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1.
Reprod Biol Endocrinol ; 22(1): 48, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38650041

RESUMO

CONTEXT: Acromegaly is a rare disease caused by excessive growth hormone (GH) secretion, mostly induced by pituitary adenomas. The care of pregnant women with acromegaly is challenging, in part due to existing clinical data being limited and not entirely consistent with regard to potential risks for mother and child. OBJECTIVE: To retrospectively examine data on pregnancy and maternal as well as neonatal outcomes in patients with acromegaly. DESIGN & METHODS: Retrospective data analysis from 47 pregnancies of 31 women treated in centers of the German Acromegaly Registry. RESULTS: 87.1% of the studied women underwent transsphenoidal surgery before pregnancy. In 51.1% a combination of dopamine agonists and somatostatin analogs were used before pregnancy. Three women did not receive any therapy for acromegaly. During pregnancy only 6.4% received either somatostatin analogs or dopamine agonists. In total, 70.2% of all documented pregnancies emerged spontaneously. Gestational diabetes was diagnosed in 10.6% and gravid hypertension in 6.4%. Overall, no preterm birth was detected. Indeed, 87% of acromegalic women experienced a delivery without complications. CONCLUSION: Pregnancies in women with acromegaly are possible and the course of pregnancy is in general safe for mother and child both with and without specific treatment for acromegaly. The prevalence of concomitant metabolic diseases such as gestational diabetes is comparable to the prevalence in healthy pregnant women. Nevertheless, larger studies with more data in pregnant patients with acromegaly are needed to provide safe and effective care for pregnant women with this condition.


Assuntos
Acromegalia , Complicações na Gravidez , Resultado da Gravidez , Sistema de Registros , Humanos , Feminino , Gravidez , Acromegalia/epidemiologia , Acromegalia/terapia , Estudos Retrospectivos , Adulto , Alemanha/epidemiologia , Resultado da Gravidez/epidemiologia , Complicações na Gravidez/epidemiologia , Diabetes Gestacional/epidemiologia , Recém-Nascido , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
2.
Front Endocrinol (Lausanne) ; 15: 1348990, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405148

RESUMO

Pasireotide is a somatostatin analogue for the treatment of acromegaly, a chronic condition caused by excess growth hormone. Despite the therapeutic benefits of pasireotide as a second-line treatment for inadequately controlled acromegaly, a major concern is its hyperglycemic side-effect. Here, we provide guidance on how to select appropriate patients with acromegaly for treatment with pasireotide. We summarize baseline characteristics of patients at high risk for pasireotide-associated hyperglycemia and recommend a monitoring strategy based on the risk profile. Self-monitoring of blood glucose levels (SMBG), measurements of fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and regular HbA1c measurements are the foundation of our proposed monitoring approach. The pathophysiology of pasireotide-induced hyperglycemia involves decreased secretion of the incretin hormones GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1). Our expert recommendations address the specific pathophysiology of pasireotide-induced hyperglycemia by recommending the incretin-based therapeutics dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in all appropriate patients as an alternative to first-line monotherapy with metformin. Furthermore, we emphasize the importance of adequate control of acromegaly, excellent diabetes education, nutrition and lifestyle guidance and advise to consult expert diabetologists in case of uncertainty in the management of patients with hyperglycemia under pasireotide.


Assuntos
Acromegalia , Hiperglicemia , Somatostatina/análogos & derivados , Humanos , Acromegalia/tratamento farmacológico , Glicemia , Incretinas , Somatostatina/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon
3.
Case Rep Neurol ; 15(1): 163-171, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901128

RESUMO

Although the prognosis in Guillain-Barré syndrome (GBS) is generally good, protracted and incomplete courses of recovery can be a heavy burden. Animal studies suggest growth hormone (GH) treatment could stimulate myelin repair and thus accelerate functional recovery in acute polyneuropathy. We report on the first use of GH in GBS. Our objective was to monitor safety and tolerability as well as to evaluate the effect of an off-label GH therapy during recovery from GBS in 1 patient. A 28-year-old male with flaccid tetraparesis caused by pure motor GBS was treated off-label with GH (1 mg/day) for 10 weeks. Muscle strength was measured regularly before, during, and after the treatment over a total span of 330 days. Serum levels of IGF-I were assessed before, during, and after GH treatment. Changes in strength gain were used as the main parameter of efficacy. No side effects of GH treatment were observed. Serum IGF-I increased from 177 ng/mL at baseline to an average of 342 ng/mL (normal range 78-270 ng/mL) during treatment. Prior to GH administration, strength (R2 = 0.99, p < 0.01) was associated with time, representing the natural course of recovery. During GH treatment, the slope of strength gain increased (Glass' ∆ = 1.08, p < 0.01). The association between alterations of strength gain and IGF-I serum levels reached trend level (R2 = 0.36, p = 0.09). In this single case, GH treatment seemed to be associated with faster muscular strength gain. Controlled studies are needed in order to establish GH as a potential therapeutic approach in motor GBS.

