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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

138
B. H. Malik and M. S. Hameed
Conclusion
Acute adrenal crisis caused by Addison’s disease that manifests as acute renal failure with hyperkalemic paralysis is highly uncommon and can cause a misdiagnosis.
In such circumstances, physicians should rule out adrenal insufciency because in
such cases hyperkalemia can be resistant to standard modes of therapy and can lead
to arrhythmias if identication is delayed.
References
1. Connor A, Care S, Taylor J. Addison’s disease and acute kidney injury. Clin Med.
2010;10(5):515–6.
2. Maki S, Kramarz C, Maria Heister P, Pasha K.First presentation of Addison’s disease as hyper-
kalemia in acute kidney injury. BMJ Case Rep. 2016;2016:bcr2015213375.
3. Fo C, Maresca B, Altieri S, Menè P, Festuccia F.Renal involvement in adrenal insufciency
(Addison disease): can we always spot it? Intern Emerg Med. 2020;15(1):23–31.
4. Michels A, Michels N.Addison disease: early detection and treatment principles. Am Fam
Physician. 2014;89(7):563–8.
5. Cannon S. Sodium channelopathies of skeletal muscle. Handb Exp Pharmacol. 2017;246:
309–30.
6. Hemachandra KHDT, Chandimal Dayasiri MBK, Kannangara T. Acute ascending accid
paralysis secondary to multiple trigger factor induced hyperkalemia. Case Rep Neurol Med.
2018;2018:1–4.
7. Panichpisal K, Gandhi S, Nugent K, Anziska Y.Acute quadriplegia from hyperkalemia: a case
report and literature review. Neurologist. 2010;16(6):390–3.

Chapter 21
Hypopituitarism Secondary
toMacroadenoma withVomiting
andHyponatremia Misdiagnosed
asEpisodes ofGastritis/Esophagitis
BilalHaiderMalik andMominaShahidHameed
Learning Objectives
By the end of this presentation, the clinician will be able to:
1. Analyze common presentations with unusual rare diagnoses.
2. Identify central causes of common symptoms like nausea and vomiting.
3. Discuss pathophysiological processes behind space occupying lesions in
the brain.
4. Enumerate metabolic changes arising secondary to macroadenoma.
5. Identify pathophysiology behind electrolyte imbalances due persistent nausea
and vomiting secondary to central space occupying lesions.
Introduction
Recurrent vomiting is a debilitating condition that has a substantial negative inuence on one’s quality of life. Vomiting can be caused by a variety of factors, ranging
from well-known to uncommon. Visual abnormalities, headaches, and signs of anterior pituitary hormone shortages are common symptoms of nonfunctioning pituitary
macroadenomas. The patient came with recurrent vomiting and acute hyponatremia, which was an uncommon presentation of a nonfunctioning pituitary macroadenoma. In the sellar area, a common type of tumor is a clinically nonfunctioning
pituitary adenoma [1]. Nonfunctioning pituitary adenomas have an incidence of
60–100 occurrences per million people [1, 2]. The incidence rate is 1.02–1.08 per
B. H. Malik (*)
Dermatology, Betsi Cadwaladr University Health Board, Mold, Wales
M. S. Hameed
Partner GP, Strathmore Medical Practice, Wrexham, Wales
© 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_21
139

140
B. H. Malik and M. S. Hameed
100,000 [1, 2]. It has a bimodal peak incidence between the ages of 25–45years and
60–70years. Both men and women are affected equally [1, 2]. These lesions are
typically discovered by chance (mostly microadenoma) or identied due to signs
and symptoms of anterior pituitary hormone insufciency, as well as compressive
symptoms such headache and vision eld abnormalities [1]. In our case patient had
been suffering from cyclical vomiting for 2 years. There are a variety of reasons
behind this vomiting. Vomiting frequently throws off the body’s acid-base and electrolyte balance. Our example demonstrates that frequent clinical presentations and
investigative abnormalities might be caused by rare etiologies. Identifying the correct etiology can save a person’s life. Intractable nausea and vomiting are seen in
patients with adrenal insufciency, according to a few case reports [3].
