Endocrine Abstracts

Increased mortality due to atherosclerotic cardiovascular disease has been described in adult patients with hypopituitarism, although the precise underlying mechanisms remain undetermined. Various abnormalities of coagulation and fibrinolysis occur in patients with thyroid diseases. Conversely, there are conflicting reports concerning the effects of growth hormone replacement on coagulation and fibrinolytic pathways in adults with hypopituitarism, and there are limited data on...

Objective: Agouti related peptide (AgRP), the endogenous antagonist of the melanocortin 3 and 4 receptors, is expressed at high levels in the arcuate nucleus of the hypothalamus. Some studies have demonstrated that intracerebroventricular AgRP administration increases plasma LH, FSH, testosterone levels. It also increases hypothalamic LHRH release in vitro, an effect that can be prevented by addition of melanocyte stimulating hormone. These findings suggest that AgRP ma...

Introduction: GH rises dose dependently during treatment with the GH receptor antagonist pegvisomant. Ghrelin stimulates GH secretion. In de novo acromegalic patients with high GH levels, ghrelin levels are lowered and fat mass is reduced. Leptin levels are positively correlated to fat mass. We performed this cross-sectional study to evaluate whether elevated endogenous GH in acromegalic patients on pegvisomant treatment (peg) reduces ghrelin and leptin levels.<p class="ab...

Introduction: Acromegaly is well known to induce hypertrophy and hyperplasia in many organs, i.e. thyroid gland, colon, prostate. This action is presumably exerted by the elevated GH and IGF1 levels. In our study, we investigated the alterations of the adrenal glands seen in acromegaly.Aim: To assess the changes in adrenal morphology and functional status in a series of patients with acromegaly.Subjects and methods: Fifty-four acro...

Aims: We aimed to investigate IGF1 and IGFBP3 gene polymorphisms in patients with acromegaly.Methods: We included 34 patients with acromegaly and 37 healthy subjects to study. At baseline examinations, antropometric measurements were done. Genomic DNA from the patients and controls were prepared. Serum, glucose, insulin, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, GH, IGF1 and IGFBP3 levels of subjects were analyzed.<p class="a...

Background: Acromegaly is associated with increased morbidity and mortality from cardiovascular disease. Hypertension is a number of common cardiovascular risk factors in acromegalic patients. The aim of this study was to investigate association between the frequencies of angiotensin converting enzyme (ACE) I/D and angiotensinogen (AGT) M235T polymorphisms, the genes belongs to the renin–angiotensin–aldosterone system, and clinical parameters of acromegaly patients.<...

A 58-year-old male patient presented with a 2 months history of bilateral frontotemporal headache, fatigue and impaired vision. Further exploration revealed short term memory losses, confusion, gait disturbances, decreased libido and erectile dysfunction. Radiological investigation showed a 4 cm pituitary mass with destruction of the upper clivus and left petrous apex associated with a 5 cm large suprasellar cyst bulging upward into the 3d ventricle with obstruction hydrocepha...

Background: Nonfunctioning pituitary adenomas are commonly diagnosed as large tumors. Most are detected incidentally during imaging studies. The aim of this study was to evaluate clinical presentation, characteristics and outcome of nonfunctioning pituitary macroadenomas incidentally (NFPMI) discovered.Methods: Twenty-seven patients (mean age 58.9 years, 45–82; 18 males:9 females) with NFPMI were studied. They represent 13.1% of NFPM followed in our...

Acromegaly is frequently diagnosed late and pituitary macroadenoma is revealed in the majority of patients. Treatment usually needs combination of several treatment modalities to suppress the disease activity. Efficacy of our treatment of acromegaly was not analysed till now.Aim: First analysis of the diagnostics of acromegaly, efficacy of treatment, its complications and status of acromegaly patients in six tertiary referral centers in the Czech Republi...

Objective: Psychopathology and maladaptive personality traits are often observed during the active phase of Cushing’s disease (CD). We hypothesized that patients with long-term cure of CD show persistent psychopathology and maladaptive personality traits.Aim: To evaluate psychopathology and personality traits in patients with long-term cure of CD.Patients and methods: We included 67 patients cured of CD (15% males, mean age 53...

Introduction: Cushing’s syndrome (CS) results from inappropriate exposure to excessive glucocorticoids. Untreated, it has significant morbidity and mortality.Case report: A 38-year-old woman with a typical appearance of CS was admitted for further evaluation of hypercortisolism. The serum cortisol level was elevated without diurnal rhythm, with no adequate supression of cortisol after 1 mg dexamethasone suppresion test. Twenty-four-hour urinary free...

Objective: To develop and validate the adult hypopituitarism questionnaire (AHQ) as a disease-specific, self-administered questionnaire for evaluation of QOL in adult patients with hypopituitarism.Methods: The development and validation of a new questionnaire were performed in a standardized manner: item development, pilot-testing and psychometric validation.Result: Content validity of the initial questionnaire was evaluated via tw...

Background: Narcolepsy is hypersomnia of central origin whose clinical features are excessive daytime sleepiness, hypnagogic hallutinations, sleep paralysis and cataplexy which comprises sudden transient loss of muscle tone often triggered by emotions. Narcolepsy with cataplexy is assiociated with hypocretin 1/orexin-A (HCRT 1/ORX-A) deficiency in central nervous system. Because of the link between ghrelin and HCRT 1/ORX-A wake-promoting effects there might be ghrelin deficien...

Background: The so-called silent pituitary adenomas are a subtype of pituitary tumors showing positive immunoreactivity for one or more pituitary hormones, but without any clinical manifestations for oversecretion of these hormones. They are clinically labeled as non-functional pituitary adenomas (NFPA), some of them with particularly aggressive behavior. Rare patients might present with big plurihormonal pituitary tumors which ‘whisper’ hormones (GH or ACTH) and pro...

Introduction: Every year 30 000 patients will suffer a traumatic brain injury (TBI) in The Netherlands. About two-thirds will develop post-TBI chronic fatigue (CF). Hormone deficiencies related to pituitary damage might contribute.Aim: To examine the clinical importance of hormonal and non-hormonal factors as issues contributing to chronic fatigue in post-TBI subjects.Patients and methods: The checklist individual strain (CIS), a w...

Introduction: Discontinuation of GH therapy in patients with COGHD after attainment of final height has been associated with impaired somatic development, altered peak bone mass and cardiovascular risk factors. A well-managed transition of care between paediatric and adult health services can improve the clinical and social outcomes in adolescents with GHD.Objective: To assess the quality of the transfer between children and adult medical services in our...

