Correlation analysis of anterior pituitary hormone and tumor size in patients with pituitary adenomas / 中华内科杂志

Objective:To summarize the correlation between anterior pituitary function and tumor size in patients with different hormone-secreting pituitary adenomas.Methods:This was a retrospective case series study. The clinical data of 1 946 patients with pituitary adenoma hospitalized in the First Medical Center of Chinese PLA General Hospital from January 1, 2005, to December 31, 2020, were collected. The correlation between tumor size and anterior pituitary hormone levels was analyzed using Spearman rank correlation analysis in different types of pituitary adenomas.Results:The median age of the 1 946 patients was 45.1 years, of which 857 (44.0%) were men. The maximum tumor diameter of the patients [ M ( Q1, Q3)] was 22 (14, 30) mm. Tumor size in nonfunctioning adenomas ( n=1 191) was negatively correlated with adrenocorticotropic hormone (ACTH) ( r=-0.11, P<0.001), growth hormone ( r=-0.13, P<0.001), and luteinizing hormone (men: r=-0.26, P<0.001, women: r=-0.31, all P<0.001). The tumor size of somatotropic adenomas ( n=297) was positively correlated with growth hormone ( r=0.46, P<0.001), but negatively correlated with male testosterone ( r=-0.41, P<0.001). The tumor size of ACTH-secreting pituitary adenomas ( n=155) was positively correlated with the ACTH level at 8∶00 AM ( r=0.25, P<0.001); however, no correlation was found with cortisol at 8∶00 AM ( P>0.05). The tumor size of prolactinomas ( n=303) was positively correlated with the prolactin level (men: r=0.34, P=0.001; women: r=0.13, P=0.070). Conclusions:The correlation between the function of the anterior pituitary and size of the tumor depends on the cellular origin of the pituitary adenoma and specific type of hormone secretion. In somatotroph adenomas, ACTH-secreting pituitary adenomas, and prolactinomas, there is a positive correlation between tumor size and level of hormones secreted by the corresponding tumors. In patients with nonfunctioning adenomas, the tumor size was negatively correlated with the hormone levels of the pituitary-adrenal and pituitary-growth hormone axes.

Acromegalia por macroadenoma hipofisiario en paciente con síndrome de McCune-Albright. Reporte de caso y revisión de la literatura / Acromegaly due to pituitary macroadenoma in a patient with McCune-Albright syndrome. Case report and literature overview

Introducción: El síndrome de McCune-Albright (SMA) es una enfermedad rara caracterizada por la triada: manchas cutáneas de color café con leche, displasia fibrosa poliostótica y pubertad precoz. Puede afectar a diversos ejes hormonales, entre ellos el de la hormona de crecimiento (GH), pudiendo asociarse a acromegalia. Reporte de caso: describimos el caso de una mujer de 44 años, con pubertad precoz periférica, hemorragia uterina anormal, crecimiento de manos y pies, prognatismo, prominencia frontal, manchas café con leche y tumoraciones pétreas en cara y antebrazos. Resultados: Apoyados con exámenes laboratoriales y de imágenes, se llegaron a los diagnósticos de acromegalia, hipogonadismo hipogonadotropo y síndrome de McCune-Albright. La paciente fue sometida a tratamiento quirúrgico con persistencia de enfermedad clínica y laboratorial. Conclusión: El diagnóstico y tratamiento oportunos de la acromegalia y sus complicaciones brindará un mejor pronóstico a los pacientes con SMA.

Background: McCune-Albright syndrome (MAS) is a rare disease characterized by the triad: café-au-lait skin spots, polyostotic fibrous dysplasia, and precocious puberty. It can affect various hormonal axes, including growth hormone (GH), and may be associated with acromegaly. We describe the case Case report:of a 44-year-old woman with peripheral precocious puberty, abnormal uterinebleeding, growthof thehands and feet, prognathism, frontal prominence, café-au-lait spots, and stony tumorsonthefaceandforearms.Supportedby Results:laboratory and imaging tests, the diagnoses of acromegaly, hypogonadotropic hypogonadism and McCune-Albright syndrome were reached. The patient underwent surgical treatment with persistence of clinical and laboratory disease. Conclusion: Timely diagnosis and treatment of acromegaly and its complications will provide a better prognosis for patients with MAS

