Thickening Of Pituitary Stalk Research Articles

A case of IgG4-related hypophysitis maintained remission of diabetes insipidus for over 3 months after completion of steroid treatment.

IgG4-related disease is a multiorgan disorder in which nodules and hypertrophic lesions are observed simultaneously, or separately, in areas including the pancreas, liver, lungs, salivary glands, thyroid glands, and pituitary glands. IgG4-related hypophysis is one of several IgG4-related diseases and is characterized by pituitary gland and pituitary stalk thickening, various degrees of hypopituitarism, and increased serum IgG4 levels. Steroid therapy is effective for patients with IgG4-related hypophysis, but the reported effectiveness of steroid therapy for restoring pituitary function differs between studies. Following an episode of autoimmune pancreatitis 10 years prior, enlargement of the pituitary gland and stalk along with panhypopituitarism and polyuria developed in a 73-year-old male. A high serum IgG4 level and biopsy of the submandibular gland showing infiltration of IgG4-positive plasma cells led to a clinical diagnosis of IgG4-related hypophysitis. Prednisolone treatment reduced the swelling of the pituitary gland and stalk and improved anterior pituitary function. Although arginine vasopressin secretion remained insufficient, polyuria was relieved and kept in remission even after prednisolone treatment was completed. This is the first reported case in which prednisolone was able to maintain both normal anterior pituitary function and remission of polyuria caused by IgG4-related hypophysitis. IgG4-related hypophysitis has previously been associated with a relapse of symptoms during treatment. However, the patient reported in this case study remained in remission for over 3 months after completion of steroid treatment and should be monitored closely for changes in pituitary function. Steroid therapy is the first-line therapy for pituitary dysfunction and pituitary stalk swelling in IgG4-related hypophysitis. In this case, although posterior pituitary function remained insufficient, polyuria was relieved and kept in remission for over 3 months even after prednisolone treatment was completed. IgG4-related hypophysitis has been associated with the relapse of symptoms during steroid tapering, and changes in pituitary function and symptoms should be monitored closely. When we encounter cases of adrenal insufficiency and polyuria during observation of autoimmune pancreatitis or other IgG4-related disease, we should consider the possibility of IgG4-related hypophysitis in mind.

Incidence and Predictors for Oncologic Etiologies in Chinese Children with Pituitary Stalk Thickening.

With the increasing use of magnetic resonance imaging (MRI) in the evaluation of children with endocrine disorders, pituitary stalk thickening (PST) poses a clinical conundrum due to the potential for underlying neoplasms and challenges in obtaining a tissue biopsy. The existing literature suggests Langerhans cell histiocytosis (LCH) to be the commonest (16%) oncologic cause for PST, followed by germ cell tumors (GCTs, 13%) (CCLG 2021). As the cancer epidemiology varies according to ethnicity, we present herein the incidence and predictors for oncologic etiologies in Hong Kong Chinese children with PST. Based on a territory-wide electronic database, we reviewed patients aged < 19 years who presented to three referral centers with endocrinopathies between 2010 and 2022. Records for patients who underwent at least one MRI brain/pituitary were examined (n = 1670): those with PST (stalk thickness ≥ 3 mm) were included, while patients with pre-existing cancer, other CNS and extra-CNS disease foci that were diagnostic of the underlying condition were excluded. Twenty-eight patients (M:F = 10:18) were identified. The median age at diagnosis of PST was 10.9 years (range: 3.8-16.5), with central diabetes insipidus (CDI) and growth hormone deficiency (GHD) being the most frequent presenting endocrine disorders. At a median follow-up of 4.8 years, oncologic diagnoses were made in 14 patients (50%), including 13 GCTs (46%; germinoma = 11, non-germinoma = 2) and one LCH (4%). Among patients with GCTs, 10 were diagnosed based on histology, two by abnormal tumor markers and one by a combination of histology and tumor markers. Three patients with germinoma were initially misdiagnosed as hypophysitis/LCH. The cumulative incidence of oncologic diagnoses was significantly higher in boys and patients with PST at presentation ≥6.5 mm, CDI or ≥2 pituitary hormone deficiencies at presentation and evolving hypopituitarism (all p < 0.05 by log-rank). A higher rate of GCTs was observed in Chinese children with endocrinopathy and isolated PST. The predictors identified in this study may guide healthcare providers in Asia in clinical decision making. Serial measurement of tumor markers is essential in management.

