Caloric restriction as a possible pitfall for persistent acromegaly follow-up - case report.

BACKGROUND: Acromegaly diagnosis is established when plasma levels of IGF-1 are increased and the Oral Glucose Tolerance Test (OGTT) with 75gr of glucose can't suppress Growth Hormone (GH) levels. These two parameters are also useful during follow-up, after surgical/radiologic therapy and/or during medical therapy. CASE PRESENTATION: A 29-year-old woman was diagnosed with acromegaly after a severe headache. Previous amenorrhea and facial and acral changes were noticed. A pituitary macroadenoma was found, biochemical evaluation was in agreement with the suspected acromegaly and a transsphenoidal adenectomy was performed. As the disease recurred, a surgical reintervention and radiosurgery (Gamma Knife, 22 Gy) were necessary. No normalization of IGF-1 was achieved during three years after radiosurgery. Surprisingly, then, and although clinical features seemed getting worse, IGF-1 levels became consistently controlled to 0.3-0.8 times the upper limit of the reference range. Questioned, the patient referred that she was following an intermittent fasting dietary plan. However, based on the dietary questionnaire, she was found to be under severe caloric restriction. First OGTT (under caloric restriction) showed absence of GH suppression and an IGF-1 value of 234 ng/dL (Reference Range 76-286 ng/mL). A second OGTT, one month after an eucaloric diet was instituted, showed an increased IGF-1 of 294 ng/dL, maintaining an unsuppressed, yet less elevated, GH. CONCLUSIONS: GHRH/GH/IGF-1 axis controls somatic growth. Regulation is complex, and nutrition status and feeding pattern have a recognized role. Like systemic inflammation or chronic liver disease, fasting and malnutrition decrease the expression of hepatic GH receptors, with consequent reduction of IGF-1 levels, through resistance to GH. This clinical report shows that caloric restriction may represent a pitfall in acromegaly follow-up.

Potential biomarkers and lncRNA-mRNA regulatory networks in invasive growth hormone-secreting pituitary adenomas.

PURPOSE: Growth hormone-secreting pituitary adenomas (GH-PAs) are common subtypes of functional PAs. Invasive GH-PAs play a key role in restricting poor outcomes. The transcriptional changes in GH-PAs were evaluated. METHODS: In this study, the transcriptome analysis of six different GH-PA samples was performed. The functional roles, co-regulatory network, and chromosome location of differentially expressed (DE) genes in invasive GH-PAs were explored. RESULTS: Bioinformatic analysis revealed 101 DE mRNAs and 70 DE long non-coding RNAs (lncRNAs) between invasive and non-invasive GH-PAs. Functional enrichment analysis showed that epithelial cell differentiation and development pathways were suppressed in invasive GH-PAs, whereas the pathways of olfactory transduction, retinol metabolism, drug metabolism-cytochrome P450, and metabolism of xenobiotics by cytochrome P450 had an active trend. In the protein-protein interaction network, 11 main communities were characterized by cell- adhesion, -motility, and -cycle; transport process; phosphorus and hormone metabolic processes. The SGK1 gene was suggested to play a role in the invasiveness of GH-PAs. Furthermore, the up-regulated genes OR51B6, OR52E4, OR52E8, OR52E6, OR52N2, MAGEA6, MAGEC1, ST8SIA6-AS1, and the down-regulated genes GAD1-AS1 and SPINT1-AS1 were identified in the competing endogenous RNA network. The RT-qPCR results further supported the aberrant expression of those genes. Finally, the enrichment of DE genes in chromosome 11p15 and 12p13 regions were detected. CONCLUSION: Our findings provide a new perspective for studies evaluating the underlying mechanism of invasive GH-PAs.

Acromegaly accompanied by diabetes mellitus and polycystic kidney disease.

