Endocrine Flashcards
What is Acromegaly and what is a genetic association to it
This is increase GH secretion from a pituitary tumour (or rarely an ectopic NET) leading to increased IGF-1 causing bone and soft-tissue growth
MEN-1 association in 5%
What are the signs and symptoms of Acromegaly
Tumour mass (4)
- Headache
- Visual fields defects
- CN Palsies
- Pituitary stalk compression
Prolactin secretion (5)
- Low libido
- Infertility
- Galactorrhea
- ED
- Amen/Oligomen
Excess IGF-1
- Skin & Soft-tissue: Oily, Sweaty, Thick skin + Skin tags + Carpal tunnel
- Resp: Snoring + Sleep Apnoea + Upper airway obstruction
- Osteo: Arthropathy + Osteoarthritis + Vertebral fractures
- CV: HTN + HF + Arrhythmias + Hypertrophic
- Met: DM
- Organomegaly: Thyroid + Prostate
- Other: Hypercalciuria
What are the investigations indicated in Acromegaly
- Oral Glucose Tolerance Test (OGTT): 75g oral load causes GH >1microgram/L
- Serum IGF-1: Elevated
- MRI Pituitary
- Visual fields: Bitemporal Hemianopia
What is the treatment for Acromegaly
Resectable 1st - Transphenoidal surgery 2nd - SS - Octreotide A - Dopamine agonist - Cabergoline 3rd - Growth hormone receptor antagonist - Pegvisomant 4th - Radiotherapy
Non-resectable
The same without Transphenoidal surgery
What are possible complications of Acromegaly
- Cardiac complications + HTN
- Sleep apnoea + Carpal tunnel
- Osteoarticular + DM
- Precancerous polyps + Hypopituitarism
What are the classifications of Adrenal insufficiency and what are their respective causes
1o - Addison’s - High ACTH
- 80% Autoimmune in UK
- TB worldwide most common cause
- Adrenal mets
- Lymphoma
- HIV
- Adrenal haemorrhage
- Congenital adrenal hyperplasia
2o - Low ACTH
- Iatrogenic - Withdrawal of steroids that have caused suppression of the pit-adrenal axis
- Hyperthalamic-pituitary disease
What sex is mostly affected by Adrenal insufficiency
Women 90%
What are the symptoms of Adrenal insufficiency
- Fatigue + Weakness (Most common PC)
- Muscle weakness + Myalgia + Arthralgia
- Anorexia + Weight loss
- N&V + Constipation + Abdominal pain
Salt cravings
Dizziness
What are signs of Adrenal insufficiency
- Mucosal/cutaneous hyperpigmentation in sights of continuous friction: Palms, Knuckles, Elbows, Scars, Inside mouth - Not in 2o
- Postural hypotension - Decreased mineralocorticoid activity
- Hx Autoimmunity - Vitiligo + Hashimoto’s + Pernicious anaemia
- Axillary and pubic hair loss in women
What are the signs of an adrenal crisis
Shock = Low BP + High HR
Fever
Coma
What are appropriate investigations in Adrenal insufficiency and the associated investigator findings
- Morning Cortisol (9am) - <83nmols/L
- Short ACTH stimulation test (Synacthen test) - 250micrograms of ACTH given - Cortisol <497nmols/L
- Serum ACTH - High in 1o; Low in 2o (Aldosterone will also be lower in 1o)
Other
- U+Es: Hyperkalaemia, Hyponatraemia, Uraemia
- FBC: Eosinophilia
- CT Adrenal
- CXR
Outline treatment for Adrenal insufficiency
Crisis
IV Hydrocortisone + Normal Saline + 5% Dextrose
Stable
Glucocorticoid + Mineralcorticoid (Prednisolone + Fludrocortisone)
- Stress dosing
DHEA - Androgen replacement in women with reduced libido
What the complications of Adrenal insufficiency
2o Cushing’s
Osteopenia/Osteoporosis
Treatment related hypertension
What are the causes of Primary hyperaldosteronism
This is excess production of aldosterone leading to low K+ and HTN
80% are due to adenomas in the zona glomerulosa - Conn’s -
Other causes include: (3)
- Bilateral adrenal hyperplasia (BAH)
- Glucocorticoid remediated aldosteronism (GRA)
- Adrenal carcinoma
What are the signs and symptoms of Primary hyperaldosteronism
Patients are usually asymptomatic
- Hypokalaemia - Weakness + lethargy
- HTN (Due to increased Na and water retention)
- Metabolic alkalosis
- Polyuria + Polydipsia
- Headaches
Normal or elevated Na
What are the appropriate investigations in Primary hyperaldosteronism and the relative findings
U+Es - Hypokalaemia, possible Hypernatraemia Renin - Low Aldosterone - Elevated Aldosterone/Renin Ratio - >20 in plasma Adrenal venous sampling CT Adrenals ECG - Arrhythmias
Lying/Standing Aldosterone/Renin Ratio
Increase by 30% in BAH. No increase in Conn’s
What are the treatment’s for Primary hyperaldosteronism
Conn’s
Laproscopic adrenalectomy with pre and postoperative spironolactone (Aldosterone antagonist)
BAH
Amiloride/Spironolactone
GRA
Dexamethasone
2 - Spironolactone
What are the complications of Primary hyperaldosteronism
HF AF MI Stroke Hyperkalaemia Impaired renal function
What are the classifications of Cushing’s syndrome and what are their respective causes
