Endocrine Abstracts

Two estrogen receptor isoforms are known to exist, ERα and ERβ. The expression of ER isoforms in breast cancer cell lines was studied to see whether both ERs, as well as any other variants, are expressed at the mRNA and protein level. Three breast cell lines: two which are known to be ER+ve (MCF7 and T47D) and one reported as ER-ve (MDA-MB231) were used in this experiment. For gene expression studies RT-PCR methodology was applied; primers were used that detect ER&#9...

Episodic hypercortisolism has been widely described in Cushing’s disease (CD) but is a less commonly recognized presentation of ectopic ACTH syndrome (EAS). We describe 4 cases whose diagnosis and management was complicated by episodic hypercortisolism. These cases highlight diagnostic and therapeutic challenges during the differential diagnosis of CS complicated by intermittent hypercortisolism. All 3 cases of EAS required various combinations of ketoconazole, metyrapone...

Introduction: Disruption of the hypothalamic dopaminergic inhibitory control of prolactin (PRL) secretion results in hyperprolactinaemia. We have previously shown in a large series of patients with non-functioning pituitary macroadenomas that serum PRL virtually never exceeds 2000 mU/l in the absence of PRL elevating medications. Current data on the effect of other sellar/parasellar masses are limited.Objective: To investigate the range of PRL values at ...

Aims: To calculate the sensitivity, specificity and positive predictive value of Parathyroid scintigraphy using Technetium-Sestamibi scan in the localization of parathyroid disease.Methods and material: This is a retrospective medical review of 161 patients who underwent the Parathyroid scintigraphy at our hospital in last six years. True positives were defined as patients with confirmed primary hyperparathyroidism (PHPT) on pathological examination. Tru...

Background: Insulinoma is an uncommon disease. The clinical profile of insulinomas among Indian patients is not well known.Aim of the study: To study the clinical characterstics, biochemical and radiological parameters,and treatment aspects of our adult patients with insulinomas.Methodology: We did a retrospective analysis of 18 patients with insulinoma treated from 1992 to 2004 in our institution. The data was analysed using a 11....

Pheochromocytomas are neuroendocrine tumors able to synthesise cathecholamines as well as to metabolise them in metanephrines (NM,M). We assayed Adrenaline, NorAdrenaline, Dopamine and metanephrines in serum (p) and urine (u), and the chromogranin A. We measured 11 parameters (Ap, Au, NAp, NAu, Du, MNp, MNu, Mp, Mp, 3Metu, CgA). Catecholamines and metanephrines were performed using HPLC with electrochemical detection, and CgA with an immunometric as...

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The survival rate is excellent, however in some cases it transforms to dedifferentiated invasive tumor. Tumor cell invasion and metastasis are major causes of cancer mortality. It is a challenging task to identify critical genes controlling metastatic potential and disease recurrance. We sought molecular prognostic markers that could improve diagnostics and planning therapy.Comparati...

Background: The use of conventional radiotherapy (CR) in the treatment of pituitary adenomas has been associated with adverse effects such as development of hypopituitarism, cognitive impairment and optic nerve damage. Fractionated stereotactic conformal radiotherapy (FSRT) provides a new treatment regimen and was introduced at our University Hospital in 1996.Objective: To evaluate the effects of FSRT on tumour size, hormonal overproduction and developme...

Malignant intra ovarian tumor secreting glucocorticoïds is extremely rare (<5 cases reported in the world). Our aim is to report the first case observed in our practice. We also try to relate different mechanisms which are discussed in literature to explain intra ovarian position of adrenocortical tissue.Case report: KM, 34 years, female, mother of two children, came for lower limbs edema which began one month after last delivery. Clinical exam ...

Efficacy of the combined therapy of somatostatin analogues and dopamine receptor antagonists in patients with growth hormone (GH) producing hypophysial adenomas was compared. 30 patients with acromegalia aged from 28 to 58 with the disease duration from 2 to 5 years receiving radio – therapy (gamma-therapy, 60 Gy) within 2001–2002 were examined. 7 of the examinees (1st group) received sandostatin in the dose of 100 mkg/day and 23 patients received parlodel in the dos...

Over the 10 percentage of all intracranial tumors are pituitary tumors.Their malignicity depends on their localisation, meanwhile their biological nature is benign. Regarding the size there are microadenomas (smaller than 10 milimeters) and macroadenomas (10 milimeters or more).Clinical manifestations of pituitary tumors depend on their localisation and hormonal activity. They are either hormonally functional or nonfunctional, resp...

The work was initiated to study histological characteristics of various pituitary adenomas (PA). We examined 47 patients with various PA undergoing surgery, 18 men (38.8%) and 29 women (61.7%) among them/ 32 patients of those (68.1%) were operated on transsphenoidally, 15 people (31.9%) and 1 patient (2.1%) undergoing the osteoplastic cranial trepanation and the diagnostic biopsy, respectively. Pre-operational CT/MRT of hypothalamohypophysial system detected infrasellar growth...

Transsphenoidal surgery is the treatment of choice in acromegaly. However, some patients do not achieve postoperative remission. The aim of our study was to identify factors that predictive of a poor surgical outcome in patients with acromegaly. In our study we included 39 acromegalic patients, who underwent transsphenoidal surgery as initial treatment. We evaluated clinical, hormonal and radiological predictors based on magnetic resonance imaging (MRI). Also we examined immun...

Pituitary enlargement with long standing hypothyroidism is well established.The clinical evolution of pituitary hyperplasia to thyroid hormone should be monitored closely during primary hypothyroidism because of the rare possibility of an incidental non thyrotropic pituitary tumor that will not regress on thyroid hormone. We report a case of a pituitary mass not responding to thyroid hormone therapy.A 46 years old women was admitte...

Background: The Olsztyn region, in the north-east of Poland, is mainly a rural area with the population of 0.77 mln. After the Chernobyl breakdown the region was classified as one of the most heavily radioactively contaminated areas of Poland. It was also characterized by mild severity of iodine deficiency and endemic goiter before iodine prophylaxis introduction in 1996/7.Aim of the study: To evaluate the incidence rate (IR), current trend and histotype...

