Pancreatic GHRHomas in Patients with or without Multiple Endocrine Neoplasia Type 1 (MEN 1) : An Analysis of 36 Reported Cases.

Pancreatic GHRHomas (pGHRHomas) with acromegaly have unique conditions, harboring the existence of multiple endocrine neoplasia type 1 (MEN 1). Moreover, pituitary lesions are affected by both protracted ectopic GHRH and loss of menin function. Of significance is the clarification of clinicopathological aspects of pGHRHomas in patients with or without MEN 1. From 1977-2016, thirty-six patients with pGHRHomas were reported. Twenty-two out of 36 patients (61%) had pGHRHomas with MEN 1 and 14 patients did not. The former had a tendency of male predominance, benign tumor behavior and fewer metastasis rather than the latter. The latter is a single pGHRHoma accompanied by pituitary enlargement with somatotroph hyperplasia (hyperplasia) caused by protracted ectopic GHRH. Nine patients with MEN 1 underwent transsphenoidal surgery (TSS). The hyperplasia associated with various pituitary adenomas (PAs) including three GH-related adenomas was observed in seven subjects (32%). In these patients, the resection of their pGHRHomas was feasible. Furthermore, all patients with acromegaly due to pGHRHomas without MEN 1 had non-TSS, whereas approximately 70% of those with MEN 1 had unnecessary TSS. The association with hyperplasia and various PAs suggested that formation of the three GH-related adenomas may be induced by the foundations of MEN 1 gene mutations. J. Med. Invest. 71 : 1-8, February, 2024.

Double pituitary adenomas: report of two cases and systematic review of the literature.

Objective: Double pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical remission after surgery is an important challenge in DPA management. This study aims to analyze independent prognostic factors in DPA patients and summarize clinical experiences to prevent surgical failure. Methods: Two cases of DPA patients with Cushing's disease diagnosed and surgically treated at Peking Union Medical College Hospital are reported. A literature review was performed on the online database Pubmed, and 57 DPA patients from 22 retrieved articles were included. Demographic characteristics, endocrine manifestations, diagnostic methods, tumor size, and immunohistochemical features of 59 patients were analyzed. Binary logistic regression models were used to identify independent prognostic factors affecting postoperative biochemical remission. Results: Among 59 DPA patients, the mean ± SD age was 43.64 ± 14.42 years, with 61.02% being female (n = 36). The most common endocrine manifestations were Cushing's syndrome (23/59, 38.98%) and acromegaly (20/59, 33.90%). The most prevalent immunohistochemical types were ACTH-immunopositive (31/118, 26.27%) and GH-immunopositive (31/118, 26.27%) tumors. Microadenomas (<1cm) were the most frequent in terms of tumor size (62/92, 67.39%). The detection rate for double lesions on 3.0T MRI was 50.00% (14/28), which significantly higher than 1.5T MRI (P = 0.034). Univariate analysis revealed that female, Cushing's syndrome and only single lesion detected by surgical exploration were associated with significantly worse prognosis (P<0.05). Multivariate analysis identified double lesion detected by surgical exploration (OR = 0.08, P = 0.003) and contiguous type tumor (OR = 0.06, P = 0.017) as independent protective factors for DPA patients. Conclusions: The double lesion detected by surgical exploration is independently associated with a better prognosis for DPA patients. Comprehensive intraoperative exploration are crucial measures to avoid missing causative lesions.

Beware of epistaxis: fatal pseudoaneurysm rupture 30 years after treatment of acromegaly.

We present a fatal complication of treatment in a patient with early-onset acromegaly, treated with two transsphenoidal operations, radiotherapy, radiosurgery and pegvisomant. He was diagnosed in his 30s, and controlled from his 40s, with stable residual tumour within the left cavernous sinus. In his 60s, 30 years after surgery/radiotherapy and 14 years after radiosurgery, he developed recurrent episodes of mild epistaxis. A week later, he presented at his local hospital's emergency department with severe epistaxis and altered consciousness. He was diagnosed with a ruptured internal carotid artery (ICA) pseudoaneurysm, but unfortunately died before treatment could be attempted.ICA pseudoaneurysms are rare complications of surgery or radiotherapy and can present with several years of delay, often with epistaxis. This case highlights the importance of life-long monitoring in patients with previous pituitary interventions and early recognition of epistaxis as a herald sign of a potentially catastrophic event, thus leading to timely treatment.

