[The androgenital syndrome: Don't just think about it in childhood!] / Das adrenogenitale Syndrom: Nicht nur im Kindesalter daran denken!

The androgenital syndrome: Don't just think about it in childhood!In adrenogenital syndrome, the body permanently produces too many male sex hormones. Rare, congenital metabolic diseases are usually discovered in infancy and can be treated at an early stage treated at an early stage, but sometimes they only become apparent in adolescence and adulthood.This article provides background knowledge for GPs.

[Pituitary insufficiency: basics in diagnosis and therapy]. / Hypophyseninsuffizienz ­ das Einmaleins in Diagnostik und Therapie.

Pituitary insufficiency is a partial or complete failure of secretion of one or more hormones from the pituitary gland. The pituitary gland is located in the hypophysial fossa of the sella turcica of the os sphenoidale and produces ACTH, LH, FSH, GH, TSH, and prolactin. Pituitary insufficiency can be caused by acute damage, such as secondary to traumatic brain injury. It can also be a result of chronic alterations, such as increasing tumor expansion.Pituitary insufficiency often presents with nonspecific symptoms (e.g. fatigue, listlessness, decreased performance, sleep disturbances, weight change) that leads to a challenging and sometimes delayed diagnosis. The symptoms correspond to the failure of the corresponding endorgans. Occasionally, symptoms such as a loss of libido, secondary amenorrhea or nausea in stressful situations are diagnostically indicative.Further clarification includes a clinical examination with endocrinological testing of the pituitary function. Alteration of pituitary hormone secretion can also occur physiologically as in pregnancy, depression or obesity. Substitution therapy of the failed corticotropic, thyrotropic and gonadotropic axis is corresponding to the therapy of a primary endorgan insufficiency. Adequate diagnosis and treatment of pituitary insufficiency is important, as this may prevent life-threatening crises such as an adrenal crisis.

[Transsexualism and transgender medicine - what every internal specialist should know about]. / Transsexualität und Transgender-Medizin ­ Was jeder Internist wissen sollte.

The authors present current findings on transsexualism and its treatment. According to the ICD-10, transsexualism is defined as the "desire to live and be accepted as a member of the opposite sex, usually accompanied by a sense of discomfort with, or inappropriateness of, one's anatomic sex, and a wish to have surgery and hormonal treatment to make one's body as congruent as possible with one's preferred sex." Synonyms of transsexualism are terms such as gender dysphoria reflecting the distress that persons feel due to a mismatch between their gender identity and their sex assigned at birth.The prevalence of transsexualism is estimated to be about 0,6 %. The diagnosis of transsexualism is made by psychiatrists, but at least five more medical specialties (endocrinologist, surgeon, ear, nose and throat specialist, speech therapist and dermatologist) are involved when treating transsexual persons. Hormonal therapy is a very important element of the treatment process; due to the complexity of transsexualism it should be undertaken by endocrinologists with experience and expertise in this field.

Inhibition of Heat Shock Factor 1 Enhances Repressive Molecular Mechanisms on the POMC Promoter.

BACKGROUND: Cushing's disease (CD) is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumours. They express high levels of heat shock protein 90 and heat shock factor 1 (HSF1) in comparison to the normal tissue counterpart, indicating activated cellular stress. AIMS: Our objectives were: (1) to correlate HSF1 expression with clinical features and hormonal/radiological findings of CD, and (2) to investigate the effects of HSF1 inhibition as a target for CD treatment. PATIENTS/METHODS: We examined the expression of total and pSer326HSF1 (marker for its transcriptional activation) by Western blot on eight human CD tumours and compared to the HSF1 status of normal pituitary. We screened a cohort of 45 patients with CD for HSF1 by immunohistochemistry and correlated the HSF1 immunoreactivity score with the available clinical data. We evaluated the effects of HSF1 silencing with RNA interference and the HSF1 inhibitor KRIBB11 in AtT-20 cells and four primary cultures of human corticotroph tumours. RESULTS: We show that HSF1 protein is highly expressed and transcriptionally active in CD tumours in comparison to normal pituitary. The immunoreactivity score for HSF1 did not correlate with the typical clinical features of the disease. HSF1 inhibition reduced proopiomelanocortin (Pomc) transcription in AtT-20 cells. The HSF1 inhibitor KRIBB11 suppressed ACTH synthesis from 75% of human CD tumours in primary cell culture. This inhibitory action on Pomc transcription was mediated by increased glucocorticoid receptor and suppressed Nurr77/Nurr1 and AP-1 transcriptional activities. CONCLUSIONS: These data show that HSF1 regulates POMC transcription. Pharmacological targeting of HSF1 may be a promising treatment option for the control of excess ACTH secretion in CD.

