ENDOCRINE Flashcards
What are the messengers in the endocrine system?
Hormones
How can hormones exert their effect at receptors?
The rate of enzymatic reactions
The transport of ions and molecules across cell
membranes
Gene expression and the synthesis of proteins
Electrical signalling pathways
What does the thyroid gland secrete?
Thyroxine
Calcitonin
What does thyroxine do?
Regulates metabolism
What does calcitonin do?
Inhibits release of calcium from the bones
What do parathyroid glands secrete?
Parathyroid hormone
What does parathyroid hormone do?
Stimulates the release of calcium from bones
What do islet cells in the pancreas secrete?
Insulin
Glucagon
What do the testes secrete?
Testosterone
What do the ovaries secrete?
Oestrogen
Progesterone
What does the adrenal medulla secrete?
Adrenaline
What does the adrenal cortex secrete?
Corticosteroids
Aldosterone
Testosterone
What does the pineal gland secrete?
Melatonin
Types of hormones?
Peptides
Steroids
Amino acid derivatives
Examples of peptide hormones?
Insulin
Glucagon
Prolactin
ACTH
Examples of steroid hormones?
Cortisol
Aldosterone
Oestrogen
Progesterone
Testosterone
Examples of amino acid derivative hormones?
Adrenaline
Thyroxine
How are peptide hormones synthesized?
As prohormones requiring further processing to activate
How are steroid hormones synthesized?
From cholesterol
How are amino acid derivative hormones synthesized?
From tyrosine
How are peptide hormones stored?
In vesicles, secretion regulated
How are steroid hormones stored?
They are not, they are released immediately
How are amino acid derivative hormones stored?
Stored in various ways
What is reproductive endocrinology?
The study of hormones involved in reproduction and reproductive development
What are the main sex hormones?
- Androgens
- Oestrogens
- Progestogens
What is the role of androgens?
Male sex hormones/Masculinising agents
What is the function of testosterone?
Critical for generation of sperm and development and maintenance of masculine characteristics
What does oestradiol control?
Development and maintenance of feminine characteristics and stimulates growth of the egg follicle
What is the function of progesterone?
Stimulates growth of the endometrial lining of the uterus to prepare it for pregnancy
How is the synthesis and release of sex hormones regulated?
By the hypothalamic-pituitary axis
What does GnRH stand for?
Gonadotropin-Releasing Hormone
What are the functions of FSH and LH?
- Promote sex hormone production
- Promote gametogenesis
What is the primary function of the testes?
- Produces testosterone
- Produces spermatozoa
What is the primary function of the ovaries?
- Produces oestradiol
- Produces progesterone
- Produces ova
What is spermatogenesis?
The process of sperm cell development
What triggers the onset of puberty in males?
High pulses of GnRH
What does testosterone stimulate in males?
- Development of secondary sex characteristics
- Spermatogenesis
What is the role of Sertoli cells?
- Provide nutrients to developing germ cells
- Regulate FSH production
- Secrete seminal fluid
How long does the entire process of spermatogenesis take?
60-64 days
What is the average sperm production per day in males?
Approximately 30 million sperm
What are the three phases of the menstrual cycle?
- Follicular Phase
- Ovulation Phase
- Luteal Phase
What happens during the follicular phase of the menstrual cycle?
A follicle develops into a mature follicle
What is the average onset of puberty in females?
Age 11
What hormones promote ovulation and sex hormone production in females?
- Follicle Stimulating Hormone (FSH)
- Luteinising Hormone (LH)
The menstrual cycle lasts how many days?
21-35 days
What occurs if fertilisation does not take place during the menstrual cycle?
The endometrial lining is shed (menstruation)
What regulates the menstrual cycle tightly?
Hormones
What are the critical roles of Leydig cells?
Respond to LH and promote testosterone synthesis
What is inhibin’s role in male reproductive endocrinology?
Regulates FSH production in a negative feedback loop
Fill in the blank: The testes are the site of _______.
[testosterone production and spermatogenesis]
True or False: Oestradiol is produced in the testes.
False
What are the three phases of the menstrual cycle?
- Follicular Phase 2. Ovulatory Phase 3. Luteal Phase
What is the duration of the Follicular Phase?
Lasts from 9 to 23 days
What occurs during the Ovulatory Phase?
The release of the oocyte
How long does the Ovulatory Phase last?
1 to 3 days
What marks the beginning of the Luteal Phase?
Development of the corpus luteum
What is the duration of the Luteal Phase?
13 to 14 days
What hormone surge stimulates ovulation?
LH (Luteinizing Hormone)
What stimulates follicular growth in the Follicular Phase?
Increase in FSH (Follicle Stimulating Hormone)
What do theca cells respond to and what do they synthesize?
Respond to LH and synthesize testosterone
What do granulosa cells respond to and what do they synthesize?
Respond to FSH and synthesize oestradiol from testosterone
What is the role of inhibin released by the follicle?
Inhibits the production of FSH
What is the corpus luteum and what does it produce?
A yellow mass of cells that secretes progesterone, oestradiol, and inhibin
What is the function of progesterone during the menstrual cycle?
Stimulates the growth of the endometrial lining of the uterus
What happens if fertilization occurs?
HCG ensures survival of the corpus luteum
What does the combined oral contraceptive pill (COCP) contain?
An estrogen and progestogen
How does the COCP prevent ovulation?
By suppressing the release of gonadotropins (FSH and LH)
What is the significance of human chorionic gonadotropin (HCG)?
Ensures survival of the corpus luteum
What is a zygote?
The cell formed by the union of two gametes
What term describes the early developmental stage after fertilization?
Conceptus
What does totipotent mean?
The cell has the capacity to develop into a complete organism
What are trophoblasts and their role?
Form the outer layer of a blastocyst and provide nutrients to the developing embryo
What does the presence of HCG in urine or blood indicate?
Pregnancy
What happens to the corpus luteum after three months of pregnancy?
Degenerates due to a fall in HCG
What is the role of oxytocin during labor?
Important in contractions
What is menopause?
The ending of menstruation
Fill in the blank: The mucous membrane that lines the uterus is called the _______.
endometrium
True or False: The corpus luteum is responsible for producing oestradiol during the luteal phase.
True
What is hCG and its role during pregnancy?
hCG is produced by trophoblasts and ensures the survival of the corpus luteum.
hCG stands for human chorionic gonadotropin, a hormone crucial for maintaining pregnancy.
What hormones are involved in the preparation of the uterus for delivery?
Progesterone and oestrogen prepare the uterus for delivery.
These hormones are essential for maintaining pregnancy and preparing the body for childbirth.
What is the function of human placental lactogen?
Human placental lactogen is involved in metabolism, breast development, and lactation.
This hormone is produced by the placenta and plays a significant role in preparing the mother’s body for breastfeeding.
What is the role of oxytocin during childbirth?
Oxytocin is important for contractions of the uterus.
It is released from the posterior pituitary gland and plays a crucial role in labor.
What is the difference between an embryo and a fetus in terms of development?
An embryo is present for the first 2 months, while it is referred to as a fetus from 2 months onward.
How long does a typical pregnancy last?
Approx. 40 weeks.
What triggers the release of oxytocin during childbirth?
Baby pushing against the cervix activates stretch receptors, sending a message to the hypothalamus to release oxytocin.
This process is part of the body’s natural response to labor.
What effect does oxytocin have on the uterus during labor?
Oxytocin causes contractions of the smooth muscles of the uterus, pushing the baby further down the birth canal.
What is the mechanism of positive feedback in childbirth?
The release of oxytocin causes further contractions, which activate more stretch receptors, leading to more oxytocin release.
What happens to the release of oxytocin upon birth?
The stretching of the cervix halts, stopping the release of oxytocin.
List some medical uses of oxytocin.
- To induce labor
- To accelerate labor
- To stop bleeding after delivery (routinely administered after caesarean delivery)
What is endocrinology?
The study of hormones.
What are hormones?
Chemical messengers secreted into the blood that exert their effect on a distal target.
What is the typical concentration range for hormones in the body?
Nanomolar (10^-9 M) to picomolar (10^-12 M).
List some functions regulated by hormones.
- Growth * Development * Metabolism * Temperature * H2O balance * Reproduction
Where is the hypothalamus located?
Below the thalamus.
What is the sella turcica?
A bone socket at the base of the skull that houses the pituitary gland.
What is the role of the hypothalamic pituitary axis?
It serves as a major link between the endocrine and nervous system.
What is the anterior pituitary often referred to as?
The master gland.
How many different tropic hormones does the hypothalamus secrete?
7 different tropic hormones.
What is a tropic hormone?
Hormones that act on other endocrine glands to stimulate synthesis/release of a hormone.
Name one hormone synthesized and secreted from the anterior pituitary.
TSH (Thyroid Stimulating Hormone).
What does ACTH stand for?
Adrenocorticotropic Hormone.
What does LH do?
Acts on gonads and stimulates production and secretion of sex hormones/ovulation.
What is the function of FSH?
Stimulates the development of egg and sperm and secretion of sex hormones.
What is the role of Prolactin?
Stimulates milk secretion.
What does Growth Hormone (GH) stimulate?
Growth and energy metabolism.
What are the two hormones synthesized in the posterior pituitary?
- Oxytocin * Antidiuretic Hormone (ADH)
What is the function of oxytocin?
Controls uterine contractions during labor and promotes milk flow in nursing mothers.
What is the role of Antidiuretic Hormone (ADH)?
Increases water reabsorption and regulates water balance in the body.
What is an endocrine disorder?
Results from the improper function of the endocrine system.
Name a common endocrine disorder.
Type 1 Diabetes Mellitus.
What causes an endocrine disorder?
Hormone imbalance, genetic disorder, infection or disease, injury to endocrine gland, endocrine tumor.
What is primary hypofunction?
The cause of the disorder is in the peripheral (target) endocrine gland.
What is secondary hyperfunction?
The cause of the hormonal secretion disorder of the peripheral gland is in the anterior pituitary.
What does tertiary hypofunction refer to?
The cause of secretion disorder of peripheral gland is in the hypothalamus.
What is cortisol?
A steroid hormone released from the adrenal gland
How does cortisol increase blood glucose?
By promoting gluconeogenesis, causing breakdown of skeletal muscle protein, and enhancing lipolysis
These processes provide substrates for glucose production and fatty acids for other tissues.
What is the permissive effect of cortisol?
It requires the presence of glucagon for its action
What is the synergistic effect of cortisol?
It works synergistically with glucagon and catecholamines
What effect does cortisol have on the immune system?
It suppresses the immune system by preventing cytokine release and antibody production
What is hydrocortisol used for?
As an immunosuppressive drug
What impact does cortisol have on plasma calcium levels?
Decreases plasma calcium by causing bone breakdown and increasing intestinal calcium absorption while increasing renal calcium excretion
How does cortisol influence brain function?
It affects memory and mood
What is hypercortisolism?
A condition characterized by excessive cortisol, often referred to as Cushing’s syndrome
What are the common causes of hypercortisolism?
Tumor of the adrenal gland, pituitary tumor secreting excess ACTH, corticosteroid treatment for autoimmune disorders, ectopic ACTH production
List some symptoms of hypercortisolism.
- Increased appetite and food intake
- Weight gain
- Increased fat deposits in face and trunk
- Immunosuppression
- Osteoporosis
- Hyperglycaemia
- Depression and difficulties with learning and memory
What is hypocortisolism?
A condition characterized by low cortisol levels, often associated with Addison’s disease
What causes hypocortisolism?
Autoimmune destruction of the adrenal cortex, rare genetic causes, exogenous cortisol leading to adrenal atrophy
List some symptoms of hypocortisolism.
- Muscle weakness and fatigue
- Weight loss and decreased appetite
- Darkening of the skin (hyperpigmentation)
- Low blood pressure
- Salt craving
- Low blood sugar (hypoglycaemia)
- Nausea, diarrhea, or vomiting
- Muscle or joint pains
- Irritability/Depression
- Body hair loss or sexual dysfunction in women
What is diabetes mellitus?
