Rare disease month, day 1: Adrenal insufficiency (Addison’s disease)

Adrenal insufficiency is a condition defined by inadequate production of glucocorticoids. Other hormones, such as mineralocorticoids and androgens, may also be deficient. Adrenal insufficiency was first characterized by Thomas Addison in 1855. For this reason, adrenal insufficiency is often called Addison’s Disease, particularly the primary form.

Cortisol is the dominant glucocorticoid in humans and performs a wide array of essential functions. It is well known as a driver of stress response and modifies metabolic functions to lessen the impact of stress on the body. Its primary functions include increasing blood sugar, blood pressure, and heart rate; bronchodilation; and dampening immune response and inflammation. Patients with adrenal insufficiency are dependent upon replacement steroids and require them daily.

Common symptoms of adrenal insufficiency include fatigue, weakness, weight loss, low blood pressure (sometimes seen as orthostatic hypotension), anxiety, nausea, vomiting, diarrhea, sweating, and personality changes, among others. Darkening of the skin is often a clinical sign seen in primary adrenal insufficiency.

Adrenal insufficiency is life threatening and can be fatal. Prior to 1949, when synthetic cortisone became available, AI was universally fatal via adrenal crisis (also called Addisonian crisis). Adrenal crisis is the manifestation of critical cortisol deficiency. Symptoms can include fever; seizures; psychosis; severe abdominal, back and leg pain; fainting; vomiting and diarrhea; and dysregulation of electrolytes, including elevated potassium and calcium and low sodium. The only treatment for adrenal crisis is immediate corticosteroid replacement. Patients with adrenal insufficiency are recommended to always carry hydrocortisone for IM injection in the event of an emergency.

Primary adrenal insufficiency affects approximately 4.4-6 people per million. 80-90% of cases in developed countries result from autoimmune adrenalitis/ autoimmune Addison’s disease. This condition is sometimes seen as part of autoimmune polyendocrinopathy syndrome, in which several other endocrines are also impacted. Certain infections, such as histoplasmosis, coccidioiodomycosis, and tuberculosis; adrenoleukodystrophy; adrenal hyperplasia; and use of certain medications can cause primary adrenal insufficiency.

Secondary adrenal insufficiency affects approximately 150-280 people per million. It is most commonly caused by long term use of glucocorticoids which disrupts the HPA axis, the collective term for the hormonal system the body uses to regulate cortisol levels. Other causes for secondary AI include curing Cushing’s Syndrome, tumors of the hypothalamus, pituitary tumors, and trauma to or surgical removal of the pituitary. Complete cessation of glucocorticoids for up to a year is often necessary to trigger endogenous cortisol production but this cannot always be done safely. Many patients with secondary AI require replacement steroids for life.

Cortisol impacts mast cells in several ways, which have been rehashed extensively here and here.

For more information on adrenal insufficiency: http://www.nadf.us



Charmandari E, et al. (2014) Adrenal insufficiency. The Lancet. (Seminar)

The effects of cortisol on mast cells: Part 3 of 3

In some cases, glucocorticoids can immediately treat issues with immune activation. This immediate action is not well understood.  In animal models, glucocorticoids can stop allergic reactions in five minutes and significantly decrease short term histamine release. Mostly though, glucocorticoids mitigate mast cell activation through delayed actions. This is one of the reasons why premedication with steroids prior to surgery or procedures is recommended to start the day before.

Glucocorticoids affect gene expression, which is one of the reasons they take time to work. Gene expression is very complicated and is highly regulated by cells. Genes are part of your DNA. Think of each gene as a message.  When your cell wants to make something using a gene, like a protein, it makes a copy of the message in the gene and then takes it to another part of the cell to make the protein. There are many molecules that affect how easy it is to make something from a gene.  Some molecules make it easier and others make it harder.  Transcription factors are molecules that sit by genes that make it easier for their message to be made. Interfering with making the message and getting it to the part of the cell where it can make something, like the protein, can drastically alter the behavior of a cell.

One of the major ways that glucocorticoids interfere with making the message is with glucocorticoid receptors. Many people know that receptors are often on the outside of a cell and they are activated when a molecule fits into the receptor like a key into a lock.  Glucocorticoid receptors do not work like that.  They are small molecules inside cells that are changed when glucocorticoids bind to them.

