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N Sonino

Publications and source records attributed to N Sonino.

At least 19 recordsLinked to original sources
PubMed2005

Adrenal incidentaloma in pregnancy: clinical, molecular and immunohistochemical findings.

Adrenal incidentalomas detected during pregnancy are very rare, and the natural history of these tumors during gestation is unknown. We report a case of a pregnant woman with an adrenal mass discovered serendipitously, who was followed-up during gestation and underwent adrenalectomy shortly after delivery. This allowed the evaluation of both the clinical outcome and the molecular/immunohistochemical correlates. Estrogens may indeed influence the function and proliferation of human adrenal cells, and a state of circulating estrogen excess can represent an in vivo model to test their effect on the adrenals. No evidence of adrenal change in morphology and function was found in our patient throughout pregnancy, as shown by adrenal ultrasound imaging and adrenal hormone measurements. Four months after delivery, the patient underwent laparoscopic right adrenalectomy, and pathologic analysis revealed a 2.7 cm benign adrenocortical adenoma. The diameter of the adrenal mass at ultrasonography correlated highly with post-partum mass diameter measured by abdominal computed tomography (CT). Quantitative expression of both ERalpha and ERbeta by real-time RT-PCR analysis and Western blotting findings did not differ among adenoma, normal adjacent adrenal and normal adrenal control tissues. This case of an adrenal incidentaloma discovered during pregnancy shows that a close observation with endocrine investigations and ultrasonography could be an appropriate approach, delaying the decision of surgical intervention after delivery. Estrogen receptor mRNA levels in the adrenal mass similar to those observed in normal adrenals suggest that estrogen oversecretion during pregnancy was not a risk factor for tumor progression.

Adrenal Gland Neoplasms↗
PubMed2004

Coexistence of different phenotypes in a family with glucocorticoid-remediable aldosteronism.

In glucocorticoid-remediable aldosteronism (GRA), there is a large interfamily variation of phenotype. We report three subjects with GRA in a single family (parents, two brothers and two sisters), of whom only one (proband) displayed classical features of the mineralocorticoid excess. The proband was a man found to be hypertensive and hypokalaemic at the age of 24 years. Plasma renin activity was suppressed and plasma aldosterone was repeatedly elevated. Blood pressure and aldosterone levels normalized within 5 days of dexamethasone therapy. The presence of a chimaeric CYP11B1/CYP11B2 gene was demonstrated by long-PCR and Southern blotting (crossover site at the end of intron 3) in the proband, in the younger sister (sibling 1) and in the father. In these patients, sequencing of the chimaeric portion of CYP11B1 did not reveal any mutation, while sequencing of the chimaeric portion of CYP11B2 showed a V386A polymorphism in exon 7, known to cause only a minimal impairment of enzymatic activity. Sibling 1 was normotensive, normokalaemic and had normal PRA and aldosterone. The father had normal blood pressure and potassium, low-normal PRA and normal aldosterone. All three subjects had elevated levels of urinary 18-hydroxycortisol and 18-oxocortisol. Baseline 11-deoxycorticosterone (DOC), corticosterone (B) and aldosterone were high in the proband and normal in the father and sibling 1; 11-deoxycortisol (S) and cortisol (F) were normal. ACTH induced a normal increase of B, DOC, S and F, and an excessive aldosterone increase in all three patients. Abnormalities in the chimaeric portions of CYB11B1 or CYP11B2 genes did not account for the phenotypic disparity of the different members in a single GRA family. Altered regulation of the chimaeric gene may be responsible for differences in its activity.

Adult↗
PubMed2004

Life events in the pathogenesis of hyperprolactinemia.

