Genetic diagnosis in acromegaly and gigantism: From research to clinical practice.

It is usually considered that only 5% of all pituitary neuroendocrine tumours are due to inheritable causes. Since this estimate was reported, however, multiple genetic defects driving syndromic and nonsyndromic somatotrophinomas have been unveiled. This heterogeneous genetic background results in overlapping phenotypes of GH excess. Genetic tests should be part of the approach to patients with acromegaly and gigantism because they can refine the clinical diagnoses, opening the possibility to tailor the clinical conduct to each patient. Even more, genetic testing and clinical screening of at-risk individuals have a positive impact on disease outcomes, by allowing for the timely detection and treatment of somatotrophinomas at early stages. Future research should focus on determining the actual frequency of novel genetic drivers of somatotrophinomas in the general population, developing up-to-date disease-specific multi-gene panels for clinical use, and finding strategies to improve access to modern genetic testing worldwide.

Clinical Characteristics and Management of Cosecreting Thyroid Stimulating Hormone or Prolactin Pituitary Growth Hormone Adenomas: A Case-Control Study.

OBJECTIVE: Cosecreting thyroid stimulating hormone (TSH) or prolactin (PRL) in patients with pituitary growth hormone (GH) adenomas has been rarely reported. Our study aimed to elucidate their clinical characteristics. METHODS: We retrospectively collected data of 22 cases of cosecreting GH and TSH pituitary adenomas [(GH+TSH)oma] and 10 cases of cosecreting GH and PRL pituitary adenomas [(GH+PRL)oma] from Beijing Tiantan Hospital, Capital Medical University between January 2009 and January 2023. The clinical manifestation, preoperative hormone levels, imaging features, pathologic characteristics, and biochemical remission rates were compared among 335 patients with solo-secreting GH adenomas (GHoma) and 49 patients with solo-secreting TSH adenoma (TSHoma). Patients with (GH+TSH)oma and (GH+PRL)oma were grouped according to biochemical remission to explore the risk factors leading to biochemical nonremission. RESULTS: Cosecreting pituitary GH adenomas had various clinical manifestations and a larger tumor volume and were more likely to invade the cavernous sinus bilaterally and compress the optic chiasm. GH and TSH levels were lower in (GH+TSH)oma than in GHoma or TSHoma. Solo part remission was observed both in (GH+TSH)oma and (GH+PRL)oma. Cavernous sinus invasion was an independent risk factor for biochemical nonremission in patients with (GH+TSH)oma and (GH+PRL)oma. CONCLUSIONS: The clinical manifestation of (GH+TSH)oma and (GH+PRL)oma may be atypical. When screening for pituitary adenomas, a comprehensive evaluation of all pituitary target gland hormones is needed. Cosecreting pituitary GH adenomas are more aggressive and surgery is often unable to completely remove the tumor, requiring pharmacologic or radiological treatment if necessary. Clinicians should give high priority to biochemical remission, although solo part remission may occur.

Growth Hormone Excess: Implications and Management.

Acromegaly is described as the oversecretion of growth hormone (GH) and, subsequently, insulin-like growth factor 1 (IGF-1), ascribed in most cases to a pituitary adenoma. This disease presents a progressive disfigurement, along with other systemic manifestations, which altogether diminishes the quality of life in the patients. Prolonged exposure to abnormally high levels of GH and IGF-1 levels results in cardiovascular, cerebrovascular, and pulmonary dysfunction which overall produces a fall in life expectancy. Timely diagnosis and further treatment decreased the mortality rate of the patients and showed an improvement in the quality of life. Surgical procedures, advanced radiation therapy tools, and the availability of pharmacological compounds that act on pituitary growth hormone-producing cells have enabled an improved approach to treating the disease. Pharmacological treatment is currently an important management option, and it may also be the first-line treatment in patients with acromegaly who do not benefit from or are ineligible for first-line surgical procedures. From its inception until 2021, we used a comprehensive search strategy on Medline/PubMed, Scopus, Embase, Web of Science, and the Cochrane Library electronic databases. All human research articles and review articles published in English were considered for the review. In this review, we describe the clinical implications and management of patients with acromegaly, consisting of scientific improvements underlying the developing understanding of pathogenesis and diagnosis, associated comorbidities and mortality rate with the disease, and major improvements in the treatment of the disease, along with novel strategies including quality of life and patient-reported outcomes.

