Utility of copeptin in predicting non-pathological postoperative polyuria in patients affected by acromegaly undergoing pituitary neurosurgery.

PURPOSE: Copeptin efficiently predicts post-neurosurgical central diabetes insipidus (CDI) in patients with hypothalamic-pituitary lesions, but its role in characterizing changes in diuresis in individuals with acromegaly undergoing neurosurgery remains unexplored. Our study aimed to assess changes in postoperative fluid balance in acromegaly patients and correlate them with both copeptin and growth hormone (GH) levels. METHODS: This was a secondary analysis of a prospective study involving 15 acromegaly patients undergoing endoscopic endonasal resection at our University Hospital. Fluid balance was assessed daily, and copeptin and GH levels were evaluated preoperatively (T0), and serially on the morning of the first (T2) and second (T3) postoperative day, with an additional measurement of copeptin one hour post-extubation (T1). Patients with pre-existing or post-neurosurgical CDI were excluded from the analysis. RESULTS: Most patients (11/15) exhibited a negative fluid balance on the second postoperative day, with 4 developing polyuria. Postoperative GH levels did not differ significantly between polyuric and non-polyuric patients, but GH measured at T2 correlated significantly with negative total balance (r = -0.519, p = 0.048). Copeptin levels at T1 were significantly higher in those who developed polyuria (p = 0.013), and a copeptin value > 39.9 pmol/L at T1 showed excellent ability (Sensitivity 100%, Specificity 90.9%, p < 0.001) in predicting postoperative polyuria. Additionally, polyuric patients exhibited a higher T1 / T3 copeptin ratio (p = 0.013) and a negative fluid balance was associated with the remission of acromegaly at 12 months (p = 0.046). CONCLUSION: The early assessment of copeptin, in addition to facilitating the rapid identification of individuals at increased risk of developing CDI, could also allow the recognition of subjects with a tendency towards non-pathological polyuria in the postoperative setting, at least in individuals affected by acromegaly.

Prolactin-secreting tumors, dopamine agonists and pregnancy: a longitudinal experience of a tertiary neuroendocrine center.

PURPOSE: Prolactin (PRL)-secreting tumours are associated with infertility and can be reverted by dopamine agonist (DA) therapy. The suspension of DA is recommended once pregnancy is established, as all DAs cross the placenta. The aim of the study was to evaluate the rate of maternal-foetal complications in women treated with cabergoline (CAB) or bromocriptine (BRM) for prolactinoma during gestation and the effect of pregnancy on prolactinoma progression. METHODS: This was a retrospective observational study involving 43 women affected by prolactinoma who became pregnant during therapy with CAB or BRM for a total of 58 pregnancies. For each patient, medical records were analysed by integrating the data with outpatient or telephone interview. RESULTS: At the time of conception, 18 women were in the BRM group, while 40 were in CAB group. No differences were found in obstetric or neonatal outcomes between the two groups. There was a significant difference (p = 0.046) in child complications reported in maternal interview found exclusively in the CAB group. No further confounding factors were detected. Disease remission rate after the first pregnancy was 42.9% and the main predictor was a lower PRL nadir before pregnancy (p = 0.023). No difference was detected between the two groups in terms of tumor remission. Breastfeeding did not modify the outcome. CONCLUSION: Foetal exposure to DAs during the first weeks of embryogenesis is not associated with a greater risk of complications. The transient and mild developmental disorders recorded resolved spontaneously and the prevalence was substantially overlapping with that observed in the general population.

Trabecular Bone Score as an Index of Bone Fragility in Patients with Acromegaly: A Systematic Review and Meta-Analysis.

