A healthy immune system is a very
important part of maintaining one's health and well-being. The
immune system is important for protection against infections,
cancer surveillance, and maintaining a healthy balance for most
bodily functions. A compromised immune system or inadequate
immune response may lead to serious infections because of the
inability of the immune system to respond to, or contain, the
infection (see table 1). Certain viral infections can directly
suppress the immune system, the most dramatic example of which
is HIV. However, it is becoming evident that a number of viruses
can substantially and adversely affect the immune response
through several different mechanisms, not the least of which is
through the contributory role of growth hormone deficiency.
Premise
Statistics show complex diseases including
chronic illness have been steadily on the rise for over a
century. Deaths from infectious disease from 1980 to 1992 are up
58%, making it the #3 cause of death. If we exclude HIV, all
other infectious diseases have risen by a total of 22%. Despite
overall gains in life expectancy, today many adult men and woman
face the possibility of succumbing to a myriad of symptoms that
characterize chronic diseases such as Chronic Fatigue Syndrome (CFS),
Fibromyalgia Syndrome (FMS), Irritable Bowel Syndrome (IBS),
autoimmune disease such as Systemic Lupus Erethematosus (SLE),
sinusitis, bronchitis, and psychiatric disorders.
The onset of chronic illness begins with
inflammation, immune system dysfunction, and a hypercoagulation
state leading to anoxia and dysfunction. At times, only one part
of the body may be affected, while at other times the entire
body - including the HPA Axis (hypothalamus-pituitary adrenal
axis) - will be involved.
The portals of entry for chronic illness
include the respiratory tract, periodontal pathology, the
gastrointestinal (GI) tract, and/or trauma. Onset may be acute
or chronic, achieving a cumulative effect on the adrenals, GI
tract, respiratory tract, urinary tract, and liver, hormones,
thyroid, immune system and CNS function.
A New Reference Point for Understanding
the Role of Growth Hormone Deficiency in Chronic Illness
Making a Diagnosis
The evaluation of the chronically ill
patient is a great challenge to the clinician, researcher and
health care professional. It requires a broad and interpretative
view of disease, a psychosocial sensitivity, astuteness to
mental health disorders, as well as formulating a good ongoing
relationship with the patient to promote his/her openmindedness
in assessing all possible medical considerations.
Many - if not all - of the following
factors contribute to the etiology and disease process of many
chronic illnesses.
- Psychiatric disorders
- Defect in immune system, such as
allergies
- Infections - bacterial, viral,
fungal, parasitic
- Coagulation cascade defect
- Environmental toxins
- Trauma, accidents, surgery
- Stress - physical and emotional
- Growth Hormone Deficiency (GHD)
- Genetic defects
Proper diagnosis and effective treatment
of chronic illness necessitates that the physician understands
the interrelationship between infections, coagulation defect,
toxins, trauma, stress, and growth hormone deficiency.
My clinical experience with chronically
ill patients has led me to establish the following working
definition that is characterized by a series of specific
biological processes (Figure 1):
Figure 1. Activation of Coagulation in CFS/FMS/Chronic
Illness: Immune System Activation of Clotting
Table 1. Components of the Immune System
Implicated in Chronic Disease
Humoral Immunity |
Cell-mediated Immunity (CMI) |
Phagocytic cells |
Natural Killer (NK) Cells |
Cytokines |
Antibodies formed by B
lymphocytes with the help of T cells after contact of an
antigen develops into antibodies producing plasma cells
or memory B cells that bind to antigens. Humoral
immunity is important for certain types of bacteria and
some viruses. |
Responsible for recognition of
invading organisms and activation of various "killing
cells" that eradicate infection. Involves T helper cells
(CD4 cells), cytotoxic T-cells (CD cells), and many
cytokines. CMI is important for many viruses, some
bacteria, and fungus invaders. |
Including the cell types of
neutrophils and macrophages, responsible for engulfing,
digesting, and killing infecting organisms. Phagocytic
cells fight bacteria and some fungus infections, as well
as parasites. |
First line of defense that can
quickly kill invaders, without having to be specifically
primed ahead of time. NK cells are involved in
elimination of viral infections and cancer. |
Chemicals produced by immune
cells in order to communicate and orchestrate the attack
against unwanted infections and altered cells. Cytokines
can act on other immune cells, especially cells that are
proximally located. |
- Chronic illness is a coagulation
protein defect that leads to a hypercoagulation state when
the patient is subjected to a pathogen, trauma, and/or
toxins.
- Excess thrombin (IIa) generation
converts fibrinogen to soluble fibrin monomer (SFM), causing
fibrin (fibroid) deposition.
