RESUMO
OBJECTIVE: There are few published comparisons between paediatric and adult-onset Cushing's disease (CD). We compare the epidemiology, diagnostic features and cure rate by transsphenoidal surgery (TSS) in these groups. DESIGN: Retrospective review of patient databases in a single university hospital centre. PATIENTS: Totally, 41 paediatric (mean age 12.3 ± 3.5 years; range 5.7-17.8) and 183 adult (mean age 40 ± 13 years; range 18.0-95.0) patients with CD were investigated. RESULTS: Paediatric CD was characterised by male (63%) and adult CD by a female predominance (79%, P<0.0001). There were small but significant differences in clinical presentation. Biochemical features of CD were comparable except the serum cortisol increase during a CRH test: mean change (105%, n=39) in paediatric and (54%, n=123) in adult subjects (P<0.0001). Macroadenomas were more common in adult (15%, 28/183) than in paediatric (2%, 1/41, P=0.04) CD. Corticotroph microadenomas were more easily visualised by pituitary magnetic resonance imaging (MRI) in adult (76%, 50/66) compared with paediatric (55%, 21/38, P=0.045) CD with poorer concordance of imaging with surgical findings in children (P=0.058). The incidence of ACTH lateralisation by bilateral simultaneous inferior petrosal sinus sampling was comparable in paediatric (76%, 25/33) and adult (79%, 46/58; P=0.95) patients with good surgical concordance in both (82% paediatric and 79% adult). Cure rates by TSS were comparable, with a paediatric cure rate of 69%. CONCLUSION: Several features of paediatric CD are distinct: increased frequency of prepubertal CD in males, the different clinical presentation, the decreased presence of macroadenomas and the frequent absence of radiological evidence of an adenoma on MRI.
Assuntos
Hipersecreção Hipofisária de ACTH/epidemiologia , Hipersecreção Hipofisária de ACTH/cirurgia , Seio Esfenoidal/cirurgia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/diagnóstico , Estudos Retrospectivos , Seio Esfenoidal/patologia , Resultado do Tratamento , Adulto JovemAssuntos
Hormônio do Crescimento Humano/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Neoplasias Embrionárias de Células Germinativas/patologia , Adolescente , Adulto , Bases de Dados Factuais , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Estudos Longitudinais , Masculino , Recidiva Local de Neoplasia/patologia , Fatores de RiscoRESUMO
OBJECTIVE: It is suggested that patients with acromegaly have an increased risk of colorectal cancer and pre-malignant adenomatous polyps. However, the optimum frequency with which colonoscopic screening should be offered remains unclear. DESIGN: To determine the optimum frequency for repeated colonoscopic surveillance of acromegalic patients. METHODS: We retrospectively reviewed the case records of all patients with acromegaly seen in our centre since 1992: 254 patients had at least one surveillance colonoscopy, 156 patients had a second surveillance colonoscopy, 60 patients had a third surveillance colonoscopy and 15 patients had a fourth surveillance colonoscopy. RESULTS: The presence of hyperplastic or adenomatous polyps was assessed in all patients, while one cancer was detected at the second surveillance. At the third surveillance, mean (+/-s.d.) serum IGF1 levels (ng/ml) in patients with hyperplastic polyps were significantly higher than those with normal colons (P<0.05). The presence of an adenoma rather than a normal colon at the first colonoscopy was associated with a significantly increased risk of adenoma at the second (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.9-10.4) and at the third (OR 8.8, 95% CI 2.9-26.5) screens. Conversely, a normal colon at the first surveillance gave a high chance of normal findings at the second (78%) or third surveillance (78%), and a normal colon at the second colonoscopy was associated with normality at the third colonoscopy (81%). CONCLUSIONS: Repeated colonoscopic screening of patients with acromegaly demonstrated a high prevalence of new adenomatous and hyperplastic colonic polyps, dependent on both the occurrence of previous polyps and elevated IGF1 levels.
