Pituitary Biopsy Research Articles

Hypophysitis in COVID-19: a systematic review.

This systematic review aims to collect and examine recent research findings regarding hypophysitis in COVID-19 patients. We conducted a comprehensive literature review in English on the topic "Hypophysitis in COVID-19," using the MEDLINE (PubMed) database in July 2024. The selected articles were systematically tabulated and we have assessed in this review patient demographics, symptom presentation, imaging results, diagnosis, clinical management, and outcomes. Seven reported cases of post-COVID-19 hypophysitis were identified, comprising 4 (57%) females and 3 (43%)males, with a median age of 37 years. The interval between COVID-19 infection symptoms and the onset of hypophysitis ranged from 2 to 3 weeks. Initial symptoms included frontal headache in 4 (57%) cases and polyuria and polydipsia in 3 (43%)cases. Anterior or posterior hypopituitarism was observed in 6 (85%)patients. Radiological findings varied: 2 (28.5%) cases showed panhypophysitis, 3 (43%) cases exhibited gland enlargement with homogeneous contrast enhancement on magnetic resonance imaging (MRI), 1 case involved the loss of the posterior pituitary bright spot, and 1 case involved pituitary apoplexy/enlargement of the gland and infundibulum. No pituitary biopsies were performed. Four (57%) patients received glucocorticoid (GC) treatment. Long-term follow-up was documented in only one case, a 16-year-old female followed for 2 years reporting complete clinical and radiological resolution. Although rare, hypophysitis related to COVID-19 is documented in the literature exhibiting distinct characteristics such as a homogeneous gender prevalence, an average age of onset around 35 years, and primary symptoms of headache, polyuria, and polydipsia which are indicative of angiotensin-vasopressin deficiency. This is in contrast with primary autoimmune hypophysitis characterized by a female prevalence and typical symptoms with headache and visual impairment. Longer-term follow-up of these patients is needed to better understand the potential lasting impact on pituitary function and radiological improvement. Future research should also explore the presence of anti-pituitary antibodies and the other possible pathophysiological mechanisms potentially involved in these cases.

8155 Isolated Hypothalamic-Pituitary Langerhans' Cell Histiocytosis in Adult Patients

Abstract Disclosure: A. Vu: None. M. Aguilera: None. J. Shakil: None. R. Al-Ward: None. Introduction: Langerhans cell histiocytosis (LCH) is an infiltrative disease due to clonal proliferation of immature dendritic cells mainly affecting children and seen in adults in less than 30% of cases. It can present as localized or with systemic manifestations, with isolated hypothalamic-pituitary lesions being exceptionally rare. Our report adds to the limited published literature by presenting two cases of isolated hypothalamic-pituitary LCH diagnosed in adults. Furthermore, one of the cases reveals a rare association with papillary thyroid cancer (PTC). Case 1: 35-year-old woman with no past medical history presented with 4 year history of amenorrhea and weight gain and more recently, polyuria and polydipsia. Further investigations showed hypogonadotropic hypogonadism, central hypothyroidism, and mildly elevated prolactin. She couldn’t complete water deprivation test due to extreme thirst. A dedicated pituitary MRI showed marked infundibular enlargement, concerning for hypophysitis. An extensive workup including assessments for autoimmune etiology, sarcoidosis, infections, and low-grade tumors, did not identify a definitive etiology. A PET scan was obtained (to rule out LCH and Erdheim Chester disease), which showed increased uptake in the pituitary stalk. Due to otherwise negative workup, transsphenoidal biopsy of the pituitary lesion was done. Post-procedure, diabetes insipidus (DI) was diagnosed due to elevated sodium while fasting for the procedure. Tissue examination revealed increased histiocytes and lymphocytes, and a positive BRAF V600E mutation confirming LCH as the underlying diagnosis. Case 2: 26-year-old male with history of LCH limited to the skull, in remission for 8 years after chemotherapy, presented with 4-week history of polyuria, polydipsia and weight loss. A 24-hour urine collection resulted in 6.5L of urine. During water deprivation test, there was notable increase in serum sodium, serum osmolarity, and urine osmolarity. Initial pituitary MRI was normal, but subsequent imaging revealed the loss of the posterior pituitary bright spot. PET scan showed focal FDG avidity in the right lower thyroid lobe, confirmed on fine needle aspiration as PTC with BRAF mutation. He underwent total thyroidectomy and is currently receiving chemotherapy for LCH recurrence. Discussion: LCH is infrequent in adults, presenting with variable manifestations based on affected organs. In the multifocal form, the hypothalamic-pituitary axis is involved in 5-50% of cases. Our report describes two unique cases with only four other reported cases of isolated hypothalamic-pituitary axis LCH in adults. Central diabetes insipidus can be seen before the diagnosis or as the disease progresses. Pituitary biopsy, although invasive, should be considered when the diagnosis is not clear. The association of PTC with a BRAF mutation is extremely rare and has been reported. Presentation: 6/2/2024

