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Purpose: Patients with Cushing’s syndrome (CS) have an increased venous thromboembolism (VTE) risk with most studies focusing on the perioperative period. The purpose of this study was to assess the 5-year VTE risk and identify predictors of VTE at CS diagnosis. Methods: A comparative nationwide retrospective cohort study of 609 patients (mean age 48.1 ± 17.2 years, 65.0% women) with CS, and 3018 age-, sex-, body mass index-, and socioeconomic status-individually matched controls. Ectopic CS and adrenal cancer were excluded. The time-to-event of pulmonary embolism (PE) or deep vein thrombosis (DVT) within 5 years of CS diagnosis was examined. VTE risk was calculated with death as competing event. Results: VTE occurred in 16 cases (2.6%), compared to 17 (0.56%) controls (hazard ratio [HR] 4.71, 95% CI, 2.38–9.33). The 5-year HRs for PE and DVT were 7.47 (95% CI, 2.66–20.98) and 3.32 (95% CI, 1.36–8.12), respectively. After excluding patients and controls with current or prior malignancy the risk for VTE was 7.57 (95% CI, 2.98–19.20). Patients with CS ≥ 60 years at diagnosis (HR, 3.49; 95% CI, 1.30–9.35), with hypertension (HR, 5.53; 95% CI, 1.26–24.27), ischemic heart disease (HR, 3.60; 95% CI, 1.25–10.36), kidney disease (HR, 4.85; 95% CI, 1.39–16.90), or VTE event prior to CS diagnosis (HR, 33.65; 95% CI, 10.07–112.42) had an increased risk of VTE within five years. Conclusions: In this large cohort of patients with CS, the 5-year VTE risk was 5 times higher compared with matched controls. Key baseline predictors included age ≥ 60, hypertension, heart/kidney disease, and prior VTE. [ABSTRACT FROM AUTHOR]

Hypopituitarism is a rare but significant endocrine disorder characterized by the inadequate secretion of one or more pituitary hormones. The intricate relationship between hypopituitarism and bone health is a topic of growing interest in the medical community. In this review the authors explore associations between hypopituitarism and bone health, with specific examination of the impact of growth hormone deficiency, central hypogonadism, central hypocortisolism, and central hypothyroidism. Pathogenesis, diagnosis, and treatment options as well as challenges posed by osteopenia, osteoporosis, and fractures in hypopituitarism are discussed. [ABSTRACT FROM AUTHOR]

Purpose: The aims of the current study were to describe clinical and biochemical features of patients with Paget disease of bone (PDB) followed at our medical center, and to examine the long-term effectiveness of zoledronate. Methods: Retrospective cohort study included consecutive patients≥18 years with a diagnosis of PDB, followed in the Rabin Medical Center (RMC) Institute of Endocrinology from 1973 to 2023. The cohort comprised two groups: patients treated/not treated with zoledronic acid (ZOL/NZOL). The primary outcome was the percentage of patients who achieved a biochemical therapeutic response. Results: Overall, 101 patients with PDB were included, 68 in the ZOL group and 33 in the NZOL group. The mean age was 65.2 ± 10.0 years, and 47% were female. Notably, 77% exhibited monostotic involvement, and only 3% had experienced fractures attributed to PDB. Mean ALP level at diagnosis was 160 ± 70.6 U/L. The median follow-up duration was 17 years since PDB diagnosis, comparable between the groups. Primary outcome was more prevalent in the ZOL compared to the NZOL group [42 patients (88%) VS 11 patients (52%) respectively, P = 0.004]. At the end of follow-up, mean ALP levels in the NZOL group were significantly higher than the levels in the ZOL group irrespective of the number of infusions received. Conclusion: The majority of patients with PDB experience a mild disease course, marked by monostotic involvement and a low prevalence of fractures. Zoledronic acid effectively manages PDB, providing sustained biochemical response. The necessity for multiple zoledronic acid injections remains questionable, often implemented due to osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to characterize the erythrocytic profile in patients with cushing's syndrome (CS) versus controls from the normal population according to etiology, sex, presence of diabetes mellitus (DM) and hypercortisolemia remission status. Methods: This retrospective cohort analysis compared erythrocytic parameters between patients with CS of pituitary (CD) and adrenal (aCS) etiology and age, sex, body mass index (BMI) and socioeconomic status-matched controls in a 1:5 ratio. Laboratory values at baseline were calculated as mean values during the year preceding CS diagnosis, and over one year thereafter. Results: The cohort included 397 CS patients (68.26% female; mean age 51.11 ± 16.85 years) and 1970 controls. Patients with CS had significantly higher baseline median levels of hemoglobin (Hgb) (13.70 g/dL vs. 13.12 g/dL [p < 0.0001]) and hematocrit (Hct) (41.64% vs. 39.80% [p < 0.0001]) compared to controls. These differences were observed for both CD and aCS and for both sexes. Patients who attained remission had Hgb and Hct levels comparable to controls (13.20 g/dL and 40.08% in patients with CD and aCS vs. 13.20 g/dL and 39.98% in controls). Meanwhile, those with persistent/recurrent disease maintained elevated levels. Patients with comorbid DM had similar Hgb but higher Hct (p = 0.0419), while patients without DM showed elevated erythrocytic values compared to controls (p < 0.0001). Conclusion: Our data illustrates that erythrocytic parameters are directly influenced by glucocorticoid excess as Hgb and Hct are higher in patients with CS, and normalize after remission. We have identified the influence of DM on erythrocytic parameters in patients with CS for the first time. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical presentation, biochemical profile, and etiology of Cushing's syndrome (CS) in women stratified by age. Methods: Retrospective study of patients with CS, treated at Rabin Medical Center from 2000 to 2020, or Maccabi Healthcare Services in Israel from 2005 to 2017. Disease etiology, presentation and biochemical profile were compared according to age at diagnosis: ≤ 45, 46–64, or ≥ 65 years. Study was approved by the Ethics Review Boards of both facilities with waiver of consent. Results: The cohort included 142 women (mean age, 46.0 ± 15.1 years):81 (57.0%) with Cushing's disease (CD), and 61 (43.0%) with adrenal CS. Pituitary etiology was more common among women < 45 (70.6%), compared with patients ≥ 65 years (31.6%) (P < 0.05). Among CS patients, hypercortisolism was diagnosed in the context of screening after an adrenal incidentaloma detection in 15.0% of patients < 45 and 53.8% of ≥ 65 years (P < 0.001). Weight gain was evident in 57.4% of women < 45 (56.3% CD, 60.0% CS), and 15.8% of women ≥ 65 years (50% CD, 0% CS) (P = 0.011). Mean UFC levels were highest for women < 45 (3.8 × ULN) and lowest for ≥ 65 years (2.3 × ULN) (P < 0.001). Conclusion: We have shown for the first time that women with CS ≥ 65 years of age more commonly have adrenal etiology. The initial presentation of CS also differs between age groups, where women < 45 years are likely to present with weight gain, while those ≥ 65 years are frequently diagnosed incidentally, when screening for hypercortisolism in the presence of an adrenal incidentaloma. [ABSTRACT FROM AUTHOR]

Purpose: To study the baseline characteristics predicting hypogonadotropic hypogonadism (HH) persistence in men with macroprolactinoma that achieved prolactin normalization. Design: Retrospective cohort study. Methods: Male patients diagnosed with macroprolactinoma and HH that received cabergoline treatment with subsequent prolactin normalization were included: men that achieved eugonadism, and men that remained hypogonadal. Patient's demographic, clinical and biochemical parameters, sellar imaging, and visual fields tests were obtained. Univariate and multivariate models were used to identify predictors of HH persistence. Results: Fifty-eight male patients (age 49.2 ± 12.6 years) with a median baseline prolactin of 1154 ng/mL (IQR 478–2763 ng/mL) and adenoma (maximal) diameter of 25.9 ± 14.8 mm were followed for a median of 5.6 years (IQR 3.0–10.7). Twelve men (21%) suffered from HH persistence at the end of follow-up and 46 men achieved eugonadism. Forty-two out of 46 men (91%) accomplished eugonadism within the first year following prolactin normalization. In a multivariate logistic regression model, hypopituitarism (OR 10.1; 95% CI 1.10–101.94), visual field defect (OR 9.9; 95% CI 1.07–92.33), and low baseline testosterone levels (OR 0.5; 95% CI 0.29–0.93) were independent predictors of HH persistence. Conclusion: In our cohort of men with macroprolactinoma that reached prolactin normalization with cabergoline treatment, 21% had HH persistence. Pituitary hormone deficiency, visual field defects, and low baseline testosterone levels were independently associated with HH persistence. 91% of men achieved eugonadism within the first year following prolactin normalization. These findings may support informed clinical decision-making regarding the initiation of testosterone replacement in men with macroprolactinomas. [ABSTRACT FROM AUTHOR]

