Response to GH treatment in adult GH deficiency is predicted by gender, age, and IGF1 SDS but not by stimulated GH-peak.

Objective: We studied whether the severity of GH deficiency (GHD) defined as i) GH-peak on stimulation tests (insulin tolerance test (ITT), arginine, and glucagon), ii) number of additional pituitary deficits, or iii) baseline IGF1 SDS could impact the response to GH treatment. We further explored whether iv) IGF1 SDS after 24 months of GH replacement or v) ΔIGF1 SDS from baseline to 24 months was related to the phenotypic response to GH treatment. DESIGN, PATIENTS, AND MEASUREMENTS: The patient cohort (n=1752; 50% women) was obtained from KIMS (Pfizer International Metabolic Database).

Overall and cause-specific mortality in GH-deficient adults on GH replacement.

Objective: Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients.

Design: In KIMS (Pfizer International Metabolic Database) 13,983 GH-deficient patients with 69,056 patient-years of follow-up were available.

Similar clinical features among patients with severe adult growth hormone deficiency diagnosed with insulin tolerance test or arginine or glucagon stimulation tests.

Objective: To determine whether insulin tolerance tests (ITTs), arginine stimulation tests (ASTs), and glucagon stimulation tests (GST) identify patients who have similar clinical features of growth hormone (GH) deficiency when a diagnostic GH threshold of 3 μg/L is used.

Methods: Data were obtained from the KIMS database (Pfizer International Metabolic Database). Comparisons were made between patients who underwent ITT, AST, or GST for GH peak, body mass index, lipids, waist circumference, waist-to-hip ratio, and quality of life.

Structured assessment of hypopituitarism after traumatic brain injury and aneurysmal subarachnoid hemorrhage in 1242 patients: the German interdisciplinary database.

Clinical studies have demonstrated that traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) are frequent causes of long-term disturbances of hypothalamo-pituitary function. This study aimed to assess the prevalence and associated factors of post-traumatic hypopituitarism in a large national registry of patients with TBI and SAH. Data were collected from 14 centers in Germany and Austria treating patients for TBI or SAH and performing endocrine assessments.

Cardiovascular risk factors in patients with uncontrolled and long-term acromegaly: comparison with matched data from the general population and the effect of disease control.

Context: Data on cardiovascular risk in acromegaly are scanty and lack a clear correlation to epidemiological data.

Objective: Our aim was an evaluation of cardiovascular risk factors in patients with active acromegaly, a calculation of the Framingham risk score (FRS) compared with age- and gender-matched controls of the general population, and an evaluation of the effect of IGF-I normalization.

Design And Setting: We conducted a retrospective, comparative study at a university referral center.

Change of symptoms and perceived health in acromegalic patients on pegvisomant therapy: a retrospective cohort study within the German Pegvisomant Observational Study (GPOS).

Objective: This study aimed at investigating how symptoms and perceived health changes in acromegalic patients during pegvisomant treatment in respect to IGF-1 levels and disease characteristics.

Design/patients: Retrospective, multicentre cohort study in 131 acromegalic patients within the German Pegvisomant Observational Study (GPOS).

Measurements: Outcome measure was the change of perceived health evaluated by the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) between baseline and after 1 year of pegvisomant therapy.

Experience from the German pegvisomant observational study.

Background: The German Pegvisomant Observational Study (GPOS) was created immediately after marketing authorisation was received in Germany for Somavert (pegvisomant) for the treatment of patients with acromegaly. In August 2006, the database underwent its fifth interim analysis of 263 patients, the vast majority of whom previously had insufficient disease control with other treatment modalities. The GPOS documents both safety and efficacy aspects of the treatment of patients with acromegaly by the first growth hormone-receptor antagonist, pegvisomant.

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.

Influence of GH substitution therapy in deficient adults on the recurrence rate of hormonally inactive pituitary adenomas: a case control study.

Objective: Several studies documented metabolic and psychological benefits of GH substitution in deficient adults, most of them suffering from benign pituitary adenomas. Since GH substitution is considered to promote tumour regrowth, adequate treatment is performed with some reservation. Therefore, we aimed to elucidate the effect of GH replacement therapy on tumour recurrence following surgery.

Clinical implications of residual growth hormone (GH) response to provocative testing in adults with severe GH deficiency.

Context: The diagnosis of GH deficiency (GHD) in adults is based on provocative tests of GH release, all influenced by clinical factors. It is unknown whether the amount of residual GH reserve under the cutoff value has any physiological implication.

Objectives: We used a large pharmacoepidemiological database of adult GHD (KIMS) and tested the impact of confounding factors on GH release of no greater than 3 microg/liter after an insulin tolerance test (ITT) and evaluated its potential physiological role.

