ADENOMA SECRETOR DE GH DE POTENCIAL MALIGNO INCIERTO
GH secreting adenoma of uncertain malignant potential
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Hospital de León." "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "GH secreting adenoma of uncertain malignant potential" ] ] "textoCompleto" => "<p class="elsevierStylePara"> Pituitary adenomas are usually benign but there are some isolated cases of pituitary carcinomas described in the literature. More than 50% of pituitary carcinomas are non-functioning but PRL, ACTH, GH and TSH secreting carcinomas have also been described. Regarding somatotroph carcinomas, 11 patients have been reported since the beginning of the century<span class="elsevierStyleSup"> 1-9</span>. Metastasis in central nervous system occurred in all the cases except in the fourth. In other four cases, metastasis were localised in lymph nodes of neck<span class="elsevierStyleSup">1,7-9</span>. We describe here a patient with refractory acromegaly after four craniotomies, two radiotherapy sessions and apparently biochemical cure of GH excess without any medical treatment. </p><p class="elsevierStylePara"><span class="elsevierStyleBold">CASE REPORT</span></p><p class="elsevierStylePara"> The patient is a 42 years old man first seen in 1994 after two surgical procedures and one irradiation. He was studied in another medical center in 1990 to investigate the cause of a confusional state and the diagnosis of acromegaly due to a GH secreting pituitary macroadenoma was made (fig. 1). He was operated in 1990 by subfrontal way. The postoperative magnetic resonance imaging (MRI) showed tumoral persistence because of the patient was irradiated with 50 Gy. In 1993, the patient complaint of loss of vision in the left eye and the MRI showed a very large tumour with suprasellar invasion and hydrocephalus. Another adenomectomy by subfrontal way was then necessary to partially remove the tumour. </p><p class="elsevierStylePara"><img src="1741.GIF" width="229" height="350"></img></p><p class="elsevierStylePara"> In 1994, at the moment of the first visit to the hospital, the hormonal values of the patient were GH 3.7 µ g/l and IGF-I 420 ng/ml (normal range < 400 ng/ml) with abnormal suppression of GH (GH > 2 µ g/l) following an oral glucose load. In August 1994, the patient developed neurological alterations as loss of vision in the left eye, disturbance of intellectual function and somnolence. It was necessary another surgery because the MRI showed an important tumoral regrowth. Three months after the craniotomy, MRI showed an important cyst involving tumoral nodes in the left hemisphere and the patient underwent stereotaxic radiosurgery with a total dose of 1,000 cGy (fig. 2). Endocrine investigations revealed GH levels of 6 µ g/l and IGF-I 708 ng/ml. The patient did not present GH paradoxical responses after infusion of TRH (250 µ g i.v.) or GnRH (100 µ g i.v.). Treatment with somatostatin analogues was then initiated (lanreotide 0.03 g i.m./28 days) and after 3 months of therapy, GH and IGF-I levels decreased to 2 µ g/l and to 325 ng/ml respectively, and normal suppression of GH after an oral glucose load was observed. The patient continued with the same treatment but in the sixth month of therapy an unexpected recurrence was observed. In fact, GH levels raised to 14 µ g/l with IGF-I to 925 ng/ml and the patient developed neurological alterations as progressive weakness in the lower limbs and abnormal gait. MRI demonstrated a large tumoral mass in the anterolateral part of the frontal lobe and an enlargement of the posterior cyst (fig. 3) and in October 1996, the patient underwent his forth surgical procedure by subfrontal way. The excision was nearly complete except for tumoral tissue around cavernous sinus. Following surgery, MRI scan of the brain revealed 4 