The diagnostic approach to GH deficiency (GHD) in obese patients is complicated by the reduced spontaneous and stimulated GH secretion associated with overweight. A GH response to GHRH+arginine lower than 4.2 μg/l is currently considered indicative of GHD in obesity (Corneli et al., Eur J Endocrinol 2005). Aim of the study was to verify the diagnostic validity of this cut-off value by investigating the effect of acute pharmacological blockade of lipolysis on...

Biochemical control of acromegaly is currently defined by the achievement of GH suppression after oral glucose tolerance test (OGTT) and of normal age- and gender-matched IGF1 levels. OGTT is believed to inhibit somatotropin secretion by enhancing central somatostatinergic tone; thus, the use of this test in evaluating biochemical control in acromegalic patients on somatostatin analogues (SSA) is questionable. To gain further insights into this topic, we analyzed basal and nad...

Introduction: Anorexia nervosa (AN) is a chronic disorder characterized of profound reduction in body weight and amenorrhoea. A product of complex interactions between psychological and clinical variables are important for the presence of the disease.Aim: The aim of the study was to investigate the variables which might predict full reproductive recovery of patients with anorexia nervosa.Material and methods: We studied closely mat...

The Nelson’s syndrome (NS) is characterized by hyperpigmentation, sellar growing mass, and increased plasma ACTH concentrations The management of NS remains difficult: neurosurgery represent the first choice therapy. Many drugs have been used with variable results: cyproeptadine, GABA-agonists, somatostatin analogues, chemiotherapy, PPAR-γ-agonists, and dopamin-agonists.Aim of this study was to evaluate the efficacy of cabergoline administratio...

Temozolomide, an alkylating agent used in malignant gliomas, has been recently used too in the treatment of aggressive pituitary tumors. To date, two cases of Nelson’s syndrome has successfully treated with 5 days of 28-day cycle, but the follow-up has been shorter than 12 months. We reported the third patient with Nelson’s syndrome treated with temozolomide, who after an initial goal response to three 300 mg 5 days of 28-day cycles shown a clinical and biochemical (...

Introduction: TSH-secreting adenomas represent <2% of pituitary tumors. Surgery and/or radiotherapy are primary treatment options. Somatostatin analogues and also dopamine agonists, represent valuable alternatives or adjuvant therapies.Objective: To report a case of euthyroidism and tumor stability achieved in a TSH-secreting pituitary macroadenoma, treated with octreotide-LAR, as first line therapy, and then added cabergoline. To review the efficacy...

Objectives: It has been recently recognized that GH may have a role in hematopoiesis and immune system. However, there are conflicting data regarding the effects of GH deficiency (GHD) and/or GH replacement therapy in GH deficient patients on hematopoiesis and immune system. The aim of the present study was to investigate the peripheral blood cell counts, T- and B-lymphocyte subsets and immunoglobulin levels before and after GH replacement therapy in patients with adult onset ...

Objectives: Evaluation of the HPA axis is still a big challenge. This study was performed to compare 1 μg ACTH, 250 μg ACTH and glucagon tests for evaluation of HPA axis in healthy male and female subjects with different ages.Materials and methods: This study was carried out on 57 healthy individuals (29 men, 28 women) between 20 and 70 years of age (the number and gender of the subjects are approximately equal for each decade). Low dose short ...

Background: Acromegaly is a multi-systemic dysfiguring disease caused by pituitary GH secreting tumour. Pituitary surgery, medical treatment with somatostatin analogues and radiotherapy have been cornerstone in the management of acromegaly. However, all these treatment modalities do not provide sufficient disease control especially in patients with macroadenomas.Objective: To evaluate the follow-up outcomes and remission rates of acromegaly patients....

Aim: To analyse the epidemiology and presentation of pituitary tumours in Uzbekistan.Materials and methods: Over a period of 1.5 years, we studied 53 consecutive patients with tumours in the sellar and suprasellar region (mean age 41.5 years) in terms of neurological and ophthalmological status, MRI imaging and detailed neuroendocrine functional assessment. A detailed examination of the sellar area by means of computer and magnetic resonance tomography w...

Introduction: Cushing’s disease (CD) is a rare condition, associated with significant morbidities and potentially fatal, if untreated.Objective: To assess the long-term morbidities in a large series of patients with CD during a prolonged follow-up period.Patients and methods: All subjects with CD who presented/followed-up in our Department between 01/1967 and 06/2009 were studied. All information was collected as documented in...

Aim of the research: To study relationship between GH levels and acromegaly complications development in different therapy approaches.Patients and methods: We evaluated 50 patients with GH secreting adenomas referred to CCSSE from 1999 to 2004. Age of patients was from 19 to 63 years-old (mean age 40±19 years-old). Duration of the disease was from 1 to 23 years.Methods: Clinical and biochemical tests of neurological status; RI...

Aim of the research: To study clinical and epidemiologic features of acromegaly in the Republic of Uzbekistan.Patients and methods: We observed acromegalic patients registered from 2007 to 2009 who are dispensarized in the regions of the country. Of the 369 patients 143 were males (38.7%) and 226 females (61.3%). Mean age of the patients was 42.6 years-old. Duration of the disease varied from 1 to 31 years.Results: According to the...

Study objective: To study the frequency of neuroendocrinal disturbances in patients with different pituitary adenomas.Material and methods: Under our observation there were 53 patients with various pituitary adenomas, of them female – 31, male – 22, middle age of 41.5 years. According to the aetiology of the underlying disease patients were sorted out as follows: 39 patients had an inactive pituitary adenoma, 2 – craniofaringeoma, 3 –...

Study objective: To estimate frequency of a postoperational hypopituitarism after transnasal hypophysectomies (TNHE) in patients with pituitary adenomas.Material and methods: Under our observation there were 24 patients with various pituitary adenomas, of them: 14 females, 10 males; the middle age being 36.4 years. According to the aetiology of the basic disease the patients were sorted out as follows: 17 patients had an inactive pituitary adenoma, 1 &#1...

Aim of the research: To study manifestation factors of the disease in patients with acromegaly in patients from Aral sea regions of the Republic of Uzbekistan.Patients and methods: Of the 43 patients with acromegaly assessed in Khorezm Region and Republic of Karakalpakstan (RKK) in 2009 22 were men (51.1%) and 21 women (48.8%).Of the 17 acromegalic patients registered in RKK 4 male patients and 13 female patients. Mean age of men 4...

