Browsing by Author "Uslar Nawrath, Thomas Hermann"

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    Clinical Update on Congenital Adrenal Hyperplasia: Recommendations from a Multidisciplinary Adrenal Program
    (2023) Uslar Nawrath, Thomas Hermann; Olmos Borzone, Roberto Ignacio; Martinez Aguayo, Alejandro; Baudrand Biggs, René
    Congenital adrenal hyperplasia (CAH) is a common genetic disorder in endocrinology, especially its milder clinical presentation, often caused by a partial or total deficiency of the 21-hydroxylase enzyme located in the adrenal cortex. CAH is characterized by the overproduction of androgen, along with variable degrees of cortisol and aldosterone deficiency. The age at diagnosis can provide some information about underlying mutations, with those diagnosed at birth/early infancy more likely to have severe enzymatic defects, which may include adrenal insufficiency, sexual development disorders, short stature in adulthood, hirsutism, and a higher risk for metabolic syndrome and infertility. Non-classic CAH, a milder form of CAH, is usually manifested later in life and is a common differential diagnosis of Polycystic Ovary Syndrome and should be actively evaluated during initial studies of clinical or biochemical hyperandrogenism. The main goals of CAH treatment are hormone supplementation for severe cases, controlling adrenal androgen overproduction to minimize long-term side effects, managing fertility and genetic counseling, and optimizing patients' quality of life.
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    Discriminative Capacity of CT Volumetry to Identify Autonomous Cortisol Secretion in Incidental Adrenal Adenomas
    (ENDOCRINE SOC, 2022) Olmos Borzone, Roberto Ignacio; Mertens Folch, Nicolas Andres; Vaidya, Anand; Uslar Nawrath, Thomas Hermann; Fernández Walker, Paula Soledad; Guarda Vega, Francisco; Zuñiga, Alvaro; San Francisco Reyes, Ignacio Felipe; Huete Garin, Isidro Alvaro; Baudrand Biggs, Rene Felipe
    Context: Incidentally discovered adrenal adenomas are common. Assessment for possible autonomous cortisol excess (ACS) is warranted for all adrenal adenomas, given the association with increased cardiometabolic disease.
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    Genotype-specific neoplastic risk profiles in patients with VHL disease
    (Bioscientifica Ltd., 2025) Ganner, Athina; Ferrara, Alfonso Massimiliano; Sekula, Peggy; Schiavi, Francesca; Joo, Julia H.; Sanso, Gabriela; Almeida, Madson; Knoblauch, Anna Laura; Gizaw, Christine Julia; Krzystolik, Karol; Astheimer, Sophie Charlotte Astheimer; Achatz, María Isabel; Vieites, Ana; Donegan, Diane; Hundsberger, Thomas; Lubinski, Jan; Yildirim Simsir, Ilgin; Bandgar, Tushar; Hasse-Lazar, Kornelia; Pawlaczek, Agnieszka; Kater, Claudio E.; Baudrand Biggs, René Felipe; Andreescu, Corina E.; Uslar Nawrath, Thomas Hermann; Ishak, Tada
    Hereditary tumor predisposition syndromes pose a challenge for early detection and timely treatment of tumors. In von Hippel-Lindau disease, desirable personalized surveillance programs are lacking due to insufficient data on genotype-specific risk profiles of individual mutations. To describe neoplastic risk profiles for carriers of pathogenic and likely pathogenic VHL germline mutations, our observational study recruited 1,350 participants from 40 centers worldwide. 432 different VHL germline mutations were observed, with p.Asn78Ser, p.Arg161Ter, p.Arg161Gln, p.Arg167Gln, p.Arg167Trp and p.Tyr98His being the six most frequent, occurring in a total of 493 carriers (36.5%) and in ≥30 patients each. Age-related penetrance risks for retinal hemangioblastoma, central nervous system hemangioblastoma, renal cell carcinoma, pancreatic neuroendocrine tumors and pheochromocytoma/paraganglioma in carriers of the most frequent VHL mutations were assessed. In addition, the number of organs affected, the frequency of surgery and the outcome are reported. Pairwise comparisons of the age-dependent tumor penetrance of these six mutations showed that 47 out of 90 pairs were significantly different. The most significant associations were found in p.Tyr98His (n = 19), followed by p.Arg161Ter (n = 10). All pairwise comparisons of mutations affecting different codons showed at least one significant (P < 0.05) difference, except for p.Asn78Ser vs p.Arg161Ter. Thus, tumor risk varied by VHL mutation type and location, but did not differ between the truncating mutation p.Arg161Ter and the missense mutation p.Asn78Ser. Our study demonstrates the importance of mutation-specific phenotype prediction. With appropriate validation, the data have important implications for risk assessment and decision making in tumor prevention for carriers of the respective VHL mutations.
