Biomedical subjects

Antongiulio Faggiano

Publications and source records attributed to Antongiulio Faggiano.

16 recordsLinked to original sources

PubMed2025

Genetic insight into lung neuroendocrine tumors: Notch and Wnt signaling pathways as potential targets.

BACKGROUND: The molecular landscape of lung neuroendocrine neoplasms is still poorly characterized, making it difficult to develop a molecular classification and personalized therapeutic approaches. Significant clinical heterogeneity of these malignancies has been highlighted among poorly differentiated histotypes and within the subgroup of well-differentiated neuroendocrine tumors (NET). Currently, the main prognostic factors of lung NET include stage, histotype, grade, peripheral location, and demographic parameters. To gain deeper insights into the genomic underpinnings of lung NETs, we conducted a pilot investigation to uncover potential genetic mutations and copy number variations (CNVs) implicated in their pathogenesis. METHODS: Formalin-fixed, paraffin-embedded intraoperative tumor biopsies and matched peripheral blood mononuclear cell samples were collected from six consecutive patients with lung NETs. The whole exome sequencing (WES) was performed to profile germline and somatic mutations, identify novel genetic alterations, and detect CNVs. Clinical and pathological data were systematically documented at diagnosis and during follow-up. RESULTS: The WES analysis identified a subset of mutations shared between germline and somatic; some were of particular clinical interest as they were associated with tumor proliferation and potential therapeutic targets such as the genes KDM5C, ATR, COL7A1, NOTCH4, PTPRS, SMO, SPEN, SPTA1, TAF1. These mutations were predominantly linked to chromatin remodeling and were involved in critical oncogenic pathways such as Notch and Wnt signaling. CONCLUSIONS: This pilot study highlights the potential role of NGS analysis on solid biopsy in the assessment of the mutational profile of lung NET. A comparison of germline and somatic mutations is critical to identifying putative tumor driver mutations. In perspective, the enrichment of a subpopulation of cancer cells in the blood, with one or more specific mutations, is information of enormous clinical relevance, either for prognosis or therapeutic decisions. Translational studies on large prospective series are required to establish the role of liquid biopsy in lung NET.

Humans↗

PubMed2025

Exploring the tumor suppressor role of RIN1 in familial thyroid carcinoma.

The genetic component is thought to play an important role in the development of familial non-medullary thyroid carcinoma (fNMTC), but the involved molecular mechanisms and genes are poorly understood. The MAPK kinase cascade, particularly involving RAS and BRAF, is crucial in cancer development, with RIN1 emerging as a notable gene due to its differential expression across various tumor types. We identified a frameshift mutation (c.798delC: p.V267Sfs*83) in the RIN1 gene in a family with non-medullary thyroid cancer (NMTC) through whole-exome sequencing. Paraffin-embedded tumor tissues were analyzed to investigate the mutation's characteristics and its potential implications within the thyroid cellular context. Functional assays and RNA sequencing using CRISPR/Cas9-edited Nthy-ori 3-1 thyroid cell line and xenograft zebrafish models confirmed the mutation effect and the putative RIN1 tumor suppressor role. The study revealed significant alterations in cellular behavior upon RIN1 knockout, including increased cell viability, proliferation and colony formation, alongside morphological changes indicative of epithelial-mesenchymal transition. Enhanced phosphorylation of ERK and AKT suggested MAPK pathway dysregulation following RIN1 depletion, supporting its potential tumor suppressive role. Phenotypic rescue experiments confirmed that reintroduction of wild-type RIN1 restored normal cellular behavior. RNA sequencing demonstrated differential gene expression between RIN1-/- and control cells, particularly affecting pathways associated with cancer progression, closely resembled signatures specific to NMTC. This study provides compelling evidence supporting RIN1 as a tumor suppressor gene within thyroid cells. In addition, the findings highlight its potential significance as novel gene involved in FNMTC pathogenesis.

Humans↗

PubMed2006

Dopamine receptor expression and function in corticotroph ectopic tumors.

