Responses of Plasma ACTH, GH, LH and 11-Hydroxycorticosteroids to Various Stimuli in Patients with Cushing's Syndrome

Demura, Reiko; Demura, Hiroshi; Nunokawa, Tohru; Baba, Hideyuki; Miura, Kiyoshi

doi:10.1210/jcem-34-5-852

Cited by 73 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is a classic observation that chronic hypercortisolism inhibits somatic growth as well as GH secretion [25, 26]. In Cushing’s syndrome, GH responses appear blunted towards all stimuli tested so far [27, 28]; ghrelin can now be added to this list.…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Is No Longer Able to Stimulate Growth Hormone Secretion in Patients with Cushing’s Syndrome but Instead Induces Exaggerated Corticotropin and Cortisol Responses

et al. 2002

View full text Add to dashboard Cite

Growth and growth hormone (GH) secretion are blunted or severely impeded in chronic hypercortisolism and in patients with Cushing’s syndrome. A mechanistic explanation for the effect however has yet to be provided. On the other hand, several properties of ghrelin, a new peptide recently identified as the endogenous ligand of the GH secretagogue receptor, are still largely unknown. The two aims of this study were to observe whether ghrelin-mediated GH secretion was altered, and to characterize the corticotropin (ACTH) and cortisol response to this new stimulus in patients with Cushing’s disease. Ten patients with active Cushing’s disease (6 harboring microadenomas and 4 with macroadenomas) and 10 sex- and age-matched controls were studied. Ghrelin was administered at a dose of 1 µg/kg i.v. and GH, ACTH and cortisol analyzed in duplicate. In control women, ghrelin induced GH secretion to levels of 74.4 ± 12.8 µg/l, while chronic hypercortisolism severely reduced the ghrelin-mediated GH release in all patients with Cushing’s disease (peak values 17.7 ± 5.2 µg/l). The slightly, but significantly higher adiposity of patients vs. controls may have contributed to the effect, since a significant negative correlation (r = 0.639) was found between the amplitude of the GH peak and body mass index. In control women, ghrelin increased ACTH and cortisol levels, with peaks at 57.4 ± 19.0 ng/l and 162 ± 16 µg/l, respectively. This secretion was enhanced in Cushing’s syndrome patients, with ACTH and cortisol values of 380.7 ± 109.8 ng/l and 338 ± 81 µg/l respectively, both significantly higher than in controls. In conclusion, ghrelin-induced GH secretion was severely blunted in patients with active Cushing’s syndrome, in addition to a remarkable hyper-response in ACTH and cortisol secretion. These findings could have implications for the understanding of the physiology and physiopathology of interactions between GH and ACTH regulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Ghrelin Is No Longer Able to Stimulate Growth Hormone Secretion in Patients with Cushing’s Syndrome but Instead Induces Exaggerated Corticotropin and Cortisol Responses

et al. 2002

View full text Add to dashboard Cite

show abstract

“…As for the gonadotropins, the capacity of gonadotrope to release FSH and LH during hypercortisolemia due to Cushing's syndrome is either impaired or not altered in the previous reports [6,7,18]. Additionally, Lado-Abeal et al found that menstrual abnormality in women with Cushing's diseases can be correlated with hypercortisolemia rather than increased androgen levels caused by ACTH excess [19].…”

Section: Discussionmentioning

confidence: 93%

“…In particular, blunted response of TSH secretion by excessive glucocorticoids has been widely recognized [1,2] and this phenomenon is also observed in patients with Cushing's syndrome [3,4]. Subsequent research has shown that pituitary responses of TSH and GH were likely to be impaired by glucocorticoid excess in such Cushing conditions [5][6][7]. The difference of secretory capacity of anterior pituitary hormones in the patients with hypercortisolemia due to Cushing's syndrome has been demonstrated in Demura et al [6] and Hashimoto [7], which shows the presence of a certain suppressibility of the anterior pituitary hormones caused by Cushing' syndrome.…”

mentioning

confidence: 99%

Reversible Pituitary Dysfunction in a Patient with Cushing's Syndrome Discovered as Adrenal Incidentaloma

et al. 2004

View full text Add to dashboard Cite

Abstract. We report a 45-year-old woman with Cushing's syndrome showing reversible pituitary dysfunction. Left adrenal tumor was incidentally discovered by a screening examination of abdominal computed tomography. Although this patient lacked typical Cushingoid features except hypertension and leg edema, endocrine examinations revealed moderate suppression of plasma ACTH (~6.3 pg/ml) with relatively high levels of serum cortisol (~22.9 mg/dl) without normal circadian rhythm. Plasma ACTH failed to respond to either CRH or metyrapone, and dexamethasone failed to suppress her daily steroid production. Surgical removal of left adrenocortical adenoma and 6-month replacement of hydrocortisone have ameliorated both ACTH and cortisol responses to CRH loading test. Postoperative responses of TSH and GH to TRH and GRH, respectively, were two fold higher than the preoperative levels. In contrast, basal and TRH-induced levels of serum PRL were decreased after surgery although both the basal and stimulated PRL levels were markedly high before surgery. In addition, gonadotropin response to GnRH examined in the same ovarian cycle was decreased in accordance with an increase in serum estradiol and progesterone levels after surgery. Improvement of hypercortisolemia even in a moderate case of Cushing's syndrome not only ameliorates hypertension, obesity and glucose intolerance, but also restores the accompanying dysfunctions of anterior pituitary, suggesting the clinical importance of early discovery and treatment of functioning adrenocortical incidentalomas.

