Headache, Pituitary Apoplexy and Diabetes insipidus: Suspect Necrotizing Hypophysitis

Background: Necrotizing hypophysitis (NH) is an exceedingly rare clinical entity; we found only 5 reported cases in a literature review. CASE: A 34-year-old female with a history of primary hypothyroidism developed a headache, double vision, nausea, vomiting, decrease in appetite, galactorrhea, and weight loss. An MRI of the brain showed a 0.9 cm T2 hyperintense pituitary lesion with features suggestive of cystic degeneration or apoplexy of an adenoma There was effacement of the optic nerve anterior to the optic chiasm. Eye examination revealed optic nerve edema and a cranial nerve VI palsy. Laboratory studies revealed a normal prolactin 20.0 (3.3-26.7 ng/ml), and IGF-1 189 (RR: 66 - 303 ng/ml). The pituitary-adrenal axis and pituitary-gonadal axis appeared intact. After short treatment with dexamethasone, her primary symptom of severe headache improved but she later developed polyuria. The evaluation confirmed diabetes insipidus. Her headache worsened after the completion of the brief course of steroids. After a repeat MRI showed mild interval enlargement of the hypo-enhancing posterior pituitary, she underwent transsphenoidal pituitary tumor surgery. A biopsy showed necrotizing inflammation with foci of acute necrosis accompanied by polymorphonuclear cells. There was no granuloma seen. Special stains were negative for fungal, acid-fast, and bacterial organisms. Laboratory studies revealed negative ANA, negative ANCA, PR-3 Ab, MPO Ab, and anti-TPO Abs. The ACE enzyme was elevated at 85 (RR: 8-53 U/l), but the repeat test was within the normal range. A chest CT was not suggestive of pulmonary sarcoidosis. A post-surgery MRI demonstrated a decrease in pituitary size. Her headache worsened with a reduction in prednisone below 20 mg daily. In order to attempt further reduction in prednisone, azathioprine was started as a steroid-sparing agent. Titration of azathioprine up to 175 mg allowed prednisone to be reduced to the replacement dose of prednisone 5 mg daily. An MRI showed the pituitary mass to be unchanged. DISCUSSION: Hypophysitis is associated with diffuse enlargement and dysfunction of the pituitary gland. This case of NH is of unclear cause. There was no evidence of other inflammatory causes such as sarcoidosis, IgG4-related disease, ANCA-associated vasculitis, or infectious cause. As with typical lymphocytic hypophysitis, NH can present with sudden-onset hypopituitarism, neural compression, diabetes insipidus, and radiologic features of ischemic pituitary apoplexy. Signs and symptoms at diagnosis, as well as pituitary hormone abnormalities, vary on the degree of pituitary involvement. Pituitary adenoma commonly does not cause diabetes Insipidus. Radiologic findings consistent with ischemic pituitary apoplexy coupled with the presence of diabetes insipidus is suggestive of NH. A definitive diagnosis of NH, however, requires histopathology.