Endocrine Abstracts

Background: Dopamine agonists are first-line agents for the treatment of prolactinomas and sometimes are used in patients with acromegalia. There is evidence that these drugs, especially cabergoline, are associated with an increased risk of new cardiac valve regurgitation in patients treated for Parkinson’s disease.Objective: Our objective was to evaluate the prevalence of cardiac valve regurgitation in patients with prolactinomas and acromegalia tr...

Background: Nicotinamide phosphoribosyltransferase (NAMPT)/PBEF/visfatin is a widely expressed cytokine with various effects on glucose and lipid metabolism, cell survival, and inflammation. Despite a favorable body composition profile, acromegalic patients present insulin resistance, increased cardiovascular risk, and higher incidence of secondary tumors.Aim: Based on its relation to glucose and lipid metabolism and inflammation we hypothesized that NAM...

Introduction: A 59-year-old gentleman with longstanding poorly controlled type 2 diabetes mellitus, obesity, hypertension, obstructive sleep apnoea, depression and type 2 respiratory failure was seen in diabetes review clinic and noted to have truncal obesity, moon facies and wasting of the proximal muscles.Investigations: Urinary free cortisol was 782 nmol/24 h (NR <200). Midnight cortisol was 595 and 532 nmol/l on consecutive days. After low dose d...

It was shown that estrogens decreased the POMC gene expression level in female rats. The aim of the present study was to examine the morphometric parameters of immunohistochemically labeled ACTH cells in juvenile female rat pituitaries after estradiol dipropionate (EDP) treatment. The females in juvenile period (16th day) were divided into two groups, each of seven animals. The experimental group received five injections of EDP (i.p. 0.25 mg/kg b.w.) every second day from the ...

The most common cause of hyperprolactinemia is a prolactinoma in women after pregnancy is excluded. A 34-year-old female presented to our clinic with a 1.5 year history of secondary amenorrhea, galactorrhea and malaise. Prolactin (PRL) level was found to be 151.89 ng/ml. Pituitary imaging was reported to be normal. An examination of the patient revealed that PRL level was still high so the dose of cabergoline was further increased and subsequently, bromocriptine was added to t...

Context and objective: Coping strategies may affect quality of life (QoL), which is decreased in patients after treatment for Cushing’s disease, acromegaly, or non-functioning macroadenomas (NFMA). We aimed to explore coping strategies in these patients, since this has never been done before.Design: A cross sectional study.Subjects: We included patients treated for Cushing’s disease (n=42), for acromegaly (n...

Introduction: Prolactinoma account for 40% of all pituitary tumors. It is the most common cause of hyperprolactinemia. Infertility, galactorrhea and hirsutism are the significant symptoms. Polycystic ovary syndrome affects the 5–10% of the women in reproductive age. The most common symptoms are irregular menses, hirsutism and infertility. However, prolactinoma and PCOS association is rare. A case of PCOS and prolactinoma is reported.Case: A 21-year-...

Introduction: GH substitution in GH deficiency (GHD) must be subcutaneously administered daily. Recently, a new sustained release formulation of GH (LB03002) has been developed which has to be injected only once per week. As a sub-study to the double-blind, randomized, placebo-controlled, multicenter, phase-III-study we performed this prospective study to evaluate influences of the new GH formulation on metabolic parameters and the hormones leptin and ghrelin in adult patients...

Objective: Few studies have determined the effects of more than 5–10 years of GH replacement in adults on bone mass and density.Design/patients: In this prospective, single-centre, open-label study, the effects of 15 years of GH replacement on bone mineral content (BMC) and bone mineral density (BMD) were determined in 126 hypopituitary adults (72 men) with adult onset GH deficiency (GHD). Mean age was 49.4 (range 22–74) years at study start. B...

Context: The effect of GH replacement in elderly GH deficient (GHD) adults on bone mineral density (BMD) is not known.Objective: In this prospective, single-centre, open-label study, the effects of 3-year GH replacement were determined in 45 GHD adults above 65 years of age and in 45 younger GHD patients with a mean age of 39.5 (S.E.M. 1.1) years. All patients had adult onset disease and both groups were comparable in terms of number of an...

Objective: Cardiovascular diseases (CVD) are the most important cause of mortality in acromegaly patients. Noninvasive assessment of aortic stiffness which can be used as an predictor of atherosclerosis, may be of benefit in acromegaly patients for early diagnosis of CVD. We evaluated the aortic elasticity parameters of acromegalic patients in remission and compared with healthy controls.Methods and results: Study subjects consisted of 20 patients with a...

Context: Little is known of the importance of previous irradiation therapy for baseline characteristics and responsiveness to GH replacement in GH deficient (GHD) adults.Objective/design/patients: In this prospective, single-centre, open-label study, the effects of 10-year GH replacement on metabolic variables and safety were determined in 18 GHD adults that had previously received pituitary irradiation therapy and 18 non-irradiated GHD patients. All pat...

Introduction: Dopamine agonists such as cabergoline and bromocriptine are used in the treatment of hyperprolactinemia to provide normoprolactinemia, to improve gonodal functions and to decrease the size of tumour if there is. Besides common side effects, fibrosis is another rare side effect of dopamine agonists. Long-term use of these drugs has been reported to cause fibrotic changes in heart valves. In addition, there are a few case reports about dopamine agonist-related pleu...

The study analyses direct postoperative and long-term results of surgical treatment of ACTH-secreting pituitary adenomas in 158 patients, operated between 2004 and 2009. There were 143 (91%) female and 15 (9%) male. The mean age of the patients was 36 years, S.D. 10.7. In all patients the diagnosis of Cushing’s disease was confirmed by high dose dexamethasone suppression test. Preoperative hormonal evaluation: ACTH (0800 h), pg/ml (Me-78.5 (50.5 (25th perce...

