Summary A 26-year-old woman presented with persistent headache and tiredness. Biological investigations disclosed a moderate inflammatory syndrome, low PTH-hypercalcemia and complete anterior ...hypopituitarism. A magnetic resonance imaging (MRI) of the pituitary gland was performed and revealed a symmetric enlargement with a heterogeneous signal. Ophthalmological examination showed an asymptomatic bilateral anterior and posterior uveitis, and a diagnosis of pituitary sarcoidosis was suspected. As the localization of lymphadenopathies on the fused whole-body FDG-PET/computerized tomography (CT) was not evoking a sarcoidosis in first instance, an excisional biopsy of a left supraclavicular adenopathy was performed showing classic nodular sclerosis Hodgkin’s lymphoma (HL). A diagnostic transsphenoidal biopsy of the pituitary gland was proposed for accurate staging of the HL and surprisingly revealed typical granulomatous inflammation secondary to sarcoidosis, leading to the diagnosis of a sarcoidosis–lymphoma syndrome. The co-existence of these diseases constitutes a diagnostic challenge and we emphasize the necessity of exact staging of disease in order to prescribe adequate treatment. Learning points: The possibility of a sarcoidosis–lymphoma syndrome, although rare, should be kept in mind during evaluation for lymphadenopathies. In the case of such association, lymphoma usually occurs after sarcoidosis. However, sarcoidosis and lymphoma can be detected simultaneously and development of sarcoidosis in a patient with previous lymphoma has also been reported. An accurate diagnosis of the disease and the respective organ involvements, including biopsy, is necessary in order to prescribe adequate treatment.
Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus
. ...The gut microbiota is a new key contributor involved in the onset of obesity-related disorders
. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension
. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 10
A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), and reduced insulinemia (-34.08 ± 7.12%, P = 0.006) and plasma total cholesterol (-8.68 ± 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (-2.27 ± 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (-1.37 ± 0.82 kg, P = 0.092) and hip circumference (-2.63 ± 1.14 cm, P = 0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115 ) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters.
We report and discuss the case of a 51-year-old patient undergoing elective laparoscopic surgery for pheochromocytoma after 10 days of medical pre-treatment. After anaesthetic induction, a deep level ...of anaesthesia could not prevent the onset of repeated hypertensive peaks, followed by severe hypotensive periods. Once the surgical incision was made, the patient developed acute pulmonary oedema along with significant oxygen desaturation. The decision was made to stop the surgery and transfer the patient to the intensive care unit (ICU) for further support and management. Unfortunately, additional monitoring and symptomatic treatment did not help haemodynamic stabilisation. In the absence of any external stimulation or medical support, the oscillation of blood pressure (BP) continued with peaks every 20 minutes up to 300 mmHg systolic blood pressure (SBP) and falls down to 30 mmHg SBP. The patient also sustained two episodes of cardiac arrest from which he recovered. Facing this unmanageable situation, a decision was made after a multi-disciplinary discussion to go back to surgery in order to remove the source of adrenergic stimulation. Surgery by laparotomy was performed and catecholamine substitution was provided. Nevertheless, after tumour removal, BP dropped leading to a third cardiac arrest that was successfully managed. Following a 10-day stay in the ICU, the patient left with subsequent cardiac stabilisation and full recovery.
ContextFew studies have recently re-examined the efficacy of neurosurgery in prolactinoma patients operated for various indications.ObjectiveTo analyze outcomes of patients with a prolactinoma ...treated by transsphenoidal surgery, to identify factors associated with remission and relapse, and to evaluate if surgical debulking allows for better hormonal control in patients with preoperative resistance to dopamine agonists (DAs).Patients and methodsThis was a retrospective review of patients with a benign prolactinoma followed preoperatively and postoperatively in our department and treated by transsphenoidal surgery (n=63; 45 women; mean age: 31±14 years).ResultsPostoperative remission was obtained in 63% of microprolactinomas, 60% of noninvasive macroprolactinomas, and none of the invasive macroprolactinomas. Better remission rate was independently predicted by lower diagnostic prolactin (PRL) levels and by the lack of abnormal postoperative residual tissue (P<0.05). A recurrence of hyperprolactinemia was observed in 34% of patients after a median follow-up period of 36 (7–164) months. In patients with preoperative DA resistance treated again after surgery, there was a significant reduction in PRL levels postoperatively (26 (6–687) ng/ml) vs preoperatively (70 (22–1514) ng/ml; P<0.01) under a lower DA dose, and about half of the patients had PRL normalization.ConclusionsRecurrence of hyperprolactinemia is observed in one-third of prolactinoma patients after surgical remission and may occur as late as 13 years after surgery. Resistance to DA can be considered as a good surgical indication, as partial tumor resection allows for better hormonal control with a lower dose of DAs.
