A case of low cortisol-binding globulin: use of plasma free cortisol in interpretation of hypothalamic–pituitary–adrenal axis tests

ContextIt is unknown whether the metabolic effects of the removal of an adrenal incidentaloma (AI) can be predicted by the assessment of cortisol hypersecretion before surgery.ObjectiveTo evaluate the accuracy of several criteria of hypothalamic–pituitary–adrenal axis activity in predicting the metabolic outcome after adrenalectomy.DesignRetrospective longitudinal study.PatientsIn 55 surgically treated AI patients (Group 1) before surgery and in 53 nontreated AI patients (Group 2) at the baseline, urinary free cortisol (UFC), cortisol after 1 mg overnight dexamethasone-suppression test (1 mg-DST), ACTH, and midnight serum cortisol (MSC) were measured. In Groups 1 and 2, metabolic parameters were evaluated before and 29.6±13.8 months after surgery and at the baseline and after 35.2±10.9 months respectively.Main outcome measuresThe improvement/worsening of weight, blood pressure, glucose, and cholesterol levels (endpoints) was defined by the presence of a >5% weight decrease/increase and following the European Society of Cardiology or the ATP III criteria respectively. The accuracy of UFC, 1 mg-DST, ACTH, and MSC, singularly taken or in combination, in predicting the improvement/worsening of ≥2 endpoints was calculated.ResultsThe presence of ≥2 among UFC>70 μg/24 h (193 nmol/l), ACTH<10 pg/ml (2.2 pmol/l), 1 mg-DST>3.0 μg/dl (83 nmol/l) (UFC–ACTH–DST criterion) had the best accuracy in predicting the endpoints' improvement (sensitivity (SN) 65.2%, specificity (SP) 68.8%) after surgery. In the nontreated AI patients, this criterion predicted the worsening of ≥2 endpoints (SN 55.6%, SP 82.9%).ConclusionsThe UFC–ACTH–DST criterion seems to be the best for predicting the metabolic outcome in surgically treated AI patients.

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Effect of Inhaled Beclomethasone Dipropionate on Hypothalamic-Pituitary-Adrenal Axis Function in Children with Asthma

PEDIATRICS ◽

10.1542/peds.72.1.60 ◽

1983 ◽

Vol 72 (1) ◽

pp. 60-64

Author(s):

David E. Goldstein ◽

Peter König

Keyword(s):

Beclomethasone Dipropionate ◽

Serum Cortisol ◽

Urinary Free Cortisol ◽

Hypothalamic Pituitary Adrenal Axis ◽

Hypothalamic Pituitary Adrenal ◽

Adrenal Axis ◽

Normal Limits ◽

Free Cortisol ◽

Significant Difference ◽

Pituitary Adrenal Axis

The hypothalamic-pituitary-adrenal axis was investigated in 15 asthmatic children treated with inhaled beclomethasone dipropionate (mean 490 µg/day) and 11 asthmatic control subjects receiving no corticosteroid therapy. Measurements of 24-h urinary free cortisol and 17 hydroxy corticosteroids, serum cortisol, response to ACTH, and the oral metyrapone test showed no significant difference between the two groups. All the patients' results were within normal limits, and carbohydrate metabolism, as shown by blood glucose and hemoglobin A1c, was not affected by beclomethasone therapy. Thus, in the above dose, inhaled beclomethasone does not cause suppression of the hypothalamic--pituitary-adrenal axis.

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Hypothalamic-Pituitary-Adrenal Axis Function after Inhaled Corticosteroids: Unreliability of Urinary Free Cortisol Estimation

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2002-020287 ◽

2002 ◽

Vol 87 (10) ◽

pp. 4541-4546 ◽

Cited By ~ 36

Author(s):

Richard S. Fink ◽

Lisa N. Pierre ◽

Peter T. Daley-Yates ◽

David H. Richards ◽

Anthony Gibson ◽

...

Keyword(s):

Inhaled Corticosteroids ◽

Urinary Free Cortisol ◽

Hypothalamic Pituitary Adrenal Axis ◽

Hypothalamic Pituitary Adrenal ◽

Adrenal Axis ◽

Free Cortisol ◽

Pituitary Adrenal Axis

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Hypothalamic-Pituitary-Adrenal Axis Activity in Obese Men with and without Sleep Apnea: Effects of Continuous Positive Airway Pressure Therapy

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-0774 ◽

2007 ◽

Vol 92 (11) ◽

pp. 4199-4207 ◽

Cited By ~ 76

Author(s):

A. N. Vgontzas ◽

S. Pejovic ◽

E. Zoumakis ◽

H.-M. Lin ◽

C. M. Bentley ◽

...

