SGLT-2 Inhibitors in Heart Failure: Guide for Prescribing and Future Perspectives.

PURPOSE OF REVIEW: Heart failure is responsible for a significant part of diabetes-associated cardiovascular mortality and morbidity. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are novel agents approved for the treatment of diabetes mellitus; in recent clinical trials, these agents have shown a significant reduction in cardiovascular death and hospitalization secondary to heart failure. RECENT FINDINGS: Clinical trials with specific heart failure outcomes have shown the benefit of SGLT-2 inhibitors in reducing the mortality and morbidity associated with heart failure. The guidelines for the management of diabetes mellitus recommend the preferential use of SGLT-2 inhibitors in patients with a history of cardiovascular disease. SGLT-2 inhibitors are potential game changers in the treatment of heart failure. Guidelines for prescription of these agents help assess risk-benefit analysis and personalize treatment for maximal benefit.

Familial hypocalciuric hypercalcaemia type 3: AP2S1 missense mutation.

A 45-year-old man was referred to endocrine for the evaluation of hypercalcaemia. The calcium was elevated, vitamin D was low with a normal parathyroid hormone. Dual-energy X-ray absorptiometry scan revealed osteoporosis at the lumbar spine and femoral neck. A 24-hour urine collection revealed low urinary calcium, which was believed to be secondary to vitamin D deficiency. A diagnosis of primary hyperparathyroidism was made. The patient underwent a four-gland parathyroid exploration surgery in which three of his parathyroid glands were removed. The pathology was consistent with benign parathyroid tissue. Post surgery, the patient had persistently elevated calcium levels. He was then started on bisphosphonate and cinacalcet for osteoporosis and hypercalcaemia, respectively. Genetic analysis of familial hypocalciuric hypercalcaemia (FHH) showed a p.arg15cys mutation in the AP2S1 gene, confirming the diagnosis of FHH type 3.

A case of catecholamine-induced cardiomyopathy treated with extracorporeal membrane oxygenation.

A 55-year-old female patient was presented with severe dyspnea due to sudden onset of heart failure (ejection fraction (EF) <10%). Echocardiogram showed a takotsubo pattern with an akinetic apical segment. Coronary angiography did not reveal any obstructive disease. She became hypotensive which was refractory to conventional pressor agents. Catecholamine-induced cardiomyopathy was suspected after the CT scan of the abdomen showed a 4 cm necrotic right adrenal mass consistent with pheochromocytoma (PHEO). Venous arterial extracorporeal membrane oxygenation and α blockers were initiated. There was a rapid improvement in cardiac function with EF normalising in 1 week. Subsequently, ß-blockers were added and right adrenalectomy was done 3 weeks after the admission. She did extremely well after surgery with her blood pressure normalising without the need for antihypertensive therapy. Genetic evaluation revealed no pathogenic mutations implicated in the development of PHEO.

Systemic mastocytosis: a rare cause of osteoporosis.

A 61-year old female patient who was referred to the endocrine clinic for evaluation of an elevated alkaline phosphatase. She was originally referred to gastroenterology (GI), however no GI causes of elevated alkaline phosphatase was found. Upon fractionation, it was noted that she had elevation in bone specific alkaline phosphatase. Past history was significant for hypertension, atrial fibrillation and menopause 6 years ago. She was also noted to have multiple drug allergies manifesting as urticaria and flushing. Review of the past records revealed a persistently elevated alkaline phosphatase over the last two years. She had no history of falls or fractures. Computed tomography (CT) abdomen done to rule out biliary pathology, revealed osteosclerotic and osteolytic lesion in the pelvis concerning neoplastic disease. Bone marrow biopsy however, was negative for cancer but consistent with systemic mastocytosis (SM). Dual Energy X-ray absorbimetery (DEXA) scan revealed osteoporosis Serum tryptase levels were elevated; further genetic analysis showed a positive CKIT D816 mutation. She was started on bisphosphonates (initially alendronate and then ibandronate). Upon follow up at two years she had not experienced any fractures and her bone mineral density also had improved significantly.

Primary hyperparathyroidism: Labs to order, Tx to consider.