Caracterización de tumores secretores de hormona de crecimiento de acuerdo al patrón granular y su rol en el pronóstico / Prognostic value of granular pattern of growth hormone secreting tumors

Background: Classification of growth hormone (GH) - secreting tumors by the granular pattern might predict their clinical behavior in acromegalic patients. There are several other prognostic factors. Aim: To compare the features at presentation and cure rates of patients with GH secreting tumors according to the granular pattern, and to define independent prognostic factors for surgical treatment in these patients. Material and Methods: A retrospective, observational study of 85 active acromegalic patients surgically treated in two medical centers. Results: Seventy-four patients (87%) were classified as having densely granulated (DG) and 11 (13%) as sparsely granulated (SG) tumors. The latter were less active biochemically, had a higher rate of macroadenoma and cavernous sinus invasion and had a lower rate of biochemical cure than the DG group. Several characteristics were associated with disease persistence but only age (Odds ratio (OR) = 0.93) and cavernous sinus invasion (OR = 21.7) were independently associated in the logistic regression model. Conclusions: The sparsely granulated pattern is associated with a more aggressive behavior, but the main determinants of prognosis are age and cavernous sinus invasion.

Correlation analysis of serum uric acid level and disease activity in patients with growth hormone-secreting pituitary adenoma / 中国医师进修杂志

Objective@#To explore the correlation between serum uric acid level and disease activity in patients with growth hormone-secreting pituitary adenoma.@*Methods@#The clinical data of 76 patients with growth hormone-secreting pituitary adenoma in the Department of Endocrinology of Beijing Tiantan Hospital, Capital Medical University from 2012 to 2018 were retrospectively analyzed. The patients were divided into 4 groups according to serum uric acid quartiles with 19 cases each, uric acid <233.9 μmol/L in Q1 group, uric acid 233.9 to 275.9 μmol/L in Q2 group, uric acid 276.0 to 366.7 μmol/L in Q3 group, uric acid >366.7 μmol/L in Q4 group. The sex, age, duration of disease, height, weight and blood pressure were collected, and the body mass index (BMI) was calculated. The fasting blood glucose (FBG), glycated hemoglobin, fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), uric acid, basal growth hormone, insulin-like growth factor-1 (IGF-1) were examined, and the IGF-1 index and homeostasis model assessment of insulin resistance (HMOA-IR) were calculated. Pearson correlation analysis was performed to explore the correlation between serum uric acid levels and disease activity.@*Results@#In 76 patients, 8 cases were diagnosed with hyperuricemia, accounting for 10.5%. There were no statistical differences in sex constituent, duration of disease, systolic blood pressure, diastolic blood pressure, FBG, glycated hemoglobin, TG, TC, LDL-C, growth hormone and IGF-1 index among 4 groups (P>0.05). As uric acid level increased, age and HDL-C decreased gradually from Q1 group to Q4 group: (43.58 ± 8.95), (42.58 ± 10.89), (36.58 ± 9.79), (35.37 ± 11.51) years, (1.28 ± 0.22), (1.29 ± 0.23), (1.17 ± 0.28), (1.04 ± 0.22) mmol/L; while BMI, uric acid, IGF-1 and HOMA-IR increased gradually: (25.75 ± 2.86), (27.33 ± 3.94), (26.16 ± 2.94), (28.76 ± 3.69) kg/m2, (190.73 ± 28.80), (249.57 ± 12.00), (325.75 ± 25.61), (430.39 ± 58.41) mmol/L, (594.50 ± 222.45), (733.06 ± 212.42), (774.90 ± 287.87), (962.00 ± 323.36) μg/L, 2.09 (1.64, 2.09), 3.02 (0.94, 3.55), 3.53 (2.31, 6.48), 4.09 (2.52, 5.41), there were statistical differences (P<0.05 or <0.01). Pearson correlation analysis result showed that uric acid was positive correlation with IGF-1, IGF-1 index, HOMA-IR, TG and systolic blood pressure (r = 0.491, 0.341, 0.372, 0.240 and 0.266; P<0.01 or <0.05), and uric acid was negative correlation with HDL-C (r = -0.367, P<0.01). After adjustment for sex, age, duration of disease and BMI, uric acid was still positive correlation with IGF-1 and IGF-1 index (r = 0.352 and 0.318, P<0.01).@*Conclusions@#Serum uric acid level is associated with disease activity in patients with growth-hormone secreting pituitary adenoma.

