Significant pituitary siderosis is common in transfusion-dependent sickle cell disease.

ABSTRACT: Chronically transfused patients with sickle cell disease typically do not exhibit iron-mediated extrahepatic toxicity. However, we demonstrate that the pituitary gland is vulnerable to iron deposition, and it occurs regardless of other extrahepatic involvement. Severe pituitary siderosis is associated with early organ dysfunction.

Pituitary-related immune adverse events induced by programmed death Protein-1 inhibitors differ clinically from hypophysitis.

OBJECTIVE: We aimed to elucidate the clinical features of pituitary immune-related adverse events (irAEs) induced by PD-1 inhibitors in a Chinese cohort and the previous literatures. PATIENTS AND DESIGN AND MEASUREMENTS: We retrospectively analysed the clinical manifestations, laboratory examination findings, imaging features and treatments of 14 patients with pituitary irAEs caused by PD-1 inhibitors in our cohort. In addition, we searched PubMed for all English articles on pituitary irAEs induced by PD-1 inhibitors published from 1950 to 2023. A total of 47 articles were included, and the clinical characteristics of 94 patients with pituitary irAEs induced by PD-1 inhibitors in these literatures were compared to the characteristics of our cohort. RESULTS: Among the 14 patients in our cohort with pituitary irAEs induced by PD-1 inhibitors, 12 patients (85.71%, 12/14) exhibited isolated ACTH deficiency (IAD), 100.0% (14/14) of the central adrenocortical insufficiency, and 2 patients showed more than one hypothalamic-pituitary axis injury (14.29%, 2/14). Pituitary magnetic resonance imaging in all the 14 patients showed no pituitary enlargement. In previous studies we reviewed, 82.98% of the total (78/94) presented with pituitary irAEs as IAD, 100.0% (94/94) of the central adrenocortical insufficiency, and 78.33% of the patients showed no abnormality of the pituitary gland (47/60). The pituitary irAEs caused by PD-1 inhibitors did not involve typical manifestations of hypophysitis, such as pituitary enlargement, headache, visual field defects, and multiple pituitary function impairments in our cohort and the previous literatures. CONCLUSION: In our study, pituitary immune-related adverse reactions induced by PD-1 inhibitors mainly manifested isolated ACTH deficiency rather than hypophysitis.

Enlarged pituitary gland volume: a possible state rather than trait marker of psychotic disorders.

BACKGROUND: Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders. METHODS: The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration. RESULTS: Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006). CONCLUSIONS: Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis.

Metabolic Syndrome Components in Patients with Pituitary Adenoma.

Pituitary adenomas are benign tumors of the anterior portion of the pituitary gland (adenohypophysis), representing the 25% of all the tumor alterations. Pituitary adenomas are classified by the type of hormone secreted, cellularity, size, and structural alterations by the hormonal segregation. The diagnosis consists on the histopathological identification of cell types and the image-guided by magnetic resonance or tomography; the treatment can be both pharmacological and surgical. Metabolic Syndrome is the set of clinical conditions that increase the risk of cardiovascular diseases with an estimated prevalence of 25% worldwide. The alterations of metabolic syndrome are obesity, hypertension, dyslipidemia, insulin resistance, and diabetes mellitus type II. Pituitary adenomas and metabolic syndrome have an important relationship, hormone-secreting by pituitary adenomas affects a myriad of signaling pathways, which allows a favorable environment for the appearance of the metabolic syndrome. Moreover, patients with pituitary adenomas are shown to have an improvement in metabolic parameters after the medical/surgical treatment. The objective of this review is to explore the possible mechanisms through which PAs contributes to MetSx.

Post-traumatic pituitary stalk transection syndrome (PSTS) expeditiously manifested after a fall from a height combined with acute traumatic spinal cord injury: a rare case report with review of literature.