Introduction: Insulinomas are usually singular adenomas <1 cm. Less than 5% have diameter >3 cm. Multiple adenomas frequency is estimated on 3 do 9%. Malignant insulinomas are diagnosed in 3–6% patients. The oldest patient with insulinoma described in literature was 95 years old. About 30–50% of patients are previously misdiagnosed.Aim of the study: The aim of the study was presentation of patients with rare clinical characteristics of ...

We present the observation of a patient in whom the diagnostic of insulinoma was difficult in front of normality on the classically used indexes. A 63-year-old patient, whithout any antecedent or drug used, was admitted in our service after a hypoglycaemic coma (glycaemia 1.21 mmol/l, insulinemia not measured). Clinical examination was normal. We performed a fasting testing. Results are listed in this table:<ca...

A 27-year-old woman with Carney Complex, with inactivating mutation of the PRKAR1α gene [(a 2-bp deletion of nucleotides T and G at positions 576 and 577 with frame-shift mutation beginning with aminoacid residue threonine 163 (ΔFSterThr163)], bearing a GH secreting microadenoma, Cushing syndrome from PPNAD and with high operatory risk because of the neurological sequelae of cerebral embolism from atrial myxomas, underwent a low-dose mitotane (MT) regimen.<p clas...

In some patients with Cushing’s disease (CD), magnetic resonance imaging (MRI) fails to detect small pituitary ACTH-secreting adenomas despite the results of endocrine evaluation indicating Cushing’s disease.Aim: The aim of this paper is to study frequency of hypocorticism after radiosurgery – protonotherapy (PT) for patients with normal MRI for Cushing’s disease and for patients with confirmed adenomas.Methods:...

Background: Organ infiltration and metastasis are the only parameters defining malignancy of pancreatic endocrine tumors. Several studies had demonstrated the prognostic value of Ki-67 expression measured on histological sections obtained from the removed pancreatic endocrine tumors. We postulate that Ki-67 expression measured on fine needle aspiration cytology provides pre-operative indications of the malignancy of pancreatic endocrine tumors.Aim: Aims ...

Criteria to define biochemical remission of acromegaly following surgery have changed over the years, but still the controversy about current consensus exists. We assessed seventy newly diagnosed patients with acromegaly (43 females and 27 males, mean age 46.9±1.4 years, range 17–66 yrs) 8 weeks after transsphenoidal pituitary adenomectomy done by the same neursurgeon. Current consensus criteria were used to define postoperative remission: glucose-suppressed (nadir) ...

Aim: To study the carbohydrate metabolism in patients with Itsenko-Kushing’s disease (IKD) and Itsenko-Kushing’s syndrome (IKS).Materials and Methods: 23 patients with hypercorticism were investigated. From which in 8 patients IKD was diagnosed, and in 15 – IKS. In patients with IKD the amount of cortizol was at 8.00 – 273.3±56.8 ng/ml (N- 50–250 ng/ml); 20.00 – 343.3±43.8 ng/ml (N- 50–250 ng/ml); the value of...

Objective: Acromegaly is a rare pituitary disease due to excessive secretion of GH. Insulin resistance, impaired glucose tolerance (IGT) and diabetes mellitus (DM) are common features in acromegaly. Seventy-four active acromegalic patients were retrospectively evaluated in order to determine the impact of family history for diabetes mellitus on glucose tolerance, insulin resistance and beta-cell function.Patients and methods: We studied 74 patients with ...

Acromegaly is usually regarded as a disease which occurs sporadically. Familial occurence of acromegaly due to pituitary adenoma without any other endocrinopathy in a family is extremely rare. These patients should be evaluated for multiple endocrine neoplasia type 1 (MEN 1) and Carney complex. We report here two cases of acromegaly due to pituitary macroadenomas. Subject 1 is a 50-year-old woman and subject 2 is her 23-year-old son with elevated growth hormone (GH) levels dur...

Somatostatin (SRIH) inhibits cell proliferation by interacting with five distinct SRIH receptor subtypes (SSTR) by several pathways in many tissues. We previously demonstrated that SRIH, by activating SHP-1, inhibits cell proliferation of the human Medullary Thyroid Carcinoma (MTC) cell line, TT, which expresses all SSTR. However, the effects of SRIH on cell cycle proteins have not been investigated, so far. We therefore investigated the effects of SRIH and of a selective SSTR...

Medullary thyroid carcinoma (MTC) is a malignant tumour deriving from parafollicular C cells, with a highly chemoresistant phenotype. Failure of medical therapy has been ascribed, at least in part, to multi drug resistance (MDR1) gene over-expression. MDR1 encodes for a transmembrane glycoprotein, P-gp, which hampers intracellular accumulation of cytotoxic drugs. It has been demonstrated that P-gp expression and function depend on cyclo-oxygenase 2 (COX-2) expression, which is...

Intracranial germinomas are malignant neoplasms which are supposed to arise from primitive germ cells failed to migrate to the genital crest during embryonic development. Most of them are located in the intra-suprasellar region and may cause anterior and particularly posterior pituitary hormone deficits. Early establishment of the histological diagnosis is important for optimum treatment planning and a successful outcome. Intracranial germinomas are radiosensitive and potentia...

Male prolactinomas are rare and considered as bad responders to medical treatment compared to female cases. Our aim was to evaluate response of pituitary macrolesions secreting prolactin (PRL) to dopamine agonists. Our population was composed of 34 men (mean age =36.6 years) with a diagnosis of macroprolactinomas: mean tumor size =35.5 mm (12 – 118) and mean PRL =2505 ng/ml (132 – 19996). Bromocriptine was used with a mean dose of 22.94 mg/day (3.75 – 80) and a ...

Non functioning pituitary adenomas (NFPA) are considered as rare (about 20% of all tumors of pituitary area) but severe regarding to their complications.In this retrospective study we have analyzed 60 subjects with NFPA in order to study clinical, hormonal, visual and radiological abnormalities.Diagnosis of NFPA is made when there is a pituitary tumor demonstrated by CT-scan and or MRI with normal or discreetly elevated PRL (&#8804...

