Endocrine Flashcards
Define Diabetes Mellitus
A group of chronic disorders characterised by the body’s impaired ability to produce/respond to insulin resulting in abnormal glucose metabolism
Types of diabetes
- Type 1
- Type 2
- Gestational (oft improves after birth )
- Maturity Onset Diabetes of the Young (autosomal dominant)
- Neonatal
- Steroid induced
- Wolfram’s syndrome and Alstrom syndrome
- Type 3 (including cystic fibrosis)
- Latent Autoimmune Diabetes in Adults
RFx for T1DM
- Northern European
- Family Hx/Personal Hx of Diabetes/other AI conditions
- Genetic predisposition: HLA-DR3/DR4 or DQ8
- Environmental factors
Pathophys T1DM
- GLUT4 is insulin dependant
- Is unable to bind to cell membrane if low insulin
- Glucose unable to enter cells leading to starvation state and gluconeogenesis
- hyperglycaemia as glucose builds up in blood
Typical presentation T1DM
- Polyuria (osmotic diuresis as kidneys are unable to reabsorb excess glucose)
- Polydipsia (thirst centre in hypothalamus stimulated)
- Weight loss (from excessive lipolysis, proteolysis and fluid depletion)
T1DM diagnosis
If symptomatic:
- only 1 raised plasma glucose reading is needed
- Fasting >= 7mmol/L
- Random glucose >= 11.1 mmol/L
If asymp:
- 2 positive readings needed
Can also do oral glucose test and measure fasting and 2 hours post-prandial glucose levels
Normal blood sugar range
- Fasting: 4.0 - 5.4 mmol/L
- 2 hours post-prandial: up to 7.8
Definition of diabetic ketoacidosis
Medical emergency characterised by:
- Hyperglycaemia (>11.1)
- Ketosis i.e ketones > 3 mmol/L (norm < 0.6)
- Acidosis i.e pH < 7.3 (norm 7.35-7.45)
RFx for DKA
- untreated T1DM
- Infection/Illness
- Myocardial Infarction (also more likely to happen if ketotic)
Presentation of DKA
Diabetes:
- Polydipsia/polyuria/nocturia -> Dehydration -> hypotension
Ketosis:
- Fruity breath
Acidosis:
- N+V
- Abdo pain
- Kussmaul breathing
Drowsy/Confused
DKA pathophys
- 0 insulin -> decreased uptake into cells + uncontrolled hepatic gluconeogenesis
- hyperglycaemia -> osmotic diuresis -> DEHYDRATION
- Peripheral lipolysis -> raised free fatty acids -> converted to KETONES in mitochondria -> METABOLIC ACIDOSIS
- Low intracellular potassium (insulin drives potassium into cells)
Investigations for DKA
Clinical diagnosis +
- Blood glucose
- ABG
- U+E (raised due to dehydration)
- Urine dipstick (glycosuria + ketonuria)
DKA Tx
- ABCDE if unconscious
- Slow FLUID REPLACEMENT (IV 0.9% NaCl)
- Insulin + Glucose
- Monitor Potassium
- Treat any underlying infections/triggers
Complication of DKA Tx
Cerebral oedema
- from OSMOTIC SHIFT due to sudden decreased osmolality
RFx for T2DM
Non-modifiable:
- Older age
- Black, Chinese, south Asian ethnicity
- FHx
- MALE
Modifiable:
- Obesity
- Sedentary lifestyles
- High carb diet
- HYPERTENSION
- Smoking
T2DM Sx
- Polyuria
- Polydipsia
- Polyphagia (significant weight loss uncommon initially)
- Glycosuria
- Acanthosis nigricans
T2DM investigations
Gold:
- HbA1c > 48 mmol/mol
- >42 - 72 = pre-diabetes
Blood glucose
Oral glucose tolerance test
Only 1 +ve needed if symp; 2 if asymp
T2DM Tx
- Life style mods
- weight loss
- diet
- stop smoking
- exercise
- control blood pressure + cholesterol
- Metformin if HbA1c >48
- Sulfonylurea, thiazolidinedione, GLP-1 analogue, DPP-4 inhib, SGLT-2 inhib
- Potentially insulin in late stage
T2DM complications
Macrovascular:
- Atherosclerosis (hyperglycaemia induces oxidative stress) -> CVD
Microvascular:
- Nephropathy
- Retinopathy
- Peripheral neuropathy
- Autonomic neuropathy
+ decreased immunity due to hyperglycaemia
Pathophys of Hyperosmolar Hyperglycaemic state
- Decreased insulin -> hyperglycaemia + gluconeogenesis
- BUT Sufficient insulin to stop ketogenesis