A condition with chronically raised blood glucose concentration due to a lack of insulin and/or a deficiency in insulin action.
What fasting glucose level is classified as diabetes according to WHO?
Over 7mM.
What is the peak age of onset for Type 1 diabetes mellitus?
12 years.
What percentage of all diabetics does Type 1 diabetes account for?
Approx. 8%.
What is the peak age of onset for Type 2 diabetes mellitus?
60 years.
What percentage of all diabetics does Type 2 diabetes account for?
Approx. 90%.
What is a common characteristic of over 85% of Type 2 diabetics?
They are obese.
What is gestational diabetes?
Diabetes occurring in 4-5% of pregnancies.
What percentage of diabetics in the UK have Type 1 diabetes?
Approx. 8%.
What causes Type 1 diabetes?
T cell mediated autoimmune destruction of pancreatic beta-cells.
What are the clinical features of Type 1 diabetes?
- Hyperglycaemia
- Glycosuria
- Polyuria
- Polydipsia
- Weight loss
- Pear drop breath.
What is glycosuria?
High levels of glucose in the urine.
What causes polyuria in diabetes?
Exceeding renal threshold creates osmotic drag and increased diuresis.
What is the significance of C-peptide in Type 1 diabetes?
No C-peptide detectable.
What is diabetic ketoacidosis (DKA)?
A life-threatening condition due to starvation activating ketogenesis.
What is the normal HbA1c level?
Below 42 mmol/mol (6.0%).
What is the HbA1c level range for prediabetes?
42 to 47 mmol/mol (6.0 to 6.4%).
What is the HbA1c level for diabetes?
48 mmol/mol (6.5% or over).
Who discovered insulin and when?
Frederick Banting and Charles H. Best in 1921.
What is the treatment for Type 1 diabetes?
- Insulin injections
- Insulin pumps
- Pancreas transplantation
- Islet transplantation.
What causes hypoglycaemia?
Too much insulin and/or not enough food, vigorous exercise, or excessive alcohol.
What are common symptoms of hypoglycaemia?
- Shakiness
- Anxiety
- Tiredness
- Weakness
- Sweating
- Hunger
- Dizziness.
What is the primary cause of diabetic ketoacidosis?
Cellular glucose starvation activating ketogenesis.
What are the long-term complications of hyperglycaemia?
- Eye damage (retinopathy)
- Kidney damage (nephropathy)
- Nerve damage (neuropathy)
- Heart disease
- Stroke.
What percentage of Type 1 diabetes cases are caused by autoimmune response?
90%.
What triggers the adaptive immune response in Type 1 diabetes?
Exposure to self antigens.
What are the two arms of the adaptive immune response?
- Cell-mediated immune response
- Humoral/antibody-mediated immune response.
What are the two arms of the adaptive immune response?
Cell-mediated immune response and Humoral/antibody mediated immune response
Cell-mediated involves T cells, while humoral involves B cells.
What is the role of Helper T-Cells (CD4 cells)?
Secrete cytokines when activated and recruit other immune cells
They stimulate B cells to proliferate.
What do Cytotoxic T-cells (CD8 cells) secrete when activated?
Enzymes perforin and granzyme
These enzymes kill ‘infected’ cells.
What is the function of the T-cell receptor (TCR)?
T cells express an antigen-binding receptor on their membrane.
What does Major Histocompatibility Complex (MHC) do?
Presents antigens to T cells and activates them.
Which cells express MHC I?
All nucleated cells
They present antigenic peptides to Cytotoxic T cells.
What type of cells express MHC II?
Antigen Presenting Cells (APCs) including dendritic cells, macrophages, Langerhans cells, and B cells.
What do MHC CLASS 1 molecules present?
Endogenous antigens originated from the cytoplasm.
What do MHC CLASS 2 molecules present?
Exogenous antigens originated extracellularly from foreign bodies such as pathogens.
What is evidence for a cell-mediated immune response in Type 1 diabetes?
Healthy islet insulitis with many T-cells in the infiltrate, predominance of cytotoxic T-cells (CD8+VE).
What percentage of type-1 diabetics have antibodies directed against islet cell proteins?
85-90%.
Name some antibodies detected in type-1 diabetics.
- Proinsulin (IAA) * Glutamic acid decarboxylase (GAD) * IA-2 (IA-2A) * Zinc transporter (ZnT8A)
What is the genetic concordance in identical twins for Type 1 Diabetes?
50% concordance.
What are diabetes susceptibility genes?
Single nucleotide polymorphisms that increase the probability of developing type 1 diabetes.
What major genetic determinants are associated with Type 1 Diabetes?
Polymorphisms of class II HLA genes encoding DQ and DR.
What percentage of Caucasian type 1 diabetic subjects carry HLA-DR3/DR4 haplotype?
95%.
What environmental triggers are associated with Type 1 diabetes?
- Viruses: Coxsackie-B virus, Rubella, Mumps * Toxins: streptozotocin and alloxin * Diet: cow’s milk, smoked fish (nitrosamines) * Vitamins: low vitamin D
What happens during the autoimmune destruction of beta-cells?
Beta cell injury results in release of antigens and cytokines.
What do B cells generate in response to beta-cell injury?
Autoantibodies.
What role do activated autoreactive CD4+ T cells play in Type 1 Diabetes?
They recruit CD8+ cytotoxic T cells and other inflammatory cells, resulting in destructive insulitis.
What leads to the further recruitment and activation of T lymphocytes?
Production of pro-inflammatory cytokines by APCs and T-cells.
What is a sign of beta cell injury?
Apoptosis/necrosis.
What is the normal plasma glucose concentration range when fasting?
4.0 to 5.4 mmol/L (72 to 99 mg/dL)
What is the plasma glucose concentration two hours after eating?
7.8 mmol/L (140 mg/dL)
What is the total glucose content in a 380ml bottle of Lucozade that contains 17.9g of glucose per 100ml?
68.02g of glucose
What is the average blood volume in an adult male?
Approximately 5 litres
What is the glucose concentration in blood if all glucose from Lucozade was absorbed?
75.5 mmol/L or 1350 mg/dL
What hormone is secreted from pancreatic beta-cells?
Insulin
What is the primary function of insulin?
Lowers blood glucose
What percentage of the pancreas is composed of exocrine tissue?
98%
What is the role of the exocrine pancreas?
Secretes digestive enzymes and bicarbonate ions into the pancreatic duct
What are the Islets of Langerhans?
Clusters of endocrine cells in the pancreas that secrete hormones into the blood
What percentage of islet cells are beta cells, and what do they secrete?
70% secrete insulin
What is the function of glucokinase in beta cells?
Phosphorylates glucose
What triggers the exocytosis of insulin from beta cells?
Rise in intracellular calcium
What is the characteristic pattern of glucose-stimulated insulin secretion?
Biphasic: rapid first phase followed by prolonged second phase
What is the primary receptor type for insulin action?
Receptor Tyrosine Kinase
What processes does insulin promote in the liver?
- Glycogenesis * Lipogenesis * Glycolysis
What hormone increases blood glucose levels and is secreted from pancreatic alpha cells?
Glucagon
What is the effect of cortisol on glucose metabolism?
Promotes gluconeogenesis and enhances lipolysis
True or False: Glucagon acts on muscle cells.
False
What is the diurnal cycle of cortisol secretion linked to?
Stress and low blood-glucose concentration
Fill in the blank: The pancreas lies below the ______ and behind the ______.
[liver], [stomach]
What is the role of insulin in glucose homeostasis?
Maintains glucose levels by promoting uptake and storage
What is the effect of hyperglycemia on the body?
Can lead to coma and death
What does the oral glucose tolerance test (OGTT) measure?
Changes in blood glucose after glucose ingestion
What is the importance of insulin’s biphasic release pattern?
Allows for rapid response to changes in blood glucose
What are the components of the pancreatic juice secreted by exocrine cells?
- Digestive enzymes * Bicarbonate ions
What is the role of sodium-glucose cotransporter (SGLT1)?
Facilitates glucose absorption in the small intestine
What condition can corticosteroids lead to in relation to blood glucose?
Steroid-induced diabetes
What effect does cortisol have on glucose production when combined with glucagon or epinephrine?
Cortisol markedly accentuates hyperglycaemia produced by glucagon and/or epinephrine
This effect is significant in the context of glucose metabolism regulation.
What is the mechanism of action (MOA) of cortisol in glucose production?
- Promotes gluconeogenesis in liver
- Causes breakdown of skeletal muscle protein for gluconeogenesis
- Enhances lipolysis to provide fatty acids for other tissues
- Counteracts effects of insulin
These actions help maintain blood glucose levels.
What can synthetic cortisol medication lead to in diabetic patients?
Insulin resistance
This may require diabetic patients to take more medication.
What hormones increase during exercise to promote glucose availability?
- Glucagon
- Noradrenaline
- Adrenaline
These hormones increase glycogenolysis and gluconeogenesis.
What role does cortisol play during sustained aerobic exercise?
Promotes gluconeogenesis when carbohydrate resources are depleting
This is crucial for maintaining energy levels during prolonged exercise.
What hormones increase lipase enzyme activity during sustained exercise?
- Cortisol
- Growth hormone
- Noradrenaline
- Adrenaline
Increased lipase activity enhances the oxidation of fatty acids (lipolysis).
Fill in the blank: Cortisol promotes ______ during aerobic exercise when carbohydrate resources are depleting.
gluconeogenesis
True or False: Insulin has a positive effect on glucose production from the liver.
False
Insulin generally decreases glucose production.
What is the effect of glucagon on glucose production?
Increases glucose production from the liver
Glucagon plays a critical role in raising blood glucose levels.
What are the states that affect glucose homeostasis?
- Fed
- Fasted
- Stress
- Exercise
These states influence hormonal responses and glucose metabolism.
Who were the first to isolate insulin for clinical use?
Banting and Best in 1921.
What process did Walden discover to maintain insulin potency?
Isoelectric precipitation.
What type of insulin was first marketed by Lilly in October 1923?
Iletin®.
When was the first human insulin marketed?
1982.
What is recombinant insulin?
Human insulin obtained through recombinant DNA technology.
What are the main groups of insulin based on their molecular association?
- Hexamer
- Dimer
- Monomer
What is the lag phase associated with soluble human insulin?
The time between injection of hexamers and availability of biologically active dimers and monomers.
What is NPH insulin and when was it introduced?
Intermediate-acting insulin introduced in 1946.
What is the primary characteristic of NPH insulin?
Crystalline suspension with prolonged action.
What are the characteristics of Semilente, Ultralente, and Lente insulins?
- Semilente: Amorphous, duration of action 12-14 hours
- Ultralente: Crystalline, duration of action >30 hours
- Lente: Mixture of Ultralente and Semilente, duration of action ~24 hours
What modification does insulin glargine have?
Replaces one amino acid with two at the end of the B chain.
What is the significance of the pH change in insulin glargine upon injection?
It microprecipitates due to reduced solubility at physiological pH.
How does insulin detemir differ from other insulins?
One amino acid is omitted and replaced with a fatty acid.
What is the mechanism of action for rapid-acting insulins like Lispro?
Modifications prevent dimer and hexamer formation, allowing only monomers.
What is the FDA’s recent guidance regarding insulin biosimilars?
To help sponsors bring insulin biosimilars and interchangeable products to market more quickly.
What are the risks associated with insulin pumps?
- Skin infection
- Ketoacidosis if flow is interrupted
- Pump site must be moved every 2-3 days
What is the function of Medtronic’s MiniMed 670G system?
Automatically monitors glucose and provides appropriate basal insulin doses.
What is inhaled insulin and its market history?
A dry powder formulation of recombinant human insulin; Exubera marketed briefly but removed due to poor sales.
What technology does Buccal insulin (Oralin®) use for delivery?
RapidMist™ technology.
What is CholestosomeTM technology in oral insulin delivery?
A lipid-based particle used to encapsulate insulin for oral administration.
What recent development has shown promise for oral insulin delivery?