Assuntos
Acromegalia/diagnóstico , Neoplasias do Colo/etiologia , Colonoscopia , Acromegalia/complicações , Pólipos Adenomatosos/etiologia , Idoso , Colo/patologia , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , RadioimunoensaioRESUMO
OBJECTIVES: Cushing's disease (CD) in prepubertal children is very rare and presents important diagnostic and therapeutic challenges. We report experience of the management of this subpopulation of CD patients. STUDY DESIGN/METHODS: Retrospective patient case note review. RESULTS: Between 1985 and 2008, 17 prepubertal children (13M, 4F), aged 5.7-14.1 years presented to our centre for diagnosis and management of CD. All children had subnormal linear growth and excessive weight gain at presentation. A high proportion (85% of males, 75% of females) had evidence of excessive virilisation. Striae and hypertension were seen in 41% of patients. The investigation with highest sensitivity (100%) for CD was excessive increase of serum cortisol to i.v. CRH (mean increase 113%). Pituitary imaging performed in all the patients showed poor concordance with findings at surgery (31%). In contrast bilateral simultaneous inferior petrosal sinus sampling (BSIPSS), performed in 11/16 subjects showed a high correlation with surgical findings (91%). In 16 patients, transsphenoidal selective adenomectomy (TSS) achieved a cure rate of 44%. However, in the 11 patients who had pre-operative BSIPSS, the cure rate was 64%. Of the 16 patients, 9 patients who were not cured by TSS received external pituitary radiotherapy. CONCLUSIONS: Prepubertal CD had distinctive features with increased frequency in males, abnormal auxology and excessive virilisation. The cortisol response to i.v. CRH administration was particularly exuberant and contributed to diagnosis. BSIPSS was much more helpful than pituitary imaging in localisation of the microadenoma and was associated with improved cure rate by TSS.
Assuntos
Adenoma/terapia , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/terapia , Neoplasias Hipofisárias/terapia , Adenoma/complicações , Adenoma/diagnóstico , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Hormônio Liberador da Corticotropina , Feminino , Humanos , Hidrocortisona/sangue , Hipertensão/etiologia , Imunoensaio , Imageamento por Ressonância Magnética , Masculino , Sobrepeso/etiologia , Hipersecreção Hipofisária de ACTH/complicações , Hipófise/fisiopatologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Estudos Retrospectivos , Resultado do Tratamento , Virilismo/etiologiaRESUMO
OBJECTIVE: We report the use of 'gamma knife' (GK) radiosurgery in 25 patients with pituitary adenomas not cured despite conventional therapy, including external beam radiotherapy. PATIENTS AND METHODS: All patients had previously received conventional radiotherapy for a mean of 11.8 years prior to receiving GK; 23 out of 25 had also undergone pituitary surgery on at least one occasion. Seventeen had hyperfunctioning adenomas that still required medical therapy without an adequate biochemical control--ten somatotroph adenomas, six corticotroph adenomas and one prolactinoma, while eight patients had non-functioning pituitary adenomas (NFPAs). RESULTS: Following GK, mean GH fell by 49% at 1 year in patients with somatotroph tumours. Serum IGF1 fell by 32% at 1 year and by 38% at 2 years. To date, 80% of the patients with acromegaly have achieved normalisation of IGF1, and 30% have also achieved a mean GH level of <1.8 ng/ml correlating with normalised mortality. A total of 75% NFPAs showed disease stabilisation or shrinkage post GK. The patient with a prolactinoma showed a dramatic response: 75% reduction in prolactin at 2 years, with a marked shrinkage on magnetic resonance imaging. The results in corticotroph adenomas were variable. Prior to GK, 72% of the patients were panhypopituitary, and 42% of the remainder have developed new anterior pituitary hormone deficiencies to date. No other adverse events have been detected at a mean follow-up of 36.4 months. CONCLUSIONS: These data indicate that GK is a safe and effective adjunctive treatment for patients with NFPAs and acromegaly not satisfactorily controlled with surgery and radiotherapy.
Assuntos
Neoplasias Hipofisárias/cirurgia , Radiocirurgia , Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/cirurgia , Adulto , Idoso , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/radioterapia , Prolactinoma/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Published data suggest that growth hormone replacement (GHR) may be given safely to patients with hypopituitarism consequent upon a pituitary/peripituitary tumour. However, a preponderance of patients treated with external pituitary irradiation were included. OBJECTIVE: To assess the safety of GHR in nonirradiated pituitary/peripituitary tumour. DESIGN: Prospective audit. SETTING: Tertiary university referral centre. PATIENTS: We imaged prospectively the pituitary glands of 48 patients (18 males; mean age 51.6 years range 21-77) who had adult onset growth hormone deficiency (AO-GHD) after appropriate treatment for a pituitary/peripituitary tumour but who did not receive external pituitary irradiation. INTERVENTION: All patients were treated with a dose titration regimen of GH to maintain serum IGF-1 between the median and upper end of the age-related reference range. Pituitary surveillance imaging was performed prior to the commencement of GHR, at 6-12 months and then yearly. For patients with secretory tumours, biochemical markers (cortisol and prolactin) were used as evidence of tumour recurrence. RESULTS: 48 patients with median follow up since commencement of GHR was 38 months (range 9-104). Three patients were judged to have an apparent increase in tumour volume and/or marker, although only one was thought to be possibly GH related--a patient with a cystic chromophobe adenoma who demonstrated a marginal increase in residual tumour volume 4 years after commencement of GHR. CONCLUSION: These data add to the growing body of evidence for the safety of GHR in hypopituitary patients consequent upon pituitary/peripituitary mass lesions and represents the first reported series in a heterogeneous group of nonirradiated patients.
