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M Losa

Publications and source records attributed to M Losa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Somatostatin receptor subtype 2 and 5 in human GH-secreting pituitary adenomas: analysis of gene sequence and mRNA expression.

The role of somatostatin receptor subtypes 2 and 5 (SSTR2 and SSTR5) in determining the secretory and proliferative phenotype as well as the sensitivity to somatostatin analogue treatment is not clearly established. We quantified the expression of SSTR2 and SSTR5 mRNA using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 19 human growth hormone (GH) -secreting adenomas. Tumour characteristics and in vivo sensitivity to somatostatin analogues were assessed; tumours were screened for Gsalpha gene mutations. PCR products of SSTR2 and SSTR5 DNA from tumours resistant to somatostatin analogues were directly sequenced. All tumours expressed both SSTR2 and SSTR5 mRNA at variable levels. No significant correlation between SSTR2 and SSTR5 expression and the presence of Gsalpha mutation, GH levels, or tumour size and invasiveness was observed. A negative correlation between SSTR2 and SSTR5 mRNA levels was observed (r = 0.5; P < 0.05). No significant correlation between the levels of SSTR2 and SSTR5 expression and the in vivo responsiveness to somatostatin analogues was observed, although a tendency to a low SSTR2 expression in resistant tumours was found. No mutations in the coding or bordering regions of either SSTR2 or SSTR5 adenomatous DNA from patients totally or partially resistant to somatostatin analogues were found. The study shows that the different expression of SSTR2 and SSTR5 in GH-secreting adenomas is not significantly correlated with the secretory and proliferative phenotype, although the large, hypersecretory tumours and those with a poor sensitivity to somatostatin analogues seem to express low levels of SSTR2 mRNA. Moreover, both SSTR2 and SSTR5 DNA from tumours resistant to somatostatin analogues were found to possess intact coding sequences.

Adenoma↗
PubMed2001

Vascular endothelial growth factor production and regulation in rodent and human pituitary tumor cells in vitro.

Angiogenesis, the formation of a new blood supply, is an essential step in tumorigenesis. Although vascular endothelial growth factor (VEGF) is known to be a very potent angiogenic factor in most solid tumors, little is known about its production and regulation in pituitary adenomas. We have investigated basal and stimulated VEGF production by rodent pituitary tumor cells (mouse corticotrope AtT20, rat lactosomatotrope GH3, mouse gonadotrope alpha T3-1 and mouse folliculostellate TtT/GF cells), and by hormone-inactive (27), corticotrope (9), lactotrope (3) and somatotrope (21) human pituitary adenoma cell cultures. All 4 pituitary cell lines secreted VEGF, which in the case of AtT20, GH3 and TtT/GF cells was inhibited by approximately 50% by dexamethasone. TtT/GF cells were the most responsive to the different stimuli used since basal values were augmented by pituitary adenylate cyclase activating polypeptide-38 (PACAP-38), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha), IGF-I and the somatostatin analogue ocreotide. However, in GH3, AtT20 and alpha T3-1 cells, basal VEGF levels where not enhanced with any of the stimuli tested. The majority of the human adenomas tested (92%) basally secreted measurable VEGF which was inhibited by dexamethasone in most cases (84%). VEGF levels were increased in hormone inactive adenomas, somatotrope tumors and prolactinomas by TGF-alpha, PACAP-38, and 17 beta-estradiol, respectively. In conclusion, pituitary tumor cells are capable of producing VEGF which may be involved in tumoral angiogenesis. Our results concerning the suppression of VEGF by dexamethasone suggest that glucocorticoids may have anti-angiogenic properties and therefore therapeutic relevance for the treatment of pituitary adenomas.

Adenoma↗
PubMed2001

Retinoic acid prevents experimental Cushing syndrome.

