Endocrine Flashcards
Define hyperthyroid disease/thyrotoxicosis
(NB: this section includes Grave’s, thyroid nodules, viral thyroiditis)
Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland,
whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source
Thyrotoxicosis may be either due to increased thyroid hormone synthesis (hyperthyroidism) OR increased release of stored thyroid hormone from an inflamed thyroid gland (thyroiditis)
Explain the aetiology / risk factors of hyperthyroid disease/ thyrotoxicosis
Please read the definition of these two things, it’s very important
A bit of detail on the cause of grave’s
What antibody type?
Thyrotoxicosis= umbrella term for both hyperthyroidism (i.e. overactive thyroid) and thyroiditis (release of thyroid stored thyroid hormone from an inflamed thyroid gland)
Hyperthyroidism:
- Primary
1. Grave’s disease (=Plasma IgG to thyroid TSH receptor stimulates thyroid hyperplasia and thyroid hormone hypersecretion, causing exaggerated thyroid hormone action and autonomic overactivity.)
2. Toxic multinodular goitre
3. Single toxic adenoma - Secondary
4. TSH-secreting pituitary tumours
5. TSH producing tumours
Choriocarcinoma (raised hCG, which is structurally similar to TSH)
Thyroiditis:
- Post partum
- De Quervain’s (post viral)
Drugs: amiodarone &; self administration of T4
RISK FACTORS
- Grave’s: other AI diseases
- Toxic multinodular: older women
Summarise the epidemiology of hyperthyroid disease/ thyrotoxicosis (IMPORTANT)
Thyrotoxicosis affects 1% of all females and 0.1% of all males.
Grave’s disease accounts for 70-80% of all cases of hyperthyroidism
Toxic multinodular goitre most common cause of hyperthyroidism in the elderly
Recognise the presenting symptoms of hyperthyroid disease/thyrotoxicosis
How might you use these to differentiate the different causes
GENERAL thyrotoxicosis symptoms:
- Heat intolerance, sweating, anxiety and irritability, palpitations
- Weight loss (BUT INCREASED APPETITE), diarrhoea, pruritis
- Tremor
- Menstrual irregularities in females
- Reduced libido, impotence in males
SPECIFICS:
- de Quervain’s thyroiditis: fever, malaise and pain in the neck (tender goitre)
- Grave’s: opthalmopathy (blurred vision, double vision, eye grittiness, eye protrusion)
Recognise the signs of hyperthyroid disease/thyrotoxicosis on physical examination
How might you use these to differentiate the different causes
What are the signs specifically of a thyroid crisis
GENERAL:
- Underweight, restless, irritable, sweating. Signs of associated AI conditions (vitiligo)
- Warm vasodilated peirpheries, systolic HTN, cardiac failure
- Rapid irregular pulse, palmar erythema,
- Proximal myopathy
GRAVE’S SPECIFIC:
- Dermopathy: thyroid acropachy (clubbing) , pretibial myxoedema
- Exophthalmos, lid lag & stare, ophthalmoplegia, periorbital oedema
Thyroid crisis : Hyperpyrexia, signs of dehydration, tachycardia, restlessness, coma.
Identify appropriate investigations for hyperthyroid disease/thyrotoxicosis and interpret the results
How might you use these to differentiate the different causes
Thyroid function tests: Primary hyperthyroidism (increased T4, T3, reduced TSH) Secondary hyperthyroidism (increased T4, T3, raised or inappropriately normal TSH)
Radioisotope uptake scan (99 technetium pertechnetate):
- Grave’s: diffuse increased uptake
- Toxic multinodular goitre: multiple areas of increased radio-isotope uptake (hot nodules) WITH suppression of uptake in the rest of the gland
- Solitary toxic adenoma: single area of “ radio-isotope uptake (hot nodules) with suppression of uptake in the rest of the gland.
- de Quervain’s thyroiditis: absent uptake
TSH receptor stimulating antibodies: positive in Grave’s disease (expensive, and the aetiology can be established using the above)
CT/MRI of orbits (STIR sequence- nulls signal from fat): Assessment and follow-up of patients with Grave’s opthalmology
Describe pretibial myxoedema
raised pigmented orange-peel textured nodules or plaques on the shins
specific to Grave’s disease
Explain proctosis in Grave’s disease, what is the name for it specifically?
secondary to increased glycosaminoglycans secreted by fibroblasts stimulated by activated T cell cytokines and TSH receptor antibodies
called exopthalmos
Management of hyperthyroidism/thyrotoxicosis
Indications for each
- Medical
- Anti-thyroid drugs: carbimazole, propylthiouracil (both inhibit thyroid peroxidase and hormone synthesis)
Rarely cause agranulocytosis. Must be stopped and have FBC checked if develop fever, sore throat, mouth ulcers or other signs of infection. If this toxicity occurs, propylthiouracil used instead
After 4-6 weeks at full dose, carbimazole gradually reduced over 6-24 months and discontinued when patient is euthyroid. 50% of patients with Grave’s relapse and then need further treatment (radioactive iodine or surgery)
- KI: Inorganic iodide given in pharmacological doses (as Lugol׳s solution or as saturated solution of potassium iodide, SSKI) decreases its own transport into the thyroid, inhibits iodide organification (the Wolff–Chaikoff effect), and rapidly blocks the release of T4 and T3 from the gland. ALSO REDUCES VASCULARITY OF THE GLAND (see why this is relevant in “surgery”)
- b blockers (as clinical benefit not apparent for 10-20 days, b blockers provide symptomatic control)
- Radio-iodine
- Must avoid pregnancy/breast feeding for 4 months and close contact with pregnant women and young children for 2 weeks after radioactive iodine therapy.
It accumulates in the gland and results in local irradiation over 4-12 wks.
- Surgery:
- Reserved for patients with large goitres causing upper airway obstruction or dysphagia, and those who cannot take ATD (e.g. due to allergy/agranulocytosis) and are either pregnant or have moderate/severe Graves’ ophthalmopathy (which may be exacerbated by radioiodine).
Should only be performed in patients who have been rendered euthyroid. ATD stopped 10-14 days before operation and replaced with oral PI which inhibits thyroid hormone release AND reduces vascularity of the gland
Pre-operative prep: control hyperthyroidism with ATD, give oral potassium iodide and propanolol. Examination of vocal cords by ENT specialists
Lifelong measurement of TSH to look for hypothyroidism is indicated after surgery or radioiodine treatment
Ophthalmopathy : Corneal protection (artificial tears, lateral tarsorrhaphy), surgery for realignment
Complications of hyperthyroidism/thyrotoxicosis
Thyrotoxic crisis. Heart failure. Osteoporosis. Infertility. Complications of surgery (recurrent laryngeal nerve palsy, hypothyroidism, hypoparathyroidism) or radioiodine (exacerbation of ophthalmopathy, hypothyroidism, recurrence).
Patients with subclinical hyperthyroidism have increased long-term risk of atrial fibrillation and reduced bone density.
Prognosis of hyperthyroidism/thyrotoxicosis
Many patients eventually become hypothyroid
Differentiate the two types of amiodarone induced hyperthyroidism
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Define prolactinoma
Physiological reasons for huperprolactinaemia
Prolactin release under tonic inhibition by dopamine from hypothalamus.
Physiological reasons: pregnancy, lactation and severe stress
Explain the aetiology / risk factors of prolactinoma
do general causes of hyperprolactinaemia
Commonest cause of hyperprolactinaemia is a prolactinoma
- Prolactin secreting adenoma (prolactinoma)
- Other pituitary/hypothalamic (e.g. craniopharyngioma) tumours can cause hyperprolactinaemia by interfering with dopamine inhibition (due to stalk compression) or prolactin release.
- Use of a dopamine antagonist (e.g. metaclopramide haloperidol) or other drugs (e.g. oestrogens, ecstasy)
Other causes of primary hypothyroidism (because TRH levels stimulate prolactin)
PCOS
Acromegaly (co-secretion of prolactin with GH by the tumour)
Note that a PRL >5000 is likely to be a prolactinoma
Summarise the epidemiology of prolactinoma
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Recognise the presenting symptoms/signs of prolactinoma (do hyperprolactinaemia generally)
Macroprolactinoma?
Hyperprolactinaemia presents earlier in women (menstrual disturbance) than men (erectile dysfunction/mass effects)
Galactorrhoea in women
Amenorrhoea/oligomenorrhoea (as prolactin inhibits GnRH)
Decreased libido, subfertility and erectile dysfunction in men.
Osteoporosis
Local effects of headache and visual field defects if there is a pituitary tumour
Macroprolactinoma:
-reduced visual acuity, diplopia, opthalmoplegia, visual field loss and optic atrophy
Identify appropriate investigations for prolactinoma and interpret the results
Basal PRL; non stressful venepuncture between 9am and 4pm. PREGNANCY TEST, TFT, U&E, MRI pituitary if other causes ruled out
Generate a management plan for prolactinoma
What is macroprolactinoma
What is preferred in pregnancy
FOR MICRO-prolactinomas
Dopamine agonists first line e.g. bromocriptine and cabergoline. BROMOCRIPTINE PREFERRED IN PREGNANCY
Bromocriptine reduces PRL and also reduces tumour size
Transphenoidal surgery if intolerant of dopamine agonists.
