Analysis of characteristics and outcomes by growth hormone treatment duration in adult patients in the Italian cohort of the Hypopituitary Control and Complications Study (HypoCCS).

PURPOSE: To examine differences in effects according to growth hormone (GH) treatment duration in adult GH-deficient patients. METHODS: In the Italian cohort of the observational Hypopituitary Control and Complications Study, GH-treated adults with GH deficiency (GHD) were grouped by duration of treatment; ≤ 2 years (n = 451), > 2 to ≤ 6 years (n = 387) and > 6 years (n = 395). Between-group differences in demographics, medical history, physical characteristics, insulin-like growth factor-I standard deviation score (IGF-I SDS) and lipid profile at baseline, last study visit and changes from baseline to last study visit were assessed overall, for adult- and childhood-onset GHD and by gender using ANOVA for continuous variables and Chi-squared test for categorical variables. RESULTS: At baseline, treatment duration groups did not differ significantly for age, gender, body mass index, GHD onset, IGF-I SDS, lipid profile, and quality of life. Mean initial GH dose did not differ significantly according to treatment duration group in any subgroup, except female patients, with highest mean dose seen in the longest duration group. In the longest duration group for patients overall, adult-onset patients and male patients, there were significant decreases in GH dose from baseline to last visit, and in total and low-density lipoprotein (LDL)-cholesterol concentrations. IGF-I SDS increased, to a greater extent, in the longest duration group for patients overall and female patients. CONCLUSIONS: The results show that long-term GH treatment is associated with decreasing GH dose, increased IGF-I, decreased LDL-cholesterol and the presence of surrogate markers that help to give confidence in a diagnosis of GHD.

Somatostatin analogs therapy in gastroenteropancreatic neuroendocrine tumors: current aspects and new perspectives.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors that present many clinical features secreting peptides and neuroamines that cause distinct clinical syndromes such as carcinoid syndrome. However most of them are clinically silent until late presentation with mass effects. Surgical resection is the first line treatment for a patient with a GEP-NET while in metastatic disease multiple therapeutic approaches are possible. GEP-NETs are able to express somatostatin receptors (SSTRs) bounded by somatostatin (SST) or its synthetic analogs, although the subtypes and number of SSTRs expressed are very variable. In particular, SST analogs are used frequently to control hormone-related symptoms while their anti-neoplastic activity seems to result prevalently in tumor stabilization. Patients who fail to respond or cease to respond to standard SST analogs treatment seem to have a response to higher doses of these drugs. For this reason, the use of higher doses of SST analogs will probably improve the clinical management of these patients.

Intraorbital injection of rituximab: a new approach for active thyroid-associated orbitopathy, a prospective case series.

AIM: The aim of this paper was to examine the efficacy and the safety of intraorbital administration of the monoclonal anti-CD20 antibody rituximab (RTX) to treat patients affected by thyroid-associated orbitopathy (TAO) unresponsive to conventional therapy. METHODS: Five patients with active moderately-severe TAO unresponsive to systemic glucocorticoids were studied. After a complete ophthalmological examination, disease activity and severity were assessed by the clinical activity score (CAS) and the NO SPECS scoring system. Computed tomography scans were performed in all patients. Patients were treated with intraorbital injection of RTX 10 mg once a week for one month repeated once one month apart. The patients were followed every three months until 18 months. RESULTS: In all patients treated with RTX, CAS was significantly reduced (p< 0,005), inactive phase of TAO was reached in four out of five patients. No patients experienced major side effects, minor side effects were reported in two patients. CONCLUSION: Intraorbital injection of RTX is a safe and useful promising therapeutic option for active TAO.

Thyroid scintigraphy: an old tool is still the gold standard for an effective diagnosis of autonomously functioning thyroid nodules.