Cushing’s syndrome is excess cortisol production
High ACTH - Ectopic no suppression with high dose
- Cushing’s disease (Most common endogenous cause of Cushing’s syndrome) - Pituitary adenoma
- Ectopic ACTH production - Small cell lung cancer and carcinoid tumours - Atypical presentations
Low ACTH
- Iatrogenic oral steroids (Most common cause of Cushing’s syndrome)
- Adrenal adenoma/carcinoma
- Adrenal nodular hyperplasia
What are the atypical presentations of Cushing’s syndrome when it is caused by ectopic ACTH production
Symptoms of high ACTH from Addison’s
- Pigmentation
Symptoms of high mineralocorticoid from Conn’s
- Hypokalaemia
- Metabolic alkalosis
Weight loss due to Carcinoma
High dose dexamethasone will still not suppress ectopic ACTH production
What are the signs and symptoms of Cushing’s syndrome
Excess cortisol
- Obesity + Supraclavicular fat pad + Interscapular hump (Buffalo hump)
- Facial fullness + Plethora
- Proximal myopathy
- Bruising
- Red striae
- Fractures - Osteoporosis
Hyperglycaemia
- Diabetes
- HTN
- Increased risk of CVD
- Increased infections
- Poor wound healing
- Amenorrhea
- Psychiatric
What are the appropriate investigations in Cushing’s syndrome and the relative findings
1st Line
- Overnight dexamethasone suppression test (1mg) -> 8am cortisol - >50nmols/L
- 24hr Urinary free cortisol >50micrograms/24hrs
Then
- 48hr 2mg dexamethasone supression test >50nmols/L
- 12am Cortisol salivary or blood during sleep - Elevated
Localisation
- Plasma ACTH - High in Adrenal problems; Low in Pituitary or Ectopic
- Inferior petrosal sinus sampling - Central/peripheral ACTH ratio over 2 indicative of Cushing’s disease
- High dose dexamethasone - Ectopic will not suppress - No longer really done
Imaging
MRI Pituitary
CT Adrenals
CXR
Outline treatment for Cushing’s syndrome
Cushing’s disease
- Transphenoidal surgery
- Pre-op - Metyrapone/Ketoconazole/Mifepristone
- Post-op - Pituitary hormone replacement + Corticosteroid replacement
Ectopic
- Resection of tumour
- Medical therapy - Metyrapone/Ketoconazole/Mifepristone
Unilateral adrenal mass
- Mass resection
- Pre op - Metyrapone/Ketoconazole/Mifepristone
Bilateral adrenal disease
- Bilateral resection
- Permanent corticosteroid replacement
What is Diabetes insipidus
This is impaired ADH secretion (Cranial - 2o) or lack of response to ADH being secreted (Nephrogenic - 1o) leading to production of a large amount (>3L/day) of hypoosmolar (dilute) urine.
What are the causes of cranial Diabetes insipidus
Acquired
- Idiopathic
- Tumours
- Surgery
- Head injury
- Granulomata
- Infections
- Vascular disorders
- Post-radiotherapy
Congenital
- DIDMOAD - Autosomal recessive - DI, DM, Optic Atrophy and Deafness
- Autosomal dominant mutations of vasopressin gene
What are the causes of nephrogenic Diabetes insipidus
Acquired
- Idiopathic
- Hypokalaemia
- Hypercalcaemia
- Chronic kidney disease
- Other metabolic derangments
- Drugs - Lithium, Orlistat, Ofloxacin
- Renal tubular acidosis
- Pregnancy
- Post-obstructive uropathy
Congenital
- X-linked mutation in V2 ADH receptor gene
- Autosomal recessive defect in AQP2 gene
- Sporadic nephrogenic DI with general learning disability and intracerebral calcification (V rare)
What are the signs & symptoms of Diabetes insipidus
Polyuria
Polydipsia
Nocturia
Dehydration + Potential palpable bladder
What are the appropriate investigations in Diabetes insipidus and the relative findings
Urine Osmolality - <300 Serum Osmolality - Normal or elevated Serum Na - Normal or elevated Serum K - Normal or low Serum Ca - Normal or elevated Urine dipstick - -ve for glycosuria 24hr Urine collection - >3L/24hrs
Water deprivation - 8hrs of water deprivation or until 3% of body weight is lost - Only performed if not hypernatraemic - Both types of DI will show that urine osmolality will be below 700 after the test (Some patients not show optimal concentration of urine because they have primary polydipsia)
To distinguish between the 2 types of DI:
Desmopressin stimulation test
Central/Cranial DI will respond
Nephrogenic DI will not
What are the treatments for Diabetes insipidus
Hypernatraemia - Important complication
Fluids - 0.45% Normal Saline, 5% Dextrose
Central/Cranial
Desmpression
Nephrogenic
Maintain adequate intake of water
+ Treat underlying cause
What is SIADH
This is when there is hyponatraemia (<125) and low plasma osmolality (<260) with concentrated urine (>100; urine Na >20) in the absence of hypovolaemia, oedema or diuretics
Primary cause is due to ADH secretion even though the plasma is concentrated (Low osmolality)
<50% of severe hyponatraemia is caused by SIADH (It is over diagnosed)
