Endocrinology lecture kodama k
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Endocrinology lecture kodama k
- 1. Introduction to Endocrinology Keiichi Kodama MD, PhD Assistant Professor - Institute for Computational Health Sciences, Department of Pediatrics, University of California, San Francisco 11-14-16 1
- 2. 2
- 3. 3 Today’s lecture • Principles of Endocrinology Endocrine system Hormones • Endocrine Organs Pituitary gland Growth hormone • Endocrine Diseases Diagnosis
- 5. Intercellular communication Nervous system One way & one to one 5
- 6. What is Endocrine system? Endocrine system • Intercellular communication system by chemical messengers; Hormones (hormone=arouse activity). Endocrine organs Blood stream 6
- 7. What are Hormones for? Hormone Functions • Maintain Internal Environment (e.g. body temperature, blood glucose levels.) • Control Growth • Control Sex Development and Function External Stimuli Homeostasis Hormones 7
- 8. Components of endocrine system Hormones Target Tissues Activity Information (Internal disturbances) Negative Feedback R Endocrine Tissues 8
- 9. Characteristics of Hormones • Chemical messengers produced/secreted by specialized cells in endocrine tissues. • Only target cells specifically respond. • Act in very small concentrations. The concentration of the biological substances (mM=mmole/l) • Na+ ion 140 mM • Cl- ion 110 mM • Glucose 5 mM The concentration of hormones (mM=mmole/l) • Insulin 6 x 10-8 mM • Growth Hormone 5 x 10-11 mM 9
- 10. Characteristics of Hormones • Chemical messengers produced/secreted by specialized cells in endocrine tissues. • Only target cells specifically respond. • Act in very small concentrations. Disturbances Imbalance of hormones sophisticated Endocrine Diseases 10
- 11. Endocrine Organs Pituitary gland Thyroid gland Parathyroid glands Adrenal glands Pancreas Gonads 11
- 15. Acromegaly • Pituitary adenoma (benign) • GH (protein hormone) ↑ 15
- 16. Diagnosis of Endocrine Diseases • General body examination (e.g. Height, Body weight, Face, Eyes, Hands, Body temperature, etc) • Patient’s complaints • General blood test (e.g. Na, K, Calcium, P, glucose and fat metabolism etc) • Hormone blood test • Imaging test X-ray (tumor, bone density) CT, MRI (tumor) 16
- 17. Therapy of Endocrine Diseases • Hypofunction Hormone replacement therapy • Hyperfunction Hormone synthesis inhibitors, Hormone antagonists • Surgery • Radiation 17
- 18. CASE 29-year-old male 【 Major complaint 】 Excessive sweating 【 history of present illness 】 May, 2014: High serum levels of ALP (335 U/L) was detected in the health examination. March, 2016: He has noticed an excessive sweating. May, 2016: High serum levels of ALP (405 U/L) and P (4.9 mg/dl) were detected in the examination. 【 past medical history 】 N/A 【 family history 】 N/A 【First visit medical condition】 Height 181cm、BW 74.1kg、BMI 23.7 kg/㎡。 BT 37.2℃、HR 70/min、BP 135/85mmHg。 Thickening of the lips, Loss of oval facial features, Prognathism18
- 19. AST ALT ALP BUN Cr Na Cl K Ca P FPG HbA1c 10.5 mg/dL 5.8 mg/dL 112 mg/dL 5.7 % 20 IU/L 20 IU/L 339 U/L 11 mg/dL 0.65 mg/dL 143 mEq/L 104 mEq/L 4.4 mEq/L Blood count WBC RBC Hb PLT 7630 /μL 4860K/μL 14.6 g/dl 284K/μL Biochemical test 5.34 ng/mL↑ 902 ng/mL↑ 7.5 ng/mL GH IGF-1 PRL Endocrinological test 11.9GH (ng/mL) 75gOGTT 5.70 8.67 Basal 30m 60m 104PG (mg/dL) 182 227 9.60 120m 16219
- 20. Turkish saddle X-P Finger X-P Heel X-P Heel pad 21mm Double floor Cauliflower-like change Pituitary MRI ６ｘ６ｍｍ adenoma in Turkish saddle 20
- 21. Summary • Hormones regulate nutrient- and mineral-metabolism for maintaining life and health, and controlling growth and reproduction. • Hormones regulate themselves by a feedback system. • Hormones are produced/secreted by specialized endocrine cells, and they work on only specific target cells (tissues) at a very small amount. • Most of patients with endocrine diseases indicate only a few complaints. It is important to suspect the disease by careful body examinations. sophisticated 21
Editor's Notes
- First of all, I’d like to thank you for giving me an opportunity to do a simulation class. My name is Keiichi Kodama. I’ve been working as a researcher in the US for 15 years. My work focuses on endocrinology, especially diabetes. Today I’m going to give you an introduction to endocrinology.
