Implementing a screening program for acromegaly in Latin America: necessity versus feasibility.

INTRODUCTION: Acromegaly is a rare disease with a large burden due its associated comorbidities and the life-long management required. Since the occurrence and severity of associated complications are related to length of exposure to the excess growth hormone seen in acromegaly, early diagnosis is imperative. The delay in diagnosis, however, can be long, and may be the result of a lack of disease awareness and screening programs. Since acromegaly is an uncommon disease, finding ways to increase recognition and diagnosis that would permit early detection in a logical and cost-effective manner could be a challenge. METHODS: We conducted a retrospective literature review for information relating to the screening and diagnosis of acromegaly using PubMed. The aim was to assess whether an acromegaly-screening program in Latin America (and elsewhere) would be both of use and be feasible. FINDINGS AND CONCLUSIONS: An earlier diagnosis allows earlier initiation of treatment, such as surgery and/or drugs, which leads to more successful disease management (biochemical control) and better outcomes. Since the delay in diagnosis can be long, we believe that clear opportunities exist for earlier (and increased) detection of acromegaly. This can be achieved by increasing disease awareness for earlier recognition of symptoms and by using targeted screening (rather than mass screening) programs.

CONDITIONING FACTORS FOR HIGH CARDIOVASCULAR RISK IN PATIENTS WITH CUSHING SYNDROME.

OBJECTIVE: To characterize the alterations in carbohydrate and lipoprotein metabolism, to evaluate markers of lipoprotein functionality, and to identify the presence of novel atherogenic risk factors in patients with Cushing syndrome (CS) in comparison with sex- and age-matched controls. METHODS: In an open, cross-sectional study, 32 nontreated patients with active CS were consecutively recruited from the Endocrinology Service at "José de San Martín" Clinical Hospital, University of Buenos Aires, Argentina, between April 11, 2010 and December 11, 2012. The patients were compared with sex- and age-matched controls. RESULTS: Versus controls, patients with CS presented with excess weight, central obesity, and hypercortisolism. They also exhibited an insulin-resistant state, with high resistin levels (median [interquartile range], 16 [10 to 22] ng/mL versus 6 [5 to 9] ng/mL; P<.0001), a more atherogenic lipoprotein profile, high oxidized low-density lipoprotein levels (oxLDL; mean ± SD, 100 ± 31 U/L versus 75 ± 32 U/L; P<.05) and high sensitive C-reactive protein levels (median [interquartile range], 1.2 [0.6 to 3.1] mg/L versus 0.6 [0.3 to 1.1] mg/L; P<.05), and increased leukocyte count (mean ± SD, 9.5 ± 2.6 × 10(3) cells/µL versus 6.5 ± 1.4 × 10(3) cells/µL; P<.0001). Multivariate analyses showed that the increase in waist circumference was associated with both the diagnosis of CS and the degree of insulin resistance. Resistin concentration was related to a greater extent to the diagnosis of CS than to homeostasis model assessment-insulin resistance. Triglyceride and oxLDL levels were only significantly associated with the diagnosis of CS. CONCLUSION: Hypercortisolism is related to the increase observed in triglycerides and oxLDL levels, and, in combination with insulin resistance, acts to increase waist circumference and amplify the inflammatory process, key factors for the development of cardiovascular disease.

Aggressive tumors and difficult choices in acromegaly.

PURPOSE: The current article looks at some of the factors associated with pituitary adenomas displaying unusually aggressive biological and clinical behaviour in patients with acromegaly. METHODS: This was a retrospective, narrative review of previously published evidence chosen at the authors' discretion and presented from the perspective of a Latin American case study. FINDINGS AND CONCLUSIONS: Although most pituitary tumors in acromegalic patients are benign and non-aggressive many can behave more aggressively, compromising local surrounding structures. These lesions tend to respond poorly to somatostatin analogs, have a higher risk of recurrence after surgery and, thus, a worse prognosis. Patients with more aggressive tumors constitute a particular challenge, as they often require several therapeutic approaches and may be difficult to manage, especially when options are restricted due to limited resources.

[Pseudo-pituitary tumor and hypopituitarism secondary to a sphenoid sinus inverted papilloma]. / Pseudo-tumor pituitario e hipopituitarismo secundario a un papiloma invertido del seno esfenoidal.