Neuropsychiatric and metabolic aspects of dopaminergic therapy: perspectives from an endocrinologist and a psychiatrist.

The dopaminergic treatment represents the primary treatment in prolactinomas, which are the most common pituitary adenomas and account for about 40% of all pituitary tumours with an annual incidence of six to ten cases per million population. The dopaminergic treatment includes ergot and non-ergot derivatives with high affinity for the dopamine receptors D1 or/and D2. Through the activation of the dopaminergic pathway on pituitary lactotrophs, the dopamine agonists inhibit the prolactin synthesis and secretion, therefore normalizing the prolactin levels and restoring eugonadism, but they also lead to tumour shrinkage. Treatment with dopamine agonists has been associated - apart from the common side effects such as gastrointestinal symptoms, dizziness and hypotension - with neuropsychiatric side effects such as impulse control disorders (e.g. pathological gambling, compulsive shopping, hypersexuality and binge eating) and also with behavioral changes from low mood, irritability and verbal aggressiveness up to psychotic and manic symptoms and paranoid delusions not only in patients with prolactinomas but also in patients with Parkinson's disease and restless leg syndrome. They usually have de novo onset after initiation of the dopaminergic treatment and have been mainly reported in patients with Parkinson's disease, who are being treated with higher doses of dopamine agonists. Moreover, dopamine and prolactin seem to play an essential role in the metabolic pathway. Patients with hyperprolactinemia tend to have increased body weight and an altered metabolic profile with hyperinsulinemia and increased prevalence of diabetes mellitus in comparison to healthy individuals and patients with non-functioning pituitary adenomas. Treatment with dopamine agonists in these patients in short-term studies seems to lead to weight loss and amelioration of the metabolic changes. Together these observations provide evidence that dopamine and prolactin have a crucial role both in the regard and metabolic system, findings that merit further investigation in long-term studies.

Neuroendocrine Disturbances One to Five or More Years after Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage: Data from the German Database on Hypopituitarism.

Neuroendocrine disturbances are common after traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH), but only a few data exist on long-term anterior pituitary deficiencies after brain injury. We present data from the Structured Data Assessment of Hypopituitarism after TBI and SAH, a multi-center study including 1242 patients. We studied a subgroup of 351 patients, who had sustained a TBI (245) or SAH (106) at least 1 year before endocrine assessment (range 1-55 years) in a separate analysis. The highest prevalence of neuroendocrine disorders was observed 1-2 years post-injury, and it decreased over time only to show another maximum in the long-term phase in patients with brain injury occurring ≥5 years prior to assessment. Gonadotropic and somatotropic insufficiencies were most common. In the subgroup from 1 to 2 years after brain injury (n = 126), gonadotropic insufficiency was the most common hormonal disturbance (19%, 12/63 men) followed by somatotropic insufficiency (11.5%, 7/61), corticotropic insufficiency (9.2%, 11/119), and thyrotropic insufficiency (3.3%, 4/122). In patients observed ≥ 5 years after brain injury, the prevalence of somatotropic insufficiency increased over time to 24.1%, whereas corticotropic and thyrotrophic insufficiency became less frequent (2.5% and 0%, respectively). The prevalence differed regarding the diagnostic criteria (laboratory values vs. physician`s diagnosis vs. stimulation tests). Our data showed that neuroendocrine disturbances are frequent even years after TBI or SAH, in a cohort of patients who are still on medical treatment.

The Development of Neuroendocrine Disturbances over Time: Longitudinal Findings in Patients after Traumatic Brain Injury and Subarachnoid Hemorrhage.