BACKGROUND: Acromegaly is characterized by impaired bone quality and increased fracture risk. However, due to the pathophysiology of acromegalic osteopathy, bone mineral density (BMD) does not represent a reliable predictor for fragility fractures in this setting. Trabecular bone score (TBS) has been recently evaluated as an alternative index of skeletal fragility in acromegalic patients. However, no conclusive data are still available in this regard. METHODS: PubMed/Medline, EMBASE, Cochrane Library, Ovid, and CINAHL databases were systematically searched until June 2022 for studies reporting data either about the comparison of TBS values between acromegalic patients and non-acromegalic controls or about the relationship - within acromegalic patients - between TBS values and fracture risk. Effect sizes were pooled through a random-effect model. RESULTS: Eight studies were eligible for inclusion in the meta-analysis, encompassing 336 acromegalic patients and 490 non-acromegalic controls. Overall, TBS was significantly lower in acromegalic patients compared to controls (-0.089, 95% CI: [-0.111, -0.067], p < 0.01), irrespective of acromegaly disease activity and gonadal status. With respect to fracture risk, TBS was significantly lower in acromegalic patients with vertebral fractures than in those without (-0.099, 95% CI: [-0.166, -0.032], p < 0.01). CONCLUSION: In this meta-analysis, we specifically assessed the role of TBS as an index of bone quality and fracture risk in patients with acromegaly. Our results support the notion that TBS could be of value in the assessment and management of skeletal fragility in acromegalic patients, especially in light of the poor information provided in this setting by BMD.

The Cut-off Limits of Growth Hormone Response to the Insulin Tolerance Test Related to Body Mass Index for the Diagnosis of Adult Growth Hormone Deficiency.

INTRODUCTION: The diagnosis of growth hormone deficiency (GHD) in adults is based on a reduced GH response to provocative tests, such as the insulin tolerance test (ITT) and the GH-releasing hormone (GHRH) + arginine (ARG) test. However, the cut-off limits of peak GH response in lean subjects are not reliable in obese patients; this is noteworthy since adult GHD is often associated with obesity. To date, there are no ITT cut-offs related to body mass index (BMI). OBJECTIVE: We aimed to evaluate the diagnostic cut-offs of GH response to the ITT in the function of BMI. METHODS: The GH response to the ITT was studied in 106 patients with a history of hypothalamic-pituitary disease, a mean age of 48.2 ± 12.4 years, and a mean BMI of 26.8 ± 6.1 kg/m2). Patients were divided into lean, overweight, and obese groups according to their BMI. The lack of GH response to GHRH + ARG test was considered the gold standard for the diagnosis of GHD. The best GH cut-off in the ITT, defined as the one with the best sensitivity (SE) and specificity (SP), was identified using receiver-operating characteristics curve (ROC) analysis. RESULTS: The best GH cut-off in the ITT was 3.5 µg/L in lean subjects (SE 82.1%; SP 85.7%), 1.3 µg/L in overweight subjects (SE 74.1%; SP 85.7%), and 2.2 µg/L in obese subjects (SE 90.0%; SP 50.0%). The diagnostic accuracy was 97.2, 76.5, and 76.7%, respectively. CONCLUSIONS: Our data show that the ITT represents a reliable diagnostic tool for the diagnosis of adult GHD in lean subjects if an appropriate cut-off limit is assumed. Overweight and obesity strongly reduce the GH response to the ITT, GH BMI-related cut-off limits, and the diagnostic reliability of the test.

Second-Day Morning Cortisol Levels after Transsphenoidal Surgery Are Accurate Predictors of Secondary Adrenal Insufficiency with Diagnostic Cut-Offs Similar to Those in Non-Stressed Conditions.

