Pseudoephedrine for ejaculatory dysfunction after retroperitoneal lymph node dissection in testicular cancer.

OBJECTIVE: To assess the impact of ejaculatory dysfunction (EjD; failure of emission or retrograde ejaculation) on health-related quality of life (HRQoL) after retroperitoneal lymph node dissection (RPLND) for testicular cancer and explore the efficacy of pseudoephedrine hydrochloride as treatment. PATIENTS AND METHODS: In a single arm, phase II trial, patients at ≥6 months after RPLND were invited to complete patient-reported outcome measures (European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaire [QLQ]-30-item core, EORTC QLQ-testicular cancer-26, and Brief Male Sexual Function Inventory) evaluating HRQoL and sexual function in follow-up (ACTRN12622000537752/12622000542796). If EjD was reported, post-ejaculatory urine ± semen analysis was undertaken. In eligible patients, pseudoephedrine hydrochloride 60 mg was administered orally every 6 h for six doses. The primary endpoint was sperm count >39 million sperm/ejaculate (>5th centile) following treatment. The trial was powered to detect a clinically relevant 36% achieving sperm count of >39 million sperm/ejaculate. Secondary endpoints included semen volume >1.5 mL, total motile sperm count, safety, and HRQoL impacts. RESULTS: Of the 58 patients enrolled, the median (interquartile range [IQR]) age was 35 (29-41) years, with a median (IQR) of 37 (18-60) months from RPLND. EjD was reported in 33 (57%), including 27/52 (52%) receiving follow-up at our centre. There were no differences in global HRQoL; however, role functioning (P = 0.045), sexual problems (P < 0.005), and sexual enjoyment (P = 0.005) was poorer if EjD was present. In all, 24/33 (73%) patients with EjD consented to pseudoephedrine treatment. Of 22 evaluable patients, four (18%) achieved a sperm count of >39 million/ejaculate (P = 0.20), and four (18%) had a semen volume of >1.5 mL (P = 0.20). There was a mean increase of 105 million sperm/ejaculate (P = 0.051) and 1.47 mL increase in semen volume (P = 0.01). No safety concerns arose. CONCLUSION: Ejaculatory dysfunction is common after RPLND but did not impact global HRQoL in our cohort. Pseudoephedrine improved EjD for some; however, its efficacy was lower than expected. Pseudoephedrine may be considered on an individualised basis.

Insulinoma: Metastatic Recurrence 38 Years Following Initial Diagnosis in Pregnancy.

A case of recurrent insulinoma spanning 4 decades is described. Following a delayed diagnosis, hyperinsulinemic hypoglycemia was confirmed in a 24-year-old woman during early pregnancy. Initial surgery, culminating in subtotal pancreatectomy, was noncurative. A 1-cm insulinoma was subsequently resected from the head of the pancreas postpartum, with postoperative resolution of hypoglycemia. However, 32 years later, the patient experienced a recurrence of hypoglycemic symptoms. Eventually, a subcentimeter extrapancreatic lesion was identified anterior to the pancreatic head on gallium-68 DOTA-Exendin-4 positron emission tomography/computed tomography. In 2022, a third operation was performed, with excision of a 4 × 3 mm tumor adjacent to the pancreatic head, and histology confirming insulinoma. She was again cured of symptoms.

Pseudo-Cushing Syndrome With an Atypically High Cortisol Burden and Clinical Improvement With Adrenal Enzyme Inhibitor.

Distinguishing between Cushing syndrome (CS) and pseudo Cushing syndrome (PCS), also known as physiological hypercortisolism, can be difficult. PCS is caused by nonneoplastic overactivity of the hypothalamic-pituitary-adrenal axis and may be secondary to a range of conditions, including obesity, physical stress, malnutrition, and chronic alcoholism, and typically results in a lesser degree of hypercortisolism and fewer clinical features than CS. Management of PCS includes treatment of the underlying cause and reassessment of hypercortisolemia following improvement in the underlying etiology, as this may result in normalization of cortisol levels. The role of adrenal enzyme inhibitors in lowering cortisol levels in those with PCS is poorly understood. We report a case of a man presenting with weight loss who was found to have severe hypercortisolemia and elevated adrenocorticotropin (ACTH) complicated by infection, neuropsychiatric disturbance, and hypokalemia. Despite high cortisol levels, he was phenotypically not cushingoid, and the circadian rhythm of cortisol was preserved. Extensive investigations did not demonstrate a cause of symptoms or source of ACTH. Medical management with ketoconazole improved neuropsychiatric symptoms, and weight gain with nasogastric feeds resulted in the normalization of cortisol levels and resolution of symptoms following ketoconazole cessation.

Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent but morbid and potentially serious condition associated with antiresorptive and antiangiogenic therapies. Although MRONJ can be prevented by optimizing oral health, management of established cases is supportive and remains challenging. Teriparatide, an osteoanabolic agent that improves bone healing in preclinical studies and in chronic periodontitis, represents a potential treatment option. PATIENTS AND METHODS: In a double-blind, randomized, controlled trial, 34 participants with established MRONJ, with a total of 47 distinct MRONJ lesions, were allocated to either 8 weeks of subcutaneous teriparatide (20 µg/day) or placebo injections, in addition to calcium and vitamin D supplementation and standard clinical care. Participants were observed for 12 months, with primary outcomes that included the clinical and radiologic resolution of MRONJ lesions. Secondary outcomes included osteoblastic responses as measured biochemically and radiologically and changes in quality of life. RESULTS: Teriparatide was associated with a greater rate of resolution of MRONJ lesions (odds ratio [OR], 0.15 v 0.40; P = .013), and 45.4% of lesions resolved by 52 weeks compared with 33.3% in the placebo group. Teriparatide was also associated with reduced bony defects at week 52 (OR, 8.1; P = .017). The incidence of adverse events was balanced between groups, including nausea, anorexia, and musculoskeletal pain, most of mild severity. CONCLUSION: Teriparatide improves the rate of resolution of MRONJ lesions and represents an efficacious and safe treatment for it.

Denosumab failure associated with escape from suppression of bone resorption.

Denosumab leads to sustained suppression of bone turnover if given every 6 months, with escape occurring approximately 2 to 3 months after the last dose. Whilst escape from denosumab has been reported in malignancy, there has only been one reported case in the setting of osteoporosis. We present the case of a 62-year old woman with systemic sclerosis who did not respond to denosumab secondary to premature escape from suppression of bone resorption. Our patient was diagnosed with osteoporosis 15 years previously based on bone densitometry, with no prior fragility fractures. Initial treatment with oral bisphosphonates was changed to denosumab due to patient choice and intermittent compliance. Over the subsequent 5 years, she received denosumab 60 mg via subcutaneous injections every 6 months, however there was no improvement in her bone mineral density. Significantly, whilst markers of bone turnover demonstrated initial suppression at 3 months post denosumab dose, these were elevated prior to the next dose at 6 months, suggesting escape from the suppressive effects of denosumab. Although this is the second case report of escape from denosumab in osteoporosis and the first in a patient with systemic sclerosis, this phenomenon may be under-reported in patients who do not respond to denosumab. We suggest that clinicians consider the possibility of escape in patients with poor response to denosumab who are compliant, and suggest the measurement of bone turnover markers in these patients.

Declining Incidence of Medication-Related Osteonecrosis of the Jaw in Patients With Cancer.

CONTEXT: Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent, but severely debilitating condition. Given the significant morbidity attributable to MRONJ and the challenges associated with its management, prevention is crucial. OBJECTIVE: We sought to evaluate the effectiveness of an active dental intervention in reducing MRONJ incidence. DESIGN AND SETTING: We identified all patients who received antiresorptive drug therapy at a specialized cancer center between January 2003 and December 2013 through hospital pharmacy records, whereas confirmed cases of MRONJ were identified through a hospital database. MAIN OUTCOME MEASURES: The incidence of MRONJ before and after the implementation of active dental intervention in July 2008 was quantified and compared. RESULTS: A total of 1243 patients received antiresorptive drug therapy, with 34 confirmed cases of MRONJ (crude overall incidence, 2.7%). The incidence of MRONJ was significantly lower in patients who received antiresorptive therapy after the implementation of guidelines that emphasized active dental input (0.8 vs 4.6%; χ(2) = 16.2; P = .00006). Using a binominal logistic regression model that adjusted for the number of doses of antiresorptive drug received, patients who received active dental input had an odds ratio of developing MRONJ of 0.24 (95% confidence interval, 0.09, 0.61; P = .004). CONCLUSION: The likelihood of developing MRONJ can be minimized through the implementation of prophylactic dental assessment and active dental intervention. This reinforces the importance of increased dental awareness and enhanced dental intervention in the prevention of MRONJ.

