Diagnosis and treatment of an intramedullary cavernoma in a young male with an implanted cardiac pacemaker.
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Adult↗
Biomedical subjects
J Flitsch
Publications and source records attributed to J Flitsch.
Salivary cortisol measurement--a reliable method for the diagnosis of Cushing's syndrome.
The measurement of cortisol in saliva is becoming more widely accepted as a screening test for the diagnosis of hypercortisolism. Since 1986, cortisol measurement in saliva has been continuously used in our department. In this study we compared salivary cortisol profiles from proven Cushing's disease patients with profiles from healthy subjects and obese children. The purpose was to evaluate the predictive value of the method for the diagnosis of hypercortisolism and to define cut-off levels to exclude or identify hypercortisolism. Cortisol in saliva was measured in 150 Cushing's disease patients (30 children, 120 adults, ranging from age 4-70), 100 healthy subjects (55 children, 45 adults, ranging from age 6-60), and 31 children (age 7-15) with an age-related body-mass-index above the 90th percentile. Generally, five saliva samples were taken over the day at 6:00-8:00 a.m., 11:00-12:00 a.m., 4:00-6:00 p.m., 7:00-8:00 p.m., and 10:00 p.m. The samples were measured using a radioimmuno-assay (INCSTAR Corporation, Stillwater, Minnesota, USA). For healthy subjects, morning levels of cortisol in saliva between 3-19 microg/l were found. These levels dropped to levels in between <1-11 microg/l at 11:00-12:00 a.m., <1-6 microg/l at 4:00-6:00 p.m., <1-4.5 microg/l at 7:00-8:00 p.m., and <1-2.9 microg/l at 10:00 p.m. The measured values showed a correlation with age, height, and weight. In Cushing's disease patients, the circadian salivary cortisol rhythm was missing, compared to healthy subjects. There was no significant difference in salivary cortisol levels or circadian rhythm between healthy or obese children. We found a high sensitivity for the detection of hypercortisolism at the 10:00 p.m. salivary cortisol measurement. The following, age dependent cut-off levels for salivary cortisol at 10:00 p.m. were calculated for the exclusion of hypercortisolism. Age 6-10: 1.0 microg/l (specificity 100%, sensitivity 87.5%); age 11-15: 1.7 microg/l (specificity 100%, sensitivity 100%); age 16-20: 1.6 microg/l (specificity 100%, sensitivity 76.2%); age 21-60: 1.6 microg/l (specificity 100%, sensitivity 90.9%) [corrected] For the proof of Cushing's syndrome, the following age-dependent cut-off levels at 10:00 p.m. were found: age 6-10: 1.9 microg/l (specificity 100%, sensitivity 80%); age 11-15: 1.7 microg/l (specificity 100%, sensitivity 100%); age 16-20: 2.5 microg/l (specificity 100%, sensitivity 84.2%); age 21-60: 1.9 microg/l (specificity 100%, sensitivity 97.6 %) [corrected] The cortisol assessment in saliva is a sensitive and reliable method to discriminate normocortisolemic from hypercortisolemic patients. From our view, the major advantages of this method are the reliability, non-invasiveness, and use in ambulatory patients.
Adolescent↗
Spondylodiscitis caused by occult endocarditis.
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Discitis↗
The use of postoperative ACTH levels as a marker for successful transsphenoidal microsurgery in Cushing's disease.
