at presentation. The results demonstrate sinus
tachycardia, right heart axis deviation, and T-wave inversions in leads II and aVF, with additional
T-wave abnormalities in V3 to V6.
The patient was admitted to the hospital and received 50 mg of hydrocortisone intravenously every 6
hours. Post-admission day 1, the patient had significantly improved symptoms including blood
pressure (117/73 mm Hg), and heart rate (79 beats per minute). The patient was still reporting
persistent left chest pain with radiation to his left shoulder as well as generalized abdominal pain. A
transthoracic echocardiogram was obtained, which showed an ejection fraction of 50 to 55% with no
evidence of structural or functional abnormalities, no pericardial effusion, and only trace mitral and
tricuspid valve regurgitation. Follow-up ECGs demonstrated sinus rate and rhythm with resolution of
the previously noted T-wave inversions in leads II and aVF (Fig. 2). During his hospital course, his
intravenous steroid regimen was continued, tapered, and converted to an oral regimen. Following
resolution of his symptoms, the patient was discharged with outpatient endocrinology follow up.

Fig. 2.
Twelve-lead electrocardiogram on day 1 following treatment with hydrocortisone and intravenous
fluids. The results demonstrate normal sinus rhythm, normal heart axis, and resolution of inverted
T-waves in leads II and aVF, as well as resolution of T-wave abnormalities in leads V3 to V6.
Go to:
DISCUSSION
Primary adrenal insufficiency is rare with a prevalence of 4 to 11 per 100,000 and an incidence of 0.6
per 100,000 (1). In developed nations, the primary etiology is autoimmune whereas in developing
countries other causes such as tuberculosis, sepsis, and human immunodeficiency virus also
contribute to disease prevalence. Rarely, systemic diseases such as sarcoidosis and amyloidosis can
lead to AD. Patients with AD are often first diagnosed following an incident addisonian crisis. Adrenal
crisis in AD patients can lead to mortality if treatment is delayed, so it would be beneficial to identify
early clinical diagnostic factors (2).
Our patient presented with hypotension, recent episodes of vomiting, generalized weakness,
potential angina, abdominal pain, and dyspnea. His symptoms had progressively worsened with no
obvious etiology to trigger the event (no trauma, infection, missed steroid doses, etc.). His labs were
unremarkable and atypical of severe adrenal crisis with no significant hyponatremia, hyperkalemia,
or hypoglycemia. His known history of AD was valuable in the rapid diagnosis and treatment of
adrenal crisis. Had he presented with an unknown past medical history, the diagnosis would have
likely been delayed.
The patient's ECG was noteworthy for sinus tachycardia, T-wave inversions, diffused T-wave
abnormalities, and right axis deviation (Fig. 1). These findings are interesting given the patient's
negative cardiac history and family history of cardiovascular disease. T-wave inversions are
frequently seen in the context of subendocardial ischemia, hypertrophic cardiomyopathy, cerebral
disorders, and pulmonary disorders (3). The labs did not reveal any rise in cardiac enzymes and the
echocardiogram showed normal heart function.
Previous studies have noted ECG abnormalities associated with corticosteroid deficiency and chronic
AD (4–6). However, few case reports have examined specific ECG changes in the context of
addisonian crisis. A literature search revealed 3 prior reports of T-wave abnormalities associated with
addisonian crisis in 1992 and 2005 (7,8). In 1 case, the patient had ST depressions and inverted
T-waves in leads V4 through V6, reduced heart size on chest X-ray, and no associated angina. This
patient recovered completely 1 week following prednisolone treatment. In the other 2 cases, the
patients had deep inverted T-waves with wall motion abnormalities in the apex of the left ventricle. In
these patients, negative T-waves were present in leads V3 through V6 and T-wave abnormalities in
leads I, II, and V2. These patients recovered following 4-week courses of corticosteroids.
Our patient had similar ECG findings of T-wave abnormalities in leads II, aVF, and V3 through V6; the
most prominent T-wave inversions were in leads II and aVF, consistent with inferolateral ischemia.
Our patient's T-wave inversions quickly resolved 1 day after hydrocortisone treatment (Fig. 2). It is
likely that his abnormal ECG changes coincided with his 2 days of antecedent chest pain.