Inverted papilloma (IP) is a benign uncommon epithelial tumor, arising mostly from the lateral nasal wall. Though benign, this lesion is highly invasive into surrounding tissues and malignant transformation may occur. Primary IP of the sphenoid sinus and intracranial extension with dural invasion, even without histological evidence of malignancy, has only rarely been described. Hypopituitarism as a complication of this lesion has never been reported. We describe the case of a 59-year-old woman who was evaluated because of a 5-year-history of severe headaches and abnormalities in the visual field. Magnetic resonance imaging (MRI) showed a 1.4 per 2.0 cm heterogeneous sellar lesion with suprasellar and sphenoid sinus extension, eroding the sellar floor with optic chiasm compression. Otolaryngologists gave her 16 mg/day of prednisone during approximately 3 months with a near total regression of the mass on MRI. The endocrine biochemical evaluation showed pituitary gonadal, thyroid and adrenal insufficiency. A new MRI showed growth of the tumor with obliteration of the sphenoid sinus. An endoscopic sinus biopsy revealed an IP, so a transnasal endoscopic sinus surgery was performed with complete resection evidenced by MRI a year later.

Macrocorticotropinoma shrinkage and control of hypercortisolism under long-term cabergoline therapy: case report.

Cushing's disease is the result of chronic overproduction of ACTH by a pituitary tumor. Although the optimal treatment is surgical removal of the adenoma, medical treatment might be an option in selected cases. A 40-year old woman with Cushing's disease was treated with cabergoline, a neuromodulatory drug, for a corticotrophic macroadenoma. Treatment was initiated at a weekly dose of 0.5 mg and then, on the basis of the evolution of UFC values, adjusted until it reached 6 mg/week. With cabergoline treatment the patient was asymptomatic, the pituitary adenoma showed a significant shrinkage on MRI and urinary cortisol excretion remained within the normal range during 7 years. We show the effectiveness of cabergoline in maintaining long-term biochemical control of hypercortisolism with significant reduction and stabilization of macroadenoma volume in a patient with Cushing's disease.

Comparison of two immunoassays in the determination of IGF-I levels and its correlation with oral glucose tolerance test (OGTT) and with clinical symptoms in acromegalic patients.

The aim of our study was to evaluate two different methodologies in IGF-I levels determination, its correlation with GH nadir in OGTT <1 and <0.4 ng/ml and with clinical symptoms in acromegalic patients. We analyzed 37 patients. Sixteen patients had not undergone any kind of treatment (Group 1). Twenty-one patients underwent surgery as primary treatment, and after that, some of them another kind of treatment (except pegvisomant) (Group 2). Serum IGF-I levels were measured by Immulite-1000 (IMM) and by an immunoradiometric assay (DSL) and, GH by immunochemiluminometric assay. IGF-I levels by IMM and by DSL showed a significant difference. When we analyzed in both groups the concordance by crosstabs-Kappa coefficients, between different parameters, GH nadir <1 and <0.4 ng/ml with IGF-I by DSL and IMM showed concordance in group 1, but in group 2 only GH nadir <1 and <0.4 ng/ml had a weak concordance with IGF-I by IMM. When we analyzed clinical symptoms in the patients and, GH nadir <1 and <0.4 ng/ml and IGF-I levels by both methodologies, more than 90% of clinically active patients had abnormal GH response or/and elevated IGF-I levels in group 1, but less than 70% in group 2. In the 8 patients under medical treatment, GH nadir was higher than 0.4 ng/ml in all patients, and IGF-I levels were elevated in 8/8 by DSL and in 6/8 by IMM. In conclusion, discrepant GH and IGF-I levels in the diagnosis and follow-up of patients with acromegaly requires consideration of many factors that influence these parameters.

Effects of cabergoline on pregnancy and embryo-fetal development: retrospective study on 103 pregnancies and a review of the literature.