Nonfunctioning pituitary macroadenoma can present atypically with cyclical vomiting. The case demonstrates that organic pathology should be investigated despite
the presence of multiple psychosocial difculties, instead of linking the symptoms
to a psychiatric disorder. As a result, we chose to share our clinical expertise by
reporting this case.
Clinical Case Presentation
A 35-year-old female presented to the emergency department (ED) after experiencing many episodes of vomiting for the last 4 days. She had 7–8 episodes of vomiting
each day, which were accompanied by scorching chest discomfort and regurgitation. Vomiting was not a projectile, bilious, or fecal occurrence. Hematemesis was
not present. Fever, stomach discomfort, dysuria, abdominal distention, or changed
bowel habits were not seen. She did, however, complain of a loss of appetite and
overall bodily weakness for the past 3 years, as well as symptoms of dizziness. She
denied experiencing photophobia, headaches, vision problems, or weight loss as a
result of the treatment. Further examination of her medical history revealed that she
had repeated hospital trips in the previous 3 years owing to similar types of recurrent vomiting episodes. These episodes always started with a quick onset of nausea,
followed by vomiting that lasted for 3 days. Every day, there were seven instances
of nausea along with vomiting. She was treated by her general practitioner for these
episodes of vomiting with prokinetics, antiemetics, and proton pump inhibitors
without being thoroughly evaluated. She was otherwise leading a normal life. The
rst episode took place 3 years prior. Initially, these episodes of nausea and vomiting were less frequent, with only three occurrences every 4 months, but these symptoms had progressed to be more frequent recently. She rejected excessive exercise,
as well as any medication intake to reduce weight, all of which can be seen in eating
disorders. She had no preconceptions about body image distortion. She refused to
drink a considerable amount of water. Polyuria, polydipsia, and nocturia were not
present. She had reached menarche at the age of 12. She didn’t have galactorrhea.
She had been prescribed anxiolytics for a 5-year period following the end of her
relationship. The anxiolytics were only used for a month. She revealed that her

21 Hypopituitarism Secondary to Macroadenoma with Vomiting and Hyponatremia…
141
mother died 7 years ago from an astrocytoma. Her stepmother, siblings, and father
all lived with her. Her GCS was 15/15. Her BMI was only 16kg/m2. Her blood pressure was 85/55mmHg and her heart rate was 94 beats per minute. There were no
parotid enlargement, dental cavities, brittle hair, or erosions over the knuckles of the
hands, which are all symptoms of eating disorder. The rest of her systems examination was normal. On admission, her blood glucose level was normal at 77mg/
dL.The hemoglobin, platelet count, white cell count, serum albumin, alkaline phosphatase, liver transaminases, total bilirubin level, and serum amylase level were all
within acceptable limits. Her urine analysis, ECG, and X-ray all came out unremarkable. Her pregnancy test (ẞHCG) was negative. CRP and ESR were also normal. Her serum electrolyte levels, on the other hand, were signicantly out of
whack. Her sodium level in her blood was 120mmol/L.Serum potassium and chloride were 2.9mmol/L and 69mmol/L, respectively. Serum electrolyte levels were
consistently low. Respiratory alkalosis was detected on arterial blood gas measurement. Her urea level in her blood was normal. The creatinine level in the blood was
44.9mol/L.The osmolality of the blood was 221mOsm/kg, while the osmolality of
the urine was 264 mosm/kg. Daily urine production averaged 1230ml. Urinary
electrolyte tests revealed low potassium and sodium levels in the urine. The chloride
level in urine was 22mmol/L.The electrolyte abnormalities that were discovered
were thoroughly investigated. Her random blood cortisol level was low when she
was admitted. TSH was 0.26 IU/mL, free triiodothyronine (T3) was 1.44 pg/mL,
and normal free tetraiodothyronine (T4). Her luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels were also low. A hypoplastic uterus was discovered during an ultrasound abdomen check. The ultrasound scan of the abdomen