Correlation analysis of serum uric acid level and disease activity in patients with growth hormone-secreting pituitary adenoma / 中国医师进修杂志

Objective To explore the correlation between serum uric acid level and disease activity in patients with growth hormone-secreting pituitary adenoma. Methods The clinical data of 76 patients with growth hormone-secreting pituitary adenoma in the Department of Endocrinology of Beijing Tiantan Hospital, Capital Medical University from 2012 to 2018 were retrospectively analyzed. The patients were divided into 4 groups according to serum uric acid quartiles with 19 cases each, uric acid﹤233.9 μmol/L in Q1 group, uric acid 233.9 to 275.9 μmol/L in Q2 group, uric acid 276.0 to 366.7 μmol/L in Q3 group, uric acid＞366.7 μmol/L in Q4 group. The sex, age, duration of disease, height, weight and blood pressure were collected, and the body mass index (BMI) was calculated. The fasting blood glucose (FBG), glycated hemoglobin, fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), uric acid, basal growth hormone, insulin-like growth factor-1 (IGF-1) were examined, and the IGF-1 index and homeostasis model assessment of insulin resistance (HMOA-IR) were calculated. Pearson correlation analysis was performed to explore the correlation between serum uric acid levels and disease activity. Results In 76 patients, 8 cases were diagnosed with hyperuricemia, accounting for 10.5% . There were no statistical differences in sex constituent, duration of disease, systolic blood pressure, diastolic blood pressure, FBG, glycated hemoglobin, TG, TC, LDL-C, growth hormone and IGF-1 index among 4 groups (P＞0.05). As uric acid level increased, age and HDL-C decreased gradually from Q1 group to Q4 group: (43.58 ± 8.95), (42.58 ± 10.89), (36.58 ± 9.79), (35.37 ± 11.51) years, (1.28 ± 0.22), (1.29 ± 0.23), (1.17 ± 0.28), (1.04 ± 0.22) mmol/L; while BMI, uric acid, IGF-1 and HOMA-IR increased gradually: (25.75 ± 2.86), (27.33 ± 3.94), (26.16 ± 2.94), (28.76 ± 3.69) kg/m2, (190.73 ± 28.80), (249.57 ± 12.00), (325.75 ± 25.61), (430.39 ± 58.41) mmol/L, (594.50 ± 222.45), (733.06 ± 212.42), (774.90 ± 287.87), (962.00 ± 323.36) μg/L, 2.09 (1.64, 2.09), 3.02 (0.94, 3.55), 3.53 (2.31, 6.48), 4.09 (2.52, 5.41), there were statistical differences (P﹤0.05 or﹤0.01). Pearson correlation analysis result showed that uric acid was positive correlation with IGF-1, IGF-1 index, HOMA-IR, TG and systolic blood pressure (r=0.491, 0.341, 0.372, 0.240 and 0.266; P﹤0.01 or﹤0.05), and uric acid was negative correlation with HDL-C (r =-0.367, P﹤0.01). After adjustment for sex, age, duration of disease and BMI, uric acid was still positive correlation with IGF-1 and IGF-1 index (r=0.352 and 0.318, P﹤0.01). Conclusions Serum uric acid level is associated with disease activity in patients with growth-hormone secreting pituitary adenoma.

Long term follow-up of growth hormone-secreting pituitary adenomas submitted to endoscopic endonasal surgery / Seguimento de longo prazo de adenomas hipofisários secretores do hormônio do crescimento submetidos à cirurgia endoscópica endonasal

ABSTRACT Objective The aim of this study was to evaluate the results of the endoscopic transsphenoidal technique for growth hormone (GH)-secreting adenomas. Methods A retrospective analysis based on medical records of 23 acromegalic patients submitted to endoscopic transsphenoidal surgery. Biochemical control was defined as basal GH < 1ng/ml, nadir GH < 0.4ng/ml after glucose load and age-adjusted IGF-1 normal at the last follow-up. Results The overall endocrinological remission rate was 39.1%. While all microademonas achieved a cure, just one third of macroadenomas went into remission. Suprasellar extension, cavernous sinus invasion and high GH levels were associated with lower rates of disease control. The most common complication was diabetes insipidus and the most severe was an ischemic stroke. Conclusion The endoscopic transsphenoidal approach is a safe and effective technique to control GH-secreting adenomas. The transcavernous approach may increase the risk of complications. Suprasellar and cavernous sinus extensions may preclude gross total resection of these tumors.

