GH-secreting Pituitary Macroadenoma Research Articles

Prognostic Factors of Acromegalic Patients with Growth Hormone–Secreting Pituitary Adenoma After Transsphenoidal Surgery

Acromegaly is a rare, chronic disorder that mostly results from growth hormone (GH)-secreting pituitary adenoma. Transsphenoidal surgery is the first-line treatment of this adenoma. This study aimed to identify factors associated with remission outcome in patients with GH-secreting pituitary adenomas following transsphenoidal surgery. Patients with GH-secreting pituitary adenomas who underwent transsphenoidal surgery for tumor removal at Songklanagarind Hospital between January 2003 and December 2019 were retrospectively reviewed. The primary outcome was the remission of disease at the last follow-up using 2000 and 2010 consensus criteria. Using logistic regression analysis, various factors were analyzed for association with disease remission outcome. This study included 51 patients. The remission rate of GH-secreting pituitary microadenomas and macroadenomas following transsphenoidal surgery were 100% and 43.75%, respectively. Multivariate analysis showed that preoperative insulin-like growth factor 1 index ≥2.5 and Knosp classification grade 3-4 were significantly associated with nonremission outcome (P < 0.001 and P=0.012, respectively). Patients with both of these factors had poor outcomes and never achieved remission after treatment, while patients with neither of these factors had high remission rates (87.5%) following surgery. Four of 6 (66.7%) patients who underwent repeat surgery gained remission. Preoperative insulin-like growth factor 1 index ≥2.5 and Knosp classification grade 3-4 were important prognostic factors that determined remission outcome after treatment. Patients who have both of these poor prognostic factors should be aggressively treated with surgery, medication, and probably radiation to optimally control the disease.

Presurgical somatostatin receptor ligand treatment does not affect tumor consistency in GH-secreting pituitary macroadenomas.

PurposeTo evaluate whether presurgical treatment using long-acting somatostatin receptor ligands (SRL) may change pituitary tumor consistency and improve surgical outcome in GH-secreting pituitary macroadenomas.MethodsRetrospective study of 40 patients with GH-secreting pituitary macroadenomas operated for the first time by endoscopic transsphenoidal approach. Tumor consistency was evaluated intraoperatively and then correlated with histopathological fibrosis parameters and surgical outcomes. Surgical remission was reported based on the 2010 criteria.ResultsThe mean tumor size of GH-secreting macroadenomas was of 16.9 ± 8.2 mm and 25 were invasive pituitary adenomas (PAs). Presurgical treatment with long-acting SRL was performed in 17 patients (11 lanreotide, 6 octreotide). The cure rate was higher in those patients pre-treated with monthly doses ≥30 mg of octreotide or ≥90 mg of lanreotide than in those treated with lower doses or untreated (8/11 (72.7%) vs 11/29 (37.9%), P = 0.049). However, although the proportion of soft tumors increased as higher doses of SRL were considered in the pre-treated group, no statistical significance was reached, even when the highest approved monthly doses were used (6/6 (100%) vs 23/34 (67.7%), P = 0.102). Moreover, we found that the remission rate was similar between fibrous and soft tumors (P = 0.873) and also of surgical complications (P = 0.859), despite of the higher prevalence of Knosp >2 (P = 0.035) and very large PA (P = 0.025) in fibrous tumors than in soft tumors.ConclusionsAlthough presurgical treatment with high doses of SRL was associated with a 2.2-fold greater chance of surgical remission, this benefit was not related with changes in tumor consistency induced by the presurgical treatment.