Post-traumatic pituitary stalk transection syndrome (PSTS) is an extremely rare cause of combined pituitary hormone deficiency (CPHD), affecting approximately 9 per 100,000 cases of traumatic brain injury. In contrast, pituitary stalk interruption syndrome (PSIS) is also a rare cause of CPHD. Importantly, these conditions are often confused due to their similar names and resembling findings on magnetic resonance imaging (MRI). PSIS has been thought to be a prenatal developmental event resulting from a couple of genetic aberrations. In typical PSIS, anterior pituitary hormone deficiencies are restricted to growth hormone (GH) and gonadotropin during the pediatric age, gradually and generally progressing to panhypopituitarism in most cases. In contrast, global deficiencies of the anterior pituitary hormones in PSTS are temporally associated with trauma. To the best of our knowledge, no case reports of PSTS combined with acute traumatic spinal cord injury have been reported. A 34-year-old female was transferred to our hospital after jumping from the fourth building floor. She was diagnosed as an acute traumatic spinal cord injury and underwent the operation of elective posterior spinal fusion. On postoperative day 7, the blood tests revealed considerable hyperkalemia, hyponatremia and eosinophilia. Notably, menstruation stopped after falling from a height. Pituitary function tests revealed GH deficiency, hypogonadism, hypothyroidism and hypoadrenocorticism. MRI revealed loss of the pituitary stalk, whilst the hyperintense signal from distal axon of hypothalamus was still identified. Based on these findings, she was diagnosed as PSTS. Our case highlights endocrinological landscape of transection of the pituitary stalk by acute trauma.

Secondary vs. primary pituitary xanthogranulomas: which yellow is more mellow?

Pituitary xanthogranulomatomas (XG) are a rare pathological entity caused by accumulation of lipid laden macrophages and reactive granuloma formation usually triggered by cystic fluid leakage or hemorrhage. Our aim was to compare clinical characteristics and presenting features of patients with secondary etiology of XG and those with no identifiable founding lesion (primary -"pure" XG) in order to gain new insights into this rare pituitary pathology. In a retrospective review of 714 patients operated for sellar masses, at tertiary center, we identified 16 (2.24%) with histologically confirmed diagnosis of pituitary XG over the period of 7 years (2015-2021). Patients were further analyzed according to XG etiology: "pure"- XG (n = 8) with no identifiable founding lesion were compared to those with histological elements of pituitary tumor or cyst - secondary XG (n = 8). We identified 16 patients (11 male), mean age 44.8 ± 22.3 years, diagnosed with pituitary XG. Secondary forms were associated with Ratke's cleft cyst (RCC, n = 2) and pituitary adenoma (PA, n = 6). The most common presenting features in both groups were hypopituitarism (75%), headache (68.5%) and visual disturbances (37.5%). Predominance of male sex was noted (males 68.75%, females 31.25%), especially in patients with primary forms. Patients with primary pituitary XG were all males (p = 0.0256) and more frequently affected by panhypopituitarism (87.5% vs. 25%, p = 0.0406) compared to patients with secondary causes. Hyperprolactinemia was noted in pituitary tumor group with secondary etiology only (p = 0.0769). Majority of lesions were solid on magnetic resonance imaging - MRI (81.25%). Distinct clinical phenotype was observed dependent on the etiology of XG.

A case of hypophysitis after COVID-19 vaccination with a detection of anti-pituitary antibody, with review of literature.

COVID-19 vaccines have resulted in a remarkable reduction in both the morbidity and mortality associated with COVID-19. However, there are reports of endocrine rare clinical conditions linked to COVID-19 vaccination. In this report, we present a case of hypophysitis following COVID-19 vaccination and review the literature on this condition. This case involved a 72-year-old male with type 1 diabetes who experienced symptoms such as vomiting, appetite loss, and headaches following his fifth COVID-19 vaccine dose. He was diagnosed with secondary adrenal insufficiency; subsequent assessment revealed an enlarged pituitary gland. Unlike previous cases, our patient has partial recovery from pituitary insufficiency, and his pituitary function gradually improved over time. Anti-pituitary antibodies (APAs) against corticotrophs, thyrotrophs, gonadotrophs, and folliculo stellate cells (FSCs) were detected in serum samples taken 3 months after onset. Hypophysitis after COVID-19 vaccination is a rare clinical condition, with only eight cases reported by the end of 2023, most occurring after the initial or second vaccination. Symptoms of hypophysitis after COVID-19 vaccination are similar to those of classic pituitary dysfunction. Pituitary insufficiency is persistent, with five of the above eight patients presenting posterior pituitary dysfunction and three patients presenting only anterior pituitary dysfunction. Two of those eight patients had autoimmune diseases. Our case suggests a potential link between acquired immunity, APA production, and pituitary damage. To elucidate the etiology of hypophysitis associated with COVID-19 vaccination, detailed investigation of patients with nonspecific symptoms after vaccination against COVID-19 is necessary.