Previous reports suggest that neuroendocrine disturbances in patients with traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (SAH) may still develop or resolve months or even years after the trauma. We investigated a cohort of n = 168 patients (81 patients after TBI and 87 patients after SAH) in whom hormone levels had been determined at various time points to assess the course and pattern of hormonal insufficiencies. Data were analyzed using three different criteria: (1) patients with lowered basal laboratory values; (2) patients with lowered basal laboratory values or the need for hormone replacement therapy; (3) diagnosis of the treating physician. The first hormonal assessment after a median time of three months after the injury showed lowered hormone laboratory test results in 35% of cases. Lowered testosterone (23.1% of male patients), lowered estradiol (14.3% of female patients) and lowered insulin-like growth factor I (IGF-I) values (12.1%) were most common. Using Criterion 2, a higher prevalence rate of 55.6% of cases was determined, which correlated well with the prevalence rate of 54% of cases using the physicians' diagnosis as the criterion. Intraindividual changes (new onset insufficiency or recovery) were predominantly observed for the somatotropic axis (12.5%), the gonadotropic axis in women (11.1%) and the corticotropic axis (10.6%). Patients after TBI showed more often lowered IGF-I values at first testing, but normal values at follow-up (p < 0.0004). In general, most patients remained stable. Stable hormone results at follow-up were obtained in 78% (free thyroxine (fT4) values) to 94.6% (prolactin values).

IGF-I in major depression and antidepressant treatment response.

We analyzed insulin-like growth factor I (IGF-I) in serum of 78 inpatients with depression and 92 healthy controls. Patients were selected according to remission status after 6 weeks of antidepressant treatment with remission defined by Hamilton depression rating scale (HAM-D) 21-item score <10 (39 remitters and 39 non-remitters). IGF-I was analyzed in patients at admission and after 6 weeks of psychopharmacological treatment. IGF-I levels were compared between patients and controls and between remitters and non-remitters with general linear model using age, gender, and body mass index as covariates. In patients, IGF-I levels were significantly higher at admission (p=3.29E-04) and in week 6 (p=0.002) compared to controls. Furthermore, non-remitters showed significantly higher IGF-I levels at admission (p=0.046) and a trend for higher IGF-I levels in week 6 (p=0.11) compared to remitters. In remitters change in IGF-I levels during treatment was significantly correlated with change in cortisol levels (p=0.019). A genetic association analysis of polymorphisms in 10 genes contributing to the IGF-I system (IGF1, IGF1R, IGFBP1 to IGFBP7, and IGFBPL1) in the currently largest genetic databases for major depression (Psychiatric Genomics Consortium) revealed nominal associations with susceptibility for depression and treatment response, although results did not remain significant after multiple testing correction. In our study, elevated IGF-I levels were significantly associated with depression and impaired treatment response. Based on these findings IGF-I signaling could play a role in the pathophysiology of depression and could possibly influence the response to antidepressant treatment.

Screening for hypopituitarism in 509 patients with traumatic brain injury or subarachnoid hemorrhage.

We performed a screening on patients with traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH) to determine the prevalence of post-traumatic hypopituitarism in neurorehabilitation in a cross-sectional, observational single-center study. In addition, the therapeutic consequences of our screening were analyzed retrospectively. From February 2006 to August 2009, patients between 18 and 65 years (n=509) with the diagnosis of TBI (n=340) or SAH (n=169) were screened within two weeks of admittance to neurorehabilitation as clinical routine. Blood was drawn to determine fasting cortisol, free thyroxine (fT4), prolactin, testosterone or estradiol, and insulin-like growth factor I (IGF-I). Patients with abnormalities in the screening or clinical signs of hypopituitarism received further stimulation tests: growth hormone releasing hormone -L-arginine-test and adrenocorticotrophic hormone (ACTH)-test (n=36); ACTH-test alone (n=26); or insulin tolerance test (n=56). In our screening of 509 patients, 28.5% showed lowered values in at least one hormone of the hypothalamus-pituitary axis and 4.5% in two or more axes. The most common disturbance was a decrease of testosterone in 40.7% of all men (in the following 13/131 men were given substitution therapy). Low fT4 was detected in 5.9% (n=3 were given substitution therapy). Low IGF-I was detected in 5.8%, low cortisol in 1.4%, and low prolactin in 0.2%; none were given substitution therapy. Further stimulation tests revealed growth hormone deficiency in 20.7% (n=19/92) and hypocortisolism in 23.7% (n=28/118). Laboratory values possibly indicating hypopituitarism (33%) were common but did not always implicate post-traumatic hypopituitarism. Laboratory values possibly indicating hypopituitarism were common in our screening but most patients were clinically not diagnosed as pituitary insufficient and did not receive hormone replacement therapy. A routine screening of all patients in neurorehabilitation without considering the time since injury, the severity of illness and therapeutic consequences seems not useful.

