Endocrinology Flashcards
Hypothalamus and Pituitary
The hypothalamus releases hormones that stimulate the pituitary gland. The pituitary gland has an anterior and posterior part.
The anterior pituitary gland releases:
Thyroid-stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Follicle-stimulating hormone (FSH) and luteinising hormone (LH)
Growth hormone (GH)
Prolactin
The posterior pituitary releases:
Oxytocin
Antidiuretic hormone (ADH)
The Thyroid Axis
The hypothalamus releases thyrotropin-releasing hormone (TRH). TRH stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH). TSH stimulates the thyroid gland to release triiodothyronine (T3) and thyroxine (T4).
The hypothalamus and anterior pituitary respond to T3 and T4 by suppressing the release of TRH and TSH, resulting in lower amounts of T3 and T4. The lower T3 and T4 offer less suppression of TRH and TSH, causing more of these hormones to be released, resulting in a rise of T3 and T4. This way, the thyroid hormone level is closely regulated to keep it within normal limits.
When the end hormone (e.g., T3 and T4) suppresses the release of the controlling hormones (e.g., TRH and TSH), this is called negative feedback.
The Adrenal Axis
Cortisol is secreted by the two adrenal glands, which sit above each kidney. The hypothalamus controls the release of cortisol. Cortisol is released in pulses throughout the day and in response to a stressful stimulus. It is a “stress hormone”. It has diurnal variation, meaning it is high and low at different times of the day. Typically cortisol peaks in the early morning, triggering us to wake up and get going, and is at its lowest late in the evening, prompting us to relax and fall asleep.
The hypothalamus releases corticotropin-releasing hormone (CRH). CRH stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH stimulates the adrenal glands to release cortisol.
The adrenal axis is also controlled by negative feedback. Cortisol is sensed by the hypothalamus and anterior pituitary, suppressing the release of CRH and ACTH. This results in lower amounts of cortisol. This way, cortisol is closely regulated to keep it within normal limits.
Actions of cortisol on the body
Increases alertness
Inhibits the immune system
Inhibits bone formation
Raises blood glucose
Increases metabolism
The growth hormone axis
The hypothalamus produces growth hormone-releasing hormone (GHRH). GHRH stimulates the anterior pituitary to release growth hormone (GH). Growth hormone stimulates the release of insulin-like growth factor 1 (IGF-1) from the liver.
Actions of growth hormone on the body
Through this mechanism, growth hormone works directly and indirectly on almost all cells and has many functions. Most importantly, growth hormone:
Stimulates muscle growth
Increases bone density and strength
Stimulates cell regeneration and reproduction
Stimulates growth of internal organs
The parathyroid axis
Parathyroid hormone (PTH) is released from the four parathyroid glands (situated at the four corners of the thyroid gland) in response to a low calcium level in the blood. PTH is also released in response to low magnesium or low phosphate level. The role of PTH is to increase serum calcium concentration.
PTH increases the activity and number of osteoclasts in bone, causing reabsorption of calcium from the bone into the blood, increasing serum calcium concentration.
PTH also stimulates calcium reabsorption in the kidneys, meaning less calcium is excreted in the urine.
PTH also stimulates the kidneys to convert vitamin D3 into calcitriol, the active form of vitamin D. Vitamin D is a hormone that promotes calcium absorption from food in the intestine.
These three effects of PTH (increased calcium absorption from bone, the kidneys and the intestine) all help to increase the serum calcium. When the serum calcium level is high, it suppresses the release of PTH (via negative feedback), helping to reduce the serum calcium level.
The Renin-Angiotensin-Aldosterone System
Renin is an enzyme secreted by the juxtaglomerular cells in the afferent (and some in the efferent) arterioles in the kidney. They sense the blood pressure in these vessels. They secrete more renin in response to low blood pressure and less renin in response to high blood pressure. Renin acts to convert angiotensinogen (released by the liver) into angiotensin I. Angiotensin I converts to angiotensin II in the lungs with the help of an enzyme called angiotensin-converting enzyme (ACE).
Angiotensin II acts on blood vessels, causing vasoconstriction. Vasoconstriction increases blood pressure. Angiotensin II also stimulates the release of aldosterone from the adrenal glands, and contributes to cardiac remodelling by promoting hypertrophy of heart muscle cells (myocytes).
Aldosterone is a mineralocorticoid steroid hormone. It acts on the nephrons in the kidneys to:
Increase sodium reabsorption from the distal tubule
Increase potassium secretion from the distal tubule
Increase hydrogen secretion from the collecting ducts
When sodium is reabsorbed in the kidneys, water follows it by osmosis. This leads to increased intravascular volume and, subsequently, blood pressure.
TOM TIP: Understanding the renin-angiotensin-aldosterone system is essential to understanding the mechanism of action of ACE inhibitors and angiotensin II receptor blockers. By blocking the action of angiotensin-converting enzyme or angiotensin II receptors, they reduce the activity of angiotensin II, reducing vasoconstriction, cardiac remodelling and the secretion of aldosterone. Reduced aldosterone leads to reduced sodium reabsorption in the kidneys and less water retention. However, the reduced potassium secretion means these medications can cause hyperkalaemia (raised potassium).
