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Key Clinical Message Hypophyseal dysfunction may be overlooked by the currently generally accepted laboratory routine for the differential diagnosis in patients suffering from symptoms of depression or dementia. Abstract Hypothyroidism is an important cause of depression and potentially reversible cognitive impairment. Whereas the determination of the plasma concentration of thyrotropin (TSH) is generally considered part of the laboratory screening tests for dementia, the measurement of total or free triiodothyronine (T3, FT3), thyroxine (T4, FT4) and cortisol in plasma does not belong to the routine diagnostic workup in patients with depression or suspected dementia. In an 87‐year‐old lady suffering from increasingly poor general health, decreased fluid and food intake, mood depression and lack of energy, three measurements of plasma TSH produced normal values. A cranial computed tomography (cCT) 2 days prior to hospital admission had been assessed as apparently normal. A second cCT performed following a loss of consciousness complicated by tongue bite showed a hypophyseal tumor. Then, low plasma levels of FT3, FT4 and cortisol were found. Following hormone replacement and transsphenoidal tumor resection, the patient recovered rapidly. The present case report illustrates the pitfalls of measuring merely the TSH level in the detection of thyroid and hypophyseal dysfunction.

Abstract Demyelinated lesions in human pons observed after osmotic shifts in serum have been referred to as central pontine myelinolysis (CPM). Astrocytic damage, which is prominent in neuroinflammatory diseases like neuromyelitis optica (NMO) and multiple sclerosis (MS), is considered the primary event during formation of CPM lesions. Although more data on the effects of astrocyte-derived factors on oligodendrocyte precursor cells (OPCs) and remyelination are emerging, still little is known about remyelination of lesions with primary astrocytic loss. In autopsy tissue from patients with CPM as well as in an experimental model, we were able to characterize OPC activation and differentiation. Injections of the thymidine-analogue BrdU traced the maturation of OPCs activated in early astrocyte-depleted lesions. We observed rapid activation of the parenchymal NG2+ OPC reservoir in experimental astrocyte-depleted demyelinated lesions, leading to extensive OPC proliferation. One week after lesion initiation, most parenchyma-derived OPCs expressed breast carcinoma amplified sequence-1 (BCAS1), indicating the transition into a pre-myelinating state. Cells derived from this early parenchymal response often presented a dysfunctional morphology with condensed cytoplasm and few extending processes, and were only sparsely detected among myelin-producing or mature oligodendrocytes. Correspondingly, early stages of human CPM lesions also showed reduced astrocyte numbers and non-myelinating BCAS1+ oligodendrocytes with dysfunctional morphology. In the rat model, neural stem cells (NSCs) located in the subventricular zone (SVZ) were activated while the lesion was already partially repopulated with OPCs, giving rise to nestin+ progenitors that generated oligodendroglial lineage cells in the lesion, which was successively repopulated with astrocytes and remyelinated. These nestin+ stem cell-derived progenitors were absent in human CPM cases, which may have contributed to the inefficient lesion repair. The present study points to the importance of astrocyte-oligodendrocyte interactions for remyelination, highlighting the necessity to further determine the impact of astrocyte dysfunction on remyelination inefficiency in demyelinating disorders including MS.