Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma: A Case Report and Literature Review.

We describe a very rare case of nonfunctional pituitary adenoma (NFPA) that exhibited corticotrophic activity after resection and radiotherapy. The possible mechanisms of the transformation from NFPA to Cushing disease (CD) are discussed.A 43-year-old man presented with impaired vision, bilateral frontal headaches, and hyposexuality. He had no symptoms suggestive of hypercortisolism, and 8 am plasma cortisol concentration was 67.88 ng/mL. Brain imaging revealed a 15 × 15 × 21-mm sellar mass suggestive of a macroadenoma. The tumor was resected by transsphenoidal surgery and identified by immunohistochemical analysis as a chromophobic adenoma that did not stain for pituitary hormones. The patient was treated with prednisone and levothyroxine replacement therapy. After a third recurrence, the patient presented with clinical features and physical signs of Cushing syndrome. Plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations were elevated, and there was a loss of circadian rhythms. Inferior petrosal sinus sampling after desmopressin showed the central-peripheral ACTH ratio was greater than 3:1. A repeat transsphenoidal resection was undertaken. Immunohistochemistry revealed ACTH positivity. Three months following surgery, imaging showed little residual tumor, but plasma ACTH remained elevated. He was referred for postoperative Gamma Knife radiotherapy.The immunological activity and biological features of the hormones secreted from a pituitary adenoma vary with time. Because long-term outcomes are unpredictable, postoperative follow-up is essential to detect postoperative transformation from NFPA to CD.

Charlson score as a single pertinent criterion to select candidates for active surveillance among patients with small renal masses.

PURPOSE: The aim of the study was to assess the outcome after nephron-sparing surgery (NSS) of patients with small renal masses (SRMs) who would have been eligible for active surveillance (AS). METHODS: Data were collected retrospectively for 758 patients who underwent NSS over a 5-year period. Outcomes were assessed in two groups of patients who were eligible for AS according to different criteria. Group 1 criteria were as follows: age >75 years, renal mass ≤4 cm, significant comorbidities [Charlson Comorbidity Index (CCI) >2]. Group 2 criteria were as follows: any SRM ≤ 4 cm regardless of age, severe comorbidities with a 10-year mortality risk >50 % (CCI > 4). The two groups were not compared statistically because some patients were included in both. RESULTS: Fifty-five patients (7.3 %) were included in Group 1 and 62 (8.2 %) in Group 2. There was a significant proportion of benign tumours in Group 1 (N = 6; 11 %) and Group 2 (N = 6; 10 %). Six (11 %) positive margins were observed in Group 1 and 8 (13 %) in Group 2. The 2- and 5-year recurrence-free survival rates were 100 and 77.4 %, respectively, in Group 1, and 88.5 and 79.6 % in Group 2. The 2- and 5-year overall survival rates were 100 and 74.7 % in Group 1, and 96.7 and 78.1 % in Group 2. CONCLUSIONS: The majority of patients with SRMs who would have been eligible for AS had no recurrence after initial tumour removal. In these patients, a CCI > 4 appeared to be a pertinent criterion to identify those patients less likely to benefit from immediate surgery.

Clipless and sutureless laparoscopic adrenalectomy carried out with the LigaSure device in 32 patients.