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    Primary aldosteronism in a hispanic cohort: responses to mineralocorticoid receptor antagonism and remission in a case
    (2025) Tapia Castillo, Alejandra; Vecchiola Cárdenas, Andrea Paola; Quiñones, Paola; Baudrand Biggs, Rene Felipe; Uslar Nawrath, Thomas Hermann; Delgado García, José Frobel; Carvajal Maldonado, Cristian Andrés; Fardella Bello, Carlos Enrique
    Background: Primary aldosteronism (PA) is the main cause of secondary arterial hypertension. In this study, we present the medical treatment of Hispanic patients with PA followed for up to 5 years, highlighting the complete cure with pharmacological treatment in one of our patients. Methods: We studied 32 PA patients, followed every 6 months after starting MRA. A clinical response was the normalization of blood pressure (BP) in the absence of other antihypertensive drugs. The biochemical response was considered with normalization of potassium and renin. Responses to treatment were compared using the defined daily dose (DDD). The effect of MRA was evaluated in vitro. The HAC15 cells were cultured and stimulated with aldosterone and spironolactone for 24-72h, and the apoptotic cell death was measured. Results: At 12 months posttreatment with MRA, 68% of the patients had a total clinical response, and 67% had a total biochemical response. Response to MRA treatment reduced DDD by an average of 74%. Additionally, we observed one PA patients treated with spironolactone after three years, he presented a pharmacological cure with normalization of aldosterone and renin without treatment with spironolactone. The in vitro study shows that spironolactone increased early apoptosis in a 60% and late apoptosis in a 50%. Conclusion: These results suggest the importance of timely diagnosis of PA and specific treatment with MRA, especially in patients with a poor response to treatment. Moreover, remission of PA may occur in some patients after spironolactone treatment due to its suggestive role as an apoptotic agent.
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    The Spectrum from Overt Primary Aldosteronism to Mild Dysregulated Aldosterone Production in Incidentally Discovered Adrenocortical Adenomas
    (2024) Uslar Nawrath, Thomas Hermann; Olmos, Roberto; Burnier, Alberth; Sanfuentes, Benjamín; Böhm, Pauline; Orellana, Maria Paz; Guarda, Francisco J.; Huete, Alvaro; Mertens, Nicolás; Besa, Cecilia; Andia, Marcelo E.; Majerson, Alejandro; Cartes, Jaime; Fardella, Carlos; Allende, Fidel; Solari, Sandra; Vaidya, Anand; Baudrand Biggs, René
    Background Incidental adrenocortical adenomas (IA) are common. Current guidelines suggest screening for primary aldosteronism (PA) only in cases of hypertension or hypokalemia. This study aimed to evaluate the spectrum from overt PA to mild dysregulated aldosterone production with a sensitive protocol irrespective of blood pressure (BP) and potassium in patients with IA.Methods 254 consecutive patients (excluding hypercortisolism) were evaluated. The spectrum of PA was defined as a suppressed renin plus the following criteria: 1)Overt PA: aldosterone-to-renin-ratio (ARR) >30 ng/dL-to-ng/mL/hr, plasma aldosterone concentration (PAC) >15ng/dL, and/or 24h urinary aldosterone >10 ug/24h; 2)Moderate PA: ARR 20-30 ng/dL-to-ng/mL/hr, PAC 10-15 ng/dL; 3)Mild dysregulated aldosterone production: ARR <20 ng/dL-to-ng/mL/hr and PAC >5-10 ng/dL.Results 35% (n=89/254) met criteria for PA spectrum, 20% (34/89) were initially normotensive and 94% (84/89) normokalemic. Overt, moderate, and mild groups were 10%, 12%, and 13%. There were trends across groups of clinical severity: systolic BP (153±19, 140±14, 137±14 mmHg, p-trend<0.05), resistant hypertension (50%, 23%, 7% p-trend=<0.001), daily defined dose of antihypertensives (DDD) (3.2±1.6, 1.2±1.5, 0.4±0.6 p-trend=0.001), and lower eGFR (75.5±30.8, 97.8±38.5, 101±25.5, p-trend<0.01). At follow-up (mean 28±15 months), 87% had treatment with MR antagonists or surgery with decreased systolic BP relative to clinical severity, −31.3 ±23, −12.7 ±19, and −11.4 ±19 mmHg, (p-trend<0.001). Similar trends were observed for DDD, with significant increase in renin.Conclusions There is a prevalent spectrum of clinically-relevant PA and dysregulated aldosterone production in IA, irrespective of BP or potassium, usually undetected. Aldosterone-directed treatment improved BP and normalized renin even in milder cases.