ENDOCRINE Flashcards
Give 5 parathyroid hormone actions
- Increase Ca2+ reabsorption
- Decrease phosphate reabsorption
- Increase 1 alpha-hydroxylation of 25-OH vit D
- Increase bone remodelling (bone resorption >bone formation)
- Increase Ca2+ absorption because of increase 1,25(OH)2D (no direct effect)
When serum calcium levels are low, what are PTH levels?
PTH levels are high
When serum calcium levels are high, what are PTH levels?
PTH levels are low
What is the effect of hyperparathyroidism on serum calcium levels?
Hyperparathyroidism –> hypercalcaemia
what are the clinical features of hyperparathyroidism?
SYMPTOMS
- BONES – excess bone resorption caused by PTH Pain, fractures, osteopenia, osteomalacia, osteoporosis - STONES – due to excess Ca. Renal colic from renal calculi and biliary stones - GROANS – abdominal pain, malaise, nausea, constipation, polydipsia, polyuria, dehydration, confusion, risk of cardiac arrest - MOANS – depression, anxiety, cognitive dysfunction, insomnia, coma
SIGNS
hypercalcaemia
Give 2 causes of primary hyperparathyroidism
- Parathyroid adenoma
- Hyperplasia
- Parathyroid cancer
what is the the pathophysiology of secondary hyperparathyroidism
Physiological compensatory hypertrophy of all parathyroid resulting in excess PTH due to hypocalcaemia
Often due to CKD and vitamin D deficiency
what is the pathophysiology of tertiary hyperparathyroidism?
Prolonged uncorrected hypertrophy - glands become autonomous producing excess PTH
What blood results would you see in the 3 types of hyperparathyroidism?
PRIMARY =
- PTH = high
- calcium = high
- phosphate = low
- alk phos = high
SECONDARY =
- PTH = high
- calcium = low
- phosphate = high
- alk phos = high
TERTIARY -
- PTH = high
- calcium = high
- phosphate = high
- alk phos = high
Describe the treatment for hyperparathyroidism
- adenoma = surgical removal
- hyperplasia = all 4 glands surgically removed
- calcimimetric = ORAL CINACALET
How does a calcium mimetic work?
Increases sensitivity of parathyroid cells to calcium so less PTH secretion occurs
What is the affect of hypoparathyroidism on serum calcium levels?
Hypoparathyroidism –> hypocalcaemia
what are the clinical features of hypoparathyroidism?
SYMPTOMS:CATs go numb
- convulsions / seizures
- arrhythmias / anxious
- tetany / muscle spasms
- numbness
SIGNS:
- CHVOSTEK’S SIGN - tap over facial nerve and look for spasm of facial nerves
- TROUSSEAU’S SIGN - inflate BP cuff 20 mmHg above systolic for 5 mins = hand spasm - hypocalcaemia
what are the causes of hypoparathyroidism?
- secondary to increased serum phosphate
- severe vitamin D deficiency
- reduced PTH function
- drugs - calcitonin, bisphosphonates
What are blood results for someone with hypoparathyroidism?
Calcium = Low PTH = Low Phosphate = High
What is the treatment for hypoparathyroidism?
Acute = IV calcium Persistant = Vitamin D analogue - ORAL ADCAL
what are the causes of Hypercalcaemia?
Hyperparathyroidism Malignancy Sarcoidosis Thyrotoxicosis Drugs
What is the treatment for hypercalcaemia?
- Treat underlying cause
- increase circulation volume, increase excretion
.- Bisphosphonates, glucocorticoids, gallium, dialysis
Give 2 ECG changes that you might see in someone with hypercalcaemia
- Tall T waves
2. Shortened QT interval
Name 3 causes of hypocalcaemia
Hypoparathyroidism Vitamin D deficiency Hyperventilation Drugs Malignancy Toxic shock
what are the investigations for hypocalcaemia?
Corrected Calcium levels,
ECG (prolonged QT)
Parathyroid function - PTH
what is the treatment for hypocalcaemia?