Increased mortality in acromegaly is due to vascular and respiratory disease and is normalised by control of GH levels-A retrospective analysis from the UK Acromegaly Register 1970-2016.

CONTEXT: Epidemiological studies involving patients with acromegaly have yielded conflicting results regarding cancer incidence and causes of mortality in relation to control of growth hormone (GH) excess. OBJECTIVE: The objective of this retrospective cohort study is to clarify these questions and identify goals for treatment and monitoring patients. METHODS: We studied 1845 subjects from the UK Acromegaly Register (1970-2016), obtaining cancer standardised incidence rates (SIR) and all causes standardised mortality rates (SMR) from UK Office for National Statistics, to determine the relationship between causes of mortality-age at diagnosis, duration of disease, post-treatment and mean GH levels. RESULTS: We found an increased incidence of all cancers (SIR, 1.38; 95% CI: 1.06-1.33, p < .001), but no increase in incidence of female breast, thyroid, colon cancer or any measure of cancer mortality. All-cause mortality rates were increased (SMR, 1.35; 95% CI: 1.24-1.46, p < .001), as were those due to vascular and respiratory diseases. All-cause, all cancer and cardiovascular deaths were highest in the first 5 years following diagnosis. We found a positive association between post-treatment and mean treatment GH levels and all-cause mortality (p < .001 and p < .001), which normalised with posttreatment GH levels of <1.0 µg/L or meantreatment GH levels of <2.5 µg/L. CONCLUSION: Acromegaly is associated with increased incidence of all cancers but not thyroid or colon cancer and no increase in cancer mortality. Excess mortality is due to vascular and respiratory disease. The risk is highest in the first 5 years following diagnosis and is mitigated by normalising GH levels.

Predictive factors and the management of hyperglycemia in patients with acromegaly and Cushing's disease receiving pasireotide treatment: post hoc analyses from the SOM230B2219 study.

Introduction: Pasireotide, a somatostatin receptor ligand, is approved for treating acromegaly and Cushing's disease (CD). Hyperglycemia during treatment can occur because of the drug's mechanism of action, although treatment discontinuation is rarely required. The prospective, randomized, Phase IV SOM230B2219 (NCT02060383) trial was designed to assess optimal management of pasireotide-associated hyperglycemia. Here, we investigated predictive factors for requiring antihyperglycemic medication during pasireotide treatment. Methods: Participants with acromegaly or CD initiated long-acting pasireotide 40 mg/28 days intramuscularly (acromegaly) or pasireotide 600 µg subcutaneously twice daily during pre-randomization (≤16 weeks). Those who did not need antihyperglycemic medication, were managed with metformin, or received insulin from baseline entered an observational arm ending at 16 weeks. Those who required additional/alternative antihyperglycemic medication to metformin were randomized to incretin-based therapy or insulin for an additional 16 weeks. Logistic-regression analyses evaluated quantitative and qualitative factors for requiring antihyperglycemic medication during pre-randomization. Results: Of 190 participants with acromegaly and 59 with CD, 88 and 15, respectively, did not need antihyperglycemic medication; most were aged <40 years (acromegaly 62.5%, CD 86.7%), with baseline glycated hemoglobin (HbA1c) <6.5% (<48 mmol/mol; acromegaly 98.9%, CD 100%) and fasting plasma glucose (FPG) <100 mg/dL (<5.6 mmol/L; acromegaly 76.1%, CD 100%). By logistic regression, increasing baseline HbA1c (odds ratio [OR] 3.6; P=0.0162) and FPG (OR 1.0; P=0.0472) and history of diabetes/pre-diabetes (OR 3.0; P=0.0221) predicted receipt of antihyperglycemic medication in acromegaly participants; increasing baseline HbA1c (OR 12.6; P=0.0276) was also predictive in CD participants. Investigator-reported hyperglycemia-related adverse events were recorded in 47.9% and 54.2% of acromegaly and CD participants, respectively, mainly those with diabetes/pre-diabetes. Conclusion: Increasing age, HbA1c, and FPG and pre-diabetes/diabetes were associated with increased likelihood of requiring antihyperglycemic medication during pasireotide treatment. These risk factors may be used to identify those who need more vigilant monitoring to optimize outcomes during pasireotide treatment.

