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Doctoral Thesis
DOI
Document
Author
Full name
Fabio Yoshiaki Tanno
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Srougi, Miguel (President)
Castilho, Lisias Nogueira
Chambô, José Luis
Gomes, Larissa Garcia
Title in Portuguese
Cirurgia poupadora de adrenal: uma nova abordagem no tratamento da hiperplasia macronodular adrenal primária
Keywords in Portuguese
Adrenalectomia
Glândulas suprarrenais/cirurgia
Hiperplasia macronodular adrenal primária
Insuficiência adrenal
Laparoscopia
Síndrome de Cushing/cirurgia
Síndrome de Cushing/diagnóstico
Testes de função do córtex suprarrenal
Tomografia
Tomografia por emissão de pósitrons
Abstract in Portuguese
INTRODUÇÃO: A hiperplasia macronodular adrenal primaria (HMAP) e uma doenca rara, caracterizada pela presenca de macronodulos nas adrenais e por uma producao aumentada, autonoma e sustentada de cortisol. Constitui uma causa incomum de sindrome de Cushing. O tratamento cirurgico e indicado visando o controle do hipecortisolismo e de suas consequencias. Estudamos uma nova abordagem cirurgica, a cirurgia poupadora de adrenal (adrenalectomia total laparoscopica do lado de maior volume/ atividade metabolica com adrenalectomia parcial laparoscopica contralateral), no tratamento da HMAP com o objetivo de possibilitar o controle do hipercortisolismo sem a necessidade de reposicao hormonal. OBJETIVOS: Os objetivos do estudo foram: 1) avaliar a efetividade e seguranca da cirurgia poupadora de adrenal e como foi a evolucao dos pacientes operados, do ponto de vista metabolico e clinico; 2) definir quais os fatores que influenciaram no tempo de recuperacao da funcao do eixo hipotalamo-hipofise-adrenal no pos-operatorio; 3) avaliar correlacao entre o volume das adrenais e a captacao de radioisotopo na tomografia por emissao de positrons com fluorodesoxiglicose marcada (18F-FDGPET/ CT). MÉTODOS: Dezessete pacientes com diagnostico de HMAP submetidos a cirurgia poupadora de adrenal, com pelo menos 12 meses de seguimento (mediana de seguimento de 41 meses), foram incluidos no estudo. A mediana da idade no momento da indicacao da cirurgia foi de 50 anos (41-69), e a mediana do IMC de 29 kg/m2, sendo 5 homens (29,5%) e 12 mulheres (70,5%). A adrenalectomia total foi realizada no lado com maior volume nos estudos de tomografia e maior atividade na 18F-FDGPET/ CT. O desfecho primario avaliado foi a recuperacao do eixo hipotalamo-hipofiseadrenal associada ao controle do hipercortisolismo, bem como a evolucao dos parametros clinicos e metabolicos no periodo pos-operatorio. Os desfechos secundarios incluiram a identificacao de fatores que influenciaram na recuperacao da funcao hormonal, juntamente com o estudo da correlacao entre o volume das adrenais e atividade glicolitica das glandulas. Utilizou-se tomografia com 3 meses de posoperatorio para avaliar a volumetria da adrenal remanescente. RESULTADOS: O tempo cirurgico medio foi de 199 } 39 minutos (variacao de 160-300); o tempo anestesico medio foi de 322}72 minutos (210-510). Nao ocorreram complicacoes intra-operatorias. Doze pacientes (70,5%) recuperaram a funcao da adrenal para producao de cortisol, enquanto os demais 5 (29,5%) permanecem dependentes de reposicao hormonal. O tempo medio de recuperacao da funcao da adrenal foi de 32 meses. O volume medio de glandula adrenal remanescente foi de 4,1 cm3. O nivel serico de ACTH mensuravel se mostrou um fator preditivo de menor tempo de recuperacao da funcao hormonal (p=0,003). Os pacientes operados apresentaram melhora significante do peso (88 para 82kg), da pressao arterial sistolica (145 para 121mmHg), da pressao arterial diastolica (91 para 78mmHg) e no numero de medicamentos para hipertensao arterial (2,8 para1,1). Por fim, foi confirmada a correlacao entre volume da adrenal e a captacao desta em SUV no exame de 18F-FDGPET/ CT (p=0,024). CONCLUSÕES: A cirurgia poupadora de adrenal se mostrou uma opcao segura no tratamento da HMAP, com bons resultados no controle do hipercortisolismo e na recuperacao da funcao hormonal. A cirurgia contribuiu para a melhora no peso, pressao arterial sistolica, pressao arterial diastolica e numero de medicamentos para hipertensao. Pacientes com ACTH mensuravel apresentaram melhor chance de recuperacao da funcao hormonal. Na HMAP, adrenais de maior volume tendem a apresentar maior atividade glicolitica na 18F-FDG-PET/CT
