Pathophysiology week 6

Cells communicate through many kinds of signal molecules and may occur in three ways:

1. Receptors are displayed on the plasma membrane of the cell. Think of the receptors as signaling molecules that brings the hormone to where it specifically needs to be. 2. Affects receptor proteins inside the target cell where the signal molecule must enter the cell to bind with them. 3. Forms protein channels (gap junctions) that coordinate the activities of adjacent cells (this is nothing more than a way for cells to communicate with one another).

2-h PG

2-h PG ≥200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water*

Parathyroid hormone function.

4 parathyroid glands Chief cells produce PTH in response to low blood calcium. PTH increases absorption of calcium from intestines PTH increases reabsorption of calcium in the kidneys. PTH increases osetoclast activity in the bones. PTH converts vitamin D into its active form.

Thyroid function, High TSH

A high TSH indicates that the thyroid is not making enough thyroid hormone (low FT4)When the pituitary gland sense that there is too little thyroid hormone in the blood, it produces more TSH in order to stimulate the thyroid gland to produce more active hormone.

A1C

A1C ≥6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay*

Hypothalamus Hormones Which of the following hormones are produced by the hypothalamus? Follicle-stimulation hormone. Luteinizing hormone. Thyroid stimulating hormone. Antidiuretic hormone.

ADH is the only hormone listed that is produced by the hypothalamus.

Hyperthyroidism Which of the following is used in the treatment of hyperthyroidism? Methimazole Radioactive Iodine Propylthiouracil All of the above

All are treatment options for hyperthyroidism.

Hypoglycemia

An individual is considered hypoglycemic when the blood glucose level is less than 70 mg/dL. Causes range from medications, exercise and alcohol ingestion. Other causes of hypoglycemia include a pancreatic tumor, receiving hyperalimentation or liver disease.

Prediabetes

Categories of Increased Risk for Diabetes (Prediabetes) 1. FPG 100 to 125 mg/dL 2. 2-hr PG in the range of 140 to 199 mg/dL during an OGTT 3. HbA1c 5.7% to 6.4%

TYpe 1 diabetes

Cause:Autoimmune:Genetic and environmental factors, resulting in gradual process of autoimmune destruction in genetically susceptible individuals Nonautoimmune:Unknown Strong association with HLA-DQA and HLA-DQB genes Age:< 10-20 years of age Genetic association: Weak association Acute complications: Diabetic ketoacidosis Associated with obesity: No Presenting symptoms: Polyuria, polyphagia, polydipsia

Type 2 diabetes

Cause:Results from genetic susceptibility (polygenic) combined with environmental determinants and other risk factors Inherited defects in beta-cell mass and function combined with peripheral tissue insulin resistance Associated with long-duration obesity Age:Usually > 40 years of age Genetic Association:Strong associationAcute complications:Hyperosmolar nonketotic coma Associated with Obesity:Yes Presenting symptoms: weakness, weight loss, infections

Secondary Hyperparathyroidism Pathology

Caused by Low vitamin D or chronic renal failure leading to hypocalcemia. In response the parathyroid secretes more PTH. Serum Calcium level will be low or normal. PTH levels will be high. treated by correcting underlying cause.

Tertiary hyperparathyroidism

Caused by long term stimulation of parathyroid which leads to hyperplasia.

Signaling Hormone Amine

Class: Amine Description: Derived from aromatic amino acid Properties: Hydrophilic-cannot cross membrane undergoes regulator secretion example: Thyroxine

Signaling hormone peptide

Class: Peptide Description:Short polypeptide chainsProperties: Properties:Hydrophilic - cannot cross membrane Undergoes regulatory secretion Examples: Insulin Glucagon

Signaling hormone steroid

Class: Steroid Description: Lipids derived from cholesterol Properties:Lipophilic - can cross membrane Undergoes constitutive secretion Example:Testosterone Estrogen / Progesterone

Hypothyroidism Diagnosis and Treatment

Clinical symptoms of primary hypothyroidism, increased TSH level and decreased total T3, total T4 and free T4 provide the basis for a diagnosis. Treatment Hormone replacement therapy is indicated. Levothyroxine is the drug of choice for hypothyroidism. Dosing will be based on the patient's age, the severity of the symptoms and the presence of other associated disorders.

