Cushing's syndrome in children and adolescents: current diagnostic and therapeutic strategies.
Explore the source record for details and available documents.
Adenoma↗
Biomedical subjects
M A Magiakou
Publications and source records attributed to M A Magiakou.
The hypothalamic-pituitary-adrenal axis and the female reproductive system.
The hypothalamic-pituitary-adrenal (HPA) axis and the female reproductive system are intertwined and exhibit a complex relationship. Thus, the HPA axis exerts profound, mostly inhibitory effects, on the reproductive axis, with corticotropin-releasing hormone (CRH) and CRH-induced propiomelanocortin peptides inhibiting hypothalamic GnRH secretion, and with glucocorticoids inhibiting pituitary LH and ovarian estrogen and progesterone secretion and rendering estrogen-target tissues, such as the endometrium, resistant to the gonadal steroid. These effects of the HPA axis are responsible for the "hypothalamic" amenorrhea of stress, depression and eating disorders, and the hypogonadism of Cushing's syndrome. Conversely, estrogen directly stimulates the CRH gene, which may explain the slight hypercortisolism of females and the preponderance of depressive, anxiety, and eating disorders, as well as Cushing's disease in women. Interestingly, several components of the HPA axis and their receptors are present in reproductive tissues, as autocoid regulators of their various functions. These include ovarian and endometrial CRH, which may participate in the inflammatory processes of the ovary, that is, ovulation and luteolysis, and of the endometrium, that is, implantation and menstruation. Finally, the hypercortisolism of the latter half of pregnancy can be explained by high levels of placenta CRH in plasma. This hypercortisolism causes a transient adrenal suppression in the postpartum period, which may explain the postpartum blues/depression and autoimmune phenomena of this period.
Corticotropin-Releasing Hormone↗
Thyroid function in children with Cushing's disease before and after transsphenoidal surgery.
The degree of thyroid impairment and the effects on growth have not been investigated in children with Cushing's disease. We followed the thyroid function of 24 children and adolescents (12 males and 12 females) with CD (age, 12.9 +/- 3.2 years; mean +/- SD), who were successfully treated by transsphenoidal surgery. Patients were evaluated before, and 3, 6, and 12 months after TSS. Analysis of variance and linear correlation were performed between thyroid function tests and body weight and mass index and bone age. Preoperative free thyroxine levels (1.37 +/- 0.03 ng/dl) were significantly higher than those at 3 months (1.17 +/- 0.05 ng/dl, p < 0.05), but similar to those at 6 and 12 months postoperatively. Preoperative T3 (114.2 +/- 7.7 ng/dl) and TSH (1.36 +/- 0.2 IU/ml) were significantly lower than the postoperative values at 3 (158.9 +/- 6.8 and 2.3 +/- 0.3, respectively), 6 (159.1 +/- 10.8 and 2.5 +/- 0.3, respectively), and 12 months (136 +/- 6.5 and 2.2 +/- 0.3, respectively) (all p < 0.05). One patient had frank hypothyroidism (fT4 < 1 ng/dl) before surgery. Five additional patients had secondary hypothyroidism in the immediate postsurgical period; two of them had normal thyroid function 2 and 3 years postoperatively. One patient has remained hypothyroid for more than 5 years since surgery. No significant correlation was found between thyroid function and body weight, BMI, or BA. We conclude that hypothyroidism was an infrequent complication of CD and TSS. Mild suppression of thyroid function occurs in most children and adolescents with CD before and in the first few months after TSS, but it fully resolves after 6 months and does not correlate with the growth delay and obesity of these patients.
Adolescent↗
Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis.