Assuntos
Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Neoplasias Hipofisárias/tratamento farmacológico , Adulto , Idoso , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIMS: This study was designed to determine the sensitivity and specificity of conventional criteria for diagnosis of impaired glucose tolerance (IGT) in a high-risk population of GH-treated GH deficient (GHD) adults. METHODS: 33 hypopituitary GHD patients with HbA(1c) >5.1% and 13 gender- and age-matched control GHD patients were selected. Oral glucose tolerance test (OGTT), fasting plasma glucose (FPG), HbA(1c), and homeostatic model assessment (HOMA) parameters were determined in all patients. Receiver operator characteristic curves were used to determined sensitivity and specificity for the detection of glucose intolerance as defined by plasma glucose >7.8 mmol/l at 120 min during OGTT. RESULTS: Sensitivity and specificity for this purpose for HbA(1c) (>5.1%) were 89 and 17%; for FPG (>5.5 mmol/l): 78 and 67%; for FPG (>6.1 mmol/l): 56 and 89%; for HOMA-derived beta-cell function (betaCF) (<40%): 78 and 58%; for HOMA-derived insulin sensitivity (IS) (<70%): 11 and 89%, and for betaCF-IS hyperbolic product (betaCF-IS) (<54%): 89 and 75%, respectively. CONCLUSIONS: This study shows that FPG (>5.5 mmol/l) and betaCF-IS have high sensitivity and relatively high specificity for the detection of IGT and confirms that measurement of FPG or calculation of betaCF-IS provides appropriate safety surveillance in hypopituitary patients on GH replacement.
Assuntos
Glicemia/análise , Jejum/fisiologia , Intolerância à Glucose/diagnóstico , Hemoglobinas Glicadas/análise , Hormônio do Crescimento/uso terapêutico , Terapia de Reposição Hormonal , Hipopituitarismo/tratamento farmacológico , Modelos Biológicos , Estudos Transversais , Complicações do Diabetes/sangue , Diabetes Mellitus/diagnóstico , Diagnóstico Precoce , Feminino , Intolerância à Glucose/complicações , Teste de Tolerância a Glucose/métodos , Homeostase/fisiologia , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/complicações , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Paediatric Cushing's disease is frequently associated with abnormal puberty. We addressed the hypothesis that prepubertal patients show excessive virilization and pubertal patients show suppression of LH and FSH secretion. DESIGN AND MEASUREMENTS: Serum androstenedione (A4), dehydroepiandrosterone sulphate (DHEAS), testosterone (T), and sex hormone binding globulin (SHBG) were determined at diagnosis and converted to standard deviation scores. LH, FSH concentrations were also determined. Severity of CD was assessed from the sleeping midnight cortisol concentration. Puberty was staged and excessive virilization defined as advance in pubic hair stage for breast stage or testicular volume (TV). PATIENTS: Twenty-seven CD patients (17 male, 10 female), median age 13.4 years (range 5.9-17.8) were studied. RESULTS: In the CD group as a whole, A4, DHEAS, T standard deviation scores (SDS) values were normal. SHBG SDS values (n = 19) were low (median -1.93, -4.32-0.86) correlating with BMI (r = -0.49). A4, DHEAS, T, SHBG, LH and FSH did not correlate with midnight cortisol, but A4 and T SDS correlated with ACTH at 09.00 h (both r = 0.51). Thirteen patients (11 male, 2 female) had excessive virilization with increased A4 (P = 0.033), DHEAS (P = 0.008), testosterone (P = 0.033) and decreased SHBG (P = 0.004) compared with subjects without excessive virilization. Pubertal boys (TV > or = 4 ml) (n = 7) and girls (breasts > or = stage 2) (n = 8) had low median LH and FSH. Boys had an LH concentration of 1.2 mU/l (0.3-3.5), FSH, 0.9 mU/l (0.2-6.4) and median T SDS, -1.95 (-3.8-4.65), while girls had an LH concentration of 1 mU/l (0.3-7.4). CONCLUSIONS: Many patients had abnormal puberty and excessive virilization associated with increased adrenal androgens and decreased SHBG. Pubertal patients had low LH and FSH suggesting impaired pituitary-gonadal axis function.