[Ectopic acromegaly due to bronchial neuroendocrine tumors: the first description in Russia of three clinical cases].

 Acromegaly is a neuroendocrine disorder caused by excessive production of growth hormone (GH). In the majority of cases the cause of acromegaly is a pituitary tumor producing GH. Cases of ectopic acromegaly are much rarer. Ectopic acromegaly occurs in cases of tumors which produce growth hormone-releasing hormone (GHRH) or extrapituitary tumors which produce GH. The main sources of excessive GHRH production are neuroendocrine tumors (NETs) of the lung or pancreas. Treatment of ectopic acromegaly consists of surgical removal of the source of GHRH hyperproduction and in cases where surgery is not an option, somatostatin analogues, pegvisomant, chemotherapy, immunotherapy or radiation therapy are used.In this article three cases of ectopic acromegaly due to GHRH-producing lung NETs are presented, each of them being notable for a number of features. In the first two cases, clinical symptoms were mild, besides in the second case ectopic acromegaly was accompanied by primary hyperparathyroidism. In the third case ectopic acromegaly was accompanied by pituitary macroadenoma, and after surgical removal of the lung NET remission of acromegaly was not achieved. In all three cases, lung NETs were detected incidentally on radiologic chest screening for other conditions.

Tall stature and gigantism in adult patients with acromegaly.

OBJECTIVES: Increased height in patients with acromegaly could be a manifestation of growth hormone (GH) excess before epiphysis closure. The aim of this study was to evaluate the relationship between the height of adult patients with GH excess related to mid-parental height (MPH) and population mean and to find whether taller patients with acromegaly come from tall families. METHODS: This is a single-centre, observational study involving 135 consecutive patients with acromegaly diagnosed as adults and no family history of GH excess. We established three categories for height for patients with acromegaly: normal stature, tall stature (TS, height above the 97th percentile (1.88 standard deviations (SD)) to <3 SD for gender- and country-specific data or as a height which was greater than 1.5 SD but less than 2 SD above the MPH) and gigantism (height which was greater than 3 SD) above the gender- and country-specific mean or greater than 2 SD above MPH). RESULTS: Thirteen percent (17/135) of patients (53% females) met the criteria for gigantism, 10% (14/135) fulfilled the criteria for TS (57% females). Parents and adult siblings were not taller than the population mean. CONCLUSION: In a group of 135 consecutive adult patients with acromegaly, 23% had increased height based on country-specific and MPH data: 13% presented with gigantism while 10% had TS. The frequency of gigantism and TS in patients diagnosed with GH excess as adults is not higher in males than in females. Patients with acromegaly come from normal-stature families.

Glucose intolerance in acromegaly is driven by low insulin secretion; results from an intravenous glucose tolerance test.

PURPOSE: Insulin sensitivity (Si) and its role in glucose intolerance of acromegaly has been extensively evaluated. However, data on insulin secretion is limited. We aimed to assess stimulated insulin secretion using an intravenous glucose tolerance test (IVGTT) in active acromegaly. METHODS: We performed an IVGTT in 25 patients with active acromegaly (13 normal glucose tolerance [NGT], 6 impaired glucose tolerance [IGT] and 6 diabetes mellitus [DM]) and 23 controls (8 lean NGT, 8 obese NGT and 7 obese IGT). Serum glucose and insulin were measured at 20 time points along the test to calculate Si and acute insulin response (AIRg). Medical treatment for acromegaly or diabetes was not allowed. RESULTS: In acromegaly, patients with NGT had significantly (p for trend < 0.001) higher AIRg (3383 ± 1082 pmol*min/L) than IGT (1215 ± 1069) and DM (506 ± 600). AIRg was higher in NGT (4764 ± 1180 pmol*min/L) and IGT (3183 ± 3261) controls with obesity than NGT (p = 0.01) or IGT (p = 0.17) acromegaly. Si was not significantly lower in IGT (0.68 [0.37, 0.88] 106*L/pmol*min) and DM (0.60 [0.42, 0.84]) than in NGT (0.81 [0.58, 1.55]) patients with acromegaly. NGT (0.33 [0.30, 0.47] 106*L/pmol*min) and IGT (0.37 [0.21, 0.66]) controls with obesity had lower Si than NGT (p = 0.001) and IGT (p = 0.43) acromegaly. CONCLUSION: We demonstrated that low insulin secretion is the main driver behind glucose intolerance in acromegaly. Compared to NGT and IGT controls with obesity, patients with NGT or IGT acromegaly had higher Si. Together, these findings suggest that impaired insulin secretion might be a specific mechanism for glucose intolerance in acromegaly.

