Hypothyroidism in patients with pseudohypoparathyroidism?

....In light of my last post, I found the article by Balavoine, et al, Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical evidence of resistance to TSH and TRH, intriguing, also.

Objective: Hypothyroidism is a manifestation of multi-hormonal resistance in pseudohypoparathyroidism type Ia (PHP Ia). The objective of the study was to determine the mechanisms of hypothyroidism in PHP Ia.

Hypoparathyrodism is another endocrine problem considered "rare". Many of us with Cushing's Disease have other endocrine and auto-immune dysfunctions. Malfunctions. Non-functions. You get the idea. Although only the MEN varieties have been considered hereditary, there is new evidence of a familial link to Cushing's and other endocrine disorders. And this may be even another.

In Update in Pituitary Disease, Schlomo Melmed of Cedars-Sinai Medical Center, Los Angeles writes:

A recent paper (8), for the first time, proposed the aryl hydrocarbon receptor interacting protein (AIP) gene as predisposing to pituitary adenoma......Drouin and colleagues (3) discovered that glucocorticoid resistance of ACTH-secreting tumors can be attributed to loss of Brg1 or histone deacetylase (HDAC)-2 nuclear expression. This transrepression of the POMC gene in corticotrophs could therefore be a mechanism underlying the formation of ACTH-secreting tumors (3)."

Also, the following:

A large body of work was published relating to the genetic analysis of pituitary tumors. A comprehensive study from Belgium (6) characterized familial isolated pituitary adenomas. These very rarely encountered index families comprised patients with heterogenous features of acromegaly, prolactinoma, and Cushing’s disease. Significantly affected individuals were younger, some were giants, and some harbored more invasive tumors than sporadic patients. The challenge in these rarely encountered and similar families (7) has been that they appear to harbor a mutation in the 11q region, distinct from multiple endocrine neoplasia-1 or any other related tumor suppressor gene. The challenging question in these families has been that the identity of the gene on 11q that predisposes to these traits has remained elusive.

And there is more....but I am tired. My non-functions, malfunctions and dysfunctions rule tonight.

Mr. Sandman, bring me your.....

.....CPAP! No, you don't want me to sing it. Trust me.

Sleep apnea. Yes, another gift from Cushing's Disease or its related symptoms. What? You don't believe me? In Sleep Apnea Syndrome in Endocrine Diseases the authors go through the literature and summarize it well. Here is a quote from the article:

...the occurrence of SAHS [sleep apnea-hypopnea syndrome ] was clearly shown only recently in endocrine diseases such as acromegaly, hypothyroidism, diabetes mellitus, especially when complicated by autonomic neuropathy, Cushing's syndrome and hyperandrogenism due to ovarian and adrenal neoplasms. Endocrine diseases (ED) may help to understand the mechanisms involved in both central and obstructive SAHS.

There is a lot of information in that article for those who really want to know more. I was diagnosed 8 years ago with sleep apnea, and I know I had it at least 10 years prior to that. My parents were instrumental in persuading me to be tested. I actually had some problems in my teen years which may have been due to sleep apnea. I'd wake up terrified and not know why. I did that more and more as the sleep apnea got worse. I have never done that since I started sleeping with my CPAP until I had to do without it for two weeks after surgery. I know it was related.

My CPAP. I call him "Darth". Why? Just think about it! How does Darth Vader sound when he talks? Have you ever heard someone try to talk while wearing a functioning CPAP? Just too funny.... Anyhow, he's my bedfeller and best buddy. I don't sleep without him. I can't sleep without him. I even sleep with him when I take a nap.

I HATE CPAP has some great information on the dangers of sleep apnea and why anyone with it needs to be tested and treated. I cannot tell you the remarkable difference it has made in my life.

"You have only begun to discover your power..."

One for the money, two for the show, three to make ready....

Just how many kinds of tumors are there associated with Cushing's? Wait, are we talking about pituitary tumors? Or adrenal tumors? How about ectopic tumors? Are you beginning to get the picture of why this illness is so hard to diagnose?

