Real-life data of Pasireotide LAR in acromegaly: a long-term follow-up.

OBJECTIVE: Pasireotide LAR (PAS-LAR) was released in Italy in 2017 to treat acromegaly patients resistant to SRLs (Somatostatin Receptors Ligands). The long-term follow-up data of PAS-LAR therapy in Italy are limited. This study aimed to evaluate the efficacy and safety of PAS-LAR in acromegaly. DESIGN: Patients with acromegaly in PAS-LAR treatment were enrolled in three tertiary Italian endocrinological centers and evaluated by a retrospective observational real-life multicentre study. METHODS: Patients have been studied before (baseline) and 1, 6, 12, 24 and > 36 months after PAS-LAR start. Clinical, biochemical, and pituitary magnetic resonance data were collected, along with information on adverse events. Acromegaly disease activity was classified according to the IGF-1 index (normal value < 1.0). RESULTS: Fifty patients (female 23) were enrolled. PAS-LAR treatment (mean follow-up 24 ± 16 months) significantly decreased IGF-1 levels (IGF-1 index baseline vs last visit: 1.9 ± 0.6 vs 1.2 ± 0.6, p < 0.0001). At the last visit, 67% of patients had controlled disease, and 44% showed a decrease in tumor volume. Clinical and biochemical efficacy was observed as early as after 1-month of PAS-LAR treatment (IGF-1 index baseline vs 1-month: 1.9 ± 0.6 vs 1.4 ± 0.7, p < 0.0001). Also, 50% of patients referred headache improvement or disappearance. Fifteen patients discontinued PAS-LAR due to failure of treatment and poor glycaemic control. The prevalence of diabetes increased from 33% at the baseline to 54% at the last visit (p = 0.0072). CONCLUSION: In real-life settings, PAS-LAR significantly decreases symptoms, IGF-1 levels, and the size of adenoma in patients with acromegaly resistant to SRLs. Beneficial effects may occur early after the first injection.

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.

Short review: novel concepts in the approach to patients with amiodarone-induced thyrotoxicosis.

INTRODUCTION: Amiodarone-induced thyrotoxicosis is associated with high morbidity and mortality rates. The approach to this condition is widely variable across different medical specialists and even among expert endocrinologists. As a matter of fact, the approach to amiodarone-induced thyrotoxicosis has always been considered difficult, due to diagnostic uncertainties easily resulting in missteps, and therapeutic challenges easily resulting in unresponsiveness or slow-responsiveness to the administered drugs. PURPOSE: Our purpose is to review novelties emerged during the last years about this condition, with the aim to provide novel insights on the diagnostic and therapeutic management of this challenging condition.

An altered state of consciousness while using anticoagulants and the incidental discovery of a pituitary lesion: considering pituitary apoplexy.

Summary: Pituitary apoplexy (PA) is a medical emergency with complex diagnosis and management. In this study, we describe a case of PA in a 63-year-old male treated with oral anticoagulant therapy for atrial fibrillation. In the patient, PA manifested itself with asthenia and severe headache not responsive to common analgesics. Despite the finding of a pituitary mass through CT, and in anticipation of the endocrinological evaluation and pituitary MRI, the patient's clinical condition worsened with an escalation of headache and asthenia associated with deterioration of the visual field and impairment of consciousness level. The emergency assessments revealed an adrenal failure, whereas MRI showed a haemorrhagic pituitary macroadenoma with compression of the optic chiasm. Intravenous fluids repletion and high-dose hydrocortisone were started with a rapid improvement of the patient's health and visual field abnormalities. Hydrocortisone was gradually reduced to a replacement dose. During the follow-up, panhypopituitarism was documented, and replacement therapies with l-thyroxine and testosterone were introduced. Three months later, a pituitary MRI showed a 50% reduction in the pituitary adenoma volume. Learning points: Pituitary apoplexy (PA) is a medical emergency that can result in haemodynamic instability and abnormalities in the level of consciousness. The management of PA requires a multidisciplinary team that includes endocrinologists, ophthalmologists, neuro-radiologists, and neuro-surgeons. Pituitary MRI with gadolinium is the diagnostic gold standard for PA. PA therapy aims to improve general conditions and treat compression symptoms, especially visual field abnormalities. Adrenocorticotrophic hormone deficiency is a common and severe complication of PA. Thus, all patients with PA must be promptly treated with injective synthetic glucocorticoids (e.g. hydrocortisone 100 mg) and i.v. saline. PA must be taken into consideration in case of sudden headache in patients with a pituitary macroadenoma, especially if other risk factors are recognized.

