Silent Corticotroph Adenoma Transformed in Secreting Adenoma with Severe Cushing's Disease after Two Pituitary Surgeries

Ghervan, Cristina

doi:10.4183/aeb.2014.283

Cited by 3 publications

(6 citation statements)

References 24 publications

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“…There are 14 reports in the literature of secondary occurrence of CD from a tumor previously diagnosed as an SCA or NFPA. 4 – 17 These cases share a variety of clinical features. All but one of the patients was women, and most were fertile when the tumor became active.…”

Section: Discussionmentioning

confidence: 99%

“…Rarely, nonfunctional pituitary adenomas (NFPAs) may gain secretory function, but there have been a few case reports of metamorphosis to CD. 4 – 17 We describe the clinical course of a man with a proven NFPA whose tumor became functional and began to secrete biologically active ACTH that led to severe Cushing syndrome, review published reports of other cases, and discuss the putative mechanisms of tumor transformation.…”

Section: Introductionmentioning

confidence: 99%

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Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma

Fang

Tian

Wu³

et al. 2015

Medicine

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We describe a very rare case of nonfunctional pituitary adenoma (NFPA) that exhibited corticotrophic activity after resection and radiotherapy. The possible mechanisms of the transformation from NFPA to Cushing disease (CD) are discussed.A 43-year-old man presented with impaired vision, bilateral frontal headaches, and hyposexuality. He had no symptoms suggestive of hypercortisolism, and 8 am plasma cortisol concentration was 67.88 ng/mL. Brain imaging revealed a 15 × 15 × 21-mm sellar mass suggestive of a macroadenoma. The tumor was resected by transsphenoidal surgery and identified by immunohistochemical analysis as a chromophobic adenoma that did not stain for pituitary hormones. The patient was treated with prednisone and levothyroxine replacement therapy. After a third recurrence, the patient presented with clinical features and physical signs of Cushing syndrome. Plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations were elevated, and there was a loss of circadian rhythms. Inferior petrosal sinus sampling after desmopressin showed the central–peripheral ACTH ratio was greater than 3:1. A repeat transsphenoidal resection was undertaken. Immunohistochemistry revealed ACTH positivity. Three months following surgery, imaging showed little residual tumor, but plasma ACTH remained elevated. He was referred for postoperative Gamma Knife radiotherapy.The immunological activity and biological features of the hormones secreted from a pituitary adenoma vary with time. Because long-term outcomes are unpredictable, postoperative follow-up is essential to detect postoperative transformation from NFPA to CD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma

Fang

Tian

Wu³

et al. 2015

Medicine

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“…Several hypotheses have been suggested as possible precipitating factors. Subclinical haemorrhage or infarction could modify the tumour hormone secretion and induce the phenotype switch [13,43,44]. This could be a possibility in PA with changing phenotype from functioning to non-functioning.…”

Section: Changing Phenotype Precipitating Factorsmentioning

confidence: 99%

Pituitary Adenomas with Changing Phenotype: A Systematic Review

Guerrero-Pérez

Marengo

Vidal

et al. 2020

Exp Clin Endocrinol Diabetes

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Purpose and Methods Phenotype transformation in pituitary adenomas (PA) is a little known and unexpected clinical phenomenon. We describe two illustrative cases and performed a systematic review of cases reported in literature. Results Case 1: A 24-year-old woman underwent surgery because of Cushing’s disease. A complete tumor resection and hypercortisolism resolution was achieved. Two years later, tumor recurred but clinical and hormonal hypercortisolism were absent. Case 2: A 77-year-old woman underwent surgery due to acromegaly. A complete tumor resection and GH excess remission was achieved. Four years later, tumor recurred but clinical and hormonal acromegaly was ruled out. Search of literature: From 20 patients (including our cases), 75% were female with median age 45 (19) years. Ten patients (50%) had initially functioning PA: 8 switched to NFPA (5 ACTH-secreting PA, 2 prolactinomas and 1 acromegaly) and 2 exchanged to acromegaly from TSH-secreting PA and microprolactinoma. One patient developed a pituitary carcinoma from ACTH-secreting PA. Ten patients (50%) initially had NFPA; 9 developed Cushing’s disease (4 silent corticotroph adenomas, 4 null cell PA and 1 managed conservatively). One patient with silent somatotroph PA changed to acromegaly. Treatments before transformation were surgery (80%), radiotherapy (40%), pharmacological (40%) and in 2 patients switching happened without any treatment. Median follow-up until transformation was 72 months (range 12–276). Conclusion PA can change from functioning to (NF) non-functioning (vice versa) and even exchange their hormonal expression. Clinicians should be aware and a careful lifelong follow-up is mandatory to detect it.

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“…They are seen typically in females, but they are more aggressive in males than in females. They usually generate invasive adenomas (19). To our knowledge, there are no studies investigating the relationship between invasiveness and histopathologic subtypes of pituitary adenomas in the literature.…”

Section: Invasiveness and Prolactinomasmentioning

confidence: 99%

“…Typically, GH-secreting, ACTH-secreting, and prolactin-secreting adenomas had more aggressive features (19). Shimon I et al found "hst" protein in prolactinomas but not in normal pituitary tissue.…”

Section: Invasiveness and Prolactinomasmentioning

confidence: 99%

Low 06-Methylguanine-DNA Methytransferase (MGMT) and Pan-Cytokeratin (PAN-CK) Expression via Immunohistochemistry in Pituitary Adenomas

et al. 2017

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Introduction. Pituitary adenomas (PA) are the third most common intracranial tumors, with an incidence rate of 10-15%. More than half are invasive, infiltrating adjacent structures. The primary objective of this project was to determine whether MGMT expression is associated with the invasiveness of PA. Material and Method. All patients who underwent surgical decompression consecutively between 2007-2012 were included. All data were obtained from the case records. Formalin-fixed paraffin-embedded (FFPE) tissue specimens were stained with hematoxylin and eosin (HE) and then examined via light microscope. Paraffin blocks that lacked necrosis and hemorrhage were chosen for histologic examination. In addition to an immunoprofile battery that consisted of Ki-67 and p53, MGMT, S-100 and Pan-CK were evaluated as well. Results. The subjects included 25 women and 15 men. The mean age was 48.9 ± 14.5 years. Of these, 63% of cases involved the invasion of adjacent structures. Of the PA, 17 (42%) were non-functioning pituitary adenomas (NFPA). There was a statistically significant relationship between the invasiveness and Ki-67, p53, MGMT expression, and prolactinoma. Gonodotropinomas were mostly non-invasive. FPAs presented invasive features more frequently than NFPAs. Pan-CK was positive in GH-secreting adenomas but negative in FSH-and LH-secreting adenomas. Conclusion. Ki-67 and p53 in lower expression level can be used for evaluating invasiveness but not for recurrence. MGMT expression can be a useful IHC indicator for invasiveness. However, Pan-CK cannot be used for invasiveness or aggressiveness.

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Silent Corticotroph Adenoma Transformed in Secreting Adenoma with Severe Cushing's Disease after Two Pituitary Surgeries

Cited by 3 publications

References 24 publications

Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma

Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma

Pituitary Adenomas with Changing Phenotype: A Systematic Review

Low 06-Methylguanine-DNA Methytransferase (MGMT) and Pan-Cytokeratin (PAN-CK) Expression via Immunohistochemistry in Pituitary Adenomas

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