Treatment outcome of metastasis to the pituitary gland: a case series of 21 patients with pathological diagnosis.

The aim of this study was to report the treatment course of histologically confirmed metastases to the pituitary gland (pituitary metastasis). The Mayo data explorer was used to find patients with pituitary metastasis. Twenty-one patients were identified between the years 2001 and 2021, and their data were retrospectively collected. The most common primary cancer origin was lung in men (45%) and breast in women (33%). The median age was 66 years (IQR 56-68 years). Patients presented with headache (67% [14/21]), vision problems (86% [18/21]), anterior hypopituitarism (71% [15/21]), and arginine vasopressin deficiency (38% [8/21]). Pituitary metastases were found before the diagnosis of the primary cancer in 5 patients (24%). The mean ± SD tumor size was 2.0 ± 0.7 cm, and 90% (19/21) presented as a solitary pituitary mass with no other intracranial metastatic lesions. Common radiological features were pituitary stalk thickening (90% [19/21]), cavernous sinus involvement (71% [15/21]), and constriction at the diaphragma sellae (52% [11/21]). Transsphenoidal surgery was performed in 20 patients, and subtotal resection was most frequently attained (76% [16/21]). Fourteen patients (67%) had adjuvant radiation therapy, and 15 patients (71%) were treated with systemic therapy. The median time from surgery to the initiation of radiation therapy was 16 days (IQR 11-21 days), and that from surgery to the initiation of systemic therapy was 5.0 months (IQR 1.5-14 months). During management, headaches improved in 57% (8/14) and vision problems improved in 61% (11/18) of cases; new hypopituitarism occurred in 5 patients. Six patients developed recurrence, and the median progression-free survival was 24 months (95% CI 5.4-43 months). After recurrence, 1 patient with adenoid cystic carcinoma was treated with rescue radiotherapy twice, and 4 patients responded well to systemic therapy. The median overall survival (OS) was 25 months (95% CI 7.1-43 months). The mean OS was better in patients with neuroendocrine lung tumor (261 months) and papillary thyroid carcinoma (80 months) and worse in patients with small cell lung cancer (4 months) and unknown origin (5 months). Surgery with or without adjuvant radiotherapy is effective for mass reduction, rapid symptomatic improvement of vision and headaches, and definitive diagnosis. Even after local tumor control failure, some patients still benefit from radiation and/or systemic therapy.

Central diabetes insipidus with anti-rabphilin-3A antibody positivity causing hypovolemic shock after resection of tumorous lesions in the pelvic cavity.

A 36-year-old female was pointed out to have liver enzyme elevation by routine health checkup. Subsequent contrast-enhanced CT scan identified gigantic uterine fibroids and retroperitoneal tumor. She was referred to the gynecologist at JA Toride Medical Center and planned to undergo a uterus enucleation and biopsy of the retroperitoneal tumor. The surgery was conducted without any troubles. After the surgery, the patient presented polyuria with urine volume 10-20 L a day and developed hypovolemic shock. Laboratory test revealed hypotonic urine and hypernatremia. Arginine vasopressin (AVP) loading test suggested shortage of endogenous vasopressin. Since the subcutaneous administration of AVP was not sufficient to control the urine volume, continuous intravenous infusion of AVP was initiated. After achieving hemodynamic stability, the treatment was switched to oral desmopressin. MRI finding indicated attenuation of high signal in posterior pituitary in T1 weighted image while neither enlargement of pituitary nor thickening of pituitary stalk was indicated by enhanced MRI. Hypertonic salt solution test indicated no responsive elevation of AVP, confirming the diagnosis of central diabetes insipidus (CDI). Her anterior pituitary function was preserved. Only anti-rabphilin-3A antibody was found positive in the serum of the patient, while other secondary causes for CDI were denied serologically and radiologically. Hence, lymphocytic infundibuloneurohypophysitis (LINH) was suspected as the final diagnosis. Hormonal replacement therapy by nasal desmopressin was continued and the patient managed to control her urine volume. In cases of CDI considered idiopathic with conventional examinations, anti-rabphilin-3A antibody may be a clue for determining the cause as LINH.