The diagnostic features of HHNKS include:

Elevated serum glucose (>600 mg/dL) Near normal serum bicarbonate level and pH Serum osmolarity > 320 mOsm/L Absent or low ketone levels in the urine and serum

Response to Insulin

Factors that affect an individual's response to insulin include weight, height, activity level, and abdominal fat.

Lipid Hormone To be considered a lipid hormone, it must be bound to a protein and it must bind to receptors inside the cell membrane. True False

False It must be bound to a protein and it bind to receptors on the cell membrane rather than inside the cell membrane.

Parathyroid Glands The parathyroid glands are located on the anterior lobe of the thyroid gland. True False

False They are located on the posterior lobes of the thyroid gland.

Grave's Disease In Grave's disease, overproduction of thyroid hormone is due to parafollicular cell production of thyroid hormone. True False

False Thyroid hormone is produced by the follicular cells.

TSH Production TSH production is decreased in hypothyroidism. True False

False, TSH production is increased in hypothyroidism.

Posterior Pituitary The posterior pituitary produces its own hormones. True False

False, The posterior pituitary receives its hormones (oxytocin and ADH) from the hypothalamus. The anterior pituitary produces its own hormones.

Hormones The only way for a hormone to reach a target cell is through the blood stream. True False

False: The endocrine cell can also secrete hormones that target cells directly close it. When this occurs, this type of secretion is known as paracrine signaling. Hormones activate target cells by diffusing through the plasma membrane of the target cells (lipid-soluble hormones) to bind a receptor protein within the cytoplasm of the cell, or by binding a specific receptor protein in the cell membrane of the target cell (water-soluble proteins).

Visual changes-Blurred vision

Fluid balance in the eye fluctuates because of elevated blood glucose Diabetic retinopathy is another cause of visual loss

Diagnosis of hyperthyroidism

For primary hyperthyroidism, there will be decreased TSH levels with elevated T4, (T3) and FT4 levels. Radioactive iodine is also used to test for increased uptake in primary hyperthyroidism as indicated in the diagram below.

Ghrelin hormone

Ghrelin is produced in the stomach and pancreatic islets. It regulates food intake, energy balance and hormonal secretion. When Ghrelin is decreased, it contributes to insulin resistance. Incretins (previously discussed) are also released from the GI tract when food is ingested. It increases synthesis and secretion of insulin as well as beta cell proliferation and regeneration. In Type 2DM, beta-cells have a decreased responsiveness to incretin.

Clinical Manifestations of Hyperthyroidism

Goiter, hypercalcemia, decreased parathyroid hormone secretion, decreased sensitivity to insulin, increase in SHBG, weight loss, frequent stools

Hyperosmolar Hyperglycemic Non-Ketoacidosis Syndrome (HHNKS)

HHNKS involves insulin deficiency but it is not as pronounced as the insulin deficiency seen in DKA. Also, the degree of elevated blood glucose and fluid deficit is more pronounced in HHNKS than in DKA. The follow factors contribute to the development of HHNKS: Insulin deficiency Increased levels of counter-regulatory or stress hormones (glucagon, catecholamines, cortisol and growth hormone) Increased gluconeogenesis and glycogenolysis Inadequate use of glucose by peripheral tissues (primarily muscle)-characterized by lack of ketosis Proinflammatory mediators (TNF-α, IL-6, IL-1β) are also involved that also contribute to insulin resistance and hyperglycemia. Less insulin is needed to inhibit fat breakdown needed for effective glucose transport. Therefore, insulin levels are enough to prevent excessive lipolysis but not to use glucose effectively.

hypothyroidism Primary vs secondary

Hashimoto disease, an autoimmune thyroiditis, is the most common cause of primary hypothyroidism. Secondary issues are related to a pituitary or hypothalamic issue.