OBJECTIVES: The declines of ACTH and other POMC metabolites immediately after tumor extirpation do not predict the complete tumor removal of an ACTH-secreting pituitary adenoma in Cushing's disease. However, the pituitary surgeon should be in a position to evaluate the surgical result as soon as possible for the eventual planning of early repeat surgery. So far, subnormal serum cortisol levels after surgery are widely accepted as the criterion for cure. We investigated whether the early postoperative ACTH concentration is a reliable marker for the initial surgical outcome as well as the long-term remission. METHODS: In a prospective study, 147 patients undergoing primary transsphenoidal microsurgery for Cushing's disease between 1990 and 1996 were investigated. The early postoperative ACTH courses were reviewed and compared with the long-term outcome. ACTH measurements were performed immediately after tumor excision, 1, 2, 4, 8, and 12 hours later, and the following morning. Further ACTH levels were determined on various days of the hospital stay. Glucocorticoids were not given until hypocortisolism was proven. RESULTS: Ninety-five patients (65 %) presented with subnormal ACTH levels (< 10 ng/l) during their postoperative stay, of whom two patients (2 %) experienced recurrence of disease after 66 and 100 months. Of 29 procedures with early postoperative ACTH levels ranging from 10-20 ng/l (20 %), one patient received further treatment for persistent (3.5 %) and one patient for recurrent Cushing's disease (3.5 %). Of 12 patients (8 %) with early postoperative ACTH levels in between 20 to 30 ng/l, one patient received further treatment for persistent (8 %) and four patients for recurrent disease (33 %). ACTH levels of more than 30 ng/l, found in 11 patients (7 %), were accompanied by persistent (8 patients, 73 %) or recurrent (2 patients, 18 %) Cushing's disease. CONCLUSION: Subnormal (< 10 ng/l) or low normal (< 20 ng/l) postoperative ACTH levels within the first 7 days after surgery can be regarded as early markers for complete removal of an ACTH adenoma as well as indicators for long-term outcome in Cushing's disease. The risks of persistence or recurrence of Cushing's disease rise with the level of early postoperative ACTH values. Normal ACTH levels should result into further evaluation of the ACTH-cortisol secretion, for example by stimulation- or suppression tests.
Adenoma↗
HERG K(+) currents in human prolactin-secreting adenoma cells.
To investigate the presence and possible function of ether-à-go-go-related gene (erg) K(+) channels in human lactotroph cells (HERG channels), primary cultures were prepared from human prolactinoma tissue. In almost all primary cultures, HERG currents could be recorded in identified prolactin cells using an external high-K(+) solution. The antiarrhythmic agent E-4031, a specific blocker of erg channels, served to isolate HERG currents as the drug-sensitive currents. In cells of two tumours tested, thyrotropin-releasing hormone significantly reduced the amplitude of the HERG currents. The potential dependence of HERG current availability and the deactivation kinetics differed significantly even between prolactin cells derived from one adenoma. For comparison, corresponding values were obtained for heterologously expressed rat erg1, erg2 and erg3 channels. The expression of the three HERG channel subunits was investigated in nine human adenomas using RT-PCR. Transcripts for HERG1 were present in all adenomas and although transcripts for HERG2 and HERG3 were also detected, their expression level was more variable. The results demonstrate the functional expression of HERG channels in human prolactin-secreting tumours and are compatible with a physiological role for these channels in the control of prolactin secretion, as has been shown in normal rat lactotroph cells.
Animals↗
Cavernous sinus sampling in selected cases of Cushing's disease.
The classical trias in Cushing's disease, normal or moderately elevated plasma ACTH, significant suppression of cortisol in the high-dose dexamethasone test, and stimulation of ACTH and cortisol in the CRH test, confirms the diagnosis in most cases. However, as a referral centre for complex Cushing's disease cases, we are confronted with problems in the differentiation of pituitary and ectopic Cushing's syndrome and with problems in the localisation of minute ACTH-secreting pituitary adenomas. In this study, cavernous sinus sampling (CSS) was evaluated as a diagnostic tool in complex Cushing's disease cases. Thirty-five patients were transferred to our unit for the treatment of Cushing's disease between January 1999 and August 2000. Of those, 17 patients (including five children) had the combination of equivocal results in endocrinological testing and negative MRI prior to admission. In these cases, CSS was performed preoperatively to confirm the diagnosis and to obtain further information about the localisation of pituitary microadenomas. Twelve of these 17 patients showed the classical trias for Cushing's disease after equivocal tests were repeated. A central-peripheral gradient was also found using CSS. In ten of the 11 patients, where CSS could be successfully performed, the lateralisation of the ACTH-adenoma was correctly predicted (91%). In the eleventh case, a right ACTH-gradient was found in a stalk tumour. In one patient (a child), the catheterisation of the cavernous sinus failed due to anatomical reasons. Eleven of these 12 patients successfully underwent transnasal adenomectomy. In two of the 17 patients, active Cushing's syndrome was excluded. In the remaining three cases, ectopic Cushing's syndrome was suspected based on CSS results. Therefore, these patients did not undergo pituitary exploration. In complex cases, we recommend CSS for diagnostic purposes, especially for the localisation of ACTH-secreting microadenomas within the pituitary. In our experience, CSS has a higher accuracy than inferior petrosal sinus sampling (IPSS) in the localisation of ACTH-adenomas.
