Hormone Hypersecretion Research Articles

Comparative mortality in pituitary adenomas subtypes: a tertiary referral center study.

Mortality in pituitary adenomas (PAs) has been extensively compared to general population. However, direct comparisons between PA subtypes are scarce. We aimed to compare mortality in various subtypes of PA (acromegaly, Cushing's disease (CD), macroprolactinomas and non-functioning pituitary macroadenomas (MacroNFPA)), within a single referral center. We retrospectively analyzed mortality and survival time in all 962 PAs admitted in our department between 2011 and 2023: acromegaly (n = 306), CD (n = 69), macroprolactinoma (n = 168) and MacroNFPA (n = 419). Median follow-up was 10.2 (5.2, 15.2) years. The overall survival probability was 90.9% and 78.1% after 10 and 20 years respectively with age at diagnosis as the only significant predictor. There were no significant differences in survival probability between various PA subtypes in the whole cohort. In patients over 45 years of age at diagnosis there was a significant difference in survival probability between the four groups (p = 0.01) in the first 15 years of follow-up. In head-to-head comparisons CD had a significantly higher mortality risk than patients with acromegaly (HR 3.38 [CI 95% 1.07 to 10.60]) even after adjusting for age and sex. Patients diagnosed with CD after 45 years of age have a significantly lower survival probability than other PA subtypes in the first 15 years of follow-up. All other PA subtypes had a similar survival probability after adjusting for age and sex. Due to advances in medical treatment of hormone secreting tumors, mortality in patients with PAs might increasingly depend more on tumor mass than on hormonal hypersecretion.

Two-hit model for the development of aldosterone-producing adenoma: supporting from two new cases.

Recently, a two-hit model for the development of aldosterone-producing adenoma (APA) was proposed but until now, only two cases supporting the model have been reported. Here, we present two new cases of primary aldosteronism (PA), both of which had large functional adenomas with somatic mutations in aldosterone-driving genes. Furthermore, the first patient, who had a history of colorectal cancer, was found to have a germline and an additional somatic mutation in APC, and APC inactivation was confirmed by immunohistochemistry. The other patient had pathogenic somatic mutation inCTNNB1. These pro-proliferation mutations resulted in abnormal activation of the Wnt/β-catenin pathway. Two consecutive events apparent in these patients, namely, the first event leading to cell proliferation and the second driving hormonal hypersecretion, supported the two-hit model of APA development. The two-hit model usually occurs in the larger adenomas, and the driving factors of the first hit that promote cell proliferation still require further research and exploration.

6823 A Puzzling Case: Complete Regression of Pituitary Macroadenoma

Abstract Disclosure: N.T. Mazengia: None. D.R. Vangipuram: None. S.K. Majumdar: None. Introduction: The natural course of nonfunctioning pituitary macroadenomas remains poorly understood, largely because the majority are surgically treated [1]. There are a few case reports describing the spontaneous regression of nonfunctioning pituitary macroadenomas. Here we describe a case of pituitary macroadenoma which completely regressed following childbirth and two months of cabergoline therapy. Case Presentation: A 25-year-old female presented with bilateral nipple discharge and persistently elevated prolactin levels ranging from 31µg/liter to 45.9 µg/liter (NV <25 µg/L). She did not have any signs and symptoms of hypo or hypersecretion of the pituitary hormones. All her pituitary hormone levels were within normal range. Initial MRI revealed a pituitary mass measuring 9x13x9mm (AP, TR, CC). Given her lack of symptoms, the decision was made to follow up without any intervention. A repeat MRI after one year showed the size of the mass to be 11x13x11mm. Two years after her initial diagnosis, the patient had a spontaneous pregnancy, during which she remained asymptomatic with normal pituitary hormone levels. She had Cesarean delivery at term with no complication. She was lost to follow-up for about two years after childbirth then presented with breast discomfort and galactorrhea at which time, she was started on cabergoline. A subsequent MRI done two months after the start of cabergoline showed asymmetric fullness of the pituitary gland on the right with no discrete measurable lesion. Conclusion: We currently lack a comprehensive explanation for the regression observed in our patient. Silent ischemia may have played a role, particularly considering the natural increase in pituitary gland size during pregnancy. We are not sure if the regression can be solely attributed to the two months of cabergoline treatment. In asymptomatic patients diagnosed with nonfunctioning pituitary macroadenoma, tumor regression can potentially occur through either a "wait and watch" strategy or medical management using dopamine agonists, specifically cabergoline. However, the use of cabergoline as a primary treatment for asymptomatic nonfunctioning pituitary adenoma warrants further investigation. This is especially crucial given that, in most cases, nonfunctioning pituitary macroadenomas tend to increase in size during follow-up without any intervention.