BACKGROUND: Laparoscopic adrenalectomy has become the standard procedure for treating patents with adrenal masses. The purpose of this study was to evaluate the use of the LigaSure vessel closure system during laparoscopic adrenalectomy. METHODS: The LigaSure device was used in 32 patients undergoing laparoscopic adrenalectomy for adrenal masses. Adrenalectomy was carried out without the use of clips or sutures for vessel closure. In 1 patient the adrenal tumor had invaded the ipsilateral kidney, so laparoscopic nephrectomy was also carried out during the same operation. In another patient, a renal cell carcinoma in the left kidney had metastasized to the right adrenal gland. Both the kidney and the contralateral adrenal gland were removed laparoscopically during the same operation. RESULTS: Adrenal masses had a mean greatest diameter of 3.48 cm (range 2 to 11 cm). Mean operative time was 83.2 minutes (range 30 to 190 min). Mean blood loss was 36.2 mL (range 10 to 140 mL). No conversions to open surgery were necessary. No patients experienced major bleeding intraoperatively or postoperatively. Adrenal tumor types included adrenocortical adenoma (16 patients), pheochromocytoma (13 patients), malignant pheochromocytoma (1 patient), chromophobic carcinoma (1 patient), and metastasis from a renal cell carcinoma (1 patient). CONCLUSIONS: For vessel closure during laparoscopic adrenalectomy, the LigaSure device seems to be safe and effective. For patients with conditions such as renal cell carcinoma combined with metastasis to the contralateral adrenal gland, nephrectomy, and contralateral adrenalectomy can be carried out during the same laparoscopic operation.

Gonadotrofinomas: análisis multicéntrico y retrospectivo de 66 pacientes / Gonadotrophinomas: multicenter and retrospective analysis of 66 patients

Objetivo: Analizar la presentación clínica, radiológica, bioquímica y el comportamiento posquirúrgico de una cohorte de pacientes portadores de gonadotrofinomas. Pacientes y Métodos: Se evaluaron pacientes con gonadotrofinomas estudiados en nueve centros endocrinológicos de la ciudad de Bs.As. durante el período 1983 a 2003. El criterio de inclusión fue la inmunohistoquímica (IH) positiva para hormona luteinizante (LH), folículoestimulante (FSH) y/o alfa subunidad (ASU). Los adenomas plurihormonales fueron excluidos. Resultados: Fueron analizados 66 pacientes de 51,8 ± 12,1 (X +/- DS) años (39 varones). Los síntomas mas frecuentemente observados fueron las alteraciones visuales (72,8%), seguidas por el hipogonadismo y las cefaleas. El 10,6% se diagnosticaron en forma incidental. El 98,5% fueron macroadenomas, 56,9% de los cuales correspondieron a un estadio Hardy (EH) 3 y 29,6% a un EH 4. El tiempo de seguimiento fue de 47,8 meses (r: 5-168). El hipogonadismo definido bioquímicamente se presentó en el 82,4% de los pacientes. En su mayoría presentaban niveles bajos o inapropiadamente normales de gonadotrofinas, pero 4 mujeres y 3 varones presentaron niveles séricos elevados y disociados de FSH y LH. La hiperprolactinemia por desconexión fue observada en 45,2% de la población (X: 65.6 ng/ml r: 30-172). El hipopituitarismo se detectó en 25,7% de los casos. La cirugía fue transeptoesfenoidal (TSE) en 80%; una segunda operación fue realizada en el 28% de la población. La IH fue positiva por orden de frecuencia para LH, FSH y ASU o las 3 combinaciones. La evolución posquirúrgica evidenció mejoría en el campo visual (CV) en el 41%. La presencia de restos tumorales y/o recidiva fue del 84%. Se indicó radioterapia en 37% y la sustitución hormonal fue necesaria en el 65% de los pacientes.

The aim of our study was to describe the clinical-biochemical and radiologic presentation and the post surgery outcome in a cohort of patients with gonadotrophinomas. Patients were selected from nine Endocrinology Units of the city of Buenos Aires from 1983 at 2003. The inclusion criteria was defined by nonfunctinoning pituitary adenomas with positive innmunohistochemical (IH) for luteinizing hormone (LH), follicle-stimulating hormone (FSH) and/or alpha subunit (ASU). Innmunohistochemically plurihormonal adenomas were excluded. Sixty six patients were analyzed, aged 51,8 ± 12,1 (X +/- DS) years; (39 men). More prevalent symptoms were visual alterations (72,8%), hypogonadism and headaches. Eleven percent was diagnosed as incidentalomas. Ninety eight percent were macroadenomas, 56,9% was Hardy stage (HS) 3 and 29,6% was HS 4. The patients were followed up for 47,8 months (r: 5-168). Hypogonadism was biochemically found in 82,4%. The majority showed low or inappropriately normal levels of gonadotrophins except for 4 women and 3 men that had high and dissociated levels. Hyperprolactinemia was observed in 45,2% and was interpreted as an interference with normal dopamine inhibition of prolactin secretion (X+/-DS: 65.6+/- ng/ml, r: 30-172). Hypopituitarism was found in 25,7% of the patients. Transsphenoidal surgery was carried out in 80% and in 28% a second surgery was needed. The IH was positive for LH, FSH and ASU in this order of frequency or its combinations. Tumor persistency and/or recurrency were found in 84% of the patients. Forty one percent showed improvement of visual defects. Radiotherapy was indicated in 37% and hormonal replacement was needed in 65% of the patients.

