Amanda Wilde (Host): This is Expert Insights with the Carle Foundation Hospital. I'm Amanda Wilde. And my guest is endocrinologist, Dr. Shruti Dave, to offer her expertise on the uncommon condition called hormonal hyperhidrosis. Welcome, Dr. Dave. Thanks for being here.

Shruti Dave, MD: Hello!

Host: So, it is an uncommon condition. Can you give us a brief overview of what hyperhidrosis is?

Shruti Dave, MD: Yes. So hyperhidrosis, simply put, is sweat production that's exceeding thermoregulatory needs of the body; too much sweating, more than what's needed to maintain body temperature.

Host: What causes that?

Shruti Dave, MD: So, there are many reasons for too much sweating or excessive sweating. One of the ways to divide reasons behind too much sweating is a method called primary versus secondary. Primary hyperhidrosis would be a situation where you don't necessarily have a reason behind it. It's also commonly known as primary focal hyperhidrosis. As I mentioned, it's idiopathic. It tends to be localized, bilateral, symmetrical.

And then, there is a whole category of secondary hyperhidrosis, which as the name implies, there is generally a reason behind it. It's also referred to as generalized hyperhidrosis. And then, among this secondary hyperhidrosis, there are many reasons for the secondary hyperhidrosis. Hormonal or endocrine reasons for hyperhidrosis is what we are going to talk about today.

Host: Well, now, excessive sweating, hyperhidrosis can be normal, can't it, in certain life stages?

Shruti Dave, MD: Correct. So, there are certain situations where if the outside temperature is high, your body's going to sweat. If you exercise, your body's going to sweat. These are like physiologic conditions, but then there can be pathologic conditions where you have excess sweating also.

Host: So for the secondary form of hyperhidrosis where we know some reasons, what are some of those reasons? What are some of the endocrine causes of hyperhidrosis?

Shruti Dave, MD: Yes. So, endocrine causes for hyperhidrosis, common ones are disturbances in estrogen-androgen hormone balances. And so, those would be your perimenopause, menopause, which is a physiologic condition, and then ovarian insufficiency or premature ovarian failure would be a pathologic condition that would lead to excessive sweating as a result of those hormone disturbances.

The other common endocrine reason would be hyperthyroidism, overactivity of thyroid gland. That would lead to too much sweating. There are many reasons that diabetic patients will have excessive sweating. Some of them have it because of peripheral neuropathy, which is a complication of longstanding diabetes. That leads to actually absence of sweating in the area that's affected by neuropathy, but then is a compensation, compensatory proximal hyperhidrosis is seen. So, area proximal to the part that's affected by neuropathy will show too much sweating at times. Something called gustatory hyperhidrosis that's related to eating is much more common in diabetics than it is in non-diabetic population. And then, low blood sugars associated with diabetes treatment can lead to hyperhidrosis because your autonomic nervous system gets activated.

Some of the other little less common conditions would be hypogonadism. So, men with low testosterone, whether it is because of a reason associated with some other regulating hormones or a testicular problem, or it is iatrogenic In situations where there has been androgen deprivation therapy that can lead to excessive sweating just like menopause.

Pheochromocytoma is a condition of excess catecholamines coming from adrenal gland that can lead to hyperhidrosis. Insulin release, insulinoma and other conditions that have excess insulin release can also lead to hyperhidrosis. And then acromegaly, which is excess growth hormone, also leads to too much sweating.

Other rarely associated conditions where there is limited literature would be obesity, pituitary tumor, adrenal insufficiency, argininevasopressin deficiency, the older name for it is central diabetes insipidus, pituitary adenoma, and then carcinoid tumors can also lead to too much sweating.

Host: So, those are obviously all risk factors, everything that you've mentioned. If you're diabetic, if you're going through some stage of menopause, for example. With all those possibilities of causes, what specific tests are conducted to diagnose this condition, hormonal hyperhidrosis?

Shruti Dave, MD: Yes. So in general, for hyperhidrosis, first of all, there is limited amount of literature. A lot of studies and literature is in form of case studies or retrospective analysis. So, there are not very well-defined criteria or guidelines. So, a lot depends upon clinical expertise. And knowing the associated features for conditions is important.

With hyperhidrosis, you do want to rule out some of the more dangerous or life-threatening situations like infection, malignancies at first. I don't wanna miss that part, that there is some differential diagnosis associated with hyperhidrosis that's not related to endocrinology.

But coming back to the hormonal hyperhidrosis, so history and physical evaluation will guide you. For perimenopause, menopause, you are going to have the typical age at which the symptoms start. Menstrual irregularities are going to be present. In most situations, you don't need testing. History is sufficient to make the diagnosis. You may need some testing to rule out other non-hormone-related conditions.

When there is menstrual cycle irregularities though, conditions like polycystic ovary syndrome, someone has had endometrial ablation done where you don't have the irregular menstrual cycle history, FSH is a hormone that typically is elevated. That, along with estrogen level, can be helpful in making sure you're making the right diagnosis. For overactive thyroid, you'll have associated symptoms like weight loss, heat intolerance, diarrhea. Some signs that you look for on exam would be tremors or shaky hands, exophthalmos, enlargement of thyroid. And for this, TSH and free T4 are the most basic tests. In some situations, free T3 test, and at times Graves antibody testing is needed. There are also some scans of thyroid that may need to be done once you have established that hyperthyroidism seems to be the diagnosis.