Erectile function and androgen and estrogen beta receptor gene polymorphisms in acromegalic men.

PURPOSE: Sexual dysfunctions are often experienced by male patients with acromegaly, due to a combination of hypogonadism and other comorbidities, but are a scarcely investigated complication. Erectile dysfunction is also closely related to cardiovascular diseases through endothelial dysfunction. Therefore, this project aimed to assess the prevalence of erectile dysfunction in a population of acromegalic men and evaluate its association with cardio-metabolic disorders, also exploring associations with androgen and estrogen receptor gene polymorphisms. METHODS: Sexually active men aged 18-65 with previous diagnosis of acromegaly were recruited. Clinical and laboratory data were retrospectively collected. Each patient also provided a blood sample for AR and ERß gene polymorphisms analyses and filled out the IIEF-15 questionnaire. RESULTS: Twenty men with previous diagnosis of acromegaly (mean age 48.4 ± 10.0 years) were recruited. 13/20 subjects (65%) had erectile dysfunction, but only four had a concurrent biochemical hypogonadism, with no significant correlation with IIEF-15 scores. Total testosterone negatively correlated with sexual intercourse satisfaction domain (ρ = - 0.595; p = 0.019) and general satisfaction domain (ρ = - 0.651; p = 0.009). IGF-1 levels negatively correlated with biochemical hypogonadism (ρ = - 0.585; p = 0.028). The number of CAG and CA repeats in AR and ERß receptors genes was not significantly associated with IIEF-15 scores or with GH/IGF-1 levels, but a negative correlation between CA repeats and the presence of cardiomyopathy (ρ = - 0.846; p = 0.002) was present. CONCLUSIONS: Men with acromegaly have a high prevalence of erectile dysfunction, but it does not appear to be correlated with treatments, testosterone levels and AR/ER-beta signaling. Nonetheless, a shorter CA polymorphic trait (ERbeta) is associated with the presence of cardiomyopathy. If confirmed, these data may suggest an association between an incorrect hormonal balance and increased cardiovascular risk in acromegaly subjects.

Conventional X-rays in the diagnosis and follow-up of vertebral fractures in patients with acromegaly: a real-life study.

OBJECTIVES: To explore the role of conventional X-ray imaging in detecting vertebral fractures (VFs) in patients with acromegaly, both at diagnosis of disease and at the last clinical visit. The risk factors for VFs were also evaluated. DESIGN AND METHODS: A retrospective cohort study was conducted on 60 consecutive patients with acromegaly, in a tertiary referral centre. Thoracolumbar spine radiography (X-spine) was performed at the last clinical visit during the follow-up in order to detect VFs. Routine chest radiograph, performed as a part of the general evaluation at diagnosis of acromegaly, were retrospectively analysed to screen for baseline VFs. RESULTS: At diagnosis of acromegaly, chest X-ray revealed that 10 (17%) patients had VFs. Of the 50 patients without VFs at diagnosis of acromegaly, 33 (66%) remained unfractured at the last clinical visit (median [IQR] time, 144 [96-192] months after the diagnosis of acromegaly), whereas 17 (34%) had VFs. Overall, 22 patients (37%) had novel VFs detected on X-spine including five patients with previous VFs. Risk factor for incident VFs was the presence of hypogonadism at diagnosis of acromegaly (p = 0.016). CONCLUSIONS: In acromegaly patients, conventional X-rays can detect vertebral fractures early at diagnosis of acromegaly. They can also reveal incident VFs, which may occur several years later even in patients without VFs at diagnosis, above all in relation to hypogonadism.