Pilot Findings on SARS-CoV-2 Vaccine-Induced Pituitary Diseases: A Mini Review from Diagnosis to Pathophysiology.

Since the emergence of the COVID-19 pandemic at the end of 2019, a massive vaccination campaign has been undertaken rapidly and worldwide. Like other vaccines, the COVID-19 vaccine is not devoid of side effects. Typically, the adverse side effects of vaccination include transient headache, fever, and myalgia. Endocrine organs are also affected by adverse effects. The major SARS-CoV-2 vaccine-associated endocrinopathies reported since the beginning of the vaccination campaign are thyroid and pancreas disorders. SARS-CoV-2 vaccine-induced pituitary diseases have become more frequently described in the literature. We searched PubMed/MEDLINE for commentaries, case reports, and case series articles reporting pituitary disorders following SARS-CoV-2 vaccination. The search was reiterated until September 2022, in which eight case reports were found. In all the cases, there were no personal or familial history of pituitary disease described. All the patients described had no previous SARS-CoV-2 infection prior to the vaccination episode. Regarding the type of vaccines administered, 50% of the patients received (BNT162b2; Pfizer-BioNTech) and 50% received (ChAdOx1 nCov-19; AstraZeneca). In five cases, the pituitary disorder developed after the first dose of the corresponding vaccine. Regarding the types of pituitary disorder, five were hypophysitis (variable clinical aspects ranging from pituitary lesion to pituitary stalk thickness) and three were pituitary apoplexy. The time period between vaccination and pituitary disorder ranged from one to seven days. Depending on each case's follow-up time, a complete remission was obtained in all the apoplexy cases but in only three patients with hypophysitis (persistence of the central diabetes insipidus). Both quantity and quality of the published data about pituitary inconveniences after COVID-19 vaccination are limited. Pituitary disorders, unlike thyroid disorders, occur very quickly after COVID-19 vaccination (less than seven days for pituitary disorders versus two months for thyroid disease). This is partially explained by the ease of reaching the pituitary, which is a small gland. Therefore, this gland is rapidly overspread, which explains the speed of onset of pituitary symptoms (especially ADH deficiency which is a rapid onset deficit with evocative symptoms). Accordingly, these pilot findings offer clinicians a future direction to be vigilant for possible pituitary adverse effects of vaccination. This will allow them to accurately orient patients for medical assistance when they present with remarkable symptoms, such as asthenia, polyuro-polydipsia, or severe headache, following a COVID-19 vaccination.

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

PMON81 A Case of Hypophysitis Associated With SARS-CoV2 Vaccination

Abstract Objective Although SARS-CoV2 vaccines have been developed with multiple novel technologies and rapidly disseminated worldwide, the full profile of adverse effects has not been known. Recently, there are sporadic but increasing reports of endocrinopathies in relation to SARS-CoV2 vaccination. Here, we report a rare case of hypophysitis with acute onset of diabetes insipidus after SARS-CoV2 vaccination. Case Report A 48-year-old female who had been in her usual state of health until she received the first SARS-CoV2 vaccine. Two days after the vaccination, she started to have flu-like symptoms including severe headache and myalgia as well as persistent headache, polydipsia and polyuria. On presentation, her vital signs were stable, with her pulse being 81 bpm, BP: 122/84 mm Hg, temperature: 98.6F. Her physical examination was unremarkable. Laboratory evaluation revealed normal values of the basic metabolic panel including sodium level of 142 mmol/L and normal complete blood count. Due to her prolonged and worsening headache, she underwent a brain MRI which revealed a 4 mm round shape of thickening pituitary stalk and partial empty sella. The polydipsia, polyuria, and the thickening of the pituitary stalk led to further pituitary work-up. She underwent the overnight water deprivation test followed by the desmopressin challenge test. Her overnight water deprivation test revealed hypernatremia (Na 147 mmol/L), elevated serum osmolarity (309 mmol/kg), and low urinary osmolarity (83 mmol/kg) which were compatible with diabetes insipidus. Her IGF1 level revealed low normal range (66 ng/mL). Her 250 mcg cosyntropin test showed appropriate response without adrenal insufficiency. DDAVP was started. 3 months after the vaccination, her symptoms have partially improved, and on repeating the MRI brain she has persistent pituitary stalk thickening. Discussion We report a rare case of diabetes insipidus from hypophysitis associated with SARS-CoV2 vaccine. Mechanisms of SARS-CoV2 vaccination-associated endocrinopathy is unknown. From our literature search, we found increasing numbers of the cases of endocrinopathy reported after the SARS- CoV2 vaccination. The thyroid seems the most frequently reported endocrine organ (83%), followed by the pituitary (11%) and adrenal (6%). Average onset is 1-5 days after the vaccinations and reported with all types of SARS-CoV2 vaccines. More mid-age (average age 46) female (78%) cases have been reported. Although associations are not confirmed, endocrinopathies may be underestimated in the post vaccinated population. Further studies are warranted to better understand SARS-CoV2 vaccinations and potential associations of endocrinopathy. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

