ACTA ENDOCRINOLOGICA (BUC)

Glucose intolerance (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] or diabetes mellitus) due to insulin resistance is a frequent complication of acromegaly due to excessive growth hormone (GH) production. Long-acting somatostatin analogs are known to reduce the GH and IGF-1 serum levels, and to inhibit at the same time the pancreas insulin release. The effect upon acromegalic patients who express IFG before therapy is controversial. We here present two male patients, 66 and 36 years old, with active acromegaly and IFG who were submitted to a treatment with long-acting somatostatin analog lanreotide. After being diagnosed with active acromegaly with high nadir serum GH levels along oral glucose tolerance test (OGTT), i.e. 149 ng/mL and 43 ng/mL respectively, the patients underwent complex therapy (surgery and radiotherapy) which reduced the GH serum levels (20.7 ng/mL and 3.5 ng/mL respectively) without curing the disease. The patients developed IFG with fasting serum glucose levels of 113 mg/dL and 101 mg/dL, respectively. The treatment with the long-acting somatostatin analog lanreotide (30 mg i.m., every two weeks) decreased the GH serum levels close to normal limits (1.5 ng/mL and 1.6, ng/mL respectively). The treatment with lanreotide normalised the fasting serum glucose levels (91 mg/dL and 81 mg/dL, respectively) together with a reduction of serum insulin levels from 14.2 mU/mL to 8.7 mU/mL and from 25.4 mU/mL to 11.5 mU/mL, respectively (HOMA decreased form 3.96 to 1.97 and 6.33 to 2.3, respectively). We discuss the mechanisms by which lanreotide can improve glucose tolerance in patients with active acromegaly despite lowering the serum insulin levels through a direct effect on insulin secretion.

Context. We aimed to examine the factors affecting adverse gestational outcome in gestational diabetes (GDM) patients, who were grouped as obese and normal- weight, having only-diet, or insulin treatments. Subjects and Methods. The study included 373 patients, treated with diet or insulin. These patients were sub-grouped as obese and non-obese, and examined retrospectively. The variables affecting adverse gestational outcome in obese GDM patients having dietary and/ or insulin treatments were detected with multiple regression analysis. Results. The weight gained during pregnancy in the GDM group having insulin treatment was more than the one in only-diet treated GDM group (p=0.004). Pre-pregnancy body mass index, the weight gained during pregnancy, hemoglobin A1C levels in the second and third trimesters, caesarian rates were higher in the insulin-treated obese patients than in the other groups (p<0.001). The odds ratio for fasting blood glucose level in insulin-treated obese GDM group was 1.081 (95% CI =1.004 - 1.163) (p=0.039); and it was 0.982 (95% CI =0.924 - 1.002) (p=0.048) for the weight gained during pregnancy, in only-diet treated obese GDM patients. Conclusion. The control of weight gained during pregnancy, and of fasting blood glucose levels in obese patients having GDM, is important to decrease adverse gestational outcome.

Aims. In August 2015, FDA published a black box declaring that DPP-4 inhibitors may cause severe joint pains. The impact on autoimmunity marker positivity of these drugs has not been comprehensively evaluated. We compared the incidence of arthritis/arthralgia in patients with T2DM who were using DPP-4 inhibitors and patients who were not using. Methods. A number of 93 DPP-4 inhibitor users and 107 non-users were included into the study. Arthritis/ arthralgia were found in 41 of 93 (44.1%) DPP-4 inhibitor users and in 19 of 107 (17.8%) non-users (p<0.05). Results. No inflammatory rheumatological condition was identified in 27 of 41 (65.9%) patients in DPP-4 inhibitor user group as well as in 13 of 19 (68.4%) patients in non-user group (p>0.05). After adjusting for gender the incidence for arthritis/arthralgia was significantly increased in the DPP-4 inhibitor user group (p value for any DPP-inhibitor <0.05). There was 3.77 times increased risk for arthritis/arthralgia in the DPP-4 inhibitor using group (p value= 0.001) and this risk increases 2.43 times for each year of DPP-4 inhibitor usage. Conclusions. Arthritis/arthralgia were more common among T2DM patients who were using DPP-4 inhibitors compared to non-users, but the seropositivity did not differ between DPP-4 inhibitor users and non-users.