Acromegalic Cardiomyopathy: An Entity on its own? The Effects of GH and IGF-I Excess and Treatment on Cardiovascular Risk Factors.

Acromegaly is a chronic disease resulting from constantly elevated concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I). If not adequately treated, GH and IGF-I excess is associated with various cardiovascular risk factors. These symptoms mainly include hypertension and impaired glucose metabolism, which can be observed in approximately one-third of patients. Other comorbidities are dyslipidemia and the presence of obstructive sleep apnea syndrome. However, even in the absence of conventional cardiovascular risk factors, myocardial hypertrophy can occur, which reflects the impact of GH and IGF-I excess itself on the myocardium and is defined as acromegalic cardiomyopathy. Whereas previous echocardiography-based studies reported a high prevalence of cardiomyopathy, this prevalence is much lower in cardiac magnetic resonance imaging-based studies. Myocardial hypertrophy in acromegaly is due to a homogeneous increase in the intracellular myocardial mass and extracellular myocardial matrix and improves following successful treatment through intracellular changes. Intramyocardial water retention or ectopic lipid accumulation might not be of relevant concern. Successful treatment significantly improves myocardial morphology, as well as cardiovascular risk factors. In addition to GH/IGF-I-lowering therapy, the diagnosis and treatment of cardiovascular complications is crucial for the successful management of acromegaly.

Update on Current Evidence for the Diagnosis and Management of Nonfunctioning Pituitary Neuroendocrine Tumors.

Pituitary neuroendocrine tumors (PitNETs) are the third most frequently diagnosed intracranial tumors, with nonfunctioning PitNETs (nfPitNETs) accounting for 30% of all pituitary tumors and representing the most common type of macroPitNETs. NfPitNETs are usually benign tumors with no evidence of hormone oversecretion except for hyperprolactinemia secondary to pituitary stalk compression. Due to this, they do not typically present with clinical syndromes like acromegaly, Cushing's disease or hyperthyroidism and instead are identified incidentally on imaging or from symptoms of mass effects (headache, vision changes, apoplexy). With the lack of effective medical interventions, first-line treatment is transsphenoidal surgical resection, however, nfPitNETs often have supra- or parasellar extension, and total resection of the tumor is often not possible, resulting in residual tumor regrowth or reoccurrence. While functional PitNETs can be easily followed for recurrence using hormonal biomarkers, there is no similar parameter to predict recurrence in nfPitNETs, hence delaying early recognition and timely management. Therefore, there is a need to identify prognostic biomarkers that can be used for patient surveillance and as therapeutic targets. This review focuses on summarizing the current evidence on nfPitNETs, with a special focus on potential new biomarkers and therapeutics.

Risk of cancer in acromegaly patients: An updated meta-analysis and systematic review.

The incidence of cancer in acromegaly patients may be higher than that in the general population, although this has not been fully elucidated yet. This study analyzed the risk of various important types of cancer in acromegaly patients. The study was registered in INPLASY (registration number: INPLASY202340037). The PubMed, Web of Science, and EMBASE databases were searched for studies based on strict inclusion and exclusion criteria, from the time of database inception up to June 30, 2022. All observational studies of acromegaly patients with cancer were included, without language restrictions. We used the Newcastle-Ottawa scale (NOS) checklist to assess the quality of evidence. A meta-analysis revealed the relationship between acromegaly and cancer using the standardized incidence rates (SIRs) and 95% confidence intervals (CIs) retrieved from the included studies. Nineteen studies were included and analyzed. The overall incidence of cancer (SIR = 1.45, 95%CI = 1.20-1.75), as well as that of thyroid (SIR = 6.96, 95%CI = 2.51-19.33), colorectal and anal (SIR = 1.95, 95%CI = 1.32-2.87), brain and central nervous system (SIR = 6.14, 95%CI = 2.73-13.84), gastric (SIR = 3.09, 95%CI = 1.47-6.50), urinary (SIR = 2.66, 95%CI = 1.88-3.76), hematological (SIR = 1.89, 95%CI = 1.17-3.06), pancreatic and small intestine (SIR = 2.59, 95%CI = 1.58-4.24), and connective tissue (SIR = 3.15, 95%CI = 1.18-8.36) cancers, was higher among patients with acromegaly than among the general population. No association between acromegaly and hepatobiliary, respiratory, reproductive, skin, breast, or prostate cancer was observed. This study demonstrated that acromegaly patients have a modestly increased chance of cancer as compared to the general population. Risk factors for cancer need to be further explored to monitor patients with acromegaly at a high risk for cancer more carefully.