BACKGROUND: Patients with autonomously functioning thyroid nodules (AFTN) may not have an abnormal TSH value, particularly in iodine-deficient areas. AIM: To verify the accuracy of TSH as screening test in detecting AFTN and to evaluate ultrasonographic features of thyroid nodules which have resulted autonomously functioning at thyroid scintigraphy (TS). METHODS: Seventy-eight patients with nodular goiter, no marker of autoimmunity and at least one AFTN at TS were selected and divided in: Group 1 (no.=25) with TSH>0.35 IU/l, and Group 2 (no.=53) with TSH≤0.35 IU/l. RESULTS: In Group1 the mean nodule diameter was 19.8±9.4 mm; 12 nodules were isoechoic, 2 hyperechoic, and 11 hypoechoic. Vascular pattern was type I in 4, type II in 6 and type III in 15 nodules. In Group 2 the mean nodule diameter was 28.6±14.2 mm; 27 nodules were isoechoic, 9 hyperechoic and 17 hypoechoic. Vascular pattern was type I in 14, type II in 15 and type III in 24 nodules. CONCLUSION: In our study TSH alone was not able to identify AFTN in 32% of the patients. All hot nodules predominantly showed an isoechoic pattern with peri-intranodular vascularization; however, the presence of this pattern was not statistically significant. Moreover, we noticed a weak inverse correlation between the diameter of AFTN and TSH level. In conclusion, TS is the most sensitive tool to detect AFTN, allowing a precocious diagnosis even in the presence of a normal TSH value.

The treatment of neuroendocrine tumors with long-acting somatostatin analogs: a single center experience with lanreotide autogel.

The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing and diarrhea which improved by 85.7% and 55.6%, respectively, bronchoconstrinction and abdominal pain also ameliorated. A complete, partial or no-changed response in the tumor markers behavior was observed, respectively, in 42.9%, 22.9%, and 17.1% of cases. According to RECIST (Response Evaluation Criteria In Solid Tumors) criteria (version 1.1), there were 2 partial regression (8.7%) and 15 stable disease (65.3%); 6 patients (26.0%) progressed. No patient complained from any severe adverse reaction. The results of our study suggest that lanreotide autogel is effective in the symptoms, biochemical markers, and tumor progression control of WD metastatic NET and confirm that the treatment is well tolerated.

Biological aspects of gender disorders.

The scientific community is very interested in the biological aspects of gender disorders and sexual orientation. There are different levels to define an individual's sex: chromosomal, gonadic, and phenotypic sex. Concerning the psychological sex, men and women are different by virtue of their own gender identity, which means they recognize themselves as belonging to a determinate sex. They are different also as a result of their own role identity, a set of behaviors, tendencies, and cognitive and emotional attitudes, commonly defined as "male" and "female". Transsexuality is a disorder characterized by the development of a gender identity opposed to phenotypic sex, whereas homosexuality is not a disturbance of gender identity but only of sexual attraction, expressing sexual orientation towards people of the same sex. We started from a critical review of literature on genetic and hormonal mechanisms involved in sexual differentiation. We re-examined the neuro-anatomic and functional differences between men and women, with special reference to their role in psychosexual differentiation and to their possible implication in the genesis of homosexuality and identity gender disorders. Homosexuality and transsexuality are conditions without a well defined etiology. Although the influence of educational and environmental factors in humans is undeniable, it seems that organic neurohormonal prenatal and postnatal factors might contribute in a determinant way in the development of these two conditions. This "organicistic neurohormal theory" might find support in the study of particular situations in which the human fetus is exposed to an abnormal hormonal environment in utero.

Medullary thyroid cancer: a promising model for targeted therapy.

In recent years, the clinical validation of molecular targeted therapies inhibiting the action of pathogenic tyrosine kinase (TK) has been one of the most exciting developments in cancer research. In this context, medullary thyroid carcinoma (MTC) represents a promising model. It is well known that in MTC, the RET receptor TK and its signal transduction pathways, lead to subsequent neoplastic transformation. Several strategies aimed at blocking the activation and signaling of RET have been preclinically tested. The most advanced results have been obtained by competitive inhibition of RET-TK activity by tyrosine kinases inhibitors (TKI). However, although the inhibition of the RET pathway is actually one of the most studied for therapeutic purposes, other signal transduction pathways have been recognized to contribute to the growth and functional activity of MTC and are considered attractive therapeutic targets. To date, surgery represents the only curative treatment of MTC. Despite promising initial results, studies on targeted agents are in early stages and several issues regarding preclinical evaluations and clinical trials of new targeted agents in MTC are still unresolved. Now, available mouse models bearing mutations of RET or other genes, which spontaneously develop MTC, promise to improve preclinical evaluation of activity of targeted compounds. Furthermore, the rarity of the disease and the number of patients available for enrollment may lessen the relevance of clinical trials. A major effort needs to be made by endocrinologists and oncologists to refer their patients for multi-institutional trials in order to optimize them, perform translational studies and expedite the availability of novel beneficial selective therapies.

