Novel AIP mutation in exon 6 causing acromegaly in a German family.

The most frequent genetic alteration of familial isolated growth hormone producing pituitary neuroendocrine tumors is a germline mutation of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Various AIP mutations are already known; however, an AIP mutation in exon 6 (c.811_812del; p.Arg271Glyfs*16) has not been reported yet. Here, we report a German family with two identical twins who were both affected by acromegaly and carried the above-mentioned novel AIP mutation. The father was found to be an unaffected carrier, while the paternal aunt most likely suffered from acromegaly as well and died from metastatic colorectal cancer. Apart from reporting a novel AIP mutation, this study does not only highlight the different clinical and histological features of the AIP mutated growth hormone producing pituitary neuroendocrine tumors but also confirms the poor responsiveness of dopamine agonists in AIP mutated acromegaly. Furthermore, it highlights the increased mortality risk of comorbidities typically associated with acromegaly.

Typing of inflammatory lesions of the pituitary.

Inflammatory pituitary lesions account for 1.8% of all specimens from the German Pituitary Tumor Registry. They occure in 0.5% of the autoptical specimens and in 2.2% of the surgical cases. Women are significantly more often affected than men and are often younger when first diagnosed. In general, primary and secondary inflammation can be distinguished, with secondary types occurring more frequently (75.1%) than idiopathic inflammatory lesions (15.4%). In primary inflammation, the lymphocytic type is more common (88.5%) than the granulomatous type of hypophysitis (11.5%). The most common causes of secondary inflammation are Rathke's cleft cysts (48.6%), followed by tumors (17.4%) such as the craniopharyngioma (9.1%), adenoma (5.5%) or germinoma (2.0%). More causes are tumor-like lesions (7.1%) such as xanthogranuloma (3.5%) or Langerhans histiocytosis (3.5%), abscesses (5.5%), generalized infections (5.1%), spreaded inflammations (4.7%) and previous surgeries (4.0%). In 1.6% of all specimens the reason for the inflammation remains unclear. The described classification of hypophysitis is important for specific treatment planning after surgery.

Specificity of late-night salivary cortisol measured by automated electrochemiluminescence immunoassay for Cushing's disease in an obese population.

PURPOSE: Data about the specificity of late-night salivary cortisol (LNSC) in obese subjects are still conflicting. Therefore, with this study, we aimed to evaluate the specificity of LNSC measurement in an obese cohort with or without type 2 diabetes mellitus (T2DM) using an automated electrochemiluminescence immunoassay (ECLIA). METHODS: A total number of 157 patients involving 40 healthy subjects (HS) with BMI < 25 kg/m2, 83 obese subjects (OS) with BMI ≥ 35 kg/m2, and 34 histopathologically proven Cushing's disease (CD) were included. All patients underwent LNSC testing. Salivary cortisol was measured at 11 p.m. for all groups using an ECLIA. Reference range was established using values of LNSCs of HS and ROC curves were used to determine diagnostic cutoffs. RESULTS: In the HS group, mean LNSC was 4.7 nmol/l (SD ± 3.1), while the OS group had a mean value of 10.9 nmol/l (SD ± 7.5) and the CD group of 19.9 nmol/l (SD ± 15.4). All groups differed significantly (p < 0.001). The ROC analysis of CD against HS alone showed a sensitivity of 85.3% and a specificity of 87.5% with a cut-off value of 8.3 nmol/l. The ROC analysis between OS and CD showed a maximum sensitivity of 67.6% and specificity of 78.3% for a cut-off value of 12.3 nmol/l. Taken both (HS and OS) groups together against the CD group, ROC analysis showed a maximum sensitivity of 67.6% and specificity of 85.4% for a cut-off value of 12.3 nmol/l. No correlation was found between BMI, T2DM, and LNSC for all groups. CONCLUSIONS: In our obese cohort, we found that LNSC assayed by ECLIA had a low specificity in the diagnosis of CD.

