Hypothalamic-Pituitary-Thyroid axis (HPT axis) Imbalance
The Hypothalamic-Pituitary-Thyroid axis (HPT axis) is a neuroendocrine system that regulates metabolism. When the hypothalamus senses low circulating levels of the hormones T3 and T4, it signals to the pituitary to produce Thyroid Stimulating Hormone (TSH), which then signals the thyroid gland to release T3 and T4. T4 normally is converted to the more active T3, but T4 can also be converted to reverse T3 (rT3). Reverse T3 antagonizes the T3 receptor, so high levels can be detrimental.
During illness, profound changes may occur in the hypothalamic-pituitary-thyroid (HPT) axis. There are several main contributing factors that contribute to an imbalanced HPT Axis.
Vasomotor Control – Hepatic Portal Hypertension
The first is Vasomotor control of the blood supply. Nerves are particularly vulnerability to ischemic challenges from altered blood flow resulting in low oxygen delivery to the brain and nerves. Of the entire brain, the neurons of the hippocampus are the most vulnerable.
All nerves depend wholly upon the arterial system for their nutrition and the quality of their function, such as sensation, signal transmission and motion, even though by the law of reciprocity they furnish force for vasomotor control to the artery itself. Nerves control the diameter of the blood and lymph vessels but they do not control what is flowing in the vessels.
With Hepatic Portal Hypertension, mesenteric blood bypasses the liver, going directly into systemic circulation. Bacteria translocating into the blood would produce somatostatin to suppress the inflammatory immune response to their presence. This production of somatostatin could reach the pituitary and hypothalamus shutting off thyroid and endocrine hormone production. This would then be diagnosed as a thyroid or hormone conditions.
Somatostatin Suppresses the Hypothalamic-Pituitary Axis
Somatostatin from the hypothalamus inhibits the pituitary gland’s secretion of Growth Hormone (GH) and Thyroid Stimulating Hormone (TSH). The hypothalamus is a region of the brain that regulates secretion of hormones from the pituitary gland located below it.
Somatostatin that has earned itself the nickname ‘Endocrine Cyanide’ due to its slowing down a number of biological processes in the body, might add another feature to its ubiquitous nature – that of reducing antigen production to microbes, i.e. Parasites (Schistosoma mansoni, Plasmodium falciparum), Bacteria (E. Coli, Bacillus species), Yeast (Sacchromyces – used as a probiotic). Yeast (Saccharomyces) synthesizes a mature bioactive peptide somatostatin (SMS).
Somatostatin that has earned itself the nickname ‘Endocrine Cyanide’
The hypothalamus contained the highest concentration of Somatostatin (SST), with small amounts in brain-stem, cerebral cortex, cerebellum, pineal gland and spinal cord. Somatostatin (SST) concentrations are increased with neurologic disorders in the hypothalamus and extrahypothalamic brain. The wide variety of diseases with Somatostatin elevation suggests nonspecific leakage from the damaged Blood-Brain-Barrier and brain tissue.
Hypothalamic atrophy occurs with loss of orexin-and somatostatin-containing cell populations. Several symptoms such as sleep disturbances, alterations in circadian rhythm, and weight gain may be due to hypothalamic dysfunction. Endocrine changes including altered cortisol levels, altered hormone levels and increased prevalence of insulin resistance. As many neuroendocrine factors are secreted into the cerebrospinal fluid, blood and urine, it is possible that their levels may reflect the disease state in the central nervous system.
With the loss of orexin and somatostatin producing cells. Damaged Blood-Brain-Barrier allows exogenously produced somatostatin, which is longer acting and more potent than endogenously produced somatostatin to shut down the Hypothalamic-Pituitary Axis.
With Hepatic Portal Hypertension, mesenteric blood bypasses the liver, going directly into systemic circulation. Bacteria translocating into the blood produce somatostatin to suppress the inflammatory immune response to their presence. This production of somatostatin could reach the pituitary and hypothalamus shutting off thyroid and endocrine hormone production. This would then be diagnosed as a thyroid or hormone conditions.
Somatostatin is classified as an inhibitory hormone, whose actions are spread to different parts of the body. Read More…
Melatonin & Low Thyroid Function
Melatonin drives the molecular clockwork in the pituitary by acting on the MT1 receptors.