PITUITARY TUMORS/ADENOMAS:

So, let's talk about tumors. These are also sometimes called adenomas. Pituitary adenomas are classified several ways. They may be classified by pathology, by size, and by hormone production. I'm going to keep it simple here and list the basic types of tumors by the hormones they produce. Bear in mind that many pituitary adenomas produce more than one hormone. This production is not held in check by the body's normal feedback loops, thus they aren't controlled.

• Corticotroph (ACTH-Producing) Adenomas :
  The corticotroph adenoma secretes adrenocorticotropic hormone (ACTH), which results in Cushing Disease because it stimulates the adrenal glands to overproduce cortisol. These tumors are initially confined to the sella turcica, but they may enlarge and become invasive especially after bilateral adrenalectomy. This is called Nelson's Syndrome.
  
• Somatotroph (GH-Producing) Adenomas:
  Somatotroph adenomas produce growth hormone (GH), resulting in gigantism in younger patients and acromegaly in adults. These tumors may also extend beyond the sella.
  
• Thyrotroph (TSH-Producing) Adenomas:
  Thyrotroph adenomas secrete thyroid-stimulating hormone (TSH), also known as thyrotropin, which results in hyperthyroidism without TSH suppression. Many are large and invasive and typically have other types of adenoma cells included, such as ACTH and/or GH.
  
• Lactotroph (PRL-Producing) Adenomas:
  Lactotroph adenomas secrete prolactin (PRL) and are typically an intrasellar tumor. However, they can become large enough to enlarge the sella turcica.
  
• Nonfunctioning (Endocrine-Inactive) Adenomas:
  These tumors cause symptoms when they extend beyond the sella, which results in pressure on the surrounding structures such as optic nerves and carotid veins. They are not associated with clinical and biochemical evidence of hormone excess.
  
• Carcinomas:
  Pituitary carcinomas, although extremely rare, are usually endocrinologically functional, and ACTH-producing and PRL-producing tumors are the most frequent.
  
• Other Tumors:
  Other tumors of the pituitary include craniopharyngiomas, meningiomas, and germ cell tumors. Even rarer are the granular cell tumors, pituicytomas, and gangliogliomas. Most rare include gangliocytomas, lymphomas, astrocytomas, and ependymomas.

ADRENAL TUMORS/ADENOMAS:

When a tumor in an adrenal gland overproduces hormones, the tumor is called a functioning tumor. A tumor in an adrenal gland that does not produce hormones is, understandably, called a nonfunctioning tumor. A tumor can start in an adrenal gland (called a primary adrenal tumor) or it can begin in another organ, such as the lungs, and then metastasize (spread) to the adrenal glands. I'm going to focus on primary adrenal gland tumors.

• Adenoma:
  An adenoma is a benign nonfunctioning tumor of the adrenal cortex. Also called an adrenocortical adenoma, this tumor usually does not cause symptoms, and, if it is small, may not require any treatment. However, as it grows it can put pressure on parts of the gland causing it to under or overproduce hormones. The cause of adrenal adenomas is unknown, but the current accepted theory is that they arise because of mutations in certain genes. Adrenal adenomas are more common in some inherited diseases, including multiple endocrine neoplasia type I, Beckwith-Wiedemann syndrome and the Carney complex.
  
  Chronic adrenal stimulation by ACTH leads to bilateral adrenocortical hyperplasia and, if long-standing, nodular transformation according to recent research. Thus, an ACTH producing tumor of the pituitary or ectopic tumor may stimulate the adrenals to form tumors or become hyperplastic (more about hyperplasia in a bit).
  
• Adrenocortical carcinoma:
  Although exceedingly rare this is the most common type of malignant adrenal gland tumor, affecting the cortex, also called an adrenal cortical carcinoma. Adrenocortical carcinoma can be a functioning or nonfunctioning tumor. If the tumor is functioning, it may produce more than one hormone.
  
