Objective: primary empty sella (PES) represents a frequent finding, but data on hormonal alterations are heterogeneous, and its natural history is still unclear. Our aim was to evaluate the pituitary function of patients with PES over a long follow-up.Design: multicenter retrospective cohort study enrolling patients referred between 1984-2020 to five Pituitary Units, with neuroradiological confirmed PES and a complete hormonal assessment.Methods: we analyzed hormonal (including basal and dynamic evaluations), clinical and neuroradiological data collected at diagnosis and at the last visit (at least 6 months of follow-up).Results: we recruited 402 patients (females=63%, mean age=51.5 ± 16 years) with PES (partial, total, undefined in 66%, 13% and 21%, respectively). Hypopituitarism was present in 40.5% (hypogonadism=20.4%, hypoadrenalism=14.7%, growth hormone deficiency=14.7%, hypothyroidism=10.2%, diabetes insipidus=1.5%; multiple deficiencies=11.4%) and hypeprolactinemia in 6.5%. Interestingly, hormonal alterations were diagnosed in 29% of incidental PES. Hypopituitarism was associated with male sex (p=0.02), suspected endocrinopathy (p<0.001), traumatic brain injury (p=0.003) and not with age, BMI, number of pregnancies and neuroradiological grade. A longitudinal assessment was possible in 166/402 (median follow-up=58 months). In 5/166 (3%), new deficiencies occurred, whereas 14/166 (8.4%) showed a hormonal recovery. A progression from partial to total PES, which was found in 6/98 patients assessed with a second imaging, was the only parameter significantly related to the hormonal deterioration (p=0.006).Conclusions: this is the largest cohort of patients with PES reported. Hypopituitarism is frequent (40%) but hormonal deterioration seems uncommon (3%). Patients need to be carefully evaluated at diagnosis, even if PES is incidentally discovered.

Primary hyperparathyroidism represents the third most prevalent endocrine disease in the general population, consisting of an excessive secretion of parathyroid hormone from one or, more frequently, more of the parathyroid glands, leading to a dysregulation of calcium homeostasis. Schematically, its development occurs primarily by pathophysiological events with genetic mutation, at the germline and/or somatic level, that favor the neoplastic transformation of parathyroid cells and promote their aberrant proliferation, and mutations determining the shift in the PTH “set-point”, thus interfering with the normal pathways of PTH secretion and leading to a “resetting” of Ca²⁺-dependent PTH secretion or to a secretion of PTH insensitive to changes in extracellular Ca²⁺ levels. Familial syndromic and non-syndromic forms of primary hyperparathyroidism are responsible for approximately 2–5% of primary hyperparathyroidism cases and most of them are inherited forms. The history of the genetic/molecular studies of parathyroid tumorigenesis associated with multiple endocrine neoplasia type 1 syndrome (MEN1) represents an interesting model to understand genetic–epigenetic–molecular aspects underlying the pathophysiology of primary hyperparathyroidism, both in relation to syndromic and non-syndromic forms. This minireview aims to take a quick and simplified look at the MEN1-associated parathyroid tumorigenesis, focusing on the molecular underlying mechanisms. Clinical, epidemiological, and observational studies, as well as specific guidelines, molecular genetics studies, and reviews, have been considered. Only studies submitted to PubMed in the English language were included, without time constraints.

Primary hyperparathyroidism represents the third more prevalent endocrine disease in general population consisting of an excessive secretion of parathyroid hormone from one, more frequently, or more of the parathyroid glands, leading to a dysregulation of calcium homeostasis. Schematically, its development occurs primarily by pathophysiological events with genetic mutation, at germline and/or somatic level, that favor the neoplastic transformation of parathyroid cells, and promoting their aberrant proliferation, and mutations determining the shift of PTH "set-point”, thus interfering with the normal pathways of PTH secretion, and leading to a “resetting” of Ca2+-dependent PTH secretion or to a secretion of PTH insensitive to changes in extracellular Ca2+ levels. Familial syndromic and non-syndromic forms of primary hyperparathyroidism are responsible for approximately 2-5%, of primary hyperparathyroidism cases and most of them are inherited forms. The history of the genetic/molecular studies of parathyroid tumorigenesis associated with Multiple Endocrine Neoplasia type 1 Syndrome (MEN1) represents a fascinating topic and model to understand genetic-epigenetic-molecular aspects underlying the pathophysiology of primary hyperparathyroidism, both in relation to the syndromic and non-syndromic forms. This minireview aims to take a quick and simplified look at the MEN1-associated parathyroid tumorigenesis, focusing on the molecular underlying mechanisms. Clinical, epidemiological, and observational studies, as well as specific guidelines, molecular-genetics studies, and reviews, have been considered. Only studies submitted to PubMed in English language were included, without time constraints.

Purpose: Transgender and gender diverse (TGD) individuals have various medical needs, but limited healthcare professionals’ expertise remains a major barrier to care. Data on the preparedness of Italian endocrinologists to provide TGD care are scarce. This study assessed Italian endocrinologists’ knowledge, clinical practice, and educational needs in gender-affirming care. Methods: A nationwide survey developed by the Association of Medical Endocrinologists (AME), with support from the Italian Society for Gender, Identity and Health, was distributed to all AME members in 2023. Multivariable logistic regression identified factors associated with knowledge, self-reported ability to manage gender-affirming hormone therapy (GAHT) and interest in further education. Results: Overall, 703 endocrinologists completed the survey. Only 8.4% reported frequent clinical involvement with TGD patients, and fewer than 15% considered themselves able to initiate and monitor GAHT. Previous education in gender-affirming care was the strongest determinant of knowledge (OR 14.3) and self-reported ability to manage GAHT (OR 4.4). Younger age was associated with greater knowledge but not with perceived clinical competence. Nevertheless, 90.4% expressed interest in further education. Conclusion: Italian endocrinologists show substantial gaps in preparedness for transgender care. Structured education in gender-affirming care is strongly associated with greater knowledge and self-reported ability to manage GAHT, supporting the implementation of educational programs to improve access to competent endocrine care for TGD individuals.