New insights into corticosteroid-binding globulin and glucocorticoid delivery.

Corticosteroid-binding globulin (CBG) binds cortisol with high affinity and facilitates its transport in the blood. A recent discovery suggests that CBG may have a role beyond that of a simple transport carrier protein. CBG functions as a protein thermocouple that is exquisitely sensitive to temperature change, releasing cortisol in response to increasing temperatures within the human physiological range. It is also expressed in the human hypothalamus and cerebrospinal fluid, while in the rodent it is also found in other intracellular neuronal locations, suggesting a role in regulating access of glucocorticoids to their receptors in the CNS. Genetic variants of CBG have been detected in man and have been associated with fatigue-pain syndromes and hypotension, again suggesting a potential effect of CBG on the access of cortisol to brain glucocorticoid receptors. These new findings provide the basis for a novel concept of the mechanisms through which the body regulates access of glucocorticoids to the brain and other tissues of the body.

Novel corticosteroid-binding globulin variant that lacks steroid binding activity.

BACKGROUND: Corticosteroid-binding globulin (CBG) is the principal carrier for glucocorticoids in the circulation and a regulator of their bioavailability. Inherited CBG deficiencies are rarely reported, and only three causative mutations in four families have been described. PATIENTS, METHODS, AND RESULTS: In a 26-yr-old female with hypotension, fatigue, and undetectable total serum cortisol at presentation, we have identified a novel homozygous c.776g>t transversion in exon 3 of the CBG (SERPINA6) gene. This results in a p.Gly237Val substitution that is predicted to influence the positioning of two ß-sheets that constitute part of the CBG steroid-binding site. Two siblings were also homozygous for the variant, whereas her mother and an unaffected sibling were heterozygous. No other symptomatic family members were identified apart from the proband. Individuals homozygous for the variant had serum CBG levels below the reference range when measured by RIA, but CBG was unmeasurable in cortisol-binding capacity assays. In the same individuals, we observed very low baseline and stimulated total serum cortisol levels but normal free serum and salivary cortisol and plasma ACTH. In a study of ultradian cortisol pulsatility, increased pulse frequency was only observed in the proband. CONCLUSION: We describe a novel CBG variant that lacks steroid binding activity. All mutant homozygotes have very low total serum cortisol, but normal free serum cortisol levels. The only biochemical feature to distinguish the symptomatic subject was increased cortisol pulsatility, and we suggest that this may influence glucocorticoid signaling and contribute to symptoms previously associated with CBG deficiency.

Development of an automated blood sampling system for use in humans.

Many hormones are released in a pulsatile or burst-like pattern resulting in fluctuating blood levels that can undergo rapid modulation by physiological and pathological signals. To accurately measure these changes in hormone concentration requires frequent blood sampling, often over extended periods as the overall rhythmicity may vary over 24 hours. The aim of this study was to develop a computerized, automated blood sampling system which allows repeated stress-free blood sample collection from humans over an extended period under basal or test conditions. The system incorporates a peristaltic pump, fraction collector and standard infusion pump together with a custom built electronic control unit linked to a personal computer. Disposable tubing prevents cross-contamination between study participants. The computer programme is modifiable to adjust for the number of specimen tubes and volume of blood collected per sampling cycle. Patency of the collecting line is maintained with 0.9% saline, without the need for heparinization. To validate the system, 10-minute samples for cortisol were collected over 24 hours from five healthy volunteers, of whom two had additional concomitant ACTH sampling. Deconvolution analysis revealed an expected number of hormone secretory episodes and a non-pathological degree of orderliness within the data. There was high concordance between ACTH and cortisol secretory events. The ability of the system to allow multiple measurements and of the software program to link with other physiological monitoring equipment provides a powerful tool to study physiologic/pathophysiologic change in relation to blood hormone and other biomarker levels.

New CPT codes: hospital, consultation, emergency and nursing facility services.

New evaluation and management codes were created by the Current Procedural Terminology (CPT) Editorial Panel to ensure more accurate and consistent reporting of physician services. The new hospital inpatient codes describe three levels of service for both initial and subsequent care. Critical care services are reported according to the total time spent by a physician providing constant attention to a critically ill patient. Consultation codes are divided into four categories: office/outpatient, initial inpatient, follow-up inpatient and confirmatory. Emergency department services for both new and established patients are limited to five codes. In 1992, nursing facility services are described with either comprehensive-assessment codes or subsequent-care codes. Hospital discharge services may be reported in addition to the comprehensive nursing facility assessment. Since the 1992 CPT book will list only the new codes, and since all insurance carriers will not be using these codes in 1992, physicians are encouraged to keep their 1991 code books and contact their local insurance carriers to determine which codes will be used.

A guide to the new office evaluation and management codes for 1992.

The new office evaluation and management codes require an understanding of definitions that have been recently created by the Current Procedural Terminology (CPT) Editorial Panel. Code selection is based on seven components; the three key components are the history, the physical examination and medical decision making. Office visit codes are divided into five levels of visits, based on service. New-patient office visits require all three key components for any level visit; established-patient office visits require only two of the three components. The new office code descriptions were created to assist physicians in code selections. Only when counseling or coordination of care dominates the visit (e.g., more than 50 percent) is time to be considered a controlling factor. Physicians are urged not to code only from time descriptors. The 1992 CPT book will list only the new evaluation and management codes, deleting the old level-of-service codes. Physicians are encouraged to contact local insurance carriers to ensure that they will also be using the new codes in 1992.