Adenoma mimicking hyponatremia of SIAD

Abstract

Hyponatremia is a common electrolyte disorder, with prevalence as high as 20% in inpatient settings. It is classified based on volume status, urine sodium and osmolality results. While this approach might help narrow down the differential diagnoses, it can leave other diagnoses unentertained. In this case, we report recurrent and refractory hyponatremia secondary to hypocortisolism due to non-functioning pituitary macroadenoma. Interestingly, urine studies mimicked syndrome of inappropriate antidiuresis, but exclusively responded to hydrocortisone replacement. Hospital course was also complicated by hyponatremia-induced rhabdomyolysis, which is a rare complication of severe hyponatremia. We also discuss the role of anchoring heuristics and how they influence the physician’s decision leading to possible diagnostic errors. One way to minimise the effect of anchoring bias on physicians is their cognitive awareness of such bias. In addition, discussing complicated cases with all members of medical team can highlight the clinician’s thought processes, share uncertainty and help broaden differential diagnoses.

Background

Hyponatremia is a common electrolyte disorder with prevalence as high as 20% in inpatient settings. It is commonly classified based on volume status and urine study results in order to identify possible aetiologies. While this approach might help narrow down the differential diagnoses, it can leave possible diagnoses undiscovered. In this report, we present a case of recurrent and refractory hyponatremia secondary to a non-functioning pituitary macroadenoma. However, urine studies mimicked syndrome of inappropriate antidiuresis (SIAD) on presentation. We also discuss the role of anchoring heuristics and how they influence the physician’s decision leading to possible diagnostic errors.

Case presentation

A 50-year-old man with a previous admission for hyponatremia attributed to possible gastroenteritis presented with muscle aches over 3 days. Patient also reports diffuse abdominal pain, as well as light-headedness and weight loss of 6–7 lbs over 4 weeks. Patient denies any associated emesis, diarrhoea, fever or chills.

Patient’s history is significant for hyperlipidaemia, treated with atorvastatin. Patient was also previously admitted to the hospital 10 months prior to this presentation due to hyponatremia (sodium (Na) 121 mmol/L), which was felt to be secondary to gastroenteritis at that time and resolved following volume expansion with normal saline. In regard to his social history, patient works in construction business. He denies any tobacco, alcohol or drug use. He is married and has four children.

Investigations

Workup on admission revealed Na 118 mmol/L, chlorine 86 mmol/L. CPK 2447 u/L, urine osmolality 637 mOsm/kg and urine Na 151 mg/dL. Thyroid stimulating hormone (TSH) level was 1.2 uIU/mL. Given evidence of rhabdomyolysis on presentation, gentle volume expansion with normal saline was administered. However, both hyponatremia and rhabdomyolysis worsened (Na 113 mmol/L and CPK 3831 u/L). Urine studies suggested SIAD (table 1) which was then managed with 3% saline infusion and fluid restriction, but did not result in any improvement in Na levels. Further workup revealed low free and total cortisol (2.7 ug/dL, 0.17 ug/dL, respectively). On further questioning, patient did report a remote history of a brain tumour diagnosed in 2006 that was lost to follow-up. Brain MRI showed a pituitary tumour measuring 4.2×3.2×3.0 cm extending into the cavernous and sphenoid sinuses and displacing the optic chiasm (figure 1). Further hormonal workup revealed pan-hypopituitarism adrenocorticotropic hormone (ACTH) <0.5 pg/mL, luteinising hormone (LH) 1.9 IU/L, follicle stimulating hormone (FSH) 3.3 IU/L and insulin-like growth factor 1 52 ng/dL and prolactin 21 ng/mL (table 1).

Table 1.

Results of urine studies as well as hormonal workup performed

Test	Lab value	Reference range
Urine osmolality	637 mOsm/L	250–900 mOsm/L
Urine sodium	151 mg/dL	40–220 mg/dL
Serum creatine kinase	3831 u/L	39–308 u/L
Serum thyroid stimulating hormone	1.2 mIU/L	0.5–4.5 mIU/L
Serum free thyroxine	0.92 ng/dL	0.7–1.8 ng/dL
Serum free triiodothyronine	1.67 pg/mL	2.18–3.98 pg/mL
Serum morning cortisol	2.7 ug/dL	4.3–22.4 ug/dL
Serum adrenocorticotropic hormone	<0.5 pg/mL	<46 pg/mL
Serum follicle stimulating hormone	3.3 IU/L	0.7–10.8 IU/L
Serum luteinising hormone	1.9 IU/L	1.5–9.3 IU/L
Serum total testosterone	121 ng/dL	241–827 ng/dL
Serum insulin-life growth factor 1	52 ng/dL	59–201 ng/dL
Serum prolactin	21 ng/mL	2.5–17.4 ng/mL

Note the inappropriately normal thyroid stimulating hormone level in the setting of low free triiodothyronine, as well as undetectable adrenocorticotropic hormone levels with low morning serum cortisol levels. Gonadotrophs were also affected.

