ACTA ENDOCRINOLOGICA (BUC)

We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient’s health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. Conclusion. This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

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controversial. Aim. This study retrospectively reviews the tumor evolution in patients with NFA macroadenomas treated with surgery and conventional RT, as compared to surgery alone. Methods. Of 107 unselected patients with operated NFA (aged 19 - 77 years), evaluated between 1977 - 2008, 71 patients were follow-up without RT (group A), while 36 patients were submitted to RT (group B). Patients submitted to radiosurgery were not included. Both groups underwent serial imaging studies with computed tomography or magnetic resonance. Tumor evolution was conventionally defined as a change of minimum 25% of diameter. Results. The surgical approach was transfrontal in 47% of patients, transsphenoidal in 43% or both in 10% of patients, similar in both study groups. In group B, 30 patients underwent highvoltage RT (mean total dose 50.5 Gy) and 6 patients low-voltage RT (mean emission dose 16,775 R). Mean follow-up after surgery in group A was 3.4 years (range 6 months - 10 years) and after RT in group B it was 6.8 years (range 2 &#8211; 24 years), p < 0.001. In group A, 16 out of 71 patients had no visible tumor remnants. In this subgroup, 2 patients (12.5%) showed tumor recurrence. Fifty-five out of 71 patients had residual tumors, 21 with extrasellar extension after surgery. In this subgroup, 21 patients (38%) showed tumor re-growth and 7 (13%) showed tumor decrease. In group B (n=36) all patients had tumor remnants after surgery with extrasellar extension in 30 patients. After RT, tumor re-growth occurred in 5 out of 36 patients (14%) as compared to subgroup A with residual tumors (p< 0.05) and tumor decrease in 14 out of 34 (41%), as compared to the same subgroup A (p < 0.01). The 5 year-tumor re-growth free survival rate of 88% in irradiated patients was significantly better than in non-irradiated patients with residual tumors (31%, log-rank test, p < 0.01, Kaplan-Meier analysis), but similar to that in patients without remnants (87.5%). Age, sex, tumor parasellar extension and size of residual tumor were not predictors of recurrency. Conclusion. Postoperative radiotherapy provides a significant improvement of local control in patients with residual NFA compared to surgery alone. It is necessary a long term follow-up due to recurrency noticed up to 8 years postsurgery. In patients without tumor remnants, a wait-and-see policy is indicated after surgery.

Detecting the primary tumours in carcinoid malignancies is a critical challenge. We report the case of a 25 year old male patient with a typical clinical carcinoid syndrome. Metastatic carcinoid malignancy was easily diagnosed by very high plasma chromogranin, plasma serotonin and urinary 5-Hydroxy-Indol Acetic Acid levels, and the detection of multiple liver metastases by ultrasound. Somatostatin receptor scintigraphy (SRS) failed to detect the primary lesion, as did upper and lower gastrointestinal (GI) tract endoscopy, bronchoscopy, total body CT, MRI, and GI video tract endoscopy; only F-DOPA PET-scan ascertained and accurately localized the primary ileal tumor. Surgery confirmed the localisation, and pathology revealed a 3 cm highly differentiated carcinoid tumor with low proliferation grade (Ki67<2). The therapy with short and long acting somatostatin analogues was started before surgery and continued after surgical intervention. There was a regression of the clinical carcinoid syndrome and a numerical involution of liver metastases, but the levels of chromogranin A and serotonin remained elevated. Other therapeutical option should be discussed.

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.

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.

Background. Patients with acromegaly (caused by growth-hormone-secreting pituitary adenomas) are at increased risk of hypopituitarism, in particular hypogonadotropic hypogonadism, before and after multimodal therapy. In affected women of reproductive age, fertility is impaired and complex fertility treatments are needed to achieve conception. C ase presentation. We present the case of a young woman with acromegaly caused by a GH-secreting macroadenoma with suprasellar and bilateral cavernous sinus extension; hypogonadotropic hypogonadism and secondary hypothyroidism were present from the initial evaluation. Neurosurgical intervention was repeatedly recommended but the patient refused it initially; also she was non-compliant to the medical treatment of acromegaly. Transsphenoidal tumor debulking with adjuvant gamma-knife radiotherapy was eventually performed. Following treatment persistent active acromegaly and hypogonadotropic hypogonadism were diagnosed. Under chronic estroprogestative replacement therapy, the patient conceived and delivered a full-term healthy newborn without any complications. Possible mechanisms are discussed. Conclusions. Secondary hypogonadotropic hypogonadism in pituitary patients, even when considered permanent (after surgery and radiotherapy), can exceptionally allow spontaneous conception and normal course of pregnancy.

The gastrointestinal (GI) motility, which is important for the digestion and absorption, may be altered in obesity. The aim of this review is to present the GI motility changes occurring in obesity, as well as their underlying mechanisms. We have conducted a systematic review of the published literature concerning GI motility and obesity and have described recent published data on the changes throughout the entire GI tract. Most recent discoveries include evidence supporting the increase of gastroesophageal reflux disease in obesity and inhibition of gastric motility. Intestinal transit of the distal small bowel generally slows down, ensuring enough time for digestion and absorption. Constipation is more frequent in obese patients than in those with a normal weight. The gut-brain axis plays an important role in the pathophysiology of GI motility disorders in obesity. This bidirectional communication is achieved by way of neurons, hormones, metabolites derived from intestinal microbiota and cytokines. The molecular mechanisms of GI motility changes in obesity are complex. Current data offer a starting point for further research needed to clarify the association of obesity with GI motility disorders.

Background. Craniopharyngiomas are benign but locally invasive tumours of the sellar region that arise from ectopic embryonic remnants of Rathke's pouch, affecting both children (adamantinomatous type -aCP) and adults (papillary type -pCP) and associated with significant morbidity. Objective. To study the clinical presentation of CRF as well as the posttreatment evolution of craniopharyngioma in children versus adults in a large mixed cohort. Material and methods. We performed a retrospective review of CRF patients evaluated in the National Institute of Endocrinology in Bucharest between 1990 and 2016. Results. A total of 107 patients (72 adults, 35 children) with a mean follow-up of 6.2 years were included. The presenting symptoms were mostly headache, visual impairment, symptoms of hypopituitarism, diabetes insipidus. Some symptoms or hormonal abnormalities were significantly more prevalent in the children group (p<0.05): nausea/ vomiting (47.8% vs 16.7%), photophobia (21.7% vs 5.6%), diabetes insipidus(28.5% vs 8.3%), GH deficiency (68.8% vs 17.1%). Impaired visual acuity (67.6%of cases) or visual fields (71.4%) were more frequent in adults compared to children (44.1%; 51.6%). The tumor dimensions were similar in both groups (3.05± 1.05 cm in children; 2.7± 1.07 cm in adults). Massive suprasellar extension reaching the third ventricle was frequently present in all cases. All cases underwent surgery but only a minority of those not cured received postoperative adjuvant radiotherapy. Frequent postoperative complications were: aggravation of the endocrine deficit (>80% of cases in both groups needed chronic replacement therapy), central diabetes insipidus (68.2% children, 34.3% of adults). Conclusions. Despite similar tumor dimensions and extension compared to adults, craniopharyngioma in children is more frequently associated with signs of intracranial pressure. The results and complications of treatment are similar in adults and children