Gloria Tsvetov

Introduction: There are limited data on the prevalence and treatment of low bone density in young lung transplant recipients (LTRs), even though osteoporosis is common in patients with end-stage lung disease and transplant recipients. This study aimed to assess bone health in young LTRs. Methods: We retrospectively reviewed medical records for LTRs aged 18–50 at transplant. Outcomes included posttransplant low bone density (Z score < −2), osteoporotic fractures, and treatment data. Results: Among 150 LTRs (45% female, mean age 38 ± 9 years), with a median follow-up of 6.2 years, 103 (69%) underwent bone density scans; 82 occurred within the first year posttransplant. Of these, 19 (23%) showed low bone density within the first year. Posttransplant osteoporotic fractures occurred in 34 patients (23%), including femoral neck (32%) and vertebral fractures (29%) as first events. Eleven patients (32%) experienced multiple fractures. Pretransplant fracture history significantly predicted posttransplant fractures (HR 6.720, 95% CI: 1.572–28.724). Osteoporosis treatment was given to 41 patients (27%), primarily with bisphosphonates (93% as first line). Of those treated, 49% remained fracture free during follow-up. Conclusion: Young LTRs face high rates of low bone density and fractures, including serious and recurrent fractures. These findings underscore the need for early screening and intervention to reduce osteoporosis-related morbidity in this vulnerable population.

Purpose: Due to the low incidence of male microprolactinoma, there is a paucity of data in the literature regarding its management. Our aim was to investigate the long-term outcomes of cabergoline treatment in men with microprolactinoma. Methods: In this single-center retrospective cohort study, we reviewed patient’s records at prolactinoma diagnosis, following cabergoline discontinuation (if occurred), and at the last clinic visit. We collected all available clinical data, laboratory tests, and pituitary magnetic resonance imaging. We report response rates, gonadal axis recovery, and outcomes following cabergoline discontinuation. Results: The study cohort included 47 men with microprolactinoma [age at diagnosis 45.6 ± 17.6 years; median prolactin 70.0 ng/ml (IQR 51.0–103.4); low testosterone, 34 men (72.3%); adenoma diameter 5.6 ± 2.0 mm; median follow-up 7.1 years (IQR 3.5–10.4)]. Forty-two patients (89.4%) achieved normal prolactin levels within a median treatment time of 4.0 months (IQR 3.0–5.5) and had normal testosterone at last clinic visit. Five men (10.6%) did not achieve prolactin normalization, of whom 3 men remained hypogonadal. Mild side effects occurred in 4.3% of patients and disappeared with dose reduction. Thirteen men that achieved normal prolactin attempted drug discontinuation, but only 5 remained with normoprolactinemia. Men who maintained normal prolactin levels were treated longer with cabergoline [median treatment of 10 years (IQR 4.6–10.3) vs 2.0 years (IQR 1.5–3.2); p < 0.01]. Conclusions: Ninety percent of men harboring microprolactinoma achieved normoprolactinemia and subsequent testosterone normalization with cabergoline treatment. Men that discontinued cabergoline after prolonged prolactin suppression (>5 years) achieved sustained remission. These findings assist informed decision-making, between medical and surgical treatment.

Purpose Patients with hypoparathyroidism (hypoPT) have low bone turnover and high bone mineral density (BMD). However, data on fracture risk are conflicting. The objectives of this study were: 1. To describe clinical/biochemical characteristics of hypoPT patients followed at a single medical center. 2. To identify postsurgical hypoPT patients and investigate their fracture rate compared with gender/age-matched post-surgical normocalcemic patients. Methods Retrospective analysis of patient’s medical records treated at the tertiary medical center in 2010–2021 identified by computerized medical database search. Results The cohort included 133 patients (91% women, mean age 64 ± 13 years) of whom 105 (79%) had post-thyroidectomy hypoparathyroidism and the remainder had an autoimmune/idiopathic/other etiology. Mean follow-up time was 21 ± 12 and 27 ± 12 years, respectively. The control group included 142 post-thyroidectomy patients without hypoparathyroidism. Patients in the postsurgical hypoparathyroidism group were older and had higher calcium and PTH levels at diagnosis than the non-surgical hypoPT patients. Comparing the postsurgical hypoPT and postsurgical normocalcemic control patients revealed a significantly higher BMD in the hypoPT group. Yet, fracture rates were 31% in the postsurgical hypoparathyroidism group and 21% in the control group (P = 0.1) over a similar median follow-up period (17 and 18.4 years, respectively). In both groups the most common fracture site was the spine (50% and 70%, respectively; p = 0.33), mainly nonclinical morphometric fractures. Higher phosphorus blood level was associated with increased fracture risk. Conclusions The relatively high BMD in patients with postsurgical hypoparathyroidism is not associated with lower fracture risk. Silent morphometric fractures are quite common in this group of patients.