The immunosuppressive effect of corticosteroids is well known. In some circumstances prophylactic antibiotic therapy is routinely used to lower the risk of opportunistic infections in immunocompromised patients with exogenous hypercortisolemia. The incidence of opportunistic infection in endogenous hypercortisolemia in Cushing’s syndrome is 11–17%, correlating with degree of hypercotisolemia. Only several case reports have been published about pneumocystis pneumonia ...

Context: The desmopressin (DDAVP) test has been proposed to discriminate Cushing’s disease (CD) from Pseudo-Cushing states (PC); however, current information on its value is scarce and contradictory.Objective: To assess the ability of the DDAVP test in distinguishing between these conditions, with emphasis on subjects with mild hypercortisolism.Design: Retrospective/prospective study.Setting: Division of...

The efficiency of the prolonged medical therapy of acromegaly with the somatostatin analogues (SA) strictly correlates with the initial sensitivity to the drug. Before the onset of SA therapy 114 patients with acromegaly (35 men and 79 women) aged 54 (48/61) years old (Me (25/75%) underwent the test with Octreotide (Sandostatin®): 300 μg sc within 3 days. The decrease of IGF1 level positively correlated with the age of the acromegaly onset (r=0.38) and negativ...

Aim of the research: To study the visual complications rate in patients with different pituitary adenomas.Patients and methods: We observed 24 patients with different pituitary adenomas, among them 14 women and 10 men. Mean age of patients was 36.4 years-old. According to the ethiology pattern patients were divided as follow; 17 patients with non-functioning pituitary adenomas, 1 patient with craniopharingioma, 2 patients with Cushing disease, 2 patients...

Aim of the research: To study the rate of vascular complications in acromegaly in the Republic of Uzbekistan.Patients and methods: We observed acromegalic patients registered from 2007 to 2009 who are dispensarized in the regions of the country. Of the 369 patients 143 were males (38.7%) and 226 females (61.3%). Mean age of the patients was 42.6 years-old. Duration of the disease varied from 1 to 31 years.Results: We assessed the r...

Aim of the research: To study long and short-term therapy effectiveness with dopamine agonists in acromegaly.Patients and methods: Three hundred and sixty-nine patients with acromegaly registered by December, 1 2009 in the Republic of Uzbekistan. Of these patients we observed 20 cases with GH-secreting pituitary adenoma. Age of the patients was from 19 to 63 years-old (mean age 40±19 years-old), duration of the disease was from 1 to 23 years. Patien...

Aim: Acromegaly is associated with accelerated atherosclerosis and cardiovascular disease. Nitric oxide (NO) is enzimatically formed from L-arginine by endothelial nitric oxide synthase (eNOS). Several studies have shown that reduction in NO synthesis causes endothelial dysfunction and impaired endothelium-dependent vasodilation. Asymmetric dimethylarginine (ADMA), the endogenous inhibitor of NOS, accumulation plays a prominent role in the pathogenesis and in pr...

Background: Pituitary adenomas are monoclonal neoplasms that may be either functional (hormone-secreting) or non-functional. The processes associated with pituitary tumor development and progression are mostly unknown. Remodeling of the extracellular matrix (ECM) and cell adhesion were suggested to be involved in pituitary tumorigenesis. Heparanase, an endoglycosidase capable of degrading heparan sulfate, the main polysaccharide constituent of the ECM, is implicated in diverse...

Objective: To identify MetS and non-MetS in subjects with adult-onset GHD before start of GH replacement and to compare prevalence of cardiovascular risk factors.Subjects and methods: MetS was defined (IDF criteria) by the obligatory presence of increased waist circumference (WC) and presence of at least two of following components: hypertension, decreased HDL-cholesterol, increased triglycerides, diabetes mellitus. The complementary group was defined as...

We evaluated the volume of pituitary adenoma in patients treated with ocreotide LAR (SSLAR) prior to surgery.Materials and methods: Twenty-six patients (22 females and 4 males, mean age 57.5±15.0 years) were treated with SSLAR: 5 patients with microadenoma – during 6 months, and 21 patients with macroadenoma – during 12 months before surgery, as recommended by the Polish Society of Endocrinology. Concentration of hGH and IGF1 was evaluated...

Treatment of acromegalic patients with somatostatin analogues decreases hGH and IGF1 concentrations, improves general and metabolic conditions and decreases morbidity and mortality in these patients. We assessed the efficacy of octreotide LAR (SSLAR) in treating acromegalic patients following non-radical surgery of pituitary adenoma at a single centre.Materials and methods: At our Centre we follow 85 acromegalic patients who underwent surgery, including ...

Introduction: Traumatic brain injury (TBI) is considered a rare cause of pituitary dysfunction. Recently, some retrospective studies demonstrated that TBI-mediated hypopituitarism is more frequent than previously known. However, its prevalence and natural history are still unclear.Objectives: To evaluate the prevalence of hypopituitarism 1 year after TBI and the association between the seriousness of the traumatism and the pituitary deficits.<p class...

Acromegaly (A) is associated with the bone overgrowth and soft tissue abnormalities due to anabolic, lipolytic and sodium retaining actions of GH.Aim: To investigate the effects of medical treatment on bone mineral density (BMD) of proximal femur, lumbar spine and tissue distribution. We observed 56 patients (14 M and 42 F) with A. BMD was measured using dual-energy X-ray absorptiometry with ‘total body’ program. The patients were treated with ...

The aim of the study: Acromegaly is associated with respiratory and cardiovascular morbidities and high mortality rate. The present study evaluates clinical aspects in acromegalic and obese patients with sleep apnea syndrome (SAS).Material and method: The patients were diagnosed and followed-up in the Clinic of Endocrinology, Timisoara, in the period 2006–2009. All the cases were confirmed and investigated as present guidelines recommend. The polyso...

Introduction: Both GH deficiency (GHD) and male hypogonadism are thought to be associated with an increased cardiovascular morbidity and mortality which is at least partly attributed to higher Insulin resistance. Potential reversibility of increased risk factors after gonadal replacement was assessed in this study, by comparing replaced and unreplaced hypogonadal men with GHD.Subjects and methods: Seventy-seven hypogonadal adult male patients with GHD ha...