The aim of the study is to assess the rate of any potential adverse effects on women who became pregnant under cabergoline (CAB) treatment and to evaluate any effects on the embryo-fetal development and on children who were born from mothers exposed to CAB in early weeks of gestation. Observational, retrospective and multicenter study on 103 pregnancies in 90 women with hyperprolactinemia. All patients were under CAB at conception. Serum prolactin at baseline was between 30 and 1921 ng/ml. Duration of therapy before pregnancy ranged from 1 to 120 months and doses ranged from 0.125 to 5 mg/week. Fetal exposure ranged from 3 to 25 weeks, 96.9% of patients received CAB during the first trimester of pregnancy and the rest until the second one. No significant complications during pregnancy were found. Seven women (7.2%) had spontaneous abortions. Preterm deliveries were recorded in eight (8.8%), only one with low weight for gestational age. Neonatal abnormalities were observed in 3 (3.6%): 1 major (Down syndrome) and 2 minor malformations (umbilical and inguinal hernia). We were able to asses the children's development in 61. Two had epilepsy and two had Pervasive Developmental Disorder (PDD). No significantly higher frequency of complications was found in pregnancies and/or offspring exposed to CAB than in the normal population. We registered 2 abnormalities in the development of the children: epilepsy and PDD. Larger series of patients are needed to assess the safety of this drug during pregnancy.

[Therapeutic management in 154 acromegalic patients]. / Enfoque terapéutico en 154 pacientes con acromegalia.

Acromegaly is a chronic, invalidating disease due in over 95% of cases to a growth hormone (GH) secreting pituitary adenoma. Its clinical manifestations are associated to local complications related to the tumor growth and/or to the metabolic consequences of GH excess. We report here our experience on 154 acromegalic patients. Surgical remission rate using stringent biochemical criteria was 32%, a figure relatively low due to the great number of patients bearing macroadenomas with invasive complications. Primary or adjuvant radiotherapy was able to obtain normalization of biochemical parameters in as much as 65.4% of treated patients. In only 14.0% of acromegalics drug therapy with dopaminergic agents was effective in controlling the disease. By contrast, somatostatinergic analogues were more effective, obtaining a clinical and biochemical remission in 45.7% of the patients. In summary, multimodal therapy of acromegaly can lead to a global safe control of the disease in 55.2% of the cases. The ongoing development of new drugs represents promising alternatives in the management of this disabling condition.

High prevalence of thyroid disorders in relatives of patients with familial papillary thyroid cancer.

In the familial form of papillary thyroid cancer (PTC), two or more members of the same family have to be affected with PTC. Prevalence is around 5% of all PTC. We performed a clinical analysis in 79 relatives of 16 patients of 7 unrelated kindred with the diagnosis of familial papillary thyroid carcinoma (FPTC). The results were compared with a control group. Thyroid palpation and TSH and TPO-Ab assessment was carried out in the relatives without a diagnosed PTC. Additionally, molecular analysis was performed in the sixteen affected patients. Clinical screening of the 79 family members showed the presence of goiter in 22/79 (29 %). This frequency was much higher than that observed in the control group (8.7%), p < 0.001. Hypothyroidism was found in 4 of the relatives (5%) vs. 2.5% observed in the control group, p < 0.01, and anti-thyroid antibodies (TPO-Ab) were positive in 14% of the relative's group vs. 10 % in the control group, (p = NS). In the molecular analysis, only a protooncogene TRK rearrangement was observed in family # 6. In conclusion, we found a higher incidence of goiter and hypothyroidism in the relatives of patients with FPTC. Nevertheless, TPO-Ab frequency was not different. No molecular abnormalities were indicative of a specific pattern in this subset of patients with FPTC.

[Analysis of a pituitary adenoma registry]. / Análisis de un Registro de adenomas pituitarios.

Collection and analysis of data obtained during the clinical treatment of pituitary tumours are of great utility in the decision making process, when facing clinical situations. We report here data on 519 from 670 patients with pituitary adenomas obtained from a computerized registry. Three hundred and forty five were females (66%) and 174 males (34%), aged 14-80. Final diagnosis was acromegaly in 176, Cushing's disease in 153, prolactinoma in 101 and clinically non-functioning adenoma in 89. Mean age at diagnosis was 43.9 ± 13.5 (16-80) for acromegalics, 35.7 ± 12.9 (14-72) for Cushing's, 30.0 ± 13.4 (15-79) for prolactinoma and 52.1 ± 15.2 (17-79), for non-functioning tumours. The setup of an institutional registry on pituitary tumours constitutes a useful tool to analyze clinical experience, optimize the cost/benefit ratio of procedures used for diagnosis and to ameliorate therapeutic strategies, improving patient's care. It greatly contributes to teaching medical students as well as to post-graduate physicians and provides a basis for developing clinical research.

