Acromegaly caused by growth hormone-releasing hormone-producing tumors: long-term observational studies in three patients

Biermasz, Nienke R.; Smit, Johannes W. A.; Pereira, Alberto M.; Frölich, Marijke; Romijn, Johannes A.; Roelfsema, Ferdinand

doi:10.1007/s11102-007-0045-7

Cited by 52 publications

(39 citation statements)

References 75 publications

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“…In transgenic mice overexpressing hGHRH, somatotrope hyperplasia develops and converts into pituitary adenoma after a sufficient period of time [27]. In humans, ectopic GHRH production from peripheral tumors results in somatotrope hyperplasia and acromegaly [28], but coexistence of hyperplasia and adenoma formation was also described [23,29]. Because GHRH antagonists competitively inhibit GHRH actions, they can suppress both GH secretion and somatotrope cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of GHRH Antagonists on Human GH-Secreting Adenoma Tissue

et al. 2012

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Experimental data indicate that antagonists of growth hormone-releasing hormone (GHRH) could be used clinically in disorders characterized by excessive GHRH/growth hormone (GH) secretion, but direct evidence for the effectiveness of GHRH antagonists on human pituitary tissue is still lacking. In this study, we investigated the inhibitory effect of our GHRH antagonists MZ-4-71 and JV-1-36 and the somatostatin (SST) analog RC-160 on superfused pituitary cells obtained from a human GH-secreting adenoma. Using Western blot analysis and immunohistochemistry, we demonstrated profuse expression of the GHRH receptor and its major splice variant SV1 and an increase in the expression of Gsa protein in the adenoma tissue. Exposure of the tumor cells to exogenous pulses of GHRH induced definite GH responses, causing a 3- to 5-fold elevation of the basal GH level. The antagonists MZ-4-71 and JV-1-36 did not alter basal GH secretion, indicating that the adenoma cells did not secrete GHRH in an autocrine manner. However, both antagonists prevented the stimulatory effect of exogenous GHRH. Similarly to the GHRH antagonists, neither SST-14 nor the SST analog RC-160 had an effect on the basal GH secretion of the tumor cells, but both peptides inhibited the stimulatory effect of exogenous GHRH, with RC-160 being more potent than SST. Our study provides direct evidence for the effectiveness of potent GHRH antagonists such as MZ-4-71 and JV-1-36 on human pituitary GH-secreting adenoma tissue and strongly suggests that these drugs could be used for therapy of GHRH-associated forms of acromegaly, particularly for those patients in whom surgery fails or is not an option.

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Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of GHRH Antagonists on Human GH-Secreting Adenoma Tissue

et al. 2012

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“…increased pattern regularity. Conversely, more irregular hormone secretion patterns arise commonly from tumors, as demonstrated by highly irregular ACTH and cortisol secretion in pituitary-dependent hypercortisolism, irregular GH secretion in GHRH-secreting neuroendocrine tumors, and GH and TSH secretion in active acromegaly (40)(41)(42). Feedback signaling by tumor-driven cortisol patterns was irregular, as quantified by grossly elevated cortisol ApEn.…”

Section: Discussionmentioning

confidence: 99%

Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome

Roelfsema¹,

Pereira²,

Biermasz³

et al. 2009

European Journal of Endocrinology

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Context: The hypothalamus-pituitary-thyroid axis in Cushing's syndrome may be altered. Previous reports have shown diminished serum TSH concentration and decreased response to TRH. Objective: We analyzed serum TSH profiles in relation to cortisol profiles in patients with hypercortisolism of pituitary (nZ16) or primary-adrenal origin (nZ11) and after remission by pituitary surgery (nZ7) in order to delineate aberrations in the hypothalamus-pituitary-thyroid system. Intervention: Patients and controls (nZ27) underwent a 24-h blood sampling study. Serum TSH and cortisol were measured with precise methods, and data were analyzed with a deconvolution program, approximate entropy (ApEn), and cosinor regression. Results: Pulsatile TSH secretion and mean TSH pulse mass were diminished during hypercortisolism, independently of etiology (P!0.001). TSH secretion was increased in patients in remission only during daytime due to increased basal secretion (P!0.01). Pulse frequency and half life of TSH were similar in patients and controls. TSH ApEn (irregularity) was increased in patients with hypercortisolism (P!0.01), but was normal in cured patients. Cross-ApEn between TSH and cortisol, a measure of pattern synchrony loss, was increased in active disease, indicating (partial) loss of secretory synchrony. The TSH rhythm was phase delayed in hypercortisolemic patients, but normal in cured patients (P!0.01). Free thyroxine levels were decreased only in pituitary-dependent hypercortisolism compared with controls (PZ0.003). Total 24-h TSH correlated negatively and linearly with logtransformed cortisol secretion (RZ0.43, PZ0.001). Conclusion: Cortisol excess decreases TSH secretion by diminishing pulsatile release, whereas surgically cured patients have elevated nonpulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic/annexin-1 control.

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“…Acromegaly is a rare disease caused by a GH-secreting adenoma or (rarely, about 1%) by excessive GH-releasing hormone secretion, usually by a carcinoid tumour of the lung or gastrointestinal tract (1). The incidence of acromegaly is about 3-4 per million per year and the prevalence is 60-70 per million, and there are no geographical or sex differences (2).…”

Section: Introductionmentioning

confidence: 99%

Preoperative lanreotide treatment in acromegalic patients with macroadenomas increases short-term postoperative cure rates: a prospective, randomised trial

Mao

Zhu

Tang

et al. 2010

European Journal of Endocrinology

104

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Objective: To investigate whether 4-month preoperative lanreotide treatment would improve the surgical cure rate of newly diagnosed acromegalic patients with macroadenomas. Design: A prospective, randomised study. Methods: After a baseline evaluation, patients were randomly assigned to 4-month preoperative treatment with lanreotide (starting with 30 mg/2 weeks i.m. and increasing to 30 mg/week i.m. at week 8 if mean GH O2.5 mg/l on GH day curves; pretreatment group, Group 1) or to transsphenoidal surgery (direct surgery group, Group 2). Cure was evaluated 4 months postoperatively primarily by fasting IGF1 less than or equal to age-adjusted upper limit of normal. Results: A pool of 108 patients was randomly divided into two groups. Five patients in each group were lost to follow-up during the study period, so 49 patients in each group were analysed. At baseline, no difference was observed between the two groups. Cure was established in 24 of 49 (49.0%, 95% confidence interval (CI), 35.0-63.0%) pretreated patients (Group 1) versus 9 of 49 (18.4%, 95% CI, 7.6-29.

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Acromegaly caused by growth hormone-releasing hormone-producing tumors: long-term observational studies in three patients

Cited by 52 publications

References 75 publications

Inhibitory Effects of GHRH Antagonists on Human GH-Secreting Adenoma Tissue

Inhibitory Effects of GHRH Antagonists on Human GH-Secreting Adenoma Tissue

Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome

Preoperative lanreotide treatment in acromegalic patients with macroadenomas increases short-term postoperative cure rates: a prospective, randomised trial

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