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1. Is it possible for only one hormone to be significantly underproduced by the hypothalamus or is it an “All or nothing” kind of deal?
2. Can years of hypothalamic dysfunction eventually lead to significant deterioration of the pituitary gland—> hypogonadism etc.
3. Would an inhaled steroid such as Advair interfere with an AM blood cortisol test? Is there a linear ratio between ACTH and cortisol? (I.e., inappropriately high cortisol levels for a low-normal ACTH?)
4. Does methylphenidate (Concerta/Ritalin) interfere with prolactin levels?
5. How is a diagnosis made between a hypothalamic vs. a pituitary dysfunction?
-Thanks in advance. Both of you guys are pretty knowledgeable!
@avast322 1343 wrote:
1. Is it possible for only one hormone to be significantly underproduced by the hypothalamus or is it an “All or nothing” kind of deal?
2. Can years of hypothalamic dysfunction eventually lead to significant deterioration of the pituitary gland—> hypogonadism etc.
3. Would an inhaled steroid such as Advair interfere with an AM blood cortisol test? Is there a linear ratio between ACTH and cortisol? (I.e., inappropriately high cortisol levels for a low-normal ACTH?)
4. Does methylphenidate (Concerta/Ritalin) interfere with prolactin levels?
5. How is a diagnosis made between a hypothalamic vs. a pituitary dysfunction?
-Thanks in advance. Both of you guys are pretty knowledgeable!
I am going to sit back on this one let the Boss handle 2-5
1. Yes it is possible for only one area of the pituitary to be effected to alter production of on only one hormone. If a person was in an accident resulting in head trama that damaged specific part of the pituitary then only that area would be affected. This also could happen with hidden infections or inflammations that can occupy a specific area of the pituitary. People that are true hypopituitary this means that all hormones are affected. Pmgamer was hypopit but not all areas where effected because he only takes certain hormones. Then there are people that appear to be hypopit but when hormones are started to being balanced out other hormones that were low also start to return to normal range. This is why it is crucial to understand the interaction between the hormones and other bodily systems.
Truth be known I am pretty knowledgeable. DR. M is EXTREMELY knowledgeable
Thanks HAN, I appreciate your feedback. I must admit that the subject of endocrinology has really captured my interest lately.
Off the top of my head, and thus without deeper analysis:
@avast322 1343 wrote:
1. Is it possible for only one hormone to be significantly underproduced by the hypothalamus or is it an “All or nothing” kind of deal?
Yes. The hypothalamus has multiple compartments – or groups of cells – with different functions. Individual groups may become dysfunctional.
2. Can years of hypothalamic dysfunction eventually lead to significant deterioration of the pituitary gland—> hypogonadism etc.
They are fairly independent though functionally interrelated groups of cells. The deterioration of one doesn’t necessarily lead to the deterioration in the other. However, there are processes – such as diabetes, aging, other metabolic issues – which may affect both.
3. Would an inhaled steroid such as Advair interfere with an AM blood cortisol test?
Advair contains a glucocorticoid – i.e. an artificial cortisol which is more potent than cortisol itself. Thus, the use of Advair may reduce cortisol production by the adrenal glands since Advair already provides some of the glucocorticoid signal requested by the brain via ACTH production.
Is there a linear ratio between ACTH and cortisol? (I.e., inappropriately high cortisol levels for a low-normal ACTH?)
The dose-response curve between ACTH stimulation and Cortisol production is not linear. It is logarithmic – an s-shaped curve where ACTH dose on the x-axis is on a logarithmic scale. This means past a certain dose, the cortisol production plateaus. And there is a middle dose where there is a robust response to ACTH, below which, there is a ramp up in cortisol production. In one study: Plasma ACTH levels between 50 and 60 ng/L (11-13 pmol/L) stimulated cortisol to almost 80% of the maximal increment obtained with plasma ACTH levels above 300 ng/L (greater than 66 pmol/L).
There may be significant variability, however. Multiple factors affect the response to ACTH. This, for example, includes sex (women may be more sensitive to ACTH than men), age (ACTH potency decreases with age in men, may increase with age in women), weight (ACTH potency decreases with higher body mass index). Testosterone affects responsiveness to ACTH.
4. Does methylphenidate (Concerta/Ritalin) interfere with prolactin levels?
The effect of methylphenidate on prolactin is variable.
Dopamine signaling controls prolactin signaling. Dopamine reduces Prolactin production.
Methylphenidate increases both dopamine and norepinephrine signaling. The increase in norepinephrine signaling may account for the variable effects on prolactin production. Increasing norepinephrine may lead to further signalign changes (e.g. low cortisol production, depending on the dose and duration of treatment) which may or may not reduce dopamine signaling, thus potentially counteracting or not counteracting the increase in dopamine signaling from Methylphenidate. Thus in some people, prolactin is decreased, in others it may not change, or it may perhaps increase.