The GH/IGF axis has been implicated in the pathogenesis of retinopathy in diabetic subjects, the aim of this study is to evaluate the prevalence of diabetic retinopathy in hypersomatotropic patients.Subjects and methods: Twenty four hypersomatotropic patients (12 females, 12 males mean age =49 years, mean hypersomatotropic duration =11 years) have diabetes for 7.25 years in average. To search for diabetic retinopathy a funduscopy was performed in all pat...

We present a case of 32-year old male patient who was admitted to hospital because of newly discovered hypertension with symptoms of 4P (pain, pallor, perspiration and palpitation). During hospitalization the patient presented with polyuria, polydipsia, hyperglycemia and psychotic disorders. The suspicion of secondary hypertension was made.Catecholamine examination test was done and revealed very high levels of adrenalin (five times more than normal), no...

Active acromegaly is associated with significant comorbidity and reduced quality of life. Cross-sectional studies have shown that quality of life did not significantly change in long-term cured acromegalic patients. However, the effect of medical treatment on the quality of life in the short term is unknown.We evaluated the quality of life by a disease-specific questionnaire in a longitudinal study before and after a 6-month course with somatostatin anal...

35-year old female patient with bilateral pheochromocytoma and operated medullary carcinoma of thyroid gland (MEN II B sy.) is put in the octreotide therapy as she doesn’t accept operation as a therapy because of religious reasons (transfusion of blood) and attacks of artery hypertension couldn’t be control with alfa-adrenergic receptors antagonists.12 MONTH 2004 ADRENALIN-urine 890 nmoldU/l (10.2–65.5); NORADRENALIN-urine >5000...

Treatment of adrenocortical carcinoma (ACC) is still unsatisfactory. As IGF-II and IGF-I receptor are frequently overexpressed in human ACC and inhibitors of the IGF system are currently under preclinical investigation, interference with IGF-signaling might have an additive effect in antitumour treatment. We have therefore analyzed several cytotoxic agents (etoposide, doxorubicine, cisplatin, streptocozin; 0.01–100 μM) on adrenal cell proliferation in vitro an...

Objectives: The TNM classification is a worldwide benchmark for reporting the extent of malignant disease and is intended as a prognostic tool to predict the outcome in patients with cancer. Until 2004, no TNM classification was available for adrenocortical carcinoma (ACC) and different staging systems were used. Due to the rarity of this malignancy, the prognostic value of different staging systems has never been compared directly in a large series of patients.<p class="a...

Growth hormone deficiency frequently occurs as consequence of radiation therapy in pituitary disorders. However, it not known whether radiation therapy in acromegaly results in comparable diminution of GH secretion. We therefore hypothesized that stimulated and spontaneous GH release is ultimately indistinguishable in irradiated acromegalic patients and irradiated patients with other pituitary disorders. For this study 10 acromegalic patients and 10 patients with other pituita...

Members of the secreted WNT glycoprotein family are important in embryogenesis and adult tissue homeostasis, and defects in the signal transduction of several WNT ligands including WNT4 have been linked to a variety of clinical conditions. Deletion of Wnt4 gene in mice leads to improper development of many organs including the adrenals in which the zona glomerulosa forms imperfectly. The objective of this study was to investigate the expression of WNT4 in human adult and fetal...

The aim of the present investigation was to study first signs of disease, effectiveness of the cabergoline treatment for prolactinomas in men. We studied 53 patients with pituitary adenomas. Patients are divided into 2 groups depending on size of the tumor: group I - microadenomas (11), group II - macroadenomas (42). PRL level before treatment in group I on average was 5890±7.4 mU/l; in group II - 29790±18.2 mU/l. Testosterone level in group I was 9.45±0.6 nmol/...

The purpose of the study was to assess the peculiarities of diagnostic and treatment of thyroid cancer in children.Material and method: Between 2000–2005 we screened 234 patients age 3–18 years that presented for various complaints suggesting possible thyroid disease (thyroid enlargement, dysphonia, dysphagia, delayed growth). They were submitted to clinical examination, ultrasonography, T4 and TSH test. The solitary nodules and polinodular goi...

We have studied 5 cases of insulinomas presented in our clinic in 2004–2005 with typical signs and symptoms of hypoglycemia correlated with high insulinemia. The medium insulin value in the morning was 57.9 mUI/ml, but we found values ranging from 10–98 mUI/ml for medium and severe hypoglycemia. There was no correlation between severity of hypoglycemia and insulin level, proven by repeated insulin dosages.The purpose of our analysis was to iden...

Background: Due to its cross-talk with estrogen receptor (ER) signalling, increased IGF-I signalling through the IGF-I receptor (IGF-IR) has been postulated as an important factor in the development of tamoxifen resistance in breast cancer.Aims: To investigate the importance of IGF-I signalling in tamoxifen resistant (TR) and wild-type (WT) MCF-7 breast cancer cells by (i) assessing cell proliferation in response to IGF-I and tamoxifen and (ii) using sma...

Adrenocortical carcinoma (ACC) is a rare and highly malignant tumour with a poor prognosis with an incidence of 1 – 2 per million population per year. We report 2 cases of functioning ACC.Case 1: An 80 yr old with a history of hypertension, paroxysmal atrial fibrillation and cerebrovascular disease presented with leg ulcers, peripheral oedema, tiredness, weight gain, plethora and proximal myopathy. ACTH-independent Cushing’s syndrome was confir...

Cushing’s disease (CD) may recur despite early remission following transsphenoidal surgery (TSS). We evaluated whether early post-operative serum cortisol (sF) levels on post-operative days 3, 4, 5 predict recurrence.Methods: Patients with CD treated at NIH completed a questionnaire regarding remission status, treatment, and recent biochemistry. We analyzed patients with adenomectomy or hemihypophysectomy at initial TSS, with ACTH-staining tumor and...