Assuntos
Androgênios/sangue , Gonadotropinas Hipofisárias/sangue , Hipersecreção Hipofisária de ACTH/complicações , Puberdade Precoce/etiologia , Globulina de Ligação a Hormônio Sexual/análise , Adolescente , Hormônio Adrenocorticotrópico/sangue , Androstenodiona/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hidrocortisona/sangue , Hormônio Luteinizante/sangue , Masculino , Hipersecreção Hipofisária de ACTH/sangue , Puberdade Precoce/sangue , Estatísticas não Paramétricas , Testosterona/sangue , Virilismo/sangue , Virilismo/etiologiaRESUMO
BACKGROUND/OBJECTIVE: Pituitary radiotherapy (RT) is an effective second-line treatment for paediatric Cushing's disease (CD). Although the short-term effects of pituitary RT are well documented, there are less data on possible long-term sequelae. We report the long-term anterior pituitary function in a cohort of paediatric CD patients treated with pituitary RT. PATIENTS AND METHODS: Between 1983 and 2006, 12 paediatric CD patients (10 males and 2 females) of mean age 11.4 years at diagnosis (range 6.4-17.4) underwent second-line pituitary RT (45 Gy in 25 fractions), following unsuccessful transsphenoidal surgery. Out of 12, 11 patients were cured by RT (cure interval 0.13-2.86 years) defined by mean serum cortisol of <150 nmol/l on 5-point day curve and midnight sleeping cortisol of <50 nmol/l. Long-term data are available for six male patients, who received RT at the age of 7.0-17.6 years. The mean follow-up from the completion of RT was 10.5 years (6.6-16.5). RESULTS: At a mean of 1.0 year (0.11-2.54) following RT, GH deficiency (peak GH <1-17.9 mU/l) was present in five out of six patients. On retesting at a mean of 9.3 years (7.6-11.3) after RT, three out of four patients were GH sufficient (peak GH 19.2-50.4 mU/l). Other anterior pituitary functions including serum prolactin in five out of six patients were normal on follow-up. All the six patients had testicular volumes of 20-25 ml at the age of 14.5-28.5 years. CONCLUSION: This series of patients illustrates the absence of serious long-term pituitary deficiency after RT and emphasises the importance of continued surveillance.
Assuntos
Hipersecreção Hipofisária de ACTH/metabolismo , Hipersecreção Hipofisária de ACTH/radioterapia , Adeno-Hipófise/metabolismo , Irradiação Hipofisária , Adolescente , Hormônio Adrenocorticotrópico/sangue , Criança , Seguimentos , Gonadotropinas/sangue , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/metabolismo , Humanos , Hidrocortisona/sangue , Masculino , Hipersecreção Hipofisária de ACTH/sangue , Hipersecreção Hipofisária de ACTH/fisiopatologia , Neuro-Hipófise/metabolismo , Puberdade , Testículo/crescimento & desenvolvimento , Tireotropina/sangueRESUMO
BACKGROUND/AIMS: This study was designed to determine whether previous Cushing's disease (CD) or prolactinoma (PRL) could exert adverse effects additional to those of growth hormone (GH) deficiency as a consequence of variable degrees of prior hypogonadism or hypercatabolism. We report the effects of 5 years GH treatment in 124 GH deficiency adults; 42 patients with non-functioning pituitary adenomas (NFPA), 43 with treated PRL and 39 with treated CD. METHODS: Fasting plasma glucose, HbA(1c), lipoprotein profile, anthropometry and bone mineral density (BMD) were measured at baseline, 6 months and annually up to 5 years. RESULTS: Mean body mass index remained unchanged in the PRL group and tended to increase in the NFPA group. In contrast, body mass index decreased in the CD group. Decreases in waist and waist/hip ratio were seen in all groups at 6 months. Decreases in total cholesterol and low-density lipoprotein cholesterol were seen in all groups and remained sustained at 5 years. Plasma glucose and HbA(1c) increased at 6 months. Subsequently, plasma glucose returned to baseline values at 5 years; in contrast, HbA(1c )remained unchanged at the end of the study. Baseline lumbar spine and hip BMD were lower in the PRL and CD groups than in the NFPA group, decreased over 1 year in all groups and subsequently increased by 2 years in NFPA with a subsequent increase in lumbar spine BMD in PRL and CD groups delayed to 3-5 years. CONCLUSIONS: Baseline characteristics and response to GH replacement are qualitatively similar in NFPA, PRL and CD patients. Because improvements in BMD occur later in PRL and CD patients, an extended trial of GH therapy may be indicated in those patients who were commenced on GH therapy as an additional treatment for reduced BMD.