The mechanism causing T-wave inversions in AD patients is not entirely known. T-wave inversions are
classically associated with myocardial ischemia. Our patient presented with non-exertional chest
pain and dyspnea. Moreover, a patient from one of the published case reports had ST depressions,
another marker for myocardial ischemia. It has been well documented that prolonged intake of
high-dose corticosteroids is associated with negative cardiovascular risks (9). Conversely, and as first
reported by Dr. Addison himself, prolonged glucocorticoid deficiency causes decreased heart
function (10). Previous studies have shown the importance of glucocorticoids in improving heart
contractility (11–13). Additionally, separate work also revealed a role for glucocorticoids in protecting
against cardiac ischemia and eventual necrosis (14,15). Thus, it seems reasonable to propose that in
the acute setting of adrenal crisis, these patients suffer from transient, reversible myocardial damage
due to acute glucocorticoid deficiency from baseline. However, how the myocardial ischemia is
caused in these cases from a molecular standpoint remains to be answered.
Go to:
CONCLUSION
AD is often initially misdiagnosed and identification commonly occurs following an acute adrenal
crisis. Delay in treatment can be highly detrimental for patients in both chronic AD and in acute
addisonian crisis. Moreover, patients presenting with ECG changes concerning for ischemia receive a
costly and time-intensive medical evaluation for potentially serious cardiovascular damage, which
may include significant laboratory testing, cardiac stress testing, and, in some cases, coronary
catheterization.
A clearer understanding of the clinical presentation in patients with AD will be useful to clinicians
when encountering these patients. T-wave inversions in addisonian crisis have been previously
published in limited cases in the literature. In each of these cases, the patients received extensive
medical evaluation and imaging, yet ultimately fully recovered with exogenous corticosteroid
treatment with no obvious permanent damage to the myocardium.
Given the rarity of patients with AD undergoing acute adrenal crisis, accumulating enough clinical
data will be challenging. However, studying ECG abnormalities in patients with AD will hopefully lead
to earlier recognition and avoidance of unnecessary and expensive medical testing with an overall
benefit to the patient.
Go to:
Abbreviations
AD Addison disease
ECG electrocardiogram
Go to:
Footnotes
DISCLOSURE
The authors have no multiplicity of interest to disclose.
Go to:
REFERENCES
1. Munir S, Waseem M. Addison Disease. StatPearls Publishing LLC. Available at:
https://www.ncbi.nlm.nih.gov/books/NBK441994/ Accessed July 15, 2019.
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the precordial leads in adult subjects: a Dutch case series and review of the literature. World J Cardiol.
4. Somerville W, Levine HD, Thorn GW. The electrocardiogram in Addison's disease. Medicine
(Baltimore) 1951;30:43–79. [PubMed] [Google Scholar]
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crisis. J Natl Med Assoc. 2005;97:1539–1540. [PMC free article] [PubMed] [Google Scholar]
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11. Penefsky ZJ, Kahn M. Inotropic effects of dexamethasone in mammalian heart muscle. Eur J
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Review Acute adrenal crisis and mortality in adrenal insufficiency: Still a concern in 2018!
[Ann Endocrinol (Paris). 2018]
Cardiac and non-cardiac causes of T-wave inversion in the precordial leads in adult subjects: A Dutch
case series and review of the literature.
[World J Cardiol. 2015]
The electrocardiogram in Addison's disease.
[Medicine (Baltimore). 1951]
Deep negative T waves associated with reversible left ventricular dysfunction in acute adrenal crisis.
[Heart Vessels. 1992]
Inverted T waves in patient with Addisonian crisis.
[J Natl Med Assoc. 2005]
Review Adverse effects of corticosteroids on the cardiovascular system.
[Can J Cardiol. 2000]
Review Glucocorticoid signaling in the heart: A cardiomyocyte perspective.
[J Steroid Biochem Mol Biol. 2015]
Inotropic effects of dexamethasone in mammalian heart muscle.
[Eur J Pharmacol. 1971]
Reduction of experimental myocardial infarct size by corticosteroid administration.
[J Clin Invest. 1973]
Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional
activation of endothelial nitric oxide synthase.
[Nat Med. 2002]
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