First-line surgery in prolactinomas: lessons from a long-term follow-up study in a tertiary referral center.

CONTEXT: Although consensus guidelines recommend dopamine agonists (DAs) as the first-line approach in prolactinomas, some patients may opt instead for upfront surgery, with the goal of minimizing the need for continuation of DAs over the long term. While this approach can be recommended in selected patients with a microprolactinoma, the indication for upfront surgery in macroprolactinomas remains controversial, with limited long-term data in large cohorts. We aimed at elucidating whether first-line surgery is equally safe and effective for patients with micro- or macroprolactinomas not extending beyond the median carotid line (i.e., Knosp grade ≤ 1). METHODOLOGY: Retrospective study of patients with prolactinomas Knosp grade ≤ 1 treated with upfront surgery. The primary endpoint was patients' dependence on DAs at last follow-up. The secondary endpoint was postoperative complications. Independent risk factors for long-term dependence on DAs were analyzed. RESULTS: A microadenoma was noted in 45 patients (52%) and a macroadenoma in 41 (48%), with 17 (20%) harboring a Knosp grade 1 prolactinoma. Median follow-up was 80 months. First-line surgery resulted in long-term remission in 31 patients (72%) with a microprolactinoma and in 18 patients (45%) with a macroprolactinoma (p = 0.02). DA therapy was ultimately required in 11 patients (24%) with microadenomas vs. 20 (49%) with macroadenomas (p = 0.03). As for the latter, DA was required in 13 patients (76%) with Knosp grade 1 macroadenomas vs. 7 patients (29%) with Knosp grade 0 macroadenomas (p = 0.004). There was no mortality, and morbidity was minimal. Knosp grade 1 prolactinomas (OR 7.3, 95% CI 1.4-37.7, p = 0.02) but not adenoma size (i.e., macroprolactinomas) were an independent predictor of long-term dependence on DAs. CONCLUSIONS: First-line surgery in patients with microprolactinomas or macroprolactinomas Knosp grade 0 resulted in a good chance of non-dependency on DA therapy. However, in patients with prolactinomas Knosp grade 1, first-line surgery cannot be recommended, as adjuvant DA therapy after surgery is required in the majority of them over the long term.

Clinical presentation and management of patients with primary hyperparathyroidism of the Swiss Primary Hyperparathyroidism Cohort: a focus on neuro-behavioral and cognitive symptoms.

PURPOSE: To describe the clinical and biochemical profile of patients with primary hyperparathyroidism (PHPT) of the Swiss Hyperparathyroidism Cohort, with a focus on neurobehavioral and cognitive symptoms and on their changes in response to parathyroidectomy. METHODS: From June 2007 to September 2012, 332 patients were enrolled in the Swiss PHPT Cohort Study, a nationwide prospective and non-interventional project collecting clinical, biochemical, and outcome data in newly diagnosed patients. Neuro-behavioral and cognitive status were evaluated annually using the Mini-Mental State Examination, the Hospital Anxiety and Depression Scale, and the Clock Drawing tests. Follow-up data were recorded every 6 months. Patients with parathyroidectomy had one follow-up visit 3-6 months' postoperatively. RESULTS: Symptomatic PHPT was present in 43 % of patients. Among asymptomatic patients, 69 % (131/189) had at least one of the US National Institutes for Health criteria for surgery, leaving thus a small number of patients with cognitive dysfunction or neuropsychological symptoms, but without any other indication for surgery. At baseline, a large proportion showed elevated depression and anxiety scores and cognitive dysfunction, but with no association between biochemical manifestations of the disease and test scores. In the 153 (46 %) patients who underwent parathyroidectomy, we observed an improvement in the Mini-Mental State Examination (P = 0.01), anxiety (P = 0.05) and depression (P = 0.05) scores. CONCLUSION: PHPT patients often present elevated depression and anxiety scores and cognitive dysfunction, but rarely as isolated manifestations. These alterations may be relieved upon treatment by parathyroidectomy.

Total Thyroidectomy for Amiodarone-induced Thyrotoxicosis in the Hyperthyroid State.

