Any of the enzymes involved in the adrenal cascade can be affected, as seen by this picture:
The rectangular areas are enzymes. Because of the feedback loop involved with the hypothalamus-pituitary-adrenal axis, downregulation of any enzyme can have different effects. The body always has in mind a "set point" for where cortisol should be and will jack up pregnenolone via ACTH (and therefore norepinephrine) to reach this set point.
For example, in women who have 3B hydroxysteroid dehydrogenase, 21 hydroxylase, or 11B hydroxylase downregulations, you often seen excessive body hair or other masculine secondary sex characteristics. Why? Because when one of these enzymes is downregulated/lowered, the body has to pump out *that much more* ACTH/norepinephrine and therefore pregnenolone and other adrenal hormones preceding the downregulated enzyme. Given that women get half of their testosterone from the adrenals, and higher testosterone goes along with this increased pump out of pregnenolone on down adrenal hormones, you get considerably higher levels of all adrenal hormones before cortisol, including DHEA, androstenedione, and testosterone, the latter two which are "male" hormones.
So there are different types
of symptoms you get depending on the enzymes that are affected. From the site I just linked on 3B hydroxysteroid dehydogenase enzyme deficiency/downregulation:
"3β-Hydroxysteroid dehydrogenase (3β-HSD) deficiency, due to HSD3B2 gene mutation, is a rare form of CAH characterized by increased levels of pregnenolone, 17-hydroxypregnenolone, and DHEA and decreased levels of all other adrenal steroids (Table 1). Affected individuals usually present in infancy with signs of adrenal insufficiency. Female (XX) infants will typically have mild virilization, and a nonclassic form may appear at adrenarche or at puberty. Phenotypic variation in male (XY) infants may range from hypospadias to complete male pseudohermaphroditism."
This site refers to types of what's called congenital adrenal hyperplasia, and despite the "congenital" term there are two types that aren't congenital and are "acquired". However, you can have partial downregulations of adrenal enzymes such that you don't qualify for CAH but can still have problems if some of your hormone levels are "on the edge". Importantly, exogenous testosterone has been shown to slightly reduce enzyme activity of 3B-HSD
and possibly (it's been a while since I've looked through the research) one or two other enzymes.
So if you really want to comprehensively rule out adrenal issues, it's important to get ACTH and cortisol in the same blood draw; the higher the ratio (more ACTH and less cortisol) the more you know that *somewhere* in the adrenal cascade you have an enzyme that's downregulated. If so, just "backfilling" with pregnenolone doesn't help given how pregnenolone is at the top of the cascade; DHEA often doesn't help either but might (if you have 17 ketosteroid reductase downregulation -- which hasn't been shown to be effected by TRT). All you can do is take low doses of supplemental hydrocortisone (synthetic cortisol) to correct the ACTH:cortisol imbalance.
So not only does exogenous testosterone (less so with hCG given that the body recognizes it as LH, and not at all with clomid given that it stimulates LH and FSH) cause LH and FSH to drop to zero, leading to less overall pregnenolone and therefore all adrenal hormones; it also slightly (or perhaps in some people moreso) lowers the 3B-HSD enzyme, slightly (or more) unbalancing the ACTH:cortisol ratio in favor of higher ACTH given lower cortisol (which leads via feedback to the hypothalamus to higher accumulation of CRH, and in turn higher ACTH from the pituitary).
But again, I wouldn't let this worry you if you're on exogenous testosterone; in the vast majority of cases "backfillng" with pregnenolone and DHEA should be more than enough given that most of the effect is with LH and FSH going to zero, not so much 3B-HSD being downregulated -- but again, if you're already low in some adrenal enzymes, exogenous testosterone could put you "over the edge". If so, it still isn't testosterone by itself that's to blame, but rather your precedent flagging adrenal physiology.
If anyone wants I can try and dig up more detailed threads on this stuff.