Although compensated hypothyroidism (CH) is the most common thyroid impairment in Down syndrome (DS), its pathogenesis remains elusive. Because primary gonada l failure is another DS-associated endocrinopathy,we hypot...Although compensated hypothyroidism (CH) is the most common thyroid impairment in Down syndrome (DS), its pathogenesis remains elusive. Because primary gonada l failure is another DS-associated endocrinopathy,we hypothesized that an impai red signal-transduction pathway shared by several organs may provide a unifying explanation for both endocrinopathies. We assessed two possible transduction-p athway components associated with CH in DS: the G-protein adenylate-cyclase (A C) system and β-adrenergic responsiveness, previously reported to be enhanced in DS fibroblasts. Twenty-one DS patients and 14 control subjects were studied. Peripheralmononuclear cells (PMCs)were incubated with G-proteinmodulators [pro stag-landin E1 (PGE1) and cholera toxin (CTx)], an AC stimulator (forskolin), and a β-adrenergic agonist (isoproterenol), and cAMP levels were determined. All pa rticipants had normal plasma thyroid hormone levels, but 11 of the DS patients h ad elevated TSH levels (hTSH), whereas in the 10 others, they were normal (nTSH) . cAMP levels in response to forskolin, PGE1, and CTx were similar in all groups , whereas isoprotereriol-stimulated cAMP levels were significantly higher in th e hTSH group than in the nTSH group and control subjects (45 ±30 versus 22 ±9 and 21 ±9 pmol ·106 cells-1 ·10 min-1, respectively; p = 0.02). Four patien ts in the DS hTSH subgroup had impaired sexual development. We found hyperrespon siveness of PMCs to a β-adrenergic agonist in a subgroup of DS patients with C H. If this observation is applicable to the thyroid gland, then it may reflect a mechanismin which negative effects on cell growth or responsiveness to TSH lead to CH.展开更多
Background: Crohn’ s disease (CD) is characterized, among other features, by intestinal malabsorption of miner als, vitamins,and various food ingredients. This may cause a suboptimal peak bone mass and thereby suscep...Background: Crohn’ s disease (CD) is characterized, among other features, by intestinal malabsorption of miner als, vitamins,and various food ingredients. This may cause a suboptimal peak bone mass and thereby susceptibility to osteoporosis at an early age. Objective: Longitudinal measurement of bone in CD during active disease and during remissi on. Design: We evaluated 24 patients with CD (16 males) 14 to 16 years of age lo ngitudinally, every 3 months over 12 months, for disease activity. Longitudinal follow- up by quantitative ultrasound measurement using a bone sonometer (Sunli ght Omnisense, Tel Aviv, Israel) that obtains axial speed of sound (SOS) was als o performed. Eight of the CD patients were in remission (R- CD), characterized by accelerated weight and height gain and near- normal erythrocyte sedimentatio n rate and serum iron. Eight patients had active CD(A- CD), and 8 patients were under treatment with oxandrolone. Results: By two- way repeated- measures ana lysis of variance, the change in SOS Z- score of tibia at 0, 6, and 12 months w as as follows: - 0.5 ± 0.2 to - 0.3 ± 0.2, - 0.6 ± 0.2 to - 1.0 ± 0. 5 and - 0.6 ± 0.2 to - 0.4 ± 0.2 in the remission, active disease, and oxa ndrolone- treated groups, respectively (P < 0.001). Similarly, the change in SO S Z- score of radius during the study was as follows: - 0.5 ± 0.3 to - 0.6 ± 0.3, - 0.6 ± 0.3 to - 1.0 ± 0.3 and - 0.6 ± 0.2 to - 0.4 ± 0.2 i n the remission, active disease, and oxandrolone- treated groups, respectively (P < 0.001). While a small change over time in patients in remission was noted, SOS decreased in patients with active disease and increased in oxandrolone- tre ated patients. Despite the fact that SOS remained in the normative range in all patients, a clear deterioration was demonstrated for patients with active diseas e. Conclusions: We conclude that longitudinal follow- up of patients with activ e disease may detect an early pattern of deterioration in quality of bone.展开更多
