Endocrinology Flashcards
T1DM
Autoimmune disorder where the insulin-producing beta cells of the islets of Langerhans in the pancreas are destroyed by the immune system
- Absolute deficiency of insulin resulting in raised glucose levels
- Childhood
- BMI below 25
- Weight loss
- Polydipsia
- Polyuria
- Can initially present as DKA (Vomitting, Abdo pain, keto breath, Kussmaul respiration)
Diagnosis
- Random Glucose (or 75gOGTT): 11.1 mmol Fasting: 7.0 mmol
- If pt ASYMPTOMATIC above criteria must be met on 2 separate occassion
- HbA1c not as effective in T1DM due to nature of presentation
- C-peptide levels and diabetes-specific autoantibodies are the investigations of choice. CPeptide=LOW
- Other Antibody tests: antiGAD, ICA, IAA
Management
- HbA1c monitor every 3-6m, Target: below 48mmol
- Daily self monitoring of Blood sugar (4x Daily, mealtime, sleep time)
- Target: Below 7mmol before meals and waking up.
- SC Insulin
- Multiple daily injection basal-bolus insulin regimens, (Background, long-acting insulin injected once a day
Short-acting insulin injected 30 minutes before consuming carbohydrates) - Injecting into the same spot can cause lipodystrophy So you can get insulin pumps but may be complicated to use for some patients, or cycle injection sites
- NICE recommend considering adding metformin if the BMI >= 25 kg/m²
Side Fx Insulin
- Hypoglycaemia
- Weight gain
- Lipodystrophy
polyuria and polydipsia are due to water being ‘dragged’ out of the body due to the osmotic effects of excess blood glucose being excreted in the urine (glycosuria).
T2DM
- Relative deficiency of insulin due to an excess of adipose tissue.
- Polydipsia
- Polyuria
Diagnosis
- Random Glucose (or 75gOGTT): 11.1 mmol Fasting: 7.0 mmol
- If pt ASYMPTOMATIC above criteria must be met on 2 separate occassion
- HbA1c of greater than or equal to 48 mmol/mol (6.5%) is diagnostic of diabetes mellitus
- A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG) - offer them oral glucose tolerance test
- HbA1c should be checked every 3-6 months until stable, then 6 monthly
Misleading HbA1c results can be caused by increased red cell turnover
- haemoglobinopathies
- haemolytic anaemia
- untreated iron deficiency anaemia
- suspected gestational diabetes
- children
- HIV
- chronic kidney disease
- people taking medication that may cause hyperglycaemia (for example corticosteroids)
T2DM Treatment Pathway
Should only add a second drug if the HbA1c rises to 58 mmol/mol (7.5%)
First line
- Lifestyle Intervention
- Metformin ( titrated up slowly to minimise risk of GI upset)
- add SGLT-2 Inhibitor (dapagliflozin) if CVD risk or Heart failure
Gliclazide, a sulfonylurea, is often used second-line if metformin is not tolerated
Second Line
- Considered if blood glucose >58mmol
1. Metformin (+/-SGLT2inhib) + DPP-4 inhibitor (gliptin) or pioglitazone or sulfonylurea (Gliclazide)
Thrid Line
- Metformin + 2 of the above drugs
- Metformin + Insulin
- NPH insulin (isophane, intermediate-acting) taken at bed-time or twice daily according to need
- metformin should be continued.
