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- •Preface
- •Contents
- •Contributors
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Diagnostic Approach Toward Fixed Drug Eruptions
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Hypereosinophilic Syndrome Treatment Options
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Differential Diagnosis
- •Clinical Case Presentation
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Discussion
- •Differential Diagnosis
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Alternative Diagnosis/Potential Misdiagnosis
- •Note
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Alternative Diagnosis/Potential Misdiagnosis
- •Note
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Alternative Diagnosis Considered/Potential Misdiagnosis
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Alternative Diagnoses
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Alternative Diagnoses
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Plan of Action, the Points Clinician Should Consider, Pitfalls to Avoid, and Pearls of Knowledge to Consider
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnoses
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Plan of Action, the Points Clinician Should Consider, Pitfalls to Avoid, and Pearls of Knowledge to Consider
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Case 1
- •Case 2
- •Differential Diagnosis
- •Discussion
- •Plan of Action, the Points Clinician Should Consider, Pitfalls to Avoid, and Pearls of Knowledge to Consider
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Plan of Action, the Points Clinician Should Consider, Pitfalls to Avoid, and Pearls of Knowledge to Consider
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Plan of Action, the Points Clinician Should Consider, Pitfalls to Avoid, and Pearls of Knowledge to Consider
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •The Plan of Action, Points to Consider, Pitfalls to Avoid, and Pearls of Knowledge
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •Clinical Case Presentation
- •Differential Diagnosis
- •Discussion
- •Conclusion
- •References
- •Introduction
- •The Lawyers Are Watching
- •Misdiagnosis Versus Missed Diagnosis
- •Prostate Cancer Misdiagnosis
- •Breast Cancer Misdiagnosis
- •Exemplar Cases
- •Cardiac Misdiagnosis
- •COVID Misdiagnosis
- •References
- •Introduction
- •Conclusion
- •References

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B. H. Malik and M. S. Hameed
tissues and are responsible for all thyroid activities [12, 17]. Urinary protein losses
are negligible under normal circumstances. In NS, however, substantial urinary protein losses occur, including T4 and T3 along with their binding proteins, as well as
the free fractions fT4 and fT3 to a lesser extent [2, 4, 5, 18, 19]. This explains why
thyroid function abnormalities are so common in people with NS, which is a renalendocrine illness [2]. Milder symptoms and normal levels of free hormones are seen
early in the disease process [2, 4]. fT4 and fT3 are also dramatically lowered if the
protein losing processes carry on for longer periods causing subclinical hypothyroid
state [4, 19]. High urinary protein levels and increased serum creatinine were found
to be independent risk factors for thyroid dysfunction in a study of individuals who
had been ofcially diagnosed with NS, while a greater level of plasmatic albumin
was found to be an independent protective factor [5]. In ve children with congenital NS, lasting cure of hypothyroidism after bilateral nephrectomy had already been
documented [14]. This nding demonstrates that hypothyroidism was not caused by
an intrinsic abnormality in the thyroid gland. Corticosteroids may contribute to thyroid dysfunction by suppressing serum TSH levels, impairing peripheral T4 to T3
conversion, and lowering TBG synthesis (which might be the contributory factor in
this case) [9]. In addition to NS, hypothyroidism has been linked to some glomerulonephritides (GN) [2, 20, 21].
Conclusion
Renal disease evaluation should be commenced when diagnosis of hypothyroidism
is made. Severity of thyroid dysfunction and treatment response are determined
jointly by clinical circumstances and proteinuria severity. The necessity of a clearer
understanding of the relationships between thyroid and renal functions is highlighted in this case study. When nephrotic syndrome is rst identied, it is fair to
evaluate thyroid function and then perform serial testing.
References
1. Bradley SE, Stephan F, Coelho JB, Reville P. The thyroid and the kidney. Kidney Int.
1974;6(5):346–65.
2. Dousdampanis P, Trigka K, Vagenakis GA, Fourtounas C.The thyroid and the kidney: a complex interplay in health and disease. Int J Artif Organs. 2014;37(1):1–12.
3. Chonchol M, Lippi G, Salvagno G, Zoppini G, Muggeo M, Targher G. Prevalence of subclinical hypothyroidism in chronic kidney disease patients. Clin J Am Soc Nephrol.
2008;3(5):1296–300.