The hypothalamic peptide, nesfatin-1, derived from the precursor NEFA/nucleobindin2 (NUCB2), was recently identified as central anorexigenic molecule, acting in a leptin-independent manner. Yet, its potential involvement in the regulation of other biological functions gated by body energy status remains unexplored. We show herein that NUCB2/nesfatin-1 is involved in the control of female puberty. NUCB2/nesfatin mRNA and protein were detected at the hypothalamus of pubertal fem...

Introduction: Presence of GH receptor in human skin and its appendages suggests a direct effect of GH on skin characteristics. Wet and oily skin due to hyperhidrosis and increased sebum production were described in acromegaly patients.Objective: The aim of the study was to examine the hydration via capacitance, sebum content, transepidermal water loss, pH and temperature of the skin in patients with acromegaly. The data were compared with that of control...

The GH-receptor antagonist PEG, used as monotherapy or in combination to SA, has been demonstrated to normalize IGF1 levels in up to 90% of acromegalic patients after unsuccessful surgery and/or radiotherapy and resistant to conventional SA treatment. The aim of this study is to evaluate the efficacy and safety of combined treatment with SA plus PEG in a cohort of acromegalic patients resistant to conventional SA therapy. Thirty-two acromegalic patients (17 M, 15 F, age 39.6&#...

Certain degree of hypopituitarism has been revealed in a significant number of patients who suffered traumatic brain injuries or subarachnoid hemorrhage. Microhemorrhages, necrosis, tissue infarcts and vasoconstriction are reported as mechanism of hypothalamo-pituitary dysfunction. Assessment of hypothalamo-pituitary endocrine functions in patients with chronic subdural hematomas has not been published yet, although dysfunction of hypothalamo-pituitary unit can be expected (he...

Indications to GH therapy in children with short stature are still a matter of discussion.We compared first-year response to GH therapy in 80 children (62 boys, 18 girls), age 12.7±2.4 years (mean±S.D.) with different disorders of GH secretion. In all the patients nocturnal GH secretion assessed during 3 h after falling asleep was decreased (<10 ng/ml). In 40 children GH deficiency (GHD) was diagnosed on the ground of decreas...

Background: There is an increasing interest to find specific prognostic markers of the aggressive behaviour of some pituitary adenomas (PA). The most studied markers have been the immunohistochemical staining for Ki-67 and p53. The aim of this study was to evaluate the relevance as possible prognostic markers of growth factors (IGF1R), angiogenic factors (VEGF and his receptor) and new genes (PTTG) versus the immunohistochemical expression of Ki-67 and p53 in PA.<p class="...

Normal thyroid hormone secretion (or appropriate L-thyroxin substitution) is necessary for the optimal effect GH administration on growing rate. The decrease of free thyroxin (FT4) levels at GH therapy onset was reported in several studies.The aim of our study was to assess the incidence of hypothyroidism (HT) during the initial phase of GH administration in previously euthyroid children with GH deficiency (GHD) and to compare t...

Introduction: Cushing’s disease (CD) is associated with persistent risk of cardiovascular complications, which were found to be four times higher than in age- and sex-matched population. The main cause is cardiovascular disease with thrombotic complications due to the activation of changes in haemostatic and fibrinolytic system with high level of cortisol secretion.Objective: To study hemostatic and fibrinolytic state in patients with CD.<p clas...

Prolactinoma (PRM) treatment is based upon dopamine agonists, cabergoline (CAB) being one of the most used in the last decade. Sensitivity to CAB varies in terms of tumour volume and PRL secretion, up to 8–15% of PRM being defined as resistant. Since it is known that increasing the dosage improves the response rate, we aimed to measure plasma CAB levels in PRM patients under this treatment in a prospective interventional study.Patients and methods: ...

GH secretion is usually impaired in active Cushing’s syndrome (CS), due to concomitant mechanisms, including diminished GHRH and/or increased somatostatin release and impaired pituitary somatotrope responsiveness. Differently, IGF1 levels not parallel GH insufficiency in CS, being reported reduced, normal or increased. Both ghrelin and GHRH+arginine (ARG) are powerful GH secretagogues, influenced by age and/or BMI. In 27 CS (42.7±2.9 years, 28.8±0.9 kg/m2</...

Context: The determination of human chorionic gonadotropin (hCG) in cerebrospinal fluid (CSF) is useful for the differential diagnosis of suprasellar lesions. However, the concentrations that prove diagnostic for neurohypophyseal germinoma have not been well defined. In addition, the immunoassays used for such determination are the same as those applied in serum, and few studies have been performed regarding the validation of such techniques in CSF.Objec...

Endotoxemia induces behavioral changes, including a decrease of food intake. Several studies have demonstrated that ADX modifies central nervous system responsiveness to different paradigms. Control of energy homeostasis is regulated by interplay of peripheral signaling conveyed to the hypothalamus and brainstem that control appetite and meal size. We investigated the activity of oxytocin (OT) neurons in the paraventricular nucleus of the hypothalamus (PVN) and tyrosine hydrox...

The endocannabinoid system is involved in several homeostatic and neuroendocrine functions. In the present study, we evaluated the effects of type 1 cannabinoid (CB1) receptor antagonist, rimonabant (10 mg/kg, p.o.), on hormone secretion, neuronal activation and mRNA expression in the hypothalamus following isotonic (I−) or hypertonic (H−) blood volume expansion (BVE). Our results showed that the secretion of both oxytocin (OT) and vasopressin (AVP) were increased ...

Male transgenic (TG) mice overexpressing both the hCGα- and hCGβ- subunits present elevated levels of circulating hCG, Leydig cell hyperplasia/hypertrophy, elevated androgen levels and infertility (Rulli et al. 2003). In addition, serum FSH is significantly reduced in prepuberal and adult TG males compared with wild-types (WT), and does not change after treatment with the antiandrogen flutamide. The aim of this study was to evaluate the regulation of the hypot...

Current therapies for acromegaly are unsatisfactory for some patients. High dose thiazoledinedines have been reported to shrink tumor size and reduce serum GH levels in animal models of acromegaly. To study the effects of increasing doses of rosiglitazone on serum GH and IGF1 concentrations in acromegalic patients, we designed a phase two clinical trial. We enrolled five consecutive patients with active acromegaly uncontrolled under conventional therapies. They received increa...

