Laboratory Testing for Endocrine Hypertension: Current and Future Perspectives.

BACKGROUND: Secondary hypertension (SH) is a form of high blood pressure caused by an identifiable underlying condition. Although, it accounts for a small fraction of the overall hypertensive population, detection and management of SH is of utmost importance, because SH phenotypes carry a high cardiovascular risk and can possibly be cured by timely treatment. CONTENT: This review focuses on the endocrine causes of SH, such as primary aldosteronism, Cushing syndrome, thyroid disease, pheochromocytoma and paraganglioma, acromegaly, and rare monogenic forms. It discusses current biomarkers, analytical methods, and diagnostic strategies, highlighting advantages and limitations of each approach. It also explores the emerging -omics technologies that can provide a comprehensive and multidimensional assessment of SH and its underlying mechanisms. SUMMARY: Endocrine SH is a heterogeneous and complex condition that requires proper screening and confirmatory tests to avoid diagnostic delays and improve patient outcomes. Careful biomarker interpretation is essential due to potential interferences, variability, and method-dependent differences. Liquid chromatography-tandem mass spectrometry is a superior method for measuring low-concentration hormones and metabolites involved in SH, but it requires expertise. Omics approaches have great potential to identify novel biomarkers, pathways, and targets for SH diagnosis and treatment, especially considering its multifactorial nature.

Recovery from hypogonadism in men with prolactinoma treated with dopamine agonists.

PURPOSE: In men with prolactinoma treated with dopamine agonists (DA), the extent, timeline, and predictive factors of gonadotropic axis recovery are still unclear. METHODS: We analyzed data of 97 men with a prolactinoma treated with DA (77/97 macroprolactinomas). We excluded patients with primary hypogonadism, surgery < 12 months after DA initiation, and patients with tumors < 5 mm or prolactin < 45 µg/l at diagnosis. RESULTS: Among the 97 patients, 12 had normal total testosterone (NT group) and 85 had low testosterone at diagnosis (LT group). In the NT group, testosterone rose from a mean of 13.5 nmol/l to 17.1nmol/l at 6 months (n = 11; p < 0.05) then remained stable at 12 months (n = 8). In the LT group, testosterone rose from a mean of 5.2 nmol/l to 9.6 nmol/l at 6 months (n = 66; p < 0.001) and further to 13.1nmol/l at 12 months (n = 40; p < 0.001) then remained stable. Recovery from hypogonadism occurred in 43%, 50%, and 54% of patients at 6, 12 and 24 months, respectively (61%, 69 and 69% if prolactin was normal). Factors independently associated with persistent hypogonadism at 12 months were at baseline the presence of visual field deficit and lower testosterone levels, while the most significant independent predictor of persistent hypogonadism at one year was a testosterone level < 7.4 nmol/l at 6 months, with 91% sensitivity and 94% specificity. CONCLUSION: Testosterone levels recover in a small majority of men with prolactinoma mostly during the first year of DA treatment. However, testosterone replacement could be considered earlier in patients with large and compressive tumors, and in whom testosterone remains below 7.4 nmol/l after 6 months of DA treatment.

Sexual dysfunction in male patients treated with methorexate for arthritis: Analysis of the IIEF5 questionnaire and hormonal status.

OBJECTIVE: The aim of this study is to evaluate the impact of methotrexate (MTX) on erectile function in male patients through the International Index of Erectile Function (IIEF5) questionnaire and hormonal dosage. METHODS: Male patients affected by inflammatory arthritis (rheumatoid arthritis [RA] or psoriatic arthritis [PsA]) with good disease control and treated with chronic MTX were enrolled. Age-matched patients affected by chronic arthritis not treated with MTX were enrolled as controls. Each patient had a complete sexual hormone evaluation. IIEF5 questionnaire was administered to each patient. RESULTS: One hundred and nine patients were included, 77 in the MTX group and 32 as controls. The median weekly MTX dose was 10mg (IQR 7.5) with a median MTX duration therapy of 8 years (IQR 17). The total IIEF5 score was lower in patients MTX exposed compared to the control group without a significant result. The total IIEF5 score of patients treated with MTX≥5 years was statistically significantly lower when compared to those non-MTX exposed patients (17 [IQR 15] versus 20 [IQR 7.7]; P=0.04) and compared to those treated for<5 years (17 [IQR 15] versus 20 [IQR 7]; P=0.01). A negative correlation was identified between the total IIEF5 score and MTX time exposure (r=-0.20 CI [-0.38 to -0.04]; P=0.039). MTX exposure was still associated with a lower IIEF5 score when adjusted for age (ß Estimate=-2.63; CI [-5.13 to -0.13]; P=0.039). Hormonal dosage was similar in both groups for all hormones evaluated. CONCLUSION: MTX exposure was associated with a lower IIEF5 score in male patients adjusted for age. The preliminary results need to be confirmed in larger prospective studies.

How often should we perform magnetic resonance imaging (MRI) for the follow-up of pituitary adenoma?