INTRODUCTION: Multiple studies tried to identify cortisol cut-offs after pituitary surgery that could accurately assess hypothalamic-pituitary-adrenal (HPA) axis function; however, there is no consensus nowadays. This study aimed to evaluate the accuracy of morning cortisol after transsphenoidal surgery in predicting long-term secondary adrenal insufficiency. METHODS: In our tertiary center, we prospectively determined first- and second-day cortisol after transsphenoidal surgery in 92 patients without preoperative adrenal -insufficiency and not treated with glucocorticoids perioperatively. Definitive diagnosis of secondary adrenal insufficiency was obtained with re-evaluation 3 months after trans-sphenoidal surgery and clinical follow-up of at least 1 year. RESULTS: Ten patients (10.8%) developed long-term postoperative secondary adrenal insufficiency. The ROC curves demonstrated that first-day cortisol had a moderate diagnostic accuracy, while a second-day cortisol ≤9.3 µg/dL (257 nmol/L) showed the best performance in predicting adrenal insufficiency (sensitivity [Se] 88.9%, specificity [Sp] 86.9%, AUC 0.921). Moreover, a second-day cortisol ≤3.2 µg/dL (89 nmol/L) was able to diagnose adrenal insufficiency in 100% of cases (Se 22.2%, Sp 100%) and >14 µg/dL (386 nmol/L) was able to exclude ACTH deficiency (Se 100%, Sp 57.4%). CONCLUSIONS: Adrenal function can be carefully studied on the second day after pituitary surgery, using cut-off values that international guidelines suggested for non-stressed conditions. In fact, second-day cortisol levels ≤3.2 µg/dL (89 nmol/L) and >14 µg/dL (386 nmol/L) are diagnostic of secondary adrenal insufficiency and normal function, respectively. We also suggest performing a definitive re-evaluation with an HPA axis stimulation test when second-day cortisol values are between 3.3 and 14 µg/dL (90-386 nmol/L).

Morning Serum Cortisol Level Predicts Central Adrenal Insufficiency Diagnosed by Insulin Tolerance Test.

INTRODUCTION: According to guidelines, a morning serum cortisol level <83 nmol/L is diagnostic for central adrenal insufficiency (CAI), a value >414 nmol/L excludes CAI, while values between 83 and 414 nmol/L require stimulation tests. However, there are no currently reliable data on morning serum cortisol for prediction of cortisol response to insulin tolerance test (ITT). OBJECTIVE: Using the receiver-operating characteristic curve analysis, the purpose of this study was to detect the morning serum cortisol cutoff with a specificity (SP) or a sensitivity (SE) above 95% that identify those patients who should not be tested with ITT. METHODS: We included 141 adult patients (83 males) aged 42.7 ± 12.3 (mean ± standard deviation) years old. Based on the serum cortisol response to ITT, patients have been divided into 2 groups: subjects with CAI (peak serum cortisol <500 nmol/L; 65 patients) and subjects with preserved adrenocortical function (peak cortisol >500 nmol/L; 76 patients). RESULTS: The best morning cortisol cutoff, in terms of SE (87.7%) and SP (46.1%), was ≤323.3 nmol/L. The cutoff of morning serum cortisol concentration that best predicted a deficient response to ITT was ≤126.4 nmol/L (SE 13.8%, SP 98.7%). The cutoff of morning serum cortisol concentration that best predicted a normal response to ITT was >444.7 nmol/L (SE 96.9%, SP 14.5%). CONCLUSIONS: This is the first study that identifies a morning serum cortisol cutoff that best predict the response to ITT in order to simplify the diagnostic process in patients with suspected CAI. A new diagnostic flow-chart for CAI is proposed.

Early Copeptin Determination Allows Prompt Diagnosis of Post-Neurosurgical Central Diabetes Insipidus.

INTRODUCTION: Central diabetes insipidus (CDI) is a frequent complication of pituitary surgery, but its diagnosis lacks standardized criteria. Copeptin, a surrogate marker of arginine vasopressin release, is triggered by psycho-physical stresses such as pituitary surgery. Low postoperative copeptin could predict CDI onset. The aims of this study were the validation of copeptin as a predictor of post-neurosurgical CDI and the identification of the optimal timing for its determination. METHODS: Sixty-six consecutive patients operated for a hypothalamic-pituitary lesion were evaluated. Copeptin was determined preoperatively and at 1, 6, 12, 24 and 48 h post-extubation. Fifty-eight patients were reassessed after 3-6 months post-surgery to confirm transient (3 cases) or permanent CDI (5 cases) diagnosis. RESULTS: A marked copeptin peak was identified at 1 h after extubation, when a value below or equal to 12.8 pmol/L had a good accuracy in identifying CDI cases (AUC 0.866, 95% CI 0.751-0.941). Moreover, a copeptin peak above 4.2 pmol/L excluded permanent forms (AUC 1, 95% CI 0.629-1). Regression analysis identified copeptin as the only significant predictor of CDI (OR 0.86, 95% CI 0.75-0.98, p = 0.02). A copeptin T1/T0 ratio below or equal to 1.47 identified patients at risk of isolated biochemical alterations even in the absence of an overt CDI. CONCLUSIONS: A prompt increase of copeptin is expected at 1 h after extubation. The absence of this peak is a reliable predictor of post-neurosurgical CDI.