Assuntos
Adenoma/fisiopatologia , Adenoma/terapia , Glicemia/metabolismo , Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Hipersecreção Hipofisária de ACTH/fisiopatologia , Hipersecreção Hipofisária de ACTH/terapia , Neoplasias Hipofisárias/fisiopatologia , Neoplasias Hipofisárias/terapia , Prolactinoma/fisiopatologia , Prolactinoma/terapia , Adulto , Índice de Massa Corporal , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: To investigate two patients with the hyperparathyroidism-jaw tumour (HPT-JT) syndrome and three patients with familial isolated hyperparathyroidism (FIHP), together with 31 parathyroid tumours (2 HPT-JT, 2 FIHP and 27 sporadic) for HRPT2 mutations. The HPT-JT syndrome and FIHP are autosomal dominant disorders that may be caused by abnormalities of the HRPT2 gene, located on chromosome 1q31.2. HRPT2 encodes a 531 amino acid protein, parafibromin, which interacts with human homologues of the yeast Paf1 complex. DESIGN: Leukocyte and tumor DNA was used with HRPT2-specific primers for polymerase chain reaction amplification of the 17 exons and their splice junctions, and the DNA sequences of the polymerase chain reaction products determined. RESULTS: Three heterozygous germline HRPT2 mutations, two in HPT-JT and one in FIHP patients, were identified. These consisted of one 1-bp duplication (745dup1bp), 1 nonsense (Arg234Stop) and 1 missense (Asp379Asn) mutation. One parathyroid tumour from an FIHP patient was demonstrated to harbour a germline deletion of 1 bp together with a somatic missense (Leu95Pro) mutation, consistent with a 'two-hit' model for hereditary cancer. The 27 sporadic benign parathyroid tumours did not harbour any HRPT2 somatic mutations. Six HRPT2 polymorphisms with allele frequencies ranging from 2% to 15% were detected. CONCLUSIONS: Our results have identified three novel HRPT2 mutations (two germline and one somatic). The Asp379Asn mutation is likely to disrupt interaction with the human homologue of the yeast Paf1 complex, and the demonstration of combined germline and somatic HRPT2 mutations in a parathyroid tumour provide further evidence for the tumour suppressor role of the HRPT2 gene.
Assuntos
Hiperparatireoidismo/genética , Neoplasias Maxilomandibulares/genética , Neoplasias das Paratireoides/genética , Proteínas Supressoras de Tumor/genética , Adulto , Criança , DNA de Neoplasias/genética , Saúde da Família , Feminino , Frequência do Gene , Humanos , Perda de Heterozigosidade/genética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Linhagem , Polimorfismo Genético/genética , SíndromeRESUMO
BACKGROUND: Multimodal therapy for acromegaly affords adequate disease control for many patients; however, there remains a subset of individuals that exhibit treatment-resistant disease. The issue of treatment-resistant pituitary tumor growth remains relatively under-explored. METHODS: We assessed the literature for relevant data regarding the surgical, medical and radiotherapeutic treatment of acromegaly in order to identify the factors that were predictive of aggressive or treatment-resistant pituitary tumor behavior in acromegaly and undertook an assessment of the rates of failure to control tumor progression with available treatment modalities. RESULTS: Young age at diagnosis, large tumor size, high growth hormone secretion and certain histological markers are predictors of future aggressive tumor behavior in acromegaly. Significant tumor regrowth occurs in less than 10% of cases thought to be cured surgically, whereas failure to control tumor growth is seen in less than 1% of patients receiving radiotherapy. Somatostatin analogs induce a variable degree of tumor shrinkage in acromegaly but up to 2.2% of somatostatin analog-treated tumors continue to grow. Relative to other therapies, limited data are available for pegvisomant, but these indicate that persistent tumor growth occurs in 1.6-2.9% of cases followed up regularly with serial magnetic resonance imaging scans. CONCLUSIONS: Treatment-resistant tumor progression occurs in a small minority of patients with acromegaly, regardless of treatment modality. Young patients with large tumors or those with high pre-treatment levels of growth hormone particularly warrant close monitoring for continued tumor progression during treatment for acromegaly.
