Endocrine Abstracts

Introduction: Patients with Sheehan’s syndrome (SS) may experience alterations in blood pressure (BP) regulation, possibly due to hormones deficiencies and hormone replacement treatment. The aim of the present study was to assess the 24h ambulatory BP in women with Sheehan syndrome.Methods: This was a monocentric cross-sectional study involving 50 women with complete anterior hypopituitarism secondary to SS and 50 age and body-mass index (BMI) match...

Background: Cushing Syndrome (CS) is associated with metabolic disturbances, including obesity. The 1 mg Dexamethasone Suppression Test (1mgDST) is widely used to assess cortisol regulation in suspected CS patients. However, its interpretation may require adjustments based on individual factors, such as body mass index (BMI), due to obesity’s influence on cortisol metabolism. The literature offers differing cutoff values for obese patients. This study aimed to establish B...

Background: Improved survival rates from brain tumours have resulted in patients living longer with the effects of radiotherapy. Advances in conventional fractionated radiotherapy, such as intensity-modulated radiotherapy (IMRT), enable radiation to be delivered more precisely while partially sparing surrounding structures including the hypothalamic-pituitary axis. Despite these advances, the precise risk of hypopituitarism associated with IMRT in survivors of adult-onset non-...

Introduction: A change in the biological behaviour of Small-Intestinal Neuroendocrine Tumours (SiNETs), as reflected by an increase in the Ki-67 proliferation index may occur over time. The purpose of this study was to evaluate longitudinal changes in Ki-67 indices of SiNETs and assess the impact of these in overall survival (OS).Patients and methods: We screened 551 patients with SI-NETs diagnosed from 1993, through 2021, identified using the SI-NET dat...

Introduction: Infections are very frequent in Cushing’s disease with impact on quality of life.Objective: The aim of our study is to describe infectious manifestations in Cushing’s diseaseMaterial and methods: Retrospective study of 51 patients diagnosed for Cushing’s disease followed at the Ibn Rochd CHU Endocrinology from Casablanca from 2012 to 2023. Infectious complications were detected either at diagnosis or du...

Aim: To assess the diagnostic value of a 3% hypertonic saline infusion test in comparison with a set of clinical and laboratory data (including a water deprivation test and MRI data) for the purpose of differential diagnosis between ADH deficiency and primary polydipsia (PP).Materials and Methods: An interventional comparative study included 90 patients with confirmed polyuria-polydipsia syndrome. In order to assess the diagnostic characteristics, all su...

In vitro studies suggest that glucocorticoids (GC) long-term exposure downregulates SSTR2 but not SSTR5 expression in human and mouse ACTH-secreting tumor cells (AtT20), limiting the efficacy of octreotide (OCT), a somatostatin-receptor ligand with high affinity for SSTR2, in the treatment of Cushing’s disease (CD). In AtT20, dexamethasone treatment increased miR-375 expression, whose analysis revealed a seed-sequence for SSTR2, supporting the hypothesis that exc...

Introduction: Active acromegaly is diagnosed based on clinical symptoms and biochemical tests, such as elevated GH concentration, IGF-1 concentration above the reference range for sex and age. However, due to certain limitations associated with IGF-1 measurements, alternative biomarkers are being sought that may be useful at various stages of the diagnostic and therapeutic process.Purpose: Evaluation of the usefulness of serum soluble α-klotho prote...

Background: Hyperprolactinemia is a biochemical finding with a broad differential diagnosis and is commonly measured during the work up for amenorrhea, galactorrhea, or hypogonadism. Diagnostic workup of hyperprolactinemia should be performed in a stepwise fashion to avoid incorrect diagnoses and/or unnecessary investigations. As mild hyperprolactinemia (i.e. <100 mg/l) can be physiologic or spurious, repeating the prolactin level is a crucial step in the initial workup. U...

Background: It is well known that both genetic backgroup and lifestyle influence the development of ‘general’ obesity. However, the role of parental body mass index (BMI) on the development of obesity in long-term survivors of childhood-onset craniopharyngioma (CP) is not well understood. This study aimed to analyze the correlation of patients’ BMI at diagnosis, and last visit and parental BMI at CP diagnosis and further explored potential risk factors for obesi...

Background: Acromegaly is a rare endocrine disorder characterised by excess growth hormone (GH) and insulin-like growth factor 1 (IGF-1) that is associated with significant morbidity and impaired quality of life (QoL). Standard-of-care (SoC) treatments for acromegaly typically require healthcare provider administration, pose a substantial treatment burden, and leave scope for improved disease control. CAM2029, an octreotide subcutaneous depot with ~5x higher bioavailability th...

Introduction: Sheehan’s syndrome (SS) is characterized by a deficiency in pituitary hormone secretion. It is now being closely inspected for its implication in the onset of metabolic syndrome (MS). The aims of this study were to determine the prevalence of MS and assess its associated factors in women with SS.Methods: We carried out a cross-sectional study involving 50 patients diagnosed with SS and 50 controls, matched for age and body-mass index (...

Introduction: 2-[18F]FDG PET/CT, commonly used for neoplastic lesions detection, also allows assessment of the severity of the inflammatory processes. Moreover, glucose uptake in spleen and bone marrow may be a useful biomarker of systemic inflammation. Patients with Cushing syndrome demonstrate many metabolic changes involving muscles and fat tissue. Some mechanisms are known, but their relationship to glucose metabolism is not well investigated. Our study aimed to correlate ...

Introduction: The diagnosis of Cushing’s syndrome (CS) can be challenging for endocrinologists due to its multifaceted presentation. Accurate differentiation between Pseudo-Cushing syndrome (PCS) and true CS is crucial as their treatment approaches and outcomes vary significantly.Case Report: A 43-year-old male patient with grade III obesity (BMI: 49.9 kg/m2) presented to our Endocrinology outpatient clinic with a complex medical history ...

Introduction: Immunohistochemistry (IHC) of somatostatin receptor subtype 2 (SST2) is a predictive factor for first-generation somatostatin receptor ligand (fg-SRL) response in acromegaly patients. A semi-quantitative immunoreactivity score, IRS, has been proposed as the gold-standard to evaluate SST2 IHC expression. Recently, our group developed a quantitative method to determine SST2 expression using an open-source digital image analysis (DIA...