Primary Pituitary Lymphoma As Rare Cause Of A Pituitary Mass And Hypopituitarism In Adulthood.

OBJECTIVE: Differential diagnosis of nonadenomatous sellar masses causing hypopituitarism is still a challenge. Among these masses, growing evidence has demonstrated that primary pituitary lymphoma is a specific and emerging entity. The aim of our study was to describe our experience with a case of primary pituitary lymphoma and to perform a review of the available literature. METHODS: We searched relevant databases up to March 2020, identifying 36 suitable articles basing on inclusion criteria (primary pituitary lymphoma in adult immunocompetent subjects). Overall, 43 cases were included in the review, adding a new case diagnosed and treated in our hospital. Epidemiologic data, clinical presentation, hormonal status, radiologic findings, pathology, treatment, and outcome were extracted. RESULTS: Mean age at diagnosis was 58.9 years, without gender difference. Symptoms related to mass were common (52.3%), in particular cranial nerve palsy (70.5%), headache (56.8%), and alteration in visual field (40.9%). Impaired hormonal status was detected in 89.7% of patients; of them, 58.9% presented with anterior pituitary failure (partial or total), while 25.6% presented with panhypopituitarism. Overall, diabetes insipidus was present in 30.8% and hyperprolactinemia in 41.0% of patients. The majority of patients presented a radiologically invasive mass in the suprasellar region and cavernous sinus (65.9% and 40.9%, respectively) and histologic diagnosis of diffuse B-cell lymphoma (54.5%). CONCLUSION: The differential diagnosis of sellar and parasellar masses causing hypopituitarism should include primary pituitary lymphoma, even in absence of systemic symptoms or posterior pituitary dysfunction. The disease has a heterogeneous pattern, so a collaboration between endocrinologists, neuroradiologists, neurosurgeons, and hematologists is desirable.

Pituitary Hyperplasia Due to Longstanding Primary Hypothyroidism: A Case Report and Comprehensive Review of the Literature.

Hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include fatigue, cold intolerance, hoarseness, dry skin, constipation, a slow relaxation phase of deep tendon reflexes, and bradycardia. However, some patients may exhibit atypical signs and symptoms, which can result in diagnostic confusion. Pituitary hyperplasia resulting from longstanding primary hypothyroidism was first described by Niepce in 1851. It is usually asymptomatic, but sometimes, in addition to symptoms of overt hypothyroidism, patients may complain of headaches, hypopituitarism, visual field impairment, and hyperprolactinemia. Furthermore, on imaging, pituitary hyperplasia can be mistaken for a pituitary adenoma. Distinguishing between the two is crucial, as their management differs; the former often responds to thyroid hormone replacement therapy, while the latter might need treatment with surgery and/or radiotherapy. Here we describe a patient who developed pituitary hyperplasia in the setting of longstanding uncompensated primary hypothyroidism due to a lack of compliance with levothyroxine replacement therapy. We also review the clinical, laboratory, and radiologic findings of the case reports available in the literature up to now in order to improve the knowledge and the care of the disease.

Are prolactin levels efficient in predicting a pituitary lesion in patients with hyperprolactinemia?