Comparison of the sensitivity of histopathological and immunohistochemical analyses and blood hormone levels for early detection of antithyroid effects in rats treated with thyroid peroxidase inhibitors.

Although measurements of blood triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels in rodent toxicity studies are useful for detection of antithyroid substances, assays for these measurements are expensive and can show high variability depending on blood sampling conditions. To develop more efficient methods for detecting thyroid disruptors, we compared histopathological and immunohistochemical findings in the thyroid and pituitary glands with blood hormone levels. Six-week-old male and female Sprague-Dawley rats (five rats per group) were treated with multiple doses of the thyroid peroxidase inhibitors propylthiouracil (PTU) and methimazole by gavage for 28 days. Significant decreases in serum T3 and T4 and increases in TSH were observed in the ≥1 mg/kg PTU and ≥3 mg/kg methimazole groups. An increase in TSH was also detected in male rats in the 0.3 mg/kg PTU group. Histopathological and immunohistochemical analyses revealed that follicular cell hypertrophy and decreased T4 and T3 expressions in the thyroid gland were induced at doses lower than doses at which significant changes in serum hormone levels were observed, suggesting that these findings may be more sensitive than blood hormone levels. Significant increases in thyroid weights, Ki67-positive thyroid follicular cell counts, and TSH-positive areas in the pituitary gland were detected at doses comparable with those at which changes in serum T4 and TSH levels were observed, indicating that these parameters may also be useful for evaluation of antithyroid effects. Combining these parameters may be effective for detecting antithyroid substances without relying on hormone measurements.

Unravelling pituitary tumours in medically treated patients with acromegaly: the impact of systematic MRI reassessment.

BACKGROUND: In acromegaly, the primary tumor is usually found during magnetic resonance imaging (MRI) of the pituitary gland. A remnant tumor after surgery is, however, harder to depict. When a tumor is missed, the remaining option is usually lifelong pharmacological treatment. PURPOSE: To identify tumors by reassessment of all available MRI scans in pharmacologically treated patients, operated or not, and to compare our results with the routine MRI reports. MATERIAL AND METHODS: Adult patients diagnosed with acromegaly and managed at a tertiary care center between 2005 and 2021 and currently on pharmacological treatment were included. MRI scans were evaluated in a standardized manner and classified independently by a radiologist and an endocrinologist into "certain," "suspected," or "no tumor." In case of disagreement, consensus was achieved with a senior neuroradiologist. The results were compared using the clinical radiologists' routine MRI reports. RESULTS: We identified certain and suspected tumors in 29/74 and 36/74 patients, respectively. No tumor was identified in nine patients. In five of these, no MRI contrast agent was given. Discrepancy between our results and the routine MRI reports was found in 31/74 patients (P = 0.01). In 22 patients, the routine reports described no tumor while we identified certain tumors in 2/22 patients and suspected tumors in 13/22 patients. CONCLUSION: In most patients with pharmacologically treated acromegaly, we identified a certain or suspected pituitary tumor. These findings were more frequent compared to the routine MRI reports. Based on our results, patients will be considered for a change in long-term treatment modality.

Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland.

Stem cells in the adult pituitary are quiescent yet show acute activation upon tissue injury. The molecular mechanisms underlying this reaction are completely unknown. We applied single-cell transcriptomics to start unraveling the acute pituitary stem cell activation process as occurring upon targeted endocrine cell-ablation damage. This stem cell reaction was contrasted with the aging (middle-aged) pituitary, known to have lost damage-repair capacity. Stem cells in the aging pituitary show regressed proliferative activation upon injury and diminished in vitro organoid formation. Single-cell RNA sequencing uncovered interleukin-6 (IL-6) as being up-regulated upon damage, however only in young but not aging pituitary. Administering IL-6 to young mice promptly triggered pituitary stem cell proliferation, while blocking IL-6 or associated signaling pathways inhibited such reaction to damage. By contrast, IL-6 did not generate a pituitary stem cell activation response in aging mice, coinciding with elevated basal IL-6 levels and raised inflammatory state in the aging gland (inflammaging). Intriguingly, in vitro stem cell activation by IL-6 was discerned in organoid culture not only from young but also from aging pituitary, indicating that the aging gland's stem cells retain intrinsic activatability in vivo, likely impeded by the prevailing inflammatory tissue milieu. Importantly, IL-6 supplementation strongly enhanced the growth capability of pituitary stem cell organoids, thereby expanding their potential as an experimental model. Our study identifies IL-6 as a pituitary stem cell activator upon local damage, a competence quenched at aging, concomitant with raised IL-6/inflammatory levels in the older gland. These insights may open the way to interfering with pituitary aging.

