A widely used assay technique for plasma tyrosine determination has been found to give rise to la... more A widely used assay technique for plasma tyrosine determination has been found to give rise to large errors. It was modified to improve accuracy, and the relationship between the values derived by the modified and unmodified procedures was studied. The plasma tyrosine concentrations in thyro toxic and hypothyroid patients during oral tyrosine loading are reported. Tyrosine tolerance in thyrotoxicosis reverts to normal after successful treatment. In hypothyroidism, most patients had normal tyrosine tolerance before and after treatment.
A widely used assay technique for plasma tyrosine determination has been found to give rise to la... more A widely used assay technique for plasma tyrosine determination has been found to give rise to large errors. It was modified to improve accuracy, and the relationship between the values derived by the modified and unmodified procedures was studied. The plasma tyrosine concentrations in thyrotoxic and hypothyroid patients during oral tyrosine loading are reported. Tyrosine tolerance in thyrotoxicosis reverts to normal after successful treatment. In hypothyroidism, most patients had normal tyrosine tolerance before and after treatment.
Hyperandrogenism and chronic anovulation are the most common endocrine disorders of premenopausal... more Hyperandrogenism and chronic anovulation are the most common endocrine disorders of premenopausal women. Most patients have polycystic ovary syndrome (PCOS), which is essentially benign, but might be associated with increased cardiovascular morbidity; PCOS is associated with specific endocrine and ultrasonographic features. Some patients exhibiting similar features to PCOS might have other underlying diagnoses, such as adrenal and ovarian steroidogenic deficiencies, adrenal and ovarian androgen-secreting tumours, other medical or endocrine disorders, and/or be on medications thought to cause PCOS, such as anti-epileptics. Unlike PCOS, some of these conditions can occasionally be life threatening and require prompt diagnosis and treatment. Here, we focus on these disorders, including their pathogenesis, and attempt to define the clinical and biochemical features that distinguish them from PCOS.
To describe the magnetic resonance (MR) imaging features of the adrenal glands in primary hyperal... more To describe the magnetic resonance (MR) imaging features of the adrenal glands in primary hyperaldosteronism and assess MR imaging in the detection and characterization of aldosterone-producing adenoma (APA). The authors retrospectively reviewed the cases of 20 patients (13 female and seven male patients; age range, 14-67 years; median age, 46 years) with primary hyperaldosteronism who underwent 1.5-T MR imaging between 1995 and 1998. All patients underwent transverse T1- and T2-weighted imaging, and chemical shift imaging was performed in 17 patients. Imaging results were correlated with findings at biochemical testing, venous sampling, or surgery. Among the 20 patients, 10 (50%) had APA and 10 (50%) bilateral adrenal hyperplasia (BAH). In the detection of APA, MR imaging had a sensitivity of 70%, specificity of 100%, and accuracy of 85%. APAs (mean size, 20 x 16 mm) were iso- or hypointense relative to the liver on T1-weighted images and slightly hyperintense on T2-weighted images. With chemical shift imaging, the signal intensity decreased on the out-of-phase images in six of seven (86%) patients with APA and in eight of nine (89%) patients with BAH. MR imaging has a high specificity in the detection of APA. As with nonhyperfunctioning adenoma, APA and BAH show evidence of intracellular lipid at chemical shift imaging.
Familial multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant disorder characteri... more Familial multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant disorder characterized by the combined occurrence of tumors of the parathyroid glands, the pancreas, and the pituitary gland. Pancreatic tumors have previously been shown to be associated with the loss of alleles on chromosome 11; we therefore looked for similar genetic alterations in specimens of parathyroid tumors, which are the most common feature of MEN-1. We obtained parathyroid tumors and peripheral-blood leukocytes from six patients with MEN-1; 18 cloned human DNA sequences from chromosome 11 were then used to identify restriction-fragment-length polymorphisms. A loss of heterozygosity was detected in parathyroid tumors from three of the six patients with MEN-1; this finding demonstrated that allelic deletions on chromosome 11 are involved in the monoclonal development of parathyroid tumors in patients with MEN-1. In addition, studies of three affected families (with 17 affected members and 51 unaffected members) established linkage with the oncogene INT2 (peak lod score, 3.30, at 0 percent recombination); the MEN-1 gene was thus mapped to the pericentromeric region of the long arm of chromosome 11 (11q13). Our location of the MEN-1 gene at 11q13 is close to the location previously reported. We conclude that a single inherited locus on chromosome 11, band q13, causes MEN-1 and that the monoclonal development of parathyroid and pancreatic tumors in patients with MEN-1 involves similar allelic deletions on chromosome 11.