Reappraisal of microscopic microsurgical transsphenoidal surgery for GH-secreting pituitary macroadenoma in patients with acromegaly: Historical data from Vietnam (2010–2013)

ObjectiveIn Vietnam, microscopic transsphenoidal surgery has been implemented to treat acromegaly patients since 2000. However, no specific outcome studies have been conducted. We assess outcomes of this technique and factors associated with remission. MethodsThis prospective observational study was conducted in 43 patients with acromegaly resulting from Growth Hormone (GH)-secreting pituitary macroadenoma. The primary outcome of interest was remission status, as defined by random GH levels below 2.5 ng/mL and Insulin-like Growth Factor-1 (IGF-1) within the normal range three months post-operation. ResultsThe proportion of patients with remission three months after surgery was 69.8% with a 95% confidence interval (CI) = 53.9–82.8%. The proportions of residual tumors three months after surgery in the remission and non-remission groups were 10.0% (3/27) and 23.1% (3/10), respectively, but there was no significant difference between these proportions (Fisher's exact test, p = 0.35). In a multivariate logistic regression analysis adjusted for sex and age, remission was associated with the absence of cavernous sinus invasion, with an odds ratio (OR) = 5.2 (95% CI = 1.1–26.5). In addition, remission was also associated with a post-operative GH level < 2.5 ng/mL (OR = 7.4, 95% CI = 1.1–48.0). ConclusionWe report that the proportion of patients with disease remission three months after surgery was high, indicating that microscopic transsphenoidal surgery was efficacious. More studies should be conducted to assess outcomes of various acromegaly treatment methods in the current context of Vietnam.

A Rare Case of Acromegaly and Autosomal Dominant Polycystic Kidney Disease: Case Report and Brief Review of Literature

Acromegaly is a classic endocrine disorder caused by a growth hormone (GH)-secreting pituitary adenoma in an overwhelming majority of patients. The diagnosis may be delayed by several years due to the slow growing and insidious nature of the disease. Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by multiple renal cysts and various other systemic manifestations. The purpose of this article is to report a rare case of acromegaly with coexistent ADPKD. We report a case of 42-year-old female with acromegaly and ADPKD along with a brief review of literature. The patient was referred to us for evaluation of progressive acral enlargement and coarsening of facial features. Endocrine evaluation confirmed the diagnosis of acromegaly due to an underlying GH-secreting pituitary macroadenoma. She was also found to have ADPKD. We discuss the clinical features and management of the patient. The association of pituitary adenomas and ADPKD is very rare and interesting. All affected individuals with pituitary adenomas and ADPKD in the literature are women. Furthermore, all reported pituitary adenomas in these individuals (including ours) are functional GH-secreting ones. These findings argue against a mere chance association between the two diseases.

Long-Term Effects of Intracapsular Debulking and Adjuvant Somatostatin Analogs for Growth Hormone-Secreting Pituitary Macroadenoma: 10 Years of Experience in a Single Institute

Long-term effects of endoscopic endonasal transsphenoidal intracapsular debulking and adjuvant somatostatin analogs (SSAs) were evaluated in patients with growth hormone- (GH) secreting pituitary macroadenomas. We retrospectively reviewed the medical records of 45 patients with acromegalic macroadenoma who underwent endonasal endoscopic transsphenoidal intracapsular debulking and received adjuvant SSAs (octreotide) between 2006 and 2015 who had >1 year of follow-up. To evaluate the predictive factors for 1 year and long-term biochemical outcomes, univariate and multivariate analyses were performed. Biochemical remission was achieved in 1 year in 20 of the 45 (44.4%) patients, and in 31 of the 45 patients after long-term adjuvant SSA treatment. Tumor control was achieved in 43 of the 45 (93.3%) patients. The univariate analysis showed age (≥55 years), tumor size (diameter ≤1.5 cm), premedication GH levels (≤2.8 ng/mL), premedication insulin-like growth factor 1 levels (≤2-fold of upper limit of normal range), cavernous sinus invasion (Knops grades 2, 3, and 4), and near-total tumor resection were associated with long-term outcomes. The multivariate analysis showed near-total resection was a significant predictor for long-term outcomes (P= 0.019). There were no new pituitary dysfunctions. The observed complications included one case of cerebrospinal fluid leakage and one case of epistaxis requiring intervention. Intracapsular debulking and adjuvant SSAs are a safe and viable treatment for patients with GH secreting pituitary macroadenoma to achieve biochemical remission and tumor control. Although adjuvant SSA treatment enhances residual tumor control, cavernous sinus invasion impedes the remission of endocrine tumors.

MRI T2 signal intensity and tumor response in patients with GH-secreting pituitary macroadenoma: PRIMARYS post-hoc analysis.