What are causes of SIADH
Brain (6)
- Haemorrhage/thrombosis
- Meningitis
- Abscess
- Trauma
- Tumour
- Guillain-‐Barre syndrome
Lung (3)
- Pneumonia
- TB
- Other: Abscess, Aspergillosis, Small cell carcinoma
Tumours (4) - Small cell lung caner - Lymphoma - Leukaemia - Others: Pancreatic cancer, prostate cancer, mesothelioma, sarcoma, thymoma
Drugs (4)
- Vincristine
- Opiates
- Carbamazepine
- Chlorpropamide
Metabolic (2)
- Porphyria
- Alcohol withdrawal
What are the signs and symptoms of Hyponatraemia
Mild: Usually Asymptomatic
Moderate: Headache, N&V, Claudication, Irritability
Severe: Confusion, Drowsiness, Convulsions, Coma
What are the appropriate investigations in SIADH and the relative findings
Diagnosis: Plasma osmolality - Low Urine osmolality - High Plasma Na - Low Urine Na - High Absence of hypovolaemia, oedema or diuretics
Things to check:
- Creatinine - Renal function
- Glucose, Protein, Lipids - Rule out pseudohyponatraemia (When sodium is reported as low due to high lipids or protein)
- T4 and TSH - Hypothyroidism
- Synacthen test - Adrenal insufficiency
How is SIADH treated
- Treat the underlying cause
- Fluid restriction
- Vasopressin receptor antagonists - Vaptans (tolvaptan)
Severe - Slow IV hypertonic saline and furosemide with close monitoring
What are the possible complication of SIADH
Convulsions
Coma
Death - <110
Central pontine myelinolysis - Occurs with rapid correction of hyponatraemia
- Quadriparesis
- Respiratory arrest
- Fits
What are the causes of Hypothyroidism
1o - 95%
Acquired:
- Hashimoto’s thyroiditis: Goitre due to lymphocytic and plasma cell infiltration. Potential initial state of hyperthyroid
- Primary atrophic hypothyroidism - Diffuse lymphocytic infiltration of the thyroid, leading to atrophy, hence no goitre
- Iodine deficiency - World wide main cause
- Post-thyroidectomy or radio iodine treatment
- Drugs induced: Amiodarone, lithium, iodine
Congenital:
- Thyroid dysgenesis
2o - 5%
Pit-Hypo disease
What are the signs and symptoms of Hypothyroidism
Weakness + Lethargy Cold sensitivity Constipation Weight gain Depression Menstraul irregularity Myalgia Dry and coarse skin Facial oedema Thick tongue Bradycardia Deep voice Goitre Delayed tendon relaxation Diastolic hypertension with or without narrow pulse pressure
How is Hypothyroidism investigated
TFTs - 1o High TSH, Low T4,
Lipids - Hyperlipidaemia and cholsterolaemia
FBC - Macrocytosis
How is Hypothyroidism treated
Levothyroxine - Rule out Addisons first - Check TSH after 4 weeks
Myxoedema coma = IV T4/T3
- Oxygen
- Rewarming
- Rehydration
- IV hydrocortisone
- Treat underlying cause
What is Thyroiditis and what are its causes
Thyroiditis is inflammation of the thyroid
Hashimoto’s thyroiditis is an autoimmune condition that is the most common cause of hypothyroidism in the UK.
Other types include:
- de Quervan’s thyroiditis
- Postpartum thyroiditis
- Drug-induced thyroiditis
- Acute or infectious thyroiditis
- Riedel’s thyroiditis
In Hashimoto’s there is lymphocyte infiltration of the thyroid causing the formation of a goitre
What are the signs and symptoms of Thyroiditis
Symptoms of hypothyroidism
- Bradycardia
- Constipation
- Lethargy
- Weakness
- Weight gain
- Los of appetite
- Hair loss
- Low mood
- Menstrual irregularities
- Cold intolerance
- Dry skin
Goitre formation leads to:
- Dyspnoea
- Dysphagia
- Tenderness
What are the appropriate investigations for Thyroiditis
- Serum TSH - High
- Antibodies - Anti-TPO Abs + Anti-thyroglobulin Abs
- Thyroid US
- Radionuclide isotope scanning
- Histology - Diffuse lymphocytic and plasma cell infiltration with formation of lymphoid follicles
How is Thyroiditis treated
Pharmacological
Levothyroxine - Titre based on patients need
Surgical
If there is a large goitre that is impeding on the surrounding structures
What are possible complications of Thyroiditis
2o Hyperthyroid
Hyperlipidaemia
Myxoedema coma
Hashimoto’s encephalopathy
What are the different types of Prolactinoma
Micro-adenoma - <1cm
Macro-adenoma - >1cm
Giant Pituitary adenoma - >4cm
Malignant Prolactinoma (Rare)
Association to MEN-1 syndrome
There is a risk of tumour enlargement in pregnancy
What are the signs and symptoms of Prolactinoma
Women
- Amen/Oligomen
- Galactorrhea
- Osteoporosis
- Low libido
- Hirsuitism
- Infertility
Men
- ED
- Reduced beard growth
- Low libido
Tumour size
- Headache
- Visual field defects
- CN palsies
- Pituitary stalk compression
What are appropriate investigations for Prolactinoma
Serum prolactin - Elevated
Visual fields - Bitemporal hemianopia
MRI Pituitary - Prolactinoma
