Theme 6:
Endocrinology
Summary
1
,Content
Week 21: Obesity, metabolic syndrome and diabetes mellitus type II................................................... 6
Diabetes mellitus ................................................................................................................................. 6
Metabolic syndrome ....................................................................................................................... 6
Obesity............................................................................................................................................. 6
The endocrine gut ........................................................................................................................... 8
Carbohydrate metabolism................................................................................................................... 9
Transport of glucose through the cell membrane .......................................................................... 9
Storage of glycogen in liver and muscle .......................................................................................... 9
Release of energy from glucose molecules by the glycolytic pathway ........................................... 9
Oxidative phosphorylation .............................................................................................................. 9
Anaerobic glycolysis ........................................................................................................................ 9
Pentose phosphate pathway ......................................................................................................... 10
Gluconeogenesis ........................................................................................................................... 10
Lipid metabolism ............................................................................................................................... 11
Transport ....................................................................................................................................... 11
Fat deposits ................................................................................................................................... 11
Use of triglycerides for energy ...................................................................................................... 11
Synthesis of triglycerides from carbohydrates .............................................................................. 12
Regulation of energy release from triglycerides ........................................................................... 12
Phospholipids and cholesterol ...................................................................................................... 12
Atherosclerosis .............................................................................................................................. 12
Protein metabolism ........................................................................................................................... 14
Transport and storage of amino acids........................................................................................... 14
Functional roles of plasma proteins .............................................................................................. 14
Hormonal regulation of protein metabolism ................................................................................ 14
Dietary balances; regulation of feeding; obesity and starvation; vitamins and minerals ................. 16
Methods for determining utilisation of nutrients by the body ..................................................... 16
Regulation of food intake and energy storage .............................................................................. 16
Factors that regulate quantity of food intake ............................................................................... 17
Obesity........................................................................................................................................... 17
Vitamins ......................................................................................................................................... 17
Mineral metabolism ...................................................................................................................... 19
Energetics and metabolic rate........................................................................................................... 20
Anaerobic vs aerobic energy ......................................................................................................... 20
Metabolic rate ............................................................................................................................... 20
2
, Introduction to endocrinology .......................................................................................................... 21
Coordination of body function by chemical messengers .............................................................. 21
Chemistry, synthesis, storage and secretion of hormones ........................................................... 21
Mechanisms of hormonal action................................................................................................... 21
Feedback loops .............................................................................................................................. 22
Insulin, glucagon and diabetes mellitus ............................................................................................ 24
Chemistry, synthesis and metabolism of pancreatic hormones ................................................... 24
Insulin and its metabolic effects.................................................................................................... 24
Control of insulin secretion ........................................................................................................... 25
Glucagon and its functions ............................................................................................................ 25
Somatostatin ................................................................................................................................. 25
Diabetes mellitus ........................................................................................................................... 25
Diabetes mellitus ............................................................................................................................... 27
Gestational diabetes...................................................................................................................... 29
MODY ............................................................................................................................................ 29
Diabetic complications .................................................................................................................. 29
Lipid and metabolic disorders ........................................................................................................... 30
Hyperlipidaemia ............................................................................................................................ 30
Pharmacology .................................................................................................................................... 32
Treatment for diabetes ................................................................................................................. 32
Management of lipid disorders ..................................................................................................... 35
Week 22: Shoes do not fit ..................................................................................................................... 37
Pituitary hormones and their control by the hypothalamus ............................................................ 37
The pituitary gland and its relation to the hypothalamus............................................................. 37
Neurohypophysis........................................................................................................................... 37
Adenohypophysis .......................................................................................................................... 37
Hypothalamus ............................................................................................................................... 38
Adrenocortical hormones.................................................................................................................. 39
Chemistry of adrenocortical secretion .......................................................................................... 39
Physiological stress response ........................................................................................................ 40
Cushing’s syndrome ...................................................................................................................... 41
Cohn’s syndrome ........................................................................................................................... 41
Addison’s disease .......................................................................................................................... 42
Diagnosing endocrine disorders ........................................................................................................ 43
Measuring the hormone................................................................................................................ 43