8386 The Evolving Face of The Great Masquerader - Panhypopituitarism Associated with Neurosyphilis

Abstract Disclosure: M. Yabe: None. Z. Lin: None. F. Joseph: None. G. Philip: None. R. Silver: None. L. Callejas: None. J. Giunta: None. Untreated syphilis is on the rise in the United States. The CDC reported syphilis cases in newborns have increased 10-fold over a decade in November 2023, signifying the emergence of untreated infections. Pituitary involvement in syphilis is a very rare phenomenon, and endocrinological investigation is often overlooked. This will be the second reported case of neurosyphilis with pituitary involvement in a non-HIV infected patient. A 45-year-old female with no significant past medical history was admitted to the hospital with progressive neurological symptoms of intermittent left-side headache, hearing loss with tinnitus, and gait instability. Postcontrast MRI Brain revealed multifocal leptomeningeal enhancement involving supratentorial and infratentorial regions. Thickening of the enhanced pituitary infundibulum was also noted. Subsequent RPR titer showed 1:16 and lumbar puncture revealed CSF-VDRL titer 1:32, with pleocytosis 83 cells/uL, CSF-glucose 19 mg/dL, and CSF-protein 370 mg/dL. The patient completed Penicillin G 4 million/units intravenous every 4 hours for 14 days, with repeat MRI showing significant interval decrease in previously described extensive supratentorial and infratentorial leptomeningeal enhancement. However, there is no record of her sexual partner receiving treatment. The patient was readmitted one year later after a fall while displaying dysmetria. MRI Brain with contrast revealed a small subacute infarct along the right frontal corona radiata and pituitary gland measuring up to 1.2 cm in craniocaudal dimension compared to 0.4 cm on the prior exam. This prompted evaluation of pituitary hormones: FSH 0.8 IU/L, LH <0.3 IU/L, and ACTH 6.3 pg/mL, with normal serum growth hormone and prolactin levels. Further investigation revealed morning cortisol 2.5 ug/dL, thyrotropin < 0.2 uIU/mL, and free thyroxine 0.63 ng/dL. Radiological evidence is suspicious of inflammatory etiology of the pituitary gland. The patient was discharged with endocrinology follow-up and plan to perform a pituitary gland biopsy as an outpatient for confirmatory result. The association of neurosyphilis and hypophysitis leading to panhypopituitarism in a non-HIV infected patient was first reported in 2015. Since then, there remains limited research regarding their association due to rarity of pituitary involvement in neurosyphilis. With untreated syphilis on the rise and increased availability of MRI, clinicians should expect to encounter more cases of neurosyphilis with pituitary involvement in the future. Early detection of panhypopituitarism in those with positive CSF-VDRL titer could lead to better clinical outcomes. It is paramount that these cases are documented to emphasize pituitary involvement in neurosyphilis and encourage a low threshold to initiate endocrinological testing in the future. Presentation: 6/3/2024

Arginine vasopressin deficiency onset after COVID-19 vaccination with positive anti-rabphilin-3A antibodies: a case report and literature review

BackgroundArginine vasopressin deficiency (AVP-D) can occur due to various conditions, so clarifying its cause is important for deciding treatment strategy. Although several cases of AVP-D following coronavirus disease 2019(COVID-19) infection or COVID-19 vaccination have been reported, the diagnosis of the underlying disease has not been reported in most cases.Case presentationA 75-year-old woman who presented with polydipsia and polyuria 9 weeks after contracting COVID-19 and 5 weeks after receiving the SARS-CoV-2 vaccination, leading to the final diagnosis of AVP-D 8 months after the first appearance of symptoms. Interestingly, pituitary magnetic resonance imaging (MRI) still revealed stalk enlargement frequently observed in patients with SARS-CoV-2 vaccination-induced AVP-D. Although this finding could not rule out any malignancies, we additionally measured anti-rabphilin-3A antibodies, a known marker for lymphocytic infundibulo-neurohypophysitis (LINH), and found that the results were positive, strongly suggesting LINH as the cause of this disease. Thus, we avoided pituitary biopsy. At the follow-up MRI conducted 12 months after the initial consultation, enlargement of the pituitary stalk was still observed.ConclusionWe experienced a case with LINH probably induced by SARS-CoV-2 vaccination. In SARS-CoV-2 vaccination-related LINH, unlike typical LINH, there is a possibility of persistent pituitary stalk enlargement on MRI images for an extended period, posing challenges in differential diagnosis from other conditions. Pituitary stalk enlargement and positive anti-rabphilin-3A antibodies may help in the diagnosis of AVP-D induced by SARS-CoV-2 vaccination.

Metastasis or macroadenoma - the role of pituitary biopsy in a non-typical clinical presentation - a case report

Metastasis or macroadenoma - the role of pituitary biopsy in a non-typical clinical presentation - a case report