10ml calcium gluconate/chloride 10% slow IV,
oral calcium and Vit D
Give 2 ECG changes that you might see in hypocalcaemia?
- Small T waves
2. Long QT interval
What does the parathyroid control?
Serum calcium levels
A low serum calcium triggers the release of PTH and a high serum calcium triggers c-cells to release calcitonin
What hormone does the parathyroid secrete and what is its function?
PTH - secreted in response to low serum calcium
What is released by c-cells in the parathyroid in response to high serum calcium?
Calcitonin
What biochemical test might you want to do to establish the cause of hypercalcaemia?
PTH measurement
What disease is described as being a ‘disorder of carbohydrate metabolism characterised by hyperglycaemia’?
Diabetes mellitus
what is T1DM?
Autoimmune destruction of pancreatic beta cells leading to complete insulin deficiency.
what is the pathophysiology of T1DM
- autoimmune destruction of beta cells in the Islets of Langerhans by autoantibodies cause insulin deficiency and continued breakdown of liver glycogen
- this causes hyperglycaemia and glycosuria
Is T1DM characterised by a problem with insulin secretion, insulin resistance or both?
Characterised by impaired insulin secretion - severe insulin deficiency
what are the risk factors for developing T1DM?
- Northern European
- Family History:
- HLA DR3-DQ2 or
- HLA-DR4-DQ8 - Other autoimmune diseases:
- Autoimmune thyroid
- Coeliac disease
- Addison’s disease
- Pernicious anaemia
what are the clinical features of T1DM?
Polydipsia - Thirst (fluid and electrolyte losses)
Polyuria (due to osmotic diuresis)
Weight loss
- usually short history of severe symptoms
Describe the epidemiology of T1DM
Onset younger (<30 years) Usually lean More Northern European ancestry
A diagnosis of diabetes can be made by measuring plasma glucose levels. What would a persons fasting plasma glucose be if they were diabetic?
Fasting plasma glucose >7 mmol/L
A diagnosis of diabetes can be made by measuring plasma glucose levels. What would a persons random plasma glucose be if they were diabetic?
Random plasma glucose >11 mmol/L
What might someone’s HbA1c be if they have diabetes?
> 48 mmol/L>6.5%
What happens to C-peptide in T1DM?
C-peptide reduces
How do you treat T1DM?
Education
Glycaemic control through diet (low sugar, low fat, high starch)
Insulin SC
Give 6 complications of Diabetes Mellitus
- Diabetic ketoacidosis
- Diabetic nephropathy
- Diabetic retinopathy
- Diabetic neuropathy
- Hyperosmolar hyperglycaemic coma
- Stroke, ischaemic heart disease, peripheral vascular disease
Give 2 potential consequences of T1DM
- Hyperglycaemia
2. Raised plasma ketones –> ketoacidosis
How is insulin administered in someone with T1DM?
Subcutaneous injections
Other than SC injections, how else can insulin be administered?
Insulin pump
what are the different types of insulin used to treat T1DM?
- short acting - 4-6hrs
- short acting analogues -
- long acting - 12-24hrs
Give 4 potential complications of insulin therapy
- Hyperglycaemia
- Lipohypertrophy at injection site
- Insulin resistance
- Weight gain
- Interference with life style
What is the affect of cortisol on insulin and glucagon?
Inhibits insulin
Activates glucagon
Describe the pathophysiology of diabetic ketoacidosis
Results from a reduced supply of glucose and an increase in fatty acid oxidation.
The increased production of Acetyl-CoA leads to ketone body production that exceeds the ability of peripheral tissues to oxidise them.
Ketone bodies are relatively strong acids (pH 3.5), and their increase lowers the pH of blood
it IMPAIRS THE ABILITY OF HAEMOGLOBIN TO BIND TO OXYGEN
Name 3 ketone bodies
- Acetoacetate
- Acetone
- Beta hydroxybutyrate
Where does ketogenesis occur?
