PH Kan - Academia.edu (original) (raw)

Papers by PH Kan

Research paper thumbnail of Growth hormone deficient patients after traumatic brain injury – Baseline characteristics and benefits after growth hormone replacement – An analysis of the German KIMS database

Growth Hormone & IGF Research, 2008

Objective: In recent years, traumatic brain injury (TBI) has been identified as a significant cau... more Objective: In recent years, traumatic brain injury (TBI) has been identified as a significant cause of growth hormone deficiency (GHD). The aim of the present study was to characterize adult TBI patients with GHD to elucidate the effect of human growth hormone (hGH) replacement in TBI patients as documented in the German Pfizer International Metabolic (KIMS) database. Design: As of October 2006, 84 TBI patients had been included in the German KIMS database (n = 28 childhood-onset and 54 adult-onset GHD). All 84 TBI patients were matched with 84 patients with GHD due to non-functioning pituitary adenoma (NFPA) also included in this database. Analysis of clinical and outcome variables was performed, with comparisons of childhood vs. adult TBI, and TBI vs. NFPA patients, at baseline and one-year follow-up. Results: TBI patients with GHD were significantly younger at the onset of pituitary disease and exhibited a significantly longer time span between GHD diagnosis and KIMS entry than NFPA patients. Those KIMS patients who had sustained their TBI in childhood were of significantly shorter stature than adult-onset TBI patients. At 1-year follow-up, insulin-like growth factor I (IGF-I) standard deviation score levels had returned to the normal range and quality of life (QoL), as measured by QoL-Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire, improved significantly in TBI as in NFPA patients. Conclusion: This analysis provides preliminary data that TBI patients with GHD benefit from hGH replacement in terms of improved QoL in a similar fashion as do NFPA patients. Moreover, it suggests that belated diagnosis and treatment in childhood-onset GHD due to TBI might be related to a shorter final height in these children.

Research paper thumbnail of Short stature and decreased insulin-like growth factor I (IGF-I)/growth hormone (GH)-ratio in an adult GH-deficient patient pointing to additional partial GH insensitivity due to a R179C mutation of the growth hormone receptor

Growth Hormone & IGF Research, 2007

Objective: Genetic factors play an expanding role in understanding growth hormone (GH) disorders,... more Objective: Genetic factors play an expanding role in understanding growth hormone (GH) disorders, therefore the German KIMS Pharmacogenetics Study was initiated with the aim of genotyping various GH-/IGF-I-axis-related genes of GH-deficient adult patients to investigate genotype:phenotype relationships and response to GH therapy. Patients and methods: 129 consecutively enrolled GH-deficient adult patients were genotyped for variant 1 (V1) of the alternatively spliced noncoding exons in the 5 0-untranslated region and for the nine coding exons of the GH receptor (GHR) gene, which obviously play a striking role in the function of the GH-IGF-I-axis. After detection of a heterozygous, non-synonymous mutation R179C in exon 6 in one single patient with acquired GH-deficiency (GHD) in late adulthood, analysis of her clinical data followed, leading to the diagnosis of mild short stature (À1.5 SD). For further endocrine evaluation, five pituitary stimulation tests (arginine) of this patient were statistically compared to stimulation tests (arginine) of ten GH-deficient control patients, retrospectively. Results: The formerly in patients with Laron syndrome and idiopathic short stature reported mutation R179C leads to an amino acid change from an arginine residue (codon CGC) to a cysteine residue (codon TGC) in position 179 of the extracellular domain of the GHR. Statistical analysis revealed significant decreased IGF-I/GH 0 ratio (p = 0.004) and IGF-I/GH max ratio (p = 0.