4. Jain D, Aggarwal HK, Pavan Kumar YM, Jain P.Evaluation of thyroid dysfunction in patients
with nephrotic syndrome. Med Pharm Rep. 2019;92(2):139–44.
5. Li L-Z, Hu Y, Ai S-L, etal. The relationship between thyroid dysfunction and nephrotic syndrome: a clinicopathological study. Sci Rep. 2019;9(1):6421.

22 Hypothyroidism withNephrotic Syndrome Misdiagnosed asCardiac Failure
6. Lo JC, Chertow GM, Go AS, Hsu C-Y.Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease. Kidney Int. 2005;67(3):1047–52.
7. Rhee CM, Kalantar-Zadeh K, Streja E, etal. The relationship between thyroid function and
estimated glomerular ltration rate in patients with chronic kidney disease. Nephrol Dial
Transplant. 2015;30(2):282–7.
8. Chandurkar V, Shik J, Randell E.Exacerbation of underlying hypothyroidism caused by proteinuria and induction of urinary thyroxine loss: case report and subsequent investigation.
Endocr Pract. 2008;14(1):97–103.
9. Burch HB.Drug effects on the thyroid. N Engl J Med. 2019;381(8):749–61.
10. Fonseca V, Thomas M, Katrak A, Sweny P, Moorhead JF.Can urinary thyroid hormone loss
cause hypothyroidism? Lancet. 1991;338(8765):475–6.
11. Jung SH, Lee JE, Chung WY. Changes in the thyroid hormone proles in children with
nephrotic syndrome. Korean J Pediatr. 2019;62(3):85–9.
12. Maiden MJ, Torpy DJ.Thyroid hormones in critical illness. Crit Care Clin. 2019;35(2):375–88.
13. Benvenga S, Vita R, Di Bari F, Fallahi P, Antonelli A.Do not forget nephrotic syndrome as a
cause of increased levothyroxine replacement therapy. Eur Thyroid J. 2015;4(2):138–42.
14. Chadha V, Alon US.Bilateral nephrectomy reverses hypothyroidism in congenital nephrotic
syndrome. Pediatr Nephrol. 1999;13(3):209–11.
15. Karethimmaiah H, Sarathi V. Nephrotic syndrome increases the need for levothyroxine
replacement in patients with hypothyroidism. J Clin Diagn Res. 2016;10(12):OC10.
16. Soh S, Aki O, Manabu O, Norimasa K, Hiroshi K, Masao N.A case of minimal change
nephrotic syndrome with hypothyroidism deterioration. CEN Case Rep. 2016;5:95.
17. Bartalena L, Robbins J.Thyroid hormone transport proteins. Clin Lab Med. 1993;13(3):583–98.
18. Levey AS, Stevens LA, Schmidetal CH.A new equation to estimate glomerular ltration rate.
Ann Intern Med. 2009;150(9):604–12.
19. Alam ABM, Hasan ANM, Khan AH, Quader MMU, Begum SA, Banik SK. Association
between primary hypothyroidism and nephrotic syndrome: a case report. Chattagram Maa-oShishu Hosp Med College J. 2013;12(2):63–5.
20. Mariani LH, Berns JS. The renal manifestations of thyroid disease. J Am Soc Nephrol.
2012;23(1):22–6.
21. Connie MR. Thyroid and kidney disease interactions: a review of the evidence. Curr Opin
Endocrinol Diabetes Obes. 2016;23(5):407–15.
149

Chapter 23
Adrenal Insufciency Misdiagnosed
asSyndrome ofInappropriate ADH
Secretion
IvanCancarevic
Learning Objectives
By the end of this presentation, the clinician will be able to:
1. Identify the clinical ndings associated with adrenal insufciency.
2. Discuss and enumerate the classication and common causes of hyponatremia.
3. Apply the aforementioned concepts in a clinical scenario.
4. Analyze the basics of hyponatremia management.
5. Discuss the potential for misdiagnosis of the cause of hyponatremia in the setting of adrenal insufciency.
Introduction
Hyponatremia is generally dened as a sodium level below 136mEq/L and can be
seen in a variety of clinical settings. Pseudohyponatremia refers to a falsely low
reading of serum sodium levels, usually due to the presence of very high amounts of
protein or lipid in the blood, giving the appearance of a larger serum volume [1].