FOR MACRO-prolcatinomas:
A tumour >10mm on MRI. Treat initially with dopamine antag (bromocriptineif fertility is the goal). Surgery rarely needed BUT considered if there are visual symptoms or pressure effects which fail to respond to medical treatment.
Bromocriptine and in some cases radiation therapy, may be required post-op as complete surgical resectuin is uncommon.
Identify the possible complications of prolactinoma and its management
Increased risk of expansion of (macro)prolactinoma when pregnant (you have to check visual fields (perimetry) if pregnant because prolactin level will be off anyway
Management complications:
Bromocriptine SEs: nausea, depression, postural hypotension (give at night). If pregnancy is planned, use barrier contraception until 2 periods have occurred. If they get pregnant, stop bromocriptine after 1st missed period
Cabergoline (an ergot alkaloid) can cause fibrosis (echos needed), but generally has less SEs than bromocriptine, but less data of safety of this drug during pregnancy
Transphenoidal surgery: high success rate but risks of permanent hormone deficiency and prolactinoma recurrence, so usually reserved as 2nd line
Summarise the prognosis for patients with prolactinoma
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What are the 3 major conditions usually caused by secretion from pituitary adenomas
GH excess –> gigantism in children and acromegaly in adults
Prolactin excess –> causing galactorroea or clinically silent
Excess ACTH secretion –> cushings disease and nelsons syndrome
What are the local effects of pituirary adenoma
- Optic chiasm causing a bitemporal hemianopia
- Cavernous sinus with II, IV nad VI cranial nerve lesions
- Bony structures and the meninges cuasing headache
- Hypothalamic centres: obesity, altered appetite and thirst, prcocious puberty
- The ventricles, cuasing interruption of CSF and hydrocephalus
Define carcinoid syndrome
A consetllation of symptoms caused by systemic release of “humoral factors” (note humoral here is talking about hormones)
E.g. tumour of neuroepithelial cells. You can have a carcinoid tumour that is benign and doesn’t release anything, in which cause it isn’t carcinoid syndrome
Outline the aetiology of carcinoid syndrome
- Where are the carcinoid tumours in those with carcinoid syndrome often located?
- Which tumours will produce symptoms, which will not?
- What hormones and what is the tumour cell type
~80% of the tumours in people with carcinoid syndrome are located in the small intestine
Carcinoid tumours are slow-growing neuroendocrine tumours mostly derived from serotonin-producing enterochromaffin cells.
Common sites for carcinoid tumours that DO NOT result in carcinoid syndrome (because they are non-secretory) include appensix and rectum. Also other parts of large intestine, stomach, thymus, bronchus and other organs.
The hormones that are released into the portal circulation are metabolised by the liver, so symptoms won’t appear until there are hepatic metastases (resulting in secretion of tumour products into hepatic veins), OR release into systemic circulation from bronchial or extensive retroperitoneal tumours
Summarise the epidemiology of carcinoid syndrome
Rare, annual UK incidence is one in 1 000 000. Asymptomatic carcinoid tumours are more common and may be an incidental finding after rectal biopsy or appendectomy.
Ten percent of patients with multiple endocrine neoplasia (MEN) type 1 have carcinoid tumours.
Recognise the presenting symptoms of carcinoid syndrome
What can worsen the symptoms and why
- Diarrhoea
- SoB, wheezing, asthma due to seratonin leading to bronchoconstriction
- Flushing (due to release of histamine and bradykinin, both vasodilators)- key!
- Itching (due to histamine)
ALCOHOL AND STRESS can worsen as they stimulate the neuroendocrine cells
Confusion/inflamed skin due to pellagra (which is due to reduced niacin (=vit B3). Niacin is reduced because the increased seratonin production leads to reduced production of tryptophan, which is required for niacin)
Recognise the signs of carcinoid syndrome on physical examination
Carcinoid crisis signs?
Facial flushing, telangiectasia, wheeze
Right side heart valve dysfunction and murmurs (seratonin leads to thickening and fibrosis of heart valve). Tricuspid regurg /stenosis and pulmonary stenosis
Nodular hepatomagaly in metastatic disease
Carcinoid crisis: profound flushing, bronchospasm, tachycarrdia and fluctatuating BP
Identify appropriate investigations for carcinoid syndrome and interpret the results
When might the 24hr urinalysis be falsely postiive
Medical imaging (CT scan and octreoscan)
Octreoscan:
-Inject radiolabelled somatostatin analogue called octreotide. Because somatostatin receptor number is paradoxically increased in carcinoid, there will be increased uptake of the radiolabelled analogue in carcinoid areas
24 hr Urinalysis:
- Gold standard- chromogranin A (CgA)
- increased level of 5-hydroxyindoleacetic acid (5-HIAA) (breakdown product of seratonin). NOTE THIS MAY BE FALSELY +VE WITH HIGH INTAKE OF CERTAIN FRUITS/DRUGS e.g bananas and avacados, caffeine and paracetemol
Blood tests
- Niacin deficiency
- Chromogranin A and B (non-specific released from neuroendocrine cells)
Investigations for MEN-1
Where are neuroendocrine cells present
What do they do
What is different in normal neuroendocrine cells vs carcinoid tumour endocrine cells with regard to receptor
Mostly in the epithelial layer of the GI organs and the lungs
They release hormones in response to stimulation by neurones but can also be inhibited by hormonal mechanism (e.g. somatostatin can bind receptors to stop release of seratonin)
There are INCREASED somatostatin receptor expression on carcinoid tumour cells (perhaps unexpectedly!)
Differentiate MEN1 and MEN2A/MEN2B
MEN type 1 (mutation in menin gene on chromosome 11): Parathyroid adenoma or hyperplasia, pancreatic endocrine tumours, pituitary adenomas. (3Ps) and carcinoid
MEN type 2 (mutation in RET gene on chromosome 10): Medullary thyroid carcinoma, phaeochromocytoma and either parathyroid hyperplasia (MEN-2A) or mucosal neuromas on the lips or tongue (MEN-2B).
What happens to GnRH, LH and FSH in PCOS?
GnRH pulsatile secretion increases, which preferentially increases LH secretion.
So LH is high and FSH is low.
LH stimulates theca cells to produce androstenedione.
But there is reduced conversion of androstenedione into oestrogen by granulosum cells in the ovary because granulosa cells respond to FSH, of which there is reduced secretion.
But there is increased conversion of androstenedione into testosterone in the theca cells (because they are being stimulated by LH) rather than it being metabolised to oestrogen in granulosa cells
Note that peripheral adipocytes produce more oestrogen than usual due to the increased production of adrostenedione. They do this using aromatase (note that both granulosa cells and adipose tissue contain aromatase, but granulosa cell aromatase responds to FSH stimulation)
What are the precipitants of a thyroid crisis
Thyroid surgery
Infection
Myocardial infarction
Diabetic ketoacidosis
Radioactive iodine administration
Hip replacement
Cause of weight loss + increased appetite
Thyrotoxicosis, T1DM
Why should a patient on carbimazole who develops a sore throat and mouth ulcers stop taking it immediately and have an urgent blood test?
Should they be switched to PTU?
They may have developed the rare neutropaenic side-effect of Carbimazole (agranulocytosis)
A patient who develops neutropaenia on Carbimazole should NOT be treated with Propylthiouracil (PTU) either: PTU has a similar low risk of causing agranulocytosis (<0.5%) and cross-reactivity has been reported.
Somebody on thyroxine who has a high TSH but a normal free T4?
This is characteristic of erratic compliance: patients who don’t take the medication regularly, but remember to take it immediately before a blood test is due. This is enough to put their FT4 up, but not to suppress their TSH.
A gentle chat about remembering to take the medication, and repeat TFTs in 6-8 weeks would be appropriate before adjusting the dose.
Secondary causes of HTN
Renal artery stenosis Cushings syndrome Polycystic kidney disease Conns syndrome Phaeochromocytoma Acromegaly Aortic coarctation
What symptoms is someone with cushing most likely to present with
Round face, centripetal obesity and thin legs
Causes of SIADH
Sepsis and neurological disease (stroke) are some of the commoner causes.
Also malignancy and lung abscess
What is the complication of increasing sodium too quickly in hyponatraemia
pontine and extra-pontine myelinolysis
Treatment of SIADH induced hyponatraemia
Fluid restriction (usually all that’s needed in mild cases)
Demeclocycline
Hypertonic sodium chloride 1.8% IV (CAREFUL, in specialist care to avoid pontine and extra-pontine myelinolysis)
What are the features of diabetic retinopathy
Background:
- Blot haemorrhages
- Microaneurysms (blot)
- Hard exudates (leeked lipids from blood vessels)
Pre-proliferative:
-Above + soft exudates (regions of retinal ischaemia)
Proliferative: new blood vessels begin to
form in response to retinal ischaemia.
Maculopathy (a sub-type, not part of the above progression):
In maculopathy, hard exudates are found near the macula. This can
threaten direct vision.
Define type 1 diabetes mellitus
Metabolic hyperglycaemic condition caused by absolute insufficiency of pancreatic insulin production.
Explain the aetiology / risk factors of type 1 diabetes mellitus
Which genes is it associated with
Destruction of the beta cells in the centre of the islets of langerhans in the pancreas resulting in absolute insulin deficiency
Type IV hypersensitivity response (genetic abnormality that causes loss of self tolerance of T cells that react to beta cell antigens)
It’s associated with HLA-DR3 and HLA-DR4 (but not everyone with these genes has DM, so it’s environmental trigger too)
Pancreatic beta cell autoantigens may also play a role in initiation or progression of T1DM, including GAD, insulin, insulinoma -associated protein 2 (IA-2) and ZnT8.
