Primary Hypophysitis Research Articles

Primary hypophysitis and other autoimmune disorders of the sellar and suprasellar regions.

The pituitary gland and the hypothalamus can be affected by autoimmune-mediated structural and functional disruption. These autoimmune-mediated diseases occur more commonly in females and are often found during pregnancy or in the post-partum period. Autoimmune diseases can either affect parts of the pituitary or hypothalamus, or can involve both sellar and suprasellar structures. Most of these cases comprise primary hypophysitis (PRH). Over the years, there has been a tremendous increase in the number of reported PRH cases and related disorders, including hypophysitis induced by immune checkpoint inhibitors. With this increasing data, more light is being shed on the spectrum of clinical presentations, biochemical and imaging abnormalities of these disorders. Regardless, these disorders are still relatively rare. The clinical presentation can vary vastly, based on the type of pituitary cell or the area of the suprasellar region affected. The severity can range from clinically silent disease to progressive and rapid deterioration and death, likely due to unrecognized central adrenal insufficiency. Although biopsy remains a gold standard for diagnosing these disorders, the current standard of practice is biochemical assessment for hormonal deficiencies and imaging studies. In several instances, these disorders spontaneously resolve, but medical or surgical intervention might be necessary to treat symptomatic disease. Due to the subtlety and a vast spectrum of clinical manifestations which could often be asymptomatic, and the rarity of the occurrence of these diseases in clinical practice, the diagnosis can be easily missed which could potentially lead to substantial morbidity or mortality. Therefore, it is crucial to have a strong clinical suspicion and pursue timely biochemical and imaging studies to initiate prompt treatment. In this article, we review the various autoimmune conditions that affect the sellar and suprasellar structures, their diagnostic approach and management of these disorders.

Hypophysitis Outcome and Factors Predicting Responsiveness to Glucocorticoid Therapy: A Prospective and Double-Arm Study.

Primary autoimmune hypophysitis (PAH) evolves in most untreated cases in irreversible hypopituitarism. PAH outcome, instead, after immunosuppressive treatment has not been completely clarified. To evaluate hypophysitis and pituitary function outcomes. A prospective, double-arm study with a 2-year follow-up. Referral center for pituitary disease. Twenty PAH cases. Oral prednisone 50 mg/d or conservative strategy by observation. Primary endpoint was the improvement/stabilization/worsening of PAH from baseline to a 2-year visit. Secondary endpoint was the improvement/stabilization/worsening of pituitary function from baseline to a 2-year visit. Twelve patients (57.1%) were treated with a glucocorticoid-immunosuppressive therapy, and eight patients (42.9%) were observed. At the 2-year visit, PAH improvement/recovery occurred in eight immunosuppressive-treated (66.7%) patients and in two untreated patients (25%). PAH worsened in three untreated patients (37.5%) and was considered stable in four immunosuppressive-treated (33.3%) and three untreated patients (37.5%). Improvement/recovery of pituitary function occurred more frequently in immunosuppressive-treated patients (58.3%) compared with untreated ones (25%; P = 0.04). Responsiveness to immunosuppressive treatment is correlated with antipituitary antibody presence (P = 0.01), occurrence of diabetes insipidus at PAH diagnosis (P = 0.01), absence of the physiological neuropituitary "bright spot" on T1-weighed images (P = 0.01), and pituitary stalk at optical chiasm larger than 3.9 mm (area under the curve: 0.97, sensibility: 100%, specificity: 100%; P = 0.04). On the other hand, we failed to identify factors predicting the outcome, among untreated patients. Glucocorticoid treatment of hypophysitis improves pituitary secretion and should be encouraged in accordance with the evaluation of endocrine-, immunological-, and morphological-predictive markers.