Cushing syndrome is caused by an excess of adrenocorticotropic hormone (ACTH) production by neuroendocrine tumors, which subsequently results in chronic glucocorticoid excess. We found that retinoic acid inhibits the transcriptional activity of AP-1 and the orphan receptors Nur77 and Nurr1 in ACTH-secreting tumor cells. Retinoic acid treatment resulted in reduced pro-opiomelanocortin transcription and ACTH production. ACTH inhibition was also observed in human pituitary ACTH-secreting tumor cells and a small-cell lung cancer cell line, but not in normal cells. This correlated with the expression of the orphan receptor COUP-TFI, which was found in normal corticotrophs but not in pituitary Cushing tumors. COUP-TFI expression in ACTH-secreting tumor cells blocked retinoic acid action. Retinoic acid also inhibited cell proliferation and, after prolonged treatment, increased caspase-3 activity and induced cell death in ACTH-secreting cells. In adrenal cortex cells, retinoic acid inhibited corticosterone production and cell proliferation. The antiproliferative action and the inhibition of ACTH and corticosterone produced by retinoic acid were confirmed in vivo in experimental ACTH-secreting tumors in nude mice. Thus, we conclude that the effects of retinoic acid combine in vivo to reverse the endocrine alterations and symptoms observed in experimental Cushing syndrome.

Adrenocorticotropic Hormone↗
PubMed2001

Effects of octreotide treatment on the proliferation and apoptotic index of GH-secreting pituitary adenomas.

To investigate the effects of octreotide administration on the growth rate of GH-secreting pituitary adenomas, we measured both the Ki-67 labeling index (LI) and the apoptotic index in tumor specimens from octreotide-treated or matched untreated acromegalic patients. Thirty-nine patients who received octreotide until the day of or the day before surgery and 39 untreated patients matched for sex, age, tumor size, extension, and invasiveness were studied. Immunocytochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick endlabeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. The Ki-67 LI and apoptosis were counted on separate slides in at least 1000 evaluable cells. Octreotide-treated patients showed a lower Ki-67 LI (1.8 +/- 0.3%) than untreated controls (3.8 +/- 0.7%; P < 0.02). Overall, the mean Ki-67 LI of treated patients was 53% lower than that in untreated patients. The antiproliferative effect of octreotide occurred independently of tumor extension and invasiveness. Octreotide-treated and untreated patients showed similar apoptotic indexes (0.6 +/- 0.2% and 0.8 +/- 0.3%, respectively). There was a positive correlation between the Ki-67 LI and the apoptotic index (r = 0.29; P < 0.03). Our study demonstrates that acromegalic patients receiving chronic octreotide treatment have a lower value of the proliferation marker Ki-67, but no significant difference in the apoptotic index compared with matched untreated patients. The antiproliferative effect of octreotide on GH-secreting adenomas should imply a lower risk of tumor growth during long-term chronic treatment with the drug.

Acromegaly↗
PubMed2001

Normal human pituitary gland and pituitary adenomas express cannabinoid receptor type 1 and synthesize endogenous cannabinoids: first evidence for a direct role of cannabinoids on hormone modulation at the human pituitary level.

Little is known about the expression and function of cannabinoid receptor type 1 (CB1) in the human pituitary gland. The aim of this study was to investigate CB1 expression in human normal and tumoral pituitaries by in situ hybridization and immunohistochemistry using an antibody against CB1. CB1 was found in corticotrophs, mammotrophs, somatotrophs, and folliculostellate cells in the anterior lobe of normal pituitary. After examination of 42 pituitary adenomas, CB1 was detected in acromegaly-associated pituitary adenomas, Cushing's adenomas, and prolactinomas, whereas faint or no expression was found in nonfunctioning pituitary adenomas. Experiments with cultured pituitary adenoma cells showed that the CB1 agonist WIN 55,212--2 inhibited GH secretion in most of acromegaly-associated pituitary adenomas tested and that the CB1 antagonist SR 141716A was generally able to reverse this effect. Moreover, WIN 55,212--2 was able to suppress GHRH-stimulated GH release, and this effect was not blocked by coincubation with SR 141716A, possibly indicating a non-CB1-mediated effect. In contrast, WIN 55,212--2 was ineffective on GH-releasing peptide-stimulated GH release. In four Cushing's adenomas tested, WIN 55,212--2 was not able to modify basal ACTH secretion. However, simultaneous application of CRF and WIN 55,212--2 resulted in a synergistic effect on ACTH secretion, and this effect could be abolished by SR 141716A, demonstrating a CB1-mediated effect. In the single case of prolactinomas tested, WIN 55,212--2 was able to inhibit basal secretion of PRL. Finally, the presence of endocannabinoids (anandamide and 2-arachidonoylglycerol) was investigated in normal and tumoral pituitaries. All tumoral samples had higher contents of anandamide and 2-arachidonoylglycerol compared with the normal hypophysis. Moreover, endocannabinoid content in the different pituitary adenomas correlated with the presence of CB1, being elevated in the tumoral samples positive for CB1 and lower in the samples in which no or low levels of CB1 were found. The results of this study point to a direct role of cannabinoids in the regulation of human pituitary hormone secretion.