Fourth Line
- Metformin + Insulin + GLP1 mimetic (semaglutide/ozempic)
- Only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months
metformin should be avoided in moderate to severe renal failure,
you can use SGLT2 as combo therapy in non CVD if NICE criteria met
Targets:
Lifestyle 48mmol
Metformin 48mmol
Treatment regimen Includes any drug which may cause hypoglycaemia (e.g. lifestyle + sulfonylurea) 53 mmol/mol (7.0%)
Already on one drug, but HbA1c has risen to 58 mmol/mol (7.5%) 53 mmol/mol (7.0%)
MoA Diabetic Drugs
- Biguanide: Metformin
Increases insulin sensitivity
Decreases hepatic gluconeogenesis - SGLT2 Inhib: Dapagliflozin
Inhibits reabsorption of glucose in the kidney - DPP4 inhib: Sitagliptin
Increases incretin levels which inhibit glucagon secretion - Thiazolidinedione: Pioglitzone
Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake - Sulfonylurea: Gliclazide
Stimulate pancreatic beta cells to secrete insulin - GLP1 agonists: Semaglutide
Incretin mimetic which inhibits glucagon secretion
Side Effects of Diabetic Drugs
Drug Classes
- Biguanide: Metformin
- SGLT2 Inhib: Dapagliflozin
- DPP4 inhib: Sitagliptin
- Thiazolidinedione: Pioglitzone
- Sulfonylurea: Gliclazide
- GLP1 mimec: Semaglutide
- Sulfonylurea: Gliclazide: Hypoglycaemia Weight gain yponatremia
- Biguanide: Metformin: Gastrointestinal upset
Lactic acidosis - SGLT2 Inhib: Dapagliflozin: Urinary tract infection
- DPP4 inhib: Sitagliptin: increased risk of pancreatitis
- Thiazolidinedione: Pioglitzone: Weight gain
Fluid retention - Sulfonylurea: Gliclazide
Hypoglycaemia Weight gain Hyponatraemia - GLP1 mimec: Semaglutide: Nausea and vomiting
Pancreatitis
Ramadan + Diabetic Treatment Regiment
Metformin: one-third before sunrise (Suhoor) and two-thirds after sunset (Iftar)
Sulfonylureas: after iftar
Gliclazide: Bigger dose after iftar
Pioglitazone: no adjustment is needed for patients
Diabetic Sick Day rules
T1DM
- if a patient is on insulin, they must **not **stop it due to the risk of diabetic ketoacidosis
- Drink 3L water
- eat as normal
- monitor blood sugars closely
T2DM
- metformin: stop treatment if there is a risk of dehydration, to reduce the risk of lactic acidosis.
- sulfonylureas: may increase the risk of hypoglycaemia
- SGLT-2 inhibitors: check for ketones and stop treatment if acutely unwell and/or at risk of dehydration, due to the risk of euglycaemic DKA
- GLP-1 receptor agonists: stop treatment if there is a risk of dehydration, to reduce the risk of AKI
Ketoacidosis
complication of existing type 1 diabetes mellitus, very rarely it occurs in T2DM
Predisposing Factors
- Incorrect Insulin Regiment, MI, Infection, Missed Insulin Dose
Pathophysiology
- Uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty acids that are ultimately converted to ketone bodies
Presentation:
- Vomitting
- Polydypsia, Polyuria, Dehydration
- Abdo pain
- keto breath
- Kussmaul respiration
Diagnosis
- Blood Glucose >11mmol
- Ketones: >3mmol
- pH < 7.3
- bicarbonate < 15 mmol/l
Managment
- IV Fluids: isotonic saline
- IV infusion Insulin at 0.1 unit/kg/hour
- potassium may need to be added to the replacement fluids
- IV Dextrose once Glucose below 14mmol
- long-acting insulin should be continued, short-acting insulin should be stopped
Further
- Resolution: pH>7.3, Ketones <0.3
- Watch out for Cerebral Oedema in Children
- ketonaemia and acidosis should have been resolved within 24 hours. If this hasn’t happened the patient requires senior review from an endocrinologist
Complications may occur from DKA itself or the treatment:
gastric stasis
thromboembolism
arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia
iatrogenic due to incorrect fluid therapy: cerebral oedema*, hypokalaemia, hypoglycaemia
acute respiratory distress syndrome
acute kidney injury
Hyperosmolar Hyperglycaemic State
Compared to DKA, HHS comes on over many days, and consequently, the dehydration and metabolic disturbances may be more extreme
Predisposing Factors
- intercurrent illness
- dementia
- sedative drugs
- Pathophysiology
- hyperglycaemia → ↑ serum osmolality → osmotic diuresis → severe volume depletion
Presentation
- clinical signs of dehydration
- polyuria
- polydipsia
- Lethargy
- N&V
- focal neurological deficits
Diagnosis
- No set criteria
- Blood Glucose 30mmol
- raised serum osmolarity (> 320 mosmol/kg)
- no ketonaemia or acidosis
Management
- IV 0.9% sodium chloride solution
- No insulin unless blood glucose stops falling while giving IV fluids
- VTE Prophylaxis
Complications
- vascular complications may occur due to hyperviscosity:
- such as myocardial infarction
- stroke
Maturity onset diabetes of the young (MODY)
- A group of inherited genetic disorders affecting the production of insulin.