8653 A Rare Cause of a Pituitary Mass

Abstract Disclosure: L. El Musa Penna: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. I.C. Arroyo Gomez: None. J. Segarra-Villafane: None. Z. Maisonet -Feliciano: None. M. Ramirez: None. L.A. Gonzalez-Rodriguez: None. M. Alvarado: None. J. Feneque González, MD: None. M. Marcos Martínez, MD: None. M. Correa Rivas: None. Pituitary gland masses are the second most common tumor of the central nervous system (CNS) across all age group, as per Central Brain Tumor Registry in the United States. Most common lesions are adenomas, which can be categorized as functional and non-functional based on the presence of hormonal hypersecretion. In the differential diagnosis, there is also craniopharyngiomas, Rathke’s cleft cysts, pituitary hyperplasia, inflammatory lesions, malignancy and abscess. Pituitary abscess is a rare condition, and only 0.2-0.6% of pituitary lesions are diagnosed as abscesses.This is the case of a 42-year-old female with history of hypothyroidism, chronic sinusitis with nasal polyps, severe asthma, and chronic steroid use complicated by iatrogenic adrenal insufficiency and osteonecrosis of the hips bilaterally, who was evaluated for intractable headaches. On brain imaging was found with a pituitary macroadenoma. She denied any symptoms suggesting hypersecretion of hormones and was scheduled for transsphenoidal surgery. All hormonal work up was found within normal limits, except for prior iatrogenic adrenal insufficiency due to multiple systemic steroids courses to treat asthma exacerbation throughout her life.During surgery, upon mass resection, purulent secretions were found. Frozen section was done intraoperatively, showing respiratory epithelium, pus and actinomyces species. All infectious material was removed. Infectious Diseases services was consulted and patient was promptly started on IV antibiotics. Blood cultures were negative, and patient remained afebrile. Final pathology confirmed the presence of respiratory epithelium, actinomyces colonization and a fibrous capsule with acute and chronic inflammation. Special stains report was negative for fungi. She was discharge to continue home infusion of antibiotic regimen to complete 8 weeks of treatment.There is no specific imaging finding to identify pituitary abscesses so, most of them, are diagnosed intraoperatively. They can arise from hematogenous spread or from adjacent tissues or structures (ie. patient with meningitis or sinusitis). The condition is considered a life-threatening however, the majority of cases have a chronic course. Based on different reports, theses abscesses have a higher female predominance; the age range is between 12 to 76 years and the average period between onset of symptoms and diagnosis is 8 months on average. Most pituitary abscesses are sterile, however most common organisms isolated are: Gram-positive cocci (Staphylococcus and Streptococcus), and Gram-negative organisms such as Neisseria, Escherichia coli and Corynebacterium. The rarity of cases often leads to delayed diagnosis and treatment initiation, contributing to increased morbidity and mortality. Presentation: 6/2/2024