Background: In 2017, the World Health Organization (WHO) adjusted the histopathological classification of pituitary adenomas (PAs) by including pituitary cell lineage specific transcription factors (TFs), elucidating a continuous spectrum between true null cell (NCA), silent, clinically silent, and functioning adenomas. The definitions of non-functioning (silent) gonadotroph, corticotroph, somatolactotroph and thyrotroph adenomas were previously reserved for immunohistochemica...

Background: Proton beam therapy (PBT) provides high doses of radiation to the targeted tissues while minimizing exposure to surrounding structures. Although rarely used in patients with functional pituitary adenomas (FPA) it might be nessesary in certain clinical situations. There is paucity of data regarding short- and long-term endocrinologic outcomes.Objectives: In patients undergoing PBT, determine rate of remission of FPA(normal hormonal values off ...

Background: Hyponatremia has been related to worse outcomes from COVID-19 infection during hospital admission. However, little is known about the incidence and prevalence of hyponatremia after discharge and the associated risk factors.Methods: Prospective observational 24-month follow-up study of patients admitted at a tertiary hospital during the first COVID-19 wave. Kaplan-Meier curves and Cox proportional hazard models were used to assess the main var...

Introduction: Approximately 20% of neuroendocrine tumor (NET) patients experience carcinoid syndrome (CS), primarily associated with metastatic ileal NETs. CS manifests with symptoms such as diarrhea, flushes, and cardiac complications. Carcinoid heart disease (CHD) is a negative prognostic factor in NETs. However, the considerable variability in reported diagnoses and treatment approaches in the literature creates uncertainty about optimal management in this specific populati...

Over 40 years ago, the first enkephalin analogs that stimulated growth hormone (GH) release were synthesized in 1984, leading to the development of GHRP-6. In 1995, Merck developed a potent non-peptide orally active long-acting growth hormone GHS, ibutamoren, and cloned the GHS receptor in 1996, which led to ghrelin being identified as its natural ligand in 1999. These discoveries uncovered a new physiological pathway for GH regulation linking the GI tract and the hypothalamic...

Introduction: Craniopharyngiomas are rare tumors which are typically located in the sellar and suprasellar region. They can be solid or mixed, cystic-epithelial. Treatment options include surgery, radiation or intracystic therapy. Adipsic diabetes insipidus is a rare, life-threatening disease which can sometimes be associated with craniopharyngioma, either because of tumor mass effect, or as a postprocedure complication. Ultimately, this can cause severe hypernatremia, so long...

Introduction: Cushing’s Syndrome is caused by elevated levels of cortisol and is characterized by dozens of non-specific physical, metabolic, and neuropsychological symptoms. The extent of damage a patient will face is directly related to time to diagnosis, experience of the doctors and surgeon, and the support and education they receive after surgery. The spectrum of long-term needs faced by patients who have been exposed to prolonged elevated cortisol are not well repre...

Objective: There is increasing evidence that multisystem morbidity in patients with Cushing’s disease (CD) is only partially reversible following treatment. We investigated complications from multiple organs in hospitalized patients with CD compared to patients with non-functioning pituitary adenoma (NFPA) after pituitary surgery.Design: Population-based retrospective cohort study using data from the Swiss Federal Statistical Office between January ...

Background: Psychopathological distress is a significant burden in acromegaly, mostly in terms of depression and anxiety. Patients are also reported to experience an impairment in cognitive performance, yet literature is highly heterogeneous.M&M: We conducted a cross-sectional study recruiting 44 acromegalic patients (59% females, 29.5% with active disease, 70.5% controlled/in remission) referring to our tertiary center between 2011 and 2023 and 40 h...

Background: Growth hormone deficiency (GHD) is a rare disorder characterized by pronounced and symptomatic hypo secretion of growth hormone (GH) from the anterior pituitary gland. Biochemical tests are used as part of the diagnosis in both children and adults but controversies remain as regards whom, when, and how to test, and also how to interpret a given biochemical test result.Aim: To map the current clinical practice of GHD diagnosing in children and...

Background: Glucocorticoid-induced adrenal insufficiency (GIA) may occur after termination of long-term glucocorticoid (GC) treatment. GIA is usually diagnosed by a short-synacthen-test (SST), but peak cortisol response to SST may not validly assess normalisation of the diurnal hypothalamic-pituitary-adrenal (HPA)-axis. In patients with polymyalgia rheumatic (PMR) and giant cell arteritis (GCA), we report at this meeting a surprisingly low prevalence of GIA of 1.6% after cessa...

Gonadotroph pituitary tumors (GnPiT) account for ~40% of pituitary tumors surgically treated and 70-75% of non-functional pituitary tumors. Functional gonadotropin-secreting tumors are rare and clinical manifestations vary according to the age and sex of the patient. They are benign tumors which, due to their silent nature, can grow and invade surrounding structures, making complete resection impossible and leading to recurrence in ~30% of cases.Objectiv...

Background: Posterior pituitary tumors (PPTs) present as clinically nonfunctioning space-occupying lesions of the sellar region. The diagnosis of PPTs is not possible on the basis of their clinical, radiological and biochemical features. Immunohistochemistry identifies them for their expression of TTF. They are virtually always mistakenly defined as one of the more common pituitary tumours. Due to their rarity, the long-term endocrine aspects and outcomes of PPTs are not well ...

Objective: This study aims to assess the utility of salivary cortisol (SC) in diagnosing adrenal insufficiency (AI) and to analyze the integrity of the hypothalamic-pituitary-adrenal axis. This involves evaluating cortisol rhythm, its correlation with plasma levels, and the impact of exogenous hydrocortisone (HC) substitution on SC determination.Methods: A prospective study was conducted on all patients with suspected AI undergoing adrenocorticotropic ho...

69-year old male was diagnosed with non-secreting pituitary macroadenoma (25x 15x 15mm) in 2008. Patient underwent two transsphenoidal surgeries and stereotactic radiotherapy in 2008 and 2009. Tumor recurrence was noticed on MRI in 2016. In 2017 urgent right pterional craniotomy was performer due to right eyelid dropping with ocular nerves palsy. Despite surgery further growth of the tumor (32x 22x 31mm) was reported in 2018, followed by increased ACTH level and hypercortisole...