PURPOSE: Data regarding the presence of a prolactin (PRL) threshold above which a pituitary magnetic resonance imaging (MRI) is mandatory in patients with hyperprolactinemia (hyperPRL) are controversial and derived primarily from studies focused on female populations. Aim of our study was to evaluate in a cohort of patients of both sexes with confirmed hyperPRL, the possible correlation between PRL values and the presence of pituitary abnormalities. METHODS: We retrospectively analyzed data from patients who underwent serial PRL sampling at our Division between January 2015 and December 2022. Patients diagnosed with monomeric hyperPRL at serial sampling and with subsequent contrast-enhanced MRI results available for the pituitary region were included in the study. Exclusion criteria were prior pituitary disease, severe renal insufficiency, liver cirrhosis, uncompensated primary hypothyroidism and ongoing therapy with hyperprolactinemic drugs. Physiological causes of hyperPRL were also ruled out. RESULTS: Out of the 1253 patients who underwent serial PRL sampling, 139 patients (101 women and 38 men) met the inclusion criteria: 106 (76.3%) patients had some form of pituitary disease, with microlesions observed in 69.8%, macrolesions in 25.5% and other findings in 4.7% of subjects. PRL values showed a modest accuracy in predicting the presence of a pituitary abnormality and the best cut-offs identified were >25 µg/L (AUC 0.767, p = 0.003) and >44.2 µg/L (AUC 0.697, p < 0.001) in men and women, respectively; however, if only patients with PRL values > 500 µg/L were excluded from the analysis, as they were already supposed to harbor a macroprolactinoma, PRL levels were not able to predict the presence of a macrolesion neither in men nor women. CONCLUSION: Given the high prevalence of pituitary abnormalities in patients of both sexes with hyperPRL at serial sampling, performing a pituitary imaging in all cases of hyperPRL, even if mild, appears to be a cautious choice.

Radiomic Analysis in Pituitary Tumors: Current Knowledge and Future Perspectives.

Radiomic analysis has emerged as a valuable tool for extracting quantitative features from medical imaging data, providing in-depth insights into various contexts and diseases. By employing methods derived from advanced computational techniques, radiomics quantifies textural information through the evaluation of the spatial distribution of signal intensities and inter-voxel relationships. In recent years, these techniques have gained considerable attention also in the field of pituitary tumors, with promising results. Indeed, the extraction of radiomic features from pituitary magnetic resonance imaging (MRI) images has been shown to provide useful information on various relevant aspects of these diseases. Some of the key topics that have been explored in the existing literature include the association of radiomic parameters with histopathological and clinical data and their correlation with tumor invasiveness and aggressive behavior. Their prognostic value has also been evaluated, assessing their role in the prediction of post-surgical recurrence, response to medical treatments, and long-term outcomes. This review provides a comprehensive overview of the current knowledge and application of radiomics in pituitary tumors. It also examines the current limitations and future directions of radiomic analysis, highlighting the major challenges that need to be addressed before a consistent integration of these techniques into routine clinical practice.

Mild hyponatremia is not associated with degradation of trabecular bone microarchitecture despite bone mass loss.

CONTEXT: Hyponatremia is associated with increased risk of osteoporosis and fractures. The impact of hyponatremia on non-invasive indices of bone quality, however, is unknown. OBJECTIVE: To evaluate whether trabecular bone microarchitecture, assessed non-invasively by trabecular bone score (TBS), is altered in patients with hyponatremia. METHODS: We conducted a cross-sectional analysis of the population-based 2005-2008 cycles of the National Health and Nutrition Examination Survey (NHANES), in which TBS measurement was performed. The main outcome measures were TBS values and bone mineral density (BMD) T-scores at the lumbar spine, total hip and femoral neck. RESULTS: A total of 4204 subjects aged 50 years or older were included (4041 normonatremic, 163 hyponatremic - 90.8% with mild hyponatremia). Univariate analyses did not show any difference in TBS between patients with and without hyponatremia (1.308 ± 0.145 vs 1.311 ± 0.141, p = 0.806). Hyponatremic subjects had lower BMD T-score at total hip (-0.70 ± 1.46 vs -0.13 ± 1.32, p < 0.001) and femoral neck (-1.11 ± 1.26 vs -0.72 ± 1.14, p = 0.004), while no difference was observed at lumbar spine (-0.27 ± 1.63 vs -0.31 ± 1.51, p = 0.772). After adjustment for relevant confounders, hyponatremia was confirmed as an independent predictor of lower BMD T-score at the total hip (ß=-0.20, 95%CI:[-0.39, -0.02], p = 0.029), while the significance was lost at the femoral neck (p = 0.308). Again, no association between hyponatremia and lumbar spine BMD (p = 0.236) or TBS (p = 0.346) was observed. CONCLUSIONS: Hyponatremia, at least in mild forms, is not associated with a degradation of trabecular microarchitecture, assessed non-invasively by TBS. An independent association between hyponatremia and loss of bone mass is confirmed, particularly at the total hip.