For diabetes-related reasons, you're going to find findings of peripheral neuropathy, lack of sensation in the feet is where it is most commonly going to manifest. You're going to of course have the history of diabetes. For gustatory hyperhidrosis, it's typically associated with eating. It affects the face and neck area more. With the low glucose levels as a result of medications, you're going to have history of medication use and also a low glucose recording that goes along with symptoms.

Similarly, the insulin insulinoma and other tumors that make too much insulin, you're going to have low glucose potentially, if a person is aware that this could be one of the reasons for sweating. Sometimes there is history of night sweats with insulinoma because during the daytime, patients will manage by eating. They have recognized this because when they feel poorly or have some of the associated symptoms, anxiety, sweating, they will eat and it goes away. But at nighttime, when they're sleeping, they may not recognize it. You will oftentimes find weight gain with insulinoma-type condition. Testing there involves simultaneously testing glucose and C-peptide level. So, testing can be complicated, typically done by endocrinologists. But as a screening test, you can, during the symptoms, do glucose test and if possible doing C-peptide insulin levels at the same time, is how you will approach it.

Pheochromocytoma is diagnosed based on either 24-hour urine measurement of metanephrines or plasma fractionated metanephrines. Generally, plasma test is used when your suspicion for pheochromocytoma is high. For the hypogonadism, low testosterone is how you diagnose it. It is important to do testosterone testing early in the morning, in a fasting state, and often repeated testing is needed because there is a lot of fluctuation in testosterone levels throughout the day. And there are differences among labs as far as normal ranges go. So, you need to evaluate it based on what your labs normal ranges are. And then, there are additional hormones, prolactin and luteinizing hormone that are often included in the initial testing.

For acromegaly, you are going to find high levels of IGF-1, insulin-like growth factor 1. And additional tests sometimes involves glucose tolerance test, where you measure repeated levels of growth hormone after drinking the certain amount of glucose. For carcinoid, you're going to find some other associated symptoms like diarrhea, wheezing, flushing is actually an important symptom of carcinoid. Testing, there is going to involve, again, 24-hour urine, checking it for 5-HIAA is the chemical. For low vitamin D, vitamin D level tested will help you make the diagnosis

Host: So, there are many ways to pinpoint the cause of the hyperhidrosis. That says to me from what you said earlier, that we're talking in this context only about secondary hyperhidrosis.

Shruti Dave, MD: Correct.

Host: And whether it is primary or secondary hyperhidrosis, how is hormonal hyperhidrosis managed?

Shruti Dave, MD: Yes. So, secondary hyperhidrosis primarily is managed by addressing the underlying condition. In many cases, it is possible and necessary to treat. For example, overactive thyroid or hyperthyroidism is treated and that resolves the symptoms. If there are low glucose-related issues, whether they are in diabetes due to medication or condition like insulinoma, you would either adjust the medication or localize the tumor and remove it, is the treatment. Similarly, pheochromocytoma, localizing, remove the tumor.

For menopause, perimenopause, hormone replacement therapy, and some non-hormonal medications are available. For hypogonadism, you would do similarly, testosterone replacement treatment. For androgen deprivation therapy related patients, again, because of low testosterone is why they have these symptoms. We have, in this particular category, very little data, but we use medications that have historically been tried in treatment of menopause; medications like venlafaxine, gabapentin. And in resistant cases, oxybutynin has some data to treat. So it primarily depends upon figuring out the cause, addressing the cause, and that resolves sweating.

Acromegaly is probably one of the exceptions where, in longstanding cases of acromegaly, sometimes sweating does not resolve after you do treatment of acromegaly. For gustatory hyperhidrosis, it is difficult to pinpoint etiology. So, topical agents like glycopyrrolate or aluminum chloride hexahydrate. These are agents that are used in primary hyperhidrosis by dermatologists, so you could use those to treat.

Host: Yeah. I was going to ask you lastly, how you would rate the efficacy of these approaches, but it does sound like you have to sort of zero in on each patient's individual situation to come up with the appropriate treatment.

Shruti Dave, MD: Yes, that is correct. You absolutely have to individualize the treatment because reasons are so varied and different that each patient requires an individualized approach.

Host: Well, doctor, this is fascinating and very relevant for those who have those underlying or primary conditions. Thank you for this information on diagnosis and management of hormonal hyperhidrosis.

Shruti Dave, MD: You are welcome.

Host: That was endocrinologist, Dr. Shruti Dave. And that wraps up this episode of Expert Insights with the Carle Foundation Hospital. I'm Amanda Wilde. For more information and to get connected with one of our providers, visit carle.org or for a list of Carle providers and to view Carle-sponsored educational activities, head on over to our website at carleconnect.com. That wraps up this episode of Expert Insights with the Carle Foundation Hospital. Thanks for listening.