Acromegaly is characterized by autonomous excessive growth hormone (GH) secretion, generally due to GH-producing pituitary adenoma, and is associated with various systemic comorbidities including diabetes mellitus. Polycystic kidney disease (PKD) is characterized by the growth of numerous cysts in the kidneys that deteriorate renal function. While possible renal effects of excessive GH exposure have been a current issue in experimental medicine, only five cases of coexisting acromegaly and PKD have been reported previously, and little is known regarding the influence of acromegaly on renal disease. We treated a 50-year-old male with diabetes mellitus who showed a sudden and rapid decline of renal function along with increasing proteinuria, which led to diagnoses of PKD and acromegaly. His urinary protein levels were increased together with excessive GH secretion and worsening glycemic control. An increase of total kidney volume was also noted. Transsphenoidal surgery for the pituitary adenoma was successfully performed. Marked improvement of hyperglycemia and proteinuria were observed after the surgery, but renal function was unchanged. The patient's clinical course suggested common aspects of excessive GH secretion as an accelerating factor of the progression of diabetic nephropathy and PKD via direct and indirect pathways. Although coexisting acromegaly and PKD is clinically rare, vigilance for early diagnosis of acromegaly is appropriate in patients with diabetes and/or PKD, especially in those showing unexpected exacerbation of renal dysfunction.

Ectopic GH-secreting pituitary adenoma of the clivus: systematic literature review of a challenging tumour.

PURPOSE: Acromegaly is usually due to growth hormone (GH)-secreting pituitary adenomas, but it may be exceptionally caused by GH-secreting ectopic pituitary adenomas (EPA). EPA are defined as extra-sellar pituitary tumours, extra- or intra-cranially sited, entirely separated from the pituitary stalk and gland. The aim of the study is to address the challenges in the management of clival GHEPA. METHODS: We reported a case of a 53-year-old acromegalic patient with a primary clival GHEPA and reviewed systematically the relevant English literature between 1975 and 2019, in keeping with the PRISMA guidelines. RESULTS: Four cases of primary clival GHEPA have been described in literature apart from ours. All patients presented with acromegalic features, elevated circulating GH and/or insulin-like growth factor-1 levels. Hyperprolactinemia and empty sella were described in two cases, respectively. These tumours show the typical imaging characteristics of pituitary adenomas, but their neuroradiological diagnosis may be challenging due to their sizes and the difficulty in defining the absence of connections with the pituitary fossa. CONCLUSION: Although primary clival GHEPA are exceedingly rare, even if likely under-reported in literature, they should be considered in the differential diagnosis of clival tumours because of their specific management. Surgery represents the first-line treatment option, while medical and radiation therapies can be adopted as neo-adjuvant, adjuvant or primary treatments according to tumour and patient characteristics.

A registry of acromegaly patients and one year following up in Taiwan.

BACKGROUND/PURPOSE: The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. METHODS: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. RESULTS: The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4 ± 12.9 years. Their mean age at diagnosis was 41.8 ± 12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7 ± 9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9 ± 8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and the insulin-like growth factor 1 levels were 2.7 ± 4.9 µg/L, 2.4 ± 6.1 µg/L, and 291.5 ± 162.4 ng/mL, respectively. The remission rate assessed by random GH level (≦2 µg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0 ± 19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. CONCLUSION: This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly.

[Endocrine paraneoplastic syndromes]. / Endokrine paraneoplastische Syndrome.

Endocrine paraneoplastic syndromes result from the production of bioactive substances from neoplastic cells, of endocrine or neuroendocrine origin. Typically these are located in the lungs, the gastrointestinal tract, pancreas, thyroid gland, adrenal medulla, skin, prostate or breast. In endocrine paraneoplastic syndromes the secretion of peptides, amines or other bioactive substances is always ectopic and not related to the anatomical source. The clinical presentation, however, is indistinguishable from a suspected eutopic endocrine tumor posing a diagnostic challenge. The most common endocrine paraneoplastic syndromes are based on the secretion of antidiuretic hormone (ADH) resulting in hyponatremia, secretion of adrenocorticotropic hormone (ACTH) or rarely corticotropin-releasing hormone (CRH) resulting in Cushing syndrome as well as secretion of growth hormone-releasing hormone resulting in acromegaly. Paraneoplastic endocrine syndromes mainly occur in highly malignant tumors; however, the development of these tumors does not necessarily correlate with tumor stage, malignant potential or prognosis. As endocrine paraneoplastic syndromes are a rare complication, there are hardly any evidence-based therapeutic recommendations. Treatment of the underlying tumor is the first choice and in a palliative setting symptomatic therapy is possible.

PREDICTORS OF QUALITY OF LIFE IN 165 PATIENTS WITH ACROMEGALY: RESULTS FROM A SINGLE-CENTER STUDY.