- Accumulation of fibrin on endothelial
cell (EC) surfaces prevents oxygen and nutrients from
entering tissues and cells, resulting with focal ischemia.
- Blood viscosity increases (slows)
blood flow resulting in endocrine (HPA Axis) dysregulation,
sleep disorder, central nervous system (CNS) dysfunction,
decreased blood flow, fatigue, decrease in heart stroke
volume, lowered blood pressure, lowered immune system
function, and dysregulation of the adrenal glands.
Etiologies of Activation of
Hypercoagulation State
At my clinic, we find that activation of
the immune system and promotion of a hypercoagulation state are
often prompted by viruses, toxins, bacteria, trauma, and
vaccines (Table 2).
The immune system is the first-line
defense against disease, and normal immune systems successfully
manage the entry of pathogens, toxins, stress, etc.
Immunocompromised individuals are thus at
increased susceptibility because:
- The immune system activates cytokines
and endotoxins. An example of this is when a person has the
flu, experiencing malaise, cognitive dysfunction, fever,
etc. The infection activates the immune system, which then
activates clotting. The end result is the accumulation of
soluble fibrin monomer deposits (SFM), leading to anoxia.
- Infections actively release cytokines
and chemokines, causing pain and discomfort. For most of us,
this is a temporary infection response but in
immunocompromised people the recovery is sometimes
protracted.
- One in five people have a protein
defect that creates clotting problems, resulting with an
inability to clean up the SFM. As a result, fibrinoid
deposits develop and lead to anoxia and disease.
Figure 2: Pro-inflammatory Cytokines -
Possible Mechanism of Activation for Growth Hormone Deficiency
Stress - the way in which we react
(mentally, emotionally, and physically) to life's demands -
creates a number of physiological effects.
Stress is often responsible for fatigue
(and an increased demand for nutrients), as well as an increase
in the adrenaline-causing platelets to stick together -
resulting with decreasing oxygen to the medulla region of the
adrenal. This is what I refer to as a "hypercoagulation state."
Destruction of endothelial cells (that
line capillaries), occurring over 15 to 20 years, causes chronic
illness. At my practice, we observe these patients have anxiety:
they express feeling as if they have not been getting enough
oxygen, thereby creating depression, anxiety, pain and
neuropathy. We evaluate these patients for viruses, bacteria,
toxins, trauma, and history of vaccines.
Individuals diagnosed with SFM and chronic
inflammation may present as having the antiphosphyolipid
antibody syndrome (APS) with the EC as the disease target. These
patients have a hypercoagulable state, which is demonstrated by
increased makers of coagulation activation and increased blood
viscosity due to the generation of SFM.
The CFS/FMS, chronically ill process is
triggered by a variety of pathogens (Table 2). As a result:
- The offending pathogen mediates
immune system activation that induces antibodies that
cross-react with the EC protective proteins BGPI and Annexin
V.
- These antibodies dislodge the
protective protein from EC surface exposing
phosphatidylserine (PS) on the EC surface in the capillary
bed.
- Through a process of interaction,
this results in thrombin generation leading to SFM
formation.
- The SFM causes increased viscosity
and is precipitated out on the EC as fibrin (fibroid)
deposits. This increases ischemia, blocking nutrients and
oxygen delivery in the microcirculation .
Table 2. Immune System/Hypercoagulation
Activators
Virus |
Toxin |
Bacteria |
Trauma |
Vaccine |
Human HerpesVirus (HHV-6)
|
Mercury |
Mycoplasma |
Injury |
Anthrax |
Epstein-Barr Virus |
Cadmium |
Chlamydia |
Loss |
Polio |
Measles |
Arsenic |
Staphylococcus |
Surgery |
Measles |
Cytomegalovirus (CMV)
|
Silver |
Nanobacteria |
Emotion |
|
Chicken Pox |
Lead |
Beta Strep |
|
|
Stealth virus |
Other environmental exposures
|
Klebsiella Pneumoniae
|
|
|
Coxsackie |
|
|
|
|
Note: There is not a clot, as observed in
D-Dimer formation that causes thrombosis in cardiovascular
disease resulting in acute blockage.
Growth Hormone Deficiency and the
Chronically Ill
Growth Hormone Deficiency (GHD) (Table 3)
occurs in patients with pituitary tumors, trauma, and
post-surgically, comprising approximately 50% of the total
etiology of GHD. I submit that the remaining 50% is associated
with chronic inflammatory diseases, characterized by immune
system dysregulation, adrenal dysregulation and hypercoagulation
state.
The GHD symptom complex can occur after a
chronic illness and has been studied extensively in relation to
CFS, FMS, rheumatoid arthritis, and other diseases. The concept
of anoxia caused by the immune system activation of coagulation
with infection cytokine excess and vasculitis contributes to the
decline and dysregulation of HPA axis.