Objective Pituitary adenoma MRI T2 signal intensity associates with tumor characteristics including responsiveness to somatostatin analogs (SSAs). These analyses determined whether baseline T2 signal intensity predicts response to primary medical treatment with long-acting SSA. Design Post-hoc analyses of the prospective multicenter, open-label, single-arm PRIMARYS study in which patients with treatment-naïve GH-secreting pituitary macroadenomas received fixed-dose lanreotide autogel (120mg) every 4-weeks for 48-weeks. Methods Associations were investigated between adenoma T2-signal hypo/iso/hyperintensity and treatment responses at week 48/last visit: hormonal control (GH ≤2.5μg/L and IGF-1 normalization); tumor response (tumor volume reduction [TVR] ≥20%); separate GH/IGF-1 control; and change-from-baseline in GH/IGF-1 and tumor volume. Results Adenomas were hypointense at baseline in 50/85 (59%) patients using visual assessment. Of these, 40% achieved hormonal control and 76% achieved a tumor response. Significant univariate associations arose for hypo- vs isointensity with tumor response and achievement of GH ≤2.5 μg/L, but not IGF-1 normalization or overall hormonal control. In multivariate analysis, tumor response was 6-times more likely for hypo- vs isointense tumors (=6.15; 95% CI [1.36;27.88]). In univariate change-from-baseline analyses, hypo- vs isointensity was associated with greater TVR and IGF-1 reduction but not change in GH. In multivariate analysis, IGF-1 decreased by an estimated additional 65 μg/L [P=0.0026]) for hypo- vs isointense. Conclusions Patients with hypointense vs isointense GH-secreting macroadenomas had greater reductions in IGF-1 following primary treatment with lanreotide autogel, and were more likely to achieve tumor response. Assessment of T2 signal intensity at baseline may help to predict long-term responses to primary treatment with SSAs.

Predicting response to somatostatin analogues in acromegaly: machine learning-based high-dimensional quantitative texture analysis on T2-weighted MRI.

To investigate the value of machine learning (ML)-based high-dimensional quantitative texture analysis (qTA) on T2-weighted magnetic resonance imaging (MRI) in predicting response to somatostatin analogues (SA) in acromegaly patients with growth hormone (GH)-secreting pituitary macroadenoma, and to compare the qTA with quantitative and qualitative T2-weighted relative signal intensity (rSI) and immunohistochemical evaluation. Forty-seven patients (24 responsive; 23 resistant patients to SA) were eligible for this retrospective study. Coronal T2-weighted images were used for qTA and rSI evaluation. The immunohistochemical evaluation was based on the granulation pattern of the adenomas. Dimension reduction was carried out by reproducibility analysis and wrapper-based algorithm. ML classifiers were k-nearest neighbours (k-NN) and C4.5 algorithm. The reference standard was the biochemical response status. Predictive performance of qTA was compared with those of the quantitative and qualitative rSI and immunohistochemical evaluation. Five hundred thirty-five out of 828 texture features had excellent reproducibility. For the qTA, k-NN correctly classified 85.1% of the macroadenomas regarding response to SAs with an area under the receiver operating characteristic curve (AUC-ROC) of 0.847. The accuracy and AUC-ROC ranges of the other methods were 57.4-70.2% and 0.575-0.704, respectively. Differences in predictive performance between qTA-based classification and the other methods were significant (p < 0.05). The ML-based qTA of T2-weighted MRI is a potential non-invasive tool in predicting response to SAs in patients with acromegaly and GH-secreting pituitary macroadenoma. The method performed better than the qualitative and quantitative rSI and immunohistochemical evaluation. • Machine learning-based texture analysis of T2-weighted MRI can correctly classify response to somatostatin analogues in more than four fifths of the patients. • Machine learning-based texture analysis performs better than qualitative and quantitative evaluation of relative T2 signal intensity and immunohistochemical evaluation. • About one third of the texture features may not be excellently reproducible, indicating that a reliability analysis is necessary before model development.