Long-term outcomes of patients with acromegaly: a report from the Swedish Pituitary Register.

OBJECTIVE: To describe the treatment and long-term outcomes of patients with acromegaly from all healthcare regions in Sweden. DESIGN AND METHODS: Analysis of prospectively reported data from the Swedish Pituitary Register of 698 patients (51% females) with acromegaly diagnosed from 1991 to 2011. The latest clinical follow-up date was December 2012, while mortality data were collected for 28.5 years until June 2019. RESULTS: The annual incidence was 3.7/million; 71% of patients had a macroadenoma, 18% had visual field defects, and 25% had at least one pituitary hormone deficiency. Eighty-two percent had pituitary surgery, 10% radiotherapy, and 39% medical treatment. At the 5- and 10-year follow-ups, insulin-like growth factor 1 levels were within the reference range in 69 and 78% of patients, respectively. In linear regression, the proportion of patients with biochemical control including adjuvant therapy at 10 years follow-up increased over time by 1.23% per year. The standardized mortality ratio (SMR) (95% CI) for all patients was 1.29 (1.11-1.49). For patients with biochemical control at the latest follow-up, SMR was not increased, neither among patients diagnosed between 1991 and 2000, SMR: 1.06 (0.85-1.33) nor between 2001 and2011, SMR: 0.87 (0.61-1.24). In contrast, non-controlled patients at the latest follow-up from both decades had elevated SMR, 1.90 (1.33-2.72) and 1.98 (1.24-3.14), respectively. CONCLUSIONS: The proportion of patients with biochemical control increased over time. Patients with biochemically controlled acromegaly have normal life expectancy, while non-controlled patients still have increased mortality. The high rate of macroadenomas and unchanged age at diagnosis illustrates the need for improvements in the management of patients with acromegaly.

Final Outcome in Growth Hormone-Secreting Adenomas After Combination of Maximal Tumor Resection and Medical Treatment.

OBJECTIVE: Gross total resection (GTR) is not always possible in acromegalic patients, especially in patients with invasive growth hormone-secreting adenomas. We analyzed the biochemical remission outcome in relation to extent of tumor resection and effectiveness of medical treatment in cases of remnant tumor. METHODS: Retrospective analysis was performed of acromegalic patients operated on between 2002 and 2017. Preoperative imaging, tumor invasiveness, extent of resection, and biochemical remission were collected. Patients with tumor remnant not amenable to second surgery began medical treatment. The relationship between pituitary adenoma remnant volume and final biochemical outcome was analyzed. RESULTS: Of 120 acromegalic patients operated on, 82 underwent transsphenoidal microsurgery and 38 underwent endonasal endoscopic approach. GTR was achieved in 72 cases (60%); subtotal resection (STR), 21 (17.5%) cases; and partial resection, 27 (22.5%) cases. There was a nonsignificant higher rate of GTR/STR in patients who underwent endonasal endoscopic approach. However, a significantly higher remission rate (89.45% vs. 67.1%) was achieved in these patients (P < 0.01). Greater tumor volume and invasiveness were associated with a lower remission (P < 0.05). Patients with tumor remnant who achieved biochemical remission with added medical therapy had a significantly smaller tumor volume (P < 0.001). CONCLUSIONS: The more aggressive surgical resection is, the greater the chance of attaining final biochemical remission, whether or not GTR is achieved. Medical therapy effectiveness is enhanced in cases with STR. Invasive growth hormone-secreting macroadenomas that are not surgically amenable to total resection are best managed with a combination of safe STR and medical treatment.

The association between treatment and systemic inflammation in acromegaly.

OBJECTIVE: Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function. DESIGN: Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment. RESULTS: Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment. CONCLUSIONS: Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.

Discordant GH and IGF-1 Results in Treated Acromegaly: Impact of GH Cutoffs and Mean Values Assessment.