Quality of life and psychiatric sequelae following aneurysmal subarachnoid haemorrhage: does neuroendocrine dysfunction play a role?

Objective: Patients who have sustained aneurysmal subarachnoid haemorrhage (SAH) often suffer persistent impairments in their quality of life (QoL) and psychological disturbances despite a good neurological outcome. In the light of the high prevalence of partial hypopituitarism in SAH survivors demonstrated in recent investigations, we aimed to determine whether neuroendocrine dysfunction has an impact on QoL and neurobehavioural symptoms in these patients.

Design/patients: QoL, depression and psychological distress were assessed in 40 SAH survivors who had undergone endocrine function testing at least 1 year after the haemorrhage.

Healthcare utilization, quality of life and patient-reported outcomes during two years of GH replacement therapy in GH-deficient adults--comparison between Sweden, The Netherlands and Germany.

Objective: This study set out to determine the change in quality of life (QoL) and healthcare utilization during 2 years of growth hormone (GH) replacement therapy in adults with GH deficiency. Data were compared from three European countries.

Design: Analysis was made from KIMS, the Pfizer International Metabolic Database on adult GH deficiency.

Opposite associations of age-dependent insulin-like growth factor-I standard deviation scores with nutritional state in normal weight and obese subjects.

Objective: Insulin-like growth factor-I (IGF-I) has been suggested to be a prognostic marker for the development of cancer and, more recently, cardiovascular disease. These diseases are closely linked to obesity, but reports of the association of IGF-I with measures of obesity are divergent. In this study, we assessed the association of age-dependent IGF-I standard deviation scores with body mass index (BMI) and intra-abdominal fat accumulation in a large population.

Prevalence of pituitary deficiency in patients after aneurysmal subarachnoid hemorrhage.

After aneurysmal subarachnoid hemorrhage (SAH), patients frequently present with persistent bodily, psychosocial, and cognitive impairments that resemble those of patients with untreated partial or complete pituitary insufficiency. Because of these similarities, the authors hypothesized that aneurysmal SAH may cause pituitary dysfunction. Pituitary function testing was performed in 40 aneurysmal SAH patients between 12 and 72 months after the SAH.

Autoantibodies to thyroperoxidase (TPOAb) in a large population of euthyroid subjects: implications for the definition of TPOAb reference intervals.

Objective: Measurement of autoantibodies against thyroperoxidase (TPOAb) plays an important role in the diagnosis of autoimmune thyroid disease. The assessment of reference intervals for TPOAb, however, is a controversial issue since elevated TPOAb values are sometimes found in subjects without other evidence of thyroid disease.

Methods: TPOAb were measured in 1,295 euthyroid individuals using a highly sensitive, fully automated chemiluminescence assay (Advantage A-TPO, Nichols Institute Diagnostics, CA, USA).

Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study.

Background: Analysis of insulin-like growth factor I in serum (S-IGF-I) is an integral component in the diagnosis of GH-related disorders and is going to be of interest in the diagnosis and follow-up of many disorders. The objective of the present study was to develop cross-sectional reference values for S-IGF-I measured by an automated chemiluminescence immunoassay (Nichols Advantage).

Methods: The study included samples from 3,961 healthy subjects (2,201 males, 1,760 females) aged 1 month to 88 years.

Sensitive calcitonin measurement by two-site immunometric assays: implications for calcitonin screening in nodular thyroid disease.

The aim of this study was to investigate the impact of analytical aspects on the clinical usefulness of calcitonin (CT) measurement. In a retrospective analysis, CT levels measured by a polyclonal immunometric assay (Scantibodies Laboratory, CA, USA) were evaluated in various clinical situations. CT in newly diagnosed medullary thyroid cancer (MTC) (n = 20) ranged from 15.

Characterization of T(4)-binding globulin cleaved by human leukocyte elastase.

T(4)-binding globulin (TBG) serves to maintain an important serum pool of thyroid hormones and to prevent their excessive loss in urine. TBG has also been implicated in the tissue distribution and targeted delivery of the hormones, the mechanisms of which remain unclear. By virtue of sequence homology, TBG belongs to the serine proteinase inhibitors superfamily of proteins that are characterized by a reactive site loop serving as a recognition site for serine proteinases.

Characterization and primary structures of bovine and porcine thyroxine-binding globulin.

Thyroxine-binding globulin (TBG) is the major serum transport protein for iodothyronines in most of the large, omni- or herbivorous mammals. Characterization of human TBG (hTBG), including its 20 known natural variants, allowed the identification of the ligand-binding site and a correlation of diminished synthesis or loss of function with mutations in the TBG gene. Further refinement of the structure-function correlation, especially the high binding affinity and heat stability, requires characterization of other mammalian TBGs, of which only rat and sheep TBG were available.