Unexplained kidney stones, osteoporosis, or certain subtle clues may point to hyperparathyroidism. These tests and imaging options can help you to be sure.

Osteitis fibrosa cystica masquerading as bone neoplasm.

A 50-year-old female patient with no significant medical history presented with left knee pain. Radiographs of the knee showed a circumferential swelling of the distal femur suggestive of neoplasia. Further evaluation revealed multiple lesions in the left iliac bone and proximal femur. Biopsy was suggestive of a reparative granuloma or an aneurysmal bone cyst. Laboratory assessment showed hypercalcaemia and elevated parathyroid hormone consistent with severe primary hyperparathyroidism. Osseous survey was significant for salt and pepper appearance of the skull. Ultrasound of the neck and 99mTc-sestamibi parathyroid scintigraphy localised a left parathyroid adenoma/carcinoma. Parathyroidectomy was successful, and a large parathyroid adenoma was excised. Six months later, the patient was doing fine with her gait returning to normal. On follow-up 2 years later, she had no recurrence of the lesions.

Thyrotoxic periodic paralysis: case report and review of the literature.

INTRODUCTION: Thyrotoxic periodic paralysis (TPP) is a rare and potentially lethal complication of hyperthyroidism. It is characterized by sudden onset paralysis associated with hypokalemia. Management includes prompt normalization of potassium, which results in resolution of the paralysis. Definitive treatment of hyperthyroidism resolves TPP completely. CASE PRESENTATION: A 23-year-old African American male patient presented to the emergency room at the University of Mississippi Medical Center, USA in November 2016 with sudden onset quadriplegia. He also endorsed a history of weight loss, palpitations, heat intolerance and tremors. The patient reported similar episodes of quadriplegia in the past, which were associated with hypokalemia and resolved with normalization of potassium levels. Physical examination was significant for exophthalmos, smooth goiter with bruit consistent with the diagnosis of Graves' disease. Laboratory assessment showed severe hypokalemia, hypomagnesemia, suppressed thyroid stimulating hormone (TSH) and high free thyroxine (T4). Urine potassium creatinine ratio was less than one, indicating transcellular shift as the cause of hypokalemia. After normalization of potassium and magnesium, the paralysis resolved in 12 hours. He was started on methimazole. On follow up, the patient was clinically and biochemically euthyroid with no further episodes of paralysis. TAKE-AWAY LESSON: TPP is a rare and reversible cause of paralysis. Physicians need to be aware of the diagnostic and treatment modalities as delayed recognition in treatment could result in potential harm or unnecessary interventions.

Pancytopenia: a rare complication of Graves' disease.

A 27-year-old male patient who presented to the emergency room with complaints of sweating, palpitations, heat intolerance, insomnia and weight loss for the last 3 months. His medical history was significant for hypertension. On examination, he was tachycardic, hypertensive, had tremors of the upper extremities and a smooth goitre with a thyroid bruit. Laboratory assessment revealed a suppressed thyroid-stimulating hormone, high free thyroxine and positive thyroid receptor antibodies. Complete blood count showed pancytopenia. As part of the work-up for pancytopenia, haptoglobin, ferritin, Coombs test, reticulocyte count hepatitis B and C antibodies were done, all of which were normal. Patient was started on methimazole, propranolol and hydrocortisone. His symptoms improved through the hospital course and he was subsequently discharged. Thyroidectomy was done once the patient's hyperthyroidism was controlled. Levothyroxine was started for the control of postsurgical hypothyroidism. Six months after thyroidectomy, the patient was euthyroid and the pancytopenia resolved.

Hungry bone syndrome secondary to prostate cancer successfully treated with radium therapy.

A 50-year-old man with a history of prostate cancer with extensive bone metastasis and hypocalcaemia presented with muscle aches and cramps. Physical exam was significant for Chvostek's and Trousseau's sign. Laboratory assessment was consistent with profound hypocalcaemia. This was believed to be due to hungry bone syndrome secondary to advanced prostate cancer. He was treated with intravenous calcium, vitamin D and calcitriol. He also received three doses of radium223 therapy. After therapy, hypocalcaemic episodes resolved. Follow-up after 2.5 years showed continued resolution of hypocalcaemia.