Primary Granulomatous Hypophysitis Presenting with Secondary Hypothyroidism

Objective: We present a case of a 45-year-old woman with history of Graves disease treated with thyroidectomy who developed panhypopituitarism due to granulomatous hypophysitis. Methods: The details of the case presentation, evaluation, diagnosis, and treatment are reviewed. On routine follow-up visits for thyroid condition, the patient complained of symptoms of hyperthyroidism, despite being on a previously adequate dose of levothyroxine. Work-up led to the diagnosis of hypophysitis. Results: The patient responded to corticosteroid therapy, but 5 months later, magnetic resonance imaging of the brain showed recurrence of the disease. Eventually, the patient underwent partial transsphenoidal hypophysectomy, later developed recurrence of disease, and had total hypophysectomy. The postoperative pathology report was consistent of granulomatous hypophysitis. Conclusion: Granulomatous hypophysitis is an uncommon inflammatory disease affecting the pituitary. It is commonly misdiagnosed as a macroadenoma because ...

MECHANISMS IN ENDOCRINOLOGY: Hypophysitis: diagnosis and treatment.

Hypophysitis is a rare condition characterised by inflammation of the pituitary gland, usually resulting in hypopituitarism and pituitary enlargement. Pituitary inflammation can occur as a primary hypophysitis (most commonly lymphocytic, granulomatous or xanthomatous disease) or as secondary hypophysitis (as a result of systemic diseases, immunotherapy or alternative sella-based pathologies). Hypophysitis can be classified using anatomical, histopathological and aetiological criteria. Non-invasive diagnosis of hypophysitis remains elusive, and the use of currently available serum anti-pituitary antibodies are limited by low sensitivity and specificity. Newer serum markers such as anti-rabphilin 3A are yet to show consistent diagnostic value and are not yet commercially available. Traditionally considered a very rare condition, the recent recognition of IgG4-related disease and hypophysitis as a consequence of use of immune modulatory therapy has resulted in increased understanding of the pathophysiology of hypophysitis. Modern imaging techniques, histological classification and immune profiling are improving the accuracy of the diagnosis of the patient with hypophysitis. The objective of this review is to bring readers up-to-date with current understanding of conditions presenting as hypophysitis, focussing on recent advances and areas for future development. We describe the presenting features, investigation and diagnostic approach of the patient with likely hypophysitis, including existing conventional techniques and those in the research/development arena. Hypophysitis usually results in acute and persistent pituitary hormone deficiency requiring long-term replacement. Management of hypophysitis includes control of the inflammatory pituitary mass using a variety of treatment strategies including surgery and medical therapy. Glucocorticoids remain the mainstay of medical treatment but other immunosuppressive agents (e.g. azathioprine, rituximab) show benefit in some cases, but there is a need for controlled studies to inform practice.

Neuro-radiological features can predict hypopituitarism in primary autoimmune hypophysitis.

Primary autoimmune hypophysitis (PAH) is considered an underdiagnosed disease, due to the difficulty in reaching a definitive diagnosis. PAH clinical diagnosis remains an exclusion diagnosis. We aimed to correlate PAH neuro-radiological signs to endocrine features and evaluate their prognostic role. 24 PAH cases were enrolled and classified according to neuro-radiological signs: in 12 adeno-hypophysitis (AHs), 8 infundibulo-neuro-hypophysitis (INHs) and 4 pan-hypophysitis (PHs). Secondary hypogonadism developed more frequently in INHs as compared to AHs (54.5% vs. 27.3%, p = 0.05), without no difference with PHs (p = 0.6). Diabetes insipidus occurred more frequently in INHs cases (72.7%, p < 0.001) and in PHs cases (27.3%, p = 0.007), as compared to AHs cases (0%). Similarly, all cases of GHD occurred in INHs (100%) as compared to AHs (0%, p < 0.001) and PHs (0%, p < 0.001). The pituitary stalk (PS) showed a pseudo-triangular shape (larger at the optical chiasma) in INHs and a pseudo-cylindrical shape (larger both at the optical chiasma and at the pituitary insertion) in PHs. The PS pseudo-triangular shape correlated to the occurrence of GHD and diabetes insipidus (p < 0.001/p = 0.03). At the 1-year follow-up, improvement of baseline radiological features positively correlated with the loss of the neuro-pituitary "bright spot" on T1-weighted images (OR 0.16; 95% CI 0.03-0.9 p = 0.02) and with a PS diameter at the optical chiasma level larger than 4.1mm (AUC 0.97, sensibility 80%, specificity 100%, OR 6; 95% CI1.1-28.8, p = 0.01) Our data suggest that neuro-radiological PAH classification in PH, AH and INH can predict pituitary dysfunction and that some neuro-radiological features, such as the pituitary stalk diameter and the loss of the neuro-pituitary bright spot on T1w images can play a role as a positive prognostic marker of the radiological hypophysitis outcome.