Liver
what are the clinical features of diabetic ketoacidosis?
SIGNS
- Breath smells of pear drops (ketones)
- Kussmaul’s breathing - deep, rapid breathing
- Tachycardia
- Hypotension
- Reduced tissue turgor
SYMPTOMS
- Nausea and vomiting
- Dehydration
- exacerbated by vomiting
- Weight loss
- Drowsy/confused
- Abdominal pain
Give 3 microvascular compilation of DM
- Diabetic retinopathy
- Diabetic nephropathy
- Diabetic peripheral neuropathy
Give 2 macrovascular complications fo DM
CV disease
Stroke
What is the main risk factor for diabetic complications?
Poor glycemic control
What is the treatment for diabetic ketoacidosis?
- ABC
- Replace fluid loss with 0.9% saline IV
- IV insulin
- Restore electrolytes e.g. K+
Give 3 endocrine diseases that can cause diabetes
- Cushing’s
- Acromegaly
- Phaeochromocytoma
What class of drugs can cause diabetes?
Steroids
Thiazides
Anti-psychotics
Is T2DM characterised by problem with insulin secretion, insulin resistance or both?
Characterised by impaired insulin secretion and insulin resistance
what is the aetiology of T2DM?
- Decreased insulin secretion and increased insulin resistance
- No immune disturbance
- No HLA disturbance but strong genetic link
- Polygenic
- Associated with obesity, lack of exercise, calorie and alcohol excess
Describe the pathophysiology of T2DM
Insulin binds normally to its receptor – insulin resistance develops post-receptor
Circulating insulin levels are higher than in healthy patients but inadequate to restore glucose homeostasis
Increased glucose production in liver- inadequate suppression of gluconeogenesis and there’s reduced glucose uptake in peripheral tissues
Hyperglycaemia and lipid excess are toxic to beta cells - reduced beta cell mass
Don’t tend to develop ketoacidosis but do get glycosuria
Why is insulin secretion impaired in T2DM
Due to lipid deposition in the pancreatic islets
what are the risk factors for T2DM?
Increase w/ age M > F Ethnicity: African-Carribean, Black African and South Asian Obesity Hypertension
What happens to insulin resistance, insulin secretion and glucose levels in T2DM?
Insulin resistance increase Insulin secretion decreases Fasting and post-prandial glucose increase
Why do you rarely see diabetic ketoacidosis in T2DM?
Insulin secretion is impaired but there are still low levels of plasma insulin
Low levels of insulin prevent muscle catabolism and ketogenesis
By how much has the beta cell mass reduced in T2DM when diagnosis usually occurs?
50% of normal beta cell mass
Describe the epidemiology of T2DM
Onset older (>30)
Usually overweight
More common in African/Asian populations
Males > Females
Describe the treatment pathway for T2DM
- Lifestyle changes - lose weight, exercise, healthy diet and control of contributing conditions
- Monotherapy - Metformin
- dual therapy
- triple therapy
i) metformin
ii) DPP4 inhibitor
iii) SU, gliclazide
iv) SGLT-2 inhibitor
v) pioglitazone
vi) insulin
How does metformin work in treating T2DM?
Increase insulin sensitivity and inhibits glucose production
How does sulfonylurea work in treating T2DM?
Stimulates insulin release
block ATP dependent K+ channels in beta cells -> causes depolarisations and opening of voltage gated Ca2+ channels -> stimulates insulin secretion
what are the side effects of Sulfonylurea?
Hypoglycaemia
weight gain
hyponatraemia
What is hypoglycaemia classified as?
Plasma glucose <3.9 mmol/L and if <3.0 mmol/L it is severe hypoglycaemia
Give 5 symptoms of hypoglycaemia
- Hunger
- Sweating
- Tachycardia
- Anxious
- Shaking
- Confusion
- Weakness
- Vision changes
Why does hypoglycaemia continuously get worse?