• Pheochromocytoma:
  A pheochromocytoma is a rare tumor that develops in the core of an adrenal gland. It secretes excessive amounts of catecholamines, usually epinephrine and norepinephrine.
  
• Neuroblastoma:
  Neuroblastoma is a disease in which malignant cells form in nerve tissue of the adrenal gland. It is very rare.

If that isn't enough, there is another form of tumor that isn't a tumor. It's called hyperplasia. These tumor cells may invade the pituitary or the adrenals in nests throughout the gland. Rather than go in-depth right now, I'll post some links to articles so you can explore the topic:

Pituitary Hyperplasia: A Review
Adrenal Hyperplasia

This is just a basic, no-frills outline of various tumors/adenomas associated with Cushing's Disease. And now....four to go.....to bed, that is....

Fast forward...

.....

I meant to get back here before now to add more information. Right now, all I can do is try to not get sick from the sinus infection that is pulling me down. Yep, went to the doctor, got the antibiotic, and you'd think it would be simple as that. Not.

Since the removal of my pituitary adenoma involved transsphenoidal endoscopic surgery which went through said sinuses to the base of my brain, it is a tad worrisome. Not mention the fact that any stress on the body (good, bad, or indifferent) causes some degree of adrenal insufficiency (AI). This includes infections. In fact, it often is the first indication I have of any infection.

Back to the doctor. My doctor. She is a sweet person. In fact, she was the only one in all these years of suffering with Cushing's Disease who realized I had something "endocrine" going on until I saw Dr. Friedman in Los Angeles. However, that's about as far as she went with the understanding of the disease. Since she is willing to listen and work with me, I don't hold it against her. I do hold it against medical schools who don't teach their doctors enough about this disease. She doesn't understand AI. She doesn't understand what the tumor did or how it messed up my system even beyond removal. She doesn't get "stress dosing" to combat the AI. But she does understand a sinus infection. Just not how bad it can be. At least she now asks "what works" and then prescribes it. And she cares. There's a lot to be said for that. A whole lot.

I wish I could get rid of the headache. It won't go away.

A horse of a different color

Or should I say zebra? In med school, potential doctors are told ""When you hear hoofbeats, think horses, not zebras". Well, what about those of us who are zebras? What does that say to those who don't fit any mold of illness or have multiple illnesses which paint stripes?

As I said earlier, my primary care doctor sees horses, but every now and then she does notice a stripe. The thing is, she tries to get rid of the stripe instead of looking at what caused it. And she's not alone. Frankly, I'm wondering if there really are any horses out there? Ok...ok....I guess there are. Maybe.

Diabetes, you say, is a horse. Nope.... Did you know that endocrine disease can cause it? And that it is just a secondary symptom? You didn't know that? Don't worry. Most endocrinologists don't seem to, either. Thankfully, I never had that particular stripe.

Ok, how about thyroid function/disease? Nope, not that one either. It's actually a stripe in the zebra of endocrine disease, especially a pituitary tumor. Secondary/central hypothyroidism is linked to a pituitary tumor suppressing the pituitary, and hyperthyroidism can be linked to a TSH producing tumor.

Low hormones? Oh, that must be early menopause or pre-menopause with females, right? Wrong. Just stripes of another color in the zebra of pituitary tumors.

How about high hormones? Well, guess what? Do I need to say it? More stripes...... Pituitary adenomas are famous for growth hormone and ACTH overproduction.

PCOS and metabolic syndrome are often the horses with which a Cushing's patient is diagnosed. Too often, it's just too easy to camouflage the stripes with those diagnoses.

Oh, and my favorite. Obesity. "You need to eat less and get more exercise." How many people do you know who want to be extremely overweight? Those doctors who don't listen, ignore the stripes (some literal ones called striae) and keep repeating that mantra need a A Swift Kick in the ASP. They don't know that fat is an endocrine organ. They also don't know it is actually possible to literally starve while remaining obese.

I do not know the answers. I do know there is a problem. Instead of heading to the dude ranch, maybe med schools ought to take their future doctors on a safari.