Natural history and surgical outcome of incidentally discovered clinically nonfunctioning pituitary macroadenomas

Objectives: The incidental diagnosis of nonfunctioning pituitary macroadenomas (NFPMAs) is becoming more prevalent with the spread of modern brain imaging techniques. We sought to uncover new data about their natural history and surgical outcome. Design: This is a retrospective single-center observational study. Methods: Among 210 patients seen for a NFPMA between 2010 and 2019, 70 ( 33%) were discovered incidentally (i-NFPMA). We analyzed outcomes in a total of 65 patients with available follow-up data. Results: Mean age at diagnosis (± s.d.) was 60 ± 14 years and mean maximal diameter was 20.0 ± 7.3 mm. At diagnosis, 29 patients (45%) had pituitary hormone deficits (LH/FSH 41%, TSH 29%, ACTH 15%) and 12% had visual field deficits. 26 patients underwent initial surgery, while 12 had delayed surgery after initial surveillance. In the surveillance group, the risk of tumor growth was estimated at 10%/year. Patients with hormonal deficits at diagnosis experienced earlier growth at 24 months (P < 0.02). Overall, surgical resection of the i-NFPMA led to stable or improved endocrine function in 91% of patients, with only 6% postoperative permanent diabetes insipidus. Moreover, surgery was more effective in preserving intact endocrine function (10/12) than restoring altered endocrine function to normal (6/22, P = 0.03). Conclusion: About one-third of NFPMAs are now discovered incidentally and a significant subset may be responsible for unrecognized endocrine and visual deficits. Under surveillance the risk of further tumor growth is significant (10 %/year) and seems to occur faster in patients already harboring an endocrine deficit. Early surgical removal before onset of endocrine deficits appears to lead to better endocrine outcome

An update on diagnosis and treatment of adult growth hormone deficiency

Adult growth hormone deficiency (AGHD) is nowadays recognized as a distinct clinical entity and replacement therapy has become a standard practice. The benefits of GH treatment seem to outweigh its potential risks but issues concerning long term efficacy and safety are still a subject of debate. More research is needed in some key areas and it remains essential to monitor patients by means of longitudinal surveillance studies

La déficience en hormone de croissance chez l'adulte (AGHD) : Qui, comment et pourquoi traiter ?

La déficience en hormone de croissance de l’adulte (AGHD) est unanimement reconnue aujourd’hui comme un syndrome clinique à part entière et son traitement est devenu une pratique courante. Avec le recul et la réflexion objective, certaines questions se posent néanmoins : faut-il traiter tous les patients déficients ? À quelle dose et pendant combien de temps ? Quels sont les réels bénéfices à long terme, en particulier sur l’espérance de vie ? Si le diagnostic de GHD sévère est clairement établi et en l’absence de contre-indication évidente (cancer actif, diabète déséquilibré…), un essai thérapeutique parait justifié dans la plupart des cas. Le traitement par GH permet de corriger les anomalies de la composition corporelle secondaires à l’AGHD, améliorer divers paramètres et facteurs de risque cardio-vasculaires, augmenter la force musculaire et la densité minérale osseuse et, de manière variable, améliorer la qualité de vie et le sentiment de bien-être du patient. Le traitement sera commencé à faibles doses pour éviter les effets secondaires liés à une rétention hydro-saline, puis progressivement adapté en quelques mois en fonction des valeurs d’IGF-I, de la réponse clinique et de la tolérance individuelle. Il n’existe malheureusement pas de facteur prédictif évident de la réponse thérapeutique globale chez un individu donné et la décision de poursuivre ou non la thérapeutique dépendra du rapport bénéfices/[coût + risques] et, surtout, de la motivation du sujet trait

Pituitary disorders and pregnancy

Abstract The management of pituitary disorders in pregnant women can be complex. Two major issues arise: (a) the effects of pregnancy on the pre-existing pituitary disease and (b) the effects of the pituitary disease and its treatment on the early foetal development and on the course of the pregnancy. These issues will be reviewed here and underline the importance of the proper, multidisciplinary management of the pituitary disorders during gestation. Résumé La prise en charge des affections hypophysaires pendant la grossesse peut être complexe. Deux problématiques se posent : (a) les effets de la grossesse sur la maladie hypophysaire préexistante, et (b) les effets de l’affection pituitaire et de son traitement sur le développement embryonnaire et fœtal. Ces problèmes sont revus dans cet article et soulignent l’importance d’une prise en charge multidisciplinaire des affections hypophysaires pendant la grossesse

Présentation clinique sévère d'une apoplexie hypophysaire

L’apoplexie hypophysaire résulte d’une nécrose et/ou d’un infarcissement hémorragique brutal de la glande pituitaire, survenant le plus souvent au sein d’un adénome hypophysaire préexistant ou plus rarement dans une glande saine. Sa présentation clinique classique est celle de céphalées violentes, associées à un ou plusieurs déficits visuels ou oculomoteurs. Nous rapportons ici l’observation d’un homme âgé de 54 ans qui présenta un tableau clinique et biologique particulièrement sévère de méningite aseptique secondaire à une apoplexie hypophysaire. L’exploration hormonale a révélé un panhypopituitarisme antérieur précoce et l’imagerie par IRM cérébrale a objectivé dans les jours suivants l’apparition de lésions cérébrales ischémiques et la présence d’une sinusite aiguë réactionnelle. A la lumière de ce cas clinique, nous revoyons la littérature concernant la présentation clinique variable de l’apoplexie hypophysaire dont l’évolution est conditionnée par un diagnostic précoce et un traitement urgent, médical et souvent neurochirurgica