Objectives: Endogenous Cushing’s syndrome (CS) is a rare, chronic condition that results in high morbidity, caused by prolonged exposure to elevated levels of circulating free cortisol. A previous comparative analysis showed osilodrostat increases the odds of complete response (CR; mean urinary free cortisol [mUFC] ≤ 1.0 x the upper limit of normal) at Weeks 12 and 36 vs metyrapone1; however, analyses were limited by small osilodrostat effective sample si...

Background: Soluble alpha klotho (sαKL) is a peptide hormone, that has been shown to be elevated in serum of patients with uncontrolled acromegaly. One early pilot study suggested that sαKL is also detectable in urine from patients with acromegaly, and significantly drops after surgery. Notably, in this study, urine sαKL concentrations were undetectable in the control group, and fell consistently below the detection limit of the ELISA in postoperative patients i...

Adult growth hormone deficiency (GHD) is widely acknowledged for its association with heightened mortality, primarily linked to an increased risk of cardiovascular complications. Endothelin-1 (ET-1) is implicated in various cardiovascular conditions, including hypertension, atherosclerosis, and heart failure, where imbalances in its levels or signaling have been identified. Despite the distinct primary functions of growth hormone and endothelin within the body, both hormones a...

Design: Macroprolactinemia may influence the interpretation of serum prolactin levels – a recognised phenomenon since 19781. The degree of macroprolactinaemia over time is less well described. We determined how macroprolactin status (based on polyethylene glycol (PEG) precipitation varied by analysing serial measurements in hyperprolactinaemic individuals over nine years.Patients and Measurements: Results from 1810 individuals were includ...

Intracranial Tumors comprise a diverse group of endocrine-related tumors [ERTs; e.g. craniopharyngiomas (CPs) and pituitary-tumors (PTs)], representing significant challenges for the diagnosis/prognosis/treatment of patients, their families and health systems due to their heterogeneity, associated neurological impairment and endocrine comorbidities. However, despite recent advances, the current treatment (e.g. surgery plus irradiation in CPs, pharmacological treatment with som...

Background and Objectives: The differential diagnosis between arginine vasopressin (AVP) deficiency (AVP-D, formerly known as central diabetes insipidus) and primary polydipsia (PP) remains challenging. To date, the method with the highest diagnostic accuracy is osmotically-stimulated copeptin – a surrogate marker of AVP – using hypertonic saline infusion. However, this method is often limited to experienced hospitals, requires close monitoring, and may be cumbersome...

Introduction: Dopamine agonists are the first line treatment for prolactinomas. However, some patients may develop dopamine-agonist-resistant hyperprolactinemia, leading to surgery and/or radiotherapy. The persistence of hypogonadism requires testosterone replacement therapy which could theoretically reduce the efficacy of dopamine agonists due to the conversion of testosterone to estradiol, thus, in turn, increasing the resistance to dopamine agonists. Consequently, in these ...

Introduction: Prolactinomas, prevalent among young women, are the most frequently encountered secreting pituitary tumors. Pituitary apoplexy is a rare and severe complication of prolactinomas, which manifests with rapid onset symptoms like severe headaches, visual disturbances, hormonal imbalances, requiring urgent medical care.Case report: We report the case of a 46-year-old female patient with history of type 2 diabetes, early menopause (30 years old, ...

Introduction: Infundibulo-neurohypophysitis (INH) is an uncommon inflammatory disorder. Because of the location of inflammation, it selectively affects the neuropituitary and pituitary stalk. The differential diagnosis remains often challenging with neoplastic lesions, such as germ cell neoplasia, Langerhans cell histiocytosis, Erdheim-Chester Disease, metastasis. Our clinical case is emblematic for pitfalls in diagnosis of the pituitary stalk lesionCase...

Background: Precise mechanism(s) responsible for stimulation of growth hormone (GH) and cortisol during Glucagon Stimulation Test (GST) are not clear, but seem to be related to glucagon-induced fluctuations in glucose and/or insulin with an initial increase followed by a subsequent fall in glucose and insulin concentrations. We have endeavoured to assess whether elimination of fall in glucose concentrations during GST would obliterate any significant increase in GH and cortiso...

Background: Maternal cortisol levels increase during pregnancy and prenatal cortisol exposure have been linked to cognitive function in childhood. Higher activity of the enzyme 11β-hydroxysteroid-dehydrogenase type 2 (11β-HSD2) downregulates the amount of maternal cortisol crossing the placenta by inactivation of cortisol to cortisone. In childhood, boys perform significantly poorer in tests of intelligence than girls.Aim: To investigate associ...

Objective: Transforming growth factor beta receptor 3 like (TGFBR3L) has been recently described as a pituitary-specific membrane protein detected in a proportion of the gonadotroph cells in non-neoplastic and tumour tissue (1). Furthermore, mouse studies have indicated that TGFBR3L is an inhibin B co-receptor that regulates FSH levels (2). We hypothesized that TGFBR3L expression in gonadotroph non-functioning pituitary neuroendocrine tumours (NF-PitNETs) is related to clinica...

Introduction: Paragangliomas are rare neuroendocrine tumors, that manifest as painless, slow-growing masses, becoming evident only when symptoms of catecholamine overproduction or mass effects emerge. Paragangliomas exhibit a broad spectrum of characteristics, existing as solitary or multiple entities, and may be sporadic or hereditary. These tumors can be either benign or malignant and have origin in the sympathetic or parasympathetic tissues. Paragangliomas are commonly foun...

Introduction: Distinguishing arginine vasopressin deficiency (AVP-D, central diabetes insipidus) from primary polydipsia (PP) is challenging. The method with the highest diagnostic accuracy, hypertonic saline-stimulated copeptin, is often limited to experienced hospitals, requires close monitoring, and may be cumbersome for patients. A standardised, validated stepwise assessment and probability score to rule out AVP-D in the initial baseline evaluation is currently lacking.</p...

Genetic discoveries improved the understanding of the etiology and pathogenesis of several diseases, including acromegaly. Germline mutations involving AIP, MEN1, CDKN1B, GPR101, PRKAR1A, and GNAS genes have been described in GH-secreting PitNETs, but realistically many genetic alterations have not been identified yet. Nowadays, RET mutations have not been reported in acromegaly, if not exclusively in the context of a multiple endocrine neoplasia (MEN). A 48-year-old patient w...

