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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 insufciency because in such cases hyperkalemia can be resistant to standard modes of therapy and can lead to arrhythmias if identication 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 insufciency
(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 toMacroadenoma withVomiting andHyponatremia Misdiagnosed asEpisodes ofGastritis/Esophagitis
BilalHaiderMalik andMominaShahidHameed
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 inu­ence 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 25–45years and 60–70years. Both men and women are affected equally [1, 2]. These lesions are typically discovered by chance (mostly microadenoma) or identied due to signs and symptoms of anterior pituitary hormone insufciency, 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 insufciency, 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 difculties, 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 16kg/m2. Her blood pres­sure was 85/55mmHg 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 77mg/ 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 signicantly out of whack. Her sodium level in her blood was 120mmol/L.Serum potassium and chlo­ride were 2.9mmol/L and 69mmol/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
44.9mol/L.The osmolality of the blood was 221mOsm/kg, while the osmolality of
the urine was 264 mosm/kg. Daily urine production averaged 1230ml. Urinary electrolyte tests revealed low potassium and sodium levels in the urine. The chloride level in urine was 22mmol/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 73ng/mL and 90.8ng/ 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 inuence 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 100mg intrave­nous hydrocortisone was given, followed by 50 mg intravenous hydrocortisone every 6h. Vomiting was assumed to be the cause of low serum chloride and potas­sium levels, which were rectied following oral hydration. Due to stress induced hyperventilation, she developed respiratory alkalosis. The patient was commenced on levothyroxine. Her serum sodium level stabilized around 134mmol/L 4 days following hormone replacement. Her vomiting had subsided. Her appetite and widespread body weakness both improved signicantly. After 21days 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 andAction 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 (20–34years) [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 insufciency and mass inuence on neighboring structures, par­ticularly the optic chiasma [1, 2]. One or more anterior pituitary hormone decits are found in the majority of patients with nonfunctioning pituitary adenomas [1, 6,
7]. Two or more hormone decits 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 dif­culties, it is necessary to rule out organic factors before making a psychological diagnosis. This case emphasizes the signicance 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 signicance of thoroughly ana­lyzing it. When examining chronic or persistent hyponatremia, a high index of sus­picion is required [8]. Hyponatremia is dened as a sodium level in the blood that is less than 135mmol/L.When serum sodium falls below 125mmol/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 decit. 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
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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, Towq 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, etal. Diagnosis, evaluation, and treatment of hypo-
natremia: expert panel recommendations. Am J Med. 2013;126(10):S1–S42.
Chapter 22
Hypothyroidism withNephrotic Syndrome Misdiagnosed asCardiac Failure
BilalHaiderMalik andMominaShahidHameed
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 (>3.5g/24h), 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
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B. H. Malik and M. S. Hameed
nephrotic syndrome (NS). Excessive excretion of urinary proteins which is because of a signicant 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 92kg. Cardiac failure was considered as a possible diag­nosis by the junior member of the team. Proteinuria of 62g/L was detected in urine and PCR (protein-to-creatinine ratio) of 17g/g. eBlood tests revealed low serum protein levels of 3.5g/dL, low albumin levels of 1.9g/dL, and increased serum lipid levels. Renal function was retained with serum creatinine: 0.82mg/dL, eGFR of 128mL/min/1.73m2. 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, 2g/dL; fT4, 0.24 g/dL; total T3,
0.5ng/mL; and fT3, 0.70pg/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 withNephrotic Syndrome Misdiagnosed asCardiac 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 7days following surgery indicated TSH of 1.9 UI/mL, fT4 of 1.1g/dL, and fT3 of 1.8ng/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 andPlan ofAction
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