Assuntos
Acromegalia/terapia , Neoplasias Hipofisárias/terapia , Acromegalia/epidemiologia , Acromegalia/cirurgia , Humanos , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/cirurgia , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
OBJECTIVE: GH replacement is widely used in the management of patients with adult-onset (AO)-GH deficiency (GHD). In most cases, AO-GHD arises as a result of pituitary/peripituitary tumours and/or their treatment, but the effect of GH replacement on recurrence/regrowth of these tumours is unknown. The aim of this study was to examine the effect of GH replacement in a group of patients with primary tumours of the parasellar region, many of which (e.g. craniopharyngioma, glioma or germ cell tumours) might be anticipated to have a higher recurrence rate than secretory and nonsecretory anterior pituitary tumours. PATIENTS AND DESIGN: We report here our experience of prospective imaging in 50 consecutive patients (21 males; mean age 45.9 years) with nonanterior pituitary parasellar tumours treated with GH. All had severe GHD (peak serum GH 9 mU/l or less on dynamic testing) and were treated with an identical dose-titration regimen to maintain serum IGF-I concentrations between the median and upper end of the age-adjusted normal range. The primary diagnoses were: craniopharyngioma (28), germ cell tumour (8), arachnoid cyst (4), meningioma (4), glioma (4) and mensenchymal tumour (2). External pituitary irradiation had been given to 37 (74%) of patients. Measurements Surveillance imaging (magnetic resonance imaging (MRI) 70%, computed tomography (CT) 16%, both 14%) was performed at baseline (prior to GH), at 6--12 months, and then again yearly or as clinically indicated. Median follow-up was 36 months (range 7--129 months). All images were reviewed by the same radiologist. RESULTS: Four patients had an apparent increase in tumour volume but in only one patient was it considered necessary to abandon GH replacement. In two of the four cases marginal increases in cystic parasellar tumours were not progressive; and in the fourth case apparent recurrence of a suprasellar germ cell tumour was shown to be acellular fibrous tissue only on biopsy. In all other cases either the appearances were unchanged or the amount of tissue was reduced during long-term follow-up on GH. CONCLUSIONS: Overall, GH appears safe with respect to tumour recurrence over this time period in this patient group. Comparison with similar prospective series in patients not receiving GH replacement is desirable.
Assuntos
Encéfalo/patologia , Hormônio do Crescimento/uso terapêutico , Terapia de Reposição Hormonal , Hipopituitarismo/tratamento farmacológico , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico , Adulto , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/terapia , Terapia Combinada , Craniofaringioma/complicações , Craniofaringioma/terapia , Feminino , Seguimentos , Germinoma/complicações , Germinoma/terapia , Glioma/complicações , Glioma/terapia , Hormônio do Crescimento/efeitos adversos , Humanos , Hipopituitarismo/etiologia , Masculino , Pessoa de Meia-Idade , Irradiação HipofisáriaRESUMO
OBJECTIVE: Linear growth data after cure of paediatric Cushing's disease (CD) have been reported infrequently. We evaluated final adult height (FH) and body mass index (BMI) in a cohort of paediatric patients treated successfully for CD. PATIENTS AND METHODS: Fourteen patients (10 male, age range 6.4-16.6 years) fulfilled the diagnostic criteria for CD. All had had transsphenoidal surgery (TSS), combined with pituitary irradiation (RT) (45 Gy in 25 fractions) in six. All were cured (post-TSS cortisol < 50 nmol/l or mean cortisol post-RT < 150 nmol/l). Subjects analysed had bone ages at diagnosis of < 15 'years' (male) and < 13 'years' (female). RESULTS: At diagnosis, height SDS was [mean (range)]-2.5 (-4.2 to -0.8) and body mass index (BMI) SDS +2.7 (0.8-5.1). Following cure, 13 patients had GH deficiency (peak GH < 20 mU/l) and were treated with hGH (+ GnRH analogue in four). Height SDS at FH (n = 10) or latest assessment (n = 4) was -1.3 (-3.9-0.2) and increased compared to diagnosis (P < 0.01). The difference between final or latest height SDS and target height SDS was -1.2 (-3.3-0.5), that is less (P < 0.01) than the difference between the height SDS at diagnosis and target height SDS of -2.4 (-3.9 to -0.5). At final height or latest assessment, BMI SDS was +1.7 (0.4-6.2), being decreased compared to diagnosis (P < 0.05) but greater than the normal population (P < 0.01). CONCLUSION: Catch-up growth was demonstrated in paediatric patients cured from CD, with the majority achieving FH within target height range. Early diagnosis and treatment of GH deficiency is recommended to achieve optimal long-term growth. Excess adiposity remains a potential long-term complication.
