Endocrine Abstracts

A 47-year-old male with a history of severe persistent asthma and recurrent respiratory infections with admissions to the Pulmonology Department. The patient underwent a study due to weight loss, diarrhoea and Ca 19.9 elevation. Imaging tests (abdominal CT and MRI cholangio) were performed, which highlighted severe pancreatic fat infiltration. The cystic fibrosis study was completed with genetics (positive: two heterozygous switches F508del and D1152H), sweat test (45 mmol/l --> Intermediate, suggests possible CF) and pancreatic elastase in feces (<5.50 mg/g). Finally, the patient was diagnosed with cystic fibrosis, heterozygous for F508del and D1152H associated with exocrine pancreatic insufficiency. He was referred for follow-up in the Pulmonology and Endocrinology consultation to optimize treatment and follow-up, as well as to assess the start of new therapies. Patients diagnosed in adulthood have slightly impaired lung function and a low incidence of pancreatic involvement, so their prognosis tends to be favorable. On the basis of the foregoing, they will require less intensive treatment and often will not need digestive enzymes or nutritional supplements. An accurate diagnosis through imaging tests is essential for the correct management of this entity. In our case, it was the key clue, since the disease was not suspected by the patient’s condition. With the advent of new modulator drugs (potentiators and correctors) of the CFTR protein, a very hopeful future opens up, since it radically changes the natural history of the disease. At present, the available pCFTR modulators are divided into potentiators, such as ivacaftor (IVA), which increases the probability of opening/activation of the chloride channel; and the correctors lumacaftor (LUM), tezacaftor (TEZ), and elexacaftor (ELX), which facilitate protein processing and transport to the cell membrane, increasing the amount of pCFTR on the cell surface. Currently, there are 4 pCFTR modulator drugs authorized by the European Medicines Agency (EMA): Kalydeco® (IVA) for over 4 months, Orkambi® (LUM/IVA) for over 2 years, Symkevi® (TEZ/IVA) for over 6 years and Kaftrio® (ELX/TEZ/IVA) for ages 6 and up; in the EU the last two in combination treatment with Kalydeco® (IVA). Each of the medications described is approved for specific CF patients and mutations, so not every approved modulating therapy is indicated for all of the CFTR genotypes. Our patient benefited from treatment with Kaftrio, an oral therapy approved for patients with at least one Phe508del mutation in the CFTR gene.