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

Management of children and young people with idiopathic pituitary stalk thickening, central diabetes insipidus, or both: a national clinical practice consensus guideline.

Management of children and young people with idiopathic pituitary stalk thickening, central diabetes insipidus, or both: a national clinical practice consensus guideline.

Characterization of Endocrine Glands Involved in Erdheim-Chester Disease

Objective To investigate the clinical and imaging characteristics of endocrine glands involved in Erdheim-Chester disease (ECD).Methods A retrospective analysis was performed on 48 ECD cases pathologically diagnosed from January 2014 to October 2020 in Peking Union Medical College Hospital,including 22 cases of endocrine gland involvement.The clinical,imaging,and pathological characteristics were summarized. Results Pituitary was involved in 17 cases (17/48,35.4%),adrenal gland in 8 cases (8/48,16.7%),and both pituitary and adrenal gland in 3 cases (3/48,6.25%).The most common symptom in patients with pituitary involvement was central diabetes insipidus (13/17,76.5%),and the T1-weighted imaging showed posterior pituitary hypersignal disappearance,pituitary stalk thickening,and abnormally enhanced pituitary nodules.The most common symptom in patients with adrenal gland involvement was adrenal function reduction (3/8,37.5%),and the CT scanning showed diffuse thickening of adrenal glands.BRAF V600E mutation was positive in 13 (13/22,59.1%) cases with ECD involving endocrine glands.Conclusion Pituitary and adrenal glands are the most common sites of ECD involving endocrine glands.A definite diagnosis can be achieved by combining clinical,imaging,and pathological characteristics for timely treatment.

Pituitary Stalk Thickening: Causes and Consequences. The Children's Memorial Health Institute Experience and Literature Review.

BackgroundPituitary stalk thickening (PST) is a rare abnormality in the pediatric population. Its etiology is heterogeneous. The aim of the study was to identify important clinical, radiological and endocrinological manifestations of patients with PST and follow the course of the disease.Materials and MethodsIt is a study conducted in 23 patients (13 boys) with PST with/without central diabetes insipidus (CDI) diagnosed between 1990 and 2020 at Children’s Memorial Health Institute (CMHI) in Warsaw, Poland. We analyzed demographic data, clinical signs and symptoms, radiological findings, tumor markers, hormonal results, treatment protocols and outcomes.ResultsThe median age at the diagnosis of PST was 9.68 years (IQR: 7.21-12.33). The median time from the onset of the symptoms to the diagnosis was 2.17 years (IQR: 1.12-3.54). The most common initially reported manifestations were polydipsia, polyuria and nocturia (82.6%); most of the patients (56.5%) also presented decreased growth velocity. Hormonal evaluation at the onset of PST revealed: CDI (91.3%), growth hormone deficiency (GHD) (56.5%), hyperprolactinemia (39%), central hypothyroidism (34.8%), adrenal insufficiency (9%), precocious puberty (8.7%). The majority of the patients were diagnosed with germinoma (seventeen patients – 73.9%, one of them with teratoma and germinoma). Langerhans cell histiocytosis (LCH) was identified in three patients (multisystem LCH in two patients, and unifocal LCH in one patient). A single case of atypical teratoid rhabdoid tumor, suspected low-grade glioma (LGG) and lymphocytic infundibuloneurohypophysitis (LINH). The overall survival rate during the observational period was 87.0%.ConclusionsThe pituitary infundibulum presents a diagnostic imaging challenge because of its small size and protean spectrum of disease processes. Germinoma should be suspected in all children with PST, especially with CDI, even when neurological and ophthalmological symptoms are absent.