Are there country-specific differences in the use of pegvisomant for acromegaly in clinical practice? An analysis from ACROSTUDY.

OBJECTIVE: A comprehensive picture of pegvisomant use for treating acromegaly in routine clinical practice in different countries is lacking. We aimed, therefore, to document country-specific behaviors in real-life pegvisomant use, and the main safety and effectiveness outcomes in the ACROSTUDY. DESIGN: ACROSTUDY is an open-label, non-interventional, post-marketing safety surveillance study. METHODS: A descriptive analysis was performed using data from the six top-recruiter ACROSTUDY countries, i.e., Germany (n = 548 patients), Italy (n = 466), France (n = 312), USA (n = 207), Spain (n = 200) and the Netherlands (n = 175). These nations accounted for > 85% of the ACROSTUDY cases. RESULTS: The mean pegvisomant dose at treatment start was lowest in the Netherlands (9.4 mg/day), whereas it ranged between 10.9 and 12.6 mg/day in the other countries. At year 5, the mean pegvisomant dose was around 15 mg/day in all countries, except France (18.1 mg/day). At starting pegvisomant, patients treated with monotherapy ranged between 15% in the Netherlands and 72% in Spain. Monotherapy remained lowest over time in the Netherlands. In all countries, the percentage of patients with normal IGF-1 increased steeply from < 20% at baseline to 43-58% at month 6 and 51-67% at year 1. After that, we observed minor changes in the rate of acromegaly control in all countries. The Netherlands peaked in disease control at year 2 (72%). The proportion of patients reporting changes in pituitary tumor size was generally low. Serious treatment-related adverse events were < 5% in all countries. CONCLUSIONS: Our study provided a detailed summary of real-life use of pegvisomant in the six top-recruiter ACROSTUDY nations.

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients.

BACKGROUND: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD). METHODS: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. RESULTS: The prevalence of APS-1 was 2.6 cases/million (range 0.5-17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. CONCLUSIONS: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

Effect of high-dose intravenous glucocorticoid therapy on serum thyroid hormone concentrations in type 2 amiodarone-induced thyrotoxicosis: an exploratory study.

PURPOSE: Type 2 amiodarone-induced thyrotoxicosis (AIT2) is a form of drug-induced destructive thyroiditis, usually treated with oral glucocorticoids (oGCs). Our objective was to investigate the short-term effects of intravenous glucocorticoids (ivGCs) on serum thyroid hormone concentrations in patients with AIT2. METHODS: Exploratory study of three naive AIT2 patients treated with iv methylprednisolone (two pulses of 400 mg with no interpulse oGCs), followed by oGCs, matched 1:3 with AIT2 patients treated with oGCs alone. Changes in serum thyroid hormone concentrations were evaluated in the short-term period (24 h and 7 days) and after a cumulative dosage of 400 and 800 mg equivalents of methylprednisolone; in addition, healing time and duration of exposure to GCs were calculated. RESULTS: During the first 24 h of treatment, serum FT4 concentrations increased in ivGCs patients, and decreased in oGCs patients (+ 3.3% vs - 10.7%, respectively, p = 0.025). After 7 days, serum FT4 and FT3 concentrations decreased significantly in both groups, with no statistical difference between them (p = 0.439 for FT4 and p = 0.071 for FT3), even though the cumulative GCs dose was higher in ivGCs than in oGCs patients (800 mg vs 280 mg, p = 0.008). Furthermore, the iv administration of single 400 mg pulses of methylprednisolone resulted in a less significant decrease in serum thyroid hormone concentrations when compared to equivalent GCs doses fractionated in several consecutive days (p = 0.021 for FT4 and p = 0.052 for FT3). There were no significant differences in the healing time (p = 0.239) and duration of exposure to GCs (p = 0.099). CONCLUSIONS: High-dose ivGCs therapy does not offer advantages over standard oGCs therapy in the rapid, short-term control of AIT2.

Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE).

BACKGROUND: Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications. PURPOSE: We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life.

Correction to: Pegvisomant in acromegaly: an update.

Unfortunately, in page 584, second column, the first sentence under the heading "Type of switch" has been published incorrectly. The complete correct sentence is given below.

Pegvisomant in acromegaly: an update.

BACKGROUND: In 2007, we published an opinion document to review the role of pegvisomant (PEG) in the treatment of acromegaly. Since then, new evidence emerged on the biochemical and clinical effects of PEG and on its long-term efficacy and safety. AIM: We here reviewed the emerging aspects of the use of PEG in clinical practice in the light of the most recent literature. RESULTS: The clinical use of PEG is still suboptimal, considering that it remains the most powerful tool to control IGF-I in acromegaly allowing to obtain, with a pharmacological treatment, the most important clinical effects in terms of signs and symptoms, quality of life and comorbidities. The number of patients with acromegaly exposed to PEG worldwide has become quite elevated and the prolonged follow-up allows now to deal quite satisfactorily with many clinical issues including major safety issues, such as the concerns about possible tumour (re)growth under PEG. The positive or neutral impact of PEG on glucose metabolism has been highlighted, and the clinical experience, although limited, with sleep apnoea and pregnancy has been reviewed. Finally, the current concept of somatostatin receptor ligands (SRL) resistance has been addressed, in order to better define the acromegaly patients to whom the PEG option may be offered. CONCLUSIONS: PEG increasingly appears to be an effective and safe medical option for many patients not controlled by SRL but its use still needs to be optimized.

The presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase antibodies (TPOAb) does not exclude the diagnosis of type 2 amiodarone-induced thyrotoxicosis.

PURPOSE: It is widely accepted that type 2 amiodarone-induced thyrotoxicosis (AIT) generally occurs in patients with a normal thyroid gland without signs of thyroid autoimmunity. However, it is currently unknown if the presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase antibodies (TPOAb) in AIT patients without other signs of an underlying thyroid disease may impair the response to glucocorticoid therapy. METHODS: We performed a pilot retrospective cohort study with matched-subject design and an equivalence hypothesis, comparing the response to glucocorticoid therapy between 20 AIT patients with a normal thyroid gland, low radioiodine uptake, undetectable TSH receptor antibodies and positive TgAb and/or TPOAb (Ab+ group), and 40 patients with the same features and absent thyroid antibodies (Ab- group). RESULTS: The mean cure time was 54 ± 68 days in the Ab+ group and 55 ± 49 days in the Ab- group (p = 0.63). The equivalence test revealed an equivalent cure rate after 60, 90 and 180 days (p = 0.67, 0.88 and 0.278, respectively). The occurrence of permanent hypothyroidism was higher in the Ab+ group than in the Ab- group (26.3 vs 5.13 %, p = 0.032). CONCLUSIONS: The presence of TgAb and/or TPOAb does not affect the response to glucocorticoid therapy, suggesting that the patients with features of destructive form of AIT should be considered as having a type 2 AIT irrespective of the presence of TGAb or TPOAb. These patients have a higher risk of developing hypothyroidism after the resolution of thyrotoxicosis and should be monitored accordingly.

Does pegvisomant treatment expertise improve control of resistant acromegaly? The Italian ACROSTUDY experience.