Diagnosing Diabetes Mellitus

HbA1C >= 6.5%*. Fasting Plasma Glucose >= 126mg/dL (7.0mmol/L)*. 2-hour plasma glucose >= 200mg/dL (11.1mmol/L) during an oral glucose tolerance test*. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose >=200mg/dL (11.1mmol/L) *repeat testing required to confirm diagnosis*

The purpose of the endocrine system is to maintain the body's homeostasis using hormones. Hormones are signaling molecules. Although a wide variety of hormones function within the body, they share certain general characteristics:

Hormones have specific rates and rhythms of secretion. Three basic secretion patterns are: (1) circadian or diurnal patterns, (2) pulsatile and cyclic patterns, and (3) patterns that depend on levels of circulating substrates (e.g., calcium, sodium, potassium, or the hormones themselves). Hormones operate within feedback systems, either positive or negative, to maintain an optimal internal environment. Hormones affect only cells with specific receptors and then act on those cells to initiate specific cell functions or activities.

Primary Hyperparathyroidism Pathology

Hyperfunction of parathyroid cells due to adenoma. Tumor creates increase in PTH which increases calcium to much.

Hyperthyroidism Pathophysiology

Hyperthyroidism (thyrotoxicosis) is characterized by an increase the amount secreted thyroid hormone (TH) from the thyroid gland. Thyroid hormones are regulated by the negative feedback system that involves the hypothalamus, anterior pituitary gland and thyroid gland shown in the diagram below:

Low TSH in thyroid function

If the TSH is low, the pituitary senses too much thyroid hormone (high FT4) in the blood, and it will decrease the production of TSH so that the thyroid gland decreases the amount of thyroid hormone. Patients who do not existing thyroid disease are screened by assessing serum TSH levels. If the TSH is too high or too low, a FT4 is drawn to more accurately assess the thyroid production of hormone available for use. The TSH and FT4, when used together, aid in the diagnosis of hypothyroidism and hyperthyroidism.

When not to use A1C in diagnosing diabetes

In conditions associated with an altered relationship between A1C and glycemia, such as hemoglobinopathies including sickle cell disease, pregnancy (second and third trimesters and the postpartum period), glucose-6-phosphate dehydrogenase deficiency, HIV, hemodialysis, recent blood loss or transfusion, or erythropoietin therapy, only plasma blood glucose criteria should be used to diagnose diabetes.

Gonads

In males, the gonads secrete the androgen testosterone that is responsible for promoting male characteristics and sperm production. In females, the ovaries secrete estrogen and progesterone that are important in developing female characteristics and egg production.

Insulin Synthesis

Insulin Synthesis Insulin is only synthesized in the beta cells. To understand its synthesis, we start with preproinsulin. This is a biologically inactive precursor to an active insulin hormone. Preproinsulin is converted by signal peptidases to proinsulin. Proinsulin is in the endoplasmic reticulum of the cell. It is exposed to endopeptidases that separate the C-peptide to generate the active form of insulin. Insulin, along with the free C-peptide are packaged in the Golgi apparatus into secretory cells. When the beta cell is stimulated, insulin is secreted from the cell and diffuses into the islet capillary blood. The C-peptide is also secreted in the blood, but its action is unknown.

Iodine and thyroid hormones

It is important to know how T4 and T3 are produced. Refer to the diagram below as we explore their production. Iodine is mentioned first in its role in thyroid hormone production. Through diet, iodine is absorbed from the gastrointestinal tract (GI) and then taken up by the thyroid gland and transported into the follicular cells. Energy is required for this to happen. The energy source is a N+/I- cotransport system and ATPase pump. It is activated when TSH binds to the thyroid epithelial cells. Once iodine is taken up by the thyroid gland, it becomes oxidized by peroxide where I- becomes I+. The oxidized form of iodine enters the follicular cells to assist in producing the thyroid hormones.