Assuntos
Estatura , Índice de Massa Corporal , Síndrome de Cushing/cirurgia , Hipófise/cirurgia , Adolescente , Criança , Síndrome de Cushing/fisiopatologia , Síndrome de Cushing/radioterapia , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Gosserrelina/uso terapêutico , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Irradiação Hipofisária , Estudos Retrospectivos , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: The efficacy of transsphenoidal surgery in the treatment of patients with acromegaly is largely dependent on tumour size. A reduction in pituitary tumour volume by medical therapy might therefore improve subsequent surgical cure rates. This study prospectively determined the effects of the depot somatostatin analogue octreotide LAR on pituitary tumour size, GH and IGF-I levels and clinical symptoms in a cohort of previously untreated patients with acromegaly. METHODS: Six patients newly diagnosed with acromegaly (mean age 53 years; range 42-76 years) received intramuscular octreotide LAR every 28 days for 6 months. The initial dose of LAR was 20 mg, but increased to 30 mg after the initial 3 injections if mean GH levels were >5 mU/l. Prior to commencing LAR therapy, each patient received 3 injections of subcutaneous octreotide (50, 100 and 200 mug) in a randomized order on separate days, and the serum GH response was measured. Pituitary tumour volume was calculated from MRI or computed tomography scans at baseline, then 3 and 6 months after initiation of treatment, and assessed by a 'blinded' radiologist in random order. At baseline, 4 patients had a macroadenoma and 2 patients had a microadenoma. For the latter, the whole gland volume was measured. RESULTS: Serum GH levels decreased from 29.6 +/- 19.2 mU/l (mean +/- SD) at baseline to 12.1 +/- 10.5 mU/l at 3 months and 10.4 +/- 9.3 mU/l at 6 months. Three patients achieved a mean serum GH level of <5 mU/l. In these patients, the serum GH had declined to <5 mU/l in response to a single 100 mug subcutaneous octreotide injection. Serum IGF-I levels decreased by a mean of 45 +/- 7.4%. Tumour volume decreased in all patients: mean baseline volume 2,175 mm(3) (range 660-6,998) decreasing to 1,567 mm(3) (range 360-4,522) at 3 months (p < 0.05) and 1,293 mm(3) (range 280-4,104) at 6 months (p < 0.002). The mean percentage decrease in size was 29% (range -54 to +4%) at 3 months (p < 0.02) and 47% (range 21-97%) at 6 months (p < 0.002). There was no statistically significant correlation between GH response and tumour shrinkage. CONCLUSIONS: A single test dose of subcutaneous octreotide may be useful in predicting the subsequent efficacy of octreotide LAR. Octreotide LAR results in significant shrinkage of pituitary tumours of newly diagnosed patients with acromegaly. Whether its administration to such patients for 6-12 months can improve the efficacy of subsequent transsphenoidal surgery will require further study.
Assuntos
Acromegalia/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Octreotida/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Acromegalia/patologia , Adulto , Idoso , Antineoplásicos Hormonais/administração & dosagem , Preparações de Ação Retardada , Hormônio do Crescimento/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/etiologia , Neoplasias Hipofisárias/patologia , Estudos ProspectivosRESUMO
The aim of the present study is to compare the diagnostic performance of CT and MR imaging in detecting aldosterone-producing adenoma and to compare the interobserver variability in the detection of an aldosterone-producing adenoma on CT and MR. A retrospective study of 34 patients with primary hyperaldosteronism was performed. A total of 17 cases of aldosterone-producing adenoma and 17 cases of bilateral adrenal hyperplasia were included. The final diagnosis of an adenoma was made by surgery with histological confirmation, whereas that of bilateral adrenal hyperplasia was made on adrenal venous sampling or a good biochemical and clinical response following medical treatment alone and in the absence of a unilateral radiological abnormality. The CT (n=30) and MR (n=24) scans were reviewed independently by two radiologists experienced in adrenal imaging, who were unaware of the cause of the primary hyperaldosteronism. The diagnostic performances of both observers in detecting an aldosterone-producing adenoma on CT and MR imaging were compared. The 16 adenomatous nodules that were detected on imaging ranged from 1 to 4.75 cm in diameter. The calculated sensitivity and specificity for detecting aldosterone-producing adenoma were 87 and 93% for one observer and 85 and 82% for the other observer on CT, and 83 and 83% for one observer and 92 and 92% for the other observer on MR, respectively. Receptor operating characteristics curve analysis showed similar performances of both observers in detecting an aldosterone-producing adenoma on CT and MR imaging. There was good interobserver agreement on CT (k=0.71) and on MR (k=0.67). We have demonstrated comparable diagnostic performance and good interobserver agreement on CT and MR imaging for the detection of aldosterone-producing adenoma.