RESUMO Objetivo O objetivo do estudo é analisar os resultados da cirurgia de ressecção endoscópica transesfenoidal para adenomas secretores do hormônio do crescimento (GH). Métodos Revisão retrospectiva baseada em análise de prontuários de 23 pacientes acromegálicos submetidos à cirurgia endoscópica. Remissão foi definida por GH < 1ng/ml, nadir de GH ≤ 0,4ng/ml no teste oral de tolerância a glicose e IGF-1 normal para idade. Resultados A taxa de remissão endocrinológica foi 39,1%. Enquanto todos microadenomas alcançaram controle hormonal, apenas um terço dos macroadenomas obtiveram remissão. Extensão suprasselar, invasão do seio cavernoso e altos níveis de GH foram associados a menores taxas de controle da doença. A complicação mais comum foi diabetes insipidus e a mais grave foi acidente vascular encefálico isquêmico. Conclusão A abordagem endoscópica transesfenoidal é segura e efetiva para controle de adenomas hipofisários secretores de GH. A abordagem ao seio cavernoso pode aumentar a morbidade da cirurgia. Extensões suprasselares e no seio cavernoso podem dificultar a ressecção completa e o controle da doença.

Clinical study on the effectiveness of long-acting octreotide in acromegaly patients after surgery or gamma knife therapy of growth hormone-secreting pituitary adenoma / 中国医师进修杂志

Objective To observe the effectiveness of long-acting octreotide in the treatment of acromegaly patients who did not achieve biochemical control after neurosurgery or gamma knife therapy of growth hormone-secreting pituitary adenoma. Methods Six acromegaly patients who received long-acting octreotide treatment regularly were included. Five patients had received prior trans-sphenoidal surgery and 1 patient had received prior gamma knife therapy before admission. All patients were admitted monthly for evaluation of pituitary-target gland function and octreotide therapy. Data of treatment with octreotide for 6 months were retrospectively summarized. Results Symptoms were reported to be alleviated. Two patients achieved biochemical control of the disease. Two patients had fasting growth hormone level less than 2.5 μg/L,but insulin-like growth factor-1(IGF-1)level was still higher than the age-adjusted normal range.Another 2 patients had decreased growth hormone and IGF-1 level, but both still higher than the normal range. Compared with baseline, IGF-1 level was decreased after treatment:(371.83 ± 217.46)μg/L vs.(713.33 ± 198.29)μg/L,and there was statistical difference (P = 0.017). There were no statistical differences in glycated hemoglobin and fasting plasma glucose before and after octreotide treatment (P > 0.05). Conclusions For acromegaly patients who do not achieve biochemical control after neurosurgery or gamma knife therapy, long-acting octreotide can effectively control IGF-1 level and increase the biochemical control rate of the disease.

Nursing of patients undergoing operations on growth hormone-secreting pituitary adenoma complicated by sleep apnea syndrome / 现代临床护理

Objective To summarize the effect of surgical treatment and nursing strategies of patients with growth hormone-secreting pituitary adenoma complicated by sleep apnea syndrome. Method Forty-three cases with growth hormone-secreting pituitary adenoma complicated by sleep apnea syndrome underwent surgical treatment in our department , with their history retrospectively analyzed to compare the hormone levels and blood oxygen saturation between pre-and post-operation. Result After the operation, both levels of the hormone and blood oxygen saturation were improved than those before operation; the incidence of sleep apnea syndrome was also lower than that before operation (all P<0.05). Conclusions Surgical treatment is better for patients with growth hormone-secreting pituitary adenoma complicated by sleep apnea syndrome. Reasonable treatment and effective nursing are favorable for the recovery of patients.