Figure 1.

​MRI of the brain performed without using intravenous contrast. (A) Image represents T2-axial plane. (B) Image represents T1-sagittal plane. Note the large pituitary tumour in both images.

Differential diagnosis

1. SIAD.

2. Hypovolemic hyponatremia.

3. Hypocortisolism.

4. Neoplasm leading to hyponatremia.

Treatment

Hydrocortisone 50 mg intravenously twice daily was started with significant improvement in sodium levels over 48 hours (113->125->134 mmol/L) and was later reduced to physiologic dosing. Trans-sphenoidal hypophysectomy was performed and pathology results post-op revealed a non-functioning adenoma.

Outcome and follow-up

Patient was seen 1 month following his surgery and was doing well, requiring only hydrocortisone and testosterone replacement post-op.

Discussion

Hyponatremia is a common abnormal lab findings in both inpatient and outpatient settings, with SIAD being the most common cause of hyponatremia in hospitalised patients.¹ Fluid restriction or hypertonic saline infusion in severe cases is the cornerstone treatment of SIAD. Adrenal insufficiency is a rare cause of euvolemic hyponatremia. In this article, we present a case of large pituitary adenoma leading to compression mass effect and diminished secretion of ACTH, thus resulting in hypocortisolism. Interestingly, urine studies including urine osmolality and sodium levels mimicked SIAD (high osmolality and elevated urine sodium), but exclusively responded to hydrocortisone replacement. The exact mechanism by which adrenal insufficiency cause hyponatremia remains unclear. Current evidence suggests that hypocortisolism decreases free water clearance throughout the renal tubule by a direct, antidiuretic hormone independent effect.² Different electrolyte disturbances have been described in the setting of hypopituitarism. Liamis et al reported a prevalence of 15% of at least one electrolyte disorder in patients with hypopituitarism, with hyponatremia (7.7%) and hypernatremia (3.4%) being the most common.³

What is also worth noting in this case is the presence of hyponatremia-induced rhabdomyolysis, which is a relatively rare disorder associated with severe hyponatremia. It is accepted that low sodium levels lead to dysfunction of the sodium/calcium pump, which can activate intracellular proteases and lipases that are responsible for lysis of rhabdomyocytes.⁴ Of note, rhabdomyolysis significantly improved within 48 hours following correction of hyponatremia.

While reflecting back, one cannot help but ask, ‘why was the diagnosis of hypocortisolism not entertained earlier?’. Most of physician’s heuristics rely on anchoring bias, which is the common human tendency to use the first piece of information offered when making decisions. Errors occur when seeking only as much information as necessary to form an initial clinical impression, or by sticking with the initial impression even when new information is available.⁵ For example, our patient’s symptoms on previous admission were attributed to gastroenteritis and treated as such. Whereas hyponatremia on this admission was attributed to SIAD, a diagnosis that can not be pursued without ruling out adrenal and thyroid aetiologies, including hypothyroidism and hypocortisolism. Urine studies served as a confirmatory tool for the clinicians, feeding into anchoring bias and leading to further delay of appropriate workup. In medical literature, Jessani et al described selective serotonin reuptake inhibitor-induced SIAD as another common confounder that can mask hyponatremia of hypocortisolism in patients with psychiatric history. Furthermore, lack of hyponatremia normalisation following first-line treatment should prompt physicians to pursue further workup for alternative diagnoses, as it has been described as an independent prognostic factor of survival in patients with known malignancies.⁶ One way to minimise the effect of anchoring bias on physicians is their cognitive awareness of such bias. In addition, discussing complicated cases with all members of medical team can help highlight the clinician’s thought processes and help broaden differential diagnoses.⁷

Learning points.

• Differential diagnosis of hyponatremia is broad and can be misleading.

• Hypocortisolism can mimic hyponatremia of syndrome of inappropriate antidiuresis.

• Hyponatremia-induced rhabdomyolysis is a relatively rare disorder associated with severe hyponatremia.

• Increasing physician’s awareness of anchoring bias can help minimise its effect.