Journal of Postgraduate Medicine, Education and Research
Volume 57 | Issue 3 | Year 2023

Refractory Hyponatremia as an Initial Presentation of Panhypopituitarism with Partial Empty Sella

Deepak Thakran1, Yogesh Kumar2, Amit S Nachankar3

1Department of Medicine, Military Hospital Ramgarh, Jharkhand, India

2Department of Endocrinology, Base Hospital, Delhi, India

3Department of Endocrinology, Army Hospital Research and Referral, Delhi, India

Corresponding Author: Amit S Nachankar, Department of Endocrinology, Army Hospital Research and Referral, Delhi, India, Phone: +91 9599386195, e-mail:

Received on: 10 March 2021; Accepted on: 15 May 2023; Published on: 26 July 2023


Introduction: Hyponatremia of varying severity is a fairly common disorder of water homeostasis encountered in the practice of internal medicine and has a variety of etiologies. Here we present a case of refractory hyponatremia secondary to an uncommon endocrine disorder.

Case description: Our patient, a 55-year-old woman with a known case of hypothyroidism for 5 years, presented with complaints of moderate, symptomatic, and persistent hyponatremia. An evaluation revealed chronic euvolemic hyponatremia refractory to 3% saline. Further workup to rule out the syndrome of inappropriate antidiuretic hormone (SIADH) revealed panhypopituitarism with partial empty sella (PES).

Discussion: Though usually not associated with any hormonal deficiency, rarely PES is associated with a deficiency of one or more pituitary hormones. Equally rare is the syndrome of euvolemic hyponatremia secondary to empty sella syndrome with hypopituitarism. Panhypopituitarism can have life-threatening consequences if left undiagnosed and untreated.

Conclusion: In any case of euvolemic hyponatremia, it is important to work up for hypopituitarism as a rare cause before ruling in SIADH.

How to cite this article: Thakran D, Kumar Y, Nachankar AS. Refractory Hyponatremia as an Initial Presentation of Panhypopituitarism with Partial Empty Sella. J Postgrad Med Edu Res 2023;57(3):137–139.

Source of support: Nil

Conflict of interest: None

Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.

Keywords: Case report, Empty sella, Hyponatremia, Hypopituitarism.


Hyponatremia is one of the commonest electrolyte disorders encountered in internal medicine. Patients with hyponatremia can present with a variety of mild to severe symptoms ranging from nonspecific lethargy, fatigue, and nausea to life-threatening seizures and coma. Etiological diagnosis of hyponatremia requires a thorough evaluation, which is often challenging and sometimes cumbersome.

Hyponatremia as the presenting manifestation of empty sella syndrome was first reported in 1987.1 Its clinical presentation resembles the syndrome of SIADH, but fluid restriction alone cannot correct it. Our case highlights the importance of keeping the diagnosis of panhypopituitarism in mind during the evaluation of recurrent, refractory hyponatremia. It also provides insights into a comprehensive approach to a patient with euvolemic hyponatremia.


Our patient was a 55-year-old postmenopausal lady with previously diagnosed subclinical hypothyroidism on levothyroxine replacement of 25 µg/day for the last 5 years. She had initially visited the Internal Medicine Outpatient Department three times in the previous month with complaints of generalized weakness, loss of appetite, and decreased oral intake of 2 months duration. Her previous laboratory reports showed moderately severe persistent chronic hyponatremia. She had a past history of altered behavior and aggressiveness. However, she had never been prescribed any antipsychotic medicines in the past. There was no history suggestive of the presence of sellar mass, previous intracranial surgery, head injury, or recent diuretic use. Her obstetric history was unremarkable, with four living births after normal vaginal deliveries at home without any documented antenatal, intrapartum, or postpartum complications. She was regularly taking 25 µg levothyroxine every day.

Clinically she had a body mass index of 20.9 kg/m2, was euvolemic, and was normotensive without postural hypotension. Fundoscopy revealed no evidence of papilledema. There was bilateral breast atrophy with absent axillary and pubic hair. Systemic examination was unremarkable. The clinical diagnosis of altered sensorium due to chronic hyponatremia was made with the likely etiology of SIADH.


The evaluation showed normocytic normochromic anemia (hemoglobin 8.1 gm/dL) and leucopenia (3200/cmm). A biochemical evaluation revealed hyponatremia with the lowest serum sodium (112 mmol/L) at admission, low serum uric acid (3.4 mg/dL), normal renal functions, and high urine spot sodium 117 mmol/L (normal urine spot sodium <30 mmol/L). To exclude SIADH, hormonal workup showed decreased free triiodothyronine—0.84 pmol/L (4.0–8.5) and free tetraiodothyronine (FT4)—2 pmol/L (8.5–22) with thyrotropin stimulating hormone—4.34 uIU/mL (0.27–4.2). Basal serum cortisol was 2.60 µg/dL along with inappropriately normal plasma adrenocorticotrophic hormone (ACTH)—33.9 pg/mL (normal ACTH 5—46 pg/mL). Despite her postmenopausal state, she had inappropriately low luteinizing hormone—0.31 mIU/mL and low follicular stimulating hormone—0.49 mIU/mL. Additionally, her serum prolactin was 6.37 ng/mL (5–25). She had osteoporosis in bone mineral densitometry by dual X-ray absorptiometry. In view of multihormonal deficiency, she underwent contrast-enhanced magnetic resonance imaging (CEMRI) brain, which revealed PES (Figs 123).