Adenoma↗
PubMed2000

The expression of the antiproliferative gene ZAC is lost or highly reduced in nonfunctioning pituitary adenomas.

The ZAC gene encodes a new zinc-finger protein that concomitantly induces apoptosis and cell cycle arrest and localizes to chromosome 6q24-q25, a well-known hot spot related to cancer. ZAC is highly expressed in the anterior pituitary gland, and its ablation by antisense targeting promotes pituitary cell proliferation. Here we investigate ZAC status in pituitary tumors to evaluate its role in pituitary tumorigenesis. Interest ingly, a strong reduction or absence of ZAC mRNA and protein expres sion was detected in nonfunctioning pituitary adenomas, whereas in clin ically active pituitary neoplasias, the decrease in ZAC expression was variable. Loss of expression was not associated with a mutation of the ZAC gene. Our observations suggest that alternative mechanisms of gene inactivation and/or altered regulation of the ZAC gene occur in nonfunctioning pituitary adenomas.

Adenoma↗
PubMed2000

Non-random trisomies of chromosomes 5, 8 and 12 in the prolactinoma sub-type of pituitary adenomas: conventional cytogenetics and interphase FISH study.

Specimens from 53 pituitary adenomas (PAs), including 17 NFPA, 16 PRL-, 9 ACTH-, 9 GH- and 2 TSH-secreting tumors, underwent cytogenetic analysis by the direct and short-term culture methods. Only 8 tumors (15%) appeared to have an abnormal karyotype. To increase the resolution of cytogenetic analysis, direct preparations from 31 PAs were investigated by interphase FISH with probes specific for chromosomes 5, 8, 12 and X, for which gain in pituitary tumors has been reported. Of these 31 PAs, 17 (54.8%) had an abnormal dosage of one or more of the 4 chromosomes tested. Separate or combined trisomies of chromosomes 5, 8 and 12 were found in 10/10 prolactinomas and in 4/9 NFPA, whereas the combined loss of chromosomes 5 and 8 was observed in 1/6 ACTH- and 1/6 GH-secreting PAs. Present and earlier data on 23 PAs showed that tumors with the highest frequency of abnormal karyotypes revealed by cytogenetics and/or interphase FISH were PRL (78%), followed by NFPA (26%) and GH (18%). Recurrent structural rearrangements affecting chromosomes 1, 3 and 12 were also identified in prolactinomas, which therefore appear to be the only pituitary adenoma sub-type with a defined trend of tumor-specific chromosomal changes. Cytogenetic and FISH analyses of different pituitary tumor sub-types indicate that they may harbour genetically distinct lesions.

Adult↗
PubMed2000

Comprehensive critical incident monitoring in a neonatal-pediatric intensive care unit: experience with the system approach.

OBJECTIVE: To examine the occurrence of critical incidents (CIs) in order to improve quality of care. DESIGN: Prospective survey. SETTING: Multidisciplinary, neonatal-pediatric intensive care unit (ICU) of a non-university, teaching children's hospital. PATIENTS: Four hundred and sixty-seven admissions over a 1-year period. METHODS: A CI is any event which could have reduced, or did reduce, the safety margin for the patient. Comprehensive, anonymous, non-punitive CI monitoring was undertaken. CI severity with respect to actual patient harm was graded: major (score 3), moderate (2) or minor (1). The system approach incorporates the philosophy that errors are evidence of deficiencies in systems, not in people. We undertook 2-monthly analyses of CIs. RESULTS: There were 211 CI reports: 30 % major, 25 % moderate, 45 % minor. The CI categories were management/environment 29 %, drugs 29 %, procedures 18 %, respiration 14 %, equipment dysfunction 7 %, nosocomial infections 3 %. The respiratory CIs were the most severe, the drug-related CIs the least severe (score mean, SD: 2.9, 0.26 vs 1.4, 0.76; p < 0.001). However, 20 out of 62 drug-related CIs were potentially life-threatening. Thirteen percent of drug CIs were decimal point errors. Eleven of the 29 respiratory CIs were accidental extubations (2.6/100 ventilator days). CIs were most often precipitated by consultants (32 %), followed by residents (23 %, over-represented in drug CIs, 22/62) and specialized nurses (21 %). Doctors had a greater proportion of major CIs than nurses (p < 0.01). Fifty percent of the CIs were detected by routine checks. The most important method of detection was patient inspection (44 %), alarms accounted for only 10 %. Contributing factors were human errors (63 %), communication failure (14 %), organizational problems (10 %), equipment dysfunction (7 %) and milieu (3 %). CONCLUSIONS: CIs are very common in pediatric intensive care. Knowledge of them is a precious source for quality improvement through changes in the system.