[Preoperative and postoperative management of adrenal masses]. / Terapia medica pre e post-operatoria della patologia espansiva surrenalica.

The surgical approach of adrenal masses requires a careful preoperative and postoperative management. In order to avoid iatrogenic hypocortisolism, Cushing patients have to be treated, before adrenal surgery and then every eight hours, with hydrocortisone 100 mg iv. The therapy should be gradually reduced to 10-20 mg/die by mouth for six-twelve months. In primary hyperaldosteronism the target of medical treatment is to control blood pressure and serum potassium values as well as to normalize the circulating aldosterone levels or to obtain mineralocorticoid receptor blockade. Epleronone and spironolactone are the most common used drugs. Spironolactone has long been the drug of choice while epleronone represents a newer more expensive alternative with fewer side effects. Postoperative management generally does not require steroid replacement therapy. The management of pheochromocytoma requires a careful medical preparation for surgery: in fact, the surgical removal of a pheochromocytoma is a high-risk procedure and an experienced surgeon/anesthesiologist team is required. The preoperative medical therapy is aimed at controlling hypertension (including preventing a hypertensive crisis during surgery) and at avoiding cardiac arrhythmia. The most common used drugs are alpha-adrenergic blockade: phenoxybenzamine is an irreversible, long-acting, nonspecific alpha-adrenergic blocking agent. Doxazosine is a selective alpha1-adrenergic blocking agent with a more favorable side-effect profile, being less related to postoperative hypotension. Postsurgical management is aimed at expanding plasma volume: a copious hydration is required while the use of dopamine in hemodynamin support is not effective because of the preoperative use of alpha-blocking agents.

Levothyroxine therapy in preventing nodular recurrence after hemithyroidectomy: a retrospective study.

AIM: To determine the effect of levothyroxine (L-T4) therapy on the recurrence rate of nodular disease in patients previously treated with lobectomy for benign nodular goiter. METHODS: Two hundred and thirty-tree patients (38 males, 195 females; age 49.9+/-13.1 yr) with no post-surgical evidence of nodular disease in the remnant, were followed- up yearly with serum TSH and ultrasound (US). Nodular recurrence was defined as a lesion of at least 5 mm at US. Patients were divided in 2 groups based on whether or not they had been treated with L-T4 after surgery: Group 1 (45 patients) who did not receive any L-T4, and Group 2 (188 patients) treated with L-T4. Group 2 was further subdivided in Group 2a (123 patients) receiving L-T4 substitutive therapy (TSH>or=0.5 and

Value of routine measurement of serum calcitonin concentrations in patients with nodular thyroid disease: A multicenter study.

BACKGROUND: The routine measurement of serum calcitonin (CT) has been proposed for patients with nodular thyroid disease (NTD), to detect unsuspected medullary thyroid carcinoma (MTC) before surgery. OBJECTIVE: To assess the prevalence of hypercalcitoninemia and MTC in NTD patients; to compare the ability of CT measurement and fine needle aspiration cytology (FNAC) to predict MTC; to identify age groups of NTD patients who should be better candidates than others to undergo routine measurement of CT. PATIENTS AND METHODS: 1425 consecutive patients, referred from April 1, 2003, through March 31, 2004, to four Italian endocrine centers due to NTD, were grouped depending on age, and underwent basal and, in some cases, pentagastrin (Pg)-stimulated CT measurement, FNAC and, when indicated, surgery. Serum CT concentrations were measured by an immunoluminometric assay (ILMA). RESULTS: Hypercalcitoninemia was found in 23 out of 1425 patients. MTC was discovered in 9 patients, all >40 yr old and showing high CT levels. Sensitivity of basal and Pg-stimulated CT to predict MTC before surgery was 100% for both tests, whereas specificity was 95 and 93%, respectively. CT specificity reached 100% when a cutoff value of 20 pg/ml was taken. FNAC showed an overall 86% sensitivity. When >10 mm MTC nodules were considered, FNAC sensitivity approached 100%. On the contrary, a correct cytological diagnosis was obtained in only one out of five patients with <10 mm MTC nodules (microMTC); in one patient with histologically proved microMTC, FNAC even demonstrated a benign lesion. Hypercalcitoninemia or MTC were associated with chronic thyroiditis in 30 or 33% of cases, respectively. C-cell hyperplasia was found in 57% of hypercalcitoninemic patients without MTC. CONCLUSIONS: Basal CT measurement detects elevated CT values in 1.6% of NTD patients. Although CT is not a specific marker of MTC, its routine measurement represents a useful tool in the pre-operative evaluation of NTD patients, particularly those >40 yr old presenting with nodules <10 mm, even when FNAC does not show malignant features. To our knowledge, this is the first trial using ILMA to assess the ability of pre-operative CT measurement to predict MTC in a large series of NTD patients.