Real hyponatremia usually also indicates serum hyperosmolality. It is further
divided based on the patient’s volume status into hypovolemic hyponatremia,
euvolemic hyponatremia, and hypervolemic hyponatremia [2]. Hypovolemic hyponatremia develops in the setting of a loss of both free water and sodium; however,
the loss of sodium exceeds the loss of free water [2, 3]. Hypervolemic hyponatremia, on the other hand, develops in the setting of disproportionate retention of free
water in comparison to sodium, leading to decreased concentration of serum sodium,
typically in patients with underlying heart or liver disease [2, 4, 5]. Euvolemic
I. Cancarevic (*)
Icahn School of Medicine at Mount Sinai, New York, NY, USA
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
H. Tohid et al. (eds.), The Misdiagnosis Casebook in Clinical Medicine,
https://doi.org/10.1007/978-3-031-28296-6_23
151

152
I. Cancarevic
hyponatremia refers to the setting where the patient is euvolemic, but the serum
concentration of sodium is low. The most common causes are the syndrome of inappropriate antidiuretic hormone (SIADH), primary polydipsia, and endocrinopathies, such as hypothyroidism and adrenal insufciency [2, 6, 7].
Aldosterone, the end hormone of the renin-angiotensin-aldosterone system
(RAAS), acts on the distal nephron stimulating potassium secretion and sodium
reabsorption. Adrenal insufciency, therefore, tends to present with impairment of
both processes resulting in hyponatremia and hyperkalemia [8]. Patients are typically hypovolemic, although it can be difcult to assess since volume loss is not
always signicant [2].
Clinically, there are a number of ways to assess volume status, although it is not
always easy to do. Vital signs, physical exam, and even ndings on the point-of-care
ultrasound testing all help get a sense of the patient’s volume status, but unless the
volume decit is severe, it may go unnoticed [9]. Therefore, it is easy to understand
why diagnosing the etiology of hyponatremia is challenging, and misdiagnosis
is common.
Clinical Case Presentation
A 53-year-old female with a past medical history of hypothyroidism managed with
a stable dose of levothyroxine was admitted to the hospital for a syncopal episode,
which happened while walking to the bathroom in her apartment. The patient also
reported a recent history of fatigue, nonspecic abdominal discomfort, and anorexia.
Vitals signs on admission were signicant for blood pressure of 100/64mmHg and
heart rate of 105/min. Initial laboratory tests revealed hemoglobin of 10.7g/dL (the
patient at the time still had regular periods), sodium of 126mEq/L, and potassium
of 5.1mEq/L.Initial EKG showed sinus rhythm. A head CT was ordered, and it was
unrevealing. The physical exam was unremarkable, and there was no evidence of
volume depletion– skin turgor was normal, and the patient’s mucosal surfaces were
not appearing to be dry. Due to the patient’s apparent euvolemic state and lack of
clinical ndings suggestive of acute hyponatremia, the admitting resident initially
diagnosed the patient with SIADH-induced euvolemic hyponatremia, and water
restriction was ordered. The resident feared that, in the setting of low hemoglobin
levels, the patient might have an underlying malignancy that may have triggered the
SIADH, and he recommended pursuing a malignancy workup in this patient.
Additionally, in order to rule out a cardiogenic cause of syncope, the patient was
placed on telemetry monitoring. The next day, the patient got dizzy when she
attempted to go to the bathroom, and her morning sodium level was 124mEq/L
despite having less than 1200mL of water the previous day. Thyroid-stimulating
hormone (TSH) levels obtained on admission were found to be within normal range,
effectively ruling out thyroid disease causing any of the patient’s symptoms or ndings. On the physical exam, her volume status was notably changing, and her mucosal surfaces appeared much drier than on admission. Telemetry revealed no abnormal

23 Adrenal Insufciency Misdiagnosed asSyndrome ofInappropriate ADH Secretion
rhythms at any time, although sinus tachycardia was noted around the time when the
patient went to the bathroom and became dizzy. Supine blood pressure remained
stable. Orthostatic vital signs were obtained, and the patient became hypotensive to
74/52mmHg, and a 1L bolus of normal saline was administered, leading to mild
symptomatic improvement and blood pressure elevation. Urine electrolytes were
obtained and showed sodium of 45mmol/L with markedly decreased urine potassium, indicating simultaneous sodium wasting and potassium retention. Those ndings, combined with postural hypotension, generalized fatigue, and anorexia, were
consistent with the diagnosis of adrenal insufciency, and an endocrine workup was
initiated. Aldosterone levels were found to be markedly decreased with elevated
levels of renin, indicating primary adrenal disorder. The patient was subsequently
started on udrocortisone which led to the normalization of her electrolyte levels.