CONTEXT: Discordant growth hormone (GH) and insulin-like growth factor-1 (IGF-1) values are frequent in acromegaly. OBJECTIVE: To evaluate the impact of different GH cutoffs on discordance rate. To investigate whether the mean of consecutive GH measurements impacts discordance rate when matched to the last available IGF-1 value. DESIGN: Retrospective study. SETTING: Referral center for pituitary diseases. PATIENTS: Ninety acromegaly patients with at least 3 consecutive evaluations for GH and IGF-1 using the same assay in the same laboratory (median follow-up 13 years). INTERVENTIONS: Multimodal treatment of acromegaly. MAIN OUTCOME MEASURES: Single fasting GH (GHf) and IGF-1 (IGF-1f). Mean of 3 GH measurements (GHm), collected during consecutive routine patients' evaluations. RESULTS: At last evaluation GHf values were 1.99 ± 2.79 µg/L and age-adjusted IGF-1f was 0.86 ± 0.44 × upper limit of normality (mean ± SD). The discordance rate using GHf was 52.2% (cutoff 1 µg/L) and 35.6% (cutoff 2.5 µg/L) (P = 0.025). "High GH" discordance was more common for GHf <1.0 µg/L, while "high IGF-1" was predominant for GHf <2.5 µg/L (P < 0.0001). Using GHm mitigated the impact of GH cutoffs on discordance (GHm <1.0 µg/L: 43.3%; GHm <2.5 µg/L: 38.9%; P = 0.265). At receiver-operator characteristic curve (ROC) analysis, both GHf and GHm were poor predictors of IGF-1f normalization (area under the curve [AUC] = 0.611 and AUC = 0.645, respectively). The prevalence of disease-related comorbidities did not significantly differ between controlled, discordant, and active disease patients. DISCUSSION: GH/IGF-1 discordance strongly depends on GH cutoffs. The use of GHm lessen the impact of GH cutoffs. Measurement of fasting GH levels (both GHf and GHm) is a poor predictor of IGF-1f normalization in our cohort.

Multimodal therapy in aggressive pituitary tumors / Tratamiento multimodal de los tumores hipofisarios agresivos

The concept of aggressive pituitary tumor (APT) has been precisely defined in recent years. These tumors are characterized by morphological (radiological or histopathological) data of invasion, proliferative activity superior to that of typical adenomas and a clinical behavior characterized by resistance to standard therapies and frequent recurrences. The absence of cerebrospinal or distant metastases differentiates them from the pituitary carcinoma. APTs account for about 10% of all pituitary neoplasm. Proper diagnostic implies participation not only of radiological and hormonal investigation but also a thorough pathological assessment including proliferation markers and immunohistochemistry for hormones and transcription factors. Surgical resection, aiming gross total resection or tumor debulking, is the mainstay initial therapy in most patients. Most patients with APTs need more than one surgical intervention, pituitary radiation, sometimes on more than one occasion, and multiple sequential or combined medical treatments, to finally be doomed to unusual treatments, such as alkylating agents (temozolomide alone or in combination), molecular targeted therapies, or peptide receptor radionuclide therapy. Multimodal therapy, implemented by experts, preferably in specialized centers with high volume caseload, is the only way to improve the prognosis of patients with these uncommon tumors. The research needs in this area are multiple and include a greater knowledge of the molecular biology of these tumors, establishment of protocols for monitoring and sequencing of treatments, development of multicenter studies and international registries

El concepto de tumor hipofisario agresivo (THA) se ha definido con más precisión en los últimos años. Son tumores caracterizados por signos morfológicos (radiológicos o histopatológicos) de invasión, actividad proliferativa superior a la de los adenomas típicos y un comportamiento clínico caracterizado por resistencia a los tratamientos habituales y recidivas frecuentes. La ausencia de metástasis cefalorraquídeas o a distancia los diferencia del carcinoma hipofisario. Los THA suponen alrededor del 10% de todas las neoplasias hipofisarias. Un diagnóstico apropiado exige no solo investigación radiológica y hormonal, sino también una valoración histopatológica detenida que incluya marcadores de proliferación e inmunohistoquímica para hormonas y factores de transcripción. La resección quirúrgica encaminada a la resección total o la reducción del volumen tumoral es el tratamiento inicial clave en la mayoría de los pacientes. La mayoría de los pacientes con THA necesitan más de una intervención quirúrgica, irradiación hipofisaria, a veces en más de una ocasión, y diversos tratamientos médicos consecutivos o combinados, y están predestinados a terminar recibiendo tratamiento inhabituales como fármacos alquilantes (temozolomida sola o en combinación), tratamientos multidiana o tratamientos con péptidos radiomarcados. El tratamiento multimodal aplicado por expertos, preferiblemente en centros especializados con gran volume de pacientes, es el único modo de mejorar el pronóstico de los pacientes con estos tumores poco frecuentes. Las necesidades de investigación en este campo son enormes, e incluyen la de un mayor conocimiento de la biología molecular de estos tumores, el establecimiento de protocolos de vigilancia y secuenciación de los tratamientos, el desarrollo de estudios multicéntricos y registros internacionales