Adrenocortical, somatotropic, and antidiuretic response to nasal glucagon in healthy subjects.

OBJECTIVE: The glucagon stimulation test involves the peptide intramuscular or subcutaneous administration for the diagnosis of hypopituitarism. To date, no data are available regarding its intranasal formulation. Our study intended to investigate the role of intranasal glucagon as a potential stimulus test for the evaluation of the corticotropic, somatotropic, and antidiuretic axes. DESIGN: Non-randomized, single-blinded, cross-over study including 10 healthy subjects (50% women). METHODS: All participants underwent 2 days of testing, and intranasal glucagon or placebo was administered. At baseline, every 15' up to +90', and then every 30' up to +180', a blood sample was taken for adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), copeptin, glucose, insulin, sodium, potassium, and plasma osmolarity. At baseline and at the end of the test, urinary osmolarity was evaluated as well. RESULTS: After administration of both glucagon and placebo, ACTH and cortisol values decreased progressively (P < 0.001), but in the drug group, the reduction in cortisol was less accentuated up to +90' (P < 0.05). Growth hormone values decreased after placebo administration (P < 0.001); on the other hand, after glucagon, an increasing, yet non-significant trend was observed (P = 0.096) with the difference between the two groups evident starting from +120' onwards (P < 0.005). The placebo administration led to a reduction of copeptin, while its stability was observed after glucagon administration. Six subjects developed hypokalemia (ie, potassium <3.5 mmol/L) post-glucagon, with the nadir at 45' (3.6 [3.2-3.8] mmol/L) significantly correlated with the immediate post-glycemic rise insulin peak (Spearman's rho -0.719; P = 0.019). No significant differences were observed compared to the other analytes tested. CONCLUSIONS: Intranasal glucagon administration is not an effective stimulus for hypophyseal secretion. Hypokalemia secondary to hyperinsulinemic rebound appears to be a frequent complication of its acute administration.

Isolated anterior pituitary dysfunction in adulthood.

Hypopituitarism is defined as a complete or partial deficiency in one or more pituitary hormones. Anterior hypopituitarism includes secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency and prolactin deficiency. Patients with hypopituitarism suffer from an increased disability and sick days, resulting in lower health status, higher cost of care and an increased mortality. In particular during adulthood, isolated pituitary deficits are not an uncommon finding; their clinical picture is represented by vague symptoms and unclear signs, which can be difficult to properly diagnose. This often becomes a challenge for the physician. Aim of this narrative review is to analyse, for each anterior pituitary deficit, the main related etiologies, the characteristic signs and symptoms, how to properly diagnose them (suggesting an easy and reproducible step-based approach), and eventually the treatment. In adulthood, the vast majority of isolated pituitary deficits are due to pituitary tumours, head trauma, pituitary surgery and brain radiotherapy. Immune-related dysfunctions represent a growing cause of isolated pituitary deficiencies, above all secondary to use of oncological drugs such as immune checkpoint inhibitors. The diagnosis of isolated pituitary deficiencies should be based on baseline hormonal assessments and/or dynamic tests. Establishing a proper diagnosis can be quite challenging: in fact, even if the diagnostic methods are becoming increasingly refined, a considerable proportion of isolated pituitary deficits still remains without a certain cause. While isolated ACTH and TSH deficiencies always require a prompt replacement treatment, gonadal replacement therapy requires a benefit-risk evaluation based on the presence of comorbidities, age and gender of the patient; finally, the need of growth hormone replacement therapies is still a matter of debate. On the other side, prolactin replacement therapy is still not available. In conclusion, our purpose is to offer a broad evaluation from causes to therapies of isolated anterior pituitary deficits in adulthood. This review will also include the evaluation of uncommon symptoms and main etiologies, the elements of suspicion of a genetic cause and protocols for diagnosis, follow-up and treatment.

Psychiatric disorders and anger in patients with controlled acromegaly.

