Resumen en Inglés:

Abstract 11β-hydroxylasedeficiency (11β-OHD) is a rare form of congenital adrenal hyperplasia caused by biallelic pathogenic variants in the CYP11B1 gene. It leads to impaired cortisol synthesis, resulting in increased adrenocorticotropic hormone stimulation and consequent accumulation of steroid precursors, which are diverted to androgen synthesis. In addition, the accumulation of 11-deoxycorticosterone, which is a potent mineralocorticoid, causes hyporeninemic hypokalemic hypertension. We report the clinical, hormonal, and genetic profiles of five children with 11β-OHD, emphasising phenotypic variability, a median 2-year diagnostic delay, the crucial role of hormonal profile in diagnosis, and management challenges, including post-treatment central precocious puberty. Two novel CYP11B1 variants were identified in two unrelated patients. Hydrocortisone replacement resolved hypertension in only one of the three hypertensive patients; others required spironolactone. Early differentiation of 11β-OHD from 21-hydroxylase deficiency is critical to prevent hypertension-related morbidity.

Resumen en Inglés:

Abstract Neonatalsevere hyperparathyroidism (NSHPT) is a rare, life-threatening disorder caused by biallelic inactivation of the CASR gene, resulting in severe hypercalcemia and markedly elevated parathyroid hormone (PTH) levels in early life. Although total parathyroidectomy is often curative, long-term calcium balance and treatment requirements remain poorly understood. We describe the 25-year follow-up of a woman with NSHPT due to a homozygous CASR p.Arg680His variant who underwent total parathyroidectomy with autotransplantation at 32 days of age. Despite initial normalization of calcium levels, graft failure led to permanent hypoparathyroidism requiring long-term calcium and active vitamin D supplementation. Over time, calcium and calcitriol requirements progressively decreased despite persistently undetectable PTH, with recurrent episodes of hypercalcemia requiring careful dose adjustments. This case represents one of the longest documented follow-ups of genetically confirmed homozygous CASR-related NSHPT. The progressive decline in calcium requirements reflects impaired renal calcium excretion and an altered calcium-PTH set point characteristic of CASR inactivation. These physiological adaptations challenge the conventional supplementation strategies and suggest that standard hypoparathyroidism guidelines - largely derived from acquired or autoimmune forms - may require cautious individualization in patients with homozygous CASR variants, given their distinct renal calcium handling and the possibility of lower urinary calcium excretion. Our findings reinforce the complexity of long-term management in NSHPT patients and illustrates how calcium requirements may change over time. Long-term follow-up cases such as this may contribute to a better understanding of the physiological mechanisms and inform future guideline development for this rare condition.

Resumen en Inglés:

Abstract Objective: Obesity and diabetes are widely recognized risk factors for cardiovascular disease, and their increase among Indigenous populations has been documented in the medical literature. Given the regional differences in the prevalence of metabolic disorders, this study aimed to evaluate the prevalence of obesity, diabetes, and other metabolic conditions in the Bororo population of the Central-West region of Brazil. Subjects and methods: In this cross-sectional study, 152 Bororo individuals from the Meruri Reservation in Mato Grosso, Brazil, underwent clinical, anthropometric, and laboratory assessments. Results: Women presented a worse metabolic profile than men, demonstrating significantly higher body mass index, waist circumference, total cholesterol, LDL-c, and 2-hour glucose levels, whereas men exhibited higher systolic blood pressure. Obesity was observed in 30.2% of the participants, with a higher prevalence among women (40.0% vs. 21.9%, p = 0.02). Prediabetes affected 51.3% of the participants, showing a higher prevalence in older men than in younger men (70.6% vs. 43.7%, p = 0.02). Diabetes was diagnosed in 9.2% of the participants, exclusively among women (20.0%), and rose to 38.7% in women aged ≥40 years. Hypertension was present in 23.0% of the participants and was positively associated with age. Central obesity was highly prevalent in this study cohort (72.3%). Conclusion: Our findings revealed an unfavorable metabolic profile among the Bororo Indigenous population, particularly in older women. This underscores the critical need for sexand age-specific preventive measures and management strategies for metabolic diseases in this population.