TFTs - High TRH can cause hyperprolactinaemia
Outline the treatment of Prolactinomas
Men
Dopamine agonist
Transphenoidal surgery
Sellar radiotherapy
Women Dopamine agonist Combined oral contraceptive (If not desiring pregnancy) Transphenoidal surgery Sellar radiotherapy
What are possible complications of Prolactinomas
Osteoporosis
ED
Infertility
What is Hypopituitarism
This is partial or complete reduction in secretion of 1 or more anterior pituitary hormone
Panhypothyroidism is deficiency in all pituitary hormones
What are the causes of Hypopituitarism
- Pituitary masses
- Pituitary trauma - Radiation, surgery, fracture
- Hypothalamic dysfunction - Anorexia, Kallman’s, starvation, over-exercise
- Infiltrative disease - Sarcoidosis, Haemochromatosis, Langerhans’ cell histiocytosis
- Vascular - Pituitary apoplexy, Sheehan’s syndrome
- Infection
- Genetic mutation - Pit-1 and PROP-1 genes
What are the signs and symptoms of Hypopituitarism
Depends on the hormone affected
GH
- Short stature in children
- Low mood + Fatigue + Reduced exercise capacity and strength + Increased fat in adults
LH or FSH
- Delayed puberty, Decreased libido, Loss of 2o sexual hair
- Females: Breast atrophy + Amen/Oligomen + Painful sex, Infertility
- Males: Testicular atrophy + Gynaecomastia, Impotence
ACTH - Adrenal insufficiency
TSH - Hypothyroidism
Prolactin - Not clinically noticed
Apoplexy:
Headache
Visual loss
CN palsies
What are appropriate investigations for Hypopituitarism
PFTs 9am Cortisol + ACTH - Both low LH + FSH - Both low Testosterone - Low Oestrogen - Low IGF-1 - Low Prolactin - Slightly elevated Free T4 and TSH level - Low High serum and urine osmolality Low sodium
Insulin induced hypoglycaemic - GH and Cortisol will show no increase
MRI Pituitary
Visual field testing
How is Hypopituitarism treated
Hormone replacement:
- Hydrocortisone
- Levothyroxine
- Testosterone in males
- Oestrogen with/without progesterone in females
- Growth hormone - Somatropin
- Desmopressin
What are the complications of Hypopituitarism
Addisonian crisis Myxoedema coma Infertility Osteoporosis Dwarfism
Bitemporal hemianopia
Hydrocephalus
Temporal lobe epilepsy
What is Hyperlipidaemia
High:
Total cholesterol and/or
LDL cholesterol and/or
Triglycerides
What are causes of Hyperlipidaemia
Primary - Inherited
- Familial Dyslipidaemias
- Familial Hypercholesterolaemia
- Familial combined Hyperlipidaemia
- Apoprotein disorders
Acquired
- Saturated/Trans fat diets
- Obesity
- Medical conditions: Hypothyroidism + Obstructive jaundice + Cushing’s syndrome + Anorexia nervosa + Nephrotic syndrome + DM + CKD
- Drugs: Thiazide diuretics + Glucocorticoids + Ciclosporin + Antiretroviral therapy + Beta-Blockers + Combined oral contraceptive pill + Atypical antipsychotics + Retinoic acid derivatives.
- Pregnancy
- Alcohol use
What are signs and symptoms of Hyperlipidaemia
- Premature corneal arcus
- Tendon xanthomata or Xantholasma
Familial Hypercholesterolaemia:
High total cholesterol + Hx of premature CHD
Confirm with 2 high fasted LDL-Cs
What are appropriate investigations for Hyperlipidaemia
- Lipid profile - TChol, LDL-C, TGs - High
- Fasting blood glucose - Exclude Hyperlipidaemia secondary to DM
- Renal function - Exclude CKD
- LFTs - Exclude Liver disease so statins can be given
- TSH - Exclude Hypothyroidism
DNA testing - Familial disease
What is the treatment for Hyperlipidaemia
Lifestyle changes
Statins - Atorvastatin
What are complications of Hyperlipidaemia
High CHD risk
Pancreatitis
What are the different classifications of Hyperparathyroidism
1o hyperparathyroidism - Increased secretion of PTH unrelated to the plasma calcium concentration - Adenoma, hyperplasia, carcinoma, MEN syndrome
2o - Increased secretion of PTH secondary to hypocalcaemia - Chronic renal failure, Vitamin D Deficiency
3o - Autonomous PTH secretion following chronic 2o hyperparathyroidism
What are the signs and symptoms of Hyperparathyroidism
Many people have mild hypercalcaemia and it is asymptomatic
Symptoms of Primary:
Stones: Kidney/Gallstones
Thrones: polyuria
Bones: Bone pain + Hx Osteopenia/osteoporosis
Groans: Constipation + Myalgias + Muscle cramps
Psychiatric overtones: Anxiety + Depression + Memory loss
Symptoms of Secondary & Tertiary:
The same + bone resorption leading to renal osteodystrophy + Calcification in blood vessels + soft tissue
What are appropriate investigations for Hyperparathyroidism
PTH - High
Calcium - 1o & 3o High, 2o Low
Phosphate - 1o Low, 2o High
Vitamin D - 2o Low
Renal ultrasound - Osteodystrophy
How is Hyperparathyroidism treated
1o or 3o
Parathyroidectomy
+ Vitamin D supplementation