revealed no additional abnormalities. Her prolactin level was revealed to be somewhat higher than normal. The level of serum prolactin was 73ng/mL and 90.8ng/
mL following a 5:1 dilution. She had hypothyroidism, hypoadrenalism, mild hyperprolactinemia, and hypogonadotropic hypogonadism in her biochemistry. An MRI
of the pituitary was performed to further investigate her hypothalamic- pituitary
axis. MRI scan revealed a mass occupying the sellar and suprasellar areas, with
mass inuence on the optic tract and optic chiasma, optic tracts. Bitemporal hemianopia was seen on examination. Pituitary nonfunctioning macroadenoma with
mass effect was diagnosed, resulting in hypothyroidism, hypoadrenalism, hyperprolactinemia, and hypogonadotropic hypogonadism. She was given antiemetics when
she was admitted. Vomiting-induced volume loss was replenished with the same
amount of uid given via oral route. Because she seemed to tolerate low levels of
serum sodium, we diagnosed her with chronic hyponatremia. As a result, aggressive
care of hyponatremia was avoided. Suspecting hypoadrenalism, a 100mg intravenous hydrocortisone was given, followed by 50 mg intravenous hydrocortisone
every 6h. Vomiting was assumed to be the cause of low serum chloride and potassium levels, which were rectied following oral hydration. Due to stress induced
hyperventilation, she developed respiratory alkalosis. The patient was commenced
on levothyroxine. Her serum sodium level stabilized around 134mmol/L 4 days
following hormone replacement. Her vomiting had subsided. Her appetite and
widespread body weakness both improved signicantly. After 21days of treatment,

142
hydrocortisone was switched to oral route, and the patient’s condition improved
even more. Four weeks following the diagnosis, the pituitary tumor was removed
via transsphenoidal resection. A pituitary adenoma was discovered in histology. She
was discharged with a daily dose of hydrocortisone and levothyroxine.
B. H. Malik and M. S. Hameed
Differential Diagnosis
1. Functional causes of vomiting– Self-induced vomiting can mimic such presentation and need a keen observing physician to decipher such a cause.
2. Psychiatric illness– Psychiatric causes are becoming more prevalent in the current medical landscape and must not be discounted.
3. Stress– Different lifestyle choices can have an impact on different psychosocial
reactions manifested by the patients.
4. Multiple concomitant endocrinopathies– Endocrinopathies can be challenging
to diagnose as one can mimic the other with similar signs and symptoms so need
to be investigated thoroughly.
Alternative Diagnosis/Potential Misdiagnosis
1. Gastritis
2. Esophagitis
Note
Patient was initially treated for gastritis and functional causes were considered.
Finally the right diagnosis was made after detailed evaluation. No legal
proceedings.
Discussion andAction Plan
Pituitary tumors are responsible for 15.5% of all central nervous system (CNS)
neoplasms [1, 4]. Pituitary adenomas are responsible for 30% of CNS malignancies
in young adults (20–34years) [1, 4]. Nonfunctioning pituitary adenomas make up
around a third of all pituitary adenomas, which is less than prolactinomas, which
make up about half of all pituitary adenomas [1, 5]. Pituitary adenomas that aren’t
working. Pituitary macroadenomas are the most prevalent type of pituitary tumor
[1]. In 60–80% of instances, their symptoms and signs are caused by anterior

21 Hypopituitarism Secondary to Macroadenoma with Vomiting and Hyponatremia…
143
pituitary hormone insufciency and mass inuence on neighboring structures, particularly the optic chiasma [1, 2]. One or more anterior pituitary hormone decits
are found in the majority of patients with nonfunctioning pituitary adenomas [1, 6,
7]. Two or more hormone decits affect more than 20% of patients with nonfunc-
tioning pituitary adenoma [1, 6]. Hypogonadotropic hypogonadism affects 40–75%
of individuals with a nonfunctioning pituitary adenoma, and central hypothyroidism
and hypocortisolism affect 20–40% of cases [1, 6]. Due to the tumor compressing
the pituitary stalk and disrupting the descending dopaminergic effects, moderate
hyperprolactinemia (100 mg/mL) can occur [1]. Pituitary apoplexy can occur in
8–10% of pituitary adenomas [6]. The patient in this case had unusual symptoms of
a nonfunctioning pituitary macroadenoma. She had recurrent episodic vomiting.