Corticotroph tumours, comprising around 15% of pituitary tumours, express ACTH and other peptides originating from TPIT-lineage adenohypophyseal cells. Their tumorigenesis involves a complex interplay of genetic and epigenetic factors and hormonal and growth factor stimulation. Silent corticotroph tumours (SCT) share immunopositivity for ACTH and TPIT with functioning corticotroph tumours (FCT) but do not exhibit evidence of hypercortisolism. Despite their aggressive growth an...

Background: Glucocorticoids (GC) are potent entrainers of the circadian clock, however their effect on biological rhythms in human chronic exposure have been poorly studied. Endogenous hypercortisolism (Cushing’s Syndrome, CS) is a rare condition, in which circadian disruption is sustained by a tumorous source of GC excess, offering the unique opportunity to investigate the in vivo chronic effects of GC.Methods: In a 12-month prospective mu...

Objective: To evaluate the natural history of Rathke’s cleft cysts (RCC).Materials and Methods: A multicenter retrospective clinical practice study of adult patients with radiologically diagnosed RCCs since 2000 in 15 tertiary hospitals (SPAIN-QBR study) with a diameter greater than 5 mm, in whom non-surgical follow-up was decided.Results: A total of 177 patients were followed for 65.8 ± 42.3 months. The mean age was 42.8...

Introduction: Patients with prolactinomas suffer from a wide range of symptoms, of which the effect on health-related quality of life (HR-QoL) needs further investigation. Moreover, the first-line treatment for patients with prolactinomas, dopamine agonists (DAs), albeit being effective in lowering prolactin levels, might further hamper HR-QoL due to side effects. To assess the impact of symptoms and treatment modality on HR-QoL, a cohort of patients with prolactinoma was cros...

Introduction: Glucose-induced osmotic diuresis and free water loss induced by the SGLT2 inhibitor empagliflozin effectively increase sodium levels in patients with a chronic syndrome of inappropriate antidiuresis (SIAD) where arginine vasopressin (AVP) levels are inappropriately increased in relation to osmolality. The hormone apelin opposes the actions of AVP in salt and water homeostasis and administering exogenous apelin increases sodium levels in rats with SIAD. In patient...

Introduction: Growth hormone (GH) replacement therapy is safe and confers significant benefits in body composition, bone health, cardiometabolic risk factors, and quality of life in adults with GH deficiency. However, longer term safety and efficacy data are limited by the lack of consistency in data collection between studies. The study aim was to develop a simple global register by standardising and developing a minimum data set (MDS) to facilitate international collection o...

Background: Corticotroph tumours are a heterogenous group of pituitary neuroendocrine tumours (PitNETs) in terms of their histological type, clinical presentation and tumour behaviour. These tumours are overrepresented in recurrent PitNETs and pose an important clinical and therapeutic challenge1. Although risk factors such as radiological invasion and elevated proliferative markers have been identified for PitNET recurrence, an improvement in proposed prognostic mo...

Background: Granulomatous mastitis (GM) is a rare inflammatory condition of the breast typically affecting women during postpartum period. GM can mimic inflammatory breast cancer and only be reliably distinguished through histopathology. While there is no generally accepted treatment for GM, therapeutic options include - antibiotics, wide surgical excision, and corticosteroids.Clinical Case: A 54-year-old female presented to her family physician with wit...

Introduction: Cyclic Cushing’s syndrome is a rare disease characterized by episodes of cortisol hypersecretion followed by periods of normal cortisol secretion, ranging from days to months. We report a case of cyclic Cushing’s syndrome whose diagnosis was delayed for years.Case presentation: A 50-year-old female with a 16-year history of non-Hodgkin’s lymphoma was referred to the Endocrinology Unit due to suspected hypercortisolemia. She h...

Rationale: Pituitary tumours (PiTs) are a common and heterogeneous group of benign, slow-growing intracranial neoplasms arising from the sellar region. While recent advances have improved our knowledge of their cellular composition and the contribution of their tumour microenvironment (TME), most of PiT subtypes lack effective therapeutic treatments. Moreover, the mechanisms that occur in the early stage of PiT initiation remain to be elucidated partly due to the limited numbe...

Objective: Studies have demonstrated that patients with acromegaly have compromised bone health and an increased risk of vertebral fractures (VFs). However, the prevalence of VFs in Chinese patients with acromegaly has not been investigated by far. This study aimed to evaluate the prevalence and determinants of VFs in patients with acromegaly in a tertiary hospital in China.Methods: We enrolled patients diagnosed with acromegaly consecutively at West Chi...

Taking into account heterogeneity of somatotrophic tumors (STs), intragroup differential diagnostics is of practical importance, since it allows to predict scenario of acromegaly clinical course, as well as the efficacy of secondary drug therapy (DT).The aim of this study was to determine prognostic power of cytological, immunological&radiological predictors of sensitivity/resistance to fg-SRLs in patients with pure somatotropinomas.Materials and Met...

Background: Adamantinomatous craniopharyngioma (CP) is a rare embryonal malformation originating from remnants of the craniopharyngeal duct and located in the sellar and/or parasellar area. Overall survival rates are high (92%), but frequently quality of life (QoL) is severely impaired in patients with CP involving hypothalamic structures. Tumor- and/or treatment-related hypothalamic lesions result in disturbances of circadian rhythms including increased daytime sleepiness.</p...

Introduction: Insulinomas are the most common functioning endocrine neoplasms of the pancreas. 53% of patients are diagnosed within five years of experiencing their first symptoms. Surgical resection is the primary treatment modality. However, patients awaiting surgery or who are not surgical candidates have achieved symptomatic relief from medical therapy. Cases of insulinoma masking diabetes has been described but are rare and diabetes often presents following surgery. Here,...

35y male presented with extreme fatigue and symptomatic hypogonadism. He had history of multiple infections since childhood due to combined immunodeficiency syndrome and hypogammaglobulinemia, autoimmune haemolytic anaemia, sensorineural deafness, cytopenias, acute hepatitis with hepatosplenomegaly. Liver biopsy (age 15y) showed chronic hepatitis with necrosis. In 2020 (age 32y) he underwent bone marrow biopsy for progressive pancytopenia demonstrating hypercellularity, but no...