BACKGROUND: Dopamine receptor (DR) expression and dopamine agonist (DA) effectiveness have never been demonstrated in neuroendocrine tumors associated with ectopic ACTH syndrome (EAS). AIM: The aim of the current study was to evaluate DR and particularly D2 subtype expression in neuroendocrine tumors associated with EAS and to evaluate the in vivo effectiveness of the DA cabergoline in the treatment of EAS. PATIENTS AND METHODS: Six ACTH-secreting neuroendocrine tumors, including four lung, one pancreatic, and one thymic carcinoid, were used for the evaluation of D2 expression by immunohistochemistry. DR subtypes and D2 isoforms and number were evaluated by RT-PCR in three cases of persistent EAS after surgery. These patients were treated with cabergoline at the dose of 3.5 mg/wk for 6 months. Clinical parameters, hormonal levels, and tumor size were monitored during the treatment period. RESULTS: At immunohistochemistry, D2 was expressed in five (83.3%) tumors. At RT-PCR, D2 was confirmed in all three cases but at variable numbers, whereas D4 was expressed in two cases. D(2long) was expressed in all three cases, together with D(2short) in one case. A normalization of urinary cortisol levels was found in two patients (66.7%) after 3 months of treatment. However, treatment escape was demonstrated in one of these patients afterward. CONCLUSION: The results of this study demonstrated that DR are expressed in neuroendocrine tumors associated with EAS and that cabergoline treatment could be effective in controlling cortisol excess in a subgroup of patients with EAS. Further studies on a larger number of patients are mandatory to confirm the usefulness of DA in EAS.

ACTH Syndrome, Ectopic↗

PubMed2006

Rapidly progressing high o,p'DDD doses shorten the time required to reach the therapeutic threshold with an acceptable tolerance: preliminary results.

INTRODUCTION: It has been reported that the therapeutic threshold of mitotane, plasma level above 14 microg/ml, is achieved within 3-5 months after o,p'DDD treatment initiation in patients with adrenocortical carcinoma (ACC). OBJECTIVE AND DESIGN: We evaluated pharmacokinetic and tolerance of a high-dose schedule of pure o,p'DDD treatment given in 500-mg tablets of mitotane (Lysodren, Bristol-Myers Squibb, HRA Pharma, Paris, France) in four patients with ACC and two patients with Cushing's syndrome-related endocrine tumours. It was administered at a starting dosage of 3 g/day, which was rapidly increased to 6-9 g/day within 2 weeks according to digestive tolerance and then adjusted according to tolerance and plasma o,p'DDD monitoring. Patients were followed up until they reached the therapeutic threshold of mitotane, and toxicity was recorded. A relationship between o,p'DDD dose and plasma level was sought. RESULTS: The highest starting dosage given ranged between 6 and 9 g a day, during the first two weeks. The daily maintenance dose ranged 4.5-9 g during the next 2 weeks and 3-9 g by the second month of treatment. The therapeutic threshold was reached in all four patients who received o,p'DDD treatment for at least 1 month. Among these four patients, the toxic threshold (plasma mitotane level > 20 microg/ml) was even reached at 6 weeks of therapy in three patients. Grade 1, 2 or 3 toxicity was observed in 3, 2 and 1 patients, respectively. Toxicity resolved after reduction or discontinuation of o,p'DDD therapy. A significant linear correlation was found between plasma mitotane dose and plasma level. CONCLUSIONS: These results suggest that a high-dose o,p'DDD therapeutic schedule is feasible with an acceptable toxicity and may shorten the time required to reach the therapeutic schedule from 3-5 months to 4 weeks. These patients require a close follow-up, combining clinical and plasma o,p'DDD level monitoring every second week. A confirmatory study is ongoing.

Adrenocortical Carcinoma↗

PubMed2006

Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas: a clinical and immunohistochemical study.

