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

Background Symptomatic 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 presentation A 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. Conclusions In 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.

Application of Artificial Intelligence in Diagnosis of Craniopharyngioma

Craniopharyngioma is a congenital brain tumor with clinical characteristics of hypothalamic-pituitary dysfunction, increased intracranial pressure, and visual field disorder, among other injuries. Its clinical diagnosis mainly depends on radiological examinations (such as Computed Tomography, Magnetic Resonance Imaging). However, assessing numerous radiological images manually is a challenging task, and the experience of doctors has a great influence on the diagnosis result. The development of artificial intelligence has brought about a great transformation in the clinical diagnosis of craniopharyngioma. This study reviewed the application of artificial intelligence technology in the clinical diagnosis of craniopharyngioma from the aspects of differential classification, prediction of tissue invasion and gene mutation, prognosis prediction, and so on. Based on the reviews, the technical route of intelligent diagnosis based on the traditional machine learning model and deep learning model were further proposed. Additionally, in terms of the limitations and possibilities of the development of artificial intelligence in craniopharyngioma diagnosis, this study discussed the attentions required in future research, including few-shot learning, imbalanced data set, semi-supervised models, and multi-omics fusion.

Immune checkpoint inhibitor-induced hypophysitis: lessons learnt from a large cancer cohort

Immune checkpoint inhibitors (ICIs) can cause pituitary dysfunction due to hypophysitis. We aimed to characterize ICI-induced hypophysitis and examine its association with overall survival in this single-center retrospective cohort study of adult patients with cancer who received an ICI from January 1, 2012 through December 31, 2016. A total of 896 patients were identified who received ipilimumab alone (n=120); ipilimumab and nivolumab (n=50); ipilimumab before or after pembrolizumab (n=70); pembrolizumab alone (n=406); and nivolumab alone (n=250). Twenty-six patients (2.9%) developed hypophysitis after a median of 2.3 months. Median age at the start of ICI was 57.9 years and 54% were men. Hypophysitis occurred in 7.9% of patients receiving ipilimumab alone or in combination or sequence with a programmed cell death protein 1 inhibitor; 1.7% after pembrolizumab alone, never after nivolumab alone. Secondary adrenal insufficiency occurred in all hypophysitis cases. Use of ipilimumab alone or in combination was associated with pituitary enlargement on imaging and mass effects more frequently than pembrolizumab alone. Occurrence of hypophysitis was associated with improved overall survival by univariate analysis (median 50.7 vs 16.5 months; p=0.015) but this association was not observed in multivariable landmark survival analysis (HR for mortality 0.75; 95% CI 0.38 to 1.30; p=0.34) after adjusting for age, sex and malignancy type. To conclude, hypophysitis occurred most frequently after ipilimumab and manifested as anterior hypopituitarism affecting the corticotrophs more commonly than thyrotrophs and gonadotrophs. Mass effects and pituitary enlargement occurred more frequently in ipilimumab-induced hypophysitis. The association of hypophysitis with overall survival needs further investigation.

NCOG-35. THE LATE INTRACRANIAL ADVERSE EVENTS OCCUR MORE FREQUENTLY IN INTRACRANIAL GERMINOMAS TREATED WITH HIGH DOSE RADIOTHERAPY