Introduction: Treatment options for acromegaly include surgery or radiation to remove or reduce the size of the tumor and medication to help normalize the hormone levels. While improving the prognosis, patients with acromegaly treated with radiotherapy are at risk of long-term development of secondary malignancies (1-2% at 10-20 years). We report the case of a 55-year old woman diagnosed with high-grade sarcoma of the sphenoid sinus developed 34 years after receiving 60Cobalt ...

While somatostatin analogs (SSA) are the primary medical therapy for treatment of acromegaly, they fail to normalize insulin-like growth factor 1 (IGF1) levels in the majority of patients when used as monotherapy. Even in patients with controlled IGF1, growth hormone (GH) levels can remain elevated and induce symptoms by interacting with GH receptors throughout the body. AZP-3813 is a 16-amino acid, bicyclic peptide GH receptor antagonist (GHRA) which has been demonstrated to ...

Aim: Evaluate the predictive value of the Pituitary Apoplexy Score (PAS) for predicting hormonal and visual recovery after surgery or conservative management of patients with pituitary apoplexy (PA).Methods: Multicenter retrospective study of patients presenting with clinical PA in three Spanish tertiary hospitals between 2008 and 2022. The PAS was calculated following the UK Pituitary Apoplexy Guidelines Development Group evaluation grid.<p class="a...

Background: In the last few decades, the association between pituitary disorders and cardiovascular disease has been demonstrated. Furthermore, the importance of gender as a non-modifiable risk of factor is increasingly emerging.Methods: We retrospectively analyzed data of 112 patients diagnosed with nonfunctioning pituitary tumor (NFPT) attending the outpatient clinic at our tertiary center. In this study we report only preliminary data of the retrospec...

Introduction: In 2013 Trouillas et al. reported a new prognostic clinicopathological classification of pituitary adenomas. This classification analyses the impact of the intensity of proliferation and invasiveness of the tumor on patients’ prognosis. The aim of the study was to review this new classification in giant pituitary adenomas (GPAs) treated with endoscopic transsphenoidal approach.Material and methods: The study is a retrospective...

Background: A subset of patients with prolactinomas does not respond satisfactorily to first-line medical therapy with dopamine agonists (DA). DA resistance is defined as failure to normalize prolactin (PRL) levels and/or to achieve ≥50% reduction in maximal tumor diameter under maximally tolerated doses (or a weekly cabergoline dose of ≥3mg). The predictive factors for DA resistance are male gender and tumor invasiveness.Aim: To characterize...

Background: Acromegaly is an uncommon chronic endocrine disorder which is associated with considerable comorbidities. Many patients fail to achieve biochemical control with current medical therapies, including surgery and first-generation somatostatin analogs. We aimed to perform a systematic review and single-arm meta-analysis to evaluate the efficacy of the multi-receptor ligand somatostatin analog Pasireotide in patients with acromegaly.Methods: We sy...

Aim: To investigate T2-signal intensity (SI) and histopathological characteristics of the somatotroph PitNETs (S-PitNET).Methods: 41 out of 109 consecutive patients with newly diagnosed acromegaly and available histopathological results were included. 36 results contained the electron microscope examination. Tumors were divided into 3 SI groups: hyperintensive (HyPER), isointensive (ISO) and hypointensive (HyPO). SI was assessed qualitatively using Visua...

Introduction: Diabetes mellitus (DM) and hypertension are common comorbidities that pose significant clinical burden in Cushing’s syndrome patients and may be improved by normalising cortisol. In two Phase III trials (LINC3 [NCT02180217]; LINC4 [NCT02697734]), osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided reductions in cortisol and improved clinical manifestations of hypercortisolism in most Cushing’s disease (CD) patients. Here, we describe ch...

The spectrum of lesions in the sellar and parasellar region includes a wide range of diseases, from the most common adenoma to various non-adenomatous lesions i.a. empty sella syndrome, stroke and congenital conditions. We identified a case of meningitis in which the images initially suggested the presence of a pituitary macroadenoma. The 45-year-old patient without chronic diseases was admitted to the Department of Neurology due to severe headaches and vomiting that had woken...

Background: Pituitary neuroendocrine tumours (PitNETs) that cause acromegaly are often collectively categorised as ‘growth hormone (GH) secreting adenomas’. The 2022 WHO classification however identifies 7 histological variants that can secrete GH: densely granulated somatotroph (DGST), sparsely granulated somatotroph (SGST), mammosomatotroph (MST), mixed somatotroph and lactotroph (MSLT), mature plurihormonal PIT1 (MPPT), immature PIT1 (IPT) and acidophil stem cell ...

Introduction: Giant pituitary adenomas (GPAs) are traditionally defined as the tumors with the greatest diameter at or above 40 mm. However, some clinical series of GPAs include tumors with maximal diameter of 35 to 40 mm, and those tumors can be named ‘nearly giant’ pituitary adenomas (nearly GPAs). The treatment of GPAs is challenging and has a higher risk of complications due to the size and complex anatomical relations. This study was conducted to compare GPAs an...

Background: GH potently stimulates collagen turnover which underlies its anabolic effects on bone in children, whereas it may promote fibrosis in adults. Fibroblast activation protein-α (FAPα) is involved in collagen turnover by its collagen-cleaving and fibroblast-stimulating activity, which predominantly is expressed in association with fibrosis. FAPα also cleaves and inactivates fibroblast growth factor 21 (FGF21), a multi-faceted metabolic hormone. We have p...

Introduction: While there is a significant risk of recurrence in nonfunctioning pituitary adenoma (NFPA) after surgery, it is challenging to predict which NFPAs will recur based solely on routine histopathology. To better understand markers of recurrence, we assessed the established tumor markers linked to aggressive tumor behavior including X-linked IAP (XIAP), the most potent inhibitor of the apoptosis protein family, vascular epithelial growth factor (VEGF) which facilitate...

Study Objective: Sevoflurane is a halogenated inhalational anesthetic increasingly used in the intensive care unit (ICU) for its potentially beneficial effects in patients with acute respiratory distress syndrome. However, safety data on prolonged sevoflurane sedation are lacking and cases of diabetes insipidus (DI) have been observed. The objective of this study was to assess the incidence and risk factors of DI during prolonged sevoflurane sedation.Des...

