Acromegaly with 'normal' serum growth hormone levels. Clinical features, diagnosis and results of transsphenoidal microsurgery.

Among 216 consecutive patients with growth hormone secreting pituitary adenomas who underwent primary neurosurgical treatment at the University of Erlangen-Nürnberg, 8 cases of acromegaly with 'normal' basal growth hormone levels (less than or equal to 5 ng/ml) were seen. They all had the typical clinical features of acromegaly, exhibited an abnormal growth hormone secretion following an oral glucose load, and had markedly elevated somatomedin C levels. The GRH- and TRH/GnRH-tests were not found helpful in establishing the diagnosis. Neuroradiology could demonstrate a pituitary adenoma in all of the patients. Following transsphenoidal microsurgical resection of the tumours, growth hormone secretion during oral glucose tolerance testing was normalised in 7 of the 8 patients. Immunohistology and explant culture studies documented growth hormone secreting pituitary adenomas in all cases. The authors conclude that even the finding of repetitive 'normal' (less than or equal to 5 ng/ml) serum GH levels does not exclude active acromegaly and when the clinical diagnosis of acromegaly is suspected, dynamic endocrine testing may reveal abnormal secretion patterns of GH in these cases. Transsphenoidal microsurgical resection of a pituitary adenoma offers a good chance of clinical and endocrinological remission in these cases.     

Formation of trideuteromethane from deuterated trimethylamine or methylamine by Methanosarcina barkeri.

Methanosarcina barkeri was grown on trimethylamine, methylamine, or methanol containing completely deuterated methyl groups. Methane was collected and analyzed in a mass spectrometer. It contained 79 to 83% CD3H and 14 to 18% CD2H2. This demonstrated that the methyl groups of the above compounds served primarily as direct precursors of methane.     

Panhypopituitarism associated with diabetes insipidus in a girl with a suprasellar arachnoid cyst

We report on a female patient with a large suprasellar arachnoid cyst (3.5 x 2.5 cm) combined with right optic nerve hypoplasia. She developed growth hormone deficiency and hypothyroidism at the age of 8.5 years, adrenal insufficiency at the age of 11 years, diabetes insipidus and hypogonadotropic hypogonadism at the age of 15 years. When last seen at the age of 19 years she was extremely obese (+5.9 BMI SDS). The endocrine picture suggests that arachnoid cysts might be involved in far more complex hypothalamic-pituitary disturbances than previously thought.     

Results of dynamic endocrine testing of hypothalamic pituitary function in patients with a primary "empty" sella syndrome

A total of 52 patients (38 women, 14 men) with a primary "empty" sella syndrome underwent dynamic endocrine testing consisting of insulin-induced hypoglycaemia and a combined anterior pituitary stimulation test utilizing GnRH and TRH. The diagnosis of an "empty" sella turcica was made on the basis of thin collimation CT reconstructions and in addition either metrizamide cisternography or magnetic resonance (MR) imaging. Only 16 of the patients presented with endocrine problems. Hyperprolactinaemia was the most common endocrine disturbance detected, and was found in 17 individuals. Panhypopituitarism was found in 3 patients. Nine other patients had some degree of partial pituitary insufficiency, but only two of them required replacement therapy. However, 31 patients had no evidence of endocrine dysfunction.     

Feedback equilibrium control during human standing

Equilibrium maintenance during standing in humans was investigated with a 3-joint (ankle, knee and hip) sagittal model of body movement. The experimental paradigm consisted of sudden perturbations of humans in quiet stance by backward displacements of the support platform. Data analysis was performed using eigenvectors of motion equation. The results supported three conclusions. First, independent feedback control of movements along eigenvectors (eigenmovements) can adequately describe human postural responses to stance perturbations. This conclusion is consistent with previous observations (Alexandrov et al., 2001b) that these same eigenmovements are also independently controlled in a feed-forward manner during voluntary upper-trunk bending. Second, independent feedback control of each eigenmovement is sufficient to provide its stability. Third, the feedback loop in each eigenmovement can be modeled as a linear visco-elastic spring with delay. Visco-elastic parameters and time-delay values result from the combined contribution of passive visco-elastic mechanisms and sensory systems of different modalities     

Effect of Sfrp5 on Cytokine Release and Insulin Action in Primary Human Adipocytes and Skeletal Muscle Cells

Secreted frizzled-related protein 5 (Sfrp5) is an adipokine with anti-inflammatory and insulin-sensitizing properties in mice. However, the mechanism of Sfrp5 action, especially in humans, is largely unknown. Therefore, cytokine release and insulin signaling were analyzed to investigate the impact of Sfrp5 on inflammation and insulin signaling in primary human adipocytes and skeletal muscle cells (hSkMC). Sfrp5 neither affected interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1) and adiponectin release from human adipocytes, nor IL-6 and IL-8 release from hSkMC. In tumor necrosis factor (TNF) α-treated adipocytes, Sfrp5 reduced IL-6 release by 49% (p<0.05), but did not affect MCP-1 and adiponectin release. In MCP-1-treated hSkMC, Sfrp5 did not affect cytokine secretion. In untreated adipocytes, Sfrp5 decreased the insulin-mediated phosphorylation of Akt-Ser473, Akt-Thr308, GSK3α-Ser21 and PRAS40-Thr246 by 34% (p<0.01), 31% (p<0.05), 37% (p<0.05) and 34% (p<0.01), respectively, and the stimulation of glucose uptake by 25% (p<0.05). Incubation with TNFα increased the phosphorylation of JNK and NFκB, and impaired insulin signaling. When Sfrp5 and TNFα were combined, there was no additional effect on insulin signaling and JNK phosphorylation, but phosphorylation of NFκB was reversed to basal levels. Sfrp5 had no effect on insulin signaling in untreated or in MCP-1 treated hSkMC. Thus, Sfrp5 lowered IL-6 release and NFκB phosphorylation in cytokine-treated human adipocytes, but not under normal conditions, and decreased insulin signaling in untreated human adipocytes. Sfrp5 did not act on hSkMC. Therefore, the cellular actions of Sfrp5 seem to depend on the type of tissue as well as its inflammatory and metabolic state.     

Mikroevolution — Makroevolution — Punktualismus Ein Diskussionsbeitrag am Beispiel miozäner Eomyiden (Mammalia,Rodentia)

Based on new material of the rodent genus Pseudotheridomys from the lower Miocene fissurefilling of Schaffhausen near Harburg (Nördlinger Ries, Bavaria) the process of continuous development from Pseudotheridomys to Ligerimys can be demonstrated. Within homogeneous populations of Pseudotheridomys the origin of a new morphotype can be observed. In following populations from several biostrati-graphic levels in southern Germany this type becomes more and more dominant, up to homogeneous populations of Ligerimys florancei. For this example of microevolutionary origin of a new genus — for a long time separated from its forerunner by a large gap in documentation — it is shown that neither a dichotomy nor any special mechanism of macroevolution nor a speciation in the sense of punctualism is necessary to explain its development. The process continued for at least 3 million years. It quite corresponds to the synthetic theory of evolution.