The patient had generalized body weakness with loss of appetite, which could be
generic hypoadrenergic symptoms. Our patient experienced a variety of psychological concerns, including the loss of her mother at a young age and the end of a relationship recently. The patient linked the onset of all of her symptoms to the
dissolution of her relationship, which occurred shortly after she started university.
Having a number of psychosocial issues may cause clinicians to deviate from the
proper diagnosis path. Although there may have been coexisting psychological difculties, it is necessary to rule out organic factors before making a psychological
diagnosis. This case emphasizes the signicance of ruling out organic factors before
reaching a psychiatric conclusion. Another uncommon symptom of a nonfunctioning pituitary macroadenoma was severe hyponatremia, as seen in this patient. With
a history of recurrent vomiting, it’s easy to mistake vomiting for the source of the
electrolyte imbalance. Because there can be several underlying etiologies for an
electrolyte imbalance, this instance emphasizes the signicance of thoroughly analyzing it. When examining chronic or persistent hyponatremia, a high index of suspicion is required [8]. Hyponatremia is dened as a sodium level in the blood that is
less than 135mmol/L.When serum sodium falls below 125mmol/L, severe hyponatremia develops, which is linked to increased morbidity and death [8] and must be
investigated thoroughly. Secondary hypoadrenalism rather than central hypothyroidism is the commonest cause of hyponatremia caused by hypopituitarism [9]. In
the absence of normal cortisol action in the kidney, hyponatremia related to secondary hypoadrenalism is produced by reduced electrolyte-free water excretion [9].
Higher secretion of arginine vasopressin, a secondary adrenocorticotropic hormone
(ACTH) secretagogue, results in increased urine concentration and can worsen
hyponatremia [9]. Hypothyroidism causes changes in renal perfusion and a reduction in glomerular ltration. The inability to eliminate free water causes hyponatremia in hypothyroidism. The hormone arginine vasopressin has an effect on urine
dilution. Hypothyroidism produces hyponatremia because a lower glomerular ltration rate reduces water supply to the tubules, lowering free water excretion [9].
Patients with secondary hypoadrenalism are less prone to develop hyperkalemia
than those with primary hypoadrenalism since there is no mineralocorticoid decit.
Due to the persistent nature of our patient’s hyponatremia, she experienced limited
hyponatremic symptoms. However, the patient’s hyponatremia was exacerbated by
episodic vomiting and reduced salt intake, as seen by low serum chloride and

144
B. H. Malik and M. S. Hameed
potassium levels, as well as low urinary potassium and sodium levels. Her urine
production was normal, and she denied polydipsia and polyuria. Her plasma osmolality was low, but her urine osmolality was slightly higher. Her urea level in her
blood was normal. This prompted an investigation into the cause of hidden euvolemic
chronic hyponatremia. This led to the discovery of a pituitary macroadenoma
beneath the surface. Vomiting and a reduced salt intake were blamed for the low
serum potassium and chloride levels.
Conclusion
Although symptoms and signs of anterior pituitary hormone shortages and mass
effect on neighboring structures are common in nonfunctioning pituitary macroadenomas, they can sometimes show in unique ways. Atypical symptoms of nonfunctioning pituitary macroadenomas include cyclical vomiting and severe hyponatremia.
In a patient with recurrent vomiting and hyponatremia, numerous etiologies might
be found. The precise etiology can save a person’s life. When examining recurrent
vomiting with hyponatremia, a high level of suspicion is required.
References
1. Mercado M, Melgar V, Salame L, Cuenca D.Pathogenic, diagnostic, and therapeutic aspects
of clinically non-functioning pituitary adenomas. Endocrinol Diabetes Nutr (English ed).
2017;64(7):384–95.
2. Molitch ME. Pituitary incidentalomas. Best Pract Res Clin Endocrinol Metab.
2009;23(5):667–75.