- Slide 2 This photo shows a very tall guy! His name was Robert Wadlow. He was the tallest man to have ever lived on Earth. The man standing next to him was his father, who was 1.8 meters tall. Robert was 2.7 meters tall, and he had an endocrine disease that made him keep growing. Let’s think what happened in his body by studying endocrinology. https://en.wikipedia.org/wiki/Robert_Wadlow
- This slide shows the overview of today’s lecture. First, I want to start from the basic Principles of Endocrinology. I will explain about endocrine system and its chemical messengers; hormones In the system, endocrine organs make many kinds of hormones. I want to show an example of them. I will focus on pituitary gland and growth hormone. Then, I want to talk about an example of endocrine diseases and its diagnosis.
- Slide 3 We have over 100 trillion cells in our bodies. Have you ever thought about so many cells in different parts of our bodies communicate? It’s interesting to think about how this can happen.
- When you hear about intercellular communication, your first thought might be about the nervous system. This communication is very quick. For instance, when you want to contract your muscle, you send a signal from your brain, which goes down a nerve that directly attaches to your muscle and makes it contract. This communication is one-way and one-to-one, and terminates in a second. This system is good when you need a quick response. But, as you know, our cells are damaged every day by environmental factors and external stimuli. To protect them and keep them healthy, we need another communication system that can send information to the 100 trillion cells in our body. This system is the endocrine system. It operates more slowly.
- The endocrine system is an intercellular communication system. It’s managed by chemical messengers called hormones. The word hormone is derived from a Greek word that means “arouse activity.” Hormones are made by endocrine organs in the body. These organs have cells that make hormones and secrete them into the blood stream. An example is the pituitary gland, which makes growth hormone. As you can probably guess, Robert Wadlow had a problem with his pituitary gland. It made too much growth hormone. Hormones are secreted into your blood stream, which transports them to your whole body. As different hormones arrive at different places, they are captured by target cells in organs with specific receptors for them. At this point, the target cells can affect your body. Cells without hormone receptors can’t respond to hormones. Hormones are kind of like radio waves. Endocrine cells are radio stations, and target cells are your radio, which is tuned to a certain station. Even if you’re far from the radio station, you can pick up music if your radio is tuned to the right station. A similar process occurs with the endocrine system. A hormone can be received only if there is a very specific receptor on a cell.
- This slide shows hormone functions. Hormones maintain your internal environment, such as your body temperature and your blood glucose levels. These are very important to our health, and they have to be kept in very narrow range. The process of keeping our internal systems balanced is called homeostasis. Hormones also control growth and sex development and function.
- The endocrine system is composed of 2 basic elements: endocrine tissues and target tissues. Endocrine tissues secrete hormones and target tissues receive them. Endocrine tissue can send information about internal disturbances via hormones. Target tissues receive the hormones and fix the disturbance. Here, one question may come to you — how does endocrine tissue know when to stop making a particular hormone? The answer is that endocrine tissues also have hormone receptors. When hormones reach the endocrine tissue and bind to it, they send a signal to stop making the hormone. This system is called a negative feedback system. It’s the basic system that hormones use to regulate themselves.
- This slide shows some important characteristics of hormones. First, they act in very small concentrations. The picture on the left shows the concentration of biomedical substances like salt and sugar in human body. If you have a spoon, you can make the same concentration in a cup of water. But if you want to make a physiological concentration of hormones using a spoon, you need to add the material to a 25 meter swimming pool.
- The endocrine system is very sophisticated, but this makes it susceptible to disturbances. For example, say that hormone production is changed inappropriately or a target cell’s receptor function is decreased. Hormone imbalance can occur, and you end up with endocrine disease.
- OK, here’s a list of endocrine organs. The first one is the pituitary gland at the base of the brain. This gland is called the master gland because it secretes stimulating hormones for other endocrine tissues. It’s very important because it activates other endocrine organs. The next one is thyroid gland, located right here in your neck. It wraps around your trachea. It makes thyroid hormones, whose main job is to regulate your body's metabolism. At the back side of thyroid gland, there are four spots known as the parathyroid. They’re hard to see here. Parathyroid hormone regulates blood calcium. It's also involved in muscle contraction and bone growth. The adrenal glands are on top of the kidneys. They help fight against body’s various stresses. The pancreas is here (point). It secretes insulin hormone. This hormone is vital, and problems with it result in diabetes. Moving down the body, we have the gonads. Gonad hormones are related to sex development and reproduction.
- This is the pituitary gland. As you can see, it makes hormones that stimulate other endocrine tissues and hormones that act directly on target tissues. For instance, it makes growth hormone. This hormone has a direct effect on most of cells in human body (such as bone, muscle, skin and hair) and involved in our growth. Problems with the pituitary can result in growth disorders. Robert Wadlow’s pituitary never stopped making growth hormone. The result was that he was still growing when he died at age 22.