[Diagnostics and treatment of acromegaly : Necessity for targeted monitoring of comorbidities]. / Diagnostik und Therapie der Akromegalie : Notwendigkeit der gezielten Überwachung von Komorbiditäten.

Acromegaly is a rare and severe condition, presenting with typical signs and symptoms. The diagnosis is often initially made years after the first manifestations of the disease. In more than 99% of patients the disease is caused by a benign pituitary tumor that secretes growth hormone (GH). The diagnosis is based on the presence of increased insulin-like growth factor 1 (IGF-1) levels and a lack of GH suppression in the oral glucose tolerance test. The standard imaging procedure for tumor detection is magnetic resonance imaging in the region of the sella turcica. Treatment includes surgical, drug and radiation therapy. Important factors are an intensive aftercare of the patient, controls for detection of tumor recurrence and pituitary insufficiency as well as assessment of various organ functions and risk constellations. Patient care should involve close cooperation between endocrinologists, neurosurgeons and general practitioners as well as other specialist disciplines.

Surgical management of pituitary metastases.

BACKGROUND: Pituitary metastases are rare and commonly described in case reports or small case series. Due to its rarity this entity is not subject to standardized treatment guidelines, there is debate about typical initial symptoms that may lead to finding the correct diagnosis and information about the clinical course is also sparse. METHODS: We have conducted a retrospective analysis of patients with pituitary metastases who were surgically treated via a transsphenoidal procedure at our institution between 2006 and 2014. Underlying primary disease, clinical and surgical course as well as adjuvant radiotherapy and follow-up data are presented. RESULTS: 14 patients met the inclusion criteria (8 female, 6 male). Mean age was 61.5 years. Most patients became symptomatic with visual symptoms--both visual deterioration and/or diplopia (n = 13)--and anterior lobe insufficiency (n = 8). Surprisingly diabetes insipidus was only seen in three patients. All patients underwent transsphenoidal surgery initially, four patients had to undergo surgery for residual tumor or recurrence, two of them via a transcranial route. Breast cancer was the most common entity (n = 6), followed by prostate cancer (n = 3), nsclc (n = 2) and melanoma, thyroid cancer and renal cancer in one case each. Postoperative MRI showed gross total resection in four cases and residual disease in eight cases (subtotal resection, partial resection and biopsy), two patients files were incomplete regarding MRI-results. All patients underwent adjuvant radiotherapy. Survival after the initial diagnosis of cancer was 36 and 16 months after diagnosis of pituitary metastases. CONCLUSION: Our results indicate that transsphenoidal surgery is a safe method to resect pituitary metastases and that the extend of resection does not have an influence on survival time. Our results also indicate that diabetes insipidus may not be the most common initial symptom of pituitary metastases and lack thereof should not lead to making a wrong diagnosis and delaying appropriate therapy.

A pitfall in diagnosing Cushing's disease: ectopic ACTH-producing pituitary adenoma in the sphenoid sinus.

PURPOSE: To show a rare case of Cushing's disease and possible cause of failed transsphenoidal surgery. METHOD: We report on a 50-year-old woman suffering from ACTH-dependent Cushing's syndrome. Endocrinological work-up including low-dose/high-dose dexamethasone test (Liddle-test) and CRH test were clearly compatible with pituitary origin. Although an MRI showed no pituitary tumor, CRH-stimulated petrosal sinus sampling revealed a significant central-peripheral gradient in ACTH concentrations, rendering Cushing's disease very likely. The patient underwent transsphenoidal surgery with negative exploration of the pituitary gland. After intraoperative re-evaluation of the preoperative MRI, a "polyp" at the bottom of the sphenoid sinus was identified. The intraoperative microscopic aspect as well as instantaneous sections and cytology of a biopsy confirmed an adenoma, which was then removed. Histological analysis demonstrated an ACTH-producing pituitary adenoma adjacent to respiratory mucous membrane consisting of ciliated epithelium with submucous connective tissue. Postoperatively, ACTH concentrations were decreased and intermittent hydrocortisone substitution treatment was initiated. At the 3-month follow up, Cushing's stigmata were found to be alleviated and the hydrocortisone dosage could be reduced. CONCLUSION: Ectopic pituitary adenoma tissue causing Cushing's disease is extremely rare but a potential cause for surgical failure or re-evaluation.