Glucagon is not produced so rely only on adrenaline and the threshold for adrenaline release gradually lowers after time
Give 6 consequences of hypoglycaemia
- Seizures
- Comas
- Cognitive dysfunction
- Fear
- Decrease in qualitative life
- Accidents
Briefly describe the treatment of hypoglycaemia
Oral sugar and long acting starch
50% GLUCOSE IV or IM GLUCAGON
If episodes persist, suggest many small high starch meals
Re-educate diabetics on insulin use
Why are patient with diabetes at a particular risk of hypoglycaemia?
In Diabetes there are defects in the physiological defences to hypoglycaemia and there is reduced awareness
What does prevention of hypoglycaemia include?
Eduction
Correct choice of therapy
Adjusting glucose targets in those at high risk
Specialist support from a MDT
Is insulin secretion or insulin resistance the driving force of hyperglycaemia in T2DM?
Hepatic insulin resistance is the driving force
Give a potential consequence of acute hyperglycaemia
Diabetic ketoacidosis and hyperosmolar coma
Give a potential consequence of chronic hyperglycaemia
Mirco/macrovascular tissue complications
A man presents with a history of weight loss, polyuria and nocturia. He is very unwell. The GP performs a capillary blood glucose which is found to be 17.2mmol/l. What is the most likely diagnosis of this mans symptoms?
Type 1 Diabetes Mellitus
Name 5 possible diseases of the pituitary
- Benign pituitary adenoma
- Craniopharygioma
- Trauma
- Apoplexy/Sheehans
- Sarcoid/TB
Give 3 potential consequences of a pituitary tumour
- Pressure on local structures - e.g. optic chasm = bilateral hemianopia
- Pressure on normal pituitary (lack of function) - Hypopituitarism
- Functioning tumours - e.g. Cushing’s, acromegaly, prolactinoma
Describe the growth hormone secretion from the anterior pituitary
It is secreted in a pulsatile fashion and increases during deep sleep
What is acromegaly?
Overgrowth of all organ systems due to excess growth hormone in adults
What is gigantism?
Excess GH production in children before fusion of the epiphyses of the long bones
what are the clinical features of acromegaly?
SYMPTOMS: large hands, box jaw, thick skin, arthritis, sight problems weight gain
SIGNS: hypertension, insulin resistance, bitemporal hemiopia large tongue
what is the pathophysiology of acromegaly?
GH exerts activity indirectly through IGF-1 or directly on tissue
Excessive IGF- levels mediate most of the skeletal and soft tissue growth like features of acromegaly
What can cause acromegaly?
- A benign pituitary adenoma producing excess GH
- rarely due to hyperplasia
Describe the epidemiology of acromegaly
Average age is 40 years
male = female
Reduces life expectancy by 10 years
What complications are associated with acromegaly?
type 2 diabetes
sleep aponea
heart disease
arthritis
What are the investigations for acromegaly?
1st line = IGF-1
2nd line = oral glucose tolerance test
3rd line = pituitary function tests
4th line = MRI
also investigate for complications
What is the gold standard diagnostic test for acromegaly?
Oral glucose tolerance test - failure of glucose to suppress serum GH
what is the management for acromegaly?
1st line = trans sphenoidal surgery
2nd line = OCTREOTIDE (somatostatin analogue) +/- CABERGOLINE (dopamine agonist) if GH secretions persist
3rd line = PEGVISOMANT (GH receptor antagonist)
4th line = radiotherapy
Give 3 potential complications of transsphenoidal surgical resection for the treatment of acromegaly
- Hypopituitarism
- Diabetes insidious
- Haemorrhage
- CNS injury
- Meningitis
What types of medical therapy can be used to treat acromegaly?
somatostatin analogue = octreotide
dopamine agonist = cabergoline
GH receptor antagonist = pegvisomant
Give 3 advantages of using dopamine agonists in the treatment of acromegaly
- No hypopituitarism
- Oral administration
- Rapid onset
Give 2 disadvantages of dopamine agonists in the treatment of acromegaly
- Can be ineffective
2. Risk of side effects
Name a dopamine agonist that can be used as a treatment for acromegaly
Cabergoline
Why can somatostatin analogues be used in the treatment of acromegaly?
