COVID-19 in persons aged 70+ in an early affected German district: Risk factors, mortality and post-COVID care needs-A retrospective observational study of hospitalized and non-hospitalized patients.

BACKGROUND: Cohorts of hospitalized COVID-19 patients have been studied in several countries since the beginning of the pandemic. So far, there is no complete survey of older patients in a German district that includes both outpatients and inpatients. In this retrospective observational cohort study, we aimed to investigate risk factors, mortality, and functional outcomes of all patients with COVID-19 aged 70 and older living in the district of Tübingen in the southwest of Germany. METHODS: We retrospectively analysed all 256 patients who tested positive for SARS-CoV-2 in one of the earliest affected German districts during the first wave of the disease from February to April 2020. To ensure inclusion of all infected patients, we analysed reported data from the public health department as well as the results of a comprehensive screening intervention in all nursing homes of the district (n = 1169). Furthermore, we examined clinical data of all hospitalized patients with COVID-19 (n = 109). RESULTS: The all-cause mortality was 18%. Screening in nursing homes showed a point-prevalence of 4.6%. 39% of residents showed no COVID-specific symptoms according to the official definition at that time. The most important predictors of mortality were the need for inpatient treatment (odds ratio (OR): 3.95 [95%-confidence interval (CI): 2.00-7.86], p<0.001) and care needs before infection (non-hospitalized patients: OR: 3.79 [95%-CI: 1.01-14.27], p = 0.037, hospitalized patients: OR: 2.89 [95%-CI 1.21-6.92], p = 0.015). Newly emerged care needs were a relevant complication of COVID-19: 27% of previously self-sufficient patients who survived the disease were not able to return to their home environment after discharge from the hospital. CONCLUSION: Our findings demonstrate the importance of a differentiated view of risk groups and long-term effects within the older population. These findings should be included in the political and social debate during the ongoing pandemic to evaluate the true effect of COVID-19 on healthcare systems and individual functional status.

Insulin sensitivity predicts cognitive decline in individuals with prediabetes.

INTRODUCTION: Epidemiological studies indicate an association between type 2 diabetes and cognitive dysfunction that appear to start already in the prediabetic state. Although cross-sectional studies have linked insulin resistance to impaired cognition, the potential predictive value of insulin resistance has not yet been sufficiently studied longitudinally without confounding by overt diabetes (and its pharmacological treatment). RESEARCH DESIGN AND METHODS: We investigated longitudinal data from participants of the 'Tübinger Evaluation of Risk Factors for Early Detection of Neurodegeneration' Study. Subjects underwent a neurocognitive assessment battery (CERAD Plus battery; Consortium to Establish a Registry for Alzheimer's Disease) at baseline and followed every 2 years (median follow-up 4.0 Q1-3: 2.2-4.3 years). Subjects within a pre-diabetic glycated hemoglobin range of 5.6%-6.5% underwent 5-point 75 g oral glucose tolerance tests (OGTTs) with assessment of insulin sensitivity and insulin secretion (n=175). Subjects with newly diagnosed diabetes mellitus or with major depressivity (Beck Depression Inventory >20) were excluded (n=15). Data were analyzed by mixed models using sex, age and glycemic trait as fixed effects. Subject and time since first measurement were used as random effects. RESULTS: Insulin sensitivity was positively associated with the CERAD sum score (higher is better) in a time-dependent manner (p=0.0057). This result is mainly driven by a steeper decrease in the memory domain associated with lower insulin sensitivity (p=0.029). The interaction between age and insulin sensitivity was independent of glycemia (p=0.02). There was also no association between insulin secretion and cognition. CONCLUSIONS: Insulin resistance rather than sole elevation of blood glucose predicts cognitive decline, specifically in the memory domain, in persons with prediabetes. Treatments of diabetes that improve insulin sensitivity might therefore have the potential to postpone or even prevent cognitive decline in patients with diabetes.

Response of Mitochondrial Respiration in Adipose Tissue and Muscle to 8 Weeks of Endurance Exercise in Obese Subjects.