Oramed Pharmaceuticals’ insulin capsule trials have shown significant glucose level reduction.
What is the purpose of a glucose-responsive nanogel?
Acts as an artificial liver to maintain glucose concentrations safely.
What was discovered about taking oral insulin once a day at night?
It had a statistically meaningful effect on lowering blood glucose over a full 24 hours.
What is the purpose of the glucose-responsive nanogel?
It acts as an artificial liver for hyperglycemia treatment.
How long do the nanogels keep glucose concentrations within a safe range?
At least 6 hours.
What is a key feature of the glucose-responsive nanogel?
It cannot reduce blood sugar to an unsafe level.
What type of insulin delivery system provides both rapid and slow release?
Glucose-responsive nanoparticles.
How long does a single subcutaneous injection of glucose-responsive nanoparticles provide glycemic control in diabetic mice?
16 hours.
What is the title of the review article on oral delivery of insulin?
Oral delivery of insulin for treatment of diabetes: status quo, challenges and opportunities.
What is one method of insulin delivery mentioned that uses microneedles?
Transdermal delivery.
What type of nanoparticles are used for oral delivery of insulin?
Lipid nanoparticles.
What emerging technology is discussed in the context of insulin delivery?
Micro- and nano-technology delivery.
What is Type 1 diabetes?
A chronic condition where the pancreas produces little or no insulin.
At what age is Type 1 diabetes most commonly diagnosed?
It is most commonly diagnosed in children and young adults.
True or False: Type 1 diabetes can be prevented.
False.
What is the primary method for diagnosing Type 1 diabetes?
Blood tests measuring blood glucose levels.
What is the normal range for fasting blood glucose levels?
Less than 5.6 mmol/L.
Fill in the blank: A fasting blood glucose level of ___ mmol/L or higher indicates diabetes.
7.0
What are common symptoms of Type 1 diabetes?
Increased thirst, frequent urination, extreme fatigue, and blurred vision.
Which blood test is used to measure average blood glucose over the past 2-3 months?
HbA1c test.
What HbA1c level indicates diabetes?
An HbA1c of 6.5% or higher.
True or False: Type 1 diabetes is an autoimmune disease.
True.
What is the role of insulin in the body?
Insulin helps regulate blood glucose levels by facilitating the uptake of glucose into cells.
What is the typical treatment for Type 1 diabetes?
Insulin therapy.
Fill in the blank: Type 1 diabetes is also known as ___ diabetes.
insulin-dependent
What is the significance of ketones in Type 1 diabetes?
Ketones are produced when the body starts breaking down fat for energy due to lack of insulin.
What is diabetic ketoacidosis?
A serious complication that occurs when ketone levels become dangerously high.
How often should individuals with Type 1 diabetes monitor their blood glucose levels?
Typically several times a day.
What is the purpose of a Continuous Glucose Monitor (CGM)?
To provide real-time blood glucose readings throughout the day.
True or False: Type 1 diabetes can develop suddenly.
True.
What is the typical onset age range for Type 1 diabetes?
Usually between ages 5 and 20.
Which hormone is absent in individuals with Type 1 diabetes?
Insulin.
What lifestyle changes are recommended for managing Type 1 diabetes?
Healthy eating, regular physical activity, and blood glucose monitoring.
Fill in the blank: The UK screening program for Type 1 diabetes focuses on ___ symptoms.
classic
What is the role of the healthcare team in managing Type 1 diabetes?
To provide education, support, and medical care for effective diabetes management.
What is the long-term risk of poorly managed Type 1 diabetes?
Increased risk of complications such as heart disease, kidney failure, and neuropathy.
True or False: People with Type 1 diabetes can lead a normal life.
True.
What type of insulin regimen is commonly used in Type 1 diabetes management?
A combination of basal and bolus insulin.
What is the function of the ovaries?
Production of oocytes and hormones such as estrogen and progesterone
Ovaries play a crucial role in the female reproductive system.
What are granulosa and theca cells?
Granulosa cells nourish developing oocytes and produce estrogen; theca cells synthesize testosterone.
Both cell types are essential for follicular development.
What are the stages of the menstrual cycle?
Follicular phase, ovulatory phase, luteal phase
Each phase is characterized by specific hormonal changes and physiological events.
How are female sex hormones regulated?
Hormones such as GnRH, FSH, and LH regulate the production and release of estrogen and progesterone.
This regulation is critical for the menstrual cycle and reproductive health.
What hormonal changes occur during pregnancy?
Increased levels of progesterone and human chorionic gonadotropin (HCG).
These hormones support pregnancy and maintain the uterine lining.
What are the primary causes of female infertility?
Hormonal imbalances, structural issues, age, and health conditions.
Factors affecting fertility can vary widely among individuals.
What is gametogenesis?
The process of producing gametes (sperm and eggs) through meiosis.
This process results in genetically distinct daughter cells.
What determines genetic sex?
Sex chromosomes: XX for females and XY for males.
The inheritance of sex chromosomes from parents determines an individual’s genetic sex.
What is the role of the SRY gene?
Encodes a transcription factor that initiates male sexual differentiation.
The presence of the Y chromosome and SRY gene leads to the development of male characteristics.
What is the significance of the Anti-Müllerian hormone (AMH)?
Induces degeneration of Müllerian ducts, preventing female reproductive tract development in males.
AMH is critical for male sexual differentiation.
Describe oogenesis.
The process of egg formation in the ovaries, starting in fetal life and resuming at puberty.
It involves meiotic division leading to the production of a secondary oocyte and a polar body.
What triggers the onset of puberty in females?
High pulses of Gonadotropin Releasing Hormone (GnRH).
GnRH stimulates the release of FSH and LH from the anterior pituitary.
What are the phases of the menstrual cycle based on follicular histology?
Follicular phase, ovulatory phase, luteal phase
Each phase is defined by specific hormonal and physiological changes.
What is the role of the corpus luteum?
Produces progesterone and estrogen to prepare the uterine lining for potential pregnancy.
If fertilization does not occur, the corpus luteum degenerates.
What is the average length of the menstrual cycle?
21-35 days from the first day of bleeding to the last day before the next bleed.
The cycle length can vary among individuals.
What hormones are involved in the regulation of the menstrual cycle?
Gonadotropin Releasing Hormone (GnRH), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), estrogen, and progesterone.
These hormones work together to regulate the cyclic nature of the menstrual cycle.
Fill in the blank: The combined oral contraceptive pill (COCP) includes an estrogen and _______.
progestogen
COCP is used to prevent ovulation and regulate menstrual cycles.
True or False: The luteal phase follows ovulation and involves the development of the corpus luteum.
True
This phase is critical for preparing the uterus for possible implantation.
What occurs during the ovulatory phase?
Release of the oocyte from the mature follicle.
This phase is characterized by a surge in LH levels.
What happens if fertilization does not occur?
The endometrial lining sheds during menstruation.
This process is a key part of the menstrual cycle.
How does the contraceptive implant work?
Releases progestogen to prevent pregnancy for up to 3 years.
It is an effective long-term contraceptive method.
What is the impact of menopause on the menstrual cycle?
Cessation of menstruation due to depletion of ovarian follicles and reduced sensitivity to FSH and LH.
Menopause typically occurs between ages 45-55.
What is the role of corpus luteum?
Secretes progesterone to either regrow the uterine lining or support pregnancy.
What primarily causes menopause?
Depletion of the finite pool of follicles and reduced sensitivity to FSH and LH.
What are the consequences of menopause?
Cessation of the menstrual cycle, excess of LH and FSH, deficiency in Oestrogen and Progesterone.
Define corpus luteum.
A yellow mass of cells that forms from an ovarian follicle during the luteal phase of the menstrual cycle.
What is menopause?
The ending of menstruation; the time in a woman’s life when this happens.
What is endometrium?
The mucous membrane that lines the uterus in mammals.
What is oestradiol?
A potent oestrogenic hormone produced in the ovaries of all vertebrates.
What is menstruation?
The periodic discharging of the menses, the flow of blood and cells from the lining of the uterus.
Where does fertilization need to occur?
In the fallopian tube within a couple of days of ovulation.
What triggers the acrosomal reaction in sperm?
The binding of the sperm to the zona pellucida.
What is a zygote?
The cell formed by the union of two gametes, especially a fertilized ovum before cleavage.
What does totipotent mean?
The cell has the capacity to develop into a complete organism.
What is a conceptus?
Term for everything derived from the zygote.
What happens after 3/4 days post-fertilization?
Conceptus reaches the uterus, totipotency is lost, and it develops into a blastocyst.
What role does progesterone play during pregnancy?
Prepares the lining of the uterus for implantation.
When can human chorionic gonadotropin (hCG) be detected?
In urine or blood after implantation, which occurs six to twelve days after fertilization.
What do trophoblasts do?
Provide nutrients to the developing embryo during the first 3 months.
What is the critical switch in pregnancy maintenance?
The switch from the corpus luteum to the placenta producing progesterone and oestradiol.
What is the primary cause of female infertility?
Ovulation disorders, accounts for about 25% of infertile couples.
What is polycystic ovary syndrome (PCOS)?
Most common cause of female infertility, caused by increased androgen and LH secretion.
What is endometriosis?
Tissue that normally grows in the uterus implants and grows in other locations.
What is cervical stenosis?
A cervical narrowing that can be caused by an inherited malformation or damage.
What is unexplained infertility?
Infertility with no identified cause after evaluation.
True or False: The corpus luteum continues to function throughout the entire pregnancy.
False
Fill in the blank: The blastocyst develops into an _______ about 10 to 12 days after fertilization.
embryo
What hormone is crucial for contractions during labor?
Oxytocin
What are fertility medicines usually prescribed for?
To help ovulation problems
Examples include Clomifene (Clomid) and Tamoxifen.
What is Metformin used for in fertility treatment?
Stimulating ovulation, encouraging regular monthly periods, lowering the risk of miscarriage, and managing polycystic ovary syndrome
It also has long-term health benefits.
What are Gonadotrophins used for?
If unsuccessful with Clomid and/or Metformin, also used in men to improve sperm production
High risk of multiple births.
What is a trans-vaginal ultrasound scan used for?
To check the health of ovaries and womb
Can help identify conditions like endometriosis and fibroids.
What is endometriosis?
A condition where tissue that behaves like the lining of the womb is found outside the womb.
What is laparoscopy?
Keyhole surgery to examine the health of the womb, fallopian tubes, and ovaries
A dye may be injected to highlight blockages.
What percentage of cases of persistent failure to become pregnant can be explained by fertility tests?
80%
What is the recommended daily dose of folic acid for women at risk of neural tube defects?
5 milligrams until 12 weeks pregnant
Regular 400 micrograms advised while trying to conceive.
What is the purpose of a chlamydia test in fertility assessments?
To identify the most common STI that can cause pelvic inflammatory disease and fertility problems.
What is a hysterosalpingogram (HSG)?
An X-ray of the fallopian tubes using opaque dye to check for blockages.
At what stage do women have about 4 million eggs?
Zygote stage
How many eggs do women have at birth?
About 1 million
What is the average lifespan of sperm in a woman’s body?
Up to 5 days, or up to 7 days under optimal conditions.
What is the average daily sperm production in men?
Around 150-1,000 million sperms
What is the role of folic acid during pregnancy?
Important for the development of a healthy foetus and reduces the risk of neural tube defects.
What hormone do ovulation test kits detect?
Luteinising hormone (LH)
What are signs of ovulation?
- Change in cervical fluid
- Increase in basal body temperature
- Change in cervical position or firmness
What is a zygote?
The very first stage of life after the union of egg and sperm.
What is the embryonic period?
The active cell division period of conception from 24 hours to 8 weeks after fertilization.
What is assisted conception?
Methods like intrauterine insemination (IUI) and in vitro fertilisation (IVF) to help with fertility issues.
What is the legal requirement for egg and sperm donors in the UK since April 1, 2005?
Donors must provide information about their identity.
What is the definition of infertility?
Failure to conceive after a year of regular intercourse without contraception.
What are the two types of infertility?