Cortisol, or other glucocorticoids, bind to the glucocorticoid receptors inside mast cells. When this happens, they interfere with the transcription factors so it is really hard to use the genes. Some of these transcription factors are called NF-kB and AP-1.  When glucocorticoid receptors have been activated in the mast cell, the transcription factors can’t help to use the genes.

Cytokines are molecules that cells use to “talk” to each other. Another kind of signal.  Glucocorticoids directly interfere with use of cytokine genes so that they aren’t made.  Mast cells make many cytokines and they are responsible for a lot of late phase allergic symptoms.  Manufacture of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, GM-CSF, TNF and IFN-g (interferon gamma) can all be suppressed with glucocorticoids.

If the cytokine genes have already been used, glucocorticoids can still prevent them from being made. When you use a gene to make something, it creates a messenger RNA (mRNA) that carries the message.  If the mRNA falls apart, nothing will be made from the gene. Glucocorticoids make the messages fall apart before making anything for many cytokines, including IL-1, IL-2, IL-6, IL-8, TNF and GM-CSF.


Oppong E, et al. Molecular mechanisms of glucocorticoid action in mast cells. Molecular and Cellular Endocrinology 2013: 380, 119-126.

Varghese R, et al. Association among stress, hypocortisolism, systemic inflammation and disease severity in chronic urticaria. Ann Allergy Asthma Immunol 2016: 116, 344-348.

Zappia CD, et al. Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways. Scientific Reports 2015: 5.

Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 2011: 335(1), 2-13.

Sinniah A, et al. The role of the Annexin-A1/FPR2 system in the regulation of mast cell degranulation provoked by compound 48/80 and in the inhibitory action of nedocromil. International Immunopharmacology 2016: 32, 87-95.

The effects of cortisol on mast cells: Part 2 of 3

Glucocorticoids, like cortisol, can affect mast cells in many ways. As I discussed in my previous post, there are many ways for mast cells to release mediators when activated. In all of these pathways, there are many molecules involved that carry the signal, like people passing the Olympic torch. In mast cells, one of the molecules that suppresses inflammatory activation signal is called SLAP (yes, really).  Cortisol increases the amount of SLAP in mast cells so inflammatory activation signals are suppressed.

An important step in degranulation is changing the amount of calcium inside the cell and moving it to different parts of the cell. In some studies, glucocorticoids can affect this movement of calcium. Other studies have found that in some pathways, glucocorticoids don’t affect calcium movement, but instead interfere with things like the IgE receptor.

Cortisol is also thought to directly inhibit stem cell factor (SCF) binding to the CKIT receptor. When SCF binds to the CKIT receptor, this sends a signal to the mast cell to stay live.  This means that taking glucocorticoids can let mast cells die at the appropriate time. SCF also tells mast cells to go to inflamed spaces.  By blocking this signal, glucocorticoids suppress inflammation.

One of the ways that molecules carry a signal is by changing the next molecule in the pathway. A big way that cells changing molecules is by chopping off a piece of them called a phosphate group.  This is done by special enzymes called phosphatases.  Glucocorticoids affect the availability of phosphatases so they aren’t able to get to the right part of the cell to carry the signal.  When this happens, there is less activation and less histamine release.

Arachidonic acid is the molecule modified to make eicosanoids (leukotrienes, thromboxanes and prostaglandins.) Glucocorticoids directly interfere with the production of these molecules in multiple ways.  The first way is by interfering with COX-2, one of the enzymes that makes prostaglandins.  Another way is by preventing arachidonic acid from being released to a place where they can be turned into leukotrienes, thromboxanes and prostaglandins.  This occurs because glucocorticoids increase the amount of a powerful anti-inflammatory molecule called annexin-I.  Annexin-I inhibits the molecule that releases the arachidonic acid, called phospholipase A2.

Annexin-I was the subject of an important paper earlier this year. In trying to identify exactly how mast cell stabilizers like ketotifen and cromolyn work, the researchers discovered that treatment with mast cell stabilizers decreased degranulation and increased annexin-I made by mast cells.  They also found that glucocorticoids had the same effect.


Oppong E, et al. Molecular mechanisms of glucocorticoid action in mast cells. Molecular and Cellular Endocrinology 2013: 380, 119-126.