4.
Eur J Endocrinol ; 189(2): R1-R10, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37536267

RESUMO

Acromegaly is a rare and insidious disease characterized by chronic excess growth hormone, leading to various morphological changes and systemic complications. Despite its low prevalence, acromegaly poses a significant socioeconomic burden on patients and healthcare systems. This review synthesizes the current state of knowledge on the psychosocial burden, disability, impact on daily life, and cost of acromegaly disease, focusing on the quality of life, partnership, medical care and treatment afflictions, participation in daily activities, professional and leisure impairment, and cost of treatment for acromegaly and its comorbidities. It also examines management strategies, coping mechanisms, and interventions aimed at alleviating this burden. A comprehensive understanding of the extent of the socioeconomic burden in acromegaly is crucial to develop effective strategies to improve treatment and care. Further research is warranted to explore the myriad factors contributing to this burden, as well as the efficacy of interventions to alleviate it, ultimately enhancing the quality of life for patients with acromegaly.


Assuntos
Acromegalia , Humanos , Acromegalia/diagnóstico , Acromegalia/epidemiologia , Acromegalia/terapia , Qualidade de Vida , Comorbidade , Fatores Socioeconômicos
5.
Clin Pract ; 13(3): 616-620, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37218807

RESUMO

We report the case of a 49-year-old male who suffered from a myocardial infarction with subsequent cardiac arrest. The emergency medical team began cardiopulmonary resuscitation, including defibrillation of ventricular fibrillation. Although a return of spontaneous circulation was achieved after approximately 30 min of continued efforts, the patient went back into cardiac arrest on the way to the hospital and resuscitation had to be resumed. On admission, the patient was severely acidotic with a pH of 6.67, lactatemia of 19 mmol/L, and pronounced hypercapnia (pCO2 127 mmHg). Despite the poor prognosis, all possible efforts including coronary intervention and therapeutic hypothermia were carried out and the patient made a quick recovery with discharge from the intensive care unit on day 5. Survival of extreme acidosis, such as in this case, is rare. This is the first report of survival with good neurologic outcome in a patient with myocardial infarction, cardiac arrest, and pH of under 6.7 on admission at the clinic.

6.
Dtsch Med Wochenschr ; 148(7): 380-385, 2023 03.
Artigo em Alemão | MEDLINE | ID: mdl-36940688

RESUMO

Acromegaly is a rare disease in which chronic growth hormone overproduction (usually from an anterior pituitary adenoma) leads to various systemic complications. The management of acromegaly and the comorbidities of the disease is complex and requires a multidisciplinary approach. Early diagnosis is extremely important, as then the chances of a complete cure are significantly higher. The operation is the therapy of first choice and should be performed at a specialized center with an experienced neurosurgeon. With good patient information and guidance, the drug therapy of acromegaly patients in specialized practices and clinics can usually lead to biochemical control and thereby normalization of mortality risk. As with numerous rare diseases, care in specialized centers and recording and evaluation in registry studies can contribute to better patient care and the optimization of therapy and diagnostic guidelines. We assume that with the help of the German Acromegaly Registry, which currently includes more than 2500 patients with acromegaly, we will be able to present a realistic picture of the care situation in Germany in the coming years.


Assuntos
Acromegalia , Adenoma , Humanos , Acromegalia/diagnóstico , Acromegalia/epidemiologia , Acromegalia/terapia , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/terapia , Comorbidade , Alemanha/epidemiologia
7.
J Clin Med ; 12(4)2023 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-36836189

RESUMO

Acromegaly is a rare and disabling disease with some distinct and striking clinical features that have fascinated (and frightened) laypeople and medical experts alike throughout history [...].

