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SUMMARY: Cushing's syndrome is associated with increased morbidity and mortality. Although surgery is the first-line treatment, drugs can still play a role as an ancillary treatment to be employed while waiting for surgery, after unsuccessful operation or in patients unsuitable for surgery. We were asked to evaluate a 32-year-old male waiting for cardiac transplantation. Idiopathic hypokinetic cardiomyopathy had been diagnosed since 6 years. He was on treatment with multiple drugs, had a pacemaker, an implantable cardioverter and an external device for the support of systolic function. Physical examination showed severely impaired general status, signs of hypercortisolism and multiple vertebral compression fractures. We administered teriparatide, and the few evaluable parameters supported the diagnosis of ACTH-dependent hypercortisolism: serum cortisol was 24.2 µg/dL in the morning and 20.3 µg/dL after overnight 1 mg dexamethasone, urinary free cortisol (UFC) was 258 µg/24 h and ACTH 125 pg/mL. Pituitary CT was negative. Pasireotide 300 µg bid was administered and uptitrated to 600 µg bid. Treatment was well tolerated, achieving dramatic improvement of clinical picture with progressive normalization of serum cortisol and ACTH levels as well as UFC. After 4 months, the patient underwent successful heart transplantation. Many complications ensued and were overcome. Pituitary MRI was negative. On pasireotide 300 µg bid and prednisone 2.5 mg/day (as part of immunosuppressive therapy), morning serum cortisol and ACTH were 15.6 µg/dL and 54 pg/mL respectively, UFC was 37 µg/24 h, fasting glucose: 107 mg/dL and HbA1c: 6.5%. In conclusion, primary treatment with pasireotide achieved remission of hypercortisolism, thus allowing the patient to undergo heart transplantation. LEARNING POINTS: Untreated Cushing's syndrome is associated with ominous prognosis.First-line treatment is surgery (at pituitary or adrenal, according to disease localization).A few drugs are available to treat hypercortisolism.Pasireotide is a multi-ligand somatostatin analog approved for treatment of hypercortisolism.Primary treatment with pasireotide was effective in a patient with severe Cushing's syndrome, allowing him to undergo heart transplantation.
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INTRODUCTION: Homozygous familial hypercholesterolaemia (HoFH) is a rare form of inherited dyslipidemia resistant to conventional cholesterol-lowering medications so that lipoprotein apheresis (LA) is usually required. Lomitapide has been approved for the treatment of HoFH. The aim of this study was to evaluate the benefits of lomitapide in HoFH patients followed with the usual clinical care. METHODS: Clinical and biochemical data were retrospectively collected in 15 HoFH patients (10 with mutations in the LDLR gene and 5 in the LDLRAP1 gene) treated for at least 6 months with lomitapide in addition to lipid-lowering therapies (LLT) in different Lipid Clinics across Italy. RESULTS: The mean follow-up period was 32.3 ± 29.7 months. During background therapies, HoFH patients showed a mean LDL-C level of 426.0 ± 204.0 mg/dl. The addition of lomitapide at the average dosage of 19 mg/day lowered LDL-C levels by 68.2 ± 24.8%. At their last visit, 60% of patients showed LDL-C <100 mg/dl and 46.6% <70 mg/dl. During follow-up, 8 of 10 patients receiving LA (80%) stopped this treatment due to marked LDL-C reduction. A wide range (13-95%) of individual LDL-C reduction was observed, but this was not related to genotype. During follow-up, 53.3% of patients reported at least one episode of diarrhea, but none was referred as severe; none had liver transaminase >5× ULN or had to stop treatment due to side effects. A subset of patients was evaluated by liver ultrasound and fibroscan (n = 5) or nuclear magnetic resonance with spectroscopy (MRS) (n = 1) not showing clinical evidence of liver damage. CONCLUSION: In this real-world experience, lomitapide was confirmed to be a very powerful cholesterol-lowering agent in HoFH showing a good safety profile.