Research paper thumbnail of Endoscopic Ultrasound Imaging of Insulinomas: Limitations and Clinical Relevance

Experimental and Clinical Endocrinology & Diabetes, 2005

Compared to other imaging methods, endoscopic ultrasound is the best procedure to localize insuli... more Compared to other imaging methods, endoscopic ultrasound is the best procedure to localize insulinomas preoperatively. Positive finding furthermore confirms endocrinological diagnosis, especially considering the differential diagnosis of hypoglycaemia factitia by oral antidiabetics. However, it always has to be considered that endoscopic ultrasound imaging may reveal false positive and false negative results, and quality of the findings obtained by endoscopic ultrasound imaging depends to a large extent on the examiner's experience. An important issue of endoscopic ultrasound imaging in insulinomas nowadays is planning surgical strategy. As illustrated by three cases, endoscopic ultrasound imaging enables to identify patients that qualify for laparoscopic, minimal invasive surgery.

Research paper thumbnail of Preoperative diagnosis of insulinoma: low body mass index, young age, and female gender are associated with negative imaging by endoscopic ultrasound

European Journal of Endocrinology, 2007

Objective: Endoscopic ultrasound (EUS) is a highly reliable procedure to localize insulinomas pre... more Objective: Endoscopic ultrasound (EUS) is a highly reliable procedure to localize insulinomas preoperatively. It has been considered to be important in planning surgical strategy, especially considering a minimal invasive approach. However, even under ideal conditions experienced examiners miss about 10–20% of insulinomas by EUS imaging. Design and methods: This retrospective study aimed to identify factors associated with negative EUS imaging. Twenty-nine consecutive patients (24 benign and 5 malignant) with sporadic pancreatic insulinomas confirmed by successful surgery and positive histopathology were included. All EUS examinations were performed by one single experienced examiner over a period of one decade. Results: Three of the tumors were not detected by preoperative EUS as they were isoechoic to the surrounding healthy pancreatic tissue; 25 could be detected as hypoechoic lesions, (including all malignant tumors), and one lesion was hyperechoic. Low body mass index (P=0.053)...

Research paper thumbnail of Pitfalls in endosonographic imaging of suspected insulinomas: pancreatic nodules of unknown dignity

European Journal of Endocrinology, 2003

OBJECTIVE: Endosonography enables localization and characterization of gastroenteropancreatic neu... more OBJECTIVE: Endosonography enables localization and characterization of gastroenteropancreatic neuroendocrine tumors. We have studied the problem of misleading abnormalities of pancreatic morphology as obtained by endosonographic imaging. DESIGN AND METHODS: A total of 438 endosonographies performed for known or suspected diseases of the adrenal glands and/or the pancreas and/or suspected metastases in the neighboring tissues were analyzed. RESULTS: In the pancreas, nine benign insulinomas, four non-metastatic islet cell carcinomas, and multiple benign neuroendocrine tumors in one patient with multiple-endocrine neoplasia-1 (MEN-1) disease were detected and correctly localized as proven by postoperative histology. In three further patients with genetic diagnosis of MEN-1, asymptomatic tumors were detected and are under observation. However, we also found an 8 x 4 mm hypoechoic tumor in the cauda pancreatis of a patient with severe factitial hypoglycemia (glimepiride). In another pati...

Research paper thumbnail of Clinical Predictors and Algorithm for the Genetic Diagnosis of Pheochromocytoma Patients

Clinical Cancer Research, 2009

Purpose: Six pheochromocytoma susceptibility genes causing distinct syndromes have been identifie... more Purpose: Six pheochromocytoma susceptibility genes causing distinct syndromes have been identified; approximately one of three of all pheochromocytoma patients carry a predisposing germline mutation. When four major genes (VHL, RET, SDHB, SDHD) are analyzed in a clinical laboratory, costs are ∼$3,400 per patient. The aim of the study is to systematically obtain a robust algorithm to identify who should be genetically tested, and to determine the order in which genes should be tested. Experimental Design: DNA from 989 apparently nonsyndromic patients were scanned for germline mutations in the genes VHL, RET, SDHB, SDHC, and SDHD. Clinical parameters were analyzed as potential predictors for finding mutations by multiple logistic regression, validated by bootstrapping. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Results: Of 989 apparently nonsyndromic pheochromocytoma cases, 187 (19%) harbored germline mutations. Predictors for pres...

