13 March 2010

40 % of Celiac Patients have Anti-Pituitary Gland Antibodies

In 2006, an Italian group noted that children with celiac disease often suffered from failure to thrive (i.e. they were short and slight) (Iughetti, 2006). They were able to link this to a deficiency in growth hormone, which is produced by the pituitary gland. Now, growth hormone itself doesn't regulate bone growth, but insulin-like growth factor-1 (IGF-1) does and it is regulated by growth hormone. After removing gluten from the diet, most children had a growth spurt and caught up to their peers but seven did not. Those that didn't catch up were then tested for anti-pituitary antibodies, and five of the seven presented them.

Now 5 of 7 is not a sufficient statistical sample, so the group went back to work over the next three years and tested for anti-pituitary antibodies in many of their newly diagnosed celiac patients (all children) (Delvicchio, 2009, also see editorial by Fasano, 2010). 50 of 119 (42 %) tested positive for anti-pituitary antibodies. There is an interesting comment by Delvicchio to the extent shortness can appear independently of the destruction of intestinal vilae,
It is well established that short stature can be the only presenting clinical feature of CD (31) and in unselected cases admitted for short stature, the prevalence of CD reaches 8%, CD being by far more common than GHD or any other organic disorder. The pathogenesis of CD-associated short stature is still unclear and although growth retardation has traditionally been attributed to generalized or selective malnutrition, new insights on its pathogenesis are emerging.
This suggests that something like one in ten children who are short are short because they eat wheat (notwithstanding selection bias). This isn't the first time autoimmune disease of the pituitary gland has been linked to stunted growth either. A child with lymphocytic hypophysitis (including diabetes insipidus) was previously found to have the same bone-age retardation symptoms as the celiac patients (Weimann, 1997).

The pituitary gland is a small bulbous organ that sits at the base of the brain smack dab in the middle of the skull. The pituitary is often called the master endocrine gland, but it is in turn is controlled by the hypothalamus, a portion of the brain that is the nexus of the autonomic nervous system. The hypothalamus, the posterior pituitary, and the anterior pituitary can all be considered to be different tissues of a single organ system often called the hypothalamic/pituitary axis. Because the pituitary controls such a diverse set of endocrine tissues, if something goes wrong with the hypothalamus/pituitary axis the symptoms can be very diverse. Furthermore, the area is small, located in the center of the skull and hence largely impossible to safely biopsy.

Like other endocrine organs, the pituitary can be victim to the helper and killer T cells of the adapted immune system. This condition is typically called lymphocytic hypophysitis, but also autoimmune hypopitutarism, and typically affects the anterior pituitary which is the hormone-producing portion of the pituitary (Rivera, 2006). The neural portion of the pituitary, the posterior portion, can also be affected and this typically causes diabetes insipidus through arginine vasopressin deficiency (not to be confused with the insulin disorder diabetes mellitus). Autoimmune disease of the pituitary gland is thought to be quite uncommon, with a series of 2500 surgical cases finding an incidence of 0.24 % (6 of 2500) (Sautner, 1995).

Although the Italians appear to have examined primarily growth hormone deficiency, lymphocytic hypophysitis usually results in more than one hormonal deficiency. Rivera (2006) notes in a review for lymphocytic hypophysitis that 60-65 % of cases have ACTH deficiency, 47 % have TSH deficiency, 42 % have gonadotropin deficiency, 37 % growth hormone deficiency, and 34 % prolactin deficiency. For those of you who aren't familiar with the hypothalamus/pituitary hormones I present the following summarizing table:

Table 1: The hypothalamic/pituitary axis hormones and their actions on the human body.

Hypothalamus/Pituitary hormones


Corticotropin-Releasing hormone (CRH) /

Adrenocorticotropic hormone (ACTH)

Stimulates the adrenal glands to produce cortisol, a very important general stress hormone that among other things regulates activity of the immune system.

Growth-hormone Releasing Hormone (GHRH) /

Growth-Hormone (GH)

Turns on fat metabolism and turns off protein and carbohydrate metabolism, putting the body in a fasted state. Circumstantially may stimulate production of insulin-like growth factor (IGF1) which is responsible for much protein synthesis in bone, skeletal muscle, and many other tissues.