153
Differential Diagnosis
1. Adrenal insufciency– it is frequently diagnosed late because the symptoms are
highly nonspecic, and even the laboratory ndings, other than decreased hormone levels, can be seen with a number of other conditions– notably, a combination of hyponatremia and hyperkalemia is characteristic.
2. Hyponatremia– rarely symptomatic unless acute and/or severe, in which case
patients usually present with neurological symptoms. It can be caused by a number of factors and is classied according to the patient’s volume status.
3. SIADH– a common cause of euvolemic hyponatremia, frequently in the setting
of another disease or condition, such as malignancies or brain or lung disease,
and is typically managed with water restriction.
Alternative Diagnoses
Initially, due to the lack of obvious signs of hypovolemia, an inexperienced clinician
diagnosed the patient with SIADH and placed the patient on uid restriction, which
made her symptoms worse.
Discussion
As illustrated in this case, determining the etiology of hyponatremia is not always
straightforward, and the consequences of inaccurate diagnosis and treatment can be
life-threatening for the patient. The initial step in the assessment of hyponatremia is
to ensure that it is not pseudohyponatremia by doing the appropriate corrections.
Afterward, as previously stated, carefully assessing volume status is crucial in

154
I. Cancarevic
patients with newly diagnosed hyponatremia. Moreover, analysis of osmolality and
electrolyte levels both in the blood and in the urine is necessary to determine the
exact etiology. For example, hypovolemic patients are likely to have very low levels
of urinary sodium, whereas someone like the patient presented in this case, who has
adrenal insufciency, will have higher levels of urinary sodium, indicating sodium
wasting. Serum potassium levels are important, in particular, to assess adrenal function since adrenal or aldosterone receptor diseases have the opposite effects on
sodium and potassium. Treatment, importantly, also varies based on the etiology of
hyponatremia. Volume repletion is generally needed in cases of hypovolemia, while
water restriction is encouraged with euvolemic and hypervolemic hyponatremia
[10]. In cases of euvolemic hyponatremia, psychogenic polydipsia needs to be ruled
out– usually by assessing urine osmolality and, as needed, doing a water deprivation test which will result in a prompt increase in urine osmolality [11]. Frequently,
in the hospital setting, SIADH becomes the “default” diagnosis even before the
entire workup has been completed, which, like in this case, increases the probability
that subtler presentations of other conditions may be missed. Another thing worth
mentioning is that, in this case, the patient already had a history of hypothyroidism,
which predisposes her to other autoimmune endocrine disorders, such as adrenal
insufciency. Moreover, hypothyroidism itself could be a cause of hyponatremia in
some patients, although this patient’s current TSH level is normal, so it is not a
likely cause in her. Obtaining hormone levels if there is any suspicion of endocrine
disease needs to be part of the workup since the condition can progress and become
life-threatening [12]. For instance, had this patient not been diagnosed, it is feasible
that in the near future, she could have developed an adrenal crisis. Treatment of
adrenal insufciency depends on the hormones that are affected (which depends on
the zones of the adrenal gland that are affected) but typically involve glucocorticoids, such as hydrocortisone or prednisone, as well as udrocortisone. Hormonal
supplementation should lead to the normalization of electrolyte levels.
Conclusion
When a patient is found to be hyponatremic, it is extremely important not to assume
the diagnosis without performing an adequate workup. Moreover, assessment of volume status is essential and should include vital orthostatic signs. Endocrine disorders, such as hypothyroidism or adrenal insufciency, should not be overlooked as a
possible cause of hyponatremia. Treatment depends on the underlying etiology, and
misdiagnosing and incorrectly treating hyponatremia can have dire consequences.

23 Adrenal Insufciency Misdiagnosed asSyndrome ofInappropriate ADH Secretion
155
References
1. Weisberg LS.Pseudohyponatremia: a reappraisal. Am J Med. 1989;86(3):315–8. https://doi.
org/10.1016/0002- 9343(89)90302- 1.
