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ClinChem Test 3

Chpt 11 Endocrinology

Endocrinology is the study of hormones and disorders associated with abnormalities of these hormones
Hormones are substances that serve as vehicles for intracellular and extracellular communication
Endocrine hormones typically bind to a receptor at a site distant from their production
There are 3 basic chemical types of hormones : steroids, proteins, and amines
Steroids are not water soluble and must be carried in the blood bound to protein
Proteins and amines are similar to each other in that, they are water soluble and most are synthesized as prohormones then travel to the site of use and are cleaved into their active form
Steroids have a much longer half-life than proteins or amines, and are capable of crossing the cell membrane
Protein hormones are either peptides or glycoproteins
Amine hormones are derived from amino acids and share properties found in both the steroid and protein -based hormones. Proteins and amines hormones can NOT cross the cell membrane.
catecholamines tend to have characteristics similar to the protein hormones
Exposure of receptors to high concentrations of hormone may decrease the number and affinity of surface receptors. This effect has been given various names, including downregulation and desensitization
The reason that type 2 diabetes occurs is there is enough hormone produced but the bodies response is decreased
some hormones can have varying affinity levels, such as strong affinity for their receptors and a weaker affinity for other receptors. This phenomenon is called specificity spillover
Cortisol is a good example of spillover becoming a problem. At normal levels Cortisol acts as a glucocorticoid, but at high levels Cortisol can produce the same effects as an excess of mineralcorticoids as well.
The hypothalamus and anterior pituitary glands are important in the regulation of many hormones
Feedback control plays a major role in the regulation of hormone levels and are an important feature of the endocrine system
Feedback control mechanisms are systems in which the function of one hormone (A) affects the function of another hormone (B).
Negative Feedback control mechanisms occur when the concentration of hormone A causes a decrease in hormone B Negative Feedback control is the most common type of feedback control found in the human body
Positive Feedback control mechanisms occur when the function of hormone A results in an increase in hormone B.
Positive Feedback is less common than negative feedback, and rarely operates in isolation. It is usually a part of a complex control mechanism
The hypothalamus is composed of neuroendocrine tissue and has a variety of hormone receptors within its cells
Adrenocorticotropin (ACTH) levels peak about 8 am and then gradually fall during the day. The lowest point is reached late in the evening typically around 8pm
Cortisol also demonstrates this same pattern and is usually collected at 8am and 8 pm
The pituitary gland or hypophysis is composed of two segments, the neurohypophysis and adenohypophysis. The adenohypophysis aka anterior pituitary provides the secondary level of control and stimulation
The pituitary gland produces and secretes stimulating hormones , or “tropins” usually glycoprotein hormones
The neurohypophysis or posterior pituitary, is closely associated with the hypothalamus and is connected to it via a stalk
The Anterior Pituitary is sometimes referred to as the “Master Gland” due to the many hormones it secretes, including: thyroid stimulating hormone (TSH) or thyrotropin, ACTH, reproductive hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), and many others
The two adrenal glands are located immediately anterior to the kidneys. Each gland consists of two distinct regions, an inner adrenal medulla surrounded by the adrenal cortex
Cortisol is the main glucocorticoid, meaning it affects carbohydrate and fat metabolism, while mineralcorticoids affect mineral and electrolyte balance.
Cortisol raises blood glucose levels by suppressing secretion of insulin, inhibiting peripheral cell uptake of glucose, and promoting hepatic glucose synthesis. Glycogen synthesis and protein catabolism are also induced in the liver
Truncal obesity, buffalo hump, moon face are all associated with Cushing’s Syndrome
Cortisol can be measured in a 24 hour urine as well as measuring total 17-hydroxycorticosteroids.
Urine free cortisol levels (UFC) correlate well with Cushing’s Syndrome
Hypocortisolism is also called Addison’s disease
Measurement of ACTH level can determine if the cause of the hypocortisolism is primary, secondary or tertiary
Aldosterone, and its immediate precursors corticosterone, and 11-deoxycorticosterone, are NOT 17-hydroxycorticosteroids
The adrenal medulla is a functional extension of the sympathetic nervous system, a division of the autonomic nervous system, which accelerates heartbeat, increases blood sugar, slows digestion, and dilates arteries
Adrenal Medullary hormones affects are longer lasting than direct nerve stimulation and can also effect cells that are NOT directly innervated
Pheochromocytomas are tumors that produce excess catecholamines
Neuroblastoma occurs mostly in children under the age of 5
Diagnosis of Neuroblastoma uses both immunohistochemical identification of a tissue biopsy and increased levels of plasma and urinary catecholamines.
