Stress hyperglycaemia (SH) is frequent in critical illness, increases morbidity and mortality and is strongly associated with acute kidney injury (AKI). It remains unanswered whether insulin resistance or decreased adiponectin contribute to SH as they do to chronic hyperglycaemia. Our aims were to identify potential relationships between insulin resistance, serum high molecular weight (HMW) adiponectin and SH, while controlling for and excluding other risk factors and confounders of both SH and chronic hyperglycaemia such as diabetes, as well as potential relationships between HMW-adiponectin and subsequent AKI. We studied 158 critically ill patients admitted to intensive care units. SH was defined by blood glucose > 140 mg/dl, insulin resistance as Homeostasis model assessment-2-scores above the 75th percentile, decreased HMW-adiponectin as values below the 25th percentile, and AKI by Kidney-Disease-Improving-Global-Outcomes criteria. Seventy-seven patients (48.7

Stress hyperglycaemia (SH) and acute kidney injury (AKI) occur frequently in critically ill patients, and particularly non-diabetics are associated with adverse outcome. Data is scarce on the effect of SH on AKI. We assessed whether SH (i) preceded AKI, (ii) was a risk factor of subsequent AKI, and (iii) how SH and tubular injury interacted in AKI development in critically ill, non-diabetics. Case–control study of 82 patients each with and without SH matched by propensity score for multiple demographic characteristics. AKI was defined by KDIGO criteria, SH either as blood glucose (BG) > 140 mg/dl (BG140), > 200 mg/dl (BG200), or stress hyperglycemia rate (SHR) ≥ 1.47 (SHR1.47) as measured 2 days before AKI. Urinary cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) indicated tubular injury. In AKI, SH rates were frequent using all 3 definitions applied, but highest when BG140 was applied. SH by all 3 definitions was consistently associated with AKI. This was independent of established risk factors of AKI such as sepsis and shock. Increments of BG, urinary NGAL or cystatin C, and its products, were independently associated with the likelihood of subsequent AKI, demonstrating their reciprocal potentiating effects on AKI development. SH is frequent in critically ill, non-diabetics with AKI. SH was identified as an independent risk factor of AKI. Higher BG combined with tubular injury may potentiate their adverse effects on AKI.

Background Subacute thyroiditis (SAT) is a rare inflammatory disease that presents diagnostic challenges. The underlying pathophysiology and prediction of outcomes are elusive. We investigated the long-term follow-up of SAT for up to 30 years and determined predictors for later hypothyroidism. Methods SAT outcome data from 127 patients (age: 47.6 +/- 11.0 yrs., BMI: 24.7 +/- 4.8 kg/m(2)) were analyzed retrospectively. Patients with pre-existing and known causes of hypothyroidism unrelated to SAT were excluded. We also excluded patients without an accelerated erythrocyte sedimentation rate. SAT outcome parameters included anterior neck pain or tenderness of the thyroid, inflammation markers, hypoechoic areas in thyroid ultrasound, hyperthyroidism, fine-needle aspiration, and thyroid scan. Pre-treatment TSH-levels, gender, age, ultrasound findings, anti-thyroid antibodies and markers of inflammation were considered as possible predictors of SAT outcome. Results More than 26.8 % of SAT patients developed permanent hypothyroidism within 3 years of treatment. The patient groups later developing hypothyroidism did not differ in age, BMI, pre-treatment TSH levels or initial dosage of prednisolone treatment. However, high cumulative doses of prednisolone were associated with a higher prevalence of hypothyroidism. Also, women were more likely to develop hypothyroidism (OR: 3.18 (95 % CI: 1.14-8.65); p = 0.0176). Conclusions Our study suggests that one-quarter of patients with SAT develop hypothyroidism in the long-term. Hypothyroidism was predicted by high cumulative doses of prednisolone treatment and female gender. The reported lower prevalence of hypothyroidism in other countries may represent the faster establishment of diagnosis, different treatment protocols, or lower susceptibility to loss of thyroid function. Swift establishment of the diagnosis and rapid tapering of steroids may result in a higher proportion of patients with euthyroidism.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