They inhibit GH release
Why can GH receptor antagonists be used in the treatment of acromegaly?
They suppresses IGF-1
What is prolactinoma?
Lactotroph cell tumour of the pituitary
Prolactin secreting tumour
Name the 2 types of prolactinoma
- Microprolactinoma = most common, >90%
2. Macroprolactinoma = >10mm
what are the causes of prolactinoma?
- Pituitary adenoma
- Anti-dopaminergic drugs
- Head injury - compression of the pituitary stalk
what are the clinical features of prolactinoma
SYMPTOMS: amenorrhea, galactorrhoea, gynaecomastia, low libido, possible cerebral symptoms
SIGNS:
low testosterone,
infertility
Briefly describe the pathophysiology of Prolactinoma
Increased release of prolactin can cause galactorrhoea and can inhibit FSH and LH
Compression of the pituitary stalk
Prevents secretion of dopamine from hypothalamus - stops inhibition of prolactin
what are the investigations for prolactinoma?
Serum prolactin levels - HIGH
CT head
What is the treatment for prolactinoma?
Dopamine agonists - cabergoline - inhibits prolactin release
Occasionally transsphenoidal pituitary resection
What is Cushing’s Syndrome?
Chronic, excessive and inappropriate elevated levels of circulating plasma glucocorticoids (cortisol)
What is Cushing’s Disease?
When Cushing’s syndrome is caused by a pituitary tumour so excess glucocorticoids due to inappropriate ACTH secretion
what is the clinical presentation of Cushing’s disease?
Central obesity Plethoric complexion Moon face Mood change Proximal muscle weakness Purple abdominal striae Gastric ulcers Osteoporosis Hirsutism
what are the causes of excess cortisol?And are they ACTH dependent or independent?
ACTH dependent:
- Cushing’s disease
- Ectopic ACTH production
- ACTH treatment
ACTH independent
- adrenal adenoma
- iatrogenic
What is a differential diagnosis of Cushing’s syndrome?
Pseudo-Cushing’s = excessive alcohol consumption can mimic the clinical and biochemical signs but resolved on alcohol recession
Describe the epidemiology of Cushing’s syndrome
women > men
majority diagnosed 20-50y/o
most common cause is oral steroids
what are the investigations for Cushing’s syndrome?
- drug history - oral steroids
- random plasma cortisol - high
- overnight dexamethasone suppression test and urinary free cortisol (24hr) - positive (no suppression = cushings)
- test plasma ACTH
How does a dexamethasone suppression test work?
Give synthetic steroids that suppress pituitary and adrenals and then measure the cortisol
In Cushing’s there is no suppression of cortisol
What is the treatment for Cushing’s syndrome?
Tumours = surgical removal
- pituitary adenoma = transsphenoidal surgical resection
- adrenal adenoma = adrenalectomy
Drugs to inhibit cortisol synthesis - metyrapone, ketoconazole
What are some complications associated with Cushing’s Syndrome?
cardiovascular disease
hypertension
diabetes mellitus
osteoporosis
What is the circadian system?
Body clock that regulates your body
Clear rhythm of cortisol production follows circadian rhythm
When do cortisol levels peak?
At around 8:30 am
What’s the primary cue that synchronises an organism’s biological rhythms?
Light
What is adrenal insufficiency?
Adrenocortical insufficiency resulting in a reduction of mineralocorticoids, glucocorticoids and androgens
what is Addison’s disease?
Destruction of entire adrenal cortex resulting in mineralocorticoid (aldosterone), glucocorticoid and androgen deficiency
what are the causes of Addison’s disease?
- autoimmune destruction (21-hydroxylase present in 60-90%) - most common in developed countries
- TB - most common in developing countries
- adrenal metastases- long term steroid use
what are the clinical features of Addison’s disease?