or
Bisphophonate - Alendronic acid treat osteoporosis
Calcimimetic - Cinacalcet
+ Vit D
2o
Surgery
Vitamin D supplementation
What is Osteomalacia
This is low bone mineral content after epiphyseal closure
What are the causes of osteomalacia
Vitamin D deficiency - Due to malabsorption + poor diet + lack of sunlight + Decreased 25‐hydroxylation (due to liver disease or anticonvulsants) + Decrease 1a‐hydroxylation (due to CKD hypoparathyroidism) + Vitamin D resistance
Tumour-induced osteomalacia
What are the symptoms of Osteomalacia
Bone pain (mainly in the axial skeleton)
Weakness
Malaise
What are the signs of Osteomalacia
Bone tenderness
Proximal myopathy
Waddling gait
Signs of hypocalcaemia:
- Trousseau’s - Inflation of a blood pressure cuff to above the systolic pressure for >3 mins causes tetanic spasm of the wrist and fingers
- Chvostek’s - Tapping over the facial nerve causes twitching of the ipsilateral facial muscles
How is Osteomalacia investigated
Bloods: Low Ca Low phosphate Low Vitamin D High PTH (2o Hyperparathyroidism) LFTs: High ALP U&Es: May be deranged
X-ray - Looser zones - Pseudo-fractures
DXA - Low bone density
Iliac crest biopsy with double tetracycline labelling - Reduced distance between tetracycline bands
How is Osteomalacia treated
If deficient
Calcium + Vitamin D
Calcium + Vitamin D metabolite/DHT
Phosphate wasting
+ Phosphate too
What are complications of Osteomalacia and Vitamin D deficiency
CATs go NUMB
Convulsions
Arrhythmias
Tetany
Numbness/paraesthesias
Depression
Overcorrection problems
What is T1DM
Hyperglycaemia caused by absolute insufficiency of pancreatic insulin production
10% of people with diabetes have T1DM
What causes T1DM
Type 4 hypersensitivity response (Cell mediated) against the Beta cells in the islet - Autoimmune destruction
The autoantibodies associated with T1DM:
- Glutamic acid decarboxylase (GAD)
- Insulin
- Insulinoma-associated protein 2
- Cation efflux zinc transporter
What HLA are associated with T1DM
HLA-DR3/4
>90% Association
What is LADA
This is latent autoimmune diabetes of adults and is a form of type 1 DM
What are signs and symptoms of TD1M
Juvenile onset <30yrs Polyuria/Nocturia Polydipsia Glycosuria Weight loss Polyphagia
Other autoimmunities:
Vitiligo
Hashimoto’s Thyroiditis
Addison’s
What are appropriate investigation in T1DM
- Random plasma glucose - >11mmol/L
- Fasting plasma glucose - 8hr fast - >6.9mmol/L
- 2hr plasma glucose - 75g Glucose load - >11mmol/L
- Plasma or urine ketones - Medium or high quantity
- HbA1c - Reflects hyperglycaemic control over the preceding 3 months
- Fasting C-peptide - Low or undetectable
- Autoimmune markers - Positive
How is T1DM managed
Insulin!
- Basal-Bolus insulin
Basal - Glargine - SC usually at night daily
Bolus - Lispro/Aspart - Before meals depending on meal size and amount of carbs in meal
Total per day 0.2-0.4 units/kg/day - Half given as Basal doses and half given as Bolus
- Correction dose based on pre-meal blood glucose
- Amylin analogue - Pramlintide - Prolongs gastric emptying so glucose levels don’t spike as much
Pregnant
- Basal-Bolus
- Low dose aspirin
What are complication of T1DM
Diabetic ketoacidosis Hypoglycaemia Retinopathy Nephropathy Neuropathy CVD
What is DKA
Excess Ketoacidosis production from lipolysis due to the lack of glucose being taken up into the adipose cells. This is a serious complication of T1DM
The combination of hyperglycaemia and Ketoacidosis can be fatal and is a medical emergency
- Bicarbonate below 15 or venous pH less than 7.3
- Blood glucose over 11 (Or known DM)
- Ketonaemia >3 or significant ketonuria
Hyperglycaemia is not always present and low blood kentone levels do not exclude DKA
What are precipitating factors to DKA
Infection Discontinuation of insulin Inadequate insulin CVD - Stroke/MI Drug treatments - Steroids, Thiazide diuretics, SGLT2 inhibitors
What are signs and symptoms of DKA
- Kussmaul respiration - Deep breathing to reduce CO2 in blood
- Ketotic breath
- N+V
- Dehydration
- Mental status changes
- Abdominal pain
- Polyuria
- polydipsia
- Lethargy
- Coma
Signs of dehydration
- Dry mucous membranes
- Decreased skin turgor/skin wrinkling
- Sunken eyes
- Slow capillary refill
- Tachycardia with weak pulse
- Hypotension
What are investigative findings of DKA
- Plasma glucose - Elevated
- ABG - pH 7-7.3
- Serum Ketones - Elevated
- Urinalysis - +ve for glucose and ketones
- U+Es - Elevated urea and creatinine + Low Na/Cl/Mg/Ca + High K/Phos
- Anion gap - Na-Cl+HCO3 - >10-12
- Creatine phosphokinase - Elevated in Rhabdo
- Lactate - Elevated in lactic acidosis
- Amylase - Elevated
- FBC - Elevated WCC