Systemic symptoms in rheumatoid arthritis (RA) are mediated, at least in part, by elevated levels of circulating interleukin (IL)-6, and this cytokine is also a potent stimulus of the hypothalamic-pituitary-adrenal axis. To evaluate the 24-h circadian secretory dynamics of ACTH, cortisol, and IL-6 and their interactions in patients with early untreated RA, we recruited and studied five newly diagnosed, untreated RA patients early in the course of their disease and five age-, gender-, and race-matched control subjects. We collected serial blood samples over 24 h and measured plasma ACTH and cortisol every 30 min and IL-6 every hour. The 24-h collection was followed by administration of ovine CRH (oCRH) and post-oCRH serial blood samples over 2 h. We analyzed the 24-h overall levels of these hormones and their circadian variations and performed time-lagged cross-correlation analyses among them. The untreated RA patients had 24 h time-integrated plasma ACTH, plasma cortisol levels, and urinary free cortisol excretion that were not significantly different from control subjects, in spite of their disease activity. However, an earlier morning surge of plasma ACTH and cortisol in the patients was suggested. Plasma ACTH and cortisol responses to oCRH were similar in RA patients and controls. IL-6 levels were significantly increased in the RA patients compared with control subjects during the early morning hours (P < 0.05). There was pronounced circadian variation of plasma Il-6 levels. In the RA patients, we detected a positive temporal correlation between plasma levels of IL-6 and ACTH/cortisol, with elevated levels of IL-6 before the elevations of ACTH and cortisol by 1 and 2 h, respectively. In the same patients, we detected a negative effect of cortisol upon IL-6 exerted with a delay of 5 h. The data presented here suggest that although endogenous IL-6 may stimulate secretion of ACTH and cortisol, overall activity of the hypothalamic-pituitary-adrenal axis remains normal and apparently is insufficient to inhibit ongoing inflammation in early untreated RA patients.
Adrenocorticotropic Hormone↗
Blood pressure in children and adolescents with Cushing's syndrome before and after surgical care.
Approximately half of children and adolescents with Cushing's syndrome develop hypertension. To examine the role of hypercortisolism in the pathogenesis of hypertension in young patients and to establish its reversibility, we studied 31 hypertensive children and adolescents with Cushing's syndrome (systolic, diastolic, and/or mean blood pressure more than 2 SD U for age and sex) from a total of 63 patients before, and for a period of 1 yr after surgical cure. Preoperatively, 93.5%, 42%, and 45% of these patients presented with an increase of the systolic, diastolic, and mean blood pressure, respectively. The systolic blood pressure remained increased in 30.7%, 15.8%, and 5.5% of patients at 3, 6, and 12 months after surgical cure, respectively. The diastolic and mean blood pressure completely normalized by 3 months after surgical cure. A significant, positive correlation was observed between the systolic blood pressure and the duration of the disease, but no correlation was seen with the 24-h urinary free cortisol values and/or the patients' body mass indices. The lack of correlation between 24-h urinary free cortisol values and blood pressure suggests that hypercortisolism influences blood pressure through multiple pathways. The positive correlation between the systolic blood pressure and the duration of the disease points towards the deleterious effects of prolonged hypercortisolism and the significance of early diagnosis and treatment. The fact that the blood pressure normalized within a year from the correction of hypercortisolism suggests that, as a rule, young patients with hypercortisolism do not develop essential hypertension.
Adolescent↗
Corticosteroid therapy, nonendocrine disease, and corticosteroid withdrawal.
Explore the source record for details and available documents.
Adrenal Cortex Hormones↗
The maternal hypothalamic-pituitary-adrenal axis in the third trimester of human pregnancy.