Expression analysis of GADD45γ, MEG3, and p8 in pituitary adenomas.

Preceding studies have indicated that aberrant expression levels rather than genetic changes of GADD45γ, MEG3, and p8 gene might play a role in the pathogenesis of pituitary adenomas. We analysed their expression in various normal human tissues and in different pituitary tumour types, and investigated GADD45γ mutations in a subset of adenomas. Absolute quantification by real-time RT-PCR was performed in 24 normal tissues as well as in 34 nonfunctioning, 24 somatotroph, 12 corticotroph adenomas, 4 prolactinomas, 1 FSHoma, and in 6 normal pituitaries. Furthermore, we investigated the relationship between clinical data and gene expression. A subset was screened for GADD45γ mutations by single strand conformation polymorphism analysis (SSCP) and sequencing. All normal human tissues expressed GADD45γ, MEG3, and p8 mRNA. For GADD45γ, significantly lower expression levels were found in nonfunctioning adenomas compared with normal pituitary and somatotroph adenomas. P8 and MEG3 mRNA levels were significantly lower in nonfunctioning and corticotroph adenomas compared with normal pituitary. Expression of GADD45γ was significantly higher in pituitary adenomas of female patients. No mutation was found in the GADD45γ gene. GADD45γ, MEG3, and p8 appear to have physiological functions in a variety of human tissues. GADD45γ, MEG3, and P8 may be involved in the pathogenesis of nonfunctioning and corticotroph pituitary tumours. Female gender seems to predispose to slightly higher GADD45γ expression in pituitary adenomas. Mutations of the GADD45γ are unlikely to be involved in the pathogenesis of pituitary adenomas.

Hyponatremia after trans-sphenoidal surgery.

Fluid and electrolyte imbalances are the most frequent complications following pituitary surgery. Among the several patterns of occurrence, hyponatremia can occur in an isolated fashion or as part of a bi- or triphasic pattern. The frequency of hyponatremia after trans-sphenoidal surgery is between 2% and 25%, according to the literature. However, these numbers are probably underestimating the real prevalence, since mild hyponatremia does not lead to symptoms and measurement of sodium level. No association has been described between entity of the pituitary tumor or tumor size and hyponatremia. Therefore no predictors exist to determine patients with a higher risk for electrolyte imbalances after surgery. However, since delayed hyponatremia occurs mainly around the 8-10th day after surgery, routine measurement of sodium should be recommended on the day of hospital dismission. In case of a symptomatic hyponatremia, insufficiency of the corticotrophe pituitary function as the leading differential diagnosis needs to be ruled out. If the patient is euvoleme, pretest probability of syndrome of inadequate antidiuretic hormone production (SIADH) is very high and therapy may be started according to this. In case of SIADH, therapeutic options include fluid restriction or vaptane therapy. Only in severe cases infusion of hypertonic saline is appropriate. Usually SIADH following pituitary surgery is a self-limiting condition and will cease within 2-5 days.

Long-term follow-up and quality of life in patients with intracranial germinoma.

Intracranial germinomas are fairly rare tumors occurring mostly in children or young adults with a comparatively good prognosis. Radiation is the preferred treatment of choice for this diagnosis. It has been thoroughly studied to what extent radiation doses and fields can be limited in order to avoid side effects in these young patients. The role of chemotherapy remains unclear, whereas surgery is limited to biopsy for proof of histology. Regarding the good overall survival rate, quality of life is a significant aspect to consider in these patients. We present a single institution analysis of patients with intracranial germinoma and analyze the long-term outcome with special regard to quality of life. Thirty-three patients with intracranial germinomas were analyzed by chart review, telephone interview, and neurological assessment. Additionally, a survey on quality of life was performed. The 10-year overall survival rate was 82.1 % at a mean follow-up of 141 (22-306) months. Three quarters (76 %) of the patients reached a favorable neurological outcome on the Modified Rankin Scale (mRS 0-2). However, the self-reported quality of life was significantly worse in germinoma patients compared with a healthy control group (p < 0.001). Surgical resection of the tumor led to no improvement regarding overall survival, neurological outcome, and quality of life. In terms of cognitive functioning, patients with tumor resection were significantly more impaired than biopsied patients (p = 0.04). Although germinomas are efficiently treatable tumors, the restrictions in quality of life in these often young patients are considerable, including financial difficulties. There seems no justification for tumor resection in newly diagnosed cases suspicious for germinoma as the cognitive outcome is worse than in biopsied patients, and there is no effect on overall survival.