OBJECTIVE The standard treatment for intracranial germinoma has been radiotherapy covering the whole ventricle together with chemotherapy. Radiotherapy is important, but it is a cause of the late brain damages. Therefore, the recent clinical trials have been planned to evaluate the reduced radiation dose. The aim of this study was to evaluate the intracranial adverse events in the patients with intracranial germinomas treated in our hospital. PATIENTS AND METHODS 65 patients were diagnosed as intracranial germinoma. Patients with hCG > 100 IU/l and/or AFP > 10 ng/ml were excluded. Patients, who were diagnosed as germinoma by imaging without histology, were included. RESULTS Follow-up time was from 2 to 467 months (median 136 months). Until 2005, 37 patients were treated with radiotherapy >30 Gy alone or with chemotherapy. After then, 23 patients received whole-ventricle radiotherapy 24-30 Gy with chemotherapy. 2 patients were treated with chemotherapy alone, 3 were unknown. 10-year PFS was 82.05% in radiotherapy >30 Gy alone, 86.36% in radiotherapy >30 Gy with chemotherapy and 100% in radiotherapy 24-30 Gy with chemotherapy. The intracranial adverse events after the initial treatment were identified, such as pituitary dysfunction: 6 (9.2%), hearing disturbance: 2 (3.1%), neurocognitive dysfunction 6 (9.2%), microbleeds 10 (15.4%), cavernous angioma 6 (9.2%), brain tumor 1 (1.5%), cerebral artery stenosis 1 (1.5%). The frequency of late adverse brain events is higher in radiotherapy >30 Gy with/without chemotherapy than 24-30 Gy (total events, 25 vs. 9, P< 0.03). CONCLUSION Patients with intracranial germinoma obtain long-term survival but suffer from the late intracranial adverse events. The late intracranial adverse events occur more frequently in intracranial germinomas treated with radiotherapy >30 Gy than 24-30 Gy. Long-term follow-up is important to promptly identify and deal with the late brain damages.

Anterior Pituitary Volume in Patients with Transfusion Dependent Anemias: Volumetric Approaches and Relation to Pituitary MRI‑R2

Purpose Anterior pituitary iron overload and volume shrinkage is common in patients with transfusion-dependent anemia and associated with growth retardation and hypogonadotropic hypogonadism. We investigated the accuracy of different MRI-based pituitary volumetric approaches and the relationship between pituitary volume and MRI-R2, particularly with respect to growth and hypogonadism. Methods In 43 patients with transfusion-dependent anemia (12–38 years) and 32 healthy controls (12–72 years), anterior pituitary volume was measured by a sagittal T1 GRE 3D sequence at 1.5T and analyzed by 3D semi-automated threshold volumetry (3D-volumetry). This reference method was compared with planimetric 2D-volumetry, approximate volume calculations, and pituitary height. Using a multiple SE sequence, pituitary iron as MRI-R2 was assessed by fitting proton signal intensities to echo times. Growth and hypogonadism were obtained from height percentile tables and patients’ medical charts. From body surface area and age adjusted anterior pituitary volumes of controls, Z‑scores were calculated for all subjects. Separation of controls and patients with respect to Z and pituitary R2 was performed by bivariate linear discriminant analysis. Results Tuned 2D volumes showed highest agreement with reference 3D-volumes (bias −4.8%; 95% CI:−8.8%|−0.7%). A linear discriminant equation of Z = −17.8 + 1.45 · R2 revealed optimum threshold sensitivity and specificity of 65% and 100% for discrimination of patients from controls, respectively. Of correctly classified patients 71% and 75% showed hypogonadism and growth retardation, respectively. Conclusion Accurate assessment of anterior pituitary size requires 3D or precise 2D volumetry, with shorter analysis time for the latter. Anterior pituitary volume Z‑scores and R2 allow for the identification of patients at risk of pituitary dysfunction.

Assessment of Neuroendocrine Changes and the Hypothalamo-Pituitary Autoimmunity in Patients With COVID-19

Purpose: The SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, particularly, secondary adrenal insufficiency using a dynamic test and the role of autoimmunity in pituitary dysfunction in the patients with COVID-19.Methods: The single-center, prospective, case-control study included PCR-confirmed COVID-19 patients and healthy controls. Basal hormone levels were measured and ACTH stimulation test was performed. Anti-pituitary (APA) and anti-hypothalamic antibodies (AHA) were also determined. Results: We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. The patients with COVID-19 had lower free T3, IGF-1, total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also, demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. Conclusions: The COVID-19 may result in adrenal insufficiency, so the routine screening of adrenal functions is these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Also, pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormality in COVID-19.