Background: Estrogen replacement therapy is the most effective treatment for postmenopausal (PMP) flushing, but its use is often contraindicated. An effective and safe alternative is urgently needed.Aim: To explore the effects of the LHRH receptor antagonist cetrorelix in women with severe PMP flushing who have a mean daily flush score >15.Methods: Open-label treatment with cetrorelix 250 μg twice a day in nine women with ...

Background: Currently, multiple treatment options are available for the treatment of acromegaly. However, cure is obtained only in 50% of patients with macroadenomas after surgery. Persistent tumor enlargement occur in 2.2% of the patients treated with somatostatin analogs and in 1.6–2.9% of the patients treated with pegvisomant. The nuclear antigen Ki-67 is related to growth potential and is also a major prognostic indicator for pituitary adenomas. Studies demonstrated t...

LHX3, a member of the LIM-homeodomain family of developmental transcription factors, is required for establishment of mammalian anterior pituitary hormone-secreting cell types as well as the formation of specialized neurons of the nervous system. Paediatric patients with pituitary insufficiency are sometimes diagnosed with combined pituitary hormone deficiency disease (CPHD). This disease can be linked to mutations in essential pituitary developmental transcription factor gene...

Introduction: Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy and accounts for 25% of all childhood cancer. The survival rate is now 85% which emphasis the importance of long-term treatment complications. ALL patients treated with cranial radiotherapy (CRT) and chemotherapy are particularly at risk for GH deficiency (GHD), but little is known about central adrenal deficiency. Partial ACTH deficiency is often asymptomatic, but it may lead to deleteri...

Background: Hyponatraemia (HN) is the most common electrolyte disorder of hospitalised patients with a frequency approximating 15%. HN is associated with multiple co-morbidities as well as increases in length of stay (LOS), rehospitalisation, cardiovascular events, and death. This novel HN registry represents the first large-scale international effort to document the impact of HN on clinically relevant outcomes.Methods: The HN registry is an ongoing, glo...

Introduction: Recent reports showed that 2–9.4% of diabetic patients have Cushing’s syndrome (CS) including its mild form, subclinical CS (subCS), but there is no report about screening of acromegaly in diabetic patients. Either 1-mg or 0.5-mg dexamethasone suppression test (DST) is used as the screening test of adrenal CS or Cushing’s disease (CD). The aim of the present study was to screen CS including CD and acromegaly in Japanese diabetic patients.<p cla...

Introduction: It has been previously described that prolactinomas may have a more aggressive behaviour in men than in women.Methods: We performed a retrospective study in 59 patients diagnosed of prolactinoma (19 men). The variables collected were: age at diagnosis, clinical presentation, tumor size and stage (Hardy classification) and treatment response. The results were compared between both genders.Results: Age at diagnosis was ...

Introduction: The recombinant GH receptor antagonist pegvisomant (PGV) is actually used for the treatment of acromegaly when surgery and medical therapy with somatostatin analogues (SSA) have failed. Long term safety and effectiveness need to be evaluated.Material and methods: Retrospective analysis of clinical data from all patients treated with pegvisomant in a pituitary disorders unit.Results: Thirteen patients are being treated...

Introduction: Pendred syndrome is a rare autosomal recessive disease and the classic triad is congenital sensorineural hearing impairment, goiter and impaired iodine organification with abnormal perchlorate discharge test, but hypothalamic tumors are not a feature of this syndrome.Case report: We report a case of a 32-year-old female with Pendred syndrome confirmed by genetic testing and perchlorate discharge test, with goiter, hypothyroidism treated wit...

Studies that consolidate the results of medicamentous and surgical treatment of pituitary adenomas are scarce. Pure endoscopic endonasal transsphenoidal surgery is rather new technique.The aim of this study is to report on early postoperative outcome of pure endoscopic endonasal transsphenoidal surgery and to present the results of multimodal treatment in patients with postsurgical failure.We reviewed 117 consecutive patients who u...

Context and objective: Illness perceptions pertain the pattern of beliefs patients develop about their illness. These views are determinants of behavior directed at the illness. Illness perceptions are determinants of quality of life (QoL). QoL remains impaired in patients after treatment of endogenous hypercortisolism, however, illness perceptions were never studied in these patients. The objective of the current study was to explore illness perceptions and its relation with ...

Introduction: Somavert is a GH receptor blocker, which inhibits hepatic production of IGF1. While it has been approved for the treatment of acromegaly since 2003 there are few data regarding its effects in everyday clinical practice.Methods/design: ACROSTUDY is an open-label, international, prospective, non-interventional, post-marketing surveillance study monitoring the long-term safety and efficacy of Somavert.Results: As of Dece...

Objects: Based on the recently published literature, the incidence of single- or multi-axis anterior pituitary insufficiency following severe craniocerebral injury was between 33 and 68%. The mean patient age was between 36 and 45 years.Methods: Using a prospective and standardized protocol, we investigated anterior and posterior pituitary function following craniocerebral injury III° (determined by Glasgow Coma Score) in 35 young patients 14–4...

Objectives: Long-term results of medical treatment of macroprolactinoma in children and adolescents (<20 years).Patients and methods: Retrospective analysis of all the cases of macroprolactinoma occurring in children and adolescents, medically treated in two university centers.Results: 38 patients, 25 girls 13 boys, age at diagnosis: 15.7±2.8 years (only two cases before 12 years). At diagnosis, 2/3 presented with headache...