OBJECTIVE: The third trimester of pregnancy is characterized by a mildly hyperactive hypothalamic-pituitary-adrenal (HPA) axis, possibly driven by elevated circulating levels of corticotrophin releasing hormone (CRH) of placental origin. In-vitro studies have demonstrated that glucocorticoids and oestrogen stimulate while progesterone inhibits the expression of CRH mRNA and/or protein, suggesting that several potential interactions between the placenta and the HPA axis may exist. DESIGN AND PATIENTS: To investigate the detailed pattern of circulating immunoreactive (ir) CRH, ACTH, cortisol, oestradiol and progesterone during the third trimester of pregnancy, plasma samples were drawn serially every 30 minutes from 22 healthy pregnant women (age 32.0 +/- 1.1 years, mean +/- SE) between the 34th and 36th week of gestation. Ten women had plasma samples drawn between 0800 h and 2000 h (daytime group), and 12 between 2000 h and 0800 h (night-time group). The hormone concentrations obtained were analysed for pulsatility by the Detect program, for detection of circadian rhythmicity by comparison between the first and second 6-hour periods within each group by Student's t-test, and for time-dependent correlations by cross-correlation analysis. RESULTS: All five hormones were secreted in a pulsatile fashion. There was no apparent circadian rhythm of CRH or oestradiol secretion, whereas there was a clear circadian rhythm in plasma ACTH, cortisol and progesterone secretion, with the latter in reverse phase (P < 0.05). No significant correlations were observed between CRH and ACTH, whereas, as expected, ACTH and cortisol concentrations were strongly correlated with each other over time (r = 0.32 and 0.70 at lag time 30 minutes for the daytime and night-time groups, respectively), with ACTH leading cortisol. A weak positive correlation was observed between CRH and cortisol concentrations for the night-time group at lag time 0 minute, suggesting that the latter may have a positive effect on the former in vivo. CONCLUSIONS: These data suggest that placental CRH, although pulsatile, drives quantitatively the maternal HPA axis in the third trimester of pregnancy in a non-circadian, non-pulsatile fashion. The maternal HPA axis is probably driven in a circadian and pulsatile fashion by another major ACTH secretagogue, most likely AVP of parvocellular paraventricular nucleus origin.
Adrenocorticotropic Hormone↗
Spontaneous cortisol and growth hormone secretion interactions in patients with nonclassic 21-hydroxylase deficiency (NCCAH) and control children.
Both exogenous and endogenous hypercortisolism result in reduced GH secretion and decreased somatic growth. However, little is known about the relation between endogenous cortisol and GH secretion under physiological or slightly disturbed conditions. To examine this, we measured and evaluated the pulsatility and circadian rhythmicity, and we cross-correlated the secretory patterns of cortisol and GH in six prepubertal patients with nonclassic 21-hydroxylase deficiency (NCCAH) and seven age-matched short-normal children. Cortisol and GH were secreted in a pulsatile fashion in both the NCCAH and control groups. The nocturnal peak cortisol increment and time-integrated area were lower in the NCCAH patients than in controls, whereas there was no difference in the total 24-h cortisol secretion between the two groups. The nocturnal increase of GH in NCCAH children, on the other hand, was associated with a significant augmentation of the pulse amplitude, whereas in control children there was an elevation of the baseline component. The cross-correlation analysis of the 24-h raw data showed that cortisol and GH were negatively correlated at brief lag times of 0-30 min, and positively correlated at long lag times of 12-12.5 h in both groups, with cortisol leading GH. The negative correlation might reflect either the negative effect of glucocorticoids on the adrenergic system, which stimulates GH secretion through GH-releasing hormone (GHRH) elevations and somatostatin (SRIH) decreases, or the absence of an inhibitory effect of CRH on SRIH. The positive correlation may reflect the positive effect of glucocorticoids on the GH gene. In conclusion, NCCAH children have a mild nocturnal cortisol deficiency compared with control children, as previously reported, and a distinct circadian pattern of pulsatile GH secretion. The hypothalamic-pituitary-adrenal (HPA) axis exerts both negative and positive influences on GH secretion, with mild disturbances in cortisol biosynthesis associated with slight alterations of GH secretion.
Adrenal Hyperplasia, Congenital↗
Hypothalamic corticotropin-releasing hormone suppression during the postpartum period: implications for the increase in psychiatric manifestations at this time.