Pituitary stalk thickening in patients under 18 years of age - the most common causes and diagnostic procedures.

Pituitary stalk thickening (PST) is a rare abnormality in children, and it may be challenging due to its diverse clinical picture. The aim of the study is to summarize the data on the causes and diagnostic procedures of PST. Papers were searched in the PubMed database identifying published randomized clinical trials, reviews, systematic reviews, meta-analyses, and case reports. The most common causes of a thickened pituitary stalk in children are germ cell tumours (GCTs), Langerhans cell histiocytosis (LCH), and lymphocytic infundibulo-neurohypophysitis (LINH). Neurosarcoidosis, pituitary tuberculosis, granulomatosis, or specific inflammations were only reported in the paediatric population as case studies. PST mainly affects teenagers and is often detected with brain magnetic resonance imaging (MRI) in patients with central diabetes insipidus (CDI). It is not possible to differentiate the causes of PST with the use of the MRI image alone. Although various biochemical and oncological markers and other imaging tests are used, the diagnosis of PST remains a significant diagnostic challenge for clinicians. The final diagnosis is made based on histopathological examination. The indications for a biopsy are not uniform. Most experts, including the authors of the 2021 British consensus, recommend biopsy in the case of PST with a stalk lesion diameter ≥ 6.5-7 mm. The differential diagnosis of PST is a challenge. The diagnostic and treatment strategy should be individually adapted. Patients should be diagnosed in large clinical centres with experience in this field.

Neoplastic Etiology and Natural Course of Pituitary Stalk Thickening.

Pituitary stalk thickening (PST) is often identified on magnetic resonance imaging (MRI), either incidentally or during diagnostic workup of hypopituitarism. However, the neoplastic etiology and natural course of PST are not fully understood, although this knowledge is required to establish diagnostic and surveillance strategies. This work aimed to investigate the neoplastic etiology and natural course of PST. MEDLINE/PubMed and EMBASE databases were searched up to February 2021 to identify original research investigating the etiologies of PST. The proportion of neoplastic etiology in patients with PST was meta-analytically pooled. Supplementary analysis exploring factors suggesting neoplasm was also performed. For initially indeterminate cases without confirmed diagnosis, the proportion of patients showing progression of PST during follow-up was evaluated. Eighteen studies covering 1368 patients with PST were included. The pooled proportion of neoplasm was 45.2% (95% CI, 33.3%-57.8%), with substantial heterogeneity across studies (I2 = 93%). The most common neoplasm was germ cell tumor (14.0% of study population), followed by Langerhans cell histiocytosis (10.2%) and metastasis (4.7%). The studies on pediatric populations and those with more than 50% of patients having at least one pituitary hormone deficiency tended to show a higher proportion of neoplasm. The pituitary stalk was thicker in neoplasms, but the difference was not significant (pooled mean difference, 2.08 mm; P = .08). In initially indeterminate cases, 18.5% (95% CI, 7.6%-38.3%) showed progression of PST during follow-up. PST was commonly confirmed to be neoplastic, especially in pediatric populations. As isolated PST frequently progresses, follow-up imaging is essential in initially indeterminate cases.

Second-line regimen for CNS-involved pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) can affect any organ. Central nervous system (CNS) involvement is rare, and its management is poorly understood. This study aimed to analyze the clinical response and prognosis of pediatric LCH with central diabetes insipidus (CDI) treated with second-line therapy with cytarabine (Ara-c), cladribine (2-cdA), dexamethasone, and vindesine. This retrospective case series study included pediatric LCH with CDI treated at Beijing Children's Hospital affiliated with Capital Medical University (11/2012-01/2018). After the first-line 2009-LCH regimen, patients with active disease/worse response, relapse, or no significant improvement in risk organs, pituitary, or lung were given the second-line therapy. Baseline characteristics, clinical response and adverse reactions were observed. Twenty-six children with CDI and disappearance of hyperintensity in the posterior pituitary were included. They received "Regimen A" Ara-c + dexamethasone + vindesine (n = 7) or "Regimen B" Ara-c + dexamethasone + vindesine + 2-cdA (n = 19) as second-line therapy. There were 14 patients with CDI but without pituitary stalk thickening (PST) and 12 with CDI and PST. In patients with CDI alone, 4/4 patients receiving Regimen A and 3/10 receiving Regimen B improved. All patients with CDI and PST showed improvement for PST. The reappearance of hyperintensity at the posterior pituitary was observed in 10 patients with CDI. All 26 children were alive after a median follow-up of 40.5months. There were no chemotherapy-related deaths. A combined therapy with Ara-c, 2-cdA, dexamethasone, and vindesine could partially alleviate pituitary disease conditions in pediatric LCH with CNS involvement, with good tolerance.

