The recovery of the hypothalamo-pituitary-ad renal axis after transsphenoidal operation in three patients with Cushing's disease. The effect of prior external pituitary irradiation

1981 ◽  
Vol 98 (4) ◽  
pp. 580-585 ◽  
Author(s):  
Steven W.J. Lamberts ◽  
Jan G. M. Klijn ◽  
Frank H. de Jong ◽  
Jan C. Birkenhäger
Keyword(s):  
Growth Hormone ◽  
Cushing’S Disease ◽  
Plasma Cortisol ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Cushing's Disease ◽  
Plasma Acth ◽  
Basal Plasma ◽  
Pituitary Irradiation ◽  
Pituitary Adrenal Axis

Abstract. The recovery of the hypothalamo-pituitary-adrenal axis after selective transsphenoidal adenomectomy was studied in 3 patients with Cushing's disease by measuring basal plasma ACTH and cortisol concentrations, cortisol secretion rate, the diurnal rhythm of cortisol, and the reaction of cortisol to lysine vasopressin (LVP), of compound S to metyrapone and of cortisol and growth hormone to an insulin-induced hypoglycaemia. The third patient had been treated previously by external pituitary irradiation. In 2 patients basal plasma ACTH levels returned within normal values before plasma cortisol, but no supra-physiological plasma concentrations of ACTH were seen as has been observed after withdrawal of exogenous glucocorticoids. With regard to the different stimulation tests: at first the normal reaction of plasma cortisol to LVP returned after 3 months, at the same time as the restoration of growth hormone secretion in response to hypoglycaemia. A normalization of the reaction to metyrapone was seen thereafter while finally the reaction of cortisol to an insulin-induced hypoglycaemia and the diurnal rhythm of plasma cortisol returned 15 to 18 months after operation in the first patient and after 12 months in the second patient. Selective adenomectomy had also been carried out in the third patient, as evidenced by normal TSH, LH and FSH secretion. Hypocortisolism, and a deficient ACTH and growth hormone secretion in response to the stimuli mentioned, however, did not normalize up till 22 months after operation. The restoration of the hypothalamo-pituitary-adrenal axis after selective pituitary adenomectomy in Cushing's disease was prevented in this patient by prior external pituitary irradiation.

Marked differences in functioning of the hypothalamicpituitary-adrenal axis between groups of men

1997 ◽  
Vol 82 (6) ◽  
pp. 1979-1988 ◽  
Author(s):  
John S. Petrides ◽  
Philip W. Gold ◽  
Gregory P. Mueller ◽  
Anita Singh ◽  
Costas Stratakis ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Plasma Cortisol ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Strenuous Exercise ◽  
Plasma Acth ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Low Responders ◽  
Exercise Induced

Petrides, John S., Philip W. Gold, Gregory P. Mueller, Anita Singh, Costas Stratakis, George P. Chrousos, and Patricia A. Deuster.Marked differences in functioning of the hypothalamic-pituitary-adrenal axis between groups of men. J. Appl. Physiol. 82(6): 1979–1988, 1997.—To compare profiles of hypothalamic-pituitary-adrenal (HPA) responsiveness, healthy, moderately trained men ( n = 15) were classified as high ( n = 7) or low responders ( n = 8) on the basis of plasma adrenocorticotropic hormone (ACTH) responses to strenuous treadmill exercise 4 h after 4 mg of dexamethasone (Dex). These groups were then evaluated to compare 1) HPA and growth hormone responses to exercise at 90% maximal oxygen uptake 4 h after placebo, Dex (4 mg), and hydrocortisone (100 mg); 2) pituitary-adrenal responses to infusion of arginine vasopressin (AVP); 3) plasma cortisol after a Dex suppression test (1 mg); and 4) behavioral characteristics. In comparison to low responders, high responders exhibited significantly 1) higher plasma ACTH responses to exercise after placebo and Dex; 2) higher plasma AVP secretion with exercise after placebo and marked Dex- and hydrocortisone-induced enhancement of exercise-induced AVP secretion; 3) lower Dex-induced increases in basal and stimulated growth hormone secretion; 4) higher plasma ACTH responses to infusion of AVP; and 5) a trend ( P = 0.09) for higher trait anxiety ratings. Similar suppression of plasma cortisol was noted after 1 mg Dex. We conclude that subgroups of healthy male volunteers exhibit unique profiles of HPA responsiveness. We also believe that glucocorticoid pretreatment combined with strenuous exercise allows functional HPA responsiveness to be distinguished between subgroups of healthy controls and may be useful in the determination of susceptibility to disorders characterized by hyper- and hypo-HPA activation.