Tissue specimens of human hypothalami, pituitaries and gastrointestinal tract were studied with a... more Tissue specimens of human hypothalami, pituitaries and gastrointestinal tract were studied with an indirect immunoperoxidase technique using 6 different rabbit ovine corticotrophin-releasing factor (oCRF-41) antisera. All these antisera detected oCRF-41-like immunoreactivity in parvocellular neurones of the paraventricular nucleus of the hypothalamus and their nerve terminals adjacent to portal capillaries in the infundibular stem and posterior pituitary. 1 antiserum recognised oCRF-41-like immunoreactivity in the growth hormone cells of the anterior pituitary. 3 other antisera recognised oCRF-41-like immunoreactivity in mucosal cells of the gastric antrum. Pre-treatment of the antisera with sauvagine did not affect the immunostaining of the hypothalamic and gastric cells, but quenched the immunostaining of growth hormone cells in the anterior pituitary. It is concluded that (1) in human hypothalami a CRF is synthesized that is structurally very similar to oCRF-41; (2) in growth hormone cells of the anterior pituitary oCRF-41-like immunoreactive material can be detected which shares antigenic determinants with sauvagine; (3) in mucosal cells of the gastric antrum oCRF-41-like immunoreactivity is present that is comparable but probably not identical to hypothalamic CRF and is not sauvagine-like.
Background: Low- and high-dose dexamethasone suppression tests (LDDST, HDDST) are used in the inv... more Background: Low- and high-dose dexamethasone suppression tests (LDDST, HDDST) are used in the investigation of Cushing’s syndrome (CS). In adults with Cushing’s disease (CD), cortisol suppression during LDDST predicts suppression during the HDDST. Methods: We reviewed the results of the LDDST (0.5 mg 6 hourly × 48 h), HDDST (2.0 mg 6 hourly × 48 h) and corticotrophin-releasing hormone (CRH) test in 32 paediatric patients with CS: 24 had CD, 1 ectopic ACTH syndrome, 5 nodular adrenal hyperplasia and 2 adrenocortical tumours. Results: In CD, LDDST suppressed cortisol from 590.7 ± 168.8 (mean ± SD) to 333.7 ± 104.0 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 45.1%; CI (30.8, 59.4%); 16/24 (66%) suppressed >30%; mean suppression 68.1%, CI (58.1, 77.9%)). The HDDST suppressed cortisol from 596.3 ± 174.5 to 47.1 ± 94.8 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 93.5%; CI (88.2, 98.8%) with 17/24 (71%) suppressing to <50 nmol/l and 100% to <50%...
A widely used assay technique for plasma tyrosine determination has been found to give rise to la... more A widely used assay technique for plasma tyrosine determination has been found to give rise to large errors. It was modified to improve accuracy, and the relationship between the values derived by the modified and unmodified procedures was studied. The plasma tyrosine concentrations in thyro toxic and hypothyroid patients during oral tyrosine loading are reported. Tyrosine tolerance in thyrotoxicosis reverts to normal after successful treatment. In hypothyroidism, most patients had normal tyrosine tolerance before and after treatment.
A widely used assay technique for plasma tyrosine determination has been found to give rise to la... more A widely used assay technique for plasma tyrosine determination has been found to give rise to large errors. It was modified to improve accuracy, and the relationship between the values derived by the modified and unmodified procedures was studied. The plasma tyrosine concentrations in thyrotoxic and hypothyroid patients during oral tyrosine loading are reported. Tyrosine tolerance in thyrotoxicosis reverts to normal after successful treatment. In hypothyroidism, most patients had normal tyrosine tolerance before and after treatment.
Hyperandrogenism and chronic anovulation are the most common endocrine disorders of premenopausal... more Hyperandrogenism and chronic anovulation are the most common endocrine disorders of premenopausal women. Most patients have polycystic ovary syndrome (PCOS), which is essentially benign, but might be associated with increased cardiovascular morbidity; PCOS is associated with specific endocrine and ultrasonographic features. Some patients exhibiting similar features to PCOS might have other underlying diagnoses, such as adrenal and ovarian steroidogenic deficiencies, adrenal and ovarian androgen-secreting tumours, other medical or endocrine disorders, and/or be on medications thought to cause PCOS, such as anti-epileptics. Unlike PCOS, some of these conditions can occasionally be life threatening and require prompt diagnosis and treatment. Here, we focus on these disorders, including their pathogenesis, and attempt to define the clinical and biochemical features that distinguish them from PCOS.