OBJECTIVE: Even if treated, acromegaly has a considerable impact on patient quality of life (QoL); despite this, the exact clinical determinants of QoL in acromegaly are unknown. This study retrospectively examines a cohort of treated patients with acromegaly, with the aim of identifying these determinants. METHODS: Retrospective survey analysis, with 165 patients included in the study. All patients completed a survey, which included demographic data and the clinical details of their disease, the Short Form-36 Health Survey (SF-36), the revised Beck Depression Inventory (BDI-II), and the Bern Embitterment Inventory (BEI). Stepwise regression was used to identify predictors of QoL. RESULTS: The strongest predictors of the physical component score of the SF-36 were (in order of declining strength of association): Delay between first presentation of the disease and diagnosis, body mass index (BMI), number of doctors visited before the diagnosis of acromegaly, and age at diagnosis. For the mental component score, the strongest predictors were: number of doctors visited, previous radiotherapy, and age at study entry; and, for the BDI-II score: number of doctors visited, previous radiotherapy, age at study entry, and employment status at the time of diagnosis. The following were predictors of the BEI score: number of doctors visited, and age at study entry. CONCLUSION: Diagnostic delay and lack of diagnostic acumen in medical care provision are strong predictors of poor QoL in patients with acromegaly. Other identified parameters are radiotherapy, age, BMI, and employment status. An efficient acromegaly service should address these aspects when devising disease management plans. ABBREVIATIONS: BDI-II = Beck Depression Inventory II BEI = Bern Embitterment Inventory BMI = body mass index IGF-1 = insulin-like growth factor 1 MCS = mental component summary (score) PCS = physical component summary (score) QoL = quality of life SDS = standard deviation score SF-36 = Short Form-36 Health Survey.

[Diagnostics and treatment of acromegaly : Necessity for targeted monitoring of comorbidities]. / Diagnostik und Therapie der Akromegalie : Notwendigkeit der gezielten Überwachung von Komorbiditäten.

Acromegaly is a rare and severe condition, presenting with typical signs and symptoms. The diagnosis is often initially made years after the first manifestations of the disease. In more than 99% of patients the disease is caused by a benign pituitary tumor that secretes growth hormone (GH). The diagnosis is based on the presence of increased insulin-like growth factor 1 (IGF-1) levels and a lack of GH suppression in the oral glucose tolerance test. The standard imaging procedure for tumor detection is magnetic resonance imaging in the region of the sella turcica. Treatment includes surgical, drug and radiation therapy. Important factors are an intensive aftercare of the patient, controls for detection of tumor recurrence and pituitary insufficiency as well as assessment of various organ functions and risk constellations. Patient care should involve close cooperation between endocrinologists, neurosurgeons and general practitioners as well as other specialist disciplines.

ACROSCORE: a new and simple tool for the diagnosis of acromegaly, a rare and underdiagnosed disease.

OBJECTIVE: Acromegaly, a disease caused by GH/IGF-I hypersecretion, is associated with a high mortality rate; early recognition is therefore necessary to ensure successful treatment and to avoid comorbidities. We have created a symptom/sign scoring tool (ACROSCORE) for physicians to use to identify acromegaly. DESIGN: To compare cases of acromegaly diagnosed between 1990 and 2014 against a control group affected by non-GH-secreting pituitary tumours to identify symptoms and signs that are most discriminative for acromegaly. PATIENTS: Confirmed acromegaly patients and patients affected by non-GH-secreting pituitary tumours. MEASUREMENTS: In all patients, signs, symptoms and comorbidities were recorded from medical records and collected using a specifically designed questionnaire. RESULTS: A total of 194 acromegaly patients [115 women; mean (SD) age 47·2 (14·2) years] and 243 patients affected by non-GH-secreting pituitary tumours [131 women; mean (SD) age 45·8 (15·8) years] were included. A strong association was observed for type 2/secondary diabetes [odds ratio (OR) 3·7], hyperhidrosis (OR 6·1), thyroid hyperplasia (OR 13·9), colorectal polyps (OR 10·4), spaced teeth (OR 25·4) and carpal tunnel syndrome (OR 4·3). Based on this information, a multivariable logistic model was built and a 14-point scoring system developed. A score of 0 excludes the risk of acromegaly [positive predictive value (PV(+)) = 0·6%]; scores 1-5 comprise a grey area; scores >5 indicate that a diagnosis of acromegaly cannot be excluded (PV(+) = 46·1%). CONCLUSIONS: Once validated in independent studies, ACROSCORE may represent a new tool for the clinical screening of acromegaly that can be used by general practitioners and nonendocrinology specialists.