Human leucocyte antigens coeliac haplotypes and primary autoimmune hypophysitis in caucasian patients.

Primary hypophysitis is a rare disease, with an autoimmune aetiology. As few papers have investigated genetic of hypophysitis, our aim was to evaluate HLA status in a single-centre series of patients. A retrospective, longitudinal and cross-sectional study was conducted. In consecutive Caucasian patients, clinically or histologically diagnosed for primary autoimmune hypophysitis (PAH), the HLA genotype having been determined. This cohort was compared with a control group. Anti-pituitary and anti-hypothalamus auto-antibodies evaluation was included. 16 patients were enrolled. Fourteen patients were female (87.5%). According to HLA-DR status, we found the following: 9 of 16 patients (56.3%) haplotypes that were associated with coeliac disease (CD). Among these, 5 carried the DR7-DQ2 heterozygote haplotype (55.5%) while the remaining ones only the following haplotypes: DR3-DQ2 homozygote (25%), DR4-DQ2 heterozygote (25%), DR4-DQ8 heterozygote (50%) and DR4-DQ8 homozygote (25%), respectively. A total of 12 CD-associated haplotypes were identified. In PAH, we found a significantly higher frequency of patients carrying CD-associated HLA haplotypes as compared to the control group (respectively, 75% vs 48% P=.03; OR: 3.25 95%IC:1.1-10.3), particularly, for DQ2 and DQ8 haplotypes. DQ2 haplotype was detected in 50% of PAH and 38.4% of the control group (P=.3), while DQ8 haplotype in 25% of PAH and 7.2% of the control group (P=.01 OR:4.3 95%IC:1.3-14.7). Our data suggest that PAH and CD share some HLA haplotypes, reinforcing the knowledge of their association. HLA haplotypes, particularly DQ8, may play a role in PAH management and diagnosis, also suggesting the predisposition to other autoimmune diseases.

Clinical, Endocrine and Imaging Characteristics of Patients with Primary Hypophysitis.

Primary hypophysitis (PH) is a rare disease with a poorly-defined natural history. Our aim was to characterise patients with PH at presentation and during prolonged follow-up. Observational retrospective study of 22 patients was conducted from 3 centres. In 14 patients, PH was confirmed histologically and in the remaining 8 clinically, after excluding secondary causes of hypophysitis. All patients had hormonal and imaging investigations before any treatment. Median follow up was 48 months (25-75%: 3-60). There was a female predominance with a female/male ratio: 3.4:1. Eight out of 22 patients had another autoimmune disease. Headaches and gonadal dysfunction were the most common symptoms. Five patients presented with panhypopituitarism; 17 patients had anterior pituitary deficiency, and 7 had diabetes insipidus. At presentation, 9 patients were treated surgically, 5 received replacement hormonal treatment, and 8 high-dose glucocorticoids from whom 5 in association with other immunosuppressive agents. Six patients showed complete recovery of pituitary hormonal deficiencies while 6 showed a partial recovery during a 5-year follow-up period. No difference was found between patients treated with surgery and those treated medically. The overall relapse rate was 18%. PH can be manifested with a broad spectrum of clinical and hormonal disturbances. Long-term follow-up is required to define the natural history of the disease and response to treatment, since pituitary hormonal recovery or relapse may appear many years after initial diagnosis. We suggest that surgery and immunosuppressive therapy be reserved for exceptional cases.

