Patients with apparently nonfunctioning adrenal incidentalomas may be at increased cardiovascular risk due to excessive cortisol secretion.

CONTEXT: Although adrenal incidentalomas (AIs) are associated with a high prevalence of cardiovascular risk (CVR) factors, it is not clear whether patients with nonfunctioning AI (NFAI) have increased CVR. OBJECTIVE: Our objective was to investigate CVR in patients with NFAI. DESIGN AND SETTING: This case-control study was performed in a tertiary general hospital. SUBJECTS: SUBJECTS included 60 normotensive euglycemic patients with AI and 32 healthy controls (C) with normal adrenal imaging. MAIN OUTCOME MEASURES: All participants underwent adrenal imaging, biochemical and hormonal evaluation, and the following investigations: 1) measurement of carotid intima-media thickness (IMT) and flow-mediated dilatation, 2) 2-hour 75-gram oral glucose tolerance test and calculation of insulin resistance indices (homeostasis model assessment, quantitative insulin sensitivity check, and Matsuda indices), 3) iv ACTH stimulation test, 4) low-dose dexamethasone suppression test, and 5) NaCl (0.9%) post-dexamethasone saline infusion test. RESULTS: Based on cutoffs obtained from controls, autonomous cortisol secretion was documented in 26 patients (cortisol-secreting AI [CSAI] group), whereas 34 exhibited adequate cortisol and aldosterone suppression (NFAI group). IMT measurements were higher and flow-mediated vasodilatation was lower in the CSAI group compared with both NFAI and C and in the NFAI group compared with C. The homeostasis model assessment index was higher and quantitative insulin sensitivity check index and Matsuda indices were lower in the CSAI and NFAI groups compared with C as well as in CSAI compared with the NFAI group. The area under the curve for cortisol after ACTH stimulation was higher in the CSAI group compared with the NFAI group and C and in the NFAI group compared with C. In the CSAI group, IMT correlated with cortisol, urinary free cortisol, and cortisol after a low-dose dexamethasone suppression test, whereas in the NFAI group, IMT correlated with area under the curve for cortisol after ACTH stimulation and urinary free cortisol. CONCLUSIONS: Patients with CSAI without hypertension, diabetes, and/or dyslipidemia exhibit adverse metabolic and CVR factors. In addition, NFAIs are apparently associated with increased insulin resistance and endothelial dysfunction that correlate with subtle but not autonomous cortisol excess.

An adolescent with a rare midline neck tumor: thyroid carcinoma in a thyroglossal duct cyst.

Occurrence of malignancy in a thyroglossal duct cyst (TDC) in children and adolescents is very rare, preoperative diagnosis is a challenge, and appropriate management is still debated. We report a 19-year-old male patient referred for a midline neck mass diagnosed as an atypical TDC after initial and subsequent investigations. Ultrasound-guided fine-needle aspiration (FNA) of the mass was diagnostic for papillary thyroid carcinoma. Sistrunk procedure and total thyroidectomy were performed. Histologic analysis confirmed the presence of papillary thyroid carcinoma within TDC, infiltrating surrounding soft tissues. Postoperatively, radioiodine ablation treatment was administered, followed by TSH suppression therapy.

Association of lean body mass with cardiometabolic risk factors in healthy postmenopausal women.

OBJECTIVE: Aim of this study was to investigate the association of total and regional lean body mass (LBM) with cardiometabolic risk factors in healthy obese and nonobese postmenopausal women. METHODS: A total of 150 postmenopausal women (age 54 ± 7 years, BMI 29.6 ± 5.8 kg/m2) underwent a comprehensive assessment of cardiometabolic risk, including metabolic syndrome (MS). Body composition analysis was performed with Dual-energy X-ray Absorptiometry, and multiple height-adjusted indices of total and regional LBM were evaluated. RESULTS: After controlling for age, diet, physical activity, and total fat mass, most indices of total, central, and peripheral LBM displayed significant positive correlations with cardiometabolic risk factors. Most associations were no longer significant after controlling for waist circumference, with the only exception of lean mass in the arms, which remained significantly associated with the presence and severity of MS (number of MS abnormalities), independently of central adiposity. A significant additive interaction was found between lean mass in the arms and waist circumference in increasing the prevalence of MS. CONCLUSIONS: LBM is unfavorably associated with cardiometabolic risk factors in healthy postmenopausal women. Whether LBM, especially in arms, is associated with cardiometabolic health independently of central fat distribution in postmenopausal women, merits further investigation.