Activating mutations of the RET proto-oncogene, encoding a tyrosine kinase receptor, are associated with inherited syndromes, MEN2A and MEN2B, and with both familial and sporadic medullary thyroid cancer (MTC). Single base-pair missense mutations in the extracellular cysteine-rich domain are responsible for the majority of MEN2A and familial MTC (FMTC) cases. Rarely, somatic deletions and germline duplications of variable segments of the gene have been reported in spora...

Prolactinoma represents 27 to 35% of pituitary adenomomas and 40 to 75% of secreting adenomas. However, the macroprolactinomas are not frequent. We report clinical, biological and therapeutic aspects of 5 cases of macroprolactinomas. It concerns 3 women and 2 men. The average age is 43.4 years (19–68). The reason for seaking medical advice was amenorrhea – galactorrhea syndrom in 2 women and infertility in one case. The diagnosis of pituitary adenoma is incidentally ...

Insulinoma causes fasting hypoglycemia due to inappropriate insulin secretion. The diagnosis of insulinoma is based on Whipple’s triad (1. symptoms precipitated by fasting with 2. associated blood sugars of 50 mg/dl or less and 3. relief of symptoms by glucose administration) during a supervised 72 h fasting test. After introducing reliable assays for measurement of insulin and proinsulin, there is an ongoing debate whether a 48 h fasting test is sufficient for diagnosis ...

Introduction: Characteristic localisations of metastases of differentiated thyroid carcinoma (DTC) include local lymph nodes, the lungs and bones, while the incidence of DTC metastases onto the liver, the brain and skin is clearly lower. The localisation of metastases in other organs, including the kidneys, is very rare.Material and methods: A case of a 73–year-old patient with thyroid oxyphilic carcinoma is reported, the case being diagnosed in 199...

The purpose of our study was to establish an assay for the measurement of aldosterone in saliva which utilises a simple, non-invasive sampling technique on an out-patient basis. For this we have developed a non-isotopic, time-resolved fluorescence immunoassay. The assay only requires a volume of 100 μl for each duplicate value obtained and involves an overnight incubation after extraction of samples. Cross-reactivity with potentially interfering steroids is below 0.01%. T...

Thyroid autoimmunity and BC are strongly related, but the cause of this association is unknown. In BC an increase of lymphoid cell infiltrates may be detected very early during tumor development. BC cells share some antigenic properties similar to those detected in thyroid tissue, as NIS and peroxidase activity and it is possible that in patients with BC and thyroid autoimmunity, should be present serum immunoglobulins reacting with these specific antigenes.<p class="abste...

Pituicytoma is a rare hypophyseal tumour with very few case reports in literature so far. We report a 76 years old gentleman, with know hypertension, hypercholesterolemia and T2DM, who presented initially with features of hypogonadism and a bilateral inferior quadrantanopia. Initial Hormonal assessments revealed Testosterone of <0.05 nmol/l, FSH 2U/l, LH 2U/l and Prolactin 586 mU/l, confirming hypogonodotrophic hypogonadism. He was started on testosterone replacement using...

VEGF exerts its effects by binding to two tyrosine kinase receptors, KDR and VEGFR1. KDR is critical for transmitting signals for proliferation and migration of endothelial cells but is also expressed in several non-endothelial cells, and is elevated in some human tumour cells. We investigated KDR expression in human thyroid epithelial cells in vitro and thyroid cancers compared with normal thyroid samples examined ex vivo. Expression of KDR was demonstrated usin...

MEN 1 is an autosomal dominant syndrome associated with benign and malignant neuroendocrine neoplasia. It is characterised by primary hyperparathyroidism, pituitary neoplasia and foregut lineage neuroendocrine tumours. It has also been associated with premature cardiovascular death. Since diabetes is associated with an increased risk of cardiovascular mortality we investigated the prevalence of diabetes (DM) and impaired fasting glucose (IFG) in a large cohort of patients with...

Tissue samples from adrenal tumors provide the basis for standard diagnostic procedures such as pathological examination. In addition, these tumor samples have been an invaluable source for the discovery of novel molecular pathways involved in adrenal tumorigenesis. Information on the molecular phenotype are based on DNA mutation analysis and epigenetic changes, RNA and protein expression pattern and sub-cellular localization as well as post transcriptional protein modificatio...

Adrenal incidentalomas are referred as clinically silent adrenal masses discovered incidentally during diagnostic testing or treatment for conditions not related to suspicion of adrenal disease. Certain percent of them are hormonally active and autonomous cortisol secretion is reported with increasing frequency. The aim of the study was to assess value of 1mg-DST in subclinical Cushing’s syndrome (CS) compared to the other forms of adrenal incidentalomas. We have evaluate...

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We have previously shown PTTG and PBF to be over-expressed in differentiated thyroid cancer and to be prognostic indicators for recurrence. Subsequently we reported PBF to be a transforming gene in vitro and tumourigenic in vivo. Since over-expression of PTTG results in the same findings, we examined whether PBF-induced tumourigenesis was an independent effect, or else a result of increased PTTG activity. Two HA-tagged mutants of PBF were generated, firstly subst...

Carney’s complex was first identified as the association of primary adrenal nodular dysplasia, lentigines and cardiac and skin myxomas. Several other endocrine and non-endocrine disorders were subsequently added to the complex, including pituitary tumors and melanotic Schwannomas. We herewith describe a kindred with Carney’s complex featuring acromegaly as the common denominator.Patients & methods: A 42-year-old woman first presented to our...

In supine subjects aldosterone daily variations are determined by spontaneous PRA rhythmicity and ACTH secretory bursts. The aim of this study was to analyze diurnal and pulsatile aldosterone secretion in two patients with primary aldosteronism (PA): a 33-year-old woman with aldosterone producing adenoma (APA) and a 40-year-old woman with idiopathic adrenal hyperplasia (IAH). Blood samples were taken hourly during 24 hours at the time of the diagnosis and three months later, a...