BACKGROUND: The pituitary tumour transforming gene (pttg) plays a central role in pituitary tumorigenesis, but PTTG protein expression is poorly documented and its relationship with tumour cell proliferation and the prognosis of pituitary adenomas is unclear. AIM: The aim of this study was to evaluate the immunohistochemical expression of PTTG and Ki-67 in 45 human pituitary adenomas according to the tumour histotype, aggressiveness and persistence/recurrence status. PATIENTS AND METHODS: The tumours comprised 37 macroadenomas and 8 microadenomas. Twenty patients experienced disease persistence or recurrence after transsphenoidal surgery. Disease recurrence was observed in 16 patients, 8-72 months after surgery. RESULTS: No PTTG or Ki-67 expression was detected in normal pituitary tissue. In pituitary adenomas, tumour nuclei were positive for PTTG and Ki-67 in 89 and 98% of samples, respectively, and there was a strong correlation between the expression of the two proteins (P < 0.001). By the ROC curves method, a PTTG score of 3.3% was the best cut-off for distinguishing between recurrent and nonrecurrent pituitary adenomas (P < 0.05; sensitivity 60%; specificity 76%). A 2.9% cut-off was obtained for both PTTG (P < 0.01; sensitivity 77%; specificity 71%) and Ki-67 (P < 0.05; sensitivity 85%; specificity 64%) among patients with more than 1 year of follow-up. Neither PTTG nor Ki-67 expression was influenced by the maximal tumour diameter, tumour grade, age, gender or presurgical medical treatment. Both PTTG and Ki-67 tumour score > 2.9% identified a subgroup of patients with a significantly higher recurrence-free interval (P < 0.01). By multivariate analysis, a > 2.9% Ki-67 tumour score was the best predictor of pituitary tumour persistence/recurrence after surgery (chi(2) = 8.2, P < 0.01). CONCLUSION: PTTG is expressed in approximately 90% of pituitary tumours of different histotypes but with a high variability from one case to another. As expected, PTTG expression parallels that of Ki-67 and both are correlated to a more aggressive behaviour. However, a 2.9% Ki-67 cut-off proved to be the most reliable biological marker for predicting the recurrence potential of these tumours, when an adequate postsurgical follow-up is considered.

Adenoma↗

PubMed2005

Sulfur amino acids in Cushing's disease: insight in homocysteine and taurine levels in patients with active and cured disease.

BACKGROUND: Cushing's syndrome is associated with an increased cardiovascular risk. Although a series of cardiovascular risk factors have been identified, sulfur amino acids (SAAs), recently indicated as independent cardiovascular risk factors, have been poorly investigated in patients with Cushing's syndrome. AIM: The aim of this cross-sectional controlled study was to evaluate serum and urinary levels and urinary excretion rate (ER) of SAAs in patients with Cushing's disease (CD) during the active disease and after long-term disease remission. SUBJECTS AND METHODS: Forty patients with CD (20 with active disease and 20 with cured disease for at least 5 yr) and 40 controls entered the study. Serum and urinary concentrations and urinary ER of SAAs, namely methionine, cystine, homocysteine, and taurine, were measured by means of cationic exchange HPLC. Serum folic acid and vitamin B12 levels were also evaluated in patients and controls and correlated to SAA levels. RESULTS: CD patients with active disease had higher serum and urinary concentrations of cystine and homocysteine, and lower serum and higher urinary concentrations and ER of taurine than cured patients and controls. Vitamin B12 levels were significantly decreased in patients with active disease compared with cured patients and controls, whereas folic acid levels were slightly decreased in patients than in controls. In patients with active CD, urinary cortisol concentrations were significantly and inversely correlated to serum taurine and directly correlated to taurine urinary ER, and fasting serum glucose levels were significantly correlated to taurine urinary ER. At the multiple regression analysis, urinary cortisol concentrations were the best predictors of taurine ER. CONCLUSIONS: CD is associated with hyperhomocysteinemia and hypotaurinemia. Glucocorticoid excess, acting directly or indirectly, seems to be the most responsible for this imbalance in SAA levels. The long-term disease remission is accompanied by normalization of SAA levels. Hyperhomocysteinemia and hypotaurinemia might contribute to the increased cardiovascular risk of CD.