show abstract

“…The increases in serum GH concentrations in response to commonly used pharmacological stimuli are typically inhibited in patients with significant endogenous hypercortisolism (10,31). Recent clinical experiments on the neuroendocrine mechanisms involved in …”

Section: Discussionmentioning

confidence: 99%

Growth Hormone (GH) Responses to GH-Releasing Hormone Alone or Combined with Arginine in Patients with Adrenal Incidentaloma: Evidence for Enhanced Somatostatinergic Tone

Terzolo

Bossoni

Alı̀

et al. 2000

The Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

Spontaneous and stimulated GH secretion is blunted in hypercortisolemic states due to increased hypothalamic somatostatinergic tone. However, no data are available on the characteristics of GH secretion in patients with incidentally discovered adrenal adenomas. They represent an interesting model for studying GH secretion, as a slight degree of cortisol excess may frequently be observed in such patients who do not present with any clear Cushingoid sign. In the present study, 10 patients (3 men and 7 women, aged 48 -63 yr) with an adrenal mass discovered serendipitously underwent, on separate occasions, a GHRH injection alone or combined with an infusion of the functional somatostatin antagonist, arginine. Thirteen age-matched healthy volunteers served as controls. Briefly, arginine (30 g) was infused from Ϫ30 to 0 min, and GHRH (100 g) was injected as a bolus at 0 min, with measurement of serum GH [immunoradiometric assay (IRMA)] every 15 min for 150 min. Plasma IGF-I (RIA after acidethanol extraction) was measured in a morning sample. The diagnosis of cortical adenoma was based on computed tomography features and pattern of uptake on adrenal scintigraphy. Patients with obesity and/or diabetes were excluded. The study design included also an endocrine work-up aimed to study the hypothalamic-pituitary-adrenal axis [urinary free cortisol (UFC) excretion, serum cortisol at 0800 h, plasma ACTH at 0800 h, morning cortisol after overnight 1 mg dexamethasone]. Five of 10 patients showed abnormalities of the hypothalamic-pituitary-adrenal axis, including borderline or increased UFC excretion in 4 of them accompanied by blunted ACTH in 2 cases and failure of cortisol to suppress after dexamethasone in 1; the fifth patient displayed low ACTH and resistance to dexamethasone suppression. However, all patients had a unilateral uptake of the tracer on the side of the mass with suppression of the contralateral normal adrenal gland. As a group, the patients displayed greater UFC excretion and lower ACTH concentrations than the controls. GH release after GHRH treatment was blunted in patients bearing adrenal incidentaloma compared with controls (GH peak, 5.7 Ϯ 5.2 vs. 18.0 Ϯ 7.0 g/L; P Ͻ 0.0001), whereas GHRH plus arginine was able to elicit a comparable response in the 2 groups (GH peak, 33.5 Ϯ 20.3 vs. 33.7 Ϯ 17.5 g/L; P ϭ NS). The ratio between GH peaks after GHRH plus arginine and after GHRH plus saline was significantly greater in patients than in controls (751 Ϯ 531% vs. 81 Ϯ 45%; P ϭ 0.0001). Similar data were obtained when comparing GH area under the curve after GHRH plus saline or GHRH plus arginine between the 2 groups. In summary, the present data suggest that in patients with incidental adrenal adenomas the GH response to GHRH is blunted due to increased somatostatinergic tone, as it can be restored to normal by pretreatment with the functional somatostatin antagonist arginine. The blunted GH release to GHRH may be an early and long lasting sign of autonomous cortisol secretion by the adrenal adenoma. (J Cli...

show abstract

Responses of Plasma ACTH, GH, LH and 11-Hydroxycorticosteroids to Various Stimuli in Patients with Cushing's Syndrome

Cited by 73 publications

References 0 publications

Ghrelin Is No Longer Able to Stimulate Growth Hormone Secretion in Patients with Cushing’s Syndrome but Instead Induces Exaggerated Corticotropin and Cortisol Responses

Ghrelin Is No Longer Able to Stimulate Growth Hormone Secretion in Patients with Cushing’s Syndrome but Instead Induces Exaggerated Corticotropin and Cortisol Responses

Reversible Pituitary Dysfunction in a Patient with Cushing's Syndrome Discovered as Adrenal Incidentaloma

Growth Hormone (GH) Responses to GH-Releasing Hormone Alone or Combined with Arginine in Patients with Adrenal Incidentaloma: Evidence for Enhanced Somatostatinergic Tone

Contact Info

Product

Resources

About