- Results in younger patients developing symptoms similar to those with T2DM, i.e. asymptomatic hyperglycaemia with progression to more severe complications such as diabetic ketoacidosis
Latent autoimmune diabetes of adults (LADA)
- The majority of patients with autoimmune-related diabetes present younger in life. There are however a small group of patients who develop such problems later in life.
- These patients are often misdiagnosed as having T2DM
Causes of Raised Bloodsugar (hyperglycaemia)
Other than Diabetes
- Pancreatitis
- haemochromatosis
- Glucocorticoid use (Prednislone)
Complications of Diabetes
DOUBKE CHECK THIS CARD NOT ALL IS ACCURATE
Diabetic retionopathy: cotton wool spots (‘soft exudates’ - represent areas of retinal infarction)panretinal laser photocoagulation, VEGF inhibs
Peripheral Neuropathy: Sensory loss, glove stock distribution, treat with gapapentin, TCA (amitryptaline) , Duloxetine, pregablin
Gastric Neuropathy: Gastroparesis treatment: metoclopramide, domperidone
Diabetic Nephropathy albumin:creatinine ratio (ACR), reduce protein, start ACE Inhib to control BP
Hormone Axis Phsiology
Thyroid, Adrenal, GH, Parathyroid Axis’ -ve feedback loops
The hypothalamus releases hormones that stimulate the pituitary gland. The pituitary gland has an anterior and posterior part.
Thyroid Axis
* Hypothalamus -> TRH -> AP -> TSH ->Thyroid Gland -> T3 +T4
Adrenal Axis
- Hypothalamus -> CRH -> AP -> ACTH -> Adrenal Glands -> Cortisol (stress hormone)
Growth Hormone Axis
- Hypothalamus -> GHRH -> AP -> GH -> Liver -> IGF1
Parathyroid Axis (different)
- Low Ca2+ -> Parathyroid Glands -> PTH Hormone -> Bone Resorption, less Ca2+ secreted in kidneys, PTH also stimulates the kidneys to convert vitamin D3 into calcitriol, the active form of vitamin D. Vitamin D promotes calcium absorption from food in the intestine.
Anterior Pituitary
- ACTH
- TSH
- FSH
- LH
- GH
- Prolactin
Posterior Pituitary
- Vasopressin/Anti Diuretic Hormone
- Oxytocin
AUTOIMMUNE
Hyperthyroidism
aka thyrotoxicosis
Graves most common cause
Others incl.:
- Amiodarone use
- Toxic multinodulare goitre
- Initial stages of De Quervians + Post Partum Thyroditis (these later become hypo)
Signs
- Weight loss
- Manic Restlessness - Tachycardic + Palipitations
- Heat intolerance - sweating
- Pretibial myoxedema
- Oligomennhoria - infrequent periods
- Diarrhoea
- Anxiety + Tremor
- High output cardiac failure in elderly
Ix
- Low TSH + High T4 (High T3 but irrelevant)
- Anti TPO antibodies
Management
- Propranalol - initial symptom management
- Carbimazole - watch out of agranulocytosis (reduced granulocytes- neutrophils)
Agranulocytosis can present with symptoms such as fever, chills, sore throat, mouth ulcers, and severe infections.
Subclinical hyperthyroidism is an entity which is gaining increasing recognition. It is defined as:
- normal serum free thyroxine and triiodothyronine levels
- with a thyroid stimulating hormone (TSH) below normal range (usually < 0.1 mu/l)
Grave’s Disease
Most common cause of thyrotoxicosis/Hyperthyroidism
Common in F - 30-50y
Signs
- typical features of thyrotoxicosis (heat intolerance, palpitations, Pretibial myoxedema etc)
- Exopthalmos - Big eyes
- Opthalmoplegia
- Thyroid acropachy: 1. digital clubbing 2. soft tissue swelling of hands + feet 3. periosteal new bone formation
Ix
- TSH receptor stimulating antibodies raised
- anti-thyroid peroxidase antibodies (75%) raised
- Thyroid scintigraphy: diffuse, homogenous, increased uptake of radioactive iodine
Management
- referred to secondary care for ongoing treatment.