Adult↗

PubMed2005

The metabolic syndrome and cardiovascular risk in Cushing's syndrome.

Cushing's syndrome (CS) is characterized by a series of systemic complications that increase cardiovascular risk and cause severe atherosclerotic damage that develops in parallel with an acquired metabolic syndrome. Short-term remission from hypercortisolism improves metabolic and vascular damages, but long-term remission from CS seems to be associated with similar or worse metabolic and vascular damage, probably because of persistent abdominal obesity or insulin resistance years after normalization of cortisol secretion. Study results suggest that an increased cardiovascular risk also may persist in patients who undergo treatment with exogenous glucocorticoids after therapy withdrawal. Considering the many patients subjected to corticosteroid treatment, this could be of great clinical relevance and should be investigated thoroughly.

Cardiovascular Diseases↗

PubMed2005

Growth hormone response to arginine test distinguishes multiple system atrophy from Parkinson's disease and idiopathic late-onset cerebellar ataxia.

OBJECTIVE: Multiple system atrophy (MSA) is difficult to distinguish from idiopathic Parkinson's disease (PD) and idiopathic late-onset cerebellar ataxia (ILOCA). This study aimed to evaluate GH response to three different GH stimulation tests in order to establish a reliable test to differentiate these degenerative disorders. DESIGN: Twelve patients with MSA, 10 with PD, eight with ILOCA and 30 healthy controls entered the study. They were submitted to clonidine, arginine, and GH-releasing-hormone (GHRH) + arginine tests in a random manner on three different nonconsecutive days. The peak serum GH response was used as a primary variable for analysis of stimulation tests. By ROC analysis, the optimum cut-off level was considered as the cut-off with the maximal sum of sensitivity and specificity. RESULTS: After clonidine administration, GH peak was significantly lower in patients with MSA than in those with ILOCA (P < 0.05) and in the controls (P < 0.001). At the optimum cut-off level of 5 mU/l, the clonidine test distinguished patients with MSA from those with PD with a sensitivity and specificity of 78%. Moreover, this test distinguished patients with MSA from those with ILOCA with a sensitivity of 100% and a specificity of 75% at a cut-off level of 5 mU/l, and with a sensitivity of 75% and a specificity of 100% at the cut-off level of 7.6 mU/l. After arginine administration, the GH peak was significantly lower in patients with MSA than in those with ILOCA (P = 0.001) and in controls (P < 0.001). At the optimum cut-off level of 5 mU/l, the arginine test distinguished patients with MSA from those with PD with a sensitivity and a specificity of 100%. At a GH peak cut-off value of 3.6 mU/l the arginine test distinguished patients with MSA from those with ILOCA with a sensitivity and specificity of 100%. After GHRH + arginine administration, a significant GH increase was found in all groups of patients and controls. CONCLUSIONS: The GH response to arginine administration is impaired in MSA. Therefore, the arginine test showed the highest diagnostic accuracy to distinguish MSA from both PD and ILOCA, and could be used in the clinical practice of these neurodegenerative diseases.

Arginine↗

PubMed2004

Age-dependent variation of follicular size and expression of iodine transporters in human thyroid tissue.

