Type 1 Diabetes
Syndrome of chronic hyperglycaemia due to relative insulin deficiency
Type 2 Diabetes
Syndrome of chronic hyperglycaemia due to relative insulin resistance
Gestational Diabetes
When pregnant women without previous DM develop high blood sugar
Cause of Type 1 Diabetes
Insulin deficiency due to autoimmune destruction of insulin-secreting pancreatic B-cells. Destruction of B-cells causes hyperglycaemia and metabolic acidosis.
Causes of Type 2 Diabetes
Decreased insulin secretion and insulin resistance due to B-cell dysfunction. Insulin resistance primarily occurs in liver, muscle and fat tissue. Typically progresses from impaired glucose tolerance or impaired fasting-glucose
How common is Type 1 DM
Younger usually <30 yo
Usually leand
Increased in Northern Eastern ancestry
How common is Type 2 DM
Older usually > 30 yo
Often overweight
All racial groups. Increase in peoples of Asian, African Polynesian ancestry
Higher concordance in identical twins
Risk factors for Type 2 DM
Obesity, increasing age, male, low exercise, alcohol, high calorie intake, poor diet, family Hx, Hx of gestational diabetes, polycystic ovary syndrome, HTN, dyslipidaemia
Symptoms for Diabetes Mellitus
Polyuria, polydipsia (increased thirst), polyphagia (increased hunger), lethargy, frequent infections, weight loss, psychosocial implications, blurred vision for type 2
Symptoms for Type 1 Diabetes
Dehydration, ketonuria, hyperventilation, abdominal pain, vomiting, fetor hepaticus (breath smells like pear drops)
all due to ketoacidosis
Symptoms for Type 2 Diabetes
Candida infections, skin infections, UTIs, fatigue, blurred vision, polydipsia and polyuria, acanthosis nigricans
Investigations for Type 1 Diabetes
Random Plasma glucose >11mmol/L fasting plasma glucose >6.9 2-hour plasma glucose >11 Plasma or urine ketones HbA1C >48 Fasting C-peptide low or undectable
Investigations for Type 2 Diabetes
Fasting plasma glucose >6.9
HbA1C of 48 or greater
Abnormal glucose tolerance tests
Random plasma glucose of >11.1 plus symptoms of hyperglycaemia
Investigations for Pre-diabetes
Single fasting plasma glucose of 5.6-6.9
HbA1c of 39-46
Differentials for Type 1 Diabetes
Maturity onset diabetes of the young
Type 2 Diabetes
Differentials for Type 2 Diabetes
Pre-diabetes
Type 1 diabetes
Latent autoimmune diabetes in adults (LADA)
Treatment plan for treating Diabetes
1. Lifestyle changes \+ Glycaemic management \+ BP management \+ Lipid management \+ Antiplatelet therapy 2. Metformin
Treatment for Type 1 Diabetes
Patient will always need insulin
Short-acting insulin in twice daily regimen
Long-acting insulin works well for those who dislike injecting
Inhaled forms also available
Treatment for Type 2 Diabetes
3 drugs:
- Biguanide (metformin)
- Sulfonylureas (tolbutamide, glibenclamide, glipzide, glicazide, chlopropamide)
- Thiazolidinediones
Others: intestinal enzyme inhibitors, orlistat, rimonbant
Bariatric surgery for some
Complications of Diabetes
Stroke, MI Amputation for foot gangrene Diabetic retinopathy, nephropathy, neuropathy Diabetic foot ulcers Diabetic ketoacidosis Cataracts Dehydration Coronary artery disease, cerebrovascular disease, peripheral vascular disease Diabetic Kidney Disease
Prognosis of Type 1 Diabetes
Untreated Type 1 is fatal due to DKA.
Prognosis of Type 2 Diabetes
When diagnoses at age 40:
men lose 5.8 years of life
women lose 6.8 years of life
Primary and Secondary Hypothyroidism
Hypothyroidism is underproduction of T3 and T4. Primary hypothyroidism (95% of cases) is failure of the thyroid gland to produce thyroid hormones. Secondary hypothyroidism is underproduction of TSH by the pituitary gland.