- Primary infertility
- Secondary infertility
What is oligozoospermia?
Low sperm count, < 15 million spermatozoa per millilitre of ejaculate.
What is azoospermia?
No sperm count due to production issues or blockage.
What is the average menstrual cycle length for women of childbearing age?
Approximately 28 days, but can vary between 24 and 35 days.
What physical examinations can be performed on couples trying to conceive?
- Weigh (BMI)
- Pelvic examination for women
- Penile/testicular examination for men
What is thromboprophylaxis?
A preventive treatment to reduce the risk of blood clots during surgery
Includes the use of unfractionated or low molecular weight heparin and compression stockings.
What factors increase the risk of pregnancy while using LAM?
Pregnancy risk increases if:
* Breast-feeding decreases
* Menstruation resumes
* The woman is more than six months postpartum
LAM stands for Lactational Amenorrhea Method.
What is the standard regimen for Combined Hormonal Contraceptive (CHC) use?
21 days of active pills followed by a 7-day hormone-free interval
This regimen mimics natural menstrual cycles.
What are the drawbacks of the 7-day hormone-free interval (HFI) in CHC use?
Drawbacks include:
* Heavy or painful withdrawal bleeding
* Symptoms like headache and mood changes
* Reduced ovarian suppression
* Risk of ovulation and potential pregnancy
It highlights the risks associated with the standard use of CHC.
What are the tailored CHC regimens?
Tailored regimens include:
* Shortened HFI
* Extended use (tricycling)
* Flexible extended use
* Continuous use
These regimens aim to reduce or avoid HFI-associated symptoms.
What are key indications for medical review for women using CHC?
Key indications include:
* High blood pressure
* High body mass index (>35 kg/m2)
* Migraine or migraine with aura
* Deep vein thrombosis or pulmonary embolism
* Blood clotting abnormalities
* Cardiovascular diseases
* Certain cancers
This ensures the safety and suitability of CHC use.
What should be assessed before prescribing CHC?
Assessment should include:
* Medical history
* Drug history
* Recent blood pressure recording
* BMI
Pelvic examination is not routinely required.
What is the Lactational Amenorrhea Method (LAM)?
A method of avoiding pregnancy based on natural postpartum infertility associated with fully breast-feeding
It is about 98% effective if certain conditions are met.
What should a woman do if she vomits within 2 hours of taking a contraceptive pill?
She should take another pill immediately if she is not sick again
This ensures continued protection against pregnancy.
What are the suitable alternatives to Combined Oral Contraceptives (CoC) for certain medical conditions?
Alternatives include:
* Progestogen-only contraceptives
* Long-acting reversible contraceptives (LARCs)
These are suitable for women with a history of venous thrombosis, heavy smokers, and others at high risk.
What is the risk associated with using anti-epileptic drugs and hormonal contraceptives?
Most anti-epileptic drugs can reduce the efficacy of hormonal contraceptives
Women on these medications should consider LARCs.
What are the methods of contraception that have no user failure?
Methods include:
* Contraceptive injection
* Implant
* Intra-Uterine System (IUS)
* Intra-Uterine Device (IUD)
* Vasectomy
* Female sterilization
These methods are effective without reliance on user compliance.
What are the methods of contraception that may have user failure?
Methods include:
* Patch
* Combined oral contraceptives
* Progestogen-only pills
* Condoms (male and female)
* Diaphragms
* Natural methods
* Vaginal rings
User failure can occur due to improper use or non-compliance.
What defines a missed pill for Combined Oral Contraceptives (COC)?
A missed pill is defined as one that is more than 24 hours late
For Progestogen-only Pill (POP), it is more than 3 hours late.
What are the non-contraceptive health benefits of CHC?
Benefits include:
* Reduction in heavy menstrual bleeding and pain
* Improvement of acne
* Reduced risk of endometrial and ovarian cancer
* Management of symptoms associated with PCOS
These benefits can enhance quality of life.
What are the risks associated with CHC use?
Risks include:
* Increased risk of VTE
* Small increased risk of myocardial infarction and stroke
* Increased risk of breast and cervical cancer
The absolute risks remain low for individual users.
What are dietary sources of folic acid?
Sources include:
* Green, leafy vegetables
* Brown rice
* Granary bread
* Fortified breakfast cereals
Supplements are often necessary to meet recommended levels.
What is the preferred action regarding CoC prior to major elective surgery?
CoC should be discontinued 4 weeks prior to major elective surgery
Ensure an alternative contraceptive is in place.
What is a contraceptive implant?
A long-acting reversible contraceptive method that is inserted under the skin
What is a contraceptive injection?
A hormonal method of contraception administered via injection
What is a contraceptive patch?
A transdermal patch that releases hormones to prevent pregnancy
What are diaphragms?
Barrier devices inserted into the vagina to prevent sperm from reaching the uterus
What is an intrauterine device (IUD)?
A small T-shaped device inserted into the uterus to prevent pregnancy
What is an intrauterine system (IUS)?
A type of IUD that releases hormones to prevent pregnancy
What is natural family planning?
A method of tracking fertility to avoid or achieve pregnancy
What is progestogen-only pill?
A hormonal contraceptive pill that contains only progestogen
What is a vaginal ring?
A flexible ring inserted into the vagina that releases hormones
What is female sterilisation?
A permanent method of contraception involving surgical procedures to block or seal the fallopian tubes
What is male sterilisation (vasectomy)?
A permanent method of contraception involving surgical procedures to cut or seal the vas deferens
Why are female sterilisation and male sterilisation considered permanent methods?
Reversal is difficult and not always successful
What does LARC stand for?
Long-Acting Reversible Contraceptives
What are the two types of hormonal contraception?
Combined Hormonal Contraception (CHC) and Progestogen Only Contraception (POC)
What does Combined Hormonal Contraception (CHC) contain?
Both estrogen and progesterone
What is the mechanism of action (MOA) for Combined Hormonal Contraception (CHC)?
Acts on the hypothalamopituitary-ovarian axis to suppress LH & FSH and thus inhibit ovulation
What are the forms of Combined Hormonal Contraception (CHC)?
- CoC (pill) * CTP (patch) * CVR (ring)
What is the mechanism of action (MOA) for Progestogen Only Contraception (POC)?
Inhibit ovulation and thicken cervical mucus
What are the forms of Progestogen Only Contraception (POC)?
- PoP (pill) * PTP (patch) * PVR (ring)
What can uncontrolled hypothyroidism impair?
Fertility
Insufficient thyroid hormone can have teratogenic effects and even lead to miscarriage.
What should patients with confirmed thyroid disease planning a pregnancy do?
Consult with their GP/specialist and have frequent TSH level monitoring.
By how much should the levothyroxine dose be increased once pregnant?
By 25-50 micrograms immediately.
How often should TSH levels be monitored during pregnancy?
Every 4-6 weeks.
What is the target TSH level in the first trimester?
<2.5 mU/L.
What is the target TSH level in the third trimester?
<3.0 mU/L.
When should TSH levels be re-checked post-birth?
2-4 weeks post-birth.
What is the usual starting dose of Levothyroxine?
1.6 micrograms per kg rounded to the nearest 25 microgram dose.
What are the symptoms of primary hypothyroidism?
- Fatigue
- Hoarse voice
- Bradycardia
- Diastolic hypertension
- Pericardial effusion
- Weight gain
- Decreased appetite
- Abdominal distension
- Constipation
- Increased sensitivity to cold
- Low mood
- Impaired cognition
- Paraesthesia
- Peripheral neuropathy
- Non-specific muscle weakness or pain
- Joint pain
- Irregular menstrual cycle and menorrhagia
- Infertility or subfertility
- Dry, flaking, thickened skin
- Goitre
- Reduced sweating
- Yellow complexion
- Facial swelling, particularly of the eyelids
- Brittle nails
- Coarse hair
- Hair loss, particularly of the eyebrows.
What hormone does the thyroid secrete to maintain calcium levels?
Calcitonin.
What does a raised TSH level and low FT4 suggest?
Overt primary hypothyroidism.
What indicates subclinical primary hypothyroidism?
Slightly raised TSH level with FT4 still within the normal reference range.
What does a low TSH level and low FT4 suggest?
Secondary hypothyroidism arising from hypothalamic or pituitary dysfunction.
What is Liothyronine?
Synthetic form of T3, x5 more potent than Levothyroxine.
What is the first line treatment for hypothyroidism?
Levothyroxine (T4) replacement.
What are the side effects of Levothyroxine?
- Flushing
- Restlessness
- Palpitations
- Insomnia
- Angina
- Thyroid crisis.
How should Levothyroxine be taken?
30 to 60 minutes before food or other medication.
What is the importance of brand consistency for patients on Levothyroxine?
It can be important for maintaining stable hormone levels.
What are the additional investigations for thyroid function?
- Thyroid antibodies testing
- Thyroid Peroxidase Antibodies (TPOAb)
- Thyroglobulin Antibodies (TgAb)
- Thyroid Stimulating Hormone Receptor Antibodies (TSHR Ab, also known as TRAb).
What should be done if TSH is within normal limits but symptoms are still present?
Test FT4 to investigate for secondary hypothyroidism.
What adjustments are made for patients over 65 years or with pre-existing CVD?
Reduced starting dose of 25-50 micrograms OD due to risks of overtreatment.
What should be done for those with glucocorticoid deficiency before starting thyroxine?
They should be given replacement therapy.
What is the usual stabilization dose for most adult patients on Levothyroxine?
Between 100 micrograms – 200 micrograms daily.
How long can it take for TSH to normalize?
Up to 6 months.
What is the initial monitoring frequency for TFTs until stable?
Every 3 months.
What are the two main antithyroid drugs mentioned?
Carbimazole and Propylthiouracil
What is the first-line treatment for Graves’ disease unless contraindicated?
Thionamides; carbimazole
How long does it typically take for carbimazole to show therapeutic benefit?
6-8 weeks
What is the remission induction rate for patients with Graves’ disease using antithyroid drugs?
Around 50%
What are the two regimen choices for antithyroid drug treatment?
- Titration
- Block and Replace
What is the first-line treatment for patients unlikely to go into remission from Graves’ disease?
Radioactive iodine
What is the first-line treatment for multinodular goitre?
Radioactive iodine
What is the first-line treatment for a single nodular adenoma?
- Radioactive iodine
- Surgical intervention (total or hemi-thyroidectomy)
What is contraindicated in both pregnancy and breastfeeding?
Radioactive iodine
What should be checked every 6-8 weeks during treatment with antithyroid drugs?
Thyroid function tests (TFTs)
What does a low TSH level with raised FT4 and FT3 suggest?
Hyperthyroidism of thyroidal origin
What can be a rare cause of hyperthyroidism indicated by high TSH and raised FT4 and FT3?
Hyperthyroidism of extrathyroidal origin
What are the symptoms of thyroiditis?
- Painful and tender thyroid follicles
- Fever
- Sore throat
What are the symptoms of thyrotoxicosis?
- Tachycardia
- Shortness of breath
- Weight loss
What are some neuromuscular symptoms of hyperthyroidism?
- Insomnia
- Muscle weakness
- Fine motor tremor
What is myxedema crisis?
Extreme manifestation of hypothyroidism that can be fatal
What are the symptoms of myxedema crisis?
- Hypothermia
- Macroglossia
- Periorbital swelling
What does the GREAT score assess?
Relapse risk in Graves’ disease
What are the classes of the GREAT score and their relapse distribution?
- Class I (0-1 points): 33.8%
- Class II (2-3 points): 59.4%
- Class III (4-6 points): 73.6%
What is the initial dose range for carbimazole?
20-60mg daily in divided doses
What is a side effect of carbimazole?
Bone marrow suppression
What should patients be counseled about when starting carbimazole?
Signs and symptoms of blood dyscrasias
What is the mechanism of action of propylthiouracil?
Inhibits organification of iodide and conversion of T4 to T3
What is the initial dose range for propylthiouracil?
200-400mg once daily
What is a serious side effect of propylthiouracil?