Regional fat distribution and cardiometabolic risk in healthy postmenopausal women.

BACKGROUND: Regional fat distribution is an important determinant of cardiometabolic risk after menopause. The aim of the present study was to investigate the association between indices of fat distribution obtained by Dual-energy X-ray Absorptiometry (DXA) and representative cardiometabolic risk factors in a cohort of healthy postmenopausal women. METHODS: In this cross-sectional study, cardiometabolic risk factors were correlated with a variety of central and peripheral fat depots obtained by DXA, in a total of 150 postmenopausal women, free of diabetes and cardiovascular disease (age 54 ± 7 years, BMI 29.6 ± 5.8 kg/m(2), mean ± 1 SD). RESULTS: After adjusting for age and total adiposity, DXA-derived indices of central and peripheral fat distribution displayed opposite associations (positive versus negative) with the examined cardiometabolic risk factors. In multivariate regression analysis, thoracic fat mass % was an independent predictor of blood pressure, HOMA index and triglycerides, abdominal fat mass % was an independent predictor of high sensitivity C-reactive protein, and abdominal-to-gluteofemoral fat ratio was an independent predictor of high density lipoprotein cholesterol. An index of peripheral fat distribution, gluteofemoral fat mass %, proved to be the most important determinant of metabolic syndrome (Odds Ratio 0.76, 95% confidence intervals 0.67-0.87, p<0.001), independent of total and central adiposity. CONCLUSION: DXA-derived indices of regional fat distribution such as thoracic, abdominal and gluteofemoral fat, correlate significantly with cardiometabolic risk factors in healthy postmenopausal women, and may serve as clinically useful tools for evaluating cardiometabolic risk after menopause.

Body composition determinants of metabolic phenotypes of obesity in nonobese and obese postmenopausal women.

OBJECTIVE: Although obesity is typically associated with increased cardiovascular risk, a subset of obese individuals display a normal metabolic profile ("metabolically healthy obese," MHO) and conversely, a subset of nonobese subjects present with obesity-associated cardiometabolic abnormalities ("metabolically obese nonobese," MONO). The aim of this cross-sectional study was to identify the most important body composition determinants of metabolic phenotypes of obesity in nonobese and obese healthy postmenopausal women. DESIGN AND METHODS: We studied a total of 150 postmenopausal women (age 54 ± 7 years, mean ± 1 SD). Based on a cardiometabolic risk score, nonobese (body mass index [BMI] ≤ 27) and obese women (BMI > 27) were classified into "metabolically healthy" and "unhealthy" phenotypes. Total and regional body composition was assessed with dual-energy X-ray absorptiometry (DXA). RESULTS: In both obese and nonobese groups, the "unhealthy" phenotypes were characterized by frequent bodyweight fluctuations, higher biochemical markers of insulin resistance, hepatic steatosis and inflammation, and higher anthropometric and DXA-derived indices of central adiposity, compared with "healthy" phenotypes. Indices of total adiposity, peripheral fat distribution and lean body mass were not significantly different between "healthy" and "unhealthy" phenotypes. Despite having increased fat mass, MHO women exhibited comparable cardiometabolic parameters with healthy nonobese, and better glucose and lipid levels than MONO. Two DXA-derived indices, trunk-to-legs and abdominal-to-gluteofemoral fat ratio were the major independent determinants of the "unhealthy" phenotypes in our cohort. CONCLUSIONS: The "metabolically obese phenotype" is associated with bodyweight variability, multiple cardiometabolic abnormalities and an excess of central relative to peripheral fat in postmenopausal women. DXA-derived centrality ratios can discriminate effectively between metabolic subtypes of obesity in menopause.

Primary mucosa-associated lymphoid tissue thyroid lymphoma: a rare thyroid neoplasm of extrathyroid origin.