Acromegaly: Update on Management and Long-Term Morbidities.

Acromegaly is a systemic disease associated with great morbidity and increased mortality if not adequately treated. In the past decades much improvement has been achieved in its treatment and in the knowledge of its comorbidities. We provide an update of acromegaly management with current recommendations. We also address long-term comorbidities emphasizing the changing face of the disease in more recent series, with a decrease of cardiovascular disease severity and an increased awareness of comorbidities like bone disease, manifested mainly as vertebral fractures and the change in the main cause of death (from cardiovascular disease to cancer in more recent series).

Thyroid and colorectal cancer screening in acromegaly patients: should it be different from that in the general population?

The literature on an association between acromegaly and cancer is particularly abundant on either colorectal cancer or thyroid cancer, and an endless debate is ongoing whether patients with acromegaly should be submitted to specific oncology screening and surveillance protocols. The aim of the present work is to review the most recent data on the risk of either colorectal cancer or thyroid cancer in acromegaly and discuss the opportunity for specific screening in relation to the accepted procedures in the general population.

Progression of vertebral fractures in long-term controlled acromegaly: a 9-year follow-up study.

OBJECTIVE: Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) excess results in both reversible and irreversible musculoskeletal damage, including increased vertebral fracture (VF) risk. The prevalence of VFs is approximately 60% in controlled acromegaly patients, and these VFs can progress in time. We aimed to identify the course of VFs in a cohort of acromegaly patients in long-term remission and their associated risk factors during prolonged follow-up. METHODS: Thirty-one patients with acromegaly (49% female, median age 60 years (IQR 53-66)), who were in remission for ≥2 years, were included in this longitudinal, prospective, follow-up study. Spine radiographs of vertebrae Th4 to L4 were assessed for VFs using the Genant score, at baseline, after 2.6 years and 9.1 years. Progression was defined as either a new fracture or a ≥1-point increase in Genant score. RESULTS: The prevalence of VF at baseline was 87% (27/31 patients). Progression of VFs was observed in eleven patients (35.5%) during the 9.1-year follow-up period, with a total incidence rate of 65.5 per 1000 person years (males 59.8 per 1000 person years vs females 71.6 per 1000 person years). Patients treated with surgery or radiotherapy had a higher risk of VF progression in this cohort (P = 0.030). CONCLUSIONS: In this cohort of long-term, well-controlled acromegalic patients, the prevalence and progression of VFs was high, showing that the deleterious effects of GH and IGF-1 excess on bone persist despite achievement of longstanding remission.

Prevalence, incidence, comorbidities, and treatment patterns among Japanese patients with acromegaly: a descriptive study using a nationwide claims database.

Epidemiological data of rare diseases are important for understanding disease burden, improving treatment, and planning healthcare systems. However, those of acromegaly in Japan are not well known. Our study aimed to describe the prevalence, incidence, prediagnostic comorbidities, and treatment patterns of patients with acromegaly in Japan. Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan, we retrospectively identified 12,713 patients with acromegaly aged ≥20 years between January 2014 and December 2017 (the prevalence cohort), 2,552 newly diagnosed patients between January 2013 and December 2017 (the incidence and comorbidity cohort), and 2,125 patients enrolled in the database at least 365 days after the diagnosis (the treatment-pattern cohort). The average annual prevalence in 2015-2017 was 9.2 cases per 100,000 in the prevalence cohort, and the average annual incidence in 2013-2017 was 0.49 cases per 100,000 in the incidence and comorbidity cohort. The most common prediagnostic comorbidities included hypertension (43%), diabetes (37%), and hyperlipidemia (27%). In the treatment-pattern cohort, 54% and 45% of patients received surgery and medical treatment as the primary treatment, respectively. Between the first surgery and 365 days after diagnosis, 15% of the patients in this cohort received medical treatment as the secondary treatment, mostly with somatostatin analogs (83%). Of the 1,569 patients who underwent surgery, 29% received medical treatment before surgery. The prevalence and incidence of acromegaly in Japan were similar to those in other countries. This epidemiological study provides the basis for better management of acromegaly nationwide.