Screening test for thyroid disease
Thyroid-stimulating hormone (TSH) is used as a screening test for thyroid disease. When TSH is abnormal, triiodothyronine (T3) and thyroxine (T4) can be measured to gain more information.
Primary hyperthyroidism
Primary hyperthyroidism is where the thyroid behaves abnormally and produces excessive thyroid hormones. TSH is suppressed by the high T3 and T4, causing a low TSH level.
Secondary hyperthyroidism
Secondary hyperthyroidism is where the pituitary behaves abnormally and produces excessive TSH (e.g., pituitary adenoma), stimulating the thyroid gland to produce excessive thyroid hormones. TSH, T3 and T4 will all be raised.
Primary hypothyroidism
Primary hypothyroidism is where the thyroid behaves abnormally and produces inadequate thyroid hormones. Negative feedback is absent, resulting in increased production of TSH. TSH is raised, and T3 and T4 are low.
Secondary hypothyroidism
Secondary hypothyroidism is where the pituitary behaves abnormally and produces inadequate TSH (e.g., after surgical removal of the pituitary), resulting in under-stimulation of the thyroid gland and insufficient thyroid hormones. TSH, T3 and T4 will all be low.
Thyroid disease antibodies
Anti-thyroid peroxidase (anti-TPO) antibodies are antibodies against the thyroid gland. They are the most relevant thyroid autoantibody in autoimmune thyroid disease. They are usually present in Grave’s disease and Hashimoto’s thyroiditis.
Anti-thyroglobulin (anti-Tg) antibodies are antibodies against thyroglobulin, a protein produced and extensively present in the thyroid gland. They can be present in normal individuals without thyroid pathology. They are usually raised with Grave’s disease, Hashimoto’s thyroiditis and thyroid cancer.
TSH receptor antibodies are autoantibodies that mimic TSH, bind to the TSH receptor and stimulate thyroid hormone release. They cause Grave’s disease and will therefore be present in this condition.
Thyroid imaging
Ultrasound of the thyroid gland helps diagnose thyroid nodules and distinguish between cystic (fluid-filled) and solid nodules. Ultrasound can also be used to guide a biopsy of a thyroid lesion.
Radioisotope scans are used to investigate hyperthyroidism and thyroid cancers. Radioactive iodine is given orally or intravenously and travels to the thyroid, where it is taken up by the thyroid cells. Iodine used by thyroid cells to produce thyroid hormones. The more active the thyroid cells, the faster the radioactive iodine is taken up. A gamma camera detects gamma rays emitted from the radioactive iodine. The more gamma rays emitted from an area, the more radioactive iodine has been taken up. This gives functional information about the thyroid gland:
Diffuse high uptake is found in Grave’s Disease
Focal high uptake is found in toxic multinodular goitre and adenomas
“Cold” areas (abnormally low uptake) can indicate thyroid cancer
Thyrotoxicosis
Thyrotoxicosis refers to the effects of an abnormal and excessive quantity of thyroid hormones in the body.
Subclinical hyperthyroidism
Subclinical hyperthyroidism is where the thyroid hormones (T3 and T4) are normal and thyroid-stimulating hormone (TSH) is suppressed (low). There may be absent or mild symptoms.
Toxic multinodular goitre
Toxic multinodular goitre (also known as Plummer’s disease) is a condition where nodules develop on the thyroid gland, which are unregulated by the thyroid axis and continuously produce excessive thyroid hormones. It is most common in patients over 50 years.
Hyperthyroidism and exophthalmos
Exophthalmos (also known as proptosis) describes the bulging of the eyes caused by Graves’ disease. Inflammation, swelling and hypertrophy of the tissue behind the eyeballs force them forward, causing them to bulge out of the sockets.
Pretibial myxoedema
Pretibial myxoedema is a skin condition caused by deposits of glycosaminoglycans under the skin on the anterior aspect of the leg (the pre-tibial area). It gives the skin a discoloured, waxy, oedematous appearance over this area. It is specific to Grave’s disease and is a reaction to TSH receptor antibodies.
Goitre
Goitre refers to the neck lump caused by swelling of the thyroid gland.
Causes of hyperthyroidism
G – Graves’ disease
I – Inflammation (thyroiditis)
S – Solitary toxic thyroid nodule
T – Toxic multinodular goitre
Thyroiditis (thyroid gland inflammation) often causes an initial period of hyperthyroidism, followed by under-activity of the thyroid gland (hypothyroidism). The causes of thyroiditis include:
De Quervain’s thyroiditis
Hashimoto’s thyroiditis
Postpartum thyroiditis
Drug-induced thyroiditis
Presentation of hyperthyroidism
Anxiety and irritability
Sweating and heat intolerance
Tachycardia
Weight loss
Fatigue
Insomnia
Frequent loose stools
Sexual dysfunction
Brisk reflexes on examination
Presentation of Graves’ disease
Graves’ disease has specific features relating to the presence of TSH receptor antibodies:
Diffuse goitre (without nodules)
Graves’ eye disease, including exophthalmos
Pretibial myxoedema
Thyroid acropachy (hand swelling and finger clubbing)