tumoral deposits. Three of them localised in the frontal lobe and the other one, in the cavernous sinus. Then, the patient received near 1,000 cGy in each deposit by stereotaxic radiosurgery. Nowadays, the patient follows periodic controls in order to detect another recurrence. Endocrine investigations have shown normal levels of GH and IGF-I (0.5 µ g/l and 314 ng/ml, respectively) so the patient does not receive any medical treatment. Last MRI, performed after 1 year of the last adenomectomy, shows tumoral nodes of approximately 1 cm of diameter around the cyst in the left frontal lobe. He has also undergone a <span class="elsevierStyleSup">99</span>Tc octreotide scintiscanning that has not shown evidence of somatostatin receptors. Gastrointestinal tract examination, chest X-ray film, gallium scintigram and abdominal ultrasonography have not revealed any metastatic lesion. </p><p class="elsevierStylePara"><img src="1742.GIF" width="229" height="377"></img><img src="1743.GIF" width="229" height="377"></img></p><p class="elsevierStylePara"> Histological studies of the resected specimen from the last three craniotomies were similar, showing high pleomorphism in cytoplasms and in nucleus. The tumour was poorly vascularizated with diffuse arrangement of well-defined polygonal cells. Cellular cytoplasms were large with a high number of acidophilic granules. Mitotic activity was increased in some areas of the tumoral pieces. There were not signs of vascular invasion. No cells were obtained from the liquid in the cyst. </p><p class="elsevierStylePara"> In all the tumoral pieces, immunocytochemistry staining demonstrated presence of positive cells for GH and absence for the rest of pituitary hormones. As it has been proposed that indices of cellular proliferation be increased in invasive adenomas an often high in carcinomas<span class="elsevierStyleSup">10</span>, the expression of Ki67 antigen was evaluated. This antigen is a proliferation marker selectively expressed during G1, S1, G2 and M phases of the cell cycle. The presence of p53 tumour suppressor gene was also studied because is thought to play a role in the development or evolution of adenohypophysial neoplasms. In 1993, there were not positive cells for these markers but surgical pieces of 1995 and 1996 showed positivity for both of them. In 1995, the proliferating cell nuclear Ki67 antigen was present in 2.0% of cells and p53 in 1.6% of cells. In 1996, Ki67 was present in 1.5% of cells and p53 in 1.0% of cells. </p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara"> Earlier literature considered locally aggressive tumours to be malignant; however, current classification describes these lesions as "invasive adenomas". Pituitary carcinomas are distinctly uncommon and diagnosis is normally made when metastasis appear in a patient with a pituitary adenoma but the period between the onset of the primary lesion and distant metastasis tends to be long (4 to 19 years)<span class="elsevierStyleSup">3,10</span>. Therefore, defining the difference between invasive pituitary adenoma and pituitary carcinoma only when metastasis appears could be a matter of time. In fact, the clinical course of most reported cases of pituitary adenocarcinoma has been one of progressive intracranial expansion of a pituitary neoplasm with metastatic lesions discovered post-mortem<span class="elsevierStyleSup">5</span>. As in the case described before, in all pituitary carcinomas producing GH, the patients had previously diagnosed pituitary tumours with features of acromegaly. All primary tumours were large, with suprasellar extension, requiring a transcranial surgical approach. Primary resection was incomplete in all cases, with residual tissue remaining in the cavernous sinus and/or adherent to the frontal lobes. As a result, all patients also received