Clinical features and prognosis of 18 cases of primary lymphocytic hypophysitis

Objective: To analyze clinical features, prognosis and treatment of lymphocytic hypophysitis (LYH). Methods: The clinical data, treatments and outcomes of 18 cases diagnosed as LYH at Chinese PLA General Hospital between January 2001 and July 2017 was respectively reviewed. Results: Eighteen patients with histology-proven LYH (13 females and 5 males ) were identified. All lymphocytic adenohypophysitis (LAH) were females(n=6), two of whom were associated with pregnancy. Eleven patients (6 females and 5 males) had lymphocytic panhypophysitis (LPH) and one(female) had hypothalamitis. Pre-treatment evaluation revealed that 11 patients presented with symptoms of intracranial space-occupying lesions, 12 patients had symptoms of anterior pituitary hormone deficiencies, and 12 patients had central diabetes insipidus (CDI). All patients had space-occupying lesions on magnetic resonance imaging (MRI), which were symmetrically enlarged and homogenously enhanced with or without pituitary stalk thickening. Before or after surgery, 11 patients received immunosuppressant therapy or radiotherapy to alleviate space-occupying effect. After 4-204 months follow-up, 5 patients had a relapse and received immunosuppressants, radiotherapy or surgery to achieve remission. Full recovery (both symptomatic and radiographic) was seen in 6 patients, and 11 patients maintained stable replacement therapy. Conclusions: LYH presents with acute space-occupying effects such as headache, visual disturbances, hypopituitarism, CDI and mild hyperprolactinemia, especially with characteristic radiographic manifestations. Usually, surgery reliably establishes diagnosis, and immunosuppressant therapy is a necessity. On the whole, LYH has a good prognosis.

Primary lymphocytic hypophysitis: Clinical characteristics and treatment of 50 cases in a single centre in China over 18years.

Primary lymphocytic hypophysitis (LYH) is rare, and it is often evaluated in a small case series. This study aimed to describe the diagnosis and treatment of primary LYH in a larger cohort. A retrospective study of the diagnosis and treatment of primary LYH was conducted at Peking Union Medical College Hospital from 1999 to 2016. Fifty patients (28 histologically diagnosed and 22 clinically-diagnosed) were eligible for inclusion. Clinical, endocrine, pathological and imaging findings; therapies and outcomes were assessed. Ordinal logistic regression analysis was used to evaluate the association between the clinical parameters and outcomes (eg, improvements in pituitary function, regression of lesion size on MRI and disease recurrence). Central diabetes insipidus (CDI) (72.0%) was the most common endocrine dysfunction. Hypogonadotropic hypogonadism was the most frequently observed (60.0%) manifestation of anterior pituitary dysfunction; adrenal insufficiency was the third most common (26.0%) manifestation; and IGF-1 axis defects were the least frequent (22.0%). Thickening of the pituitary stalk was the most frequent (96.0%) imaging finding, and 78.0% of the patients exhibited both intrasellar and suprasellar expansion. Pharmacological dose of glucocorticoids was identified to be significantly associated with increased odds of anterior pituitary function improvement. No observed covariates were significantly associated with improvement of CDI and recurrence. The sequence of anterior pituitary deficiencies in Chinese primary LYH patients was atypical (LH/FSH>TSH>ACTH>IGF-1 axis deficiency). A pharmacological dose of glucocorticoids was significantly associated with the improved anterior pituitary insufficiency.

IgG4‐related hypophysitis is highly prevalent among cases of histologically confirmed hypophysitis

IgG4-related disease is an immune-mediated disease with manifestations in most organ systems among them the pituitary gland. To date, few cases of histologically confirmed cases of IgG-related hypophysitis have been reported. The aim of this study was to retrospectively determine the prevalence of IgG4-related hypophysitis among cases previously diagnosed as primary hypophysitis (lymphocytic hypophysitis, granulomatous hypophysitis and hypophysitis not otherwise specified). Histological and immunohistochemical analysis revealed that 12 of 29 cases (41.4%) previously diagnosed as primary hypophysitis fulfilled the criteria for IgG4-related disease and, thus, IgG4-related hypophysitis should always be considered in the differential diagnosis of primary hypophysitis. All cases of IgG4-related hypophysitis showed a dense lymphoplasmacytic infiltrate with more than 10 IgG4-positive cells per high power field and a ratio of IgG4/IgG-positive cells of more than 40%, whereas storiform fibrosis was an inconsistent histological feature and was also seen in few cases of non-IgG-related hypophysitis, thus lacking sensitivity and specificity. Obliterative phlebitis was not seen in any case. Thus, histological criteria defined for IgG4-related disease in other organs should be modified for IgG4-related hypophysitis, accordingly.