Endocrine disorders........................................................................................................................... 46
3
, Growth hormone deficiency.......................................................................................................... 46
Acromegaly .................................................................................................................................... 46
Cushing’s syndrome ...................................................................................................................... 51
Primary and secondary adrenal insufficiency ............................................................................... 53
Prolactinoma ................................................................................................................................. 54
Diabetes insipidus.......................................................................................................................... 55
Syndrome of inappropriate ADH secretion ................................................................................... 56
Pharmacology .................................................................................................................................... 58
Week 23: The menstrual cycle .............................................................................................................. 61
Life course approach in women’s health .......................................................................................... 61
Risks of female reproductive characteristics................................................................................. 61
Mismatch hypothesis .................................................................................................................... 62
Reproductive medicine and ethical reflections................................................................................. 63
Anatomy of the female pelvis ........................................................................................................... 64
The pelvis ....................................................................................................................................... 64
Female reproductive organs.......................................................................................................... 68
Blood supply .................................................................................................................................. 71
Lymphatics..................................................................................................................................... 73
Innervation .................................................................................................................................... 74
Paediatric and adolescent gynaecology ............................................................................................ 76
Puberty .......................................................................................................................................... 77
Diagnostics..................................................................................................................................... 78
Disorders of the genital tract ........................................................................................................ 78
Vulvar pathology ........................................................................................................................... 78
Precocious puberty........................................................................................................................ 79
Delayed puberty ............................................................................................................................ 79
The menstrual cycle........................................................................................................................... 80
Sex steroids.................................................................................................................................... 80
Abnormal vaginal blood loss ............................................................................................................. 82
Abnormal cervical blood loss ........................................................................................................ 82
Abnormal uterine blood loss ......................................................................................................... 82
Uterus myxomatosis ...................................................................................................................... 83
Amenorrhoea .................................................................................................................................... 84
WHOI amenorrhoea ...................................................................................................................... 84
WHOII amenorrhoea ..................................................................................................................... 85
WHOIII amenorrhoea .................................................................................................................... 85
4
,Sexual differentiation and embryology of genital organs ................................................................. 87
Embryology .................................................................................................................................... 87
Chromosomal differentiation ........................................................................................................ 88
Male somatic differentiation ......................................................................................................... 88
Female somatic differentiation ..................................................................................................... 89
Uterine abnormalities ................................................................................................................... 91
Development of the external genitalia ......................................................................................... 91
The menopause, perimenopause and the postmenopause ............................................................. 93
Menopause .................................................................................................................................... 93
Postmenopausal bleeding ............................................................................................................. 96
Guidelines ...................................................................................................................................... 96
Hormonal contraception ................................................................................................................. 101
Forgotten pill ............................................................................................................................... 104
5
,Week 21: Obesity, metabolic syndrome and diabetes mellitus type II
Diabetes mellitus
Type I diabetes Type II diabetes
Definition Autoimmune disorder Often an cause of obesity
Presentation Usually slim, young people Usually obese, middle-aged people
Onset Sudden Gradual
Pathway Destruction of the β-cells by the Decreased insulin sensitivity
immune system → no more Lowered production of insulin
production of insulin
Complications Vascular:
Blindness
Myocardial infarction
Coronary heart disease
Amputations
Kidney failure
After >5-15 years after diagnosis
→ 20% presents with complications at diagnosis
Prevention Keep blood sugar stable
LADA = latent autoimmune diabetes of the adult
Type II diabetes is complicated:
• Hyperglycaemia
• Hypertension
• Dyslipidaemia
• Obesity
→ Multiple problems
Metabolic syndrome
= insulin resistance syndrome
Features:
• Central obesity
• Dyslipidaemia
• Low HDL
• Hypertension
• High fasted blood glucose
→ the patient must have 3/5
Obesity
BMI:
6
, • Normal weight: 18-25
• Overweight: 25-30
• Obesity: >30
Important: a lot of diseases people develop are comorbidities of obesity
Epidemiology: huge rise since 1985
Obesity lowers life expectancy: 8-10 years
Pathophysiology of appetite and food intake:
Causes of obesity:
• Genetic: e.g. FTO gene and MC4R (most frequent mutation)
• Hypothalamic
• Endocrine
• Medication
• Mental disorders
7
, • Lifestyle
The endocrine gut
Hormone Production Function
Gastrin Duodenum (G cells) Stimulate production of
stomach acid and motility
CCK Duodenum, jejunum (I cells) Stimulates bile and pancreatic
juice secretion
Secretin Duodenum, jejunum ( S cells) Stimulates HCO3- secretion
Inhibits gastrin
Vasoactive intestinal Enteric nervous system Stimulates water and
polypeptide (VIP) electrolyte secretion from the
gut
Motilin Throughout the gut Increases small intestine
motility
Gastric inhibitory Duodenum, jejunum (K cells) Stimulates insulin release
polypeptide
Somatostatin Stomach, small intestine and Inhibits digestive hormones
pancreas (D cells)
Ghrelin Stomach Hunger
Growth hormone release
Gastrin Stomach Acid secretion
Insulin Pancreas Uptake of glucose by the cells
Glucagon Pancreas Storage of glucose in the form
glycogen
Pancreas polypeptide Pancreas Gastric motility
Satiation
Amylin Pancreas Glucose homeostasis
Gastric motility
GLP-1 Intestines Incretin activity
Satiation
GLP-2 Intestines GI-motility and growth
Oxyntomodulin Intestines Satiation
Acid secretion
PYY Intestines Satiation
Leptin Adipose tissue Satiation
