Transsphenoidal Pituitary Exploration Research Articles

Cavernous sinus sampling in patients with Cushing's disease.

OBJECT Correct diagnosis and precise localization of adenomas in patients with Cushing's disease are essential for avoiding unsuccessful transsphenoidal pituitary exploration. In addition to the well-established inferior petrosal sinus sampling, preoperative cavernous sinus sampling (CSS) was introduced as a potentially improved way to predict adenoma lateralization. The authors present their results with CSS in a consecutive series of patients with Cushing's disease. METHODS During 1999-2014, transsphenoidal surgeries were consecutively performed in 510 patients with Cushing's disease. For most patients, suppression of cortisol in high-dose dexamethasone tests and stimulation of adrenocorticotropic hormone and cortisol after administration of corticotropin-releasing hormone were sufficient to prove the diagnosis of adrenocorticotropic hormone-dependent hypercortisolism. Of the 510 patients, 67 (13%) were referred to the department of neuroradiology for CSS according to the technique of Teramoto. The indications for CSS were unclear endocrine test results or negative MRI results. Data for all patients were retrospectively analyzed. RESULTS A central/peripheral gradient was found in 59 patients; lateralization to the left or right side was found in 51. For 8 patients with a central/peripheral gradient, no left/right gradient could be determined. For another 8 patients with equivocal test results, no central/peripheral gradient was found. No severe CSS-associated complications were encountered. Of the 51 patients who underwent transsphenoidal surgery, the predicted lateralization was proven correct for 42 (82%). CONCLUSIONS As MRI techniques have improved, the number of potential candidates for this invasive method has decreased in the past decade. However, because detecting minute adenomas remains problematic, CSS remains a useful diagnostic tool for patients with Cushing's disease.

Acromegaly with negative pituitary MRI and no evidence of ectopic source: the role of transphenoidal pituitary exploration?

Growth hormone (GH) producing adenomas of the pituitary gland are usually macroadenomas (>10 mm in size). Often these adenomas are locally invasive by the time of diagnosis. Acromegaly secondary to a very small pituitary microadenoma not visualized on pituitary magnetic resonance (MR) imaging is rare. We report a patient with acromegaly and an unremarkable pituitary MR imaging who had negative work up for ectopic growth hormone-releasing hormone (GHRH) or GH secreting tumors. Transsphenoidal pituitary exploration revealed a pituitary adenoma located on the left side of the sella against the medial wall of the cavernous sinus extending posteriorly along the floor of the sella all the way to the right side. The acromegaly was treated with resection of the pituitary adenoma and normalization of serum insulin-like growth factor 1 (IGF-1) and GH levels. In a patient with acromegaly and unremarkable pituitary MR imaging, with no evidence of ectopic GH and GHRH production, transsphenoidal pituitary exploration is a reasonable approach and may result in clinical improvement and biochemical cure in the hand of experienced surgeon. This approach may avoid long term medical treatment with its associated cost.

Early repeat surgery for persistent Cushing's disease.

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 micrograms/day was considered evidence of recurrence). Of the 17 patients with repeat surgery, 12 (71%) had resolution of hypercortisolism (morning plasma cortisol level < 5 micrograms/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.

TRANSSPHENOIDAL SURGERY FOR CUSHING'S DISEASE: DOES WHAT IS REMOVED DETERMINE THE ENDOCRINE OUTCOME?

Fifty-seven patients with pituitary-dependent Cushing's syndrome and eight with Nelson's syndrome underwent transsphenoidal pituitary exploration, with removal of macroscopically abnormal tissue in 64 patients and detailed histology of this in 63. The cure rate by stringent criteria 1 month later was 48 (83%) of the 58 with assessable data, who were followed for 225 patient-years. Two patients relapsed later, a rate of one per 112 patient-years of follow-up. In 27% of patients, the macroscopically abnormal tissue removed was histologically indistinguishable from normal pituitary gland but the cure rate was 82%, and a quarter of the patients in this group assessable for recovery of normal ACTH function gained it. Another 53% of biopsies showed corticotroph adenomas, and the cure rate in these was 89% though rather more (69%) recovered normal ACTH function. The remaining 20% of biopsies were consistent with corticotroph hyperplasia. The cure rate varied little whether the lesion was diffuse or localized, whether or not it was in the invasion zone/interlobar cleft, whether or not there was pituitary enlargement, or whether the surgery was radical or selective. Six patients, of whom three are cured, showed surgical or radiological evidence of invasion outside the pituitary fossa. The data are consistent with the idea that pituitary adenoma is merely the end stage of some other process in the corticotrophs, and cure often follows removal of a lesion other than adenoma. Of patients who were permanently cured, 47% regained normal ACTH function within 3 years of operation (none later), 53% remaining ACTH-deficient at 3 years or more. Of all patients 48% acquired gonadotrophin deficiency, 28% have TSH deficiency and 25% permanent diabetes insipidus. All these pituitary function deficits were more common after radical surgery and in patients with normal histology, The literature contains so little objective data on these functions that we cannot say whether the endocrine damage in our patients is exceptional or not.