Prevalence and characteristics of sellar masses in the city of Al Ain, United Arab Emirates: 2010 to 2016.

BACKGROUND: The prevalence of sellar masses (SMs) is reported in Europe and North America but only limited data are available from the Middle East and North Africa (MENA) region. OBJECTIVES: Assess the prevalence and characteristics of SMs in Al Ain city, United Arab Emirates. DESIGN: Retrospective, descriptive multicenter study. SETTING: Three endocrine centers in Al Ain. PATIENTS AND METHODS: All patients diagnosed with SMs in the city of Al Ain, Emirate of Abu Dhabi, between 2011 and 2016 were evaluated. Cases were identified using ICD 9 and 10 codes and demographic and clinical data were collected. The prevalence rate was calculated for patients alive and residing in Al Ain city until 31 December 2016. MAIN OUTCOME MEASURES: Clinical presentations and prevalence rate. SAMPLE SIZE: 272. RESULTS: The mean (SD) age on presentation was 40.8 (14.3) years (range: 6-114 years, median: 40.0). The 170 (61.8%) females and 128 (46.5%) were native citizens of the United Arab Emirates. Two hundred and forty five (90%) patients had pituitary adenomas (PAs) while 27 (10%) had non-pituitary sellar lesions. The four most common SMs were prolactinoma (n=139, 51.1%), nonfunctioning adenoma (NFA) (n= 69, 25.4%), somatotroph adenoma (n=32, 11.8%) and craniopharyngioma (n=15, 5.5%). Patients with prolactinoma, corticotroph adenoma, and Rathke's cleft cyst had small sellar masses (<1 centimeter) while the majority of patients with other SMs had macroadenomas. Hypogonadism and growth hormone deficiency was present in 41.8% and 20.5% of the patients, respectively. Of 268 patients with available data, 82 patients underwent surgery while 25 patients received radiotherapy. At the end of 2016, 197 patients were residing in Al Ain city. The overall prevalence of SMs was 25.7/100 000 with PAs constituting most of these masses (n=177) for a prevalence of 23.1/100 000. CONCLUSIONS: This is the first study of SMs in the United Arab Emirates and the MENA region. Prolactinoma and NFA were the two most common SMs. Further studies are needed to explore the reasons for the lower prevalence of SMs in our region compared with other countries. LIMITATIONS: Retrospective design, relatively small sample size. CONFLICT OF INTEREST: None.

The evaluation of the tendon and muscle changes of lower extremity in patients with acromegaly.

PURPOSE: Although it is well known that acromegaly causes enlargement in the extremities, studies investigating the effects of acromegaly on tendons, muscles and soft tissue are limited. The aims of our study were to investigate tendons, the presence of enthesitis, soft tissue, muscle groups in terms of thickness and pennation angle (PA) which is an indicator of microstructure and strength of the muscle, of the lower extremities. METHODS: Thirty-nine patients with acromegaly and thirty-nine healthy control subjects similar for age, sex and body mass index were enrolled. Lower extremity tendons, skin, muscle groups were evaluated by ultrasound. RESULTS: The thicknesses of heel skin, heel pad, plantar fascia and Achilles tendon were higher in acromegaly than the control group (p < 0.05). The incidence of Achilles enthesitis were increased in the acromegaly group (p < 0.05). The thicknesses of the gastrocnemius medial head, vastus medialis, lateralis muscles for both sides and the left rectus femoris muscle were found to be lower in the acromegaly patients than controls (p < 0.05). However, thicknesses of vastus intermedius, gastrocnemius lateral head and soleus were similar between the acromegaly and control groups (p > 0.05). PA values of the right and left vastus medialis and the right vastus lateralis were found to be decreased in the acromegaly group (p < 0.05). Myostatin levels were lower in acromegaly group (p < 0.05). CONCLUSIONS: Acromegaly may cause to an increase in tendon and soft tissue thickness, enthesitis formation, decrease in the thickness of some muscles, and deterioration in microstructures in lower extremity.