- Robert Wadlow had a pituitary disease called pituitary hypertrophy. This term means that his pituitary was very big. His pituitary made much more growth hormone compared to other people. This disease occurred in his very young age when he was baby. For example, when he was 5 years old, attending kindergarten, his height was already 1.7 meters tall, that was equal to the average of high school students. He grew so tall, his bones could not support him and he needed to use braces on his legs so that he could stand up. 発症頻度は100万人あたり40 - 60人程度と言われている。 2万人に一人
- I want to indicate another example of hyper growth hormone disease. If a person has a tumor called a pituitary adenoma in adult age, and it makes too much growth hormone, the person would become acromegary. Acromegaly causes several characteristic symptoms in the face and hands. You can see skin and soft tissue thickness, and the enlargement of the end of chin and the enlargement of distal finger bones. 発症頻度は100万人あたり40 - 60人程度と言われている。 2万人に一人
- This slide shows how to think about diagnosing endocrine diseases. The most important thing is a general examination of the whole body. You need to look carefully at a patient’s face, eyes, hands, and whole body. You also have to listen carefully to the patient’s complaints. Some patients with endocrine disease have very few complaints, so sometimes you need to suspect the disease from careful body examination and only a little information. A general blood test is also helpful. You may be able to find abnormalities in electrolytes and glucose and fat metabolism. Those abnormalities may suggest a disturbance of homeostasis in your patient. Once you suspect an endocrine disease, you can order a hormone blood test. You can measure hormone levels directly in your patient’s blood, and you can diagnose hyper- or hypo-hormone disease. Imaging tests are also important. For example, you might find a tumor with imaging. You can also evaluate bone density with X-rays because some endocrine diseases induce osteoporosis.
- Now we can talk about treating endocrine diseases. When a patient has hypofunction, you can give the hormone itself. For example, in adrenal insufficiency, steroid hormones can be given orally. In diabetes, they can inject insulin. Antidiuretic hormones can be given by nasal drops. When a patient has hyperfunction, you can give synthesis inhibitors or antagonists. For, example, in hyperthyroidism, you can give the thyroid-hormone synthesis inhibitors or antagonists. If a patient has a hormone-producing tumor, you need to remove the tumor by surgery. If it’s malignant, you may be able to use radiation to reduce its size.
- Finally, I want to show an example of a person with an endocrine disease. This case is a 29-year-old man. His major complaint was excessive sweating for the last few months. A blood test 2 years ago showed an abnormality in alkaline phosphate (or ALP). He had the same problem recently. His phosphorus levels are also high. ALP and phosphorus are important for forming bone. So we can guess that the bone formation is increased in this patient. Then he visited our hospital. We found some characteristic features in his face. We found the thickening of the lips and loss of oval facial features. His chin seems to be long and turned up. From these features, we suspected acromegaly in this patient, and… 発症頻度は100万人あたり40 - 60人程度と言われている。 2万人に一人 リンを英語に訳すと phosphorus
- We performed a blood hormone test. We found that the levels of growth hormone and insulin-like growth factor-1 levels were elevated. We also performed an oral glucose tolerance test. In normal subjects, this test suppresses GH hormone levels. Growth hormone stayed high in this patient. GH <5 ng/ml IGF-1 <200 ng/ml ALP分画 ３の上昇あり（１：０％、２：17％（正常値 74-36）、３：76％（正常値 59-25）、４：０％、５：７％、６：０％）
- In an imaging test, we found a double floor in the Turkish saddle in his skull. This indicates that the pituitary is swelling. Next,a finger X-ray, showed that his distal finger bones were enlarged. We also found heel pad thickness, indicating soft tissue overgrowth. A brain MRI showed a pituitary adenoma. So, we diagnosed acromegaly caused by a pituitary adenoma. We performed surgery and removed the tumor. His symptoms are dramatically reduced now. Turkish saddle Heel pad 22mm以上で肥厚あり 冠状断T1強調画像 Gd造影早期 トルコ鞍上部左側に６ｘ６ｍｍ大の類円形の腫瘤性病変を認める。T1強調画像・T1強調画像のGd造影早期において低信号cauliflower-like change Although diabetic ketoacidosis (DKA) is recognized one of complications of acromegaly, it is very rare as only five cases ... There were double floor and ballooning in sella turcica Xp, a cauliflower-like change of the distal phalanx in finger Xp. in sella turcica
- At last, I would like to summarize the today’s lecture. Hormones regulate nutrient- and mineral- metabolism and keep homeostasis. They are crucial for maintaining life and health in humans, and hormones also control systemic growth and sexual reproduction. Hormones regulate themselves by a negative feedback system. Hormones are produced/secreted by specialized cells in endocrine organs, and they work on only target cells that have specific receptors, and hormones act at a very small amount. So this system is very sophisticated, but this makes it very susceptible to the disturbances. Most of patients with endocrine diseases indicate only a few complaints. So, it is very important to suspect the disease by finding the characteristic symptoms in careful body examinations. OK these are the last messages to all of you, today. Thank you very much. Do you have any questions?