How common is hypothyroidism
More common in women and white people.
Increases with age
Pathophysiology of Hypothyroidism
T4 is produced in the thyroid gland and converted to T3 in target tissues. Failure of the thyroid to produce T4 and T3 stimulates the pituitary to increase production of TSH.
Causes of Hypothyroidism
- Hashimoto’s Disease (Autoimmune thyroiditis)
- Iodine deficiency
- Damage to thyroid gland from Thyroidectomy, radioactive iodine therapy
- Infiltrative diseases: Sarcoidosis, Haemochromotosis
- Primary atrophic hypothyroidism (Thyroid infiltrated with lymphocytes)
Risk factors for Hypothyroidism
Iodine deficiency Female Middle Age Autoimmune disorders Graves disease Radiotherapy
Symptoms of Hypothyroidism
Constipation, weight gain, decreased appetite, cold intolerance, tiredness and lethargy, difficulty concentrating, menorrhagia, dry skin, loss of outer 3rd of eyebrows, alopecia, loss of libido, hoarse voice, cramps, dementia, weakness
Signs of Hypothyroidism
Myxoedema (puffy hands, face and feet), dry coarse skin, cold peripheries, bradycardia, delayed tendon reflex relation, cavity effusion e.g. pleural effusion, pericarditis, goitre, pretibial myxoedema, exophthalmos, ophthalmopegia (paralysis of muscles around eyes)
Differentials for Hypothyroidism
Phaechromocytoma
Depression
Investigations for Hypothyroidism
TFTs: Elevated TSH, low T3 and T4
Anti-thyroid peroxidase antibodies (anti-TPO)
Treatment for Hypothyroidism
Levothyroxine (T4)
Lower dose for pre-existing CAD or > 60 yo and some with subclinical hypothyroidism TSH > 10
Complications of Hypothyroidism
Angina due to Levothyroixine, AF, Osteoporosis Myxoedema coma (severe form of hypothyrodism with multi-organ failure, decreased mental status, hypothermia)
Hyperthyroidism aka Grave’s Disease
Hyperfunction and over-activity of the thyroid gland
Pathophysiology
Anti-TSH receptor antibodies cause thyroid hormone overproduction as well as thyroid hypertrophy and hyperplasia of thyroid follicular cells
How common is Hyperthyroidism
More common in women
40-60yo
Lower prevalence in black people
Causes of Hyperthyroidism
Grave's disease Toxic Thyroid Adenoma Toxic Multinodular Goitre Ectopic Thyroid Tissue Struma Ovarii
Secondary Hyperthyroidism
TSH, T3 and T4 are all high
Caused by TSH-secreting pituitary adenoma, thyroid hormone-resistance syndrome, HCG-secreting tumour, gestational thyrotoxicosis
Risk Factors for Hyperthyroidism
High Iodine Intake
Female
Smoking
Symptoms and signs of Hyperthroidism
Diarrhoea, weight loss despite overeating, increased appetite, sweating, heat intolerance, palpitations, resting tremor, irritability, mood swings, oligomenorrhoea (infrequent period), psychosis, itch, alopecia, urticaria, loss of libido, palmar erythema, tachycardia, goitre, gynaecomastia, lid lag
Signs of Grave’s Disease
Exopthalmos, opthalmoplegia, pretibial myxoedema, thyroid acropachy, thyroid bruit
Differentials for Hyperthyroidism
Phaeochromocytoma
Toxic nodular goitre
Painless and postnatal thyroiditis
TSH-producing pituitary adenoma
Investigations for Hyperthyroidism
TFTs: Low TSH, High T3 and T4 Mild normocytic anaemia Mild neutropenia High ESR, CPR Raised LFTs Thyroid Antibodies Isotope Scan
Treatment for Hyperthyroidism
- Anti-thyroid drug e.g. Carbimazole
+ corticosteroids, beta blockers, iodine solution - Radioactive iodine
- Thyroid surgery
Complications of Hyperthyroidism
Hypothyroidism due to radio-iodine treatment
Hoarse voise, heart failure, Angina, AF, Osteoporosis, Opthalmopathy, gynaecomastia
Goitre
A goitre is a swelling in the neck caused by an enlarged thyroid gland. May be due to hypo/hyper thyroidism
Types of Goitre
Uninodular
Multinodular
Diffuse
Risk Factors for Goitre
- Excess iodine