- Volume depletion -> raised osmolarity + hyperviscosity
Presentation of HHS
General:
- Fatigue/lethargy
- N+V
Neuro:
-
Raised ICP
- Papilloedema, headaches, altered consiousness
- weakness
Haem:
- Hyperviscosity (risk of MI, stroke, DVT/thrombosis)
Cardio:
- Dehydration -> Hypotension -> Tachycardia
NO significant acidosis
HHS Diagnosis
- Serum glucose > 30 mmol/L
- Hypotension
- Hyperosmolarity (>32 mosmol/kg)
- NO significant acidosis (> 7.3) or ketosis
HHS Tx
- FLUID REPLACEMENT
- VTE prophyl (LMWH)
- Insulin if persisting w/ treatment (risk of hypoglycaemia/kalaemia so oft give w/ glucose/dextrose + monitor potassium)
Define Hypoglycaemia
Serum glucose < 4.0 mmol/L
Normal physiological response to hypoglycaemia
- Alpha islet cells stimulated -> glucagon + inhibits insulin production -> hepatic gluconeogenesis/lysis
- Increased production of adrenaline, growth hormone and CORTISOL -> gluconeogenesis
Non-diabetic causes of hypoglycaemia
ExPLAIN:
- Exogenous medication (alcohol, aspirin overdose, IGF-1 which inhibits hepatic gluconeogenesis)
- Pituitary insufficiency
- Liver failure
- Addison’s disease
- Insluinoma/Islet cell tumours
- Non-pancreatic neoplasm (fibrosarcoma)
Presentation of hypoglycaemia
Blood glucose <3.3 = AUTONOMIC:
- Sweating
- Shaking
- Hunger
- Anxiety
- Nausea
Blood glucose <2.8 = NEUROGLYCOPENIC:
- Weakness
- Vision changes
- Confusion
- Dizziness
Severe + uncommon:
- Convulsion
- Coma
Wipple’s triad
- signs and symptoms of hypoglycaemia
- low blood glucose
- resolution of symptoms with correction of blood sugar
Investigation of hypoglycaemia in non-diabetic
Gold = 48 - 72 hour FAST with serial blood glucose
Hypoglycaemia Tx
Community:
- ORAL GLUCOSE 10-20g
- May have ‘hypokit’ -> IM/SC glucagon
Hospital:
- Quick acting carbs/oral glucose
- Unconscious/unable to swallow:
- SC/IM glucagon
- OR IV 20% glucose solution
Define hypothyroidism
Syndrome of thyroid hormone deficiency leading to generalised slowing of metabolic processes
Causes of primary hypothyroidism
- Hashimoto’s thyroiditis
- de Quervain’s thyroiditis
- Radiotherapy
- Drugs:
- Lithium
- Amiodarone
- Antithyroid drugs e.g. carbimazole
- Dietary iodine deficiency
Secondary vs tertiary hypothyroidism
- Secondary = pituitary failure (low TSH)
- Tertiary = hypothalamic failure (low TRH)
- basically non-existant
Which genetic conditions are associated with a higher risk of developing hypothyroidism
- Down’s
- Turner’s (only in females - due to reduced/missing X chromosome)
- Coeliac’s
- Type 1 DM
Presentation of hypothyroidism
- Wight gain
- Cold intolerance
- Lethargy
- Dry coarse scalp
- CONSTIPATION
- MENHORHAGIA
- general myxoedema - waxy, non-pitting -> looks doughy
Hashimoto’s is also associated with losing the lateral aspect of eyebrow
Investigations for hypothyroidism
-
1st line = Thyroid function tests
-> esp look at TSH and T4 levels - Thyroid peroxidase antibodies
- elevated in Hasimoto’s
- Fasting blood glucose
- T1DM is a differential for non-specific fatigue + weight gain AND it’s often associated with autoimmune thyroid conditions
Tx for hypothyroidism
Levothyroxine
Pathophys of Hashimoto’s thyroiditis + conditions that are often associated with it
- Anti-TPO and Anti-thyroglobulin Ab are formed/elevated
- These attack the thyroid tissue causing progressive fibrosis
- Damage is primarily caused/mediated in an immune response by CYTOTOXIC T CELLS
- Can cause transient thyrotoxicosis in acute phase as thyroid tries to compensate
Oft associated with:
- T1DM
- Addison’s
- Pernicious anaemia
Hyperthyroidism vs thyrotoxicosis
- Hyperthyroidism = increased synthesis of T3 and T4 in the thyroid gland
- Thyrotoxicosis = Increased T3 and T4 in circulation (clinical syndrome)
Causes of hyperthyroidism