DHEA(S)--a novel marker in Cushing's disease.

INTRODUCTION: Dehydroepiandrosterone sulfate (DHEA(S)) is a multi-functional steroid implicated in a broad range of biological effects, including obesity, diabetes, bone metabolism, neuroprotection, and anti-tumorigenesis. It has not yet undergone wider research in the context of Cushing's disease. The objective of this study was to determine if perioperative blood levels of DHEA(S) correlate with levels of ACTH and cortisol, and therefore may be useful as a new, additional marker for the early definition of cure in patients suffering from Cushing's disease. METHODS: Forty-two consecutive patients undergoing transsphenoidal surgery for Cushing's disease from September 2009 to September 2010 were perioperatively monitored for ACTH, cortisol, and DHEA(S). RESULTS: Pre-operative blood samples revealed ACTH levels of median 65 ng/l (range 11-1,183 ng/l, standard deviation 183.76), cortisol of median 257 µg/l (range 93-803 µg/l, standard deviation 140.88), and DHEA(S) of median 2.22 mg/l (range 0.44-7.79 mg/l, standard deviation 1.82) according to the pathology of Cushing's disease. Postoperative blood samples drawn over a 7-day time span showed a drop in median ACTH to just 14.5 % (median: 9 ng/l, range 2-44, standard deviation 12.75) of its median preoperative figure. Median cortisol levels were reduced to 6.9 % (median: 18 µg/l, range 10-190 µg/l, standard deviation 38.04) of their preoperative values and DHEA(S) levels decreased to 17 % (median: 0.38 mg/l, range 0.05-2.29, standard deviation 0.51). In persistent disease, no patient showed a drop in DHEA(S) below 38 % of its preoperative figures. CONCLUSIONS: DHEA(S) shows the potential to become an additional marker in the diagnosis and follow-up of patients. However, it needs to be examined further, including whether DHEA(S) may also be a useful predictor of recovery of the HPA-axis after successful surgery.

Carney complex- why thorough medical history taking is so important - report of three cases and review of the literature.

PURPOSE: To present a new case series and to review the literature on Carney complex (CNC) with an emphasis on highlighting key clinical features of the disease and pointing out possibilities of shortening the diagnostic process. METHOD: Searches of PubMed, identifying relevant reports up to April 2022. RESULTS: CNC is a rare, autosomally dominant inherited neoplasia -endocrinopathy syndrome with high clinical variability, even among members of the same family. Data on length of diagnostic process are scarce with numerous case series reporting a diagnostic delay of decades. Suggestions to shorten the diagnostic process includes awareness of the multi-faceted clinical presentations of CNC, thorough history taking of index patients and family members and awareness of diagnostic pitfalls. Importantly, unusual symptom combinations should alert the clinician to suspect a rare endocrinopathy syndrome such as CNC. Already present and coming on the horizon are databases and novel phenotyping technologies that will aid endocrinologists in their quest for timely diagnosis. CONCLUSION: In this review, we examine the current state of knowledge in CNC and suggest avenues for shortening the diagnostic journey for the afflicted patients.

Experiences with a 3D4K Digital Exoscope System (ORBEYE) in a Wide Range of Neurosurgical Procedures.