GH-secreting pituitary macroadenoma (acromegaly) associated with progressive dental malocclusion and refractory CPAP treatment

BackgroundA link between progressive dental malocclusion, the use of a continuous positive airway pressure mask and GH-secreting pituitary macroadenoma (acromegaly) has not been previously reported. The present clinicopathological analysis stresses that tooth malposition should not be seen exclusively as a local process.Case presentationA 62-year-old caucasian man with no relevant medical history reported difficulty chewing food and perceived voice alteration during his annual periodontal check-up. He also referred stiffness of the tongue, face, and submandibular area. The patient had been diagnosed with obstructive sleep apnea syndrome two years previously, since when he had worn a continuous positive airway pressure device during sleep. Exploration of the occlusion revealed significant changes: an atypical left lateral and anterior open bite with major buccoversion of teeth 33, 34, 35, 36. Inspection of the soft tissue revealed only macroglossia, although external palpation indicated a subcutaneous stiffness of the submandibular area. General analytical tests, including hormone profiles, and magnetic resonance imaging confirmed the diagnosis of acromegaly induced by a pituitary adenoma. Intrasellar tumor resection via transsphenoidal approach was performed. After surgery, the patient already noted a marked improvement of all symptoms associated with the acromegaly. Desaturation data also evolved favourably and the pulmonologist advised the patient to abandon the continuous positive airway pressure treatment.ConclusionProgressive dental malocclusion may be associated with a systemic disease and the use of a nasal mask with premaxillary support may distort the diagnosis of acromegaly.

Treatment effects analysis of preoperative long-acting somatostatin analogs combined trans-sphenoidal endoscopic surgery for patients with growth hormone secreting pituitary macroadenomas

Objective: To evaluate the treatment effects of preoperative long-acting somatostatin analogue (SSA) combined trans-sphenoidal endoscopic surgery for patients with growth hormone (GH)-secreting pituitary macroadenomas. Methods: Retrospective analysis was carried out on 20 patients with GH-secreting pituitary macroadenomas who were treated with preoperative SSA and trans-sphenoidal endoscopic surgery in our apartment from January 2010 to January 2016. We also selected 20 patients with only trans-sphenoidal endoscopic surgery treatment and 20 patients with preoperative SSA and non-trans-sphenoidal endoscopic surgery treatment. The changes of tumor imaging, endocrine and blood pressure before and after treatment were analysed. Results: The Gross total resection (GTR) rate of invasive GH-secreting pituitary macroadenomas of preoperative SSA combined trans-sphenoidal endoscopic surgery group (8/13) were higher than that if only trans-sphenoidal endoscopic surgery group (4/16) and preoperative SSA combined non endoscopic surgery group (1/8) (P<0.05). Meanwhile, preoperative SSA combined trans-sphenoidal endoscopic surgery group had significantly improved the GH levels, blood glucose, lipid metabolism and blood pressure levels (P<0.05). Conclusion: The trans-sphenoidal endoscopic surgery on patients with GH-secreting pituitary macroadenomas has a significant improvement on GH levels, blood glucose, lipid metabolism and blood pressure levels. Through the treatment of preoperative long-acting SSA, the gross total resection rate is higher than other two groups.

Growth Hormone–Secreting Pituitary Carcinoma Presenting With Isolated Leptomeningeal Involvement: A Challenging Diagnosis

ABSTRACT Objective: To raise awareness of the clinical presentation of growth hormone (GH)-producing pituitary carcinoma and its unique clinical presentation. Methods: A case report of a GH-secreting pituitary carcinoma with predominant leptomeningeal spread presenting as persistent acromegaly post–macroadenoma excision and radiation therapy. Results: A 39-year-old male, diagnosed with a GH-secreting pituitary macroadenoma with acromegaly 3 years prior, presented with persisting acromegalic phenotypic features with associated diabetes mellitus and hypertension. He had undergone an endoscopic transnasal, transsphenoidal adenoma resection, followed 3 months later by conventional cranial irradiation at another center 2 years prior to his current presentation to us. Serum insulin-like growth factor 1 and post 1-hour 100-g oral glucose administration serum GH levels were 1,198 and 393 ng/mL, respectively. Magnetic resonance imaging of the brain with spine screening revealed an empty sella, diffuse enhancing co...

Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.

Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75%) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.

Evaluation of MRI T2-signal intensities of GH-secreting pituitary macroadenoma in treatment-naive acromegalic patients receiving primary treatment with lanreotide autogel (LAN-ATG) 120 mg

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Cost-effectiveness analysis of preoperative treatment of acromegaly with somatostatin analogue on surgical outcome

ContextThere is no uniform standard of care for acromegaly. Due to the high costs involved, steps must be taken to ensure the cost-effective delivery of treatment. ObjectiveTaking the results of an earlier meta-analysis as a starting point, this study aims to determine whether treatment with long-acting somatostatin analogue (SSA) prior to surgery improves the cost-effectiveness of the treatment of acromegaly. MethodsThe results are presented as an Incremental Cost Effectiveness Ratio (ICER) immediately after surgery, for the following year and over the next four decades. The cure rates percentage (95% CI) for the three randomized prospective controlled trials were 44.4% (34.2–54.7) and 18.2% (10.1–26.3) for preoperative treated and untreated patients respectively. The cost of pharmacological treatments was based on the number of units prescribed, dose and length of treatment. ResultsThe mean (95% CI) ICER immediately after surgery was €17,548 (12,007–33,250). In terms of the postoperative SSA treatment, the ICER changes from positive to negative before two years after surgery. One decade after surgery the ICER per patient/year was €−9973 (−18,798; −6752) for postoperative SSA treatment and €−31,733 (−59,812; −21,483) in the case of postoperative pegvisomant treatment. ConclusionsIn centres without optimal surgical results, preoperative treatment of GH-secreting pituitary macroadenomas with SSA not only shows a significant improvement in the surgical results, but is also highly cost-effective, with an ICER per patient/year one decade after surgery, of between €−9973 (−18,798; −6752) and €−31,733 (−59,812; −21,483) for SSA and pegvisomant respectively.

Preoperative somatostatin analogs treatment in acromegalic patients with macroadenomas. A meta-analysis.

Several studies have investigated the biochemical remission rate of presurgical somatostatin analogs treatment on acromegaly, but the remission criteria were diversed and the results were contradicting. Aim of this paper is to provide enhanced evidence for the effectiveness of preoperative SSA treatment to improve on surgical results of macroadenomas in acromegaly. Literature is cited from the PubMed, Embase and Cochrane Library, dating from December, 1985 to August, 2013. Eligibility criteria included patients with acromegaly caused by GH-secreting pituitary macroadenomas, patients pretreated with somatostatin analogs versus direct surgery and a stricter remission criteria defined as the GH nadir<1μg/l during an oral glucose tolerance test (OGTT) and the age- and sex- adjusted IGF-1 concentration was normal. Primary end points included Short term and long term postoperative biochemical remission. A total of 1421 publications were found by the electronic search. After full-text review, 8 were included in our study. 7 of them focus on the postoperative remission in short term; 3 of them focus on the outcomes in long term. For the analysis of the postoperative biochemical remission, a random effect model was used to account for differences. The meta analysis shows that patients in the SSA pretreatment groups have had a more significantly cure rate than those in the direct surgery groups (RR=1.72, 95%CI: 1.14-2.60, P=0.009) with a short term follow-up. Subgroup analysis proves benefit from lanreotide pretreated groups (RR=2.27, 95%CI: 1.34-3.84, P=0.002) but not octreotide pretreated groups (RR=1.51, 95%CI: 0.82-2.75, P=0.183). No significant differences appeared between the two groups (RR=1.03, 95%CI: 0.86-1.24, P=0.751) with a long term follow-up. 2 Retrospective trial was included and most of the trials included was designed as single-center study. Based on the analysis of this paper, the preoperative SSA treatment was beneficial in the group with short-term follow-up, while it was not advantageous in the group with long-term follow-up. For the limitations in this study, to drawn more solid conclusions, further large, randomized, multi-center, and long-term follow-up trials were required.