The drug of choice for the treatment of hypothyroidism is: Levothyroxine Indomethacin Iodine Prolactin

Levothyroxine is the first drug of choice for the treatment of hypothyroidism.

Lipophilic hormones

Lipid-soluble hormones, in contrast, are transported bound to a protein. Because they are bound, they can remain in the blood for hours to days. It is very important to note here that when a hormone is bound to a protein, it cannot exert its effects. Only free circulating hormones can initiate responses inside of a target cell. This will be revisited as we delve into the diseases of the endocrine system. Upon arrival to the cell membrane, the protein-bound hormone must disengage from the protein in order to diffuse into the cell where its effects can be exerted.

Metabolic Syndrome Metabolic syndrome is characterized by: Cachexia, hypotension, normal cholesterol Normal blood pressure, obesity, hyperlipidemia Hypertension, stroke, peripheral edema Hyperlipidemia, obesity, hypertension

Metabolic syndrome is characterized by hyperlipidemia, obesity, hypertension.

Thyroglobulin

Next, we consider the role of tyrosine that is located on thyroglobulin. Thyroglobulin (Tg) is a glycoprotein that is produced in the follicular cells and is used exclusively in the thyroid gland. It is the main precursor to thyroid hormones. Thyroid hormones are produced when tyrosine on the thyroglobulin combines with I+. I+ essentially splits the thyroglobulin that results in diiodotyrosine and monoiodotyrosine. Diiodotyrosine is associated with the production of T4 while monoiodotyrosine is associated the production of T3. Note the amount of T4 and T3 produced. Although T3 is produced in much smaller amounts, it is the most active of the two.

hydrophillic hormones

Note that peptide and amine hormones are hydrophilic (water-soluble). This means that they are easily dissolved in fluid and do not have to bind to a protein in order to circulate. Characteristically, they also have a short half-life of just seconds to minutes as they are catabolized by circulating enzymes. Insulin, for example is a peptide hormone. Shortly after its release, it is catabolized by insulinase enzymes within 3-5 minutes.

Insulin pathway

Now that insulin is released, it needs to travel to the target cell. To do this, insulin binds with an enzyme-linked plasma membrane receptor depicted in the diagram below. This receptor contains tyrosine kinase. Once insulin binds to the receptor, a cascade of activity occurs. Signals are sent to activate glucose transporters (primarily GLUT4) to allow entry of glucose into the cell. GLUT4 is activated by the insulin receptor and then translocated to the surface of the cell to facilitate diffusion of glucose into the cell. Let's pause here to think about insulin sensitivity, an individual's response to insulin. This can be affected by the individual's age, weight, physical activity and the amount of abdominal fat. Under these conditions, insulin resistance may occur. Obesity, as well as lack of exercise is a major factor in the development of insulin resistance because adipocytes release hormones altered by obesity that reduces the individual's reaction to insulin. As an NP in clinical practice, it will be extremely important to educate patients on the benefits of weight loss and exercise.

Insulin Secretion

Now that the insulin has been produced, it is waiting to be stimulated and released to its target cell. Insulin secretion increases when the beta cells are stimulated by the parasympathetic nervous system. This usually occurs before eating a meal. Insulin secretion is primarily stimulated when blood glucose levels rise. Other factors that increase insulin secretion are increased amino acids and gastrointestinal hormones (glucagon, gastrin, cholecystokinin, secretin). Factors that decrease insulin secretion include hypoglycemia, high insulin levels through the negative feedback to the beta cells and sympathetic stimulation of the islet cells. Prostaglandins also inhibit insulin secretion.