Adrenocorticotropic Hormone↗
Cranial neuroendocrine carcinoma primarily diagnosed as malignant paraganglioma with rapid progress to a fatal outcome.
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Carcinoma, Neuroendocrine↗
Cushing's disease: a surgical view.
The management of adrenocorticotropic hormone (ACTH)-dependent Cushing's disease implies difficulties in the differential diagnosis, in the detection of minute pituitary adenomas, as well as in the radical removal of invasive adenomas. Magnetic resonance imaging (MRI) is unspecific and often negative in minute adenomas of three or less millimeters diameter. The trias of detectable ACTH, suppression of cortisol in the high-dose dexamethasone test, and stimulation in the corticotropin-releasing-hormone (CRH)-test has a high accuracy to prove pituitary dependency. In unclear cases, the use of inferior petrosal sinus sampling (IPSS) or cavernous sinus sampling (CSS) for the exclusion of ectopic ACTH-syndrome is currently advised especially in cases where cranial MRI is negative. The reliability of these methods to localize the mostly lateralized microadenomas is still discussed. Transsphenoidal microsurgical adenomectomy, the accepted primary therapy of Cushing's disease, has been published from experienced pituitary centers with remission rates ranging from 70% to 98% in the last decade. False diagnosis (pseudo-Cushing, ectopic ACTH-syndrome), incorrect adenoma localization by IPSS or CSS, and the rate of minute or non-resectable invasive tumors influence the results. The handling of minute specimen implies problems for surgeon and pathologist. Intraoperative tumor localization was improved by ACTH measurement from the cavernous sinus and the adenoma itself, by cytology, and frozen sections. The histology of the anterior lobe (rate of Crooke's cells) bears information of clinical relevance. Invasive macroadenomas may deserve repeat microsurgery, medical treatment, and radiosurgery.
Adenoma↗
The value of intraoperative cytology during transsphenoidal surgery for ACTH-secreting microadenoma.
BACKGROUND: Microsurgical selective adenomectomy is the best established method available for the treatment of Cushing's disease. However, this surgical method warrants still more efforts to improve the results in minute microadenomas. In this paper the authors evaluate a method of intraoperative cytological investigations during transsphenoidal surgery. METHOD: Between January 1997 and September 1999, transsphenoidal surgery was performed in 75 patients with the diagnosis of Cushing's disease. Fifty-one cases of proven microadenomas were reviewed. FINDINGS: Of 51 cases, 33 tumors were 3 mm or less in diameter, here after called minute adenomas. In 49 of 51 (96.1%) microadenomas, adenoma tissue was identified by intraoperative cytological techniques. Postoperatively, only 35 of 51 ACTH-secreting microadenomas (68.6%) were confirmed by immunostaining methods. This lower percentage was most probably due to the small amount of tissue obtained. Therefore, in 14 cases (including 12 minute adenomas) the presence of the adenoma was only proven by cytological preparation and clinical outcome. The sensitivity of cytological preparations in cases of confirmed Cushing's disease was 100%. INTERPRETATION: The method described here was particularly well suited for the intraoperative discrimination and documentation of minute adenomas. Cytological preparation appears to be effective in improving the adenoma finding rate and the surgical outcome in cases of Cushing's disease.
Adenoma↗
Transsphenoidal surgery for pituitary gigantism and galactorrhea in a 3.5 year old child.