CONTEXT: Exercise training improves glycemic control and increases mitochondrial content and respiration capacity in skeletal muscle. Rodent studies suggest that training increases mitochondrial respiration in adipose tissue. OBJECTIVE: To assess the effects of endurance training on respiratory capacities of human skeletal muscle and abdominal subcutaneous adipose tissue and to study the correlation with improvement in insulin sensitivity. DESIGN: Using high-resolution respirometry, we analyzed biopsies from 25 sedentary (VO2 peak 25.1 ± 4.0 VO2 mL/[kg*min]) subjects (16 female, 9 male; 29.8 ± 8.4 years) with obesity (body mass index [BMI] 31.5 ± 4.3 kg/m2), who did not have diabetes. They performed a supervised endurance training over 8 weeks (3 × 1 hour/week at 80% VO2 peak). RESULTS: Based on change in insulin sensitivity after intervention (using the Matsuda insulin sensitivity index [ISIMats]), subjects were grouped in subgroups as responders (>15% increase in ISIMats) and low-responders. The response in ISIMats was correlated to a reduction of subcutaneous and visceral adipose tissue volume. Both groups exhibited similar increases in fitness, respiratory capacity, and abundance of mitochondrial enzymes in skeletal muscle fibers. Respiratory capacities in subcutaneous adipose tissue were not altered by the intervention. Compared with muscle fibers, adipose tissue respiration showed a preference for ß-oxidation and complex II substrates. Respiratory capacities were higher in adipose tissue from female participants. CONCLUSION: Our data show that the improvement of peripheral insulin sensitivity after endurance training is not directly related to an increase in mitochondrial respiratory capacities in skeletal muscle and occurs without an increase in the respiratory capacity of subcutaneous adipose tissue.

A pitfall of bilateral inferior petrosal sinus sampling in cyclic Cushing's syndrome.

BACKGROUND: Clinical care of patients with cyclic Cushing's syndrome (CS) is challenging. Classical pitfalls include incorrect subtyping, unnecessary surgical procedures and delayed definite treatment. CASE PRESENTATION: A 43-year-old female suffered from a rapidly cycling ectopic CS. She experienced six cycles of severe hypercortisolism within a 2 year period (maximum plasma cortisol 5316 nmol/L, normal range 124.2-662.4 nmol/L; maximum urinary free cortisol 79,469 nmol/24 h, normal range < 414 nmol/24 h) lasting 2-9 weeks. The episodes were associated with pronounced hypokalemia (lowest K+ value recorded 2.4 mmol/l) and progressive signs and symptoms of CS. A bilateral inferior petrosal sinus sampling (BIPSS) performed during a trough phase was false positive for pituitary ACTH overproduction resulting in unnecessary transsphenoidal surgery while a second BIPSS performed during an active phase was indicative for ectopic CS. The 18F-DOPA PET/CT showed a pancreatic lesion, which was subsequently partially removed. Surprisingly, the histopathology was conclusive for ACTH-positive lymph node metastasis located in the retro-duodenal tissue of an occult neuroendocrine tumor WHO grade II. The primary tumor has not been identified so far and, because of the persistent hypercortisolism, the patient underwent bilateral adrenalectomy. Two years later, ACTH levels started to increase progressively. Percutaneous biopsy of a newly identified suspected lesion in the fifth thoracic vertebra revealed a metastasis with positive staining for ACTH, synaptophysin and chromogranin A. Therapy with carboplatin and etoposide was started and, since then, the patient underwent 12 cycles of chemotherapy. CONCLUSIONS: We report the challenging case of a rapidly cycling CS secondary to ACTH-secreting neuroendocrine intestinal tumor of unknown primary. We highlight the importance of performing diagnostic tests only during the phases of active cortisol secretion and as soon as first symptoms appear to avoid pitfalls.

TGF-ß Contributes to Impaired Exercise Response by Suppression of Mitochondrial Key Regulators in Skeletal Muscle.

A substantial number of people at risk of developing type 2 diabetes could not improve insulin sensitivity by physical training intervention. We studied the mechanisms of this impaired exercise response in 20 middle-aged individuals at high risk of developing type 2 diabetes who performed 8 weeks of controlled cycling and walking training at 80% individual Vo2 peak. Participants identified as nonresponders in insulin sensitivity (based on the Matsuda index) did not differ in preintervention parameters compared with high responders. The failure to increase insulin sensitivity after training correlates with impaired upregulation of mitochondrial fuel oxidation genes in skeletal muscle, and with the suppression of the upstream regulators PGC1α and AMPKα2. The muscle transcriptomes of the nonresponders are further characterized by the activation of transforming growth factor (TGF)-ß and TGF-ß target genes, which is associated with increases in inflammatory and macrophage markers. TGF-ß1 as inhibitor of mitochondrial regulators and insulin signaling is validated in human skeletal muscle cells. Activated TGF-ß1 signaling downregulates the abundance of PGC1α, AMPKα2, the mitochondrial transcription factor TFAM, and mitochondrial enzymes. Thus, the data suggest that increased TGF-ß activity in skeletal muscle can attenuate the improvement of mitochondrial fuel oxidation after training and contribute to the failure to increase insulin sensitivity.

[Can water be poisonous?]. / Kann man sich mit Wasser intoxikieren? - Fall 5 / 2015.