Primary thyroid lymphoma is a rare malignancy, representing 2-8% of all thyroid malignancies and 1-2% of all extranodal lymphomas. The majority of cases concern non-Hodgkin's lymphoma of B cell origin, following by Hodgkin's disease, T cell lymphomas and rarely marginal zone B-cell mucosa-associated lymphoid tissue (MALT) lymphomas. MALT lymphomas have been associated with long-standing autoimmune Hashimoto's thyroiditis. We present the case of a 44-years-old woman with thyroid MALT lymphoma in the background of multinodular goiter of autoimmune origin.

Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism.

OBJECTIVE: Although clinical hyperthyroidism (HR) is associated with insulin resistance, the information on insulin action in subclinical hyperthyroidism (SHR) is limited. DESIGN AND METHODS: To investigate this, we assessed the sensitivity of glucose metabolism to insulin in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes) in 12 euthyroid subjects (EU), 16 patients with HR, and 10 patients with SHR. RESULTS: HR and SHR patients displayed higher postprandial glucose levels (area under the curve, AUC(0)(-)(300) 32,190±1067 and 31,497±716,mg/dl min respectively) versus EU (27,119±1156 mg/dl min, P<0.05). HR but not SHR patients displayed higher postprandial insulin levels (AUC(0)(-)(300) 11,020±985 and 9565±904 mU/l min respectively) compared with EU subjects (AUC(0)(-)(300) 7588±743 mU/l min, P<0.05). Homeostasis model assessment index was increased in HR and SHR patients (2.81±0.3 and 2.43±0.38 respectively) compared with EU subjects (1.27±0.16, P<0.05), while Matsuda and Belfiore indices were decreased in HR (4.21±0.41 and 0.77±0.05 respectively, P<0.001) and SHR patients (4.47±0.33 and 0.85±0.05 respectively, P<0.05 versus EU (7.76±0.87 and 1 respectively). At 100 µU/ml insulin, i) GLUT3 levels on the monocyte plasma membrane were increased in HR (468.8±7 mean fluorescence intensity (MFI)) and SHR patients (522.2±25 MFI) compared with EU subjects (407±18 MFI, P<0.01 and P<0.05 respectively), ii) glucose transport rates in monocytes (increases from baseline) were decreased in HR patients (37.8±5%) versus EU subjects (61.26±10%, P<0.05). CONCLUSIONS: Insulin-stimulated glucose transport in isolated monocytes of patients with HR was decreased compared with EU subjects. Insulin resistance was comparable in patients with both HR and SHR.

Insulin resistance and metabolic syndrome in patients with nonfunctioning adrenal incidentalomas: a cause-effect relationship?

The objective of the study was to assess insulin resistance (IR) and metabolic syndrome (MS) in patients with nonfunctioning adrenal incidentalomas (NFAIs). Among a total cohort of 46 patients with adrenal incidentalomas, we studied 29 patients with NFAIs (mean age, 54 ± 9 years; body mass index, 29 ± 3 kg/m(2)) and 37 age-, sex-, and body mass index-matched healthy controls. Besides the endocrine workup, IR was evaluated using fasting glucose and insulin concentrations, homeostasis model assessment of IR, and quantitative insulin sensitivity check index. In a subgroup of patients undergoing an oral glucose tolerance test, Matsuda index and total area under the curve for glucose and insulin were also evaluated. Total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and other biochemical parameters were measured with standard techniques. Body composition was determined with dual-energy x-ray absorptiometry. Patients with NFAIs exhibited higher fasting glucose, insulin, and homeostasis model assessment of IR values; decreased quantitative insulin sensitivity check index and Matsuda index; and an increased-although not statistically significant-area under the curve for glucose and insulin compared with controls (P < .05). In addition, they exhibited higher systolic and diastolic blood pressure, triglycerides, and γ-glutamyltransferase and lower high-density lipoprotein cholesterol levels compared with controls (P < .05). Patients with NFAIs were all obese with a central type of fat accumulation and increased appendicular lean mass. Indices of IR showed a positive correlation with indices of MS (P < .05), but no correlation with markers of hormonal activity. Nonfunctioning adrenal incidentalomas are characterized by IR, hypertension, dyslipidemia, and fatty liver disease, all of them being components of MS. Thus, patients with NFAIs should be screened for MS during their initial workup to identify those at cardiometabolic risk and implement the appropriate interventions.

Large adrenal oncocytoma with uncertain malignant potential: case report and review of literature.