Diagnosis and management of acromegaly: the patient's perspective.

PURPOSE: Early diagnosis is a success factor for the prevention of long-term comorbidity and premature death in patients with acromegaly, but large-scale data on the diagnostic process and disease management are scarce. Therefore, we aimed to evaluate the diagnostic process, implementation of treatment and changes in life situation in patients with acromegaly, focusing on sex-specific differences. METHODS: Non-interventional patient-reported outcome study. 165 patients with clinically and biochemically proven acromegaly were questioned about the diagnostic process and utilization of health care by means of a self-developed standardized postal survey including questions on acromegaly symptoms experienced before diagnosis, number and specialty of consulted doctors, time to diagnosis and aftercare. RESULTS: The diagnostic process took 2.9 (SD 4.53) years, during which 3.4 (SD 2.99) physicians were consulted. Women waited longer [4.1 (SD 5.53) years] than men [1.6 (SD 2.69) years; p = 0.001] for the correct diagnosis, and consulted more doctors in the process [4.0 (SD 2.99) vs. 2.7 (SD 2.84) doctors, p < 0.001, respectively]. In 48.5 % of patients, acromegaly was diagnosed by an endocrinologist (men: 45.1 %; women: 52.4 %). Overall disease duration from symptom onset until last surgery was 5.5 (SD 6.85) years, with no sex differences. A change in employment status was the most commonly reported event after diagnosis and a quarter of the patients stated that the illness had changed their lives. CONCLUSIONS: Our findings confirm the urgent need to increase awareness of the clinical manifestation of acromegaly to facilitate an earlier diagnosis of the disease and to provide diagnostic equality across the sexes.

Challenges in the diagnosis and management of acromegaly: a focus on comorbidities.

INTRODUCTION: Acromegaly is a rare, insidious disease resulting from the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), and is associated with a range of comorbidities. The extent of associated complications and mortality risk is related to length of exposure to the excess GH and IGF-1, thus early diagnosis and treatment is imperative. Unfortunately, acromegaly is often diagnosed late, when patients already have a wide range of comorbidities. The presence of comorbid conditions contributes significantly to patient morbidity/mortality and impaired quality of life. METHODS: We conducted a retrospective literature review for information relating to the diagnosis of acromegaly, and its associated comorbidities using PubMed. The main aim of this review is to highlight the issues of comorbidities in acromegaly, and to reinforce the importance of early diagnosis and treatment. FINDINGS AND CONCLUSIONS: Successful management of acromegaly goes beyond treating the disease itself, since many patients are diagnosed late in disease evolution, they present with a range of comorbid conditions, such as cardiovascular disease, diabetes, hypertension, and sleep apnea. It is important that patients are screened carefully at diagnosis (and thereafter), for common associated complications, and that biochemical control does not become the only treatment goal. Mortality and morbidities in acromegaly can be reduced successfully if patients are treated using a multimodal approach with comprehensive comorbidity management.

LIMITATIONS OF CURRENT APPROACHES FOR THE TREATMENT OF ACROMEGALY.

OBJECTIVE: Acromegaly is a rare disease characterized by hypersecretion of growth hormone (GH), typically from a benign pituitary somatotroph adenoma, that leads to subsequent hypersecretion of insulin-like growth factor 1 (IGF-1). Patients with acromegaly have an increased risk of mortality and progressive worsening of comorbidities. Surgery, medical therapy, and radiotherapy are currently available treatment approaches for patients with acromegaly, with overall therapeutic goals of lowering GH levels and achieving normal IGF-1 levels, reducing tumor size, improving comorbidities, and minimizing mortality risk. Although surgery can lead to biochemical remission in some patients with acromegaly, many patients will continue to have uncontrolled disease and require additional treatment. METHODS: We reviewed recently published reports and present a summary of the safety and efficacy of current treatment modalities for patients with acromegaly. RESULTS: A substantial proportion of patients who receive medical therapy or radiotherapy will have persistently elevated GH and/or IGF-1. Because of the serious health consequences of continued elevation of GH and IGF-1, there is a need to improve therapeutic approaches to optimize biochemical control, particularly in high-need patient populations for whom current treatment options provide limited benefit. CONCLUSION: This review discusses current treatment options for patients with acromegaly, limitations associated with each treatment approach, and areas within the current treatment algorithm, as well as patient populations for which improved therapeutic options are needed. Novel agents in development were also highlighted, which have the potential to improve management of patients with uncontrolled or persistent acromegaly.