Abstract Objective: Pheochromocytomas/paragangliomas (PPGL) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or from neural-crest derived sympathetic tissue. They ...secrete catecholamines in varying amounts, which accounts for their symptomatology. Hypertension is the most common sign, found in approximately 95% of patients. Nowadays, biochemical testing remains the simplest and most widely available method to assess PPGL in first intention. Identification of mutations in known susceptibility genes may help further refining tumor characterization and prognosis assessment. The objective of this study was to analyze clinical characteristics of PPGL from Belgium according to their secretory and genetic profiles. Design and method: We retrospectively analyzed a cohort of 120 cases of non-syndromic PPGL diagnosed in 19 Belgian centres. Clinical characteristics were correlated with three catecholamine phenotypes based on urinary metanephrines (noradrenergic, adrenergic and silent) and with the results of genetic screening. Results: Our cohort included a majority of women (59%). The mean age at diagnosis was 47 ± 7 years. We documented the prevalence of pediatric (7.5%), extra-adrenal (13.3%), bilateral (2.9%), multifocal (5.1%), recurrent (8.5%), metastatic (7.6%) and familial (5.9%) cases. While the yield of positive genetic screening was low (15%), the presence of at least one of these criteria was associated with a 4-fold increased prevalence of mutation (30.3 vs 8.5%; p = 0.03). In the subset in whom metanephrines values were available (n = 62), the prevalence of adrenergic, noradrenergic and silent phenotypes was 58%, 34% and 8% respectively. Patients belonging to these three subsets differed by age at diagnosis (51 ± 14; 38 ± 17; 42 ± 13 years; p = 0.009), the proportion of extra-adrenal tumors (2.8%; 9.5%; 40%; p = 0.016), pediatric (2.8%; 19%; 0%; p = 0.074) and familial (0%; 18.8%; 0%; p = 0.041) cases. Finally, an excess of dopamine secretion was associated with a higher prevalence of metastatic disease (25% vs 1.9%; p = 0.005). Conclusions: Secretory phenotypes and genetic profiles deserve to be integrated in the preoperative characterization of PPGL and may help orienting management and follow-up. Simple clinical features are associated with an increased probability of inherited tumor. Identification of an increased dopamine secretion should raise the suspicion of metastatic PPGL.
This study investigated the outcome of transsphenoidal surgery (TSS) for Cushing disease (CD) and the influence of our surgical strategy on remission rates and postoperative pituitary function.
We ...retrospectively reviewed data from 71 patients with CD who underwent microscope navigation TSS (MN-TSS) in Saint-Luc Hospital between 1996 and 2017. True remission was defined as normal fasting cortisol level, normal 24-hour urinary free cortisol, or continued need for hydrocortisone replacement for 1 year after surgery.
Overall remission rate after 1 or repeated MN-TSS was 83%. Highest remission rate was found in patients with macroadenomas (92%). Successful first MN-TSS was correlated with a high final remission rate (95%), whereas failed first MN-TSS was correlated with a low final remission rate (36%). Although day 1 cortisol levels were significantly lower in patients with long-term remission, high levels were still observed in a few patients, especially those who had had CD for many years. We found a low rate of postoperative pituitary long-term hypofunction (9.7%).
MN-TSS is a safe and effective procedure to treat CD, allowing remission rates of 83%. One-year remission period after first surgery is correlated with a final remission rate of 95%. Although day 1 morning cortisol value is the most significant predictor for long-term remission, some patients with CD for many years may keep high postoperative cortisol levels and be in later remission, likely because of secondary adrenal hyperplasia. Our focused approach with microscope navigation resulted in low rates of postoperative pituitary hypofunction and kept a recurrence rate comparable to that in the literature.
•The overall remission rate in our center (mainly 1 surgeon) was 83%. Highest remission rate in patients with macroadenomas (92%).•Successful first MN-TSS was correlated with a high final remission rate (95%), failed first MN-TSS remained associated with a low final remission rate (36%) even after additional surgery.•For patients with CD for many years, a high-level day 1 cortisol level was regularly observed even if followed by long-term remission.•Less than 10% of postoperative pituitary long-term hypofunction.