SYMPTOMS
Fatigue
Weakness
Weight loss
SIGNS Hyperpigmentation Postural hypotension Hypoglycaemia Other signs of autoimmunity
What is the treatment for adrenal insufficiency?
Hormone replacement - any steroids
ORAL HHYDROCORTISONE
ORAL FLUDROCORTISONE
What is the pathophysiology of Addison’s disease?
Destruction of the adrenal cortex results in decreased production of the hormones
All steroids reduced
Reduced cortisol levels = increased CRH and ACTH production through feedback
What are the investigations for Addison’s disease?
- SynACTHen test = giving synthetic ACTH does not increase cortisol levels
- Serum electrolytes = low Sodium, high Potassium
- FBC: Anaemia and eosinophilia
- Morning serum cortisol = Reduced
- Adrenal CT or MRI
What investigations would you do to determine whether Adrenal insufficiency is primary or secondary?
Primary = adrenal antibodies, very long chain fatty acids, imaging and genetics Secondary = any steroids?, imaging and genetics
what are the features of addisonian crisis?
Vomiting abdominal pain profound weakness hypoglycaemia hypovolemic shock
What is the management of adrenal crisis?
Immediate IV Hydrocortisone
Fluid resuscitation - saline (IV)
What would sodium and potassium levels be in someone with adrenal insufficiency?
Hyponatraemia = low sodium
Hyperkalaemia = high potassium
Lack of aldosterone and so less sodium reabsorbed and less potassium excreted
Why is it important to take a drug history when speaking to someone with potential Cushing’s?
To exclude steroid use as a potential cause
Briefly describe the mechanism of thyroid destruction
Cytotoxic (CD8+) T cell mediated thyroglobulin and Thyroid peroxidase (TPO) antibodies may cause secondary damage (alone have no effect)
Antibodies against the TSH receptor may block the effect of TSH (uncommon)
What are the main 3 types of cells that cause thyroid destruction?
- Cytotoxic T cells
- Thyroglobulin
- TPO antibodies
Briefly describe the pathophysiology of Grave’s disease
Specific serum IgG (TSH receptor stimulating antibodies) bind to TSH receptors in thyroid
Behave like TSH – stimulate T3 and T4 production
This results in excess secretion and hyperplasia of thyroid follicular cells – causing hyperthyroidism and graves ophthalmopathy
what is the clinical presentation of Grave’s opthlmopathy?
SYMPTOMS Eye discomfort Grittiness increased tear production Photophobia Diplopia reduced acuity
SIGNS Exophthalmos – protruding eye Proptosis – eye protrudes beyond orbit Conjunctival oedema Corneal ulceration Ophthalmoplegia – paralysis of eye muscles
what is the clinical presentation of grave’s dermopathy?
Pretibial myxoedema – raised, purple red symmetrical skin lesions over anterolateral aspects of shin
Thyroid acropachy – clubbing, swollen fingers and periosteal bone formation
what is the treatment for Grave’s ophthalmology?
Conservative treatment – smoking cessation and sunglasses
IV METHYLPREDNISOLONE and surgical decompression/eyelid surgery
Name 5 risk factors for Graves disease
- Female
- Genetic association
- E.coli
- Smoking
- Stress
- High iodine intake
- Autoimmune diseases
Name 5 autoimmune diseases associated with thyroid autoimmunity
- T1DM
- Addison’s disease
- Pernicious anaemia
- Vitiligo
- Alopecia areata
- Rheumatoid arthritis
What would you see histological in someone with Graves disease?
Lymphocyte infiltration and thyroid follicle destruction
What is goitre?
Palpabel and visible thyroid enlargement
Why does goitre occur and when is is most commonly found?
Due to TSH receptor stimulation resulting in thyroid growth
Seen in hypo and hyperthyroidism
Name 4 types of sporadic non toxic goitre
- Diffuse –> physiological –> Graves
- Multi nodular
- Solitary nodule
- Dominant nodule
Define hyperthyroidism
Overactivity of the thyroid gland