8
Endocrinology
Summary
1
,Content
Week 21: Obesity, metabolic syndrome and diabetes mellitus type II................................................... 6
Diabetes mellitus ................................................................................................................................. 6
Metabolic syndrome ....................................................................................................................... 6
Obesity............................................................................................................................................. 6
The endocrine gut ........................................................................................................................... 8
Carbohydrate metabolism................................................................................................................... 9
Transport of glucose through the cell membrane .......................................................................... 9
Storage of glycogen in liver and muscle .......................................................................................... 9
Release of energy from glucose molecules by the glycolytic pathway ........................................... 9
Oxidative phosphorylation .............................................................................................................. 9
Anaerobic glycolysis ........................................................................................................................ 9
Pentose phosphate pathway ......................................................................................................... 10
Gluconeogenesis ........................................................................................................................... 10
Lipid metabolism ............................................................................................................................... 11
Transport ....................................................................................................................................... 11
Fat deposits ................................................................................................................................... 11
Use of triglycerides for energy ...................................................................................................... 11
Synthesis of triglycerides from carbohydrates .............................................................................. 12
Regulation of energy release from triglycerides ........................................................................... 12
Phospholipids and cholesterol ...................................................................................................... 12
Atherosclerosis .............................................................................................................................. 12
Protein metabolism ........................................................................................................................... 14
Transport and storage of amino acids........................................................................................... 14
Functional roles of plasma proteins .............................................................................................. 14
Hormonal regulation of protein metabolism ................................................................................ 14
Dietary balances; regulation of feeding; obesity and starvation; vitamins and minerals ................. 16
Methods for determining utilisation of nutrients by the body ..................................................... 16
Regulation of food intake and energy storage .............................................................................. 16
Factors that regulate quantity of food intake ............................................................................... 17
Obesity........................................................................................................................................... 17
Vitamins ......................................................................................................................................... 17
Mineral metabolism ...................................................................................................................... 19
Energetics and metabolic rate........................................................................................................... 20
Anaerobic vs aerobic energy ......................................................................................................... 20
Metabolic rate ............................................................................................................................... 20
2
, Introduction to endocrinology .......................................................................................................... 21
Coordination of body function by chemical messengers .............................................................. 21
Chemistry, synthesis, storage and secretion of hormones ........................................................... 21
Mechanisms of hormonal action................................................................................................... 21
Feedback loops .............................................................................................................................. 22
Insulin, glucagon and diabetes mellitus ............................................................................................ 24
Chemistry, synthesis and metabolism of pancreatic hormones ................................................... 24
Insulin and its metabolic effects.................................................................................................... 24
Control of insulin secretion ........................................................................................................... 25
Glucagon and its functions ............................................................................................................ 25
Somatostatin ................................................................................................................................. 25
Diabetes mellitus ........................................................................................................................... 25
Diabetes mellitus ............................................................................................................................... 27
Gestational diabetes...................................................................................................................... 29
MODY ............................................................................................................................................ 29
Diabetic complications .................................................................................................................. 29
Lipid and metabolic disorders ........................................................................................................... 30
Hyperlipidaemia ............................................................................................................................ 30
Pharmacology .................................................................................................................................... 32
Treatment for diabetes ................................................................................................................. 32
Management of lipid disorders ..................................................................................................... 35
Week 22: Shoes do not fit ..................................................................................................................... 37
Pituitary hormones and their control by the hypothalamus ............................................................ 37
The pituitary gland and its relation to the hypothalamus............................................................. 37
Neurohypophysis........................................................................................................................... 37
Adenohypophysis .......................................................................................................................... 37
Hypothalamus ............................................................................................................................... 38
Adrenocortical hormones.................................................................................................................. 39
Chemistry of adrenocortical secretion .......................................................................................... 39
Physiological stress response ........................................................................................................ 40
Cushing’s syndrome ...................................................................................................................... 41
Cohn’s syndrome ........................................................................................................................... 41
Addison’s disease .......................................................................................................................... 42
Diagnosing endocrine disorders ........................................................................................................ 43
Measuring the hormone................................................................................................................ 43