We describe a case of severe osteoporosis with vertebral fractures in a 30-year-old male with very active Beh?et?s disease treated for nine months with high doses of Prednisone. He was admitted to our department because of classical manifestations of the autoimmune disorder (bipolar aphthous) and also for acute mechanical back pain developed after a minor fall. The X-ray evaluation revealed a spinal fracture confirmed by the CT scan. The DXA evaluation revealed a T-score of -3.4 with an identical Z-score. The patient was diagnosed with severe secondary (glucocorticoid induced) osteoporosis with vertebral fracture and active Beh?et disease.

Context. Diabetes is a serious public health problem that is increasing worldwide. Objectives. The aim of this study is to evaluate acceptance of the illness, emotional distress, depression and quality of life in individuals with type 2 diabetes mellitus. Subjects and Methods. This study was conducted in 145 individuals with type 2 diabetes mellitus, 73 males (50.3%) and 72 females (49.7%), ranging in age from 20 to 65 years old. Research data were collected using the face-to-face interview technique by the researchers. The Acceptance of Illness Scale for the determination of individuals’ acceptance of the illness, Problem Areas in Diabetes Scale for emotional distress, Beck Depression Inventory for depression and Short Form-36 scales for quality of life was used. Results. The mean score of individuals’ Acceptance of Illness Scale was 30.2±5.62. Compared to women, men had lower emotional distress, depression levels (p<0.05), higher physical, mental quality of life (p<0.001). Correlations among acceptance of illness, emotional distress, depression and quality of life were found to be significant (p<0.05). Also, models of multiple linear regression analysis were statistically significant (p=0.000). Conclusions. The main goal in the treatment of diabetes should be to eliminate complaints in patients, to reduce, prevent or delay the development of complications, to increase the quality of life, to ensure that the individual has a physically, emotionally, spiritually and mentally regular life in addition to metabolic control. For this reason, it is beneficial to carry out the treatment with a multidisciplinary approach in type 2 diabetes mellitus.

Context. The intravenously administered selective α1 antagonist urapidil represents an alternative to phenoxybenzamine in the preoperative treatment of pheochromocytoma patients. Objective. The aim of the study was to investigate the blood pressure changes in pheochromocytoma patients with urapidil pretreatment with special regards to the need for interventions in order to estimate the safety of this treatment in a normal ward setting. Design. The medical records of all patients who underwent adrenalectomy for PCC were reviewed retrospectively. Systolic blood pressure values >180mmHg were defined as hypertensive episodes and systolic blood pressure values < 50mmHg as hypotensive episodes. Episodes of blood pressure instabilities were considered significant and recorded as intervention if they led to a direct action. Results. Twenty consecutive patients who received urapidil pretreatment were enrolled in this retrospective study. Preoperatively, a median of 9 blood pressure measurements per day have been performed on the ward. A total of 2 episodes of hypertension occurred, and 1 episode of hypotension has been recorded. In the period from 25-72 hours postoperatively the median number of blood pressure measurements was 5 per 24 hours. The blood pressure deviations led to a total of 3 interventions for hypertension in 1 (5%) patients and 5 interventions for hypotension in 3 (15%) patients. All interventions could be managed on the normal ward, without the need to transfer the patient to an ICU. Conclusions. Intravenous urapidil can safely be administered on a normal ward without putting patients at risk. Intensive monitoring beyond 24 hours postoperatively was not necessary, the blood pressure measurements during the shift on a normal ward were sufficient for maintaining patients’ safety.

Introduction. Acromegaly is a chronic disease associated with high mortality rate if untreated. The aim of the study is to evaluate mortality ratio in Romanian patients with acromegaly in latest years, with new therapeutic options. Patients and Methods. This retrospective study analyzed 336 (111M/225F, mean age 48.13±12.40 years) consecutive patients with acromegaly between 1st January 2001 and 31 December 2014, median follow-up 7.36 years (0.48-13.99 years). PAMCOMP computation program assessed standardized mortality ratio (SMR). Kaplan Meier curve was used for comparison between of different cut-off levels of the last GH level on survival. Serum GH levels were measured by IRMA (sensitivity 0.1 ng/mL). Results. During follow-up 2596.34 person-years, 41 patients died, with a SMR of 1.34 (CI 0.96-1.82). Mean age at death was 63.19±11.66 years. Females with acromegaly died 83% more frequently than women in general population: SMR-1.83 (CI 1.21-2.67). Females were older at diagnosis (p=0.006), and were less probable to receive substitution of gonadotrophic failure than males (p<0.001). Independent factors correlated with mortality were age at baseline (p<0.001, HR=1.07), last GH level (p=0.003, HR=1.01) and systolic blood pressure (p=0.029, HR=1.02). Patients with last GH level ≤ 1 ng/mL had a better survival than patients with GH>1 ng/mL (p Log Rank=0.002). SMR of patients with last GH >1 ng/mL was 1.59 (CI 1.08-2.26) for the entire group, 2.2 (CI 1.32-3.44) for females and 1.3 (CI 0.67-2.29) for males. Conclusion. Patients with acromegaly have a high mortality ratio compared to general population, especially in women and those with post-therapeutic serum GH levels over 1 ng/mL. Longer follow-up is needed for the evaluation of the effect of new therapies on mortality.