Severe hepatic reaction causing acute liver injury
What is a common side effect of Propylthiouracil?
Macropapular rash
Can be treated with a generic antihistamine.
What severe reaction can Propylthiouracil cause?
Severe hepatic reaction causing acute liver injury
Some cases were fatal and some required liver transplant.
What are potential blood-related side effects of Propylthiouracil?
Bone marrow suppression, thrombocytopenia, risk of agranulocytosis
Patients need to be counselled on signs and symptoms of blood dyscrasias.
What signs and symptoms should patients be counselled on regarding blood dyscrasias?
- Sore throat
- Bruising
- Bleeding
- Mouth ulcers
- Fevers
- Malaise
How often should a full blood count be checked during treatment with Propylthiouracil?
Baseline and every 6 months during treatment
What is a contraindication for Propylthiouracil?
Severe hepatic impairment
Unable to be metabolised to active methimazole.
What history may exacerbate the use of Propylthiouracil?
History of pancreatitis
What additional medications may be needed for symptom management when using Propylthiouracil?
Beta blockers
How long may it take for Propylthiouracil to show observable effects?
Six to eight weeks
Does not alter existing levels of T3 and T4.
What symptoms should patients report urgently when taking Propylthiouracil?
- Severe sore throats
- Bruising or bleeding
- Mouth ulcers
- Fever
- Malaise
What serious hepatic reactions have been reported with Propylthiouracil?
Severe hepatic reactions, including fatal cases and cases requiring liver transplant
Report any jaundice, dark urine, abdominal pain, pruritis, nausea, and vomiting.
When should treatment with Propylthiouracil be stopped?
If significant hepatic enzyme abnormalities develop
What is Carbimazole classified as?
Pro-drug
Undergoes metabolism by hepatic enzymes to the active metabolite, thiamazole (methimazole).
Why is Carbimazole the first line choice?
Due to quick thyroid hormone correction (4-8 weeks)
What is the mechanism of action of Carbimazole?
Inhibition of the organification of iodide and thyroglobulin, and the coupling of iodothyronine residues
Suppresses the synthesis of thyroid hormones.
What effect does excess dietary iodine have on thyroid hormone release?
Inhibits thyroid hormone release due to the Wolff-Chaikoff effect
The Wolff-Chaikoff effect describes how high levels of iodine can suppress thyroid hormone production.
What is the recommended dosage of Lugol’s Solution for inhibiting hormone release?
1ml every 6 to 8 hours
Dosage may vary depending on patient presentation.
What is the minimum gap required between thionamide and iodine administrations?
At least one hour
This ensures adequate uptake of thionamides into the thyroid.
What is the risk associated with lithium carbonate when used for inhibiting hormone release?
High risk of lithium toxicity
Lithium carbonate is rarely used due to this significant risk.
How often should TSH be measured post radioactive iodine treatment?
Every 6 weeks until within reference range
What should be done if hyperthyroidism persists 6 months post ablation?
Consider alternative therapy
When should thionamides be stopped after radioactive iodine treatment?
Once TSH is within reference range
What percentage of patients post ablation will require levothyroxine?
50%
What should be done 1 week prior to receiving radioactive iodine treatment?
Stop carbimazole or propylthiouracil
How long does it take for radioactive iodine to have a clinical effect?
2-3 months
For how long are patients considered radioactive after a standard dose of radioactive iodine?
Up to 6 weeks
What precautions should patients take after radiation exposure?
Avoid close contact with others for 14 days and completely avoid pregnant women and children for 24 days
What is the aim of radioactive iodine treatment?
To resolve hyperthyroidism without post-ablation hypothyroidism
What are the two methods of dosing radiation administered?
- Fixed dose regardless of other factors
- Adjusted dose based on size of enlarged thyroid/goiter
How often should TSH, T4, and T3 be monitored after starting treatment?
Every 6 weeks until TSH is within reference range
What is the post-treatment TSH monitoring schedule after stopping treatment?
8 weeks post-cessation, then every 3 months for 1 year
What is a vital indication for thyroidectomy?
Symptoms of windpipe compression due to the size of goiter or enlargement
What should be monitored at 2 and 6 months post hemithyroidectomy?
TSH
What is the risk of thyroid crisis?
It can lead to multiorgan failure and is often fatal
What can precipitate a thyroid crisis?
- Infection
- Trauma
- Medications (e.g., amiodarone)
- Sudden cessation of thionamides
- Surgery
What are some symptoms of thyroid crisis?
- Hyperthermia (over 41°C)
- Tachycardia (heart rate > 140 bpm)
- Hypotension
- Confusion or agitation
What are the treatment mechanisms for thyroid crisis?
- Inhibition of thyroid hormone synthesis
- Inhibition of thyroid hormone release
- Inhibition of peripheral action of excess thyroid hormone
- Supplementary management
What is the typical first agent of choice for inhibiting peripheral hormone action?
Propranolol
What is the standard loading dose for propylthiouracil?
600mg loading dose, followed by 200-250 mg every 4-6 hours
What medication should be administered for high temperature in thyroid crisis?
Paracetamol
What is the function of cholestyramine in thyroid crisis management?
Enhances thyroid hormone excretion by increasing enterohepatic circulation
What is the role of glucocorticoids in thyroid crisis?
Inhibit peripheral T4 to T3 conversion
What are the key features of emergency contraception?
Intended for emergency use, not regular contraception, can be used 5 days after abortion or miscarriage, can be used on any day of the menstrual cycle.
What types of emergency contraception (EC) are available?
- Copper Intrauterine Device (Cu IUD)
- Oral EC
- Levonorgestrel (LNG-EC)
- Ulipristal (UPA-EC)
What is the most effective form of emergency contraception?
Copper Intrauterine Device (Cu IUD)
How does the Copper IUD work?
- Inhibits fertilisation
- Affects movement and viability of sperm
- Causes local inflammatory reaction preventing implantation
How does Levonorgestrel (LNG-EC) work?
Inhibits ovulation by delaying or preventing follicular rupture and causing luteal dysfunction for five days.
What is the licensed timeframe for Levonorgestrel after unprotected sexual intercourse (UPSI)?
Licensed for UPSI which has occurred in the last 72 hours (3 days).
What is the licensed timeframe for Ulipristal after UPSI?
Licensed for UPSI occurring in the last 120 hours (5 days).
What are common adverse effects of emergency contraception?
- Headache
- Nausea
- Dysmenorrhoea
True or False: Ulipristal is effective even after the start of the LH surge.
True
What should be done if vomiting occurs within 3 hours of taking emergency contraception?
Need another supply.
What is the age limit for Levonorgestrel sale?
Not licensed for sale to under 16 years.
What is the recommendation for breastfeeding women taking UPA-EC?
Advise expressing and discarding breast milk for one week following the dose.
What are some interactions that affect emergency contraception?
- Ulipristal and St John’s Wort
- Levonorgestrel and Carbamazepine
- Levonorgestrel and Sodium Valproate
Fill in the blank: Emergency contraception is intended for _______ use and not as a form of regular contraception.
emergency
What should be considered if a patient is under 16 years requesting emergency contraception?
Fraser competency applies.
What should be done if a girl under 13 years presents for emergency contraception?
Cannot consent to have sex; safeguarding concerns arise.
What risk is associated with taking emergency contraception if pregnancy is suspected?
Risk of ectopic pregnancy.
What advice should be given regarding menstruation after taking emergency contraception?
Alteration in menstruation can occur; advise seeking help if period is delayed more than 7 days.
What is the role of consultation in the emergency contraception process?
To assess needs, provide information, and ensure appropriate supply.
What is the significance of a Patient Group Directive (PGD) in emergency contraception?
Allows supply of emergency contraception under specific guidelines.
What is the recommended action if a patient has missed progesterone-only pills?
Consider if UPA will be effective.
What should be done if a patient requests advance supply of emergency contraception?
Discuss potential scenarios and assess necessity.
What is the effectiveness of LNG-EC compared to UPA-EC?
UPA-EC is generally more effective than LNG-EC.
What resources are available for guidance on emergency contraception?
- NICE CKS
- FSRH guidance
- SPC / BNF
- NHS UK
- GPhC
- Stockley Interactions
- CPPE
- C&D
Define what type 2 diabetes is
A condition with chronically raised blood glucose concentration due to a lack of insulin or deficiency in insulin action.
What is the peak age of onset for type 1 diabetes mellitus?
12 years
What percentage of all diabetics does type 1 diabetes account for?
Approx. 8%
What is the peak age of onset for type 2 diabetes mellitus?
60 years
What percentage of all diabetics does type 2 diabetes account for?
Approx. 90%
What is the relationship between obesity and type 2 diabetes?
> 85% of type 2 diabetics are obese
What is gestational diabetes?
A type of diabetes that occurs in approximately 16% of pregnancies.
What is the normal HbA1c level?
Below 42 mmol/mol (6.0%)
What HbA1c level indicates diabetes?
48 mmol/mol (6.5% or over)
What is the purpose of an Oral Glucose Tolerance Test (OGTT)?
To measure blood glucose levels after fasting and consuming a glucose solution.
What are the diagnostic criteria for fasting plasma glucose levels?
Normal: Below 5.5 mmol/l; Prediabetes: 5.5 to 6.9 mmol/l; Diabetes: 7.0 mmol/l or more.
What are the two main components in the development of type 2 diabetes?
- Insulin Resistance * Beta-cell dysfunction and death
What is insulin resistance?
A condition where insulin-sensitive tissues fail to fully respond to insulin.
What is the concordance rate of type 2 diabetes in monozygotic twins?
About 70%
What are the risk factors for developing type 2 diabetes?
- Obesity * Age * Low birth weight * Gestational diabetes * Social economic status * Ethnicity
True or False: The prevalence of type 2 diabetes is more common in deprived social groups.
True
What is the estimated percentage of type 2 diabetes risk attributed to genetics?
30%-70%
Fill in the blank: The fasting plasma glucose test is usually taken after at least _______ hours of fasting.
eight
What is the significance of elevated ectopic fat in relation to insulin resistance?
It increases FA metabolites that inhibit key insulin signaling proteins.
What is the effect of aging on insulin resistance?
Increases risk of insulin resistance.
What is the relationship between genetics and family history in type 2 diabetes?
If either parent has type 2 diabetes, the risk of inheritance is 15%; if both parents have it, the risk is 75%.
What is the role of adipocytes in insulin resistance?
Adipocytes that are ‘stuffed’ cannot store more TAG, leading to increased release of FAs.
What does the term ‘hyperlipidemia’ refer to?
Increased levels of circulating lipids.
What can reduce insulin sensitivity?
- Obesity * Aging * Lack of exercise * Certain medications
What is ectopic fat?
Ectopic fat refers to fat stored in locations outside of the usual fat depots, which can lead to metabolic issues.
What effect does elevated ectopic fat have on insulin signaling?
Elevated levels of ectopic fat cause an increase in FA metabolites that inhibit key insulin signaling proteins.
What is hyperinsulinemia?
Hyperinsulinemia is the overactivation of the insulin signaling pathway, leading to reduced insulin receptor signaling through negative feedback mechanisms.
What causes cellular stress related to insulin signaling?
Increased metabolism due to over-nutrition causes cellular stress (oxidative and ER stress) which inhibits insulin signaling.
How does inflammation affect insulin signaling?
Chronic inflammation from increased adipose tissue size and cytokine levels activates signaling pathways that inhibit insulin signaling.
What is beta cell mass?
Beta cell mass is defined by the number and size/volume of beta cells in the pancreas.
What are the manifestations of beta cell dysfunction?
- Loss of pulsatile insulin secretion
- Loss of first phase insulin secretion
- Reduced glucose-stimulated insulin secretion
- Reduced insulin content
- Increased secretion of proinsulin
What is glucolipotoxicity?
Glucolipotoxicity refers to the harmful effects of high circulating levels of glucose and free fatty acids on beta cells.
What role does ER stress play in beta cell function?
ER stress occurs when the demand for insulin exceeds the processing capacity of the beta cells, leading to dysfunction.