An Infundibular Unidentified Object (IUO): a new pituitary stalk marker?

Measurement of the pituitary stalk (PS) diameter does not always solve the issue of minimal PS thickening. A previously undescribed image is found at the infundibular level on high resolution thin section T2W MRI in a large number of normal individuals. We speculate that this image-whose exact origin is still unknown-may serve as a marker of the normal infundibulum. In the last 6months, 350 consecutive adult patients suspected of sellar pathology or controlled after medical or surgical treatment prospectively underwent a pituitary MRI including a sagittal T2W high resolution sequence. One hundred twelwe patients presenting a pituitary mass with suprasellar extension or those whose PS was not entirely visible were excluded. A short focal annular T2 hypointense thickening of the wall of the infundibular recess of the third ventricle, more pronounced anteriorly was found in 151/238 patients. Additionally, a more or less tiny ventral extension was demonstrated on sagittal T2W sequence in 105/151 patients. These images were not identified on T1W or on T1W gadolinium enhanced sequences. The ring-like infundibular thickening and/or its ventral extension were not identified in 87/238 patients; in 43/87 of these patients the PS was found severely stretched mainly in case of primary or secondary empty sella. If patients with empty sella were excluded, our finding was observed in 194/238 cases, i.e. in 82%. A detailed appearance of the PS on T2W MRI is described for the first time. A previously unreported T2W hypointense annular focal image prolonged by a tiny spicular or nodular ventral bud is found at the lower part of the infundibulum in a majority of normal patients, but not if the PS is stretched such as in empty sella. This image has to be recognized as a normal anatomical landmark. The possible origin of this image is discussed but not totally elucidated. An ongoing research will demonstrate or not if this image may serve as a marker to improve the early diagnosis of PS lesions.

Neuroinfundibulitis: Pituitary Stalk Thickening Presenting as Diabetes Insipidus

Background: Isolated pituitary stalk thickening (PST) from neuroinfundibulitis is a rare entity that requires thorough evaluation of secondary causes and understanding of treatment options. Clinical Case: A 55-year-old male presented with progressive polyuria and polydipsia over several months. He had no significant head injuries, headache, weight loss, fatigue or inability to exercise. His serum sodium level was 148 (135 - 145 mmol/L) with a serum osmolality 310 (275-305 mOsm/kg), and urine osmolality was 246 (40-1200 mOsm/kg) suggestive of partial diabetes insipidus (DI). A 24-hour urine collection had a volume of 9.2 liters. He had a normal hemoglobin A1c. Hormonal work-up was unremarkable with normal range his prolactin, IGF-1, and a.m. cortisol (19 mcg/dl). He was already on levothyroxine with normal thyroid function tests and negative thyroid antibodies. Water deprivation testing confirmed a diagnosis of central DI and he was started on desmopressin. Magnetic resonance imaging (MRI) of the pituitary demonstrated diffuse PST with T2 hyperintensity and loss of normal T1 hyperintensity (“bright spot”) of the posterior pituitary. Repeat imaging 3 months later showed progressive thickening. He underwent full body positron emission tomography-computerized tomography (PET-CT) which demonstrated increased metabolism of the pituitary stalk, but no other suspicious uptake in other areas. Chest X-ray, tuberculin screen, angiotensin converting enzyme, and calcium were all normal. Patient underwent transsphenoidal stalk biopsy. Pathology demonstrated fibrosis and chronic inflammation without malignancy but otherwise was nondiagnostic. Based on these findings, he was presumed to have neuroinfundibulitis and is being actively followed with MRIs and labs. Conclusion: Isolated PST is exceedingly rare, especially in adults. The differential diagnosis includes neoplastic (germinomas, lymphoma, metastatic disease), autoimmune, and infiltrative disease (sarcoidosis, histiocytosis). One review of 38 adult patients with central DI and PST showed that almost half had neuroinfundibulitis. Of those, 4 were treated with corticosteroids and 7 were not. All patients showed reduction or resolution of PST on subsequent MRIs indicating that resolution of thickening can be spontaneous without steroid use, and can be followed by MRI and with hormone replacement for deficiencies (1). Because of the rarity of isolated neuroinfundibulitis, it is important that neoplastic and systemic diseases be ruled out in all patients with PST, as in the case of our patient.1.Devuyst F, Kazakou P, Baleriaux D, Alexopoulou O, Burniat A, Salenave S, et al. Central diabetes insipidus and pituitary stalk thickening in adults: distinction of neoplastic from non-neoplastic lesions. European Journal of Endocrinology. 2020;183(1):95-105.