Magnetic resonance imaging (MRI) is the examination of choice for diagnosing and monitoring pituitary adenoma (also known as pituitary neuroendocrine tumor or PitNET), whether treated or not. However, repeating the examination too often (and sometimes unnecessarily) is costly, and worrying data on tissue accumulation (brain, bone, etc.) of gadolinium atoms dissociated from their carrier molecule (chelator) have led European authorities to ban contrast agents based on linear chelators of gadolinium, which are particularly susceptible to rapid dissociation, in favor of chemically more stable macrocyclic chelators. It is therefore important to determine the optimal frequency for pituitary MRI monitoring in order to safely assess the natural history or therapeutic response of pituitary adenomas. The aim of this article is to summarize the most recent data on optimal follow-up intervals depending on the type, size and location of the pituitary tumor and the clinical situation in general, in order to generate monitoring algorithms to guide clinicians.

Personalized non-invasive diagnostic algorithms based on urinary free cortisol in ACTH-dependant Cushing's syndrome.

CONTEXT: 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. OBJECTIVE: To establish non-invasive personalized diagnostic strategies based on the probability of EAS estimated from simple baseline parameters. DESIGN: Retrospective study. SETTING: University hospitals. PATIENTS: 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. RESULTS: 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. CONCLUSION: UFC accurately predicts EAS and can serve to define personalized and non-invasive diagnostic algorithms.

Long-term hypothyroidism in patients started on levothyroxine during pregnancy.

Background: Current guidelines recommend different postpartum approaches for patients started on levothyroxine (LT4) during pregnancy. Objective: We studied the postpartum management of these patients and determined factors associated with long-term hypothyroidism. Methods: A retrospective study was conducted at a tertiary center between 2014 and 2020, with LT4 initiation according to 2014 ETA recommendations. We performed multivariate logistic regression (MVR) and a receiver operating characteristic curve analysis to determine variables associated with long-term hypothyroidism and their optimal cutoffs. Results: LT4 was initiated in 177 pregnant women, and 106/177 (60%) were followed at long-term (at least 6 months post partum) (28.5 (9.0-81.9) months). LT4 could have been stopped in 45% of patients who continued it immediately after delivery. Thirty-six out of 106 (34%) patients were long-term hypothyroid. In them, LT4 was initiated earlier during pregnancy than in euthyroid women (11.7 ± 4.7 vs 13.7 ± 6.5 weeks, P = 0.077), at a higher thyroid-stimulating hormone (TSH) level (4.1 (2.2-10.1) vs 3.5 (0.9-6.9) mU/L, P = 0.005), and reached a higher dose during pregnancy (62.8 ± 22.2 vs 50.7 ± 13.9 µg/day, P = 0.005). In the MVR, only the maximal LT4 dose during pregnancy was associated with long-term hypothyroidism (odds ratio (OR) = 1.03, 95% CI: 1.00-1.05, P = 0.003). The optimal cutoffs for predicting long-term hypothyroidism were an LT4 dose of 68.75 µg/day (87% specificity, 42% sensitivity; P = 0.013) and a TSH level ≥ 3.8 mU/L (68.5% specificity, 77% sensitivity; P = 0.019). Conclusion: One-third of the patients who started on LT4 during pregnancy had long-term hypothyroidism. The TSH level at treatment initiation and the LT4 dose during pregnancy could guide the decision for continuing long-term LT4.

Patients' perspective on the medical pathway from first symptoms to diagnosis in genetic lipodystrophy.

OBJECTIVE: Underdiagnosis is an important issue in genetic lipodystrophies, which are rare diseases with metabolic, cardiovascular, gynecological, and psychological complications. We aimed to characterize the diagnostic pathway in these diseases from the patients' perspective. DESIGN: Cross-sectional study conducted through a self-reported patient questionnaire. METHODS: Patients with genetic lipodystrophy were recruited throughout the French national reference network for rare diseases of insulin secretion and insulin sensitivity. Patients completed a self-reported questionnaire on disease symptoms, steps leading to the diagnosis, and healthcare professionals involved. Descriptive analyses were conducted. RESULTS: Out of 175 eligible patients, 109 patients (84% women) were included; 93 had partial familial lipodystrophy and 16 congenital generalized lipodystrophy. Metabolic comorbidities (diabetes 68%, hypertriglyceridemia 66%, hepatic steatosis 57%), cardiovascular (hypertension 54%), and gynecologic complications (irregular menstruation 60%) were frequently reported. Median age at diagnosis was 30 years (interquartile range [IQR] 23-47). The overall diagnostic process was perceived as "very difficult" for many patients. It extended over 12 years (IQR 5-25) with more than five different physicians consulted by 36% of respondents, before diagnosis, for lipodystrophy-related symptoms. The endocrinologist made the diagnosis for 77% of the patients. Changes in morphotype were reported as the first symptoms by the majority of respondents. CONCLUSIONS: Diagnostic pathway in patients with genetic lipodystrophy is rendered difficult by the multisystemic features of the disease and the lack of knowledge of non-specialized physicians. Training physicians to systematically include adipose tissue examination in routine clinical evaluation should improve diagnosis and management of lipodystrophy and lipodystrophy-associated comorbidities.