- Iodine insufficiency
- Family History
- Autoimmune deficiency
Causes of Goitre
Iodine deficiency (hyperplasia)
Hashimoto’s (infiltration of lymphocytes)
Pituitary adenoma (hypersecretion of TSH)
Graves (Autoantibodies activating the TSH receptor)
Thyroid cancer
Symptoms and signs of Goitre
Heat intolerance and weight loss, depression, nervousness, palpitations, tachycardia, resting tremor
Large goitre= oesophageal compression, dysphagia, tracheal compression
Investigations for Goitre
TSH suppressed
T3, T4 elevated
Thyroid USS
TSH receptor antibodies. : negative but positive in Graves
Treatment for Goitre
Radioactive iodine therapy
Anti-thyroid drugs i.e. thiamazole
Thyroid surgery
Cushing’s Syndrome
Condition in which the pituitary gland releases excess adrenocorticotrophic hormone (ACTH) causing excess cortisol release from adrenal glands. Involves abnormal feedback of HPA axis
How common is Cushing’s syndrome
More common in women
20-50yo
Cushing’s Syndrome
Condition involving hypercortisolism. Can
either be ACTH-dependent Cushing’s syndrome or ACTH-independent hypercortisolism.
Cushing is when the adrenal glands secrete excess cortisol and involves abnormal feedback of the HPA axis.
How common is Cushing’s Syndrome
More common in women
20-50yo
Cushing’s Syndrome
Condition in which the adrenal glands secrete excess cortisol and involves abnormal feedback of the HPA axis.
Causes of Cushings
- Increased ACTH secretion from anterior pituitary
- Ectopic ACTH production i.e. small cell lung carcinoma
- Ectopic CRH production
- Adrenal adenomas
- Adrenal nodular hyperplasia
Causes of hypercortisolism where HPA axis is not involved
Pregnancy Malnutrition Alcoholism Obesity, Diabetes Stress, anxiety, depression
3 Zones of the Adrenal Cortex and the steroids they make
Zona Glomerulosa - mineralocorticoids (aldosterone)
Zona Fisculate - glucocorticoids (cortisol)
Zona Reticularis - sex steroids (androgens)
Effect of High and Low Cortisol
High cortisol causes gluconeogenesis, glycogen depostion
Low cortisol causes protein synthesis and initiation of host response to infection
Risk factors for Cushing’s Syndrome
Obestity Diabetes Hypertension Osteoporosis Iatrogenic steroid use Female
Symptoms and signs of Cushing’s Syndrome
Facial plethora and rounding, weight gain and central obesity, acne, striae, amenorrhoea, oligomenorhoea, depression, HTN, diabetes, osteoporosis, easy bruising, muscle weakness, insomnia, psychosis, hirsutism
Investigations for Cushing’s Syndrome
- Dexamethasone suppression test: Give dexamethasone at midnight then measure cortisol levels at 8am. If cortisol levels arn’t suppressed, then Cushing’s.
- Midnight cortisol test. Elevated cortisol at night if Cushing’s.
- Urine pregnancy test
- Serum glucose
Differentials for Cushing’s
Obesity
Metabolic Syndrome
Treatment for Cushing’s Syndrome
- If iatrogenic cause- stop medication when possible
- Adrenal adenoma- requires resection of tumour or adrenalectomy
- Adrenal carcinoma- adrenalectomy + radiotherapy
- Ectopic ACTH -surgery
- Metyrapone - 11B-hydroxylase blocker used to reduce cortisol levels
Complications of Cushing’s Syndrome
Metabolic Syndrome Hypertension Diabetes Obesity Hyperlipidaemia Thrombophilia Osteoporosis
Addison’s disease
Adrenal insufficiency leading to glucocorticoid and mineral corticoid deficiency. 90% of the adrenal cortex needs to be destroyed to produce adrenal insufficiency
Types of Addison’s disease
- Primary - adrenal pathology
- Secondary - hypothalamic/ pituitary pathology
- Autoimmune (most common) destruction of the adrenal cortex
How common is Addison’s disease
Most common in women- 90% of cases
Cause of Addison’s disease
- Destruction of the 3 layers of the adrenal cortex.