UNLABELLED: The high sensitivity of the thyroid gland to the carcinogenic effects of radiation during childhood contrasts with the absence of demonstrable carcinogenic effects of radiation in adults. To better understand these age-related variations, we studied follicular morphometry, functional status, and proliferative activity in 31 thyroid glands removed from relatives of medullary thyroid carcinoma patients, with ages ranging from 3 to 39 y. METHODS: The mean follicular diameter (MFD) was estimated, and immunohistochemistry was performed with antibodies directed to molecules involved in iodide transport (Na(+)/I(-) symporter [NIS], pendrin, and apical iodide transporter), in organification (thyroperoxidase [TPO] and Duox), in cell cycle and growth (Ki-67, cyclin A and D1, and galectin-3), and in angiogenesis (vascular endothelial growth factor and nitric oxide synthase III [NOSIII]). RESULTS: Compared with older patients, patients who were < or =12 y old had a smaller MFD (P < 0.001) and more frequently positive NIS, pendrin, and Duox (P < 0.01). Proliferation rate as indicated by cyclin A expression was also higher in patients < 12 y (P < 0.01) but peaked at the time of puberty. Staining for NIS, pendrin, TPO, Duox, and NOSIII was stronger in thyroid glands with a smaller MFD (P < 0.001). On multiple tests adjusted for age and thyroid mass, TPO, Duox, and NOSIII remained significantly correlated to MFD (P < 0.001), whereas staining for NIS and pendrin did not. This finding suggests that NIS and pendrin expression is related mainly to the age of the patient. CONCLUSION: Smaller follicles with a higher expression of proteins involved in iodide metabolism were found in younger children. In cases of radioiodine contamination in children, the result will be a higher radioactive concentration and, hence, higher radiation doses. This event may induce the development of thyroid cancer under conditions of accelerated proliferation, as evidenced at puberty.

Adolescent↗

PubMed2003

Effect of 2 years of cortisol normalization on the impaired bone mass and turnover in adolescent and adult patients with Cushing's disease: a prospective study.

BACKGROUND: Osteoporosis is a frequent, severe and often underestimated consequence of long-term hypercortisolism, often presenting as bone fracture. OBJECTIVE: This prospective study was designed to evaluate whether the abnormalities of bone mass and turnover can be similarly reversed in adolescent and adult patients with Cushing's disease, after correction of hypercortisolism. PATIENTS AND METHODS: Bone mineral density (BMD) at lumbar spine, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were measured at diagnosis and 2 years after cure of Cushing's disease (CD) in six patients with childhood-onset and nine with adulthood-onset disease. Fifteen age-, sex- and body mass index (BMI)-matched healthy subjects served as controls. RESULTS: At diagnosis, BMD Z scores at lumbar spine and OC levels were lower (2.3 +/- 0.1 vs.-0.2 +/- 0.01; P < 0.01 and 1.6 +/- 0.1 vs. 9.6 +/- 1.2; P < 0.01 respectively) while urinary Ntx levels were significantly higher (139.9 +/- 6.1 vs. 82.0 +/- 1.6; P < 0.01) in CD patients than in controls. Among CD patients, similar values of Z scores (-2.4 +/- 0.3 vs.-2.2 +/- 0.1, P = 0.4) and OC levels (1.7 +/- 0.2 vs. 1.6 +/- 0.2, P = 0.6) were observed in adolescent and adults patients, whereas urinary Ntx levels were significantly higher (159.7 +/- 7.9 vs. 125.9 +/- 3.3, P < 0.001) in the former than in the latter group. Two years after remission from hypercortisolism, OC levels (P < 0.001) and lumbar BMD Z scores (-2.2 +/- 0.3, P < 0.05; and -1.9 +/- 0.2; P < 0.01, respectively) increased significantly, while urinary Ntx levels reduced significantly (P < 0.001) in both adolescent and adult patients. However, biochemical markers and Z scores of BMD remained significantly suppressed compared to controls. CONCLUSIONS: Bone impairment in childhood- and adulthood-onset Cushing's disease patients can be partly, but not completely, reversed 2 years after normalization of cortisol levels. Longer recovery times or additive therapeutic approaches are necessary to maximize peak bone mass in children and restore bone mass in adults with Cushing's disease.

Adolescent↗

PubMed2003

Central diabetes insipidus and autoimmunity: relationship between the occurrence of antibodies to arginine vasopressin-secreting cells and clinical, immunological, and radiological features in a large cohort of patients with central diabetes insipidus of known and unknown etiology.