FRI326 Hypophysitis: A Formidable Diagnostic Challenge

Abstract Disclosure: S. Pandey: None. C. Houston: None. Background: Hypophysitis, defined as inflammation of the pituitary gland, may pose a formidable diagnostic challenge due to its protean clinical manifestations and growing spectrum of potential causes. We present a case of a young man with presumed hypophysitis in whom the etiology remains unknown. Case Summary: A previously healthy 20-year-old male with bilateral gynecomastia was referred to the endocrinology clinic. He reported a 1-year history of worsening fatigue, weight gain, intermittent headaches, bilateral breast enlargement, lack of morning erections, polydipsia, and polyuria. His childhood growth and pubertal development were reportedly normal. He denied prior head or testicular trauma, major systemic illnesses, and chronic opiate or glucocorticoid use. His physical exam was remarkable only for scant facial hair and bilateral nontender gynecomastia. His visual fields were normal, and sense of smell was intact. Laboratory evaluation at 8am revealed low total and free testosterone of 32 ng/dL (240-950) and 0.98 ng/dL (5.25-20.7), respectively, with LH of 1.4 mIU/mL (1.0-12.0) and FSH of 1.9 mIU/mL (1.0-12.0). Free T4, prolactin, IGF-1, and serum sodium were all within normal ranges. Serum cortisol was modestly elevated at 22.3 ug/dL (3.7-19.4) with normal ACTH of 49 pg/mL (7.2-63.0). Pituitary MRI showed diffuse thickening and enhancement of the pituitary stalk, compatible with infundibular hypophysitis, without evidence of mass effect upon the native gland or surrounding structures. Additional testing showed normal levels of serum calcium, iron, ferritin, ESR, and antinuclear antibodies. After overnight water deprivation, his serum sodium was elevated at 156 mmol/L (134-144) with low urine osmolality of 121 mOsmol/kg (300-900). He was started on desmopressin and testosterone, and close clinical monitoring was enacted. Conclusion: The diagnosis of hypophysitis poses multiple challenges. Its clinical manifestations can vary widely, including symptoms related to mass effect and/or symptoms of pituitary dysfunction. Diagnosis is often presumptive based on history and exam, biochemical evaluation, and neuroimaging. The spectrum of potential causes is broad and growing, including infiltrative, infectious, neoplastic, immunoglobulin G4-related, immunotherapy-induced, other autoimmune, and paraneoplastic causes. It is often a humbling experience for clinicians to narrow this exhaustive differential. Pituitary biopsy is the gold standard for diagnosis but poses significant risks, so is reserved for cases when the diagnosis remains uncertain or malignancy is suspected. Close clinical monitoring and re-evaluation is an acceptable alternative in select cases. Presentation: Friday, June 16, 2023

FRI339 Hypophysitis Secondary To Small Vessel Anca Vasculitistreated With Rituximab

Abstract Disclosure: A. Rivadeneira: None. N. Kumar: None. S. Banerjee: None. M. Gubbiotti: None. D. Yoshor: None. J. Kharlip: None. C.A. White: None. Introduction: Granulomatosis with polyangiitis (GPA) is an autoimmune small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs) that rarely involves the pituitary. Conventional treatment of GPA includes high dose glucocorticoids with cyclophosphamide. Rituximab has been used in refractory cases with high rates of remission. We present a case of pituitary GPA treated with and excellent response to rituximab. Case: 51-year-old woman with hypothyroidism, post I-131 treatment for Graves’ disease. Patient presented with 1 year of worsening fatigue, myalgias, frontal headaches, sinus congestion and epistaxis. CT sinus showed pituitary enlargement and chronic mucosal disease. MRI pituitary showed diffusely enlarged pituitary with non-visualized posterior pituitary bright spot and thickened stalk. CT chest showed 18x11 mm nodular opacity and peribronchial fibrosis. Laboratory evaluation showed ACTH 26.7 pg/mL, cortisol 13.4 mcg/dL, TSH 1.1, T4 9.7, prolactin 53 ng/dL, estradiol <20, LH 4, FSH 23. Sodium 140 and urine osm 488. There was positive p-ANCA staining and elevated serum anti-proteinase 3 antibody (PR3), 74 units (0-20). Myeloperoxidase antibody was not elevated. ESR 73 mm/h (0 - 30) and CRP 7.9 (<7.4). Due to atypical ANCA pattern (p ANCA typically is associated with MPO not PR3), pituitary biopsy was performed and showed adenohypophysis with dense lymphoplasmacytic infiltration with nodularity of the inflammatory infiltrates, some arranged peri vascularly, compatible with involvement of the pituitary gland by GPA. She began rituximab 375 mg/m2 weekly for four weeks with plan to continue every 6 months. After treatment, the patient experienced resolution of daily frontal headaches, congestion, cough and epistaxis. CT chest showed improvement of prior lung findings, and ESR/CRP normalized. Repeat pituitary MRI is pending. Discussion: Pituitary involvement is uncommon in GPA, occurring in only 3.9% of cases. It may lead to partial or complete pituitary dysfunction, particularly central diabetes insipidus (87.5%) and hypogonadism (75%). Typical MRI abnormalities include diffusely enlarged pituitary gland, thickened pituitary stalk and absence of posterior bright spot. Treatment of GPA includes a combination of corticosteroids, Cyclophosphamide, Azathioprine and Rituximab. Remission is achieved in up to two thirds of patients. Treatment of lymphocytic hypophysitis, another common cause of diffuse pituitary enlargement, relies on high dose glucocorticoids, leading to many side effects and taper is limited by worsening symptoms. This case highlights the critical role in serologic evaluation and targeted pituitary biopsy to identify the specific etiology of pituitary infiltration to help guide alternate treatment options, and the emerging role of Rituximab as a steroid sparing agent for treatment of pituitary inflammation. Presentation: Friday, June 16, 2023