Introduction: Since aggressive pituitary tumors are rare, there are no clear guidelines considering treatment of these tumors. A wide range of treatments have been used, with various success.Case report 1: A 58-year old lady presented with sudden severe headache and ptosis of the left eye. MRI revealed an expansive intrasellar, suprasellar and bilateral parasellar process with extension to the skull base which was inaccessible for neurosurgery. Pituitary...

Introduction: Lymphocytic hypophysitis is an uncommon autoimmune disease usually presenting during or just after pregnancy. It may be followed by panhypopituitarism. In such case is extremely rare for a woman to have a normal delivery again.Case report: We report the case of a 28-year-old woman who had a successful delivery 2 years after lymphocytic hypophysitis which had resulted in panhypopituitarism. The young woman presented with amenorrhea, symptoms...

Case report: We present the case of a patient with somatotroph adenoma combined with neuronal choristoma Pituitary Adenoma Neuronal CHoristoma (PANCH). A female patient, 44 years of age, manifested with acromegaly type features since 1993, while mentioning also headaches, amenorrhea, and peripheral type visual disturbances since 1997. The clinical examination revealed an obese woman with typical acromegalic features. The laboratory evaluation before pituitary surgery showed a ...

Pomc synthesis and ACTH secretion by the anterior pituitary are controlled by two major, opposing players namely CRH and glucocorticoids. Most studies were performed on the AtT-20 mouse corticotroph tumor cell line or Pomc-transfected cells.Aim: Aim of the present study was to evaluate the effect of CRH and DEX on Pomc expression and ACTH secretion in normal rat corticotropes in vitro.Methods: Rat anteri...

Introduction: The proto-oncogene KIT (CD117) is widely expressed in neoplastic tissues. Gain-of-function mutations of the KIT gene were found in some types of leukaemia, gastrointestinal stromal tumours, germinal cell tumours and rarely in other malignancies. Studies on the KIT protein and gene in different tumours have been intensified by the availability of imatinibe mesylate, KIT/PDGFRA inhibitor.Methods: We have immunohistochemically investiga...

Radiation therapy is a useful adjuvant tool for the management of difficult acromegalic patients. Its effects on cardiovascular morbidity are still unknown. Aim of the study was to investigate the long-term effects of radiotherapy on metabolic parameters and cardiovascular risk factors.A total of 42 acromegalic patients (11 M and 31 F, age: 55±12 years, RT group), cured after conventional RT (CRT, n=31) or radiosurgery by gamma-knife (GKRS, <...

Introduction: Functional GH deficiency has been described in fibromyalgia (FM). The efficacy of GH as add-on treatment has been suggested in small studies, but little is known in larger and homogeneous populations.Design: Patients (120) were enrolled in a multicenter, randomized, placebo-controlled trial for 18 months (NCT00933686). FM impact questionnaire (FIQ) >75 (severe), duration of FM >18 months, and stability of the standard therapy (amitr...

GH replacement is widely used in adults with hypopituitarism, but its effect on tumor occurrence and pituitary tumor recurrence is unknown. Furthermore, in literature there are scant with short follow-up time. The available data do not seem to suggest that rhGH replacement increased the incidence of regrowth of pituitary tumor and of cancer in adults with GHD, provided that IGF1 concentrations remain within the normal range for age.The aim of our study w...

Introduction: Several data suggest that male hypogonadism occurs frequently in men with type 2 diabetes mellitus (T2DM) but underlying pathophysiological mechanism remains partially unknown. In order to investigate the short term effect of hyperglycaemic state on hypothalamic–pituitary–gonadal axis we prospectively studied 18 men with T2DM younger than 55 years at the time of first diagnosis of T2DM. We compared men with HbA1c≥9.0% with men with HbA1c≤9.0...

Introduction: GH and its receptor (GHR) are expressed in retinal ganglion cells (RGCs) in the eyes of chick embryos, and in mouse, rat and human eyes. Within the retina, exogenous GH has neuroprotective actions, mediated by caspase-dependent and caspase-independent mechanisms that may also be dependent upon IGF1 signaling. Conversely, the immunoneutralization of endogenous GH promotes apoptosis in the retina and in isolated RCGs. The functional relevance of retinal GH was furt...

Background: Pituitary apoplexy occurs when a tumor undergoes acute hemorrhage, infarct, or both. This often leads to acute severe symptoms (clinical) but can also occur without them and diagnosed on CT/MRI, surgery, pathology (subclinical). To investigate clinical and subclinical apoplexy in nonfunctioning tumors (n=221) from our database.Design: Retrospective review of clinical presentation, tumor characteristics and outcome of 24 patients, 11 fe...

Introduction: In this study, we aimed to compare GH values obtained in oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT) in healthy individuals.Material and methods: Data of 18 healthy volunteers were analysed (10 male and 8 female). Firstly all subjects were evaluated with 75 g oral glucose tolerance test. In another day, intravenous glucose tolerance test was performed. Serum glucose, insulin and GH levels obtained durin...

Objective: To evaluate the reliability of GH stimulation tests in multiple pituitary hormone deficiency (MPHD) and isolated GHD.Materials and methods: In 19 children with MPHD, we analysed the results of insulin tolerance test (ITT), clonidine and sleep tests, anthropometric parameters, IGF1, bone age, pituitary hormone levels±MRI. GH provocation tests were repeated after variable periods, mostly 6–24 months. The GH provocation tests were consi...

Background: The water deprivation test (WDT) with direct or indirect measurement of plasma vasopressin (AVP) is the method of choice for the differential diagnosis of the polydipsia–polyuria syndrome. In theory, direct measurement of AVP is highly attractive but hampered by technical difficulties.Objective: To evaluate the utility of copeptin, a surrogate of AVP secretion, in the diagnostic work-up of the polyuria–polydipsia syndrome, and to co...