The third trimester of human pregnancy is characterized by a hyperactive hypothalamic-pituitary-adrenal axis, possibly driven by progressively increasing circulating levels of placental CRH and gradually decreasing levels of CRH-binding protein. The postpartum period, on the other hand, is characterized by an increased vulnerability to psychiatric manifestations (postpartum "blues," depression, and psychosis), a phenomenon compatible with suppressed hypothalamic CRH secretion. To investigate the hypothesis that the postpartum period is associated with suppression of hypothalamic CRH secretion, we studied prospectively 17 healthy euthymic women (mean +/- SE age, 32.0 +/- 1.1 yr) with no prior history of depression, starting at the 20th week of gestation. Psychometric testing was performed monthly during pregnancy and postpartum on day 2 and weeks 2, 3, 6, 8, 12, 16, and 20, whereas serial ovine (o) CRH tests were performed postpartum at 3, 6, and 12 weeks. While pregnant, all 17 subjects remained euthymic; in the postpartum period, 7 women developed the "blues," and 1 developed depression. Overall, the mean plasma ACTH response to an iv bolus of 1 microgram/kg oCRH was markedly blunted at 3 and 6 weeks, but normal at 12 weeks postpartum, whereas the mean plasma cortisol response was at the upper limit of normal at all 3 times. These data are compatible with a suppressed hypothalamic CRH neuron that gradually returns to normal while hypertropic adrenal cortexes are progressively down-sizing. When the postpartum ACTH responses to oCRH were analyzed separately for the euthymic women and the women who had the "blues" or depression, the blunting of ACTH was significantly more severe and long lasting in the latter group; this was observed at all 3 times of testing. We conclude that there is central suppression of hypothalamic CRH secretion in the postpartum, which might explain the increased vulnerability to the affective disorders observed during this period. The suppressed ACTH response to oCRH might serve as a biochemical marker of the postpartum "blues" or depression.
Adrenocorticotropic Hormone↗
24-hour secretion of growth hormone (GH), insulin-like growth factors-I and -II (IGF-I, -II), prolactin (PRL) and thyrotropin (TSH) in young adults of normal and tall stature.
Studies of the growth hormone (GH) secretory dynamics of children with normal and idiopathic short stature (ISS) have revealed that the regulation of the GH-somatomedin (GHS) axis can differ significantly among normal individuals. Information on the GH secretion in idiopathic tall stature (ITS) is scarce. We previously showed that the GH response to stimulation with GH-releasing hormone (GHRH) in male, late adolescents and young adults with ITS is significantly greater than that of their sex and age-matched controls of average height. In the present study, we studied the 24-hour (hr) GH, insulin-like growth factor-I and -II (IGF-I and -II), prolactin (PRL) and thyroid-stimulating hormone (TSH) secretion by every 30 minutes (min) sampling in 12 young, healthy male Greek army recruits. Group I [n = 6, age 22 + 1.4 years (y.), mean + standard deviation (SD)] had a height of 198.5 + 4.2cm, at least 3 SD's above the mean of the Greek male population. Group II (n = 6, age 20.5 + 1.05 y.) had a height of 169.2 + 3.4cm, within 2SD's of the normal mean. Serum IGF-I levels were determined in both unextracted and extracted samples. Our results indicated that the number of secretory bursts and the circadian panel of GH, IGF-I and -II, PRL and TSH were similar in the two groups. Both the amplitude of the secretory GH peaks (5.08 + 3.07 vs. 3.3 + 0.8 ng/ml, p = 0.19,) and the area under the curve (AUC) of the 24-hour GH secretion (9.8 + 5.5 vs. 6.6 + 1.3 ng/ml/hr, p = 0.2) were higher in group I than in group II, but the difference was not significant. A significant nocturnal increase of both IGF-I and -II levels was found only in extracted human plasma (p < 0.001), whereas measurements of IGF-I in unextracted samples failed to reveal circadian variation (p < 0.1). We conclude that no significant differences were found in this pilot study of the neurosecretory regulation of the GHS axis between individuals of tall and normal stature. A tendency for greater amount of GH secretion per secretory peak was found in persons with tall stature; however, this finding needs to be confirmed in a larger study. IGF-I and -II levels had a significant circadian variation with a large nocturnal surge, when measured in extracted plasma. The latter, might be explained by circadian variation of the circulating IGF-binding proteins and its detection appears to be method of extraction-dependent.