Insulin Actions

Once in the cell, insulin promotes glucose uptake mostly in the liver, muscle and adipose tissue. It also affects proteins, carbohydrates, and lipids by increasing their synthesis. The overall effect of insulin in the tissues is stimulation of protein and fast synthesis and a decreased blood glucose level. Insulin also drives the transport of potassium, phosphate and magnesium into the cell.

Parathyroid glands

Parathyroid glands: The parathyroid glands are located on the posterior surface of the thyroid gland. They secrete parathyroid hormone (PTH) that is responsible for regulating calcium and phosphate levels in the body.

Patesthesia

Paresthesias are common manifestations of diabetic neuropathies

Type 2 Diabetes Mellitus (T2DM)

Pathophysiology Insulin resistance involves insulin-sensitive tissues (liver, muscle, adipose tissue) becoming less responsive to insulin and is associated with obesity. Obesity contributes greatly to insulin resistance and the development of Type 2 DM because of: 1. Increased production of leptin, an adipokine hormone produced in adipose tissue and inflammation that decreases insulin synthesis and insulin resistance. 2. Elevated serum free fatty acid and triglyceride and cholesterol deposition into the cells that interfere with insulin signaling. There is also decreased tissue response to insulin, altered incretin function that promotes inflammation leading to beta cell destruction. 3. Release of inflammatory cytokines from intraabdominal adipocytes induces insulin resistance. 4.Alterations in oxidative phosphorylation in the cell's mitochondria that contributes to insulin resistance.

posterior pituitary

Posterior lobe: The posterior lobe secretes oxytocin and ADH after it is produced by the hypothalamus. The hypothalamus sends oxytocin and ADH to the posterior pituitary where they are secreted into the blood. When secreted, ADH targets the kidney tubules to retain water. Oxytocin targets breast tissue (lactation) and the uterus (uterine contraction during childbirth). Does not create own Hormones

Grave's Disease The two most distinguishing factors of Grave's disease is: Pretibial myxedema and truncal obesity Lethargy and weight gain Pretibial myxedema and exophthalmos Goiter and exophthalmos

Pretibial myxedema and exophthalmos are the two most distinguishing factors of Grave's disease.

signal transduction

Signal Transduction Signal transduction involves communication between the outside of the cell and the inside of the cell. Remember that the hormone that has traveled to the specific target cell wants to get inside of the cell. To help, extracellular chemical messengers (first messengers) are available to convey signals or instructions from outside of the cell to the interior cell. Signal transduction pathways help with this process by allowing cells to respond to external signals. Signals pass between the cells when a certain type of molecule is produced by one cell (the signaling cell) and received by another cell (the target cell) by way of a receptor protein that recognizes and responds to that specific signaling molecule. The diagram below provides a general view of the signal transduction pathway.

What are the three type of signaling hormones?

Steroid, Peptide and amine

The thyroid gland consists of two types of cells: Follicular cells: these are most abundant and are the secretory cells. They secrete thyroid hormone (Thyroxine or T4). Note that T4 is a lipid-soluble hormone. Parafollicular cells (C cells): these are fewer in number and secrete calcitonin.

T4 is stored in the colloid area of the cell

2-H Plasma Glucose

The FPG and 2-h PG may be used to diagnose diabetes (Table 2.2). The concordance between the FPG and 2-h PG tests is imperfect, as is the concordance between A1C and either glucose-based test. Compared with FPG and A1C cut points, the 2-h PG value diagnoses more people with prediabetes and diabetes (20). In people in whom there is discordance between A1C values and glucose values, FPG and 2-h PG are more accurate (21).

