Table 4.
Metabolites/metabolite ratios identified using the machine learning approach
| Metabolite | PHT vs. | Metabolite | PHT vs. | Metabolite | PHT vs. | Metabolite ratio | PHT vs. | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CS | PA | PPGL | CS | PA | PPGL | CS | PA | PPGL | CS | PA | PPGL | ||||
| Acylcarnitines | Biogenic amines | Glycerophospholipids (cont.) | (C2 + 3)/C0 | x | |||||||||||
| C2 | x | x | alpha-AAA | x | PC aa C42:4 | x* | C2/C0 | x | |||||||
| C8 | x | x | Spermidine | x* | x* | x* | PC ae C32:1 | x | Citrulline/Arginine | x | x* | x* | |||
| C7-DC | x | x* | Glycerophospholipids | PC ae C32:2 | x | Citrulline/Ornithine | x* | x* | x* | ||||||
| C9 | x* | x* | x | lysoPC a C16:0 | x* | x* | PC ae C34:2 | x* | CPT-I ratio | x* | x | ||||
| C10:1 | x | x | lysoPC a C16:1 | x* | PC ae C34:3 | x | x | Fischer ratio | x | x | |||||
| C12 | x | lysoPC a C18:0 | x | x | PC ae C36:1 | x* | Met-SO/Met | x | x* | ||||||
| C14:1 | x* | lysoPC a C18:2 | x* | PC ae C38:1 | x | Ornithine/Arginine | x* | x* | x* | ||||||
| C14:2 | x | x* | lysoPC a C20:4 | x* | x | x | PC ae C40:3 | x | Putrescine/Ornithine | x | x* | x* | |||
| C16 | x* | lysoPC a C24:0 | x | x | x* | PC ae C42:0 | x | x* | Spermidine/Putrescine | x* | x* | x* | |||
| C16:1 | x* | x* | PC aa C32:1 | x | PC ae C44:3 | x* | Total DMA/Arginine | x | x* | x* | |||||
| C16:1-OH | x | x | PC aa C32:2 | x* | PC ae C44:4 | x* | Tyrosine/Phenylalanine | x* | x | x* | |||||
| C18:1 | x* | x* | x* | PC aa C34:2 | x | x | Sphingolipids | Metabolite sum | |||||||
| C18:2 | x* | x* | x* | PC aa C34:4 | x | SM (OH) C16:1 | x | AAA | x | ||||||
| Amino Acids | PC aa C36:2 | x* | SM (OH) C24:1 | x | BCAA | x | |||||||||
| Alanine | x* | PC aa C36:3 | x | SM C16:1 | x* | Essential AA | x | ||||||||
| Arginine | x* | x* | PC aa C36:4 | x | SM C18:0 | x* | Glucogenic AA | x | x | ||||||
| Aspartate | x* | x* | x | PC aa C38:6 | x* | SM C18:1 | x* | x | x* | Nonessential AA | x | ||||
| Glutamine | x | PC aa C40:1 | x* | SM C20:2 | x* | Total AA | x | X | |||||||
| Histidine | x | PC aa C40:6 | x* | SM C24:1 | x* | ||||||||||
| Ornithine | x* | x* | x* | PC aa C42:0 | x* | Monosaccharides | |||||||||
| Threonine | x* | PC aa C42:1 | x | x* | H1 | x | x |
List of metabolites and metabolite ratios/sums found in at least 1 of the considered comparison subgroups (all patients, male, female, age <50 and ≥50 years) of PHT with CS, PA, and PPGL, respectively. “x” indicates in which comparison group the metabolite/metabolite ratio has been identified. Metabolites/metabolite ratios found using both approaches (classical and machine learning) are marked with an asterisk (*). Sex and age were included as variables in the analyses: sex was a relevant variable in the comparison between PHT and CS (metabolites and metabolite ratios) as well as PHT vs PA and vs PPGL (metabolite ratios); age was a relevant variable in the comparison of PHT vs PA and vs PPGL (metabolites and metabolite ratios) and PHT vs CS (metabolite ratios).
Abbreviations: a, acyl; aa, diacyl; ae, acyl-alkyl; alpha-AAA, alpha-Aminoadipic acid; CPT-I, carnitine palmitoyl transferase I; CS, Cushing syndrome; Cx:y indicates the lipid chain composition where “x” is the number of carbons and “y” the number of double bonds. DMA, dimethylarginine; H1, sum of Hexoses (including Glucose); LysoPC, lysophosphatidylcholine; Met-SO, Methionine sulfoxide; PA, primary hyperaldosteronism; PC, phosphatidylcholine; PHT, primary hypertension; SM, sphingomyelin (see also Table 1 (30)); PPGL, pheochromocytoma/paraganglioma.
Abbreviations metabolite ratios and sums: AAA, sum of aromatic amino acids; BCAA, sum of branched chain amino acids; CPT-I ratio, ratio of long chain acylcarnitines to free carnitine ([C16+C18]/C0); Essential AA, sum of essential amino acids; Fischer ratio, ratio of BCAA to AAA; Glucogenic AA, sum of selected glucogenic amino acids (Ala, Gly, Ser); Met-SO/Met, fraction of sulfoxidized Met of unmodified Met pool; Non-essential AA, sum of the nonessential amino acids; Total AA, sum of all amino acids; Total DMA/Arg, fraction of dimethylated Arg of the unmodified Arg pool.