Surgical Remission of Pituitary Adenomas Confined to the Neurohypophysis in Cushing’s Disease

Abstract Context: Partial or total removal of the pituitary cures 60–80% of patients with Cushing’s disease (CD) in whom an adenoma cannot be identified at surgery. Many patients who fail complete or partial hypophysectomy are cured by sellar and parasellar irradiation. Design/Patients: As part of a series of prospective studies of CD, we identified 12 patients (34.5 ± 19.9 yr; 11 females; four children) with tumors located completely within the neurohypophysis among 730 patients undergoing surgery for CD. Setting: The study was conducted at a tertiary referral center at a clinical research hospital. Results: All 12 patients had clinical and biochemically defined CD. Tumor was visible at surgery in 11 patients; all 12 tumors were positive for ACTH by immunohistochemistry. Two tumors were excised at repeat surgery because of persistent hypercortisolism within 14 d of negative exploration of the adenohypophysis. There were no long-term complications. At follow-up of 71.9 ± 34.2 months (range, 30–138 months), all patients are in remission of CD. Adult patients have had significant improvement in weight and body mass indices, with restoration of normal menses in all women. In the four pediatric patients, height, weight, and body mass indices have been restored toward normal by surgical remission of CD. Hypopituitarism or long-term neurohypophysial dysfunction has not occurred. Conclusion: We report a new subset of patients with CD, ACTH-secreting adenomas that arise wholly within the posterior lobe of the pituitary gland. In cases of CD in which an adenoma is not identified in the adenohypophysis and in patients with persistent hypercortisolism after complete or partial excision of the anterior lobe, tumor within the neurohypophysis should be considered; selective adenomectomy of a neurohypophyseal, ACTH-secreting tumor can produce long-term remission.

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Long-term results of treatment in patients with ACTH-secreting pituitary macroadenomas

Acta Endocrinologica ◽

10.1530/eje.0.1490195 ◽

2003 ◽

pp. 195-200 ◽

Cited By ~ 56

Author(s):

S Cannavo ◽

B Almoto ◽

C Dall'Asta ◽

S Corsello ◽

RM Lovicu ◽

...

Keyword(s):

Cavernous Sinus ◽

Cushing’S Disease ◽

Long Term Results ◽

Cushing's Disease ◽

Tumor Diameter ◽

Pituitary Macroadenoma ◽

Second Surgery ◽

Acth Secreting

OBJECTIVE: Since Cushing's disease due to large pituitary tumors is rare, we evaluated biochemical characteristics at entry and the results of first surgical approach and of adjuvant therapeutic strategies during a long-term follow-up period. DESIGN: We studied 26 patients (nine male, 17 female; 42.5+/-12.7 years, mean+/-s.e.) with ACTH-secreting pituitary macroadenoma (tumor diameter: 11-40 mm). METHODS: At entry, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were measured in all patients, a high-dose dexamethasone (dexa) suppression test was evaluated in 22 cases and a corticotrophin releasing hormone (CRH) test in 20 cases. Patients were re-evaluated after operation and, when not cured, they underwent second surgery, radiotherapy and/or ketoconazole treatment. The follow-up period was 78+/-10 months. RESULTS: Before surgery, dexa decreased ACTH (>50% of baseline) in only 14/22 patients. The CRH-stimulated ACTH/cortisol response was normal in six patients, impaired in six patients and exaggerated in eight patients. After operation eight patients were cured, nine had normalized cortisol levels and nine were not cured. Pre-surgery, mean ACTH values were significantly higher in the not cured patients than in those normalized (P<0.05) and cured (P<0.01); the ACTH response to CRH was impaired in only six patients of the not cured group. The tumour diameter was significantly less in cured patients (P<0.02) and in normalized patients (P<0.05) than in the not cured ones. Magnetic resonance imaging (MRI) showed invasion of the cavernous sinus in 2/9 normalized, and in 6/9 not cured patients. After surgery, ACTH, cortisol and UFC were significantly lower than at entry in cured and in normalized patients, but not in not cured patients. In the cured group, the disease recurred in one patient who was unsuccessfully treated with ketoconazole. In the normalized group, a relapse occurred in eight patients: radiotherapy and ketoconazole induced cortisol normalization in one case, hypoadrenalism in one case and were ineffective in another one, while five patients were lost at follow-up. In the not cured group, eight patients underwent second surgery, radiotherapy and/or ketoconazole, while one patient was lost at follow-up. These therapies induced cortisol normalization in two patients and hypoadrenalism in one. CONCLUSIONS: (i) A sub-set of patients with ACTH-secreting pituitary macroadenoma showed low sensitivity to high doses of dexamethasone and to CRH, (ii) pituitary surgery cured Cushing's disease in a minority of patients, (iii) high baseline ACTH levels, impaired ACTH response to CRH, increased tumor size or invasion of the cavernous sinus were unfavourable prognostic factors for surgical therapy, and (iv) second surgery, radiotherapy and/or ketaconazole cured or normalized hypercortisolism in half of the patients with recurrence or not cured.