Pituitary macroadenoma presenting as a nasal tumor: case report / Macroadenoma hipofisário, apresentando-se como um tumor nasal: relato de caso

CONTEXT: Pituitary macroadenomas are rare intracranial tumors. In a few cases, they may present aggressive behavior and invade the sphenoid sinus and nasal cavity, causing unusual symptoms. In this paper, we report an atypical case of pituitary adenoma presenting as a nasal mass. CASE REPORT: The patient was a 44-year-old woman who had had amenorrhea and galactorrhea for ten months, with associated nasal obstruction, macroglossia and acromegaly. Both growth hormone and prolactin levels were increased. Magnetic resonance imaging showed a large mass originating from the lower surface of the pituitary gland, associated with sella turcica erosion and tumor extension through the sphenoid sinus and nasal cavity. Histopathological analysis demonstrated a chromophobe pituitary adenoma with densely packed rounded epithelial cells, with some atypias and rare mitotic figures. There was no evidence of metastases. CONCLUSION: Macroadenoma invading the nasal cavity is a rare condition and few similar cases have been reported in the literature. This study contributes towards showing that tumor extension to the sphenoid sinus and nasopharynx needs to be considered and investigated in order to make an early diagnosis when atypical symptoms like nasal obstruction are present. .

CONTEXTO: Macroadenomas hipofisários são tumores intracraniais raros. Em alguns casos, podem apresentar comportamento agressivo e invadir o seio esfenoidal e a cavidade nasal, causando sintomas não usuais. Neste relato de caso, descrevemos um caso atípico de adenoma hipofisário manifestando-se como uma massa nasal. RELATO DE CASO: A paciente de 44 anos, do sexo feminino, apresentava amenorreia e galactorreia por 10 meses associando-se a obstrução nasal, macroglossia e acromegalia. Os níveis do hormônio de crescimento e de prolactina apresentaram-se aumentados. Ressonância magnética mostrou uma grande massa originada da superfície inferior da glândula hipofisária associada com erosão da sela túrcica e extensão do tumor através do seio esfenoidal e cavidade nasal. Análise histopatológica demonstrou adenoma hipofisário cromófobo com células epiteliais arrendondadas densamente agrupadas com algumas atipias e escassas figuras de mitose. Não houve evidências de metástase. CONCLUSÃO: O macroadenoma invasivo para a cavidade nasal é uma condição rara e há poucos relatos similares descritos na literatura. Este trabalho contribui para mostrar que, na presença de sintomas atípicos como a obstrução nasal, a extensão para o seio esfenoidal e para a nasofaringe deve ser considerada e investigada para um diagnóstico precoce. .

Postoperative structural complications after microscopic transsphenoidal surgery of GH secreting pituitary adenomas / Complicações estruturais pós-operatórias após microcirurgia transesfenoidal de adenomas pituitários produtores de GH

Objective: Analyzing the rate of structural complications after transsphenoidal surgery for removal of growth hormone (GH) secreting pituitary adenomas. Methods: Retrospective study of 58 patients who underwent microscopic transsphenoidal neurosurgery for GH secreting pituitary adenomas exeresis in Curitiba, Parana state, Brazil, between 1998 and 2011 by the same neurosurgeon. The Criteria for diagnosis of complications were clinical. Results: Five (8,6%) of the 58 patients who underwent transsphenoidal surgery developed postoperative anatomical complications, which was due to sixth cranial nerve palsy (3,4%), surgical wound infection (1,7%) and CSF fistula (3,4%). Conclusion: The rate of postoperative complications observed in the present study is likely the literature review. There is a drop in the rate of complications with increasing experience of the neurosurgeon.

Objetivo: Analisar a taxa de complicações anatômicas após cirurgia transesfenoidal para remoção de adenoma hipofisário produtor de hormônio do crescimento (GH). Métodos: Estudo retrospectivo de 58 pacientes operados por microcirurgia transesfenoidal para exérese de adenomas pituitários produtores de GH em Curitiba, Paraná, Brasil, entre 1998 e 2011, realizados pelo mesmo neurocirurgião. Diagnóstico das complicações foi clínico. Resultados: Dos 58 pacientes submetidos à cirurgia transesfenoidal, 5 (8,6%) desenvolveram complicações anatômicas, 3,4% foram em decorrência de paresia temporária do sexto nervo craniano, 1,7%, de infecção da ferida operatória, e 3,4%, de fístula liquórica. Conclusão: A taxa de complicações pós-operatórias observada no presente estudo está semelhante à da revisão literária. Há uma queda no índice de complicações conforme aumenta a experiência do neurocirurgião.