Long-term outcome after bilateral adrenalectomy in Cushing's disease with focus on Nelson's syndrome.

OBJECTIVE: We analyzed the clinical, biochemical, and imaging findings of adrenalectomized patients with Cushing's disease (CD) in order to compare the characteristics of those who developed Nelson's syndrome (NS) versus those who did not develop this complication (NNS), aiming to identify possible predictive factors for its occurrence. SUBJECTS AND METHODS: We performed a retrospective review of the clinical records of a group of patients with CD who underwent TBA between 1974 and 2011. RESULTS: Out of 179 patients with CD, 13 (7.3%) underwent TBA. NS occurred in 6 of them (46%) after a mean of 24 months from the total bilateral adrenalectomy (TBA). Age at diagnosis, duration of Cushing's syndrome (CS) until TBA, and steroid replacement doses were similar in both groups. Initial urinary cortisol levels (24-hour urinary free cortisol [UFC]) were significantly higher in the NS group than in the NNS group (p = 0.009). Four patients in the NS group and three of those in the NNS group received radiotherapy before TBA (p = 0.26). Three patients in the NS group presented residual tumors before TBA, compared with none in the NNS group (p = 0.04). At 1 year after TBA, the median ACTH level was 476 ng/L (240-1500 ng/L) in the NS group and 81 ng/L (48-330 ng/L) in the NNS group (p = 0.0007). CONCLUSION: In conclusion, a residual tumor before TBA, higher 24-hour UFC at diagnosis, and increasing ACTH levels within 1 year after TBA emerged as predictive factors of development of NS.

Pegvisomant in acromegaly: a multicenter real-life study in Argentina.

OBJECTIVE: To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. SUBJECTS AND METHODS: We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. RESULTS: Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). CONCLUSION: this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7.

Pituitary abscess: a report of two cases.

Pituitary abscess (PA) is an infrequent disease, which consists of an infection within the sella turcica that might be life-threatening. We present here two cases of this rare entity. Case 1: A 53-year-old woman was followed for an incidentally found pituitary cyst. Six years later the cyst enlarged and transsphenoidal surgery was performed. Two years later, the patient developed sudden onset of intense headache and nausea. The MRI showed a 2 by 2.5 cm sellar and suprasellar mass, that enhanced peripherally with gadolinium contrast and became hyperintense in T2-weighted images, suggesting a new-onset cystic lesion. During transsphenoidal surgery, large amounts of purulent material were drained from the sella. The cultures were positive for Klebsiella Ozaenae. Case 2: A 63-year-old woman, 4 years after transsphenoidal resection of a GH-secreting macroadenoma, developed a new sellar 2.6 cm cystic mass. On re-operation, purulent material was drained from the sella. The lesion persisted on the MRI and visual acuity worsened so a repeat pituitary decompression was carried out 6 months later, obtaining the same pathological results. Three years later, the MRI still shows the same mass. She feels well and her physical examination and clinical history are unremarkable. These cases illustrate the difficulties in the diagnosis and management of this rare entity.

Follicular carcinoma presenting as autonomous functioning thyroid nodule and containing an activating mutation of the TSH receptor (T620I) and a mutation of the Ki-RAS (G12C) genes.

Most autonomous functioning thyroid nodules (AFTN) are benign thyroid follicular neoplasms. There are rare reports of malignant hot nodules, in which activating mutations of the TSH receptor (TSHR) were found. We report a case of follicular carcinoma presenting as an AFTN causing subclinical hyperthyroidism in a 64-year-old woman who had a 6-cm hot nodule in the left thyroid lobe. Genomic DNA was extracted from paraffin-embedded tissues from the tumor and extratumoral thyroid tissue. Sequence analyses revealed point mutations in two different genes: the normal ACC sequence at codon 620 of the TSHR gene was replaced by ATC, changing the threonine by isoleucine (T620I); and the wild-type GGT at codon 12 of Ki-RAS mutated to TGT, replacing glycine by cysteine (G12C). In transfection experiments the T620I mutant showed constitutive activity in terms of cyclic adenosine monophosphate (cAMP) production when permanently transfected in 3T3 cells. Here, we describe for the first time an activating mutation in 3codon 620 of the TSHR. In addition, the cancerous AFTN also contained a G12C Ki-RAS mutation. We hypothesize that the combination of these two mutations might have played an important role in both the hyperfunction of the tumor and the carcinogenetic process.

