Delayed cure of Cushing's disease after transsphenoidal surgery of pituitary microadenomas

1978 ◽  
Vol 49 (4) ◽  
pp. 593-596 ◽  
Author(s):  
Stephen D. McDonald ◽  
Stanley E. Von Hofe ◽  
Steven G. Dorfman ◽  
Richard M. Jordan ◽  
James R. LaMorgese ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Normal Tissue ◽  
Adrenocorticotropic Hormone ◽  
Early Postoperative Period ◽  
Cushing's Disease ◽  
Content Type ◽  
Pituitary Microadenoma ◽  
Dexamethasone Suppression ◽  
Fine Print

✓ Transsphenoidal microdissection has been proposed as a preferred means of treating Cushing's disease. This procedure allows the surgeon to remove a pituitary microadenoma and at the same time to preserve normal tissue. Two cases described here were treated by this method. An interesting and important observation was that neither patient appeared to be cured for 2 to 6 weeks after surgery, as assessed by dexamethasone suppression. Later, normal suppressibility occurred and the course of each patient was compatible with cure. Patients treated by this method should not be automatically retreated because of adrenocorticotropic hormone (ACTH) non-suppressibility in the early postoperative period.

Radiosurgery for Cushing's disease after failed transsphenoidal surgery

2000 ◽  
Vol 93 (5) ◽  
pp. 738-742 ◽  
Author(s):  
Jonas M. Sheehan ◽  
Mary L. Vance ◽  
Jason P. Sheehan ◽  
Dilantha B. Ellegala ◽  
Edward R. Laws
Keyword(s):  
Gamma Knife ◽  
Cushing’S Disease ◽  
Tumor Size ◽  
Transsphenoidal Surgery ◽  
Gamma Knife Radiosurgery ◽  
Magnetic Resonance Images ◽  
Cushing's Disease ◽  
Content Type ◽  
Fine Print

Object. Although transsphenoidal surgery has become the standard of care for Cushing's disease, it is often unsuccessful in normalizing cortisol production. In this study the authors investigate the safety and efficacy of gamma knife radiosurgery (GKRS) for Cushing's disease after failed transsphenoidal surgery.Methods. The records of all patients who underwent GKRS at the authors' institution after unsuccessful transsphenoidal surgery for Cushing's disease were retrospectively reviewed. Successful treatment was considered a normal or below-normal 24-hour urinary free cortisol (UFC) level. Records were also evaluated for relapse, new-onset endocrine deficiencies, interval change in tumor size, and visual complications.Forty-three patients underwent 44 gamma knife procedures with follow up ranging from 18 to 113 months (mean 39.1, median 44 months). Normal 24-hour UFC levels were achieved in 27 patients (63%) at an average time from treatment of 12.1 months (range 3–48 months). Three patients had a recurrence of Cushing's disease at 19, 37, and 38 months, respectively, after radiosurgery. New endocrine deficiencies were noted in seven patients (16%). Follow-up magnetic resonance images obtained in 33 patients revealed a decrease in tumor size in 24, no change in nine, and an increase in size in none of the patients. One patient developed a quadrantanopsia 14 months after radiosurgery despite having received a dose of only 0.7 Gy to the optic tract.Conclusions. Gamma knife radiosurgery appears to be safe and effective for the treatment of Cushing's disease refractory to pituitary surgery. Delayed recurrences and new hormone deficiencies may occur, indicating the necessity for regular long-term follow up.

Surgical treatment of Cushing's disease

1987 ◽  
Vol 66 (2) ◽  
pp. 204-212 ◽  
Author(s):  
William F. Chandler ◽  
David E. Schteingart ◽  
Ricardo V. Lloyd ◽  
Paul E. McKeever ◽  
Gloria Ibarra-Perez
Keyword(s):  
Cushing’S Disease ◽  
Immunohistochemical Staining ◽  
Adrenocorticotropic Hormone ◽  
Cushing's Disease ◽  
Content Type ◽  
Acth Secreting ◽  
Endocrine Symptoms ◽  
Lung Carcinoid ◽  
Fine Print ◽  
Pharyngeal Pituitary