[Differential diagnosis in visual field defects of glaucoma patients]. / Differenzialdiagnose bei glaukomatösen Gesichtsfeldausfällen.

In both cases optic disc neuropathy with perimetry defects and loss of vision is caused by a cerebral tumour. The progression of optic damage was stopped by resection of the tumor in both patients. We recommend the performance of a radiological examination in patients with visual field defects if the intraocular pressure is normal and thus glaucoma may not be the cause of the defects.

[A case of GH and TSH secreting pituitary macroadenoma]. / Przypadek makrogruczolaka przysadki wydzielacego hormon wzrostu i tyreotropin.

A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).

[The strange case of a patient affected by acromegaly with osteoporomalacia without hypogonadism]. / Lo strano caso di un paziente affetto da acromegalia con osteoporomalacia senza ipogonadismo.

Acromegaly is a rare disease that, in the majority of cases, is due to the presence of a benign growth hormone (GH)-producing tumor of the pituitary. Growth hormone has profound effects on linear bone growth, bone metabolism, and bone mass. In acromegaly, the skeletal effects of chronic GH excess have been mainly addressed by evaluating bone mineral density (BMD). Most data were obtained in patients with active acromegaly, and apparently high or normal BMD was observed in the absence of hypogonadism. The Autors describe a case of patient affected by acromegaly without hypogonadism with serious osteoporosis and biological signs of osteomalacia.

Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness.

BACKGROUND: Prognostic markers for renal cell carcinoma (RCC), such as patient symptoms, tumor stage, tumor size, and tumor grade, are useful for determining appropriate follow-up and selecting patients for adjuvant therapy. Histologic coagulative tumor necrosis, also reported to be a prognostic marker for RCC, has not previously been extensively described or investigated. Hence, the objective of the current study was to characterize tumor necrosis as a prognostic feature of RCC. METHODS: The authors of the current study identified 3009 patients treated surgically for RCC between 1970 and 2002 from the Mayo Clinic Nephrectomy Registry (Rochester, MN). Associations of tumor necrosis with clinical, laboratory, and pathologic features were examined with chi-square, Fisher exact test, and Wilcoxon rank-sum tests. Cancer-specific survival was estimated with the Kaplan-Meier method, and associations with outcome were assessed with Cox proportional hazard models. RESULTS: Tumor necrosis was present in 690 of 2445 (28%) clear cell, 196 of 421 (47%) papillary, and 28 of 143 (20%) chromophobe RCCs. The risk ratio for death from RCC in patients with necrotic compared with non-necrotic tumors was 5.27 (95% confidence interval [CI]: 4.56-6.09; P < 0.001) for clear cell, 4.20 (CI: 1.65-10.68; P < 0.001) for chromophobe, and 1.49 (CI: 0.81-2.74; P = 0.199) for papillary RCC. The survival difference for clear cell RCC persisted even after multivariate adjustment for tumor stage, size, and grade (risk ratio 1.90; P < 0.001). CONCLUSIONS: Histologic coagulative tumor necrosis is an independent predictor of outcome for clear cell and chromophobe RCC, and it should be routinely reported and used in clinical assessment.

Comparison of presentation and outcome for patients 18 to 40 and 60 to 70 years old with solid renal masses.