Aim: To assess the impact of acromegaly on quality of life (QoL) as evaluated by the acromegaly QoL (AcroQoL) questionnaire in Maltese patients with cured, controlled and uncontrolled acromegaly.Design: Cross-sectional survey study.Methods: The AcroQol questionnaire was completed by all patients during their routine outpatient visit. Clinical and hormonal data including GH and IGF1 levels were also taken at the time of survey.<...

Aim: To ascertain epidemiology and outcomes in Maltese patients with acromegaly.Method: Retrospective case record study of acromegalic patients diagnosed between 1979 and 2008.Results: Forty-seven patients were recruited (25 females and 22 males). The prevalence of acromegaly in the Maltese population was 11.4 per 100 000 population. Of 77% had a macroadenoma (53% extrasellar, 24% intrasellar). Of 15% had a microadenoma. Two tumour...

We report a case of 28-year-old girl with panhypopituitarism and ectopic neurohypophysitis due to absent pituitary stalk. She was admitted to endocrinology policlinic with short stature, growth retardation and primary amenorrhea. Basal hormones indicated tahat she has secondary hypothyroidism, adrenal insufficiency, hypogonadism and GH insufficiency. Peak cortisol response to the short ACTH test was normal but inadequate to insulin tolerance test. The other dynamic pituitary f...

Aim: To evaluate epidemiology, clinical presentation, treatment and subsequent outcomes in Maltese patients with NFPA.Methods: Retrospective case record study of all patients with NFPA.Results: Forty-eight patients with a NFPA were identified with an estimated prevalence of 1.16 per 10 000 population. 58% of these were male and the mean age at presentation was 50.6 years (S.D. 13.4 years) (men – 52.5 years; wome...

Background: Anorexia nervosa (AN) is prevalent in modern societies, this pathogenesis is not yet well understood.Aim: The aim of this study is to evaluate circulating levels of adiponectine (Apn) and the relationship between these levels and anthropometric and metabolic parameters.Methods: The study included 40 women, 20 with AN (BMI 15.7±2.1 kg/m2, age 30.2±10.5 years), 12 restricter (BMI 14.9±1.6 kg/m<su...

Somatostatin analogues (SSA) are widely used for the treatment of patients with acromegaly, and the responses are variable. We investigated the possible predictive factors of the response to SSA therapy in Korean acromegalic patients. Twenty-eight patients were retrospectively analysed, who were treated by surgery and adjunctively SSA. Somatostatin suppression tests (SST, hourly GH measurements for 3 h following 100 μg somatostatin injection) were done before SSAs were gi...

Serum pituitary antibodies (Pit Abs) and tumor infiltrating lymphocytes (TILs) have been described in a small percentage of pituitary adenomas but their clinical significance remains unknown.Aim of the study was to assess Pit Abs and TILs prevalence in patients with pituitary adenomas and to determine their influence on the clinical outcome. In this prevalence case–control study were enrolled 291 pituitary adenoma cases, (110 non-secreting, 30 ACTH-...

Metabolic and immunological disturbances may be associated with hyperprolactinemia.Aim: The aim of this study was examination the presence of some metabolic and immunological disturbances, like as the changes in and body composition, as risk factors for development of atherosclerosis, in young women with hyperprolactinemia.Material and methods: The investigation was performed as prospective study in a group of 20 premenopausal wome...

Context: There is scant evidence of tumoral mass reduction in Thyrotropin-secreting pituitary adenomas (TSPA) treated with long-acting somatostatin analogs. There are no reports that evaluate TSPA shrinkage after deep subcutaneous (sc) Lanreotide-ATG (L-ATG) therapy.Objective: The primary objective was to observe if L-ATG could reduce TSPA tumor mass.Methods: A literature review on the subject was made. The biochemical and radiolog...

Objectives: It is known that patients with pituitary adenomas, especially acromegaly, frequently suffer from pain syndromes such as headache and arthralgia. Whether pain exists and to what extent in Cushing’s disease (CD), reflecting chronic cortisol excess, is not clear. We hypothesized that pain patterns should be also altered and investigated pain laterisation, clinical characteristics, phenotypes as well as underlying predictors.Methods: In a cr...

Background: Craniopharyngioma may be associated with severe morbidity. Few data exist on incidence rate (IR) and possible changes with time. The epidemiology of craniopharyngioma in Denmark has never been evaluated in detail.Objectives: To review the literature on craniopharyngioma incidence and to study the epidemiology of craniopharyngioma in Denmark during a recent 20-year period.Material and methods: Publications including data...

The potential side effects of the rhGH therapy have been evaluated only during treatment and the accessible databases have been developed as a post-marketing surveillance only by the Companies distributing rhGH. Aim of the present study was to evaluate health consequences (metabolic diseases and/or malignancies) in adults previously treated with rhGH during childhood. We recruited 284 patients (median age at diagnosis 12 years, range 3–17) who underwent rhGH treatment bet...

Objective: To characterize patients with GH deficiency associated with lymphocytic hypophysitis (LyH).Method: Patients with a diagnosis of LyH were identified in the KIMS database. The responsible clinicians were asked to confirm the diagnosis and to provide more detailed information on the patient by filling in a questionnaire.Results: One hundred and fifty patients with a diagnosis of LyH were identified in the database and 100 c...

Aim of this study is to present preliminary epidemiological data on a population of 1512 acromegalic patients attending 22 tertiary centers in Italy from 1980 to 2002. At our knowledge this is the first large–scale epidemiological Italian study on acromegaly. Gender was 624 (41.2%) men and 888 (58.8%) women. Mean age at diagnosis was 45±13 years, 43±13 for men and 47±13 for women. Median estimated duration of acromegaly before diagnosis was 74 months (range...

Introduction: Patients with Cushing’s syndrome might present a variety of brain alterations. There is however little evidence from MRI studies demonstrating atrophy of either frontal or medial temporal brain regions.Aims: To study cortical alterations (decreased cortical thickness) on MRI in patients with Cushing’s syndrome (CS), as compared to controls (C), and long-standing major depressive disorder (MDD).Material and m...

Objective: To examine whether prolactinoma patients have an altered personality profile.Methods: In this cross-sectional study 84 prolactinoma patients were enrolled. As reference groups, we compared 58 patients with non-functioning pituitary adenomas and secondly 168 age and gender matched healthy control subjects. Personality traits were measured with the standardized Eysenck (EPQ) and Cloninger personality (TPQ) questionnaires.R...