Treatment modalities and outcomes of granular cell tumors and spindle cell oncocytomas of the pituitary gland: an analysis of two national cancer databases.

BACKGROUND: Spindle cell oncocytomas (SCO) and granular cell tumors (GCT) are rare primary pituitary neoplasms; the optimal treatment paradigms for these lesions are unknown and largely unexplored. Thus, using national registries, we analyze the epidemiology, management patterns, and surgical outcomes of SCOs and GCTs. METHODS: The National Cancer Database (NCDB; years 2003-2017) and the Surveillance, Epidemiology, and End Results Program (SEER; years 2004-2018) were queried for patients with pituitary SCOs or GCTs. Incidence, extent of surgical resection, and rate of postoperative radiation use for subtotally resected lesions comprised the primary outcomes of interest. All-cause mortality was also analyzed via time-to-event Kaplan-Meier curves. RESULTS: SCOs and GCTs have an annual incidence of 0.017 and 0.023 per 1,000,000, respectively. They comprise 0.1% of the benign pituitary tumors registered in NCDB. A total of 112,241 benign pituitary tumors were identified in NCDB during the study period, of which 83 (0.07%) were SCOs and 59 (0.05%) were GCTs. Median age at diagnosis was 55 years, 44% were females, and median maximal tumor diameter at presentation was 2.1 cm. Gross total resection was achieved in 54% patients. Ten patients (7%) had postoperative radiation. Comparing patients with GCTs versus SCOs, the former were more likely to be younger at diagnosis (48.0 vs. 59.0, respectively; p < 0.01) and female (59% vs. 34%, p = 0.01). GCTs and SCOs did not differ in terms of size at diagnoses (median maximal diameter: 1.9 cm vs. 2.2 cm, respectively; p = 0.59) or gross total resection rates (62% vs. 49%, p = 0.32). After matching SCOs and GCTs with pituitary adenomas on age, sex, and tumor size, the former were less likely to undergo gross total resection (53% vs. 72%; p = 0.03). Patients with SCOs and GCTs had a shorter overall survival when compared to patients with pituitary adenomas (p < 0.01) and a higher rate of thirty-day mortality (3.1% vs 0.0%; p = 0.013). CONCLUSION: SCOs and GCTs are rare pituitary tumors, and their management entails particular challenges. Gross total resection is often not possible, and adjuvant radiation might be employed following subtotal resection.

Experimental Autoimmune Encephalomyelitis Influences GH-Axis in Female Rats.

Inflammation, demyelination, and axonal damage to the central nervous system (CNS) are the hallmarks of multiple sclerosis (MS) and its representative animal model, experimental autoimmune encephalomyelitis (EAE). There is scientific evidence for the involvement of growth hormone (GH) in autoimmune regulation. Previous data on the relationship between the GH/insulin like growth factor-1 (IGF-1) axis and MS/EAE are inconclusive; therefore, the aim of our study was to investigate the changes in the GH axis during acute monophasic EAE. The results show that the gene expression of Ghrh and Sst in the hypothalamus does not change, except for Npy and Agrp, while at the pituitary level the Gh, Ghrhr and Ghr genes are upregulated. Interestingly, the cell volume of somatotropic cells in the pituitary gland remains unchanged at the peak of the disease. We found elevated serum GH levels in association with low IGF-1 concentration and downregulated Ghr and Igf1r expression in the liver, indicating a condition resembling GH resistance. This is likely due to inadequate nutrient intake at the peak of the disease when inflammation in the CNS is greatest. Considering that GH secretion is finely regulated by numerous central and peripheral signals, the involvement of the GH/IGF-1 axis in MS/EAE should be thoroughly investigated for possible future therapeutic strategies, especially with a view to improving EAE disease.