OBJECTIVE: To report a case of oncocytoma, a relatively rare adrenal tumor, which most commonly is detected as an adrenal incidentaloma. METHODS: We present a case report, including laboratory, imaging, and pathologic findings, of a 47-year-old obese woman who had hypertension and an incidentally found large, left adrenal mass. RESULTS: On the basis of the hormonal evaluation, this mass was a nonsecreting adrenal tumor, which histologically proved to be an oncocytoma with borderline malignant characteristics. A collective analysis of the few cases of adrenal oncocytoma published in the medical literature showed that our case corresponded to the previously published cases in preponderant location (left side) as well as the general size (11.4 cm in the largest dimension) and weight (372 g). CONCLUSION: Adrenal oncocytoma should be included in the differential diagnosis of adrenal incidentalomas, especially if large tumors are detected. In addition, a longterm follow-up is suggested because there are no certain clues about the true potential of this tumor.

The efficacy and safety of gonadotropin-releasing hormone analog treatment in childhood and adolescence: a single center, long-term follow-up study.

OBJECTIVE: The objective of the study was to evaluate the long-term effect of GnRH analog (GnRHa) treatment on final height (FH), body mass index (BMI), body composition, bone mineral density (BMD), and ovarian function. SUBJECTS/METHODS: Ninety-two females, evaluated in adulthood, were categorized as follows: group A, 47 girls with idiopathic central precocious puberty (33 GnRHa treated and 14 nontreated); group B, 24 girls with isolated GH deficiency (15 GnRHa and GH treated and nine GH treated); group C, 21 girls with idiopathic short stature (seven GnRHa and GH treated, seven GnRHa treated, and seven nontreated). RESULTS: FH, BMD, and percent fat mass of GnRHa-treated patients in all three groups were comparable with those of the respective nontreated subjects. BMI values of GnRHa-treated and nontreated subjects in groups A and C were comparable, whereas in group B, a higher BMI was found in subjects treated only with GH. Nontreated patients with ICPP had greater maximal ovarian volumes, higher LH and LH to FSH ratio, and more severe hirsutism than GnRHa-treated ones. Menstrual cycle characteristics were not different between treated and nontreated subjects. The prevalence of polycystic ovary syndrome in treated and untreated girls with ICPP was comparable, whereas in the entire cohort, it was 11.1% in GnRHa treated and 32.1% in the untreated (P = 0.02). CONCLUSIONS: Girls treated in childhood with GnRHa have normal BMI, BMD, body composition, and ovarian function in early adulthood. FH is not increased in girls with ICPP in whom GnRHa was initiated at about 8 yr. There is no evidence that GnRHa treatment predisposes to polycystic ovary syndrome or menstrual irregularities.

Increased bone resorption is implicated in the pathogenesis of bone loss in hemophiliacs: correlations with hemophilic arthropathy and HIV infection.

Osteoporosis has been recently recognized as a severe comorbidity factor in hemophilia. However, its pathogenesis is still obscure. We evaluated the incidence of osteoporosis in 90 hemophilia patients and investigated possible correlations with clinical and laboratory data. Out of the 90 patients, 80 (89%) had severe hemophilia, and 35 (38.9%) were human immunodeficiency virus (HIV)-positive. Hemophilic arthropahty was assessed using World Federation of Hemophilia clinical score and Petterson radiological score. Bone mineral density of the lumbar spine (LS) and femoral neck (FN) were measured using dual-energy X-ray absortiometry. Bone turnover was evaluated by the measurement of: (1) bone resorption markers [N-terminal cross-linking telopeptide of collagen type I (NTX), C-terminal cross-linking telopeptide of collagen type I (CTX), and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)], (2) bone formation markers [bone-alkaline phosphatase (bALP) and osteocalcin], and (3) osteoclast stimulators (receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, and tumor necrosis factor-alpha). Osteopenia or osteoporosis was observed in 86% and 65% of the patients in FN and LS, respectively. Osteoporosis was more common among HIV-positive patients in both FN (65.3% vs 41.6%; p = 0.007) and LS (17.86% vs 5.41%, p = 0.004). The severity of osteoporosis in FN correlated with the patients' total clinical and radiological score (p = 0.001). Hemophilia patients showed increased osteoclastic activity (significant increase of TRACP-5b, NTX, and CTX), which was not accompanied by a comparable increased bone formation (reduced osteocalcin and borderline increase of bALP). In multivariate analysis, HIV infection (p = 0.05) and total clinical score (p = 0.001) were independent risk factors for osteoporosis development. We conclude that there is a high prevalence of osteoporosis among hemophiliacs, which is related to the severity of arthropathy and is enhanced by HIV infection. We report for the first time a high bone resorption that seems not to be balanced by a comparable bone formation.

