Background
Hyponatremia is one of the commonly presenting electrolyte abnormalities, especially in elderly people [1]. There is a wide spectrum of differentials for hyponatremia but it can be an important clinical presentation of pituitary disease when we taper-off our differentials and it indicates the steroid deficiency which can often be so severe that it can be life-threatening. Miljic et al. [2] reported that in the older age group, non-functioning pituitary adenoma (NFPA) is the most common cause of hypopituitarism complicated by hyponatremia. It is a very rare phenomenon that hypopituitarism secondary to pituitary adenoma can present with hyponatremia [3]. Nowadays, we can easily diagnose pituitary adenomas in the older age group because of increased life expectancy and improved diagnostic, as well as management systems. Diagnosis of pituitary adenoma can often be difficult in elderly patients because of modifiers of clinical presentation like age-related changes and associated diseases [4].
Pituitary adenomas are a benign neoplasm of the pituitary gland. Most pituitary adenomas are non-functioning (NFPA) and do not cause pituitary hypersecretory syndrome by clinical and laboratory evaluation and these are usually macroadenomas [5]. By overall estimation in general population, the prevalence of pituitary adenoma is about 10% and clinically non-functioning macroadenomas account for about 80% of all pituitary macroadenomas [6].
The most common complaint of patients with NFPA is a headache. Others include visual field defects with or without decreased visual acuity, features of hypopituitarism, or rarely hyponatremia. Typically, macroadenomas causes bitemporal hemianopia (also known as tunnel vision), which can be explained by the mass effect of tumor on visual pathways in optic chiasm [5]. Among all, hyponatremia is the most alarming and life-threatening presentation, especially in elderly people [6].
Diagnostic tools include baseline laboratory evaluation, hormonal assays for hormonal hypersecretion or hypopituitarism, and imaging techniques [7]. Pituitary adenomas are best evaluated by MRI brain with contrast [6].
Treatment in patients with hypopituitarism caused by NFPA is with steroid and hormone replacement which can completely recover symptoms such as hyponatremia [8].
Trans-sphenoidal endoscopic endonasal surgery is a safe, effective, and the first-line treatment for pituitary adenomas, especially in elderly patients for both symptom control and better functional outcomes [9]. With the use of improved peri-operative care, the technique used in trans-sphenoidal surgery is associated with good outcomes, minimal morbidity, and generally well tolerated by patients of all age groups [10]. A wait-and-see approach may be adopted in non-functioning pituitary macroadenomas not encroaching or involving the optic chiasm. Postoperative radiotherapy should be individualized according to patients after a surgical procedure but can be considered in patients having large post-operative remnants of the tumor. Careful examination, laboratory evaluation, and replacement of pituitary insufficiencies should be considered during follow-up of the patient. Magnetic resonance imaging of the brain is advised with an interval of 1–3 years [6].
While comparing endoscopic endonasal and microscopic trans-sphenoidal surgery, endoscopic endonasal surgery has a better outcome and complete cure on follow-up [11].
We present one such case where it was challenging to diagnose pituitary adenoma in a patient who presents simply with hyponatremia.