3. Mandadi S, Sattar S, Towq B, Bachuwa G.A case of nausea and vomiting to remember. BMJ
Case Rep. 2015;2015:bcr2014207251.
4. Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C.CBTRUS statistical report:
primary brain and central nervous system tumours diagnosed in the US in 2008–2012. Neuro
Oncol. 2015;17(4):iv1–iv62.
5. Raappana A, Koivukangas J, Ebeling T, Pirila T.Incidence of pituitary adenomas in Northern
Finland from 1992 to 2007. J Clin Endocrinol Metab. 2010;95(9):4268–75.
6. Vargas G, Gonzalez B, Ramirez C, Ferreira A, Espinosa E, Mendoza V.Clinical characteris-
tics and treatment outcome of 485 patients with nonfunctioning pituitary. Int J Endocrinol.
2015;2015:756069.
7. Molitch ME.Diagnosis and treatment of pituitary adenomas. JAMA. 2017;317(5):516–24.
8. Pituitary macroadenoma presenting as severe hyponatremia: a case report. J Med Case Rep.
2019;13(1):40.
9. Verbalis JG, Goldsmith SR, Greenberg A, etal. Diagnosis, evaluation, and treatment of hypo-
natremia: expert panel recommendations. Am J Med. 2013;126(10):S1–S42.

Chapter 22
Hypothyroidism withNephrotic Syndrome
Misdiagnosed asCardiac Failure
BilalHaiderMalik andMominaShahidHameed
Learning Objectives
By the end of this presentation, the clinician will be able to:
1. Understand the relationship between nephrotic syndrome and hypothyroidism.
2. Apply the knowledge gained from the case in a clinical setting where appropriate.
3. Understand the pathophysiology of cardiac failure.
4. Apply the knowledge to understand pathophysiology behind presentations mim-
icking cardiac failure.
5. Understand pathophysiological changes in the body secondary to nephrotic
syndrome.
Introduction
The kidney and thyroid work together in a vital way to ensure that both organs operate properly. Thyroid is important for renal development and glomerular and tubular
processes; the kidney also engages in metabolism of thyroid hormone and disposal
[1, 2]. Thyroid function problems, particularly hypothyroidism, have long been
linked to chronic kidney disease (CKD) [3–7]. Thyroid function test results in this
clinical scenario are highly variable, based on renal disease’s severity [4, 5], as well
as the thyroid reserve and h/o thyroid disease previously [8], as well as other factors
(such as furosemide, glucocorticoids, or other drugs) [9]. Edema, proteinuria
(>3.5g/24h), hyperlipidemia, and hypoalbuminemia are all symptoms indicating
B. H. Malik (*)
Dermatology, Betsi Cadwaladr University Health Board, Mold, Wales
M. S. Hameed
Partner GP, Strathmore Medical Practice, Wrexham, Wales
© 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_22
145

146
B. H. Malik and M. S. Hameed
nephrotic syndrome (NS). Excessive excretion of urinary proteins which is because
of a signicant increase in glomerular permeability leading to urinary losses of
transthyretin, albumin, and thyroxine binding globulin (TBG) in addition to thyroxine (T4) and triiodothyronine (T3) [8, 10]. Furthermore, renal tubule damage can
coexist with free thyroid hormone reabsorption and compromise it [11]. In the
absence of thyroid disease previously, levels of free T4 and T3 (fT4 & fT3) remain
within acceptable ranges in the early stages of the NS, and we see euthyroid state
biochemically and clinically. In individuals with prolonged and severe proteinuria
and inadequate thyroid reserve, urinary losses of free and protein-bound thyroid
hormones are enough to cause subclinical hypothyroidism [2, 4, 5]. Regular changes
to replacement therapy doses is necessitated in patients who have previously
received hormone replacement therapy [2, 8, 11]. The use of immunosuppressive
medications and steroids in addition to euthyroid sick syndrome [9, 12] should be
considered while diagnosing and managing problematic NS patients. Several studies have been reported that relate hypothyroidism to NS patients, mainly in adolescents and patients with prior thyroid dysfunction [11, 13–16].