PURPOSE: We compared histological subtype, pathological features and outcome of patients with solid renal masses who were 18 to 40 years old vs patients who were 60 to 70 years old. MATERIALS AND METHODS: We conducted a retrospective review of the Mayo Clinic Nephrectomy Registry from 1970 to 2000, and identified 124 patients 18 to 40 years old and 1,067 patients 60 to 70 years old available for analysis. RESULTS: There was no significant difference in the incidence of benign solid renal masses between patients 18 to 40 years old and those 60 to 70 years old (13.7% vs 10.2%). Among patients with renal cell carcinoma (RCC), younger patients were more likely to have chromophobe RCC (13.1% vs 3.6%) and less likely to have clear cell RCC (70.1% vs 81.5%) than older patients. Among patients with clear cell RCC, younger patients were more likely to have stage pT2b or lower tumors (82.7% vs 69.9%) and a higher incidence of cystic clear cell RCC (10.7% vs 2.2%) than older patients. Younger patients had an improved cancer specific survival compared with older patients but this difference was not statistically significant (risk ratio 0.71, p =0.127). CONCLUSIONS: We found that patients 18 to 40 years old were more likely to have chromophobe and less likely to have clear cell RCC compared with patients 60 to 70 years old. We did not identify a higher incidence of papillary RCC in younger patients. Patients with clear cell RCC 18 to 40 years old had a higher incidence of low stage and cystic tumors compared with patients 60 to 70 years old, features which have been shown to have a favorable prognosis. These factors likely contributed to improved cancer specific survival for younger patients.

[Mental changes in course of pituitary gland tumour--a case study]. / Zmiany psychiczne u chorego z guzem przysadki mózgowej--opis przypadku.

The aim of this paper is to present a case of a 59-year old patient diagnosed with a pituitary gland tumour. The psychiatric examination at the day of admission to the clinic suggested the manic episode was based upon the disseminated organic brain lesion. The patient presented mood elevation, carefree joviality, excitement, loss of social inhibition, inability to sustain attention. In course of the clinical observation and diagnostic progress the pituitary gland tumour was revealed and neurosurgical treatment was applied. The psychopathological course of the disorder was not typical for the established location. The psychopathological syndrome that was presented by the patient gave the global clinical impression of frontal and temporal lobes' dysfunction. This case report supports the present neurobiological opinions criticizing the direct relation of the location to the function within the central nervous system.

[Hypophyseal ACTH-cell carcinoma after several surgical interventions and radiotherapy]. / Hypophysäres ACTH-Zellkarzinom nach mehreren chirurgischen Eingriffen und Strahlentherapie.

HISTORY AND ADMISSION FINDINGS: A 56-year-old woman was admitted to our hospital with headache, especially on the left temporal side, dizziness and exercise intolerance. She had been operated three times and radiotherapy once because of pituitary adenoma with intermittend hypercortisolism. The clinical examination was without abnormal findings apart from left temporal pain on pressure on the top of the skull. INVESTIGATIONS: Blood tests were entirely normal. At cranial magnet resonance imaging (cMRI) a left temporal tumor of 10 mm diameter was diagnosed. TREATMENT AND COURSE: The first histological study of the excized lesion could not clarify the diagnosis completely. Because of a local recurrent tumor of 20 mm, a second operation was necessary two months later. Due to structural and immunohistological similarities this tumor was identified as a metastasis of a pituitary ACTH-cell carcinoma. The patient was given adjuvant stereotactic radiotherapy. Two years after the treatment, no tumor recurrence was seen by cMRI. CONCLUSION: Carcinomas of the pituitary are very rare. They can be diagnosed only by their metastases. The pathogenesis is still unclear. It is debatable, whether surgery and/or X-ray therapy in the past may influence tumor development.

Synchronous subarachnoid drop metastases from a pituitary adenoma with multiple recurrences. Case report.