Amiodarone is a potent antiarrhythmic agent, indicated for the treatment of refractory arrhythmias, which may lead to thyrotoxicosis. In these patients, thyroidectomy is a valid therapeutic option. Antithyroid therapy in the immediate preoperative setting and the subsequently accepted minimal delay until thyroidectomy have not been clearly defined yet. The aim of the present study was to show, that total thyroidectomy under general anaesthesia in patients with amiodarone-induced thyrotoxicosis (AIT) is safe without necessarily obtaining an euthyroid state preoperatively.We conducted a retrospective cohort study of prospectively gathered data on 11 patients undergoing total thyroidectomy under general anaesthesia between January 2008 and December 2013 for AIT at our University Hospital.All patients were preoperatively treated with carbimazole, steroids and ß-receptor antagonists. Additionally, 3 patients received potassium perchlorate and in one patient carbimazole was changed to propylthiouracil. Plasmapheresis was performed in 3 patients. Only one patient was euthyroid at the time of operation. There were no significant intra- and postoperative complications, especially no signs of thyroid storm. One patient could postoperatively be removed from the cardiac transplant waiting list due to improved cardiac function.Improvements in the interdisciplinary surgical management for AIT between cardiologists, endocrinologists, anaesthetists and endocrine surgeons provide the basis of safe total thyroidectomy under general anaesthesia in hyperthyroid state. Early surgery without long delay for medical antithyroid treatment (with its potential negative side effects) is recommended.

The effect of GH replacement therapy on different fat compartments: a whole-body magnetic resonance imaging study.

OBJECTIVE: Patients with GH deficiency (GHD) are insulin resistant with an increase in visceral fat mass (FM). Whether this holds true when sedentary control subjects (CS) are matched for waist has not been documented. GH replacement therapy (GHRT) results in a decrease in FM. Whether the decrease in FM is mainly related to a reduction in visceral FM remains to be proven. The aim was to separately assess visceral and subcutaneous FM in relation to insulin resistance (IR) in GHD patients before and after GHRT and in sedentary CS. METHODS: Ten patients with GHD were investigated before and 6 months after GHRT. Sedentary CS matched for age, gender, body mass index, and waist were assessed. Exercise capacity was measured as VO(2max) using an incremental work load on a treadmill. Visceral and subcutaneous FM were measured using whole-body magnetic resonance imaging and IR by the homeostasis model assessment of IR (HOMA-IR) index. RESULTS: GHD patients had a non-significantly lower VO(2max) but did not have increased subcutaneous and visceral FM compared with CS. GHRT resulted in a similar relative decrease in subcutaneous and visceral FM. Compared with CS, GHD patients showed a lower HOMA-IR. GHRT tended to increase HOMA-IR. CONCLUSION: Matching for waist and separate assessment of visceral and subcutaneous FM may be critical in the evaluation of body composition and IR in GHD patients before and after GHRT.

Pineal melatonin synthesis is altered in Period1 deficient mice.

Melatonin is an important endocrine signal for darkness in mammals. Transcriptional activation of the arylalkylamine-N-acetyltransferase gene encoding for the penultimate enzyme in melatonin synthesis drives the daily rhythm of the hormone in the pineal gland of rodents. Rhythmic arylalkylamine-N-acetyltransferase expression is controlled by the cAMP-signal transduction pathway and involves the activation of ß-adrenergic receptors and the inducible cAMP early repressor. In addition, the rat arylalkylamine-N-acetyltransferase promoter contains an E-box element which can interact with clock proteins. Moreover, the pineal gland of mice shows a circadian rhythm in clock proteins such as the transcriptional repressor Period1, which has been shown to control rhythmic gene expression in a variety of tissues. However, the role of Period1 in the regulation of pineal melatonin synthesis is still unknown. Therefore, circadian rhythms in arylalkylamine-N-acetyltransferase, ß-adrenergic receptor, and inducible cAMP early repressor mRNA levels (real time PCR), arylalkylamine-N-acetyltransferase enzyme activity (radiometric assay) and melatonin concentration radio immuno assay (RIA) were analyzed in the pineal gland of mice with a targeted deletion of the Period1 gene (Per1-/-) and the corresponding wildtype. In Per1-/- the amplitude in arylalkylamine-N-acetyltransferase expression was significantly elevated as compared to wildtype. In contrast, ß-adrenergic receptor and inducible cAMP early repressor mRNA levels were not affected by the Period1-deficiency. This indicates that the molecular clockwork alters the amplitude of arylalkylamine-N-acetyltransferase expression. In vitro, pineal glands of Per1-/- mice showed a day night difference in arylalkylamine-N-acetyltransferase expression with high levels at night. This suggests that a deficient in Period1 elicits similar effects as the activation of the cAMP-signal transduction pathway in wildtype mice.