Context: Recombinant human GH (rhGH) is indicated for the treatment of adult subjects with GH deficiency (GHD). However, conflicting data are available on the efficacy of rhGH treatment in elderly GHD patients.Objective: To assess the efficacy of rhGH treatment in elderly GHD subjects.Methods: We searched PubMed, Cochrane Library, Web of Science, and EMBASE.Study selection: Eligible studies included GHD patie...

Introduction: Adults with GH deficiency (GHD) have a decreased life expectancy due to cardiovascular diseases (CVD). Recombinant GH treatment has made replacement therapy an option in adults with GHD. Data on long-term efficacy and safety are limited and the implication for life expectancy remains to be established.Methods: The Dutch National Registry of GH Treatment in Adults was founded to gain more insight into long-term efficacy and safety of GH ther...

Introduction: Cardiovascular complications are the most relevant cause of mortality in patients with acromegaly.Aims: To evaluate the effects of chronic excess of GH, IGF1 and PRL on blood pressure, heart rate and pulse in patients with active acromegaly.Subjects and methods: Sixty-three patients (22 men and 41 women; aged 18–76 years) with macroadenoma of hypophysis (45 – somatotropinoma, 19 – somatomammotropinoma) ...

Wnt developmental pathways, have been implicated in a number of cancers. Wnt signaling proteins activate the B-catenin transcription factor which induces transcription of the oncogenes Cyclin D1 and Myc (Luo et al. 2007). Elston et al. (2008) found that Wnt inhibitors were down-regulated in pituitary tumours. Overexpression of Survivin, an inhibitor of apoptosis,correlates with poor prognosis and drug resistance (Altieri 2003, Ghosh et al. 20...

Objective: To assess the influence of use of long-acting somatostatin analogs on long-term health-related quality of life (HR-QoL) in relation to disease control in patients surgically-treated for acromegaly.Design: Cross-sectional study in two University Medical Centers in The Netherlands.Patients: One hundred and eight patients (47 m/61 f, mean age 54±11 years) with a minimal follow up period of 1 year after pituitary surger...

Introduction: Cardiovascular disease is present in up to 60% of patients diagnosed of acromegaly and is responsible of the major related morbidity and mortality.Case report: A 79-year-old-woman with previous history of diabetes mellitus and hypertension was admitted for acute pulmonary edema. Transthoracic echocardiogram showed a severe left ventricular dysfunction with an ejection fraction of 20%, dilated left ventricle and left atrium with a moderate m...

Introduction: Pituitary aplopexy is rare (0.6 to 12.3%). Sudden expansion of pituitary tumor, from hemorrhage or infarction, may lead to permanent vision loss, paresis or death. We describe two cases of apoplexy as the initial manifestation of pituitary tumor.Case 1: Male, 30 years, healthy, observed in the emergency room (ER) complaining of headache, visual deficit and left ptosis for 3 days. He had left ptosis and bilateral paresis of the IV pair. Magn...

Lymphocytic hypophysitis is a rare endocrine autoimmune disorder. Principal laboratory markers for diagnosis are antipituitary antibodies (APA). So far there are no standardized methods for the detection of APA and it is not completely clear which antigens are they targeted to as well. At present the indirect immunofluorescence technique is commonly used for their detection. For this purpose cryostat sections of pituitary gland are used. Commercially accessible sections are ac...

Periodontal disease frequency was screened and compared in 15 acromegalic patients with age and sex matched 50 healthy subjects. Periodontal evaluation included panographic radiography, plaque and gingival index and depth determination and clinical parameters. Estimated disease duration was 2–10 years in acromegalic patients (8 female, 7 male patients, 52±13 years). Five patients on somatostain analog therapy had inactive disease for at least 2 years and 10 patients ...

Introduction: Observations in patients with GH disturbances and in normal populations have suggested that GH/IGF1 activity could have anti-inflammatory effects. On the other hand, in vitro studies have shown that IGF1 may stimulate the immune system.Methods/design: The study population consisted of 12 healthy volunteers (mean age 36, range 27–49 years) treated with GH for 3 weeks (1st week 0.01 mg/day, 2nd 0.02 mg/day, 3rd 0.03 mg/day) and su...

GH excess is considered as one of the causes of secondary osteoporosis with an increased risk of vertebral fractures in men and post-menopausal women with acromegaly. GH excess in acromegaly is also frequently associated with type 2 diabetes which is considered as a risk factor for fragility fractures in the general population. In this cross-sectional study, we evaluated whether type 2 diabetes may influence the prevalence vertebral fractures in acromegaly. Fifty-seven males w...

Hyperprolactinemia may cause bone loss in pre-menopausal women and men. Data on fractures are scanty and it is still unclear which is the skeletal impact of hyperprolactinemia in post-menopausal women. The aim of this study was to evaluate the prevalence of vertebral fractures in post-menopausal women with hyperprolactinemia.Forty post-menopausal women (median age 57 years, range: 47–81) with prolactin (PRL)-secreting adenoma and 119 control post-me...

Introduction: Daily administration of Pegvisomant normalizes IGF1 levels >71% of acromegalics (1). Few studies have assessed the efficacy of weekly administration. We assessed the efficacy of weekly pegvisomant for 12 months, after withdrawal of long-acting somatostatin analogs (SSA) in acromegalics previously controlled on combination therapy.Design: Fifteen subjects (8 males), age 58 (35–80) (median (range)) years on combination therapy of hig...

Two nationwide surveys on acromegaly (AcroBel-1 and 2) have been performed in Belgium at an interval of five years, including centralized GH and IGF1 measurements in most patients. A normal IGF1 for age was observed in 56% of 311 vs 74% of 365 treated patients, in 2004 and 2009 respectively.Factors responsible for this improvement were investigated. A selection bias was unlikely as the follow-up rate was higher in patients with active (83%) or medically ...

