Disorders in the initial steps of steroid hormone synthesis.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic pathways and genetic phenotypes without systematic search methodology
PubMed 26960203 · doi:10.1016/j.jsbmb.2016.03.009
What was done
This narrative review synthesized the biochemical mechanisms and clinical phenotypes associated with disorders of early steroid hormone synthesis, specifically examining cholesterol internalization, mitochondrial delivery mediated by steroidogenic acute regulatory protein (StAR), and conversion to pregnenolone by cholesterol side-chain cleavage enzyme (P450scc, encoded by CYP11A1).
What was found
The abstract reports qualitative mechanistic and clinical findings without numerical metrics. Early cholesterol processing defects (Adrenoleukodystrophy, Wolman Disease, Cholesterol Ester Storage Disease, and Niemann-Pick Type C) cause adrenal insufficiency. Severe StAR mutations produce classic congenital lipoid adrenal hyperplasia (lipoid CAH) with adrenal lipid accumulation, adrenal insufficiency, and 46,XY disordered sexual development via a two-hit model, while partial-function mutations cause milder non-classic glucocorticoid deficiency. Rare CYP11A1/P450scc mutations present with clinical and hormonal features indistinguishable from lipoid CAH (including classic and non-classic forms) but lack massive adrenal hyperplasia, often requiring DNA sequencing for differentiation.
Why it matters
The review delineates the pathophysiology of rare monogenic adrenal disorders and highlights the diagnostic overlap between StAR and CYP11A1 mutations, reinforcing the necessity of genetic testing when adrenal imaging is inconclusive.
Limits
As a narrative review, no systematic search criteria, meta-analytic pooling, sample sizes, or quantitative outcome data were reported. Evidence is limited to descriptive pathophysiology and case phenotypes.
Cited by
- supports Testosterone, estrogen, progesterone, and cortisol are synthesized from cholesterol.