Tumors derived from chromaffine tissue include pheochromocytomas (tumors located in adrenal medulla) and paragangliomas (extraadrenal tumors). These tumors are in 20–25% inherited. Paragangliomas are even rarer and are presented either as familial disease or pheochromocytoma-paraganglioma syndrome (PPS). The mutations in SDH genes (SDHB, SDHD) are suspected for causing the syndrome.The aim of present study is to look for germline mutat...

Neuroendocrine molecules play a significant role in the progression of human prostate cancer (PCa) and its neuroendocrine differentiation has been associated to a worse prognosis. Among these molecules, the pleiotropic peptide neuropeptide Y (NPY) was found to be expressed in the human prostate and may show some relevance in PCa progression. In this study, we evaluated the direct effect of NPY on the growth of the human PCa cell lines LNCaP (androgen dependent) and DU145 and P...

The beta-HLH transcription factors NeuroD1 and ASH1 are frequently expressed by pituitary adenomas, both being present in all corticotroph, most clinically non-secreting (CNS) and a subset of GH and/or PRL-secreting adenomas. We wished to investigate the expression of the related beta-HLH factors neurogenins (Ngn) 1, 2 and 3 in the pituitary (n=4) and in a series of pituitary adenomas (n=45). RT-PCR was performed at different amplification cycles (up to 45) in al...

Epithelial Ovarian Cancer (EOC) is the leading cause of death from gynaecological malignancy in the developed world. Epidemiological evidence indicates number of lifetime ovulations as being a major risk factor for the development of the disease. As ovulation is an inflammatory process, it is thought that repetitive inflammation-associated damage to the ovarian surface epithelium (OSE) leads to oncogenic events within these cells. Previous studies have demonstrated that health...

The usefulness of long-term medical treatment with somatostatin analogs has not been evaluated in insulinomas. 22 patients with hypoglycaemia related to endogenous hyperinsulinism (62±21 years, M±S.D., 27–88 years) were not treated by surgery: aged patients (n=10), patients with malignant unresectable insulinomas (n=6; locally invasive, n=1; multimetastatic, n=5), multiple insulinomas (n=2), diffuse beta cell pat...

Dopamine agonist therapy is an effective long-term treatment in >90% of patients with hyperprolactinaemia, controlling both prolactin secretion and tumour growth. We describe the unusual late emergence of resistance to high-dose dopamine agonist treatment in two recent female patients. Both women presented with secondary amenorrhoea, were shown to have high prolactin levels and a pituitary microadenoma. Each had an excellent initial response to bromocriptine but years late...

Early 2005 we reported on a new insertion-deletion mutation (insTTCTdelG) at codon 666 (exon 11) of the RET proto-oncogene. The index patient, a 12 year old boy with locally metastasized MTC, inherited the mutation from his maternal grandfather. His mother had a basal calcitonin of 30 ng/l and underwent a prophylactic total thyroidectomy at age 48, showing C-cell hyperplasia in both lobes and early MTC with a maximum size of 1.5 mm. At age 82, his grandfather did not have clin...

Aim: We previously reported preliminary evidence that use of TRH with CRH during inferior petrosal sinus sampling (IPSS) in Cushing’s syndrome gave additional information about quality of pituitary venous sampling and significance of gradients. We now report long-term experience of this technique in 40 patients investigated 1993–2005. We used standard central:peripheral ratios (C:P) of 2:1 basally and 3:1 after stimulation to indicate pituitary secretion and intersin...

Malignant glucagonomas are slow-growing tumours which more commonly cause symptoms through glucagon hypersecretion than through effects of tumour bulk. The glucagonoma syndrome includes necrolytic migratory erythema (NME), diabetes mellitus, weight loss, anaemia, chelitis, venous thrombosis and neuropsychiatric symptoms. The syndrome probably results from unrestrained proteolysis1, and rapid consumption of B-vitamins through accelerated intermediate metabolism2...

Headaches associated with acromegaly are common even after hypophysectomy. Medical treatment with dopamine agonists and Somatostatin analogues often help. We report two cases when pharmacological therapy failed but further surgical removal of residual pituitary tissue cured the headaches.A 38 year-old lady presented with an eight year history of headaches, unresponsive to simple analgesia. Acromegaly was confirmed by a raised serum growth hormone (GH) 33...

Adrenal incidentalomas are incidentally discovered adrenal tumors by imaging methods without any prior suspicions of adrenal disease. Most of these tumors are functionally inactive but thorough investigations can reveal discrete hormone excess. Chromogranin A(CgA) is expressed in neuroendocrine cells throughout the body, including large and small intestine, adrenal medulla and pancreatic islets. It is a marker for carcinoid tumors, paragangliomas, and other neuroendocrine tumo...

Familial medullary thyroid carcinoma (FMTC) is an autosomal dominant inherited disease, characterized by germ-line mutations in the RET proto-oncogene, mainly in exons 10 and 11, but also in exons 13, 14 and 15. Recently, there were described also mutations in exon 8 and 16 associated with FMTC. In our laboratory the screening of six risk exons of the RET proto-oncogene in 141 families with MTC was performed. 10 families were classified as clinically FMTC. In 4 of them mutatio...

Contemporary management of macroprolactinomas relies heavily on the use of dopamine agonist (DA) therapy. However, historically a proportion of patients may have undergone surgery and/or pituitary radiotherapy. We aimed to determine the long-term outcome in terms of tumour control and prolactin normalisation in a large cohort of patients with macroprolactinoma who received various treatment modalities. 80 patients (54 male) with macroprolactinoma (tumour diameter >10 mm, p...

Obesity is a major cause of chronic hypoventilation and/or obstructive sleep apnea syndrome (OSAS). Aim of this study was to evaluate the prevalence of pulmonary dysfunction and the relationship between OSAS and several clinical, functional and polysomnographics parameters in severely obese patients. 101 subjects (68 females and 33 males) aged 49.2±13.2 years (mean±S.D.), with BMI 46.8±6.5 Kg/m2 were enrolled. Sleep quality and daytime ...