Acromegaly and Cancer: An Update.

Acromegaly is a chronic and rare disease. The diagnosis usually takes several years. Multiple comorbidities are associated with acromegaly. Long-term exposure to growth factors may lead to complications such as the development of benign or malignant tumors. However, the association between acromegaly and cancer remains a matter of debate due to multiple limitations in epidemiological data. There is controversy between acromegaly and mortality, but evidence shows a significant improvement in mortality rates with disease control and careful management of comorbidities. Older age, increased growth hormone levels (GH) at last follow-up, higher insulin-like growth factor-1 (IGF-1) levels at diagnosis, malignancy and radiotherapy were proposed as independent predictors of mortality. In this review we summarize the current state of knowledge in this field. Incidence of different cancer types is described. Rigorous surveillance of endocrine diseases may contribute to increased tumor detection. Personalized screening should probably be recommended.

Ectopic Hormonal Syndromes: Cushing's Syndrome and Acromegaly.

Ectopic hormone production may be present in neuroendocrine and non-endocrine neoplasms. Ectopic sources of growth hormone, adrenocorticotropin (ACTH), or their releasing factors are uncommon but clinically relevant. Ectopic ACTH tumors have been studied more than the rest, but there are still no comprehensive multidisciplinary guidelines that include all the pitfalls in the diagnosis and management of ectopic hormonal syndromes and the neoplasms associated with ectopic Cushing or acromegaly. The frequency of neuroendocrine neoplasms and other neoplasms with neuroendocrine differentiation has been increasing in recent decades. The review of the available data on these tumors, their classification, and improvements in diagnostic and therapeutic procedures is important to understand the relevance of ectopic Cushing's syndrome and acromegaly in clinical practice.

Use of speckle tracking echocardiography in evaluating cardiac dysfunction in patients with acromegaly: an update.

In recent years, cardiovascular disease has garnered increasing attention as the second leading cause of death in individuals with acromegaly, following malignancy. Identifying cardiac dysfunction early in acromegaly patients for timely intervention has become a focal point of clinical research. Speckle tracking echocardiography, a well-established ultrasound technique, surpasses conventional Doppler ultrasound in its sensitivity to assess both local and global cardiac mechanics. It can accurately detect subclinical and clinical myocardial dysfunction, including myocardial ischemia, ventricular hypertrophy, and valvular changes. Over the past five years, the use of speckle tracking echocardiography in acromegaly patients has emerged as a novel approach. Throughout the cardiac cycle, speckle tracking echocardiography offers a sensitive evaluation of the global and regional myocardial condition by quantifying the motion of myocardial fibres in distinct segments. It achieves this independently of variations in ultrasound angle and distance, effectively simulating the deformation of individual ventricles across different spatial planes. This approach provides a more accurate description of changes in cardiac strain parameters. Importantly, even in the subclinical stage when ejection fraction remains normal, the strain parameters assessed by speckle tracking echocardiography hold a good predictive value for the risk of cardiovascular death and hospitalization in acromegaly patients with concomitant cardiovascular disease. This information aids in determining the optimal timing for interventional therapy, offering important insights for cardiac risk stratification and prognosis. In the present study, we comprehensively reviewed the research progress of speckle tracking echocardiography in evaluating of cardiac dysfunction in acromegaly patients, to pave the way for early diagnosis of acromegaly cardiomyopathy.

Impulse Control Disorders in Patients with Pituitary Tumors Treated with Dopamine Agonists: A Systematic Review.