Thyroid hormones are secreted based upon a complex interaction of the hypothalamus and the anterior pituitary (adenohypophysis), and the thyroid gland
The hypothalamus has thyroid receptors and serves as a tertiary level of control and stimulation of the thyroid gland by secreting thyroid releasing hormone (TRH) or thyrotropin-releasing factor (TRF) in response to lower than normal levels of thyroid hormone
TRH stimulates the adenohypophysis to release thyroid stimulating hormone (TSH) or thyrotropin. IF thyroid hormone levels are high they influence the hypothalamus and pituitary to discontinue release of TRH and TSH.
The adenohypophysis is the second line of control of the thyroid. It produces and secretes TSH which in turn stimulates the thyroid gland.
The thyroid gland produces and releases triiodothyronine (T3) and thyroxine (T4) which are both made from tyrosine and iodine
T3 and T4 are present in the blood stream in BOTH the bound and unbound forms. T3 is more physiologically active than T4
The bound forms are INACTIVE and make up what portion of the hormone present the largest portion of the hormone present about 99% of T4 is bound and 99.9% of T3 is bound
Thyroid Stimulating Hormone (TSH) or Thyrotropinis is produced in the anterior pituitary or adenohypophysis
TSH is a glycoprotein hormone and has a short half life of a few minutes to hours
Thyroid Stimulating Hormone (TSH) or Thyrotropin travels in the free form it is NOT bound to a carrier protein like the thyroid hormones. It binds to receptor cells in the thyroid cells and causes the release of T4 and T3
It should be NOTED that TSH can have an INVERSE relationship to thyroid hormone levels. (When the condition is primary rather than secondary
T4 is present in normal blood at the concentration of 5.5 – 11.0 ug/dl
T3 is present in normal blood at the concentration of 87 – 180 ng/dl
FT4 is present in normal blood at the concentration of .8 – 2.7 ng/dl
FT3 is present in normal blood at the concentration of 230-340 pg/dl
NOTE 100ng/dl = .1 ug/dl + 300 pg/dl = .3 ng/dl
T4 is about 100 times more prevalent than T 3 and FT4 is about 10 times more prevalent than FT3
Thyroid hormones are involved with growth and maturation of bones, nerves and in regulation of growth hormones
Thyroid hormones also regulate the metabolic rate, fat, protein and carbohydrate metabolism, heart rate, respiration rate. This includes gluconeogenesis, glycogenolysis, lipolysis, and degradation of cholesterol and triglycerides
Primary hypothyroidism means the disease causing the low thyroid hormones is in the thyroid gland itself
This disorder is associated with increased levels of TSH and decreased levels of FT4. (there would probably be decreased levels of T4 and T3 also)
If the hypothyroidism is due to autoimmunity such as Hashimoto’s thyroiditis,what antibodies are present anti-microsomal antibodies or anti-thyroid antibodies
Other possible causes of hypothyroidism in the adult include: thyroidectomy, anti-thyroid drugs, and radioiodine therapy
When Hypothyroidism occurs in adults one of the clinical manifestations is myxedema or puffiness in the face and around the eyes
Other manifestations of Hypothyroidism include: cold intolerance, dry hair and skin, weight gain, personality change and memory impairment
In a Neonate Primary Hypothyroidism may be caused by a congenitally absent, atrophic, or dysfunctional thyroid gland.
As mentioned before thyroid hormones are needed for development, therefore untreated neonatal Hypothyroidism results in profound impairment of growth and mental retardation. (This was previously known as cretinism)
Secondary Hypothyroidism is associated with decreases in BOTH TSH and FT4. (And decreases in T4 and T3)
The clinical manifestations of Secondary Hypothyroidism are similar to the ones for primary hypothyroidism in the adult
It is generally of pituitary origin usually following pituitary surgery, head trauma, CVA, or obstetric complications
TSH and FT4 are the two most commonly performed tests to assess thyroid function
It is preferred that TSH be performed initially to assess thyroid function and then FT4 if the TSH value is abnormal. The test ordering at that point is dependent on what was learned from the first two tests and correlation with the patients condition
These tests are usually performed using immunoassay on serum in the chemistry department.