BACKGROUND: Exoscopic 3D4K video systems (EX) have recently been introduced as an alternative to conventional operating microscopes (OM). However, experience in handling and setup remains scarce. This study evaluated the practicability of exoscopic surgery in a wide range of procedures. MATERIAL AND METHODS: All EX operations performed between August 2018 and May 2020 were evaluated and compared with procedures using OM. A standardized questionnaire was used to evaluate surgeons' comfort, image quality (including fluorescence modes), and handling. RESULTS: In all, 513 EX operations were performed during the investigated period. EX was generally rated as a valuable surgical tool. In particular, the digital 5-aminolevulinic acid (5-ALA) fluorescence and the comfort level of posture during surgery were stated to be superior to OM (100 and 83%, respectively). CONCLUSION: EX has been used for a significant number of neurosurgical procedures. While presuming that the technical methodology as such will not influence outcome of glioma surgery, proof of equipoise between different techniques expands the spectrum of surgical environments giving neurosurgeons a choice to work according to their preferred ergonomics.

[Acromegaly-associated lesions of the nasal mucosa. Case report]. / Mit Akromegalie assoziierte Veränderungen der Nasenschleimhäute. Fallbericht.

Acromegaly is a rare disease caused by a growth-hormone-secreting pituitary adenoma. Symptoms include enlargement of the hands, feet, and jaw with growing dental interspaces, as well as hypertrophy of the tongue and nasal and sinusoidal mucosa. The two latter symptoms are mostly responsible for the accompanying obstructive sleep apnea syndrome. Besides these "cosmetic" symptoms, the disease is associated with hypertension and diabetes mellitus, as well as with an increased risk for adenomas and carcinomas of the colon. The average time span from first symptom to diagnosis is well over 6 years; a single determination of insulin-like growth factor 1 in serum can confirm the disease. The treatment of choice remains surgical resection of the adenoma in suitable patients, whereas in extensive disease with invasion of surrounding tissue, drug therapy and/or radiotherapy may be necessary.

Health-related Quality of Life in Patients After Treatment of Cushing's Disease.

BACKGROUND: Patients suffering from Cushing's disease are known to be restricted due to a wide range of symptoms. Despite biochemical cure, symptoms might last life-long. These include - among well-known somatic symptoms - several neuropsychiatric symptoms that cannot be as easily tested, but lead to a serious negative impact on quality of life. We aimed to evaluate what factors diminish the self-perceived quality of life the most using 3 questionnaires visualizing those impairments. Furthermore we investigated whether there would be differences in quality of life between patients still being affected by the disease and those that are already in remission. PATIENTS AND METHODS: We reviewed patient charts treated between April 2008 and June 2012 for Cushing's disease and sent 3 questionnaires to the patients for evaluation. For this purpose we used the SF-36, the BDI and the Tuebingen CD-25. 54 patients complied with our request and returned the completed questionnaires. The average time after surgery was 36 months. RESULTS: In all 8 dimensions of the SF-36 significant differences between the patient collective and the expected age- and gender-specific scores could be observed and thus a detectable impairment in quality of life. The BDI revealed that every other patient suffering from Cushing's disease presented depressive symptoms, partially with clinical relevance. In all 6 dimensions of the Tuebingen CD-25 there were notable restrictions in patients. Those restrictions particularly concerned bodily restrictions and cognitive performance. The self-perceived quality of life of active patients was - although not statistically significant - in almost all measured fields worse than the test results of patients in remission after TSS. CONCLUSION: Former and active Cushing's disease patients suffer from a wide range of neuropsychiatric symptoms. Those symptoms might dominate the clinical picture and lead to a serious impairment in quality of life as well as extend periods of suffering and might persist even years after being found healthy. Therefore it is important to evaluate quality of life as an independent factor in every patient being affected by Cushing's disease and to include a holistic view in their therapy. Concomitant therapeutic measures should be accessible at any time for Cushing's disease patients as the normalization of pathologically increased laboratory values doesn't obligatory lead to an improvement of the patients subjectively felt well-being.

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.

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.

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.

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.