The authors report the case of a 49-year-old man with synchronous drop metastases from a multiply recurrent somatotroph pituitary adenoma. The metastatic lesions were found in the subarachnoid space of the cauda equina and foramen magnum 18 years after the initial diagnosis of the disease. Five transsphenoidal resections had previously failed to cure the sellar tumor. Two of these, performed 4 and 5 years before the patient's current presentation, had been complicated by cerebrospinal fluid rhinorrhea that necessitated lumbar drainage. Resections of the two subarachnoid lesions, separated by 14 months, removed pathologically aggressive pituitary adenomas. There were no signs of local recurrence or subarachnoid dissemination of disease during the postoperative follow-up periods, which lasted 18 and 4 months, respectively. Previous cases of subarachnoid spread of a pituitary adenoma have been associated with multiple intracranial metastases, multiple intraspinal metastases, or widely disseminated disease. This case demonstrates that subarachnoid metastasis of a pituitary adenoma, particularly when it follows multiple operations, is not invariably widely disseminated or associated with a very poor prognosis.

Sarcomatoid renal cell carcinoma with foci of chromophobe carcinoma.

Both chromophobe carcinoma and sarcomatoid carcinoma of the kidney are rare. The former is characterized by a relatively good prognosis, while the latter is a highly aggressive tumor. Coexistence of the two components in one renal tumor, which has been reported only rarely, is therefore paradoxical. Both sarcomatoid and chromophobe renal carcinoma were diagnosed in a 52-year-old woman following nephrectomy and resection of metastases in the right lobe of the liver. She died of the disease two months after the first operation; only the sarcomatoid component of her tumor was seen in the liver metastasis and the recurrent carcinoma. Differences in phenotype, immunophenotype and DNA-ploidy patterns of the two components are reported. The intensive p53 staining observed only in the sarcomatoid area supports the role of the TP53 gene in the transformation of chromophobe renal carcinoma to sarcomatoid carcinoma.

Subclinical Cushing's disease accompanied by malignant hypertension and diabetes mellitus.

A 53-year-old woman was admitted because of hypertension and diabetes mellitus. Elevated diastolic blood pressure, hypertensive retinopathy and renal dysfunction indicated malignant hypertension. Adrenocorticotropic hormone (ACTH) and cortisol levels were high although there were no Cushingoid features. One mg dexamethasone administration decreased neither ACTH nor cortisol levels. Brain magnetic resonance imaging revealed a left pituitary tumor (7 mm x 6 mm). Upon removal, the tumor showed positive ACTH staining by immnohistochemistry, and was diagnosed as pituitary ACTH-secreting adenoma (Cushing's disease). Her blood pressure, renal function, blood glucose and hormone levels subsequently improved. Malignant hypertension and deteriorated diabetes mellitus may have been due to subclinical Cushing's disease.

Simultaneous treatment of a pituitary adenoma and an internal carotid artery aneurysm through a supraorbital keyhole approach.

We describe a case in which an incidental left carotid aneurysm was found during the preoperative evaluation of a pituitary adenoma. After magnetic resonance imaging (MRI) and angiography delineated their characteristics, we chose to treat both lesions simultaneously through a left supraorbital keyhole approach. The aneurysm clipping was followed by intracapsular resection of the tumor that was identified later as a non-secretory adenoma. The postoperative course was uneventful. This case shows that in carefully selected patients it is possible to treat successfully concurrent conditions through a minimally invasive approach, with the well known advantages of low morbidity and a short hospital stay.

Prognostic features of pathologic stage T1 renal cell carcinoma after radical nephrectomy.