Glucagon-like peptide-1 (GLP-1) receptors are not overexpressed in pancreatic islets from patients with severe hyperinsulinaemic hypoglycaemia following gastric bypass.

AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) receptors are highly overexpressed in benign insulinomas, permitting in vivo tumour visualisation with GLP-1 receptor scanning. The present study sought to evaluate the GLP-1 receptor status in vitro in other pancreatic disorders leading to hyperinsulinaemic hypoglycaemia, specifically after gastric bypass surgery. METHODS: Fresh frozen pancreatic tissue samples (n=7) from six gastric bypass surgery patients suffering from hyperinsulinaemic hypoglycaemia were evaluated for GLP-1 receptor content using in vitro receptor autoradiography, and compared with normal pancreas and with pancreatic insulinoma tissues. RESULTS: GLP-1 receptor analysis of the pancreatic tissues, which histopathologically were compatible with nesidioblastosis and originated from post-bypass hypoglycaemic patients, revealed a mean density value of GLP-1 receptors in the islets of 1,483 ± 183 dpm/mg tissue. Pharmacological characterisation indicated the presence of specific GLP-1 receptors. The density of islet GLP-1 receptor in post-gastric bypass patients did not differ from that of normal pancreas (1,563 ± 104 dpm/mg tissue, n = 10). Receptor density in pancreatic acini was low in post-bypass and control conditions. In contrast, benign insulinomas showed a high density of GLP-1 receptors, with a mean value of 8,302 ± 1,073 dpm/mg tissue (n = 6). CONCLUSIONS/INTERPRETATION: In contrast to insulinoma, hyperinsulinaemic hypoglycaemia after gastric bypass surgery is not accompanied by overexpression of GLP-1 receptor in individual islets. Thus, patients with post-gastric bypass hyperinsulinaemic hypoglycaemia are not candidates for GLP-1 receptor imaging in vivo using radiolabelled exendin. These GLP-1 receptor data support the notion that the islet pathobiology of post-gastric bypass hypoglycaemia is distinctly different from that of benign insulinomas.

Exercise-induced growth hormone response in euglycaemia and hyperglycaemia in patients with Type 1 diabetes mellitus.

AIMS: To compare exercise-induced growth hormone (GH) response in patients with Type 1 diabetes during stable euglycaemic and hyperglycaemic conditions. METHODS: We conducted a randomized, controlled, single-blinded cross-over trial in seven male patients with well-controlled Type 1 diabetes. The patients cycled twice for 120 min at a level of 55-60% maximal oxygen uptake. Euglycaemia was at 5.0 mmol/l, hyperglycaemia at 11.0 mmol/l. RESULTS: Area under the curve of GH (AUC(GH)) during exercise was significantly higher during euglycaemia [1430 ng ml(-1) min, 95% confidence interval (CI) 703-2910] compared with hyperglycaemia (1061 ng ml(-1) min, 95% CI 538-2091, P = 0.02). CONCLUSIONS: In patients with Type 1 diabetes, GH concentrations during moderate aerobic exercise during stable hyperglycaemic conditions are significantly lower compared with euglycaemia. These findings are compatible with preserved glucose-mediated GH regulation during exercise in individuals with well-controlled Type 1 diabetes.

[Thyroid nodules: which further investigations should be done]. / Schilddrüsenknoten - Welche Abklärungsschritte sind sinnvoll?

Thyroid nodules are a very common clinical finding with an age-related increase in prevalence. The clinical detection of thyroid nodules is outnumbered by the ultrasonographic assessment of thyroid nodules. The clinical challenge is to exclude thyroid cancer and clinical or subclinical hyperthyroidism. Ultrasonography is the first imaging study in all patients with palpable nodules; their size and TSH determine further diagnostic evaluations. Fine-needle aspiration (cytology) is recommended in euthyroid patients of nodules measuring more than 1-1.5 cm in diameter. Nodules more than 4 cm in diameter have to be removed surgically without preceding cytological examination. Without risk factors thyroid nodules are followed by clinical examination and ultrasonography every 6-12 months, in case of symptoms or rapid growth a follow-up assessment should be done earlier.