Research paper thumbnail of Growth hormone deficient patients after traumatic brain injury – Baseline characteristics and benefits after growth hormone replacement – An analysis of the German KIMS database

Growth Hormone & IGF Research, 2008

Objective: In recent years, traumatic brain injury (TBI) has been identified as a significant cau... more Objective: In recent years, traumatic brain injury (TBI) has been identified as a significant cause of growth hormone deficiency (GHD). The aim of the present study was to characterize adult TBI patients with GHD to elucidate the effect of human growth hormone (hGH) replacement in TBI patients as documented in the German Pfizer International Metabolic (KIMS) database. Design: As of October 2006, 84 TBI patients had been included in the German KIMS database (n = 28 childhood-onset and 54 adult-onset GHD). All 84 TBI patients were matched with 84 patients with GHD due to non-functioning pituitary adenoma (NFPA) also included in this database. Analysis of clinical and outcome variables was performed, with comparisons of childhood vs. adult TBI, and TBI vs. NFPA patients, at baseline and one-year follow-up. Results: TBI patients with GHD were significantly younger at the onset of pituitary disease and exhibited a significantly longer time span between GHD diagnosis and KIMS entry than NFPA patients. Those KIMS patients who had sustained their TBI in childhood were of significantly shorter stature than adult-onset TBI patients. At 1-year follow-up, insulin-like growth factor I (IGF-I) standard deviation score levels had returned to the normal range and quality of life (QoL), as measured by QoL-Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire, improved significantly in TBI as in NFPA patients. Conclusion: This analysis provides preliminary data that TBI patients with GHD benefit from hGH replacement in terms of improved QoL in a similar fashion as do NFPA patients. Moreover, it suggests that belated diagnosis and treatment in childhood-onset GHD due to TBI might be related to a shorter final height in these children.

Research paper thumbnail of Short stature and decreased insulin-like growth factor I (IGF-I)/growth hormone (GH)-ratio in an adult GH-deficient patient pointing to additional partial GH insensitivity due to a R179C mutation of the growth hormone receptor

Growth Hormone & IGF Research, 2007

Objective: Genetic factors play an expanding role in understanding growth hormone (GH) disorders,... more Objective: Genetic factors play an expanding role in understanding growth hormone (GH) disorders, therefore the German KIMS Pharmacogenetics Study was initiated with the aim of genotyping various GH-/IGF-I-axis-related genes of GH-deficient adult patients to investigate genotype:phenotype relationships and response to GH therapy. Patients and methods: 129 consecutively enrolled GH-deficient adult patients were genotyped for variant 1 (V1) of the alternatively spliced noncoding exons in the 5 0-untranslated region and for the nine coding exons of the GH receptor (GHR) gene, which obviously play a striking role in the function of the GH-IGF-I-axis. After detection of a heterozygous, non-synonymous mutation R179C in exon 6 in one single patient with acquired GH-deficiency (GHD) in late adulthood, analysis of her clinical data followed, leading to the diagnosis of mild short stature (À1.5 SD). For further endocrine evaluation, five pituitary stimulation tests (arginine) of this patient were statistically compared to stimulation tests (arginine) of ten GH-deficient control patients, retrospectively. Results: The formerly in patients with Laron syndrome and idiopathic short stature reported mutation R179C leads to an amino acid change from an arginine residue (codon CGC) to a cysteine residue (codon TGC) in position 179 of the extracellular domain of the GHR. Statistical analysis revealed significant decreased IGF-I/GH 0 ratio (p = 0.004) and IGF-I/GH max ratio (p = 0.