The management of pituitary macroadenomas which lead to gigantism may require multiple therapeutical approaches, including medical treatment, surgery, and radiation therapy. Transsphenoidal surgery (TSS) during early childhood that achieves total removal of a growth hormone (GH) secreting tumor is rarely reported. The surgeon is confronted with special problems regarding the infantile anatomy. In this case, a 3.5 year old child, the youngest successfully treated by TSS so far, suffered from a GH- and prolactin (PRL) secreting macroadenoma of the pituitary gland. The girl initially presented with an increasing growth rate, later with breast development, and finally, at the age of 2.8 years, with galactorrhea and secretion of blood from the nipples. Increased levels of GH [122 micrograms/l], insulin-like growth factor (IGF-1) [830 micrograms/l], insulin-like growth factor binding protein 3 (IGFBP-3) [8.6 mg/l] and PRL [590 micrograms/l] were found. MRI scans revealed a macroadenoma of 2.7 cm diameter. An eight-week trial of relatively low dose dopamine agonists led to a reduction of PRL, while the GH- and IGF-1 levels remained unchanged; the tumor showed only little shrinkage. Since there was chiasma compression, we opted for early TSS. A complete tumor removal was achieved despite the difficulties of a narrow approach. After TSS, low levels of GH, IGF-1, and PRL documented a complete tumor removal, but persistent diabetes insipidus and anterior lobe deficits resulted from surgery. In summary, if primary medical therapy alone is unable to adequately reduce hormone hypersecretion and tumor size in early childhood, TSS is recommended. Thus, radiation therapy may be reserved for surgical failure.
Bromocriptine↗
Emotional disorders in patients with different types of pituitary adenomas and factors affecting the diagnostic process.
A prospective study of 48 patients with pituitary adenomas, 19 adenomas causing Cushing's disease, 18 adenomas causing acromegaly, and 11 clinically hormone-inactive adenomas (inactive adenomas), was performed to study emotional disorders occurring before and after transsphenoidal microsurgery. Factors which led to an obvious delay in the diagnostic process were identified. - The tools utilised were an interview and repeated personality assessments. The personality assessments were begun preoperatively and continued for about half a year postoperatively. The interview data, including retrospective statements regarding somatic difficulties, was analysed. - The thesis of a uniform psychopathology due to the influence of elevated hormone levels, and a lack in patients' sensitivity towards their changed appearance in acromegaly could not be confirmed. A high variability of reported emotional problems was found. The most common psychopathological signs for Cushing's disease were excitability and depression, for acromegaly fatigue/loss of energy was the most frequent complaint. Six to eight months postoperatively, a majority of patients noticed an increase of physical well-being. In acromegaly, the time span between first consultation and diagnosis averaged 6.2 years, in Cushing's disease it was 4.3 years, and in inactive adenomas it was 3.9 years. Only a small part of the delay in diagnosis, less than two years, could be attributed to the patients' hesitation to consult a physician.
Acromegaly↗
Surgical treatment of clinically nonsecreting pituitary adenomas in elderly patients.