OBJECTIVE: GH receptor antagonist pegvisomant is indicated for treatment of patients with resistant acromegaly. We compared safety and treatment outcomes of pegvisomant therapy in patients managed by Italian centers enrolling less or more than 15 cases in ACROSTUDY, a safety surveillance study of long-term pegvisomant treatment of patients with acromegaly. A noninterventional safety surveillance study in which safety and treatment outcomes of pegvisomant were evaluated on the basis of data collected during a 7-year period. METHODS: A total of 204 acromegaly patients treated by seven centers enrolling 16-49 patients each (group A) and 137 subjects by 18 centers following 3-14 cases ( group B). RESULTS: Patients of group A and B were treated for 4.4 ± 2.7 and 4.2 ± 2.2 years, respectively. IGF-1 ULN normalized in 64.4 % (n = 56) and 54.4 % (n = 31) in group A and B, respectively, after 1-year treatment, and in 57.3 % (n = 106) and 72.5 % (n = 87) at last visit. Starting doses were significantly higher in group A. They were progressively increased during treatment in both groups, but were higher in uncontrolled patients than in controlled ones only in group A. Reported adverse events were more frequent, and the prevalence of patients with adverse events was higher in group B. CONCLUSIONS: On the basis of this original study approach, we could speculate that in the centers in which more patients are treated with pegvisomant, less adverse events are reported, but the long-term effectiveness is lower than in centers with less cases, perhaps because of an inadequate patient's selection.

ACROSTUDY: the Italian experience.

ACROSTUDY is a world-wide non-interventional, post marketing surveillance study performed to monitor the safety and outcomes of pegvisomant (PEG) in clinical practice. We report data from acromegaly patients who have been included in the Italian ACROSTUDY registry. The data of 341 acromegaly patients (171 males) were available for analysis using data freeze (12/9/2012). Patients were enrolled in 25 Italian endocrine centres. Before and during PEG treatment IGF-I, liver enzymes, metabolic parameters, and pituitary MRI were assessed. Before PEG, 54.3% patients had been treated with medical therapy and surgery, 22.9% medical therapy only, and 15.8% medical plus radiation and surgical therapy. 199 adverse events were reported in 98 patients (28.7%). Serious adverse events were documented in 29 patients (8.5%). 71.1% of patients had no significant change in tumor volume. Central MRI reading was performed in 34 patients; in 7 patients, an increase in tumor volume was found. Hormonal efficacy progressively increased since the start of PEG. After 6 years, normal IGF-I levels were found in 70.9% of patients (mean daily dose 18.1 mg). 87.1% of patients were treated with daily PEG although in 8.8% of patients, it was administered 2-6 times per week and in 3.8% with weekly injections. 74.8% received a PEG dose 10-15 mg/daily. PEG is a drug with a favorable safety profile which is efficacious also considering that in Italy it is currently available as third-line therapy.

Prognostic factors for pancreatic neuroendocrine neoplasms (pNET) and the risk of small non-functioning pNET.

BACKGROUND: Non-functioning (NF) pancreatic neuroendocrine tumors (pNET) often have an indolent outcome. A consensus to submit patients with large (>2 cm) NF-pNET to surgery already exists; but a conservative approach for small (≤2 cm) NF neoplasms has been proposed. AIM: To identify prognostic factors for survival and progression free survival (PFS) of NF-pNET, evaluating whether surgery may be avoided for small NF-pNET. SUBJECTS AND METHODS: Retrospective study of 77 consecutive patients with pNET submitted to surgery, of which 60 were NF. Pathological tissues were revised according to the 2000 and 2010 WHO classifications. Risk factors for survival and PFS were evaluated using the Kaplan-Meier method and the Cox regression model. RESULTS: The 8-year cause-specific survival of NF-pNET was 79.3%. At univariate analysis, high grading, high staging, large tumors, angioinvasion and peri-pancreatic infiltration were significantly associated with a shorter survival; at multivariate analysis only peri-pancreatic infiltration was significantly associated with a shorter NF-pNET survival. Most small NF-pNET were grade 1 (74%), compared to large NF-pNET (27%). Distant metastases were present in 29.7% (n = 11) and 17.4% (n = 4) of patients with large or small NF-pNET, respectively; among the 19 small NF-pNET without metastasis, five had a local malignancy (lymph node metastasis or local infiltration); thus, 39% of the 23 NF-pNET, turned out to have a malignant potential. CONCLUSIONS: Among NF-pNET, large neoplasms were associated with worse outcomes; however, small NF-pNET do not seem to have an invariable benign behavior. Whether surgery should be avoided in all patients with small NF-pNET is questionable.