FRI345 A Rare Case Of Pituitary Histoplasmosis Presenting With Hypopituitarism

Abstract Disclosure: A. Jung: None. J. Tan: None. S. Charatz: None. S. Azim: None. A 58-year-old female presented to the endocrine clinic with a history of headache of one year duration. Prior to the visit, she had undergone a right middle lobe lung resection. Histopathology revealed necrotizing granulomas with yeast resembling histoplasmosis on fungal stains. She had no past history to suggest that she was immunocompromised. The patient had completed a three months course of itraconazole. Shortly after, she experienced daily headaches. Pituitary MRI demonstrated an enlarged 1.5cm pituitary gland without compression of the optic chiasm. Laboratory tests showed hypogonadotropic hypogonadism with LH 2.4 mIU/mL (15.9- 54.0), FSH 9.6mIU/mL (23 -116.3), and estradiol 14 pg/mL (<32.2). Free T4 was low 0.7 ng/dL (0.9-1.8) without elevated TSH 1.81 uIU/mL (0.55-4.78). Prolactin was 29.7 ng/mL (2.8-29.2). GH, ACTH, and morning cortisol were normal. Due to the constant headache with hypopituitarism, the decision was made to proceed with transsphenoidal surgery. Pituitary biopsy reported histoplasmosis on Grocott methenamine silver and Periodic acid-Schiff stains. The patient was started on amphotericin B. Repeat MRI confirmed the decrease in size of the pituitary gland after the procedure. Pituitary fungal infections are extremely rare. To our knowledge, this is the first reported case of pituitary histoplasmosis presenting with hypopituitarism. Clinicians should be mindful of the rare etiologies of hypopituitarism when evaluating patients with pituitary enlargement and hypopituitarism. Presentation: Friday, June 16, 2023

Lymphocytic Infundibuloneurohypophysitis Diagnosis Owing to Positive Anti-rabphilin-3A Antibody Test Result in an 8-year-old Boy with Early-onset Central Diabetes İnsipidus.

Childhood-onset lymphocytic infundibuloneurohypophysitis (LINH) has rarely been reported. Pathological evaluation via pituitary biopsy is necessary for a definitive diagnosis of LINH. However, pituitary biopsy is a highly invasive procedure. Recently, anti-rabphilin-3A antibody (RPH3A-Ab) has been reported as a promising diagnostic marker for LINH in adults; however, there are few such reports in the pediatric population. We report the case of an 8-year-old boy with central diabetes insipidus (CDI) who was clinically diagnosed with LINH based on RPH3A-Ab positivity. He was diagnosed with CDI using a water deprivation test combined with desmopressin administration. Serum and cerebrospinal fluid tumor markers were negative, and T1-weighted magnetic resonance imaging (MRI) revealed the absence of high signal intensity in the posterior pituitary gland and an enlarged pituitary stalk. Anterior pituitary function tests revealed no abnormalities. No pituitary biopsy was performed because of its invasive nature, and desmopressin treatment was initiated. Three months after CDI onset, the patient tested positive for RPH3A-Ab. MRI performed 9 months after CDI onset revealed amelioration of the pituitary stalk enlargement, and the clinical course corroborated our diagnosis of LINH. RPH3A-Ab may be useful as an early diagnostic tool for LINH in the pediatric population.

Abstract #1398468: Lymphocytic Hypophysitis Successfully Treated with Prednisone

Lymphocytic Hypophysitis is an inflammatory disorder of the pituitary gland that has classically been described in pregnant and postpartum women. It is the most common type of Primary Hypophysitis which refers to inflammation of the pituitary gland that is not secondary to other systemic diseases or drugs. This is a rare group of disorders with an estimated annual incidence of 2.4 in 10 million. We present the case of a young woman diagnosed with Lymphocytic Hypophysitis and successfully treated with prednisone. A 27-year-old previously healthy female presented with daily headaches and fatigue that began 4 months after an uncomplicated vaginal delivery. She was amenorrheic despite cessation of breast milk production. Physical exam was within normal limits. Laboratory evaluation revealed an AM cortisol of 1 mg/dl (4-22), Free T4 of 0.4 ng/dL (0.8-1.8), LH of 0.5 mIU/mL (1.9-12.5), and estrogen of 30 pg/ml (12.5-166, follicular), consistent with adrenal insufficiency, hypothyroidism, and hypogonadism. Prolactin was normal. She had no evidence of Diabetes Insipidus. MRI pituitary with and without contrast revealed an intensely and homogenously enhancing sellar mass measuring 2 x 2 x 1.3 cm with suprasellar extension and mass effect on the optic chiasm. She did not have any abnormalities in her visual fields or acuity. Lymphocytic Hypophysitis was felt to be the most likely diagnosis based on her clinical presentation and imaging features. Via shared decision-making, she was started on 40 mg of oral prednisone daily in addition to levothyroxine and oral combined contraceptive pills. On reevaluation 2 months later, her symptoms improved and a repeat MRI revealed a dramatic improvement in the appearance of the lesion following which prednisone was reduced to 30 mg with a plan for revaluation after 2 more months. Lymphocytic Hypophysitis should always be suspected in pregnant and postpartum women with neurological complaints of headaches or visual abnormalities and pituitary hormonal deficiency. The investigation involves obtaining an anterior pituitary hormonal profile including TSH with free T4, ACTH with cortisol, FSH, LH, estradiol, and prolactin. Serum sodium with plasma and urine osmolality can be used to evaluate diabetes insipidus in suspected cases. MRI pituitary with and without contrast frequently reveals a symmetric sellar lesion that enhances intensely and homogeneously with gadolinium. A pituitary adenoma, in contrast, enhances less than the normal pituitary tissue. A tool based on clinical and radiological features called the Gutenberg score can also aid in differentiating lymphocytic hypophysitis from an adenoma. Treatment involves management of hormonal deficiencies including Diabetes Insipidus and relief of symptoms of mass effect. Glucocorticoids can induce remission and possible recovery of hormonal function. Follow-up with serial imaging in a few months after initiation of glucocorticoids is essential. Diagnosis needs to be reconsidered if there is no improvement in the appearance of the lesion and a pituitary biopsy may be indicated.