Fig. 1: Contrast-enhanced magnetic resonance imaging (CEMRI) brain (t2 image, coronal view) showing PES

Fig. 2: Contrast-enhanced magnetic resonance imaging (CEMRI) brain (t2 image, sagittal view) showing PES

Fig. 3: Contrast-enhanced magnetic resonance imaging (CEMRI) fluid-attenuated inversion recovery image (sagittal view) showing PES

Treatment, Outcome, and Follow-up

The patient was initially treated as a suspected case of SIADH with 3% saline and oral salt without any clinical improvement. She had persistent refractory euvolemic hyponatremia. After ruling out SIADH, subsequent treatment for panhypopituitarism with oral hydrocortisone 20 mg/day in divided doses was started along with optimization of levothyroxine dose (125 µg/day). This resulted in rapid clinical improvement with the gradual normalization of serum sodium to 125 mmol/L at the time of discharge. She was also started on oral calcium, vitamin D, and weekly alendronate for secondary osteoporosis. The patient was discharged with normalization of her serum sodium (135 mmol/L). She had a midnormal FT4 level after a month during follow-up.


Empty sella syndrome is an anatomical condition first described by Busch in 1951.2 There is remodeling of sella turcica and flattening of the pituitary gland resulting from subarachnoid space extension into an intrasellar position, making it appear flattened with partial or complete filling of the sella turcica space by cerebrospinal fluid. The severity of the syndrome depends on the absence of one or more pituitary hormones.3,4 The empty sella has been categorized as primary empty sella or secondary empty sella based on the etiology, which is mostly unclear while many hypotheses have been proposed. The congenital absence of diaphragm sella is the only established etiology for primary empty sella syndrome, while other causes may include relative changes in intracranial pressure. Secondary empty sella may result from secondary causes such as a treated pituitary tumor, head trauma, or intracranial hypertension.4,5

Hyponatremia is one of the most common electrolyte abnormalities and an independent risk factor for increased mortality in hospitalized patients. Despite its strong association with mortality and cognitive decline, it often gets neglected in clinical settings.3 It is usually not a diagnosis but a manifestation of an underlying disorder, and therefore searching for an underlying disorder (Fig. 4) should be one of the important goals.6

Fig. 4: Approach to hyponatremia diagnosis based on urine spot sodium

Since our patient with euvolemic hyponatremia presented with increased urine spot sodium in the absence of diuretic use or renal dysfunction, a provisional diagnosis of SIADH was considered.6 The diagnostic criteria of SIADH mandate the absence of any alternate cause for hyponatremia—a diagnosis of exclusion. Clinically differentiating SIADH from primary or secondary hypocortisolism can be very difficult as the clinical and biochemical features are the same.7 Also, normovolemic state, low-normal blood pressure, absence of skin pigmentation and normal serum potassium all favor central hypocortisolism compared to primary hypocortisolism. Our patient had secondary hypocortisolism and secondary hypothyroidism responsible for refractory hyponatremia. Lastly, gonadotrophins in postmenopausal women should be raised,8 which were low in our patient. Thus, the demonstration of multiple pituitary hormone deficiencies led to the diagnosis of panhypopituitarism in our case. In addition, the etiological workup of panhypopituitarism has clinched the diagnosis of the PES on MRI.

The diagnosis of hypogonadism is a diagnostic challenge in postmenopausal women when the presentation is only with hyponatremia with obvious amenorrhea compared to a premenopausal state. This case highlights how hyponatremia led to the diagnosis of panhypopituitarism with PES—a commonly encountered dyselectrolytemia leading to an uncommon diagnosis.



1. Okuno S, Inaba M, Nishizawa Y, et al. A case of hyponatremia in panhypopituitarism caused by the primary empty sella syndrome. Endocrinol Jpn 1987;34(2):299–307. DOI: 10.1507/endocrj1954.34.299

2. Busch W. [Morphology of sella turcica and its relation to the pituitary gland]. Virchows Arch Pathol Anat Physiol Klin Med 1951;320(5):437–458. DOI: 10.1007/BF00957474

3. Aijazi E, Shama F, Mukhtar S. Primary empty sella syndrome presenting with severe hyponatremia and minimal salt wasting. J Ayub Med Coll 2016;28(3):605–608. PMID: 28712246.

4. Ekhzaimy AA, Mujammami M, Tharkar S, et al. Clinical presentation, evaluation and case management of primary empty sella syndrome: a retrospective analysis of 10-year single-center patient data. BMC Endocr Disord 2020;20(1):142. DOI: 10.1186/s12902-020-00621-5

5. Empty sella syndrome. National Organisation for rare disorders. Available at:

6. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 2014;170(3):G1–G47. DOI: 10.1530/EJE-13-1020

7. Chanson P. Severe hyponatremia as a frequent revealing sign of hypopituitarism after 60 years of age. Eur J Endocrinol 2003;149(3):177–178. DOI: 10.1530/eje.0.1490177

8. Farhan A, Tanveer T, Mumtaz U, et al. Hyponatremia-finding the cause. Endocrinol Metab Syndr 2016;5(5). DOI: 10.4172/2161-1017.1000253.

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