The value of an acute octreotide suppression test in predicting short-term efficacy of somatostatin analogues in acromegaly.

Predicting the efficacy of long-acting somatostatin analogues (SSA) remains a challenge. We aim to quantitatively evaluate the predictive value of the octreotide suppression test (OST) in short-term efficacy of SSA in active acromegaly. Sixty-seven newly diagnosed acromegaly patients were assessed with OST. Subsequently, all patients were treated with long-acting SSA for 3 months, followed by reassessment. Nine parameters were tested, including GHn (the nadir GH during OST), ΔGH1 (= [GH0h-GHn]/GH0h, GH0h was the baseline GH during OST), ΔGH2 (= [GHm-GHn]/GHm, GHm was the mean GH on day curve), AUC(0-6h) (the GH area under the curve during OST) , ΔAUC1 (= [GH0h-AUC(0-6h)]/GH0h), ΔAUC2 (=[GHm-AUC(0-6h)]/GHm), AUC(m-6h) (the GH AUC during OST where GHm was used instead of GH0h), ΔAUC1' (=[GH0h-AUC(m-6h)]/GH0h) and ΔAUC2' (=[GHm-AUC(m-6h)]/GHm). The Youden indices were calculated to determine the optimal cutoffs to predict the short-term efficacy of SSA. ΔGH2 more than 86.83%, ΔAUC2 more than -57.48% and ΔAUC2' more than -57.98% provided the best predictors of a good GH response (sensitivity 93.8%, specificity 85.7%). ΔGH2 more than 90.51% provided the best predictor of a good tumor size response (sensitivity 84.8%, specificity 87.5%). The percentage fall of GHn (ΔGH) was a better predictive parameter than GHn. OST showed higher efficiency in predicting the efficacy of octreotide LAR than lanreotide SR. In conclusion, OST is a valid tool to predict both GH and tumor size response to short-term efficacy of SSA in acromegaly, especially for octreotide LAR. GHm is better to be used as basal GH than GH0 during OST.

Low insulin resistance after surgery predicts poor GH suppression one year after complete resection for acromegaly: a retrospective study.

Remission of acromegaly is defined as a nadir in GH <1.0 ng/mL during a 75-g oral glucose tolerance test (75gOGTT) and insulin-like growth factor-1 (IGF-1) normalization. Recently, a lower cut-off value for GH nadir (<0.4 ng/mL) has been proposed. We retrospectively evaluated the prevalence and clinical characteristics of postoperative cases with normalized IGF-1 levels and a GH nadir of 0.4-1.0 ng/mL one year after complete resection of GH-secreting pituitary adenoma (GHoma). We included 110 cases of acromegaly with complete adenoma resection, no preoperative treatment, preoperative glycosylated hemoglobin <6.5%, preoperative basal plasma glucose <126 mg/dL, GH nadir <1.0 ng/mL during a 75gOGTT, and normalized IGF-1 at the first postoperative year evaluation, whereupon patients were divided into two groups: control (GH nadir <0.4 ng/mL) and high GH (GH nadir >0.4 ng/mL). Clinical parameters, including measures of insulin secretion and resistance, were compared between groups. The high GH group included 10 patients (9.1%) and had a lesser level of insulin resistance immediately following surgery and at the first postoperative year evaluation. On single regression analysis, insulin resistance immediately following surgery was predictive of and correlated with the GH nadir at the first postoperative year evaluation. The GH nadir at the first postoperative year evaluation may be insufficient in patients with normalized IGF-1 with low insulin resistance immediately following complete resection of GHoma. Careful evaluation is needed to assess remission in such patients.