8.
Ann Transl Med ; 10(16): 848, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36111053
9.
J Crit Care Med (Targu Mures) ; 8(1): 61-65, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35274057

RESUMO

This report concerns a young man who attempted suicide by ingesting a cocktail with a lethal dose of chloroquine phosphate and large amounts of diazepam. On presentation, the patient was drowsy, unresponsive and in cardiogenic shock with severely impaired left ventricular function. Active charcoal and vasopressors were administered, and despite his intoxication with diazepam, a high-dose diazepam treatment was initiated in the hospital. It is concluded that diazepam in the cocktail played a vital role in the survival of this patient. With a rise in numbers, every emergency and intensive care physician should be familiar with chloroquine poisoning.

10.
Pituitary ; 25(1): 152-158, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34518996

RESUMO

OBJECTIVE: Immune checkpoint inhibitors can cause various immune-related adverse events including secondary hypophysitis. We compared clinical characteristics of immunotherapy-induced hypophysitis (IIH) and primary hypophysitis (PH) DESIGN: Retrospective multicenter cohort study including 56 patients with IIH and 60 patients with PH. METHODS: All patients underwent extensive endocrine testing. Data on age, gender, symptoms, endocrine dysfunction, MRI, immunotherapeutic agents and autoimmune diseases were collected. RESULTS: Median time of follow-up was 18 months in IIH and 69 months in PH. The median time from initiation of immunotherapy to IIH diagnosis was 3 months. IIH affected males more frequently than PH (p < 0.001) and led to more impaired pituitary axes in males (p < 0.001). The distribution of deficient adenohypophysial axes was comparable between both entities, however, central hypocortisolism was more frequent (p < 0.001) and diabetes insipidus considerably less frequent in IIH (p < 0.001). Symptoms were similar except that visual impairment occurred more rarely in IIH (p < 0.001). 20 % of IIH patients reported no symptoms at all. Regarding MRI, pituitary stalk thickening was less frequent in IIH (p = 0.009). Concomitant autoimmune diseases were more prevalent in PH patients before the diagnosis of hypophysitis (p = 0.003) and more frequent in IIH during follow-up (p = 0.002). CONCLUSIONS: Clinically, IIH and PH present with similar symptoms. Diabetes insipidus very rarely occurs in IIH. Central hypocortisolism, in contrast, is a typical feature of IIH. Preexisting autoimmunity seems not to be indicative of developing IIH.


Assuntos
Hipofisite , Estudos de Coortes , Humanos , Hipofisite/induzido quimicamente , Imunoterapia/efeitos adversos , Ipilimumab , Masculino , Estudos Retrospectivos
11.
J Clin Endocrinol Metab ; 106(8): e2887-e2899, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-33864468

RESUMO

CONTEXT: Soluble alpha klotho (sαKL) has been linked to growth hormone (GH) action, but systematic evaluation and comparisons with traditional biomarkers in acromegaly are lacking. OBJECTIVE: To evaluate the potential of sαKL to aid classification of disease activity. METHODS: This retrospective study at 2 academic centers included acromegaly patients before surgery (A, n = 29); after surgery (controlled, discordant, or uncontrolled) without (B1, B2, B3, n = 28, 11, 8); or with somatostatin analogue treatment (C1, C2, C3, n = 17, 11, 5); nonfunctioning pituitary adenomas (n = 20); and healthy controls (n = 31). sαKL was measured by immunoassay and compared with traditional biomarkers (random and nadir GH, insulin-like growth factor I [IGF-I], IGF binding protein 3). Associations with disease activity were assessed. RESULTS: sαKL was correlated to traditional biomarkers, particularly IGF-I (rs=0.80, P <0.0001). High concentrations before treatment (A, median, interquartile range: 4.04 × upper limit of normal [2.26-8.08]) dropped to normal after treatment in controlled and in most discordant patients. A cutoff of 1548 pg/mL for sαKL discriminated controlled (B1, C1) and uncontrolled (B3, C3) patients with 97.8% (88.4%-99.9%) sensitivity and 100% (77.1%-100%) specificity. sαKL was below the cutoff in 84% of the discordant subjects. In the remaining 16%, elevated sαKL and IGF-I persisted, despite normal random GH. Sex, age, body mass index, and markers of bone and calcium metabolism did not significantly affect sαKL concentrations. CONCLUSION: Our data support sαKL as a biomarker to assess disease activity in acromegaly. sαKL exhibits close association with GH secretory status, large dynamic range, and robustness toward biological confounders. Its measurement could be helpful particularly when GH and IGF-I provide discrepant information.


