Fibroblast Activation Protein is a GH Target: A Prospective Study of Patients with Acromegaly Before and After Treatment.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a circulating hormone with pleiotropic metabolic effects, which is inactivated by fibroblast activation protein (FAP). Data regarding interaction between FGF21, FAP, and growth hormone (GH) are limited, but it is noteworthy that collagens are also FAP substrates, since GH potently stimulates collagen turnover. AIM: To measure circulating FGF21 components, including FAP, in patients with acromegaly before and after disease control. METHODS: Eighteen patients with active acromegaly were studied at the time of diagnosis and ≥ 6 months after disease control by either surgery or medical treatment. Serum levels of total and active FGF21, ß-klotho, FAP, and collagen turnover markers were measured by immunoassays. Expression of putative FGF21-dependent genes were measured in adipose tissue by reverse transcriptase-polymerase chain reaction, body composition assessed by dual-energy x-ray absorptiometry scan, and insulin sensitivity estimated with homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: Total FGF21, active FGF21 and ß-klotho remained unchanged. Insulin sensitivity and body fat mass increased after disease control but neither correlated with active FGF21. Expression of FGF21-dependent genes did not change after treatment. FAP levels (µg/L) were markedly reduced after treatment [105.6 ± 29.4 vs 62.2 ± 32.4, P < 0.000]. Collagen turnover markers also declined significantly after treatment and ΔFAP correlated positively with ΔProcollagen Type I (P < 0.000) and Type III (P < 0.000). CONCLUSION: 1) Circulating FGF21 and ß-klotho do not change in response to acromegaly treatment, 2) FAP concentrations in serum decrease after disease control and correlate positively with collagen turnover markers, and 3) FAP is a hitherto unrecognized GH target linked to collagen turnover. CLINICAL TRIALS REGISTRATION: NCT00647179.

The Medium-Term Effects of Treatment for Mild Aortic Recoarctation.

OBJECTIVE: To assess medium-term effects of treatment for mild to moderate recoarctation in an adult population. DESIGN: We identified all patients who had coarctation repair between 1965 and 1985 in our institution. They were all (n = 156) invited to a thorough outpatient examination, which was accepted by 133. Eleven (median age 36 [28-53] years) were identified with isolated mild to moderate recoarctation and received reintervention. They comprise the patient population of the current study. We performed bicycle exercise testing, transthoracic echocardiography, magnetic resonance imaging, and 24-hour blood pressure monitoring before and 14 to 29 months after reintervention. RESULTS: Compared to the values before reintervention, 24-hour blood pressures were reduced, but only significantly so for nighttime values. On echocardiography, wall thickness was reduced (1.2 ± 0.3 vs 1.1 ± 0.2, P > .05), and maximum flow velocity in the distal aortic arch decreased (2.8 ± 0.5 m/s vs 2.1 ± 0.4 m/s, P < .05). The invasive coarctation gradient was significantly reduced (15 ± 7 mm Hg vs 5 ± 9 mm Hg, P < .05), and the diameter at the coarctation site was increased (11 ± 3 mm vs 15 ± 3 mm, P < .05). Maximum achieved workload increased (182 ± 51 W vs 205 ± 65 W, P < .05). Cardiac symptoms were overall reduced. CONCLUSION: Reintervention was overall beneficial in increasing exercise capacity and reducing symptoms in the medium term, but the effects on established myocardial hypertrophy and blood pressures were less profound. Larger studies are needed in order to establish the definite role of reintervention for patients with milder recoarctation.

Protracted Clinical Course of Postinfectious Glomerulonephritis in a Previously Healthy Child.

Acute postinfectious glomerulonephritis (PIGN) affects children typically after upper respiratory tract or skin infections with streptococci but can complicate the course of other infections. In children, it is generally a self-limiting disease with excellent prognosis. This paper reports a previously healthy 4-year-old boy who experienced a protracted course of PIGN with persisting episodes of gross haematuria, proteinuria, decreased complement C3c levels but normal P-creatinine levels. Due to the protracted course and the nephrotic-range proteinuria, a renal biopsy was performed 6 months after the initial presentation and the overall pathology was consistent with acute endocapillary glomerulonephritis.