O Sistema do Hormônio de Crescimento: interações com a pele / Growth Hormone System: skin interactions

O artigo descreve o Sistema do Hormônio de Crescimento (GH), enfatizando suas possíveis ações nas células da epiderme, nas estruturas da derme e na cicatrização de feridas cutâneas. Para tanto, fez-se uma revisão dos conhecimentos sobre o hormônio do crescimento, seu receptor, a proteína carreadora deste hormônio e demais proteínas envolvidas no mecanismo que o GH utiliza para a sua manifestação nos tecidos cutâneos.

This paper describes the growth hormone system, emphasizing its possible effects on epidermal cells, dermal structures and wound healing. A review of the literature was conducted on studies concerning the growth hormone molecule, its receptor and carrier proteins and the other proteins involved in the mechanisms of its manifestation in dermal tissue.

Análise do gene AIP na acromegalia familial isolada / Analysis of the AIP gene in familial isolated acromegaly

A acromegalia é doença insidiosa e desfigurante caracterizada por um crescimento desproporcional dos ossos das mãos, pés e do crânio devido à exposição crônica a altos níveis de hormônio de crescimento (GH) e de seu efetor insuline growth factor 1 (IGF-1). Trata-se de uma doença rara, com incidência estimada de 3-4 casos por milhão, com prevalência de aproximadamente 50 casos por milhão de pessoas. A principal causa da acromegalia é a presença de um tumor hipofisário secretor de GH (somatotropinoma). Caso o somatotropinoma ocorra durante a infância ou adolescência, antes do fechamento das epífises dos ossos longos, a criança crescerá longitudinalmente de forma descontrolada, caracterizando a forma clínica gigantismo. Na grande maioria dos casos a acromegalia se apresenta na forma esporádica, entretanto casos familiais da doença podem ocorrer associados à Neoplasia Endócrina Múltipla tipo 1 (NEM-1), ao complexo de Carney (CNC) e à acromegalia familial isolada (IFS). Os genes responsáveis pela NEM-1 (MEN1) e CNC (PRKAR1A) foram clonados há mais 10 anos, entretanto etiologia molecular da IFS permaneceu desconhecida até recentemente. Vierimaa et al. (2006) combinaram estudos de ligação por análise de polimorfismos e estudos de expressão gênica e identificaram mutações no gene AIP em famílias com acromegalia não-NEM-1 e não-CNC; além de perda de heterozigose (LOH) nos somatotropinomas dos pacientes com mutação AIP. No presente estudo, investigamos o gene AIP em três famílias brasileiras com IFS e em seus tumores (hipofisários e não-hipofisários). Descrevemos uma nova mutação AIP (Y268X) em uma família brasileira com IFS, confirmando o papel desse novo gene na predisposição a tumores hipofisários. A partir de dados gerados em uma extensa revisão da literatura, sugerimos que os tumores hipofisários familiais isolados são doenças multigênicas que possuiriam um gene principal, mas que sofreriam influência de outros genes/loci ainda pouco caracterizados...

Acromegaly is a rare disfigurating and insidious disease characterized by enlargement of hands, feet and skull bones due to excess of growth hormone (GH) secreted by a pituitary tumor (somatotropinoma). The majority of the cases with acromegaly is sporadic, however it may occur in association with inherited disorders as Multiple Endocrine Neoplasia type 1 (MEN1), Carney complex (CNC) and Isolated Familial Somatotropinoma (IFS). The genes associated with MEN1 syndrome (MEN1) and CNC (PRKAR1A) have been described more than a decade ago, however until very recently the molecular etiology of IFS remained unknown. Using a combined strategy of single nucleotide polymorphism (SNP) analysis and gene expression analysis, Vierimaa et al. (2006) described mutations in the AIP gene occurring in families with acromegaly not associated with MEN1 and CNC. In the current study, we investigated three Brazilian families with IFS and were able to describe two germline mutations in the AIP gene, confirming the role of this new gene in the predisposition to familial somatotropinoma. We revised the literature of genetic studies of isolated pituitary adenoma syndromes, which indicated a genetic heterogeneity as well as possible multigenic inheritance for these diseases. Thus, we investigated the role of several genes/loci (SSTR2, SSTR5, CDKN1B, AHR, PRKAR1A, PTTG, PROP1, MEG3, RB1 and 2p16) selected as potentially acting as phenotypic modulators in IFS. Our data indicate that AIP-mutated patients are prone to pituitary disease, however it is necessary the co-segregation of markers located at oncogenic regions to the development of the pituitary tumors and manifestation of the disease. Herein, we also present the first somatic analysis of non-pituitary tumors of AIP-mutated patients. A potential role of AIP, which is implicated in the cAMP pathway, could not be excluded in the development of an adrenocortical carcinoma.