BACKGROUND: Acromegaly (ACRO) is a chronic rare disease caused by a pathological increase in growth hormone (GH) secretion. In ACRO an increased prevalence of psychiatric disorders has been demonstrated, in particular depressive disorders, associated to a significant deterioration of the quality of life, independently from disease control. In addition, anger feelings, often detected in subjects affected by chronic disease, have not yet been investigated, in pituitary patients. Aim of the study was to evaluate in ACRO patients with a controlled disease, compared to patients suffering for non-functioning pituitary adenoma (NFPA) 1) prevalence of depressive and anxiety disorders, and 2) expression and control of anger feelings. The second purpose was to evaluate the correlation between psychiatric disorders, anger feelings and the "activity of disease," that is active ACRO that needs medical treatment versus cured ACRO. METHODS: This is a cross-sectional, observational study, which included 53 patients enrolled at the Neuroendocrinology Outpatient Clinic of "Città della Salute e della Scienza di Torino". Of the 53 enrolled patients (24 male and 29 female), 34 had ACRO, while 19 had NFPA, as control group. All subjects went through the following self-administered, validated psychological tools: SF-36 (Short-Form 36 Item); STAXI - 2; BDI-II (Beck Depression Inventory -II); STAI (State-Trait Anxiety Inventory). Only in ACRO group, patients completed PASQ (Patient-Assessed Acromegaly Symptom Questionnaire) and ACROQoL (Acromegaly Quality of Life Questionnaire) questionnaires. In addition 45 patients underwent the International Neuropsychiatric Short Interview to assess the presence of a psychiatric disorder. For each patient, anthropometric, clinical and biochemical information was collected. RESULTS: A higher frequency of psychiatric anxiety and mood disorders (not reported in the medical history) was observed in patients with controlled ACRO. In the SF-36 questionnaire, a lower score was found in the "emotional well-being" items in ACRO compared to NFPA, particularly in those with cured ACRO. Cured acromegalic patients had a worse score in "emotional well-being," "energy/fatigue" and "general health" items. Finally, subjects in ACRO group obtained a lower score in the ability to control anger and a higher score in the physical expression of it, demonstrating a tendency to more aggressive behaviors. CONCLUSIONS: This study showed that psychiatric illness is often hidden in patient suffering from ACRO, despite normal IGF-I levels. Recovery from the disease do not necessarily improve QoL scores, in fact in cured patients the quality of life can be even worse.

Copeptin adaptive response to SGLT2 inhibitors in patients with type 2 diabetes mellitus: The GliRACo study.

Introduction: In type 2 diabetes mellitus (T2DM), the antidiuretic system participates in the adaptation to osmotic diuresis further increasing urinary osmolality by reducing the electrolyte-free water clearance. Sodium glucose co-transporter type 2 inhibitors (SGLT2i) emphasize this mechanism, promoting persistent glycosuria and natriuresis, but also induce a greater reduction of interstitial fluids than traditional diuretics. The preservation of osmotic homeostasis is the main task of the antidiuretic system and, in turn, intracellular dehydration the main drive to vasopressin (AVP) secretion. Copeptin is a stable fragment of the AVP precursor co-secreted with AVP in an equimolar amount. Aim: To investigate the copeptin adaptive response to SGLT2i, as well as the induced changes in body fluid distribution in T2DM patients. Methods: The GliRACo study was a prospective, multicenter, observational research. Twenty-six consecutive adult patients with T2DM were recruited and randomly assigned to empagliflozin or dapagliflozin treatment. Copeptin, plasma renin activity, aldosterone and natriuretic peptides were evaluated at baseline (T0) and then 30 (T30) and 90 days (T90) after SGLT2i starting. Bioelectrical impedance vector analysis (BIVA) and ambulatory blood pressure monitoring were performed at T0 and T90. Results: Among endocrine biomarkers, only copeptin increased at T30, showing subsequent stability (7.5 pmol/L at T0, 9.8 pmol/L at T30, 9.5 pmol/L at T90; p = 0.001). BIVA recorded an overall tendency to dehydration at T90 with a stable proportion between extra- and intracellular fluid volumes. Twelve patients (46.1%) had a BIVA overhydration pattern at baseline and 7 of them (58.3%) resolved this condition at T90. Total body water content, extra and intracellular fluid changes were significantly affected by the underlying overhydration condition (p < 0.001), while copeptin did not. Conclusion: In patients with T2DM, SGLT2i promote the release of AVP, thus compensating for persistent osmotic diuresis. This mainly occurs because of a proportional dehydration process between intra and extracellular fluid (i.e., intracellular dehydration rather than extracellular dehydration). The extent of fluid reduction, but not the copeptin response, is affected by the patient's baseline volume conditions. Clinical trial registration: Clinicaltrials.gov, identifier NCT03917758.