Effect of growth hormone (GH) on fasting and postprandial metabolism in GH deficiency.

OBJECTIVE: Hypopituitarism with adult-onset growth hormone deficiency (GHD) is associated with increased cardiovascular morbidity and mortality due to premature and progressive atherosclerosis. An underlying cause of atherosclerosis is increased insulin resistance. Elevated fasting and postprandial glucose and lipid levels may contribute to premature atherosclerosis. We studied effects of growth hormone replacement (GHRT) on fasting and postprandial metabolic parameters as well as on insulin sensitivity in patients with adult-onset GHD. DESIGN: Using a standardized mixed meal, we studied insulin, glucose, non-esterified free fatty acid (NEFA) and triglycerides (TG) concentrations in the fasting state and during a 4 h postprandial period in 15 patients with adult-onset GHD before and after 4 months of GHRT. Identical investigations were performed in healthy matched control subjects. RESULTS: GHD patients before and after GHRT: GHRT did not result in significant changes in fasting glucose, insulin, NEFA and TG concentrations. In the postprandial period GHRT resulted in a non-significant increase in glucose and a decrease in NEFA levels in the presence of unchanged postprandial insulin and TG concentrations. GHD patients vs. control subjects: GHD patients showed similar fasting glucose, insulin and NEFA concentrations, but TG were increased. In the postprandial period GHD patients exhibited similar glucose and TG, but increased insulin and NEFA concentrations. GHRT patients vs. control subjects: Patients after GHRT had similar fasting glucose, insulin and NEFA, but increased TG concentrations. In the postprandial period patients after GHRT had increased glucose and insulin levels in the presence of similar NEFA and TG concentrations. CONCLUSIONS: While impaired insulin action in patients with GHD translates mainly by an impaired fasting TG metabolism, GHRT induced insulin resistance additionally encompasses postprandial glucose metabolism.

[When eating becomes dangerous...]. / Von der Frau, der das Essen nicht bekam.

We report the case of a 59-year-old women with idiopathic insulin auto-immune syndrome, a rare cause of endogenous hyperinsulinemic hypoglycemia. It is characterized by extremely high levels of insulin in the presence of high titers of insulin antibodies despite the absence of previous insulin injections. Early postprandial increase in glucose concentrations due to impaired insulin action resulting from the buffering effect of the antibodies and late postprandial hypoglycemia as a consequence of the dissociation of insulin from the antibodies was observed. A correct diagnosis is important to avoid unnecessary investigations and surgery in these patients who are best treated conservatively - with a good prognosis - by fractionating carbohydrate intake during the day.

[Pregnancy in active acromegaly]. / Schwangerschaft während aktiver Akromegalie.

HISTORY AND CLINICAL FINDINGS: A 29-year-old woman with a long-lasting history of oligoamenorrhea, fell pregnant shortly after being diagnosed with acromegaly. LABORATORY TESTS AND IMAGING: A high IGF-1 concentration and an oral glucose tolerance test confirmed the diagnosis. Cranial magnetic resonance imaging demonstrated a macroadenoma of the pituitary with suprasellar extension and compression of the optic chiasm leading to incomplete hemianopsia. TREATMENT AND COURSE: Transsphenoidal surgery was performed during the second trimester, impaired visual fields became normal and subsequent biochemical tests suggested remission. She delivered a healthy full-term infant via cesarean section after an uncomplicated pregnancy. The infant's development was unremarkable. Postpartum assessment showed persistent acromegaly activity and the patient was judged to require secondary multimodal therapy. CONCLUSIONS: Pituitary adenomas often cause oligoamenorrhea and may interfere with fertility. Although pregnancy rarely occurs during the course of active acromegaly, the maternal morbidity, including hypertension and gestational diabetes, is increased. While pregnancy may cause an increase in tumor size, biochemical improvement in acromegaly is--as illustrated by the present case--also possible. A maternal-to-fetal transfer of growth hormone or IGF-1 has not been proved.

Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus--a prospective single-blinded randomised crossover trial.