- Propranalol - initial symptom management
- Carbimazole - watch out of agranulocytosis (reduced granulocytes- neutrophils)
Hypothyroidism
underactive thyroid
1mary Hypothyroidsm: Issue with thyroid gland itself
2ndry Hypothyroidism: Issue with pituitary gland which secretes the TSH
Hashimoto’s thyroiditis - most common cause in the developed world
Others incl.: Iodine deficieny (common in developing world), lithium or amiodarone use, de Quervain’s or Post Partum thyroiditis. Secondary causes incl. Pituitary failure, Coeliac, downsydnrome, turner’s
Signs
- Weight gain
- Lethargy
- Dry (anhydrosis), cold, yellowish skin
- Dry, coarse scalp hair, loss of lateral aspect of eyebrows
- Non pitting oedema
- Constipation
- Menorrhagia - heavy periods
- Decreased Deep tendon reflexes
- Carpal Tunnel Syndrome
Ix
- Primary: High TSH low T4
- Secondary: Low TSH Low T4
- Sick euthyroid syndrome: Low TSH Low T4
Management
- Primary: levothyroxine to replace the underlying deficiency.
- starting dose of levothyroxine should be lower in elderly patients and those with ischaemic heart disease.
- 25 in elderly 50-100mg in normal
- monitor after 8-12 weeks
- women with established hypothyroidism who become pregnant should have their dose increased ‘by at least 25-50 micrograms levothyroxine’ due to the increased demands of pregnancy
- Interaction with iron and calcium carbonate (levothyroxine less available) so ask patients to go easy with spinach and milk and if they do then eat thyroxine 4hr apart
Side-effects of thyroxine therapy
- hyperthyroidism: due to over treatment
- reduced bone mineral density
- worsening of angina
- atrial fibrillation
Hashimotos Thyroditis
chronic autoimmune thyroiditis leading to hypothyroidism
Signs
- features of hypothyroidism (weight gain, cold intolerance, constipation, dry, non pitting oedema)
- goitre: firm, non-tender
- anti-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies
Associations
other autoimmune conditions e.g. coeliac disease, type 1 diabetes mellitus, vitiligo
Hashimoto’s thyroiditis is associated with the development of MALT lymphoma
Thyroglossal cyst
Differential for goitre
Features
* usually midline, between the isthmus of the thyroid and the hyoid bone
* moves upwards with protrusion of the tongue
* may be painful if infected
* common in <20y
Thyroid Cancer
4 main types
Features of hyperthyroidism or hypothyroidism are not commonly seen in patients with thyroid malignancies as they rarely secrete thyroid hormones
Papillary
- 70%
- common in Young females
Follicular
- 20%
- split in to Adenoma & carcinoma
- Adenoma: Usually present as a solitary thyroid nodule
- Carcinoma: Vascular invasion predominates
Management of papillary and follicular cancer
- total thyroidectomy
- followed by radioiodine (I-131) to kill residual cells
- yearly thyroglobulin levels to detect early recurrent disease
Medullary
- 5%
- Cancer of parafollicular (C) cells, secrete calcitonin, part of MEN-2
- Serum calcitonin levels often raised
- Both lymphatic and haematogenous metastasis are recognised, nodal disease is associated with a very poor prognosis.
Anaplastic
- difficult to treat
- pressure symptoms
- Most common in elderly females
- Local invasion is a common feature
- Treatment is by resection where possible, palliation may be achieved through isthmusectomy and radiotherapy. Chemotherapy is ineffective.
Pressure Symptoms Due to the aggressive nature of anaplastic thyroid cancer, pressure symptoms can be more pronounced and may include severe difficulty swallowing (dysphagia), difficulty breathing (dyspnea), a feeling of fullness or pressure in the neck, hoarseness, or changes in voice quality
Cushing’s Syndrome
Cushing syndrome is a condition marked by excessive cortisol levels, with Cushing’s disease specifically denoting this syndrome caused by a pituitary adenoma producing excess adrenocorticotropic hormone (ACTH).
Cushing’s syndrome refers to the features of prolonged high levels of glucocorticoids in the body.