Case Report
A 61-year-old female who was diagnosed 1 year back as hypothyroid was on thyroxine for 4 months but she left her medication without consulting her endocrinologist. This time she presented in Hospital Emergency Department with the history of vomiting, drowsiness, and fatigue for the last 2 days before presentation. There was no history of fever, headache, loss of consciousness, fits, or diarrhea. On examining the patient, she was drowsy but arousable and maintaining her vitals i.e.: Bp 125/82 mmHg, pulse 79/minute, afebrile, oxygen saturation 98% at room air, R/R 16/minute, jugular venous pressure (JVP) not raised, no signs of dehydration, or pedal edema. On central nervous system (CNS) examination, Glasgow coma scale (GCS) was 14/15 with no neurological deficit or signs of meningeal irritation, all other systemic examination was unremarkable. On investigating, complete blood picture, liver function test, renal function tests, urine R/E, and chest X-rays were normal. Serum electrolytes showed sodium levels of 112 mEq/l, potassium and chloride were normal. We made the impression of euvolemic hyponatremia in the presence of a background of untreated hypothyroidism. We started counting the differentials of the syndrome of inappropriate ADH secretion, untreated hypothyroidism or hypopituitarism and requested her following labs:
| Tests requested | Values | Impression |
|---|---|---|
| fT3 | 1.04 nmol/l | Low |
| fT4 | 11.01 pmol/l | Low |
| TSH | 3.44 mIU/l | Low |
| Serum osmolarity | 259 mOsm/kg | Low |
| Urine osmolarity | 288 mOsm/kg | Normal |
| Urinary sodium | 88 mEq/day | Normal |
| FSH | 3.33 mIU/ml | Low |
| LH | 0.59 mIU/ml | Low |
| Prolactin | 544 mIU/l | Normal |
| Estrogen | 10 pg/ml | Low |
| Progesterone | 0.01ng/ml | Low |
Post-contrast T1 brain MRI image, coronal view, showing a pituitary adenoma, showing suprasellar extension. The indent at diaphragm sellae is giving it a “snow-man” configuration, which is a differentiation between pituitary macroadenoma and meningioma.
Post-contrast T1 brain MRI images, sagittal view showing pituitary macroadenoma, suprasellar component of this lesion is elevating optic nerves and optic chiasm with stretching.
In view of these labs, we made the impression of secondary hypothyroidism or adrenal insufficiency and both coming under the umbrella of hypopituitarism. We gave her 3% saline and intravenous steroids and after that gave her thyroxine 100 μg once daily. Patient dramatically responded to this treatment within 24 hours and her GCS became 15/15. Serum sodium came up to 135 mEq/l. we further wanted to explore the cause of hypopituitarism and did the MRI brain with contrast which showed that sella was markedly enlarged and expanded, pre- and post-contrast dynamic thin section study of sella and pituitary shows sella to be occupied by 4.0 × 4.2 × 3.3 cm [transverse view (TR) × cranio-caudal view (CC) × antero-posterior view (AP)], intra- and supra-sellar mass lesion. Suprasellar component of this lesion is elevating optic nerves and optic chiasm with stretching. Pituitary stalk is not well delineated and is elevated and stretched.
In short, we would like to conclude our case as a non-functioning pituitary macroadenoma, which presented with hypopituitarism complicated by hyponatremia and was treated with hormone replacement therapy and hypertonic saline.
Discussion
Our patient was finally diagnosed as having a non-functional pituitary adenoma revealing itself as hyponatremia. The diagnosis was based on a high index of suspicion, laboratory investigations, and tapering off our differentials. She was a middle-aged lady in her early sixties, having no established pre-morbids and presented with hyponatremia. All pituitary hormonal assays were low and MRI brain gave us confirmation of our diagnosis. Most of the cases published, to date, showed that the patients were in their seventh decade of their life [3,5,9]. Also, they presented mostly with common symptoms like headache, visual impairments, or with symptoms of panhypopituitarism [4,5,7]. Our patient had certain distinct clinical features, including her age of early 60s, no clinical signs of panhypopituitarism, and presented with hyponatremia which is a very rare entity of this disease. So far, very few cases have been reported in the literature in which hyponatremia is the only presenting feature which leads to the diagnosis [3,8,12].
She was treated successfully with 3% saline, intravenous steroids, and hormone replacement therapy. Treatment response was obtained after 24 hours. In most of the cases, the patient needs the only treatment with steroids and hormone replacement [1,8,12]. Surgical intervention is needed only in those cases, in whom adenoma compresses the optic chiasm and causing distressing symptoms.
Conclusion
Hyponatremia can be the leading manifestation of hypopituitarism. It can be the first presenting feature before other common symptoms of pituitary macroadenoma appear, but it is rare and can be life-threatening.
Our patient was diagnosed as having NFPA depending on the high index of suspicion for clinical presentation and she was successfully treated with steroids and hormonal replacement therapy. Hypopituitarism can be easily diagnosed but the key to diagnosis is strong clinical suspicion. Hormone assays should be included in the initial diagnostic workup of hyponatremia, especially in elderly people.