Assuntos
Acromegalia/sangue , Adenoma/sangue , Glucuronidase/sangue , Neoplasias Hipofisárias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Proteínas Klotho , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
Exp Clin Endocrinol Diabetes ; 129(2): 112-117, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31266067

RESUMO

INTRODUCTION: GHD is a chronic and systemic disease requiring daily replacement of growth hormone (GHRT). Adherence and attitudes of adult GHD patients are not well known. We sought to assess patients' knowledge of growth hormone deficiency (GHD) in association with treatment adherence and attitudes regarding available and upcoming treatment options. METHODS: We performed a cross-sectional survey with a custom-made questionnaire at a single centre assessing data on demographics, knowledge of GHD, adherence and attitudes towards GHRT. RESULTS: Of 106 eligible patients actively followed for GHD 70 returned the completed survey (return-rate 66%, 34 m/36 f; age 56±14 years). 46 patients were actively treated, but almost one third (n=24) refused GHRT. 12 patients had participated in clinical trials with LAGH (long-acting growth hormone). Overall, patients with GHRT showed good adherence. Patients refusing GHRT mostly feared side effects and/or had a lack of information/perceived effect. Disease knowledge and level of education were higher in treated than untreated patients (p=0.023/0.017). Only 36% of respondents would initiate treatment with LAGH. Patients with prior LAGH experience and patients with childhood-onset GHD were more likely to adopt LAGH (p=0.048/0.031). DISCUSSION: Most often, misinformation causes patients to refuse GHRT. Possibly the understanding of their condition and consequences of non-treatment is limited. To improve adherence more focused educational and behavioural strategies may be needed. Willingness to begin a therapy with LAGH was lower than expected (36%). The reasons for reluctance against LAGH need to be elucidated.


Assuntos
Atitude Frente a Saúde , Cultura , Hipopituitarismo , Adesão à Medicação , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Alemanha/epidemiologia , Terapia de Reposição Hormonal/psicologia , Terapia de Reposição Hormonal/estatística & dados numéricos , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/epidemiologia , Hipopituitarismo/psicologia , Masculino , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Inquéritos e Questionários
13.
Exp Clin Endocrinol Diabetes ; 129(3): 224-233, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33285601

RESUMO

BACKGROUND: Evidence from controlled trials has shown that lanreotide autogel is effective in achieving biochemical and symptom control in patients with acromegaly. However, it is important to better understand the real-world patient population receiving lanreotide autogel treatment. METHODS: In this non-interventional study the long-term treatment response to lanreotide autogel in adult patients with acromegaly from office-based centers or clinics in Germany, Austria and Switzerland was studied. Assessments included growth hormone and insulin-like growth factor-I levels, symptoms, quality of life, lanreotide plasma levels and tumor somatostatin receptor subtype expression. The primary endpoint was achievement of full biochemical control, defined as growth hormone ≤2.5 µg/L and insulin-like growth factor I normalization at month 12. RESULTS: 76 patients were enrolled from 21 sites. 7/51 (13.7%) patients of the efficacy population had full biochemical control at baseline, 15/33 (45.5%) at month 12 and 10/26 (38.5%) at month 24 of treatment. At 12 months of treatment higher rates of biochemical control were observed in the following subgroups: older patients (>53 years [median]), females, treatment-naïve patients, and patients with a time since diagnosis of longer than 1.4 years (median). No clinically relevant differences in acromegaly symptoms or quality of life scores were observed. Median fasting blood glucose and glycated hemoglobin levels remained unchanged throughout the study. No new safety signals were observed. Overall tolerability of treatment with lanreotide autogel was judged by 80.8% of the enrolled patients at month 12 as 'very good' or 'good'. CONCLUSION: Treatment with lanreotide autogel in a real-world setting showed long-term effectiveness and good tolerability in patients with acromegaly.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Avaliação de Resultados em Cuidados de Saúde , Peptídeos Cíclicos/farmacologia , Somatostatina/análogos & derivados , Acromegalia/sangue , Adulto , Áustria , Feminino , Géis , Alemanha , Hormônio do Crescimento Humano/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/administração & dosagem , Somatostatina/administração & dosagem , Somatostatina/farmacologia , Suíça
14.
Exp Clin Endocrinol Diabetes ; 129(3): 234-240, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32770534