Tumor of follicular infundibulum - reappraisal in a series of 28 patients with critical review of the literature.

BACKGROUND AND OBJECTIVES: Tumor of follicular infundibulum (TFI) has been described as a neoplasm - isolated and multiple - and in association with other lesions. Its histopathologic definition is controversial. PATIENTS AND METHODS: We present a histopathologically analyzed series of 28 patients with TFI features. This has been supplemented by a search in MEDLINE on the literature on this subject. The corresponding figures given in these articles have been discussed and analyzed. RESULTS: Patients comprised 16 women and twelve men. TFI features were seen in five patients with nevus sebaceous, two trichofolliculomas, one dilated pore Winer, eight viral warts, one dermatofibroma, six seborrheic keratoses, three actinic keratoses, one invasive squamous cell carcinoma, and one basal cell carcinoma in association with a squamous cell carcinoma/actinic keratosis. After study of the literature especially of solitary cases of TFI, we interpret such cases mostly as variants of seborrheic keratoses with variable degree of infundibular, isthmic and/or sebaceous differentiation with or without regression. CONCLUSIONS: We regard TFI as an epithelial growth pattern which may occur in hamartomatous, inflammatory, infectious, reactive, or neoplastic conditions, in most solitary forms likely best classified within the histopathological spectrum of seborrheic keratoses.

Seminoma characterized by thickening of the pituitary stalk: A case report. / 以垂体柄增粗为特征的精原细胞瘤1例.

Intracranial seminoma is a rare malignant tumor originating from the germ cells, usually occurring in the pineal gland or pituitary gland. In June 2020, the Department of Endocrinology at the First Affiliated Hospital of Army Military Medical University admitted a 20-year-old male patient with an intracranial germ cell tumor and spinal metastases. The patient presented with headache, dizziness, and visual impairment. Enhanced magnetic resonance imaging (MRI) of the head indicated thickening of the pituitary stalk. After multidisciplinary consultation, the patient underwent endonasal transsphenoidal resection of the tumor, with the pathological diagnosis confirming germ cell tumor. The patient received regular radiotherapy postoperatively. One year later, the tumor recurred and metastasized, leading to a second surgery for tumor resection in the thoracic spinal canal, followed by continued chemotherapy. The patient's clinical symptoms, such as headache and visual disturbances, improved, but he continued to experience panhypopituitarism and required long-term hormone replacement therapy. Early diagnosis of intracranial germ cell tumors is challenging, and they are prone to metastasis and highly sensitive to radiotherapy and chemotherapy. Early diagnosis and multidisciplinary comprehensive treatment can help improve the quality of life and prognosis for patients.

Natural History of Non-Functioning Pituitary Adenomas: A Systematic Review and Meta-Analysis.

The management of non-functioning pituitary tumors (NFPTs) relies on the risk of tumor growth and new endocrinopathies. The objective of this systematic review was to assess the risk of growth, new pituitary endocrinopathies, and surgery in patients with conservatively treated NFPTs. We conducted a bibliographical search identifying studies assessing NFPTs followed conservatively. Estimates were pooled using random-effects meta-analysis reporting events per 100 person years (PYs), in case of high heterogeneity (I2>75%) only the range of observed effects was reported. We identified 30 cohort studies including 1957 patients with a mean follow-up time of 4.0 (SD 1.5) years. The overall risk of tumor growth ranged from 0.0 to 14.2/100 PYs (I2=90%), while the overall risk of new endocrinopathies was 0.9/100 PYs (95% CI. 0.5 to 1.2; I2=: 35%) and risk of surgery ranged from 0.0 to 7.7/100 PYs (I2=: 80%). Compared to microadenomas, macroadenomas had higher risk of growth (p=: 0.002), higher risk of surgery (p=: 0.006), and non-significant differences in risk of new endocrinopathies (p=: 0.15). An analysis of microadenomas found the risk of growth to be 1.8/100 PYs (95% CI. 0.9 to 2.8; I2=: 58%), the risk of new endocrinopathies 0.7/100 PYs (95% CI. 0.0 to 1.6; I2=: 37%) and the risk of surgery 0.5/100 PYs (0.1 to 0.9; I2=: 37%). These data support individualized follow-up strategies of patients with NFPTs and particularly a less rigorous follow-up of patients with microadenomas.