- CXR - Pneumonia
- ECG - May show evidence of MI
How is DKA treated
1L 0.9% Saline over 1hr
If SBP under 90mmHg then give 500ml bolus STAT if persistent give another 500ml and seek senior review
50 units soluble insulin in 50ml of 09.% Saline. Continuously at 0.1 unit/Kg/h. - Fall in Ketones of 0.5, rise in HCO3 of 3, fall in glucose of 3
Catheterisation if urine not passed by 1hr
NG if vomiting or drowsy
LMWH
K+ replacement if under 5.5
If under 3.5 ICU
What is a complication of DKA
Cerebral oedema Aspiration pneumonia Hypokalaemia Hypophosphataemia Thromboembolism Death
What is T2DM
Hyperglycaemia caused by tissue resistance to pancreatic insulin
90% of people with diabetes have T2DM
Monogenic variations:
MODY and Mitochondrial
What are the causes of T2DM
Genetic and environmental
Obesity, Lack of exercise, HTN
Pancreatic disease - Chronic pancreatitis
Endocrine disease
Drugs - Corticosteroids, Atypical antipsychotics, protease inhibitors
What are the signs and symptoms of T2DM
May be an incidental finding as it is often asymptomatic
Polyuria/Nocturia Polydipsia Glycosuria Polyphagia Tiredness
Hyperosmolar hyperglycaemic state (HHS) - 2(Cations) + Glucose + Urea - Dry brain (Corrected slowly)
High central adiposity
HTN
Diabetic foot problems
What are appropriate investigations in T2DM
HbA1c - >48mmol (6.5)
Fasting plasma glucose ->6.9
Random plasma glucose - >11.1
2hr plasma glucose - >11.1
What is Gestational diabetes
Pregnancy woman have high blood glucose usually in 3rd trimester
How is T2DM treated
Diet and exercise + Metformin Aiming for 48 (6.5)
Once HbA1c gets to 58 (7.5) Move to next level
Add 1 of the following (Target <53): (Dual therapy)
- Sulphonylureas (Gliclazide) - Ideal
- Gliptins - DPP-4 inhibitors
- Thiazolidinedione (Pioglitazone)
If HbA1c gets to 58 (7.5) again move to next level
Triple therapy (Target <53):
- Metformin + Sulphonylurea + Gliptin
- Metformin + Sulphonylurea + Pioglitazone
- Insulin based therapy
If triple therapy fails of is contraindicated Incretins (Exenatide) can be used with Metformin + Sulphonylurea if:
- BMI >35
- BMI <35 - Weight-loss beneficial or Insulin effect on occupation
Continued if weight loss of 3% in 6 months and HbA1c decrease of 11 (1%)
Contraindication to metformin:
SC SGLT2 inhibitors (Flozins) may be appropriate for some adults when metformin is contraindicated though Sulphonylureas and Pioglitazone would be indicated before SGLT2 inhibitors. You would however use a SGLT2 inhibitors over a Gliptin as monotherapy.
Dual therapy should be a combination of the any 2 of the 3 1st line 1st intensification drugs
Contra indications to pioglitazone:
HF, Liver disease, DKA, Bladder cancer, Uninvestigated Marcoscopic Haematuria
Insulin based therapy
NPH insulin ideally
If contraindicated Glargine or detemir
What are the complications of T2DM
Macrovascular
- Ischaemic heart disease
- Stroke
- PVD
Microvascular
- Neuropathy: Peripheral neuropathy - Glove and stockings distribution + Carpal tunnel + Gastroparesis + Other neuropathies
- Nephropathy: Microalbuminuria + Proteinuria + Renal failure + Prone to UTI + Renal papillary necrosis
- Retinopathy: Background, Pre-proliferative (Pan retinal photocoagulation), Proliferative (Pan retinal photocoagulation), Maculopathy
HHS
What are the parameters for pre-diabetes
Impaired fasting glucose (IFG) = Fasting glucose 5.6-6.9
Impaired glucose tolerance = Plasma glucose 7.8-11.0
Both give increased risk of T2DM
What is Carcinoid syndrome
This is the release of excess serotonin and other vasoactive peptides into the systemic circulation from a carcinoid tumour
Neuroendocrine tumours are responsible for this excess production and are usually located in the GUT
Association with MEN-1
95% of patients with carcinoid syndrome have liver metastasis
What are signs and symptoms of Carcinoid syndrome
Months of symptoms
- Diarrhoea + Cramping
- Flushing with stress and tyramine foods (Chocolate, banana, walnuts)
- Wheeze
- SOB
- Raised JVP
- Signs of RHF
- RH murmurs - TR & PS
- Hepatomegaly
- RIF masses
- Pellagra due to vitamin B3 (Niacin) deficiency
How is Carcinoid syndrome investigated
Serum Chromogranin A/B - Elevated
Urinary Serotonin acid - Increased
Metabolic Panel - Increased Creatinine
CT scan
Iodine I-123 MIBG Scintigraphy
What is Polycystic ovary syndrome (PCOS)
It is a syndrome of:
- Hyper-androgenaemia
- Oligo/Amenorrhea
- Polycystic ovarian morphology on US
What are signs and symptoms of PCOS
- Hirsutism
- Acne
- Scalp hair loss
- Weight gain
- Irregular and infrequent periods
- Infertility
- HTN
- Acanthosis nigricans
- Sweating or oily skin
