Negative surgical exploration in patients with Cushing’s disease: benefit of two-thirds gland resection on remission rate and a review of the literature

OBJECTIVEThe authors report their single-institution experience with the pathological findings, rates of remission, and complications in patients with presumed Cushing’s disease (CD) who underwent a two-thirds pituitary gland resection when no adenoma was identified at the time of transsphenoidal surgery (TSS). The authors also review the literature on patients with CD, negative surgical exploration, and histological findings.METHODSThis study is a retrospective analysis of cases found in neurosurgery and pathology department databases between 1989 and 2011. In all cases, patients had been operated on by the same neurosurgeon (K.O.L.). Twenty-two (13.6%) of 161 patients who underwent TSS for CD had no adenoma identified intraoperatively after systematic exploration of the entire gland; these patients all underwent a two-thirds pituitary gland resection. A chart review was performed to assess treatment data points as well as clinical and biochemical remission status.RESULTSOf the 22 patients who underwent two-thirds gland resection, 6 (27.3%) ultimately had lesions found on final pathology. All 6 patients were found to have a distinct adrenocorticotropic hormone (ACTH) cell adenoma. Sixteen (72.7%) of the patients had no tumor identified, with 3 of these patients suspected of having ACTH cell hyperplasia. The follow-up duration for the entire group was between 14 and 315 months (mean 98.9 months, median 77 months). Remission rates were 100% (6/6 patients) for the ACTH cell adenoma group and 75% (12/16) for the group without adenoma. Overall, 18 (81.8%) of the 22 patients had no evidence of hypercortisolism at last follow-up, and 4 patients (18%) had persistent hypercortisolism, defined as a postoperative cortisol level > 5 μg/dl. Of these 4 patients, 1 was suspected of harboring a cavernous sinus adenoma, 2 were found to have lung tumors secreting ACTH, and 1 remained with an undiagnosed etiology. Rates of postoperative complications were low.CONCLUSIONSThe diagnosis and treatment of CD can be challenging for neurosurgeons, endocrinologists, and pathologists alike. Failure to find a discrete adenoma at the time of surgery occurs in at least 10%–15% of cases, even in experienced centers. The current literature provides little guidance regarding rational intraoperative approaches in such cases. The authors’ experience with 161 patients with CD, when no intraoperative tumor was localized, demonstrates the utility of a two-thirds pituitary gland resection with a novel and effective surgical strategy, as suggested by a high initial remission rate and a low operative morbidity.

Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry

In 1996, the German Registry of Pituitary Tumors was founded by the Pituitary Section of the German Society of Endocrinology as a reference center for collection and consultant pathohistological studies of pituitary tumors. The experiences of the first 10 years of this registry based on 4122 cases will herein be reported. The data supplement former collections of the years 1970–1995 with 3480 surgically removed tumors or lesions of the pituitary region. The cases were studied using histology, immunostainings and in some cases also molecular pathology or electron microscopy. The adenomas were classified according to the current World Health Organization classification in the version of 2004. From 1996 on 3489 adenomas (84.6%), 5 pituitary carcinomas (0.12%), 133 craniophar-yngiomas (3.2%), 39 meningiomas (0.94%), 25 metastases (0.6%), 22 chordomas (0.5%), 115 cystic non-neoplastic lesions (2.8%), and 46 inflammatory lesions (1.1%, 248 other lesions or normal tissue (6.0%)) were collected by us. The adenomas (100%) were classified into densely granulated GH cell adenomas (9.2%), sparsely granulated GH cell adenomas (6.3%), sparsely granulated prolactin (PRL) cell adenomas (8.9%), densely granulated PRL cell adenomas (0.3%), mixed GH/PRL cell adenomas (5.2%), mammosomatotropic adenomas (1.1%), acidophilic stem cell adenomas (0.2%), densely granulated ACTH cell adenomas (7.2%), sparsely granulated ACTH cell adenomas (7.9%), Crooke cell adenomas (0.03%), TSH cell adenomas (1.5%), FSH/LH cell adenomas (24.8%), null cell adenomas (19.3%), null cell adenoma, oncocytic variant (5.8%), and plurihormonal adenomas (1.3%). Following the WHO classification of 2004, the new entity ‘atypical adenoma’ was found in 12 cases in 2005. Various prognostic parameters and clinical implications are discussed.

Characteristics of the pituitary immunopositive ACTH cells in rat females after chronic exposure to constant light

The effects of chronic exposure to light of adult female Wistar rats on growth and function of pituitary adrenocorticotropes (ACTH cells) were examined. The animals were exposed to continuous light of 600 lux for 95 days, starting on day 30 of age. Control rats were kept under a 12:12 h light-dark cycle, at ambient temperature. ACTH-producing cells were studied using the peroxidase-antiperoxidase immunohistochemical procedure and blood samples were collected for hormone analyses. In animals exposed to a chronic light-treatment all morphometric parameters measured throughout the present study i.e.: ACTH cell volume, nuclear volume and relative volume density were increased by 22% and the differences between this group and the controls were statistically significant (p<0.05). The concentration of plasma ACTH was elevated by 13% in light-exposed group in comparison with the control and this difference was statistically significant (p<0.05), as well. These findings suggest that continuous exposure to light is specifically involved in growth and secretory activity of ACTH cells of adenohypophysis of rat females.