Varghese R, et al. Association among stress, hypocortisolism, systemic inflammation and disease severity in chronic urticaria. Ann Allergy Asthma Immunol 2016: 116, 344-348.

Zappia CD, et al. Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways. Scientific Reports 2015: 5.

Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 2011: 335(1), 2-13.

Sinniah A, et al. The role of the Annexin-A1/FPR2 system in the regulation of mast cell degranulation provoked by compound 48/80 and in the inhibitory action of nedocromil. International Immunopharmacology 2016: 32, 87-95.

The effects of cortisol on mast cells: Cortisol and HPA axis (Part 1 of 3)

Things I’m not great at: Knowing how many posts I need to cover all the effects cortisol has on mast cells.  So this is the first of three posts on cortisol and mast cells.  Then we will get back to the tables breaking down the effects of hormones on mast cells.
Cortisol is a glucocorticoid steroid hormone with far reaching anti-inflammatory actions. It is the product of a very complex endocrine system called the HPA axis.  HPA stands for hypothalamus-pituitary-adrenal.  The hypothalamus is in the brain and the pituitary is a small structure on the edge of the hypothalamus.  The adrenal glands are above the kidneys.

The hypothalamus, pituitary and adrenal glands all release a number of hormones that affect many bodily functions. Briefly, the hypothalamus receives signals from the nervous system to make corticotropin releasing hormone (CRH).  CRH induces the pituitary to make adrenocorticotropin hormone (ACTH). ACTH induces the adrenal glands to make cortisol.

Cortisol is most well known as the stress hormone, although it has many other functions. It can be released as a response to inflammation or physical or emotional trauma.  In such instances, signals from the nervous system tell the hypothalamus that it needs to make CRH.  CRH triggers vasodilation and increased vascular permeability to allow immune cells move from the bloodstream to inflamed spaces in tissue.  CRH also triggers manufacture of ACTH, which then triggers manufacture of cortisol.

When cortisol levels are high in the adrenal gland, epinephrine can be made from norepinephrine. Cortisol is thought to regulate the enzyme that makes epinephrine at several steps in the process.  Epinephrine is also part of the stress response and participates in the fight-or-flight response.

The role for which glucocorticoids are most often prescribed is suppression of inflammation. Cortisol production is initiated very early in an inflammatory response. Cortisol counteracts vasodilation seen by many inflammatory mediators.  Cortisol also decreases vascular permeability so immune cells are not able to easily leave the bloodstream and move into tissues.  Cortisol also affects gene expression so that inflammatory products are not made as much and anti-inflammatory products are made more.  (This will be discussed in great detail when I cover how cortisol affects mast cells.)

A number of synthetic glucocorticoids, like prednisone and dexamethasone, have similar behaviors and functions. The medication hydrocortisone functions the most like cortisol in the body.  Synthetic glucocorticoids stay in the blood longer and are more bioavailable than cortisol.  The amount of cortisol produced by the body changes throughout the day in time with other functions.  Synthetic glucocorticoids cannot mimic these changes exactly and are thus inferior to cortisol.  Small changes in amount of glucocorticoid can have major effects.


Oppong E, et al. Molecular mechanisms of glucocorticoid action in mast cells. Molecular and Cellular Endocrinology 2013: 380, 119-126.

Varghese R, et al. Association among stress, hypocortisolism, systemic inflammation and disease severity in chronic urticaria. Ann Allergy Asthma Immunol 2016: 116, 344-348.

Zappia CD, et al. Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways. Scientific Reports 2015: 5.

Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 2011: 335(1), 2-13.

Mast cell medications: Everything but antihistamines

The following medications listed are available in oral, intramuscular or intravenous formulation. Not all medications are available in the US or Europe. Topical and inhaled medications are not included in these lists.

Mast cell stabilizers interfere structures on the cell membrane required for degranulation and thus prevent the release of granule contents, including histamine.

Mast cell stabilizers
Cromolyn sodium/ Cromoglicic acid/ Nedocromil
*mechanism unclear


Beta-2 adrenergic agonists cause smooth muscles to relax, which allow airways to open. These are used almost exclusively in asthma and pulmonary disease, which a secondary use in controlling uterine contractions in labor.