What are amylin deposits and their effect on beta cells?
Amylin deposits result from increased secretion of amylin with insulin, causing cellular dysfunction and death.
What is the primary action of Metformin?
Metformin improves insulin sensitivity and glucose clearance by enhancing peripheral glucose uptake and decreasing hepatic glucose production.
What is the mechanism of action (MOA) of Metformin?
Metformin inhibits the mitochondrial respiratory chain (complex I), activating AMP-activated protein kinase (AMPK).
What are thiazolidinediones (TZDs) and their primary MOA?
TZDs are drugs that bind to the peroxisome proliferator-activated receptor-γ (PPARγ) to increase the expression of insulin sensitivity genes.
Name a first-generation thiazolidinedione.
Troglitazone.
Which thiazolidinedione was withdrawn due to cardiotoxic effects?
Rosiglitazone.
What is the mechanism of action of sodium-glucose co-transporter 2 inhibitors (SGLT2i)?
SGLT2i reduce renal glucose reabsorption in proximal tubules by inhibiting SGLT2.
List examples of SGLT2 inhibitors.
- Dapagliflozin
- Canagliflozin
- Empagliflozin
What is the mechanism of action of sulphonylureas?
Sulphonylureas bind to the ATP-sensitive K+ channel, leading to channel closure and stimulating insulin secretion.
What is the incretin effect?
The incretin effect refers to the potentiation of glucose-induced insulin secretion by incretin hormones.
What are the two main incretin peptides?
- Glucagon-like peptide-1 (GLP-1)
- Gastric inhibitory peptide (GIP)
What happens to incretin action in type 2 diabetes?
There is reduced GLP-1 secretion and almost complete loss of GIP action.
What is Exenatide?
Exenatide (Byetta) is a synthetic form of exendin-4, a peptide that promotes insulin secretion.
What is the Gila monster?
A poisonous lizard found in North America. Exenatide idea from this.
How often does the Gila monster eat?
Four times a year
What is secreted in the saliva of the Gila monster when it eats?
Exendin-4
What is the role of exendin-4?
Helps the pancreas to produce insulin
What is exenatide?
A synthetic form of exendin-4
What type of drug is exenatide?
A GLP1R agonist
Is exenatide an analogue of GLP?
No
What was the first GLP-1R agonist approved for the treatment of type-2 diabetes?
Exenatide (2005)
What is the stability of exenatide?
Resistant to degradation by DPP-4 and extends its half-life
How is exenatide administered?
By injection
What is liraglutide?
An analogue of GLP1 (97% homology)
What is the brand name for liraglutide?
Victoza
What are some examples of GLP-1 receptor agonists?
- Exenatide (Byetta, Bydureon)
- Tirzepatide (Mounjaro, Zepbound)
- Liraglutide (Victoza)
- Lixisenatide (Lixumia)
- Dulaglutide (Trulicity)
- Semaglutide (Ozempic)
How many GLP-1 receptor agonists are currently available in the UK?
Six
What are Dipeptidyl peptidase-4 (DPP-4) inhibitors?
Protease inhibitors that target the enzyme DPP-4
What is the function of DPP-4?
Degrades GLP1
How are DPP-4 inhibitors administered?
Orally in tablet form
What are some examples of DPP-4 inhibitors?
- Sitagliptin (Januvia)
- Vildagliptin (Galvus)
- Saxagliptin (Onglyza)
- Alogliptin (Vipidia)
- Linagliptin (Trajenta)
What are alpha-glucosidase inhibitors?
Drugs that reduce glucose absorption
What do alpha-glucosidases do?
Breaks down polysaccharides and disaccharides to glucose
What is the effect of inhibiting alpha-glucosidase?
Delays carbohydrate digestion and absorption, lowers postprandial blood glucose
What are examples of alpha-glucosidase inhibitors?
- Acarbose (Precose)
- Miglitol (Glyset)
Are there currently any drugs that preserve beta-cell function?
No
Can the rate of decline of beta-cell function be slowed down?
Yes
What is obesity?
Excessively high amount of body fat in relation to lean body mass.
Generally agreed that men with over 25% body fat and women with more than 30% body fat are obese.
What is the Body Mass Index (BMI) formula?
BMI = Weight (Kg) / Height (m)²
BMI categories: Normal (18.5 - <25), Overweight (25 - <30), Obese (30 - <40), Morbid obesity (>40).
What was the percentage of adults aged 18 years and over who were overweight in 2016?
39% were overweight and 13% were obese.
What is the relationship between waist-hip ratio and obesity-related diseases?
Greater correlation between obesity-related disease and waist-hip ratio than BMI.
Increased waist/hip ratio indicates increased risk of obesity-related disease.
How is abdominal obesity defined according to the WHO?
Waist-hip ratio above 0.90 for males and above 0.85 for females.
What causes obesity?
Chronic imbalance between energy input and expenditure.
What is Basal Metabolic Rate (BMR)?
Measured by determining the rate of O2 utilization over a given time period at rest at a set temperature.
What factors can affect BMR?
- Body mass and composition
- Hormones (e.g., Thyroid Hormone)
- Growth Hormone
- Sleep
- Malnutrition
- Temperature
What is the impact of food availability on obesity?
Increased food availability and reduced food prices contribute to higher obesity rates.
What is leptin and its role in body weight regulation?
Leptin is a hormone synthesized and secreted from adipocytes that regulates body weight by influencing appetite and metabolism.
What is the function of ghrelin?
Ghrelin is the hunger hormone released in anticipation of food intake.
What is the impact of insulin on body weight?
Insulin promotes food intake and increases body weight by promoting glucose storage into fat.
What are the two components of weight regulation?
- Hunger varies inversely with body weight
- Metabolism varies directly with body weight
True or False: Obesity is considered a preventable condition.
True.
What are the health risks associated with obesity?
Obesity is linked to numerous health risks including heart disease, diabetes, and certain cancers.
What role do gut hormones play in appetite regulation?
Gut hormones are released in response to food intake and promote a feeling of satiety.
What is the obesity epidemic?
A global increase in obesity rates that poses significant public health challenges.
Fill in the blank: The advised daily human calorie intake is _______ calories.
2,000 calories.
What percentage of the world’s population lives in countries where overweight and obesity kill more people than underweight?
Most of the world’s population.
What is the importance of understanding the causes of obesity?
To develop effective prevention and treatment strategies.
What mediates the short-term feeling of hunger and satiety?
Signals from the gut, stomach, liver, and pancreas to the brain.
Which hormones are involved in long-term regulation of body weight?
Leptin.
What is the risk of a child being overweight if both parents are obese?
80%.
What is the risk of a child being overweight if one parent is obese?
40%.
What is the concordance rate of obesity in monozygotic twins?
65-70%.
What is the heritability estimate of obesity?
50-70%.
What do GWAS studies identify in relation to obesity?
Polymorphisms in many genes associated with increased risk of becoming obese.
What is the common polymorphism associated with obesity in the FTO gene?
Homozygotes weigh an average of 3kg more and have a 1.67-fold increased risk of obesity.
What is monogenic obesity?
Obesity caused by a mutation in a single gene.
Which receptor is most commonly associated with monogenic obesity in children?
Melanocortin 4 receptor (MC4-R).
What phenotypic characteristics are associated with mutations in the MC4-R?
- Hyperphagia starts at ~8 months
- Tendency towards being tall
- Hyperinsulinemia
- Increased bone mineral density.
Name some illnesses that can affect weight.
- Endocrinopathies
- Hypothyroidism
- Polycystic ovarian syndrome
- Tumors of the pituitary gland, adrenal glands, or pancreas.
What are some drugs that promote increased appetite or slow metabolism?
- Corticosteroids
- Oestrogen and progesterone (oral contraceptives)
- Anticancer medications
- Lithium and clozapine
- Insulin and glyburide
- Antidepressants (e.g., tricyclics, MAO inhibitors, SSRIs)
- Antibiotics.
How does gut microbiota influence metabolism?
Through metabolites produced during the fermentation of dietary substances.
What is the estimated percentage of dieters who regain weight within two to five years after losing 10% or more of their body mass?
80-95%.
What is Orlistat and what does it do?
A lipase inhibitor that prevents the digestion and absorption of fats.
What is the recommended BMI for Orlistat usage?
≥ 30 kg/m² or ≥ 28 kg/m² with risk factors.
What are GLP-1 receptor agonists used for?
To increase satiety and reduce food intake.
What are the approved GLP-1R agonists available on NHS prescription?
- Semaglutide (Wegovy)
- Liraglutide (Saxenda).
What is a key criterion for bariatric surgery eligibility?
BMI of 40 or more, or between 35 and 40 with another serious health condition.
What is the most common type of bariatric surgery?
- Gastric band
- Sleeve gastrectomy
- Gastric bypass.
What is the effect of gastric band surgery?
A band is placed around the stomach to reduce the amount of food needed to feel full.
What is sleeve gastrectomy?
Some of the stomach is removed, leading to reduced food intake.
What happens in gastric bypass surgery?
The top part of the stomach is joined to the small intestine, reducing calorie absorption.
What should patients regularly examine and wash?
Their feet
Regular foot care is crucial for diabetic patients to prevent complications.
What should be done to areas of hard skin?
Soften with regular moisturiser
Should patients remove corns and calluses themselves?
No, seek help for this!
What is advised against wearing on feet?
Socks or tights with prominent seams
How should toenails be cut?
Straight across and smooth sharp edges with a file
What is Ejaculatory dysfunction more common than?
Erectile dysfunction
What impact does sexual dysfunction have on mental health?
Huge impact
What can complications like gastroparesis lead to?
Erectile dysfunction due to pain, vomiting, or diarrhoea
What is the theory behind sexual health issues in women with diabetes?
Poor glycaemic control leads to poor quality tissue in the reproductive system
What should be considered in type 1 diabetes regarding sexual health?
Alternative causes such as thyroid disorders
How many lower limb amputations due to diabetes occur weekly in the UK?
169
What are the recommended reassessment intervals for diabetic foot problems?
- Annually for low risk
- Every 3 to 6 months for moderate risk
- Every 1 to 2 months for high risk without immediate concern
- Every 1 to 2 weeks for high risk with immediate concern
What are the three components of foot assessment?
- Patient symptoms and history
- Nail care
- Visual inspection
What is NICE IPG489 regarding?
Gastroelectrical stimulation for gastroparesis
What does the electrical pump for gastro stimulation consist of?
- A neurostimulator
- 2 leads
What is the first line management for gastroparesis?
Diet control
What should be avoided in diet for managing gastroparesis?
Fatty foods
What are second line treatments for gastroparesis?
- Mirtazapine
- Erythromycin
- Metoclopramide
- Domperidone
What are symptoms of gastroparesis?
- Nausea
- Vomiting
- Constipation or diarrhoea
- Early feeling of fullness
- Weight loss
- Bloating
- Abdominal discomfort
What is neuropathic pain caused by?
A lesion or disease of the somatosensory nervous system
What is the most common form of neuropathy in diabetes?
Peripheral neuropathy
What characterizes sensory neuropathy?
Tingling and/or numbness in the limbs, ‘pins and needles’
What are the first-line treatments for painful diabetic neuropathy?
- Oral duloxetine
- Amitriptyline if duloxetine is contraindicated
What should be considered for neuropathic pain management if no reduction in pain?
Refer to specialist pain team
What is the risk associated with tramadol?
Addiction
What cardiovascular issues can arise from autonomic neuropathy?
- Tachycardia or bradycardia
- Heart failure
- Orthostatic hypotension
What gastrointestinal issues can occur due to autonomic neuropathy?
- Oesophageal dysmotility
- Gastroparesis
- Diarrhoea or faecal incontinence
- Constipation
What genitourinary issues are related to autonomic neuropathy?
- Erectile dysfunction
- Retrograde ejaculation
- Neurogenic bladder
What is a common cause of gastroparesis in diabetes?
Neuropathic damage of the vagus nerve
What should be checked during a visual inspection of feet?