Feautures
- Round face (known as a “moon face”)
- Central obesity
- Abdominal striae (stretch marks)
- Buffalo Hump on back
- Proximal Myopathy
- Male pattern facial hair in women (hirsutism)
- Easy bruising and poor skin healing
Causes of Cushing’s Syndrome: CAPE
- C – Cushing’s disease (a pituitary adenoma releasing excessive ACTH)
- A – Adrenal adenoma (an adrenal tumour secreting excess cortisol)
- P – Paraneoplastic syndrome from small cell lung cancer
- E – Exogenous steroids (patients taking long-term corticosteroids)
Investigations
- overnight (low-dose) dexamethasone suppression test
- A hypokalaemic metabolic alkalosis may be seen, along with impaired glucose tolerance.
Management
- Trans-sphenoidal (through the nose) removal of pituitary adenoma
- Stop Steroids but taper it instead of stopping abruptly
Pseudo-Cushing’s
- mimics Cushing’s
- often due to alcohol excess or severe depression
Acromegaly
excess growth hormone secondary to a pituitary adenoma in over 95% of cases. A minority of cases are caused by ectopic GHRH or GH production by tumours e.g. pancreatic.
Features
- coarse facial appearance, spade-like hands, increase in shoe size
- large tongue, prognathism, interdental spaces
- excessive sweating and oily skin: caused by sweat gland hypertrophy
- Galactorrhoea
- headaches, bitemporal hemianopia
- Complications: Cardiomyopathy, HTN, Diabetes
Investigations
- Serum IGF-1 levels first line
- Oral Glucose Tolerance test done secondary to confirm diagnosis (GH above 2)
Management
- Trans-sphenoidal surgery is the first-line treatment for acromegaly i
- if contrainicated
- octreotide (somatostatin analogue): inhibits GH
- External irradiation is sometimes used for older patients or following failed surgical/medical treatment
6% of patients have MEN-1
The growth hormone suppression test involves consuming a 75g glucose drink with growth hormone tested at baseline and 2 hours following the drink. The glucose should suppress the growth hormone level. Failure to suppress growth hormone indicates acromegaly.
primary hyperaldosteronism
Conn’s Syndrome: primary hyperaldosteronism caused by adrenal adenoma
Hyperaldosteronism refers to high levels of aldosterone. Conn’s syndrome refers to an adrenal adenoma producing too much aldosterone.
Causes
- bilateral idiopathic adrenal hyperplasia - most common
- adrenal adenoma: 20-30% of cases
- familial hyperaldosteronism
Features
- Hypertension
- hypokalaemia - muscle weakeness
- metabolic alkalosis
Ix
- treatment resistant hypertension warrants ix for primary hypealdosteronism
- plasma aldosterone/renin ratio is the first-line investigation (high aldo + low renin)
- high-resolution CT abdomen and adrenal vein sampling used for source
- Normal CT = adrenal venous sampling (AVS) can be used to distinguish between unilateral adenoma and bilateral hyperplasia
Management
- adrenal adenoma: surgery (laparoscopic adrenalectomy)
- bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
Addison’s Disease
Primary Hypoadrenalism
Autoimmune destruction of the adrenal glands is the most common cause of primary hypoadrenalism in the UK, accounting for 80% of cases.
This is termed Addison’s disease
other causes of hypoadrenalsim
- tuberculosis
- metastases (e.g. bronchial carcinoma)
- HIV
- reduced cortisol and reduced aldosterone
Features
- lethargy, weakness, anorexia, nausea & vomiting, weight loss, ‘salt-craving’
- hyperpigmentation (especially palmar creases) - bronze
- vitiligo
- loss of pubic hair in women
- hypotension
- hypoglycaemia
- hyponatraemia and hyperkalaemia may be seen
- Crisis: collapse, shock, pyrexia
Ix
- ACTH stimulation test (short Synacthen test)
Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug - an ACTH stimulation test is not readily available (e.g. in primary care) then sending a 9 am serum cortisol can be useful:
Under 500ml warrants synachthen test
Management
- both glucocorticoid and mineralocorticoid replacement therapy
- Hydrocortisone - 2/3times daily given mostly earlier on
- Fludrocortisone
- steroid card issued
- patients should be provided with hydrocortisone for injection with needles and syringes to treat an adrenal crisis
Management of intercurrent illness
- in simple terms the glucocorticoid dose should be doubled, with the fludrocortisone dose staying the same
Addisonian crisis
Causes
- sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison’s, Hypopituitarism)
- adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
- steroid withdrawal
Management
- hydrocortisone 100 mg im or iv
- 1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
- continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
- oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