✓ The endocrinological, radiological, surgical, and pathological experience with 34 consecutive patients operated on for Cushing's disease is presented. Preoperative endocrine evaluation demonstrated that 19 patients had “typical” endocrine patterns for pituitary adrenocorticotropic hormone (ACTH)-dependent hypercortisolism and 11 had “atypical” testing. Pituitary pathology was found in 95% of the patients with typical preoperative endocrine testing but in only 55% of those with atypical testing. Eight of 34 preoperative computerized tomography scans demonstrated tumors, which correlated in all instances with the surgical findings. Microadenomas were removed from 25 patients, 22 of whom achieved postoperative remission of endocrine symptoms. Macroadenomas were found in three patients, only one of whom achieved remission after surgery. One patient had removal of an adenoma in the pharyngeal pituitary, and in another an ectopic lung carcinoid was excised; both of these patients were in postoperative remission. Four patients underwent transsphenoidal exploration but no definitive explanation was found for their hypercortisolism; these patients were not in remission. Immunohistochemical staining was performed on every specimen and all tumors showed excessive ACTH-secreting cells. A new rapid stain of the fibrovascular stroma is described.

Repeat transsphenoidal surgery for Cushing's disease

1989 ◽  
Vol 71 (4) ◽  
pp. 520-527 ◽  
Author(s):  
Robert B. Friedman ◽  
Edward H. Oldfield ◽  
Lynnette K. Nieman ◽  
George P. Chrousos ◽  
John L. Doppman ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Ct Scanning ◽  
Pituitary Surgery ◽  
Cushing's Disease ◽  
Repeat Surgery ◽  
Content Type ◽  
Preoperative Ct ◽  
Pituitary Irradiation ◽  
Fine Print

✓ Transsphenoidal resection of adrenocorticotrophic hormone (ACTH)-producing pituitary adenomas has the potential of curing most patients with Cushing's disease. However, transsphenoidal exploration of the pituitary is not always curative, and patients who have remission of hypercortisolism following surgery occasionally develop a recurrence. Whether repeat pituitary surgery should be performed for recurrent or persistent Cushing's disease has not been evaluated previously. To determine the efficacy of transsphenoidal surgery in recurrent or persistent Cushing's disease, we performed transsphenoidal surgery in 31 patients (22 women and nine men) who had previously undergone a transsphenoidal operation and two female patients who had had previous pituitary irradiation only. In 24 (73%) of the 33 patients, remission of hypercortisolism was achieved by surgery. Although preoperative computerized tomography (CT) scanning identified an adenoma in only three of the 33 patients, in 20 patients a discrete adenoma was identified at pituitary exploration. The incidence of remission of hypercortisolism was greatest if an adenoma was identified at surgery and the patient received selective adenomectomy (19, or 95% of 20 patients), if there was evidence at surgery or by preoperative CT scanning that the previous surgical exposure of the pituitary was incomplete (seven, or 78% of nine patients), if an adenoma was seen on preoperative CT scanning (three of three patients), or if the patient had had prior pituitary irradiation without surgery (two of two patients). In contrast, only five (42%) of 12 patients who received subtotal or total hypophysectomy had remission of hypercortisolism. Surgically induced hypopituitarism occurred in six (50%) of these 12 patients, but in only one (5%) of the 20 patients who underwent selective adenomectomy. Three (13%) of the 24 patients who were in remission from hypercortisolism following repeat surgery developed recurrent hypercortisolism 10 to 47 months postoperatively. Repeat transsphenoidal exploration of the pituitary and treatment limited to selective adenomectomy should be considered in patients with hypercortisolism despite previous pituitary treatment. If an adenoma is identified during surgery, the chance of remission of Cushing's disease is high and the risk of hypopituitarism is low; however, if no adenoma can be found and partial or complete hypophysectomy is performed, remission of hypercortisolism is less likely and the risk of hypopituitarism is about 50%.