Prolactinomas: evolution after menopause.

OBJETIVE: The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. SUBJECTS AND METHODS: Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results: Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. CONCLUSIONS: Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.

Temozolomide Therapy for Aggressive Pituitary Tumors: Results in a Small Series of Patients from Argentina.

We evaluated results of temozolomide (TMZ) therapy in six patients, aged 34-78 years, presenting aggressive pituitary tumors. In all the patients tested O(6)-methylguanine-DNA methyltransferase (MGMT) immunoexpression in surgical specimens was absent. Patients received temozolomide 140-320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelson's syndrome) no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushing's disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on-until now-incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration.

Ghrelin receptor (GHS-R1a) and its constitutive activity in somatotroph adenomas: a new co-targeting therapy using GHS-R1a inverse agonists and somatostatin analogs.

CONTEXT: The ghrelin receptor GHS-R1a is highly expressed in human somatotroph adenomas and exhibits unusually high basal signaling activity. In humans, the suppression of this constitutive activity by mutation induces a short stature. OBJECTIVE: Using a GHS-R1a inverse agonist, modified substance P (MSP), we explored the role of GHS-R1a constitutive activity in GH hypersecretion from somatotroph adenomas and as a putative therapeutic target. DESIGN: The effects of MSP were assessed on GH secretion from 19 human somatotroph tumors in vitro. Moreover, these effects were compared with those of octreotide (somatostatin receptor subtype 2 [sst2] agonist) and with the combination of both drugs. Expression and localization of GHS-R1a and sst2 were studied. RESULTS: For all tumors, MSP inhibited GH secretion in a dose-dependent manner from 13 to 64%. Moreover, MSP enhanced octreotide-induced GH inhibition. For five tumors, the effects of combined MSP plus octreotide treatment were significantly higher than the sum of effects of each drug alone. MSP increased the membrane localization of GHS-R1a and of microdomains colocalizing sst2-GHS-R1a, highlighting the cooperation between the two drugs. CONCLUSIONS: The GHS-R1a inverse agonist could open new therapeutic options for acromegalic patients, particularly patients partially sensitive to octreotide whose GH secretion is not completely controlled by the sst2 agonist.

Long-term outcome after bilateral adrenalectomy in Cushing's disease with focus on Nelson's syndrome

ABSTRACT Objective We analyzed the clinical, biochemical, and imaging findings of adrenalectomized patients with Cushing's disease (CD) in order to compare the characteristics of those who developed Nelson's syndrome (NS) versus those who did not develop this complication (NNS), aiming to identify possible predictive factors for its occurrence. Subjects and methods We performed a retrospective review of the clinical records of a group of patients with CD who underwent TBA between 1974 and 2011. Results Out of 179 patients with CD, 13 (7.3%) underwent TBA. NS occurred in 6 of them (46%) after a mean of 24 months from the total bilateral adrenalectomy (TBA). Age at diagnosis, duration of Cushing's syndrome (CS) until TBA, and steroid replacement doses were similar in both groups. Initial urinary cortisol levels (24-hour urinary free cortisol [UFC]) were significantly higher in the NS group than in the NNS group (p = 0.009). Four patients in the NS group and three of those in the NNS group received radiotherapy before TBA (p = 0.26). Three patients in the NS group presented residual tumors before TBA, compared with none in the NNS group (p = 0.04). At 1 year after TBA, the median ACTH level was 476 ng/L (240-1500 ng/L) in the NS group and 81 ng/L (48-330 ng/L) in the NNS group (p = 0.0007). Conclusion In conclusion, a residual tumor before TBA, higher 24-hour UFC at diagnosis, and increasing ACTH levels within 1 year after TBA emerged as predictive factors of development of NS.

Pegvisomant in acromegaly: a multicenter real-life study in Argentina

ABSTRACT Objective To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. Subjects and methods We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. Results Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). Conclusion this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7

Prolactinomas: evolution after menopause

ABSTRACT Objetive The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. Conclusions Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.