Adrenal glands

The adrenal glands consist of the adrenal cortex and adrenal medulla. The adrenal cortex secretes cortisol and aldosterone. Cortisol is involved in the stress response and aldosterone promotes sodium reabsorption and potassium excretion in the kidneys. The adrenal medulla secretes epinephrine and norepinephrine.

anterior pituitary

The anterior lobe differs from the posterior lobe in that it produces its own hormones. But these hormones can only be secreted when the hypothalamus confirms that it is fine to do so. The hypothalamus does this by secreting regulatory hormones that either stimulate or inhibit the anterior pituitary hormones. The anterior pituitary secretes prolactin that targets the breast to simulate milk production, secretes growth hormone that targets the bone to promote growth, and secretes gonadotropic hormones (Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH)) that target the testes and the ovaries. It also secretes thyroid stimulating hormone (TSH) to stimulate the thyroid gland to secrete T3 and T4. Finally, it can secrete adrenocorticotropic hormone (ACTH) which will target the adrenal gland to stimulate the release of cortisol.

Adrenal Cortex Hormones

The cells of the adrenal cortex are stimulated by the adrenocorticotropic hormone (ACTH) from the anterior pituitary as shown in the diagram below. Also note that the hormones produced in the adrenal cortex are synthesized from cholesterol, a low-density lipoprotein (LDL). In this process, cholesterol is converted to pregnenolone that is then converted to what we know as our major corticosteroids.

Diabetic Ketoacidosis (DKA)

The diagnosis of DKA is based on the signs and symptoms described above. The American Diabetes Association's criteria for the diagnosis of DKA include: Serum glucose level >250 mg/dL Serum bicarbonate level <18 Serum pH <7.30 Presence of an anion gap Presence of urine and serum ketones

Negative and positive hormone feedback loops

The negative feedback system will activate when there is a change in endocrine, chemical or neural response. It will decrease the synthesis and secretion of a hormone. In contrast, positive feedback systems result when the endocrine, chemical or neural response increases the synthesis and secretion of a hormone.

Steroid Hormones Which of the following is an example of a steroid hormone? Testosterone. Insulin. Thyroxine. Glucagon.

The only steroid hormone listed is testosterone.

Pancreas

The pancreas secretes two main hormones, insulin and glucagon. Referring to our example of hormone function above, glucagon increases blood glucose levels which insulin works opposite by decreasing blood glucose levels

Hyperthyroidism reasons

There are several reasons why an individual may have excessive thyroid hormone. In Grave's disease the overproduction of thyroid hormone is due to the follicular cells producing excessive amounts of T4 and T3 due to stimulation from the TSH receptor autoantibody (TSH-R). Other conditions that may lead to an overproduction of thyroid hormone includes: Patients with multinodular goiter who take inorganic iodine (e.g. potassium iodide) or an organic iodine such as amiodarone. Patients with multinodular goiter who develop multiple nodules and secrete excessive amounts of T4 or T3. Patients with large follicular adenomas can produce excessive thyroid hormone.

Goiters A goiter may appear in hypothyroidism because of the overproduction of TSH. True False

This statement is true. A goiter may appear in hypothyroidism because of the overproduction of TSH

Aldosterone Aldosterone promotes sodium reabsorption and potassium excretion in the kidneys. True False

This statement is true. Aldosterone promotes sodium reabsorption and potassium excretion in the kidneys.

Diabetic Ketoacidosis An individual who presents with Diabetic Ketoacidosis (DKA) will have a blood glucose level of >250 mg/dL. True False

This statement is true. An individual who presents with Diabetic Ketoacidosis (DKA) will have a blood glucose level of >250 mg/dL.

Myxedema Characteristics of myxedema include non-pitting edema around eyes. True False

This statement is true. Characteristics of myxedema include non-pitting edema around eyes.

Chvostek Sign

This statement is true. Chvostek sign is elicited by tapping the cheek that will result in twitching of the upper lip. Represents hypocalcemia

HHNKS HHNKS is characterized by increased gluconeogenesis and glycogenolysis. True False

This statement is true. HHNKS is characterized by increased gluconeogenesis and glycogenolysis.

Polydipsia Polydipsia results from elevated glucose levels that exert an osmotic diuretic effect. True False

This statement is true. Polydipsia results from elevated glucose levels that exert an osmotic diuretic effect.

