The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Sep 1998
Randomized Controlled Trial Clinical TrialOctreotide as primary therapy for acromegaly.
The effects of octreotide (up to 5 yr) as primary treatment in 26 patients with acromegaly were compared with those in 81 patients with acromegaly who received octreotide as secondary or adjunctive therapy after previous surgery and/or pituitary radiation. These patients were part of a multicenter study that took place between 1989-1995. The study was divided into 3 phases beginning with a 1-month placebo-controlled treatment period followed by a 1-month washout period. ⋯ The degree of tumor shrinkage did not correlate with the percent reduction in IGF-I or GH. In summary, octreotide was equally effective in 26 previously untreated acromegalic patients (primary treatment group) and 81 patients previously treated with either surgery or pituitary radiation (secondary treatment group). These observations call into question the current practice of surgical resection of all newly diagnosed GH-secreting pituitary adenomas regardless of the likelihood of cure. (AB
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J. Clin. Endocrinol. Metab. · Sep 1998
Serum calcitonin precursors in sepsis and systemic inflammation.
High serum levels of the calcitonin (CT) prohormone, procalcitonin (pro-CT), and its component peptides occur in systemic inflammation and sepsis. Using two different assays, we undertook a prospective study to determine the utility of serum precalcitonin peptides (pre-CT) as markers in this condition. Twenty-nine patients meeting criteria for the systemic inflammatory response syndrome were studied daily in two intensive care units. ⋯ Compared with the serum pre-CT levels, receiver operating characteristic curve analysis revealed that the APACHE II scores, although more cumbersome, were better overall predictors of mortality. Thus, pre-CT is an important serum marker for systemic inflammatory response syndrome and is predictive of outcome. It also provides data concerning the presence of severe infection and may prove to be clinically useful for proactive patient care.
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J. Clin. Endocrinol. Metab. · Jul 1998
Case ReportsFamilial hypoparathyroidism: identification of a novel gain of function mutation in transmembrane domain 5 of the calcium-sensing receptor.
Activating mutations of the extracellular calcium (Ca2+e)-sensing receptor (CaR) gene, mostly in its extracellular domain, can cause both familial and sporadic hypoparathyroidism. We report a Japanese family with severe hypoparathyroidism with pretreatment serum calcium (Ca) levels of 4.9-5.9 mg/dL. The proband presented with a seizure at 6 days of age. ⋯ There was a leftward shift in the concentration-response curve for the mutant receptor [EC50 (effective concentration of Ca2+e producing half of the maximal Ca2+i response, 2.7 +/- 0.1 vs. 4.1 +/- 0.1 mmol/L for the wild-type receptor]. HEK293 cells cotransfected with both the wild-type and mutant CaRs (to mimic the heterozygous state in affected family members) showed an EC50 (3.0 +/- 0.1 mmol/L) similar to that of the mutant CaR alone. Thus, we confirm that 1) a gain of function mutation in the fifth transmembrane domain of the CaR causes severe familial hypoparathyroidism by rendering the receptor more sensitive than normal to activation by Ca2+e; 2) some patients in the family do not experience seizures despite their severe hypocalcemia; and 3) this condition needs to be differentiated from other causes of hypoparathyroidism.
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J. Clin. Endocrinol. Metab. · Jun 1998
Glucocorticoid receptor polymorphism, skin vasoconstriction, and other metabolic intermediate phenotypes in normal human subjects.
Genetic variation of the glucocorticoid receptor (GR) locus is associated with differences in blood pressure. To define the intermediate phenotypes associated with this variation, we investigated the biochemical and clinical significance of a BclI restriction fragment length polymorphism of the GR locus in 64 normal male volunteers. Blood samples were genotyped as either AA (homozygous large allele; n = 6), Aa (heterozygous; n = 51), or aa (homozygous small allele, n = 7). ⋯ Multivariate analysis showed that several factors including GR genotype and urinary cortisol account for 10% of the variation of in vivo responses to glucocorticoid hormones; plasma calcium concentration was the only variable that contributed to in vitro sensitivity of leukocytes to dexamethasone. Glucocorticoid-dependent responses were of negligible importance in determining blood pressure or percentage body fat within the narrow physiological ranges of the present study. We conclude that GR genotype affects steroid sensitivity in a tissue-specific manner because of altered GR function or possibly because of linkage to a locus that controls hormone access to the receptor by influencing steroid metabolism.
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J. Clin. Endocrinol. Metab. · Jun 1998
Reversibility of joint thickening in acromegalic patients: an ultrasonography study.
Axial and peripheral arthropathy affects the majority of patients with acromegaly, being a leading cause of morbidity and functional disability. Treatment with octreotide (OCT) improves symptoms and signs of acromegalic arthropathy, but objective detection of structural changes in bone and cartilage has not been reported to date. This open prospective study was designed to evaluate the effect of a long term treatment with OCT on acromegalic arthropathy assessed by ultrasonography examination. ⋯ No significant change was recorded in right knee cartilage or heel tendon size. The decrease in thickness of shoulder and wrist cartilages was more pronounced than that measured at the level of left knee (26.3 +/- 3.3% and 27.2 +/- 4.2% vs. 14.2 +/- 4.2%, respectively; P < 0.05). Ultrasonography is able to reveal articular involvement in acromegalic patients and may be useful to monitor the effect of treatment.