Incidence of Post-denosumab Rebound Hypercalcaemia in Bony-Metastatic Breast Cancer.

Denosumab reduces incidence of skeletal related events in patients with bony-metastatic breast cancer, however cessation is associated with a rebound phenomenon which, rarely, has been associated with hypercalcaemia. We aimed to identify the incidence of post-denosumab cessation rebound hypercalcaemia amongst patients with breast cancer-related bony metastases. We performed a single-centre retrospective cohort analysis to determine the incident of rebound hypercalcaemia amongst patients treated with antiresorptive agents for bony metastatic breast cancer between 2016-2020. 22,320 outpatient encounters were reviewed, which identified 97 patients with bonymetastatic disease treated with antiresorptive therapy. Of the 21 patients who had denosumab ceased, six (28.6%) developed hypercalcaemia. Interval between last denosumab dose and onset of hypercalcaemia was a median 7.5 (range 2-13) months. There was a significant difference in both denosumab treatment duration as well as total treatment dose exposure between patients who developed hypercalcaemia post-denosumab cessation (median 41 months, 40 doses) and those who remained normocalcaemic (median 10 months, 5 doses), p = 0.009. In our study, hypercalcaemia occurred between two and thirteen months after denosumab cessation. Greater denosumab treatment duration as well as total denosumab dose exposure was associated with higher risk of hypercalcaemia after denosumab cessation. Hormonal therapy or previous bisphosphonate treatment was not seen to impact upon development of hypercalcaemia. Rebound hypercalcaemia is a rare but important diagnosis to consider in patients experiencing hypercalcaemia after denosumab cessation.

SGLT2 Inhibitors Increase the Risk of Diabetic Ketoacidosis Developing in the Community and During Hospital Admission.

CONTEXT: Diabetic ketoacidosis (DKA) has been associated with the use of sodium glucose cotransporter 2 inhibitors (SGLT2is). OBJECTIVE: To determine the incidence, characteristics, and outcomes of DKA in SGLT2i users vs nonusers with type 2 diabetes. DESIGN: Retrospective, multicenter, controlled cohort study. SETTING: All public hospitals in Melbourne and Geelong (combined population of 5 million), Australia, from 1 September 2015 to 31 October 2017. PATIENTS: Consecutive cases of DKA that developed in the community, or during the course of hospital admission, in patients with type 2 diabetes. MAIN OUTCOME MEASURES: In SGLT2i users vs nonusers: (i) OR of DKA developing during hospital admission, and (ii) incidence of DKA. RESULTS: There were 162 cases of DKA (37 SGLT2i users and 125 non-SGLT2i users) with a physician-adjudicated diagnosis of type 2 diabetes. Of these, DKA developed during the course of inpatient admission in 14 (38%) SGLT2i users vs 2 (2%) non-SGLT2i users (OR, 37.4; 95% CI, 8.0 to 175.9; P < 0.0001). The incidence of DKA was 1.02 per 1000 (95% CI, 0.74 to 1.41 per 1000) in SGLT2i users vs 0.69 per 1000 (95% CI, 0.58 to 0.82 per 1000) in non-SGLT2i users (OR, 1.48; 95% CI, 1.02 to 2.15; P = 0.037). Fifteen SGLT2i users (41%) had peak blood glucose <250 mg/dL (14 mmol/L) compared with one (0.8%) non-SGLT2i user (P < 0.001). CONCLUSIONS: SGLT2i users were more likely to develop DKA as an inpatient compared with non-SGLT2i users. SGLT2i use was associated with a small but significant increased risk of DKA.

Subclinical hypothyroidism during pregnancy: the Melbourne public hospitals consensus.

BACKGROUND: Interest in potential adverse outcomes associated with maternal subclinical hypothyroidism (normal free T4, elevated thyroid-stimulating hormone (TSH)) has increased significantly over recent years. In turn, the frequency of maternal thyroid function testing has risen, despite universal thyroid function screening not being recommended, leading to a marked increase in referrals to obstetric endocrinology clinics. In 2017 the American Thyroid Association revised their diagnostic and management guidelines. Although welcome, these new guidelines contain recommendations that may cause confusion in clinical practice. AIM: To ensure uniform practice in the diagnosis and management of subclinical hypothyroidism in pregnancy across all Melbourne public hospitals. METHODS: Endocrinology and obstetric representatives from all Melbourne public hospital networks reviewed the 2017 American Thyroid Association guidelines and other relevant literature to develop a consensus for diagnosing and treating subclinical hypothyroidism during pregnancy in Melbourne. The consensus guidelines were then referred to the Endocrine Society of Australia for comment and endorsement. RESULTS: Consensus was achieved and the guidelines were endorsed by the Council of the Endocrine Society of Australia. Trimester and assay-specific TSH reference intervals derived from healthy local populations should be used, where available. When unavailable, a TSH cut-off of 4 mU/L (replacing the previously recommended 2.5 mU/L) should be used to initiate treatment, irrespective of thyroid auto-antibody status. The recommended starting dose of levothyroxine is 50 µg daily, with a therapeutic TSH target of 0.1-2.5 mU/L. Levothyroxine should generally be ceased after delivery, with some exceptions. Hospitals will ensure smooth transfer of care back to the woman's general practitioner with clear documentation of pregnancy thyroid management and a recommended plan for follow-up. CONCLUSION: Fewer women will be classified as having subclinical hypothyroidism during pregnancy, which is likely to lead to reductions in emotional stress, hospital visits, repeated blood tests and financial costs. Uniform clinical practice will occur across Melbourne.