Idiopathic Hypophysitis

Introduction: Hypophysitis is a heterogeneous condition that leads to inflammation of the sella / suprasellar region, potentially resulting in hormonal deficiencies or mass effects. Prevalence of hypophysitis ranges from 0.2% to 0.88%. Annual incidence of hypophysitis is 1 case per 9 million individuals. We present an interesting case of idiopathic hypophysitis. Clinical Case: A 52-year-old female was evaluated for secondary hypothyroidism. Patient complained of excess fatigue, weight gain, headaches, polyuria with nocturia and vision changes. She was seen by ophthalmology for formal visual field testing revealing right superior quadrantanopia. Labs significant for TSH 4 uIU/mL (ref range 0.27-4.2uIU/mL), FT4 0.72ng/dL (ref range 0.93-1.7 ng/dL), Anti TPO ab negative, AM cortisol 8.9UG/dL, ACTH 18pg/mL, IGF1 127ng/mL, prolactin 7ng/mL, FSH 102MIU/mL, LH 41 MIU/mL. MRI sella revealed homogenous enhancement of the pituitary with convex superior margin - 0.8*1*0.9cm concerning for hyperplasia. Due to the concern for hypophysitis, an extensive inflammatory workup was pursued which was negative. She was started on thyroid hormone replacement and DDAVP. An empiric trial of high dose steroids failed to provide any relief. During workup, patient complained of transient right sided face and arm tingling, diagnosed with TIA and started on aspirin. Due to worsening headaches, a pituitary biopsy was pursued. Pathology significant for glandular tissue ruling out inflammatory, neoplastic, and infectious etiologies. Neurology diagnosed the patient with hemicrania continua. Patient is currently maintained on thyroid hormone replacement and DDAVP with close follow-up. Discussion: The incidence of hypophysitis has recently increased due to increased awareness and also due to the use of medications like ICI. Primary hypophysitis is mostly due to autoimmune etiology. Secondary hypophysitis could result from infections, neoplastic conditions or an adverse effect of medications. Clinical presentations ranges from being asymptomatic to having features of hypopituitarism. Usually presents with mass effect, visual symptoms due to the upward expansion of the pituitary gland impinging the dura mater and optic chiasm. This is followed by symptoms of hormone deficiency, central DI and hyperprolactinemia. Central AI has been reported in 20%-75%, central hypogonadism in 15%-60%, central hypothyroidism in 25%-58%, GH deficiency in 5%-41%, and prolactin deficiency in 13%-25%. Typical MRI findings include, homogeneous pituitary contrast enhancement, pituitary stalk thickening and loss of posterior pituitary bright spot, ‘figure of 8’ appearance, ‘dural tail’. Treatment consists of surgery, anti-inflammatory medications, and radiotherapy. Glucocorticoid treatment is the cornerstone for medical management; however, the overall recurrence rate is high.