Introduction: Considering the mitogenic potential of GH and IGF1, the safety profile of growth hormone therapy since the beginning of its use has been debated. From that point of view, adolescents in transition to adulthood who were treated in childhood for endocranial tumors or malignancies require special caution.Patients and Methods: In a monocentric, observational, retrospective cross-sectional study spanning 18 years, we analyzed 251 childhood onset...

Background: Cerebral malaria may present with altered cognition, severe hemolysis, renal and metabolic dysfunction. The endocrine abnormalities induced by malaria include: hypoglycemia, hypocalcemia, hypercortisolism and compromised pituitary function due to sequestration of drepanocytes in hypothalamo-pituitary portal microvasculature.Aim: To raise awareness for the risk of pituitary dysfunction in severe malaria.Case: A previousl...

Introduction: Prolactin is involved in lactation and reproduction. Endocrinologists should be familiar with physiological effects of prolactin in women, particular in key moments: breastfeeding and menopause. We aimed to report two females with unusual prolactin-related challenges: the first case corresponds to a postpartum woman with normoprolactinemia and breastfeeding problems; the second case concerns a menopausal woman with a prolactinoma who developed hot flashes followi...

Introduction: Insulin resistance (IR) is prevalent in patients with hypopituitarism receiving conventional replacement therapy. Recognizing and addressing IR in women with hypopituitarism is crucial for comprehensive patient management and prevention of other metabolic complications. The aims of this study were to determine the prevalence of IR and to assess its associated factors in women with hypopituitarism.Methods: This was a monocentric cross-sectio...

Objective: Cushing’s disease is caused by hypercortisolism due to adrenocorticotropic hormone (ACTH) hypersecretion from functioning pituitary adenomas (FCA). Endoplasmic reticulum (ER) protein processing is important for hormone production and is upregulated in FCA as shown previously. ER protein processing can be disturbed by ER stress. We hypothesized that ACTH production and secretion can be inhibited by agents that cause ER stress by attenuating ER protein processing...

Introduction: In polyuria-polydipsia syndrome (PPS) the differentiation between arginine vasopressin deficiency (AVP-D) and primary polydipsia (PP) remains challenging and a stimulation test is required. Apelin is an endogenous hormone that antagonises AVP and seems to play an important role in regulating salt and water homeostasis. The dynamic of apelin plasma levels in patients with PPS undergoing copeptin stimulation tests is unknown.Methods: Post-hoc...

Background: It has been reported that some Magnetic Resonance Imaging (MRI) pituitary findings may reflect specific endocrinological alterations, as in the case of adult-onset growth hormone deficiency (GHD), which has already been associated with lower MRI-derived pituitary height and volume in pediatric patients.Purpose: The objective of this study was to investigate potential associations between pituitary morphology and signal intensity on MRI with G...

Aim: To evaluate the efficacy of transsphenoidal surgery in patients with Rathke cleft cysts (RCCs), and recurrence rates after follow-upMethods: A multicenter retrospective clinical practice study in patients with RCCs operated through transsphenoidal route and followed in 15 tertiary hospitals (SPAIN-QBR study) during 64.0 ± 49.0 months.Results: A total of 85 patients with a diagnosis of RCCs underwent transsphenoidal surger...

Background: Pachydermoperiostosis (primary hypertrophic osteoarthropathy, PHO) is a rare genetic disease characterised by clinical signs and symptoms which may overlap with acromegaly (pachydermia, hyperhidrosis and enlargement of hands and feet). In the majority of cases, the disease is due to biallelic loss-of-function variants in either of two genes, SLCO2A1 and HPGD playing an important role in prostaglandin metabolism. Although PHO patients are often ref...

Multiple endocrine neoplasia (MEN) includes a group of autosomal dominant disorders, associated with the development of a variety of endocrine and non-endocrine manifestations. MEN4 is a rare and the latest reported type in the spectrum of the MEN syndromes. MEN4 was discovered initially in rats (MENX) and later in humans. It is caused by germline and somatic mutations in the cyclin-dependent kinase inhibitor 1B (CDKN1B) tumor suppressor gene, which encodes nuclear protein p27...

Introduction: IGF-1 dependence on sex is a well-known fact; however, whether IGF-1 is also influenced by body weight is still questionable, and the mechanism of a potential relationship between GH, IGF-1 and body weight is not fully explained. The effect of gender (or rather oestrogens) on IGF-1 is visible in acromegaly - women are diagnosed at an older age than men (approximately 4 years) (potentially by suppressive effect on the axis of GH-IGF-1). The aim of the study was to...

Purpose: The liver is known to be protected from steatosis under the influence of high GH/IGF-1. Cytokeratin 18 (CK18) and insulin-like growth factor binding protein 7 (IGFBP7) increase in liver steatosis and fibrosis. Whether decreasing lipid content completely protects the liver from metabolic alterations and the response of CK18 and IGFBP7 to liver changes in acromegaly is unknown.Methods: This single-center, multidisciplinary, cross-sectional study i...

Background: Prolactinomas are the most common functioning pituitary adenomas and are mostly diagnosed in fertile women. Dopamine-agonists (DAs) have always represented the cornerstone of prolactinoma treatment in terms of hormonal control and tumor shrinkage. Recent guidelines suggest surgery as an alternative option in selected cases after a joint evaluation with an expert surgeon. Prolactinoma management in women seeking fertility and during pregnancy remains challenging, an...

Giant prolactinomas (GPs) are prolactin secreting pituitary adenomas (PitNETs) ≥4 cm, usually with prolactinaemia over 1000 mg/l and without co-secretion of other hormones. Aims: evaluation of long term treatment of GPs, the effect of D2 agonists and of different doses on prolactinaemia, tumour shrinkage and complications.Patients and methods: 33 patients (27 males, 82%) diagnosed with GP in our department between 1997 - 2020...

Objective: To develop a non-invasive method of differential diagnosis for ACTH-dependent hypercortisolism using machine learning methods based on clinical data analysis.Materials and methods: This is a single-center study of a retrospective cohort to predict the probability of EAS among patients with ACTH-dependent hypercortisolism using artificial machine learning algorithms. Patients were randomly stratified into 2 samples: training (80%) and test (20%...