How is PCOS investigated
- Serum total and free testosterone - Elevated
- Serum Dehydroepiandrosterone sulfate (DHEAS) - Elevated
- Serum 17-hydroxyprogesterone - Normal
- Serum Prolactin - Normal
- Serum TSH - Normal
Fasting glucose
Fasting lipid panel
Serum androstenedione - Elevated
Pelvic US
What is Osteoporosis
This is reduced bone density defined as >2.5 standard deviations below the peak bone density of a normal young adult - T score > 2.5
What are causes of Osteoporosis
Primary
- Idiopathic if <50
- Post-menopausal
Secondary
- Myeloma + Metastatic carcinoma
- Endocrine - Cushing’s, Thyrotoxicosis, Primary Hyperparathyroidism, Hypogonadism
- Drugs - Corticosteroid, heparin
- Rheumatological - RA, AS
- GI - Malabsorption, liver disease, anorexia
What are signs and symptoms of Osteoporosis
- Neck of femur fractures after minimal trauma
- Vertebral fractures leading to loss of height, stooped posture, thoracic kyphosis
- Tenderness on percussion
- Colles fracture
How is Osteoporosis investigated
DEXA Scan - Allows calculation of T-score (The number of standard deviations the bone mineral density measurement is above or below the young normal bone mineral density) and the Z-score (The number of standard deviations the bone mineral density measurement is above or below the age-matched mean bone mineral density)
Isotope bone scans - Highlight areas of stress and micro fractures
XR - Diagnose fractures +/- Biconcave Vertbrae +/- Crush fractures
Bloods (Normal in primary osteoporosis):
- Ca + Phosphate + ALP
What is Paget’s disease of bone
Excessive bone remodelling at one or more sites resulting in bone that is structurally disorganised
Common in the elderly
What are the signs and symptoms of Paget’s disease of bone
It may be asymptomatic
- Insidious onset of pain aggravated by weight bearing and movement
- Headaches
- Deafness
- Increasing skull size
- Kyphosis
- Anterolateral bowing of femur, tibia or forearm
- Skin over the affected bone may be warm
- Sensorineural deafness
How is Paget’s disease of bone investigated
XR - Early stages: Osteolytic changes; Late stages: Sclerotic
Bone scan - Dense uptake
ALP - Elevated
Ca + Phosphate - Normal
What are the causes of Obesity
Aside from the obvious ones
Hypothyroidism
Cushing’s syndrome
Insulinoma
What is the diagnostic criteria for Obesity
BMI over 30. Morbid is over 40
BMI = Kg/m^2
What are signs and symptoms of Pituitary tumour growth
- Headache
- Visual field defects: Bitemporal Hemianopia
- CN Palsies
- Hypothalamic extension can lead to disorders in thirst and appetite, temperature regulation and consciousness
How would a Pituitary tumour be investigated
PFTs
Visual fields
MRI Pituitary
What is Graves’ disease
This is an autoimmune disorder that causes hyperthyroidism
Thyroid stimulating immunoglobulin binds to the TSH receptor causing production of T3 and T4
What are signs of symptoms of Grave’s disease
Thyrotoxicosis
- Weight loss
- Increased appetite
- Heat intolerance
- Tachycardia
- Palpitations
- Arrhythmia
- Diarrhoea
- Sweating
- Anxiety
- Insomnia
- Hair loss
Graves’ specific:
- Smooth Enlargement (Lymphocyte Infiltration) - Goitre
- Exophthalmos
- Opthalmoplegia
- Pretibial myxoedema
- Thyroid acrpoachy: Clubbing, Painful finger and toe swelling
Association to T1DM, Vitiligo, Addison’s
What investigations will be used in Graves disease
TSH - Suppressed
T3 and T4 - Elevated
Thyroid stimulating antibodies - +ve
Radioactive iodine I-123 or Tc-99 uptake scan - Diffuse uptake
What are the 4 types of Thyroid cancer
- Differentiated - Act like normal thyroid tissue - Papillary is most common then follicular
- Medullary - Type seen in MEN
- Anaplastic - Rare
Who usually get Thyroid cancer
All more common in women
Papillary - 20-40yrs
Follicular - 40-50yrs
Anaplastic - Elderly
What are signs and symptoms of Thyroid cancer
- Slow-growing neck lump
- Discomfort swallowing
- Hoarse voice
- Palpable nodules or diffuse enlargement of the thyroid gland
- Cervical lymphadenopathy
What are the investigative findings in Thyroid cancer
TSH: Normal
US Neck
FNA Cytology
CT/MRI - for staging
Isotope scan - If cause of thyroid lump is unclear
What are causes of Thyroid nodules
Vast majority are benign but a small portion turn into thyroid cancer
Most adenomatous and most are multiple
Usually non-functioning
What are appropriate investigations for Thyroid nodules
TSH: Normal
US Neck
FNA Cytology
CT/MRI - for staging
Isotope scan - If cause of thyroid lump is unclear
What is a Phaeochromocytoma
Catecholamine producing tumour that usually arise from chromatin cells of the adrenal medulla
10% Bilateral