Title in English
Adrenal sparing surgery: a new approach in the treatment of primary macronodular adrenal hyperplasia
Keywords in English
Adrenal cortex function tests
Adrenal glands
Adrenal insufficiency
Adrenalectomy
Cushing syndrome/diagnosis
Cushing syndrome/surgery
Laparoscopy
Positron-emission tomography
Primary macronodular adrenal hyperplasia
Tomography
Abstract in English
INTRODUCTION: Primary macronodular adrenal hyperplasia (PMAH) is a rare disease characterized by adrenal macronodules and increased, autonomous and sustained cortisol production. This condition is an uncommon cause of Cushing's syndrome. The objective of surgical treatment is the control of excessive hormonal production and its consequences. We studied a new surgical approach that we called adrenal sparing surgery (total laparoscopic adrenalectomy of the adrenal gland with larger volume/higher metabolic activity associated with contralateral partial laparoscopic adrenalectomy), in order to achieve control of hypercortisolism without lifetime hormonal reposition disadvantages. OBJECTIVES: The objectives of this study: 1) evaluate the effectiveness and safety of adrenal sparing surgery and how was the evolution of operated patients, with clinical and metabolic parameters; 2) define which aspects influence in the time to recover the hypothalamus-pituitary-adrenal axis function in post-operative period; 3) evaluate the correlation between adrenal volume and SUV capitation on 18F-FDG-PET/CT. METHODS: Seventeen patients with diagnosed PMAH submitted to adrenal sparing surgery and, at least 12 months follow up were include in this study (median follow up of 41 months). In the moment the surgical treatment was indicated, the median age was 53 years-old (range 41- 69), median BMI was 29 kg/m2, including 5 male (29.5%) and 12 female (70.5%) patients. Total adrenalectomy was performed in the larger gland in CT and higher metabolic activity in 18F-FDG-PET/CT. The primary endpoint was the recovery of hypothalamus-pituitary-adrenal axis associated to hypercortisolism control, as well as the evolution of clinical and metabolic parameters in post-operative period. The secondary endpoints were the identification of factors that may have influenced the recovery of hormonal function, besides the study of the correlation between adrenal volume and radioisotope uptake by the glands. We used CT three months after surgery to evaluate remaining adrenal volume. RESULTS: Average surgical time was 199 } 39 minutes (range160-300); average anesthesia time was 322}72 minutes (range 210-510). There were no intra-operative complications. Twelve patients (70.5%) recovered adrenal function in cortisol production, while the other 5 remained in adrenal insufficiency The average time to adrenal function recovery was 32 months. In post-operative CT the average adrenal volume was 4.1 cm3. Measurable ACTH level (not suppressed) was associated with a better chance to recover hormonal function (p=0.003). Operated patients showed significant improvement in clinical parameters: weight reduction (88 to 82kg); reduction of both systolic (145 to 141 mmHg) and diastolic (91 to 78mmHg) blood pressures and in the number of hypertension medications (2.8 to 1.1). Finally, a correlation between adrenal volume and glycolytic uptake in 18F-FDG-PET/CT was confirmed (p=0.024). CONCLUSIONS: Adrenal sparing surgery is a safe and effective option in PMAH surgical treatment, providing high rate of hypercortisolism control and hormonal function recovery. The surgery contributed to weight reduction and improvement in hypertension and number of medications. In PMAH, larger adrenals tend to present a higher glycolytic uptake in 18F-FDG-PET/CT
 
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Publishing Date
2019-11-18
 
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