LBODP074 Autoimmune Hypophysitis: Diagnosis Beyond Imaging

Abstract Background Lymphocytic (LH) or autoimmune hypophysitis (AH) is a rare inflammatory disorder of the hypophyseal gland, often miss-diagnosed. LH is predominant in females, occasionally related with other rheumatic disorders (1-20%). The disease can lead to pituitary dysfunction and symptoms of hypopituitarism, the most affected axes are the ACTH and TSH. Definitive diagnosis of AH can be based only on pathological examination of a pituitary biopsy sample but such invasive procedure is seldom needed. Different imaging modalities, especially MRI, can be useful but up to 30% can be unremarkable, thus clinical manifestations and biochemical evaluation is of great importance in guiding the diagnosis. Hormonal replacement therapy is the main treatment strategy. Immunosuppressive drugs are indicated by the severity of the symptoms and the underlying autoimmune disease. Clinical Case A 36 year old patient with active lupus and Sjogren disease presented to the emergency department with syncope and hypotension preceded by a 6 month history of intense fatigue. She did not take any steroids in the 6 months prior. Initial tests were consistent with secondary adrenal insufficiency; low plasma cortisol (<1ug/dl n 5-23 ug/dl) and ACTH-concentrations below detection (< 4 ng/l), central hypothyroidism; abnormal low TSH (0. 04uU/ml n 0.4-4.5 uU/ml) and low free T4 (0.56 ng/dl n 0.8-2 ng/dl), and growth hormone deficiency (IGF1 below age and sex normal values). Craneal CT and pituitary MRI didn't show any anomaly. Based on symptoms, clinical context and test results the pressumtive diagnosis was AH related to her lupus. The patient was treated with hydrocortisone and levothyroxine with excellent response and complete resolution of her symptoms. Clinical Lesson: This case demonstrates that hypophysitis is a clinical entity that can be suspected and treated based on clinical and past medical history even in the context of normal imaging were an invasive procedure such as a biopsy would likely not change the final outcome. Presentation: No date and time listed

ODP352 Steroid-sparing immunosuppressive therapy controls refractory headaches due to lymphocytic hypophysitis: a case report

Abstract Background Systemic glucocorticoid therapy has been used to control headaches associated with lymphocytic hypophysitis (LH), a rare autoimmune inflammation of the pituitary gland and stalk. Steroid-sparing immunosuppressive therapies, like mycophenolate mofetil (MM), have proven to be effective for patients with many systemic inflammatory and rheumatological conditions. However, the safety and efficacy of steroid-sparing immunosuppressive therapies for LH has not been studied. Clinical Case Here we report a case of a 31-year-old male who presented with worsening headache, fatigue, polyuria, insomnia, low libido, and decreased appetite. His laboratory results were consistent with central diabetes insipidus (DI), central hypothyroidism, central adrenal insufficiency, and hypogonadotropic hypogonadism without evidence of growth hormone deficiency. Initial pituitary MRI revealed pituitary enlargement and thickening of the stalk. He was started on desmopressin, levothyroxine, testosterone cypionate, and physiologic glucocorticoid replacement with prednisone 5mg daily. He continued to endorse incapacitating occipital headaches not relieved by ibuprofen, topiramate, gabapentin, amitriptyline, sumatriptan, or rizatriptan, and only temporary relieved by occipital nerve blocks. A pituitary biopsy confirmed the diagnosis of LH. Given his persistent, debilitating headaches, prednisone was increased to supraphysiologic doses. Headaches resolved on prednisone 40mg daily but recurred two months after tapering down to prednisone 5mg daily. Pituitary MRI after 4 months revealed a mild interval increase in enhancement and thickening of the pituitary stalk. Prednisone was increased to 20mg daily, and he was started on MM for progressive inflammation. Prednisone was tapered down to 5mg daily over the course of 3 months as MM dose was increased to 1000mg twice a day. Headaches completely resolved. After 4 months of MM therapy, pituitary MRI showed decrease in size of pituitary stalk thickening and pituitary, consistent with treatment effect. After 6 months of MM therapy, MRI brain showed further decrease in pituitary size and resolution of pituitary stalk thickening. He did not experience any adverse effect on MM. Serial complete blood counts, liver function tests, and basic metabolic panels were normal. Two years after diagnosis and one year on MM therapy, his DI resolved, his adrenal insufficiency was well managed with prednisone 4mg daily, he was euthyroid on levothyroxine 75mcg daily, and his hypogonadism was treated adequately with testosterone cypionate 50mg weekly with improved libido and energy. Conclusion MM was effective in treating intractable headaches caused by biopsy-proven LH. Radiologic signs of improvement in pituitary inflammation coincided with patient's report of headache relief and initiation of MM, without concurrent use of supraphysiologic glucocorticoids. Treatment was well-tolerated with no reported adverse effect. Steroid-sparing immunosuppressive therapy like MM may be considered as a therapy for LH, particularly in patients who depend on prolonged courses of supraphysiologic glucocorticoid treatment to alleviate symptoms. Presentation: No date and time listed

ODP292 A Xanthomatous Hypophysitis: Always Think Twice Before Pituitary Resection.