Lower prolactin levels during cabergoline treatment are associated to tumor shrinkage in prolactin secreting pituitary adenoma.

Dopamine agonists are considered as the first line therapy in prolactin (PRL) secreting pituitary adenomas inducing a normalization of serum PRL and reduction of tumor size. It is known that serum PRL levels, obtained during treatment, are a predictor of tumor shrinkage. Whether PRL suppression below the lower limit of the normal range is related to a greater chance of tumor shrinkage than just its normalization has not been established. This retrospective cohort study was carried out in a tertiary center. Clinical records of 151 patients with PRL-secreting pituitary adenomas (73 micro-, 78 macroadenomas) treated with cabergoline for at least 24 months were analyzed. The adenoma size was analyzed by MRI before and after 24 months of treatment. PRL levels were evaluated every 6 months, assigning a score at each time point (PRL 0 = suppressed; 1 = normal; 2 = above normal). The total score, after 24 months of treatment, was expressed as the sum of the score at each time point and ranged between 0 and 8. A tumor shrinkage was observed in 102/151 patients (67.5%) and it was significantly associated to a lower PRL total score (p = 0.021, OR = 0.85, CI = 0.73-0.97), being significantly more frequent in patients with suppressed PRL than in those with normal PRL (p = 0.045, OR = 0.42, CI = 0.18-0.98) at 24 months. Cabergoline therapy with the goal of achieving PRL levels below the lower limit of normal range can increase the chance to obtain tumor shrinkage of PRL-secreting pituitary adenomas.

A novel germline mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene in an Italian family with gigantism.

PURPOSE: Acromegaly usually occurs as a sporadic disease, but it may be a part of familial pituitary tumor syndromes in rare cases. Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been associated with a predisposition to familial isolated pituitary adenoma. The aim of the present study was to evaluate the AIP gene in a patient with gigantism and in her relatives. METHODS: Direct sequencing of AIP gene was performed in fourteen members of the family, spanning among three generations. RESULTS: The index case was an 18-year-old woman with gigantism due to an invasive GH-secreting pituitary adenoma and a concomitant tall-cell variant of papillary thyroid carcinoma. A novel germline mutation in the AIP gene (c.685C>T, p.Q229X) was identified in the proband and in two members of her family, who did not present clinical features of acromegaly or other pituitary disorders. Eleven subjects had no mutation in the AIP gene. Two members of the family with clinical features of acromegaly refused either the genetic or the biochemical evaluation. The Q229X mutation was predicted to generate a truncated AIP protein, lacking the last two tetratricopeptide repeat domains and the final C-terminal α-7 helix. CONCLUSIONS: We identified a new AIP germline mutation predicted to produce a truncated AIP protein, lacking its biological properties due to the disruption of the C-terminus binding sites for both the chaperones and the client proteins of AIP.

Role of UGT1A1 and ADH gene polymorphisms in pegvisomant-induced liver toxicity in acromegalic patients.

CONTEXT: Hepatotoxicity is one of the most serious adverse effects in acromegalic patients treated with pegvisomant (PEG-V). Recent studies have found an association between this adverse event and the UGT1A1 allele 28 polymorphism associated with Gilbert's syndrome. OBJECTIVE: To determine whether UGT1A1*28 and alcohol dehydrogenase (ADH) polymorphisms influence liver toxicity during PEG-V treatment. DESIGN AND SETTING: Multicenter observational retrospective study conducted in 13 tertiary care endocrinology units in Italy. PATIENTS: A total of 112 patients with active disease resistant to somatostatin analogs (SSTa) and 108 controls were enrolled. INTERVENTIONS: Clinical and biochemical data were recorded by electronic clinical reporting forms. Blood or DNA samples were sent to the coordinating center for genotyping. RESULTS: No differences in genotypes between patients and controls were found. During PEG-V therapy liver function tests (LFT), abnormalities and overt hepatotoxicity developed in 17 and 4.5% of patients respectively. Logistic and linear regression analyses showed an association between LFT abnormalities during the follow-up visit and prior events of LFT abnormalities in medical history (odds ratio=1.25; P=0.04) and the number of concomitant medications, other than SSTa (B=3.9; P=0.03). No correlation between LFT alterations and UGT1A1 allele 28 as well as ADH1C and B polymorphisms was found. CONCLUSIONS: UGT1A1 allele 28 and ADH1C and B polymorphisms do not predict increased risk of hepatotoxicity during PEG-V therapy. Conversely, patients with multi-therapies and with previous episodes of liver disease should be carefully managed, due to the observed association between these conditions and LFT abnormalities during PEG-V therapy.