Introduction: To date, two pharmacogenetic studies investigated the effect of the common exon 3 deletion of GH receptor (d3-GHR) variant in small series of acromegalic patients treated with Pegvisomant (Peg), suggesting an association of d3-GHR allele with better response to Peg.Aim: To assess the influence of d3-GHR variant in a large cohort of acromegalics with active disease and resistance to somatostatin analogues (SSA) treated with either Peg monoth...

Acromegaly is accompanied by increased morbidity and mortality. The delay between onset of first symptoms and diagnosis of the disease is 6 to 10 years. Acromegaly causes typical changes of the face. We hypothesized that face classification software might help distinguishing between subjects with and without acromegaly on regular photographs and, thus, might help improving early recognition of acromegaly.Methods: We took frontal and side photographs of t...

We present an experimental study on human prolactinoma in cell culture from a patient that partially responded to cabergoline treatment and had to have surgical treatment.Aim: The aim of the study was to assess the effect of cabergoline, dopamine and melatonin on prolactin secretion and cell proliferation in human prolactinoma cell culture from a patient that had transsphenoidal surgery.Material and methods: Tissue specimen derived...

Giant prolactinomas are rare and their treatment and outcome has been addressed only in isolated case reports. Some patients develop treatment-resistant tumors. We describe a patient with an invasive PRLoma resistant to conventional therapy. A 40-year-old female was diagnosed at age 22 a PRLoma who, although having received all available formulations of dopamine agonists over a period of 18 years, responded neither clinically, nor hormonally (PRL 9560.0 ng/ml, nv <20). At ...

Lost to follow-up (LTFU) is a frequent problem in chronic diseases not evaluated yet in acromegaly despite the long-term need of medical treatment and complications survey in this disease.Objectives: Evaluation of the prevalence of LTFU patients in a multi-center cohort, characteristics of defaulters and description of their evolution after they have been searched and found.Méthods: Observational multicentric (25 centers study...

Introduction: CD is a rare disease. Our aim was to describe demographic and clinical characteristics together with initial management of patients with CD.Patients and methods: A retrospective analysis of 437 CD patients diagnosed between 1996 and 2009, followed in 5 tertiary centers (Bordeaux, Grenoble, Lyon, Marseille, Paris) was performed in the frame of the national program for rare diseases.Results: 347 (80%) were women. Mean a...

Background: Signal intensity in T2 weighted (w) MRI in somatotroph pituitary adenomas has been described to correlate with histological granulation pattern. Long-term somato-statin analogue (SSA)-response is associated with both histological subtype and T2wMRI.Objective: To describe secretory baseline characteristics in newly diagnosed acromegalic patients in relation to T2 signal intensity. Moreover, to test whether T2 w images could predict preoperativ...

In acromegaly symptom control can be achieved by lowering insulin-like growth factor 1 (IGF1) concentrations to the age-adjusted normal range. However, even with optimal surgery and current medical therapies (dopamine agonists, somatostatin analogues), 30–50% of patients do not achieve target concentrations of IGF1 and GH. Pegvisomant (PEGV), a new GH-receptor antagonist, given as s.c. injections at variable dosages, could normalises IGF1 concentrations in ~70% of acromeg...

Introduction: Cushing’s disease (CD) is characterized by various symptoms, amongst which fatigue, muscle weakness and depression. The chronic state of hypercortisolism severely impairs quality of life (QoL). In addition, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. Transsphenoidal surgery is the primary treatment for CD, but long-term remission rates are disappointing. We performed a prospective trial in which stepwise medical treatment was applied ...

Background: The long-term prevalence of adrenal insufficiency after transsphenoidal surgery for GH secreting pituitary adenomas was unknown. However, recently a single study reported a high prevalence of adrenal insufficiency after surgical and/or medical treatment without postoperative radiotherapy in acromegalic patients.Aim: To assess the prevalence and incidence rate of adrenal insufficiency in consecutive patients during long-term follow-up after su...

Women with acromegaly present often menstrual irregularity, anovularity and infertility. A direct role of GH and IGF1 excess on the hypothalamus–pituitary–gonadal axis, hyperprolactinemia and an impaired gonadotrophin secretion related to a tumor mass effect, or polycystic ovary syndrome have been suggested as possible mechanisms related to infertility. However, no systematic data are available on fertility in these patients. The aim of this retrospective study was t...

Most kindreds of familial isolated pituitary adenomas (FIPA) with mutated AIP develop somatotropinomas, characterized by an aggressive clinical phenotype including early age at diagnosis, large tumours and frequent invasiveness. In non-family cases, the prevalence of AIP mutations in pituitary adenomas is lower than 10%. There is no information of AIP prevalence in isolated somatotropinomas characterized by poor response to conventional treatment.Aim: To...

Introduction: Pituitary adenomas are benign neoplasms which grow slowly, but that can recur even after apparent radical resection. Until now, markers predicting regrowth and invasiveness have not been completely characterized.Design: We investigated cell proliferation and apoptosis parameters in 20 radically resected pituitary macroadenomas (six GH, two PRL, two ACTH, one FSH and nine non-secreting), in order to predict recurrence risk. Tumour regrowth w...

Introduction: The multi-receptor targeted somatostatin analogue pasireotide has high affinity for sst5; this receptor may play an important role in glucose metabolism. Two studies in healthy male volunteers evaluated the mechanism and management of hyperglycemia associated with pasireotide.Methods: A randomized, Phase II study assessed insulin secretion and glucose metabolism during 8 days of pasireotide 600 or 900 μg sc bid (n=19 ...