AIMS/HYPOTHESIS: We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type 1 diabetes at euglycaemia and hyperglycaemia with identical insulin levels. METHODS: This was a single-blinded randomised crossover study at a university diabetes unit in Switzerland. We studied seven physically active men with type 1 diabetes (mean +/- SEM age 33.5 +/- 2.4 years, diabetes duration 20.1 +/- 3.6 years, HbA1c 6.7 +/- 0.2% and peak oxygen uptake [VO2peak] 50.3 +/- 4.5 ml min(-1) kg(-1)). Men were studied twice while cycling for 120 min at 55 to 60% of VO2peak, with a blood glucose level randomly set either at 5 or 11 mmol/l and identical insulinaemia. The participants were blinded to the glycaemic level; allocation concealment was by opaque, sealed envelopes. Magnetic resonance spectroscopy was used to quantify intramyocellular glycogen and lipids before and after exercise. Indirect calorimetry and measurement of stable isotopes and counter-regulatory hormones complemented the assessment of local and systemic fuel metabolism. RESULTS: The contribution of lipid oxidation to overall energy metabolism was higher in euglycaemia than in hyperglycaemia (49.4 +/- 4.8 vs 30.6 +/- 4.2%; p < 0.05). Carbohydrate oxidation accounted for 48.2 +/- 4.7 and 66.6 +/- 4.2% of total energy expenditure in euglycaemia and hyperglycaemia, respectively (p < 0.05). The level of intramyocellular glycogen before exercise was higher in hyperglycaemia than in euglycaemia (3.4 +/- 0.3 vs 2.7 +/- 0.2 arbitrary units [AU]; p < 0.05). Absolute glycogen consumption tended to be higher in hyperglycaemia than in euglycaemia (1.3 +/- 0.3 vs 0.9 +/- 0.1 AU). Cortisol and growth hormone increased more strongly in euglycaemia than in hyperglycaemia (levels at the end of exercise 634 +/- 52 vs 501 +/- 32 nmol/l and 15.5 +/- 4.5 vs 7.4 +/- 2.0 ng/ml, respectively; p < 0.05). CONCLUSIONS/INTERPRETATION: Substrate oxidation in type 1 diabetic patients performing aerobic exercise in euglycaemia is similar to that in healthy individuals revealing a shift towards lipid oxidation during exercise. In hyperglycaemia fuel metabolism in these patients is dominated by carbohydrate oxidation. Intramyocellular glycogen was not spared in hyperglycaemia.

QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up.

AIMS/HYPOTHESIS: We evaluated the association of QT interval corrected for heart rate (QT(c)) and resting heart rate (rHR) with mortality (all-causes, cardiovascular, cardiac, and ischaemic heart disease) in subjects with type 1 and type 2 diabetes. METHODS: We followed 523 diabetic patients (221 with type 1 diabetes, 302 with type 2 diabetes) who were recruited between 1974 and 1977 in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes. Duration of follow-up was 22.6 +/- 0.6 years. Causes of death were obtained from death certificates, hospital records, post-mortem reports, and additional information given by treating physicians. RESULTS: In subjects with type 1 diabetes QT(c), but not rHR, was associated with an increased risk of: (1) all-cause mortality (hazard ratio [HR] 1.10 per 10 ms increase in QT(c), 95% CI 1.02-1.20, p = 0.011); (2) mortality due to cardiovascular (HR 1.15, 1.02-1.31, p = 0.024); and (3) mortality due to cardiac disease (HR 1.19, 1.03-1.36, p = 0.016). Findings for subjects with type 2 diabetes were different: rHR, but not QT(c) was associated with mortality due to: (1) all causes (HR 1.31 per 10 beats per min, 95% CI 1.15-1.50, p < 0.001); (2) cardiovascular disease (HR 1.43, 1.18-1.73, p < 0.001); (3) cardiac disease (HR 1.45, 1.19-1.76, p < 0.001); and (4) ischaemic heart disease (HR 1.52, 1.21-1.90, p < 0.001). Effect modification of QT(c) by type 1 and rHR by type 2 diabetes was statistically significant (p < 0.05 for all terms of interaction). CONCLUSIONS/INTERPRETATION: QT(c) is associated with long-term mortality in subjects with type 1 diabetes, whereas rHR is related to increased mortality risk in subjects with type 2 diabetes.

[A rare cause of cardiogenic shock with psychotic symptoms]. / Kardiogener Schock und psychotisches Zustandsbild seltener Ursache.