Effects of medical therapies for acromegaly on glucose metabolism.

OBJECTIVE: Abnormalities of glucose metabolism are common findings of acromegaly. However, robust evidence on whether therapy with somatostatin analogs (SSAs) or pegvisomant (PEG) differently affects glucose metabolism is lacking. The purpose of this study was to evaluate the effects of therapy with SSAs, PEG, or their combination on glucose metabolism in a large series of acromegalic patients. DESIGN: This was a historical-prospective study. Among 50 consecutive acromegalic patients under SSA therapy, acromegaly in 19 patients was controlled. PEG used in combination with SSA therapy allowed the control of acromegaly in the remaining 31 patients and was then continued as monotherapy in 18 patients. METHODS: The following parameters were evaluated at the diagnosis of acromegaly and during DIFFERENT TREATMENTS: fasting plasma glucose (FPG) and insulin concentrations, insulin sensitivity (QUICK-I), homeostasis model assessment of insulin resistance (HOMA2-IR), and plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). Comparison was made using analysis for paired data. RESULTS: Insulin resistance improved when acromegaly was controlled with therapy with SSAs, PEG, or SSA+PEG. However, FPG concentrations were higher during SSA therapy (alone or combined with PEG) than at the diagnosis of acromegaly, even when corrected for disease activity, whereas they were reduced during PEG therapy. Mean glucose concentrations during the OGTT were higher in patients receiving SSA therapy than in those receiving PEG therapy. In addition, the prevalence of diabetes or impaired glucose tolerance was higher during SSA therapy than at diagnosis or during PEG therapy and was not influenced by disease control. CONCLUSIONS: Medical therapies for acromegaly reduce insulin resistance and increase insulin sensitivity; on the contrary, glucose indexes may be differently affected by SSA or PEG therapy.

Pituitary autoimmunity in patients with diabetes mellitus and other endocrine disorders.

OBJECTIVE: Pituitary autoimmunity is often found in association with other endocrine autoimmune or non-autoimmune diseases. Aim of the study was to assess the prevalence of serum pituitary antibodies (PitAb) in patients with Type 1 diabetes mellitus (T1DM) or Type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: In this casecontrol study 111 patients with T1DM, 110 patients with T2DM, and 214 healthy controls were enrolled in a tertiary referral center. Pituitary, thyroperoxidase, thyroglobulin, 21-hydroxylase, and parietal cell antibodies were assessed in all cases. Endocrine function was further assessed by basal hormone measurement and by dynamic tests, as well as a pituitary magnetic resonance imaging (MRI) was performed in those patients found positive for PitAb. RESULTS: PitAb prevalence was higher in T1DM (4 out of 111, 3.6%) than in T2DM (0 out of 110, p=0.045) and in healthy subjects (1 out of 214, 0.5% p=0.029). Prevalence of other autoimmune diseases was significantly higher in patients with T1DM (45 out of 111, 40.5%) when compared with patients with T2DM (18 out of 110 T2DM, 16.3%, p<0.001). Patients with T1DM and PitAb positivity were found with a pituitary lesion at MRI in 2 cases and pituitary dysfunction in one case. CONCLUSIONS: A significant association between pituitary autoimmunity and T1DM was found, in particular in subjects with one or more other endocrine autoimmune diseases.