Abstract Context Current guidelines for distinguishing Cushing's disease (CD) from ectopic ACTH secretion (EAS) are questionable, as they use pituitary magnetic resonance imaging (MRI) as first-line ...investigation for all patients. CRH testing is no longer available, and they suggest performing inferior petrosal sinus sampling (BIPPS), an invasive and rarely available investigation, in many patients. Objective To establish noninvasive personalized diagnostic strategies based on the probability of EAS estimated from simple baseline parameters. Design Retrospective study. Setting University hospitals. Patients Two hundred forty-seven CD and 36 EAS patients evaluated between 2001 and 2023 in 2 French hospitals. A single-center cohort of 105 Belgian patients served as external validation. Results Twenty-four-hour urinary free cortisol (UFC) had the highest area under the receiver operating characteristic curve for discrimination of CD from EAS (.96 95% confidence interval (CI), .92-.99 in the primary study and .99 95% CI, .98-1.00 in the validation cohort). The addition of clinical, imaging, and biochemical parameters did not improve EAS prediction over UFC alone, with only BIPPS showing a modest improvement (C-statistic index .99 95% CI, .97-1.00). Three groups were defined based on baseline UFC: < 3 (group 1), 3-10 (group 2), and > 10 × the upper limit of normal (group 3), and they were associated with 0%, 6.1%, and 66.7% prevalence of EAS, respectively. Diagnostic approaches performed in our cohort support the use of pituitary MRI alone in group 1, MRI first followed by neck-to-pelvis computed tomography scan (npCT) when negative in group 2, and npCT first followed by pituitary MRI when negative in group 3. When not combined with the CRH test, the desmopressin test has limited diagnostic value. Conclusion UFC accurately predicts EAS and can serve to define personalized and noninvasive diagnostic algorithms.
Summary
Context Data concerning the safety for pregnancy of cabergoline treatment in hyperprolactinaemic women are still scarce.
Objective To exclude a higher than normal risk for miscarriage and ...congenital malformation in pregnancies initiated under cabergoline treatment.
Design A retrospective study of 100 pregnancies in 72 hyperprolactinaemic women treated with cabergoline at the time of conception and follow‐up of the 88 newborn children.
Methods Cabergoline was interrupted in 99 pregnancies and continued in one case. Foetal exposure dose to cabergoline was calculated for each pregnancy. Complications of pregnancy and neonatal status were compared to those observed in an age‐and delivery time‐matched control group of 163 women.
Results The mean foetal exposure dose to cabergoline was 3·6 ± 4·7 mg. The rate of spontaneous miscarriages was 10%. Three medical terminations of pregnancy were performed for a foetal malformation (3%). Minor to moderate complications were observed in 31% of the pregnancies, a figure similar to that found in the control group. An increase in tumour size (2–8 mm) was observed in 17/37 evaluated cases, needing reintroduction of cabergoline during pregnancy in five patients. The 84 deliveries resulted in 88 infants, three of them presenting with a malformation (3·4%). Neonatal status was comparable to the control group, where a malformation rate of 6·3% was observed. Postnatal development of the children was normal.
Conclusion Cabergoline treatment at the time of conception appears to be safe for both the pregnancy and the neonate, although more data are still needed on a larger number of pregnancies.
Current guidelines for distinguishing Cushing's disease (CD) from ectopic ACTH secretion (EAS) are questionable, as they use pituitary MRI as first-line investigation for all patients, CRH testing is ...no longer available and they suggest performing inferior petrosal sinus sampling (BIPPS), an invasive and rarely available investigation, in many patients.
To establish non-invasive personalized diagnostic strategies based on the probability of EAS estimated from simple baseline parameters.
Retrospective study.
University hospitals.
247 CD and 36 EAS patients evaluated between 2001 and 2023 in 2 French hospitals. A single-center cohort of 105 Belgian patients served for external validation.
24h-urinary free cortisol (UFC) had the highest area under ROC curve for discrimination of CD from EAS (0·96 95% CI, 0·92-0·99 in the primary study and 0·99 95% CI, 0·98-1·00 in the validation cohort). The addition of clinical, imaging and biochemical parameters did not improve EAS prediction over UFC alone, with only BIPPS showing a modest improvement (c-statistic index 0·99 95% CI, 0·97-1·00). 3 groups were defined based on baseline UFC: < 3 (group one), 3-10 (group 2) and > 10 x the upper limit of normal (group 3), and were associated with 0%, 6·1% and 66·7% prevalence of EAS, respectively. Diagnostic approaches performed in our cohort support the use of pituitary MRI alone in group one, MRI first followed by neck-to-pelvis CT-scan (npCT) when negative in group 2, and npCT first followed by pituitary MRI when negative in group 3. When not combined with the CRH test, the desmopressin test has limited diagnostic value.
UFC accurately predicts EAS and can serve to define personalized and non-invasive diagnostic algorithms.
PDF