Transsphenoidal microsurgical management of Cushing's disease. Report of 100 cases.

The development of transsphenoidal microsurgery and the refinement of endocrinological and radiological diagnostic procedures have afforded therapeutic options appropriate to the individual case in patients with hypercortisolism. The present series of 100 cases is derived from 104 patients with the diagnosis of Cushing's disease who underwent transsphenoidal pituitary exploration between 1974 and 1981. Excluding four patients in whom the pituitary gland was not exposed because of intraoperative technical difficulties, an overall cure rate of 78% was achieved. Among 71 patients with tumors confined to the sella turcica, 87% had correction of their hypercortisolism, 11% represented therapeutic failures, and one patient had tumor recurrence. In contrast, among 25 patients with extrasellar extension, correction of hypercortisolism was achieved in only 48%, 40% failed to respond, and 12% of the patients had recurrence. Four patients who failed to respond to total hypophysectomy have ectopic sources of adenocorticotropic hormone. The results indicate that transsphenoidal microsurgical exploration for a basophilic adenoma is the procedure of choice in adults and children with Cushing's disease. The diagnostic and surgical approach to these tumors, as well as pitfalls in the transsphenoidal treatment of Cushing's disease, are discussed.

Transsphenoidal microadenomectomy in cases of Cushing's disease.

Hypothalamo-pituitary functions in 60 cases of Cushing's disease have been followed up after transsphenoidal selective adenomectomy. The adenoma was found and selectively removed in 56 cases. Remarkable clinical improvement followed within several months after selective adenomectomy in the successful cases, paralleled with endocrine results. Long follow-up studies demonstrated a recovery of the ACTH<ortisol system with restarting of the circadian rhythm and normal suppressibility to low-dose dexamethasone. The functions of the other anterior pituitary hormones such as GH, TSH, and gonadotropins also returned to normal after selective adenomectomy in the majority of the clinically cured cases. These results strongly suggest that transsphenoidal pituitary exploration should be accepted as an initial treatment of Cushing's disease because of its high clinical remission rate in association with fair chance of radical cure and return to normal endocrine function. ndocrinological studies by Orth and Liddle (1971) demonstrated that most cases of Cushing's syndrome were caused by hypersecretion of ACTH from the pituitary gland and approximately 25% caused by adrenal tumors and 16% by ectopic ACTH-producing tumors. Pathological changes of the sella turcica were, however, rarely found among the cases with apparent ACTH hypersecretion. Therefore, it had been generally believed that the true pathogenesis of Cushing's disease exists in the hypothalamus rather than in the pituitary itself. Contemporary operative results by transsphenoidal microsurgery have shown thata small adenoma does exist in many cases of ACTH-dependent Cushing's disease and clinical symptoms improved markedly by excision of an adenoma 6 ),7h I OI. 26 ),29),32). It sometimes happens, however, that an adenoma is not found through entire surgical procedures. In addition, there are some reports demonstrationg the presence of ACTH-cell hyperplasia in surgically excised specimens of the pituitary gland in Cushing's disease 20I ,25),27 1 • Therefore, some scholars still support the theory that the functional changes of hypothalamus or limbic system is the primary etiology. We have experienced transsphenoidal microsurgery in 60 patients with Cushing's disease. The following are the results of our experience. • ~~.,.~~~, .ill~~, ~.~~, ••~~. ~rr••

Lymphoid Hypophysitis

LYMPHOID hypophysitis is an inflammatory process characterized by the presence of isolated lymphoid follicles and diffuse lymphocytic infiltrate of the anterior pituitary. The entity has been reported as an autopsy finding in six cases 1-6 and as an antemortem diagnosis in one previous patient. 7 The following article describes a woman who underwent transsphenoidal pituitary exploration for a suspected prolactin-producing pituitary tumor. On routine histological examination of the surgical specimen, there were the characteristic inflammatory changes of lymphoid hypophysitis 1-7 without evidence of a tumor. This article documents the occurrence of elevated prolactin and enlargement of the sella turcica owing to lymphocytic infiltration of the adenohypophysis. Report of a Case A 25-year-old woman was admitted for evaluation of persistent throbbing headaches that had persisted for six months. Five months before, she had a normal vaginal delivery of her fifth child and since that time had persistent galactorrhea and amenorrhea, despite

Lymphoid hypophysitis. An unusual cause of hyperprolactinemia and enlarged sella turcica