Panhypopituitarism due to metastases to the hypothalamus and the pituitary resulting from primary breast cancer: a case report and review of the literature.

Pituitary metastasis occurs rarely in cancer patients and often remains undiagnosed. However, early detection and appropriate treatment can improve the patient's quality of life and possibly prolong survival. Herein, we describe the case of a 52-year-old woman with panhypopituitarism caused by metastases to the hypothalamus and pituitary from primary breast cancer. She had a 5-year history of breast cancer with metastases to the bones 1.5 years after initial diagnosis and mastectomy. She presented with severe headaches, generalized fatigue, dizziness, hypotension, difficulties with balance and coordination, polyuria, and polydipsia. Laboratory work-up revealed panhypopituitarism (central diabetes insipidus; hypothyroidism; and low prolactin, gonadotrophin, and adrenocorticotropic hormone levels), and magnetic resonance imaging confirmed the pituitary and hypothalamic involvement. She received hormone replacement therapy, radiation therapy of the sella turcica and suprasellar lesion, and chemotherapy, with significant improvement of her clinical status, but she died 15 months later.

Dilated cardiomyopathy as the predominant feature of Cushing's syndrome.

Cushing's syndrome, resulting from exposure to excessive amounts of circulating glucocorticoids, is accompanied with a high mortality risk mostly due to the cardiovascular complications. Cardiac involvement is mainly associated with left ventricular hypertrophy. We report the case of a patient who presented with dilated cardiomyopathy as the predominant feature of Cushing's syndrome, which was fully reversed after proper surgical treatment.

Embolization as an alternative treatment of insulinoma in a patient with multiple endocrine neoplasia type 1 syndrome.

Insulinoma is a rare neuroendocrine tumor, most commonly originating from the pancreas, which is either sporadic or familial as a component of multiple endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased insulin secretion leading to hypoglycemia. Surgical removal is considered the treatment of choice, with limited side effects and relatively low morbidity and mortality, both being improved by the laparoscopic procedure. We present the case of a 30-year-old patient with MEN1 and recurrent insulinoma with severe hypoglycemic episodes who could not be surgically treated due to the adherence of the tumor to large blood vessels and to prior multiple surgical operations. He was treated by repeated embolization using spherical polyvinyl alcohol particles, resulting in shrinkage of the tumor, improvement of the frequency and severity of the hypoglycemic episodes, and better quality of life.

Studies of insulin resistance in patients with clinical and subclinical hypothyroidism.

OBJECTIVE: Although clinical hypothyroidism (HO) is associated with insulin resistance, there is no information on insulin action in subclinical hypothyroidism (SHO). DESIGN AND METHODS: To investigate this, we assessed the sensitivity of glucose metabolism to insulin both in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes with flow cytometry) in 21 euthyroid subjects (EU), 12 patients with HO, and 13 patients with SHO. RESULTS: All three groups had comparable plasma glucose levels, with the HO and SHO having higher plasma insulin than the EU (P<0.05). Homeostasis model assessment index was increased in HO (1.97+/-0.22) and SHO (1.99+/-0.13) versus EU (1.27+/-0.16, P<0.05), while Matsuda index was decreased in HO (3.89+/-0.36) and SHO (4.26+/-0.48) versus EU (7.76+/-0.87, P<0.001), suggesting insulin resistance in both fasting and post-glucose state. At 100 microU/ml insulin: i) GLUT4 levels on the monocyte plasma membrane were decreased in both HO (215+/-19 mean fluorescence intensity, MFI) and SHO (218+/-24 MFI) versus EU (270+/-25 MFI, P=0.03 and 0.04 respectively), and ii) glucose transport rates in monocytes from HO (481+/-30 MFI) and SHO (462+/-19 MFI) were decreased versus EU (571+/-15 MFI, P=0.04 and 0.004 respectively). CONCLUSIONS: In patients with HO and SHO: i) insulin resistance was comparable; ii) insulin-stimulated rates of glucose transport in isolated monocytes were decreased due to impaired translocation of GLUT4 glucose transporters on the plasma membrane; iii) these findings could justify the increased risk for insulin resistance-associated disorders, such as cardiovascular disease, observed in patients with HO or SHO.