Aim: To investigate the efficacy of octreotide LAR therapy in acromegalic patients as primary or secondary therapy.Methods: Ten acromegalic patients diagnosed at Clinic of Endocrinology in Sarajevo (seven females and three males, mean age 55.2±7.2 years, age range 40–65 years, five patients with microadenoma and five patients with macroadenoma) were treated with octreotideLAR. Operated were 60% of patients. Concentration of hGH and IGF1 was eva...

Introduction: It has been estimated that 15–20% of FIPA families harbor an AIP gene mutation (AIPmut). To our knowledge ~50 sequence variants -pathological and otherwise- have been described to date. We report a new FIPA family with an extensive genealogy, in which 4 members have pituitary adenomas in the setting of a novel AIPmut.Patients and methods: The index patient is a 37-year-old man, who presented with childhood onset of somatotropinoma and ...

Two randomized open-label, phase II studies evaluated an octreotide hydrogel implant to suppress serum GH and IGF1 levels in adult acromegaly patients. Implants were inserted subcutaneously in the upper arm for 6 months. Patients in study 1 received 1 (n=5) or 2 (n=6) 52-mg octreotide (60 mg octreotide acetate) hydrated implants; patients in study 2 received a hydrated (H) or nonhydrated (NH) 84-mg octreotide acetate implant (n=34, 1 excluded from efficacy...

Background: Surgery of the pituitary gland is increasingly being performed through an endoscopic approach. We report the results of the first 26 patients after transition from microsurgery to endoscopic transsphenoidal surgery at our institution.Methods: Medical records of 26 consecutive patients (13 females) with a median age of 59 years who underwent endoscopic transsphenoidal surgery by a single surgeon from 2008 to 2010 and had a follow-up of at leas...

Introduction: Pasireotide is a multi-receptor targeted somatostatin analogue with high affinity for sst5, which is commonly expressed in corticotroph adenomas, thus having potential as therapy for Cushing’s disease.Methods: One hundred and sixty-two patients with persistent/recurrent or de novo (if not surgical candidates) Cushing’s disease were randomized (double-blind) to pasireotide 600 μg (n=82) or 900 μg ...

Introduction: Monoclonality of pituitary adenomas is an established fact. Still, there are exceptions and polyclonality may correlate with aggressive tumor behavior. In order to test association of clonality with pituitary adenoma characteristics in a series from Romania, we implemented a protocol for X-chromosome inactivation analysis at the androgen receptor (AR) locus (HUMARA) and validated it in a number of tumor samples.Objective: To establish and v...

Introduction: Prolactinomas, although considered benign, show various intensity of aggressiveness. Some remain constant for whole life period while some harbour initially with invasive extension to the parasellar area. We aimed to evaluate the effect of age and gender on the invasiveness of prolactinomas.Material-methods: One hundred and thirteen patients with prolactinoma were retrospectively evaluated. Magnetic resonance images were carefully examined ...

Introduction: Clinical symptoms in craniopharyngioma have been repeatedly described in the literature, but few studies have addressed the issue of acute-onset symptoms in children or adults. Refinements of diagnostic procedures and altered scanning routines over the last two decades may in theory have affected patterns of clinical presentation.Objective: To study the clinical phenotype of patients with newly diagnosed craniopharyngioma, with focus on var...

Pregnancy is associated with an increased risk of tumor growth in macroprolactinoma leading to discuss surgery in such cases.Objectives: Impact of pregnancy on prolactin secretion and tumor growth in a cohort of women with macroprolactinoma, including large tumors >20 mm, and medically treated.Methods: Retrospective study of all the women with macroprolactinomas diagnosed in two university hospitals, treated by dopamine agonist...

Introduction: Primary empty sella (PES) is a frequent ‘incidental’ finding reported in 5–25% of general population and is associated with endocrine abnormalities in 8–60% of cases. In this collaborative multicentric study we evaluated cardiovascular risk by assessing clinical characteristics, glucidic profile and lipid parameters.Design: A total of 94 PES patients (39M-55F; mean age 50.3±0.9 years; mean BMI 28.9±0.5 kg/m<sup...

Objectives: Our aim was to assess health-related quality of life in patients with Cushing’s disease (CD) and patients with non-functioning pituitary adenomas (NFPA).Methods: We assessed patients with CD and with NFPA treated at our outpatient units. Health-related quality of life (HRQoL) was assessed with the SF-36, a widely used generic measure of health status and the CushingQoL, a newly developed disease generated questionnaire to evaluate HRQoL ...

Pituitary adenomas represent more than 80% of all sella turcica tumors and 10–15% of all intracranial tumors in adults. Topoisomerase II α (TopoIIα) is recognized as a reliable tumor proliferative activity marker. Evaluation of its expression facilitates the identification of more aggressive neoplasms.Aim: To assess the topoIIα expression in pituitary adenomas as the marker of the tumor aggressiveness, recurrence and progression.<...

In many neoplasms, excessive angiogenesis is prognostic factor, independent from proliferation. Previous studies confirmed correlation between cyclooxygenase-2 (COX-2) expression and micro-vascularization density in pituitary tumors. Moreover, nonsteroidal anti-inflammatory drugs have strong inhibiting effect on COX-2 expression and possible anti-tumor activity.Aim: To assess COX-2 expression in pituitary adenomas, its relation to adenoma type as well as...

Background and objective: Pituitary adenomas (PAs) affect about half of the patients with multiple endocrine neoplasia type 1 (MEN1); in the most of cases PA is a PRL-oma and generally more aggressive than the sporadic form. The aim of this study is to evaluate the recent changes in clinical presentation and therapeutic approach of MEN1-related PAs.Patients and methods: The study population included 17 patients with MEN1-related PA followed-up between 19...