HISTORY AND ADMISSION FINDINGS: Two female patients aged over 80 years developed central nervous symptoms after drinking large amounts of water (more than 3 l per day). INVESTIGATIONS: Both had a hypoosmolar hyponatremia that was induced by concomitant treatment with hydrochlorothiazid (HCT) in the one case and in the other case relied on a distal tubular damage due to reflux nephropathy. DIAGNOSIS, TREATMENT AND COURSE: Hyponatremia was corrected after withdrawal of HCT and fluid restriction and central nervous symptoms disappeared rapidly. CONCLUSIONS: Distal tubular urinary dilution can be disturbed by HCT and parenchymal renal disease and can result in symptomatic hyponatremia after drinking large amounts of water.

[Endocrine abnormalities in a patient with borderline personality disorder--case 8/2014]. / Endokrinopathie bei einer Patientin mit Persönlichkeitsstörung vom Borderline-Typ--Fall 8/2014.

HISTORY AND ADMISSION FINDINGS: We report on a 44-year-old woman who was treated for borderline personality disorder in the Department of Psychiatry. In addition, symptoms of hyperthyroidism (anxiety, weight loss, hyperdefecation) were noticeable. Thyroid stimulating hormone (TSH) was marginally elevated, free triiodothyronine (T3) and free thyroxine (T4) were clearly elevated. Hence, the patient was transferred to the Department of Endocrinology. INVESTIGATIONS: Thyroid ultrasound revealed a diffuse goiter with a total volume of 24,8 ml. Antibody screening did not show elevated titers. The thyrotropin releasing hormone (TRH) test depicted a blunted TSH response. Serum levels of free glycoprotein hormone alpha-subunit, prolactin and insulin-like growth factor 1 were increased. DIAGNOSIS, TREATMENT AND COURSE: In cranial magnetic resonance imaging (MRI), a hypointense lesion on the left side of the anterior pituitary gland was detected indicating a thyrotropin-secreting microadenoma with concomitant secretion of prolactin and possible secretion of human growth hormone (HGH). A thyreostatic therapy was initiated aiming at euthyreosis. For symptom control, betablockers were administered. Subsequently, the patient underwent an uncomplicated transsphenoidal resection. Histological examination confirmed the diagnosis of a pituitary adenoma with expression of TSH, prolactin and HGH. As expected, thyroid hormones declined afterwards. CONCLUSIONS: TSHoma is rare. Diagnosis is confirmed by endocrinological testing and cranial imaging. Therapeutic options comprise transsphenoidal adenomectomy, drug therapy (somatostatin analogues, dopaminergic agonists) and irradiation. Resistance to thyroid hormones should be included in the differential diagnosis.

[Hyponatremia--should it be ignored or diagnosed?--Case 8/2011]. / Hyponatriämie--ignorieren oder diagnostizieren?--Fall 8/2011.

UNLABELLED: HISTORY, CLINICAL FINDINGS: A 72-year-old dehydrated female was admitted to our emergency department. She presented with a decreased level of consciousness and had experienced a fall. Her medication included hydrochlorothiazide and amiloride. DIAGNOSTIC: Laboratory findings showed a severe hyponatremia with a serum sodium concentration of 107 mmol/l and a reduced serum osmolality. Urine sodium and potassium excretion were > 30 mmol/l. A CT scan of the head did not show any signs of trauma. DIAGNOSIS, THERAPY AND CLINICAL COURSE: Using a diagnostic algorithm, the diagnosis of a hypotonic hypovolemic hyponatremia due to the intake of diuretics was confirmed. By intravenous infusion of physiological sodium chloride solution and cessation of diuretics, serum sodium concentration was raised gradually. Hereby, the patient`s state of consciousness completely normalized. CONCLUSIONS: Hyponatremia represents the most frequent electrolyte disturbance of hospitalized patients. It correlates with neurological deficits, proneness to falling and intrahospital mortality. Due to diagnostic insecurity of many physicians, the finding of a hyponatremia is often ignored or misclassified. Standardized approaches using diagnostic algorithms improve diagnostic accuracy. The here presented algorithm is based on only few parameters: serum and urine osmolality, urine sodium and potassium. Besides gradual raise of serum sodium, therapy of the underlying cause is essential, for example cessation of diuretics. For patients with syndrome of inadequate secretion of antidiuretic hormone (SIADH; hypotonic isovolemic hyponatremia), selective arginin-vasopressin-receptor 2-antagonists (vaptans) are a new therapeutic option. However, due to high costs, we only see an indication for patients with SIADH who are not able to consequently comply with fluid restriction.

[A rare cause of thyreotoxicosis]. / Seltene Ursache einer Hyperthyreose.

