Thyroid Storm and Type 1 Diabetes Mellitus Induced by Combined Ipilimumab and Nivolumab Immunotherapy: A Case Report.

Immune checkpoint inhibitors have revolutionised the management of cancer, and they are being used in combination to improve survival outcomes. Combination therapy is, however, associated with an increase in the frequency and severity of immune-related adverse events such as endocrine disorders. We report a case of simultaneous onset thyroid storm and type 1 diabetes mellitus induced by ipilimumab and nivolumab therapy in a patient with advanced melanoma. This case report suggests that combination immunotherapy can trigger a robust immune reaction leading to the development of multiple life-threatening endocrinopathies, including rapid onset destructive thyroiditis and insulitis. Prompt identification and management are essential to prevent morbidity and mortality.

A Case of Opiate-Induced Toxic Leukoencephalopathy in a Middle-Aged Woman.

Toxic leukoencephalopathy is a disorder characterized by the alteration of myelin in white matter tracts secondary to exposure to neurotoxic substances. Here we describe a case of a middle-aged woman who presented to the emergency department with a history of bizarre behaviour, speech abnormalities and generalised muscle stiffness caused due to recent opioid overdose. Further investigations and extensive neurological tests, including magnetic resonance imaging (MRI) scan of the brain, demonstrated features consistent with toxic leukoencephalopathy (TLE). The patient was managed conservatively with the care of a multidisciplinary team involving a dietician, physiotherapist and speech and language therapist. She showed gradual and slow but significant recovery following a period of neurorehabilitation. The clinical presentation of TLE varies but MRI typically shows diffuse bi-lateral white matter lesions. History of neurotoxin exposure, presenting clinical signs and symptoms and radiological findings are significant in making the diagnosis. Early recognition is crucial and can help optimize patient's recovery and prevent severe complications.

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Complicated by Generalized Tonic-Clonic Seizures After a Course of Antibiotics: A Case Report.

Nitrofurantoin and cephalexin are commonly used antibiotics for treating urinary tract infections. Hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been reported as a rare side effect of nitrofurantoin but has never been a reported side effect of cephalexin. We report a case of a 48-year-old female who developed severe hyponatremia complicated by generalized tonic-clonic seizures after a course of antibiotics (nitrofurantoin followed by cephalexin) used for treating a urinary tract infection. She presented to the emergency department with a one-week history of dizziness, nausea, fatigue, and listlessness. She also had a two-week history of persistent urinary frequency despite completing a course of nitrofurantoin followed by a course of cephalexin. While in the emergency department waiting room, she had two episodes of generalized tonic-clonic seizures. Immediate post-ictal blood test results revealed severe hyponatremia and lactic acidosis. Results were consistent with severe SIADH and she was subsequently managed with hypertonic saline and fluid restriction. She was discharged after 48 hours of admission when her serum sodium levels normalized. Though we believe that nitrofurantoin was the culprit drug, we still asked the patient to avoid future use of both nitrofurantoin and cephalexin. Healthcare providers need to be aware of antibiotic-induced SIADH when assessing patients with hyponatremia.

Acute Pulmonary Edema as a Cardiovascular Manifestation of Pheochromocytoma.

Pheochromocytoma most commonly presents with the triad of paroxysms of headache, palpitations, and diaphoresis. Pheochromocytoma crisis, caused by a supra-physiological surge of catecholamine release, is an endocrine emergency that can present with various clinical manifestations. Acute pulmonary edema is one of the manifestations of pheochromocytoma crisis and can be either cardiogenic or non-cardiogenic. Here, we report cases of acute pulmonary edema of each type, related to pheochromocytoma crisis, which were presented to our district general hospital in 2020.

A Case of Toxic Epidermal Necrolysis Caused by the Use of Trimethoprim Alone.

Toxic epidermal necrolysis (TEN) is a rare, acute, severe mucocutaneous reaction commonly presenting following medication use. Thorough history taking and clinical examination are key to early diagnosis and management; skin biopsy provides diagnostic confirmation. We present a 54-year-old man who developed a widespread erythematous rash soon after the use of trimethoprim for an episode of acute prostatitis. An initial diagnosis of Stevens-Johnson syndrome evolved into toxic epidermal necrolysis following the rapid progression of his condition to a severe, blistering, and desquamating rash affecting more than 60% of his body surface area and mucosa. Through careful management with best supportive care and clinical judgement regarding the role of pharmacological intervention, he made a steady recovery supported by the wider multidisciplinary team. This is one of the very few reports in the literature implicating trimethoprim alone as an etiological agent in a severe case of TEN.

Bilateral Testicular Epidermoid Cysts in a Man with Klinefelter Syndrome: A Case Report.

Klinefelter syndrome is a rare chromosomal disorder with at least one extra X chromosome in males resulting in male hypogonadism, androgen deficiency and impaired spermatogenesis. It is associated with an increased risk of certain malignancies; including leukemia, breast cancer, non-Hodgkin's lymphoma and mediastinal germ cell tumors, however, testicular tumors are rare in men with Klinefelter syndrome. Testicular epidermoid cysts are rare benign tumors affecting the testes. We report a case of bilateral testicular epidermoid cysts in a 30-year-old man known to have Klinefelter syndrome. He had an incidental finding of bilateral hard irregular-surfaced testes during routine assessment for testosterone replacement therapy. Biochemical investigation confirmed primary hypogonadism and ultrasound imaging demonstrated bilateral solid testicular masses with no blood flow seen within the lesions. The patient went on to have a right-sided radical orchiectomy with left-side sparing. The histology revealed features in keeping with that of a testicular epidermoid cyst with no evidence of malignancy. The patient was commenced on testosterone replacement therapy. This case emphasizes the importance of routine physical examination of the male external and internal genitalia when considering testosterone replacement therapy.

A novel CASR variant in a family with familial hypocalciuric hypercalcaemia and primary hyperparathyroidism.

SUMMARY: Familial hypocalciuric hypercalcaemia (FHH) is a dominantly inherited, lifelong benign disorder characterised by asymptomatic hypercalcaemia, relative hypocalciuria and variable parathyroid hormone levels. It is caused by loss-of-function pathogenic variants in the calcium-sensing receptor (CASR) gene. Primary hyperparathyroidism (PHPT) is characterised by variable hypercalcaemia in the context of non-suppressed parathyroid hormone levels. Unlike patients with FHH, patients with severe hypercalcaemia due to PHPT are usually symptomatic and are at risk of end-organ damage affecting the kidneys, bone, heart, gastrointestinal system and CNS. Surgical resection of the offending parathyroid gland(s) is the treatment of choice for PHPT, while dietary adjustment and reassurance is the mainstay of management for patients with FHH. The occurrence of both FHH and primary hyperparathyroidism (PHPT) in the same patient has been described. We report an interesting case of FHH due to a novel CASR variant confirmed in a mother and her two daughters and the possible coexistence of FHH and PHPT in the mother, highlighting the challenges involved in diagnosis and management. LEARNING POINTS: Familial hypocalciuric hypercalcaemia (FHH) and primary hyperparathyroidism (PHPT) can coexist in the same patient. Urinary calcium creatinine clearance ratio can play a role in distinguishing between PHPT and FHH. Genetic testing should be considered in managing patients with PHPT and FHH where the benefit may extend to the wider family. Family segregation studies can play an important role in the reclassification of variants of uncertain significance. Parathyroidectomy has no benefit in patients with FHH and therefore, it is important to exclude FHH prior to considering surgery. For patients with coexisting FHH and PHPT, parathyroidectomy will reduce the risk of complications from the severe hypercalcaemia associated with PHPT.