OBJECTIVE: The goal of this study was to evaluate the efficacy and safety of transsphenoidal pituitary surgery for elderly patients, using improved techniques of the past decade. METHODS: We retrospectively analyzed 32 surgically treated cases of clinically nonsecreting pituitary adenomas in patients more than 70 years of age (mean, 73.9+/-3.4 yr). These patients were identified in a review of 982 patients with pituitary adenomas who were treated at University Hospital Eppendorf, Hamburg, between January 1991 and November 1999. RESULTS: The mean preoperative duration of symptoms was 1.9 years (2 wk to 11 yr). The chiasmatic syndrome was present for 27 patients (84.4%). All patients underwent transsphenoidal surgery. Seven patients underwent reoperations. Preoperative assessments of anterior pituitary function revealed growth hormone deficiencies for 21 of 27 patients (77.8%), thyroid insufficiencies for 10 of 30 patients (33.3%), and adrenal insufficiencies for 13 of 29 patients (44.8%). Hypogonadism and hyperprolactinemia were observed for 76.7% and 46.9% of the patients, respectively. All tumors were macroadenomas, ranging from 18 to 50 mm (average, 33.6 mm) in size, including 7 enclosed and 25 invasive adenomas. Complete microscopic tumor resection was achieved in 24 cases, and subtotal removal was performed in 8 cases. There were no severe perioperative complications. In the cases involving hyperprolactinemia, serum prolactin levels were normalized for 8 of 11 patients (72.7%). Normal thyroid function was recovered for 1 of 10 patients (10.0%) with preoperative hypothyroidism. However, growth hormone or adrenal insufficiencies persisted for all patients with preoperative insufficiencies. Visual disturbances were improved for 19 of 23 patients (82.6%). All patients recovered well after surgery, with an average hospital stay of 16.3 days. Histological and immunohistochemical studies demonstrated gonadotroph adenomas in 56.7% of cases, null-cell adenomas in 26.7%, and oncocytomas in 13.3%. CONCLUSION: Surgical treatment of nonsecreting pituitary adenomas causing visual disturbances is standard, even for elderly patients. In this series, transsphenoidal surgery was a safe procedure, with minimal morbidity and excellent tolerance. Age alone is not a contraindication for active treatment, particularly with transsphenoidal surgery.
Adenoma↗
Direct intraoperative micromethod for hormone measurements of pituitary tissue in Cushing's disease.
BACKGROUND: During transsphenoidal surgery (TSS) for Cushing's disease, the surgeon depends on experience to find minute adenomas. Cytological slide preparations or frozen sections, even when successful, are not specific concerning the hormone activity. In an attempt to improve accurate localization of minute ACTH adenomas, we evaluated a new intraoperative method of ACTH measurements in adenoma and anterior lobe microsamples. As most ACTH adenomas are monohormonal, the possible benefit of a GH measurement was investigated. METHODS: We included pituitary tissue of 32 patients, 22 with Cushing's disease and 10 endocrine inactive pituitary adenomas as control. All patients underwent TSS by one surgeon. Preoperative data, intraoperative and perioperative hormone measurements of homogenized, weighed pituitary tissue samples, and histological findings are presented. RESULTS: In ACTH adenomas, the median ACTH content was found to be 1,688 ng/mg, minimum 345 ng/mg. The median GH was measured at 36 ng/mg. Anterior lobe tissue contained median 80 ng ACTH/mg, maximum 279 ng/mg. Median GH was 2,200 ng/mg. In hormonally inactive adenomas ACTH was less than 0.1 ng/mg, median GH was 5.5 ng/mg. There was no overlap of ACTH content in the tissues investigated. Therefore, by adopting 300 ng ACTH/mg as a cutoff level, a clear discrimination is given. Additional GH measurements are not necessary. CONCLUSION: This new intraoperative method permits a clear differentiation between adenoma and pituitary tissue. In addition to intraoperative cytology and histology, this method can serve as a specific proof that the ACTH adenoma has been identified during surgery. This may be valuable in difficult cases with unclear intraoperative findings, especially after previously negative exploration.
Adenoma↗
Correlates of long-term hypocortisolism after transsphenoidal microsurgery for Cushing's disease.
In Cushing's disease, selective total removal of a corticotroph tumor of the pituitary regularly results in subnormal ACTH- and cortisol plasma levels. The duration of secondary adrenocortical insufficiency varies widely, with an average of 17 months in our patients. The goal of this study is to elucidate the underlying causes for the variation in duration of postoperative hypocortisolism. In this retrospective study, we evaluated 35 patients with postoperative hypocortisolism lasting more than 36 months, and compared them to 51 patients with a duration of less than 36 months. Preoperative data, intraoperative findings, and postoperative results with follow-up evaluations are presented. Extensive pituitary exploration, medial localization of the tumor, and a higher age were associated with increased risk for isolated secondary long-term hypocortisolism. The histological examination of paraadenomateous tissue identified a significantly larger amount of Crooke's cells in long-term cortisol insufficient patients. Previous pituitary surgery increased the risk for hypopituitarism. In some of our patients, the long-term adrenocortical insufficiency resolved after a period of over five years.
Adenoma↗