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) should be included in differential diagnoses of thyrotoxicosis in presence of a suggestive drug history. Adequate treatment requires knowledge of the underlying type of AIT. HISTORY AND ADMISSION FINDINGS: A 68-year-old male was admitted because of progressive dyspnea and tachyarrhythmia. Symptoms of thyrotoxicosis, including agitation, sleep disturbances, and palpitations, had developed 14 days earlier and the patient's condition had worsened despite initiation of antithyroid treatment. INVESTIGATIONS: Laboratory values showed manifest hyperthyroidism. Thyroid autoantibodies proved negative. C-reactive protein and erythrocyte sedimentation rate were slightly increased. Ultrasound revealed a moderately increased thyroid without nodules and with normal perfusion. DIAGNOSIS, TREATMENT AND COURSE: Suspecting AIT type 2, treatment with high-dosed glucocorticoids and antithyroid drugs was initiated. Under additional beta-blockade and heart insufficiency therapy the patient's condition significantly improved. After achievement of euthyreosis, thyroidectomy was performed. CONCLUSIONS: In patients with preexisting thyroid disorders, such as Grave's disease or functional autonomy in multinodular goiter, the high iodine content of amiodarone may cause iodine-induced thyrotoxicosis, also known as AIT type I. Treatment comprises high-dosed antithyroid drugs. In contrast, in patients suffering from AIT type II, toxic effects of amiodarone on a previously healthy thyroid result in destructive thyroiditis. Treatment consists of glucocorticoids in a dosage of 1 mg per kg body weight per day. Antithyroid treatment could be added in cases of equivocal diagnosis. In most cases, thyroidectomy is indicated. Whether amiodarone can be discontinued, should be discussed with the responsible cardiologist. Due to the long half-life time of amiodarone, treatment discontinuation will not result in an immediate improvement.

[Hypothyroidism due to pseudo-malabsorption of levothyroxine--Case 12/2009]. / Hypothyreose infolge einer Pseudomalabsorption von L-Thyroxin--Fall 12/2009.

BACKGROUND: Hypothyroidism is a common endocrine disorder which is easily treatable by an appropriate thyroid hormone replacement therapy in the majority of patients. In some patients, hypothyroidism is refractory to oral levothyroxine substitution. Common causes of lack of response to levothyroxine replacement comprise non-compliance and impaired absorption. HISTORY: We report on a 32-year-old women who presented with persistent clinical and biochemical signs of hypothyroidism after thyroid surgery for Graves' disease despite high doses of levothyroxine replacement therapy. TREATMENT AND COURSE: An extensive evaluation for malabsorption syndromes proofed negative. Supervised absorption tests of two different levothyroxine preparations were normal. Pseudomalabsorption was presumed, though the patient continued to deny noncompliance. Supervised once weekly oral levothyroxine was advised. CONCLUSION: Non-compliance with medical therapy should be considered in patients with treatment-refractory hypothyroidism prior to initiation of an extensive evaluation for malabsorption syndromes. Supervised levothyroxine absorption test is a useful tool in the diagnostic workup for supposed pseudomalabsorption. In non-compliant patients, supervised once weekly levothyroxine replacement appears to be a safe and well-tolerated treatment option.

17alpha-hydroxylase/17,20-lyase deficiency caused by a novel homozygous mutation (Y27Stop) in the cytochrome CYP17 gene.

CONTEXT: 17alpha-Hydroxylase/17,20-lyase deficiency, a rare autosomal recessive form of congenital adrenal hyperplasia, is caused by mutations in the cytochrome P450c17 (CYP17) gene. We report on a case of complete 17alpha-hydroxylase/17,20-lyase deficiency due to a novel homozygous mutation of CYP17. DESIGN: A 20-yr-old female Turkish patient (46,XX) presented with primary amenorrhea, sexual infantilism, and easy fatigability. RESULTS: The patient's steroid metabolism showed increased levels of mineralocorticoid precursors and low or undetectable plasma concentrations of 17alpha-hydroxycorticoids, androgens, and estrogens before and after ACTH stimulation. The gas chromatography-mass spectrometry urinary steroid profile was dominated by metabolites of corticosterone and its precursors, while cortisol and C(19)-steroid metabolites were lacking. ACTH, FSH, and LH levels were elevated. These hormonal findings were consistent with a combined and total 17alpha-hydroxylase/17,20-lyase deficiency. A therapy with hydrocortisone and a cyclic estrogen/gestagen substitution was initiated. CONCLUSION: The CYP17 gene analysis revealed homozygosity of the mutation Y27Stop (TAC-->TAA) in exon 1, a mutation that has not been previously described. This novel mutation leads to a stop codon causing a total loss of 17alpha-hydroxlyase/17,20-lyase activity, as reflected biochemically by the detected concentrations of the steroid metabolites.