Beta-2 adrenergic agonists


Leukotriene receptor antagonists work by interfering with the function of leukotrienes by blocking the CysLT1 receptor. Leukotrienes are heavily involved in airway reactivity and inflammation.

Leukotriene receptor antagonists


5-lipoxygenase inhibitors prevent leukotrienes from being made.

5-lipoxygenase inhibitor
St. John’s Wort


Corticosteroids interfere with the activity of mast cells and production of mast cell mediators.

Mast cell stabilizers
*taken orally, with effects local to the GI tract


Proton pump inhibitors reduce the production of gastric acid and treat heartburn, nausea and reflux. This can also be achieved by H2 antihistamines and for this reason, the two classes are often confused. The following medications, which are taken often by mast cell patients, have no known antihistamine effect. They can safely be taken with H2 antihistamines and help many mast cell patients, but it is important to clarify that they are NOT antihistamines.

Proton pump inhibitors

Diabetes, steroids and hypoglycemia

Following alloxan induction of diabetes, rats overexpress glucocorticoids. This in turn depletes the mast cell populations in the skin, lungs and intestines. Glucocorticoids interfere with production and expression of tissue cytokines and stem cell factor, a growth factor for mast cells.

Several experiments have definitively proven that these steroids are responsible for downregulating mast cell growth and activity. Treating diabetic rats with the steroid receptor blocker RU486 or removing adrenal glands on both sides of the animal causes an increase in intestinal mast cell numbers and IgE formation.

The mechanism by which steroids confer these effects is thought to involve insulin. Glucocorticoids inhibit secretion of insulin in the pancreas. In turn, insulin release decreases systemic glucocorticoids. Additionally, insulin also activates mast cell signaling pathways. In the presence of insulin, antigen induced mast cell degranulation and survival is upregulated. In diabetic rats, administration of insulin recruits mast cells and increases response to antigen. Insulin treatment can reverse the reductions in mast cell populations, histamine production and IgE release seen following alloxan administration.

Increased activity of the HPA axis is often seen in type I and II diabetics, resulting in elevated cortisol. One study showed that appropriate activity can be restored with insulin treatment. This is achieved by a complex mechanism in which expression of glucocorticoid receptor mRNA is elevated in the pituitary, facilitating glucocorticoids to suppress expression of ACTH release.


Can hypoglycemia cause mast cell degranulation?

Yes. Activation of histamine 1 and 2 receptors as a result of insulin or hypoglycemia causes release of ACTH. Hypoglycemia (low blood sugar, which can also be induced after administration of insulin) normally increases ACTH levels in the blood. However, higher than normal histamine levels in the blood can interfere with the action of ACTH, which would normally address hypoglycemia via production of glucocorticoids. One study found that this effect can be mostly ameliorated by pretreating with antihistamines, though I suspect in mast cell patients, this may not achieve the full response seen in non-mast cell patients.


Can anaphylaxis cause hypoglycemia?

Yes. In instances of severe stress (emotional or physical), corticotropin-releasing hormone (CRH), neurotensin and substance P are released. Among other things, CRH can induce mast cell degranulation (of note, CRH does not directly induce histamine release via degranulation). CRH also causes increased expression of the IgE receptor on mast cells, which increases the likelihood of being stimulated and thus degranulation (this may cause histamine release). In tandem, neurotensin and substance P increases the expression of the CRHR-1 receptor for CRH on mast cells so that they are more sensitive to CRH. Likewise, neurotensin and substance P act on mast cells via receptors to induce degranulation (this causes histamine release). As a result of this degranulation, histamine and other mediators are present to inhibit the action of ACTH, which would otherwise increase blood sugar (via the production of cortisol, epinephrine, and norepinephrine).



Carvalho V.F., Barreto E.O., Diaz B.L. et al. (2003) Systemic anaphylaxis is prevented in alloxan-diabetic rats by a mechanism dependent on glucocorticoids. Eur. J. Pharmacol. 472, 221–227.

Carvalho V.F., Barreto E.O., Cordeiro R.S. et al. (2005) Mast cell changes in experimental diabetes: focus on attenuation of allergic events. Mem. Inst. Oswaldo Cruz 100(Suppl. 1), 121–125.