Place of Preoperative Treatment of Acromegaly with Somatostatin Analog on Surgical Outcome: A Systematic Review and Meta-Analysis

ContextTranssphenoidal neurosurgery is the accepted first-line treatment of acromegaly in the majority of patients. Previous studies addressing preoperative somatostatin analog (SSA) treatment and subsequent surgical cure rates are conflicting, reporting either benefits or no significant differences.ObjectiveThe aim of this study, based on a meta-analysis of all published reports, was to investigate whether treatment with SSA before surgery improves the surgical outcome of acromegaly.Data SourcesAll studies of preoperative treatment of acromegaly with SSA were systematically reviewed up to December 2011. We searched the Medline, Embase, Cochrane and Google Scholar electronic databases. Study Selection: The primary endpoint was the biochemical postoperative cure rate. We identified 286 studies, out of which 10 studies (3.49%) fulfilling the eligibility criteria were selected for analysis; five retrospective studies with a control group, two prospective non-randomized trials, and three prospective controlled trials. The meta-analysis was conducted using the random-effects model.Data ExtractionData were extracted from published reports by two independent observers. Data Synthesis: A borderline effect was detected in the analysis of all of the trials with control groups, with a pooled odds ratio (OR) for biochemical cure with SSA treatment of 1.62 (95% CI, 0.93–2.82). In the analysis of the three prospective controlled trials, a statistically significant effect was idenfified OR: 3.62 (95% CI, 1.88–6.96).ConclusionsPreoperative treatment with SSA og GH-secreting pituitary adenomas shows a significant improvement on surgical results. This meta-analysis suggests that in centers without optimal results all patients with a GH-secreting pituitary macroadenoma should be treated with a long-acting SSA prior to surgical treatment.

Tumour volume reduction and GH/IGF1 control with lanreotide Autogel 120 mg every 28 days for treatment-naive acromegalic patients with GH-secreting pituitary macroadenoma: the PRIMARYS study

Tumour volume reduction and GH/IGF1 control with lanreotide Autogel 120 mg every 28 days for treatment-naive acromegalic patients with GH-secreting pituitary macroadenoma: the PRIMARYS study

Early and sustained tumour volume reduction and GH/IGF1 control in patients with GH-secreting pituitary macroadenoma primarily treated with lanreotide Autogel 120 mg for 48 weeks: the PRIMARYS study

Early and sustained tumour volume reduction and GH/IGF1 control in patients with GH-secreting pituitary macroadenoma primarily treated with lanreotide Autogel 120 mg for 48 weeks: the PRIMARYS study

Acromegaly and Pregnancy: A Retrospective Multicenter Study of 59 Pregnancies in 46 Women

Few data are available on pregnancy outcomes in women with acromegaly. This was a retrospective multicenter study. The study included 46 women with GH-secreting pituitary microadenomas (n = 7) or macroadenomas (n = 39). Their mean age was 31.7 yr (±4.5 yr). Incomplete transsphenoidal surgical resection (n = 39) and pituitary radiation (n = 14) had been performed, respectively, 2.9 ± 2.6 and 7.3 ± 4.2 yr before pregnancy. The patients were receiving dopamine agonists (n = 25) and/or somatostatin analogs (n = 14), and GH/IGF-I hypersecretion was controlled and uncontrolled in, respectively, 23 and 34 cases. Five pregnancies followed the fertility treatment. Fifty-nine pregnancies resulted in 64 healthy babies. Gestational diabetes and gravid hypertension occurred in four (6.8%) and eight (13.6%) pregnancies, respectively, and both were more frequent when GH/IGF-I hypersecretion was not controlled before pregnancy. Visual field defects were diagnosed during pregnancy in four women, three of whom were diagnosed with acromegaly during the pregnancy. Seven women had isolated headache. Magnetic resonance imaging performed 3.9 ± 0.3 months after delivery showed that the size of the adenoma had increased in three cases, decreased in two cases, and remained stable in 22 cases. Seventeen women breast-fed with no complications. Four women gave birth to a small-for-gestational-age infant; all had received somatostatin analogs, alone or in combination with dopamine agonists, during pregnancy. The mean IGF-I level fell significantly during the first trimester in 12 cases (before conception 588 ± 207 ng/ml, first trimester 319 ± 126 ng/ml, P = 0.002), whereas the GH concentration did not change significantly. The following conclusions were reached: 1) pregnancy in women with active or uncontrolled acromegaly may be associated with an increased risk of gestational diabetes and gravid hypertension; 2) pregnancy is occasionally associated with symptomatic enlargement of GH-secreting pituitary macroadenomas; 3) changes in serum GH and IGF-I concentrations are variable during pregnancy, indicating that routine monitoring is not mandatory if the pregnancy is uneventful; and 4) GH-suppressive treatment can be safely withdrawn after conception in most acromegalic women.