Purpose Prolactin (PRL)-secreting tumors are the most common functional pituitary adenomas. They usually respond to dopamine agonist (DA) treatment, with PRL normalization and adenoma shrinkage. Our aim was to characterize patients with prolactinoma resistant to DA treatment. Methods This retrospective case series included patients diagnosed with DA-resistant prolactinomas between 1993–2017 in three medical centers. Resistance was defined as PRL levels above three times the upper limit of normal (ULN) despite a weekly dose of ≥2 mg cabergoline (CAB). Clinical and biochemical information, and response to treatment, were retrieved from medical records. Results Twenty-six patients were identified; 20 males. Of 25 macroadenomas, three were giant tumors (>40 mm) and 15 (57.7%) were invasive. The mean age at diagnosis was 31.8 ± 14.9 years (range: 13–62). The median maximal CAB dose was 3.5 mg/week (IQR, 2.5–5). Half the patients received only CAB in escalating doses, nine received CAB and underwent transsphenoidal surgery, and four underwent surgery and radiotherapy in addition to CAB treatment. PRL levels at baseline between patients treated only with CAB and those operated were (91.6 [51.1–296.7] vs. 73.1 [22.6–170.9] XULN p = 0.355), and under maximal CAB dose PRL levels between patients treated only with CAB and those operated were similar (5.77 [1.27–11.27] vs 5.27 (2.9–26) XULN p = 0.317). At the last visit patients who received combined therapy achieved lower PRL levels than those treated with DA only (5.22 [1.7–21.6] vs 1.1 [0.44–3.99] XULN p = 0.017) PRL normalization was attained in seven patients and levels below 3 × ULN in fourteen patients; the overall response was 56%. Conclusions Resistant prolactinomas usually require a multi-modal treatment strategy. We were able to control 14/25 (56%) of resistant tumors.

Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing’s disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Methods: Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to 31 November 2021. Results: The cohort included 105 patients (82 women, 78%; mean age, 41.5 ± 14.5 years), including 80 microadenomas (mean size, 5.2 ± 2.2 mm) and 25 macroadenomas (mean size, 18.0 ± 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, p = NS) and Cushingoid features (27.5% vs. 20.0%, p = NS). Mean 24 h urinary free cortisol (5.2 ± 5.4 × ULN vs. 7.8 ± 8.7 × ULN) and serum cortisol following low-dose dexamethasone (372.0 ± 324.5 vs. 487.6 ± 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 ± 1.2 × ULN vs. 1.3 ± 0.8 × ULN, respectively, p = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. Conclusions: While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study.

Hypocalcemia was reported at low rates (0.05–1.7%) in denosumab-treated postmenopausal women with osteoporosis. This real-life study shows a 7.4% rate of denosumab-induced hypocalcemia in community-dwelling osteoporotic men and women. Pretreatment serum calcium and creatinine levels are major predictors for this complication. Serum-calcium monitoring may help to identify and prevent severe hypocalcemia.

Introduction: Primary hyperparathyroidism (PHPT) is the third most common endocrinopathy. Data on PHPT in the elderly are scarce. Objective: To characterize elderly patients with PHTP, clinically and biochemically. Patients: A total of 216 patients (73.6% females) aged≥75 years were diagnosed and followed at a single tertiary medical center for PHPT. Results: Mean follow-up was 11.3±5.5 years. Age at diagnosis was 70.9±7.2 years, and at last follow-up, 82.3±5.2 years. Maximal serum calcium and maximal PTH were 11.6±0.7 mg/dl and 3±2.7 X upper limit of normal (UNL), respectively. Mean urinary calcium and vitamin D levels were 208±130 mg/24 hours and 51.9±19.1 nmol/l, respectively. Serum creatinine was 0.9±0.5. Osteoporosis was diagnosed in 135 patients (62.5%; 92 with fractures, 75 after PHPT diagnosis), and nephrolithiasis, in 50; only 49 patients (22.7%) had neither. Thirty-six patients underwent parathyroidectomy: they were younger than the non-operated patients at diagnosis (67.4±9.5 vs 71.6±6.3 years) and had higher serum and urinary calcium levels. Patients ≥ 70 years at diagnosis (n=128), compared to younger patients, had significantly lower levels of calcium (10.2±0.7 vs 10.4±0.8 mg/dl, P=0.05) and PTH (1.7 vs 2.1 X UNL, P=0.05) at last follow-up. The younger patients had more nephrolithiasis (29.9% vs 18.8%). In the whole cohort, serum and urinary calcium significantly (P=0.001) decreased and vitamin D level significantly increased at last visit (10.3±0.47, 172.5±116, 68.6±23, respectively) compared with levels at diagnosis (10.6±0.7, 237±148, 51.5±19, respectively). Thirty-nine patients died during follow-up: they were significantly (P=0.001) older than the remaining patients at diagnosis (75.2±6.1 vs 70.2±6.1 years) and last follow up (85.3±5.9 vs 81.6±4.8 years), with no differences in laboratory variables. Conclusions: Most elderly patients with PHPT had at least one indication for parathyroidectomy, but only 17% were operated. Serum and urinary calcium levels decreased during follow-up.