ZusammenfassungIn einer alternden Gesellschaft nimmt die Prävalenz der Osteoporose und die durch sie verursachte Morbidität und Mortalität eine zunehmende Rolle ein. Auch Schilddrüsenfunktionsstörungen sind im Alter häufiger, sodass sich ein fataler Synergismus in der Entstehung von osteoporotischen Frakturen ergibt. Im Erwachsenenalter geht eine Hyperthyreose mit Knochenverlust und erhöhtem Knochenumsatz einher, primär bedingt durch eine gesteigerte Knochenresorption durch Osteoklasten. Die manifeste Hyperthyreose gehört zu den gut etablierten Ursachen einer sekundären Osteoporose und von Fragilitätsfrakturen. Eine latente Hyperthyreose wirkt sich ebenfalls negativ auf die Knochenmineraldichte aus und ist mit Frakturen assoziiert. Bei den meisten Patienten mit manifester oder latenter Hyperthyreose führt die Wiederherstellung einer Euthyreose zu einer Normalisierung der Knochendichte und Reduktion des Frakturrisikos. Eine TSH-suppressive Substitutionstherapie nach Schilddrüsenoperation wegen eines differenzierten Schilddrüsenkarzinoms ist ebenfalls mit einem erhöhten osteoporotischen Frakturrisiko assoziiert, sodass eine zeitlich begrenzte und risikoadaptierte TSH-Suppression empfohlen wird und eine antiresorptive Behandlung indiziert sein kann. Eine Hypothyreose im Erwachsenenalter führt zu einem verlangsamten Knochenumsatz mit gesteigerter Mineralisierung. Die Assoziation mit einem erhöhten Frakturrisiko korreliert mit einer erhöhten Sturzneigung und nicht mit einer Veränderung des Knochenstoffwechsels. Bei Kindern und Jugendlichen ist eine normale Schilddrüsenfunktion zur Ausbildung einer adäquaten Knochenmasse und Knochenfestigkeit sowie zum Erreichen der vorgesehenen Körpergröße erforderlich. Sowohl Hyperthyreose als auch Hypothyreose führen im Kindes- und Jugendalter mit verschiedenen Mechanismen zu Minderwuchs und verminderter Knochenqualität.

Objective: Turner syndrome (TS) is characterized by the complete or partial loss of the second sex chromosome and associated with a wide range of clinical manifestations. We aimed to assess the medical care of adult patients with TS in Germany. Design: Retrospective multicenter observational study. Methods: Data were collected from medical records of 258 women with TS treated between 2001 and 2017 in five non-university endocrinologic cent ers in Germany. Results: Mean age was 29.8 ± 11.6 years, mean height 152 ± 7.7 cm, and mean BMI 26.6 ± 6.3 kg/m2. The karyotype was known in 50% of patients. Information on cholesterol state, liver enzymes, and thyroid status was available in 81–98% of women with TS; autoimmune thyroiditis was diagnosed in 37%. Echocardiography was performed in 42% and cardiac MRI in 8.5%, resulting in a diagnosis of cardiovascular disorder in 28%. Data on growth hormone therapy were available for 40 patients (15%) and data concerning menarche in 157 patients (61%). Conclusion: In 258 women with TS, retrospective analysis of healthcare data indicated that medical management was focused on endocrine manifestations . Further significant clinical features including cardiovascular disease, renal malformation, liver involvement, autoimmune diseases, hearing loss, and osteoporosis were only marginally if at all considered. Based on this evaluation and in accordance with recent guidelines, we compiled a documentation form facilitating the transition from pediatric to adult care and further medical management of TS patients. The foundation of Turner Centers in March 2019 will improve the treatment of TS women in Germany.

BACKGROUND:Autoimmune thyroiditis (AIT) has been found to be associated with polycystic ovary syndrome (PCOS). The aim of this retrospective cohort study using data from a fertility clinic, with patients recruited from 2009 to 2010, was to confirm the higher prevalence of AIT in PCOS and to evaluate the impact of AIT on reproductive and metabolic parameters of PCOS patients.METHODS:Patients comprised 827 PCOS subjects seen for reproductive or metabolic complaints. Patients presenting primarily for thyroid problems were excluded. All patients were tested for the presence of AIT by laboratory testing and thyroid ultrasound. The impact of AIT on PCOS was evaluated by determination of reproductive and metabolic parameters.RESULTS:Patients with PCOS and AIT as compared to those only with PCOS, had a lower prevalence of elevated testosterone (45 vs. 61%; p=0,0001), free androgen index (5,96±5,41 vs. 7,02±7,6; p<0,001) and hyperandrogenemia (66 vs. 78%; p<0,001). Also testosterone levels were lower in PCOS patients with AIT (0,50±0,30 vs. 0,63±0,71; p=0,0006). Consequently, in these patients, hirsutism was less frequent (51 vs. 66%; p=0,0021). There was no difference in the prevalence of acne, alopecia, a-/ or oligomenorrhea or PCO-morphology in the two patient groups. Patients with PCOS and AIT were more obese by 2 kg/m² BMI on average. A higher BMI correlated with a higher TSH value, although all patients were euthyroid.CONCLUSIONS:AIT is more prevalent in PCOS than in controls. PCOS patients with AIT have less severe hyperandrogenemia and hyperandrogenism but are likely to suffer from an elevated metabolic risk.