12562 Extraocular Muscle Enlargement With Proptosis In A Patient With Non Thyroidal Disease

Abstract Disclosure: S.S. Bantu: None. P.N. Kabir: None. A. Gondhi: None. T.B. Vaughan: None. Extraocular muscle enlargement with proptosis in a patient with Nonthyroidal disease Introduction: Majority of cases with extraocular muscle enlargement (EOME) is due to Graves’ disease, commonly in about 95% cases and another 5% make up other causes including inflammatory, neoplastic, vascular, infectious and acromegaly. We present a patient with sudden loss of vision, retroorbital pain with visual field deficits found to have EOME and subsequently a pituitary macroadenoma on imaging. Case: We present a 54-year-old male with history of hypertension, obstructive sleep apnea and morbid obesity who presented to us with complains of left sided vision loss. Patient was evaluated by ophthalmology and noted to have unilateral, left-sided, change in visual acuity. Physical exam was notable for macrognathia, skin tags, enlarged hands, excessive sweating. MRI brain revealed bilateral EOME with proptosis and a pituitary macroadenoma measuring 1.5x1.7x1.3cm, abutting the pre-chiasmatic left optic nerve. On biochemical evaluation he was noted to have elevated IGF1 of 979 confirming the diagnosis of acromegaly. ((hemoglobin A1C of 5.5%, prolactin 5.1, FT4 0.89, TSH 0.692, total testosterone 61, IGF1 level was 979)). He underwent transsphenoidal resection of the pituitary macroadenoma. Pathology showed sparsely granulated somatotroph adenoma. Discussion: Acromegaly has an incidence of 3-4 cases per million per year. The characteristics of the disease are due to chronic growth hormone hypersecretion resulting in the excessive growth of tissue due to the stimulation of insulin-like growth factor 1 (IGF-1). EOME with proptosis in acromegaly is seen rarely. Visual symptoms may manifest as visual field deficits due to compression of the optic pathway in 18-25% cases, increased intraocular pressure, increase in corneal thickness and a diffuse symmetrical enlargement of the extraocular muscles which cannot be distinguished from thyroid orbitopathy on imaging. The degree of enlargement appears to correlate with the duration of the disease rather than the levels of IGF1. EOME improves with the treatment of acromegaly. Although visual symptoms may be a rare presentation of acromegaly, if the clinical suspicion exists, one may consider obtaining an IGF-1 level to complete the evaluation of EOME if the thyroid levels are normal. Presentation: 6/3/2024

8801 Towards Safe and Efficacious Medical Therapy for Patients with Clinically Non-Functioning Pituitary Tumors

Abstract Disclosure: D. Zhang: None. M. Bergsneider: None. W. Kim: None. M.B. Wang: None. H. Vinters: None. A.P. Heaney: None. Clinically non-functioning pituitary tumors (CNFTs) account for one-third of all pituitary adenomas. They do not cause clinical and/or biochemical evidence of tumor-related hormone hypersecretion, grow insidiously and typically present with mass effect symptoms such as headache and visual field deficits. Surgical resection is the current standard of care for CNFTs but complete resection is infrequently achieved due to their size and invariable invasion of locally adjacent structures. CNFT remnant tumor regrowth rates approach 50% and these patients may need repeat surgery and/or radiotherapy (RT). The latter is quite effective in achieving tumor control, but carries a risk of hypopituitarism of ∼ 40% at 10 years. Although dopamine agonists and somatostatin receptor ligands have been explored as medical therapy, there are currently no consistently effective medical treatments for CNFTs. There is a clear unmet need for novel safe and effective medical therapies for these comparatively common tumors. In a highly innovative approach we have used patient-derived ex vivo 3D tumoroid human CNFTs in an automated high throughput compound screen (HTS) to identify novel tumoricidal and growth inhibitory compounds for CNFTs. To date, we have screened ∼4,000 compounds and have identified 13 potential hits that inhibited tumor cell proliferation (a reduction of 76±15%) and induced apoptosis (induction rate of 8.2 ± 6.6) in the CNFT tumoroids respectively. The hit compounds to date fall into 3 categories based on their targets, namely Na+/K+-ATPase inhibitors (n=6), reactive oxygen species (ROS) regulators (n=4), and cell cycle inhibitors (n=3). Representative “hit” compounds from each group identified in our primary screen were rescreened in triplicate in 20 concentrations from 25µM to 50pM at 2-fold dilutions. Dose-response curves characterized compound doses that inhibited cell viability by 50% (IC50) and ranged from 13nM to 103nM. Two of these 3 compounds also induced 2-3-fold apoptosis at 0.1uM with the final compound displaying a potent 5-10-fold pro-apoptotic effect at 0.15uM concentration. In parallel, we used single cell RNA sequencing to validate targets that emerged from our HTS and to characterize the mechanism of action (MOA) of these hit compounds. As proof of concept, several of the known drug targets were noted to be amongst the highest differentially expressed genes in the CNFT tumor cell population. This approach validating a candidate target in conjunction with demonstrable activity of a drug for that same target in CNFTs may simultaneously provide us with a back-bone molecule to further develop with structural activity relationship analysis and/or allow us to individualize drug choice in patients based on immunocytochemical tumor target expression. Presentation: 6/1/2024