Keyword(s):

Sleep Apnea ◽

Airway Pressure ◽

Positive Airway Pressure ◽

Hypothalamic Pituitary Adrenal Axis ◽

Sleep Laboratory ◽

Cortisol Secretion ◽

Hypothalamic Pituitary Adrenal ◽

Adrenal Axis ◽

Low Cortisol ◽

Pituitary Adrenal Axis

Abstract Context: Previous studies on the association between the hypothalamic-pituitary-adrenal axis activity and sleep apnea (SA) and obesity are inconsistent and/or limited. Objective: In this study, we evaluated the activity of the hypothalamic-pituitary-adrenal axis in nonpsychologically distressed obese subjects with and without SA and examined the impact of continuous positive airway pressure (CPAP) in SA patients. Design and Participants: In study I, four-night sleep laboratory recordings and serial 24-h plasma measures of cortisol were obtained in 45 obese men with and without apnea and nonobese controls. Sleep apneic patients were reassessed after 3 months of CPAP use. In study II, 38 obese men with and without sleep apnea and nonobese controls were challenged with ovine CRH administration after four nights in the sleep laboratory. Results: The sleep patterns were similar between obese and nonobese controls. Twenty-four-hour plasma cortisol levels were highest in nonobese controls, intermediate in obese apneic patients, and lowest in obese controls (8.8 ± 0.4 vs. 8.1 ± 0.3 vs. 7.5 ± 0.3 μg/dl, P < 0.05). CPAP tended to reduce cortisol levels in the apneic patients (difference −0.7 ± .4 μg/dl, P = 0.1). CRH administration resulted in a higher ACTH response in both obese groups, compared with nonobese controls; the three groups were not different in cortisol response. Conclusions: Nonpsychologically distressed, normally sleeping, obese men had low cortisol secretion. The cortisol secretion was slightly activated by SA and returned to low by CPAP use. The low cortisol secretion in obesity through its inferred hyposecretion of hypothalamic CRH might predispose the obese to sleep apnea.

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Effects of Suckling on Hypothalamic-Pituitary-Adrenal Axis Responses to Psychosocial Stress in Postpartum Lactating Women

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.10.7919 ◽

2001 ◽

Vol 86 (10) ◽

pp. 4798-4804 ◽

Cited By ~ 176

Author(s):

Markus Heinrichs ◽

Gunther Meinlschmidt ◽

Inga Neumann ◽

Sabine Wagner ◽

Clemens Kirschbaum ◽

...

Keyword(s):

Breast Feeding ◽

Stress Test ◽

Hypothalamic Pituitary Adrenal Axis ◽

Psychosocial Stressor ◽

Short Term ◽

Lactating Women ◽

Hypothalamic Pituitary Adrenal ◽

Adrenal Axis ◽

Free Cortisol ◽

Pituitary Adrenal Axis

In several studies lactation has been shown to be associated with a hypothalamic-pituitary-adrenal axis hyporesponsiveness to physical and psychological stressors. As it is not known whether the marked blunting of endocrine stress reactivity in women can be ascribed to suckling as a short-term effect or to lactation in general, the acute effects of suckling on the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary system responses to mental stress were investigated in lactating women. Forty-three lactating women were randomly assigned either to breast-feed or to hold their infants for a 15-min period with the onset 30 min before they were exposed to a brief psychosocial stressor (Trier Social Stress Test). Both breast-feeding and holding the infant yielded significant decreases in ACTH, total plasma cortisol, and salivary free cortisol (all P < 0.01). There were no significant differences in baseline hormone levels between the groups 1 min before the stress test. In response to stress exposure, ACTH, total plasma cortisol, salivary free cortisol, norepinephrine, and epinephrine were significantly increased in all lactating women (all P < 0.001). However, total cortisol and free cortisol responses to stress were attenuated in breast-feeding women (P = 0.001 and P = 0.067, respectively), who also showed significantly decreasing PRL levels during the stress test (P = 0.005). In addition, there was no change in plasma oxytocin or vasopressin in response to the stressor. Breast-feeding as well as holding led to decreased anxiety (P < 0.05), whereas, in contrast, stress exposure worsened mood, calmness, and anxiety in the total group (all P < 0.001). From these data we conclude that lactation in women, in contrast to that in rats, does not result in a general restraint of the hypothalamic-pituitary-adrenal axis response to a psychosocial stressor. Rather, suckling is suggested to exert a short-term suppression of the cortisol response to mental stress.

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