RESUMO

OBJECTIVE: Clinical data on primary hypophysitis are still scarce. Especially non-surgical cases are underreported. We sought to analyse clinical characteristics of primary hypophysitis, particularly in clinically diagnosed patients. DESIGN: Retrospective single centre study in 60 patients with primary hypophysitis. METHODS: Symptoms, MRI, histopathological findings, treatment and outcomes were analysed in 12 histopathologically and 48 clinically diagnosed patients. Diagnostic criteria for clinical diagnosis were: a) MRI findings compatible with primary hypophysitis; b) course of disease excluding other differential diagnoses. Mean duration of follow-up was 69 months. RESULTS: Female sex was predominant (73%). Fatigue (52%), headache (38%) and diabetes insipidus (38%) were the most frequent symptoms. 42% had a concomitant autoimmune disease. The corticotropic, thyrotropic, gonadotropic, somatotropic axis was impaired in 67%, 57%, 52%, 20%, respectively. Men had a higher number of impaired hormone axes (p=0.022) with the gonadotropic axis being affected more frequently in men (p=0.001). Infundibular thickening (56%) and space occupying lesions (46%) were typical MRI findings. Pituitary size was frequently enlarged at presentation (37%) but diminished during observation (p=0.029). Histopathologically and clinically diagnosed cases did not differ. CONCLUSIONS: The cohort of clinically diagnosed patients did not differ from our histopathologically diagnosed patients or from published cohorts with predominantly surgical patients. Thus, diagnosis of primary hypophysitis using clinical criteria seems feasible.


Assuntos
Doenças Autoimunes , Diabetes Insípido , Fadiga , Cefaleia , Hipofisite , Hipopituitarismo , Adulto , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Comorbidade , Diabetes Insípido/diagnóstico , Diabetes Insípido/epidemiologia , Diabetes Insípido/etiologia , Fadiga/diagnóstico , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Seguimentos , Cefaleia/diagnóstico , Cefaleia/epidemiologia , Cefaleia/etiologia , Humanos , Hipofisite/complicações , Hipofisite/diagnóstico , Hipofisite/epidemiologia , Hipofisite/patologia , Hipopituitarismo/complicações , Hipopituitarismo/diagnóstico , Hipopituitarismo/epidemiologia , Hipopituitarismo/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais
15.
Expert Opin Pharmacother ; 21(15): 1883-1895, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32633582

RESUMO

INTRODUCTION: Acromegaly is a rare disease due to oversecretion of growth hormone (GH). Even though the disease is often portrayed by its most apparent clinical features, given the abundance of GH receptors throughout the body, it truly is a systemic disease leading to numerous complications and comorbidities. A distinct medical issue in the context of acromegaly is diabetes: It can be a complication as a consequence of GH excess and its mediators, but it can also result from treatment of acromegaly. AREAS COVERED: This review provides an overview of the effects of acromegaly pathophysiology on glucose homeostasis. Furthermore, it devotes an extensive section on the influence that acromegaly treatment has on glucose metabolism, including approved as well as currently investigated drugs. It also summarizes observations from the use of anti-diabetic medication in patients with acromegaly. EXPERT OPINION: Glucose imbalance is an important aspect of acromegaly comorbidity and deserves more attention. Even though numerous studies have investigated glucose homeostasis in acromegaly, there is still a clear need for more basic, translational, and also clinical research to advance the understanding of the underlying mechanisms and how to best address them.


Assuntos
Acromegalia/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Glucose/metabolismo , Somatostatina/uso terapêutico , Acromegalia/complicações , Acromegalia/epidemiologia , Acromegalia/metabolismo , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Hormônio do Crescimento Humano/metabolismo , Humanos , Resistência à Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Prevalência , Somatostatina/análogos & derivados
16.
Eur J Endocrinol ; 181(1): 55-67, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31096183