OBJECTIVE: Little is known about the relationship between recent life events and onset of hyperprolactinemia, despite the well-known effect of acute psychological stress on prolactin levels in healthy subjects. Recent life events in patients with hyperprolactinemia compared with healthy controls were investigated. DESIGN: Case-control study. METHODS: Fifty-two consecutive patients with hyperprolactinemia (45 females/7 males; mean age 34.9+/-10.1 years, range 18-60 years) and 52 healthy subjects matched for socio-demographic variables were studied. Nineteen patients (18 females/1 male) had no pituitary tumor and were diagnosed as suffering from idiopathic hyperprolactinemia. Patients with additional pathology or with high prolactin due to medications were excluded. All patients were interviewed by Paykel Interview for Recent Life Events while on remission after surgery or pharmacological treatment. The time period considered was the year preceding the first signs of hyperprolactinemia, and the year before interview for controls. RESULTS: Patients with hyperprolactinemia reported significantly more life events than control subjects (P<0.001). The same significant difference compared with controls applied to patients with (n=16) and without (n=36) depression. All categories of events (except events that were likely to be under the subject's control) were significantly more frequent. There were no significant differences between patients with prolactinoma (n=33) and those with idiopathic hyperprolactinemia (n=19). CONCLUSIONS: Within the complexity of phenomena implicated in the pathogenesis of hyperprolactinemia, our findings emphasize a potential role of emotional stress in either prolactin-secreting pituitary tumors or idiopathic hyperprolactinemia. Appraisal of life stress may have implications in clinical assessment (e.g. functional hyperprolactinemia) and decisions (e.g. termination of long-term pharmacological treatment).

Adolescent↗
PubMed2003

Diagnosis and complications of Cushing's syndrome: a consensus statement.

In October 2002, a workshop was held in Ancona, Italy, to reach a Consensus on the management of Cushing's syndrome. The workshop was organized by the University of Ancona and sponsored by the Pituitary Society, the European Neuroendocrine Association, and the Italian Society of Endocrinology. Invited international participants included almost 50 leading endocrinologists with specific expertise in the management of Cushing's syndrome. The consensus statement on diagnostic criteria and the diagnosis and treatment of complications of this syndrome reached at the workshop is hereby summarized.

Cardiovascular Diseases↗
PubMed2002

Quantitative assessment of CYP11B1 and CYP11B2 expression in aldosterone-producing adenomas.

BACKGROUND: The presence and pathophysiological role of CYP11B1 (11beta-hydroxylase) gene in the zona glomerulosa of human adrenal cortex is still controversial. METHODS: In order to specifically quantify CYP11B1, CYP11B2 (aldosterone synthase) and CYP17(17alpha-hydroxylase) mRNA levels, we developed a real-time RT-PCR assay and examined the expression in a series of adrenal tIssues, including six normal adrenals from patients adrenalectomized for renal cancer and twelve aldosterone-producing adenomas (APA) from patients with primary aldosteronism. RESULTS: CYP11B1 mRNA levels were clearly detected in normal adrenals, which comprised both zona glomerulosa and fasciculata/reticularis cells, but were also measured at a lower range (P<0.05) in APA. The levels of CYP11B2 mRNA were lower (P<0.005) in normal adrenals than in APA. CYP17 mRNAlevels were similar in normal adrenals and in APA. In patients with APA, CYP11B2 and CYP11B1 mRNA levels were not correlated either with basal aldosterone or with the change from basal aldosterone in response to posture or to dexamethasone. No correlation between CYP11B1 mRNA or CYP11B2 mRNA and the percentage of zona fasciculata-like cells was observed in APA. CONCLUSIONS: Real-time RT-PCR can be reliably used to quantify CYP11B1 and CYP11B2 mRNA levels in adrenal tIssues. Expression of CYP11B1 in hyperfunctioning zona glomerulosa suggests an additional formation of corticosterone via 11beta-hydroxylase, providing further substrate for aldosterone biosynthesis. CYP11B1 and CYP11B2 mRNA levels in APA are not related to the in vivo secretory activity of glomerulosa cells, where post-transcriptional factors might ultimately regulate aldosterone production.

Adenoma↗
PubMed2001

Cushing's syndrome.

During the past 30 years, there have been advances in understanding of the pathogenesis of Cushing's syndrome and in differential diagnosis of its various forms. Improved diagnostic tests and procedures have increased the ability to recognise even mild hypercortisolism and have provided the means to obtain an accurate diagnosis. Despite these advances, the occurrence of unusual clinical presentations and laboratory shortcomings may produce diagnostic problems and challenge clinical intuition. This article reviews recent pathogenic views, new tests, and new diagnostic problems in the evaluation of Cushing's syndrome. Atypical clinical presentations of hypercortisolism and some laboratory shortcomings that may confuse the diagnosis of Cushing's syndrome are also reported.

Cushing Syndrome↗
PubMed2001

Recovery of bone mineral density after surgical cure, but not by ketoconazole treatment, in Cushing's syndrome.