文摘Although compensated hypothyroidism (CH) is the most common thyroid impairment in Down syndrome (DS), its pathogenesis remains elusive. Because primary gonada l failure is another DS-associated endocrinopathy,we hypothesized that an impai red signal-transduction pathway shared by several organs may provide a unifying explanation for both endocrinopathies. We assessed two possible transduction-p athway components associated with CH in DS: the G-protein adenylate-cyclase (A C) system and β-adrenergic responsiveness, previously reported to be enhanced in DS fibroblasts. Twenty-one DS patients and 14 control subjects were studied. Peripheralmononuclear cells (PMCs)were incubated with G-proteinmodulators [pro stag-landin E1 (PGE1) and cholera toxin (CTx)], an AC stimulator (forskolin), and a β-adrenergic agonist (isoproterenol), and cAMP levels were determined. All pa rticipants had normal plasma thyroid hormone levels, but 11 of the DS patients h ad elevated TSH levels (hTSH), whereas in the 10 others, they were normal (nTSH) . cAMP levels in response to forskolin, PGE1, and CTx were similar in all groups , whereas isoprotereriol-stimulated cAMP levels were significantly higher in th e hTSH group than in the nTSH group and control subjects (45 ±30 versus 22 ±9 and 21 ±9 pmol ·106 cells-1 ·10 min-1, respectively; p = 0.02). Four patien ts in the DS hTSH subgroup had impaired sexual development. We found hyperrespon siveness of PMCs to a β-adrenergic agonist in a subgroup of DS patients with C H. If this observation is applicable to the thyroid gland, then it may reflect a mechanismin which negative effects on cell growth or responsiveness to TSH lead to CH.
文摘Background: Crohn’ s disease (CD) is characterized, among other features, by intestinal malabsorption of miner als, vitamins,and various food ingredients. This may cause a suboptimal peak bone mass and thereby susceptibility to osteoporosis at an early age. Objective: Longitudinal measurement of bone in CD during active disease and during remissi on. Design: We evaluated 24 patients with CD (16 males) 14 to 16 years of age lo ngitudinally, every 3 months over 12 months, for disease activity. Longitudinal follow- up by quantitative ultrasound measurement using a bone sonometer (Sunli ght Omnisense, Tel Aviv, Israel) that obtains axial speed of sound (SOS) was als o performed. Eight of the CD patients were in remission (R- CD), characterized by accelerated weight and height gain and near- normal erythrocyte sedimentatio n rate and serum iron. Eight patients had active CD(A- CD), and 8 patients were under treatment with oxandrolone. Results: By two- way repeated- measures ana lysis of variance, the change in SOS Z- score of tibia at 0, 6, and 12 months w as as follows: - 0.5 ± 0.2 to - 0.3 ± 0.2, - 0.6 ± 0.2 to - 1.0 ± 0. 5 and - 0.6 ± 0.2 to - 0.4 ± 0.2 in the remission, active disease, and oxa ndrolone- treated groups, respectively (P < 0.001). Similarly, the change in SO S Z- score of radius during the study was as follows: - 0.5 ± 0.3 to - 0.6 ± 0.3, - 0.6 ± 0.3 to - 1.0 ± 0.3 and - 0.6 ± 0.2 to - 0.4 ± 0.2 i n the remission, active disease, and oxandrolone- treated groups, respectively (P < 0.001). While a small change over time in patients in remission was noted, SOS decreased in patients with active disease and increased in oxandrolone- tre ated patients. Despite the fact that SOS remained in the normative range in all patients, a clear deterioration was demonstrated for patients with active diseas e. Conclusions: We conclude that longitudinal follow- up of patients with activ e disease may detect an early pattern of deterioration in quality of bone.
