Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor use in the management of resistant hypercholesterolemia induced by mitotane treatment for adrenocortical cancer.

We report the case of a patient with probable heterozygous familial hypercholesterolemia and mitotane-induced resistant hypercholesterolemia, despite combination therapy with rosuvastatin and ezetimibe. The patient was managed with the addition of evolocumab. Use of a proprotein convertase subtilisin-kexin type 9 inhibitor, should be considered in patients who develop mitotane-related hypercholesterolemia that cannot be managed with conventional lipid-lowering treatment.

Familial partial lipodystrophy and proteinuric renal disease due to a missense c.1045C > T LMNA mutation.

Proteinuric renal disease is prevalent in congenital or acquired forms of generalized lipodystrophy. In contrast, an association between familial partial lipodystrophy (FPLD) and renal disease has been documented in very few cases. A 22-year-old female patient presented with impaired glucose tolerance, hyperinsulinemia, hirsutism and oligomenorrhea. On examination, there was partial loss of subcutaneous adipose tissue in the face, upper and lower limbs, bird-like facies with micrognathia and low set ears and mild acanthosis nigricans. Laboratory investigations revealed hyperandrogenism, hyperlipidemia, elevated serum creatine kinase and mild proteinuria. A clinical diagnosis of FPLD of the non-Dunnigan variety was made; genetic testing revealed a heterozygous c.1045C > T mutation in exon 6 of the LMNA gene, predicted to result in an abnormal LMNA protein (p.R349W). Electromyography and muscle biopsy were suggestive of non-specific myopathy. Treatment with metformin and later with pioglitazone was initiated. Due to worsening proteinuria, a renal biopsy was performed; histological findings were consistent with mild focal glomerular mesangioproliferative changes, and the patient was started on angiotensin-converting enzyme inhibitor therapy. This is the fourth report of FPLD associated with the c.1045C > T missense LMNA mutation and the second with co-existent proteinuric renal disease. Patients carrying this specific mutation may exhibit a phenotype that includes partial lipodystrophy, proteinuric nephropathy, cardiomyopathy and atypical myopathy. LEARNING POINTS: Lipodystrophy is a rare disorder characterized by the complete or partial loss of subcutaneous adipose tissue, insulin resistance, diabetes mellitus and hyperlipidemia.Proteinuric renal disease is a prevalent feature of generalized lipodystrophy but rare in familial partial lipodystrophy.Patients carrying the c.1045C > T missense LMNA mutation (p.R349W) may present with familial partial lipodystrophy, proteinuric nephropathy, cardiomyopathy and atypical myopathy.

Clinical and imaging evaluation of the response to intravenous steroids in patients with Graves' orbitopathy and analysis on who requires additional therapy.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of an individualized steroid regimen in patients with moderate-to-severe Graves' orbitopathy (GO) by monitoring clinical and imaging parameters. METHODS: In total, 47 patients with active, moderate-to-severe GO were enrolled in this study. All the patients received the proposed treatment regimen by European Group on GO of 4.5 g of intravenous (IV) methylprednisolone for 12 weeks. At the end of the IV treatment, patients with persistent active GO (Group 1) who were assessed by clinical examination and orbital imaging with short tau inversion recovery-sequence magnetic resonance imaging (STIR MRI) received additional treatment with oral prednisolone, and those with inactive GO (Group 2) received no further treatment. RESULTS: Of the 42 patients who completed the study, 22 (52.4%) patients formed Group 1 and 20 (47.6%) patients Group 2. At the 12th week, the overall response to IV treatment was 76.2%, and clinical activity score (CAS) improvement was 69%. At the 24th week, the overall response was 92.8%, and CAS improvement was 97.6%, without statistically significant difference in CAS and total eye score between these two groups (P=0.157 and P=0.856, respectively). Ophthalmic manifestations were improved, being absent or minimal in 78.6% of patients at the 24th week follow-up. Recurrence of disease activity occurred in 9.5% of patients up to 24 weeks after the completion of treatment, and major adverse events occurred in 6.4% of patients. CONCLUSION: In patients with moderate-to-severe GO, IV steroid treatment, followed by oral treatment, when needed, is an effective regimen with low rates of adverse events and recurrences. STIR MRI is a significant tool for recognizing patients who need additional steroid treatment.

Cushing's Syndrome Due to CRH and ACTH Co-secreting Pancreatic Tumor--Presentation of a New Case Focusing on Diagnostic Pitfalls.

Cushing's syndrome (CS) due to a corticotropin-releasing hormone (CRH) and adrenocorticotropin hormone (ACTH) co-secreting tumor is very rare, and diagnosis can be difficult. We describe a case of CS caused by ectopic CRH and ACTH production from a pancreatic neuroendocrine tumor (pNET) and discuss possible pitfalls in the diagnosis. A 48-year-old woman presented with gradual increase in body weight, muscle weakness, and difficult to control hypertension. Laboratory and imaging investigations revealed ACTH-dependent hypercortisolemia and a 3-cm mass at the head of the pancreas. The patient underwent partial pancreatoduodenectomy. Histological examination revealed a well-differentiated pNET, expressing both CRH and ACTH. After a follow-up period of 18 months, she remains asymptomatic with no metastatic disease. This is the fourth case report of CS in adults due to an ectopic ACTH- and CRH-secreting pNET. Co-secretion of ACTH and CRH by the same tumor may cause diagnostic problems since investigation depends on which of the two hormones is secreted in greater amounts. Measurement of plasma CRH may help in establishing the diagnosis, especially in patients in whom endocrine tests are indicative of ectopic CS, whereas imaging findings are suggestive of pituitary hyperplasia.

Severe resistant hypoglycemia in a patient with a pancreatic neuroendocrine tumor on sunitinib treatment.

OBJECTIVE: Sunitinib is a tyrosine kinase inhibitor used in the therapy of pancreatic neuroendocrine tumors (PNETs), metastatic renal cancer and gastrointestinal stromal tumors. We describe a patient with PNET who presented with severe hypoglycemia following sunitinib administration. CASE REPORT: A 64-year old man with known metastatic PNET presented with a history of recurring episodes of severe, life-threatening hypoglycemia 3 months after initiation of sunitinib treatment. Investigations during symptomatic hypoglycemia revealed inappropriately increased plasma insulin and C-peptide levels, consistent with endogenous hyperinsulinemia. No immune staining for insulin was observed in tissue samples from peritoneal metastatic tumor lesions, and serum anti-insulin antibodies were negative. Medical management with diazoxide, methylprednisolone and ocreotide was ineffective; continuous intravenous infusion of glucagon was required to maintain euglycemia. Following discontinuation of sunitinib there was gradual improvement in both the severity and frequency of the hypoglycemia. Six months later, the patient remained free of hypoglycemic episodes. CONCLUSIONS: We describe a patient with PNET who experienced severe, life-threatening hypoglycemia following sunitinib use. It is important that glucose levels of patients treated with sunitinib are monitored on a regular basis; those patients with diabetes may need to have their antidiabetic treatment adjusted to prevent hypoglycemia.