8194 Extramedullary Hematopoiesis Involving Bilateral Adrenal Glands In A Patient With Sickle Cell Anemia

Abstract Disclosure: V.T. Pham: None. L.N. Sendos: None. Title: Extramedullary hematopoiesis involving bilateral adrenal glands in a patient with sickle cell anemia Background: Extramedullary hematopoiesis refers to blood cell production occurring outside the bone marrow. It is a reactive process caused by inadequate production or excessive destruction of blood cells typically seen in patients with hereditary anemias or infiltrative bone marrow disorders. Extramedullary hematopoiesis usually occurs in the spleen, liver and lymph nodes, but it can also very rarely arise from the adrenal glands. Case Presentation:We present a case of a 42-year-old male with a history of sickle cell anemia who presented with chest pain and shortness of breath and had a chest CT angiography which incidentally showed a 5.6 x 3.8 cm left adrenal mass and a 2.9 x 2.1 cm right adrenal mass. Further evaluation with an MRI abdomen with and without contrast revealed a 5.5 cm lobulated left adrenal mass with patchy areas of microscopic fat and faint delayed heterogeneous enhancement as well as a 2.2 cm right adrenal nodule. The nodules were described as markedly T2 hypointense with heterogeneous T1 hyperintense/isointense signal on MRI with a broad differential diagnosis including extramedullary hematopoiesis in bilateral adrenal glands, lipid poor adenoma or neoplasm. Regarding his sickle cell disease history, the patient was diagnosed as an infant and had very rare episodes of sickle cell pain crisis as a child. However, once he entered adulthood, he began to have multiple episodes of sickle cell pain crisis requiring hospitalizations and transfusions. On further review of patient’s prior imaging scans during these previous hospitalizations, he was first noted to have bilateral sub centimeter adrenal nodules on a CT Abdomen without contrast done almost a decade prior to his current presentation. We ordered biochemical evaluation which did not show any evidence of adrenal hormonal hypersecretion. His case was discussed at our multidisciplinary conference with the radiology and surgery team and it was concluded that the imaging characteristics were most consistent with extramedullary hematopoiesis in the setting of bilateral adrenal gland involvement and patient’s history of sickle cell anemia. Therefore, no immediate surgical resection was recommended. Given the size of the left adrenal mass being greater than 4 cm in size, we advised follow-up imaging for surveillance. Discussion:There has been a rise in detection of adrenal incidentalomas due to the increased use of advanced diagnostic imaging in healthcare settings. When patients with hematologic diseases are found to have adrenal incidentalomas, it is important to consider extramedullary hematopoiesis in the differential diagnosis to avoid unnecessary invasive procedures and surgeries. Presentation: 6/2/2024

7109 "My Stomach hurts": A Rare Case of Adrenal Cortical Carcinoma

Abstract Disclosure: R.C. Attah: None. I. Sirisena: None. Pheochromocytoma/Paragangliomas are rare neurogenic tumors that arise from chromaffin cells present in the adrenal medulla or extra-adrenal paraganglia, these cells produce catecholamines. Typically, these tumors are discovered as incidentalomas. They can be hereditary as seen in genetic syndromes like multiple endocrine neoplasia type 2A or 2B, neurofibromatosis type 1 or Von Hippel Lindau syndrome but can occur sporadically. Patients typically present with hormonal hypersecretion signs or symptoms like abdominal pain, episodic headaches, sweating, hypertension and tachycardia, but some patients are asymptomatic. Patient is a 37-year-old female with past medical history of hypertension, type 2 diabetes mellitus and fatty liver who presented to the ED with abdominal pain for a few weeks. On arrival, her vitals were BP 205/124, HR 102, RR 14 and SpO2 100% on room air. CT abdomen was obtained which showed a 7.6 x 4.7 x 5.7 cm mass replacing left adrenal gland with small left retroperitoneal hemorrhage worrisome for adrenal cortical carcinoma, metastatic disease or pheochromocytoma. Hormonal workup revealed elevated 24-hr urine cortisol 124.2mcg (ref 4.0-50.0mcg/24h), normal aldosterone/renin ratio 10.63ng/dL (ref <30ng/dl), failed low dose dexamethasone suppression test with post-dex AM cortisol 7.20ug/dL (ref <1.8ug/dL), slightly elevated serum total catecholamine 1256pg/mL (242-1125 pg/mL), norepinephrine 1155pg/mL (ref 217-1109 pg/mL), total metanephrine and normetanephrine 341pg/mL (reg <205 pg/mL), normetanephrine 244.1 (ref <210.1pg/mL), elevated 24-hr urine normetanephrine 700ug/L (ref 131-612ug/L), metanephrine 136ug/L (ref 36-209ug/L) and DHEA-s level 285ug/dl (ref 23-266ug/dL). Due to elevation in cortisol, adrenal cortical carcinoma was suspected as these tumors are frequently associated with cortisol secretion. However, pheochromocytoma with co-secretion of ACTH could not be excluded. She was started on doxazosin for alpha blockade and eventually started on beta blockade with Metoprolol. She underwent a left adrenalectomy and was started on steroid taper post-op due to concern of cortisol co-secretion. Surgical pathology was positive for Left adrenal malignant pheochromocytoma and ganglioneuroma. Genetic panel was negative with no mutation identified in the 54 gene Hereditary paraganglioma-pheochromocytoma panel. This patient had a large adrenal tumor (>4cm mass) but mildly elevated catecholamines which could have led to misdiagnosis as her catecholamine levels were less than 2-3x ULN which is unusual for pheochromocytomas. Roughly 25% of people with pheochromocytoma are undiagnosed throughout their lifespan. This condition can be life-threatening, hence early diagnosis and intervention can be lifesaving. Prognosis of malignant pheochromocytoma is dependent on tumor size, presence of SDHB gene mutation or visceral metastases. Presentation: 6/1/2024