Health Outcomes in Acromegaly: Depression and Anxiety are Promising Targets for Improving Reduced Quality of Life.

INTRODUCTION: Remission criteria of acromegaly are based on biochemical variables, i.e., normalization of increased hormone levels. However, the established reduction in Quality of Life (QoL) is suggested to be independent of biochemical control. The aim of this study was to test which aspects predict QoL best in acromegaly. METHODS/DESIGN: This is a prospective cohort study in 80 acromegalic patients, with a cross-sectional and longitudinal part. The main outcome measure was health-related QoL, measured by a generic and a disease-specific questionnaire (the SF-36 and AcroQoL). Main predictors were age, gender, biochemical control, disease characteristics, treatment modalities, and psychopathology. RESULTS: Our cohort of 80 acromegalics had a mean age 54.7 ± 12.3 years with an average disease duration of 10.8 ± 10.0 years. Ratio macro-/microadenoma was 54/26. In adjusted mixed method models, we found that psychopathology significantly predicts QoL in acromegaly (in models including the variables age, gender, disease duration, tumor size, basal hormone levels, relevant treatment modalities, and relevant comorbidities), with a higher degree of psychopathology indicating a lower QoL (depression vs. AcroQoL: B = -1.175, p < 0.001, depression vs. SF-36: B = -1.648, p < 0.001, anxiety vs. AcroQoL: B = -0.399, p < 0.001, anxiety vs. SF-36: B = -0.661, p < 0.001). The explained variances demonstrate superiority of psychopathology over biochemical control and other variables in predicting QoL in our models. DISCUSSION: Superiority of psychopathology over biochemical control calls for a more extensive approach regarding diagnosing depression and anxiety in pituitary adenomas to improve QoL. Depressive symptoms and anxiety are modifiable factors that might provide valuable targets for possible future treatment interventions.

Changes in the prevalence, treatment and control of hypertension in Germany? A clinical-epidemiological study of 50.000 primary care patients.

INTRODUCTION: Medical societies have developed guidelines for the detection, treatment and control of hypertension (HTN). Our analysis assessed the extent to which such guidelines were implemented in Germany in 2003 and 2001. METHODS: Using standardized clinical diagnostic and treatment appraisal forms, blood pressure levels and patient questionnaires for 55,518 participants from the cross-sectional Targets and Essential Data for Commitment of Treatment (DETECT) study (2003) were analyzed. Physician's diagnosis of hypertension (HTN(doc)) was defined as coding hypertension in the clinical appraisal questionnaire. Alternative definitions used were physician's diagnosis or the patient's self-reported diagnosis of hypertension (HTN(doc,pat)), physician's or patient's self-reported diagnosis or a BP measurement with a systolic BP ≥ 140 mmHg and/or a diastolic BP ≥ 90 (HTN(doc,pat,bp)) and diagnosis according to the National Health and Nutrition Examination Survey (HTN(NHANES)). The results were compared with the similar German HYDRA study to examine whether changes had occurred in diagnosis, treatment and adequate blood pressure control (BP below 140/90 mmHg) since 2001. Factors associated with pharmacotherapy and control were determined. RESULTS: The overall prevalence rate for hypertension was 35.5% according to HTN(doc) and 56.0% according to NHANES criteria. Among those defined by NHANES criteria, treatment and control rates were 56.0% and 20.3% in 2003, and these rates had improved from 55.3% and 18.0% in 2001. Significant predictors of receiving antihypertensive medication were: increasing age, female sex, obesity, previous myocardial infarction and the prevalence of comorbid conditions such as coronary heart disease (CHD), hyperlipidemia and diabetes mellitus (DM). Significant positive predictors of adequate blood pressure control were CHD and antihypertensive medication. Inadequate control was associated with increasing age, male sex and obesity. CONCLUSIONS: Rates of treated and controlled hypertension according to NHANES criteria in DETECT remained low between 2001 and 2003, although there was some minor improvement.