Purpose: Men with mild to moderate hyperprolactinemia rarely present with normal pituitary on MRI with no visible adenoma, a condition entitled also "idiopathic hyperprolactinemia" or "non-tumoral hyperprolactinemia". We have characterized a cohort of hyperprolactinemic men with normal pituitary imaging. Design: We have identified 13 men with true hyperprolactinemia and normal pituitary MRI. Baseline clinical and hormonal characteristics and response to medical treatment were retrospectively retrieved from medical records. Results: Mean age at diagnosis was 51 ± 16 years (range, 20–77); mean serum prolactin level at presentation was 91 ng/ml (range, 28–264), eight men presented with low baseline testosterone. Initial complaints leading to diagnosis included sexual dysfunction in ten men and gynecomastia in five. All patients were treated with cabergoline, except for one who was given bromocriptine; none required pituitary surgery. All patients normalized prolactin and testosterone with subsequent clinical improvement reported by most men. Currently, after a mean follow-up of 72 months, ten patients continue treatment with caborgoline (median weekly dose, 0.25 mg), whereas three men discontinued treatment. Conclusions: Men with symptomatic hyperprolactinemia may rarely present with normal pituitary imaging. Medical treatment can lead to hormonal improvement with clinical benefit. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the risk of cataract in patients with Cushing’s syndrome (CS) and evaluate whether disease onset occurs at an earlier age compared to general population.A nationwide retrospective matched-cohort study including individuals diagnosed with endogenous CS from 2000 to 2023. Patients with CS were matched in a 1:5 ratio with a control group individually matched for age, sex, socioeconomic status, and body mass index. The primary outcome was the incidence of cataract and cataract surgery. The Cox proportional hazards model, accounting for death without cataract as a competing risk, was employed to estimate hazard ratio.The study cohort included 609 patients with CS, 65% women and 35% men, and 3018 controls. The average age at CS diagnosis was 48.1 ± 17 years. Follow-up duration was 14.6 years (IQR 9.8–20.2). The source of hypercortisolism was Cushing’s disease (CD) in 259 (42.6%) and adrenal CS (aCS) in 206 patients (33.8%). After CS diagnosis, cataract was observed in 171 patients (28.1%), and 771 controls (25.5%). Patients with CS had a 34% higher risk of developing cataract compared to their matched controls (HR = 1.34, 95% CI 1.03–1.75, p = 0.03). Cataract developed earlier in patients with CS compared to controls, with a mean age of onset at 64.7 ± 9.7 versus 67.6 ± 8.4 years, respectively (p = 0.01). A total of 49 (8.05%) patients had undergone cataract surgery after a diagnosis of CS compared to 177 (5.86%) in the control group (p = 0.07).Patients with endogenous CS have an increased likelihood of developing cataracts and they experienced onset at a younger age. Guidelines should include annual cataract monitoring for CS patients, beginning 3–5 years earlier than the current general recommendations.Methods: To investigate the risk of cataract in patients with Cushing’s syndrome (CS) and evaluate whether disease onset occurs at an earlier age compared to general population.A nationwide retrospective matched-cohort study including individuals diagnosed with endogenous CS from 2000 to 2023. Patients with CS were matched in a 1:5 ratio with a control group individually matched for age, sex, socioeconomic status, and body mass index. The primary outcome was the incidence of cataract and cataract surgery. The Cox proportional hazards model, accounting for death without cataract as a competing risk, was employed to estimate hazard ratio.The study cohort included 609 patients with CS, 65% women and 35% men, and 3018 controls. The average age at CS diagnosis was 48.1 ± 17 years. Follow-up duration was 14.6 years (IQR 9.8–20.2). The source of