Melatonin has an inhibitory action on the neuroendocrine-thyroid axis. Long nights result in reduced levels of circulating thyroxin (T4). An active pineal gland produces melatonin, which inhibits thyrotrophin-releasing hormone release from the hypothalamus. The effects of melatonin on the Hypothalamic-pituitary-thyroid (HPT) axis are similar to its effects on the Hypothalamic-pituitary-gonadal (HPG) axis, with the hypothalamus and pituitary being the common site of action for the thyroid and gonadal effects of melatonin._
Short days with long nights are interconnected with decreasing levels of TSH in the pituitary. Moreover, chronic supplementation with melatonin suppresses TSH expression in the pituitary._
Melatonin may play a role in the regulation of TSH release from the pituitary. Melatonin supplementation increases the TSH content in the pituitary by stimulating the accumulation of TSH in the pituitary via secretory granule formation.
However, Melatonin blocks the stimulatory effect of TSH on thyroid follicular cells responsible for the production and secretion of thyroid hormones thyroxine (T4) and triiodothyronine (T3). Melatonin has a thyroid function suppressing action. Free T3, T4 and TSH levels are lower with melatonin supplementation. Read More…
Chronic Illness – Multiple Organ Dysfunction Syndrome
The most consistent change is a decrease in serum tri-iodothyronine (T3) level, but in severe illness, serum thyroxine (T4) may also decrease. The persistence of a normal or even decreased serum level of thyrotropin (TSH) in the face of decreased serum thyroid hormone concentrations implies a major change in HPT axis setpoint regulation. Since these abnormalities of thyroid hormone concentration usually occur without any evidence of thyroid disease and disappear with recovery, they have been referred to as the `sick euthyroid syndrome’ or the `euthyroid sick syndrome’.
The downregulation at all levels of the HPT axis (decreased thyrotropin-releasing hormone (TRH) and TSH at the hypothalamic-pituitary level, and a decreased production of T3 at the peripheral extra-thyroidal level) in Non-Thyroid Illness is part of the neuroendocrine adaptation to disease in an attempt by the body to save energy. In this view, attempts to restore thyroid hormone levels are detrimental and should not be undertaken.
There is a neuroendocrine component in the pathogenesis of the decreased activity of the HPT and somatotropic axes in prolonged critical illness. T3 can stimulate dendritic cell (DC) maturation, leading to DC-induced T cell proliferation and IFN-γ release. The cytokines IL-1β, TNF-α, IFN-γ, and IL-6 can inhibit the conversion of T4 to T3, thereby shunting T4 towards the production of the potentially detrimental rT3.
In severe illness, profound changes occur in the hypothalamic-pituitary-thyroid axis. The observed decrease in serum concentration of both thyroid hormones and thyrotropin (TSH) are not compatible with a negative feedback loop. Read More…
Read More about the Six Patterns of Low Thyroid Function
Click on the links below:
- The only time to use Iodine or Selenium to restore normal Thyroid Function.
- Primary Hypothyroidism is a thyroid treatable condition.
- Suppressed Hypothalamus-Pituitary function from exogenous Melatonin, Somatostatin, Impaired Vasomotor control leading to Ischemia of the Blood-Brain-Barrier, Hypothalamus, Hippocampus and Pituitary.
- Hippocampus, hypothalamic and pituitary suppression of Thyroid Stimulating Hormone (TSH) production results in Low Thyroid Symptoms.
- Cortisol imbalances causing downstream production of thyroid suppressing corticosteroid hormones measured by the Genova Complete Hormone Panel.
- Thyroid hormone suppressing corticosteroid hormones mimic Low Thyroid Symptoms.
- Thyroid Overconversion is directly linked to Insulin Resistance and Polycystic Ovarian Syndrome (PCOS).
- Insulin resistance and PCOS symptoms mimic Low Thyroid Symptoms.
- Thyroid Hormone Binding Elevation is a pattern associated with elevation of Multiple Estrogens caused by impaired clearance due to Hepatic Portal Hypertension, and/or bacterial toxins preventing clearance of hormones from the body. Another factor to consider is alteration to the Hypothalamus-Pituitary-Gonad (HPG) Axis.
- Elevation in Estrogen mimic Low Thyroid Symptoms.
- Thyroid Resistance is caused by cellular inflammation occurring throughout the body. An possibility is failure to adequately monitor Thyroid Hormone Medications.
- Cellular Inflammation and improper Thyroid Hormone Medication dosage mimics Low Thyroid Symptoms.