Effects of growth hormone replacement within the KIMS survey on estimated cardiovascular risk and predictors of risk reduction in patients with growth hormone deficiency.

OBJECTIVE: There is growing evidence for an increased cardiovascular (CV) risk in untreated growth hormone deficiency of adults (GHD). We aimed at estimating CV risk with established algorithms before and during GH replacement in GHD and in healthy controls and at identifying predictors of risk reduction. DESIGN: A prospective, nested case-control study. PATIENTS: We included 344 patients (44·7 ± 14·9 years) from the German Pfizer (formerly Kabi) International Metabolic Database (KIMS) cohort and included a healthy sex- and age-matched control group from a primary care cohort. MEASUREMENTS: We calculated Framingham, Prospective Cardiovascular Münster Heart Study (PROCAM) and European Society of Cardiology (ESC) Score algorithms at all time points. In multivariate analyses, we analysed potential predictors of 2-year reduction in CV risk, defined as a higher than median reduction in risk. RESULTS: In KIMS, the estimated 10-year risks of CV events or CV mortality calculated with Framingham, PROCAM and ESC Score algorithms at baseline were 4·6%, 6·0% and 2·3%, respectively. These dropped to 2·4%, 4·8% and 0·8%, respectively, after 2 years of GH replacement (all P < 0·001 vs baseline) and returned to baseline levels after four years of GH replacement. In controls, the Framingham risk estimates were lower than in KIMS at baseline. All risk estimates increased during follow-up and were significantly higher than in KIMS after four years (all P < 0·01). In backward-selection models, high total cholesterol, low high-density lipoprotein (HDL) cholesterol and male sex were significant predictors of response in most scores. CONCLUSION: Two years of GH replacement decreased CV risk estimates approximately by half. Male sex, high total and low HDL cholesterol levels are potential predictors of good response.

Prediction of incident diabetes mellitus by baseline IGF1 levels.

OBJECTIVE: IGF1 is associated with metabolic parameters and involved in glucose metabolism. Low-IGF1 has been implicated in the etiology of glucose intolerance and subjects with pathological causes of either low- or high-IGF1 are at risk of diabetes. We hypothesized that both low- and high-IGF1 levels increase the risk of diabetes and aimed to assess the role of IGF1 in the risk of developing diabetes in a large prospective study. DESIGN: An analysis of two prospective cohort studies, the DETECT study and SHIP. METHODS: We measured IGF1 levels in 7777 nondiabetic subjects and assessed incident diabetes mellitus during follow-up. RESULTS: There were 464 cases of incident diabetes during 32 229 person-years (time of follow-up in the DETECT study and SHIP: 4.5 and 5 years respectively). There was no heterogeneity between both studies (P > 0.4). The hazard ratios (HRs) of incident diabetes in subjects with IGF1 levels below the 10th or above the 90th age- and sex-specific percentile, compared to subjects with intermediate IGF1 levels, were 1.44 (95% confidence interval (CI) 1.07-1.94) and 1.55 (95% CI 1.06-2.06) respectively, after multiple adjustment. After further adjustment for metabolic parameters, the HR for low-IGF1 became insignificant. Analysis of IGF1 quintiles revealed a U-shaped association of IGF1 with risk of diabetes. Results remained similar after exclusion of patients with onset of new diabetes within 1 year or with borderline glucose or HbA1c levels at baseline. CONCLUSIONS: Subjects with low- or high-IGF1 level are at increased risk of developing diabetes.

Modulation of growth hormone and prolactin secretion in Trypanosoma cruzi-infected mammosomatotrophic cells.

OBJECTIVE: In a previous study, we reported an imbalance in the hypothalamus-pituitary-adrenal axis of mice acutely infected with the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. METHODS: Possible effects of this parasitic infection on the endocrine function of other pituitary cell types were studied, in particular regarding the production of prolactin (PRL) and growth hormone (GH). RESULTS: In the mammosomatotrophic cell line GH3, both GH and PRL secretion were decreased, reflecting the diminished PRL concentrations in the pituitary glands of infected mice. Additionally, expression of extracellular matrix proteins, e.g. laminin, was increased in T. cruzi-infected GH3 cells, which may be related to the diminished secretory function of these cells. Lastly, the expression of Pit-1, a major transcription factor for the PRL and GH genes, is also decreased in T. cruzi-infected cultures. CONCLUSION: T. cruzi infection downregulates PRL and GH production. Combined with our previous data showing increased glucocorticoid levels following T. cruzi infection, the immunosuppression induced by T. cruzi infection may be partially related to multiple endocrine changes involving the hypothalamus-pituitary axis and corresponding target endocrine glands.