Assuntos
Adenoma/diagnóstico , Neoplasias das Glândulas Suprarrenais/diagnóstico , Aldosterona/metabolismo , Hiperaldosteronismo/diagnóstico , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Adenoma/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/secundário , Glândulas Suprarrenais/patologia , Adulto , Feminino , Humanos , Hiperaldosteronismo/etiologia , Hiperplasia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Although Cushing's disease (CD) rarely occurs in childhood, affected children commonly fail to achieve predicted adult height. Hypercortisolaemia results in reduced GH secretion and GH-deficiency may persist or demonstrate delayed recovery after successful treatment of CD in adults. Whether recovery of spontaneous GH secretion occurs following treatment of childhood CD has yet to be established. DESIGN AND PATIENTS: We performed a retrospective analysis of the GH status of 13 children (10 males; 12.8 +/- 1.0 years, mean +/- SE) who had undergone successful treatment of CD that occurred prior to the completion of linear growth. Each underwent transsphenoidal hypophysectomy, resulting in satisfactory control of glucocorticoid levels in 7/13 (54%). The remaining six patients (46%) received fractionated external beam irradiation (4500 Gy). At the time of GH assessment, circadian dynamics of cortisol were normal in eight patients and five were receiving titrated glucocorticoid replacement. MEASUREMENTS: GH status was assessed using the peak response to a provocative stimulus. Eleven out of 13 underwent testing with insulin-induced hypoglycaemia (nadir plasma glucose = 2.2 mmol/l) and glucagon provocation was used in 2/13. Severe GH-deficiency was defined as a peak GH response < 9 mU/l, and a normal response as > 30 mU/l. Intermediate values were taken to represent subnormal GH status. Assessment of GH status was performed 39 +/- 10 months (median +/- SE) following successful treatment (range 9-108 months). RESULTS: Using these criteria 4/13 (31%) patients had severe GH-deficiency. Only 2/13 (15%) had a normal response. 7/13 (54%) achieved peak GH levels in the subnormal range. Those with multiple pituitary hormone deficiencies were most likely to have lower peak GH levels, but there was no clear effect of pituitary irradiation or relationship between duration post cure and peak GH response. CONCLUSION: GH-deficiency is common and may persist for many years following successful treatment of CD prior to completion of linear growth. External radiotherapy does not necessarily result in severe GH-deficiency in the short term. Assessment of GH status and consideration of GH treatment should be considered following treatment of CD in childhood and adolescence in order to maximize the opportunities to achieve a satisfactory final adult height. In those with subnormal GH responses, continued assessment is necessary to determine whether the GH axis subsequently recovers or if these patients develop features of the adult GH-deficiency syndrome.
Assuntos
Síndrome de Cushing/terapia , Hormônio do Crescimento/deficiência , Adolescente , Criança , Síndrome de Cushing/sangue , Síndrome de Cushing/diagnóstico , Feminino , Seguimentos , Glucagon , Glucocorticoides/administração & dosagem , Hormônio do Crescimento/sangue , Humanos , Hidrocortisona/sangue , Insulina , Masculino , Hipófise/cirurgia , Estudos RetrospectivosRESUMO
The case is described of a 21-year-old woman, who developed a malignant tumour arising from a craniopharyngioma 14 years after the original diagnosis. The remarkable response of this malignant tumour ex-craniopharyngioma to cis-platin based chemotherapy, together with other midline tumour characteristics of craniopharyngioma, raise the question as to whether craniopharyngioma should any longer be separately considered from suprasellar germ cell tumour. This subject is discussed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Craniofaringioma/tratamento farmacológico , Neoplasias Hipofisárias/tratamento farmacológico , Adolescente , Adulto , Criança , Aberrações Cromossômicas , Cisplatino/administração & dosagem , Craniofaringioma/genética , Craniofaringioma/patologia , Etoposídeo/administração & dosagem , Evolução Fatal , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologiaRESUMO
We report the use of stereotactic radiosurgery delivered through an adapted linear accelerator [stereotactic multiple arc radiation therapy (SMART)] for pituitary adenomas not cured by conventional therapy. All 21 patients had undergone conventional radiotherapy (45-50 Gy); 18 had also undergone prior surgery. This cohort comprised 13 patients with somatotrope adenomas, four with corticotrope adenomas, one with a lactotrope adenoma, and three with nonfunctioning pituitary adenomas (median follow-up: 33 months, range: 3-72 months). SMART has proven effective, safe, and rapidly acting. We observed an accelerated reduction in GH and IGF-I levels in acromegaly, with normalization of GH and IGF-I levels in 58%. Mean GH fell from 21.1 mU/liter to 7.9 mU/liter (7 ng/ml to 2.6 ng/ml, P < 0.01, median 25 months) faster than our predicted fall to 50% at 2 yr with conventional radiotherapy. Mean IGF-I fell from 624 ng/ml to 384 ng/ml (P < 0.001). Tumor growth was controlled in two of three nonfunctioning pituitary adenomas, and three of four corticotrope adenomas. There were no adverse effects from SMART. Notably there have been no visual sequelae or further loss of anterior pituitary function in this heavily pretreated group. Our data indicate that SMART is an effective complementary therapy for pituitary adenomas that have displayed a suboptimal response to conventional therapy including external irradiation.