Management of bone loss due to endocrine therapy during cancer treatment.

Bone modifying agents BMAs (oral and IV bisphosphonates, denosumab) are used to treat bone loss due to endocrine therapy in patients with hormone receptor positive (HR +) early breast cancer and non-metastatic prostate cancer (NMPC). Timely initiation of appropriate sequential therapy is imperative to reduce cancer treatment-induced bone loss (CTIBL). This narrative review summarizes current literature regarding management of CTIBL in HR + early breast cancer and NMPC patients. Risk factors for fragility fractures, screening strategies, optimal timing for the treatment, dosing/duration of therapy, and post treatment monitoring have not been clearly defined in HR + early breast and NMPC patients receiving endocrine therapy. This review aims to discuss the utility of fracture risk assessment (FRAX) tool for the prevention and management of CTIBL, osteoanabolic therapy for imminent fracture risk reduction, and sequential therapy options. Using predefined terms, PubMed, MEDLINE, and Google Scholar were searched for studies on CTIBL in HR + breast and NMPC patients. We included randomized clinical trials, meta-analysis, evidence-based reviews, observational studies, and clinical practice guidelines. Fracture risk assessment tools (FRAX) guide therapy for osteoporosis in patients with early HR + breast cancer and NMPC. BMAs to prevent bone loss should be initiated at higher T-score than recommended by FRAX in premenopausal HR + breast cancer patients with chemotherapy-induced ovarian failure, oophorectomy and gonadotropin releasing hormone (GnRH) therapy, post-menopausal women with HR + breast cancer receiving aromatase inhibitor therapy, and NMPC patients with androgen deprivation therapy. Sequential therapy with osteoanabolic agents as first line treatment offers a potential therapeutic strategy in patients with high imminent fracture risk. Due to limited data in cancer patients regarding management of osteoporosis, a dosing schedule similar to osteoporosis is considered appropriate. Risk stratification to identify vulnerable patient population, choosing the appropriate sequential therapy, and close monitoring of patients at the risk of bone loss can potentially reduce the mortality, morbidity, and health care cost related to CTIBL.

Electrolyte Disturbances in Critically Ill Cancer Patients: An Endocrine Perspective.

Electrolyte disturbances are frequently encountered in critically ill oncology patients. Hyponatremia and hypernatremia as well as hypocalcemia and hypercalcemia are among the most commonly encountered electrolyte abnormalities. In the intensive care unit, management of critical electrolyte disturbances is focused on initial evaluation and immediate treatment plan to prevent severe complications. A PubMed search was performed to identify best available evidence for evaluation and management of dysnatremias, hypocalcemia, and hypercalcemia. Current literature was reviewed regarding the management of electrolyte disturbances. The role of new therapeutic options, for example, vaptans for hyponatremia, teriparatide for hypocalcemia, and denosumab for hypercalcemia, is discussed. Early diagnosis and appropriate management are expected to reduce adverse outcomes.

Molecular markers in thyroid cytology: diagnostic and prognostic implications.

The discovery of thyroid nodules in the general population has risen markedly with the greater use of ultrasound resulting in increasing use of ultrasound-guided fine needle aspiration (FNA) biopsy. Although FNA can identify the majority of nodules as either benign or malignant, one-third of aspirates demonstrate indeterminate cytologic characteristics. Though most of these nodules will be pathologically benign, thyroid surgery has usually been needed to make an accurate diagnosis, and the extent of surgery needed (lobectomy versus total thyroidectomy) is difficult to predict in advance. New molecular techniques are being investigated and used clinically to improve decision making in patients with thyroid nodules with indeterminate cytology. These molecular markers have the potential to help clinicians decide which patients may be monitored without thyroid surgery, and also the optimal strategy when surgery is felt to be necessary.

Random postoperative day-3 cortisol concentration as a predictor of hypothalamic-pituitary-adrenal axis integrity after transsphenoidal surgery.

OBJECTIVE: To determine whether a random postoperative day-3 cortisol value of 10 µg/dL or greater is predictive of adrenal sufficiency 3 to 10 weeks after transsphenoidal surgery (TSS) and during long-term clinical follow-up. METHODS: We retrospectively reviewed the case records of patients who underwent TSS at our institution between 1991 and 2008. Inclusion criteria were as follows: random cortisol measured on the morning of postoperative day 3, adrenal dynamic testing performed 3 to 10 weeks after TSS, and clinical assessment of the hypothalamic-pituitary-adrenal (HPA) axis at least 6 months after TSS. RESULTS: A total of 466 patients underwent TSS at our institution during the study period. Eighty-three patients met study inclusion criteria. Sensitivity of a random postoperative day-3 serum cortisol value of 10 µg/dL or greater for the prediction of adrenal sufficiency at a median follow-up of 42 days was 64.81% (95% confidence interval, 50.6%-77.32%), with an odds ratio of 3.1 (95% confidence interval, 1.08-8.58). Specificity was 62.1% (95% confidence interval, 42.3%-79.3%). At a median follow-up of 500 days, only 2 patients with a postoperative day-3 cortisol value of 10 µg/dL or greater required hydrocortisone replacement, both of whom had multiple anterior pituitary hormone deficiencies and evidence of pituitary dysfunction during the perioperative period. CONCLUSIONS: In the appropriate clinical context, a postoperative day-3 cortisol value of 10 µg/dL or greater accurately predicts the integrity of the HPA axis. The final decision regarding corticosteroid replacement should be personalized, considering the postoperative day-3 cortisol level, the clinical context in which the measurement was obtained, and any evidence of concomitant pituitary dysfunction in the perioperative period.

Medical management of postsurgical hypoparathyroidism.

OBJECTIVE: To provide a clinical update on the management of hypoparathyroidism with focus on postsurgical hypoparathyroidism. METHODS: Using PubMed, English-language literature was searched related to management of hypoparathyroidism after thyroid and parathyroid surgery. We discuss the incidence, pathophysiology, differential diagnosis, early diagnosis, and treatment of transient and permanent hypoparathyroidism. RESULTS: Hypoparathyroidism is a well-recognized complication after thyroid and parathyroid surgery. Transient hypoparathyroidism occurs in 10% of patients who undergo total thyroidectomy. Less than half of patients who develop transient hypoparathyroidism after thyroid surgery develop permanent hypoparathyroidism. Postsurgical hypocalcemia resulting from inadequate parathyroid hormone (PTH) secretion could cause neurologic complications and respiratory compromise. Calcium supplements and vitamin D analogues effectively treat hypocalcemia associated with postsurgical hypoparathyroidism. Measurement of PTH after thyroid and parathyroid surgery allows early identification of patients likely to require calcium supplements and vitamin D analogue therapy. Early identification and appropriate management of postsurgical hypoparathyroidism prevent hypocalcemia-related complications and allow patients to be discharged from the hospital earlier. Patients who develop permanent hypoparathyroidism should receive appropriate follow-up care to monitor for long-term complications related to supplemental therapy. PTH replacement therapy is currently being evaluated for the treatment of transient and permanent hypoparathyroidism. CONCLUSIONS: A multidisciplinary approach involving an endocrinologist and surgeon is imperative to reduce the morbidity associated with hypoparathyroidism after thyroid and parathyroid surgery. Supplemental therapy with calcium and vitamin D analogues is standard. New drugs currently in clinical trials offer promising treatment options.