Adult↗
Effects of the immune/inflammatory reaction on the hypothalamic-pituitary-adrenal axis.
Explore the source record for details and available documents.
Adrenocorticotropic Hormone↗
Cushing's syndrome in children and adolescents. Presentation, diagnosis, and therapy.
BACKGROUND AND METHODS: Cushing's syndrome is rare in children and adolescents. We analyzed the clinical presentation, diagnostic evaluation, and treatment of 59 patients with Cushing's syndrome between the ages of 4 and 20 years who were admitted to the National Institutes of Health during the period from 1982 to 1992. The cause of hypercortisolism was identified by low- and high-dose dexamethasone suppression tests, the ovine corticotropin-releasing hormone (CRH) stimulation test, imaging studies, and bilateral sampling of the inferior petrosal sinuses combined with administration of CRH. RESULTS: Fifty patients had Cushing's disease, six had primary adrenal disease, and three had ectopic corticotropin secretion. The initial signs were excessive weight gain in 90 percent of the patients and growth retardation in 83 percent. Most patients (81 percent) had normal bone age at the time of diagnosis. Forty-seven percent had hypertension, whereas only 19 percent had mental or behavioral problems. The high-dose dexamethasone suppression test and the CRH stimulation test identified 68 and 80 percent, respectively, of the patients with Cushing's disease. Magnetic resonance imaging of the pituitary indicated the presence of tumor in 52 percent of the patients with pituitary adenomas. The maximal central-to-peripheral ratio of plasma corticotropin during sampling of the interior petrosal sinuses was > or = 2.5 in all the patients with Cushing's disease and < 2.5 in those with ectopic corticotropin secretion. Remission of hypercortisolism was achieved in 48 of the 49 patients who underwent transsphenoidal surgery for Cushing's disease, in all 6 of the patients who underwent adrenalectomy for primary adrenal disease, and in the 2 patients in whom the ectopic source of corticotropin could be identified. CONCLUSIONS: Weight gain and growth retardation are common clinical characteristics of Cushing's syndrome in children and adolescents. Diagnostic evaluation of such patients with CRH stimulation alone and combined with inferior petrosal sinus sampling and imaging studies is accurate, and therapy is usually successful.
Adenoma↗
Suppressed spontaneous and stimulated growth hormone secretion in patients with Cushing's disease before and after surgical cure.