The anterior lobe of the pituitary produces its own hormones. True or False

This statement is true. The anterior lobe of the pituitary produces its own hormones. The anterior pituitary gland secretes 7 hormones: follicle -stimulating hormone, luteinizing horomone, adrenocorticotropic horomone, thyroid -stimulating horomone, prolactin, endorphins, and growth hormone.

Treatment of hyperthyroidism

Treatment of Grave's disease involves the use of antithyroid drugs (methimazole or propylthiouracil), radioactive iodine ablation or surgery. Exophthalmos and pretibial myxedema are not reversed with treatment. Topical steroids may be used for skin lesion flare-ups.

Channels can be opened by the binding of an ion or molecule to a specific membrane receptor that is closely associated with the channel (e.g. G proteins located inside the cell transmits signals from outside the cell to inside the cell).Signals are then transferred to an intracellular messenger (second messenger) which then triggers biochemical events within the cell. This is considered a second messenger? True or False

True

First messengers in cellular communication are extracellular signaling messengers that bind to the membrane receptors to either open or close specific membrane channels to regulate the movement of ions in or out of the cell. True or False

True

Glucagon Glucagon antagonizes insulin with a resulting increase in blood glucose during periods of fasting, exercise and hypoglycemia True False

True

Thyroid Cells and Substance Match the substance to the cell from which they are secreted in the thyroid below. Follicular cells: (T4) THyroxine Parafollicular cells (Calcitonin)

True Follicular cells - Thyroxine (T4) Parafollicular cells - Calcitonin

Lipid-derived hormones cross the cell membrane and bind to receptors in the cell's cytoplasm. True or False

True This statement is true. Lipid-derived hormones cross the cell membrane and bind to receptors in the cell's cytoplasm.

Pineal Gland The pineal gland is responsible for regulating the sleep-wake cycle. True False

True This statement is true. The pineal gland is responsible for regulating the sleep-wake cycle.

Diagnosing type 1 diabetes

Type 1 DM can be easily diagnosed when individuals present with the classic symptoms that include polydipsia, polyuria, polyphagia, weight loss and hyperglycemia. These are identified on fasting and postprandial glucose measurements.

Insulin Secretion due to hyperglycemia

When the beta cells are stimulated because of elevated glucose in the beta cell, it is transported via facilitated diffusion through a glucose transporter. As glucose continues to elevate in the beta cell, it causes the cell membrane to depolarize which allows an influx of calcium into the cell. Increased glucose in the beta cells also activate calcium-independent pathways that play a role in insulin secretion.

Graves disease

an autoimmune disease, is the most common cause of hyperthyroidism. It typically occurs in ages 30-40 years but may occur at any age. There is a familial connection associated with Grave's disease. Genetically, it is associated with HLA-B17 in Black individuals, HLA-Bw46 and HLA-B5 in Asian individuals, and HLA -B8 and HLA-DR3 histocompatibility antigens in Caucasian individuals. As an autoimmune disease, autoantibodies against the TSH receptor located on the follicular cells stimulate the thyroid gland. The autoantibodies involved include thyroid-stimulating antibodies (TSAbs) or thyroid receptor antibodies (TRAbs). They override the negative feedback system that normally occurs. Lymphocytes also infiltrate the receptor site. The effect of thyroid stimulating antibodies on the TSH receptor results in hyperplasia of the thyroid gland (goiter) and increased synthesis of thyroid hormone, especially T3.

polyphagia

excessive hunger

polyuria

excessive production of urine

polydipsia

excessive thirst

delta cells of pancreas

responsible for secreting gastrin and somatostatin

alpha cells of pancreas

responsible for secreting glucagon

beta cells of pancreas

responsible for secreting insulin and amylin inhibits glucagon secretion

F cells of pancreas

secrete pancreatic polypeptide that stimulates gastric secretions and antagonizes cholecystokinin.

Acanthosis nigricans

thickening and darkening of skin near axillary region, A/w Diabetes Type II and gastric carcinoma