Up to 90% of beta cells destroyed before symptoms
Summarise the epidemiology of type 1 diabetes mellitus
Usually appears in the young
Recognise the presenting symptoms of type 1 diabetes mellitus
Polyphagia- lipolysis and protein breakdown due to lack of insulin. Weight loss. Catabolic state leaves people feeling hungry.
Glycosuria- renal threshold for reabsorption of sugar is reached.
Polyuria- Water follows osmotically active glucose
Polydipsia- dehydration and thirst
Tiredness, weight loss.
Recognise the signs of type 1 diabetes mellitus on physical examination
Signs of complications:
- DKA (see below)
- Diabetic retinopathy on fundoscopy
- Neuropathy on feet examination
Signs of assicated conditions:
- Vitiligo
- Addison’s
- Autoimmune thyroid disease
Identify appropriate investigations for type 1 diabetes mellitus
and interpret the results
Blood glucose (2 positive results needed before glucose): Fasting >7. Random >11.
HbA1C: estimated overall blood glucose levels in past 2-3 months
FBC: MCV, reticulocytes (because reticulocyte turnover causes misleading HbA1c levels
U&Es: monitor nephropathy OR hyperkalaemia due to ACEi note you also get hyperkalaemia in DKA, look why below
Lipids
Urine albumin creatinine ratio (to detect microalbulinaemia)
Generate a management plan for type 1 diabetes mellitus
Glycaemia control.
Conservative: advice and education
Medical:
-SC insulin: short acting insulin (lispro, aspart, glulisine) three times daily before each meal AND long acting insulin (isophane, glargine, detemir) once daily.
ROTATE INJECTION SITES.
Pumps can give better control, but are costly, and DKA can occur if it malfunctions.
Patients can attend DAFNE (dose adjustment for normal eating) to learn how to calculate carb intake and adjust insulin accordingly
Monitor:
- Control of symptoms
- Regular finger prick tests
- Monitoring HbA1c (target <7%) ever 3-6 months
Screening for complications of DM and of cardiovascular risk factors
Treatment of DKA and hypoglycaemia below
Identify the possible complications of type 1 diabetes mellitus
and its management
Diabetic ketoacidosis (see below)
Complications of insulin treatment:
Weight gain, fat hypertrophy at insulin sites, hypoglycaemia (missing mealor overdosage of insulin- see signs of this below)
Microvascular complications: retinopathy, neuropathy, nephropathy
Macrovascular complictions: PVD, ischaemic heart disease, stroke/TIA.
Increased susceptibility to infections (particuarly on feet)
Summarise the prognosis for patients with type 1 diabetes mellitus
Depends on early diagnosis, good glycaemic control and compliance with screening and treatment. Vascular disease and renal failure are major causes of increased morbidity and mortality.
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Define diabetic ketoacidosis
Diabetic ketoacidosis is a serious complication of diabetes that occurs when your body produces high levels of blood acids called ketones. The condition develops when your body can’t produce enough insulin
Explain the aetiology / risk factors of diabetic ketoacidosis
Which other metabolic disturbance is associated with DKA and why
When does DKA actually happen
Reduced insulin leads to lipolysis which generates fatty acids. The liver turns these into ketone bodies which increase the acidity of the blood.
There is also increase of counter-regulatory hormones (e.g. epinephrine) leading to increased gluconeogenesis, but there is poor peripheral glucose utilisation.
Renal reabsorption capacity of glucose is exceeded causing glycosuria, osmotic diuresis and dehydration.
The ketones are useful because they be used by the cells for energy, but also causes acidosis.
Hyperkalaemia is associated.
Because
1) There are K+/H+ exchangers on the cells. In the acidotic state, H+ is moved INTO the cells (in an attempt to reduce the acidity of the blood), in exchange for potassium which is moved out into the blood
2) Insulin activates the Na+/K ATPase, which moves potassium into cells. In insulin deficicient state, the potassium will remain outside cells.
So note that even though the blood concentration of potassium is high, the total body store is low
It can be the first presentation of T1DM.
However, it can also be once somebody has been diagnosed with T1DM.
E.g:
In states of stress like infection, there is increased release of epinephrine which stimulataes the release of glucagon, which increase blood glucose and causes dehydration etc.
And also, it causes a need for alternative energy, leading to generation of ketone bodies and acidosis
DKA may be caused by: Infection (30%) Errors in management (15%) Newly diagnosed diabetes (10%) Other medical disease (5%) No case identified (40%!)
Recognise the presenting symptoms of diabetic ketoacidosis
Nausea Vomiting Abdominal pain Polyuria Polydipsia Drowsiness Confusion
Recognise the signs of diabetic ketoacidosis on physical examination
Signs of complications
Kussmaul respiration (deep, laboured breathing which is respiratory compensation to blow off CO2)
Coma
Fruity breath (ketone bodies are broken down further into acetone)
Signs of dehydration (dry mucous membranes, reduced tissue turgor)
Identify appropriate investigations for diabetic ketoacidosis and interpret the results
BLOOD:
FBC: Increased WCC (even without infection).
U&E: increase urea and creatinine from dehydration), hyperkalaemia
LFT
CRP
glucose
amylase (could increase)
blood cultures
ABG (metabolic acidosis with high anion gap)
blood/urinary ketones
URINE:
Glycosura, increased ketones, MSU
CXR:
Exclude infection
ECG:
Rule out ischaemic changes
Generate a management plan for diabetic ketoacidosis
Consider HDU/ICU input, central line, arterial line and urinary catheter if severe acidosis, hypotensive or oliguric
INSULIN:
50 U of soluble insulin in 50ml 0.9% saline, start at 0.1 U/kg/h (~6-7U/h) until,:
-capillary ketones <0.3, venous pH >7.3 AND venous bicarbonate >18.
Then, if patient can eat and drink, change to SC insulin. If not, change to IV sliding scale. Do not stop insulin infusion until 1-2hr after regular SC insulin is restarted.
FLUIDS:
500ml 0.9% saline over 15-30 min until systolic BP >100mmHg. Then 1L 2-hourly X3, and 1L 3-hourly X3.
IV dextrose is started in conjunction with 0.9 saline WHEN blood glucose reaches 11mmol/L:
1L 5% dextrose over 8h when blood glucose is 7-15mmol/L. Then 500ml 10% dextrose over 4h when blood glucose <7mmol/L
POTASSIUM REPLACEMENT:
-Start in the second bag of fluid, if passing urine. Adjust amoutn of ptassoim added to fluids according to plasma potassium (if >5.5: nil pottasium. If 2.5-5.5: 40mmol/L. If <2.5mmol/L, 60-80mmol/L)
MONITOR BLOOD GLUCOSE, CAPILLARY KETONES, URINE OUTPUT HOURLY; U&Es 4HRLY and VBG at 0,2,4,6,8,12 h and before stopping fixed rate insulin regimen.
Broad spectrum Abx if infection
Thromboprophylaxis
NBM for at least 6hr (gastroparesis common)
NG tube (if GCS reduced, to prevent vomiting and aspiration)
No strong evidence of IV bicarb
If they have low potassium when they come in, don’t give insulin until the potassium has come into the normal range
Identify the possible complications of diabetic ketoacidosis and its management
Mental state changes
Acute cerebral oedema
What are the signs associated with hypoglycaemia
Adrenergic signs: pallor, sweating, tremor, tachycardia, palpitations, hunger
Neuroglycopaenic signs: dizziness, personality change, fits, confusion, coma and focal neurology.
What is the management of hypoglycaemia
IF REDUCED CONSCIOUSNESS:
50ml of 50% glucose IV or 1mg glucagon IM.
If conscious and cooperative: 50g oral glucose (e.g. lucosade, milk, sugar or 3 dextrose tablets), followed by a starchy snack.
No drive for 45 minutes.
What might mask the symptoms of hypoglycaemia in diabetics
Autonomic neuropathy, b-blockers and brain adapting to recurrent episodes.
What are the diagnostic criteria for diabetes
• One fasting blood glucose measurement > 7 mmol/L in a symptomatic patient
• Two fasting blood glucose measurements > 7 mmol/L in an asymptomatic
patient
• One random blood glucose measurement > 11.1 mmol/L in a symptomatic
patient
• Two random blood glucose measurements > 11.1 mmol/L in an asymptomatic
patient
- Oral glucose tolerance test – 2 hr blood glucose > 11.1 mmol/L
- HbA1c > 48 mmol/mol or > 6.5%
More subtle signs of subacute diabetes include lethargy and opportunistic infections. What are they caused by, and what are they named in men and women?
Candida,
causing pruritus vulvae in females or penile inflammation (balantis) in
males.
Most appropriate first investigation if you suspect cushing’s?
What would we use high dose for in the past, and what about now
Urinary free cortisol level first (doesn’t confirm diagnosis, but demonstrates pathalogical excess of cortisol)
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Then low dose dexamethasone test (0.5mg) and measure cortisol.