Failure of temozolomide and conventional doses of pegvisomant to attain biochemical control in a severe case of acromegaly

It has been suggested that treatment with adequate dose titration of pegvisomant, a GH antagonist, up to a maximum of 40 mg daily, can achieve IGF-1 normalisation in virtually all patients with acromegaly. On the other hand, temozolomide (TMZ), an alkylating cytostatic agent, has been reported to reduce pituitary tumour size and hormone hypersecretion in a small number of aggressive pituitary macroadenomas. In this paper we report the case of a patient resistant to very high doses of pegvisomant used in combination with somatostatin analogs (SSA) and to TMZ therapy. The patient, initially a 22 year-old man with an invasive GH-secreting pituitary macroadenoma (IGF-1, 371% upper limit of normal), had active acromegaly despite a repeat transsphenoidal surgery followed by radiotherapy and SSA (octreotide 800 μg sc daily) (IGF-1, 262% ULN). In combination with SSA, pegvisomant was started at 20 mg daily and doses were titrated up to 60 mg daily. IGF-1 was moderately reduced and stabilized at 200% ULN after 1 year of treatment. Serum pegvisomant level was 30,500 ng/l, the denaturalized GHBP concentration 1,120 pM and the endogenous GH level was 220 μg/l. Pegvisomant was stopped and TMZ therapy was given for 5 cycles. However, the patient reported an increase of acromegaly symptoms and the serum IGF-1 was raised to the same level prior to pegvisomant therapy. Consequently, pegvisomant was tried again with doses up to 100 mg daily finally resulting in normalisation of serum IGF-1 level and improvement of acromegaly symptoms and patient well-being. We conclude that in some patients with severe acromegaly refractory to multimodal therapy, biochemical control may be difficult to attain with conventional doses of pegvisomant or TMZ therapy.

Complete disappearance of a GH-secreting pituitary macroadenoma in a patient with acromegaly: effect of treatment with lanreotide Autogel and consequence of treatment withdrawal

Somatostatin analogs (SA) are the cornerstone in the medical treatment of acromegaly, used as either primary or adjunctive therapy. In particular, SA are effective in inducing the biochemical remission of the disease and tumor shrinkage, although only few cases of complete disappearance of the pituitary tumor in patients treated with SA as long-acting formulations have been reported. SA withdrawal has been demonstrated to keep safe levels of GH and IGF1 at least in a small subset of patients well responsive to SA, although it is generally followed by disease recurrence after several months. A 61-year-old female patient bearing a very large GH-secreting pituitary macroadenoma was treated with 12-month lanreotide Autogel (ATG), at the initial dose of 120 mg/28 days. After 3 months, GH and IGF1 levels were fully normalized, to prolong the administration interval from 28 to 56 days. After 6 months of treatment, a significant tumor shrinkage (90% of baseline size) was observed, whereas GH and IGF1 excess was still well controlled. After 12-month therapy, a complete disappearance of the pituitary tumor was observed, and the hormonal evaluation confirmed the complete biochemical remission of acromegaly. Lanreotide ATG treatment was withdrawn. The clinical, biochemical, and radiological remission of acromegaly was maintained 24 months after lanreotide ATG treatment discontinuation, without evidence of disease recurrence. This report represents an exemplary case of the potentiality of treatment with lanreotide ATG in inducing a complete remission of acromegalic disease, persistent after a long period of time from treatment withdrawal.