Aim: To identify the causes and predictors of mortality in acromegaly patients diagnosed, treated, and followed in the Pituitary Center of Istanbul University-Cerrahpasa over the last three decades using machine learning (ML) models.Methods: The study sample consisted of 607 consecutive patients diagnosed with acromegaly at Cerrahpasa Faculty of Medicine during the period 1990 – 2023. The main inclusion criteria were age > 18 years and a clear-c...

Introduction: Potent 11β-hydroxylase inhibitor osilodrostat provides cortisol level control in patients with Cushing’s syndrome (CS), as demonstrated by the LINC clinical development programme in Cushing’s disease (CD) patients.1 We report data from year 1 of the prospective observational LINC6 study (NCT05382156), evaluating long-term safety and efficacy of osilodrostat in CS patients during 3 years of routine clinical practice.<p class="abstext"...

Introduction: Arginine vasopressin deficiency (AVP-D) is a rare disorder with diverse etiologies. Approximately 30% of cases are labelled idiopathic, often associated with an underlying autoimmune process. This case report presents a previously presumed idiopathic AVP-D, revealing its aetiology after more than a decade of follow-up.Case presentation: A 19-year-old male presented in 2012 with symptoms of AVP-D and non-pruritic papular skin lesions on the ...

Background: Growth hormone deficiency (GHD) in children comes in different etiologies and can be either isolated or combined with other pituitary hormone deficiencies. The diversity in GHD types and the variable duration of GH therapy complicate assessments of long-term treatment outcome. We characterized GHD patients at the end of GH therapy in Belgium and Luxemburg and evaluated height and adiposity outcomes in relation to GHD type.Methods: Anthropomet...

Aim: To evaluate the efficacy of second-line therapies in patients with acromegaly caused by a GH and PRL cosecreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) and those caused by a GH-Pit-NET.Methods: A multicenter retrospective clinical practice study of 679 patients with acromegaly in follow-up in 33 tertiary hospitals (ACRO-SPAIN study). For this analysis, only patients on treatment with pasireotide or pegvisomant in monotherapy or in combi...

Background: Pituitary apoplexy (PA) is a rare endocrine and neurosurgical syndrome characterized by pituitary hemorrhage/infarction. SARS-CoV-2 infection and vaccination have been described as possible risk factors for PA, but the real impact of COVID-19 burden on PA epidemiology is still unknown.Purpose: To investigate the incidence of PA in the pandemic period during exposure to SARS-CoV-2 infection and vaccination and possible peculiar clinical charac...

Background: Hypothalamic obesity (HO) is defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor- and/or treatment related damage of the hypothalamus. The HO epidemiology is poorly understood. We developed a database algorithm supporting the standardized identification of tumor/treatment-related HO (TTR-HO) patients.Methods: The algorithm is used to estimate incidence rates of TTR-HO patients in the German healthcare...

Background: Serum soluble alpha klotho (sαKL) is a circulating protein which had been shown to be very high in active acromegaly, and significantly reduced after disease control. Therefore, sαKL has been suggested as a new biomarker for growth hormone (GH) excess. In this study, we aimed to evaluate the impact of short-term stimulation and suppression of GH and acute modulation of glucose metabolism on sαKL concentrations.Methods: Serum s&...

Aim: To investigate the impact of pituitary surgery on glucose metabolism and to identify predictors of diabetes remission after surgery in patients with acromegaly.Methods: A national multicenter retrospective study of acromegaly patients undergoing transsphenoidal surgery for the first time at 33 tertiary Spanish hospitals (ACRO-SPAIN study, n=604) was performed. Surgical remission was evaluated according to the 2000 and 2010 criteria. Glucose...

Case description: A 32-year-old male patient was treated with remdesivir and high-dose steroid for severe COVID-19 pneumonia in an ICU for one month. He was later diagnosed with steroid-induced diabetes mellitus. An endocrinological consultation raised the possibility of endogenous Cushing’s syndrome. He was then referred to our department for further investigation of suspected Cushing’s syndrome (CS). The patient presented with typical physical signs and symptoms of...

Pasireotide is a a synthetic polypeptide second-generation somatostatin analogue that can be used in the treatment of GH- and ACTH- secreting pituitary neuroendocrine tumors (PitNETs), however, there are single reports of pasireotide treatment in other subtype of PitNETs. We present a case series of aggressive, giant PitNETs treated with pasireotide alone or as multimodal therapy.Case 1: A 33-year-old male reported to the Clinic due to severe headaches a...

Alternative splicing is a crucial mechanism of gene regulation and this process can be dysregulated in cancer. In pituitary tumors (PitNETs), alteration in the serine/arginine-rich splicing factors (SRSFs) has been reported. Newly synthetized SRSFs are phosphorylated by serine-arginine protein kinase 1 (SRPK1) to facilitate their nuclear import. In response to extracellular stimuli SRPK1 may translocate to the nucleus as well to hyperphosphorylate SRSFs and favor their interac...

Background: Acromegaly is a chronic disease which causes multiple impairments that negatively affect daily life. Telemedicine is proving to be useful in diagnosing and treating these disabling aspects, including psycho-physical comorbidities, which are difficult to investigate during conventional visits.Aim of the study: To improve the management of acromegaly, both in cured and active disease, through the use of telemedicine technologies in addition to ...

Aim: To investigate the relationship between serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, seminal plasma GH and IGF-1 levels, and sperm parameters in acromegalic patients.Methods: A cross-sectional study was conducted on 24 acromegaly patients (acromegaly group), 11 non-functioning adenoma (NFA) patients (NFA group), and 16 healthy men (control group). Seminal plasma GH and IGF-1 levels were measured. Semen parameters and se...

Silent corticotroph tumors (SCT) represent a distinct subtype of pituitary tumors (PT) known for their potential aggressiveness, surpassing other silent PTs like gonadotroph tumors (SGT). Despite their aggressive clinical behavior, the mechanisms underlying their aggressiveness remain unclear. Recent studies in various cancers, such as breast cancer, have implicated the IGF1 axis in the presence of metastases. This study aims to investigate some components of the somatotroph a...

Introduction: Cushing&grave;s Syndrome (CS) is associated with endothelial dysfunction and premature atherosclerosis, which occurs due to hypercortisolism itself and associated comorbidities including diabetes and hypertension. Advanced glycation end products (AGE) are heterogeneous compounds produced endogenously from the non-enzymatic glycation of proteins, lipids, and nucleic acids, leading to the activation of various stress-induced transcription factors through the stimul...

