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Bone mineral density in premenopausal women receiving levothyroxine suppressive therapy

Osteoporosis is a well-known complication of thyrotoxicosis. Prolonged subclinical hyperthyroidism due to L-thyroxine treatment has been associated with reduced bone mass and thus with the potential risk of premature development of osteoporosis. The aim of this study was to assess the effect of a chronic L-thyroxine suppressive treatment on bone mineral density (BMD) in a group of premenopausal women. Forty consecutive patients (mean age +/- SE = 40.95 +/- 1.56 years) affected by non-toxic goiter underwent bone mineral densitometry (dual energy X-ray absorptiometry; DEXA) of the lumbar spine (L1-L4) and right femoral neck. At the time of the study the patients had been under thyroid stimulating hormone (TSH) suppressive therapy for 74.95 +/- 10.34 months (range 17-168 months). Baseline levels of free thyroxine (fT4), free triiodothyronine (fT3), TSH, calcium and phosphorus were measured and correlated with BMD. The age of starting, duration of treatment, main daily dose, cumulative dose of treatment and body mass index (BMI) were also correlated with BMD. Statistical analysis was performed by multiple linear regression. BMD among female patients was not significantly different from that of the general population matched for age and sex. With the use of the regression model, no significant correlation was found between BMD and the variables considered. In conclusion, our data suggest that L-thyroxine suppressive therapy, if carefully carried out and monitored, has no significant effect on bone mass.

Limitations of Chromogranin A in clinical practice

Context: Usefulness of circulating Chromogranin A (CgA) for the diagnosis of neuroendocrine tumors (NEN) is controversial. The aim of the present study was to assess the actual role of this marker as diagnostic tool. Methods: Serum blood samples were obtained from 42 subjects affected with NEN, 120 subjects affected with non-endocrine neoplasias (non-NEN) and 100 non-neoplastic subjects affected with benign nodular goitre (NNG). Determination of CgA was performed by means of immunoradiometric assay. Results: The CgA levels among NEN-patients were not significantly different from NNG and non-NEN subjects. The Receiver operating characteristic (ROC) curves analysis failed to identify a feasible cut-off value for the differential diagnosis between NEN and the other conditions. Conclusion: Serum CgA is not helpful for the first-line diagnosis of NEN.

Bone mineral density and bone markers in hypogonadotropic and hypergonadotropic hypogonadal men after prolonged testosterone treatment.

After prolonged treatment (76.4±10 and 70.1±12.3 months, respectively) (mean± SE) with testosterone enanthate (250 mg im every 3 weeks), bone mineral density (BMD) and bone metabolism were evaluated in 12 patients (aged 29.3±1.4 yr) affected by idiopathic hypogonadotropic hypogonadism (IHH), in 8 patients (29.6±2.6 yr) affected by Klinefelter’s syndrome (KS), and in 10 healthy men (30.6±1.7 yr) matched according to age and BMI. Spinal BMD in IHH was significantly lower than in controls (0.804±0.04 vs 1.080±0.01 g/cm2; p<0.001), while there was no difference in neck BMD (0.850±0.01 vs 0.948±0.02 g/cm2). Neither spinal (0.978±0.05 g/cm2) nor neck (0.892±0.03 g/cm2) BMD in KS were significantly different from controls. Six IHH and one KS subjects were osteoporotic, while 6 IHH and 2 KS subjects were osteopenic. A significant inverse correlation was found between spinal BMD and age at the treatment onset in IHH (r=−0.726, p=0.007). In IHH there were significant increases in bone formation (alkaline phosphatase=318.3±33.9 vs 205.4±20.0 IU/l; osteocalcin=13.44±1.44 vs 8.57±0.94 ng/ml; p<0.05) and in bone resorption (urinary cross-linked N-telopeptides of type I collagen= 149.1± 32.3 vs 47.07±8.4 nmol bone collagen equivalents/mmol creatinine; p<0.05) compared to controls, while such differences were not present in KS. Our results outline the importance of BMD evaluation in all hypogonadal males. Nevertheless, bone loss is a minor characteristic of KS, while it is a distinctive feature of IHH. Therefore, early diagnosis and age-related replacement therapy coupled with a specific treatment for osteoporosis could be useful in preventing future severe bone loss and associated skeletal morbidity.