Foreman JC, Jordan CC, Piotrowski W. Interaction of neurotensin with the substance P receptor mediating histamine release from rat mast cells and the flare in human skin. Br J Pharmacol. 1982 Nov;77(3):531-9.

Meng, Fanyin, et al. Regulation of the Histamine/VEGF Axis by miR-125b during Cholestatic Liver Injury in Mice. The American Journal of Pathology, Volume 184, Issue 3, March 2014, Pages 662–673

Theoharides, T., et al. A probable case report of stress-induced anaphylaxis. Ann Allergy Asthma Immunol xxx (2013) 1e2

Kjaer A, et al. Insulin/hypoglycemia-induced adrenocorticotropin and beta-endorphin release: involvement of hypothalamic histaminergic neurons. Endocrinology. 1993 May;132(5):2213-20.

Carvalho V.F, et al. Reduced expression of IL-3 mediates intestinal mast cell depletion in diabetic rats: role of insulin and glucocorticoid hormones. Int. J. Exp. Path. (2009), 90, 148–155.

Carvalho V.F, et al. Suppression of Allergic Inflammatory Response in the Skin of Alloxan-Diabetic Rats: Relationship with Reduced Local Mast Cell Numbers. Int Arch Allergy Immunol 2008;147:246–254.

Carvalho VF, Barreto EO, Diaz BL, Serra MF, Azevedo V, Cordeiro RS, et al: Systemic anaphylaxis is prevented in alloxan-diabetic rats by a mechanism dependent on glucocorticoids. Eur J Pharmacol 2003; 472: 221–227.

S.C. Cavalher-Machado, et al. Down-regulation of mast cell activation and airway reactivity in diabetic rats: role of insulin. Eur Respir J 2004; 24: 552–558.

Corticotropin releasing hormone, cortisol and mast cells

The term “HPA axis” refers collectively to the signals and feedback loops that regulate the activities of three glands: the hypothalamus, the pituitary gland, and the adrenal glands. The HPA axis is a critical component of the body’s stress response and also participates in digestion, immune modulation, emotions, sexuality and energy metabolism.

The hypothalamus is part of the brain. It performs several integral functions. It regulates metabolism, makes and releases neurohormones, and controls body temperature, hunger, thirst, circadian rhythm, sleep and energy level. It is also known to affect parenting and attachment behaviors. It effectively turns nervous system signals into endocrine signals by acting on the pituitary gland.

The pituitary gland is a small gland at the bottom of the pituitary. The anterior portion of the pituitary is part of the HPA axis. It makes and releases several hormones, including human growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone (ACTH), prolactin, luteinizing hormone and follicle stimulating hormone. All of these hormones are released when hormones released by the hypothalamus act on the pituitary.

The adrenal glands are located on top of the kidneys. They primarily synthesize and release corticosteroids like cortisol and catecholamines like epinephrine and norepinephrine in response to action by the pituitary.   It also produces androgens and aldosterone.

The hypothalamus synthesizes vasopressin and corticotropin releasing hormone (CRH).   Both of those hormones stimulate the release of ACTH by the pituitary gland. ACTH stimulates the adrenals to make glucocorticoids (mostly cortisol). The cortisol then tells the hypothalamus and pituitary to suppress CRH and ACTH production. This is called a negative feedback loop.

Cortisol acts on the adrenals to make epinephrine and norepinephrine. Epi and norepi then tell the pituitary to make more ACTH, which stimulates the production of cortisol.

When you take steroids regularly, it suppresses ACTH so that your body stops making its own steroids. This is why weaning steroids is very important. By weaning, your body should gradually start making its own cortisol to replace the deficit when you lower your steroid dose. However, this doesn’t always work. People who do not make enough cortisol on their own are called adrenally insufficient and are steroid dependent. People with this condition can suffer “Addisonian crises” if their steroid levels drop dangerously low. This is a medical emergency.

CRH is released by the hypothalamus in response to stress. This drives the production of cortisol to help manage stressful situations of either a physical or emotional nature. Mast cell attacks and anaphylaxis are examples of physically stressful situations that stimulate release of CRH.