BACKGROUND: The increased prevalence of Impulse Control Disorders (ICDs) in dopamine agonist (DA) treated patients with Parkinson's disease is well described. Despite the frequent use of DAs in the management of pituitary tumors, the relationship between DAs and prevalence of ICDs in patients with pituitary tumours is unclear. AIMS: To establish the prevalence of ICDs in patients with prolactinoma or acromegaly and determine whether prevalence differs in those on DAs to those treated without. METHODS: Systematic review of the literature (registered a priori) reporting prevalence of ICDs in patients with prolactinoma or acromegaly (conducted June 2023). A narrative synthesis describing prevalence of ICDs according to assessment method was performed. Prevalence comparisons between patients with prolactinoma or acromegaly treated with DAs, to patients treated without, were summarised. RESULTS: Studies were largely retrospective, observational and heterogenous, with few patients with prolactinoma and acromegaly treated without DA. Prevalence of ICDs varied between 0-60% in patients with prolactinoma, and from 5-23% in studies with at least five patients with acromegaly. In most studies comparing DA exposed to non-DA exposed cases, DA use was not associated with ICDs. CONCLUSIONS: Reported prevalence of ICDs in patients with prolactinoma and acromegaly varies considerably. Given ICDs were reported to be highly prevalent in some studies, clinicians should be mindful of these potentially serious disorders. ICD screening tools validated for use in patients with pituitary tumors combined with prospective studies including appropriate controls, are necessary to accurately establish prevalence of ICDs and true impact of DAs in their development.

Discordant biochemical parameters of acromegaly remission do not influence the prevalence or aggressiveness of metabolic comorbidities: a single-center study.

Purpose: The discrepancy between the biomarkers of disease's activity in acromegalic patients (GH and IGF-1) is almost frequent representing a challenge for the development of comorbidities in the long term. The aim of this study was to evaluate the prevalence and severity of metabolic comorbidities (diabetes, hypertension, and dyslipidemia) in surgically treated acromegalic patients with disease control and discordant GH and/or IGF-1 levels compared with those with concordant values. Patients and methods: Retrospective monocentric observational study on acromegalic surgically treated patients with biochemical remission (group A) or mild discordant GH or IGF-1 levels (group B). Metabolic complications and medical therapy were assessed at diagnosis and at the last follow-up visit. Severity of the disease was set for drug titration or shift to another molecule or more than before. Results: There were 18 patients that met the inclusion criteria [group A: nine patients; group B: nine patients, follow-up 7 years (IQR 5.0;11.25)]. The prevalence of female patients was significantly higher in the remission group compared with the discordant group (p < 0.02). Considering metabolic complications, at the last follow-up, 61.1% was affected by hypertension, 33.3% by diabetes, and 61.1% by dyslipidemia, without differences between groups. Drug characteristics (dose, shift, number) during the follow-up did not differ significantly between groups. Conclusion: Metabolic complications, mainly dyslipidemia, are frequent in cured acromegalic patients, but GH/IGF-1 discrepancy does not seem to represent a risk factor for their presence or persistence. More extended studies are needed to confirm our results in a long-term period.

Practical therapeutic approach in the management of diabetes mellitus secondary to Cushing's syndrome, acromegaly and neuroendocrine tumours.

Cushing's syndrome, acromegaly and neuroendocrine disorders are characterized by an excess of counterregulatory hormones, able to induce insulin resistance and glucose metabolism disorders at variable degrees and requiring immediate treatment, until patients are ready to undergo surgery. This review focuses on the management of diabetes mellitus in endocrine disorders related to an excess of counterregulatory hormones. Currently, the landscape of approved agents for treatment of diabetes is dynamic and is mainly patient-centred and not glycaemia-centred. In addition, personalized medicine is more and more required to provide a precise approach to the patient's disease. For this reason, we aimed to define a practical therapeutic algorithm for management of diabetes mellitus in patients with glucagonoma, pheochromocytoma, Cushing's syndrome and acromegaly, based on our practical experience and on the physiopathology of the specific endocrine disease taken into account. This document is addressed to all specialists who approach patients with diabetes mellitus secondary to endocrine disorders characterized by an excess of counterregulatory hormones, in order to take better care of these patients. Care and control of diabetes mellitus should be one of the primary goals in patients with an excess of counterregulatory hormones requiring immediate and aggressive treatment.