Evidence for an intra-tumoral microbiome in pituitary neuroendocrine tumors with different clinical phenotypes.

PURPOSE: Bacteria have been observed in the tumor environment for decades and have been demonstrated to play important roles in the pathogenesis and development of several different tumors. So far there is a clear lack of specific studies relating to the presence of bacteria in pituitary neuroendocrine tumors (PitNETs). METHODS: In this study, we performed five region-based amplification and bacterial 16 S rRNA sequencing to identify the microbiome of PitNET tissues across four clinical phenotypes. Multiple filter procedures were performed to inhibit the risk of contamination with bacteria and bacterial DNA. Histological analysis was also conducted to validate the localization of bacteria in the intra-tumoral region. RESULTS: We identified common and diverse bacterial types across the four clinical phenotypes of PitNET. We also predicted the potential functions of these bacteria in tumor phenotypes and found that these functions were reported in certain previous mechanistic studies. Our data indicate that the pathogenesis and development of tumors may correlate with the behavior of intra-tumoral bacteria. Histological results, including lipopolysaccharide (LPS) staining and fluorescence in situ hybridization (FISH) for bacterial 16 S rRNA clearly demonstrated the localization of bacteria in the intra-tumoral region. Staining for Iba-1 suggested that the proportion of microglia was more abundant in FISH-positive regions than in FISH-negative regions. Furthermore, in FISH-positive regions, the microglia exhibited a longitudinally branched morphology that was different to the compact morphology observed in FISH-negative regions. CONCLUSION: In summary, we provide an evidence for the existence of intra-tumoral bacteria in PitNET.

Concurrent IgG4-related hypophysitis and clinically nonfunctioning gonadotroph pituitary neuroendocrine tumor.

BACKGROUND: Some patients develop immunoglobulin G4 (IgG4)-related hypophysitis associated with systemic diseases. More than 30 cases of IgG4-related hypophysitis have been reported. However, biopsy has rarely been performed in these patients, and none have had an associated pituitary neuroendocrine tumor (PitNET). We present a case of concurrent IgG4-related hypophysitis and PitNET. CASE PRESENTATION: A 56-year-old Japanese man arrived at the hospital with visual impairment, bitemporal hemianopia, and right abducens nerve palsy. Magnetic resonance imaging revealed pituitary body and stalk swelling as well as a small poorly enhanced right anterior lobe mass. Laboratory and loading test results suggested hypopituitarism. Because IgG4 level was elevated, a systemic examination was performed; multiple nodules were found in both lung fields. The diagnosis was based on an endoscopic transnasal biopsy of the pituitary gland. A histopathological examination revealed a marked infiltration of plasma cells into the pituitary gland, which was strongly positive for IgG4. The histological features of the resected tumor were consistent with those of gonadotroph PitNET, which was immunohistochemically positive for follicle-stimulating hormone-ß and steroidogenic factor-1, and no plasma cell infiltration was observed. Based on the histopathological examination results, steroid therapy was initiated, which reduced pituitary gland size and serum IgG4 levels. DISCUSSION AND CONCLUSIONS: This is the first reported case of IgG4-related hypophysitis with PitNET. Although no pathological findings indicating a relationship between the two conditions were found, we were able to preoperatively differentiate multiple lesions via detailed diagnostic imaging.

[68 Ga]-DOTATATE PET/MR-based evaluation of physiologic somatostatin receptor 2 expression in the adult pituitary gland as a function of age and sex in a prospective cohort.