Central diabetes insipidus (CDI) is a rare hypothalamus-pituitary disease due to the deficiency of arginine vasopressin (AVP) synthesis from the hypothalamus and/or secretion from the neurohypophysis. The etiology of CDI is unknown in over one third of cases, classified as idiopathic CDI. The aim of this study was 2-fold: 1) to evaluate the occurrence of circulating autoantibodies to AVP-secreting cells (AVPcAb), and 2) to correlate it to clinical (sex, age of disease onset, disease duration, and degree), immunological (clinical history of autoimmune diseases and presence of related organ-specific autoantibodies), and radiological features (neurohypophyseal bright spot, pituitary stalk thickening, and empty sella) in a large cohort of patients with apparently idiopathic CDI or CDI of known etiology. To this purpose, 150 patients with CDI were studied: 64 idiopathic, 6 familial, 12 associated to granulomatous diseases, and 68 secondary to cranial trauma, tumor, or surgery. AVPcAb were measured by an indirect immunofluorescence method. AVPcAb were found in 23.3% of CDI patients: 21 idiopathic (32.8%) and 14 nonidiopathic (16.3%; chi(2) = 13.1; P < 0.001). AVPcAb were independently associated with age less than 30 yr at disease onset (P = 0.001) in patients with idiopathic CDI and with history of autoimmune diseases (P = 0.006 and P = 0.02, respectively) and radiological evidence of pituitary stalk thickening (P = 0.02 and P = 0.003, respectively) in both idiopathic and nonidiopathic CDI. The likelihood of autoimmunity in one patient with apparently idiopathic CDI with age of disease onset less than 30 yr was 53%, it increased to 91% when history of autoimmune diseases was associated and to 99% when pituitary stalk thickening was further associated. In conclusion, autoimmunity is associated with one third of patients with apparently idiopathic CDI, which should therefore be classified as autoimmune CDI. Autoimmune CDI is highly likely in young patients with a clinical history of autoimmune diseases and radiological evidence of pituitary stalk thickening. Conversely, autoimmunity probably represents an epiphenomenon in patients with nonidiopathic CDI.

Adult↗

PubMed2003

Nephrolithiasis in Cushing's disease: prevalence, etiopathogenesis, and modification after disease cure.

The pathogenesis of nephrolithiasis in Cushing's syndrome is still not completely clarified. The current study aimed at investigating prevalence of nephrolithiasis and role of different lithogenic factors in Cushing's disease (CD). Forty-six CD patients (24 with active and 22 with cured disease) and 46 sex- and age-matched controls entered the study. Body mass index, blood pressure, fasting glucose and insulin, serum and urinary creatinine, urea, uric acid, electrolytes, and cystine, urinary volume, pH, oxalate, and citrate levels, and renal ultrasonography (US) were performed in all patients and controls. Nephrolithiasis was found in 50% of active patients, 27.3% of cured patients, and 6.5% of controls (P < 0.001). Compared with controls, patients with active disease had a significantly increased prevalence of obesity, arterial hypertension, diabetes mellitus, hypercalciuria, hypocitraturia, and hyperuricosuria, significantly higher levels of serum and urinary cystine, urinary creatinine, urea, uric acid, potassium, calcium, phosphorus, and oxalate, significantly lower levels of urinary citrate levels. Compared with controls, patients cured from CD had a significantly increased prevalence of obesity, systemic arterial hypertension, and diabetes mellitus, whereas urinary citrate was significantly decreased. At multivariate analysis, a significantly increased risk to develop kidney stones was independently associated with urinary excretion of uric acid (odds ratio = 1.6, confidence interval = 1.0-2.5) and systemic arterial blood pressure (odds ratio = 2.6, confidence interval = 1.1-6.6). In conclusion, patients with active CD have an increased prevalence of nephrolithiasis compared with general population, which decreases but not disappears in patients successfully cured from the disease. This complication is likely caused by the synergic effect of different hypercortisolism-dependent metabolic and hemodynamic abnormalities, among which systemic arterial hypertension and excessive urinary uric acid excretion seem to play a pivotal role.

Adult↗

PubMed2003

Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing's disease during active disease and 1 year after disease remission.