The aim of our study was to retrospectively assess the effect of treatment on bone mineral density (BMD) in patients with Cushing's syndrome. Nineteen patients (17 women, 2 men; mean age +/- SD, 41 +/- 10 years; preoperative duration of disease 20 +/- 15 months) were studied. Six patients had a cortisol-producing adenoma and 13 had pituitary-dependent bilateral adrenal hyperplasia. BMD of the lumbar spine (L2-L4) was measured by dual-energy X-ray absorptiometry just before and 1-10 years after adrenalectomy or pituitary adenomectomy. Patients were divided in two groups. The first group of 9 patients (6 adrenal and 3 pituitary adenomas; group A) included those treated successfully by surgery ( > 5 years follow-up in the case of pituitary surgery). The second group of 10 patients (group B) included those treated with the steroidogenesis inhibitor ketoconazole, 300-600 mg/day, after unsuccessful pituitary surgery. In group A, restoration of normal cortisol was associated with a significant increase in BMD (from 829 +/- 112 mg/cm2 to 952 +/- 107 mg/cm2; p = 0.002). In group B, no changes in BMD were observed (from 857 +/- 160 to 847 +/- 163 mg/cm2), in spite of markedly decreased or normalized cortisol levels during ketoconazole treatment. These findings indicate that definitive correction of hypercortisolism restores BMD to normal levels in patients with Cushing's syndrome. In patients treated with ketoconazole after unsuccessful pituitary surgery, even when normalization of cortisol levels was achieved, BMD remained low. This would suggest an interfering effect of this drug on bone metabolism.

Absorptiometry, Photon↗
PubMed2001

Psychiatric disorders associated with Cushing's syndrome. Epidemiology, pathophysiology and treatment.

Cushing's syndrome is caused by a chronic excess of glucocorticoids. A number of psychiatric and psychological disturbances may be associated with the condition, regardless of its aetiology. Major depression is the most common comorbid disorder. Other psychopathological aspects of Cushing's syndrome in adults include mania, anxiety disorders and cognitive dysfunction. The presence of depression connotes a severe clinical presentation and, in patients with hypothalamic-pituitary forms of Cushing's syndrome, is prognostically useful. Inhibitors of corticosteroid production (e.g. ketoconazole, metyrapone, aminoglutethimide), rather than antidepressant drugs, are generally successful in relieving depressive symptoms, as well as other disabling symptoms. These drugs can be used to control symptoms prior to surgical treatment of Cushing's syndrome. Long-standing hypercortisolism may cause some degree of irreversible pathological damage and induce highly individualised affective responses based on each patient's psychological assets and liabilities. As a result, upon normalisation of cortisol levels, treatment may still be required, and should encompass both psychotherapeutic strategies (particularly cognitive-behavioural therapies that have been found to be effective in affective disorders) and psychotropic drug treatment [antidepressants such as tricyclic agents and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors]. In patients with severe anxiety, benzodiazepines (e.g. clonazepam in small doses) may also be helpful.

Animals↗
PubMed2000

The diagnosis of Cushing's syndrome: atypical presentations and laboratory shortcomings.

In the last 3 decades, there have been several advances in understanding the pathogenesis of Cushing's syndrome and in testing for the diagnosis and differential diagnosis of its various forms. Advanced diagnostic techniques provide useful tools in discovering ectopic adrenocorticotropic hormone sources. However, the occurrence of unusual clinical presentations, laboratory shortcomings, and exogenous compound interference may lead to wrong conclusions. This article reviews the atypical presentations of hypercortisolism and some laboratory shortcomings that may confuse the diagnosis of Cushing's syndrome. Comments and suggestions are given with the aim of helping the clinician avoid diagnostic mistakes.

Cushing Syndrome↗
PubMed2000

Effect of the serotonin antagonists ritanserin and ketanserin in Cushing's disease.