Pituitary Stalk Thickening

Abstract: MRI revealed enlargement of the pituitary stalk in two patients with different clinical presentations. A 60 y/o female had autoimmune hypothyroidism associated with blunted cortisol response to ACTH, while the other, a 30 y/o female had amenorrhea and polyuria with high plasma and low urinary osmolality. Keywords: Pituitary stalk thickening; Hypothyroidism; Adrenal insufficiency; Amenorrhea; Polyuria Case Report: As a result of the advances in imaging technologies, the finding of pituitary stalk lesions presents a diagnostic challenge to clinicians and endocrinologists. They are usually discovered incidentally on magnetic resonance imaging (MRI), or during the investigation of symptoms related to hypothalamic-pituitary dysfunction such as central diabetes insipidus or hypopituitarism. The etiology of these lesions may be congenital/developmental, inflammatory, infectious or neoplastic. Due to its particular location and function, the pituitary stalk is not often biopsied and diagnosis is based generally on clinical evaluation and images Report of two cases Enlargement of the pituitary stalk was found during the endocrine evaluation of two patients with the following clinical presentations. Patient 1: A 64 year old woman was admitted to the emergency room for vomiting and high blood pressure. Otherwise normal, she had been suffering from proximal muscle weakness, fatigue, reduced appetite, cognitive impairment and pre-tibial myxedema during the last two months. The patient denied glucocorticoid intake. Mild hyponatremia (132 mEq/l) and anemia (hct: 30%) were detected. TSH was high (13.74 µU/ml) with low FT4: 0.57ng/dl. Anti-peroxidase antibodies were positive. Serum potassium was normal (4.2 mEq/l). Serum morning cortisol was less than 1.0 µg/dl and ACTH was 6.7 pg/ml and 5.0 pg/ ml in two different occasions. An ACTH stimulating test (Synacthen 250.0 µg, i.m) showed a blunted cortisol response at 30 and 60 min after stimulus, confirming adrenal insufficiency. The remaining pituitary function was normal. MRI showed a thickened pituitary stalk (Figure 1). The patient improved on hydrocortisone and LT4. Patient 2: A 30 year old woman complained of amenorrhea and polyuria (9 L/day). She had high plasma and low urinary osmolality (311 mOsm/kg and 136 mOsm/kg, respectively). Low serum estradiol and gonadotropins were found. Thyroid and adrenal functions were normal. MRI showed a thickened pituitary stalk (Figure 2). She started on desmopressin (0.1 mg/day) which reduced daily diuresis by 60% and lowered plasma osmolality (290 mOsm/day). Additionally she began on estrogen and progestin replacement. Discussion: Pituitary stalk lesions may be found by chance or during the evaluation of endocrine disorders. In a series of 152 patients, the etiologies were attributed to neoplasia in 32%, inflammatory lesions 20%, and congenital anomalies in 9% and in 39% remained unknown [2]. Primary hypophysitis is rare, between 0.2 and 6.5% among pituitary pathologies. Three histopathological types are described in this category: lymphocytic, granulomatous and xanthomatous hypophysitis [3].These conditions are usually confined to the pituitary. In secondary hypophysitis, a systemic disease is the cause of the pituitary lesion: Sarcoidosis, Wegener granulomatosis, Langerhans cell histyocitosis and IgG4 related plasmatic histiocytosis may affect the pituitary. Monoclonal antibodies against the cytotoxic T-lymphocyte antigen-4 (CTLA-4) for treating metastatic cancer, may induce hypophysitis [4,5]. In the setting of immunosuppression, fungal infection, tuberculosis and toxoplasmosis may involve the pituitary gland [4]. Interestingly, these two patients showed different clinical presentations. After excluding secondary etiologies, primary hypophysitis was suspected in both [4]. Although histological confirmation is needed, biopsy of a pituitary stalk lesion is technically demanding, and must be performed by an experienced neurosurgeon. In order to avoid invasive procedures, the approach was based on clinical, biochemical and radiological features. A close follow-up is mandatory to detect new symptoms and to determine if the lesions progress over time.