This confirms Cushing’s, but doesn’t tell you whether it’s at the pituitary gland (as this will continue to church out ACTH even with dexamethasone as -ve feedback is ineffective) or adrenal tumour (if the pituitary is working, dexamethasone will suppress the ACTH production, but the adrenal tumour no longer responds to ACTH and churns out cortisol even if ACTH is low) or an ectopic secreting ACTH (which, like the pituitary, won’t suppress its ACTH production with dexamethasone administration).
In the old days you would use high dose dexamethasone suppression, which slightly reduces cortisol production (because it ever so slightly suppresses ACTH from the pituitary).
But now, we can just measure the ACTH (without dexamethasone, which is just used for the initial confirmatory test), which is HIGH in pituitary/ectopic secreting excess ACTH, and is LOW if there is an adrenal tumour/carcinoma.
To then differentiate an ectopic from cushing disease (i.e. pituitrary), you give high dose dexamethasone, which will slightly reduce the ACTH from a pituitary adenoma (i.e. cushing’s disease) BUT NOT suppress it from an ectopic. OR
You can give meyrapone, which stops adrenal cortisol production, but not ectopic.
IMAGING:
MRI of pituitary, CT of adrenals, CT of chest, abdomen and pelvis
Enlargement of the thyroid gland with no symptoms?
A simple goitre (B) is an idiopathic enlargement of the thyroid. Often the
condition is associated with thyroid antibodies, but these do not cause any
symptoms.
“Stony/woody” feeling on palpation of thryoid gland
Riedel’s thyroiditis (C) is a rare inflammatory disease of the thyroid
gland that is characterized by fibrosis of the thyroid gland and other structures
in the neck. It is often stony or woody on palpation and patients are usually
asymptomatic.
Investigation of addison’s vs cushings
Addisons:
Firstly, a short synacthen test confirms primary Addison’s disease, whereas ACTH deficiency or suppression by
steroids can be confirmed by doing a long synacthen test.
Cushings:
Urinary free cortisol then the low-dose dexamethasone test
Define phaeochromocytoma
What are
Catecholamine-producing tumours that usually arise from chromaffin cells of the adrenal medulla but are extra-adrenal in about 10% of cases
10% bilateral, 10% malignant.
Extra-adrenal phaeochromocytoma’s are known as “paragangliomas”
Explain the aetiology / risk factors of phaeochromocytoma
Sporadic. Unknown cause
Familial (up to 30%).
Familiacl cases seen in:
1) MEN2a
2) von Hippel Lindau syndrome
3) Neurofibromatosis type 1 (NF1)
4) Mutations in subunits of mitochondrial enzyme succinate dehydrogenase (SDHB, SDHD, SDHC)
Summarise the epidemiology of phaeochromocytoma
Rare. <0.2% of hypertensive patients.
Recognise the presenting symptoms of phaeochromocytoma
PAROXYSMAL epidoes of headache and sweating
Cardio/resp: Palpitations, chest pain, dyspnoea
GI: epigastric pain, nausea, constipation
Neuo/psych: Weakness, tremor anxiety
Recognise the signs of phaeochromocytoma on physical examination
HTN (50-70%): 2/3 sustained, 1/3 paroxysmal
Postural HTN: secondary to reduced plasma volume.
Pallor, tachycardia, fever, weight loss
Identify appropriate investigations for phaeochromocytoma and interpret the results
What investigation if there is large phaeo/paraganglioma
24hr urine collection in ACID-CONTAINING bottle (vanillylmendelic acid (VMA)- catecholamine byproduct) for measurement of catecholamines, metanephrines
Urinary creatinine should be measured to verify an adequate collection.
(Note that come drugs can affect the measured catecholamines, see below)
Blood glucose and calcium may be raised, potassium might be low.
Plasma free metanephrines: in patients at high risk (sensitivity 99%)
Tumour localisation with CT or MRI
For large phaeo (>10cm) or paraganglioma, do I-MIBG scintigraphy
What drugs might affect the measured catecholamine
Certain drugs may increase the measured catecholamine (TCAs, levodopa)
What precipitates the release of catecholamine
Stress
Physical exertion
Certain foods containing tyramine: chocolate, cheese and wine
Which 3 symptoms are triad for phaeochromocytoma
It is important to note that in a hypertensive, the triad of:
headaches
palpitations and
diaphoresis (episodes of sweating)
carries a high sensitivity (91%) and specificity (94%) for pheochromocytoma
Define polycystic ovary syndrome (PCOS)
Characterised by oligomenorrhoea/amenorrhoea and hyperadrogenism (clinical or biochemical).
Associated with obesity, insulin resistance, TIIDM and dyslipidaemia
Explain the aetiology / risk factors of polycystic ovary syndrome (PCOS)
How is oestrogen usually produced in the ovaries
What happens in PCOS- which hormone is there too much of causing hyperandrogenism
Environmental: related to diet and development of obesity
Genetic variants: in genes regulating gonadotrophon, insulin etc.
Oestrogen usually produced by 2 cell types: thecal and granulosa cells.
Thecal cells respond to LH, and make androstenedione.
Granulosa cells respond to FSH convert androstenedione into oestrogen using aromatase.
In the early stages of the follicular phase, this oestrogen has negative feedback on the pituitary gland, but as the dominant follice grows (i.e. the one with most FSH and LH receptors), it produces more and more oestrogen, which eventually has a positive effect on pituitary and causes more FSH and LH release, which allows the follicle to rupture, the egg escapes and then travels down the fallopian tubes.
IMPORTANT:
In PCOS, the issue is that there is increased LH production.
This means that the thecal cells produce loads and loads of androstenedione.
It produces too much for the granulosa cells to be able to convert it all into oestrogen.
Summarise the epidemiology of polycystic ovary syndrome (PCOS)
PCOS is the most common cause of infertility in women. Affects 6–8%of women.
Recognise the presenting symptoms of polycystic ovary syndrome (PCOS)
Menstrual irregularities (oligomenorrhoea/amenorrhoea)
Dysfunctional uterine bleeding
Infertility
Symtpoms of hyperadrogenism:
Hirsutism
Acne
Male pattern hair loss
Recognise the signs of polycystic ovary syndrome (PCOS) on physical examination
Hirsutism
Acne
Male pattern hair loss
Acanthosis nigricans (signs of severe insulin resistance): velvety thickening and hyperpigmentation of the skin of axillae or neck
Identify appropriate investigations for polycystic ovary syndrome (PCOS) and interpret the results
BLOOD:
- Increased LH, increased LH:FSH ratio (>3)
- Increase testosterone, androstenedione and DHEA-S
- Reduced sex hormone binding globulin.
- Exclude hyperprolactinaemia (serum prolactin), hypo/hyperthyroidism (TFTs), congeintal adrenal hyperplasia and cushing’s syndrome
- Fasting glucose HbA1c and fasting glucose (oral glucose test if either abnormal)
- Fasting lipid profile
TRANSVAGINAL USS:
-Twelve or more follices in each ovary, measuring 2-9mm and/or increased ovarian volime >10mL
How is the diagnosis of PCOS made
Hirsutism + oligomenorrhoea= diagnosis made
Hirsutism + no olignomennoreah= measure 14 day progesterone to check for ovulation. If this revelas no ovulation, diagnose PCOS.
If it shows ovulation, perform transvaginal USS. If polycistic ovarian morpholoy (see above), diagnose PCOS.
No hirsutism= measure serum androgens (total/free testosterone and DHEAS). If any are elevated, diagnostic sequence is the same as when hirsuitsm is present (see above).
If there is no hirsutism, all androgens are normal and there is a history of oligomenorrhoea, an ovarian ultrasound should be performed. Combined with such a history, polycystic ovarian morphology allows PCOS diagnosis
First investigation for PCOS
Probably TFTs and prolactin and 17-hydroxyprogesterone to exclude thyroid dysfunction, hyperprolactinaemia, and 21-hydroxylase deficient adrenal hyperplasia, respectively
T/F LH: FSH ration is diagnostic of PCOS
In uncertain cases, elevated luteinising hormone/follicle-stimulating hormone ratio may support a diagnosis of PCOS. However, it is not diagnostic.
What are is the genetic expression of PCOS
hyperandrogenism. Although the
exact cause of PCOS is unknown, the disease has a very strong genetic component,
which follows an autosomal dominant pattern with variable expressivity.
Hyperlipidaemia definition
Elevation of one or more plasma lipid fractions
Aetiology/risk factors hyperlipidaemia
PRIMARY:
-Familial hypercholesterolaemia: reduced hepatic LDL receptors. AD inheritence
- Familial hypertriglyceridaemia: Unknown. Autosomal dominant.
- Hypertriglyceridaemia: Lipoprotein lipase or apo-CII deficiency.
Secondary:
-HIGH CHOLSTEROL:
Hypothyroidism, nephrotic syndrome, cholestatic liver disease, anorexia nervosa
-HIGH TRIGLYCERIDES:
DM, drugs (b blockers, thiazides, oestrogen), alcohol, chronic renal disease, hepatocellular disease
Epidemiology of hyperlipidaemia
50 % of the UK population have a cholesterol level high enough to be a risk for CHD.
Presenting Hx for hyperlipidaemia
Asymptomatic
Symptoms of CVS complications.