RESUMO

OBJECTIVE: Growth hormone (GH) nadir (GHnadir) during oral glucose tolerance test (OGTT) is an important tool in diagnosing acromegaly, but data evaluating the need to adjust cut-offs to biological variables utilizing today's assay methods are scarce. We therefore investigated large cohorts of healthy subjects of both sexes to define normal GHnadir concentrations for a modern, sensitive, 22 kD-GH-specific assay. DESIGN: Multicenter study with prospective and retrospective cohorts (525 healthy adults: 405 females and 120 males). METHODS: GH concentrations were measured by the IDS-iSYS immunoassay after oral application of 75 g glucose. RESULTS: GHnadir concentrations (µg/L) were significantly higher in lean and normal weight subjects (group A) compared to overweight and obese subjects (group B); (males (M): A vs B, mean: 0.124 vs 0.065, P = 0.0317; premenopausal females without estradiol-containing OC (OC-EE) (FPRE): A vs B, mean: 0.179 vs 0.092, P < 0.0001; postmenopausal women (FPOST): A vs B, mean: 0.173 vs 0.078, P < 0.0061). Age, glucose metabolism and menstrual cycle had no impact on GHnadir. However, premenopausal females on OC-EE (FPREOC) exhibited significantly higher GHnadir compared to all other groups (all P < 0.0001). BMI had no impact on GHnadir in FPREOC (A vs B, mean: 0.624 vs 0.274, P = 0.1228). CONCLUSIONS: BMI, sex and OC-EE intake are the major determinants for the GHnadir during OGTT in healthy adults. Using a modern sensitive GH assay, GHnadir concentrations in healthy subjects are distinctly lower than cut-offs used in previous guidelines for diagnosis and monitoring of acromegaly.


Assuntos
Acromegalia/diagnóstico , Teste de Tolerância a Glucose , Hormônio do Crescimento Humano/análise , Imunoensaio/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Ciclo Menstrual/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
17.
Expert Opin Pharmacother ; 19(11): 1187-1200, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30048162

RESUMO

INTRODUCTION: Cushing's disease is a rare systemic and disabling disease due to oversecretion of adrenocorticotrophic hormone (ACTH) resulting in excess cortisol levels. Diagnosis and treatment are difficult; despite the availability of various pharmaceutical treatment options, there is an ongoing, unmet need for even more effective treatment. AREAS COVERED: The present review aims at providing an overview of available drugs and presenting new developments. Focusing on the pituitary as a target, the review covers compounds targeting pituitary cell signaling or cell cycle control such as heat shock protein inhibitors (e.g. silibinin), histone deacetylase inhibitors (trichostatin A, vorinostat), kinase inhibitors (gefitinib, seliciclib), and others (such as triptolide, AT-101). Levoketoconazole and osilodrostat are in clinical testing and inhibit steroidogenesis. Blockade of ACTH receptor binding at the adrenal level is explained as a theoretical drug target. Inhibition of binding of the glucocorticoid receptor in the peripheral tissue plays a minor role due to its lack of biomonitoring options. EXPERT OPINION: In our opinion, further research and drug development of pituitary-directed targets are necessary. Combination therapies may exert synergistic effects and allow for smaller and better tolerated doses, but more experience and data are needed to guide such treatment schemes.


Assuntos
Síndrome de Cushing/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Síndrome de Cushing/patologia , Humanos
18.
GMS J Med Educ ; 35(5): Doc54, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30637318

RESUMO

Objective: The final year of undergraduate medical education in Germany is called the practical year (PY), where emphasis is placed on developing practical skills requisite of soon-to-be physicians. Many students choose to spend part of this year abroad, yet little is known about their results on the medical licensing examinations. Is there a predisposition of high-performing students to go abroad as compared to lower performers? Are international health electives during the PY followed by higher scores in the final section of the German medical licensing examination (GMLE2)? Methods: We conducted a retrospective cohort study among undergraduate medical students at the LMU Munich, who participated in the final section of the German medical licensing examination between autumn 2009 and spring 2011. Of the 1,731 eligible students, 554 (32%) participated in our study. We analyzed for statistical associations of international health electives with written test scores of both sections of the medical licensing examination as well as grades earned during medical school training. We then used multiple regression analysis to identify relevant predictors of GMLE2 scores. Results: Approximately half of study participants pursued international health electives during the PY (51.1%). The number of students going abroad increased with the scores achieved on the first section of the medical licensing examination (GMLE1, p<0.001). Stratified by their GMLE1 scores students who pursued electives abroad during their PY achieved higher GMLE2 scores (p<0.001). The strongest predictor for GMLE2 scores were grades obtained during medical school training; age and study duration indicated lower scores; and those engaging in international health electives correlated with higher scores. Conclusions: Students with higher GMLE1 scores go abroad during PY more often. Beyond that, students who pursue international health electives achieve higher GMLE2 scores than those who stay in Germany during PY. There is an unmet need for additional research to identify which factors make these students perform better and what motivates them to go abroad.


