RESUMO
Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4%) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6%) had disease control during Temozolomide treatment, while 6 patients (19.4%) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7% (95% CI 29.5-65.9%), while the 2-year disease control duration was 59.1% (95% CI 39.1-79.1%). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9% (95% CI 70.7-97.1%) and 59.6% (95% CI 40.0-79.2%), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenoma/tratamento farmacológico , Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Hipofisárias/tratamento farmacológico , Adenocarcinoma/patologia , Adenoma/patologia , Adulto , Idoso , Dacarbazina/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Hipofisárias/patologia , Prognóstico , Taxa de Sobrevida , TemozolomidaRESUMO
We report on a man with a progressively increasing pituitary mass, as demonstrated by MRI. It produced neurological and ophthalmological symptoms, and, ultimately, hypopituitarism. MRI also showed enlargement of the pituitary stalk and a dural tail phenomenon. An increased titer of antipituitary antibodies (1:16) was detected in the serum. Pituitary biopsy showed autoimmune hypophysitis (AH). Neither methylprednisolone pulse therapy nor a subsequent treatment with azathioprine were successful in recovering pituitary function, or in inducing a significant reduction of the pituitary mass after an initial, transient clinical and neuroradiological improvement. Anterior pituitary function evaluation revealed persistent hypopituitarism. AH is a relatively rare condition, particularly in males, but it represents an emerging entity in the diagnostic management of pituitary masses. This case shows that response to appropriate therapy for hypophysitis may not be very favorable and confirms that diagnostic management of nonsecreting pituitary masses can be a challenge. Clinical, imaging, and laboratory findings are useful for suggesting the diagnosis, but pituitary biopsy may be necessary to confirm it.
Assuntos
Doenças Autoimunes/patologia , Linfócitos/patologia , Doenças da Hipófise/patologia , Adulto , Doenças Autoimunes/tratamento farmacológico , Azatioprina/uso terapêutico , Diagnóstico Diferencial , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Linfócitos/efeitos dos fármacos , Masculino , Metilprednisolona/uso terapêutico , Doenças da Hipófise/tratamento farmacológico , Hipófise/efeitos dos fármacos , Hipófise/patologia , Hipófise/fisiopatologiaRESUMO
Temozolomide (TMZ) is an alkylating chemotherapeutic agent that has recently been used in some cases as a new therapeutic tool for pituitary carcinomas and aggressive pituitary adenomas. In this report, we present the case of effective TMZ treatment in a 42-year-old man with ACTH-secreting carcinoma. The tumor grew progressively over 4 years, from 2.2 to 31.1 cm³, despite three surgical approaches and γ-knife treatment. Ki-67 increased from 2 to 18%. An intradural metastasis at the foramen magnum was detected by MRI after the third operation. Thereafter, four cycles of 5-day TMZ administration (200 mg/m²/day during the first, and 150 mg/m²/day during the following cycles) induced dramatic tumor size reduction (>90%). Clinical conditions improved progressively and, after 17 months from the beginning of TMZ administration, the patient is still alive. The treatment was well tolerated except for a transient thrombocytopenia (grade 4 WHO).
Assuntos
Adenoma/tratamento farmacológico , Dacarbazina/análogos & derivados , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Neoplasias Hipofisárias/tratamento farmacológico , Adenoma/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/uso terapêutico , Humanos , Masculino , Hipersecreção Hipofisária de ACTH/metabolismo , Neoplasias Hipofisárias/metabolismo , Temozolomida , Resultado do TratamentoAssuntos
Adenoma Hipofisário Secretor de ACT/complicações , Acromegalia/complicações , Adenoma/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Hipersecreção Hipofisária de ACTH/complicações , Feminino , HumanosRESUMO
OBJECTIVE: Pituitary adenomas occur rarely in childhood and adolescence. Pituitary adenoma predisposition (PAP) has been recently associated with germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. The aim of the study was to examine the proportion of germline AIP mutations in apparently sporadic paediatric pituitary adenomas. DESIGN: Genomic DNA was analysed for mutations in the AIP gene, by PCR amplification and direct sequencing. PATIENTS: A population-based cohort consisting of 36 apparently sporadic paediatric pituitary adenoma patients, referred to two medical centres in Italy, was included in the study. Patients were either less than 18 years at diagnosis, or showed clinical evidence of adenoma development before the age of 18 years. RESULTS: A heterozygous in-frame deletion Y248del (c.742_744delTAC) was identified in one GH-secreting adenoma patient. Loss of heterozygosity (LOH) analysis of tumour DNA revealed the loss of the wild-type allele. First degree relatives carrying the mutation were clinically unaffected. CONCLUSIONS: While mutations were absent in non-GH-secreting adenoma patients, germline AIP mutations can be found in children and adolescents with GH-secreting tumours, even in the absence of family history. The present study reports the AIP mutation analysis results on patients of a single ethnic origin. Clearly, further studies are needed to improve our knowledge on the role of AIP in paediatric pituitary adenomas.
