Changes in cardiac repolarisation during spontaneous nocturnal hypoglycaemia in subjects with type 1 diabetes: a preliminary report.

AIMS: Experimental studies have revealed that hypoglycaemia can result in morphological changes in electrocardiographic repolarisation in subjects with type 1 diabetes. However, the influence of spontaneous nocturnal hypoglycaemia on repolarisation morphology in a 'real life' situation is not clear. METHODS: Adults with type 1 diabetes (n = 11) underwent continuous glucose monitoring with a subcutaneous sensor and digital 12-lead ECG recording for three nights. T-wave morphology was analysed with custom-made software during both hypoglycaemia (glucose <3.5 mmol/l at least 20 min) from ten consecutive heart beats in the middle of the deepest hypoglycaemia and from a control nonhypoglycaemic period (glucose ≥5.0 mmol/l) from the same recording. RESULTS: In the comparison of 10 hypoglycaemia-control pairs, heart rate (65 ± 12 beats/min during normoglycaemia versus 85 ± 19 beats/min during hypoglycaemia, p = 0.028) increased and the QTc interval (439 ± 5 vs. 373 ± 5 ms, respectively, p = 0.025) decreased significantly during hypoglycaemia. The spatial QRS-T angle (TCRT) was reduced, and the roughness of the T-wave loop (T-E) increased significantly (p = 0.037 for both) in the patients during hypoglycaemia. CONCLUSIONS: In adults with type 1 diabetes, spontaneous nocturnal hypoglycaemia results in morphological changes and increased heterogeneity of global cardiac repolarisation. These changes may contribute to the risk of 'dead in bed' syndrome encountered in young individuals with type 1 diabetes.

MRI-guided laser ablation of neuroendocrine tumor hepatic metastases.

BACKGROUND: Neuroendocrine tumors (NET) represent a therapeutically challenging and heterogeneous group of malignancies occurring throughout the body, but mainly in the gastrointestinal system. PURPOSE: To describe magnetic resonance imaging (MRI)-guided laser ablation of NET liver metastases and assess its role within the current treatment options and methods. MATERIAL AND METHODS: Two patients with NET tumor hepatic metastases were treated with MRI-guided interstitial laser ablation (LITT). Three tumors were treated. Clinical follow-up time was 10 years. RESULTS: Both patients were successfully treated. There were no local recurrences at the ablation site during the follow-up. Both patients had survived at 10-year follow-up. One patient is disease-free. CONCLUSION: MRI-guided laser ablation can be used to treat NET tumor liver metastases but combination therapy and a rigorous follow-up schedule are recommended.

Autonomic cardiac regulation during spontaneous nocturnal hypoglycemia in patients with type 1 diabetes.

OBJECTIVE: Experimental clamp studies have suggested that hypoglycemia evokes a reduction of cardiac vagal control in patients with type 1 diabetes. However, there are limited data on the influence of spontaneous nocturnal hypoglycemia on cardiac autonomic regulation. RESEARCH DESIGN AND METHODS: Adults with type 1 diabetes (n = 37) underwent continuous glucose monitoring via a subcutaneous sensor as well as recording of R-R interval or electrocardiogram for 3 nights. Heart rate (HR) variability was analyzed during periods of hypoglycemia (glucose <3.5 mmol/L) (minimum length of 20 min) and a control nonhypoglycemic period (glucose >3.9 mmol/L) of equal duration and at the same time of night. RESULTS: The duration of hypoglycemic and control episodes (n = 18) ranged from 20 to 190 min (mean 71 min). HR (62 ± 7 vs. 63 ± 9 beats per min; P = 0.30) or the high-frequency component of HR power spectrum (2,002 ± 1,965 vs. 1,336 ± 1,506 ms(2); P = 0.26) did not change during hypoglycemia. Hypoglycemia resulted in a significant decrease in the low-frequency component of HR variability (2,134 ± 1,635 vs. 1,169 ± 1,029 ms(2), respectively; P = 0.006). The decline in the glucose concentration displayed a significant positive correlation with the decrease of the low-frequency component of HR variability (r = 0.48; P = 0.04). The latter was closely related to an increase in muscle sympathetic nerve activity recorded in 10 subjects during controlled sympathetic activation. CONCLUSIONS: Spontaneous nocturnal hypoglycemia in patients with type 1 diabetes results in a reduction of the low-frequency component of HR, which is best explained by excessive sympathetic activation without a concomitant withdrawal of vagal outflow.

[Multiple endocrine neoplasia type 1]. / Tyypin 1 multippeli endokriininen neoplasia eli MEN 1-oireyhtymi.

Multiple endocrine neoplasia type 1 (MEN1) is a complex multisystem disease characterized by the combined occurrence of endocrine tumours of the parathyroid glands, anterior pituitary gland and adrenal glands and the neuroendocrine tumours (NET) of duodenum, pancreas, thymus and bronchus. Malignancy occurs commonly (up to 30 %) and malignant NETs are important causes of the MEN1-related morbidity and mortality. Regular clinical, biochemical and radiologic screening for the syndrome-related tumours are the basis of the life-long surveillance. Early detection and adequate management of these tumours reduce risk of death and morbidity.

Young male patients are at elevated risk of developing serious central nervous system complications during acute Puumala hantavirus infection.