HISTORY AND FINDINGS: A 40-year-old man was admitted to the emergency department with psychotic symptoms and marked hypothermia. He was known to have had a macroadenoma of the pituitary gland which had been excised 10 years before. No information about his current medication was available. Several hours after admission the patient developed signs of acute cardiac failure and cardiogenic shock. He was admitted to the intensive care unit, intubated and treated with vasoactive drugs. Later investigations revealed that the patient had stopped his hormonal therapy (hydrocortisone and thyroxine) at least 3 months previously. INVESTIGATIONS: Transthoracic electrocardiography revealed diffuse myocardial contractile abnormalities with an ejection fraction of 30%. Acute ischemic damage was ruled out by serial troponin-T test and electrocardiography. Severe hypothyroidism and hypocortisolism were confirmed by laboratory tests. DIAGNOSIS, THERAPY AND COURSE: The diagnosis of acute pituitary insufficiency with myxedema coma and hypocortisolism was suspected and the patient was treated with parenteral cortisone and L-thyroxine. The response was favorable and the patient was extubated after 5 days. Cardiac contractility and ejection fraction normalized. CONCLUSIONS: Myxedema coma can be a predominant finding of acute anterior pituitary insufficiency. There are important effects on the cardiovascular system and cerebral functions (altered mentation). Immediate diagnosis and therapy are crucial to reduce the otherwise high mortality.

Apolipoprotein B as a long-term predictor of mortality in type 1 diabetes mellitus: a 15-year follow up.

OBJECTIVES: To evaluate the association of apolipoprotein B (apo B) with mortality due to all causes, to cardiac disease and to ischaemic heart disease (IHD) in subjects with type 1 diabetes mellitus. SUBJECTS: 165 subjects with type 1 diabetes included in the Swiss Cohort of the WHO Multinational Study of Vascular Disease in Diabetes were followed for 14.7+/-0.45 years. METHODS: Causes of death were obtained from death certificates, hospital records and postmortem reports. Using a parametric proportional hazards model the association of apo B with mortality rates was assessed by time-to-event analysis, including the absolute cumulative mortality risk over time for various apo B levels at baseline. RESULTS: Apo B was positively associated with all-cause mortality [hazard ratio (HR) 2.65 per g L-1 increase of apo B, 95% CI: 1.11-6.36, P=0.029], cardiac mortality (HR 11.64, 1.03-131.11, P=0.047) and IHD mortality (HR 9.36, 1.26-69.66, P=0.029). An apo B>or=0.96 g L-1 translated into a duplication of overall mortality hazard (HR 1.93, 1.00-3.72, P=0.050), and a sevenfold increase of mortality because of cardiac disease or IHD (HR 7.44, 1.44-38.42, P=0.017 and HR 7.38, 0.78-69.82, P=0.081). A baseline apo B of 1.5 g L-1 predicted an absolute cumulative risk to die over the next 10 years of 12.1% (5.2-31.7) for male and of 10.4% (4.7-26.1) for female subjects whereas risks were 6.3% (1.8-21.4) and 5.4% (0.8-15.8) for an apo B of 0.8 g L-1. CONCLUSION: Apo B is consistently associated with an increased mortality in type 1 diabetes.

Transient MR changes and symptomatic epilepsy following gamma knife treatment of a residual GH-secreting pituitary adenoma in the cavernous sinus.

OBJECTIVE: To report a rare side effect of gamma knife treatment of pituitary macroadenoma. CASE REPORT: In a forty-one-year old female patient acromegaly was diagnosed due to a growth hormone secreting pituitary macroadenoma. Following transsphenoidal surgery the patient underwent gamma knife treatment for persistent uncontrolled acromegaly activity of residual tumor, infiltrating the left cavernous sinus. 15 months later, complex partial seizures were diagnosed and 17 months after gamma knife treatment a gadolinium enhancing lesion was detected in her left medial temporal lobe. Radiation induced changes, radiation necrosis or a glioma were considered. Neuropsychological testing indicated potentially significant post-surgical deficits. Therefore, surgical action was postponed and anti-epileptic treatment was started. Four months later she was free of seizures and an MR scan showed an almost complete regression of the gadolinium enhancing lesion, indicating that it had been due to radiation induced changes. CONCLUSION: Gamma knife surgery of a pituitary adenoma may cause radiation induced MR changes of the mesial temporal lobe mimicking glioma or radionecrosis and cause symptomatic epileptic seizures. The awareness of this rare complication is important to avoid unnecessary and potentially harmful diagnostic or therapeutic interventions.