Postpartum thyroiditis presenting as a cold nodule and evolving to Graves' disease.

We describe the case of a 30-year-old woman who, five months after giving birth, was referred with a solitary nodule in her anterior neck. Laboratory analysis, ultrasonography, pertechnetate (Tc99m) thyroid scan and cytological examination of fine needle aspiration biopsy performed on the nodule led us to diagnose postpartum thyroiditis (PPT). Twenty-eight months after parturition, overt hyperthyroidism developed, with raised thyroperoxidase and thyroid stimulating hormone receptor antibody titres, diffuse high uptake of Tc99m at thyroid scan, and high vascular flow throughout the gland at Color-Power imaging. The diagnosis of Graves' disease (GD) was established. The differential diagnosis of thyrotoxicosis in the postpartum period, and the possible aetiological relationships between PPT and GD are discussed. To our knowledge, this is the first published report of a PPT presenting as a cold nodule, and evolving to GD.

Giant prolactinomas in men: efficacy of cabergoline treatment.

OBJECTIVE: The term 'giant prolactinoma' can be used for tumours larger than 4 cm in diameter and/or with massive extrasellar extension. Cabergoline (CAB), a long-lasting dopamine agonist (DA), safe and well tolerated, is effective in normalizing PRL levels and inducing tumour shrinkage in micro- and macroprolactinomas. The purpose of this prospective study was to evaluate the efficacy and safety of CAB also for giant prolactinomas. PATIENTS AND METHODS: Ten men with giant prolactinomas with a median age of 44.8 years were treated with CAB. Before CAB, four patients had previously undergone transsphenoidal surgery without modifying the parasellar extension of the tumour or their visual defects. Pretreatment serum prolactin (PRL) levels ranged between 1230 and 22 916 micro g/l (mean +/- SEM: 5794 +/- 1996) and tumour volume was between 21.8 and 105.5 cm3 (mean +/- SEM: 50.7 +/- 8.8). CAB was administered at an initial low dose of 0.5 mg three times a week and, in five patients who did not achieve serum PRL normalization, the dose was progressively increased up to 10.5 mg/week. The duration of treatment was 13-68 months (mean 38.9). PRL levels and pituitary target organ hormones were assayed before, after 30 days and then every 3 months after the beginning of CAB treatment. Magnetic resonance imaging (MRI) was carried out before, after 1-3 months, after 6 months and then every 10-12 months to evaluate tumour shrinkage. RESULTS: In every patient, a significant PRL decrease (P = 0.0086) of at least 96% of the pretreatment values occurred (from 5794 +/- 1996 to 77 +/- 38, mean +/- SEM); a persistent normalization of PRL levels was achieved in five out of 10 patients (50%) beginning from the first 3-6 months of CAB treatment (only one patient needed 12 months of therapy). A significant tumour shrinkage (P = 0.0003) was achieved after 12 months of therapy in nine out of 10 patients (90%), with a volume reduction greater than 95% in three, of 50% in four and 25% in two patients. Tumour volume decreased from 50.7 +/- 8.8 to 28.6 +/- 9.4 and then to 22.3 +/- 8.8 cm3 (mean +/- SEM) after 6 and 12 months of CAB treatment, respectively. An improvement of visual field defects (VFD) was obtained in six of the seven patients presenting visual impairment before CAB treatment. Among the eight patients presenting libido and potency (L-P) failure, five normalized their PRL levels. In two of these a complete restoration of libido and potency was observed. Three patients with secondary hypoadrenalism and a patient with secondary hypothyroidism were treated with substitutive therapy during all the study time. The drug was well tolerated by all patients and no one discontinued the therapy. CONCLUSIONS: These data suggest that, in giant, aggressive prolactinomas, CAB represents a first-line therapy effective in reducing PRL levels and determining tumour shrinkage.