Romosozumab/CDP7851 for the treatment of osteoporosis.

Osteoporosis is an important worldwide health problem, conferring significant costs on healthcare. Current osteoporosis therapies are anti-resorptive and have proven anti-fracture efficacy, while there is a paucity of osteoanabolic therapies. Romosozumab is a humanized monoclonal antibody against sclerostin, an inhibitor of osteoblastic activity. Two-year follow-up data from initial clinical studies show rapid and robust increases in bone mineral density at all sites, except the wrist. Significant increases in bone formation markers have also been observed after administration of romosozumab. Notably, and unprecedented among any currently available therapy, this increase in bone formation is accompanied with control of bone resorption, allowing an enhanced anabolic potential compared with the only other currently available anabolic therapy, teriparatide. Romosozumab has been well tolerated in initial studies and its effects on BMD are augmented by follow-on anti-resorptive therapy. Ongoing Phase III studies will provide data regarding anti-fracture efficacy and comparisons with alendronate, as well as longer-term safety.

Treatment of osteoporosis in men with bisphosphonates: rationale and latest evidence.

Osteoporosis in men contributes to significant morbidity and mortality. Hip fractures in men are associated with greater mortality compared with women, with a mortality rate of up to 37.5% within a year following the fracture. Its timely diagnosis and treatment are therefore essential. However, despite one-third of all hip fractures worldwide occurring in men, osteoporosis in men remains an immensely under-recognized and undertreated public health problem. Bisphosphonates are well studied first-line treatments for postmenopausal women with osteoporosis and have been shown to reduce fragility fractures at all clinically important sites (vertebral, nonvertebral, hip and wrist). However, the majority of studies of oral or intravenous bisphosphonate therapy in men with osteoporosis report effects on surrogate markers, including bone mineral density (BMD) and biochemical bone turnover markers, rather than on fragility fractures. Oral or intravenous bisphosphonate therapy increases spinal, total hip and femoral neck BMD compared with placebo in men with osteoporosis. Both bone resorption and bone formation markers are decreased following bisphosphonate therapy, with the onset of the decrease in bone formation markers being delayed. In a study of intravenous zoledronic acid given to older men and women following a hip fracture, any clinical vertebral and nonvertebral fractures were all reduced compared with placebo infusions. In addition, mortality was reduced in patients who received zoledronic acid. Recent studies in men with osteoporosis have increasingly reported reductions in incident vertebral fractures with oral or intravenous bisphosphonate therapy, although all studies have been underpowered to detect effects on nonvertebral and hip fracture outcomes. Bisphosphonates have a role as monotherapy, as consolidative therapy after a course of teriparatide therapy, or in combination with testosterone replacement in men with hypogonadism and osteoporosis. Bisphosphonate therapy is validated and important in the treatment of osteoporosis in men.

Improving diagnosis of tumor-induced osteomalacia with Gallium-68 DOTATATE PET/CT.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rarely diagnosed disorder presenting with bone pain, fractures, muscle weakness, and moderate-to-severe hypophosphatemia resulting from fibroblast growth factor 23-mediated renal phosphate wasting. Tumors secreting fibroblast growth factor 23 are often small and difficult to find with conventional imaging. OBJECTIVE: We studied the utility of (68)Ga-DOTA-octreotate (DOTATATE) somatostatin receptor positron emission tomography (PET)/computed tomography (CT) imaging in the diagnosis of TIO. DESIGN AND SETTING: A multicenter case series was conducted at tertiary referral hospitals. PATIENTS AND METHODS: Six patients with TIO diagnosed between 2003 and 2012 in Australia were referred for DOTATATE PET imaging. We reviewed the clinical history, biochemistry, imaging characteristics, histopathology, and clinical outcome of each patient. RESULTS: Each case demonstrated delayed diagnosis despite severe symptoms. DOTATATE PET/CT imaging demonstrated high uptake and localized the tumor with confidence in each case. After surgical excision, there was resolution of clinical symptoms and serum phosphate, except in one patient who demonstrated residual disease on PET/CT. All tumors demonstrated high somatostatin receptor subtype 2 cell surface receptor expression using immunohistochemistry. CONCLUSIONS: In patients with TIO, DOTATATE PET/CT can successfully localize phosphaturic mesenchymal tumors and may be a practical first step in functional imaging for this disorder. Serum phosphate should be measured routinely in patients with unexplained muscle weakness, bone pain, or stress fractures to allow earlier diagnosis of TIO.