Pituitary radiotherapy (RT) has undergone important progress in the last decades due to the development of new stereotactic techniques which provide more precise tumour targeting with less overall radiation received by the adjacent brain structures. Pituitary surgery is usually firstline therapy in most patients with nonfunctioning (NFPA) and functioning adenomas (except for prolactinomas and large growth hormone (GH) secreting adenomas), while RT is used as second or third-line therapy. The benefits of RT (tumour volume control and, in functional tumours, decreased hormonal secretion) are hampered by the long latency of the effect and the potential side effects. This review presents the updates in the efficacy and safety of the new stereotactic radiation techniques in patients with NFPA, GH-, ACTH- or PRL-secreting pituitary adenomas. Methods. A systematic review was performed using PubMed and articles/abstracts and reviews detailing RT in pituitary adenomas from 2000 to 2017 were included. Results. Stereotactic radiosurgery (SRS) and fractionated stereotactic RT (FSRT) provide high rates of tumour control i.e. stable or decrease in tumour size, in all types of pituitary adenomas (median 92 - 98%) at 5 years. Endocrinological remission is however significantly lower: 44-52% in acromegaly, 54-64% in Cushing’s disease and around 30% in prolactinomas at 5 years. The rate of new hypopituitarism varies from 10% to 50% at 5 years in all tumour types and as expected increases with the duration of follow-up (FU). The risk for other radiation-induced complications is usually low (0-5% for new visual deficits, cranial nerves damage or brain radionecrosis and extremely low for secondary brain tumours), however longer FU is needed to determine rates of secondary tumours. Notably, in acromegaly, there may be a higher risk for stroke with FSRT. Conclusion. Stereotactic radiotherapy can be an effective treatment option for patients with persistent or recurrent pituitary adenomas after unsuccessful surgery (especially if residual tumour is enlarging) and/or resistance or unavailability of medical therapy. Comparison with conventional radiation therapy (CRT) is rather difficult, due to the substantial heterogeneity of the studies. In order to evaluate the potential brain-sparing effect of the new stereotactic techniques, suggested by the current data, longterm studies evaluating secondary morbidity and mortality are needed.

Context. Laparoscopic sleeve gastrectomy (SG) has gained popularity as a metabolic procedure, but its longterm effectiveness for Romanian patients remains unclear. Objectives. To assess the long-term efficacy of SG for Romanian patients and to evaluate the differences between 5 years and 1 year follow-up. Design. A longitudinal, prospective analysis of collected data from 68 patients undergoing SG between 2009 and 2014 was performed. Long-term outcomes at 5 years were analyzed in terms of total weight loss (%TWL), excess weight loss (%EWL), body composition and glucose homeostasis. Subjects and Methods. All patients meeting the standard criteria for SG before inclusion were prospectively enrolled in the study. Of the 68 patients, eight were lost to follow-up, therefore, 60 patients (41.7±12.5 years, baseline body mass index [BMI] 44.6±9.9Kg/m2) were analyzed. Results. The BMI decreased at 12 months with 30.7% from the preoperative BMI (p<0.001) and subsequently stabilized at 5 years. TWL and EWL were 30.6% and 83.1%, respectively at 1 year, with a slightly increase at 5 years. Therapeutic success rate (%EWL≥50) and diabetes remission rate (Buchwald criteria) were 93.3% and respectively 63.6% at 5 years. Insulin sensitivity index and metabolic clearance rate of glucose increased with 92.5% and 60.1% respectively, in the third month from baseline (p<0.001), while estimated second phase of insulin secretion decreased with 7.9% in the first month postoperatively (p=0.04), remaining stable afterwards. Conclusions. SG was effective in terms of %EWL, body composition and glucose homeostasis improvement for Romanian patients, the outcomes stabilizing after 1 year follow-up.