Successful treatment of childhood-onset Cushing's disease is associated with persistent reduction in growth hormone secretion

2004 ◽  
Vol 60 (2) ◽  
pp. 169-174 ◽  
Author(s):  
P. V. Carroll ◽  
J. P. Monson ◽  
A. B. Grossman ◽  
G. M. Besser ◽  
P. N. Plowman ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Successful Treatment ◽  
Cushing’S Disease ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Cushing's Disease ◽  
Childhood Onset

scholarly journals Growth and growth hormone secretion in paediatric Cushing's disease

HORMONES ◽  
2003 ◽  
Vol 2 (2) ◽  
pp. 93-97 ◽  
Author(s):  
Martin Savage ◽  
Helen Storr ◽  
Ashley Grossman ◽  
Gerasimos Krassas
Keyword(s):  
Growth Hormone ◽  
Cushing’S Disease ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Cushing's Disease

EVALUATION OF A THERAPEUTIC REGIMEN IN CUSHING'S DISEASE

1977 ◽  
Vol 86 (1) ◽  
pp. 146-155 ◽  
Author(s):  
S. W. J. Lamberts ◽  
F. H. de Jong ◽  
J. C. Birkenhäger
Keyword(s):  
Cushing’S Disease ◽  
Plasma Cortisol ◽  
Sella Turcica ◽  
Therapeutic Regimen ◽  
Cushing's Disease ◽  
Unilateral Adrenalectomy ◽  
Lysine Vasopressin ◽  
Pituitary Irradiation ◽  
Pituitary Adrenal Axis

ABSTRACT Eighteen unselected patients with Cushing's disease were treated by unilateral adrenalectomy followed by conventional external pituitary irradiation (4500 rads). In 9 of these patients (50 %) a remission has been reached as judged by the clinical picture and the cortisol secretion rate (CSR) up to an average of 5 years after operation (follow-up varying between 1 and 7.5 years). The 9 other patients showed a relapse making necessary a second adrenalectomy after an average of 15 months (5 to 57 months). Four of these patients had a slightly enlarged (two cases) or asymmetrical sella turcica (two cases). The gain of this therapeutic regimen was that no permanent adrenal insufficiency is induced in 50 % of the patients, that no pituitary tumours developed and that no loss of pituitary function occurred. Before treatment the group of 9 patients, who did not improve or relapsed after treatment, showed a greater rise of plasma cortisol in response to lysine vasopressin, a (greater) decrease of plasma cortisol in response to a single oral dose of 1 mg dexamethasone and an earlier decrease of the urinary 17-OGS in response to 2 mg dexamethasone four times daily orally. It is concluded that in the patients whose hypothalamo-pituitary-adrenal axis could be manipulated less this therapeutic regimen had a better result.

Concomitant falls of plasma cortisol and ACTH levels in a case of Cushing's disease during treatment with trilostane

1984 ◽  
Vol 105 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Kaoru Nomura ◽  
Hiroshi Demura ◽  
Toshihiro Imaki ◽  
Megumi Miyagawa ◽  
Masami Ono ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Cushing’S Disease ◽  
Plasma Levels ◽  
Plasma Cortisol ◽  
Competitive Inhibitor ◽  
Cushing's Disease ◽  
Plasma Acth ◽  
Lysine Vasopressin ◽  
Hypothalamic Pituitary Axis ◽  
Pituitary Irradiation

Abstract. A 72-year-old man with Cushing's disease was treated with trilostane, a competitive inhibitor of adrenal 3β-hydroxysteroid dehydrogenase (3β-HSDH). The treatment with trilostane successfully lowered urinary excretion of 17-hydroxycorticosteroids (17-OHCS) and plasma levels of cortisol and elevated the plasma level of dehydroepiandrosterone. Unexpectedly, plasma ACTH fell from 109.7 ± 45.0 to 42.7 ± 27.3 pg/ml (P < 0.01) in parallel with plasma cortisol. The hyperresponsiveness of plasma ACTH observed both in the metyrapone test and the lysine-vasopressin test was also ameliorated by treatment with trilostane. Then low dose of pituitary irradiation with cobalt-60 was added and his urinary excretion of 17-OHCS and plasma levels of cortisol decreased further. After treatment with trilostane was finally stopped, the plasma ACTH increased from 45.9 ± 21.9 to 69.6 ± 25.3 pg/ml (P < 0.05) in parallel with plasma cortisol. Since then he has had no recurrence for 12 months. These observations suggest that trilostane, like other adrenal enzyme-inhibiting drugs, may induce unexpected improvement of the abnormality of the hypothalamic-pituitary axis present in Cushing's disease.