Diagnosis and management of pituitary adenomas in children and adolescents.

Pituitary adenomas (PAs)-also now called pituitary neuroendocrine tumours or Pit-NETS-are rare in children and adolescents and exceptional below the age of 10. Most evidence-based high-quality data are derived from larger studies in adult patients. We will review recent knowledge on the epidemiology, clinical features, diagnosis, and treatment modalities of the different types of pituitary adenomas diagnosed in children and adolescents, emphasizing the many reasons why these cases should be discussed within pituitary-specific multidisciplinary teams with experts from both paediatric and adult practice. Paediatric PA presents multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.

Osteodystrophy Fibrosa in a Goat Kid: Clinical Assessment and Management

Fibrous osteodystrophy is a mineral based caprine metabolic disease in which bones are resorbed as a result of prolonged hypersecretion of parathyroid hormone. High phosphorus or low calcium in the diet frequently contributes to fibrous osteodystrophy. This was a case of 8 months old kid presented to the Referral Veterinary Polyclinic of ICAR-IVRI with the history of anorexia and prominent bilateral facial swelling. History-taking revealed that owner was regularly feeding wheat bran and barley to the kid in the diet. On clinical examination, goat kid was found to be dull and depressed with rectal temperature lying within the normal reference range. Haematobiochemical analysis exhibited decreased level of serum calcium (7 mg/dl) and increased level of serum phosphorus (8.2 mg/dl). In dorsovental cephalometric radiography, facial bones appeared radiolucent. Treatment of osteodystrophy began with the administration of injection AD3E at the dose of 1 ml I/M for 5 days, injection pheniramine maleate (AvilTM) at 1 ml I/M for 5 days, syrup CalcimustTM at 5 ml PO for 5 days and injection Calcium sandozTM at 10 ml mixed with 200 ml NSS I/V SD and anabolic steroid Nandrolone at 50 mg SD. Concurrently, the owner was advised to immediately stop feeding wheat bran and barley to the kid. After 5 days of the treatment, kid’s condition started to improve and uneventful recovery was achieved 14 days post-therapy.

Therapeutical Usefulness of PD-1/PD-L1 Inhibitors in Aggressive or Metastatic Pituitary Tumours.