- Suitability of footwear
- Areas of poor support
- Rubbing or worn areas
What is the pulse location for the dorsalis pedis?
On the dorsum of the foot along the lateral side of the first metatarsal shaft
What is the diagnosis criteria for diabetic kidney disease?
Urinary ACR of >30mg/g or Creatinine clearance <60ml/min
What percentage of patients with T1DM and nephropathy also suffer from retinopathy?
95%
What is the urinary ACR threshold for diagnosing diabetic kidney disease?
> 30mg/g
What is the creatinine clearance threshold indicative of diabetic kidney disease?
<60ml/min
What percentage of patients with Type 1 Diabetes Mellitus (T1DM) and nephropathy also suffer from retinopathy?
95%
What are the key factors in preventing diabetic kidney disease?
- Glycaemia (HbA1c/TIR)
- Blood pressure
- Cholesterol
What is the term for the kidney damage occurring in diabetes mellitus?
Diabetic nephropathy
What is one major cause of nephropathy in diabetic kidney disease?
High blood glucose destroys blood vessels surrounding renal tubules/nephrons
What condition results in proteins leaking into Bowman’s capsule?
Albuminuria
What is the ideal body weight formula for men?
Constant + 0.91(Height - 152.4)
What is the serum creatinine constant for women when calculating creatinine clearance?
1.04
What is the 5-year mortality rate for patients following a diabetic foot ulcer compared to colorectal cancer?
Comparable
What is the annual cost of diabetic foot complications to the NHS?
£1bn to £1.2bn
What serum tests are part of every annual review for diabetic patients?
- Serum creatinine
- ACR
Which medications should be used to achieve a blood pressure target of <130/80 in CKD treatment?
- ACE inhibitor
- ARB
- SGLT2 inhibitor
What percentage of participants using Tirzepatide achieved a weight reduction of 5% or more?
85% (5mg), 89% (10mg), 91% (15mg)
Fill in the blank: HbA1C should be checked every ______ until stable, then 6 monthly.
3-6 months
What is the primary first-line treatment for neuropathic pain in a diabetic patient?
Low dose amitriptyline
Which two tests are used to confirm renal disease screening?
- Protein:Creatinine (PCR)
- Albumin:Creatinine (ACR)
What are the signs and symptoms of diabetes?
- Excessive thirst
- Excessive urination
- Weight loss
- Blurred vision
What is the recommended initial body weight loss target for adults with type 2 diabetes who are overweight?
5% to 10%
True or False: Fad diets should be encouraged in diabetes management.
False
What is the monitoring advice for blood glucose in T2DM patients treated with insulin?
Self Monitoring of Blood Glucose (SMBG) is advised
What is the recommended follow-up for a patient with an HbA1C >48mmol/mol without diabetes symptoms?
Repeat HbA1C in 3 months
What is the significance of advanced glycation end products in diabetic kidney disease?
They cause damage to the glomerulus
What is the risk assessment outcome for a patient with A1C >48 and diabetes symptoms?
Diagnose T2DM
What is the cost of outpatient and community care for a severe diabetic foot ulcer?
Approximately £6,400
What should be recorded at an annual review for diabetic patients?
- Smoking status
- A1C
- Cholesterol
- BMI
- BP
- ACR
- SCr
What is the treatment aim for blood pressure management in CKD?
Aim for BP <130/80
Fill in the blank: If A1C <48, classify as ‘______’ risk.
high
What is the main clinical significance of serum creatinine?
Prognostic of kidney function
What HbA1c result classifies a patient as ‘high risk’?
A1C < 48
This indicates that further action is needed for patients at risk of diabetes.
What is the HbA1c diagnostic threshold for Type 2 Diabetes Mellitus (T2DM)?
A1C > 48
This result confirms the diagnosis of T2DM.
List some signs and symptoms of diabetes.
- Excessive thirst
- Excessive urination
- Recurrent urinary tract infections
- Sweet smelling urine
- Superficial infections (e.g., Ringworm or Thrush)
- Weight loss
- Blurred vision
- Confusion
- Vomiting
- Drowsiness
- Slow healing wounds
True or False: A HbA1c result of 74mmol/mol indicates good long-term diabetes control.
False
A result of 74mmol/mol signifies that long-term diabetes control is not optimal.
What is the recommended blood pressure target for patients with type 2 diabetes?
BP of 140/80 mmHg or less
Achieving this target is crucial for managing diabetes-related complications.
What is the threshold for offering blood pressure management intervention?
> 140/90 mmHg
This threshold indicates the need for intervention in blood pressure management.
What is the white-coat effect?
A discrepancy of more than 20/10 mmHg between clinic and average daytime blood pressure measurements
This effect can lead to misdiagnosis of hypertension.
What percentage of the population over 65 years suffers from Peripheral Arterial Disease (PAD)?
12-20%
Age and co-morbidities contribute to the increasing risk of PAD.
What is the most common risk factor for Peripheral Arterial Disease?
Smoking
Diabetes mellitus is also a significant risk factor.
What are common symptoms of severe cases of Peripheral Arterial Disease?
Cramping or pain at rest, known as claudication
This symptom indicates advanced disease.
What is the recommended treatment for claudication when exercise alone fails?
Naftidrofuryl 100mg TDS
Increase up to 200mg TDS in refractory cases.
What are the cholesterol target levels for total cholesterol?
Less than 4mmol/L
This target helps in managing cardiovascular risk.
What is the recommended starting dose of atorvastatin for primary prevention of CVD in type 2 diabetes patients?
Atorvastatin 20 mg
This is for patients with a 10% or greater 10-year risk of developing CVD.
What is the NICE target for LDL reduction when on statin therapy?
40% reduction in LDL
Achieving this target is essential for cardiovascular risk management.
Fill in the blank: Statins are grouped into three different intensity categories according to the percentage reduction in _______.
low density lipoprotein cholesterol
What is the definition of high-intensity statin therapy?
More than 40% LDL reduction
This category includes statins that have a significant impact on lowering LDL levels.
What should be checked if the lipid profile target is not achieved after commencing statin therapy?
- Compliance
- Possible side effects
- Re-enforce lifestyle intervention advice
What is Metformin primarily used for?
It is used for the management of type 2 diabetes.
What are the common side effects of Metformin?
- Diarrhoea
- Abdominal pain
- Nausea
What is the recommended monitoring frequency for renal function and HbA1C in patients on Metformin?
Every 6 months when stable.
What should be done with Metformin if a patient is unwell and not eating or drinking?
Omit the dose.
What is Acarbose and how does it work?
It is an alpha-glucosidase inhibitor that reduces carbohydrate absorption in the gastrointestinal tract.
What are the advantages of Acarbose?
- No hypoglycaemia risk
- Weight neutral
What are the disadvantages of Acarbose?
- Gastrointestinal side effects
- Minimal effect on HbA1C compared to other OHAs
- Impairs treatment of hypoglycaemia
What is the maximum dose of Acarbose?
600mg OD.
What are the common side effects associated with Acarbose?
- Flatulence
- Bloating
- Abdominal pain
- Diarrhoea
What are the advantages of Thiazolidinediones (e.g., Pioglitazone)?
- Little to no hypoglycaemia risk
- Good reduction in HbA1C
- Recommended option for NASH
What are the disadvantages of Thiazolidinediones?
- Weight gain (fat or fluid)
- Oedema
- Risk of cardiovascular disease
- Increased fracture risk
- Risk of bladder cancer
- Decreased visual acuity
What is the mechanism of action of Thiazolidinediones?
They stimulate PPAR gamma to increase insulin sensitivity in tissues.
What is the monitoring requirement for Thiazolidinediones?
Monitor liver function and heart failure symptoms.
What are Dipeptidyl peptidase-4 inhibitors known for?
They primarily affect blood glucose without impacting wider disease complications of T2DM.
What is a significant contraindication for Dipeptidyl peptidase-4 inhibitors?
History of pancreatitis.
What are the advantages of Dipeptidyl peptidase-4 inhibitors?
- Usually once daily dosing
- Weight neutral
- No hypoglycaemia risk
What are the common side effects of Dipeptidyl peptidase-4 inhibitors?
- Nausea
- Abdominal pain
- Peripheral oedema
What are GLP-1 Mimetics and their primary action?
They potentiate glucose-dependent insulin secretion.
List the available GLP-1 Mimetics and their dosing frequency.
- Liraglutide - Once daily
- Exenatide - Twice daily
- Dulaglutide - Once weekly
- Semaglutide - Once weekly
What is a key advantage of GLP-1 Mimetics?
- Useful for weight loss and cardioprotection.
What are common side effects of GLP-1 Mimetics?
- Diarrhoea
- Nausea
- Vomiting
What is a major disadvantage of SGLT2 Inhibitors?
They can cause urinary tract infections and volume depletion.
Name three SGLT2 Inhibitors with significant evidence for their benefits.
- Canagliflozin
- Dapagliflozin
- Empagliflozin
What are the advantages of Meglitinides?
- Good glucose control
- Less risk of prolonged hypoglycaemia
- Flexibility in dosing
What is the mechanism of action of Meglitinides?
They augment insulin secretion from pancreatic β-cells.
What are the common side effects of Meglitinides?
- Diarrhoea
- Abdominal pain
What are the advantages of Sulphonylureas?
- Well tolerated
- Quick reduction in blood glucose levels
- Good option for short-term steroid-associated hyperglycaemia
What are the disadvantages of Sulphonylureas?
- Risk of hypoglycaemia
- Risk of falls in the elderly
- Causes weight gain
What is the pharmacological action of Biguanides (Metformin)?
It sensitizes cells to insulin and reduces gluconeogenesis and glycogenolysis.
What are the common side effects of Biguanides (Metformin)?
- Nausea
- Diarrhoea
- Bloating
- Abdominal discomfort
What are the contraindications for Biguanides (Metformin)?
- Any condition that precipitates metabolic acidosis
- Renal impairment
- Severe dehydration
- Alcohol dependence
What should be monitored in patients taking Biguanides (Metformin)?
- Vitamin B12 levels
- Renal function
What is the effect of Biguanides (Metformin) on insulin secretion?
It does not affect insulin secretion and therefore does not carry a hypoglycaemia risk.
What is osteoporosis?
Progressive systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, leading to increased bone fragility and susceptibility to fracture.
What are the main functions of bones?
- Provide overall structure
- Support and protect internal organs
- Store calcium and other minerals
- Allow movement in collaboration with muscles
- Contain bone marrow for blood cell production
What are the two types of bone tissue?
- Cortical bone (thick outer shell)
- Trabecular bone (strong inner honeycomb-like mesh)
What is the process of bone remodeling?
A renewal process where older bone tissue is broken down by osteoclasts and rebuilt by osteoblasts.
What are the stages of bone remodeling?
- Resting phase
- Activation
- Resorption
- Reversal
- Formation
- Mineralisation
What happens to bone density after age 35?
The balance between bone removal and rebuilding begins to shift, leading to bone loss.
What does the term ‘osteoporosis’ literally mean?
Porous bone.
What are fragility fractures?
Fractures that occur due to reduced bone strength, often caused by osteoporosis.
What is the estimated global prevalence of osteoporosis?
Over 200 million people worldwide.
How many people in the UK are affected by osteoporosis?
Over 3 million people.
What percentage of postmenopausal women in the US and Europe have osteoporosis?
Approximately 30%.
Why are women more susceptible to osteoporosis?
Bone loss becomes more rapid after menopause due to a decrease in estrogen, and women generally have smaller bones and live longer.
What is the risk of fractures for women over the age of 50?
1 in 2 women (50%) experience fractures due to low bone strength.
Can osteoporosis affect men?
Yes, 1 in 5 men (20%) break a bone after age 50 due to low bone strength.
What is a common misconception about osteoporosis?
That it is a woman’s disease, which can hinder men from seeking help.
What are common sites for fragility fractures?
- Wrists
- Hips
- Spine
What is kyphosis?
A forward curvature of the spine caused by weakened bones.
What are primary risk factors for osteoporosis?