The Course of Obstructive Sleep Apnea Syndrome in Patients With Acromegaly During Treatment.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is common in active acromegaly and negatively influences quality of life, morbidity, and mortality. This prospective study with 3 predetermined timepoints and a standardized treatment protocol investigates changes in sleep parameters during the first 2.5 years of acromegaly treatment. METHODS: Before initiation of acromegaly treatment (medical pretreatment followed by surgery), polysomnography (PSG) was performed in 27 consecutive patients with treatment-naive acromegaly. PSG was repeated after 1 year (N = 24) and 2.5 years (N = 23), and anthropometric and biochemical parameters were obtained. RESULTS: At baseline, 74.1% of the patients was diagnosed with OSAS. The respiratory disturbance index (RDI; P = 0.001), oxygen desaturation index (ODI; P = 0.001), lowest oxygen saturation (LSaO2; P = 0.007) and the Epworth Sleepiness Scale (ESS; P < 0.001) improved significantly during treatment, with the greatest improvement in the first year. After 2.5 years of treatment, all patients had controlled acromegaly. Of the 16 patients with repeated PSG and OSAS at baseline, 11 (68.8%) were cured of OSAS. Changes in RDI, ODI, LSaO2, and ESS correlated with insulin-like growth factor 1 levels. CONCLUSION: OSAS has a high prevalence in active acromegaly. There is a substantial decrease in prevalence and severity of OSAS following acromegaly treatment, with the largest improvement during the first year. Most patients recover from OSAS following surgical or biochemical control of the acromegaly. Therefore, a PSG is advised after diagnosis of acromegaly. When OSAS is present, it should be treated and PSG should be repeated during acromegaly treatment.

Long-term safety and treatment outcomes of pegvisomant in Japanese patients with acromegaly: results from the post-marketing surveillance.

This post-marketing surveillance is to investigate the long-term safety and effectiveness of the growth hormone receptor antagonist pegvisomant, which is used in patients with acromegaly in routine clinical practice. This surveillance included all cases treated with pegvisomant during the study period from the start of marketing (June 5, 2007) to December 2015. Data for 251 patients with acromegaly treated with pegvisomant were collected from 119 institutions nationwide in Japan. Eighty-five patients received pegvisomant monotherapy throughout their treatment, while 165 patients were treated with somatostatin analogue or dopamine agonist in combination with pegvisomant. Mean dose of pegvisomant was 10.6 ± 6.1 mg/day in the entire treatment period (except for initial loading dose). The incidence of adverse drug reactions was 35.6% (89/250). No new safety concerns related to long-term treatment were observed. The major investigation items of incidence of abnormal liver function and tumor enlargement were 16.0% (40/250), and 5.2% (13/250) respectively. Efficacy at the final evaluation point was 96.4% (217/225) based on the overall clinical judgement of attending physicians, and efficacy in each observation period was over 94%. Improvement in IGF-I levels and clinical symptoms scores were also observed by comparing the data at baseline with each observation point during treatment. IGF-I normalization rate was 68.2% at 5 years. Pegvisomant monotherapy showed similar improvement here as well. These results suggest that long-term treatment with pegvisomant is effective in clinical practice.

Acromégalie : améliorer la prise en charge: Acromegaly: improving care.