A FUNDAMENTAL DEFECT OF ADRENOCORTICAL CONTROL IN CUSHING'S DISEASE

1968 ◽  
Vol 40 (1) ◽  
pp. 15-28 ◽  
Author(s):  
V. H. T. JAMES ◽  
J. LANDON ◽  
V. WYNN ◽  
F. C. GREENWOOD
Keyword(s):  
Growth Hormone ◽  
Cushing’S Disease ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Normal Growth ◽  
Cushing's Disease ◽  
Similar Degree ◽  
Primary Defect ◽  
Harvey Cushing ◽  
Adrenal Response

SUMMARY The plasma sugar, 11-hydroxycorticosteroid, and growth hormone responses to insulin have been studied in patients with Cushing's disease. They showed an impaired or absent plasma 11-hydroxycorticosteroid and growth hormone rise during the test, as compared with control subjects, despite the injection of amounts of insulin which produced a similar degree of hypoglycaemia. This test proved of value in differentiating between these patients and those with 'simple ' obesity since the latter usually showed a normal growth hormone and adrenal response provided an adequate amount of insulin was administered. The patients with Cushing's disease also had an impaired adrenal response to pyrogen and to dexamethasone administration and failed to show a normal plasma 11-hydroxycorticosteroid circadian rhythm. Their response to corticotrophin, lysine vasopressin, and metyrapone, however, was normal or enhanced. It is suggested that these findings imply an abnormality of hypothalamic or cerebral control and not a primary defect of pituitary function as proposed originally by Harvey Cushing. The growth hormone response to insulin remained impaired in four out of six patients totally adrenalectomized for Cushing's disease but was normal in three patients adrenalectomized for other reasons. It is suggested that the defect which impairs the adrenal response to insulin may, on occasions, also impair the mechanism normally operative for growth hormone secretion.

Mechanism of impaired growth hormone secretion in patients with Cushing's disease

1992 ◽  
Vol 127 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Hideo Takahashi ◽  
Hiroshi Bando ◽  
Chenyu Zhang ◽  
Ryuichi Yamasaki ◽  
Shiro Saito
Keyword(s):  
Growth Hormone ◽  
Cushing’S Disease ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Cushing's Disease ◽  
Gh Secretion ◽  
Highly Sensitive ◽  
Low Levels ◽  
Plasma Gh ◽  
Observation Period

The function of the growth hormone-releasing hormone (GHRH)-growth hormone (GH) axis in Cushing's disease was studied by monitoring (a) the GH responses to GHRH loading and L-dopa loading, (b) the GHRH response to L-dopa loading, and (c) the daytime profiles of plasma GH concentration. GH release following GHRH and L-dopa was blunted in patients as compared to that in age-matched control subjects. However, GHRH release following L-dopa was similar in patients and controls. The plasma GH levels in four patients measured every 20 min by a highly sensitive immunoradiometric assay for GH showed pulsatile GH secretion at low levels during the observation period. These results indicate that GHRH release from the hypothalamus is preserved in patients with Cushing's disease, and support the hypothesis that glucocorticoid inhibits GH secretion by altering the hypothalamic somatostatin tone.

Results of external pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing's disease

1991 ◽  
Vol 125 (4) ◽  
pp. 470-474 ◽  
Author(s):  
A. Vicente ◽  
J. Estrada ◽  
C. de la Cuerda ◽  
B. Astigarraga ◽  
M. Marazuela ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
High Efficiency ◽  
Cushing's Disease ◽  
Anterior Pituitary Function ◽  
Low Incidence ◽  
Pituitary Irradiation ◽  
Age Range ◽  
Pituitary Adrenal Axis ◽  
Tsh Deficiency

Abstract. Fourteen adult patients (10 females and 4 males; age range 20-60 years) with persistent Cushing's disease after transsphenoidal microsurgery were treated with pituitary irradiation. Supervoltage multiportal administration was employed at a total dose of 50 Gy (±0.65 sd). The interval between microsurgery and pituitary irradiation was less than 6 months in 6 patients and more than 6 months in 8. The pituitary-adrenal axis was evaluated postsurgically, before irradiation and every 6 months thereafter. The remaining anterior pituitary function was simultaneously tested. Remission rates at 12 months and 24 months after radiotherapy were 61 and 70%, respectively. Two patients developed TSH deficiency and another gonadotropin deficiency during the follow-up after radiation. We conclude that pituitary irradiation is the treatment of choice for persistent Cushing's disease after unsuccessful surgery because of its high efficiency and low incidence of adverse reactions when compared with other forms of treatment.

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