At around 12:40, I should have said carbon 17 of the androgens (and estrogens) does have a hydroxl group as you can see from the -OH group on that carbon.
I wanted to point out that carbon 13 on the estradiol should still have a methyl group (which would be carbon 18), like the androgen precursors. Sorry for the error. Steve
Does the P450 C11 (11hyd) enzyme take corticosterone to cortisol in the zona faciculata? The way that it is drawn, it's hard for me to tell whether that enzyme is just for the 11-deoxycortisol to cortisol rxn. I'm wondering this because you said that deficient P450 C21 (21 hyd) enzyme can limit cortisol production, and the only way I can see that happening is if corticosterone can be converted into cortisol. Thanks for the great lecture!
P450 C11 hydroxylates 11-deoxycorticosterone (11-DOC) to make corticosterone and 11-deoxycortisol to cortisol. The only difference between cortisol and corticosterone is that cortisol has an OH group on C17, so P450 C11 would not be converting corticosterone to cortisol, and actually both of these have an -OH group on C11 anyway! In patients who have a P450 C21 deficiency, they cannot make cortisol because there is no 11-deoxycortisol made from 17 OH progesterone. I hope that helps. Steve
I'm curious, why obtain a 17 OH progesterone level, androstenedione, a total testosterone level, and DHEA-S level when working up a patient to rule out all the ddx for a pt who may present with difficulty putting on weight, increased acne, thinning of hair and other masculinizing effects? I'm currently doing an endocrine rotation and I'm curious as to why we have to obtain all these labs? Is it redundant? Would your treatment really change if one over the other was elevated?
+Hilary Kopczenski Hi Hilary, What you are describing is a female patient with clinical findings suggesting androgen excess. Remember that the two major courses of androgens are the adrenal cortex and the ovaries. So, measurement of all of these may shed some light in helping you decide what is more or less likely on the DDx, which may require additional testing (e.g., imaging for ovarian or adrenal tumors) to come up with the most likely diagnosis and appropriate treatment plan. But the history and physical exam are essential. Galactorrhea suggests hyperprolactinemia (which can increase DHEA-S from the adrenal cortex), Cushingoid features suggests suggests Cushing's syndrome (e.g. an ACTH-secreting tumor can stimulate adrenal androgen production), rapid development of symptoms, weight loss, and more severe virilization (e.g. male-pattern baldness, deepening voice, cliteromegaly) suggests an androgen secreting tumor (ovarian or adrenal). While there is a lot of overlap of lab results between some of the disorders causing androgen excess, the magnitude of elevation combined with what is elevated and what is not elevated helps to clarify the diagnosis when combined with the history and physical exam. For example, since DHEA-S comes almost exclusively from the adrenal cortex, markedly elevated DHEA-S (>700 ng/dL) is highly suggestive an adrenocortical carcinoma, especially when combined with a history of weight loss, bloating, back pain, and virilization. In that case, an abdominal CT scan confirms the diagnosis. Treatment would obviously be surgical resection of the tumor and possibly medications that inhibit steroid synthesis. So, the diagnosis of an androgen-secreting tumor is attached to a very different treatment plan than a patient with PCOS or late-onset 21 hyd deficiency (non-classic CAH). It also wouldn't be desirable to order an unnecessary imaging test for these patients if the history/physical exam and lab results didn't not suggest a tumor.
I diagrammed this out a few times the same way as you did and it helped me memorize this much faster! thank you!
Awesome!! Very helpful.
Thank you your video is very helpful !!!!
At around 12:40, I should have said carbon 17 of the androgens (and estrogens) does have a hydroxl group as you can see from the -OH group on that carbon.
I love your logic! Thank you very much!
Thanks Alyaksandra
thank you, very helpful
I’m a bodybuilder and this all made beautiful sense to me! You are a genius sir.
I appreciate that!
I wanted to point out that carbon 13 on the estradiol should still have a methyl group (which would be carbon 18), like the androgen precursors. Sorry for the error. Steve
Thank you :)
You saved my life... Thank you
I am so happy to hear that it helped you!
Great video, thanks. One thing, I think a Ch3 might be missing from Estradiol picture
Yes, carbon 18 on the estradiol should still have a methyl group like the androgen precursors.
Great Lecture ..... Thanks
shady abdelbari My pleasure. I'm glad you found it helpful
Does the P450 C11 (11hyd) enzyme take corticosterone to cortisol in the zona faciculata? The way that it is drawn, it's hard for me to tell whether that enzyme is just for the 11-deoxycortisol to cortisol rxn. I'm wondering this because you said that deficient P450 C21 (21 hyd) enzyme can limit cortisol production, and the only way I can see that happening is if corticosterone can be converted into cortisol. Thanks for the great lecture!
P450 C11 hydroxylates 11-deoxycorticosterone (11-DOC) to make corticosterone and 11-deoxycortisol to cortisol. The only difference between cortisol and corticosterone is that cortisol has an OH group on C17, so P450 C11 would not be converting corticosterone to cortisol, and actually both of these have an -OH group on C11 anyway!
In patients who have a P450 C21 deficiency, they cannot make cortisol because there is no 11-deoxycortisol made from 17 OH progesterone.
I hope that helps.
Steve
Right, okay, that makes sense. Thank you for taking the time.
good
I'm curious, why obtain a 17 OH progesterone level, androstenedione, a total testosterone level, and DHEA-S level when working up a patient to rule out all the ddx for a pt who may present with difficulty putting on weight, increased acne, thinning of hair and other masculinizing effects? I'm currently doing an endocrine rotation and I'm curious as to why we have to obtain all these labs? Is it redundant? Would your treatment really change if one over the other was elevated?
+Hilary Kopczenski
Hi Hilary,
What you are describing is a female patient with clinical findings suggesting androgen excess. Remember that the two major courses of androgens are the adrenal cortex and the ovaries. So, measurement of all of these may shed some light in helping you decide what is more or less likely on the DDx, which may require additional testing (e.g., imaging for ovarian or adrenal tumors) to come up with the most likely diagnosis and appropriate treatment plan. But the history and physical exam are essential. Galactorrhea suggests hyperprolactinemia (which can increase DHEA-S from the adrenal cortex), Cushingoid features suggests suggests Cushing's syndrome (e.g. an ACTH-secreting tumor can stimulate adrenal androgen production), rapid development of symptoms, weight loss, and more severe virilization (e.g. male-pattern baldness, deepening voice, cliteromegaly) suggests an androgen secreting tumor (ovarian or adrenal).
While there is a lot of overlap of lab results between some of the disorders causing androgen excess, the magnitude of elevation combined with what is elevated and what is not elevated helps to clarify the diagnosis when combined with the history and physical exam. For example, since DHEA-S comes almost exclusively from the adrenal cortex, markedly elevated DHEA-S (>700 ng/dL) is highly suggestive an adrenocortical carcinoma, especially when combined with a history of weight loss, bloating, back pain, and virilization. In that case, an abdominal CT scan confirms the diagnosis. Treatment would obviously be surgical resection of the tumor and possibly medications that inhibit steroid synthesis. So, the diagnosis of an androgen-secreting tumor is attached to a very different treatment plan than a patient with PCOS or late-onset 21 hyd deficiency (non-classic CAH). It also wouldn't be desirable to order an unnecessary imaging test for these patients if the history/physical exam and lab results didn't not suggest a tumor.
Awesome! Thank you!
How come 17BHSD is adding hydrogen to the testosterone ?
why is the 11 carbon and 12 carbon in clockwise order
They’re just like that.
I'm not an intellectual but I'm watching this for fun.
Let me tell what really happened at 13:46 is causing misery for every male on this planet.