Evaluation of goiter endemia by ultrasound in schoolchildren in Val Sarmento (Italy)

Ultrasonography is an excellent and objective method for assessing thyroid volume, especially in children where clinical evaluation is inaccurate. The aim of this study was to evaluate the presence of goiter by thyroid ultrasound and palpation in 244 schoolchildren, 6 to 14 years old, living in some rural villages of Val Sarmento, a mountain area of Basilicata, Italy. In 1996 we revealed the presence of endemic goiter in 25% of the schoolchildren evaluated by palpation, according to World Health Organization (WHO) criteria, and in 15.9% of the schoolchildren evaluated by ultrasonography (7.5 MHz linear probe). The median urinary iodine excretion, taken from an extemporaneous sample of the first urines in the morning, was 62.2 μg/l. This study includes Val Sarmento, an area with mild-moderate grade (Grade I) of iodine deficiency, suggesting the need for iodine prophylaxis. Furthermore, it proves that the measurement of thyroid volume by ultrasonography is an essential instrumental method for a correct epidemiological study of endemic goiter, particularly in areas where there is mild iodine deficiency.

Gonadotropin-releasing hormone agonists administration in polycystic ovary syndrome. Effects on bone mass.

Women with amenorrhea and polycystic ovaries (PCO) seem to present a relative degree of protection against bone loss caused by hypoestrogenism. We treated 20 patients affected by polycystic ovary syndrome (PCOS) with a gonadotropin-releasing hormone agonist (GnRH-a) for 6 months. After treatment mean bone mineral density (BMD) significantly decreased. We concluded that patients with PCOS have to be considered at risk of developing osteopenia when treated with GnRH-a. The relative protection against osteoporosis, that is present in amenorrheic patients with PCO, might be attributed to the characteristics of amenorrhea in these patients.

Analysis of skeletal status by quantitative ultrasonometry in a cohort of postmenopausal women with high blood cholesterol without documented osteoporosis.

Osteoporosis and atherosclerosis are leading causes of mortality and morbidity in the Western world. A link between osteoporosis and atherosclerosis was proposed by epidemiologic and laboratory data. In the present study, we investigated skeletal status in postmenopausal women with hypercholesterolemia using quantitative ultrasonometry (QUS). Six hundred healthy postmenopausal subjects were enrolled within a 2-mo period by primary care physicians. Information on lifestyle and calcium intake was collected for each enrolled subject. Subjects (n = 256) were divided into two groups according to lipid profile: normal (n = 180) with serum cholesterol <200 mg/dL and hypercholesterolemic (n = 76) with serum cholesterol >or=200 mg/dL. Hypercholesterolemic subjects were further stratified into two groups, one receiving dietary treatment (n = 34) and the other receiving statin treatment (n = 42). We found a statistically significant reduction in amplitude dependent speed of sound (AD-SoS) in hypercholesterolemic subjects compared with subjects with normal cholesterol (p = 0.006). Calcium intake behaved similarly to AD-SoS (p = 0.0001). No statistical significant difference in AD-SoS were observed between the group on diet treatment versus the group on statin (p = 0.52). Calcium intake was lower in patients on statins treatment compared with subjects on diet treatment only (p < 0.0001). Our data suggest that hypercholesterolemia per se is a risk factor for impaired skeletal status. Our data also call attention to the risk of a poor calcium intake in patient receiving diet to lower plasma cholesterol. Moreover, our data suggest that statins per se may exert a protective effect on bone independently from calcium intake.