Hypopituitarism following brain injury: when does it occur and how best to test?

Aim of this review is to highlight how and when Traumatic Brain Injury (TBI) as well as Subarachnoid Haemorrhage (SAH) and primary Brain Tumours (pBT) of the Central Nervous System (CNS) can induce hypopituitarism, an under-diagnosed clinical problem. Moreover, this review aims to clarify, on the basis of the recent evidences, how these patients have to be tested for pituitary-function. Both retrospective and prospective studies recommended that patients with more severe form of Brain Injuries (BI) and in particular, those with fractures of the base of the skull or early diabetes insipidus, have to be closely monitored for signs and symptoms of endocrine dysfunction. Further studies will be crucial to raise awareness and remind physicians on the prevalence of hypopituitarism in patients with BI and to elucidate any incremental benefits these patients may receive from hormone replacement.

Growth hormone deficiency in a case of septo-optic-dysplasia due to SOX2 mutation: should we re-test patients during the transition period?

Gene mutations encoding transcription factors, including SOX2, have been associated with growth hormone deficiency (GHD) and abnormal pituitary development. Guidelines on GHD management in the transition period state that patients with genetic-based childhood-onset GHD can skip retesting due to a high likelihood of permanent GHD. We describe a case of septo-optic-dysplasia due to SOX2 mutation characterised by childhood-onset GHD, which showed a normal somatotropic function at the transition period. This case raises the opportunity to retest for GHD during the transition period, even in patients with a known genetic cause, in order to avoid inappropriate GH treatment.

MRI Assessment of Cardiac Function and Morphology in Adult Patients With Growth Hormone Deficiency: A Systematic Review and Meta-Analysis.

Background: Adult GH deficiency (GHD) has been described as a heterogeneous condition characterized by many clinical modifications, such as metabolic alterations, impaired quality of life, and increased mortality. The clinical relevance of cardiac involvement remains, however, only partially elucidated. Methods: PubMed/Medline, EMBASE, Cochrane library, OVID and CINAHL databases were systematically searched until February 2022 for studies evaluating cardiac function and morphology by magnetic resonance imaging in adult patients with GHD. Effect sizes were pooled through a random-effect model. Results: Four studies were considered in the meta-analysis. With respect to the left ventricle, GHD patients were characterized by a lower stroke-volume-index (-3.6 ml/m2, standardized mean difference (SMD) -0.60, 95%CI [-1.15,-0.05], p=0.03), lower end-diastolic-volume-index (-6.2 ml/m2, SMD -0.54, 95%CI [-0.97,-0.10], p=0.02) and, after accounting for possible biases, lower mass-index (-15.0 g/m2, SMD -1.03, 95%CI [-1.89,-0.16], p=0.02). With respect to the right ventricle, a lower end-diastolic-volume-index (-16.6 ml/m2, SMD -1.04, 95%CI [-2.04,-0.03], p=0.04) and a borderline-significant lower stroke-volume-index (-5.0 ml/m2, SMD -0.84, 95%CI [-1.77,0.08], p=0.07) could be observed. Data about the effect of GH replacement therapy highlighted a significant increase in left ventricular mass-index after treatment initiation (+3.7 g/m2, 95%CI [1.6,5.7], p<0.01). Conclusion: With respect to the left ventricle, our results confirmed those retrieved by echocardiographic studies. In addition, significant alterations were demonstrated also for the right ventricle, for which echocardiographic data are nearly absent. This supports the thesis of a biventricular cardiac involvement in patients with GHD, with a similar pattern of morphological and functional alterations in both ventricles.