In 1980 the ONLY thyroid testing that was routinely done in hospital laboratories was total T4 and TSH
FT4 and T3 were in too small of a concentration to be measured by the instrumentation of the day
T3 uptake is a measurement of thyroid hormone binding to thyroid binding globulin (TBG) or other proteins. This test was used to “approximate” the T3 value. The derived T3 value was used to “approximate” the FT4 value or Free T4 index (FTI)
Generally a high TSH is due to primary hypothyroidism while low TSH values usually suggest primary hyperthyroidism
Signs and symptoms of hyperthyroidism include: goiter, optical changes, muscle weakness, tachycardia and fibrillation and weight loss
Among women one of the most common causes of thyroid disease is autoimmunity. With Graves disease being more common than Hashimoto’s
Secondary Hyperthyroidism is clinically the same as primary Hyperthyroidism but without the autoimmune conditions
During pregnancy changes occur that may lead to a diagnosis of Hyperthyroidism that was previously undiagnosed
Thyrotoxicosis is an acute illness due to hyperthyroidism
Thyroid Storm is a complication that can arise with a patient that already has hyperthyroidism and then gets a severe infection, trauma, toxemia of pregnancy, or diabetic ketoacidosis
Thyroid storm is characterized by : abrupt onset of fever, muscle weakness and wasting, emotional disturbance and possible coma and death
This is a true medical emergency that requires thyroid testing done stat
Polyuric states are those in which excessive urine output occurs unrelated to fluid, alcohol, or caffeine intake
Diabetes insipidus reflects lack of anti-diuretic hormone (ADH) or lack of response to ADH
If replacement of fluids is managed with IV then electrolyte concentrations can usually be managed.Without this support a hypotonic plasma can result and electrolytes become imbalanced the usual result is Hypernatremia
About 50% of the total plasma calcium is active in the form of free ions, or Ionized calcium. The other 50% is inactive and bound to albumin
The Hormones that regulate bone remodeling are: calcitonin, parathyroid hormone (PTH) and Vitamin D a hormone-like steroid
The parathyroid gland releases PTH when ionized calcium falls below normal levels in the extracellular fluids
PTH has many functions upon bone, intestines, and kidneys.
Calcitonin is produced in the thyroid and released in response to hypercalcemia, this tends to have the opposite effects of PTH
NOTE in the kidney Phosphorous is excreted to save calcium so they have an INVERSE relationship in the body
Hypercalcemia CA > 11.0 mg/dl can result from hyperparathyroidism and will result in hypophosphatemia, hypomagnesaemia, and elevated urinary phosphate, PTH
Hypercalcemia is one of the most commonly diagnosed metabolic disorders and usually indicates serious disease
Hypercalcemia can also be caused by: malignancy, sarcoidosis, hypervitaminosis of Vitamin D, and immobilization
The effects of hypercalcemia are general and vague but can include: GI problems, neurological changes, or in extreme cases coma
Hypocalcemia is defined as total serum calcium < 8.8 mg/dl in the presence of normal serum protein
Hypocalcemia can result from the following etiologies: low calcium intake, low calcium absorption in the intestine, hypoparathyroidism, pseudohypoparathyroidism, Vitamin D deficiency, Renal tubule disease, acute renal failure, and acute pancreatitis
Ionized calcium testing is usually performed on ion selective electrodes and requires an unopened sample to avoid problems with pH change
The most common cause of hyperthyroidism is Graves' disease. This is an autoimmune disorder that attacks the thyroid gland and triggers the release of high levels of thyroid hormones. One of the hallmarks of Graves' disease is a visible and uncomfortable swelling behind the eyes.
The most common cause of hypothyroidism is Hashimoto's disease. This is an autoimmune disorder in which the body attacks the thyroid gland. The result is damage to the thyroid, preventing it from producing enough hormones. Hashimoto's disease tends to run in families.
Hyperthyroidism can also result from thyroid nodules. These are lumps that develop inside the thyroid and sometimes begin producing thyroid hormones. Large lumps may create a noticeable goiter. Smaller lumps can be detected with ultrasound.
Created by: Mgoodall