- Disruption of hormone synthesis
- Dysfunction of the autoimmune system with antibodies against the adrenal cortex
,
Risk factors to Addison’s Disease
TB Adrenal metastases Lymphoma Infections: HIV, meningoccocal infection, systemic fungal infection Adrenal Haemorrhage Coealiaac disease Female
Symptoms and Signs of Addison’s Disease
Fatigue, weakness Nausea and vomiting Abdominal pain Anorexia Weight loss Diarrhoea Constipation Dizziness Personality change/ Irritability Amenorrhoea Skin pigmentation Postural hypotension
Investigations for Addison’s Disease
- Bloods
- Low Na/high K+- low aldosterone
- Low glucose, low cortisol levels
- Anaemic - Synacthen test- ACTH stimulation test: serum cortisol <497
- U&E: Elevated Blood Urea nitrogen (BUN) and creatinine
Treatment for Addison’s Disease
Daily hydrocortisone tablets:
Glucocorticoid replacement (cortisol)
Fludrocortisone (mineralocorticoid replacement)
Complications of Addison’s Disease
Acute Adrenal Insufficiency –> Emergency –> requiring IV hydrocortisone
Hyperparathyroidism
Overproduction of PTH results in derangement of calcium metabolism
Types of Hyperparathyroidism
Primary: solitary adenoma, gland hyperplasia
Secondary: Low calcium levels, high parathyroid
Tertiary: Low calcium, very high parathyroid hormone
Malignant hyperparathyroidism
Pathophysiology of Hyperparathyroidism
- PTH is released by parathyroid glands in response to low ionised calcium levels
- When calcium levels are high, parathyroid gland excretion stops
- Effects of parathyroid hormone:
- increased osteoclast activity- to release calcium and phosphate from bones
- Increased kidney reabsorption of calcium + decreasing phosphate reabsorption
- Activate 1,25 dihyrdroxy-vitamin D3 production is to increase absorption of calcium
Risk Factors for Hyperparathyroidism
Female > Male Age > 45 Radiation therapy Currently on Lithium treatment for Bipolar Disorder Female
Symptoms and signs for Hyperparathyroidism
Stones: renal stones, polyuria, polydipsia
Bones: Osteoporosis, osteomalacia, arthritis
Moans: depression, fatigue, memory loss
Throans: polyuria, constipation
Investigations for Hyperparathyroidism
- Blood: raised calcium and PTH, reduced phosphate,
2. DEXA scan
Differentials for Hyperparathyroidism
Familial hypocalciuric hypercalcaemia Humoral hypercalcaemia of malignancy Multiple myeloma Thyrotoxicosis Leukaemia Thiazide use
Treatment for Hyperparathyroidism
Parathyroid excision (lead to hypoparathyroidism)
Vitamin D supplementation
Bisphosphonate
Complications for Hyperparathyroidism
Osteoporosis Bone fractures Nephrolithiasis Hypocalcaemia following surgery Recurrent and superior laryngeal nerve injury following surgery
Parathyroid adenoma
Benign tumour of the parathyroid gland causing hyperparathyroidism.
How common are Parathyroid adenomas
Most common cause of hyperparathyroidism (85%)
Cause of Parathyroid adenomas
MEN genes inactivate tumour suppressor genes and activate RET proto-oncogenes
Symptoms and signs of Parathyroid adenomas
Stones, Bones, Moans, Thrones
Investigation for Parathyroid Adenomas
- Bloods: raised PTH, low calcium
2. Sestamibi Parathyroid Scintigraphy: scan to localise parathyroid adenoma
Treatment for Parathyroid Adenomas
Parathyroidectomy