Abstract Background A xanthomatous hypophysitis is a rare form of primary hypophysitis common in females. Clinical case: A 47-year-old male was referred for pituitary adenoma resection. The patient presented with low libido and facial and body hair loss for 3 years. He reported increased thirst and nocturia for 2 years. 24-hr fluid intake showed 4,800 ml intake and 6,700 ml output. Physical examination revealed tanner 5 pubic hair with testicle size 12 ml bilaterally. He had a normal visual field. Laboratory testing revealed low morning total testosterone level of 108 ng/dL (241-872), low LH 0.39 mIU/mL (1.14-8.75) and low FSH 1.28 mIU/mL (1.37-13.58). Other pituitary hormones showed normal TSH 0.634 uIU/ml (0.35-4.9) with low free T4 0.64 (0.7-1.48), IGF-1 107 ng/mL (74-196), prolactin 10.92 mcg/mL (3.46-19.4), morning cortisol 8.9 mcg/dL (3.7-19.4). A 1 mcg ACTH stimulation test showed an inappropriate increase in cortisol level of 16.1 mcg/dL with baseline ACTH 28 pg/mL (0-46). Regarding polyuria, biochemical testing showed serum Na 148 mmol/L (136-145), Uosm 307 mOsm/Kg (50-1300), and Sosm 307 mOsm/kg (275-290). After the therapeutic trial with oral DDAVP, urine output significantly decreased. Subsequent tests showed serum Na 144 mmol/L, Uosm of 295 mOsm/kg, and Sosm of 278 mOsm/kg. The final diagnosis was hypopituitarism and central diabetes insipidus. MRI showed an enlarged pituitary gland with 2 decreased enhancing nodules in the post-contrast study of the anterior lobe measuring 4.2 and 6.7 mm in diameter. No stalk thickening was detected. There was no compression on adjacent organs. Since the pituitary lesions could not explain the hypopituitarism and DI. The surgery was postponed, and he underwent an endoscopic transsphenoidal biopsy. The procedure yielded a milky fluid content, and a circumferential dissection of a soft-yellow capsule was done. Pathology examination revealed a chronic hypophysitis with clusters of foamy macrophages. Immunohistochemistry showed positive for CD3, CD20, and CD138. A CD68 was positive in multiple clusters of foamy macrophages, while an IgG4 was negative. The final diagnosis is xanthomatous hypophysitis. The patient was treated with hormonal replacement therapy of levothyroxine, prednisolone, testosterone, and DDAVP. Until now, there are 36 cases in the literature reporting xanthomatous hypophysitis. The prevalences of hormonal deficits are 36.1% adrenal insufficiency, 42.4% central hypothyroidism, 54.6% central DI, 36.4% hypogonadism, 63.6% GH deficiency, and 54.6% hyperprolactinemia. The common MRI characteristic is a cystic mass with a ring or peripheral enhancement. Pituitary stalk thickening is shown in 50% of cases. Conclusion This clinical case demonstrated the rare entity of xanthomatous hypophysitis presenting with secondary AI, hypogonadotropic hypogonadism, central hypothyroidism, and DI. The discrepancy between clinical history and the MRI findings was a clue for pituitary biopsy leading to the final diagnosis and avoidance of unnecessary surgery. Presentation: No date and time listed

Pituitary Abscess as Manifestation of IgG4-Related Hypophysitis: A Case Report

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition with heterogeneous organ-specific manifestations. IgG4-related hypophysitis results from pituitary involvement and represents a rare neuro-ophthalmic complication of IgG4-RD, but the presentation as pituitary abscess is exceptional. We report the case of a 38-year-old otherwise healthy woman with a 3-year history of relapsing pituitary sterile abscess repeatedly treated with neurosurgery and antimicrobials. Histological re-examination of pituitary biopsy specimens revealed a dense inflammatory infiltrate rich in IgG4-positive plasma cells. Serum IgG4 levels were normal and circulating plasmablasts were increased. A diagnosis of IgG4-related hypophysitis was made and the patient treated with high-dose steroid pulse therapy with subsequent reduction of the pituitary lesion and resolution of symptoms. This case highlights how the diagnostic intuition on the basis of histopathology has changed management with prompt dramatic response to steroid therapy.

IgG4-related hypophysitis: a retrospective cohort study

PurposeIgG4-related hypophysitis (IgG4-RH) is a rare chronic inflammatory condition of the pituitary gland. This study reports the presentation, management and outcomes for patients with histologically proven IgG4-related hypophysitis.MethodsA prospectively maintained electronic database was searched over a 14-year period from 1 January 2007 to 31 December 2020 at a single academic centre to identify all patients with a histological diagnosis of IgG4-RH. A retrospective case note review from electronic health records was conducted for each case to extract data on their presentation, management and outcomes.ResultsA total of 8 patients (5 male) with a median age of 51 years were identified. The most common presenting symptoms were headache (4/8; 50%), fatigue (3/8; 37.5%) and visual impairment (2/8; 25%). Three patients were initially treated with high-dose steroids aiming for reduction of the pituitary mass. However, ultimately all patients underwent transsphenoidal surgery. Post-operative changes included radiological reduction in pituitary mass in all patients that had imaging (7/7; 100%), improvement in vision (1/2; 50%), residual thick pituitary stalk (5/7; 71.4%), persistent anterior hypopituitarism (4/8; 50%) and panhypopopituitarism including diabetes insipidus (3/8; 37.5%).ConclusionsIgG4-RH is an increasingly recognised entity presenting with a variety of symptoms and signs. Clinical presentation is similar to other forms of hypophysitis. It is therefore important to consider IgG4-RH as a differential and to have a low threshold for pituitary biopsy, the diagnostic gold standard. The diagnosis of IgG4-RH will guide decisions for additional workup for IgG4-related disease, multi-disciplinary team involvement and follow-up.

