Hypophysitis: A Rare Cause of Impaired Consciousness in a Middle-Aged Woman
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.299159
Source of Support: None, Conflict of Interest: None
Keywords: Hyponatremia, hypophysitis, hypopituitarism
Hypophysitis occurs predominantly in women, usually during pregnancy or postpartum period. Hypophysitis involving the anterior pituitary often presents with adrenal insufficiency. We report a middle-aged woman with hypophysitis who presented with recurrent episodes of impaired consciousness due to hyponatremia.
A 43-year-old woman initially presented with headache and vomiting for 1-day followed by impaired consciousness. There was no history of seizures, head trauma, or fever. At admission, she had E3V4M5 on Glasgow Coma Scale. On examination, she had no focal neurological deficits or any signs of meningeal irritation. However, her metabolic workup showed hyponatremia (serum sodium level = 115 mEq/L), normal thyroid stimulating hormone levels (TSH), (1.1 uIU/mL; reference range: 0.27–4.2) and fasting serum cortisol levels (7.9 ug/dl; reference range: 6.2–19.4). The computerized tomogram (CT) of brain, cerebrospinal fluid study, X-ray chest, and ultrasound abdomen showed normal findings. She had clinical improvement on correction of sodium level.
Almost a month later, she developed a similar event and was readmitted. There was no associated fever or any history of drug intake. Her serum sodium level was 112 mEq/L. In addition, a history of amenorrhea of 3-month duration was reported. Her laboratory workup during readmission showed evidence of pan-hypopituitarism [TSH = 0.19 uIU/L, free T4 = 0.39 ng/dl, fasting serum cortisol = 2.57 μg/dl, Follicle stimulating hormone (FSH) = 3.36 mIU/mL, Luteinizing hormone (LH) = 1.38 IU/L, and prolactin = 6.10 ng/mL]. Her serum Angiotensin-converting enzyme (ACE) level was 12.4 U/L (reference range: 8.0–65.0). The magnetic resonance images (MRI) of the brain showed mild pituitary enlargement and thickened pituitary stalk with homogenous contrast enhancement indicating hypophysitis of probable autoimmune origin [Figure 1]. However, her CT images of chest and abdomen with contrast were normal. Autoimmune workup including Antinuclear antibody (ANA) profile was negative. In addition, the serum IgG4 assay was also within normal limits (0.79 g/L). She was treated with oral steroids (prednisolone 20 mg twice daily, tapered over 1 month, and maintained on 5 mg daily) and thyroxine supplements (50 μg/day). In view of the clinical response to treatment, she refused for a biopsy. She remained asymptomatic at 15-month follow-up on low-dose oral steroids and thyroxine supplements.
Hypophysitis occurs predominantly in women, usually during pregnancy or postpartum period. Isolated inflammation of the pituitary leads to primary hypophysitis, while secondary hypophysitis often results from lymphocytic autoimmune neurohypophysitis, sarcoidosis, histiocytosis, tuberculosis, metastasis, and lymphoma. Additional causes of hypophysitis include IgG4-related hypophysitis and anti-PIT-1 antibody syndrome associated hypophysitis. Furthermore, recent literature also reports autoimmune hypophysitis (AH) as a complication of therapy with ipilimumab, an immune checkpoint inhibitor used in the treatment of metastatic melanoma.
Hypophysitis involving the anterior pituitary often presents with adrenal insufficiency. However, inflammation more commonly affects the posterior lobe of the pituitary (neurohypophysitis) and pituitary stalk (infundibulum). Hyponatremia in our patient was due to hypoaldosteronism secondary to hypoadrenalism from hypopituitarism suggesting anterior pituitary involvement. Involvement of posterior lobe of the pituitary and pituitary stalk may lead to severe dehydration and diabetes insipidus in contrast to pituitary adenoma which results in the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Symptoms of partial or pan-hypopituitarism occur in approximately 80% of cases and multiple deficiencies are found in approximately 75% of cases.
AH mimics nonsecreting pituitary adenomas. However, confirmatory diagnosis of AH requires histological examination which was not done in our patient. Approximately, 40% of patients with AH are misdiagnosed as having pituitary macroadenoma and undergo unnecessary surgery. Although no single radiological sign is diagnostically accurate, MRI is the best noninvasive diagnostic tool to differentiate AH from nonsecreting adenomas. Radiological findings such as homogenous enhancement of the pituitary, diffuse symmetric gland enlargement, thickened nontapering pituitary stalk, normal sellar size, dural thickening, parasellar T2-weighted hypointensity, parasellar mucosal thickening, and an absence of a posterior pituitary bright spot may however support the diagnosis of AH. All these features were favoring the diagnosis of AH in this patient. In contrast, pituitary macroadenomas are frequently asymmetric, show heterogenous enhancement, and rarely involve the stalk or erode the sellar floor.
The management strategy in lymphocytic/granulomatous hypophysitis is debatable. Steroids are considered as the first line of management in lymphocytic hypophysitis. For steroid nonresponsive patients, other chemotherapeutic agents like methotrexate, azathioprine, and cyclosporine A have been tried with a positive response. Surgical resection should be considered in the presence of optic nerve and/or chiasmal compression, and in the presence of lesions that are not responsive to medical management.
Hypophysitis presenting as recurrent hyponatremia is rare. Proper history and evaluation give an etiological clue for diagnosis. Pan-hypopituitarism due to hypophysitis may be considered in the differential diagnosis of recurrent hyponatremic encephalopathy.
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