[Renin-angiotensin-aldosterone system : brief history and questions related to the COVID-19 pandemic]. / Système rénine-angiotensine-aldostérone : bref historique et questionnements face à la pandémie COVID-19.

The breakthrough of the secrets of hypertension and the renin-angiotensin-aldosterone system (RAAS) is one of the legends of medicine. The first chapter is the one of Tigerstedt's experiments about renin, and Loesch and Gollblatt's model of renal hypertension. The race to elucidate the mechanisms of angiotensin, angiotensinogen and the angiotensin conversion enzyme cascade, by Braun Menéndez and Page teams, is a second chapter. The puzzle of this elegant cascade is completed by aldosterone isolation by the collaboration of Tait spouses and Tadeus Rechstein. As a corollary of these findings, Conn made the first description of primary hyperaldosteronism. The elucidation of RAAS pathophysiology naturally led to the synthesis of the antihypertensive captopril by Ondetti and Cushman, thereby opening the modern era of ACE inhibitors and ARII blockers. In March 2020, a viral pandemic caused by SARS-Cov-2 ignites the entire planet. This new coronavirus uses the RAAS angiotensin conversion enzyme type 2 (ACE-2) as a gateway. The SARS-CoV-2/ACE-2 signalling pathway and its pathological effects on the cardio-respiratory and renal system of these patients initiate a new chapter. The interaction of SARS-Cov-2/ACE-2 axis with anti-hypertensive agents, as well as with ACE-2 activators and ACE-2 homologs, takes a part of an active international study searching for therapeutic targets. This modern research, summarized in this article, will further develop our knowledge of RAAS and, hopefully, will improve the management of COVID-19 patients.

La percée des secrets de l'hypertension artérielle et du système rénine-angiotensine-aldostérone (SRAA) est une des histoires légendaires de la médecine. Les expériences de Tigerstedt sur la rénine, puis le modèle d'hypertension rénale de Loesch et de Gollblatt, constituent un premier chapitre. La course pour élucider le mécanisme de l'angiotensine, l'angiotensinogène et l'enzyme de conversion de l'angiotensine par les équipes de Braun Menéndez et de Page est un deuxième chapitre. Le puzzle de cette élégante cascade biochimique se complète par la description de l'aldostérone isolée par les époux Tait avec Tadeus Rechstein, et, comme corollaire, la description par Conn de l'hyperaldostéronisme primaire. La compréhension physiopathologique du SRAA amène naturellement à la synthèse de l'anti-hypertenseur captopril par Ondetti et Cushman, inaugurant l'ère moderne des inhibiteurs de l'enzyme de conversion de l'angiotensine (IEC) et des antagonistes des récepteurs AT1 de l'angiotensine 2 (ARAII ou sartans). En mars 2020, une pandémie virale déclenchée par le SARS-CoV-2 embrase la planète. Ce coronavirus utilise comme porte d'entrée cellulaire l'enzyme de conversion de l'angiotensine 2 (ACE-2) du SRAA. La voie de signalisation SARS-CoV-2/ACE-2 et ses effets, sur les systèmes cardio-respiratoire et rénal, ouvrent un nouveau chapitre. L'interaction de cet axe SARS-Cov-2/ACE-2 avec les antihypertenseurs, mais aussi les activateurs et homologues de l'ACE-2 font objet d'une étude internationale active, à la recherche de cibles thérapeutiques. Cette recherche, que nous synthétisons dans cet article, est destinée à développer notre connaissance sur le SRAA et, nous l'espérons, à améliorer peut-être la prise en charge des patients avec COVID-19.

Cabergoline for Cushing's disease: a large retrospective multicenter study.

OBJECTIVE: The efficacy of cabergoline in Cushing's disease (CD) is controversial. The aim of this study was to assess the efficacy and tolerability of cabergoline in a large contemporary cohort of patients with CD. DESIGN: We conducted a retrospective multicenter study from thirteen French and Belgian university hospitals. METHODS: Sixty-two patients with CD received cabergoline monotherapy or add-on therapy. Symptom score, biological markers of hypercortisolism and adverse effects were recorded. RESULTS: Twenty-one (40%) of 53 patients who received cabergoline monotherapy had normal urinary free cortisol (UFC) values within 12 months (complete responders), and five of these patients developed corticotropic insufficiency. The fall in UFC was associated with significant reductions in midnight cortisol and plasma ACTH, and with clinical improvement. Compared to other patients, complete responders had similar median baseline UFC (2.0 vs 2.5xULN) and plasma prolactin concentrations but received lower doses of cabergoline (1.5 vs 3.5 mg/week, P < 0.05). During long-term treatment (>12 months), cabergoline was withdrawn in 28% of complete responders because of treatment escape or intolerance. Overall, sustained control of hypercortisolism was obtained in 23% of patients for 32.5 months (19-105). Nine patients on steroidogenesis inhibitors received cabergoline add-on therapy for 19 months (1-240). Hypercortisolism was controlled in 56% of these patients during the first year of treatment with cabergoline at 1.0 mg/week (0.5-3.5). CONCLUSIONS: About 20-25% of CD patients are good responders to cabergoline therapy allowing long-term control of hypercortisolism at relatively low dosages and with acceptable tolerability. No single parameter, including the baseline UFC and prolactin levels, predicted the response to cabergoline.

[Management of prolactinoma]. / Prise en charge des prolactinomes.