- GRAVE’S = most common
- Toxic multinodular goitre
- Toxic adenoma
- De Quervain’s thyroiditis
- Drug induced
- Iodine excess
- LITHIUM
- AMIODARONE
- radiocontrast agents
Less common:
- Congenital (neonatal) hyperthyroidism
- Non autoimmune hereditary hyperthyroidism
- Subacute thyroiditis
- Silent thyroiditis
- Postpartum thyroiditis
- Hyperemesis gravidarum
- Molar pregnancy (hCG)
- Thyrotoxicosis factitia
- Metastatic differentiated thyroid - Ca
- Struma ovarii
- Pituitary resistance to thyroid hormone
- Pituitary adenoma (TSHoma)
What processes does the thyroid play an important role in
Metabolism, growth and development
Presentation of hyperthyroidism
- Weight loss,
- heat intolerance,
- palpitations/tachycardia
- increased sweating,
- anxiety,
- tremor
- diarrhoea,
- oligomenorrhea
- lid lag + stare
Investigations for hyperthyroidism
- 1ST LINE: Thyroid function tests(TFTs)- Primarily look at TSH ad T4 levels
- TSH-RECEPTOR ANTIBODIES
- elevated in GRAVE’S
- Isotope scan, MRI, CT, Ultrasound
Tx for hyperthyroidism
- PROPANOLOL to initially control symps like tremor
- Anti-thyroid meds
- 1st line = CARBIMAZOLE (blocks TPO + reduces hormone levels)
- risk of congenital malformation so CI in preg
- Agranulocytosis also common SE (lowered immunity)
- Alt = PROPYLTHIOURACIL
- Radioiodine treatment (can exacerbate any exophthalmos)
- Thyroidectomy
NB: need to render euthyroid before radioiodine/surgery
Risk factors for Grave’s Hyperthyroidism
- Smoking
- Stress
- Drugs:
- High iodine intake
- Alemtuzumab (MS drug)
-
FEMALE SEX - it mostly affects young or middle aged women
- 2% of women will get Graves’ disease or autoimmune hypothyroidism (5-10 times the frequency in men) - Family history (25% concordance in monozygotic twins)
- HLA-DR3 and other immunoregulatory genes contribute
- Myasthenia gravis is also associated with Graves’ disease
Pathophys of Grave’s disease
TSH receptor antibodies (thyroid stimulating antibodies) stimulate the TSH receptor causing more free t4 to be produced
TSH-R antibodies may cross the placenta can result in neonatal Graves’ disease. (could also result in stillbirth, miscarriage or preterm birth)
Opthalopthy caused by swelling in extraoccular muscles (probs from autoantigen similar to/reacting with thyroid autoantigen)
Sx of Grave’s disease
- EXOPHTHALMOS (bulging eyeball) and ophthalmoplegia (weakness of eye muscles)
- PRETIBIAL MYXOEDEMA
- orange peel appearance on anterior aspect of the lower legs, spreading to the dorsum of the feet, or a non-localised, non-pitting edema of the skin in the same areas
- THYROID ACROPACHY
- triad of digits clubbing, soft tissues swelling of hands/feet, and periosteal new bone formation
- DIFFUSE GOITRE
- typical Sx of hyperthyroidism
First line Tx for patients with moderate-severe/sight threatening orbitopathy
IV CORTICOSTEROIDS
Define De Quervain’s thyroiditis
Subacute granulomatous thyroiditis is a self-limited inflammation of the thyroid gland. It results in the rapid swelling of the thyroid gland resulting in pain and discomfort
(often thought occur after viral infection)
Pathophys of De Quervain’s thyroiditis
There are typically 4 phases:
- Phase 1- lasts 3-6 weeks: hyperthyroidism (initial presentation), painful goitre, Raised ESR
- Phase 2- Lasts 1-3 weeks: Euthyroid (normal function)
- Phase 3- weeks to months: Hypothyroidism
- Phase 4- Thyroid structure and function goes back to normal
Main Sx of De Quervain’s thyroiditis
- NECK PAIN + ENLARGED THYROID
- Fever
- Palpitations
investigation of De quervain’s
- 1ST LINE: Total T4, T3 resin uptake, free thyroxine index- ALL ELEVATED,
- CRP = elevated
Tx of De Quervain’s
Hyperthyroid phase
- NSAIDs and corticosteroids may be used for pain.