Endocrine disorders

Diabetes mellitus, Management of diabetes mellitus, Diabetes in children and adolescents, Hypothyroidism, Hyperthyroidism, Enlarged Thyroid Gland (Goitre), Pituitary dysfunction, Endocrine hypertension, Pheochromocytoma and paraganglioma, Cushing's syndrome, Gynaecomastia, Hypoadrenalism, Hypercalcaemia, Hypocalcaemia, Hyperkalaemia, Hypokalaemia, Hyponatraemia, Hypernatraemia

Xanthomatous Hypophysitis: A Case Report and Comprehensive Literature Review

PurposeXanthomatous hypophysitis (XHP) is an extremely rare form of primary hypophysitis for which there is a lack of clinical experience. A comprehensive understanding of its clinical characteristics, diagnosis and treatment is needed.MethodsHere, we report a case study and conduct a systematic review of XHP. Thirty-six cases were included, and their clinical manifestations, endocrine assessment, imaging features, treatment and follow-up data were collected and analyzed.ResultsThe mean age at diagnosis was 39.1 years, and females were predominant (75.0%). The most common symptom was headache (68.6%), and 66.7% of female patients presented menstrual disorders. The most common pituitary dysfunction was growth hormone (GH) deficiency. More than half of patients exhibited central diabetes insipidus (CDI). The majority of patients had an imaging presentation of a cystic lesion with peripheral enhancement. Pituitary stalk thickening was observed in half of the patients. Total lesion resection was achieved in 57.1% of cases. The recurrence rate after partial resection and biopsy was significantly higher than that after total lesion resection (57.1% vs. 0.0%, P = 0.0147). The most common pituitary hormone abnormalities to resolve after surgery were hyperprolactinemia (100.0%) and GH deficiency (91.7%). The typical pathological feature was inflammatory infiltration of foamy histiocytes, which showed positivity for CD68.ConclusionDiagnosis of XHP is difficult when relying on clinical symptoms and imaging features. Therefore, surgical histopathology is necessary. Based on the available evidence, total lesion resection is recommended for treatment. However, the long-term prognosis for this rare disease remains unclear.

Hypophysitis, the Growing Spectrum of a Rare Pituitary Disease

Hypophysitis is defined as inflammation of the pituitary gland that is primary or secondary to a local or systemic process. Differential diagnosis is broad (including primary tumors, metastases, and lympho-proliferative diseases) and multifaceted. Patients with hypophysitis typically present with headaches, some degree of anterior and/or posterior pituitary dysfunction, and enlargement of pituitary gland and/or stalk, as determined by imaging. Most hypophysitis causes are autoimmune, but other etiologies include inflammation secondary to cellar tumors or cysts, systemic diseases, and infection or drug-induced causes. Novel pathologies such as IgG4-related hypophysitis, immunotherapy-induced hypophysitis and paraneoplastic pituitary-directed autoimmunity are also included in a growing spectrum of this rare pituitary disease. Typical magnetic resonance imaging reveals stalk thickening and homogenous enlargement of the pituitary gland, however, imaging is not always specific. Diagnosis can be challenging and ultimately, only a pituitary biopsy can confirm hypophysitis type and rule out other etiologies. A presumptive diagnosis can be made often without biopsy. Detailed history and clinical examination are essential, notably for signs of underlying etiology with systemic manifestations. Hormone replacement and in selected cases careful observation is advised with imaging follow-up. High-dose glucocorticoids are initiated mainly to help reduce mass effect. A response may be observed in all auto-immune etiologies, but also in lymphoproliferative diseases, and as such should not be used for differential diagnosis. Surgery may be necessary in some cases to relieve mass effect and allow a definite diagnosis. Immunosuppressive therapy and radiation are sometimes also necessary in resistant cases.