Surgical management of adrenocorticotropic hormone—secreting macroadenomas: outcome and challenges in patients with Cushing's disease or Nelson's syndrome

2005 ◽  
Vol 103 (5) ◽  
pp. 825-830 ◽  
Author(s):  
Claudio De Tommasi ◽  
Mary Lee Vance ◽  
David O. Okonkwo ◽  
Alfa Diallo ◽  
Edward R. Laws
Keyword(s):  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Signs And Symptoms ◽  
Disease Recurrence ◽  
Cushing's Disease ◽  
Nelson’S Syndrome ◽  
Content Type ◽  
Nelson's Syndrome ◽  
Acth Secreting ◽  
Fine Print

Object. Adrenocorticotropic hormone (ACTH)—secreting pituitary macroadenomas are an uncommon cause of Cushing's disease (CD) and, subsequently, Nelson's syndrome (NS). They have been associated with low postoperative remission rates. The outcome of modern surgical treatment is unclear and thus was assessed in a series of 43 patients, with the goal of improving therapeutic results in patients with ACTH-secreting macroadenomas. Methods. Thirty-seven patients presented with CD and six with NS. They represented 15% of the patients surgically treated at the authors' institution for ACTH-secreting adenomas. The median patient age was 38 years (range 14–71 years), and the mean duration of follow up was 37 months (range 1–108 months). Remission occurred in 25 (67.6%) of 37 patients with CD, whereas the disease persisted in 12 (32.4%) of 37 patients. After an initial remission, three (12%) of 25 patients demonstrated signs and symptoms indicative of disease recurrence. Among patients with NS, only one (16.6%) displayed remission. Invasion of the dura mater by tumor was histologically demonstrated in 10 patients with CD and in two patients with NS. Conclusions. Comprehensive management of CD caused by ACTH-secreting macroadenomas through the appropriate use of combination therapy, including surgery, radiotherapy, radiosurgery, and adrenalectomy, can lead to outcomes similar to those for microadenomas. Disease recurrence and persistence rates are higher, often because of the invasiveness associated with macroadenomas. Remission of NS-associated macroadenomas is difficult to achieve. Strategies for the characterization and treatment of invasive macroadenomas are needed.

Early repeat surgery for persistent Cushing's disease

1994 ◽  
Vol 80 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Zvi Ram ◽  
Lynnette K. Nieman ◽  
Gordon B. Cutler ◽  
George P. Chrousos ◽  
John L. Doppman ◽  
...  
Keyword(s):  
Cortisol Level ◽  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Cushing's Disease ◽  
Sustained Remission ◽  
Repeat Surgery ◽  
Content Type ◽  
Initial Surgery ◽  
Early Reoperation ◽  
Fine Print

✓ The potential efficacy of early repeat transsphenoidal surgery for persistent Cushing's disease has not previously been examined. On 222 patients with no prior pituitary treatment and a preoperative diagnosis of Cushing's disease, 29 (13%) remained hypercortisolemic after an initial transsphenoidal pituitary exploration. Seventeen of these 29 patients underwent further surgery 7 to 46 days after the initial transsphenoidal approach in order to completely excise suspected residual tumor. Patients were followed for 4 to 84 months (mean ± standard deviation, 34 ± 25 months) to document sustained remission or recurrence of Cushing's disease (a urine free cortisol level > 90 µg/day was considered evidence of recurrence). Of the 17 patients with repeat surgery, 12 (71%) had resolution of hypercortisolism (morning plasma cortisol level < 5 µg/dl); however, in three of these 12, hypercortisolism recurred 5, 12, and 24 months later. In 14 patients a lesion that appeared to be a tumor was identified during the initial procedure or on histological examination. Of these, 12 had immediate resolution of hypercortisolism and nine are still in remission. Three patients, in whom no adenoma could be identified during the initial surgery or an examination of the partial hypophysectomy specimen from the initial surgery, had persistent Cushing's syndrome after the second operation. Seven (41%) of the 17 patients developed hypopituitarism requiring treatment with thyroid hormone, gonadal steroid, or vasopressin replacement. The low incidence of identification of an adenoma on computerized tomography or magnetic resonance images (three of 17 patients), the failure to find a corticotrophic adenoma during the initial surgery (10 of 17 patients), and the failure of these 17 patients to respond to the initial transsphenoidal surgery suggest that they may comprise a subset of patients who are more difficult to treat successfully with surgery than most patients with Cushing's disease. Despite that, early reoperation induced immediate remission of hypercortisolism in 71% of cases, but did so at the expense of a high risk of hypopituitarism. However, since the alternative treatments (such as radiation therapy, long-term drug therapy, or bilateral adrenalectomy) also have potential adverse effects, early reoperation deserves consideration for the management of persistent Cushing's disease, especially when an adrenocorticotrophic hormone-secreting adenoma was partially excised during the first surgery.