[Simultaneous defect of visual fields and loss of libido--a coincidence?]. / Gleichzeitiger Gesichtsfelddefekt und Libidoverlust - Zufall?

We present the case of a 60 year old male patient with incidentally detected visual abnormalities. Detailed personal history revealed a hypogonadism that had been present for several years. Further investigations established the diagnosis of an infiltrative macroadenoma. Medical treatment with cabergoline led to a rapid regression of ophthalmologic symptoms and, subsequently, of tumor size. In male subjects symptoms of hypogonadism are often reported only late in the course of the disease, thereby leading to a generally larger tumor size at the point of diagnosis. In contrast to other pituitary tumors that are mainly treated by surgery, medical treatment with dopamine agonists is the principal therapeutic option in prolactinomas.

[Endogenous hypercortisolism and immunologically-mediated disease: three cases]. / Endogener Hypercortisolismus und immunologisch vermittelte Erkrankungen: drei Fälle.

HISTORY AND CLINICAL FINDINGS: We report three women with hypercortisolism presenting with symptoms and signs of Cushing's syndrome. In two of the patients, initial symptoms of hypercortisolism were associated with spontaneous amelioration of previously known atopic dermatitis and psoriasis, respectively. DIAGNOSTIC PROCEDURES: Diagnosis was established by demonstrating both lack of responsiveness to dexamethasone (1mg) suppression test and increased 24-hour urine cortisol secretion. One patient had a low serum ACTH level indicating Cushing's syndrome of adrenal origin. In the other two patients hypercortisolism proved to be ACTH-dependent, the source being the pituitary, as demonstrated by CRH stimulation test (elevation of ACTH and cortisol by 35 % and 20 %, respectively) and sampling of the petrosus sinus. In both patients imaging confirmed the presence of a pituitary adenoma. TREATMENT AND COURSE: All three patients underwent successful surgery: the first patient had an adrenalectomy, the other two transseptal transsphenoidal hypophysectomy. As symptoms and signs of hypercortisolism improved, the previously quiescent signs of atopic dermatitis and psoriasis recurred and one patient developed Graves' disease. CONCLUSIONS: Following successful treatment of endogenous hypercortisolism, symptoms of unrelated immunologically mediated conditions, especially autoimmune thyroiditis, may occasionally appear. Furthermore, the clinical course of coexisting immunologically mediated diseases may help to diagnose Cushing's syndrome and to monitor the patients after surgical treatment.

Treatment outcomes and mortality of 94 patients with acromegaly.

BACKGROUND: Due to new therapeutic modalities and modified therapeutic goals outcome of patients with acromegaly may change over time and differ by centre. We analysed treatment outcomes and mortality of our patients with acromegaly seen between 1971 and 2003. METHOD: The cohort consisted of 94 patients who had been followed for 0.3-31 years (mean 10.6 years). Remission criteria were a normalized IGF-I concentration, a nadir GH level during oral glucose load of <1.0 microg/l and a random GH value of <2.5 microg/l. FINDINGS: Transsphenoidal surgery achieved remission in 80% of patients with micro-adenomas (<1 cm), 65% with meso-adenomas (> or = 1 cm to <2 cm) and 27% with macro-adenomas (> or = 2 cm). Patients with meso-adenomas operated on after 1995 tended to have a better outcome compared to those operated on before 1995 (Remission in 83% vs. 38%). Radiotherapy resulted in disease control in 22 of 47 patients (47%). Intramuscular depot formulation of octreotide (Sandostatin LAR) led to disease control in 17 of 26 patients (65%). After multimodal therapy persistent acromegalic activity remained in 18% of the patients; only one of them had an adenoma of <2 cm. The standardized mortality ratio was 1.30 (95% CI 0.52-2.67) for patients in remission and 1.38 (95% CI 0.51-3.00) for patients with persistent acromegalic activity. CONCLUSIONS. Most patients with adenomas of <2 cm can be expected to achieve remission by transsphenoidal surgery alone. Furthermore, virtually all patients with adenomas of <2 cm and more than 80% of patients with adenomas of > or = 2 cm can be expected to achieve remission by adjuvant treatment. Aggressive multimodal therapy is critical in the management of acromegaly reducing mortality risk close to that of the general population.