Central serotonergic regulation could have a role in the course of pituitary-dependent Cushing's disease. We studied the effects of ritanserin and ketanserin, two related selective 5HT2 receptor antagonists, in 11 patients with Cushing's disease. Treatment lasted from 1 month to 1 year (up to 4 years in one patient). Daily doses were 10-15 mg for ritanserin, and 40-80 mg for ketanserin. Since the two drugs share the same mechanism of action and no qualitative or quantitative differences in response to their administration were observed, the results were pooled together. Patients were assessed by clinical and hormonal evaluation. Urinary cortisol and ACTH were considered the parameters of interest. Short-term response: after 1 month, there was a significant decrease of urinary cortisol from 781 (160) to 331 (215) nmol/d (P < 0.02) while ACTH was 9.8 (1.5) pmol/L baseline and again 8.8 (2.2) pmol/L at 1 month (P = NS). For 9 patients, hormonal parameters were available after 1 week of treatment. In this case, also ACTH levels were significantly decreased (from 9.6 (1.7) to 5.2 (1.3) pmol/L; P < 0.01) together with urinary cortisol (from 781 (194) to 372 (165) nmol/d; P < 0.01). Long-term response: in 3 patients, hormonal parameters failed to respond to serotonin receptor antagonists, which were thus discontinued. An improvement was recorded in the remaining 8 patients, that was prolonged in 3, and transient in 5. In 3 of these latter patients, a marked increase of ACTH was observed before treatment discontinuation. Ketanserin was given to 2 patients with Nelson's syndrome, with only transient ACTH decrease in one, and no changes in ACTH response to CRH after 1 month treatment in both cases. An inhibitory effect of ritanserin and ketanserin on ACTH and cortisol production in Cushing's disease appeared to be limited both in terms of duration of response and number of patients with a satisfactory outcome. However, the results may provide a better understanding of serotonergic modulation in Cushing's disease and lead to therapeutic developments.

Adolescent↗
PubMed1999

Medical therapy for Cushing's disease.

Various drugs have been employed in the management of pituitary-dependent Cushing's disease. The neuromodulatory compounds used thus far have demonstrated true clinical efficacy only occasionally when employed as sole treatment. Steroid synthesis inhibitors are effective in the majority of cases in a dose-dependent manner. By their ability to correct hypercortisolism and its severe complications quickly, they are suitable for critical cases and in preparation for surgery. The clinical experience with the only glucocorticoid receptor antagonist that can be administered to humans is still too limited to assess its therapeutic validity. No medical strategy can be standardized for this complex condition. Different therapeutic tools should be selected according to the form of disease to be treated (hypothalamic/pituitary) and the peculiar clinical situation of each patient. Combined treatments may achieve better therapeutic efficacy.

Adrenal Glands↗
PubMed1999

Abnormalities of von Willebrand factor are also part of the prothrombotic state of Cushing's syndrome.

Glucocorticoids are known to increase plasma concentrations of factor VIII (FVIII) and von Willebrand factor (vWF), and their administration is associated with an increased incidence of thrombotic complications. Because Cushing's syndrome is characterized by an endogenous increase in glucocorticoids, we studied levels of FVIII and vWF in 20 patients with Cushing's syndrome. Plasma levels of FVIII and vWF were found to be markedly increased. Moreover, the molecular organization of plasma vWF appeared to have been altered by the presence of unusually large multimers, normally present only in the cellular compartments. Spontaneous platelet aggregation and hyperresponsiveness to ristocetin were also observed. All patients underwent therapeutic surgery. Within 1 month of the intervention, regardless of its efficacy as evaluated by the assay of plasma and urinary cortisol, an additional significant increase in levels of FVIII and vWF was observed, with a concomitant more pronounced representation of abnormally large vWF multimers in circulation. In the cured patients, a progressive decrease in the levels of FVIII and vWF was observed, beginning in the third month after surgery, with complete normalization of the pattern within 12 months of surgery; a concomitant improvement in the plasma vWF multimer pattern was also observed. In contrast, no significant changes in FVIII or vWF were found in patients with persistent Cushing's syndrome. Our findings emphasize that vWF abnormalities are also part of the prothrombotic state of Cushing's syndrome. Moreover, this study also identified a period of additional thrombotic risk immediately after surgery, as a result of the worsening of the hemostatic pattern.

Adolescent↗
PubMed1999

Slow-release lanreotide treatment in acromegaly: effects on quality of life.

BACKGROUND: It is not known whether medical treatment to lower growth hormone (GH) and insulin-like growth factor (IGF)-1 levels may improve the compromised quality of life of patients with acromegaly. METHODS: We studied the effects on quality of life of the slow-release somatostatin analogue lanreotide, 30 mg i.m., every 14 days for 2 months in 10 patients with active acromegaly (8 females/2 males, mean age 57.3 +/- 11.4). Hormone measurements and psychometric evaluation by means of self-rating scales were carried out in baseline conditions and after 1 and 2 months. The Symptom Questionnaire (SQ), the Cognitive Scale of the Screening List for Psychosocial Problems by Kellner and the Social Situation Questionnaire by Marks were employed. RESULTS: Together with a significant decrease in GH and IGF-1, treatment with lanreotide significantly improved SQ psychological distress, SQ well-being and Social Situation Questionnaire social fears. CONCLUSION: Medical treatment with lanreotide may improve the quality of life of patients with acromegaly. Being an open trial, changes could be due to nonspecific effects. However, they did not fade at 2 months. Improvement involved fears of social situations that have been linked to GH abnormalities.