Clinical analysis for 15 patients with pulmonary Langerhans cell histiocytosis and literature review.

Pulmonary Langerhans cell histiocytosis (PLCH) is a clonal disease, characterized by proliferation of Langerhans cells that derived from bone marrow infiltrating the lungs and other organs. Due to the rarity of the disease, the current understanding of the disease is insufficient, often misdiagnosed or missed diagnosis. This study aims to raise clinicians' awareness for this disease via summarizing the clinical characteristics, imaging features, and treatment of PLCH. We retrospectively analyzed clinical and follow-up data of 15 hospitalized cases of PLCH from September 2012 to June 2021 in the Second Xiangya Hospital of Central South University. The age of 15 patients (9 men and 6 women, with a sex ratio of 3 to 2) was 21-52 (median 33) years. Among them, 8 had a history of smoking and 5 suffered spontaneous pneumothorax during disease course. There were 3 patients with single system PLCH and 12 patients with multi-system PLCH, including 7 patients with pituitary involvement, 7 patients with lymph node involvement, 6 patients with bone involvement, 5 patients with liver involvement, 2 patients with skin involvement, 2 patients with thyroid involvement, and 1 patients with thymus involvement. The clinical manifestations were varied but non-specific. Respiratory symptoms mainly included dry cough, sputum expectoration, chest pain, etc. Constitutional symptoms included fever and weight loss. Patients with multi-system involvement experienced symptoms such as polyuria-polydipsia, bone pain, and skin rash. All patients were confirmed by pathology, including 6 by lung biopsy, 3 by bone biopsy, 2 by lymph node biopsy, and 4 by liver, skin, suprasternal fossa tumor, or pituitary stalk biopsy. The most common CT findings from this cohort of patients were nodules and/or cysts and nodular and cystic shadows were found in 7 patients. Three patients presented simple multiple cystic shadows, 3 patients presented multiple nodules, and 2 patients presented with single nodules and mass shadows. Pulmonary function tests were performed in 4 patients, ventilation dysfunction was showed in 2 patients at the first visit. Pulmonary diffusion function tests were performed in 4 patients and showed a decrease in 3 patients. Smoking cessation was recommended to PLCH patients with smoking history. Ten patients received chemotherapy while 2 patients received oral glucocorticoid therapy. Among the 11 patients with the long-term follow-up, 9 were in stable condition. PLCH is a neoplastic disease closely related to smoking. The clinical manifestations and laboratory examination are not specific. Pneumothorax could be the first symptom which is very suggestive of the disease. Definitive diagnosis relies on histology. There is no unified treatment plan for PLCH, and individualized treatment should be carried out according to organ involvement. Early smoking cessation is essential. Chemotherapy is the main treatment for rapidly progressing PLCH involved multiple organs. All diagnosed patients can be considered for the detection of BRAFV600E gene and relevant targeted therapies have been implemented recently.

Abstract 38: Sellar mass – An unusual presentation of metastatic thyroid carcinoma

Background: Sellar metastases are rare. They may precede the diagnosis of primary malignancy in 20-30% of the cases.Case Report: A 47year female presented with ptosis and diminished vision of right eye. She had a mass in the sellar region extending into the suprasellar area. Her serum prolactin level was 215 ng/ml. She had galactorrhea, secondary hypothyroidism, secondary hypocortisolemia. A trial of cabergoline was given for 6 weeks. She had progressive diminution in vision and a repeat MRI brain showed an increase in the size of the mass. She underwent tumour decompression. The histopathology was suggestive of metastatic tumor of the sella. Immunohistochemistry of pituitary biopsy was positive for CK and TTF-1 (nuclear). On evaluation, FDG-PET CT scan showed metabolically active nodule in the left lobe of thyroid. Ultrasound scan of thyroid showed multinodular goiter (TIRADS 5). FNAC of the left thyroid nodule was suggestive of Hashimoto's thyroiditis. With a suspicion of primary thyroid malignancy, total thyroidectomy was performed. Surgical biopsy report of thyroid showed well-differentiated follicular carcinoma. Radioablation with I-131 was performed for residual thyroid tissue in the neck and metastases.Conclusion: Metastasis to the pituitary can be a rare presentation of thyroid cancer. It may mimic a pituitary adenoma.