Growth retardation to complete growth arrest is the hallmark of Cushing's syndrome in children. The major mechanism for this has been considered the glucocorticoid-induced resistance of target tissues to insulin-like growth factor-I (IGF-I) and other growth factors. The purpose of this study was to examine the GH secretory dynamics of patients with Cushing's disease before and up to 12 months after their cure by transsphenoidal adenomectomy. In 14 patients, blood sampling every 20 min over 24 h for determination of plasma GH was performed before and 10-11 days and 3, 6, and 12 months after therapy. These patients also underwent arginine infusion and L-dopa stimulation tests and had measurements of morning baseline GH-binding protein (GHBP), IGF-I, and IGF-binding protein-3 (IGFBP-3) plasma concentrations. Fourteen sex- and pubertal stage-matched normal volunteers were used as controls. Before therapy, the patient group had an increased body mass index (31.5 +/- 5 kg/m2) and markedly decreased plasma mean 24-h GH concentration, mean peak height, and peak area values, with pulse frequency (mean number of peaks) similar to that in the controls. GH values after arginine and L-dopa stimulation were also subnormal in many of these patients, with 2 of 8 and 8 of 10 failing to show GH responses greater than 7 ng/mL in the respective test. In spite of these findings, plasma concentrations of IGF-I, IGFBP-3, and GHBP were within the normal range in these patients. Surprisingly, a pattern of GH suppression similar to that observed in patients with active disease was also seen in patients who were studied 10-11 days and 3, 6, and 12 months after their cure, when their body mass indexes were progressively normalizing, being relatively stable at 10 days, 26.9 +/- 3.8 kg/m2 at 3 months, and 24.8 +/- 3.3 kg/m2 at 12 months. In these patients, plasma IGF-I and GHBP remained normal, whereas IGFBP-3 decreased significantly, albeit within the normal range. The growth rate of 4 patients who were Tanner stage III or below and had not completed their growth at the time of the study increased the year after surgical cure. These findings suggest that patients with Cushing's disease have marked GH suppression during their illness, which, however, does not appear to be a major contributor to the growth suppression observed in this condition. GH hyposecretion continues for at least a year during convalescence, in spite of significant increases in the growth rate in all growing patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Multiple sclerosis is associated with alterations in hypothalamic-pituitary-adrenal axis function.
In the LEW/N rat model, a decreased hypothalamic-pituitary-adrenal (HPA) axis response to inflammatory and immune mediators confers susceptibility to the development of a variety of inflammatory and immune diseases, including experimental allergic encephalomyelitis. In humans with optic neuritis, early intervention with steroids is associated with a decrease in the number of patients who go on to develop multiple sclerosis (MS). The current study was designed to determine whether patients with MS show evidence of a hypoactive HPA axis. Thirteen patients with MS were studied at baseline and with provocative tests of HPA axis function [ovine CRH, arginine vasopressin (AVP), and ACTH stimulation]. Compared to matched controls, patients with MS had significantly higher plasma cortisol levels at baseline. Despite this hypercortisolism and in contrast to patients with depression who had similar elevations in plasma cortisol levels, patients with MS showed normal, rather than blunted, plasma ACTH responses to ovine CRH, suggesting that the pathophysiology of hypercortisolism in MS is different from that in depression. Patients with MS also showed blunted ACTH responses to AVP stimulation and normal cortisol responses to high and low dose ACTH stimulation. Taken together, these findings are compatible with data from studies of experimental animals exposed to chronic inflammatory stress, which showed mild increased activation of the HPA axis with increased relative activity of AVP in the regulation of the pituitary-adrenal axis. These data do not support a role for hypocortisolism in MS once the disease is established.
Adrenal Glands↗
Final stature in patients with endogenous Cushing's syndrome.
Growth retardation to complete growth arrest is the hallmark of Cushing's syndrome in children and growing adolescents; however, the effect of endogenous hypercortisolism on the final adult stature of these patients is not known. We examined this in 10 children and adolescents with endogenous Cushing's syndrome who were evaluated and successfully treated at the NIH Clinical Center before having completed their growth. The bone age was consistent with the chronological age or accelerated in four of six (67%) and delayed in two of six patients (33%). The pretreatment height of patients with Cushing's syndrome in SD units was -1.7 +/- 1.3 (mean +/- SD), the final adult height -1.3 +/- 0.9, and the midparental height was 0 +/- 0.8. All patients had a compromised final adult stature compared to their midparental height (162.8 +/- 9.0 vs. 171.7 +/- 6.3 cm; P < 0.05). The mean (midparental height - final adult height) +/- SD was 8.9 +/- 7.3 cm. The final adult height in both centimeters and SD units was significantly lower than the midparental height (P < 0.05), whereas it did not differ significantly from the predicted heights by the Bayley-Pinneau and Roche-Wainer-Thissen methods. We conclude that the growth retardation caused during the hypercortisolemic state of Cushing's syndrome is associated with a compromised final adult height, possibly as a result of inadequate postcure catch-up growth.