treatment with radiotherapy. In spite of the diagnosis of malignancy in pituitary lesions being usually made when metastasis appear, the aggressive behaviour of the pituitary lesion in this patient allows to suspect and adenoma to carcinoma transformation. In fact, 3 tumoral recurrences despite surgery, radiotherapy and medical treatment are unusual in other GH pituitary adenomas. With regard to hormonal activity, GH levels seemed to be under-control after three months of therapy with somatostatin analogues but an unexpected recurrence induced an important raise of the hormonal levels. This agrees with previous observations that tumour suppression may not ocurr with somatostatin analogues. Moreover, this patient presented a negative <span class="elsevierStyleSup">99</span>Tc octreotide scintiscanning after the last craniotomy. </p><p class="elsevierStylePara"> Histopathological criteria are also unhelpful in determining the malignant potential of pituitary tumours because pleomorphism, abundant nuclei and increased mitotic activity are commonly seen in benign pituitary adenomas and some tumours with metastasis have very regular histology. However, it has been hypothesed that the presence of proliferation indices as well as p53 immunoreactivity suggests the diagnosis of pituitary carcinoma and appears to be of prognostic significance<span class="elsevierStyleSup">11</span>. In fact, an alternative definition of pituitary carcinoma based on increased mitotic activity, high proliferation indices and the presence of p53 staining has been proposed<span class="elsevierStyleSup">10</span>. In the case described before, neither Ki67 nor p53 were expressed in 1993 but became present in subsequent surgical pieces. A clear correlation between positivity of these indices and tumoral malignancy has not been demonstrated but the presence of these indices can indicate a more aggressive behaviour of the tumour. </p><p class="elsevierStylePara"> The definition of pituitary carcinoma requires the demostration of metastasis; however the presence of an aggressive behaviour as in the case described before suggests the diagnosis and appear to be of prognostic significance. In order to confirm this hypothesis it would be necessary to survey closely the clinical evolution of this patient and other cases with similar behaviour. </p>" "tienePdf" => false "PalabrasClave" => array:2 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec204452" "palabras" => array:3 [ 0 => "Acromegalia" 1 => "Adenoma hipofisario" 2 => "Carcinoma hipofisario" ] ] ] "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec204453" "palabras" => array:3 [ 0 => "Acromegaly" 1 => "Pituitary adenona" 2 => "Pituitary carcinoma" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "Los carcinomas hipofisarios son poco frecuentes, por lo que su definición, su diagnóstico, su tratamiento y su pronóstico suscitan controversia. De hecho, en los adenomas hipofisarios, el período entre la aparición de la primera lesión y la presencia de metástasis suele ser largo. Por ello, la distinción entre adenoma y carcinoma hipofisario sólo por la existencia de metástasis puede ser un problema de tiempo. Se describe a continuación el caso de un paciente de 42 años con acromegalia persistente tras cuatro craneotomías, dos tratamientos de raditoerapia y aparente normalización bioquímica del exceso de GH." ] "en" => array:1 [ "resumen" => "Pituitary carcinomas are rare adenohypophysial neoplasms, the definition, diagnosis, therapy and prognosis of which are controversial. In fact, in pituitary adenomas, the period between the onset of the primary lesion and distant metastasis tend to be long. Then, defining the difference between invasive pituitary tumour and pituitary carcinoma only when metastasis appear could be a matter of time. We describe here, a 42 year-old patient with refratory acromegaly after four craniotomies, two radiotherapy sessions and apparently biochemical cure of GH excess." ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Intracranial dissemination of pituitary adenomas." 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| 2023 July | 8 | 3 | 11 |