Current concept about the diagnosis ang management of primary lphocytic hypophysitis

Current concept about the diagnosis ang management of primary lphocytic hypophysitis

An Overview of Diagnosis of Primary Autoimmune Hypophysitis in a Prospective Single-Center Experience

Background: Autoimmune hypophysitis is a rare disease with a natural progression that is not well known. Aim: To collect representative data on clinical features of autoimmune hypophysitis and better characterize the disease. Patients and Methods: A prospective single-center study was designed. Autoimmune hypophysitis-affected patients evaluated from 2011 at our tertiary care Pituitary Unit were enrolled. After ruling out other pituitary masses and secondary causes of hypophysitis, autoimmune hypophysitis was the diagnosis of exclusion. Autoimmune hypophysitis was classified as adenohypophysitis, panhypophysitis, and infundibuloneurohypophysitis according to clinical and neuroradiological findings. Results: A total of 21 patients met the inclusion criteria: 9 were diagnosed with adenohypophysitis, 4 with panhypophysitis, and 8 with infundibuloneurohypophysitis. The frequency of secondary hypoadrenalism was similar in adenohypophysitis, panhypophysitis, and infundibuloneurohypophysitis. Growth hormone deficit and secondary hypogonadism occurred more frequently in infundibuloneurohypophysitis than in adenohypophysitis and panhypophysitis (p = 0.009; p = 0.04). All cases of multiple pituitary secretion deficits occurred in cases of infundibuloneurohypophysitis (p = 0.04). No correlations between hypophysitis subtype and anti-pituitary and anti-hypothalamus autoantibodies were found. A higher frequency of extractable nuclear antigens (ENA) and anti-nuclear antibodies (ANA) was found in cases of panhypophysitis (OR 5.0, 95% CI 0.86-28.8, p < 0.001, and OR 1.8, 95% CI 1.1-3.2, p = 0.02, respectively) as compared to adenohypophysitis and infundibuloneurohypophysitis. Conclusion: Infundibuloneurohypophysitis should be taken into account in the etiological diagnosis of hypopituitarism, particularly if it is associated with diabetes insipidus and in cases of growth hormone deficit, secondary hypogonadism, or multiple hormone deficits. Contrast-enhanced MRI is crucial for the clinical and noninvasive diagnosis of hypophysitis. Screening for autoantibodies, particularly anti-ENA and anti-ANA, is strongly suggested in the clinical context of hypophysitis.

Granulomatous hypophysitis: experience with eight surgical cases of a single center

Although primary hypophysitis is not uncommon, a granulomatous etiology of hypophysitis is relatively rare. Radiological and diagnostic characteristics of several isolated cases have been described to date. However, to the best of our knowledge, surgical treatment of eight cases of granulomatous hypophysitis confirmed by histopathology has not yet been reported. A retrospective study was performed to review cases of granulomatous hypophysitis from November 2003 to November 2013 in our neurosurgical department. Only eight out of 1345 operations were diagnosed with granulomatous hypophysitis. The cohort included two men and six women. The most common manifestations reported were headache, fatigue and polyuria. All six female patients presented with either menstrual disorders or amenorrhea. Seven of eight patients suffered polyuria. Two patients suffered bitemporal hemianopsia. One was accompanied with eosinophilic granuloma of the skull. Prolactin levels were increased in six patients, four of them were noted to have thyroid axis imbalances, one was noted to be deficient in the gonadotropin axis and two were deficient in the adrenal axis. The lesion demonstrated homogenous enhancement and an abnormally thickened pituitary stalk. A histological diagnosis of granulomatous hypophysitis was established in all eight patients, who were treated surgically. Characteristic granulomas formed by epithelioid histiocytes and multinucleated giant cells were observed. Pure glucocorticoid therapy is less effective than surgical intervention and has not been recommended for the treatment of granulomatous hypophysitis. Although replacement therapy can relieve associated symptoms, we conclude surgical intervention, particularly minimally invasive surgery via a transsphenoidal approach, to be mandatory in establishing a diagnosis and reducing the size of the inflammatory mass. Adjuvant corticosteroids therapy is recommended.

