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

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.

Download Full-text

PC3 - 142 Gamma Knife Radiosurgery in Patients with Persistent Acromegaly or Cushing’s Disease: Long-Term Risk of Hypopituitarism

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2016.393 ◽

2016 ◽

Vol 43 (S4) ◽

pp. S22-S22

Author(s):

O. Cohen-Inbar

Keyword(s):

Gamma Knife ◽

Cavernous Sinus ◽

Cushing’S Disease ◽

Hormone Replacement ◽

Gamma Knife Radiosurgery ◽

Common Adverse Effect ◽

Cushing's Disease ◽

Pituitary Hormone

For patient with a recurrent or residual acromegaly or Cushing’s disease (CD) after resection, Gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow up has hampered understanding of the latent risks of hypopituitarism in patients with a Acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for Acromegaly or CD. Methods: From a prospectively created, IRB approved database, we identified all patients with a Acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow up of 60 months were included. The median follow-up is 159.5 months (60.1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Results: 60 patients with either Acromegaly or CD were included. Median tumor volume at time of GKRS was 1.3 cm3 (0.3-13.4), median margin dose was 25 Gy (6-30). GKRS induced new pituitary deficiency occurred in 58.3% (n=35) of patients. Growth Hormone deficiency was most common (28.3%, n=17). The actuarial overall rates of hypopituitarism at 3, 5, and 10 years were 10%, 21.7%, and 53.3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumor was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (p=0.018). Conclusions: Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.

Download Full-text

Outcomes of Therapy for Cushing’s Disease due to Adrenocorticotropin-Secreting Pituitary Macroadenomas1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.1.4525 ◽

1998 ◽

Vol 83 (1) ◽

pp. 63-67 ◽

Cited By ~ 1

Author(s):

Lewis S. Blevins ◽

James H. Christy ◽

Masheed Khajavi ◽

George T. Tindall

Keyword(s):

Confidence Interval ◽

Cavernous Sinus ◽

Cushing’S Disease ◽

Odds Ratio ◽

Remission Rate ◽

Cushing's Disease ◽

Tumor Diameter ◽

Cavernous Sinus Invasion ◽

Free Cortisol ◽

Acth Secreting

We reviewed our experience with 21 patients who had Cushing’s disease due to ACTH-secreting macroadenomas to clarify the natural history of this disease. All patients had typical clinical and biochemical features of ACTH-dependent hypercortisolism. Their mean maximal tumor diameter was 1.6 ± 0.1 cm, and the range was 1.0–2.7 cm. Six patients had cavernous sinus invasion, three had invasion of the floor of their sella, and nine had suprasellar extension. The observed remission rate was significantly lower in macroadenoma patients than in microadenoma patients (67% vs. 91%; χ2 = 5.7; P < 0.02). Cavernous sinus invasion (odds ratio, 35; 95% confidence interval, 2.6–475; P < 0.008) and presence of a maximum tumor diameter 2.0 cm or more (odds ratio, 12.9; 95% confidence interval, 1.4–124; P< 0.02) emerged as the only predictors of residual disease after surgery. The observed recurrence rate was significantly higher in macroadenoma patients than in microadenoma patients (36% vs. 12%; χ2 = 4.2; P< 0.05). Macroadenoma patients tended to suffer from recurrences earlier than did microadenoma patients (16 vs. 49 months). Stepwise multiple logistic regression did not identify any predictors of disease recurrence in macroadenoma patients. Eight macroadenoma patients underwent a total of nine repeat surgical procedures, but none of these resulted in clinical remissions. Only four of seven (57%) patients followed for a sufficient period of time achieved normal urinary free cortisol levels after conventional radiotherapy. Three (75%) of these four patients had re-recurrent hypercortisolism after brief periods of eucortisolism. Pharmacological agents and adrenalectomy were effective in the management of hypercortisolism in patients with residual and recurrent disease. Our results indicate that ACTH-secreting macroadenomas are more refractory to conventional treatments than are ACTH-secreting microadenomas.

Download Full-text

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0277 ◽

2006 ◽

Vol 91 (7) ◽

pp. 2656-2664 ◽

Cited By ~ 19

Author(s):

Robert J. Weil ◽

Alexander O. Vortmeyer ◽

Lynnette K. Nieman ◽

Hetty L. DeVroom ◽

John Wanebo ◽

...

Keyword(s):

Body Mass ◽

Cushing’S Disease ◽

Anterior Lobe ◽

Cushing's Disease ◽

Posterior Lobe ◽

Repeat Surgery ◽

Tertiary Referral Center ◽

Acth Secreting

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.

Download Full-text

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.

Download Full-text