The acid-labile subunit (ALS) is an 85 kDa glycoprotein that belongs to the leucine-rich repeat superfamily. It mainly circulates in serum bound to a high molecular weight ternary complex. The main and most widely studied function of ALS is to prolong the half-life of the binary complex formed by insulin-like growth factors type 1 and 2 and its transport proteins 3 and 5. ALS serum levels are lower in neonates, reach a peak in late puberty, and then slowly decrease throughout adulthood. ALS deficiency has consequences on growth, hydrocarbon and bone metabolism, and, in some cases, it affects pubertal development. To date, 25 patients with complete ALS deficiency due to IGFALS gene mutations have been found.

Context The low-dose (1 µg) ACTH test (LDT) is widely used to assess central adrenal insufficiency (CAI); however, the serum cortisol cutoff value is controversial. Salivary cortisol (SC) may be a more accurate measurement for CAI. Objective To assess a new maximum cutoff value of serum cortisol after LDT in pediatric patients, taking into account serum and SC measurements. Design and Setting Prospective study in a pediatric tertiary referral center. Working Hypothesis The combined analysis of serum and SC response to LDT might improve LDT for CAI diagnosis. Participant and Outcome Measurement A total of 145 pediatric patients underwent LDT. Serum and SC levels were measured. A central adrenal sufficient (CAS) response was established according to the reference serum cortisol cutoff value of ≥497 nmol/L. Results The LDT study showed central adrenal sufficiency in 72 patients and CAI in 73 patients. Considering the lower quartile of maximum SC value (21 nmol/L) in the CAS group, an intermediate CAI (InCAI) group and a real CAI (RCAI) group were defined. Regarding the median maximum value of serum cortisol levels in the InCAI group, a new serum cortisol cutoff value of 450 nmol/L was established. Furthermore, 91% of the patients in the RCAI group were below this cutoff value. Conclusion The combined evaluation of maximum serum and SC levels to LDT might be useful to define an InCAI group and to avoid unnecessary hormone replacement therapy. However, rigorous patient follow-up is required

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The use of a "grey zone" considering measurement uncertainty in pharmacological tests. The serum growth hormone stimulation test as an example.

Pediatric adrenocortical tumors are rare and heterogeneous endocrine malignancies. Objectives To report clinical, biochemical, and histological features, staging, and therapeutic interventions in a cohort of 28 patients treated at a single tertiary center. Methods A retrospective review of medical records of children with PACT (diagnosed before <18 years of age) followed between 1987–2018 at Hospital de Pediatría Garrahan, Buenos Aires, Argentina. Results Mean age at diagnosis was 4.6 years (range, 0.3–17.3 years) and median follow-up was 4.17 years (range, 0–12 years). Female to male ratio was 2.5:1. Signs and symptoms that prompted medical intervention were hormonal overproduction (57%), abdominal complaints (36%), and hypertensive encephalopathy (7%). In patients with clinically virilizing tumors (n=16) mean height standard deviation score (SDS) and bone age advance were significantly higher while body mass index (BMI) SDS was significantly lower than in those with clinical Cushing’s (n=10) (p<0.05). Serum dehydroepiandrosterone sulfate (DHEAS) levels were significantly higher in stage IV than in stage I (p=0.03). Total adrenalectomy was performed in 26 patients. Eight patients (stage III-IV) received adjuvant chemotherapy. Five-year overall and disease-free survival were 100% for ST I-II, and 51% (95% CI 21–82) and 33% (95% CI 1.2–65) for ST III-IV, respectively (p=0.002). No statistical difference was found when comparing 2-year parameters with and without adjuvant chemotherapy. Conclusions Height SDS and BMI SDS seem to mirror hormonal secretion in pediatric adrenocortical tumors. Higher DHEAS levels were found in patients with more advanced disease. Further large-scale studies are needed to validate a possible role for DHEAS as a biochemical marker of tumor stage and to draw robust conclusions on the use of adjuvant chemotherapy.