Diagnosis and management of tumor-like hypophysitis: A retrospective case series.

Tumor-like hypophysitis is an uncommon sellar condition that presents as inflammatory lesions on the structures of the pituitary gland. The diagnosis and management of hypophysitis poses a significant challenge, as its clinical manifestation and appearance in imaging studies are difficult to distinguish from that of pituitary tumors. The present retrospective study summarizes two rare cases of primary granulomatous hypophysitis, two cases of lymphocytic hypophysitis, and three cases in which a pathological diagnosis was not determined due to the use of hormone replacement therapy only. The mean age of the patients studied was 45.71±22.16 years, and the patients comprised two males and five females. The clinical signs of hypophysitis included headache, fever, gradual decrease in visual acuity, nausea and vomiting. Enhanced magnetic resonance imaging revealed sellar and pituitary stalk lesions, with iso- or hypodense signals on T1-weighted images. Transsphenoidal surgery was performed in three cases. It was challenging to diagnose hypophysitis due to the lack of any significant specific clinical signs. A transsphenoidal biopsy with fast-frozen pathology is able to diagnose hypophysitis. Glucocorticoid therapy may be a potential treatment for hypophysitis, as complete removal of pituitary masses may disable pituitary function.

Autoimmune hypophysitis

Autoimmune hypophysitis is an inflammation of the pituitary gland resulting from autoimmune response, which can be classified as primary hypophysitis and secondary hypophysitis according to the etiology. The clinical presentation includes hypopituitarism and a pituitary mass. The diagnosis is based on clinical findings and radiology, while the pathology serves as the golden standard. The treatment is aimed at reducing the size of the pituitary mass, replacing the defective hormones and decreasing hyperprolactinemia. This review is about the epidemiology, pathogenesis, diagnosis, and treatment of lymphocytic hypophysitis, hypophysitis secondary to cytotoxic T-4 blockade, and IgG4-related hypophysitis. (Chin J Endocrinol Metab, 2015, 31: 1008-1012) Key words: Autoimmune hypophysitis; Lymphocytic hypophysitis; Hypophysitis secondary to cytotoxic T-4 blockade; IgG4-related hypophysitis

RARE-07RECURRING PITUITARY CYST WITH HISTOLOGY OF XANTHOMATOUS HYPOPHYSITIS: FIRST CASE REPORT OF SURGICALLY TREATED RECURRENCE AND LITERATURE REVIEW

INTRODUCTION: Xanthomatous hypophysitis (XH) is the rarest histological type of primary hypophysitis. It is non lymphocytic in nature, and is characterized by an infiltration of pituitary gland by lipid-laden histiocytes and macrophages. Consequent to a shared location, the clinical and radiological features of XH overlap heavily with pituitary adenomas and are prone to misdiagnosis. In this report we describe a case of newly diagnosed XH, which recurred after 1 year and was treated surgically. CASE: A 45-year-old female presented with history of menstrual irregularity for 9 months and a history of amenorrhea, galactorrhea and headache for 2 months duration. Preoperative endocrinologic studies showed increased prolactin. Magnetic resonance imaging (MRI) of the sella showed a cystic lesion with suprasellar extension suggestive of a pituitary adenoma. The patient underwent transsphenoidal resection that revealed a thick yellowish colloidal material. Histopathology demonstrated necrotic tissue with no definitive diagnosis and no identified microorganisms. The patient resumed her normal menstrual cycle with serum prolactin levels normalizing at 2-months post surgery. At 1-year post surgery her menstrual cycle again became irregular. A repeat MRI showed a recurrent mass and she underwent a second transsphenoidal resection. Repeat histopathology was consistent with XH. At present, the patient is at 5-years post initial surgery and is doing very well without evidence of recurrence. CONCLUSION: To the best of our knowledge, there are 18 prior reported cases in the literature of XH and two reported cases of recurrent disease. The clinical and radiological features of XH are undistinguished form pituitary adenoma. These lesions present similarly to nonfunctional adenomas and diagnosis is often difficult without surgical pathology, necessitating meticulous immunohistochemistry to prevent misdiagnosis. As such, XH should be considered as a rare etiology in the differential of both newly diagnosed and recurrent sellar-region lesions.