Surgical Results of Growth Hormone-Secreting Pituitary Adenoma

OBJECTIVE: We retrospectively analyzed the surgical outcomes of 42 patients with growth hormone (GH)-secreting pituitary adenoma to evaluate the clinical manifestations and to determine which preoperative factors that significantly influence the remission. METHODS: Forty-two patients with GH-secreting pituitary adenoma underwent transsphenoidal surgery (TSS) between 1995 and 2007. The patient group included 23 women and 19 men, with a mean age of 40.2 (range 13-61) years, and a mean follow-up duration of 49.4 (range 3-178) months after the operation. For comparable radiological criteria, we classified parasellar growth into five grades according to the Knosp classification. We analyzed the surgical results of the patients according to the most recent stringent criteria for cure. RESULTS: The overall rate of endocrinological remission in the group of 42 patients after primary TSS was 64% (26 of 42). The remission rate was 67% (8 of 12) for microadenoma and 60% (18 of 30) for macroadenoma. The remission rate was 30% (3 of 10) for the group with cavernous sinus invasion and 72% (23 of 32) for the group with intact cavernous sinus. Cavernous sinus invasion in Knosp grade III and IV was significantly correlated with the remission rate. There was a significant relationship between preoperative mean GH concentration and early postoperative outcome, with most patients in remission having a lower preoperative GH concentration. CONCLUSION: TSS is thought to be an effective primary treatment for GH-secreting pituitary adenomas according to the most recent criteria of cure. Because the remission rate in cases with cavernous sinus invasion is very low, early detection of the tumor before it extends into the cavernous sinus and a long-term endocrinological and radiological follow-up are necessary in order to improve the remission rate of acromegaly.

In Situ Hybridization Analysis of Human Growth Hormone and Prolactin Secreting Pitultary Adenomas / 대한내분비학회지

A non-isotopic in situ hybridization method with biotin-labelled oligonucleotide probes was used to examine growth hormone(GH) and prolactin(PRL) gene expression in 32 patients with pituitary adenomas; 13 were prolactinomas, 8 GH secreting adenomas, and 11 mixed GH and PRL secreting adenomas.Positive immunostaining for GH was found in all patients with GH secreting adenomas, and mixed GH and PRL secreting adenomas. Positive immunostaining for PRL was found in all patients with prolactinomas and 9(81.8%) of 11 mixed GH and PRL secreting adenomas, 5(62.5%) of 8 GH secreting adenomas. Immunohistochemistry revealed that 13 were lactotrope adenomas, 5 somatotrope adenomas, and 14 GH and PRL cell adenomas.In situ hybridization revealed that GH mRNA expression was found in all the patients with somatotrope adenomas and GH and PRL cell adenomas, and 6(46.1%) of 13 lactotrope adenomas. PRL mRNA expression was 100% in lactotrope and GH and PRL cell adenomas, and 4(80.0%) of 5 somatotrope adenomas.The patients with a clinical diagnosis of acromegaly had detectable PRL mRNA in their neoplasm and it is suggested that the PRL cells in the adenomas did not result from dedifferentiation, but from the neoplastic stimulus for some mixed tumors probably occurred in cells previously committed to produce PRL and GH. In lactotrope adenomas, the PRL cells of the patients without expression of GH mRNA may be arised from cells programmed to secrete PRL or precussor PRL cells rather than from mixed GH-PRL cells. The finding that some patients produced mRNA detectable by in situ hybridization, but no hormone detectable by immunohistochemistry within tumor was suggested of a silent adenoma.These observations indicated that in situ hybridization studies may improve the classification of pituitary adenomas and may provide a precise knowledge of the biology of these neoplasms.