Familial pheochromocytoma is inherited as a component of one of 5 pheochromocytoma – related syndromes such as von Hippel-Lindau disease, multiple endocrine neoplasia type 2 and the paraganglioma syndromes type 1 and type 4.Neurofibromatosis type 1 is often cited as the fifth of these syndromes but a clinical-genetic characterisation does not exist. 0.1 to 5.7% of patients with neurofibromatosis type 1 have pheochromocytoma. The NF1 gene as the susc...

To evaluate the epidemiology and global quality of care of acromegaly in Belgium, all endocrinologists treating patients with acromegaly were invited to participate in a nationwide survey extending from 15-6-2003 till 30-9-2004, aiming to include all patients (including deaths) that were in follow up or newly diagnosed after 1-1-2000. The project was ethically approved and written informed consent obtained. Retrospective data on demographics, pathology, complications and treat...

The German Acrostudy is at present the largest database on acromegalics (n=184) treated with pegvisomant (Somavert®). 91% pts underwent pituitary surgery, 45% received radiation therapy, and previous medical therapy included dopamine agonists (56%), octreotide (90%) and/or lanreotide (10%). Common concomitant diseases at baseline were hypertension (47.0%), diabetes mellitus (31.7%), and gallstone disease (25.6%). Efficacy analysis was performed in 134 pt...

Medullary Thyroid Carcinoma (MTC) is a rare cancer that arises from the thyroid C-cells and occurs as sporadic in 75% of the cases. In 25% of MTC cases, mutations of the RET proto-oncogene are responsible for the development of three dominantly inherited neoplastic disorders including multiple endocrine neoplasia (MEN) 2A, MEN 2B and familial medullary thyroid carcinoma (FMTC). Since 2–8% of MTC cases considered sporadic conceal germline mutations, direct analysis of the ...

Familial medullary thyroid carcinoma (FMTC) is caused by germ-line mutations in the RET proto-oncogene. These mutations concern mainly exons 10 and 11, whereas mutations in exons 13–16 are rare. Mutations in exon 8 have been reported in the literature only twice.We performed direct analysis of exons 7–19 and 21 of RET gene in two apparently unrelated Greek index-patients with FMTC, presenting negative initial screening for mutations in exons 10...

Background: In many acromegalics neurosurgery is unable to control GH secretion while it may harm the normal pituitary.Objective: To investigate the effect of pre-treatment with octreotide on surgical outcome in acromegaly.Methods: Previously untreated acromegalics were randomised directly to surgery or octreotide for six month before transsphenoidal surgery. Three months postoperatively patients underwent OGTT and Insulin Toleranc...

Paragangliomas (PGLs) are neuroendocrine tumors arising from the neural crest and localized from the skull base to the pelvic floor. In particular, parasympathetic PGLs arise in the head/neck region (carotid body, vagal nerve, jugulare and tympanic glomus) and more rarely in the anterior thorax, while sympathetic PGLs are localized in the posterior thorax and in the abdomen and secrete catecholamines.Localization of paragangliomas might be performed by a...

Somatostatin (sst) receptors are expressed in many tissues and multiple subtypes are often present in the same cells. Their activation by endogenous sst as well as by sst-analogues leads to inhibition of secretion and growth in some tumor, such as the neuroedocrine ones.Pheochromocytomas (Pheos) and paragangliomas (PGLs) are neural crest-derived tumors which can be sympathetic or parasympathetic in origin and present themselves as sporadic or familial. T...

Background: The role of post-operative radiotherapy (RT) in the treatment of non-functioning pituitary adenomas (NFA) remains controversial. We compared the difference in outcome between patients receiving transsphenoidal surgery (TSS) alone and TSS plus RT in 93 patients treated for NFA between 1986 and 2005. 64 (69%) had TSS alone whilst 29 (31%) received TSS plus RT (45GY, 25Fr, 3 field). All patients were followed up by CT and then MRI scans repeated at increasing interval...

‘Silent’ ACTH-secreting pituitary adenomas are not characterized by specific clinical features that would suggest the presence of hypercortisolism. In contrast, they present as non-functioning pituitary macroadenomas with either visual compromise or hypercortisolism. However, immunostaining reveals ACTH-secreting cells.In order to characterize the laboratory features of these tumours, we have preoperatively assessed 56 patients with either clin...

Background: Mitotane,(o,p’-DDD)is a compound with potent adrenotoxic effect and is able to block cortisol synthesis by inhibiting 11β-hydroxylation and cholesterol chain cleavage. For these reasons, mitotane was widely used in the treatment of adrenocortical cancer. Nevertheless the biological mechanism induced by these treatments in this cancer cells remain unknown.Aim: To study whether the o,p’-DDD could increase the susceptibility to th...

The two regulatory subunits (R1 and R2) of PKA are differentially expressed in several cancer cell lines and studies indicate distinct roles for these subunits in growth control. Recently, mutations of the regulatory subunit 1A of PKA gene have been identified in patients with Carney complex (CNC). The aim of this study was to evaluate the expression of the different PKA regulatory subunits (R1A, R2A, R2B) in adrenocortical tumors not associated with CNC, as well as the effect...

The optimum management of patients with craniopharyngiomas is controversial. Evidence relies on a small number of retrospective outcome surveys that encompass time periods that are not necessarily representative of current surgical techniques and imaging modalities. We have reviewed outcome in a more contemporary group of patients managed at a single centre.Case-notes and electronic data were reviewed of all patients treated for craniopharyngioma since 1...

It has been generally believed that clinically functioning pituitary adenomas are highly specialized neoplastic lesions, which produce a unique hormone. Increasing body of evidence argue against this concept, since about half of prolactinomas (PRM) and approximately 60% of TSH-secreting adenomas are multihormonal and 30–40% of GH-secreting adenomas co-secrete PRL. Most of classically considered null cell adenomas have been proved to be immunohistochemical positive for gon...

N363S polymorphism of the human glucocorticoid receptor gene has been detected in the heterozygous state in approximately 3–9% of general European population. This variant has been associated with increased sensitivity to glicocorticoids, increased insulin response to dexamethasone, a tendency towards lower bone mineral density, increased body mass index, and unstable angina. However, other reports found no associations with these pathological conditions. We assessed the ...