Assuntos
Adenoma/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hipofisárias/genética , Adenoma/epidemiologia , Adolescente , Adulto , Idade de Início , Sequência de Aminoácidos , Sequência de Bases , Criança , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Mutação em Linhagem Germinativa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/análise , Masculino , Dados de Sequência Molecular , Linhagem , Neoplasias Hipofisárias/epidemiologia , Adulto JovemRESUMO
Recently, Basic and Clinical Neuroscience published an article by Lim et al. (2016) entitled Co-occurence of Pituitary Adenoma with Suprasellar and Olfactory Groove Meningiomas. They claimed it as the first case of co-occurence of these two malignancies. However, to our knowledge, this is not the first case reported in this regard. We reported the same case scenario in a 61-year-old woman referred to our outpatient clinic in 2007. In this commentary, we are going to discuss our reported case and present a brief review over co-occurence of intracranial meningioma with pituitary adenoma.
RESUMO
Lymphocytic infundibulo-neurohypophysitis is a rare disorder. We report the case of a 29 year-old woman with diabetes insipidus and amenorrhea, in whom the magnetic resonance imaging demonstration of a pituitary stalk lesion was intermittent. We suggest that, in patients with endocrine dysfunction and positivity of circulating antipituitary antibodies at high title, magnetic resonance imaging should be repeated after few months, if negative.
Assuntos
Amenorreia/etiologia , Diabetes Insípido/etiologia , Hipófise/diagnóstico por imagem , Neoplasias Hipofisárias/complicações , Adulto , Amenorreia/diagnóstico por imagem , Diabetes Insípido/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Neoplasias Hipofisárias/diagnóstico por imagemRESUMO
Parathyroid carcinoma is a rare malignancy, which usually occurs as a sporadic disease, and less frequently in the setting of genetic syndromes. Despite the association of parathyroid and thyroid disorders being quite common, the coexistence of parathyroid carcinoma and thyroid disease is rare. We reviewed the pertinent literature. The terms "parathyroid carcinoma" and "thyroid disease, hyperthyroidism, thyrotoxicosis, hypothyroidism, thyroid nodule(s), Graves' disease, autonomously functioning thyroid nodules" were used both separately and in reciprocal conjunction to search MEDLINE for articles published from January 2007 to March 2016. The search was prompted by the observation of a never reported association of autonomously functioning thyroid nodules and parathyroid carcinoma. Two hundred and twenty-one parathyroid carcinoma patients have been described during the last 10 years. Neck ultrasonography and parathyroid scintigraphy are the most common instrumental studies used in detecting parathyroid lesions. Serum parathyroid hormone and calcium levels are high in the majority of parathyroid carcinoma patients. Only 21 patients with parathyroid carcinoma and thyroid disorders were found. Our patient is the first casual association between parathyroid carcinoma and autonomously functioning thyroid nodules reported in literature and diagnosed using parathyroid and thyroid scintigraphies. Parathyroid carcinoma is a very rare endocrine tumor and association with thyroid disease is not frequent. Parathyroid carcinoma pre-operative diagnosis is often difficult also because available literature data are not homogenous and there is not a common operative guideline. Our case confirms the role of parathyroid scintigraphy, encouraging the association with thyroid scintigraphy, especially in the presence of (multi)-nodular goiter in order to address the most appropriate surgical management.
