Neoplastic Etiology and Natural Course of Pituitary Stalk Thickening: A Systematic Review and Meta-analysis

Context Pituitary stalk thickening (PST) is often identified on magnetic resonance imaging (MRI), either incidentally or during diagnostic work-up 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. Objectives To investigate the neoplastic etiology and natural course of PST. Methods 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. Results 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 (I 2=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 >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=0.08). In initially indeterminate cases, 18.5% (95% CI, 7.6–38.3%) showed progression of PST during follow-up. Conclusion 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.

Differences between immunotherapy-induced and primary hypophysitis—a multicenter retrospective study

Objective Immune checkpoint inhibitors can cause various immune-related adverse events including secondary hypophysitis. We compared clinical characteristics of immunotherapy-induced hypophysitis (IIH) and primary hypophysitis (PH) Design Retrospective multicenter cohort study including 56 patients with IIH and 60 patients with PH. Methods All patients underwent extensive endocrine testing. Data on age, gender, symptoms, endocrine dysfunction, MRI, immunotherapeutic agents and autoimmune diseases were collected. Results Median time of follow-up was 18 months in IIH and 69 months in PH. The median time from initiation of immunotherapy to IIH diagnosis was 3 months. IIH affected males more frequently than PH (p < 0.001) and led to more impaired pituitary axes in males (p < 0.001). The distribution of deficient adenohypophysial axes was comparable between both entities, however, central hypocortisolism was more frequent (p < 0.001) and diabetes insipidus considerably less frequent in IIH (p < 0.001). Symptoms were similar except that visual impairment occurred more rarely in IIH (p < 0.001). 20 % of IIH patients reported no symptoms at all. Regarding MRI, pituitary stalk thickening was less frequent in IIH (p = 0.009). Concomitant autoimmune diseases were more prevalent in PH patients before the diagnosis of hypophysitis (p = 0.003) and more frequent in IIH during follow-up (p = 0.002). Conclusions Clinically, IIH and PH present with similar symptoms. Diabetes insipidus very rarely occurs in IIH. Central hypocortisolism, in contrast, is a typical feature of IIH. Preexisting autoimmunity seems not to be indicative of developing IIH.

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.

GCT-75. ISOLATED PITUITARY STALK THICKENING

OBJECTIVES Only 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. METHODS A 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. RESULTS Forty-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 (&gt;5 x 106/L) in initial cerebrospinal fluid analysis was predictive of future diagnosis of germinoma or lymphoma (p=0.027). CONCLUSION In 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

BACKGROUND Diencephalic syndrome (DS) is a rare condition associated with neoplastic lesions of the sellar-suprasellar region, whose pathophysiological mechanisms are still unclear. DS occurs in &lt;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. CONCLUSION DS 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.