CRH binds to CRHR-1 and CHRH-2 receptors on various cells, including mast cells. When it binds to mast cells, it stimulates the release of VEGF, but not histamine, tryptase or IL-8. This type of release is called selective release as it does not involve the release of preformed granules (degranulation.) Additionally, CRH is also released by mast cells. This can act on the mast cells or other cells with CRHR receptors, like those in the pituitary. The exact purpose of mast cells releasing CRH is not clear.



Theoharis C. Theoharides, et al. Mast cells and inflammation. Biochimica et Biophysica Acta 1822 (2012) 21–33.



Once I hit puberty, I was a fat girl.  I wasn’t morbidly obese, but I was overweight and it was obvious on my short frame.  This was not something I hated about myself, and it wasn’t until college that I felt uncomfortable with my body, but it informed my later years.  The experience of being overweight (and therefore mocked/ridiculed/generally viewed as “unfortunate” or “unseemly” or “lazy”) has affected my ongoing relationship with myself.
In 2007, I lost 40 lbs by training for the Breast Cancer 3-Day.  I also lived alone and worked a lot, on my feet.  I was committed to training, but also still had the privilege of a largely functioning body.  I was tired and had some joint issues, but it was more occasionally annoying than anything else.  Most importantly, I had time and stamina.  I could walk 10 miles a day, in the sun, in the heat, without any fallout. 
My weight fluctuated a little bit for the next few years, until in 2009, when I lost my hearing.  My neurotologist wrote out a long, high dose steroid taper and within a month, I had gained over 20 lbs.  In 2012, after a serious effort (working out 6-8 hours a week for several months), I lost 10 of those pounds. 
This was the point at which I realized that there was some fuckery afoot with my weight.  Like no matter what I ate, or how much I exercised, my body would not lose any more weight, and especially not around my swollen midsection.  A few months later, I had my ostomy surgery and in the weeks after that, I lost 10 more pounds.  The swelling and squishiness was gone.  The proof was in the pudding.  My mast cell disease and its subsequent inflammation were keeping me swollen, and squishy, and fat. 
Fast forward several months and a prescription for high dose steroids was being slid across the desk to me.  “I don’t want to do this again,” I started, but I knew I basically had no other play.  So I took them.  And two months later, I had gained thirty pounds. 
I am still on steroids; very low dose, but still on them.  As I have stepped down the steroids, I have lost some weight, but I am still 20 lbs over where I was.  I walk a lot (10-15 miles a week), and do yoga as I’m able, but my body has taken a serious beating this year.  I got a PICC line placed in March, which meant no weight bearing with that arm, and that eliminated most strenuous forms of exercise I can safely do.  I can’t do cardio.  I couldn’t swim with the PICC.  Now I have a port, and I can’t do any exercise for at least five days.  I’m forever being told not to exert myself while also being reminded that being overweight causes me a lot of problems. 
I have almost no control over the way my body looks.  I don’t mind having a colostomy and a port, I really don’t.  But I do mind that being overweight means that people judge me for being “lazy” or “unhealthy” or “making bad choices.”  I don’t know why anyone would ever comment on a person’s diet or general fitness, but it happens to me, so I’m sure it happens to you.  People are always like, “Oh, anyone can do [insert name of cliché fitness trend],” or “Your problem is that you drink soda,” or whatever. 
Are you kidding me, people?
Are you fucking kidding me?
I think my problem is that I have a rare, severe, life threatening disease that is destroying my body.  I think that’s my problem.
I cannot eat your stupid diet food because it’s full of artificial sweeteners and garbage.
I cannot do cardio because it will cause me anaphylax. 
I cannot do most other types of exercise because my body fucking sucks and has failed me repeatedly.  And the fact that it is fat is the least of the ways it has failed me. 
I throw up a lot of what I eat.
I drink one can of Coke a day.  I will probably do this every day until I die.  And you know what?  That’s 140 calories my body needs, because while you’re thinking about how much less I should be eating, I am not getting the amount of calories or vitamins or minerals that my body needs.  And frankly, for all the shit I have to put up with on a daily basis, a can of Coke is the least of what I deserve.
I don’t like being inactive.  I don’t like lying in bed and needing to sit frequently.  I don’t like feeling weak. 
There are some days when I look in the mirror and think that can’t be me.  I am so tired of living in this shell that doesn’t even look like me.