Assuntos
Carcinoma/complicações , Neoplasias das Paratireoides/complicações , Doenças da Glândula Tireoide/complicações , Glândula Tireoide/patologia , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Humanos , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/patologia , Cintilografia , Doenças da Glândula Tireoide/diagnóstico por imagem , Doenças da Glândula Tireoide/patologia , Glândula Tireoide/diagnóstico por imagem , UltrassonografiaRESUMO
BACKGROUND: Most patients with growth hormone deficiency (GHD) show high body mass index. Overweight subjects, but GHD patients, were demonstrated to have high left ventricular mass index (LVMi) and abnormal LV geometric remodeling. We sought to study these characteristics in a group of GHD patients, in an attempt to establish the BMI-independent role of GHD. METHODS: Fifty-four patients, 28 F and 26 M, aged 45.9 +/- 13.1, with adult-onset GHD (pituitary adenomas 48.2%, empty sella 27.8%, pituitary inflammation 5.5%, cranio-pharyngioma 3.7%, not identified pathogenesis 14.8%) were enrolled. To minimize any possible interferences of BMI on the aim of this study, the control group included 20 age- and weight-matched healthy subjects. The LV geometry was identified by the relationship between LVMi (cut-off 125 g/m2) and relative wall thickness (cut-off 0.45) at echocardiography. RESULTS: There was no significant between-group difference in resting cardiac morphology and function, nor when considering age-related discrepancy. The majority of patients had normal-low LVM/LVMi, but about one fourth of them showed higher values. These findings correlated to relatively high circulating IGF-1 and systolic blood pressure at rest. The main LV geometric pattern was eccentric hypertrophy in 22% of GHD population (26% of with severe GHD) and in 15% of controls (p = NS). CONCLUSION: Though the lack of significant differences in resting LV morphology and function, about 25% of GHD patients showed high LVMi (consisting of eccentric hypertrophy), not dissimilarly to overweight controls. This finding, which prognostic role is well known in obese and hypertensive patients, is worthy to be investigated in GHD patients through wider controlled trials.
RESUMO
OBJECTIVE: Despite the well-known effects of GH/IGF1 signaling on the thyroid, few data are available on the risk of developing nodular goiter in hypopituitary subjects during GH replacement therapy (GHRT). We aimed to define the effects of GH therapy on thyroid volume (TV) and nodular growth. DESIGN: The records of 96 subjects (47 males and 49 females, median age 48 years) with GH deficit (GHD) were investigated. Seventy also had central hypothyroidism (CH). At the time of our retrospective evaluation, median treatment duration was 5 years. RESULTS: Pre-treatment TV was smaller in GHD patients than in healthy subjects (P=0.030). During GH treatment, TV significantly increased (P=0.016 for the entire group and P=0.014 in euthyroid GHD patients). Before starting GH therapy, 17 patients harbored thyroid nodules. During GH therapy, nodule size increased slightly in seven patients, and new thyroid nodules occurred in nine patients. Among the 79 patients without pre-existing thyroid nodules, 17 developed one or more nodules. There was no difference in the prevalence of CH in GHD patients with or without thyroid nodules (P=0.915; P=0.841, when patients with pre-therapy nodular goiter were excluded), the main predictor for nodule development being serum IGF1 (P=0.038). CONCLUSIONS: GHRT is associated with TV's increase in GHD patients. Thyroid nodules developed in 27% of patients, mainly in relation to pre-therapy IGF1 levels, independently of normal or impaired TSH stimulation.
Assuntos
Hormônio do Crescimento/uso terapêutico , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Glândula Tireoide/crescimento & desenvolvimento , Nódulo da Glândula Tireoide/induzido quimicamente , Adolescente , Adulto , Idoso , Peso Corporal/efeitos dos fármacos , Estudos de Coortes , Feminino , Humanos , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/patologia , Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/sangue , Nódulo da Glândula Tireoide/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: Thyroid hemiagenesis is a rare congenital disorder characterized by the absence of a lobe and/or of isthmus. Studies on the association between thyroid hemiagenesis, Graves' disease and differentiated thyroid cancer are rare. CASE PRESENTATION: We describe the medical and surgical history of a patient in whom a molecular evaluation was performed. A 36-year-old man presented with symptoms and signs of hyperthyroidism of a few months' duration. Hyperthyroidism was confirmed biochemically and anti-TSH-receptor antibodies were positive. Thyroid ultrasonography showed no left lobe and demonstrated a diffused enlargement of the right lobe; an ipoechoic, non-homogenous nodule 15 millimeters in size was identified in the middle part of the lobe. A 99mTc-pertechnetate thyroid scintigraphy (111 MBq) confirmed thyroid hemiagenesis due to the absence of the left lobe. Treatment with methimazole (30 mg/day) was started. As the patient's hyperthyroidism improved, he underwent fine-needle needle aspiration cytology (FNAC) of the right nodule. Cytology was suspicious for malignancy (THY4) and the patient was referred for surgery. Histopathological findings revealed a papillary thyroid carcinoma. The molecular analysis did not show PAX8 or TSHR mutations in the thyroid tissue nor mutations of BRAF, H-RAS, N-RAS or K-RAS genes in the tumor. CONCLUSION: Though thus far studies on the association of thyroid hemiagenesis, Graves' disease and differentiated thyroid cancer are extremely rare, the possibility of the development of thyroid cancer must be taken into account in patients affected by thyroid hemiagenesis and the nodular variant of Graves' disease.