Clinical Case Presentation
A 41-year-old male had been checked by his primary care physician for mild shortness of breath and widespread edema with swelling of the face, belly, and legs. He
was a regular smoker. He had antiphospholipid syndrome and Raynaud’s phenomenon in the past. Except for the presence of excessive edema of the abdominal wall
and lower limbs, the physical examination was normal. His weight had increased by
15% in just 3 months, to 92kg. Cardiac failure was considered as a possible diagnosis by the junior member of the team. Proteinuria of 62g/L was detected in urine
and PCR (protein-to-creatinine ratio) of 17g/g. eBlood tests revealed low serum
protein levels of 3.5g/dL, low albumin levels of 1.9g/dL, and increased serum lipid
levels. Renal function was retained with serum creatinine: 0.82mg/dL, eGFR of
128mL/min/1.73m2. TSH level was 2.9 UI/mL.Except for inadequate corticomedullary differentiation, renal ultrasonography (US) revealed maintained anatomy of
the kidneys. The patient had a kidney biopsy, which revealed C3 glomerulonephritis. We initiated glucocorticoids in high doses and showed no response, so mycophenolate mofetil and cyclosporine were initiated. Over the next few days, severe
hypoalbuminemia, worsening renal function, and recurrent episodes of cellulitis
developed in the patient. Thyroid function tests revealed abnormalities 2 weeks
after his admission TSH, 18 UI/mL; total T4, 2g/dL; fT4, 0.24 g/dL; total T3,
0.5ng/mL; and fT3, 0.70pg/mL.There was no previous history of thyroid illness in
the patient. There were no nodules and no enlargement of thyroid gland found during the examination. Thyroid US indicated a homogeneous, regular, and slightly
enlarged, with no obvious nodular lesions. Serum anti-thyroglobulin and antithyroid peroxidase titers were also negative. Clinical hypothyroidism secondary to
nephrotic syndrome came up as a differential for this case, and oral levothyroxine

22 Hypothyroidism withNephrotic Syndrome Misdiagnosed asCardiac Failure
treatment was commenced and was gradually increased. Patient’s condition
remained unresponsive to immunosuppressive medication after 6 weeks in the hospital. The patient was recommended for bilateral nephrectomy due to steroid side
effects, recurring infections, and unresponsiveness to immunosuppression. The histology of the kidney showed focal segmental glomerulosclerosis. Thyroid function
tests 7days following surgery indicated TSH of 1.9 UI/mL, fT4 of 1.1g/dL, and fT3
of 1.8ng/dL (RR: 2.66–4.33), allowing the LT dose to be reduced. The patient was
seen to be biochemically and clinically euthyroid after discharge, with gradually
reduced LT dosage requirements. The patient has been on hemodialysis since bilateral nephrectomy, waiting for a kidney transplant.
147
Differential Diagnosis
1. Hypothyroidism – Hypothyroidism can present with lethargy, generalized
edema, and shortness of breath. Causes of hypothyroidism must be deciphered
to address the underlying pathology.
2. Cardiac Failure– Cardiac failure is a pertinent differential diagnosis with all the
signs and symptoms present.
3. Hypoproteinemia (Various Causes)– Hypoproteinemia is more common than
we think for these host of signs and symptoms seen in this case.
4. Glomerulonephritides/Nephrotic Syndrome– Renal failure chronic or acute can
present with above signs and symptoms and need to be dealt with in a
timely manner.
5. Vasculitides – Multisystem involvement can be a presentation of underlying
autoimmune processes like vasculitides.
Alternative Diagnosis Considered/Potential Misdiagnosis
1. Heart failure
2. Liver failure
Alternative diagnoses were considered, but correct diagnosis was made in light
of investigation results by the senior member of the team.
Discussion andPlan ofAction
T4 and T3 both are poorly water-soluble, and more than 99.5% of them circulate in
the blood attached to proteins: roughly 10% to prealbumin, 70% to TBG, and 20%
to albumin. Only modest quantities of free hormones are metabolically active in the
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