Adolescent↗
Hypothalamic-pituitary-adrenal axis activation and stimulation of systemic vasopressin secretion by recombinant interleukin-6 in humans: potential implications for the syndrome of inappropriate vasopressin secretion.
We recently demonstrated that sc administered interleukin-6 (IL-6) strongly stimulates the human hypothalamic-pituitary-adrenal (HPA) axis, with mild toxicity and no hypotensive effects. In this study, we evaluated the response of the human HPA axis to escalating iv doses of recombinant IL-6 in six patients with cancer and good performance status who received daily, every 8 h, three equal doses of 0.3-30 micrograms/kg IL-6. The plasma levels of IL-6 assayed by a specific enzyme-linked immunosorbent assay during the 4 h following the first IL-6 injection were elevated for 2-4 h, proportionally to the amount of injected IL-6. Administration of the cytokine was followed by marked elevations of plasma ACTH (53.0-98.6 pmol/L) and cortisol (824.9-1729.9 nmol/L) independently of the IL-6 dose administered, suggesting that the doses employed were at the top of the dose-response curve for these hormones. Interestingly, plasma arginine vasopressin (AVP) levels were also elevated during the 2 h after IL-6 injection in all patients who received a dose of 3 micrograms/kg or more, suggesting that IL-6 activated the magnocellular AVP-secreting neurons and that it might be involved in the syndrome of inappropriate AVP secretion. Cortisol elevations with peaks similar to those observed after the first injection of IL-6 were also detected in plasma sampled every 2 h after the second and third injections, suggesting that there was no rapid tachyphylaxis in response to IL-6 administration. Plasma IL-1 beta and tumor necrosis factor-alpha concentrations, assayed by specific enzyme-linked immunosorbent assays during the 4 h after the first IL-6 injection, were either within the normal range or undetectable, confirming in vitro observations that IL-6 does not stimulate IL-1 beta or tumor necrosis factor-alpha secretion and suggesting that it exerts its effect on the HPA axis and AVP secretion independently of them. We conclude that IL-6 is a potent stimulator of the human HPA axis and a secretagogue of magnocellular AVP secretion, which might be employed as a challenge test of the axis and the magnocellular AVP neuron.
Adrenocorticotropic Hormone↗
Corticosteroid therapy, nonendocrine disease, and corticosteroid withdrawal.
Explore the source record for details and available documents.
Administration, Inhalation↗
The pituitary corticotroph is not the rate limiting step in the postoperative recovery of the hypothalamic-pituitary-adrenal axis in patients with Cushing syndrome.
Patients cured from endogenous Cushing syndrome usually develop postoperative adrenal suppression in the year ensuing surgery. To define whether the pituitary corticotroph is the rate limiting step in the postoperative recovery of this secondary/tertiary form of adrenal insufficiency, we examined surgically cured patients with Cushing syndrome 10 days, 3 months, and 6-12 months after surgery, by administering ovine CRH (oCRH) iv at the dose of 1 microgram/kg.h over 24 h. The pituitary corticotroph of these patients responded vigorously to oCRH, with ACTH concentrations reaching above the normal range at all three times of testing. Parallel measurements of cortisol in nonadrenalectomized patients demonstrated subnormal adrenal responsiveness at 10 days and 3 months and normalization at 6-12 months after surgery. The circadian rhythm of ACTH was maintained postoperatively at 10 days and 6-12 months, and the circadian rhythm of cortisol was also present at 6-12 months after surgery, in spite of the constant infusions of pharmacological doses of oCRH, suggesting that factors other than CRH secretion regulate this rhythm. We conclude that the corticotroph is not the rate limiting step in the recovery of the hypothalamic-pituitary-adrenal axis from glucocorticoid-induced adrenal suppression, and that the locus of the defect resides in the hypothalamic CRH neuron and/or its higher regulatory inputs.
Adolescent↗