Child↗
PubMed2000

Determination of the proliferation and apoptotic index in adrenocorticotropin-secreting pituitary tumors : comparison between micro- and macroadenomas.

We investigated the growth fraction and cell loss fraction in a large group of patients with Cushing's disease subdivided according to tumor size. Fifty-one patients, 8 males and 43 females, aged 12 through 61 years (mean age 34.6 +/- 1.5 years), were studied. Thirty-six patients had a microadenoma and the remaining 15 a macroadenoma. Immunohistochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. Ki-67 labeling index and apoptosis were counted on separate slides in at least 1000 evaluable cells. Patients with a macroadenoma had a significantly higher value of Ki-67 index (9.3 +/- 2.7%) than patients with microadenoma (2.8 +/- 0.5%; P < 0.002), whereas the apoptotic index was not significantly different in the two groups (1.7 +/- 0.8% in macroadenomas versus 0.8 +/- 0.3% in microadenomas). Our study shows that ACTH-secreting macroadenomas are characterized by a higher cell growth fraction than microadenomas, whereas the cell loss fraction is not different. A high proliferation rate seems to play a major role in determining the progression from small to large pituitary tumors in Cushing's disease.

Adenoma↗
PubMed2000

Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas.

Interleukins and their receptors are expressed intrinsically in the anterior pituitary and regulate hormone production and cell proliferation. It has previously been shown that interleukin-6 (IL-6) regulates hormone secretion in normal pituitary cells and cell lines. Here we examined the effects of IL-6 on propiomelanocortin (POMC) expression and ACTH production in corticotroph adenoma cells in vitro. We found that IL-6 stimulates both ACTH secretion and POMC gene expression in corticotroph adenoma cell cultures. This first demonstration of the stimulatory action of IL-6 on human corticotroph adenoma cell function provides further evidence for a direct action of IL-6 on corticotroph pituitary cells. We have confirmed previous reports of IL-6 production by corticotroph adenoma cells and in addition, demonstrated for the first time that the synthetic glucocorticoid dexamethasone is a potent suppressor of intratumoral IL-6 production. This intratumoral produced IL-6 may be in part responsible, in an autocrine manner, for the stimulation of ACTH synthesis and secretion. Our results suggest that IL-6 might play a role in the pathogenesis of Cushing's disease. However, elevated glucocorticoid levels in patients with Cushing's disease may prevent excessive action of IL-6 on ACTH production and tumor progression of corticotroph adenomas in vivo.

Adenoma↗
PubMed2000

The desmopressin test in the differential diagnosis between Cushing's disease and pseudo-Cushing states.

Differentiating Cushing's disease (CD) from pseudo-Cushing (PC) states may still be difficult in current practice. Because desmopressin (1-deamino-8D-arginine vasopressin, DDAVP), a vasopressin analogue, stimulates ACTH release in patients with CD but not in the majority of normal, obese, and depressed subjects, we investigated its ability to discriminate CD from PC states. One hundred seventy-three subjects (76 with active CD, 30 with PC, 36 with simple obesity, and 31 healthy volunteers) were tested with an iv bolus of 10 microg DDAVP. Sixty-one of these subjects also underwent a control study with saline. DDAVP induced marked ACTH and cortisol rises in CD (P < 0.005 vs. saline, for both ACTH and cortisol) but not in PC. A significant ACTH elevation occurred upon DDAVP administration also in normal and obese subjects, but it was much smaller than that observed in patients with CD (P < 0.0001). A peak absolute ACTH increase (> or =6 pmol/L), after DDAVP, allowed us to recognize 66 of 76 patients with CD and 88 of 97 subjects of the other groups. The same criterion correctly identified 18 of 20 patients with mild CD (24-h urinary free cortisol < or = 690 nmol/day) and 29 of 30 PC, resulting in a diagnostic accuracy of 94%, which was definitely higher than that displayed by urinary free cortisol, overnight 1-mg dexamethasone suppression test, and midnight plasma cortisol. In conclusion, the DDAVP test seems to be a useful adjunctive tool for the evaluation of hypercortisolemic patients chiefly because of its ability to differentiate mild CD from PC states.