Hypophysitis in 2014

Hypophysitis is a rare pathology. As clinical symptoms and radiologic signs are non-specific, the diagnostic is difficult. Hypophysitis's pathogenesis remains obscure but new histological and etiological variants have recently been reported. Primary hypophysitis is the main form. For the first time, hypophysitis in ANCA-associated vasculitides has been reported. An entity of immunoglobulin G4 related plasmatic hypophysitis has been described and well-defined diagnostic criteria are proven. Monoclonal antibodies directed against the cytotoxic T-lymphocyte antigen-4 (CTLA-4), investigated in metastatic cancer, can induce hypophysitis. Hypophysitis's pathogenesis remains obscure but several candidate pituitary autoantigens have been described in the last decade, although none has proven useful as a diagnostic tool.

Diagnosis of Primary Hypophysitis in Germany.

Representative data on diagnostic findings in primary hypophysitis (PrHy) are scarce. The objective of the study was to collate consistent data on clinical features in a large series of patients with PrHy. Another objective was to gain information on current practice in a diagnostic work-up. The Pituitary Working Group of the German Society of Endocrinology conducted a nationwide retrospective cross-sectional cohort study in Germany. Seventy-six patients with PrHy were identified. Clinical and endocrinological features were assessed. Headache (50%) and increase in body mass (18%) were the most frequent nonendocrine symptoms. Hypophysitis was associated with pregnancy in only 11% of the female patients. Diabetes insipidus was found in 54% of the patients at presentation. Hypogonadotropic hypogonadism was the most frequent endocrine failure (62%), whereas GH deficiency was the least frequent (37%). With 86%, thickening of the pituitary stalk was the prevailing neuroradiological sign. Compared with surgical cases, the cases without histological confirmation presented more often with suprasellar lesions and had less severe nonendocrine symptoms. Granulomatous hypophysitis was associated with more severe clinical symptoms than lymphocytic hypophysitis. Examination of cerebrospinal fluid was predominantly performed in participating neurosurgical centers, whereas thyroid antibodies were almost exclusively assessed in endocrinological centers. In contrast to the literature, hypogonadism was found to be the most frequent endocrine failure in PrHy. Weight gain was identified as a clinical sign of PrHy. In the majority of patients, PrHy can be reliably identified by characteristic clinical signs and symptoms, obviating histological confirmation. The diagnostic approach should be standardized in PrHy.

Treatment of Primary Hypophysitis in Germany.

The best treatment of primary hypophysitis (PrHy) is a matter of debate. Our main objective was to analyze the treatment practice for PrHy in Germany and to compare the outcome of the main treatment options. The Pituitary Working Group of the German Society of Endocrinology conducted a nationwide retrospective cross-sectional cohort study. Seventy-six patients with PrHy were eligible for the study. Clinical and endocrinological outcomes, side effects and complications of therapy, initial response, and recurrence rates were assessed. Outcome depending on the treatment modality was evaluated. For mere observation, regression of space-occupying lesions was observed in 46%, unchanged size in 27%, and progression reported in 27%. Pituitary function improved in 27% of patients during observation. Deterioration of pituitary function was only found in patients with progressive lesions. The initial response to glucocorticoid pulse therapy was most favorable, with early failure in only 3%. However, the overall failure and recurrence rate was 41%. Recurrence rate was not related to duration of steroid administration. Side effects of steroids occurred in 63%. The surgical approach was transsphenoidal in 94%. The histological subtype was lymphocytic hypophysitis in 70% and granulomatous hypophysitis in 30%. Progression or recurrence was observed in 25% after surgical treatment. Glucocorticoid pulse therapy is associated with a high recurrence rate. Evidence suggests that surgery is not able to prevent recurrence. Considering the favorable results of observation, conservative management is recommended in PrHy unless symptoms are severe or progressive.