Polygenic diseases with a broad phenotypic spectrum, such as polycystic ovary syndrome (PCOS), present a particular challenge in terms of identifying the underlying genetic mechanisms, nevertheless genetic variants have impact on the individual phenotype. We aimed to determine if next to genetic variations like SNPs further mechanisms might play a role in the pathogenesis of PCOS. We examined the effect of copy-number variations (CNVs) on metabolic phenotypes in PCOS. The intragenic rs1244979, rs2815752 in NEGR1 gene, and rs780094 in GCKR gene were genotyped and CNVs were determined by droplet digital polymerase chain reaction (ddPCR) in PCOS patients (n = 153) and controls without metabolic syndrome (n = 142). The study indicated that SNPs are not associated with the pathogenesis of PCOS but affect metabolic phenotypes. The CNVs investigated show a lower variability in PCOS than in CON. Furthermore, we provided direct evidence that the copy number, but not the genotype of the CNV in the genomic regions of rs780094(GCKR) is associated with low level of high-density lipoprotein cholesterol in PCOS. This study supports the hypothesis that not only genetic variants, but also CNVs in metabolically relevant genes, have an effect on metabolic phenotypes in our group of PCOS patients.

Thyroid hormones are bound to three major serum transport proteins, thyroxin-binding globulin (TBG), transthyretin (TTR) and human serum albumin (HSA). TBG has the strongest affinity for thyroid hormones, TTR is also found in the cerebrospinal fluid and HSA is the most abundant protein in plasma. Combination defects of either a high affinity TTR or HSA variant do not compensate TBG deficiency, underscoring the dominant role of TBG among the thyroid hormone transport proteins. On the other hand, coexistence of raised affinity TTR and HSA variants causes an augmented hyperthyroxinemia. Variations in thyroid hormone transport proteins may alter thyroid function tests to mimic hypo- or hyperthyroidism. As affected individuals are clinically euthyroid and do not require treatment, identification of thyroid hormone transport protein defects is important to avoid unnecessary diagnostic and therapeutic interventions. Mammals share the multilayered system of thyroid hormone binding proteins with humans. Some of them, especially carnivores, do not express TBG. In dogs, this defect has been shown to be caused by a defective hepatocyte nuclear factor-1 binding site in the TBG promoter, preventing TBG synthesis in the liver. The major endogenous thyroid hormone metabolite 3-iodothyronamine (3-T1AM) exerts marked cryogenic, metabolic, cardiac and central nervous system actions. It is bound to apolipoproteinB-100 (ApoB100), possibly facilitating its cellular uptake via interaction with the low density lipoprotein-receptor. This review summarizes the handling of hydrophobic charged thyroid hormone signaling molecules and their metabolite 3-T1AM in aqueous body fluids and the advantages and limits of their serum distributor proteins.

Zusammenfassung Die Diskussion darüber, welcher TSH-Wert die Grenze zur Hypo-thyreose markiert, ist noch im Gange. Eine Tendenz zu strengeren Schwellenwerten wird deutlich. Bereits die subklinische Hypothyreose soll künftig therapiert werden, wenn sie mit erhöhten TPO-Antikör-pern einhergeht, Kinderwunsch, Schwangerschaft oder Infertilität be-stehen oder der Patient über spezifische Symptome klagt.

Background: Thyroxine-binding globulin (TBG) is the main transport protein for T4 in blood. Until now, 22 mutations leading to complete TBG deficiency (TBG-CD) have been reported. Objective: We report two mutations associated with TBG-CD found in patients from Andrews, S.C., USA (TBG-CD-Andrews), and Berlin, Germany (TBG-CD-Berlin). Methods: Automated chemiluminescence immunoassays were used for the determination of TSH, free and total T4 and T3 (fT4, TT4, TT3) and TBG. Direct DNA sequencing was used to identify the TBG mutations in the propositi. Results: TBG-CD-Andrews was found in a 1-month-old boy who was euthyroid with normal TSH and fT4, but reduced TT4, indicating TBG deficiency. TBG was not detectable, confirming TBG-CD. No mutation in the coding region and the promoter of the TBG gene was found, but a single nucleotide substitution in intron 1 disrupts the donor splice site of exon 0 (IVS1+2T>C). Another mutation was found in an 11-year-old boy. He was also euthyroid with normal fT4 and TSH. However, TT4 and TT3 were low, suggesting TBG-CD. Sequencing revealed a 79-nucleotide deletion, ranging from intron 3 into exon 3. Conclusion: We report two novel mutations of the TBG gene associated with TBG-CD. Whereas most TBG-CDs are caused by small deletions, in TBG-CD-Andrews the disruption of a donor splice site was detected, whilst in TBG-CD-Berlin the largest deletion in the Serpina7 gene to date was found.