MEN1 family with a novel frameshift mutation

Multiple endocrine neoplasm type 1 (MEN1) syndrome predisposes to the development of endocrine and non-endocrine tumors with an autosomal dominant pattern of inheritance. Different mutations have been found throughout the gene with a variable phenotype expression. The proband, a Caucasian man, was admitted to our department in 2001, at the age of 51 because of a 1-yr history of diarrhoea and hypertension. He reported a previous intestinal resection for bowel occlusion with a histological diagnosis of unspecified mesenchymal neoplasia. He had also undergone a left adrenalectomy for a large non-functioning adrenal adenoma. Subsequently, he had suffered from gastralgia and melena; a gastroduodenoscopy showed an erosive gastritis. His family history was negative for endocrine disorders. On physical examination, multiple abdominal cutaneous lipomas and facial angiofibromas were observed. Biochemical screening revealed a primary hyperparathyroidism and an increase in circulating levels of PRL, chromogranin-A, gastrin and glucagon. The whole body computed tomography (CT) scan, the 111In-octreotide scan and the pituitary magnetic resonance imaging (MRI) did not reveal any abnormality. The presence of small neuroendocrine tumors was suspected by a positron emission tomography uptake in the epigastric region. The endoscopic ultrasound revealed a pancreatic lesion sized 1.1 cm that is under evaluation. Direct DNA sequencing analysis of the proband MEN1 gene revealed the 579delG frameshift mutation in the exon 3. The genetic screening of the family revealed the same mutation in 3 out of 5 offspring. The biochemical screening revealed some features of the MEN1 syndrome in all three of them. In conclusion, a novel frameshift MEN1 mutation was found in kindred with an apparently negative family history. Our experience confirms that MEN1 syndrome is a complex and underestimated condition, unless specifically investigated by trained specialists.

Infiltrating giant cell tumor in a case of Paget’s disease of bone

Giant cell tumor (GCT) of the bone, also called osteoclastoma, is a rare complication of Paget’s bone disease. We report a patient from Southern Italy who developed a GCT infiltrating the neighboring tissues. The natural history and the therapeutic outcomes of this unique complication of Paget’s bone disease are presented.

Efficacy and safety of everolimus in extrapancreatic neuroendocrine tumor: A comprehensive review of literature

BACKGROUND Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs. PATIENTS AND METHODS A systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary. RESULTS The present study included 22 different publications, including 874 patients and 456 extrapancreatic NETs treated with everolimus. Nine different primary sites of extrapancreatic NETs were found. The median progression-free survival ranged from 12.0 to 29.9 months. The median time to progression was not reached in a phase II prospective study, and the interval to progression ranged from 12 to 36 months in 5 clinical cases. Objective responses were observed in 7 prospective studies, 2 retrospective studies, and 2 case reports. Stabilization of the disease was obtained in a high rate of patients, ranging from 67.4% to 100%. The toxicity of everolimus in extrapancreatic NETs is consistent with the known safety profile of the drug. Most adverse events were either grade 1 or 2 and easy manageable with a dose reduction or temporary interruption and only rarely requiring discontinuation. CONCLUSION Treatment with everolimus in patients with extrapancreatic NETs appears to be a promising strategy that is safe and well tolerated. The use of this emerging opportunity needs to be validated with clinical trials specifically designed on this topic. IMPLICATIONS FOR PRACTICE The present study reviewed all the available published data concerning the use of everolimus in 456 extrapancreatic neuroendocrine tumors (NETs) and summarized the current knowledge on the efficacy and safety of this drug, not yet approved except for pancreatic NETs. The progression-free survival rates and some objective responses seem promising and support the extension of the use of this drug. The site-by-site analysis seems to suggest that some subtypes of NETs, such as colorectal, could be more sensitive to everolimus than other primary NETs. No severe adverse events were usually reported and discontinuation was rarely required; thus, everolimus should be considered a valid therapeutic option for extrapancreatic NETs.

A novel mutation in the N-terminal region of the CYP17A1 gene in a patient with 17α-hydroxylase/17,20-lyase deficiency

The deficiency of 17α-hydroxylase/17,20-lyase causes a rare autosomal recessive disorder presenting with congenital adrenal insufficiency (CAH) and sexual infantilism. Both 17α-hydroxylase and 17,20-lyase reactions are catalyzed by a single polypeptide, cytochrome P450c17 (CYP17), which is encoded by the CYP17A1 gene. We describe the clinical, hormonal, and molecular findings of a 33-yr-old patient presenting with primary amenhorrea, late onset hypertension, and hypokalemic myopathy. The molecular analysis of CYP17A1 revealed a novel homozygous missense mutation resulting in the substitution of arginine to lysine at the amino acid position 21 (p.R21L).