BACKGROUND: Our aim was to characterize clinical properties and laboratory parameters in patients with or without cerebrospinal fluid (CSF) findings suggestive of central nervous system (CNS) involvement, and especially those who developed serious CNS complications during acute nephropathia epidemica (NE) caused by Puumala hantavirus (PUUV) infection. METHODS: A prospective cohort of 40 patients with acute NE and no signs of major CNS complications was analyzed. In addition, 8 patients with major CNS complications associated with NE were characterized. We collected data of CNS symptoms, CSF analysis, brain magnetic resonance imaging (MRI) results, electroencephalography (EEG) recordings, kidney function, and a number of laboratory parameters. Selected patients were evaluated by an ophthalmologist. RESULTS: Patients with a positive CSF PUUV IgM finding or major CNS complications were more often males (p < 0.05) and they had higher plasma creatinine values (p < 0.001) compared to those with negative CSF PUUV IgM. The degree of tissue edema did not explain the CSF findings. Patients with major CNS complications were younger than those with negative CSF PUUV IgM finding (52.9 vs. 38.5 years, p < 0.05). Some patients developed permanent neurological and ophthalmological impairments. CONCLUSIONS: CNS and ocular involvement during and after acute NE can cause permanent damage and these symptoms seem to be attributable to true infection of the CNS rather than increased tissue permeability. The possibility of this condition should be borne in mind especially in young male patients.

Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study.

CONTEXT: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. OBJECTIVE: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. DESIGN: This study was an international, multicenter, retrospective case collection/database analysis. SETTING: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. PATIENTS: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. RESULTS: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. CONCLUSIONS: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.

Central nervous system-related symptoms and findings are common in acute Puumala hantavirus infection.

BACKGROUND: Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome (HFRS) also called nephropathia epidemica (NE). Recent case reports and retrospective studies suggest that NE may damage the pituitary gland. Based on these observations, our goal was to explore the nature of this complication prospectively. METHODS: A total of 58 hospitalized patients with acute NE volunteered to participate. Central nervous system (CNS) symptoms were recorded, cerebrospinal fluid (CSF) samples were collected, human leukocyte antigen (HLA) haplotype was analyzed, brain magnetic resonance imaging (MRI) was acquired, and electroencephalography (EEG) was recorded. Patients with abnormal pituitary MRI finding were examined by an endocrinologist. RESULTS: Most patients experienced CNS symptoms, and half of the CSF samples were positive for PUUV IgM, elevated protein level, or leukocyte count. CSF of patients negative for DR15(2)-DQ6 haplotype was less frequently affected. MRI revealed pituitary hemorrhage in two patients; these two patients suffered sudden loss of vision associated with headache, and they both developed hypopituitarism. Only one patient required long-term hormonal replacement therapy. CONCLUSION: CNS-related symptoms and inflammation in the CSF are common in acute NE. Genetic properties of the host may predispose to CNS involvement. It does seem that pituitary injury and subsequent hormonal insufficiency may complicate the recovery.

Pituitary adenoma predisposition caused by germline mutations in the AIP gene.

Pituitary adenomas are common in the general population, and understanding their molecular basis is of great interest. Combining chip-based technologies with genealogy data, we identified germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene in individuals with pituitary adenoma predisposition (PAP). AIP acts in cytoplasmic retention of the latent form of the aryl hydrocarbon receptor and also has other functions. In a population-based series from Northern Finland, two AIP mutations account for 16% of all patients diagnosed with pituitary adenomas secreting growth hormone and for 40% of the subset of patients who were diagnosed when they were younger than 35 years of age. Typically, PAP patients do not display a strong family history of pituitary adenoma; thus, AIP is an example of a low-penetrance tumor susceptibility gene.

Effects of sustained insulin-induced hypoglycemia on cardiovascular autonomic regulation in type 1 diabetes.

Effects of hypoglycemia on cardiac autonomic regulation may contribute to the occurrence of adverse cardiac events. This study assessed the effects of sustained hyperinsulinemic hypoglycemia on cardiovascular autonomic regulation in type 1 diabetic patients and their nondiabetic counterparts. The study consisted of 16 type 1 diabetic patients and 8 age-matched healthy control subjects who underwent euglycemic and hypoglycemic clamp procedures in a random order. Heart rate variability was measured from continuous electrocardiogram recordings by time and frequency domain methods, along with Poincare plot analysis during both a hyperinsulinemic-euglycemic and hypoglycemic clamp at three different glucose levels (4.5-5.5, 3.0-3.5, and 2.0-2.5 mmol/l). Controlled hypoglycemia resulted in an increase of supine heart rate in both the diabetic patients (from 72 +/- 9 to 80 +/- 11 bpm, P < 0.01) and the control subjects (from 59 +/- 5 to 65 +/- 5 bpm, P < 0.05) and progressive reductions of the high-frequency spectral component and beat-to-beat heart rate variability (SD1; P < 0.05 in the diabetic patients and P < 0.01 in control subjects). No significant changes in heart rate variability occurred during the euglycemic clamp. We conclude that hypoglycemia results in a reduction of cardiac vagal outflow in both diabetic and nondiabetic subjects. Altered autonomic regulation may contribute to the occurrence of cardiac events during hypoglycemia.

Hypophyseal hemorrhage and panhypopituitarism during Puumala Virus Infection: Magnetic Resonance Imaging and detection of viral antigen in the hypophysis.

We describe 3 cases of nephropathia epidemica (NE) that confirm that Puumala virus infection may cause hypophyseal injury. Autopsy revealed a hemorrhagic hypophysis positive for Puumala virus antigen in both neuroendocrine stromal and vascular endothelial cells in 1 patient, and 2 patients developed hypophyseal hemorrhage (diagnosed with magnetic resonance imaging) during or shortly after acute NE, both of whom developed panhypopituitarism.