Introduction: Adults with growth hormone deficiency (AGHD) have increased prevalence of hepatic steatosis (HS) that might be improved by growth hormone replacement therapy (rhGH). However, data on this topic are conflincting and scanty. Aim: to evaluate prevalence of HS, organ-specific distribution of adipose tissue and cardiovascular impairment in AGHD.Methods: cross-sectional collection of clinical, biochemical and instrumental data (abdominal ultrasou...

Introduction: HIST1H1E syndrome is a rare disorder caused by a de novo gene mutation encoding for histone H1-4 affecting a whole range of cellular processes. The phenotype is dominated by neurodevelopment disorders and facial deformities. Endocrinopathies and diabetes mellitus are not the main clinical features. The case of a woman with HIST1H1E syndrome associated with diabetes mellitus and panhypopituitarism is presented.Case presentation: A 19-year-ol...

Introduction: Idiopathic granulomatous hypophysitis (IGH) is a rare inflammatory disease that may present with radiological changes in the pituitary gland. Diagnosis with non-specific syndromes becomes challenging. Secondary causes of granulomatous hypophysitis include tuberculosis, sarcoidosis, syphilis, Langerhans cell histiocytosis, GPA, and Rathke’s cleft cyst rupture. GPA is a multisystem disease, characterized by necrotizing small-vessel vasculitis, mostly affecting...

Introduction: Hyponatremia is the most common electrolyte imbalance in hospitalized patients and frequent finding in intensive care units. Hyponatremia is characterized with serum sodium values less than 135 mmol/l and defined by the ratio of total sodium and total body water. It presents with lethargy, confusion, neuromuscular excitability, hyperreflexia, stupor and even coma. In addition to neurological signs and symptoms, assessment of hyponatremia is based on severity and ...

Background: Pituitary apoplexy (PA) is a rare, potentially life-threatening endocrine emergency, due to abrupt pituitary haemorrhage and/or infarction, usually within a pituitary adenoma. PA most commonly presents with severe headache, visual and oculomotor activity disturbances, nausea/vomiting and/or altered mental status. The outcome is variable and difficult to predict. Most proposed risk factors are hypertension (HTN), diabetes mellitus (DM), and anticoagulant treatment. ...

Surgical factors, in particular a higher volume of operations and a dedicated neurosurgeon, are considered the main determinants of surgical complication rates in transsphenoidal surgery (TSS). We evaluated postoperative complications in a large series of TSS for non-producing adenomas included in TESSPAIN, a retrospective multicenter nationwide registry. All TSS performed at the 29 participating centers between 2018 and 2022 were included. Globally, 1421 non-producing pituita...

The bone strain index (BSI) is a marker of bone deformation based on a finite element analysis inferred from dual X-ray absorptiometry (DXA) scans, that has been proposed as a predictor of fractures in osteoporosis. BSI value represents the average equivalent strain in a skeletal site, assuming that a higher strain level (higher BSI) indicates a lower bone’s resistance to loads with consequent higher risk of fractures. BSI index is usually calculated for specific loading ...

Introduction: Men with prolactinoma often present with larger tumors than women. Whether giant prolactinomas (≥4 cm, GP) present differently and achieve the same outcomes as non-giant macroprolatinomas (1-3.9 cm, MP) or microprolactinomas (<1 cm, mP) is not clearly established.Methods: We report retrospective data from a monocentric cohort of 129 men with prolactinoma and we compare baseline characteristics and treatment response in patients wi...

Introduction: Medullary thyroid cancer accounts only 1% to 4% of thyroid cancer cases (1). 25% of cases are familial secondary to germline RET mutation, while the remaining 75% are sporadic and also harbour a somatic RET mutation in more than half of all cases. Up to 15–20% of patients will present with distant metastatic disease. The standard treatment for MTC is total thyroidectomy and dissection of cervical lymph node compartments. Post-operative levels of serum calcit...

Introduction: Adult growth hormone (GH) deficiency has been associated with the onset of sarcopenic obesity, reduced bone mineral density, and the progression of metabolic syndrome, often accompanied by the accumulation of ectopic fat at the epicardial level and changes in echocardiographic measures.Objective and Design: This prospective pilot study aimed to assess the impact of recombinant human GH (rhGH) replacement therapy on glyco-metabolic parameter...

A 35-year-old lady presented in Feb 2022 for lower limb weakness for 2 months, easy fall and amenorrhoea for 6 months. Her potassium was 2.4mmol/l. Clinically, she had moon face and proximal muscle weakness. Her workup showed metabolic alkalosis, renal loss of potassium and high 24-hour urine free cortisol (UFC) 825 nmol/l (24-140), which was 5.9x above the upper limit of normal (ULN). The paired baseline ACTH and morning cortisol were 22.1 and 469nmol/l respectively. 1mg ONDS...

A 43-year-old female presented to the endocrine clinic with a 6-month history of polyuria and polydipsia. Investigations revealed a raised prolactin and a water deprivation test confirmed cranial diabetes insipidus. Subsequent pituitary MRI showed a likely pituitary microadenoma which however on further radiology review was thought to represent a hypothalamic/stalk lesion measuring up to 5 mm. She was commenced on intranasal desmopressin and cabergoline initially. Repeat MRI 2...

The role of growth hormone-releasing hormone (GHRH) in brain function has been suggested. Recent behavior studies by our group clearly demonstrate a powerful anxiolytic and antidepressant-like effects of a novel growth hormone releasing hormone (GHRH) antagonist of MIAMI class, MIA-690, probably related to modulatory effects on the inflammatory and oxidative status [1]. Our investigation in this work was focused on the potential beneficial effects of MIA-602, another recently ...

Background: Research indicates that prolactin, a hormone linked to lactation, may influence the brain’s reward system by interacting with dopamine. GLP-1 analogues, prescribed for diabetes and obesity, are known for their appetite-suppressant effects. With GLP-1 receptors found in mood and reward-related brain regions, a potential role of GLP-1 in reward regulation is suggested. A knowledge gap exists regarding the interaction between GLP-1 and prolactin in the context of...