LYMPHOID hypophysitis is an inflammatory process characterized by the presence of isolated lymphoid follicles and diffuse lymphocytic infiltrate of the anterior pituitary. The entity has been reported as an autopsy finding in six cases 1-6 and as an antemortem diagnosis in one previous patient. 7 The following article describes a woman who underwent transsphenoidal pituitary exploration for a suspected prolactin-producing pituitary tumor. On routine histological examination of the surgical specimen, there were the characteristic inflammatory changes of lymphoid hypophysitis 1-7 without evidence of a tumor. This article documents the occurrence of elevated prolactin and enlargement of the sella turcica owing to lymphocytic infiltration of the adenohypophysis. Report of a Case A 25-year-old woman was admitted for evaluation of persistent throbbing headaches that had persisted for six months. Five months before, she had a normal vaginal delivery of her fifth child and since that time had persistent galactorrhea and amenorrhea, despite

Cushing's Disease

In December 1976, an 18-year-old woman had symptoms typical of Cushing's syndrome. Laboratory evaluations and roentgenograms documented pituitary-dependent Cushing's disease in a patient with a pituitary microadenoma. In May 1977, she underwent transsphenoidal pituitary exploration. A 2-mm pituitary microadenoma was removed. The patient improved, and laboratory evaluation documented remission of the disease. In June 1978, she again complained of symptoms compatible with Cushing's disease. Laboratory evaluation confirmed a pituitary-dependent hypercortisonism. This case report marks the first recurrence of Cushing's disease in a patient previously cured by transsphenoidal resection of a pituitary tumor. ( Arch Intern Med 139:938-940, 1979)

Surgical treatment of prolactin-secreting microadenomas

Fourteen women (aged 19 to 38 years) with amenorrhea of 1 to 7 years' duration underwent transsphenoidal pituitary exploration for selective removal of potential prolactin secreting microadenomas. Preoperatively, serum prolactin levels were elevated in all (90 to 970 ng/ml), standard sella turcica x-ray films were normal, but polytomography revealed localized erosion in 12 women. Growth hormone reserve (assessed with insulin-induced hypoglycemia) was compromised in one of 13 women; cortisol responsiveness (to insulin-induced hypoglycemia) was attenuated in three of 10 women, while gonadotropin reserve (assessed with subcutaneous 100μg luteinizing hormone-releasing factor) was borderline in two of 13 women. At operation, pituitary adenomas were removed in 13 women, while a sellar diverticuium was found in the remaining woman. In the 13 women with pituitary adenoma removal, plasma prolactin levels decreased in all and reached normal levels in five women. Despite pituitary surgery, trophic hormone function (i.e., growth hormone reserve, cortisol responsiveness, thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone) was preserved in most instances and perhaps improved. Adjunctive radiotherapy was utilized in two patients. With follow-up of 6 months' to 3 years duration, cyclic menses have resumed in six and pregnancy occurred in three of seven women desiring fertility. Factors associated with successful surgical treatment of these microadenomas included: (1) tumor size (< 8 mm in diameter), (2) surgical technique, and (3) the surgeon's operative experience.

Treatment of Cushing??s Disease in Childhood by Transsphenoidal Resection of a Pituitary Microadenoma

A 12 yr old girl presented with typical features of Cushing syndrome. Plasma F (17.8 μg/dl) showed a normal diurnal rhythm and dexamethasone (DX)-suppressibility. Urinary 17 KS (11.1 mg/24 h) and 170H-C (20.1 mg/24 h) were increased but DX-suppressible, THE and THF showed a partial response to DX only. Free urinary F was 160 μg/m2/24 h (normal : < 50) and DX-suppressible. Plasma ACTH was 160 pg/ml (normal : < 100). Treatment with aminoglutethimide (4 × 500 mg/day) for 8 months had a transitory effect only and cyproheptadine (16 mg/day) for 1 yr was unsuccessful. Plasma ACTH increased to 340 pg/ml. Sellar enlargement became evident. At transsphenoidal pituitary exploration a cystic microadenoma was resected. After surgery and pituitary irradiation transient ACTH deficiency was observed. Menstruation started 3 months post-operatively. T4 and T3 remained normal. The blunted TSH response to TRH was normalized. Responses of LH and FSH to LHRH, PRL to TRH and GH to arginine were normal.

Initial Evaluation and Management of Patients with Suspected Pituitary Tumors

While pituitary tumors are not as rare as was once thought, it is difficult to assess how many are of clinical significance. Trans-sphenoidal pituitary exploration is a technique which can be performed with low operative morbidity and mortality, and when instituted early can prevent subsequent visual and endocrine impairment from an expanding lesion. Thus early recognition has increased importance.