| 2023 June | 10 | 1 | 11 |
| 2023 May | 8 | 4 | 12 |
| 2023 April | 2 | 0 | 2 |
| 2023 March | 10 | 1 | 11 |
| 2023 February | 33 | 0 | 33 |
| 2023 January | 17 | 0 | 17 |
| 2022 December | 21 | 0 | 21 |
| 2022 November | 21 | 0 | 21 |
| 2022 October | 14 | 0 | 14 |
| 2022 September | 14 | 3 | 17 |
| 2022 August | 14 | 1 | 15 |
| 2022 July | 17 | 1 | 18 |
| 2022 June | 18 | 1 | 19 |
| 2022 May | 30 | 1 | 31 |
| 2022 April | 35 | 0 | 35 |
| 2022 March | 23 | 0 | 23 |
| 2022 February | 8 | 0 | 8 |
| 2022 January | 11 | 0 | 11 |
| 2021 December | 31 | 1 | 32 |
| 2021 November | 10 | 0 | 10 |
| 2021 October | 10 | 0 | 10 |
| 2021 September | 11 | 2 | 13 |
| 2021 August | 11 | 0 | 11 |
| 2021 July | 7 | 3 | 10 |
| 2021 June | 17 | 1 | 18 |
| 2021 May | 13 | 6 | 19 |
| 2021 April | 57 | 20 | 77 |
| 2021 March | 17 | 6 | 23 |
| 2021 February | 6 | 1 | 7 |
| 2021 January | 13 | 0 | 13 |
| 2020 December | 15 | 0 | 15 |
| 2020 November | 6 | 0 | 6 |
| 2020 October | 11 | 3 | 14 |
| 2020 September | 9 | 0 | 9 |
| 2020 August | 10 | 0 | 10 |
| 2020 July | 15 | 1 | 16 |
| 2020 June | 8 | 2 | 10 |
| 2020 May | 8 | 0 | 8 |
| 2020 April | 11 | 1 | 12 |
| 2020 March | 21 | 0 | 21 |
| 2020 February | 22 | 0 | 22 |
| 2020 January | 21 | 0 | 21 |
| 2019 December | 24 | 0 | 24 |
| 2019 November | 8 | 0 | 8 |
| 2019 October | 13 | 0 | 13 |
| 2019 September | 19 | 0 | 19 |
| 2019 August | 7 | 0 | 7 |
| 2019 July | 19 | 0 | 19 |
| 2019 June | 28 | 3 | 31 |
| 2019 May | 93 | 0 | 93 |
| 2019 April | 30 | 1 | 31 |
| 2019 March | 14 | 1 | 15 |
| 2019 February | 11 | 1 | 12 |
| 2019 January | 12 | 1 | 13 |
| 2018 December | 16 | 6 | 22 |
| 2018 November | 10 | 8 | 18 |
| 2018 October | 19 | 2 | 21 |
| 2018 September | 4 | 0 | 4 |
| 2018 August | 5 | 0 | 5 |
| 2018 July | 5 | 0 | 5 |
| 2018 June | 4 | 0 | 4 |
| 2018 May | 1 | 0 | 1 |
| 2018 April | 9 | 0 | 9 |
| 2018 March | 1 | 0 | 1 |
| 2018 February | 2 | 0 | 2 |
| 2018 January | 5 | 0 | 5 |
| 2017 December | 7 | 0 | 7 |
| 2017 November | 5 | 0 | 5 |
| 2017 October | 10 | 0 | 10 |
| 2017 September | 13 | 0 | 13 |
| 2017 August | 6 | 0 | 6 |
| 2017 July | 3 | 17 | 20 |
| 2017 June | 3 | 14 | 17 |
| 2017 May | 12 | 18 | 30 |
| 2017 April | 4 | 23 | 27 |
| 2017 March | 14 | 0 | 14 |
| 2017 February | 26 | 0 | 26 |
| 2017 January | 9 | 0 | 9 |
| 2016 December | 16 | 2 | 18 |
| 2016 November | 13 | 1 | 14 |
| 2016 October | 24 | 0 | 24 |
| 2016 September | 10 | 0 | 10 |
| 2016 August | 9 | 1 | 10 |
| 2016 July | 16 | 6 | 22 |
| 2016 June | 19 | 0 | 19 |
| 2016 May | 15 | 2 | 17 |
| 2016 April | 18 | 0 | 18 |
| 2016 March | 18 | 1 | 19 |
| 2016 February | 17 | 1 | 18 |
| 2016 January | 10 | 0 | 10 |
| 2015 December | 12 | 0 | 12 |
| 2015 November | 26 | 0 | 26 |
| 2015 October | 43 | 0 | 43 |
| 2015 September | 32 | 0 | 32 |
| 2015 August | 14 | 0 | 14 |
| 2015 July | 11 | 0 | 11 |
| 2015 June | 7 | 0 | 7 |
| 2015 May | 10 | 0 | 10 |
| 2015 April | 25 | 0 | 25 |
| 2015 March | 16 | 0 | 16 |
| 2015 February | 14 | 0 | 14 |
| 2015 January | 21 | 0 | 21 |
| 2014 December | 12 | 0 | 12 |
| 2014 November | 10 | 0 | 10 |
| 2014 October | 12 | 0 | 12 |
| 2014 September | 3 | 0 | 3 |
| 2014 August | 5 | 0 | 5 |
| 2014 July | 6 | 0 | 6 |
| 2014 June | 3 | 0 | 3 |
| 2014 May | 2 | 0 | 2 |
| 2014 April | 26 | 0 | 26 |
| 2014 March | 2 | 0 | 2 |
| 2014 February | 4 | 0 | 4 |
| 2014 January | 5 | 0 | 5 |
| 2013 December | 3 | 0 | 3 |
| 2013 November | 7 | 0 | 7 |
| 2013 October | 5 | 0 | 5 |
| 2013 September | 9 | 0 | 9 |
| 2013 August | 8 | 0 | 8 |
Show all