2. Bufngton MA, Abreo K.Hyponatremia: a review. J Intensive Care Med. 2016;31(4):223–36.
https://doi.org/10.1177/0885066614566794.
3. Mohottige D, Lehrich RW, Greenberg A. Hypovolemic hyponatremia. Front Horm Res.
2019;52:93–103. https://doi.org/10.1159/000493240.
4. Solà E, Ginès P.Hypervolemic hyponatremia (liver). Front Horm Res. 2019;52:104–12. https://
doi.org/10.1159/000493241.
5. Rodriguez M, Hernandez M, Cheungpasitporn W, et al. Hyponatremia in heart failure:
pathogenesis and management. Curr Cardiol Rev. 2019;15(4):252–61. https://doi.org/10.217
4/1573403X15666190306111812.
6. Garrahy A, Thompson CJ. Hyponatremia and glucocorticoid deciency. Front Horm Res.
2019;52:80–92. https://doi.org/10.1159/000493239.
7. Verbali G. Euvolemic Hyponatremia Secondary to the Syndrome of Inappropriate Antidiuresis.
Front Horm Res. 2019;52:61–79. https://doi.org/10.1159/000493238.
8. Meneton P, Lofng J, Warnock DG. Sodium and potassium handling by the aldosterone-sen-
sitive distal nephron: the pivotal role of the distal and connecting tubule. Am J Physiol Renal
Physiol. 2004;287(4):F593–F601. https://doi.org/10.1152/ajprenal.00454.2003.
9. Scott MC, Mallemat H. Assessing volume status. Emerg Med Clin North Am.
2014;32(4):811–822. https://doi.org/10.1016/j.emc.2014.07.007.
10. Hoorn EJ, Zietse R. Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines.
J Am Soc Nephrol. 2017;28(5):1340–1349. https://doi.org/10.1681/ASN.2016101139.
11. Kotagiri R, Kutti Sridharan G. Primary Polydipsia. [Updated 2022 Apr 30]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK562251/.
12. Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insuf-
ciency. Lancet Diabetes Endocrinol. 2015;3(3):216–226. https://doi.org/10.1016/
S2213-8587(14)70142-1.

Chapter 24
Pheochromocytoma Misdiagnosed
asCOVID-19
AllisonFoster
Learning Objectives
By the end of this presentation, the clinician will be able to:
1. Discuss the clinical ndings associated with pheochromocytoma.
2. Enumerate the clinical ndings associated with COVID-19.
3. Apply the aforementioned knowledge to clinical scenarios.
4. Analyze the risk of misdiagnosis of pheochromocytoma.
5. Discuss the initial management of said conditions.
Introduction
Pheochromocytoma is an uncommon tumor of the adrenal medulla that secretes
catecholamines. It typically presents with hypertension, headaches, diaphoresis,
and palpitations, which may be constant or intermittent [1]. Those symptoms, however, are not specic and can be suggestive of a variety of other cardiac or pulmonary diseases. Therefore, the condition is frequently diagnosed late or misdiagnosed
[1, 2]. In those cases, it can become life-threatening [1, 2]. Symptoms are caused by
catecholamine overproduction, and the best diagnostic test is to measure metanephrines or normetanephrine in the urine [3]. It is managed with alpha-blockers, as well
as other appropriate treatments for hypertension and arrhythmias [3]. The denitive
and often curative treatment is surgery [3]. Excess catecholamines or adrenergic
agonists can lead to the development of cardiomyopathy [4, 5]. In fact, in many
cases, an underlying pheochromocytoma has been discovered in patients with cardiomyopathies even without characteristic symptoms of catecholamine excess [5].
A. Foster (*)
Icahn School of Medicine at Mount Sinai, New York, NY, USA
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
H. Tohid et al. (eds.), The Misdiagnosis Casebook in Clinical Medicine,
https://doi.org/10.1007/978-3-031-28296-6_24
157

158
A. Foster
COVID-19 is the most talked-about disease of 2020 and 2021 since it created a
global pandemic, the likes of which have not been seen in decades. It is spread
through the respiratory route, and it typically presents with a combination of upper
and lower respiratory symptoms, such as cough, shortness of breath, and fever [6].