Median nerve conduction studies and wrist magnetic resonance imaging in acromegalic patients with carpal tunnel syndrome.

PURPOSE: Carpal tunnel syndrome (CTS) often occurs with acromegaly; however, the pathophysiology of CTS in acromegalic patients remains unclear. This study evaluated the median nerve in acromegalic patients with and without CTS. METHODS: We examined the median nerves of 21 acromegalic patients (eight patients with CTS and 13 patients without CTS) using electrophysiological nerve conduction studies and wrist magnetic resonance images. They underwent transsphenoidal surgery to resect their growth hormone-secreting pituitary adenomas. The median nerves of the patients with CTS were reassessed by the same studies. RESULTS: The sensory conduction velocity was significantly later in the median nerves of patients with CTS than in patients without CTS (34.9 vs. 45.8 m/s, respectively; P = 0.006). In the wrist magnetic resonance images, the cross-sectional area of the median nerve in CTS patients and non-CTS patients was 18.7 and 10.5 mm(2), respectively. The median nerve was significantly larger in patients with CTS than in patients without CTS (P < 0.003). The flattering ratio of the median nerve and palmar deviation of the flexor retinaculum were not significantly different between the two patient groups. After tumor resection, the nerve conduction velocities improved in patients with CTS, but the nerve remained enlarged. The CTS symptoms disappeared in all patients, except one. CONCLUSIONS: The median nerves of acromegalic patients with CTS were enlarged and had impaired nerve conduction. This finding represents a predominant intrinsic feature in the pathophysiology of the disease rather than an extrinsic feature such as a thickened transverse carpal ligament.

Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, Phase III study.

PURPOSE: A large, randomized, double-blind, Phase III core study demonstrated that pasireotide LAR was significantly superior to octreotide LAR at providing GH <2.5 µg/L and normalized IGF-1 after 12 months' treatment in patients with acromegaly. We report the efficacy and safety of pasireotide LAR and octreotide LAR after up to 26 months' treatment. METHODS: Patients with GH <2.5 µg/L and IGF-1 ≤1× ULN at month 12, or patients considered to be experiencing clinical benefit, were eligible to continue receiving their randomized therapy in the extension. Efficacy and safety in the pasireotide LAR and octreotide LAR groups were evaluated for up to 26 months. RESULTS: Overall, 120 patients who completed the core study continued receiving pasireotide LAR (n = 74) or octreotide LAR (n = 46) in the extension. At month 25, biochemical control (GH <2.5 µg/L and normal IGF-1) was achieved by 48.6% (36/74) and 45.7% (21/46) of patients in the pasireotide LAR and octreotide LAR arms [60.8% (45/74) and 52.2% (24/46) when including patients with IGF-1 < LLN], respectively. In total, 74.7% of pasireotide LAR and 71.6% of octreotide LAR patients had tumor volume decrease ≥20% from baseline to month 26. Most AEs were mild or moderate. Hyperglycemia-related AEs were seen in 62.9 and 25.0% of pasireotide LAR and octreotide LAR patients, respectively. No new safety signals were observed in the extension compared with the core study. CONCLUSIONS: GH and IGF-1 suppression is maintained for up to 25 months during pasireotide LAR treatment. The safety profile of pasireotide LAR is typical of a somatostatin analogue, except for the frequency and degree of hyperglycemia.

Pituitary incidentalomas: analysis of a neuroradiological cohort.

PURPOSE: Most pituitary lesions are detected during the investigation of symptoms associated with hormonal dysfunction and vision abnormalities. When the lesion is identified in an image performed for reasons not related to the tumor, the term incidentaloma applies. Our aim was to describe the diagnosis behind pituitary incidentalomas, patient characteristics and their follow up. METHODS: We searched for the terms "pituitary", "hypophysis" and "incidentaloma" in the requisitions and reports of all CTs and MRIs performed between 1st September 2008 and 30th October 2013. We retrieved demographic data as well as information regarding presentation and follow-up. RESULTS: We detected 71 pituitary incidentalomas, 3 in children/adolescents. In adult patients, mean age was 51.6 ± 18.46 years and 42 were female (61.8 %). The most frequent reason for imaging was headache (33.8 %). The image that first detected the incidentaloma was CT scan in 63.2 and 17.6 % patients presented symptoms that could have led to earlier diagnosis. Pituitary adenoma is the most prevalent lesion (n 48; 70.6 %), followed by Rathke's cleft cyst (n 9; 13.2 %). Hormonal evaluation revealed hypopituitarism in 14 patients and hypersecretion in 6: 5 prolactinomas and 1 somatotroph adenoma. Twenty-one (28.8 %) patients underwent surgery and there was no malignancy. CONCLUSIONS: In concordance with available literature, adenomas are the most frequent incidentally found pituitary lesions. Hormonal dysfunction is quite prevalent, including symptomatic presentations, which suggests that there seems to be a low sensitivity for the diagnosis of pituitary disease.