Adolescent↗
PubMed2000

Acromegaly associated with a granular cell tumor of the neurohypophysis: a clinical and histological study. Case report.

Acromegaly is usually caused by a growth hormone (GH)-secreting pituitary adenoma, and hypersecretion of GH-releasing hormone (GHRH) from a hypothalamic or neuroendocrine tumor accounts for other cases. The authors report on the unusual association of acromegaly with a granular cell tumor of the neurohypophysis. A 42-year-old woman with a 10-year history of acral enlargement, headache, and menstrual abnormalities was referred to our department for a suspected GH-secreting pituitary adenoma. The patient's basal GH levels were mildly elevated at 4.8 microg/L, were not suppressed in response to an oral glucose tolerance test, and increased paradoxically after administration of thyrotropin-releasing hormone. The patient's insulin-like growth factor-1 (IGF-1) level was elevated at 462 microg/L, whereas a magnetic resonance image of the sella turcica revealed an intra- and suprasellar lesion that was compatible with a diagnosis of pituitary adenoma. A transsphenoidal approach to remove the lesion, which was mainly suprasellar, was successful during a second operative attempt, resulting in the clinical and biochemical regression of the patient's acromegaly. Four months postoperatively, the patient's basal GH level was 0.9 microg/L and her IGF-1 level was 140 microg/L. Histological analysis of the operative specimen demonstrated a granular cell tumor of the neurohypophysis, which when stained proved negative for pituitary hormones and GHRH. This case represents the first reported association between a granular cell tumor of the neurohypophysis and acromegaly. Granular cell tumor of the neurohypophysis could be added to the restricted list of neoplastic causes of acromegaly secondary to hypersecretion of a GH-releasing substance.

Acromegaly↗
PubMed2000

Proliferation index of nonfunctioning pituitary adenomas: correlations with clinical characteristics and long-term follow-up results.

OBJECTIVE: The recurrence of nonfunctioning pituitary adenomas (NFPAs) after surgical removal is common. The aim of our study was to investigate and correlate the growth fraction of NFPAs with clinical characteristics and long-term follow-up results. METHODS: Tumor specimens were obtained from 101 consecutive patients with NFPAs (48 female patients and 53 male patients; mean age, 52.0 +/- 1.5 yr). Specimens were immediately fixed in 10% buffered formalin and then embedded in paraffin. The Ki-67 antigen was assessed by immunocytochemical analysis using the monoclonal antibody MIB-1. The Ki-67 antigen labeling index (LI) was determined by counting a total of at least 1,000 neoplastic nuclei. RESULTS: The mean Ki-67 LI for the 101 patients was 2.4 +/- 0.3% (range, 0-23.0%). Only age at surgery was inversely correlated with the Ki-67 LI; sex, maximal tumor diameter, and invasiveness into the cavernous sinuses did not significantly affect the Ki-67 LI. The mean follow-up period was 39.7 +/- 2.1 months. During follow-up monitoring, 23 patients experienced tumor recurrence, after a mean period of 28.6 +/- 4.8 months. Invasiveness of the tumor on preoperative magnetic resonance imaging scans was the strongest predictor of late tumor recurrence, followed by previous pituitary surgery, younger age, and lack of postoperative radiotherapy. The Ki-67 LI had no independent prognostic value. CONCLUSION: Our study suggests that the clinical characteristics of patients with NFPAs, except for age at surgery, are not correlated with the Ki-67 LI. Moreover, the Ki-67 LI does not seem to provide independent information to identify patients at high risk for tumor recurrence.