Therapeutic options for pituitary neuroendocrine tumours (PitNETs) refractory to temozolomide are scarce. Immune checkpoint inhibitors (ICIs), particularly inhibitors of the programmed cell death-1 (PD-1) pathway and its ligand (PD-L1), have been experimentally used in aggressive or metastatic PitNETs. We aimed to study the therapeutic usefulness of anti-PD-1 drugs in patients with aggressive or metastatic PitNETs. Published cases and case series involving patients with PitNETs treated with PD-1/PD-L1 inhibitors were reviewed. Demographic data, clinical-pathological features, previous therapies, drug dosage and posology, and the best radiological and biochemical responses, as well as survival data, were evaluated. We identified 29 cases of aggressive (n = 13) or metastatic (n = 16) PitNETs treated with PD-1/PD-L1 inhibitors. The hypersecretion of adrenocorticotropic hormone (ACTH) was documented in eighteen cases (62.1%), seven were prolactinomas (24.1%), and four were non-functioning PitNETs. All patients underwent various therapies prior to using ICIs. Overall, a positive radiological response (i.e., partial/complete radiological response and stable disease) was observed in eighteen of twenty-nine cases (62.1%), of which ten and four were ACTH- and prolactin-secreting PitNETs, respectively. Hormonal levels reduced or stabilised after using ICIs in 11 of the 17 functioning PitNET cases with available data (64.7%). The median survival of patients treated with ICIs was 13 months, with a maximum of 42 months in two ACTH-secreting tumours. Among 29 patients with PitNETs treated with PD-1/PD-L1 inhibitors, the positive radiological and biochemical response rates were 62.1% and 64.7%, respectively. Altogether, these data suggest a promising role of ICIs in patients with aggressive or metastatic PitNETs refractory to other treatment modalities.

The Impact of Surgical Telementoring on Reducing the Complication Rate in Endoscopic Endonasal Surgery of the Skull Base.

Pituitary adenomas represent the most common pituitary disorder, with an estimated prevalence as high as 20%, and they can manifest with hormone hypersecretion or deficiency, neurological symptoms from mass effect, or incidental findings on imaging. Transsphenoidal surgery, performed either microscopically or endoscopically, allows for a better extent of resection while minimising the associated risk in comparison to the transcranial approach. Endoscopy allows for better visualisation and improvement in tumour resection with an improved working angle and less nasal morbidity, making it likely to become the preferred surgical treatment for pituitary neoplasms. The learning curve can be aided by telementoring. We retrospectively analysed the clinical records of 94 patients who underwent an endoscopic endonasal resection of a pituitary neoplasm between the years 2011 and 2023 at Maribor University Medical Centre in Slovenia. Remote surgical telementoring over 3 years assisted with the learning curve. The proportion of complication-free patients significantly increased over the observed period (60% vs. 79%). A gradual but insignificant increase in the percentage of patients with improved endocrine function was observed. Patients' vision improved significantly over the observed period. By gaining experience, the extent of gross total tumour resection increased insignificantly (67% vs. 79%). Telementoring for the endoscopic endonasal approach to pituitary neoplasms enables low-volume centres to achieve efficiency, decreasing rates of postoperative complications and increasing the extent of tumour resection.

Could CT Radiomic Analysis of Benign Adrenal Incidentalomas Suggest the Need for Further Endocrinological Evaluation?

We studied the application of CT texture analysis in adrenal incidentalomas with baseline characteristics of benignity that are highly suggestive of adenoma to find whether there is a correlation between the extracted features and clinical data. Patients with hormonal hypersecretion may require medical attention, even if it does not cause any symptoms. A total of 206 patients affected by adrenal incidentaloma were retrospectively enrolled and divided into non-functioning adrenal adenomas (NFAIs, n = 115) and mild autonomous cortisol secretion (MACS, n = 91). A total of 136 texture parameters were extracted in the unenhanced phase for each volume of interest (VOI). Random Forest was used in the training and validation cohorts to test the accuracy of CT textural features and cortisol-related comorbidities in identifying MACS patients. Twelve parameters were retained in the Random Forest radiomic model, and in the validation cohort, a high specificity (81%) and positive predictive value (74%) were achieved. Notably, if the clinical data were added to the model, the results did not differ. Radiomic analysis of adrenal incidentalomas, in unenhanced CT scans, could screen with a good specificity those patients who will need a further endocrinological evaluation for mild autonomous cortisol secretion, regardless of the clinical information about the cortisol-related comorbidities.

Pituitary Adenoma: SSTR2 rs2236750, SSTR5 rs34037914, and AIP rs267606574 Genetic Variants, Serum Levels, and Ki-67 Labeling Index Associations.