Endocrine disorders........................................................................................................................... 46
3
, Growth hormone deficiency.......................................................................................................... 46
Acromegaly .................................................................................................................................... 46
Cushing’s syndrome ...................................................................................................................... 51
Primary and secondary adrenal insufficiency ............................................................................... 53
Prolactinoma ................................................................................................................................. 54
Diabetes insipidus.......................................................................................................................... 55
Syndrome of inappropriate ADH secretion ................................................................................... 56
Pharmacology .................................................................................................................................... 58
Week 23: The menstrual cycle .............................................................................................................. 61
Life course approach in women’s health .......................................................................................... 61
Risks of female reproductive characteristics................................................................................. 61
Mismatch hypothesis .................................................................................................................... 62
Reproductive medicine and ethical reflections................................................................................. 63
Anatomy of the female pelvis ........................................................................................................... 64
The pelvis ....................................................................................................................................... 64
Female reproductive organs.......................................................................................................... 68
Blood supply .................................................................................................................................. 71
Lymphatics..................................................................................................................................... 73
Innervation .................................................................................................................................... 74
Paediatric and adolescent gynaecology ............................................................................................ 76
Puberty .......................................................................................................................................... 77
Diagnostics..................................................................................................................................... 78
Disorders of the genital tract ........................................................................................................ 78
Vulvar pathology ........................................................................................................................... 78
Precocious puberty........................................................................................................................ 79
Delayed puberty ............................................................................................................................ 79
The menstrual cycle........................................................................................................................... 80
Sex steroids.................................................................................................................................... 80
Abnormal vaginal blood loss ............................................................................................................. 82
Abnormal cervical blood loss ........................................................................................................ 82
Abnormal uterine blood loss ......................................................................................................... 82
Uterus myxomatosis ...................................................................................................................... 83
Amenorrhoea .................................................................................................................................... 84
WHOI amenorrhoea ...................................................................................................................... 84
WHOII amenorrhoea ..................................................................................................................... 85
WHOIII amenorrhoea .................................................................................................................... 85
4
,Sexual differentiation and embryology of genital organs ................................................................. 87
Embryology .................................................................................................................................... 87
Chromosomal differentiation ........................................................................................................ 88
Male somatic differentiation ......................................................................................................... 88
Female somatic differentiation ..................................................................................................... 89
Uterine abnormalities ................................................................................................................... 91
Development of the external genitalia ......................................................................................... 91
The menopause, perimenopause and the postmenopause ............................................................. 93
Menopause .................................................................................................................................... 93
Postmenopausal bleeding ............................................................................................................. 96
Guidelines ...................................................................................................................................... 96
Hormonal contraception ................................................................................................................. 101
Forgotten pill ............................................................................................................................... 104
5
,Week 21: Obesity, metabolic syndrome and diabetes mellitus type II
Diabetes mellitus
Type I diabetes Type II diabetes
Definition Autoimmune disorder Often an cause of obesity
Presentation Usually slim, young people Usually obese, middle-aged people
Onset Sudden Gradual
Pathway Destruction of the β-cells by the Decreased insulin sensitivity
immune system → no more Lowered production of insulin
production of insulin
Complications Vascular:
Blindness
Myocardial infarction
Coronary heart disease
Amputations
Kidney failure
After >5-15 years after diagnosis
→ 20% presents with complications at diagnosis
Prevention Keep blood sugar stable
LADA = latent autoimmune diabetes of the adult
Type II diabetes is complicated:
• Hyperglycaemia
• Hypertension
• Dyslipidaemia
• Obesity
→ Multiple problems
Metabolic syndrome
= insulin resistance syndrome
Features:
• Central obesity
• Dyslipidaemia
• Low HDL
• Hypertension
• High fasted blood glucose
→ the patient must have 3/5
Obesity
BMI:
6
, • Normal weight: 18-25
• Overweight: 25-30
• Obesity: >30
Important: a lot of diseases people develop are comorbidities of obesity
Epidemiology: huge rise since 1985
Obesity lowers life expectancy: 8-10 years
Pathophysiology of appetite and food intake:
Causes of obesity:
• Genetic: e.g. FTO gene and MC4R (most frequent mutation)
• Hypothalamic
• Endocrine
• Medication
• Mental disorders
7
, • Lifestyle
The endocrine gut
Hormone Production Function
Gastrin Duodenum (G cells) Stimulate production of
stomach acid and motility
CCK Duodenum, jejunum (I cells) Stimulates bile and pancreatic
juice secretion
Secretin Duodenum, jejunum ( S cells) Stimulates HCO3- secretion
Inhibits gastrin
Vasoactive intestinal Enteric nervous system Stimulates water and
polypeptide (VIP) electrolyte secretion from the
gut
Motilin Throughout the gut Increases small intestine
motility
Gastric inhibitory Duodenum, jejunum (K cells) Stimulates insulin release
polypeptide
Somatostatin Stomach, small intestine and Inhibits digestive hormones
pancreas (D cells)
Ghrelin Stomach Hunger
Growth hormone release
Gastrin Stomach Acid secretion
Insulin Pancreas Uptake of glucose by the cells
Glucagon Pancreas Storage of glucose in the form
glycogen
Pancreas polypeptide Pancreas Gastric motility
Satiation
Amylin Pancreas Glucose homeostasis
Gastric motility
GLP-1 Intestines Incretin activity
Satiation
GLP-2 Intestines GI-motility and growth
Oxyntomodulin Intestines Satiation
Acid secretion
PYY Intestines Satiation
Leptin Adipose tissue Satiation
8