Complications in a contemporary series of patients who underwent transsphenoidal surgery for Cushing's disease

1999 ◽  
Vol 91 (2) ◽  
pp. 175-179 ◽  
Author(s):  
Patrick L. Semple ◽  
Edward R. Laws
Keyword(s):  
Deep Vein Thrombosis ◽  
Cushing’S Disease ◽  
Pituitary Adenomas ◽  
Transsphenoidal Surgery ◽  
Cushing's Disease ◽  
Medical Complications ◽  
Content Type ◽  
Vein Thrombosis ◽  
Deep Vein ◽  
Fine Print

Object. Transsphenoidal surgery is the usual treatment of choice for adrenocorticotropic hormone—secreting pituitary adenomas associated with Cushing's disease. In this paper the authors investigate the complications of transsphenoidal surgery in the treatment of a contemporary series of patients with Cushing's disease.Methods. Between January 1992 and December 1997, 105 patients with Cushing's disease underwent transsphenoidal surgery at the University of Virginia Health Sciences Center. A retrospective analysis of the complications was conducted, and the mortality rate was found to be 0.9% and permanent morbidity was 1.8%. The overall number of complications was 14 (13.3%), which included seven complications directly related to surgery; one instance of permanent diabetes insipidus; one syndrome of inappropriate secretion of antidiuretic hormone; and five medical complications (four patients developed deep vein thrombosis and one developed pneumonia).Conclusions. Transsphenoidal surgery for Cushing's disease has a higher complication rate than that for pituitary adenomas in general. This is primarily related to a greater number of medical complications, most notably deep vein thrombosis, resulting from the generally debilitated state of most patients with Cushing's disease. In view of the high incidence of deep vein thrombosis in these patients, prophylaxis for thromboembolism during the perioperative period is recommended.

Antisense oligonucleotide—induced inhibition of adrenocorticotropic hormone release from cultured human corticotrophs

1999 ◽  
Vol 91 (2) ◽  
pp. 261-267 ◽  
Author(s):  
Bruce Frankel ◽  
Sharon L. Longo ◽  
Gerard S. Rodziewicz ◽  
Charles J. Hodge
Keyword(s):  
Cushing’S Disease ◽  
Antisense Oligonucleotide ◽  
Antisense Oligonucleotides ◽  
Adrenocorticotropic Hormone ◽  
Cushing's Disease ◽  
Hormone Release ◽  
Content Type ◽  
Novel Treatments ◽  
Fine Print

Object. Available therapies for Cushing's disease are often inadequate or involve the risk of significant morbidity. Accordingly, the need arises for the development of novel treatments, especially for cases caused by corticotroph hyperplasia, a condition difficult to treat using standard therapies. In this study, the authors investigated the use of phosphorothioate antisense oligonucleotides as a potential treatment for Cushing's disease.Methods. Corticotrophs, obtained from a patient with Cushing's disease in whom pathological findings showed multifocal areas of corticotroph adenoma and hyperplasia, were grown in tissue culture. By assessing cell viability and using immunoradiometric assay techniques, it was determined that these cells grew autonomously and secreted adrenocorticotropic hormone (ACTH) in vitro. A fully phosphorothioated antisense oligonucleotide was constructed to be complementary to the first 25 bp of the region coding for ACTH in exon 3 of the proopiomelanocortin precursor. After incubation of the corticotrophs with liposome-coated phosphorothioate antisense oligonucleotides, a greater than 90% decrease in ACTH release was noted on Days 3 and 6, compared with nonsense-treated controls (p < 0.05).Conclusions. Antisense oligonucleotides may prove to be a useful adjunct in treating Cushing's disease by targeting one of its fundamental problems, ACTH hypersecretion.

