XHP is the rarest form of primary hypophysitis with a female preponderance (27/35 [77.1%]) and a mean age of 39.3 years [17]. The first three cases of XHP have been reported in 1998 [9], and since then, our 35-year-old female patient is the 36th reported XHP case worldwide and the 2nd case in Turkey [19]. Headache, impaired menstrual cycles, hyperprolactinemia, diabetes insipidus, and panhypopituitarism have been reported as the most common presenting symptoms in a recent review [17] and our patient presented all these symptoms, except diabetes insipidus. In line with the literature which reported a low prevalence of visual disturbances in patients with XHP, no visual field abnormality was demonstrated in our patient [11, 12].
Since the pathophysiological mechanism of XHP has not been elucidated, yet, XHP has been classified as primary hypophysitis [2]. A possible autoimmune mechanism which might be involved in the development of XHP has been suggested by three case reports, in which the cases with ulcerative colitis, Hashimoto’s thyroiditis, rheumatoid arthritis and Sjogren’s syndrome have been presented [3, 13, 20]. Dissimilar to these reports, recent evidences suggest that the inflammatory process in a xanthomatous lesion may actually be a secondary response to mucous fluid content release from a ruptured cyst, most commonly from an RCC [1, 4, 6, 14, 15, 17, 18, 21, 23]. Moreover, Duan et al. have presented a cohort of 7 XHP cases, in which 6 cases harbored concurrent findings of a ruptured RCC and the last case had a history of a surgery for an RCC [7]. In the same cohort, thick yellowish drainage within a cystic lesion was observed in 4 cases intraoperatively, which was similar to that described in our case.
Gadolinium-enhanced pituitary MRI is the preferred modality for hypophysitis, and XHP usually presents as a cystic sellar mass, which generally shows a peripheral enhancement [5]. In addition to that, Mathkour et al. reported a case, in which the sellar lesion had a suprasellar expansion with the infiltration of the cavernous sinus which has been considered as adenoma over RCC on MRI [17]. As a result, it may be difficult to differentiate XHP on MRI from a cystic adenoma, RCC, hemorrhage, or a pituitary abscess. Heterogenous intensity on both T1- and T2-weighted imaging and diffuse pituitary enhancement which was displayed by MRI in our case were primarily suggestive of a complicated cyst/cystic adenoma or hemorrhage, while the infundibular and dural enhancement indicated a diagnosis of hypophysitis, as well.
The management of XHP may be challenging due to the ambiguous pathogenesis of the disease. Unlike the treatment for lymphocytic hypophysitis, glucocorticoid therapy is less effective in XHP and a surgical intervention is often required to alleviate the compressive symptoms and pituitary dysfunction [10, 12]. The only XHP case which was radiologically responsive to high dose steroid has been described by Joung et al. and the authors have reported a significant mass reduction at the sella and suprasellar area following a 500 mg intravenous methylprednisolone treatment for 3 days. In addition to playing an essential role in making the histological diagnosis of XHP, surgery has been generally considered in cases with progressive visual field deficits or impaired pituitary function [12]. In the literature, the first case with XHP which had a full recovery of pituitary dysfunction following a transsphenoidal surgery has been reported by Burt et al. and that patient had only a 3-month history of hypogonadism at the initial admission. In another case report, diabetes insipidus completely cured after surgery in a XHP patient with a 4-month history of polyuria and polydipsia [16]. Similarly, a case of XHP with a 2-month history of amenorrhea, galactorrhea, and mild weight gain achieved remission following a complete resection of the lesion [17]. The rate of pituitary function improvement following surgery in XHP cases has been reported less than 50%, which attributed to the duration of the impairment [3]. Chronic inflammation has been considered responsible for irreversible pituitary dysfunction via fibrosis and tissue destruction. In addition to that, headache has been reported to improve in most of patients with XHP who had surgery [11]. Headache and panhypopituitarism of our patient did not recover within 6 months after surgery, possibly due to a 2-year history of the presented symptoms. Interestingly, headache disappeared completely within a few days after the first dose of high dose steroid therapy. Moreover, the pituitary function tests showed a slight improvement, i.e., normalization of IGF-1 level and a mild increase in the other anterior pituitary function tests; however, at 10-month follow-up, our patient has still been requiring hormone replacement therapies.
In conclusion, XHP is an uncommon inflammatory process of the pituitary gland which should be included in the differential diagnoses, if a patient presents with headache, panhypopituitarism and if yellowish fluid is drained from a cystic lesion intraoperatively. In agreement with the recent reports, our case presentation may also indicate a recommendation to classify XHP as secondary hypophysitis which could be caused by a ruptured cystic lesion. Since the differentiation of XHP from other pituitary tumors may be challenging preoperatively, surgery is the major diagnostic tool and also, the most recommended therapeutic option, despite low remission rates (< 50%) reported following surgery. Here, we present a patient with XHP which developed as an inflammatory response to a ruptured RCC and the transsphenoidal surgery did not improve the symptoms/pituitary functions, while headache recovered immediately after the first dose of high dose methylprednisolone treatment.