[The management of thyrotoxicosis: a schematic approach]. / Approccio schematico alla terapia delle tireotossicosi.

Thyrotoxicosis is a well defined clinical entity, determined by an increase of plasma levels of thyroid hormones (T3 and T4). A number of causes of thyrotoxicosis are known, and it is therefore very important for the treatment to establish its etiology. In fact, metimazole or propylthiouracil are indicated for the thyrotoxic states caused by thyroid gland's hyperfunction (hyperthyroidism), but are not effective when thyrotoxicosis is determined by a follicular damage and disruption with leakage of preformed thyroid hormones, or in case of thyrotoxicosis factitia. Besides medical therapy, other two therapeutic options are available for the treatment of thyrotoxicosis: radioiodide administration (131I) and surgery. The physician can decide the best therapy on the basis of the following factors: etiology of thyrotoxicosis; patient's age and needs; presence/absence of concomitant diseases or pregnancy; presence of ophthalmopathy; goiter's size; advantages and disadvantages of each therapeutic option. A problem of particular regard is when and if to treat subclinical thyrotoxicosis (low TSH values, and normal plasma levels of thyroid hormones). On the basis of the natural history and of its consequences on the cardiovascular system and skeletal integrity, the authors propose to begin therapy whether subclinical thyrotoxicosis develop in the following four subgroups of subjects: patients with nodular goiter; women in post-menopause; patients with cardiac diseases; patients with osteoporosis.

Adrenal insufficiency as the first clinical manifestation of the primary antiphospholipid antibody syndrome.

We describe a 60-year-old man who developed clinical symptoms and signs of Addison's disease, which was subsequently confirmed biochemically; no cause was apparent. Several months later the patient represented with a fit, followed by a large and extensive venous thrombosis in the right iliac vein and in the veins of the right leg. He had strongly positive antibodies to cardiolipin, strongly suggesting a diagnosis of primary antiphospholipid syndrome. While Addison's disease is a well-recognized, albeit rare, manifestation of the antiphospholipid syndrome, the Addison's disease preceded other clinical evidence of the syndrome by several months, in our patient, at variance with previous cases described in the literature. The antiphospholipid syndrome should be considered as a possible pathogenetic process in patients presenting with Addison's disease where the aetiology is not obvious.

Diagnostic approach, genetic screening and prognostic factors of medullary thyroid carcinoma.

Medullary thyroid carcinoma is the least frequent thyroid neoplasm; it originates in thyroid parafollicular cells (calcitonin secreting C cells). In 80% of cases it is sporadic, in the remaining 20% it is familial, associated or not to other endocrinopathies as pheochromocytoma and hyperparathyroidism (MEN 2A, MEN 2B, and isolated familial medullary thyroid carcinoma). Preclinical diagnosis in relatives of affected subjects (preferably at pediatric age) is essential for successful therapy and is performed with genetic and biochemical screening tests. The genetic screening is based on DNA analysis (RET proto-oncogene mutations) of the patient, and if positive of all first degree relatives, to separate sporadic (somatic mutations) from familial (germline mutations) forms. The biochemical screening is based on calcitonin determination and its increase after pentagastrin stimulation, (a peculiar characteristic of medullary thyroid carcinoma, the first biochemical disorder in a subject at risk) and is mainly used in genetically silent familial medullary thyroid carcinoma. The principal negative prognostic factors of medullar thyroid carcinoma and the debate concerning the use of calcitonin determination in the diagnosis of the "cold" thyroid nodule have been analyzed.

Medical therapy of benign thyroid diseases.

Main guide-lines of medical therapy of benign thyroid diseases are reviewed. The most common drug therapy of the various forms of hyperthyroidism is represented by thionamide drugs (methimazole and propylthiouracil). Therapeutic protocols are diversified according to the disease. In Graves'disease medical therapy may present the definitive treatment, leading to remission in little less than 50% of cases while in hyperfunctioning nodular thyroid diseases, medical therapy is merely in preparation for ablation therapy. Other drugs used in hyperthyroidism are also mentioned (inorganic iodine, potassium perchlorate, beta-blockers). Thyroxine replacement therapy in the various forms of hypothyroidism is then analyzed, discussing in particular the therapeutic protocols and follow-up of the various forms of hypothyroidism. Finally, the controversy about the indications and efficacy of TSH-suppressive thyroxine therapy is considered.