Table 3. Manifestations of Adult Growth
Hormone Deficiency (GHD)
Disturbed lipid pattern |
Decreased exercise capacity |
Abnormal body composition
|
Defective sweat secretion &
thermoregulation |
Excess weight and central
adiposity |
Increased tone in the sympathetic
nervous system |
Impaired glucose homeostasis
|
Decreased bone mineral content
|
Impaired fibrinolysis
|
Decreased activity in osteoclast
precursor and proliferation and differentiation of
osteoclasts |
Impaired cardiac functioning
|
Problems with sleep quality
|
Reduction in arterial
distensibility (esp. carotid artery in women)
|
Decreased social contact and
stiffness |
Low nitric oxide levels,
contributing to atherosclerosis |
Significantly more health issues
than others of sex/age |
Premature atherosclerosis
|
|
Major risk factor in CHF and
heart disease and premature death |
|
There are several similarities between the
symptoms in fibromyalgia and GHD, and the two conditions are
somewhat interrelated (Table 4). A working definition of
fibromyaligia (Figure 2) is that infection releases toxins,
causing liver cells to produce cytokines including interleukin-6
(IL-6).
Table 4. FMS/GHD At a Glance
GH deficiency occurs 30% of
patients in some studies |
Muscle Weakness |
GH treatment shows significant
improvements in trigger points |
Fatigue-low energy |
Low IGF-1 levels in FMS
|
Decrease Exercise capacity
|
Disturbed circadian rhythm of
cortisol |
Social isolation |
Response to GH took 6 months and
patient experienced global improvement |
Poor general health |
Central pain state: up regulation
of N-methyl-D-asparate (NMDA) receptor at spinal synapse
|
Cold intolerance |
Dysregulation of substance P
|
Impaired cognition |
Sleep disturbance
abnormal stage 3 & 4 (when GH is not secreting)
|
Dysthymia
Decrease in body mass
Reduced IGF-1
Decrease in 24 hr GH secretion
Response to GH treatment |
The cytokines interact with nerves that
travel to the brain which signals down the spinal cord, causing
amplified pain signals.
Three cytokines, IL-1, IL-6, and IL-8,
cause severe widespread pain, fatigue and disturbed sleep. IL-6
is related to fatigue and impaired concentration. TNF alpha
activates hypothalamus corticotrophin releasing hormones (CRH)
and releases IL-1 that does not stimulate the pituitary or
adrenal glands.
Treatment of GHD should only be initiated
once infections are cleared, as acute infection can be
detrimental. It is my clinical experience that treatment of GHD
has minimal risks. In actuality, for chronically ill patients,
GHD replacement therapy imparts great psychological,
psychosocial and cardiovascular health benefits. The treatment
adds greatly to quality of life and to maintaining a healthy
life style. Benefits of growth hormone replacement therapy may
include:
- Reduction in body fat mass
- Increase in lean body mass
- Increase in total body water
- Oppose the action of insulin on
adipocytes
- Increase in fat mobilization by
hydrolysis of triglycerides into glycerol and free fatty
acids
- Stimulate fatty acid transportation
from adipose tissue to the liver
- Inhibit FFA re-esterification by
adipocytes
- Increase whole protein synthesis for
the first month then returning toward baseline with a new
steady state
- Increase body nitrogen and total body
potassium
- Antinatriumic effects - salt and
water retention GH and IGF-1 (synthesized in the heart) are
expressed in the heart. Rate is based on maturation, neural
differentiation, neuro-potential and energy metabolism (mitochrondial)
- Increase in oxygen consumption and
cardiac output
- Increase in B-endorphins in
cerebrospinal fluid, which may improve psychological
well-being (IGF-1 receptors are located in all regions of
the brain, and GH receptors are located in the choroid
plexus, hypothalamus, pituitary, and hippocampus)
- Increase in net conversion of
cortisol to cortisones, by inhibiting the activity of HB-
HSD Type I
- For thyroid, T4 replacement shows no
change in GH function
- There is a reciprocal relationship
between cortisol and GH secretion
- Reduce coronary and cerebrovascular
disease
- Reduce premature deaths
- Reduce osteoporosis
- Increase quality of life, which
reduces depression, fatigue and pain
In summary, growth hormone deficiency (GHD)
needs to be evaluated in patients who, after the primary
etiology is diagnosed and treated, still exhibit symptoms of
other illness. Based on my clinical experiences, patients who
exhibit symptoms of chronic infections, osteoporosis,
cardiovascular disease, dementia (depression), and a
hypercoagulation state all need to be evaluated for growth
hormone deficiency.