It has been hypothesized that prolactin may act on the immune system. It has been suggested that prolactin may act on the immune system and may be implicated in the pathogenesis of autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, as mild hyperprolactinemia has been found in patients with systemic lupus erythematosus.We tested the hypothesis that prolactin may act on the immune system and induce the development of autoim...

Background: Dopamine agonists (DA) are used as the first-line trearment in patients with macroprolactinomas. Late resistant to DA(cabergoline) therapy may occur. Patient with resistant macroprolactinoma may end up receiving a relative high dose of DA. These patients should be advised to take up radiotherapy option as earlier as possible to avoid the need of high dose dopamine agonist. We present a 63-year-old man who presented in 1999 with visual loss,due to giant macroprolact...

In acromegaly, an excessive GH secretion by pituitary adenoma, minimal active disease may be defined as slow progression of characteristic signs and symptoms at presence of slightly elevated or normal IGF1 levels and lack of GH suppression after glucose load. Nadir post-glucose GH level defining active disease is under permanent discussion and depends on assessment methods. IGF1 reference range is wide, must be age-adjusted and often is sex-dependent. From mid-00’s excess...

Background: This study was conducted to determine whether prolactin (PRL) influences radiological findings of benign breast lesions.Patients and methods: We observed 50 patients with nipple discharge: 23 patients with normal serum prolactin levels (group 1; n=23) and 27 patients with hyperprolactinemia (group 2a; n=27). Patients observed during this study underwent breast ultrasonography (US) and mammography. Patients with hyperprolactinemi...

Ganglion cells in the sella turcica are rarely associated with endocrinological disease. We report the case of a 72-year-old woman who presented with typical signs and symptoms of hypercortisolism. Endocrinological work-up confirmed ACTH-dependent Cushing’s syndrome with loss of circadian cortisol rhythmicity and a pathological dexamethasone suppression test. MRI revealed right-sided sellar floor excavation but no clear-cut adenoma. Via a right-sided transnasal approach, ...

Inflammatory lesions of the pituitary gland are rarely encountered. Recently, the concept of IgG4-related systemic disease was proposed and several cases associated with infundibulo-hypophysitis were reported. We report 4 additional cases and review the cases in the literature. Case 1: 75-year-old female had diabetes insipidus due to infundibulo-neurohypophysitis for 25 years and chronic thyroiditis. She developed obstructive jaundice and surgery showed autoimmune pancreatitis...

Introduction: Diabetic retinopathy (DR) is a vision threatening chronic microvascular complication of diabetes mellitus (DM). The potential roles of GH and insulin-like growth factor 1 (IGF1) in DR have been evaluated in vitro and in vivo. The present study aimed to assess the frequency and severity of retinopathy in acromegalic patients with various disease activity and glucose tolerance states (GTS).Methods: All acromegalic patients follo...

In prolactin secreting pituitary adenomas, surgery markedly reduced with the efficacy of dopamine agonists in controlling prolactin hypersecretion and reducing tumor mass. Some surgeons, instead of necessity of almost life-long medical therapy, prefer and recommend surgery as a first line treatment with potentially high success rates especially in microprolactinomas. We evaluated our patients with prolactinoma operated mostly without any evidence of resistance or intolerance t...

Background: GH deficiency (GHD) may occur in about 60% of acromegalics treated and cured by surgery or radiotherapy. Effects of GH replacement have not yet been extensively studied in such a patients.Aim: To investigate whether rhGH replacement improve metabolic parameters in acromegalic patients who become GHD.Patients and methods: Forty GHD patients (mean age (S.D.): 48±10, BMI 27±3 kg/m2) were...

Introduction: The multi-receptor targeted somatostatin analogue pasireotide has demonstrated efficacy in reducing cortisol in patients with Cushing’s disease in a large, randomized, double-blind, Phase III study. The effects of pasireotide on the signs and symptoms of Cushing’s disease were also investigated as secondary objectives in this trial.Methods: Adult patients with persistent/recurrent or de novo Cushing’s disease were rand...

Introduction: Hundred years ago Harvey Cushing attempt first human pituitary transplantation. This operation, in different modifications, was performed in the next 50 years, but now is used rather only in animal experiment. The problem of effective therapy of hypopituitarism, other that substitution, is however still open. That encouraged us to present a patient 50 years after pituitary xenotransplantation.Case: A 75-year-old woman was admitted to hospit...

Introduction: Impaired glucose tolerance and overt diabetes mellitus are frequently associated with acromegaly. The aim of this study was to find whether these alterations could be reversed after transsphenoidal surgery.Patients and methods: Two hundred and thirty-nine acromegalic patients were studied before and 6–12 months after transsphenoidal surgery. Diagnosis of active acromegaly was established on the basis of widely recognized criteria. In e...

Introduction: Parasellar extension of macroprolactinomas defined on imaging criteria was reported to be an independent predictor of hormonal resistance to dopamine agonists (DA).Methods: Two hundred and twelve patients with macroprolactinomas (87 M/125 F), treated with DA for 5 years median period; prolactin (fluoroimmunoassay or chemiluminescence), CT scan and/or MRI with contrast agents were performed; maximum diameter evolution was reported.<p cla...

Patients with acromegaly resistant to conventional drug treatment currently can advantage with GH-receptor antagonist pegvisomant. To date, at doses up to 40 mg/day, it is capable of normalizing circulating IGF1 in until 97% of patients. Here we present the multicenter experience in Rome with Pegvisomant as a therapeutic option in acromegaly. This is an observational study including a total of 61 patients (21 males and 40 females) treated with pegvisomant for up to 7 years. Of...