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Endocrinological evaluation of ACTH-secreting pituitary microadenomas: their location and α-melanocyte stimulating hormone immunoreactivity

Journal of Neurosurgery ◽

10.3171/jns.1992.76.6.0944 ◽

1992 ◽

Vol 76 (6) ◽

pp. 944-947 ◽

Cited By ~ 4

Author(s):

Takashi Nagaya ◽

Akio Kuwayama ◽

Hisao Seo ◽

Nobuhiro Tsukamoto ◽

Nobuo Matsui ◽

...

Keyword(s):

Cushing’S Disease ◽

Anterior Lobe ◽

Cushing's Disease ◽

Lower Sensitivity ◽

Intermediate Lobe ◽

Posterior Lobe ◽

Content Type ◽

Melanocyte Stimulating Hormone ◽

Acth Secreting ◽

Stimulating Hormone

✓ It has been hypothesized by Lamberts and coworkers in their analysis of 15 cases that adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas may be derived from either the anterior lobe or the intermediate lobe. The intermediate lobe type of Cushing's disease is thought to be controlled through a hypothalamic pathway and is characterized by hyperprolactinemia, suppressibility of Cortisol with bromocriptine, and lower sensitivity to dexamethasone. The authors investigated the validity of this hypothesis in 125 cases of ACTH-secreting pituitary microadenomas by analyzing the endocrine findings, the locations of the microadenomas, and α-melanocyte stimulating hormone (α-MSH) immunoreactivity in the adenoma cells. No significant differences in the basal hormone levels, Cortisol suppressibility with bromocriptine, sensitivity to dexamethasone, and recurrence rate were observed between patients with the microadenoma adjacent to the posterior lobe (considered typical of the intermediate lobe-derived tumor) or those with the microadenoma located in the anterior lobe. The locations of the microadenoma were not correlated with α-MSH immunoreactivity in the adenoma cells. No significant differences in endocrine findings were noticed between adenomas positive or negative for α-MSH. Thus, Cushing's disease cannot be simply divided into either the anterior lobe type or the intermediate lobe type by endocrinological evaluation as described by Lamberts, et al.

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Cushing’s Disease – Quality of Life, Recurrence and Long-term Morbidity

European Endocrinology ◽

10.17925/ee.2015.11.01.34 ◽

2015 ◽

Vol 11 (1) ◽

pp. 34 ◽

Cited By ~ 2

Author(s):

Isabel Huguet ◽

Georgia Ntali ◽

Ashley Grossman ◽

Niki Karavitaki ◽

◽

...

Keyword(s):

Quality Of Life ◽

Cushing’S Disease ◽

Cushing's Disease ◽

Recurrence Rates ◽

Related Quality ◽

Health Related ◽

Acth Secreting

Cushing’s disease (CD) is a rare disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Chronic exposure to hypercortisolism leads to significant morbidities, which may be only partially reversible after remission of the disease, as well as to impairment of the health-related quality of life (HRQoL) and an increase in mortality. Transsphenoidal surgery (TSS) is the treatment of choice, and recurrence rates vary widely, confirming the need for lifelong follow-up. This review summarises the studies performed on HRQoL, recurrence rates and morbidities in patients who have CD.

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