The prevalence of pituitary adenoma is of 1/1000 and has been fora long time underestimated. Prolactinomas represent the most frequent subtype (60%). From the mid eighties, their treatment is usually simple and efficient, allowing clinical, biological and tumoral control in most cases. However, management of carcinoma or resistant prolactinoma can be challenging. In these particular cases, a multimodal therapy approach is needed. Recently, progress in genetics of pituitary adenoma has allowed a better understanding and management of these particular cases. In consequence, genetic evaluation is recommended in FIPA (Familial Isolated Pituitary Adenoma) cases and in young patients with macroprolactinomas.

Resistant prolactinomas.

Prolactinomas are the most common hormonally active pituitary tumors and are usually successfully treated with dopamine agonists. A small proportion, however, appears not to respond to such treatment and such cases are termed resistant prolactinomas. Resistance is generally defined as failure to achieve normoprolactinemia and inability to induce tumor shrinkage. Reduced dopamine receptor density on lactotroph cells is currently considered the major underlying mechanism of resistance. Treatment options in resistant cases usually include substitution with another dopamine agonist, increasing the dose of the drug, as well as surgery, radiotherapy, and experimental medical therapies.

[Current opinion on primary aldosteronism]. / Concepts actuels de l'hyperaldostéronisme primaire.

In recent years, a greater interest has been focused on primary aldosteronism (PA), which shows a higher prevalence rate than previously thought. The consequences of PA are life threatening such as a refractory hypertension with serious cardiovascular damages.The evaluation of a suspected PA should follow a step-by-step approach (screening test, then confirmatory test and, in some cases, adrenal venous sampling). This protocol may seem tedious, but it allows an accurate etiologic diagnosis that leads to an appropriate therapy with better blood pressure control,improvement of quality of life, and, in some cases even,cure of hypertension.

[The endocrine effects of smoking]. / Le tabac et ses effets sur le système endocrinien.

Almost one third of men and women smoke in Belgium. Besides the well known tobacco's neck and cardiopulmonary systems adverse effects as well as associated neoplasms, today we recognize other deleterious consequences of tobacco on the neuroendocrine, thyroid and reproductive systems. Not only active smokers but also the fetus carried by a smoking mother is at risk for important health problems. Tobacco is a recognized risk factor of occurrence of ophtalmopathy. Some of the active components of tobacco as the thiocyanates are goitrogenic. Tobacco is a risk factor for men and women's infertility. Newborns from parents that smoke are at risk for sudden death. These consequences represent a major public health issue. A campaign for smoking cessation has been recently launched by the Federation of Public Health Service and the INAMI in Belgium.

Familial pituitary adenomas.

Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern because of hormonal overproduction or compression symptoms of adjacent structures. Most arise in a sporadic setting with a small percentage developing as a part of familial syndromes such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and the recently described familial isolated pituitary adenomas (FIPA) and MEN-4. While the genetic alterations responsible for the formation of sporadic adenomas remain largely unknown, considerable advances have been made in defining culprit genes in these familial syndromes. Mutations in MEN1 and PRKAR1A genes are found in the majority of MEN1 and CNC patients, respectively. About 15% of FIPA kindreds present with mutations of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Mutations in the CDKN1B gene, encoding p27(Kip)¹ were identified in MEN4 cases. Familial tumours appear to differ from their sporadic counterparts not only in genetic basis but also in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, they are more aggressive and affect patients at younger age, therefore justifying the importance of early diagnosis. In this review, we summarize the genetic and clinical characteristics of these familial pituitary adenomas.

[Traumatic brain injury and subarachnoid hemorrhage as a cause of hypopituitarism: a review]. / Hypopituitarisme consécutif aux atteintes cérébrales: le traumatisme crânien et l'hémorragie sous-arachnoïdienne mis en cause.

Brain injuries namely traumatic brain injuries (TBI) and subarachnoid haemorrhage (SAH) are relevant causes of acquired adult hypopituitarism, perhaps more prevalent than ever believed. TBI represent a major health problem with an annual incidence of 300 cases per 100.000. SAH affects six new cases per 1.000.000 habitants in USA. In Belgium we estimate nearly 30.000 new TBI cases and 600 SAH cases per year. In the English literature, TBI secondary hypopituitarism has been well documented in 14 retrospective and prospective series accounting for 1.077 cases. In all these series the main pituitary deficits were: GH (14%), ACTH (14%), gonadotrope (18%), TSH (7%) and diabetes insipidus (4%). SAH was documented as a cause of hypopituitarism in three retrospective series accounting for 110 cases and in one prospective series. In all these series main pituitary deficits were GH (25%), ACTH (15%), gonadotrope (8.5%), TSH (6%) and diabetes insipidus (4%). In this review, we analyze recent data and discuss diagnostic and treatment features of secondary hypopituitarism due TBI and SAH.

[How do you investigate an elevated calcitonin level?]. / Comment j'explore.... Une valeur elevée de calcitonine?

This article describes a case of lung cancer with associated hypercalcitoninemia in a man with a goitre. The case raises the problem of the differential diagnosis between medullary thyroid carcinoma and a neuroendocrine neoplasm with ectopic calcitonin secretion. The article first reviews the physiology of calcitonin, then outlines the diagnostic tests that are required to investigate hypercalcitoninemia and finally discusses the interpretation of test results.