Thyrotropin-Releasing Hormone (TRH) /

Thyrotropin (TSH)

Stimulates the thyroid gland to produce T4, the inactive basal metabolism hormone. T3, the active form, is produced by seleno-deiodinases (D1, D2) found in many tissues but in humans predominately the liver and skeletal muscle. T3 is required for the transcription of all proteins (via messenger RNA) from DNA.

Gonadotropin-Releasing Hormone (GnRH) /

Follicle-Stimulating Hormone (FSH)

Stimulates the gonads to mature germ cells (eggs and sperm)

Oxytocin (OT) / none

Neuropeptide that down-regulates activity of the amygdala, the anxiety-centre of the brain. Thought to have an important role in social cognition and mood, possibly responsible for “motherly” stereotypical behaviors. Also responsible for uterine contractions during childbirth and menstrual cramps. Can cause spontaneous miscarriage by this mechanism.

Arginine Vasopressin (AVP) / none

Triggers pair-bonding, jealousy, and other ‘male’ stereotypical behaviors. Also acts on the kidney to regulate water retention

Dopamine & TRH /

Prolactin Hormone

Dopamine is the Prolactin inhibiting hormone while Thyrotropin-releasing hormone serves a dual role as the stimulating hormone. Prolactin is nominally responsible for lactation during breast feeding but perhaps more interesting is responsible for sexual satisfaction and orgasm in both men and women.

Gonadotropin-Releasing Hormone (GnRH) /

Luteinizing Hormone

Triggers ovulation in females, with associated drop in estrogen and rise in progesterone. Triggers release of testosterone in males.

The study did test for thyrotropin (TSH) and didn't find any significant association between anti-pituitary antibodies and basal metabolic dysfunction at the hypothalamus/pituitary axis. However, some 10 % of the patient population did have thyroid disease which is far above the general population average (of around 1 %). Hypophysitis tends to develop over time, with more and more functions being damaged, so these results may simply be representative of the young age of the patients (average age was ~ 6 years old).

In general, persons with one autoimmune disorder are at much higher risk to develop other immune disorders. It would take more effort and text to explain why this is than I'm willing to expand here so I will simply claim this is a fact. It seems that Iughetti has been on the case of co-morbid endocrine disorders associated with celiac disease for quite awhile (Iughetti, 2003). If you go to the Wikipedia page for gluten sensitivity you will see an entire section on "idiopathic gluten-sensitivity." A lot of this could possibly be traced back to autoimmune disease of the pituitary gland.

I recall that something like 12 % of the general population present anti-gliadin antibodies (gliadin being the offending peptide found in the wheat gluten protein). Celiac disease is only one manifestation of gluten sensitivity and I am quite certain that we will continue to see new conditions linked to gluten sensitivity over the next couple of decades. The secondary plant compounds found in the wheat plant's seed seem to be quite harmful to humans and in my opinion wheat is not suitable for human consumption. Plants, after all, cannot run away so they must rely on armour and toxins to stop animals from eating them. Anyone suffering from an unknown condition that presents as a disrupted hormonal milleu should strongly consider the shotgun approach of a paleolithic diet as a potential solution.


rks said...

Always good stuff. Of course things can get complex. Once you get used to a poison (like ethyl alcohol for instance) there is the chance that it harms your internal enemies more than you. Then there's the question of whether your parasites really are your enemies: they certainly don't want to kill their host and may find ways to be helpful. And if they're ubiquitous we might evolve to only work properly when they are there. Which brings me to my question: have you looked into the hook worm cure?: http://www.abc.net.au/catalyst/stories/2823795.htm.

J. A. Deep said...

I am nominating this post for "Best of the Web" in 2010. Thanks very much!

Robert, have you any thoughts on the idea that consciousness itself (e.g. what is color) only "exists" as a communication network of organisms that we host? It seems that someone with a skeptico-physicalist background (like yours?) might be uniquely positioned to understand such an ontology.