Thyroid cancer in patients with hyperthyroidism is considered to be a rare event and its course seems to be more aggressive in patients with Graves’ disease. The coexistence of medullary thyroid cancer and hyperthyroidism is very rare and there are only 14 cases reported in the literature.The aim of this retrospective study is to assess the clinical and histological characteristics and the evolution of thyroid cancer in patients with different types...

Introduction: Diagnosis of pancreatic neuroendocrine tumours (NETs) is often a challenge and involves biochemical characterisation and anatomic localisation of the tumour. Wherever feasible, curative surgical excision is the treatment of choice.Materials and Methods: Twenty four consecutive patients with pancreatic NETs were referred for consideration of surgery over a six-year period (1999–2005). Following use of multi imaging modalities to localis...

Case report: A 56-year old man presented with a 3 month history of painful bilateral gynaecomastia and sexual dysfunction. Investigations revealed hypogonadotrophic hypogonadism with markedly elevated serum E2, but otherwise normal baseline anterior pituitary function. Tumour markers were negative and adrenal androgens and LFTs were normal. Imaging identified a ∼6 cm right adrenal mass. Preoperative workup excluded phaechromocytoma, but identified low-grade, ACTH-indepen...

Head and neck paragangliomas (HNPs) are tumors derived from the neuroectoderm. HNPs are generally hormonally silent and often asymptomatic. They can be part of the Pheochromocytoma/ Paraganglioma Syndrome, due to mutations of SDHB, SDHC and SDHD genes. SDHD founder effects have been described in the Netherland, USA, Italy and Spain.We identified a new founder effect in a small geographic area (Valsugana-Trentino, actually 50.000 inhabitants), with high a...

Hereditable forms account for 30–40% of pheochromocytomas (pheo). The role of germ-line mutation of VHL, RET, SDHB, SDHD gene has been largely elucidated. However, genotyping a group of 172 sporadic or familial pheo, we have characterize five unrelated probands with familial pheo without any sequence variants of RET (7 exons), or of the entire coding sequence of VHL, SDHB, SDHC or SDHD.The proband #1 had a bilateral pheo when 32 and a local recurren...

Endostatin, a cleaved fragment of collagen XVIII, is a potent endogenous angiogenesis inhibitor. Elevated serum endostatin levels have been recently reported in patients with various types of neoplasms. The purpose of our study was to evaluate serum concentrations of endostatin in patients harbouring various types of pituitary adenomas and to examine the relationship of serum endostatin levels to circulating vascular endothelial growth factor (VEGF) levels. Preoperative serum ...

Surgical treatment is the first therapeutic option in patients affected with medullary thyroid carcinoma (MTC). However, cure-rates are often low due to the high frequency of loco-regional metastases and recurrences. Therefore, post-operative hyper-calcitoninemia is a common feature in CMT. Despite these findings, traditional imaging techniques are often unable to localize tumour foci. In the last years the availability of new morpho-functional techniques might offer new chanc...

Introduction: Papillary thyroid micro-carcinoma (PTMC) is a well-differentiated thyroid cancer ≤10 mm in diameter. The recent higher prevalence of PTMC is due to the frequent detection of micro-carcinomas as an incidental finding in surgical specimens, but especially during routine imaging of the neck with highly sensitive techniques.Aim: To review the clinical course of PTMC so to reach its optimal management by adapting therapy and follow-up sche...

Introduction: Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) is an innovative method for the detection of primary tumours or metastases of thyroid cancer; however, recurrence or metastases of medullary thyroid carcinoma (MTC) are still difficult to detect.Aim: The objective of this study was to evaluate the clinical use of 18F-FDG PET in patients with MTC.Patients and methods: We enr...

Objective: Interindividual variation in glucocorticoid sensitivity can be partly explained by polymorphisms in the GC receptor gene. The most frequent polymorphisms of the GR gene (N363S and BclI) are associated with increased BMI, less lean mass, higher cholesterol and insulin levels. In the present study we investigated the role of the N363S and the BclI polymorphisms in patients with adrenal disease to evaluate their prevalence and the possible clinic and hormone correlatio...

Familial Hypocalciuric Hypercalcemia (FHH) is an autosomal dominant disorder characterized by moderate and lifelong hypercalcemia, relative hypocalciuria, and inappropriately normal serum PTH levels. Loss-of-function mutation of the CaR are responsible for this disease.In this study we describe three unrelated Italian kindreds (A, B and C) and one patient with FHH. The diagnosis of FHH in the propositus was suspected on the finding of hypercalcemia, norm...

Familial isolated primary hyperparathyroidism (FIPH) can result either from incomplete expression of a syndromic form of familial primary hyperparathyroidism [multiple endocrine neoplasia types 1 (MEN 1), hyperparathyroidism-jaw tumor syndrome (HPT-JT), or familial hypocalciuric hypercalcemia (FHH)] or still unrecognized causes.We investigated the involvement of MEN1, HRPT2 and CASR genes by direct sequencing of germline DNA in seven...

Carcinoid tumours are the commonest neuroendocrine neoplasms (NET) with a prevalence of less than one person per 100,000 population. The proliferative index (Ki67%) has a prognostic relevance for pancreatic neuroendocrine tumours, however its value in non-pancreatic NET tumours is unclear. Our retrospective audit was done to look at factors affecting survival. Medical records of 96 patients referred to our clinic since 1999 with a diagnosis of NET tumour (excluding pancreatic ...

For somatostatin, five receptor subtypes (sst1-5) have been identified that are widely distributed in various endocrine tissues and tumors. Potent somatostatin analogs like octreotide, lanreotide and the new multiligand SOM230 – with different binding properties to the receptor subtypes - have been developed. We examined somatostatin receptor protein expression in 134 pituitary tumors of various etiologies. Immunostaining was performed with specific polyclonal anti...