Cardiovascular accidents represent the most important cause of death in patients with Cushing's syndrome. This prospective study aims at evaluating carotid arteries by echo-Doppler ultrasonography and clinical and metabolic markers of atherosclerosis in 25 patients with Cushing's disease (CD) before and after 1 yr of remission. Thirty-two sex- and age-matched subjects (control-1) and 32 body mass index-matched subjects (control-2) served as controls. At diagnosis, CD patients had higher body mass index, waist to hip ratio (WHR), total, low-density lipoprotein-cholesterol and total/high-density lipoprotein (HDL) ratio, glucose and insulin, as well as lower HDL-cholesterol than control-1; they had higher WHR and total/HDL ratio and lower HDL-cholesterol than control-2. They also had higher intima-media thickness (IMT), and lower systolic lumen diameter and distensibility coefficient (DC) than either control group. Atherosclerotic plaques were detected in 31.2% of patients, 0 control-1, and 6.2% of control-2 subjects. One year after remission, WHR, LDL-cholesterol, and IMT significantly decreased, whereas systolic lumen diameter and DC significantly increased. However, all of the above parameters were still abnormal compared with control-1, but not control-2. A significant correlation was found between WHR, glucose and insulin levels, and right and left carotid IMT. WHR was the best predictor of left IMT and left DC in active, but not in cured, patients. The duration of hypercortisolism was the best predictor of right DC in active but not in cured patients. In conclusion, patients with CD have severe atherosclerotic damage. The persistence of a metabolic syndrome, vascular damage, and atherosclerotic plaques after cortisol level normalization makes these subjects still at high cardiovascular risk despite disease remission.

Adult↗

PubMed2003

Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia.

BACKGROUND: Gender differences in tumor size are supposed to exist in hyperprolactinemia since microadenomas are more commonly found in women and macroadenomas in men. Whether this reflects only a delay in diagnosis in men or a true gender difference in tumor pathogenesis is still unclear. OBJECTIVE: To prospectively analyze gender differences in the presentation and response to cabergoline treatment in 219 consecutive newly diagnosed patients with hyperprolactinemia. DESIGN: An open prospective design. SUBJECTS: Of the 219 patients of which 145 were women; 107 patients had macroprolactinoma, 97 had microprolactinoma, and 15 had non-tumoral hyperprolactinemia. METHODS: Presenting clinical symptoms, prolactin levels and tumor size at magnetic resonance imaging were measured before and 3-6 Months after cabergoline therapy. RESULTS: Prevalence of microprolactinomas (56% vs 22%, P=<0.0001) and non-tumoral hyperprolactinemia (10% vs 0%, P=0.01) was higher in women than in men. Men and women were of similar age (median 32 vs 29 Years; P=0.2) and a similar number had gonadal/sexual dysfunction (85 vs 83%, P=0.6); weight gain (70 vs 46%; P=<0.0001) and galactorrhea (52 vs 19%; P=<0.0001) were more common in women. Prolactin levels were higher in men than in women, whether exhibiting macro- (2848+/-2954 vs 1132+/-2351 microg/l, P=<0.0001) or microadenomas (187.8+/-51.8 vs 135.4+/-60.5 microg/l, P=0.009) and the size of the adenoma was larger in men than in women irrespective of macro- (25.8+/-12.4 vs 17.2+/-7.2 mm, P=<0.0001) or microadenoma diagnosis (8.0+/-1.4 vs 7.1+/-1.6 mm, P=0.04). After treatment, prolactin levels decreased by 89.2-96.4% in all groups, and normalized more frequently in micro- than in macroadenoma patients (86 vs 64%, P<0.0001), regardless of gender (70% vs 69%, P=0.9). Menses resumed in 82% of women, libido disturbances improved in 57% of men. Tumor size was reduced by 45+/-25% and 52+/-24% in macroprolactinoma patients and by 44+/-31 and 38+/-29% in microprolactinoma patients in women and men respectively. Visual field defects disappeared in 61% of women and in 71% of men (P=0.6). CONCLUSIONS: Prevalence of macroprolactinomas was similar in men and women; microprolactinomas and non-tumoral hyperprolactinemia were more frequent in women. Clinical symptoms at presentation differed according to gender, with galactorrhea and weight gain more frequent in women. The successful response to cabergoline treatment for 6 Months was higher in micro- than in macroprolactinoma patients and was similar in women and men.