Adrenocortical carcinoma secreting cortisol, androgens and aldosterone: a case report.

INTRODUCTION: Adrenocortical carcinoma is a rare malignancy with a poor prognosis and presents with mass effects and less often with signs of hormone excess (approximately 60% of all adrenocortical carcinoma's). Hormonally active adrenocortical carcinomas most commonly secrete cortisol while the co-secretion of multiple steroid hormones is rare. CASE PRESENTATION: We report the case of a 59 year-old woman with a medical history of hyperaldosteronism due to a right adrenal adenoma. During follow up, she showed symptoms of hypercortisolism and hyperandrogenemia and a rapid growth of the adrenal mass. She underwent right adrenalectomy and the histology revealed the presence of an adrenocortical carcinoma. Six months post-operatively being on treatment with mitotane, she was diagnosed of metastatic disease to the liver. She underwent right hepatectomy and was started on systemic chemotherapy, with no signs of tumour recurrence during the following six months. CONCLUSION: The hormonal status should be carefully investigated in all cases of suspected adrenocortical carcinoma, as the pattern of hormone secretion may be a clue to the malignancy of an adrenal lesion. In addition, more data are needed to clarify the clinical and prognostic significance of the combined production of all adrenocortical hormones affecting either the survival or the quality of life of adrenocortical carcinoma patients.

A novel germline mutation of the VHL gene in a Greek family with Von Hippel-Lindau disease.

Von Hippel-Lindau disease (VHL) is an autosomal dominant disorder, caused by mutations of the VHL gene showing a strong genotype-phenotype correlation. The present report concerns a 16-year-old girl with VHL (retinal, spinal cord and cerebellar haemangioblastomas and pancreatic cysts), her father (retinal and spinal cord haemangioblastomas) and the phenotypically healthy mother and younger brother and sister. DNA extraction, PCR and direct sequencing of the VHL entire coding and intronic flanking sequences, were performed according to standard procedures. In the index patient and her father a novel heterozygous germline was identified; nonsense mutation (p.145X) in exon 2 of VHL, leading to a truncated VHL protein lacking the last 66 amino acids. This is the first report of a novel VHL mutation in patients with VHL associated with haemangioblastomas and pancreatic cysts but not renal cell carcinoma.

Novel germline mutations of the MEN1 gene in Greek families with multiple endocrine neoplasia type 1.

INTRODUCTION: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder associated with mutations of the MEN1 gene and characterized by the combined occurrence of tumours of the parathyroid glands, the pancreatic islet cells and the anterior pituitary. AIM: To identify MEN1 gene mutations and characterize clinical manifestations in Greek patients with MEN1. PATIENTS AND METHODS: We studied four unrelated index patients with MEN1, 17 relatives and 100 control subjects. Among the relatives, seven were clinically and/or biochemically affected, while 10 were unaffected. DNA extraction, polymerase chain reaction (PCR) and direct sequencing of the MEN1 exons 2-10 and exon/intron boundaries were performed according to standard procedures. RESULTS: We identified novel MEN1 gene mutations in three out of four index patients (75%) and in all affected (100%) relatives. Novel mutations included: a frameshift mutation in exon 4 (c.684_685insG) at codon 229 (index patient A); a frameshift mutation in exon 8 (c.1160_1170dupAGGAGCGGCCG) involving codons 387-390 (index patient B); and a missense mutation in exon 4 (c.776T > C), which substitutes leucine with proline at codon 259 (L259P) (index patient C). In the fourth index patient, a common polymorphism (D418D) was detected. CONCLUSIONS: This is the first report to reveal a high prevalence of novel MEN1 gene mutations among Greek MEN1 patients with apparent absence of genotype-phenotype correlation. Because of the small number of patients examined, the high prevalence detected might be a chance phenomenon.