Adrenal carcinoma is a rare neoplasm with poor prognosis. Mitotane (o,p′-DDD) is the only known therapeutic agent with action on the adrenal. Although it has been used for many decades, its pharmacological properties and exact mechanism of action are still debated. It has been suggested that its therapeutic effect is dose-dependent (Baudin et al 2001). High performance liquid chromatography (HPLC) has been used for the exact measurement of mitotane dose.<p cla...

The presence of lipomas is a characteristic of the syndrome of multiple endocrine neoplasia type 1. The presence of myxomas, however, is a characteristic of Carney syndrome.The aim of the study is the description of a patient with the syndrome of multiple endocrine neoplasia type 1 who presented with a malignant angiomyxoma.A male patient, aged 42 years, presented with intense gastric complaints and was diagnosed with a gastroduode...

We report a family with a novel heterozygous mutation of the menin gene. This gene encodes a tumor suppressor protein which is responsible for multiple endocrine neoplasia type 1. The index female patient presented with symptoms of mild gastric hyperacidity and recurrent kidney stones. Family history revealed, that the daughter, as well as two sisters of the index patient had operations for primary hyperparathyroidism (PHPT). Clinical studies in the index patient showed elevat...

Introduction: Pituitary adenomas causing acromegaly are immunocytochemically divided into 3 main groups: growth hormone (GH) cell (A), those with GH and prolactin (PRL) cell differentiation (B) and plurihormonal (C). Recent large series comparing the hormonal and imaging features of these tumours at diagnosis are lacking.Objectives: To investigate differences in the presenting hormonal and imaging data associated with the above groups of adenomas.<p ...

A 69-year-old female presented in 2002 with symptoms of hyperthyroidism. Thyroid function tests confirmed thyrotoxicosis with elevated fT4 and fT3 but with an elevated TSH (TSH 5.8 mU/l, fT4 31.7 pmol/l, fT3 8.1 pmol/l). Pituitary function tests other than the TSH were normal. Pituitary MRI showed a mass in the left half of the pituitary fossa, displacing the stalk to the right with no suprasellar extension. A T3 suppressi...

At least one fifth of pituitary adenomas exhibit plurihormonality when using immunohistochemistry for anterior pituitary hormones. However, the correlation with clinical features is weak, without an agreement upon pathological predictors of tumour behaviour.The aim was to determine the immunoreactivity for anterior pituitary hormones and alpha subunit in 276 consecutive pituitary adenoma patients, aged 22–79 years (44.3±8), 154 F/ 122 M: 83 acr...

Without adequate treatment patients with acromegaly die prematurely from cardiovascular disease (CVD); however the contribution of atherosclerosis in this process is controversial. Increased carotid IMT is an early morphological marker of atherosclerosis and predictor of subsequent cardiovascular events. Contradictory data exist regarding IMT in patients with acromegaly.We measured carotid IMT in 79 patients with acromegaly (47 male, mean age 55±14 ...

The prevalence of gallstones (GS) is increased in acromegaly and is further increased by somatostatin analogue (SA) therapy. The incidence has variously been reported to be between 10 and 63%, but they are often asymptomatic and rarely require definitive management. However, there is evidence suggesting that discontinuation of SA therapy may precipitate acute biliary problems.We have analysed our experience of symptomatic gallstones in all 44 patients (2...

In order to investigate the correlations between immunohistochemical picture with proliferative index (Ki-67), the clinical course and outcome of GH-secreting pituitary adenomas not cured by neurosurgery, we studied 41 consecutive acromegalic patients (M 12, F 29; aged 43±10.8 yr) previously undergone neurosurgical resection of adenoma. Two patients underwent neurosurgical intervention at least twice. Post-surgical follow-up ranged from 6 to 36 months and all patients rec...

Introduction: Somatostatin analogues (SSA) represent the main therapeutic option in patients affected with functioning well-differentiated neuroendocrine tumors (NET). However, after a variable time from the start of the therapy tachyphylaxys may cause lack of control of clinical syndrome and progression of the disease.Aim: The aim of this preliminary study was to evaluate efficacy in terms of reduction of circulating markers, control of the clinical syn...

It has been suggested that primary medical treatment of patients with acromegaly using somatostatin analogues (SSA) is as effective at controlling GH levels as post-operative SSA therapy.We have carried out a prospective study in patients harbouring GH secreting macroadenomas to see, in a within-patient comparison, whether debulking pituitary surgery improved GH control on lanreotide compared with that obtained pre-operatively. Local Ethical Committee ap...

Background: Cushing’s disease (CD) may be associated with equivocal results on biochemical investigations.Aim: To evaluate the usefulness of dexamethazone suppression tests in the diagnostic work-up of CD.Patients and methods: Seventy patients with CD [median age 38 yrs(16–76), 53 females] presenting between 1976–2005 were studied. 24-hr urinary free cortisol (UFC), overnight (oDST) (1 mg at 23:00 h), low dose (LDDST...

In the Rhône Alpes region, that hosts more than 5.6 million inhabitants; thyroid illnesses are still rather common with 3,600 operations on the thyroid gland per year, comprising 650 incident cases of cancer. A progressive increase in the incidence of thyroid cancer was suspected in the 1990 s and a population based register was initiated. The collection consists of histological data validated and obtained directly from pathologists, surgical wards and controlled through ...

The stable somatostatin analog octreotide has been successfully used for imaging and treatment of a variety of human tumors. Octreotide treatment has been reported of limited value in pheochromocytoma (PHEO). PHEOs often express more than one somatostatin receptor, and it is uncertain by which receptor subtype the functional responses of octreotide are mediated. A recent study showed by immunohistochemical staining that vast majority of tumors (90%) were positive for sst(3), i...

Surgical management for parathyroid disease worldwide is on the rise. Hand in hand, parathyroid surgery has evolved from the classical bilateral approach to the more focussed unilateral approach. The failure rate in the best of hands continues to be 3–4% but this figure may rise as Minimally Invasive Surgical techniques are universally adopted.Accurate pathological diagnosis to differentiate parathyroid adenomas from hyperplasia continues to be diff...