Other CVS risk factors:
DM, family Hx, smoking, HTN
Examination for hyperlipidaemia
Usually normal
Signs of lipid deposits:
- Xanthelasmas (eyes)
- Corneal arcus
- Tendon xanthomas (extensor tendons of hand etc)
- Tuberous xanthomas (on knee and elbow)
- Xanthomas in palmar creases –> REMNANT hyperlipidaemia
SEVERE HYPERTRIGLYCERIDAEMIA: eruptive xanthomas and lipidaemia retinalis (pale retinal vessels)
Investigations for hyperlipidaemia
Blood: Fasting lipid profile, exclude secondary causes (glucose, TFT, LFT U&E)
CVS risk using framingham or Q risk
Management of hyperlipidaemia
What is the target cholesterol
What drug for:
- High total cholsterol or high LDL
- High triglycerides
Conservative: exercise, lose weight, stop smoking, control DM, reduce alcohol
Medical.
Lipid lowering for primary prevention (when heart attack risk in 10 years >10%) and secondary prevention (coronary heart disease, aortic aneurysm, carotid artery disease).
Target: total cholesterol <4mmol/L, LDL<2mmol/L.
High total cholesterol or LDL:
-Statins (high dose! 40mg simvastatin)
-Ezetimibe (inhibits cholesterol abzorption, if statin not tolerated)
High triglycerides:
-Fibrates (stimulates lipoprotein lipase activity via specific transcription factors)
Complications of hyperlipidaemia
What are the specific hypertriglyceridaemia complications
Coronary artery disease, MI, PVD, strokes
In hypertriglyceridaemia: PANCREATITIS AND RETINAL VEIN THROMBOSIS
Complications of statin treatment
Myositis
Prognosis for hyperlipidaemia
Depends on early diagnosis, treatment of hyperlipidaemia and control of other CVS risk factors. There is some evidence that lipid-lowering agents prevent cerebrovascular accidents
What are the tumour markers for:
1) Medullar thyroid cancer
2) Thryoid cancer
1) Calcitonin
2) Thryoglobulin (used post-thyroidectomy to monitor completeness
of removal- immediate follow up with radioiodine is indicated)
What is multiple endocrine neoplasia
Which genes are affected in each type
What are the inheritance of each
MEN type 1: menin gene chromosome 11
MEN type 2: RET gene on chromosome 10.
Autosomal dominant
What type of tumours are each of the multiple endocrine neoplasia associated with
MEN 1: Primary hyperparathyroidism (90% of cases), pituitary adenomas, pancreatic endocrine tumours (e.g. gastrinoma, insulinoma)
MEN2: Both present with thyroid medullary cancers (95-100%), and sometimes phaeochromocytomas.
2A: Also primary hyperparathyroidism
2B: Also marfanoid habitus and sometimes neurinomas.
phaeochromocytoma
What is the management of MEN1 and MEN2
MEN1: Parathyroidectomy, excision of pancreatic tumor, transsphenoidal surgery for excision of pituitary tumour
MEN2: Thyroidectomy (including cervical lymph nodes), rule out phaeos
What are the nrueomas in MEN-2B
On the lips or tongue
What test is used to investigate hypopituitarism
Insulin suppression test
What is hypopituitarism
Deficiency of one or more of the hromones released by the anterior pituitary gland.
What is the aetiology and RF for hypopituitarism
Pituitary mass: Adenomas
Parapituitary mass: Craniopharyndiomas, meningioma, mets, cysts etc.
Inflammatory: TB, sarcoidosis, haemochromatosis, histiocytosis X
Vascular: Pituitary apoplexy, Sheehan’s syndrome
Pituitary trauma: radiation, surgery, skull base fracture
Hypothalamus (functional): Anorexia, starvation, over-exercise
Infection: Meningitis, encephalitis, syphilis
Genetics: Pit-1, Prop-1 genes
Empty sella syndrome (see below)
What is pituitary apoplexy vs sheehan’s syndrome
1Pituitary apoplexy is the haemorrhage or infarction of a pituitary tumour.
2Sheehans syndrome is pituitary infarction, haemorrhage and necrosis following post-partum haemorrhage.
What are the features of hypopituitarism
Hormone dependent:
GH. Short stature in children. Low mood, fatigue, reduced exercise capacity/muscle strength
TSH. Weight gain, cold intolerance, constipation.
FSH/LH.
Children=delayed puberty.
Women= Loss of secondary sexual hair, breast atrophy, menstrual irregularities, dyspareunia
Men=Loss of secondary sexual hair, impotence, loss of libido, small or soft testes
Prolactin=Failure of breast milk production (in Sheehan’s!)
ACTH=orthostatic hypotension and tachycardia, weakness and lethargy,
What is a life threatening cause of hypopituitarism
Pituitary apoplexy
Life-threatening hypopituitarism with headache, visual loss and cranial nerve palsies.
Investigations of hypopituitarism
Pituitary function tests.
Basal tests: 9am cortisol, LH, FSH, testosterone, oestradiol, IGF-1, prolactin, free T4 and TSH
Dynamic tests: Insulin induced hypoglycaemia (CI in patients with epilepsy IHD, hypoadrenalism.
Give 0.15U/kg IV insulin. In hypopituitarism, peak GH and cortisol response to insulin-induced hypoglycaemia are <20mU/L and <550nmol/L, respectively.
Management of hypopituitarism
Hormone replacement.
Hydrocortisone=20mg in morning, 10mg in evening (double dose for febrile illnesses, IM hydrocortisone during surgery)
L-thyroxine= 100micrograms daily. TAKE AFTER hydrocortisone
Sex hormones
Growth hormones: SC 1.2 units/day in adults.
Posterior pituitary deficiency (damage to pituitary stalk): desmopressin intranasally
Complications of hypopituitarism
Adrenal crisis, hypoglycaemia, myxoedema coma, infertility. Osteoporosis; dwarfism (children).
Complications of pituitary mass: Optic chiasm compression, hydrocephalus (third ventricular compression), temporal lobe epilepsy.
What is empty sella syndrome
Pituitary gland shrinks due to atrophy, compression (sella turcica filled with CSF).
Primary- associated with obese women
Secondary- pituitary surgery, heard trauma, idiopathic intracranial hypertension
T/F most pituitary adenomas are hormone secreting tumours, and they cause hypopituitarism
Partly true.
Most pituitary tumours ARE hormone secreting (most common of which is prolactinoma)
BUT it’s not those tumours that cause hypopituitarism.
The most common tumors that cause hypopituitarism are macroadenomas larger than 1 centimeter that don’t secrete any hormones.
What is the treatment of macroadenomas causing hypopituitarism
For non-secreting macroadenomas, treatment is transsphenoidal resection, which is when the tumor is removed through the nose.
If the surgery is successful, the pituitary function can recover completely.
If not, hormonal replacement therapy might be needed.
What can pituitary stalk compression by a craniopharyngioma cause
Reduced ADH secretion, leading to cranial diabetes insipidus, with symtpoms like excessive thirst and frequent urination.
Increased prolactin levels, causing galactorrhoea.
This is because prolactin, unlike the other hormones, is under constant inhibition by dopamine secretion from the hypothalamus.
“Suprasellar cystic lesion with calficiation” on MRI?
Craniopharyngioma
Excruicitating headahce, and visual impairment of bitemporal heminaopsia
Pituitary apoplexy.
Sudden haemoorahge of pituitary gland, usually in presence of pituitary adenoma
Diplopia, or double vision, and ophthalmoplegia, which is the paralysis or weakness of the eye muscles, can also occur due to the blood buildup compressing cranial nerve III, which innervates the eye muscles.
T/F thyrotoxic storm causes abdo pain
T- mechsnism unclear
Acute management of thyrotoxic storm
DO NOT WAIT FOR THYROID TEST RESULTS TO BE RETURNED.
IV fluids and Abx is there is underlying infection that precipitated the crisus
Oral propanalol and PTU and steroids.
Cardiac monitoring and pulse oximetry
What is most common arrhythmia ass with thyroid storm
AF
What would blood tests show in thyrotoxic storm
Thyroid function tests demonstrate marked elevation of free T4
Thyroid function tests demonstrate marked reduction of thyroid stimulating hormone (TSH)
T/F radioisotope investigations of the thyroid should be arranged urgently in the case of thyrotoxic storm
F
Radioiodine can precipitate/worsen thyroid crisis but can be useful for later management (possible focal hot nodule or diffuse uptake).
T/F T2DM is a precipitant of thyrotoxic storm
F
What is primary vs secondary amenorrhoea
Amenorrhoea can be described as primary (menstruation has never occurred) or
secondary (menstruation has stopped for at least 6 months in a patient who has
previously menstruated).
Causes of primary amenorrhoea
Turner syndrome
Causes of secondary amenorrhoea
Prolactinoma, pregnancy,
haemochromatosis and polycystic ovarian syndrome can cease menstruation in
women have menstruated before – thus causing secondary amenorrhoea.
In conn’s syndrome, you can get polyuria and polydipsia, why is this
It’s a bit counterintuitive because an aldosterone-secreting
adenoma leads to inappropriately elevated aldosterone levels. The excessive
sodium reabsorption and potassium excretion caused by the high aldosterone leads
to hypertension and hypokalaemia.
So you would expect less urine.
But
Hypokalaemia induces nephrogenic diabetes
insipidus, which, consequently, leads to polyuria and polydipsia.
It can cause muscle weakness too
SEE ECG FEATURES OF HYPOKALAEMIA
Causes of hyperprolactinaemia
Pregnancy, medications that inhibit dopamine (e.g.
antipsychotics), hypothyroidism and benign pituitary tumours.