Adolescent idiopathic scoliosis (IS) represents an evolutive disease that occurs in puberty and progresses till the skeletal maturation. The neuroendocrine hypothesis involving a melatonin deficiency as the source for IS is one of the proposed causes of this plurifactorial disease.Objective: To investigate the hormonal changes of both the gonadal and growth axis and circadian rhythmicity in subjects with adolescent idiopathic scoliosis compared to age ma...

Subject: Use of intraoperative ultrasound (iUS) during transshenoidal surgery addresses (a) resection control of macroadenomas and (b) identification of microadenomas, thus avoiding extensive pituitary exploration.Method: (a) For resection control of 33 pituitary macroadenomas and 2 meningeomas a 13 MHz US probe with a perpendicular 10 mm linear field was introduced into the sella after intrasellar resection to investigate the suprasellar and parasellar ...

Recent studies have shown that the co-administration of lanreotide (lan) with pegvisomant (peg) was able to normalise IGF1 secretion in patients with acromegaly who were partial responders to somatostatin analogues (SSAs).Fifty seven subjects with acromegaly (mean age 51.6±12.7 years) not previously controlled by SSAs (either treated by SSAs for at least 6 months with IGF1 > ULN, or on peg for at least 3 months) with IGF1 > 1.2 ULN (n...

Antipituitary antibodies (APA) are frequently present in patients with autoimmune polyendocrine syndrome (APS) but their role in predicting autoimmune hypophysitis (LYH) is still discussed.To evaluate the predictive value of APA investigated by immunofluorescence for the occurrence of pituitary autoimmune dysfunction when considering together some methodological characteristics as immunostaining pattern and antibody titers, we studied 149 APA positive an...

Background: Treatment of choice of ACTH producing pituitary adenoma is transsphenoidal resection. Owing to difficult visual demarcation of the adenoma, peroperative feedback about the completeness of the resection would be desirable. We investigated if rapid per-operative ACTH measurements is useful in surgical strategy.Methods: Thirteen patients with pituitary adenomas were operated. An modified ACTH-assay delivered results within 30 min. Catheters were...

Objective: Hyperprolactinemia is the most common abnormality of the hypothalamic–pituitary axis. In the majority of patients with hyperprolactinemia monomeric prolactin (monoPRL) namely PRL with a molecular weight of 23 kDa predominates. But, in some patients with hyperprolactinemia high molecular weight forms of PRL namely macroprolactin (macroPRL) is detected. We aimed to investigate the clinic and radiologic features associated with the macroPRL....

We present a 58 years old woman admitted in our department for bradycardia, diarrhea, epigastralgia, anorexia and weight loss. Physical examination showed low blood pressure and inability to walk or stand due to severe flexion contractures of the lower extremities without neurological abnormalities. The biological findings showed severe hyponatremia, hyerkaliemia tendency, low levels of plasma cortisol and ACTH suggesting pituitary adrenal axis deficiency. Hormonal investigati...

Background: Patients with diabetes insipidus (DI) that suffer of adipsia usually are difficult to treat, and requiring close monitorization.Aim: To know long-term outcome of patients with DI associated to adipsia.Subjects: From January 1989 to December 2006 were attended five patients (two males) with DI plus adipsia, aged 32±14.64 years, range 10–51. Being the aetiology X histiocytosis, craneapharyngioma, suprasellar men...

Introduction: There are high levels of anterior pituitary hormones in the cerebrospinal fluid (CSF), i.e. beyond the blood–brain barrier, in many patients with pituitary tumors.Aim: To assess the influence of CSF pituitary hormones on brain functions reflected by sleep architecture and sleep apnea.Method: Twenty-nine patients (17 women, 12 men) with pituitary adenomas (20 acromegaly, 5 nonfunctioning pituitary adenomas, 4 prol...

Adult GH deficiency syndrome is characterized by visceral obesity, dyslipidemia, insulin resistance and is associated with an increased cardiovascular risk. Epicardial adipose tissue, giving its relationship with abdominal visceral adiposity, coronary artery disease, cardiac morphology and function and metabolic syndrome, has been proposed as cardio-metabolic risk indicator. In this study, we evaluated the echocardiographic epicardial fat thickness in 14 patients (8 M and 6 F,...

Background: Dopaminergic agonists have been proved to improve control of diabetes and lipids. Central dopaminergic activity can be measured by apomorphin test (apomorphin increases GH and decreases prolactin levels, which is a marker of dopaminergic activity).The aim of our study was to evaluate the relationship between central dopaminergic activity and metabolic parameters in healthy men.Methods: We examined 42 healthy men (averag...

Study aim: Pituitary function evaluation in patients with traumatic brain injury (TBI).Subjects: One hundred and forty-six patients (49 female, 97 men, age: 31.9±16.2 years) recovered from moderate to severe TBI. Prospective follow up has been performed 3/6 and 12 months from TBI for 79 subjects. Retrospective evaluation (from 0.3 to 30 years) included 67 subjects selected in front of overt clinical features (obesity, fatigue, sexual disorders)....

A 44-year-old man with 6 months history of headache, fatique, depressive mood, anorexia, impotence, decreased libido, poliuria and polidypsia. The results of the physical examination were normal, except the patient had noduler guatr. Baseline hormonal investigations and dinamic tests showed panhypopituitarism and partial central diabetes insipidus. Magnetic resonance imaging (MRI) of the pituitary gland showed enlarged pituitary gland and a marked thickening (4.5 mm) of the in...

Introduction: Acromegaly is a chronic disease with a serious impact on patients’ morbidity, mortality and health-related quality of life (HRQOL). Recently a disease-specific questionnaire assessing HRQOL in acromegaly was developed (AcroQoL). Using this tool we have compared QoL in patients with controlled versus uncontrolled acromegaly.Patients and methods: It was a prospective, cross-sectional study. For the period 2007–December 2008 163 pati...

Context: Acute lymphoblastic leukaemia (ALL) is the most common pediatric malignancy and its treatment includes many known risk factors for low bone mineral density (BMD), e.g. glucocorticosteroids, methotrexat and cranial radiotherapy (CRT).Objective: To evaluate bone mineral density (BMD) and markers of bone turn over in a group of adults with childhood onset ALL, treated with CRT and to evaluate the effect of 5 years with, and 8 years without GH thera...

The effects of conventional somatostatin analog (SSA) regimens on glucose homeostasis seem to have minor clinical impact in acromegaly. Recently, we performed a trial showing that high dose octreotide LAR significantly reduces IGF1 in acromegalic patients uncontrolled with conventional SSA doses. In this post-hoc analysis, we evaluated the effects of high doses versus high frequency octreotide LAR on glucose homeostasis (HbA1c, FPG, HOMA-R) in patients with acromegaly e...