Treatment of Adult Growth Hormone Deficiency: Who, Why and How? a Review

Adult growth hormone deficiency (AGHD) is nowadays recognized as a distinct clinical entity and replacement therapy has become a standard practice. Reflecting on the accumulated evidence, questions nevertheless arise. Should all AGHD patients be treated? What dose of GH should be given and for how long? What are the real long-term benefits, in particular regarding life expectancy? If the diagnosis of severe GHD is firmly established and if there is no contra-indication (such as an active cancer or uncontrolled diabetes), it is worthwile initiating GH replacement therapy. Treatment can indeed correct the abnormal body composition, improve various adverse cardiovascular parameters and risk factors, increase muscle strength and bone mineral density and, although to a variable degree, improve the patient's quality of life and psychological well-being. Treatment should be started with very low doses to avoid side-effects related to fluid retention and should then be gradually titrated against IGF-I values, clinical response and individual tolerance. There is unfortunately no confirmed predictive factor for the overall therapeutic response in a given individual. Thus, the decision to whether or not pursue the therapy will depend on the ratio of perceived and expected benefits over cost and risks of treatment, as well as on the persistent motivation of the patient

Evolution of Glucose Tolerance After Treatment of Acromegaly: A Study in 57 Patients.

The aim of our study was to evaluate the evolution of glucose metabolism in 57 patients after treatment of their acromegaly and to determine risk factors for the persistence of abnormal glucose tolerance. Therefore, we performed IGF-I measurements, oral glucose tolerance tests (OGTTs), and HOMA to evaluate insulin sensitivity (HOMA-S) and β-cell function (HOMA-β) at diagnosis and at last visit (median follow-up 7 years). At diagnosis of acromegaly, 14 patients (25%) were diabetic and 15 (26%) had impaired glucose tolerance, whereas at the last visit, 32% were diabetic and 26% remained glucose intolerant. There was a decrease in fasting glucose (median - 7.0 mg/dl) in the 20 patients cured by surgery, whereas it increased in the 28 patients controlled under medical therapy (median + 2.0 mg/dl; p<0.05 vs. cured group) and in the 9 patients with active disease (median + 4.0 mg/dl). Loss of β-cell function was more pronounced in the patients under medical treatment (median - 87.9%) vs. the cured group (median - 30.4%; p<0.05). There was a decrease in HbA1c between diagnosis and last visit in patients under pegvisomant (mean - 19.2 mmol/mol) vs. a small increase in patient treated by somatostatin analogues (+ 3.4 mmol/mol; p<0.05). Independent risk factors for persistent abnormal glucose tolerance were the glucose tolerance status at diagnosis and ongoing treatment with somatostatin analogues. In conclusion, we found that more than 50% of patients still have IGT or diabetes after treatment of acromegaly. Improvement of glucose metabolism is mainly observed in cured patients and in patients treated with pegvisomant

Characteristics and treatment responsiveness of patients with acromegaly and a paradoxical GH increase to oral glucose load.

OBJECTIVES: We aimed to investigate the clinical, biochemical, histological and radiological characteristics as well as the response to somatostatin analogs (SSA) in a large cohort of acromegaly patients with a paradoxical GH response (PR) to oral glucose tolerance test (OGTT). DESIGN: Retrospective study. METHODS: Of 110 patients with acromegaly included in our study, 30 (PR+; 27%) had a paradoxical GH increase of more than 25% relative to basal GH levels during OGTT. RESULTS: At diagnosis, PR+ patients were older than PR- patients (52 ± 16 years vs 44 ± 14 years, P 50% after 3-6 months in 77% vs 49%, P = 0.023) or after surgery (normalization of IGF-1 in 100% vs 44%, P = 0.011). CONCLUSIONS: Our study demonstrates that in acromegaly, a paradoxical GH increase during OGTT is associated with particular features of somatotroph adenomas and with a better prognosis in terms of response to SSA

Impact of flash glucose monitoring on glycaemic control and quality of life in patients with type 1 diabetes: A 18-month follow-up in real life.

We conducted a prospective observational study to evaluate the medium-term impact of the flash glucose monitoring system (FGM) in a type 1 diabetic population. We included 248 patients, switched from conventional blood glucose monitoring (BGM) to FGM. We evaluated glycaemic control at 2-4 (T1) and 5-11 (T2) months after initiation and at the last available visit (T3, 18 ± 4 months). We asked patients to fill in, at T0 and T2, two questionnaires based on the Diabetes Treatment Satisfaction Questionnaire; and on the Hypoglycaemia Fear Survey. Glycaemic control improved, from 8.1 ± 1.3% at T0 to 7.8 ± 1.2% at T1 (p < 0.001) and remained unchanged after. Average number of controls increased from 3.2 ± 1.2 BGM to 7.7 ± 3.9 at T1 (p < 0.001). We observed a modest decrease in daily insulin doses. We evidenced an increase in mild hypoglycaemic events, especially in well-controlled subjects, but no increase of severe events. Satisfaction score improved from 30.5 ± 7.7 points to 38.3 ± 5.1 points (p = 0.018), was correlated with the reduction in and was higher in less controlled patients at inclusion. "Behaviour" score regarding hypoglycaemias decrease from 5.7 ± 4.1 to 4.4 ± 3.6 points (p < 0.001). In conclusion, this 18-months study trial indicates that using the FGM technology in patients with T1D may improve glycaemic control, in real-life conditions, especially in less controlled patients. FGM was associated with an increase of patients' satisfaction regarding treatment. Hypoglycaemic events, however, were not reduced in frequency. Therefore, the need for an educational team and a structure program in the management of this new technology remains mandatory