What is hypogonadism (women)
Characterized by impairment of ovarian function
What is primary vs secondary hypogonadism
What is primary vs secondary amenorrhoea
Primary hypogonadism is when there is problem with the ovaries themselves (so there will be high gonadotrophins, due to low oestrogen)
Secondary hypogonadism is when there is a problem with the signals to the ovaries, so the gonadotrophins are low.
Primary and secondary amenorrhoea is different. In Primary amenorrhoea, the woman has never had a period before. In secondary, there is cessation of periods
Causes of primary and secondary hypogonadism (leading to amenorrhoea, use common sense to work out what leads to primary vs secondary amenorrhoea)
Primary:
- Premature ovarian failure
- Gonadal dysgenesis: Turner’s (note, this causes primary amenorrhoea)
- Gonadal damage: Autoimmune (chemo, radiation, surgery)
Secondary:
- Functional: stress, low BMI, excessive exercise
- Pituitary/hypothalamic tumours/infiltration: pituitary adenoma (compresses), craniopharyngioma, haemochromatosis
- Hyperprolactinaemia: prolactinomas or tumours causing stalk comrpession
- CONGENITAL GnRH deficiency (Kallman’s syndrome).
- Post pill amenorrhoea
So you can see how Turner’s and Kallman’s are both causes of PRIMARY amenorrhea, but turner’s is primary hypogonadism, whereas kallmans is secondary
WHich is more common, primary or secondary hypogonadism in women
Secondary hypogonadism is a more common cause of an ovulation and amenorrhoea than primary hypogonadism
What investigations would you do for amenorrhoea
- PREGNANCY TEST!
- LH, FSH, oestradiol
- Day 21 progesterone
- Prolactin, thyroid tests
- Androgens
- Chromosomal analysis (turners is XO)
- USS ovaries/uterus
Girl hasn’t started periods yet, has never had sense of smell
Kallmans
Short 4th and 5th metacarpal, high arched palate, widely spaced nipples and never had a period
Turners syndrome: Short stature, low posterior hairline, high arched palate, widely spaced nipples, wide carrying angle, short fourth and fifth metacarpals, congenital lymphoedema.
Addisons disease and now no periods
atients with autoimmune primary ovarian failure: Signs of other autoimmune diseases e.g. hyperpigmentation in Addisons disease or vitiligo.
Clinical features of male hypogonadism
Loss of libido Reduced muscle bulk Small testes Impotence Osteoporosis!
Primary and secondary causes of male hypogonadism
Primary hypogonadism:
- Gonadal dysgenesis: Klinefelter’s (XXY), undescended testes (cryptorchidism)
- Gonadal damage (infection e.g. mumps, torsion, trauma, autoimmune, chemo, srugery, radiation)
Secondary: Pituitary/hypothalamic lesions again GnRH deficiency (Kallman's) Hyperprolactinaemia Systemic disease
Prader Weilli syndrome, laurence moon biedl syndrome
Rarer genetic cause of male hypogonadism
Myotonic dystrophy
Short stature, small hands, almond shaped eyes, learning difficulty and hypogonadism
Prader willi
Obesity, polydactyly, retinitis pigmentosa, learning difficulty and hypogonadism
Laurence-moon-biedle syndrome
Investigations for male hypogonadism
LH, FSH, testosterone (if all low–> MRI pituitary)
Prolactin
Sperm count
Chromosomal analysis
Which HLA is implicated in hashimotos
HLADR3, HLADR5
What is primary hyperaldosteronism
Characterizedbyautonomousaldosteroneoverproductionfromtheadrenal gland with subsequent suppression of plasma renin activity.
Cause of primary aldosteronism
Adrenal adenoma (Conn’s syndrome; 70%)
or hyperplasia of the adrenal cortex (30%)
Rarely, an aldosterone producing adrenal carcinoma
Pathophysiology of having excess aldosterone
Excess aldosterone results in: raised Na and HTN, increased K renal loss and supression of renin
What is the epidemiology of adrenal adenoma vs hyperplasia of adrenal cortex
Aldosterone producing adenoma occurs more commonly in women and in younger patients (<50 years).
Bilateral adrenal hyperplasia occurs more commonly in men and usually presents at an older age
What causes adrenal hyperplasia causing hyperaldosteronism
IT’S NOT TALKING ABOUT CONGENITAL ADRENAL HYERPLASIA
It’s talking about bilateral hyerplasia of adrenal gland that happens more commonly in older people to result in hyperaldosteronism
History of hyperaldosternism
Usually asymptomatic picked up on blood tests
Hypokalaemia:
Muscle weakness, polyuria and polydipsia (nephrogenic diabetes insipidus secondary to hypokalaemia), paraesthesia, tetany.
Examination of hyperaldosternism
HTN and complications thereof
Initial investigations of hyperaldosteronism
1) Plasma potassium (low in 20% of patients with PA, normal in 80%)- so normokalaemic hypertension constitutes the most common
presentation of this disease.
2) Aldosterone/renin ratio. Stop antihypertensives (6wk for spironolactone , 2wk for most antihypertensives). Put on a blocker if anti-hypertensive needed). Correct hypokalaemia. Raised ratio.
T/F serum sodium will be elevated in conn’s syndrome
F… serum Na usually normal (due to parallel increase in the water content of the blood).
Investigation to confirm primary aldosteronism
After a raised aldosterone/renin ratio is found:
1) Saline supression test (according to Meeran) or Fludrocortisone suppression test is most reliable means to defintively confirm or exclude PA.
Failure of upright (10 a.m.) plasma aldosterone on day 4 of fludrocortisone acetate administration, to suppress to <166 picomol/L (<6 nanogram/100 mL or <6 nanogram/dL)
2) Adrenal venous sampling
How can you differentiate between conn’s and bilateral adrenal hyerplasia
Allows distinction between Conns syndrome and bilateral adrenal hyperplasia by measuring adrenal vein aldosterone levels.
What is the most common cause of primary hyperaldosteronism
Idiopathic hyperaldosteronism (Conn’s is second most common)
Which metabolic disturbance would occur with primary hyperaldosteronism
Metabolic alkalosis
What is osteomalacia/rickets
Osteomalacia is a disorder of mineralization of bone matrix (“osteoid”).
Rickets is a disorder of defective mineralization of cartilage in the epiphyseal growth plates of children.
Causes of osteomalacia/rickets
Vitamin D deficiency:
-Dietary deficiency/malabsorption (small bowel disease e.g. coeliac, IBD, bowel surgery, pancreatic insufficiency)
- Reduced 25 hydroxylation of vit D (liver disease, anticonvulsants)
- Reduced 1 hydroxylation (CKD, hypoparathyroidism, mutations in gene)
- Vitamin D resistance
History of osteomalacia and rickets
Osteomalacia: bone tenderness, proximal muscle weakness, WADDLING gait. Signs of hypocalcaemia
Rickets: Bossing of frontal and parietal bones. Swelling of costochondral junctions (rickety rosary). Bow legs in early childhood, “knock knees” in later childhood. Short stature.
What do bloods show in osteomalacia/rickets
Vitamin D is low, PTH is high (secondary hyperparathyroidism).
Due to this, Ca2+ can be low or normal (raised PTH can normalise Ca2+)
Phosphate is low (due to raised PTH), and alk phos is high.
As well as vit D deficiency, what other mineral is involved in osteomalacia
Phosphate.
It can also be caused by renal phosphate wasting.
e.g. Fanconi’s syndrome (phosphaturia, glycosuria, amino aciduria), renal tubular acidosis type II.
What might investigations show if renal tubular acidosis was the cause of osteomalacia
Patients with renal tubular acidosis have normal anion gap hyperchloraemic metabolic acidosis.
How can fractional excretion of phosphate help in cause of osteomalacia
If renal phosphate wasting or primary hyperparathyroidim are not the cause of hypophosphataemia, the fractional excretion of phosphate should be very low.
What do radiographs show in osteomalacia
May appear normal or show osteopenia. Looser’s zones or pseudofractures (radiolucent bands) in ribs, scapula, pubic rami or upper femur
What test can you do in bone biopsy with osteomalacia
Bone biopsy after double tetracycline labelling
Tetracycline is deposited at the mineralization front as a band. After two courses of tetracycline (separated by a period of days), the distance between the bands of deposited tetracycline is reduced in osteomalacia.
(not usually performed as osteomalavia can be diagnosed from lab and radiograph)
Management of osteomalacia
Vitamin D and calcium replacement.
X-linked hypophsophataemia: oral phosphate and 1,25 vit D
Complications of osteomalacia
Bone deformities, hypocalcaemia may cause epileptic seizures, cardiac arrhythmias, hypocalcaemia tetany, depression
What is subacute thyroiditis
a transient patchy inflammation of the thyroid gland that is associated either with granuloma formation (subacute granulomatous thyroiditis) or lymphocytic infiltration (subacute lymphocytic thyroiditis).
What is the cause of subacute GRANULOMA thyroiditis vs subacute LYMPHOCYTIC thryoiditis
hile subacute granulomatous thyroiditis usually occurs after a viral upper respiratory tract infection, subacute lymphocytic thyroiditis occurs either during the postpartum period, in association with other autoimmune diseases, or as a side effect of certain drugs
How can you differentiate clinically between the 2 types of thyroiditis
Both forms of subacute thyroiditis are more common among women and are characterized by a triphasic clinical course that classically transitions from hyperthyroidism to hypothyroidism, before returning to a euthyroid phase.
