The value of an acute octreotide suppression test in predicting long‐term responses to depot somatostatin analogues in patients with active acromegaly

Karavitaki, Niki; Botusan, Ileana Ruxandra; Radian, Șerban; Coculescu, Mihail; Turner, Helen; Wass, John

doi:10.1111/j.1365-2265.2004.02191.x

Cited by 53 publications

(43 citation statements)

References 33 publications

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“…The overall predictive power of the test is, however, suboptimal. The nadir GH during OGTT is correlated with safe GH and IGF1 during OCT-LAR but less so for LAN (Karavitaki et al 2005). Also, the tumoral response under SSA is only modestly correlated with the OCT test (Annamalai et al 2013).…”

Section: Medical Treatmentmentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

Căpățînă¹,

Wass²

2015

Journal of Endocrinology

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Acromegaly (ACM) is a chronic, progressive disorder caused by the persistent hypersecretion of GH, in the vast majority of cases secreted by a pituitary adenoma. The consequent increase in IGF1 (a GH-induced liver protein) is responsible for most clinical features and for the systemic complications associated with increased mortality. The clinical diagnosis, based on symptoms related to GH excess or the presence of a pituitary mass, is often delayed many years because of the slow progression of the disease. Initial testing relies on measuring the serum IGF1 concentration. The oral glucose tolerance test with concomitant GH measurement is the gold-standard diagnostic test. The therapeutic options for ACM are surgery, medical treatment, and radiotherapy (RT). The outcome of surgery is very good for microadenomas (80-90% cure rate), but at least half of the macroadenomas (most frequently encountered in ACM patients) are not cured surgically. Somatostatin analogs are mainly indicated after surgical failure. Currently their routine use as primary therapy is not recommended. Dopamine agonists are useful in a minority of cases. Pegvisomant is indicated for patients refractory to surgery and other medical treatments. RT is employed sparingly, in cases of persistent disease activity despite other treatments, due to its long-term side effects. With complex, combined treatment, at least three-quarters of the cases are controlled according to current criteria. With proper control of the disease, the specific complications are partially improved and the mortality rate is close to that of the background population.

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Section: Medical Treatmentmentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

Căpățînă¹,

Wass²

2015

Journal of Endocrinology

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“…After surgery, if unsuccessful, long-term treatment with SSAs is the most common therapy and around half of patients achieve 'safe' GH levels (23) (reviewed in (24)). Various factors have been reported to predict patient response to long-term SSA therapy, including tumour size, pretreatment serum GH levels, somatostatin receptor density and response to the octreotide suppression test (OST) (16,23,25,26,27,28). A GH nadir of !1.75 mg/l upon acute administration of 100 mg octreotide during the OST had a positive predictive value of 94% and a negative predictive value of 100% for achievement of 'safe' mean GH levels upon therapy with long-acting octreotide (23).…”

Section: Gh-secreting Adenomas Exist As Distinct Morphological Subtypesmentioning

confidence: 99%

“…Various factors have been reported to predict patient response to long-term SSA therapy, including tumour size, pretreatment serum GH levels, somatostatin receptor density and response to the octreotide suppression test (OST) (16,23,25,26,27,28). A GH nadir of !1.75 mg/l upon acute administration of 100 mg octreotide during the OST had a positive predictive value of 94% and a negative predictive value of 100% for achievement of 'safe' mean GH levels upon therapy with long-acting octreotide (23). This finding was supported by a similar study in which GH nadir !1.67 mg/l during the OST predicted achievement of 'safe' GH levels after long-term depot SSA treatment with 80% sensitivity and 83% specificity (29).…”

Section: Gh-secreting Adenomas Exist As Distinct Morphological Subtypesmentioning

confidence: 99%

Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naïve patients with somatotroph adenomas

Larkin

Reddy

Karavitaki

et al. 2013

European Journal of Endocrinology

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112

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Objective: Somatotroph adenomas causing acromegaly are histologically classified into densely granulated (DG) and sparsely granulated (SG) subtypes with different morphology, clinical characteristics and treatment outcomes. Granulation pattern has been reported to co-segregate with a recurrent mutation at codon 49 in growth hormone receptor (GHR) and GSP oncogene. This study examines response to the octreotide suppression test (OST) in relation to granulation pattern and mutation in GHR and GSP. Design: This is a retrospective, single-centre study of 52 patients with pathologically confirmed somatotroph adenoma who were naïve to medical therapy presenting between January 2001 and October 2010. Methods: Clinical, radiological and hormonal data at diagnosis were recorded. GHR and GSP were genotyped, granulation pattern determined and response to the OST measured. Results: SG adenomas were larger (PZ0.038), occurred in younger patients (PZ0.029), were more common in females (PZ0.026) and were more invasive (P!0.0001 and PZ0.001), with diminished responses to the OST (PZ0.007) compared with DG adenomas. GSP mutation was unrelated to granulation pattern but associated with smaller tumours (PZ0.027), producing more GH (PZ0.048) that responded better to the OST (PZ0.022). Codon 49 of GHR was not mutated. Conclusions: Adenoma histological phenotype, not genotype, corresponds to clinical and biochemical characteristics and response to the OST. SG adenomas constitute a clinically more unfavourable subtype but are not associated with GHR mutations in our series. Ascertainment of the adenoma subtype may become an important consideration in the management of acromegaly.

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“…Also, attaining GH levels below 5 mg/l after 3 months and IGF-I levels below 550 mg/l after 6 months of SA treatment appears to be good positive predictors of long-term control (7). GH suppression test, following a single s.c. injection of octreotide, has been extensively studied with variable results (8)(9)(10)(11)(12)(13)(14)(15). Scintillography with 111 In-pentetreotide (Octreoscan) has also been studied, with limited success at predicting SA-mediated disease control (14,16,17).…”

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

Taboada

Luque

Neto

et al. 2008

European Journal of Endocrinology

160

110

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Objective: To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment. Design and methods: Quantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging). Results: SSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046-5555), 2098, 97 (0-460), 14 (0-29 480), and 0 (0-652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (rZ0.49, P!0.027 and rZ0.49, P!0.029 respectively) and 6 (rZ0.59, P!0.006 and rZ0.58, P!0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (rZK0.52, PZ0.016, nZ21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7-10) vs 0.3 (0.1-7.7), PZ0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% -area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (rZ0.79, PZ0.002, nZ12). Conclusions: Somatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR. European Journal of Endocrinology 158 295-303

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The value of an acute octreotide suppression test in predicting long‐term responses to depot somatostatin analogues in patients with active acromegaly

Cited by 53 publications

References 33 publications

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naïve patients with somatotroph adenomas

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

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