Background: Surgery is accepted as first line treatment of somatotroph macroadenomas with involvement of the optic chiasm. However, during recent years somatostatin analogues (SA) have increasingly been used as primary treatment improving ultimate cure rate, as SA’s have anti-proliferative effects in most tumours. We demonstrate here positive effect of subacute/acute SA treatment on tumour shrinkage and chiasm decompression in two recently diagnosed acromegalic patients.<...

Introduction: Pasireotide reduced UFC levels in 22 of 29 patients with Cushing’s disease after 15 days’ treatment (Boscaro et al. JCEM 2009). Of these 22 patients, 5 achieved normalized UFC (UFC-responders) and 17 had reduced but not normalized UFC (UFC-reducers). Results of an extension phase to this study are presented.Methods: Patients with de novo or persistent/recurrent Cushing’s disease received pasireotide 600 μg ...

Isolated central hypothyroidism (ICH) is a rare disease whose pathogenesis is so far linked to germinal mutations of TSHβ (several cases) or TRH receptor (TRHR) genes (only two cases). Here, we report the studies performed to elucidate the pathogenesis of idiopathic ICH in five cases (two men, three women) with low/normal TSH levels and low freeT4 levels (3–8 pmol/l). One male, negative at neonatal TSH screening, showed signs of severe hypothyroidism at 44...

Background: Long-term treatment with dopamine agonists (DAs) is considered to be the first-choice therapy for prolactinomas. According to current guidelines DAs can be safely withdrawn in patients with negative pituitary MRI and stable normalization of prolactin levels for at least 3 years. On the other hand, recent studies have shown an increased risk for valvular heart disease in patients with Parkinson’s disease treated with high doses of cabergoline. The aim of this s...

We previously showed that GH administration to rats with induced brain injury produces a clear proliferation of neural precursors within DG and a significant reduction of apoptosis. In this study, we tried to delineate, in vitro, the signaling pathways by which GH produces these effects on neurogenesis.Methods: Neural stem cells were obtained from the Subgranular Zone of 9 days old mice and then plated on petri dishes under proliferation condition...

Background: The differential diagnosis of hyponatremia is often challenging because of its association with multiple underlying pathophysiological mechanisms, diseases and treatment options. Several algorithms are available in order to guide the diagnostic approach to hyponatremia, but their diagnostic and clinical utility has never been evaluated. We aimed to assess in detail the diagnostic utility as well the limitations of the existing approaches to hyponatremia.<p clas...

Introduction: Pasireotide (SOM230) is a multi-receptor targeted somatostatin analogue with high binding affinity for sst1,2,3 and sst5. In a Phase II study of pasireotide in patients with active acromegaly, 27% achieved biochemical control after 1 month of octreotide s.c. followed by 3 months of pasireotide, and pituitary tumor volume decreased by >20% in 39% of patients. Results from the study’s extension phase are presented.<p class="abstex...

Objective: It is still unknown how pituitary adenomas grow over years and whether growth kinetics follow a distinct growth model. Definition of adenoma growth kinetics would substantially enhance knowledge of biological behaviour. The objective of this study was to define a growth model for non-functioning pituitary adenomas.Methods: Fifteen patients who had five or more serial high-quality examinations with magnetic resonance images or computerized tomo...

Introduction: Cushing’s syndrome results from increased or aberrant expression of ACTH, CHR, or neuroendocrine receptors that leads to uncontrolled hypersecretion of cortisol. The most common cause is ACTH-secreting pituitary adenomas. Alternatively, the glucocorticoid excess may be due to adrenal neoplasia or to ectopic ACTH – secreting tumors. There are rare reports of patients with a meningioma secreting CRH presenting paraneoplasic Cushing’s syndrome.<p ...

Purpose of the study was to assess the condition of reproductive system in females with ‘empty sella’ syndrome (ESS).Material and methods: Of 159 females with ESS, mean age 37.6±0.93 years, of them 65 with primary ESS, 42 with secondary ESS, 47 with forming ESS were studied. The diagnosis of ESS was established by MRI findings. Obstetrical and gynecological anamnesis, hormonal background were investigated.Results: Di...

Objective: Evaluation of aftercare, medical therapy and remission rate in Cushing’s disease (CD) and acromegaly (AC).Methods: Of 58 CD and 83 AC patients operated over 10 years were carefully evaluated. The patients received a disease-related questionnaire and were invited for a follow-up at the outpatient clinic of the Department of Neurosurgery. 33 CD and 52 AC patients returned the questionnaire, 25 CD and 37 AC patients participated personally. ...

Objective: Cushing’s disease (CD) and acromegaly (AC) are associated with psychological and psychiatric problems. Both pathologies cause a severe impairment in quality of life (QoL) that can persist even if biochemical remission and cure are achieved. The aim of the study was to investigate the influence of the current disease status (remission vs. no remission) on neurocognitive function and QoL in treated CD and AC patients. The second objective was to determine predict...

Objective: The aim of the study was to analyze the time-to-diagnosis interval in patients with Cushing’s disease (CD) and acromegaly (AC), to assess factors that promote early disease detection and to investigate the medical fields diagnosing the pathologies.Design: Case-record retrospective study.Patients: CD and 52 AC patients operated between June 1998 and December 2007.Measurements: All patients rece...

Prolactinomas are very rare, but usually more aggressive among children, than in adults. Although treatment strategies for prolactinomas in adults are well established and at present time the preference is given to dopamine agonists, the use of these drugs in pediatric patients is limited due to lack of information on safety and efficiency in this group of patients.A 14-year old boy presented with absent puberty, obesity (weight +4σ) general weaknes...

Introduction: Leptin is a protein hormone secreted mainly by adipose tissue. It exerts its function via ubiquitously expressed receptors (LEPR). A number of LEPR isoforms are known. Metabolism of lipids and carbohydrates, that, in part, depends on leptin, might deteriorate with age. Aging is associated with a decrease of the global methylation and with hypermethylation of some promoter-located CpG islands. Such hypermethylation results in transcription inhibition.<p class=...