5. How is a diagnosis made between a hypothalamic vs. a pituitary dysfunction?
One can monitor the various signals made by each group of cells in response to stimulant signals, to distinguish where the problem may lie.
For example, in regard to growth hormone production:
1. Dopamine stimulates the release of Growth Hormone Releasing Hormone (GHRH) from the Hypothalamus.
2. Norepinephrine, on the other hand, reduces GHRH production from the Hypothalamus. Clonidine, which reduces Norepinephrine signaling, increases GHRH production from the Hypothalamus.
3. GHRH then stimulates the Pituitary to release Growth Hormone (GH).Thus, to determine if a problem in growth hormone production lies in the Hypothalamus versus Pituitary, one can:
1. Give a person L-Dopa (which becomes dopamine) or Clonidine then measure the change that occurs in GHRH production from the Hypothalamus or Growth Hormone Production from the Pituitary. If the level of increase in either GHRH or Growth Hormone is lower than expected, then one has a problem with the hypothalamus.
2. Give a person GHRH to stimulate Pituitary Growth Hormone Production. If the level of increase in Growth Hormone is lower than expected, then one has a problem with the pituitary gland.
Advair contains a glucocorticoid – i.e. an artificial cortisol which is more potent than cortisol itself. Thus, the use of Advair may reduce cortisol production by the adrenal glands since Advair already provides some of the glucocorticoid signal requested by the brain via ACTH production.
So if the AM cortisol test is HIGH and ACTH is LOW is it plausible to suspect that the cortisol is in fact coming from the Advair vs. the adrenal glands?
i.e., ACTH 16 (6-48)
Cortisol 19.4 (4.3-22.4)@avast322 1374 wrote:
So if the AM cortisol test is HIGH and ACTH is LOW is it plausible to suspect that the cortisol is in fact coming from the Advair vs. the adrenal glands?
i.e., ACTH 16 (6-48)
Cortisol 19.4 (4.3-22.4)Means that if some one pissed you off coming in or you hate needles it registered a false high. I see this all the time with people and when saliva cortisol are ran this shows a lower level.
@hardasnails1973 1375 wrote:
Means that if some one pissed you off coming in or you hate needles it registered a false high. I see this all the time with people and when saliva cortisol are ran this shows a lower level.
That isn’t a false high. This means one can actually respond to stress with higher cortisol production. This is a good thing.
When HPA Axis dysregulation occurs, one can’t respond with enough cortisol to match the stress.
@avast322 1374 wrote:
So if the AM cortisol test is HIGH and ACTH is LOW is it plausible to suspect that the cortisol is in fact coming from the Advair vs. the adrenal glands?
i.e., ACTH 16 (6-48)
Cortisol 19.4 (4.3-22.4)Advair contains fluticasone – the glucocorticoid.
The brain determines how much of a glucocorticoid signal it wants for its functions by measuring how much of a signal it is receiving.
Total Glucocorticoid signal = Cortisol + Cortisone.
The brain then sends out ACTH to the adrenals to determine how much of a glucocorticoid signal the gland will produce.
If the brain already is receiving a glucocorticoid signal from Fluticasone, then it doesn’t have to send out much ACTH to get the total glucocorticoid signal it wants.
Total Glucocorticoid signal when using Advair = Fluticasone + Cortisol + Cortisone.
Thus when adding Advair, Cortisol production is reduced since Fluticasone replaces some of the Cortisol signal.
To determine if the Glucocorticoid signal is high, add the Fluticasone signal to the cortisol signal to see if it is over a physiologic level one expects depending on one’s stress levels.
This makes sense Dr. M. Considering the popularity of Advair, I am really surprised that there is not more information out there regarding its impact on the HP axes, especially with so much concern nowadays with adrenal fatigue etc.
BTW-Dr. M, did you prepare for the MCATs or did they prepare for you? haha jk.
@DrMariano 1377 wrote:
Advair contains fluticasone – the glucocorticoid.
The brain determines how much of a glucocorticoid signal it wants for its functions by measuring how much of a signal it is receiving.
Total Glucocorticoid signal = Cortisol + Cortisone.
The brain then sends out ACTH to the adrenals to determine how much of a glucocorticoid signal the gland will produce.
If the brain already is receiving a glucocorticoid signal from Fluticasone, then it doesn’t have to send out much ACTH to get the total glucocorticoid signal it wants.
Total Glucocorticoid signal when using Advair = Fluticasone + Cortisol + Cortisone.
Thus when adding Advair, Cortisol production is reduced since Fluticasone replaces some of the Cortisol signal.
To determine if the Glucocorticoid signal is high, add the Fluticasone signal to the cortisol signal to see if it is over a physiologic level one expects depending on one’s stress levels.
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