Pasireotide (SOM230), a somatostatin (SST) analogue targeting multiple SST receptors, is effective in reducing urinary free cortisol in patients with Cushing disease (CD), due to inoperable or recurrent ACTH secreting pituitary adenomas. The efficacy of SOM230 seems to be dependent on the presence of appropriate SSTRs, mainly SSTR2 and 5, on the membrane of tumor cells. Polyclonal antibodies available up to now recognizing cellular intracellular sites of receptors and their re...

The influence of first-line transsphenoidal surgery (TSS) or first-line somatostatine analogue (SSA) treatment on coronary risk factors in patients with acromegaly has rarely been examined. Aim of this study was to evaluate risk factors for coronary heart disease in 3 different patient groups with treatment naïve, active (ACT), first-line medically controlled (MED) and first-line surgically treated (SUR) acromegaly and to calculate the Framingham Risk Score (FS).<p cl...

Background: Of the currently available treatment regimes for acromegaly, pegvisomant (PEG-V) has the highest efficacy. During PEG-V treatment, GH serum levels increase. The exact mechanism behind this is remains unclear. It could be explained by an ultra-short feedback loop via GH receptors in the anterior pituitary gland.Objective: To assess the level of GH receptor (GHR) mRNA expression in somatotroph adenomas and to evaluate whether GHR blockade by PE...

Pituitary adenomas account for ~10% of intracranial tumors and result in morbidity due to both altered hormonal patterns as well as side effects of therapy. Currently, great attention has been given to preventive strategies, and in this context, the use of functional foods with chemopreventive compounds appears to contribute much in this process. Among these substances, we highlight the consumption of carotenoids is associated with reduced risk of chronic diseases including ca...

Sleep apnea syndrome is highly prevalent in acromegaly and only partially reversible after biochemical control of the disease. Consequences of SAS are serious and are associated with increased morbidity and mortality.The present study evaluates clinical aspects in acromegalic patients with sleep apnea syndrome (SAS), diagnosed and followed-up in the Clinic of Endocrinology, Timisoara, in the period 2007–2010. All the cases were confirmed and investi...

Context and objective: Fatigue and excessive sleepiness have been reported after treatment of nonfunctioning pituitary macroadenomas (NFMA). Because these complaints may be caused by disturbed nocturnal sleep, we evaluated objective sleep characteristics in patients treated for NFMA.Design: Controlled cross-sectional study.Subjects and methods: We studied 17 patients (8 women, mean age 54 years), in remission of NFMA during long-te...

NVP-BEZ235 is an orally available ATP competitive inhibitor of class I PI3K and mTOR. As such it suppresses Akt phosphorylation downstreams to PI3K and to mTOR complex 2 in addition to p70/S6K1 phosphorylation downstreams to mTOR complex 1 and displays potent antiproliferative activity in tumors with dysregulated the PI3K/Akt pathway. Administration of NVP-BEZ235 in human nonfunctioning pituitary tumors in primary cell culture suppressed cell viability by more than 50% in 37 o...

Primary pituitary tumors are relatively rare and mainly benign.The aim was to study the primary pituitary tumors presenting during a 10-year period in a single center.The archives of all patients with primary pituitary tumors having been hospitalized from 01.01.2000 to 30.06.2010 in the Department of Endocrinology and Metabolism of Metaxa Hospital were studied. Within this cohort of patients 128 were female (63%) and 75 (37%) were ...

Pituitary apoplexy is a rare syndrome due to hemorrhagic infarction of a pituitary adenoma. We analyze the circumstances of diagnosis, clinical features and evolution in a retrospective review of patients with pituitary apoplexy admitted between 2000 and 2010, diagnosed by pathological exam and/or suggestive imaging for pituitary haemorrhage.Results: From 31 patients with pituitary apoplexy (11 women, 20 men) with a mean age of 48 years at diagnosis (20&...

Aim: To evaluate the effects of short and long-term treatment with PEG on rhythm disturbances in a cohort of acromegalic patients resistant to long-term high-dose therapy with SA.Patients and methods: Thirteen patients (4 M, 9 F, aged 44±9.25 years) entered the study. All patients started PEG at initial dose of 10 mg daily, then increased of 5 mg every 6 weeks on the basis of IGF1 levels, until IGF1 normalisation or until the achievement of the maxi...

Magnetic resonance imaging has dramatically improved the diagnostic accuracy in the evaluation of the hypothalamo-pituitary region and investigation of morphological and structural pituitary abnormalities.Aim: To estimate pituitary dysfunction types and clinical presentation of pituitary lesions on MRI investigation, assigned as hypointense intrasellar mass (microadenoma-MA).Patients and methods: We examined 19 children and adolesc...

A 53-year-old man with acromegaly was referred for neurosurgical treatment. At admission: GH 240 ME/l at all time points of glucose tolerance test, IGF1 – 415.1 ng/ml, brain MRI showed pituitary adenoma 34×32×27 mm extending suprasellar, deforming and displacing optic chiasm, parasellar to both cavernous sinuses and surrounding left internal carotid artery. Clinical blood tests revealed marked erythrocytosis – 6.1×1012, Hb – 200 g/l, HC...

A decrease in insulin sensitivity (IS) is associated with increasing visceral adiposity. An inverse correlation has been demonstrated between Intramyo-(IMTG) and intrahepatocellular triglyceride (HCTG) concentrations and IS. Patients with AA have reduced IS but IMTG and HCTG content has not been studied.Eight patients with AA (IGF-I >ULN, median 1.83×ULN (range1.16–4.38) ((6 M), median age 39.5 (range 23–66) years, median BMI 30.6(23.5...