Research paper thumbnail of Endoscopic Ultrasound Imaging of Insulinomas: Limitations and Clinical Relevance

Experimental and Clinical Endocrinology & Diabetes, 2005

Compared to other imaging methods, endoscopic ultrasound is the best procedure to localize insuli... more Compared to other imaging methods, endoscopic ultrasound is the best procedure to localize insulinomas preoperatively. Positive finding furthermore confirms endocrinological diagnosis, especially considering the differential diagnosis of hypoglycaemia factitia by oral antidiabetics. However, it always has to be considered that endoscopic ultrasound imaging may reveal false positive and false negative results, and quality of the findings obtained by endoscopic ultrasound imaging depends to a large extent on the examiner's experience. An important issue of endoscopic ultrasound imaging in insulinomas nowadays is planning surgical strategy. As illustrated by three cases, endoscopic ultrasound imaging enables to identify patients that qualify for laparoscopic, minimal invasive surgery.

Research paper thumbnail of Preoperative diagnosis of insulinoma: low body mass index, young age, and female gender are associated with negative imaging by endoscopic ultrasound

European Journal of Endocrinology, 2007

Objective: Endoscopic ultrasound (EUS) is a highly reliable procedure to localize insulinomas pre... more Objective: Endoscopic ultrasound (EUS) is a highly reliable procedure to localize insulinomas preoperatively. It has been considered to be important in planning surgical strategy, especially considering a minimal invasive approach. However, even under ideal conditions experienced examiners miss about 10–20% of insulinomas by EUS imaging. Design and methods: This retrospective study aimed to identify factors associated with negative EUS imaging. Twenty-nine consecutive patients (24 benign and 5 malignant) with sporadic pancreatic insulinomas confirmed by successful surgery and positive histopathology were included. All EUS examinations were performed by one single experienced examiner over a period of one decade. Results: Three of the tumors were not detected by preoperative EUS as they were isoechoic to the surrounding healthy pancreatic tissue; 25 could be detected as hypoechoic lesions, (including all malignant tumors), and one lesion was hyperechoic. Low body mass index (P=0.053)...

Research paper thumbnail of Pitfalls in endosonographic imaging of suspected insulinomas: pancreatic nodules of unknown dignity

European Journal of Endocrinology, 2003

OBJECTIVE: Endosonography enables localization and characterization of gastroenteropancreatic neu... more OBJECTIVE: Endosonography enables localization and characterization of gastroenteropancreatic neuroendocrine tumors. We have studied the problem of misleading abnormalities of pancreatic morphology as obtained by endosonographic imaging. DESIGN AND METHODS: A total of 438 endosonographies performed for known or suspected diseases of the adrenal glands and/or the pancreas and/or suspected metastases in the neighboring tissues were analyzed. RESULTS: In the pancreas, nine benign insulinomas, four non-metastatic islet cell carcinomas, and multiple benign neuroendocrine tumors in one patient with multiple-endocrine neoplasia-1 (MEN-1) disease were detected and correctly localized as proven by postoperative histology. In three further patients with genetic diagnosis of MEN-1, asymptomatic tumors were detected and are under observation. However, we also found an 8 x 4 mm hypoechoic tumor in the cauda pancreatis of a patient with severe factitial hypoglycemia (glimepiride). In another pati...

Research paper thumbnail of Clinical Predictors and Algorithm for the Genetic Diagnosis of Pheochromocytoma Patients

Clinical Cancer Research, 2009

Purpose: Six pheochromocytoma susceptibility genes causing distinct syndromes have been identifie... more Purpose: Six pheochromocytoma susceptibility genes causing distinct syndromes have been identified; approximately one of three of all pheochromocytoma patients carry a predisposing germline mutation. When four major genes (VHL, RET, SDHB, SDHD) are analyzed in a clinical laboratory, costs are ∼$3,400 per patient. The aim of the study is to systematically obtain a robust algorithm to identify who should be genetically tested, and to determine the order in which genes should be tested. Experimental Design: DNA from 989 apparently nonsyndromic patients were scanned for germline mutations in the genes VHL, RET, SDHB, SDHC, and SDHD. Clinical parameters were analyzed as potential predictors for finding mutations by multiple logistic regression, validated by bootstrapping. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Results: Of 989 apparently nonsyndromic pheochromocytoma cases, 187 (19%) harbored germline mutations. Predictors for pres...