It is now widely accepted that the kisspeptins (kps) and their receptor kiss1r play an essential role in the neuroendocrine regulation of the reproductive axis by stimulating hypothalamic GnRH secretion. However, kiss1 and kiss1r expression in tissues distinct from, but related to, the hypothalamus, prompted us to propose that these molecules may exert regulatory functions in additional places of the neuroendocrine system, such as the pituitary and two of its phy...

Kisspeptins (Kp), a peptide family encoded by Kiss1 gene, and their receptor Kiss1r were first identified by their anti-metastatic actions but have emerged as key regulators of the reproductive axis, where they integrate sexual, metabolic and seasonal cues to control hypothalamic GnRH release. Recent data indicates that some actions of Kps may be effected directly at the pituitary (PIT), since Kissr1 is expressed in the PIT and Kp stimulate luteinizing hormone (LH) secretion d...

Background: Diabetes mellitus is one of the serious acromegaly complication.As well known, glycemia influences growth hormone (GH) secretion. From this point of view, it is interesting to investigate feature peculiarity of GH and Insulin like Growth Factor 1 (IFG-1) secretion when acromegaly is coupled with diabetes mellitus.Aim: Of this study was to investigate diabetes mellitus influence on GH and IGF-1 levels in acromegalic pati...

The dopamine agonist cabergoline has been found to be effective in inducing normalization of cortisol secretion in 25–50% of patients with Cushing’s disease after long-term treatment. Moreover, tumor shrinkage have been documented in selected patients with pituitary corticotroph tumors. The aim of the present study was to evaluate the effect of cabergoline withdrawal in patients with a stable normalization of cortisol secretion and stable or absent visualization of p...

Introduction: Carbohydrate disorders in the form of glucose intolerance or overt diabetes are prevalent and well-documented in acromegalic patients.Aim: To assess the prevalence of carbohydrate disorders and the correlations between BMI, the duration of the disease, GH and IGF-1 concentrations depending on the stage of progression of glucose intolerance in our acromegalic patients.Methods: Acromegaly was diagnosed using standards e...

Acromegaloidism includes clinical features of acromegaly with GH and IGF1 normal levels at baseline and dynamic, without findings of extrapituitary or pituitary tumour. It has been associated with various conditions without a definite pattern. The aim was to evaluate whether there are differences in some hormonal pituitary axis from acromegaloid subjects with respect to acromegalic and healthy subjects. We designed a comparative, multicenter, case–control study in three h...

The Spanish acromegaly registry (REA) is an online epidemiological database created in 1997 to collect clinical and biochemical data of patients with acromegaly followed in Spain.Aim: To study trends in acromegaly treatment over time in Spain.Methods: REA is an online database in which registered endocrinologists collect data from all acromegalic patients seen at their practices in Spain. In the last year the neuroendocrine group o...

Polyclonal antibodies against somatostatin receptors (SSTRs) available up to now recognizing intracellular sites of receptors and their recycling products do not detect bioactive ligand binding domains (LBDs) and are of limited performance in paraffin-embedded tissues. Aim of this study was to evaluate by immunohistochemistry the expression of SSTR5 on an archival series of pituitary tumors using a new MoAbs against the SST-binding domain (Y-SSTR5).Metho...

Acromegaloidism is a very rare entity (have been 54 cases reported worldwide) that presents with clinical acromegaly and normal somatotropic axis, without findings of pituitary or extrapituitary tumour. Its origin has not been clearly established, although it is associated with several pathophysiological conditions. The local ethics committee approved to perform an observational and multicenter study in three hospitals from a region with approximately 800 000 people over 18 ye...

Ollier disease (OD) is a rare disease, with multiple enchondromas localized in the metaphysis of long bones, hands and feet, developing in the first decade of life, with potential malignant transformation into chondrosarcomas. OD is usually sporadic and probably caused by post-zygotic genetic alterations leading to mosaicism. A PTH/PTHrP receptor type 1 (PTHR1) gene mutation is present in some cases.Case report: A 21-years old male patient was referred t...

Objective: Patients with hyperprolactinemia who require medical therapy are typically treated with dopamine agonists (DA). In most cases, medical therapy with DA normalizes the level of prolactin (PRL), restores gonadal function and fertility, and substantially reduces the size of the tumor. Here, we aimed to compare the efficacy of cabergoline (CAB) and bromocriptine (BRC) in hyperprolactinemic patients retrospectively.Methods: Retrospective analysis of...

Over the last decade 824 pituitary tumours have been removed in our centre. Of these, 114 (13.8%) were corticotroph adenomas. We present four unusual cases of corticotroph adenoma showing transition from Cushing’s disease to a hormonally inactive adenoma (case 1 and 2) or vice versa (case 3 and 4).Case 1: A 51-year-old man was admitted with a 2-year history of weight gain, arterial hypertension and chiasmatic syndrome. Cushing’s disease (CD) du...

Objective: Long acting somatostatin analogs commonly used as adjuvant treatment of acromegalic patients after noncurative surgery. We aimed to compare the efficacy of octreotide LAR (OCT) and lanreotide Autogel (LAN) in acromegalic patients.Methods: Sixty-eight patients that cure could not be achieved by transsfenoidal endoscopic or microscopic pituitary surgery between 2003 and 2009 were retrospectively analyzed (25 men and 43 women; mean age 41.1±...

Objective: To document clinical and laboratory presentations of FSH-staining pituitary adenomas, and to compare pure FSH-staining adenomas with mixed FSH and other anterior pituitary hormones staining ones.Methods: We analysed our inpatient records for patients who underwent pituitary surgery, and analysed histopathological reports for FSH-staining pituitary adenomas. Immunostaining positivity was defined as immunostaining of ≥5% of the adenoma cel...

GH deficiency (GHD) in adults leads to impairment in body composition and function, as well as to deranged lipoprotein and carbohydrate metabolism implying increased cardiovascular morbidity. The morphologic and metabolic alterations in GHD syndrome are more marked in patients with the most severe GHD, even when evaluated by maximal provocative test such as GHRH + arginine. IGF1 synthesis and secretion are function of the GH status but also of major metabolic factors such as i...

A 37-years old woman was admitted to the Department of Endocrinology 3 years ago because of hypertension with headaches. The highest value of blood pressure was 210/130 mmHg. Colour doppler of renal arteries, electrolytes, cortisol, renin, aldosteron, metanefrins and normetanefrins were normal. With perindopril 4 mg and lacidipin 4 mg/day blood pressure was well controlled. After 3 years gastroscopy was performed because of stomach discomfort and it revealed soor oesophagitis,...