Prevalence of low male testosterone levels in primary care in Germany: cross-sectional results from the DETECT study.

OBJECTIVE: Low testosterone levels in men occur with increasing age and are associated with increased morbidity, particularly metabolic syndrome, and mortality. As the prevalence of hypogonadal testosterone levels has not been assessed in the primary care setting in Europe, we aimed to investigate the prevalence of low testosterone levels in this setting, and the patient characteristics and comorbidities associated with this finding. DESIGN: A cross-sectional, epidemiological study (the Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment (DETECT) study). PATIENTS: A total of 2719 male primary care patients (age 58.7 +/- 13.4 years) were included. MEASUREMENTS: Testosterone was measured in all patients. Information on diseases, risk conditions and treatments was documented by the primary care physicians. A large set of laboratory parameters was measured in a central laboratory. We calculated univariate and multivariate logistic regression models to assess the associations of low testosterone levels with different health and life style factors. RESULTS: A total of 19.3% of all men had hypogonadism as defined by testosterone levels < 3.0 ng/ml. Stepwise logistic regression analysis revealed that obesity, metabolic syndrome, cancer, intake of six or more drugs, acute inflammation and nonsmoking were associated with hypogonadal testosterone levels. Higher age, liver diseases, and cancer were associated with very low testosterone levels (< 1.0 ng/ml). CONCLUSIONS: Hypogonadal testosterone levels are common in primary care, particularly in patients with the above conditions.

Associations of age-dependent IGF-I SDS with cardiovascular diseases and risk conditions: cross-sectional study in 6773 primary care patients.

OBJECTIVE: We aimed at investigating the association of age-dependent IGF-I SDS with diabetes, dyslipidemia, hypertension, and heart diseases, in a large patient sample. BACKGROUND: IGF-I has been suggested to be associated with several diseases and a prognostic marker for the development of cardiovascular diseases and risk factors. The findings, though, have been inconsistent possibly due to the methodological factors. METHODS: We studied 6773 consecutive primary care patients, aged 18+ years, in a cross-sectional, epidemiological study in primary care, Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment study. All patients underwent a standardized clinical diagnostic and laboratory assessment. IGF-I levels were measured with an automated chemiluminescence assay system. We calculated the odds ratios (OR) for diseases in quintiles of IGF-I, and additionally analyzed the association of age-dependent IGF-I SDS with these conditions. RESULTS: After multiple adjustments for confounders, we found increased ORs for coronary artery disease in patients with high IGF-I. Women, but not men, with low IGF-I also showed increased ORs for coronary artery disease. Dyslipidemia was positively associated with IGF-I. Type 2 diabetes showed a curvilinear association with IGF-I SDS. CONCLUSIONS: The findings suggest the existence of multiple and complex interactions between IGF-I and several health conditions. The complex nature of disease- and subgroup-specific associations along with the methodological factors can be held responsible for divergent findings in previous studies.

Insulin-like growth factor-1 in plasma and brain: regulation in health and disease.

IGF-1 was first described as a growth mediating factor regulated in the context of the somatotrophic axis. During the last decade, it has gained much attention for its role in the regulation of lifespan, brain function, cell growth, and metabolism. Associations of plasma IGF-1 levels in physiological and pathological conditions such as aging, cardiovascular disease, metabolic disorders, dementia, and neurodegenerative disorders, and its potential as a neurotrophic agent, have been intensively studied. Acromegaly due to jGH and IGF-1 excess and growth hormone deficiency with decreased GH and IGF-1 might serve as models to study IGF-1 function, but the effects of GH and IGF-1 in these conditions are often indistinguishable. Due to this overlap, this article will only briefly mention pathophysiological implications in acromegaly and growth hormone deficiency. It will focus on IGF-1 and give an overview of the vast literature on the role and regulation of IGF-1 in plasma and brain, its alteration in health and disease and its possible therapeutical applications.