Adolescent↗

PubMed2002

Severe impairment of bone mass and turnover in Cushing's disease: comparison between childhood-onset and adulthood-onset disease.

BACKGROUND: Osteoporosis is an important, frequently unrecognized consequence of hypercortisolism. OBJECTIVE: To evaluate whether the age of onset of hypercortisolism influences its effects on bone mass and turnover. SUBJECTS: 10 with childhood-onset (co) and 18 with adulthood-onset (ao) Cushing's disease (CD); 28 age-, sex- and body mass index (BMI)-matched healthy subjects served as controls. STUDY DESIGN: Open, cross-sectional controlled. MEASUREMENTS: Bone mineral density (BMD) at lumbar spine, serum osteocalcin (OC), and urinary N-telopeptides of type I collagen (Ntx) levels. RESULTS: BMD at lumbar spine was significantly lower in all CD patients than in controls (Z score, -2.3 +/- 0.1 vs. -0.2 +/- 0.01; P < 0.001). co-CD and ao-CD patients had similar values of bone mass when expressed as Z score (-2.6 +/- 0.4 vs. -2.1 +/- 0.2; P = 0.27) or as BMD (0.728 +/- 0.03 vs. 0.78 +/- 0.03 g/cm2; P = 0.25). In particular, osteoporosis was observed in 16 patients (57.1%) [eight adolescents (80%) and eight adults (44.4%)] and none of the controls; osteopenia was found in two co-CD patients (20%) and none of the healthy adolescents, 10 ao-CD patients (55.6%) and four healthy adults (14.3%) (chi2 = 7.87, P < 0.01; chi2 = 2.99, P = 0.09, respectively). In co-CD and ao-CD patients, serum OC levels were similar and significantly lower than in controls (P < 0.01); urinary Ntx levels were significantly higher than in controls (P < 0.001) and were significantly higher in co-CD than in ao-CD patients (P < 0.001). No significant correlation was found between urinary cortisol levels, serum cortisol and age and lumbar Z score values, while a significant correlation was found between Ntx levels and disease duration (r = 0.434; P = 0.021) and plasma cortisol (r = 0.440; P = 0.019). CONCLUSIONS: Cushing's disease causes bone loss and abnormalities of bone turnover both in childhood-onset and in adulthood-onset patients. A strict follow-up of bone mass and turnover is mandatory in all patients with Cushing's disease to prevent fractures later in life and specific treatment for bone loss is strongly suggested.

Adolescent↗

PubMed2002

Differential expression of galectin-3 in medullary thyroid carcinoma and C-cell hyperplasia.

OBJECTIVE AND DESIGN: Galectin-3 is a beta-galactoside-binding protein that plays a role in cell adhesion and tumour progression. It was shown recently to diagnose malignant follicular thyroid lesions accurately. The reliability of this marker in the differential diagnosis between medullary thyroid carcinoma and C-cell hyperplasia was studied by immunohistochemistry. PATIENTS: Tissue specimens were obtained from 34 patients belonging to families with medullary thyroid carcinoma who underwent prophylactic thyroidectomy for RET gene mutation and/or abnormally increased plasma calcitonin levels. RESULTS: Galectin-3 was expressed in 23 of 25 cases of medullary thyroid carcinoma and in none of the nine cases of C-cell hyperplasia only, giving a sensitivity of 92% and a specificity of 100% for the diagnosis of carcinoma. A significant association was found between higher galectin-3 expression and occurrence of lymph node metastases (P < 0.05). CONCLUSIONS: Galectin-3 is a reliable diagnostic marker of medullary thyroid carcinoma, and its use may provide relevant information for prognosis and therapy.

Adolescent↗