PURPOSE: The pituitary gland has the fourth highest physiologic avidity of [68 Ga]-DOTATATE. In order to guide our understanding of [68 Ga]-DOTATATE PET in clinical contexts, accurate characterization of the normal pituitary gland is first required. This study aimed to characterize the normal pituitary gland using dedicated brain [68 Ga]-DOTATATE PET/MRI as a function of age and sex. METHODS: A total of 95 patients with a normal pituitary gland underwent brain [68 Ga]-DOTATATE PET examinations for the purpose of diagnosing CNS SSTR2 positive tumors (mean age: 58.9, 73% female). Maximum SUV of the pituitary gland was obtained in each patient. SUV of superior sagittal sinus was obtained to calculate normalized SUV score (SUVR) of the gland. The anatomic size of the gland was collected as maximum sagittal height (MSH). Correlations with age and sex were analyzed. RESULTS: The mean SUV and SUVR of the pituitary gland were 17.6 (range: 7-59.5, SD = 7.1) and 13.8 (range: 3.3-52.6, SD = 7.2), respectively. Older females had significantly higher SUV of the pituitary gland compared to younger females. When stratified by age and sex, both older and younger females had significantly higher pituitary SUV than older males. SUVR did not differ significantly by age or sex. MSH of the pituitary gland in younger females was significantly greater than in younger males at all age cutoffs. CONCLUSION: This study provides an empiric profiling of the physiological [68 Ga]-DOTATATE avidity of the pituitary gland. The findings suggest that SUV may vary by age and sex and can help guide the use of [68 Ga]-DOTATATE PET/MRI in clinical and research settings. Future studies can build on these findings to investigate further the relationship between pituitary biology and demographic factors.

Exploring the role of the tumor microenvironment in refractory pituitary tumor pathogenesis.

PURPOSE: Treatment-refractory pituitary tumors demonstrate characteristics resembling those of highly aggressive tumors, in which the local tumor microenvironment (TME) plays a dominant role in promoting aggressiveness and refractoriness. However, role of the TME in pituitary tumors is not well studied. METHODS: Literature on the TME and development of refractory pituitary tumors was reviewed RESULTS: TME harbors tumorigenic immune cells, cancer-associated fibroblasts (CAF), extracellular matrix, and other factors that have been shown to affect behavior of tumor tissue. For example, tumor-associated macrophages and tumor-infiltrating lymphocytes correlate with aggressive and invasive tumor behavior in nonfunctioning and growth hormone-secreting (GH) pituitary tumors, while CAF release of TGFß, FGF2, cytokines, chemokines, and growth factors may promote treatment resistance, tumor fibrosis, and inflammation in prolactinomas and GH-secreting tumors. In turn, Wnt pathway activation can further promote cell growth in dopamine-resistant prolactinomas. Finally, proteins secreted by extracellular matrix are associated with increased angiogenesis in invasive tumors. CONCLUSION: It is likely that multiple mechanisms, including TME, contribute to the development of aggressive refractory pituitary tumors. Given the increased morbidity and mortality associated with pituitary tumor refractoriness, more research on the role of TME is warranted.

UK practice on incidentally detected non-functioning pituitary microadenomas: analysis of two national surveys during a 12-year interval.

PURPOSE: The optimal management approach for presumed non-functioning pituitary microadenomas (microNFPAs) remains unclear. Our aim was to capture current UK practice and identify changes with time. METHODS: Two online surveys investigating clinicians' approaches were performed in 2009-2010 and 2021-2022 (advertised through Society for Endocrinology UK). RESULTS: 150 and 214 clinicians participated in the 2021 and 2009 survey, respectively (response rates 31.2% and 35.4%, respectively). At baseline, 2021 survey respondents were more likely to measure IGF-1 (96.0% vs 74.1%, p < 0.001) and morning cortisol (87.9% vs 62.6%, p < 0.001), and less likely GH (26.2% vs 42.6% p = 0.002), 24 h urine free cortisol (3.4% vs 23.2%, p < 0.0001) or dynamically assess adrenal reserve (11.4% vs 30.4%, p < 0.001). 47.2% of clinicians in 2021 would reassess pituitary function annually until discharge (in absence of tumour growth/symptoms). The 2021 survey respondents were more likely to stop imaging at or before 3 years (81.7% vs 44.3%, p < 0.001) and at or before 5 years (86.6.% vs 72.9%, p = 0.002), whilst 2009 survey respondents were more likely to continue imaging beyond 5 years (24% vs 7%, p < 0.001). Responses on imaging frequency/intervals showed notable variability in both surveys. CONCLUSIONS: Diagnostic and management approaches for microNFPAs have evolved in the UK. Biochemical investigations are performed in accord with consensus guidelines, though many clinicians perform annual biochemical surveillance without tumour growth/symptoms. A small number of clinicians request imaging beyond 5 years, but the frequency of imaging intervals until discharge remains variable. Robust evidence on the long-term natural history of microNFPAs is necessary to unify clinician approach.