BUT
The goiter is tender in subacte granulomatous thyroiditis (i.e. viral) but painless in lymphocytic (i.e. post partum)
Which viruses are known to cause subacute granulomatous thyroiditis
Viral infections: mumps virus, coxsackie virus, influenza virus, echovirus, adenovirus
Mycobacterial infections
Which drugs can cause Subacute lymphocytic thyroiditis
α-interferon, lithium, amiodarone, interleukin-2, tyrosine kinase inhibitors
Post partum thyroiditis is most prevalent in women with which other AI disease
Most prevalent in women with type 1 diabetes mellitus.
Outline the triphasic pattern in thyroiditis
- Thyrotoxic stage. 2-8 weeks. Release of pre-formed colloid.
- Hypothyroid phase. 2-8 weeks. Depletion of pre-formed colloid and impaired synthesis of new thyroid hormones
- Euthyroid phase: Thyroid function recovers and pathological changes no longer present
T/F some people can be left permanently hypothyroid following thyroiditis
T
The disease is self-limiting in most cases but a few patients may experience relapses, and permanent hypothyroidism occurs in ∼ 15% of cases of subacute granulomatous thyroiditis!
Clinical features of
Subacute granulomatous thyroiditis (De Quervain thyroiditis)
Possible history of upper respiratory tract infections a few weeks prior to the onset of subacute thyroiditis
Painful, diffuse, firm goiter, jaw pain
Fever/malaise
Features of hyperthyroidism followed by features of hypothyroidism
Clinical features of
Subacute lymphocytic thyroiditis
Painless, diffuse, firm goiter (thyroid size may be normal)
Features of hyperthyroidism followed by features of hypothyroidism
What will thyroid function tests show in the thyrotoxic vs hypothyroid stage of thyroiditis
Thyrotoxic phase: raised T3 and T4 , raised thyroglobulin, reduced TSH
Hypothyroid phase: reduced T3 and T4, raised TSH
Confirmaotry test for thyroiditis
Raised ESR in subacute granulomatous thyroidits only (not post partum), which returns to normal after the hypothyroid stage
Radioiodine uptake study shows reduced iodine uptake
Treatment for thyroiditis
Both types:
Consider beta blockers to control symptoms of hyperthyroidism (palpitations and/or anxiety)
NSAIDs for pain in acute granulomatous thyroiditis
Corticosteroids in granulomatous thyroiditis if NSAIDs don’t reduce pain/suppress inflammation. But corticosteroids not indicated in post partum thyroidits
Hypothyroid stage: levothyroxine.
The dose of levothyroxine should be as low as possible so that endogenous TSH levels are not suppressed, thus facilitating a TSH-mediated recovery to a euthyroid state. Patients who develop permanent hypothyroidism may require lifelong levothyroxine.
T/F patient should not be given anti-thyroid drugs in the hyperthyroid stage of thyroiditis, but levothyroxine should be given in low dose in the hypothyroid stage
T
Macroadenoma of pituitary on MRI, slightly raised prolactin. What type of tumour is it
It’s likely to be a non-functioning pituitary adenoma compressing the pituitary stalk (thus reducing dopaminergic inhibition of prolactin)
A prolactinoma is likely to raise prolactin above 100ng/mL. Especially if it’s big!
What is hyperparathyroidism,
Define primary, secondary and tertiary
Raised PTH in the blood
Primary= Raised secretion of PTH unrelated to plasma calcium concentration
Secondary= Raised PTH secondary to hypocalcaemia
Tertiary= Autonomous PTH secretion following chronic secondary hyperparathyroidism.
Aetiology of hyperparathyroidism
Primary= adenoma in the parathyroid gland or hyperplasia (80% single adenoma, 12% hyperplasia or multiple adenomas), rarely parathyroid carcinoma
Secondary= vitamin D deficiency or CKD
Hx of hyperparathryoidism
Primary/tertiary.
Mild hypercalacaemia is asymptomatic.
May present with: Polyuria, polydipsia, renal calculi, bone pain, abdo pain, nausea, constipation, psychological depression and lethargy.
Secondary: may present with symptoms and signs of hypocalcaemia and/or the underlying cause (chronic renal failure, vit D deficiency)
Bloods in primary/terntiary and secondary hyperpara.
Calcium
Phosphate
Alk phos
Primary/tertiary:
-Raised Ca2+, low phosphate, raised alk phos, high/inappropriately normal PTH
Secondary:
-Ca2+ low or normal, phosphate high, raised alk phos,
How can you differentiate primary hyperpara due to an adenoma vs due to carcinoma
Patients with parathyroid carcinomas are more likely to have a marked hypercalcaemia with very high serum PTH levels.
What is the most likely acid/base disturbance in primary hyperpara
Hyperchloraemic acidosis (normal anion gap) caused by PTH inhibition of renal tubular reabsorption of bicarbonate.
What would bone radiographs show in hyperpara
Subperiostial erosions of phalanges, brown tumours (osteolucent bone defects), diffuse porotic mottling of skull caused by demineralization (“pepperpot” skull), sclerosis of superior and inferior vertebral margins with central demineralization (“rugger jersey” spine), renal calculi/nephrocalcinosis.
Management of acute hypercalcaemia in primary hyperparathyroidism
What if it was hypercalcaemia due to malignancy
IV fluids.
Manage conservatively if they don’t meet surgical criteria.
Avoid thiazide diuretics
Patients with hypercalcaemia secondary to malignancy are treated with rehydration and IV pamidronate (a
bisphosphonate).
Definitive management of primary hyperparathyroidism
Subtotal parathyroidectomy, total parathyroidectomy (in MEN1).
Indications: Symptomatic patients or asymptomatic patients with:
Age <50
Bone density T score <2.5
Calculi
Creatinine
Difficult to follow up periodically
Elevated serum calcium >0.25mMol above upper limit of normal
Management of secondary hyperparathyroidism
Treat the underlying renal failure. Calcium and vitamin D supplements.
Complications of primary hyperparathyroidism
Increased bone resorption, tubular calcium reabsorption and hydroxylation of Vit D leading to hypercalcaemia
Complications of secondary hyperparathyroidism
Increased stimulation of osteoclasts and bone turnover leads to osteitis fibrosa cystica
Complications of parathyroid surgery
Hypocalcaemia (need supplement) and recurrent laryngeal nerve palsy
What is SIADH
Too much vasopressin is released from the posterior pituitary given the osmolality of the blood.
This means that more water is reabsorbed, leading to lower blood osmolality
How is ADH release usually regulated
Osmoreceptors in the organum vasculosum sense the osmolality of the blood.
These project to the hypothalamic PVN and SON to influence vasopressin release into the posterior pituitary.
Increase in plasma osmolality –> osmoreceptor shrinks –> increased osmoreceptor firing –> VP release from hypothalamic PV and SON
What happens to sodium concentration and the ECF volume in SIADH
There is increased vasopressin release
Increased H2O reabsorption from the renal collecting ducts
This leads to increased ECF volume INITIALLY
Leading to hyponatraemia.
So the sodium goes down because of the increased ECF.
But then, ANP is released from the right atrium, which causes a natriuresis (i.e. excretion of sodium and therefore water too, leading to euvolaemia and also hyponatraemia)
What would the investigations of SIADH show:
- Urine osmolality
- Urine output
- Plasma Na+
Other investigations
Urine osmolality and [Na+] goes UP because there is….
Decreased urine volume (initially)
Then this leads to reduced plasma Na+ mainly due to increased water reabsorption (and also natiuresis)
These factors diagnose SIADH, in the absence of hypovolaemia/hypotension, oedema, renal failure, adrenal insufficiency and hypothyroidism.
Investigate to identify underlying cause: CXR, CT CAP, MRI/CT head
Symptoms of SIADH
Can be symptomless
If Na+<120mM: fatigue, poor mental function and nausea
If Na+<110mM: confusion, coma and death
Aetiology of SIADH
CNS: subarachnoid haemorrhage, stroke, tumour TBI, GBS
Pulmonary disease: pneumonia, bronchiectasis
Malignancy: small cell lung cancer, lymphoma, leukaemia, pancreas etc.
Drug related
Idiopathic
Metabolic: porphyria, alcohol withdrawal
Which drugs can cause SIADH
Carbamazepine, SSRI, opiates
Management of SIADH
Treat for hyponatraemia:
- Immediate: fluid restriction (0.5-1L/day)
- Longer term: use drugs which prevent vasopressin action in the kidneys: demeclocyline (induced nephrogenic DI)
or vaptans (non-competitive V2 receptor antagonists)- very expensive
- In severe cases (seizures/reduced consciousness), slow IV hypertonic 3% saline and furesomide with close monitoring. Change in Na+ must not exceel 10mmol/L in first 24hr or 18 mmol/L in first 48hr, otherwise it could cause central pontine myelinolysis
Examination of SIADH
Mild hyponatraemia: no signs
Severe hyponatraemia: reduced reflexes, extensor plantar reflexes
Complications of SIADH
Convulsions, coma, death. Central pontine myelinolysis (quadreparesis, respiratory arrest, fits) occurs with rapid correction of hyponatraemia
Prognosis for SIADH
Depends on the underlying cause. High morbidity and mortality with [Naþ] <110mmol/L. Up to 50% mortality with central pontine myelinolysis.