Importantly, a number of atypical presentations of COVID-19 involving almost any
other organs and systems have been reported. Myocarditis is one of the most frequently reported ones [7, 8]. It typically presents with chest discomfort and dyspnea, although more dramatic presentations, including sudden cardiac death, can
occur [9]. Precise diagnosis often requires either advanced imaging, such as cardiac
MRI or even myocardial biopsy [8]. In patients suffering from COVID-19 who are
short of breath at baseline, the diagnosis of myocarditis may be delayed even further. Therefore, for a patient with acute shortness of breath and chest discomfort,
COVID-19 would likely be one of the rst differential diagnoses a clinician would
think about, while many will not even think about pheochromocytoma.
Clinical Case Presentation
A 42-year-old female presented to the emergency department with new-onset acute
shortness of breath. She had also experienced intermittent chest discomfort that she
could not describe any further, nausea, vomiting, and generalized malaise for several
days prior to this presentation. On physical exam, she was mildly febrile with a temperature of 38.2 °C (equivalent to 100.8°F), heart rate was 102 per minute, and
blood pressure was normal, but the patient desaturated on room air and was placed
on 12L of oxygen via OxyMask in order to achieve saturation of 97%. Initial lab
work was signicant for a white blood cell (WBC) count of 25,000/uL with lymphopenia. Troponin and pro-BNP were markedly elevated. Chest CT was signicant for
diffuse ground-glass opacities with septal thickening, a nding frequently associated
with COVID-19 pneumonia. EKG was signicant for ST depression in leads II, III,
and aVF.At the time, PCR testing for the SARS-CoV-2 virus took 48h, and patients
were typically treated for COVID-19 based on clinical ndings alone, pending
results of the nasal swab PCR.The patient was, therefore, diagnosed with COVID-19
pneumonia and COVID-19-related non-ST elevation myocardial infarction
(NSTEMI) . She was initially treated with broad-spectrum antibiotics for possible
secondary bacterial pneumonia and aspirin and heparin for NSTEMI.Corticosteroids
were not given. She was provided symptomatic treatment for COVID-19.
Interestingly, the PCR test for COVID-19 was negative. It was subsequently repeated
and returned negative again, so COVID-19 was ruled out as a differential diagnosis,
and another cause of pneumonia was suspected. In the meantime, pro-BNP continued trending up, tachycardia persisted, and the patient became hypotensive. An
echocardiogram was performed, which showed an ejection fraction of 25% with
segmental wall motion abnormalities. No previous echocardiograms were available,
but the patient-reported unlimited exercise tolerance and no history of chest pain or
dyspnea. A repeat CT scan was performed a week after the presentation, and

24 Pheochromocytoma Misdiagnosed asCOVID-19
ground-glass opacities mostly resolved, which supported the idea that the patient
had suffered from pneumonia that improved with treatment. At the time, the working
diagnosis became idiopathic acute heart failure. The patient started developing worsening volume overload. Overnight, 10 days after the admission, the patient complained of worsening abdominal discomfort, and the covering physician ordered a
CT scan of the abdomen which incidentally showed a mass in the left adrenal gland.
Blood pressure was on the lower end of the reference range throughout the hospitalization. Renin and aldosterone levels were within normal range.
Urine metanephrines were minimally elevated. Left adrenalectomy was performed, and the tissue biopsy conrmed the diagnosis of pheochromocytoma. All
symptoms resolved, and cardiac function returned to baseline 3 months after the
surgery. The patient was subsequently followed for a year and remained
symptom-free.
159
Differential Diagnosis
COVID-19– it is nowadays one of the most common respiratory infections that can
affect both upper and lower airways, with the most common symptoms being dyspnea, cough, and fever, although a number of nonspecic symptoms and atypical
presentations have been reported.
Myocarditis– inammation of the myocardium, frequently viral, presenting with
symptoms which can be confused for COVID-19, including shortness of breath
and cough.
Pheochromocytoma– tumor of the adrenal medulla that secretes catecholamines
and presents with constant or intermittent hypertension, headache, and
palpitations.
Alternative Diagnoses
Due to the similarity of the clinical presentation and high prevalence of COVID-19in
the general population, the patient had been initially diagnosed with COVID-19
based on the clinical picture and missed the actual diagnosis of pheochromocytomainduced myocarditis.
Discussion
This case clearly illustrates many of the issues faced by providers in clinical practice. Initially, the patient presented with nonspecic symptoms, which could be
explained by a number of different cardiovascular or pulmonary conditions. At the
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