hypercortisolism was Cushing’s disease (CD) in 259 (42.6%) and adrenal CS (aCS) in 206 patients (33.8%). After CS diagnosis, cataract was observed in 171 patients (28.1%), and 771 controls (25.5%). Patients with CS had a 34% higher risk of developing cataract compared to their matched controls (HR = 1.34, 95% CI 1.03–1.75, p = 0.03). Cataract developed earlier in patients with CS compared to controls, with a mean age of onset at 64.7 ± 9.7 versus 67.6 ± 8.4 years, respectively (p = 0.01). A total of 49 (8.05%) patients had undergone cataract surgery after a diagnosis of CS compared to 177 (5.86%) in the control group (p = 0.07).Patients with endogenous CS have an increased likelihood of developing cataracts and they experienced onset at a younger age. Guidelines should include annual cataract monitoring for CS patients, beginning 3–5 years earlier than the current general recommendations.Results: To investigate the risk of cataract in patients with Cushing’s syndrome (CS) and evaluate whether disease onset occurs at an earlier age compared to general population.A nationwide retrospective matched-cohort study including individuals diagnosed with endogenous CS from 2000 to 2023. Patients with CS were matched in a 1:5 ratio with a control group individually matched for age, sex, socioeconomic status, and body mass index. The primary outcome was the incidence of cataract and cataract surgery. The Cox proportional hazards model, accounting for death without cataract as a competing risk, was employed to estimate hazard ratio.The study cohort included 609 patients with CS, 65% women and 35% men, and 3018 controls. The average age at CS diagnosis was 48.1 ± 17 years. Follow-up duration was 14.6 years (IQR 9.8–20.2). The source of hypercortisolism was Cushing’s disease (CD) in 259 (42.6%) and adrenal CS (aCS) in 206 patients (33.8%). After CS diagnosis, cataract was observed in 171 patients (28.1%), and 771 controls (25.5%). Patients with CS had a 34% higher risk of developing cataract compared to their matched controls (HR = 1.34, 95% CI 1.03–1.75, p = 0.03). Cataract developed earlier in patients with CS compared to controls, with a mean age of onset at 64.7 ± 9.7 versus 67.6 ± 8.4 years, respectively (p = 0.01). A total of 49 (8.05%) patients had undergone cataract surgery after a diagnosis of CS compared to 177 (5.86%) in the control group (p = 0.07).Patients with endogenous CS have an increased likelihood of developing cataracts and they experienced onset at a younger age. Guidelines should include annual cataract monitoring for CS patients, beginning 3–5 years earlier than the current general recommendations.Conclusion: To investigate the risk of cataract in patients with Cushing’s syndrome (CS) and evaluate whether disease onset occurs at an earlier age compared to general population.A nationwide retrospective matched-cohort study including individuals diagnosed with endogenous CS from 2000 to 2023. Patients with CS were matched in a 1:5 ratio with a control group individually matched for age, sex, socioeconomic status, and body mass index. The primary outcome was the incidence of cataract and cataract surgery. The Cox proportional hazards model, accounting for death without cataract as a competing risk, was employed to estimate hazard ratio.The study cohort included 609 patients with CS, 65% women and 35% men, and 3018 controls. The average age at CS diagnosis was 48.1 ± 17 years. Follow-up duration was 14.6 years (IQR 9.8–20.2). The source of hypercortisolism was Cushing’s disease (CD) in 259 (42.6%) and adrenal CS (aCS) in 206 patients (33.8%). After CS diagnosis, cataract was observed in 171 patients (28.1%), and 771 controls (25.5%). Patients with CS had a 34% higher risk of developing cataract compared to their matched controls (HR = 1.34, 95% CI 1.03–1.75, p = 0.03). Cataract developed earlier in patients with CS compared to controls, with a mean age of onset at 64.7 ± 9.7 versus 67.6 ± 8.4 years, respectively (p = 0.01). A total of 49 (8.05%) patients had undergone cataract surgery after a diagnosis of CS compared to 177 (5.86%) in the control group (p = 0.07).Patients with endogenous CS have an increased likelihood of developing cataracts and they experienced onset at a younger age. Guidelines should include annual cataract monitoring for CS patients, beginning 3–5 years earlier than the current general recommendations. [ABSTRACT FROM AUTHOR]