OBJECTIVEAutoimmune thyroid disease (AITD) has been associated with adverse pregnancy outcomes in subfertile women with spontaneous and assisted reproductive technology-induced pregnancies. The underlying pathophysiology is still elusive and an association with thyroid dysfunction or other infertility causes is discussed. However, whether thyroid autoimmunity (TAI) per se has a negative impact on female fertility has not yet been clarified. In this study, we investigated whether TAI in healthy women undergoing intracytoplasmic sperm injection (ICSI) for male infertility may affect pregnancy outcome.DESIGNA retrospective, single-centre study.METHODSTHE ICSI OUTCOME DATA OBTAINED FROM 835 EUTHYROID WOMEN (AGE: 31.4±4.3 years, BMI: 23.7±4.2 kg/m(2)) were correlated with pre-ICSI TAI status. The known causes of female subfertility were excluded. Outcome parameters included rates of pregnancy, birth, miscarriage and preterm delivery. Blood analysis was carried out retrospectively using blood samples drawn before ICSI. TAI was defined by elevation of anti-thyroperoxidase- or anti-thyroglobulin-antibodies >100 U/l.RESULTSTAI-POSITIVE AND -NEGATIVE GROUPS DID NOT DIFFER IN AGE, BMI OR TSH LEVELS. TAI STATUS DID NOT INFLUENCE ANY ICSI OUTCOME PARAMETERS. IN CONTRAST, INCREASING MATERNAL AGE WAS SIGNIFICANTLY CORRELATED WITH LOWER PREGNANCY RATE (ODDS RATIO (OR): 0.94 (95% CI: 0.91-0.97); P=0.0003) and birth rate (OR: 0.93 (95% CI: 0.09-0.97); P<0.0001).CONCLUSIONSOur study suggests that TAI per se does not influence ICSI outcome. A strict definition of AITD and TAI and consideration of TAI-associated and -independent confounders are important to further elucidate the interplay between TAI and reproduction.

Das Polyzystische Ovarsyndrom gehört zu den häufigsten Endokrinopathien der Frau. Die Ätiopathogenese ist bislang noch unklar, sodass derzeit keine kausalen, sondern lediglich symptomatische Behandlungsstrategien zur Verfügung stehen.

Das polyzystische Ovarsyndrom (PCOS) ist durch Hyperandrogenämie/Hyperandrogenismus, Zyklusstörung und polyzystische Ovarien charakterisiert. Mit einer Prävalenz von 5–8% ist es die wichtigste Ursache für einen unerfüllten Kinderwunsch. Darüber hinaus verursacht es erhebliche kosmetische Probleme (Hirsutismus, Akne, Alopezie). Durch seine Assoziation mit dem metabolischen Syndrom (MBS) stellt es ein ernstzunehmendes kardiovaskuläres Risiko dar. Außerdem ist das PCOS mit einer erhöhten Prävalenz der Hashimoto-Thyreoiditis assoziiert. PCOS und die mit einer Hashimoto-Thyreoiditis assoziierte Hypothyreose stellen unabhängig voneinander ein metabolisches, kardiovaskuläres und gynäkologisches Risiko dar, sodass bei PCOS-Patientinnen ein Schilddrüsenscreening (Schilddrüsensonografie, TSH- und TPO-Antikörper-Bestimmung) empfohlen wird. Höhere TSH-Werte bei Frauen mit PCOS und Hashimoto-Thyreoiditis sind mit einem erhöhten Körpergewicht und BMI assoziiert – möglicherweise kann hier eine Schilddrüsenhormonsubstitution zur Gewichtsabnahme beitragen.

Acne is one of the most common skin diseases in the general population, especially among adolescents. Acne tarda (adult acne) is defined as acne that develops (late-onset acne) or continues (persistent acne) after 25 years of age. The disease is more common in women. The clinical features are quite specific: inflammatory acne in the lower facial region or macrocomedones (microcysts) spread over the face. Involvement of the trunk is much more common in men. The etiology of acne tarda is still controversial, as cosmetics, drugs, smoking, stress, diet, and endocrine abnormalities have been implicated. Women with acne tarda and other symptoms of hyperandrogenism have a high probability of endocrine abnormalities such as polycystic ovary syndrome. Treatment is similar to that of acne in adolescence. Long-term treatment over years or decades may be required.

Die Häufigkeit und Komplexität von Schilddrüsenerkrankungen erfordern eine interdisziplinäre Zusammenarbeit, bei der dem Gynäkologen eine besondere Rolle zukommt. Zum einen treten die meisten Thyreopathien häufiger bei Frauen als bei Männern auf, zum anderen manifestieren sie sich in einem für die Reproduktion und Frauengesundheit ganz wesentlichen Alter.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study