Hypothyroid phase
- Normally no treatment given but if severe hypothyroidism occurs give small dose of levothyroxine
Complications of De Quervain’s
Thyroid storm,
Long term hypothyroidism
Define goitre
Palpable & visible thyroid enlargement
Diff types of goitres
- Toxic vs non-toxic
- Diffuse (spread evenly)
- Multinodular
- Solitary nodule
- Dominant nodule
- Benign vs malig
4 main thyroid malignancies + where they commonly spread to
-
Papillary (70%)
- local followed by pulmonary and skeletal
- younger peak of incidence than follicular
-overall good prognosis
-
Follicular (10-20%)
- pulmonary and skeletal
- 3x more common in women
- good prognosis if caught early but still poorer than papillary
-
Anaplastic (1-5%)
- local, liver, lung, skeletal spread
- 25% familial associated with MEN type 2
- prognosis is highly dependant on age and stage
-
Medullary (<3%)
- Local, skin, brain spread (maybe co-existing differentiated thyroid cancer)
- mean age of onset 65, highly aggressive
- poor prognosis, median survival 3-6 months
RFx for thyroid cancer
Head and neck irradation
Female sex
Presentation of thyroid cancer
Palpable thyroid nodule
+/- signs of mets, hypo/hyperthyroidism etc
Investigations for thyroid cancer
- 1st line: Ultrasound neck,
- fine needle biopsy
- laryngoscopy
Treatment of thyroid cancer
Thyroidectomy followed by radioactive iodine ablation and suppression of TSH
Complications of thyroidectomy
- Risk of recurrent laryngeal nerve damage
- Hypoparathyroidism
- If whole thyroid removed -> hypothyroidism
Which test can be used to screen for medullary thyroid cancer recurrence
Serum calcitonin
Medullary thyroid cancers often secrete calcitonin and monitoring the serum levels of this hormone is useful in detecting sub clinical recurrence
Define thyroid storm
Severe thyrotoxicosis characterised by compromised organ function
Causes of thyroid storm
- Graves disease,
- Post thyroidectomy,
- Infection,
- Trauma,
- Abrupt cessation/Lack of adherence with Antithyroid drugs
- MI,
- DKA,
- Pregnancy etc,
- Exogenous iodine,
Presentation of thyroid storm
- Fever,
- cardiovascular dysfunction,
- profuse sweating,
- tachyarrhythmias,
- nausea and vomiting
investigation for thyroid storm
Free thyroxine and TSH
- in thyroid storm TSH is completely suppressed with high thyroxine if of a primary cause
Treatment for thyroid storm
1ST LINE: Antithyroid treatment- Carbimazole (or Propylthiouracil (PTU))
Hydrocortisone administration is also recommended. It treats possible relative adrenal insufficiency while also decreasing T4 to T3 conversion (t3 is active form so less free t3 means less hyperthyroidism symptoms)
Gold Standard: Thyroidectomy
What are the 2 types of Cushing’s syndrome
- ACTH independant - ACTH levels normal but cortisol levels high
- ACTH dependant - ACTH levels high anf cortisol levels high
Causes of ACTH independent Cushing’s syndrome
Iatrogenic - caused by oral steroids such as glucocorticoid e.g. PREDNISOLONE – MOST COMMON CAUSE
Adrenal adenoma - benign tumour of the adrenal gland that secretes increased levels cortisol
causes of ACTH dependant Cushings
- ACTH secreting anterior pituitary adenoma (most common)
- Ectopic ACTH production - typically small cell lung cancer or carcinoid tumour
Presentation of Cushing’s syndrome
- Round moon face
- Central obesity
- Abdominal striae
- Buffalo hump (fat pad on back)
- PROXIMAL limb muscle wasting
- Mood change
- depression, lethargy, irritability, psychosis
- Amenorrhoea
- Acne
- Hirsutism
Investigations for Cushing’s
- 1st line = Raised plasma cortisol (unreliable)
- Gold = Dexamethasone suppression test
- 24hr urinary free cortisol (accurate but less indicative of underlying cause)
MRI brain for pituitary adenoma
Chest CT for small cell lung cancer
Abdominal CT for adrenal tumours
Dexamethasone suppression test
- Low dose 1mg:
- If low cortisol then cortisol secretion normal
- if high/normal cortisol -> cushing’s
- High dose test (8mg):
- low cortisol -> cushing’s disease (i.e pituitary adenoma)
- high/normal cortisol
** ACTH low -> adrenal cushing’s
** ACTH high -> ectopic ACTH
Tx of Cushing’s
If the cause was iatrogenic - STOP taking steroids!
If adrenal adenoma - adrenalectomy
If pituitary adenoma - trans-sphenoidal surgery to remove
If ectopic ACTH production - surgery to remove neoplasm if it can be located and hasn’t metastesised
If surgical removal of cause if not possible - alternative: remove both adrenal glands and give patient replacement steroid hormones for life
Complications of Cushing’s
- DMT2
- Hypertension
- CVD
- Osteoporosis
- DVT +/- PE
Role of cortisol
