New onset autoimmune diabetes mellitus and hypothyroidism secondary to pembrolizumab in a patient with metastatic lung cancer.

SUMMARY: Immunotherapy has become an important pillar for the management of advanced cancer. Immune-related adverse events including endocrinopathies have been well described with programmed cell death 1 inhibitors such as pembrolizumab. While thyroid dysfunction is the most common endocrinopathy associated with pembrolizumab, new-onset autoimmune diabetes mellitus (DM) is extremely rare. The authors report a case of pembrolizumab-induced primary hypothyroidism and type 1 diabetes mellitus presenting with diabetic ketoacidosis (DKA). A 59-year-old female patient was treated with pembrolizumab for a stage 4 lung adenocarcinoma. She presented to the emergency department with hyperglycaemia-related signs and symptoms, such as polyuria, polydipsia, weight loss, vomiting, asthenia and dehydration, 3 weeks after her first dose of pembrolizumab. Laboratory evaluation revealed hyperglycaemia, hyperketonaemia and high anion gap metabolic acidaemia consistent with DKA. After prompt and adequate treatment of DKA, she transitioned to s.c. basal-bolus insulin. The diagnose of autoimmune DM was established based on the undetectable C-peptide levels and seropositivity for antiglutamic acid decarboxylase antibodies. Additional hormonal parameters revealed overt hypothyroidism and levothyroxine therapy was initiated. This case highlights the importance of blood glucose and thyroid function monitoring as an integral part of cancer treatment protocols for pembrolizumab and other immune checkpoint inhibitors. LEARNING POINTS: Programmed cell death 1 (PD1) inhibitors such as pembrolizumab can cause endocrine immune-related adverse events (irAE), including thyroid dysfunction and type 1 diabetes mellitus (T1DM). Thyroid dysfunction is the most frequent endocrine irAE secondary to PD1 inhibitors. Autoimmune diabetes and possible resultant diabetic ketoacidosis are rare, but life-threatening adverse events associated with pembrolizumab. Pembrolizumab-induced T1DM often present with relatively low HbAlc levels, reflecting the fulminant onset of ß-cell destruction. Patients treated with pembrolizumab and other immune checkpoints inhibitors should be monitored regularly for hyperglycaemia and thyroid dysfunction.

Multiple Brown Tumors Secondary to Parathyroid Carcinoma: A Challenging Diagnosis.

Parathyroid carcinoma is an extremely rare endocrine neoplasm that accounts for less than 1% of the cases of primary hyperparathyroidism (PHPT). Continuous exposure to high levels of parathyroid hormone (PTH) induces an increase in bone remodeling and patients may present with osteitis fibrosa cystica, which is characterized by subperiosteal resorption of the phalanges, diffuse osteopenia, salt and pepper appearance of the skull, bone cysts, and brown tumors. Brown tumors occur in less than 5% of all patients with any form of hyperparathyroidism. Due to similar clinical, radiographic, and histological appearance, differential diagnosis of brown tumors includes primary and secondary bone tumors. We report a case of a 67-year-old female diagnosed with multiple osteolytic lesions initially thought to be bone metastasis of thyroid carcinoma. Further work-up led to the diagnosis of brown tumors due to parathyroid carcinoma. We want to emphasize the inclusion of osteitis fibrosa cystic in the differential diagnosis of osteolytic lesions and the need to perform serum calcium and PTH measurements when investigating these lesions.

Applicability of Martin-Hopkins formula and comparison with Friedewald formula for estimated low-density lipoprotein cholesterol in e_COR study population.

INTRODUCTION: Low-density lipoprotein cholesterol (LDL) is essential in managing cardiovascular disease risk. Since 1972, the Friedewald formula has been used to estimate LDL concentration, although with some limitations. In 2013, Martin et al. proposed a similar but more accurate formula for calculating LDL. AIM: To assess the applicability of the new formula, which we have named the Martin-Hopkins formula, in the Portuguese population and compare it with the Friedewald formula using direct LDL. METHODS: Cross-sectional study, including 1689 participants from the e_COR study. We applied the Martin-Hopkins and Friedewald formulas for estimated LDL (LDL-M and LDL-F). The Friedewald formula was not applied in 12 cases due to triglycerides ≥400mg/dL. Direct LDL was measured and the accepted significance level was p<0.05. RESULTS: Of the total subjects, 50.2% were male and had a median age of 51 (34) years. LDL-D was 117.0 (44.0) mg/dL, LDL-M was 114.6 (43.7) mg/dL and LDL-F was 113.8 (43.2) mg/dL. The Spearman coefficient (ρ) between LDL-M/LDL-D was 0.987 and between LDL-F/LDL-D was 0.983, p=0.001. This strong correlation was maintained in the group with diabetes (LDL-M/LDL-D ρ=0.987; LDL-F/LDL-D ρ=0.978, p=0.001) and hypertriglyceridemia (LDL-M/LDL-D ρ=0.983; LDL-F/LDL-D ρ=0.982, p=0.001). In terms of agreement, the highest value of κ=0.90 was obtained for LDL-M when LDL-D <100mg/dL. CONCLUSION: The Martin-Hopkins formula performed well and had good applicability, showing superiority in relation to the Friedewald formula, especially for LDL-D values <100mg/dL, diabetes, and hypertriglyceridemia.

Applicability of Martin-Hopkins formula and comparison with Friedewald formula for estimated low-density lipoprotein cholesterol in e_COR study population. / Aplicabilidade da fórmula Martin­Hopkins e comparação com a fórmula Friedewald na estimativa do colesterol LDL na população do estudo e_COR.

INTRODUCTION: Low-density lipoprotein cholesterol (LDL) is essential in managing cardiovascular disease risk. Since 1972, the Friedewald formula has been used to estimate LDL concentration, although with some limitations. In 2013, Martin et al. proposed a similar but more accurate formula for calculating LDL. AIM: To assess the applicability of the new formula, which we have named the Martin-Hopkins formula, in the Portuguese population and compare it with the Friedewald formula using direct LDL. MATERIAL AND METHODS: Cross-sectional study, including 1689 participants from the e_COR study. We applied the Martin-Hopkins and Friedewald formulas for estimated LDL (LDL-M and LDL-F). The Friedewald formula was not applied in 12 cases due to triglycerides ≥400mg/dL. Direct LDL was measured and the accepted significance level was p<0.05. RESULTS: Of the total subjects, 50.2% were male and had a median age of 51 (34) years. LDL-D was 117.0 (44.0) mg/dL, LDL-M was 114.6 (43.7) mg/dL and LDL-F was 113.8 (43.2) mg/dL. The Spearman coefficient (ρ) between LDL-M/LDL-D was 0.987 and between LDL-F/LDL-D was 0.983, p=0.001. This strong correlation was maintained in the group with diabetes (LDL-M/LDL-D ρ=0.987; LDL-F/LDL-D ρ=0.978, p=0.001) and hypertriglyceridemia (LDL-M/LDL-D ρ=0.983; LDL-F/LDL-D ρ=0.982, p=0.001). In terms of agreement, the highest value of κ=0.90 was obtained for LDL-M when LDL-D <100 mg/dL. CONCLUSION: The Martin-Hopkins formula performed well and had good applicability, showing superiority in relation to the Friedewald formula, especially for LDL-D values <100 mg/dL, diabetes, and hypertriglyceridemia.