Masked diabetes insipidus in pituitary metastasis from breast cancer after thalamic biopsy: a case report

BackgroundSymptomatic pituitary metastasis is rare; furthermore, it can result in diabetes insipidus and panhypopituitarism. Since diabetes insipidus is masked by concurrent panhypopituitarism, it can impede the diagnosis of pituitary dysfunction.Case presentationA 68-year-old Japanese female suffering from pituitary and thalamic metastases caused by untreated breast cancer, underwent a biopsy targeting the thalamus, not the pituitary. She lacked prebiopsy pituitary dysfunction symptoms; however, these symptoms unexpectedly occurred after biopsy. Diabetes insipidus was masked by corticosteroid insufficiency, and she showed normal urinary output and plasma sodium levels. Upon commencement of glucocorticoid replacement therapy, the symptoms of diabetes insipidus appeared.ConclusionsIn this case, thalamic biopsy, as opposed to pituitary biopsy, was performed to preserve pituitary function. However, pituitary dysfunction could not be avoided. Caution is necessary for asymptomatic patients with pituitary metastases as invasive interventions, such as surgery, may induce pituitary dysfunction. Moreover, with respect to masked diabetes insipidus, there is a need to carefully consider pituitary dysfunction to avoid misdiagnosis and delayed treatment.

Diagnosis of Pituitary Adenoma Biopsies by Ultrahigh Resolution Optical Coherence Tomography Using Neuronal Networks.

ObjectiveDespite advancements of intraoperative visualization, the difficulty to visually distinguish adenoma from adjacent pituitary gland due to textural similarities may lead to incomplete adenoma resection or impairment of pituitary function. The aim of this study was to investigate optical coherence tomography (OCT) imaging in combination with a convolutional neural network (CNN) for objectively identify pituitary adenoma tissue in an ex vivo setting.MethodsA prospective study was conducted to train and test a CNN algorithm to identify pituitary adenoma tissue in OCT images of adenoma and adjacent pituitary gland samples. From each sample, 500 slices of adjacent cross-sectional OCT images were used for CNN classification.ResultsOCT data acquisition was feasible in 19/20 (95%) patients. The 16.000 OCT slices of 16/19 of cases were employed for creating a trained CNN algorithm (70% for training, 15% for validating the classifier). Thereafter, the classifier was tested on the paired samples of three patients (3.000 slices). The CNN correctly predicted adenoma in the 3 adenoma samples (98%, 100% and 84% respectively), and correctly predicted gland and transition zone in the 3 samples from the adjacent pituitary gland.ConclusionTrained convolutional neural network computing has the potential for fast and objective identification of pituitary adenoma tissue in OCT images with high sensitivity ex vivo. However, further investigation with larger number of samples is required.

S2391 Concomitant Treatment of Secondary Lymphocytic Hypophysitis and Crohn’s Disease With Adalimumab

Introduction: Lymphocytic hypophysitis (LH) results from atrophy and fibrosis of pituitary cells secondary to lymphocyte infiltration. Patients initially present with headaches, visual changes and endocrine dysfunction. Magnetic resonance imaging (MRI) and biopsy are the gold-standards of diagnosis. LH is typically treated with high-dose glucocorticoids. Secondary LH can occur in association with systemic inflammatory disorders such as inflammatory bowel disease. We describe an unusual case of LH presenting during treatment revision of Crohn’s disease (CD) and successful treatment of both conditions with the anti-tumor necrosis factor antibody, adalimumab. Case description/methods: A 37-year-old female was diagnosed with inflammatory Crohn’s ileitis and achieved rapid remission with infliximab. Nine years later, she became a secondary nonresponder, having developed active disease with high antibody levels, and was switched to vedolizumab. Within a month, she developed diabetes insipidus and bitemporal hemianopsia with no prior neurological symptoms or headaches. An MRI with and without contrast revealed abnormal T2 enhancement involving the hypothalamus and optic tracts extending to the optic chiasm (Figure 1A). A pituitary biopsy was consistent with LH and she was treated with dexamethasone with symptom resolution in three months. She was tapered off steroids, but one month later she developed visual changes, headaches, and lactation. A repeat MRI showed new/increased T2 hyperintensities along the infundibulum, hypothalamus, optic chiasm, optic nerves and optic tract/subcortical white matter (Figure 1B). With the goal of treating both LH and CD with a single nonsteroidal therapy, vedolizumab was discontinued and she was started on a adalimumab and dexamethasone taper during induction. Five months later, she remained neurologically and digestively asymptomatic on adalimumab monotherapy and an MRI showed no abnormal enhancement of the chiasmal or hypophyseal region (Figure 1C). Discussion: Lymphocytic hypophysitis can be a primary or secondary disorder. This case highlights the importance of considering treatment options that reduce steroid burden when LH is associated with other systemic disorders. In this case, we postulate that switching treatment of CD with vedolizumab, which does not cross the blood-brain barrier, may have unmasked the development of LH. Switching to an anti-inflammatory agent such as adalimumab that does penetrate into the central nervous system lead to effective therapy of both disorders.Figure 1.: A. T1 pre-contrast and T2 post-contrast coronal MRI demonstrates abnormal T2 signal involving the hypothalamus and optic tracts extending to the optic chiasm (arrow), right greater than left, with patchy enhancement. B. Repeat T1 pre-contrast and post-contrast sagittal MRI demonstrates enlargement of the pituitary gland and infundibular stalk (arrow) with abnormal contrast enhancement. C. Five months later, post- adalimumab treatment, T1 pre-contrast and post-contrast sagittal MRI demonstrates normal physiologic contrast uptake of the hypophysis with a normal appearing infundibulum.