title: Negative correlation between tumour size and cortisol/ACTH ratios in patients with Cushing's disease harbouring microadenomas or macroadenomas.
abstract: OBJECTIVE
  Pituitary macroadenomas (MACs) represent 10-30 % of Cushing's disease (CD) cases. The aim of this study was to report the clinical, laboratorial and imaging features and postsurgical outcomes of microadenoma (MIC) and MAC patients.
  
  
  METHODS
  Retrospective study with 317 CD patients (median 32 years old, range 9-71 years) admitted between 1990 and 2014, 74 (23.3 %) of whom had MAC.
  
  
  RESULTS
  Hirsutism, plethora facial, muscular weakness and muscular atrophy were more frequent in the MIC patients. Nephrolithiasis, osteopenia, hyperprolactinaemia and galactorrhoea were more prevalent in MAC patients. The morning serum cortisol (Fs), nocturnal salivary cortisol (NSC), nocturnal Fs (Fs 2400 h), low- and high-dose dexamethasone suppression test results and CRH and desmopressin test results were similar between the subgroups. MIC patients showed higher urinary cortisol at 24 h (UC), and MAC patients presented higher ACTH levels but lower Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. There were negative correlations of tumour size with Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. Overall, the postsurgical remission and recurrence rates were similar between MIC and MAC. However, patients in remission (MIC + MAC) showed smaller tumour diameters and a lower prevalence of invasion and extension on MRI.
  
  
  CONCLUSIONS
  Despite exhibiting higher plasma ACTH levels, CD patients with MAC presented lower cortisol/ACTH ratios than did patients with MIC, with a negative correlation between tumour size and cortisol/ACTH ratios. The overall postsurgical remission and recurrence rates were similar between MIC and MAC patients, with those with larger and/or invasive tumours showing a lower remission rate.
authors.affiliation: Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of Sao Paulo Medical School, São Paulo, SP, Brazil. marcioc-machado@uol.com.br.|Laboratory of Cellular and Molecular Endocrinology LIM-25, University of Sao Paulo Medical School, São Paulo, SP, Brazil. marcioc-machado@uol.com.br.|Endocrinology Division, AC Camargo Cancer Center, São Paulo, SP, Brazil. marcioc-machado@uol.com.br.
authors.forename: M C
authors.initials: MC
authors.lastname: Machado
authors.affiliation: Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of Sao Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: A E E
authors.initials: AE
authors.lastname: Alcantara
authors.affiliation: Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of Sao Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: A C L
authors.initials: AC
authors.lastname: Pereira
authors.affiliation: Division of Neurosurgery, University of Sao Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: V A S
authors.initials: VA
authors.lastname: Cescato
authors.affiliation: Division of Neurosurgery, University of Sao Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: N R
authors.initials: NR
authors.lastname: Castro Musolino
authors.affiliation: Laboratório de Hormônios e Genética Molecular LIM-42, University of Sao Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: B B
authors.initials: BB
authors.lastname: de Mendonça
authors.affiliation: Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of Sao Paulo Medical School, São Paulo, SP, Brazil.|Laboratory of Cellular and Molecular Endocrinology LIM-25, University of Sao Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: M D
authors.initials: MD
authors.lastname: Bronstein
authors.affiliation: Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of Sao Paulo Medical School, São Paulo, SP, Brazil.|Laboratório de Hormônios e Genética Molecular LIM-42, University of Sao Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: M C B V
authors.initials: MC
authors.lastname: Fragoso
mesh_terms: D000236:Adenoma / Q000097:blood* / Q000209:etiology / Q000473:pathology; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000368:Aged; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D047748:Pituitary ACTH Hypersecretion / Q000150:complications* / Q000503:physiopathology; D010911:Pituitary Neoplasms / Q000097:blood* / Q000209:etiology / Q000473:pathology; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone
keywords: Cushing’s disease; Macroadenoma; Microadenoma; Pituitary surgery