Central Diabetes Insipidus in a Child due to Histiocytosis X

Central diabetes insipidus (CDI) occur due to deficiency of vasopressin which is synthesized in supraoptic and paraventricular nuclei of hypothalamus and stored in posterior pituitary. There are many causes of CDI among them histiocytosis X or lymphohistiocytosis (LCH) is a rare cause. Here we are reporting a 2 years old boy with histiocytosis-Xor presented with CDI. The boy presented with polyuria and polydipsia, low urine specific gravity and osmolality with normal blood sugar and osmolality. Positive response to water deprivation test followed by oral DDAVP establish the diagnosis of CDI. X-Ray skull showed osteolytic punched out lesion and T1 weighted MRI of brain showed thickening of pituitary stalk with absence of bright signal of posterior pituitary. Trephine biopsy showed bone marrow was infiltrated by many eosinophil, some macrophage, lymphocyte and plasma cells. On the basis of all these diagnosis was made as CDI due to histiocytosis-X. Due to hypothalamic- pituitary axis infiltration CDI may be the earliest manifestation of LCH, even before it is diagnosed. Therefore, for diagnostic workup of CDI, LCH should be considered.&#x0D; Northern International Medical College Journal Vol. 11 No. 1 July 2019, Page 432-434

GCT-75. ISOLATED PITUITARY STALK THICKENING

OBJECTIVESOnly few studies have examined the predictive factors and outcome of isolated pituitary stalk thickening (PST) in children. We aim to describe our institutional cohort to determine predictors of future malignancy.METHODSA search of the radiology, endocrinology and neuro-oncology databases was performed to identify patients with isolated PST diagnosed between January 2000 and June 2019. Clinical data was collected. A detailed radiology review of baseline and follow up magnetic resonance imaging (MRI) was undertaken in a blinded fashion by two examiners.RESULTSForty-four patients were identified, with 37 meeting criteria for isolated PST and adequate imaging. Median age of baseline MRI was 9.9 years (range 0.9–17.5). Twenty-three were female (62%). Median follow up time was 5 (0.31–18.6) years. Indication for MRI was symptoms of diabetes insipidus (DI) in 28 patients with the remainder having other concerns for endocrine disturbance (7), headache (1) or visual impairment (1). Thirty-five subjects had pituitary dysfunction (95%), including 30 with diabetes insipidus (81%). Nine patients developed a malignancy (24%), with germinoma (5), Langerhans cell histiocytosis (3) and lymphoma (1) at a median of 0.36 years, 0.63 years and 1.1 years respectively. Elevated white blood cell count (>5 x 106/L) in initial cerebrospinal fluid analysis was predictive of future diagnosis of germinoma or lymphoma (p=0.027).CONCLUSIONIn this cohort 24% of children with PST were eventually diagnosed with a neoplasia after a median of 0.63 years. Pleocytosis in initial CSF samples was predictive for future development of germinoma or lymphoma.

OTHR-14. DIENCEPHALIC SYNDROME SECONDARY TO PITUITARY STALK THICKENING

BACKGROUNDDiencephalic syndrome (DS) is a rare condition associated with neoplastic lesions of the sellar-suprasellar region, whose pathophysiological mechanisms are still unclear. DS occurs in <10% of hypothalamic gliomas and has also been described in suprasellar germinomas, craniopharyngiomas, epidermoid cysts, rarely with non-suprasellar lesions such as brainstem gliomas. DS has not been associated with isolated pituitary stalk thickening. Isolated pituitary stalk thickening (IPST) presents a diagnostic challenge, ranging from benign (craniopharyngioma) to malignant lesions (germinoma, metastasis, histiocytoses of the Langerhans group). The coexistence of diabetes insipidus (DI) with anterior pituitary dysfunction and IPST implies more risk to harbor neoplasia. CASE REPORT: A 6-year old girl presented with DI and inadequate weight gain (despite regular caloric intake) and preservation of linear growth. Neurological examination showed no abnormalities. However, physical examination revealed a malnourished patient (both weight-for-age value and body-mass-index below the third percentile). Blood tests and negative IgA anti-endomysial antibodies excluded malabsorption as a cause of her malnutrition; endocrine work-up excluded thyroid dysfunction, growth hormone deficiency, and adrenal insufficiency. Magnetic resonance imaging (MRI) showed thickening of the pituitary stalk with a transverse diameter of 7 mm. The patient underwent a biopsy through a supraorbital eyebrow approach. Histopathological examination revealed lymphocytic hypophysitis, with tissue markers all negative for germinoma. The girl is currently under follow up with serial MRI every three months.CONCLUSIONDS should be considered as a differential diagnosis in any child with failure to thrive, and imaging studies should be performed even if there are no additional neurological symptoms.