10% Malignant
10% are extra-adrenal
What are familial causes of Phaeochromocytoma
30%
MEN 2a
Von Hippel-Lindau syndrome
Neurofibromatosis type 1
What are the signs and symptoms of Phaeochromocytoma
Paroxysmal episodes
- Headache
- Sweating
- Pallor
- Fever
- Weight loss
Cardiorespiratory symptoms
- Palpitations
- Chest pain
- Dyspnoea
- HTN
- Tachycardia
GI symptoms
- Epigastric pain
- N
- Constipation
Neuropsychiatric symptoms
- Weakness
- Tremor
- Anxiety
How is Phaeochromocytoma diagnosed
24Hr Urine collection - Check catecholamine levels (Metanephrines, normetanephrines and creatinine)
Serum free metanephrines and normetanephrines
Plasma catecholamines
Genetic testing
CT/MRI OR I-123 MIBG scintigraphy
What are the different types of Multiple endocrine neoplasia
All autosomal dominant
MEN-1 (MEN1 gene mutation)
- Pituitary
- Parathyroid
- Pancreatic islet-cell
- Gastrinomas
- Fascial angiofibromas and collagenomas
MEN-2a (RET proto-oncogene mutation)
- Parathyroid
- Medullary thyroid cancer
- Phaechromocytomas
MEN-2b
Same as 2a
- Marfanoid appearance
- Neuromas of the GI tract
What are the signs and symptoms of Multiple endocrine neoplasia
MEN-1
- Diagnosis 4th decade
- Depending on organ affected + Pituitary tumours may cause visual defects
MEN 2
- Depending on organ affected
How is Multiple endocrine neoplasia diagnosed
MEN 1
Chromogranin A - NET
Gastrin - Gastrinoma
IGF-1 - Pituitary
MEN 2
Calcitonin - Medullary thyroid tumour
Carcinoembryonic antigen - Medullary thyroid tumour
What is female Hypogonadism
This is impaired ovarian function
What are causes of female Hypogonadism
1o
- Gonadal dysgenesis (Turner’s)
- Gonadal damage (Autoimmune, chemotherapy, radiotherapy)
2o - More common
- Functional (Stress, weight loss, excessive exercise, eating disorder)
- Pituitary/Hypothalamic tumours and infiltrative lesion (Pit adenoma, haemochromatosis)
- Hyperprolactinaemia
- Congenital GnRH deficiency: Kallmann’s syndrome, idiopathic
What are the signs and symptoms of female Hypogonadism
Oestrogen deficiency:
- Night sweats
- Hot flushing
- Vaginal dryness
- Dyspareunia
- Decreased libido
- infertility
Signs
Pre-Pubescent
- Delayed puberty (Primary amenorrhoea, absent breast development, no secondary sexual characteristics)
- Eunuchoid (Long legs, arm span greater than height)
Post-Pubescent
- Regression of secondary sexual characteristics
- Perioral and periorbital fine facial wrinkles
- Signs of underlying cause
Kallmann’s - Anosmia
Turner’s
- Short stature
- Low posterior hairline
- High arched palate
- widely spaced nipples
- Wide carrying angle
- Short 4th and 5th metacarpals
- Congenital lymphoedema
How is female Hypogonadism diagnosed
Low serum oestradiol
Serum FSH/LH - High in Primary. Low in secondary
Primary
- Karyotype
- Pelvic US/MRI - In primary amenorrhoea
- Screen for FMR1 gene in patients with unexplained pre-mature ovarian failure
Secondary
- Pituitary function test
- Visual fields
- Hypothalamic-pit MRI
- Smell tests for anosmia
- Serum transferring saturation (Haemochromatosis)
What is male Hypogonadism
A syndrome of decreased testosterone production, sperm production or both
What are causes of male Hypogonadism
1o - More common
- Gonadal dysgenesis (Klinefelter’s syndrome, Undescended testicles)
- Gonadal damage (Infection, torsion, trauma, autoimmune, iatrogenic)
- Defects in enzymes involved in testosterone synthesis
2o
- Pituitary/Hypothalamic tumours and infiltrative lesion
- Hyperprolactinaemia
- Congenital GnRH deficiency: Kallmann’s syndrome, idiopathic
- Prader-Willi syndrome (Short, small hands, almond-shaped eyes, learning difficulties, postnatal hypotonia)
- Laurence-Moon-Biedl syndrome (Obesity, polydactyly, retinitis pigmentosa, learning difficulties)
What are the signs and symptoms of male Hypogonadism
Delayed puberty
Decreased libido
Impotence
Infertility
Signs
Pre-Pubescent
- Delayed puberty (High pitched voice, no secondary sexual characteristics, Small or undescended testicles, Small penis)
- Eunuchoid (Long legs, arm span greater than height)
- Gynaecomastia
Post-Pubescent
- Regression of secondary sexual characteristics
- Soft and small eyes
- Gynaecomastia
- Fine personal wrinkles
- Signs of underlying cause
How is male Hypogonadism diagnosed
Early morning serum testosterone on 2 separate occasions in a symptomatic man
Sex hormone binding globulin
Albumin
LH and FSH
1o - Low testosterone, High LH and FSH
2o - Low testosterone, Low LH and FSH
Primary
Karyotyping
Secondary
- Pituitary function test
- Visual fields
- Hypothalamic-pit MRI
- Smell tests for anosmia
- Serum transferring saturation (Haemochromatosis)