Acromegaly is characterized by increased release of growth hormone (GH) and, consequently, Insulin-Like Growth Factor I (IGF-I), most often by a pituitary adenoma. Prolonged exposure to excess hormone leads to progressive somatic disfigurement and a wide range of systemic manifestations that are associated with increased mortality. Transsphenoidal adenomectomy is the treatment of choice of GH-secreting pituitary tumors but surgical cure is not achieved in around 50% of patients, then adjuvant treatment is necessary. Mortality in acromegaly is normalized with biochemical control and has decreased in the last decade with the increased use of adjuvant therapy. Both GH and IGF-I are currently biomarkers for assessing disease activity in patients with acromegaly. However, discordance between GH and IGF-I results is encountered in a quarter of treated patients. The impacts of such a discrepancy over mortality and morbidity and the risk of biochemical and/or clinical recurrence are unclear. Moreover, despite a good biochemical control, some symptoms persist, leading to a decreased quality of life. Back pain due to vertebral fractures seem to be frequent in these patients and underdiagnosed. In patients with acromegaly, bone mineral density is not a reliable predictor of fracture risk. A more accurate evaluation of bone microstructural alterations associated with GH hypersecretion and vertebral fractures may be provided by new radiological devices analyzing alteration of trabecular microarchitecture, leading to a better prevention. © 2019 Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Les Must de l'Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.

Pituitary Adenomas: What Are the Key Features? What Are the Current Treatments? Where Is the Future Taking Us?

Pituitary tumors are a heterogeneous group of lesions (usually benign) and proper understanding of the anatomy, physiology, and pathology of the hypothalamic/pituitary region is essential to make an accurate diagnosis and define the essential treatment options (i.e., surgery, medical therapies, and radiotherapy, alone or in combination). Surgery is the primary treatment for acromegaly, Cushing disease, thyroid-stimulating hormone-secreting adenomas, resistant prolactinomas, and nonfunctioning pituitary adenomas causing mass effect. Medical and radiation therapy are reserved in cases in which surgery is not possible or does not provide a complete cure. In the last decades, tremendous innovations (i.e., targeted drugs and refined surgical tools and techniques) have expanded the treatment strategies for pituitary adenomas. We herein report the current indications for and depiction of the surgical techniques in pituitary surgery, review current medical treatments, and provide a glimpse of future possibilities.

[Acromegaly due to a pituitary tumor in a dog - diagnosis, therapy and long-term follow-up]. / Akromegalie aufgrund eines Hypophysentumors bei einem Hund ­ Diagnose, Therapie und Verlauf.

INTRODUCTION: Acromegaly due to a pituitary tumor has so far only been described in 3 dogs. The present case report describes a 7-year-old male-castrated Labrador Retriever which was referred because of difficult-to-control diabetes. Physical examination revealed markedly enlarged head, tongue and paws, widened interdental spaces and thickening of the skin in the head and neck area. IGF-1 and GH were increased and the latter continued to be abnormal after somatostatin application. Computed tomography demonstrated a space-occupying lesion in the pituitary gland and the diagnosis of acromegaly due to a GH-producing tumor of the pituitary was made. The dog underwent radiation therapy with a 6MV linear accelerator (3×8Gy) and improved substantially. Two and a half years after radiation therapy the dog developed lethargy and anorexia and was euthanized. Necropsy was not permitted. This case report represents the description of a dog suffering from pituitary-dependent acromegaly which was successfully treated and had a long-term survival.

INTRODUCTION: L'acromégalie due à une tumeur hypophysaire n'a jusqu'à présent été décrite que chez 3 chiens. Le présent rapport de cas décrit un Labrador Retriever de 7 ans mâle castré, qui a été référé en raison d'un diabète difficile à contrôler. L'examen physique a révélé une tête, une langue et des pattes de taille nettement augmentée, des espaces interdentaires élargis et un épaississement de la peau dans la région de la tête et du cou. L'IGF-1 et la GH étaient augmentées et la seconde restait anormale après l'application de somatostatine. La tomodensitométrie a mis en évidence une masse dans la région de l'hypophyse et le diagnostic d'acromégalie due à une tumeur de l'hypophyse productrice de GH a été posé. Le chien a subi une radiothérapie avec un accélérateur linéaire de 6MV (3×8Gy) et son état s'est considérablement amélioré. Deux ans et demi après la radiothérapie, le chien développa une léthargie et une anorexie et fut euthanasié. L'autopsie n'a pas été autorisée. Ce rapport de cas représente la description d'un chien souffrant d'acromégalie dépendant de l'hypophyse, traité avec succès et ayant une survie à long terme.