Effect of acute and chronic administration of tamoxifen on GH response to GHRH and on IGF-I serum levels in women with breast cancer.

Tamoxifen, an estrogen antagonist, is usually employed in the treatment of breast cancer. Its mechanism of action is not well known because an antiproliferative effect of the drug has been shown also in estrogen receptor negative tumors, most likely mediated by the inhibition of local growth factors and particularly IGF-I. However, the action of tamoxifen on the GH-IGF-I axis is still open to investigation. We have investigated the influence of acute and chronic treatment with tamoxifen on GH response to GHRH and IGF-I serum levels in six postmenopausal women with metastatic breast cancer. A GHRH test (50 microg i.v. at time 0, GH determinations at 0, 15, 30, 60, 90 and 120 min) was performed (a) basally, (b) 3 h after 40 mg oral administration of tamoxifen and (c) after 8 weeks of 20 mg twice a day oral tamoxifen treatment. IGF-I was measured basally and after chronic tamoxifen therapy. No significant modifications in GH response to GHRH were observed after acute or chronic treatment with tamoxifen vs the basal test. On the contrary, chronic tamoxifen treatment induced a significant decrease in serum IGF-I levels. Basal pretreatment levels of 123+/-18 microg/l were suppressed to 65+/-11 microg/l (mean suppression 47%, P < 0.001). These preliminary data confirm the inhibitory effect of tamoxifen on IGF-I production but seem to exclude the possibility that this effect may be due to an inhibition of GH secretion.

Severe thyrotoxicosis due to functioning pulmonary metastases of well-differentiated thyroid cancer.

We report two cases of thyrotoxicosis resulting from hyperfunctioning lung metastases from differentiated thyroid cancer. In both patients, a simultaneous diagnosis of thyrotoxicosis and metastatic thyroid cancer was made, based on thyroid function tests as well as 131I whole-body scans showing low thyroid uptake of radioiodine and multiple foci of intense 131I uptake in the lungs. After total thyroidectomy (performed in Patient 2 only) and 131I therapy (cumulative dose of 12.3 GBq in Patient 1 and 9.6 GBq in Patient 2), there was a rapid clinical improvement with significant reduction of the pulmonary metastatic disease in both patients: Patient 1 became euthyroid, while Patient 2 became hypothyroid. Analysis of the 54 cases reported in the literature, including the 2 cases described here, shows this to be a very rare cause of thyrotoxicosis and one that can pose serious problems for both the diagnostic evaluation and choice of therapeutic strategy when compared with the much more common nonhyperfunctioning metastases from thyroid cancer. Lesser degrees of thyroid hormone secretion by differentiated thyroid cancer may be detected and exploited diagnostically by the chromatographic analysis of serum for endogenously labeled thyroid hormones after 131I administration.

Intracranial and spinal dissemination of an ACTH secreting pituitary neoplasia. Case report and review of the literature.

We report a case of a 52-year-old woman presenting with a recurrence of a large pituitary adenoma with suprasellar extension and an overt Cushing's clinical picture, five years after successful transsphenoidal treatment. After transfrontal ablation of the tumour, followed by external radiotherapy, she was asymptomatic for six years before she exhibited epileptic seizures. A left frontal intracranial neoplasm was diagnosed and removed, and at histological examination it was found to be constituted by a localization of the pituitary ACTH secreting neoplasia. One month later she exhibited spinal dissemination of the ACTH secreting neoplasia which was only partially removed. After four months a Magnetic Resonance Image (MRI) revealed recurrence of the intracranial localization and further spinal dissemination. Because of compressive symptoms, spinal masses with the same histologic features, were partially removed again in three successive surgical operations. Several medical treatments for obtaining the control of corticoid excess, caused by the ACTH overproduction, were tried, but none were satisfactory. Finally a bilateral adrenal venous embolization was performed thus obtaining a critical transient fall of serum cortisol. Five months later the patient died. At necroscopy bilateral adrenal enlargement was found, spinal disseminations were confirmed, and no metastatic lesions were discovered.