Early lung function abnormalities in acromegaly.

BACKGROUND: Acromegaly is an insidious disorder caused by a pituitary growth hormone (GH)-secreting adenoma resulting in high circulating levels of GH and insulin-like growth factor I (IGF-I). Respiratory disorders are common complications in acromegaly, and can severely impact on quality of life, eventually affecting mortality. OBJECTIVES: The present study aimed to explore structural and functional lung alterations of acromegalic subjects. METHODS: We enrolled 10 consecutive patients (M/F: 5/5) affected by acromegaly. In all patients, magnetic resonance imaging (MRI) revealed the presence of pituitary tumor. All patients underwent clinical, lung functional, biological, and radiological assessments. Ten healthy age-matched subjects also served as controls. RESULTS: No statistically significant differences in lung function were detected between acromegalic and healthy subjects (p ≥ 0.05 for all analyses). However, the diffusing capacity for CO (TLCO) was significantly lower in the acromegalic group than in healthy subjects (TLCO% predicted: 78.1 ± 16 vs. 90 ± 6 %, respectively, p = 0.04; KCO% predicted: 77 ± 16 vs. 93 ± 5 %, p = 0.02, respectively). None of the lung function parameters correlated with duration of the disease, or with inflammatory marker of the airways. In acromegalics, biological (exhaled NO concentrations) and imaging (total lung volume, TLV, and mean lung density, MLD) evaluations were within normal values. The TLV measured by HRCT was 3540 ± 1555 ml in acromegalics, and the MLD was -711 ± 73 HU. None of the lung functional, radiological, and biological findings correlated with GH or IGF-I levels, and no correlation was found with duration of disease. CONCLUSIONS: In the current study, lung function evaluation allowed to detect early involvement of lung parenchyma, as assessed by TLCO and KCO, even in the absence of parenchymal density alterations of the lung by HRCT. These findings suggest to routinely include the carbon monoxide diffusing capacity in the lung function assessment for an early intervention in acromegaly.

Acromegaly: otolaryngic manifestations following pituitary surgery.

OBJECTIVES: Acromegalics present with a wide range of otolaryngic symptoms, including rhinosinusitis, changes in facial appearance, obstructive sleep apnea (OSA), and voice disturbances. Treatment typically involves transnasal-transsphenoidal (TNTS) resection of the offending pituitary adenoma. In this study, we identify the prevalence of otolaryngic symptoms of acromegalic patients, and evaluate Sinonasal Outcome Test (SNOT-22) scores preceding and following pituitary resection. DESIGN: Retrospective chart review. SETTING: Tertiary academic medical center. PARTICIPANTS: Patients diagnosed with acromegaly who underwent surgical resection of a growth-hormone secreting pituitary adenoma between August 2010 and September 2013. MAIN OUTCOME MEASURES: Subjects were asked to complete questionnaires detailing otolaryngic symptoms as well as SNOT-22 surveys before and after TNTS surgery. A Student's t-test was used to compare preoperative and postoperative SNOT-22 scores. RESULTS: Twenty-five patients underwent pituitary surgery for acromegaly. Acromegalic patients were found to have macroglossia (60%), OSA or sleep-disordered breathing (52%), thyroid neoplasia (20%), hearing loss/tinnitus (20%), sinonasal symptoms (16%), and parathyroid pathology (8%). Differences in preoperative and postoperative SNOT-22 scores were not statistically significant. CONCLUSION: Acromegalics present with assorted otolaryngic complaints. Routine screening of all acromegalics with sleep evaluations (for both surgical and perioperative planning), thyroid ultrasound, and audiologic testing should be strongly considered.