To describe the magnetic resonance (MR) imaging features of the adrenal glands in primary hyperal... more To describe the magnetic resonance (MR) imaging features of the adrenal glands in primary hyperaldosteronism and assess MR imaging in the detection and characterization of aldosterone-producing adenoma (APA). The authors retrospectively reviewed the cases of 20 patients (13 female and seven male patients; age range, 14-67 years; median age, 46 years) with primary hyperaldosteronism who underwent 1.5-T MR imaging between 1995 and 1998. All patients underwent transverse T1- and T2-weighted imaging, and chemical shift imaging was performed in 17 patients. Imaging results were correlated with findings at biochemical testing, venous sampling, or surgery. Among the 20 patients, 10 (50%) had APA and 10 (50%) bilateral adrenal hyperplasia (BAH). In the detection of APA, MR imaging had a sensitivity of 70%, specificity of 100%, and accuracy of 85%. APAs (mean size, 20 x 16 mm) were iso- or hypointense relative to the liver on T1-weighted images and slightly hyperintense on T2-weighted images. With chemical shift imaging, the signal intensity decreased on the out-of-phase images in six of seven (86%) patients with APA and in eight of nine (89%) patients with BAH. MR imaging has a high specificity in the detection of APA. As with nonhyperfunctioning adenoma, APA and BAH show evidence of intracellular lipid at chemical shift imaging.
Familial multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant disorder characteri... more Familial multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant disorder characterized by the combined occurrence of tumors of the parathyroid glands, the pancreas, and the pituitary gland. Pancreatic tumors have previously been shown to be associated with the loss of alleles on chromosome 11; we therefore looked for similar genetic alterations in specimens of parathyroid tumors, which are the most common feature of MEN-1. We obtained parathyroid tumors and peripheral-blood leukocytes from six patients with MEN-1; 18 cloned human DNA sequences from chromosome 11 were then used to identify restriction-fragment-length polymorphisms. A loss of heterozygosity was detected in parathyroid tumors from three of the six patients with MEN-1; this finding demonstrated that allelic deletions on chromosome 11 are involved in the monoclonal development of parathyroid tumors in patients with MEN-1. In addition, studies of three affected families (with 17 affected members and 51 unaffected members) established linkage with the oncogene INT2 (peak lod score, 3.30, at 0 percent recombination); the MEN-1 gene was thus mapped to the pericentromeric region of the long arm of chromosome 11 (11q13). Our location of the MEN-1 gene at 11q13 is close to the location previously reported. We conclude that a single inherited locus on chromosome 11, band q13, causes MEN-1 and that the monoclonal development of parathyroid and pancreatic tumors in patients with MEN-1 involves similar allelic deletions on chromosome 11.
Tissue specimens of human hypothalami, pituitaries and gastrointestinal tract were studied with a... more Tissue specimens of human hypothalami, pituitaries and gastrointestinal tract were studied with an indirect immunoperoxidase technique using 6 different rabbit ovine corticotrophin-releasing factor (oCRF-41) antisera. All these antisera detected oCRF-41-like immunoreactivity in parvocellular neurones of the paraventricular nucleus of the hypothalamus and their nerve terminals adjacent to portal capillaries in the infundibular stem and posterior pituitary. 1 antiserum recognised oCRF-41-like immunoreactivity in the growth hormone cells of the anterior pituitary. 3 other antisera recognised oCRF-41-like immunoreactivity in mucosal cells of the gastric antrum. Pre-treatment of the antisera with sauvagine did not affect the immunostaining of the hypothalamic and gastric cells, but quenched the immunostaining of growth hormone cells in the anterior pituitary. It is concluded that (1) in human hypothalami a CRF is synthesized that is structurally very similar to oCRF-41; (2) in growth hormone cells of the anterior pituitary oCRF-41-like immunoreactive material can be detected which shares antigenic determinants with sauvagine; (3) in mucosal cells of the gastric antrum oCRF-41-like immunoreactivity is present that is comparable but probably not identical to hypothalamic CRF and is not sauvagine-like.
Background: Low- and high-dose dexamethasone suppression tests (LDDST, HDDST) are used in the inv... more Background: Low- and high-dose dexamethasone suppression tests (LDDST, HDDST) are used in the investigation of Cushing’s syndrome (CS). In adults with Cushing’s disease (CD), cortisol suppression during LDDST predicts suppression during the HDDST. Methods: We reviewed the results of the LDDST (0.5 mg 6 hourly × 48 h), HDDST (2.0 mg 6 hourly × 48 h) and corticotrophin-releasing hormone (CRH) test in 32 paediatric patients with CS: 24 had CD, 1 ectopic ACTH syndrome, 5 nodular adrenal hyperplasia and 2 adrenocortical tumours. Results: In CD, LDDST suppressed cortisol from 590.7 ± 168.8 (mean ± SD) to 333.7 ± 104.0 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 45.1%; CI (30.8, 59.4%); 16/24 (66%) suppressed >30%; mean suppression 68.1%, CI (58.1, 77.9%)). The HDDST suppressed cortisol from 596.3 ± 174.5 to 47.1 ± 94.8 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 93.5%; CI (88.2, 98.8%) with 17/24 (71%) suppressing to <50 nmol/l and 100% to <50%...
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Papers by Michael Besser