Acromegaly↗
PubMed1999

Mutations in CYP11B1 gene converting 11beta-hydroxylase into an aldosterone-producing enzyme are not present in aldosterone-producing adenomas.

In the human adrenal cortex, cortisol and aldosterone are synthesized by the isozymes 11beta-hydroxylase and aldosterone synthase, respectively, encoded by the 93% identical CYP11B1 and CYP11B2 genes. In vitro mutagenesis of CYP11B1 complementary DNA, resulting in the replacement of CYP11B1 codons by those encoding the corresponding amino acid residues of CYP11B2 enzyme (exon 5, Ser288Gly; exon 6, Val320Ala), yields a complementary DNA encoding a mutant enzyme with an efficient aldosterone synthase activity. Identical somatic mutations in the CYP11B1 gene in vivo would produce a gene encoding an enzyme with C18 activity and that would preserve ACTH responsiveness due to the retained 5'-promoter in the mutated CYP11B1 gene. An ACTH-responsive aldosterone synthase activity of this type is commonly seen in patients with aldosterone-producing adenomas (APA). We examined the occurrence of mutations in exons 5 and 6 of the CYP11B1 gene in APA from 10 patients with primary aldosteronism. Patients were selected on preoperative evidence of a 50% or greater plasma aldosterone decrease after short term dexamethasone trial and no aldosterone response to upright posture. DNA from adenomas was amplified by PCR using two pairs of primers spanning the regions of CYP11B1 gene, i.e. exons 3-5 and exons 6-9, where mutations could be located. Targeted regions were screened for mutations by automated sequencing of PCR products. No point mutations of the CYP11B1 gene over the two regions examined were found in APA. This argues against involvement of mutations in the pathogenesis of ACTH-responsive APA.

Adenoma↗
PubMed1999

Risk factors and long-term follow-up of adrenal incidentalomas.

The natural course of adrenal incidentalomas and the risk that such lesions evolve toward hormonal hypersecretion or malignancy are still under evaluation. Of 246 consecutive patients with adrenal incidentaloma studied at our institution in the last 15 yr, 91 underwent surgery. Of the remaining patients, a group of 75 (52 females and 23 males; median age, 56 yr; range, 19-77 yr) with incidentally discovered asymptomatic adrenal masses (60 unilateral and 15 bilateral; median diameter, 2.5 cm; range, 1.0-5.6) was enrolled in an endocrine and morphological follow-up of at least 2 yr after diagnosis (median, 4 yr; range, 2-10). During follow-up, no patients developed malignancy; 9 showed mass enlargement, with appearance of a new mass in the contralateral gland in 2; 3 developed adrenal hyperfunction (overt Cushing's syndrome in 2, nonclinical hypercortisolism in 1); and 3 showed adrenal mass enlargement associated with adrenal hyperfunction (nonclinical hypercortisolism in 2, pheochromocytoma in 1). The estimated cumulative risks to develop mass enlargement and hyperfunction were 8% and 4%, respectively, after 1 yr, 18% and 9.5% after 5 yr, and 22.8% and 9.5% after 10 yr. Nine risk factors for adrenal mass enlargement or hyperfunction were arbitrarily selected and evaluated: sex, age, presence of obesity, hypertension, diabetes, abnormal endocrine tests, mass size, mass location, and scintigraphic uptake pattern. Three of them attained statistical significance: mass size of 3 cm or more at diagnosis and exclusive radiocholesterol uptake by the mass at scintigraphy had relevance for the occurrence of adrenal hyperfunction, whereas the presence of endocrine test abnormalities at diagnosis had predictive value for mass enlargement. It is concluded that subtle hormonal abnormalities are risk factors for mass size increase, which is not a sign of malignant transformation. Both mass size of 3 cm or more at diagnosis and exclusive radiocholesterol uptake, indicating higher risks of hyperfunction, should be considered to plan a more thorough endocrine follow-up.

Adolescent↗