- Age
- Gender
- Prior fracture history
- BMI
- Alcohol
- Smoking
- Medications
What are secondary causes of osteoporosis?
- Hypogonadism
- Endocrine conditions
- Conditions associated with malabsorption
- RA
- Multiple myeloma
- COPD
- Liver failure
- CKD
- Immobility
What is a DEXA scan used for?
To assess bone mineral density.
What does a T-score compare?
Bone mineral density of a patient to that of a healthy young adult of the same sex.
What is defined as osteopenia?
A T-score between -1 and -2.5 SD.
What indicates osteoporosis based on T-score?
A T-score less than -2.5.
What is the Q-fracture risk score used for?
To estimate an individual’s risk of developing osteoporotic fractures over the next 10 years.
What is Q-Fracture?
An online clinical tool used as a guide to estimate an individual’s risk of developing osteoporotic fractures over the next 10 years.
What does Q-Fracture help to identify?
People at high risk of osteoporotic fractures so they can be assessed in more detail to reduce their risk.
Who developed Q-Fracture?
ClinRisk Ltd and the University of Nottingham.
What is osteoporosis measured on?
DEXA scan.
What is a modifiable risk factor for osteoporosis related to body weight?
BMI < 18.5 kg/m2.
How does low body weight affect osteoporosis risk?
It makes osteoporosis and fractures more likely due to lower amounts of bone tissue overall.
What role does smoking play in osteoporosis risk?
Current smokers are more likely to break bones and tend to have lower body weight.
How does excessive alcohol consumption affect bone health?
It is a significant risk factor for osteoporosis and fractures.
True or False: Older people who are at risk of falling are less likely to have fractures.
False.
What are some non-modifiable risk factors for osteoporosis?
- Genetics
- Age
- Gender
- Race
- Previous fractures
What genetic factor increases the risk of osteoporosis?
Having a parent who had a broken hip.
At what age does bone loss increase significantly?
Age 75.
Why are women at higher risk for osteoporosis compared to men?
Women tend to live longer and experience menopause, which reduces estrogen production.
Which racial group is at a lower risk of osteoporosis?
Afro-Caribbean people.
What is one of the most obvious indicators of fragile bones?
Having previously broken bones easily.
Name a class of drugs that can increase the risk of osteoporosis.
Oral glucocorticoids (steroids).
What is the main mechanism of action of bisphosphonates?
They bind to bone minerals and cause osteoclasts to undergo apoptosis, reducing their resorptive capacity.
What is a key counseling point for patients taking oral bisphosphonates?
They should be taken on an empty stomach with a full glass of water.
List some side effects of bisphosphonates.
- Oesophageal reactions
- Stomach pain
- Swallowing problems (dysphagia)
- Osteonecrosis of the jaw
What is osteonecrosis of the jaw?
A condition where the cells in the jawbone die due to reduced blood flow.
What is the aim of osteoporosis treatment?
To reduce bone turnover to a level associated with low risk.
What is denosumab?
A human monoclonal antibody used as a second-line treatment for osteoporosis.
What is a potential risk associated with parathyroid hormone treatments?
Risk of osteosarcoma.
What is the role of calcium in bone health?
Calcium is important for bone formation and strength.
What is the recommended time to wait before eating after taking bisphosphonates?
30 to 120 minutes.
Fill in the blank: Osteoporosis is a significant risk factor for _______.
fractures.
What is a biochemical marker of bone turnover that can be measured in serum?
N-terminal propeptide of type 1 collagen (PINP).
What is the maximum treatment duration for parathyroid hormone analogues?
2 years.
What is the role of parathyroid hormone in the body?
It regulates the amount of calcium in bone.
What are parathyroid hormone treatments used for?
To stimulate osteoblasts and increase bone density.
Why is parathyroid hormone treatment limited to a small number of people?
It is used for those with very low bone density and when other treatments are not effective.
What is the effect of anti-sclerostin antibody treatment?
It produced a greater increase in bone mineral density than alendronate and teriparatide.
What is the recommended daily amount of calcium for most healthy adults?
700mg of calcium.
What role does vitamin D play in calcium absorption?
It helps the body absorb calcium.
What is the recommended daily intake of vitamin D for all adults?
10mcg of vitamin D.
What are potential difficulties in obtaining enough vitamin D from food?
Vitamin D is found only in a small number of foods.
What is hormone replacement therapy (HRT) shown to do?
Maintain bone density and reduce the risk of fracture.
What is a concern regarding HRT in treating osteoporosis?
It slightly increases the risk of certain cancers, stroke, and VTE.
In men, when can testosterone treatment be useful?
When osteoporosis is caused by insufficient production of male sex hormones.
True or False: HRT is specifically recommended for treating osteoporosis.
False.
Fill in the blank: For osteoporosis sufferers, more _______ is needed as supplements.
calcium
What happened to the development of cathepsin K inhibitors?
Development was discontinued at phase 3 clinical trials due to increased risk of stroke.
What is the purpose of calcium and vitamin D supplements for osteoporosis sufferers?
To ensure adequate intake for bone health.
What is Gout?
A type of arthritis in which small crystals form inside and around the joints.
What are the symptoms of Gout?
- Severe pain * Swelling in joints * Hot and tender joints * Red, shiny skin over the joint * Peeling, itchy, and flaky skin as swelling goes down.
What is the main symptom of Gout?
A sudden attack of severe pain in one or more joints, typically the big toe.
How long do Gout attacks typically last?
3-10 days.
What causes Gout?
A disorder in purine metabolism characterized by raised uric acid levels in the blood (hyperuricemia) and deposition of urate crystals in joints and tissues.
What are purines?
Specific molecules made up of carbon and nitrogen atoms found in the DNA and RNA of all living things.
What are the two categories of purines in the human body?
- Endogenous purines: manufactured by the body * Exogenous purines: enter the body via food.
What is hyperuricemia?
Raised uric acid levels in the blood, often due to impaired renal excretion.
What are the foods high in purines that Gout sufferers should avoid?
- Offal (liver, kidneys, heart) * Game (pheasant, rabbit, venison) * Oily fish (anchovies, herring, mackerel) * Seafood (mussels, crab, shrimp) * Meat and yeast extracts (Marmite, Bovril).
What is recommended for a healthy diet to prevent Gout?
- Plenty of fruit and vegetables (at least 5-a-day) * Moderate amounts of meat and fish * Moderate dairy intake * Reduce or eliminate processed foods and drinks.
How does alcohol consumption affect Gout?
It can increase the risk of developing gout and can trigger a sudden attack.
True or False: Drinking wine is associated with an increased risk of developing Gout.
False.
What are the common joints affected by Gout?
Typically affects joints towards the ends of the limbs, such as toes, ankles, knees, and fingers.
What is the epidemiology of Gout in the UK?
Approximately 1 in every 100 people are affected, more common in men over 30 and women over 45.
What are some risk factors for developing Gout?
- Obesity * Medical conditions (CVD, diabetes, renal disease) * High-risk medicines (diuretics) * High alcohol intake * Diet high in purines.
What is the single most important risk factor for developing Gout?
Hyperuricemia.
Fill in the blank: Gout can occur in people with normal plasma uric acid levels and many people with _______ never develop Gout.
hyperuricemia.
What is hyperuricemia?
The single most important risk factor for developing gout
Hyperuricemia can occur in people without gout, and many with gout can have normal uric acid levels.
What does sUA stand for?
Serum Uric Acid
sUA is the most important risk factor for gout but should be considered with other clinical features.
What are the 4 distinct stages of gout?
- Asymptomatic gout
- Acute gout
- Intercritical gout
- Chronic gout
Each stage has different characteristics and implications for treatment.
What characterizes acute gout?
Sudden and intense pain and swelling in joints
Damage to the joints begins during this stage.
How long does an acute gout attack typically last?
3-10 days
This duration can vary among individuals.
What is the main method for diagnosing gout?
Clinical history and examination
There is no single examination that confirms a diagnosis of gout.
What is the gold standard test for diagnosing gout?
Joint fluid test
It checks for uric acid crystals and can rule out septic arthritis.
What is the reference range for serum uric acid in males over 12 years old?
200-430 µmol/L
Reference ranges vary by age and gender.
What is the 5-year cumulative incidence of gout for plasma urate levels over 600 µmol/L?
305 per 1000
Higher plasma urate levels significantly increase the risk of developing gout.
What is the first-line treatment for acute gout management?
NSAIDs like Ibuprofen or Naproxen
These should be continued for 48 hours after the attack resolves.
What should be considered for patients at high risk of GI bleeding when using NSAIDs?
A PPI (Proton Pump Inhibitor)
This can help protect against gastrointestinal side effects.
What is the second-line treatment for acute gout?
Colchicine 500 micrograms 2-3 times per day
Colchicine can cause side effects like profuse diarrhea.
What are the criteria for initiating uric acid lowering therapy (ULT) in chronic gout management?
- Multiple or troublesome flares (≥2 attacks within 1yr)
- Chronic kidney disease (CKD) stages 3 to 5
- Diuretic therapy
- Tophus
- Chronic gouty arthritis
If none of these apply, ULT is not indicated.
What is the first-line ULT medication for chronic gout?
Allopurinol
It should be started at least 1-2 weeks post the last attack.
What is the maximum dose of Allopurinol recommended per day?
900 mg
This is the maximum tolerated dose for lowering uric acid levels.
What should be monitored when prescribing Allopurinol?
Serum urate levels
Levels should be checked 4 weeks after initiation and adjusted accordingly.
When should Febuxostat be considered in chronic gout management?
If Allopurinol is contraindicated, not tolerated, or ineffective
Febuxostat should be started at least 1-2 weeks post the last attack.
What is the starting dose of Febuxostat?
80 mg once daily
Starting with a lower dose may reduce the incidence of acute flares.
What is a potential interaction of Allopurinol?
It potentiates the anticoagulant effect of warfarin
Monitoring is necessary during dose titration.
True or False: X-rays are commonly used to diagnose gout.
False
X-rays rarely detect urate crystals but may help rule out similar conditions.
What is the role of ultrasound in gout diagnosis?
To detect crystals in the joints and deep in the skin
It is a simple and safe method increasingly used in practice.
What can decrease the incidence of acute flares?
May decrease the incidence of acute flares.
What should be done if sUA is >360 μmol/l after 4 weeks?
The dose can be increased by 40mg & sUA rechecked in a further 4 weeks.
What is the maximum dose of febuxostat?
Max dose = 120 mg daily.
What should be co-prescribed to prevent an acute gout flare?
Prophylactic colchicine (500 mcg b.d. for up to 6 months) or NSAID (ibuprofen 200mg b.d. or naproxen 250mg daily for up to 6 weeks).
What should be done if hypersensitivity occurs with febuxostat?
Stop febuxostat immediately, do not restart.
With which medications should febuxostat be avoided?
Azathioprine and mercaptopurine.
When should febuxostat not be started?
During an acute attack; ensure at least 1-2 weeks have passed before initiation.
What should be done if an attack develops while on febuxostat?
Continue treatment and treat the attack separately.
Should patients already stabilized on ULT interrupt therapy during a gout flare?
DO NOT interrupt uric acid lowering therapy unless there is a clinical reason.
What is NOT a clinical reason to interrupt uric acid lowering therapy?
Gout flare is NOT a clinical reason.
When should a patient be referred to Secondary Care immediately?
If septic arthritis is suspected.
What are routine reasons to refer a patient to Secondary Care?
- sUA is unresponsive to uric acid lowering therapy
- Gout persists despite uric acid levels <360 μmol/l
- Patient suffers complications relating to gout
- Patient requires intra-articular therapy and primary care are not able to provide
- There is diagnostic uncertainty.
What complications are associated with gout?
- Tophi may create problems with activities of daily living
- Hyperuricaemia-induced renal disease
- Urinary stones found in 10–25% of people with gout.
What is the correlation of urinary stones with plasma urate levels?
The incidence of urinary stones is strongly correlated with plasma urate level.
What can happen at plasma urate levels higher than 780 micromol/L?
The incidence of urinary stones increases by up to 50%.