Suppression of cortisol secretion by low-dose dexamethasone testing in Cushing's disease

1983 ◽  
Vol 58 (1) ◽  
pp. 129-132 ◽  
Author(s):  
Lucille W. King ◽  
Kalmon D. Post ◽  
Israel Yust ◽  
Seymour Reichlin
Keyword(s):  
Cushing’S Disease ◽  
Low Dose ◽  
Dexamethasone Suppression Test ◽  
Cushing's Disease ◽  
Cortisol Secretion ◽  
Content Type ◽  
Normal Individuals ◽  
Suppression Test ◽  
Peripheral Clearance ◽  
Dexamethasone Suppression

✓ Pituitary-adrenal function in a patient with classical features of Cushing's disease, increased urinary excretion of cortisol, and documented pituitary adenoma was found to be suppressed by dexamethasone in doses even less than those required to inhibit secretion in normal individuals. This response was shown to be due to inappropriately high levels of dexamethasone in plasma, presumed to be the consequence of decreased peripheral clearance. Because the dexamethasone suppression test is so widely used for diagnosis of Cushing's disease, it is important to recognize that this situation can occasionally occur.

Diagnosis of an “isodense” pituitary microadenoma by dynamic CT scanning

1984 ◽  
Vol 60 (2) ◽  
pp. 424-427 ◽  
Author(s):  
Takeshi Hasegawa ◽  
Haruhide Ito ◽  
Katsuo Shoin ◽  
Yuzaburo Kogure ◽  
Toshihiko Kubota ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Adrenocorticotropic Hormone ◽  
Ct Scanning ◽  
Ct Scans ◽  
Dynamic Ct ◽  
Content Type ◽  
Pituitary Microadenoma ◽  
Enhanced Ct ◽  
Dynamic Ct Scanning ◽  
Fine Print

✓ A case of Nelson's syndrome with an adrenocorticotropic hormone-secreting pituitary chromophobe microadenoma is presented to demonstrate the potential capability of rapid sequential (dynamic) computerized tomography (CT) scanning for the diagnosis of a pituitary microadenoma that was isodense with the adjacent pituitary gland on conventional enhanced CT scanning. The dynamic CT scans showed transient high density in this microadenoma contrasting with the pituitary gland in the early-enhancement phase, and thereafter the contrast density was indistinguishable from that of the pituitary gland in the delayed-enhancement phase. For the detection of pituitary microadenoma, dynamic CT combined with subsequent delayed CT scanning can provide diagnostic and localizing information.

Multiple pituitary adenomas in Cushing's disease

2000 ◽  
Vol 93 (5) ◽  
pp. 753-761 ◽  
Author(s):  
John K. Ratliff ◽  
Edward H. Oldfield
Keyword(s):  
Cushing’S Disease ◽  
Medical Records ◽  
Pituitary Adenomas ◽  
Cushing's Disease ◽  
Clinical Database ◽  
Null Cell ◽  
Content Type ◽  
Initial Surgery ◽  
Repeated Surgery ◽  
Fine Print

Object. Clinically evident multiple pituitary adenomas rarely occur. The authors assess the incidence and clinical relevance of multiple adenomas in Cushing's disease.Methods. A prospective clinical database of 660 pituitary surgeries was analyzed to assess the incidence of multiple pituitary adenomas in Cushing's disease. Relevant radiographic scans, medical records, and histopathological reports were reviewed.Thirteen patients with at least two separate histopathologically confirmed pituitary adenomas were identified. Prolactinomas (nine patients) were the most common incidental tumors. Other incidental tumors included secretors of growth hormone ([GH], one patient) and GH and prolactin (two patients), and a null-cell tumor (one patient). In two patients, early repeated surgery was performed because the initial operation failed to correct hypercortisolism, in one instance because the tumor excised at the initial surgery was a prolactinoma, not an adrenocorticotropic hormone—secreting tumor. One patient had three distinct tumors.Conclusions. Multiple pituitary adenomas are rare, but may complicate management of patients with pituitary disease.

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