OBJECTIVES: To assess the effect of renal cell carcinoma (RCC) subtype, tumor size, and Fuhrman grade on clinical outcome in patients with pathologic T1 (pT1) RCC treated with radical nephrectomy. METHODS: Between 1970 and 1998, 840 patients underwent radical nephrectomy for pT1 RCC. Tumors were subtyped and graded. Univariate and multivariate Cox proportional hazards models were fitted to assess the features associated with metastasis-free survival (MFS) and cancer-specific survival (CSS). We identified a range of tumor sizes of clear cell RCC in which a transition occurred from low to high risk. Cox proportional hazards models were then fitted by using size cutoffs. RESULTS: The mean follow-up (+/- SD) was 9.4 +/- 6.6 years among the patients alive at latest follow-up. At 10 years, the CSS and MFS for clear cell RCC (n = 682) were 89.1% and 88.6%, respectively; for papillary RCC (n = 122), they were 95.5% and 93.8%; and for chromophobe RCC (n = 33), they were both 100%. The differences in CSS (P = 0.013) and MFS (P = 0.023) between clear cell RCC and the other subtypes were statistically significant. For clear cell RCC, tumor size and Fuhrman grade were independently associated with CSS and MFS (P <0.001). A transition in risk occurred for tumor sizes between 4.5 and 5.0 cm, and the tumor size cutoff of 5.0 cm had the highest concordance index for predicting CSS and MFS. CONCLUSIONS: RCC subtype is a strong independent prognostic variable for patients with pT1 RCC treated with radical nephrectomy. For clear cell RCC, Fuhrman grade and tumor size are independently associated with CSS and MFS.

Atypical tentorial meningioma 30 years after radiotherapy for a pituitary adenoma.

Although the human central nervous system used to be considered relatively resistant to the carcinogenic action of ionizing radiation, several lines of evidence now document a high incidence of secondary tumors in irradiated patients. The numerous reports of radiation-induced cerebral meningiomas generally distinguish those induced by high-dose radiation from those induced by low-dose radiation. We describe the case of patient who underwent subtotal resection of a chromophobe pituitary adenoma at the age of 18 years, who was successively treated by conventional fractionated radiotherapy with gamma rays emitted by a source of 60Co until a total dose of 41 Gy. Over the next 30 years the patient experienced all the known late effects of radiation, including panhypopituitarism, cranial-nerve deficits (II, III and VI), massive radiation necrosis involving the left cerebral hemisphere and causing right hemiparesis and aphasia and, ultimately, an atypical tentorial meningioma with early recurrence after total resection.

[Nonfunctional pituitary adenoma and pulmonary sarcoidosis--a case report]. / Wspólistnienie nieczynnego hormonalnie gruczolaka przysadki i sarkoidozy--opis przypadku.

A case of the coexistence of nonfunctional pituitary adenoma and pulmonary sarcoidosis is reported. 39 years old female presented symptoms of a pituitary-gonadal axis insufficiency, visual deficit and dizziness. CT pituitary imaging revealed large intra and extrasellar tumour. Histological examination of the tissue obtained at transsphenoidal surgery showed chromophobic adenoma. Hypopituitarism and transient diabetes insipidus occurred after the surgery. The adequate replacement therapy with hydrocortisone and sex steroids was introduced. At the time of the pituitary tumour diagnosis enlargement of pulmonary lymph nodes was also observed. Based on histological examination of tracheal and bronchial epithelium specimens obtained during bronchoscopy the diagnosis of pulmonary sarcoidosis was made. No other systemic sarcoidosis localisation was confirmed. Histological re-evaluation of adenoma showed no noncaseating granuloma tissue. The overlapping symptoms of pituitary adenoma and other intrasellar masses may result in diagnostic difficulties, particularly in the presence of systemic disorders in which this gland may be involved.

[Conservative surgery of renal carcinoma in a case of synchronic bilateral involvement, with large size tumors and different histological type]. / Cirugía conservadora del carcinoma renal en un caso de afectación bilateral sincrónica, con tumoraciones de gran tamaño y extirpe histológica diferente.

OBJECTIVE: To report a case of a large, bilateral, synchronous renal tumor. METHODS/RESULTS: Treatment by conservative surgery achieved good results. The histological analysis showed two different carcinomas. The most most important steps of the surgical procedure are described. Renal preservation in patients with malignant tumors is discussed. CONCLUSIONS: The case described herein is rare since the tumors were synchronous and of uncommon histological type (one of the tumors was a chromophobic carcinoma). Despite the large size of the tumors, they were successfully managed by conservative surgery.