Adenoma↗
PubMed1999

Glycosaminoglycans treatment increases IGF-I muscle levels and counteracts motor neuron death: A novel nonanticoagulant action.

The present study shows that sciatic nerve crush in 2-day-old rats causes extensor digitorum longus (EDL) muscle atrophy and motor neuron loss and that treatment with glycosaminoglycans (GAGs) promotes muscle reinnervation, motor neuron survival, and markedly increases insulin-like growth factor-I (IGF-I) content in the denervated muscles. EDL muscle denervation-induced atrophy in saline-treated rats is progressive and reaches the greatest extent at 42 days after birth, which correlates with reduced EDL weight growth. There is also a partial reinnervation as shown by the number of reinnervated EDL muscle fibers (65.4% of control) and by the poor restoration of the indirect isometric twitch tension (62% of control) that is further reduced under tetanic stimulation (34% of control). The number of surviving motor neurons that innervate EDL muscle drops from 55 +/- 3 to 29 +/- 8. In GAGs-treated 42-day-old rats, the effects of neonatal nerve lesioning on EDL muscle atrophy and denervation are successfully reversed, and the isometric twitch tension and the capacity to hold tetanic stimulation are restored to almost control levels. The number of surviving EDL motor neurons is also increased to 43 +/- 4. Treatment with GAGs selectively affects IGF-I content in denervated hindlimb muscles, which is augmented from 7.02 +/- 0.71 ng/mg tissue to 25.72 +/- 0.7 in the EDL and from 3.2 +/- 0.18 to a robust 211 +/- 9.6 in the soleus.

Animals↗
PubMed1999

Glycosaminoglycans boost insulin-like growth factor-I-promoted neuroprotection: blockade of motor neuron death in the wobbler mouse.

Wobbler mice display forelimb weakness, altered paw positioning, reduced running speed, muscle atrophy and motor neuron loss; co-treatment with glycosaminoglycans and insulin-like growth factor-I counteracts the progression of the disease. Reportedly, treatment with glycosaminoglycans or insulin-like growth factor-I slows the early stages of progressive forelimb dysfunction in wobbler mice. Our aim was to study whether the combination of these two drugs would result in greater neuroprotective effects. In a group of wobbler mice, combined treatment with daily s.c. administration of 20 microg/kg insulin-like growth factor-I and 1 mg/kg glycosaminoglycans was begun upon diagnosis at three weeks of age and continued for the next six weeks. This treatment halted motor neuron loss and markedly reduced the decay of forelimb muscle morphometry and function. Moreover, the mouse phenotype itself was strikingly improved. The effect of the combination treatment was significantly higher than that of the single drugs, even at a dosage as high as 1 mg/kg insulin-like growth factor-I. The ability of the insulin-like growth factor-I/glycosaminoglycans pharmacological cocktail to arrest the progression of motor neuron disease in wobbler mice and the safety of the low dose of insulin-like growth factor-I used hold promise that this combination might represent a novel approach for the treatment of motor neuron disease and peripheral neuropathies.

Aging↗
PubMed1999

Surgical management of thyrotropin-secreting pituitary adenomas.

The reported cases of hyperthyroidism due to a TSH-secreting pituitary adenoma have steadily increased in previous years; however, information about the results and long term outcome after pituitary surgery is scanty. Twenty-four patients with a TSH-secreting adenoma underwent pituitary surgery at our department in the last 15 years. Hypersecretion of other pituitary hormones was diagnosed in 7 patients. Three patients were euthyroid at the time of surgery because of previous ablative thyroid therapies. The success rate of surgery strictly depends on the criteria used. Normalization of elevated FT3 and FT4 levels occurred in 17 of the 21 patients with preoperative hyperthyroidism: however, only those with early postoperative undetectable TSH level (12 cases) had no recurrence of disease during follow-up and no residual tumor tissue on postoperative MRI, whereas recurrence of hyperthyroidism occurred in 3 of the 5 patients without postoperative TSH inhibition. All 3 euthyroid patients had a subtotal removal of the tumor, as judged by postoperative MRI. Surgical removal is the therapy of choice of TSH-secreting adenomas, whereas radiotherapy and medical treatment with somatostatin analogues are usually reserved to patients with incomplete tumor removal. A thorough postoperative evaluation is necessary to discriminate between complete and partial remission of disease.

Adenoma↗