Assuntos
Carcinoma/patologia , Doença de Graves/diagnóstico , Disgenesia da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Carcinoma/epidemiologia , Carcinoma Papilar , Comorbidade , Doença de Graves/epidemiologia , Humanos , Masculino , Câncer Papilífero da Tireoide , Disgenesia da Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologiaRESUMO
PURPOSE: To investigate the association between cardiovascular (CV) risk factors and cumulative CV events in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT). METHODS: 53 non-diabetic adult GHD patients, aged 45.4±14.3years, 31 females, with a median follow up of 140months, were divided into two groups based on the presence (group A) or absence (group B) of systemic hypertension. Tertiles of age and LDL-cholesterol were considered as further potential prognosticators. Cumulative CV event rates were recorded and analyzed by Kaplan-Mayer method. Differences between patients with and without events were also evaluated. RESULTS: Seventeen patients (32%) entered the group A and 36 (68%) the group B. A composite of fatal and non-fatal CV events occurred in 22.6% of patients, 47.1% in group A and 11% in group B (p=0.01), CV deaths in 3 patients (5.7%; annual death rate 0.49%), 2 of whom were in group A. At Kaplan-Mayer analysis, hypertension and age>55years were major prognosticators. The odds ratio was 7.1 (95% CI: 1.74-29.12, p<0.003) and 6.2 (95% CI: 1.54-25.04, p<0.006), respectively. LDL-cholesterol showed borderline statistical significance. Patients with CV events also had high prevalence of left ventricular hypertrophy, left atrial enlargement and subclinical systolic dysfunction. CONCLUSIONS: In this study, outcomes were mainly related to hypertension and age (partially to LDL-cholesterol), confirming that management of GHD patients must be inclusive of treatment of conventional risk factors, being as important as GHRT. Optimal blood pressure control is crucial when a target organ damage is present and in patients older than 55years.
Assuntos
Doenças Cardiovasculares , Hormônio do Crescimento/deficiência , Terapia de Reposição Hormonal , Hipertensão , Hipertrofia Ventricular Esquerda , Hipopituitarismo , Adulto , Fatores Etários , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Feminino , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/métodos , Terapia de Reposição Hormonal/estatística & dados numéricos , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/etiologia , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/etiologia , Hipopituitarismo/sangue , Hipopituitarismo/complicações , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/epidemiologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Prognóstico , Fatores de RiscoRESUMO
INTRODUCTION: Primary growth hormone resistance or growth hormone insensitivity syndrome, also known as Laron syndrome, is a hereditary disease caused by deletions or different types of mutations in the growth hormone receptor gene or by post-receptor defects. This disorder is characterized by a clinical appearance of severe growth hormone deficiency with high levels of circulating growth hormone in contrast to low serum insulin-like growth factor 1 values. CASE PRESENTATION: We report the case of a 15-year-old Caucasian girl who was diagnosed with Silver-Russell syndrome at the age of four and a half years. Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum growth hormone levels were high, and an insulin-like growth factor 1 generation test did not increase insulin-like growth factor 1 levels (baseline insulin-like growth factor 1 levels, 52 µg/L; reference range, 75 µg/L to 365 µg/L; and peak, 76 µg/L and 50 µg/L after 12 and 84 hours, respectively, from baseline). The genetic analysis showed that the patient was homozygous for the R217X mutation in the growth hormone receptor gene, which is characteristic of Laron syndrome. On the basis of these results, the diagnosis of primary growth hormone insensitivity syndrome was made, and recombinant insulin-like growth factor 1 therapy was initiated. The patient's treatment was well tolerated, but unexplained central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age. CONCLUSION: The most important functional tests for the diagnosis of growth hormone insensitivity are the insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective treatment is daily administration of recombinant insulin-like growth factor 1 starting from early childhood. However, these patients show a dramatically impaired final height. In our case, unexplained central hypothyroidism occurred during treatment.