Hypothalamus-Pituitary-Thyroid Axis

Group 1
 Hypothalamus-Pituitary-Thyroid Axis
• AKA Thyroid homeostasis or thyrotropic feedback control.
• Hypothalamus senses low circulating levels of thyroid
hormone (T4 &T3) and responds by TRH. Which
stimulates the Pituitary to produce TSH, in turn stimulates
thyroid to produce thyroid hormone until levels of the
blood return normal.
• Thyroid hormone = exerts negative feedback control over
the hypothalamus as well as anterior pituitary, thus,
controlling the release both of TRH from the
hypothalamus and TSH from anterior pituitary gland.
 HPT Axis
• Thyroid homeostasis – results from a multi-loop feedback
system that is found in virtually all higher vertebrates.
– Proper fnx of the thyrotropic feedback control is indispensable
for: growth, differentiation, reproduction and intelligence.
• Pituitary gland = secretes thyrotropin (TSH), that
stimulates the thyroid to secrete T4 and, to a lesser
degree T3.
 HPT Axis
• The major portion of T3, however, is produced in
peripheral organs; liver, adipose tissue, glia and
skeletal muscle by deiodination from circulating T4.

• Deiodination = controlled by numerous hormones and

nerval signals including TSH, vasopressin and
catecholamines.
 HPT Axis
• TSH secretion = controlled by thyrotropin-releasing
hormone (thyroliberin, TRH), whose secretion itself is
again supressed by plasma T4 and T3 in CSF (long
feedback, Fekete-Lechan loop).
• Additional feedback loops are:
– Ultrashort feedback control (Brokken-Wiersinga-Prummel
loop)
– Linear feedback loops = controlling the plasma protein-
binding.
 Functional states of thyrotropic feedback
control
• Euthyroidism: normal thyroid function
• Hypothyroidism: Reduced thyroid function
– Primary hypothyroidism: feedback loop interrupted by low
thyroid secretory capacity. ( example: after thyroid surgery or in
case of autoimmune thyroiditis)
– Secondary hypothyroidism: feedback loop interrupted on the
level of pituitary ( example: anterior pituitary failure)
– Tertiary hypothyroidism: lacking stimulation by TRH ( example:
hypothalamic failure, pickardt-fahl busch syndrome)
• Hyperthyroidism: inappropriately increased thyroid
function
– primary hyperthyroidism: inappropriate secretion of thyroid
hormones. ( example: Grave’s disease)
– Secondary hyperthyroidism: rare condition ( example: in case
of TSH producing pituitary adenoma).
• Thyrotoxicosis: over-supply with thyroid hormones
(example: overdosed exogenously levothyroxine
supplementation).
• Resistance to thyroid hormone: feedback loop interrupted
on the level o pituitary thyroid hormone receptors
 HPT Axis
• Physiologic regulators responsible for integrating function
and the periphery include:
– Thyrotropin Releasing Hormone (TRH)
– Thyroid Stimulating Hormone (TSH)
– Serum free T4 and free T3 concentrations.
 HPT Axis
• TRH enhances TSH synthesis;
• Stimulates the secretion of any preformed TSH rom the
thyrotrophs and;
• Modulates the bioactivity of TSH
• Resulting in the secretion of bioactive TSH.
 HPT Axis
• TRH = under the negative-feedback influence of the
circulating thyroid hormones
– TRH mRNA levels are inversely related to the circulating T3
values.

• Same feedback inhibition occurs at the level of the

thyrotrophs
 Thyrotrophin-Releasing Hormone
• A modified tripeptide (pyroglutamyl-histidyl-proline-amide)
derived from a large prepro-TRH molecule.
• The molecule is released from prepro molecule by a
peptidase.
• It is found in the hypothalamus, but also in:
– the brain - Prostate
– C cells of the thyroid gland - Testis
– The beta-cells of the pancreas - Spinal cord
– Myocardium
 TRH
• Neuron bodies producing TRH are innervated by
catecholamine, leptin, and SS-containing axons;
• These hormones can influence the rate of its synthesis.
• Thyroid hormones = regulates the production by feedback
inhibition = synthesis of TRH and TSH in the
hypothalamus and pituitary gland.
• Leptin = significant role in the regulation of the TRH
gene, affecting the individual’s appetite for food intake.
 Thyroid Stimulating Hormone
• A glycoprotein consisting of two monocovalently
linked alpha and beta subunits.
• Alpha subunit =amino acid sequence similar to LH,
FSH, and hCG
• Beta subunit = carries specific info. to binding
receptors for expression of hormonal activities.
• Radioimmunoassay – first developed by Odell and
colleagues in 1965 for measuring TSH
 Thyroid Stimulating Hormone
Source of Pathology TSH Thyroid Disease causing conditions
Level Hormone Level
Hypothalamus/pituitary High High Adenoma or thyroid hormone
resistance
Hypothalamus/pituitary Low Low Secondary hypothyroidism or
“central” hypothyroidism
Hyperthyroidism Low High Primary hyperthyroidism i.e. Graves’
disease
Hypothyroidism High Low Congenital hypothyroidism, primary
hypothyroidism i.e. Hashimoto’s
thyroiditis