Background and Objectives: This study explores the complex pathogenesis of pituitary adenomas (PAs), prevalent intracranial tumors in the pituitary gland. Despite their generally benign nature, PAs exhibit a diverse clinical spectrum involving hormone hypersecretion and varying invasiveness, hinting at multifaceted molecular mechanisms and abnormalities in tumorigenesis and gene regulation. Materials and Methods: The investigation focuses on the Ki-67 labeling index, SSTR2 rs2236750, SSTR5 rs34037914, and AIP rs267606574 polymorphisms, alongside serum levels of SSTR2, SSTR5, and AIP, to discern their association with PAs. The Ki-67 labeling index was assessed using immunohistochemical analysis with the monoclonal antibody clone SP6, representing the percentage of tumor cells showing positive staining. Genotyping was performed via real-time polymerase chain reaction, and serum levels were analyzed using ELISA. The study included 128 PA patients and 272 reference group subjects. Results: The results derived from binary logistic regression analysis revealed an intriguing correlation between the SSTR2 rs2236750 AG genotype and approximately a 1.6-fold increased likelihood of PA occurrence. When analyzing SSTR5 rs34037914, statistically significant differences were found between Micro-PA and the reference group (p = 0.022). Additionally, the SSTR5 rs34037914 TT genotype, compared with CC + CT, under the most robust genetic model (selected based on the lowest AIC value), was associated with a 12-fold increased odds of Micro-PA occurrence. However, it is noteworthy that after applying Bonferroni correction, these findings did not retain statistical significance. Conclusions: Consequently, while this study hinted at a potential link between SSTR2 rs2236750 and pituitary adenoma development, as well as a potential link between SSTR5 rs34037914 and Micro-PA development, it underscored the need for further analysis involving a larger cohort to robustly validate these findings.

ScRNA sequencing technology for PitNET studies.

Pituitary neuroendocrine tumors (PitNETs) are common, most likely benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNET types are classified according to their expression of specific transcriptional factors (TFs) and hormone secretion levels. Some types show aggressive, invasive, and reoccurrence behavior. Current research is being conducted to understand the molecular mechanisms regulating these high-heterogeneous neoplasms originating from adenohypophysis, and single-cell RNA sequencing (scRNA-seq) technology is now playing an essential role in these studies due to its remarkable resolution at the single-cell level. This review describes recent studies on human PitNETs performed with scRNA-seq technology, highlighting the potential of this approach in revealing these tumor pathologies, behavior, and regulatory mechanisms.

Inhibition of somatostatin enhances the long-term metabolic outcomes of sleeve gastrectomy in mice

ObjectiveBariatric surgery is an effective treatment to obesity, leading to weight loss and improvement in glycemia, that is characterized by hypersecretion of gastrointestinal hormones. However, weight regain and relapse of hyperglycemia are not uncommon. We set to identify mechanisms that can enhance gastrointestinal hormonal secretion following surgery to sustain weight loss. MethodsWe investigated the effect of somatostatin (Sst) inhibition on the outcomes of bariatric surgery using a mouse model of sleeve gastrectomy (SG). ResultsSst knockout (sst-ko) mice fed with a calorie-rich diet gained weight normally and had a mild favorable metabolic phenotype compared to heterozygous sibling controls, including elevated plasma levels of GLP-1. Mathematical modeling of the feedback inhibition between Sst and GLP-1 showed that Sst exerts its maximal effect on GLP-1 under conditions of high hormonal stimulation, such as following SG. Obese sst-ko mice that underwent SG had higher levels of GLP-1 compared with heterozygous SG-operated controls. The SG-sst-ko mice regained less weight than controls and maintained lower glycemia months after surgery. Obese wild-type mice that underwent SG and were treated daily with a Sst receptor inhibitor for two months had higher GLP-1 levels, regained less weight, and improved metabolic profile compared to saline-treated SG-operated controls, and compared to inhibitor or saline-treated sham-operated obese mice. ConclusionsOur results suggest that inhibition of Sst signaling enhances the long-term favorable metabolic outcomes of bariatric surgery.

Risk of intracranial meningioma in patients with acromegaly: a systematic review.

https://www.crd.york.ac.uk/prospero/, identifier CRD42022376998.

Diabetes mellitus in patients with acromegaly: pathophysiology, clinical challenges and management.

Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common complication of acromegaly, occurring in approximately one-third of patients. The risk of diabetes mellitus in acromegaly is driven by increased exposure to growth hormone, which directly attenuates insulin signalling and stimulates lipolysis, leading to decreased glucose uptake in peripheral tissues. Acromegaly is a unique human model, where insulin resistance occurs independently of obesity and is paradoxically associated with a lean phenotype and reduced body adipose tissue mass. Diabetes mellitus in patients with acromegaly is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, preventive measures and optimized treatment of diabetes mellitus are essential in these patients. However, specific recommendations for the management of diabetes mellitus secondary to acromegaly are lacking due to limited research on this subject. This Review explores the underlying mechanisms for diabetes mellitus in acromegaly and its effect on morbidity and mortality. We also discuss treatment modalities for diabetes mellitus that are suited for patients with acromegaly. Improved understanding of these issues will lead to better management of acromegaly and its associated metabolic complications.

Case Report: Opposite Tumoral and Hormonal Responses to Low-dose Pasireotide in Cushing’s Disease

Background:: Pasireotide is a multireceptor somatostatin analogue approved for the treatment of patients with Cushing's disease (CD) who are ineligible or poor candidates for pituitary surgery. Here we present a patient with severe recurrent CD who was treated with pasiretide and showed opposite results between hormonal levels and pituitary tumour size. Case Presentation:: A 54-year-old woman was diagnosed with CD, a first surgical transsphenoidal procedure was performed at the time of diagnosis, and the disease recurred seven years later. She underwent a second transsphenoidal surgery, but despite apparent complete removal of the adenoma, the hypercortisolism worsened. Magnetic resonance imaging showed a tiny remnant of the adenoma adjacent to the cavernous sinus, and ketoconazole was started at a dose of 800 mg/day. Due to the persistence of pathological urinary free cortisol levels, 600 μg bid pasireotide was added. The combination therapy induced first normalisation of urinary free cortisol and later hypoadrenalism, so that ketoconazole was discontinued and pasireotide was maintained. A marked clinical improvement was achieved with pasireotide. Adrenal insufficiency persisted despite progressive tapering of the pasireotide dose to 150 mg once daily. Pituitary magnetic resonance imaging performed at 12 and 24 months during low-dose pasireotide treatment showed a few millimetres increase of the remnant. Conclusions:: This report suggests that CD Pas induces an opposite effect between hormonal profile and increase of pituitary tumor size. This peculiar phenomenon may be a consequence of the unusually low doses of pasireotide needed to control hormonal hypersecretion.

The Effect of Virgin Coconut Oil on TNFα and Cytochrome P450 Aromatase Levels in Obese Female White Rats (Rattus norvegicus) Induced with a High-Fat Diet

Background: The high level of various proinflammatory cytokines due to adipocyte hypertrophy such as TNFα in obesity increases cytochrome-P450-aromatase, further inducing increased estrogen production, hypersecretion of Luteinizing Hormone and decreased Follicle Stimulating Hormone, resulting in impaired folliculogenesis, and chronic anovulation. Virgin Coconut Oil is rich in Medium Chain Fatty Acid and phytochemicals as anti-inflammatory. Aim: The aim of this study was to determine the effect of VCO on reducing TNFα and cytochrome-P450-aromatase levels in obese female white rats. Methods: Post test only control group, 24 rats were divided into 3 groups, namely: negative control group (K-), positive control group (K+), and treatment group (P). The K+ and P groups were induced using a high-fat diet for 10 weeks, then the P group was given VCO in weeks 7-10. On the first day of week 11, blood was taken from the orbital vein of the eyes of all rats for TNFα levels. Both examinations used ELISA kits. Data analysis used Shapiro Wilks normality test. The value of p>0.05, followed by hypothesis testing using one-way annova and post hoc Bonferroni. Results: Mean TNFα in the K- group: 141.71±8.87, K+ group: 15.09±19.30, P group: 162,09±13,57. Mean cytochrome-P450-aromatase levels in the K- group: 9.00±0.77, K+ group: 12.22±1.69, P group: 10.58±0.97. The mean levels of one way ANOVA analysis showed that the administration of VCO can significantly reduce TNFα levels (p=0.001) and significantly reduce Cytochrome-P450-aromatase levels (p=0.001). Conclusion: VCO administration can reduce TNFα levels and cytochorme-P450-aromatase levels in obese female white rats. Keywords: TNFα, cytochrome-P450-aromatase, infertility, obesity