Assuntos
Desempenho Acadêmico/estatística & dados numéricos , Educação de Graduação em Medicina/métodos , Saúde Global/educação , Estudantes de Medicina/estatística & dados numéricos , Desempenho Acadêmico/normas , Adulto , Estudos de Coortes , Educação de Graduação em Medicina/tendências , Avaliação Educacional/métodos , Avaliação Educacional/estatística & dados numéricos , Feminino , Alemanha , Humanos , Licenciamento/tendências , Masculino , Análise de Regressão , Estudos Retrospectivos , Habilidades para Realização de Testes/estatística & dados numéricos
19.
Pituitary ; 20(6): 635-642, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28808855

RESUMO

PURPOSE: Acromegaly is a rare disease generally brought about by a benign tumour in the pituitary and characterized by growth hormone (GH) and insulin-like growth factor 1 (IGF-1) excess. Increased mortality has been related to cardiovascular events that could be linked to these hormones and patients suffer from high rates of diabetes and hypertension. In this study, we examine if the incidence of myocardial infarction (MI) and stroke differ from that of the general population. METHODS: Data from the German Acromegaly Registry in seven specialized endocrine centres were analysed (n = 479, 56% female, 46 years old at diagnosis, 5549 person-years from diagnosis). Standardized incidence ratios (SIR) were calculated as compared to the general population. RESULTS: MI and stroke incidences were very close to those of the general population with an SIR (95% CI) of 0.89 (0.47-1.52, p = 0.80) for MI and 1.17 (0.66-1.93, p = 0.61) for stroke. Acromegaly was uncontrolled in 16% of patients with MI or stroke versus 21% in those without (p = 0.56). Prevalence of hypertension at the initial visit was much higher in those with MI or stroke than those without (94 vs. 43%, p < 0.001). No association was seen between radiation therapy and stroke. CONCLUSIONS: For acromegaly patients being treated at specialized centres, the incidence of MIs and strokes does not seem to differ from the general population. Certainty regarding such statements requires large, prospective studies however.


Assuntos
Acromegalia/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acromegalia/metabolismo , Adulto , Idoso , Feminino , Hormônio do Crescimento Humano/metabolismo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/metabolismo , Estudos Prospectivos , Acidente Vascular Cerebral/metabolismo
20.
Eur J Endocrinol ; 177(1): 15-23, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28432267

RESUMO

OBJECTIVE: Acromegaly is associated with increased mortality due to respiratory disease. To date, lung function in patients with acromegaly has only been assessed in small studies, with contradicting results. We assessed lung function parameters in a large cohort of patients with acromegaly. DESIGN: Lung function of acromegaly patients was prospectively assessed using spirometry, blood gas analysis and body plethysmography. Biochemical indicators of acromegaly were assessed through measurement of growth hormone and IGF-I levels. This study was performed at the endocrinology outpatient clinic of a tertiary referral center in Germany. METHODS: We prospectively tested lung function of 109 acromegaly patients (53 male, 56 female; aged 24-82 years; 80 with active acromegaly) without severe acute or chronic pulmonary disease. We compared lung volume, air flow, airway resistance and blood gases to normative data. RESULTS: Acromegaly patients had greater lung volumes (maximal vital capacity, intra-thoracic gas volume and residual volume: P < 0.001, total lung capacity: P = 0.006) and showed signs of small airway obstruction (reduced maximum expiratory flow when 75% of the forced vital capacity (FVC) has been exhaled: P < 0.001, lesser peak expiratory flow: P = 0.01). There was no significant difference between active and inactive acromegaly. Female patients had significantly altered lung function in terms of subclinical airway obstruction. CONCLUSIONS: In our cross-sectional analysis of lung function in 109 patients with acromegaly, lung volumes were increased compared to healthy controls. Additionally, female patients showed signs of subclinical airway obstruction. There was no difference between patients with active acromegaly compared with patients biochemically in remission.


Assuntos
Acromegalia/fisiopatologia , Testes de Função Respiratória , Adulto , Idoso , Idoso de 80 Anos ou mais , Gasometria , Estudos de Coortes , Estudos Transversais , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Pneumopatias/complicações , Pneumopatias/fisiopatologia , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Pletismografia , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Espirometria , Capacidade Vital , Adulto Jovem
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