What is the treatment of grave’s in pregnancy
During the first trimester, the
thioamide
propylthiouracil
may be used.
Carbomazole is contraindicated in the first trimester of pregnancy, however after this
time
, it can be safely used.
What is paget’s disease
excessive bone remodelling at one (monostotic) or more (polyostotic) sites resulting in bone that is structurally disorganized
Describe the new bone formed in paget’s
Excessive bone resorption (osteoclastic overactivity) followed by a compensatory increase in bone formation (osteoblasts)
New bone formed = WOVEN bone
structurally disorganised
mechanically weaker than normal adult lamellar bone
Mosaic pattern
Marrow spaces filled by an excess of fibrous tissue
Cause of paget’s
Often +ve family hx (genetic) Evidence of viral origin (measles) Men and women affected equally Disease usually not apparent under age 50y Most patients are asymptomatic
What are the cellular abnormalities in pagets
Characterised by abnormal, large osteoclasts – excessive in number
Clinical features of paget’s
Skull, thoracolumbar spine, pelvis, femur and tibia most commonly affected
Arthritis, fracture, pain, deformity
INCREASED VASCULARITY–> WARMTH OVER AFFECTED BONE
Deafness (cochlear involvement)
Radiculopathy due to nerve compression
What might be seen in pagets of the skull on examination, what about bone radiograph
Bitemporal skull enlargement with frontal bossing
Radiograph: osteoporosis circumscripta, enlargement of frontal and occipital areas, associated with a “cotton wool” appearance
Biochemistry of paget’s disease
Calcium is normal!!!!!!!!
Alk phos usually increased
What is seen on radiograph of paget’s
Lytic lesions (early), thickened, enlarged, deformed bones (later)
What can be used to demonstrate extent of skeletal involvement in pagets
Radionuclide bone scan
What is osteoporosis
Loss of bony trabeculae, reduced bone mass, weaker bone predisposed to fracture after minimal trauma
Defined as <2.5 deviations below peak bone mass achieved by HEALTHY ADULTS.
Causes of osteoporosis
PRIMARY: Idiopathic, post menopausal
SECONDARY:
- Cushing’s/steroid use, thyrotoxicosis, primary hyperparathyroidism, hypogonadism
- Malignancy: myeloma, metastatic cancer
- Drugs: CS, heparin
- Rheum: RA ,ank spond
- GI: malabsorption syndromes (coeliac disease, partial gastrectomy), liver disease (PBC), anorexia
Risk factors for osteoporosis
Age, family history, low BMI, low calcium intake, smoking, lack of physical exercise, low exposure to sunlight, alcohol abuse, late menarche, early menopause, hypogonadism.
Clinical features of osteoporosis
Femoral neck fractures (commonly after minimal trauma).
Vertebral factures (loss of height or stooped posture or acute back pain after lifting).
Colles fracture of the distal radius after fall onto outstretched hand
Examination of osteoporosis
- tenderness on percussion (over vertebral fractures); .
- thoracic kyphosis (if multiple vertebral fractures);
- severe pain with leg shortened and externally rotated (in a femoral neck fracture).
Blood parameters for osteoporosis
Biochemistry absolutely normal unless there is a secondary cause.
X- ray findings for osteoporosis
Usually to diagnose fractures when symptomatic.
Often normal (>30% loss in density before showing radiolucency, abnormal trabeculae or cortical thinning evident), biconcave vertebrae, crush fractures.
Diagnostic test for osteoporosis
DEXA scan
T-score: The number of standard deviations the bone mineral density measurement is above or below the young normal mean bone mineral density. T-score is used to define osteoporosis. .
Z-score: The number of standard deviations the measurement is above or below the age-matched mean bone mineral density. Z-score may be helpful in identifying patients who may need a work-up for secondary causes of osteoporosis.
Where is DEXA recorded from and what does it actually measure
Dual Energy X-ray Absorptiometry (DEXA) - femoral neck and lumbar spine
Mineral (calcium) content of bone measured, the more mineral, the greater the bone density (bone mass)
What accounts for the age related deficiency in bone homeostasis in both men and women as a pre-disposing condition for osteoporosis
eg osteoblast senescence
Causes of hypothyroidism
Primary:
- Hashimoto’s thyroidits (AI destruction)
- Iatrogenic (post surgery , radioiodine, medication for hyperthyroidism)
- Severe iodine deficiency or iodine excess
- Viral/post-partum thyroidits have a hypothyroid phase
Secondary (<5%):
Pituitary or hypothalamic disease (e.g. tumours) resulting in TSH or TRH and stimulation of thyroid hormone production
Hx of hypothyroidism
Insidious onset
Cold intolerance, lethargy, weight gain, constipation, dry skin, hair loss, hoarse voice.
Mental slowness, depression, dementia, cramps, ataxia, paraesthesia.
Menstrual disturbances (irregular cycles, menorrhagia) in females.
Hx surgery/radioiodine for hyperthyroidism
Hx or family Hx of other AI conditions: Addison’s, T1DM, pernicious, pre-mature ovaran failure
What is a myxoedema coma
Hypothermia, hypoventilation, hyponatraemia, heart failure, confusion and coma.
Examination of hypothyroidism
Hands: bradycardia/cold
Head/neck/skin: pale puffy face, goitre, oedema, hair loss, dry skin, vitiligo
Chest: pericardial/pleural effusion
Ascites
Slow relaxation of reflexes, signs of carpal tunnel
Investigations for hypothyroidism
Primary: reduced t3/t4, increased TSH
Secondary: reduced t3/t4, reduced TSH (or inappropriately normal TSH)
FBC: normocytic anaemia
U&E: hyponatraemia
What antibody might be raised in primary hypothyroidism
Elevated in over 90% of patients with autoimmune thyroiditis, the most common cause of primary hypothyroidism
What further investigation if you suspected secondary hypothyroidism
CT/MRI
Management of hypothyroidism
In patients with ischaemic heart diease
Chronic:
Levothyroxine (25-200micrograms per day)
Rule out underlying adrenal insufficiency and treat prior to thyroid replacement to avoid Addisonian crisis.
Adjust dosage according to TFT and clinical picture (monitor at 6 weeks).
In patients with ischaemic heart disease, start at low dose (25mg/day) and gradually increase at 6 week intervals if ischaemic symptoms do not deteriorate.
Myxodedema coma management
Myxoedema coma - a VERY RARE complication of hypothyroidism
Oxygen, rewarming, rehydration, INTRAVENOUS T4/T3 (for uncomplicated hypothyroidism you give oral!), IV hydrocortisone (in case hypothyroidism is secondary to hypopituitarism), treat the underlying disorder e.g. infection.
The drug used to treat hypothyroidism is what thyroid hormone
T4 (thyroxine sodium)
This is not the active form.
T3 is the active form (normally 80% in the circulation is from deiodination of T4
20% from direct thyroidal secretion)
What is used to monitor medication for hypothyroidism
TSH- in primary
In secondary hypothyroidism, TSH will be low anyway due to anterior pituitary failure, so can’t be used as a guide to dose.
Here you aim for T4 in the middle of the reference range
What is the half life of t3/t4 therapy
Levothyroxine (T4) plasma half life of 6 days
Liothyronine (T3) plasma half life 2.5 days
What causes an increase and decrease in thyroxine binding globulin
Approximately 99.97% of circulating T4 and 99.7% of circulating T3 are bound to plasma proteins, mainly thyroxine binding globulin (TBG) (NB do NOT confuse with thyroglobulin)
Only the free (unbound) fraction of thyroid hormone is available to the tissues
INCREASE PLASMA BINDING PROTEINS:
- pregnancy
- prolonged oestrogen/phenothiazine treatment
FALLING PLASMA BINDING PROTEINS:
- TBG falls with malnutrition, liver disease
- Certain co-administered drugs (e.g. phenytoin, salicylates) compete for protein binding sites.
What is acromegaly
Excess secretion of GH from the anterior pituitary gland in ADULTS
(Excess GH results in gigantism before puberty)
Aetiology of acromegaly
MOST CASES:
GH-secreting pituitary adenoma.
RARELY:
Excess GRHR release from hypothalamic ganglioneuroma, bronchial carcinoid or pancreatic tumour causing somatotroph hyperplasia
Hx of acromegaly
Very gradual over many years
Sweating, headaches, carpal tunnel
Shoes getting tight
Hypopituitarism (hypogonadism, hypothyroidism, hypoadrenalism)
Visual disturbance (optic chiasm)
Hyperprolactinaemia (irregular period, reduced libido, impotence)
Examination of acromegly
Hands: Enlarged spade-like hands with thick greasy skin. Signs of carpal tunnel syndrome (see Carpal tunnel syndrome). Pre-mature osteoarthritis (arthritis also affects other large joints, temporomandibular joint).
Prominent eyebrow ridge (frontal bossing) and cheeks, broad nose bridge, prominent nasolabial folds, thick lips, “ gap between teeth, large tongue, prognathism, husky resonant voice (thickening vocal cords).
Bitemporal superior quadrantanopia progressing to bitemporal hemianopia (caused by pituitary tumour compressing the optic chiasm).
Multi-nodular goitre
Investigation if you suspect acromegaly
Serum IGF-1 (screening test)
Definitive test: Oral glucose tolerance test: Failure of suppression of GH after 75 g oral glucose load
Imaging: MRI brain
Anorexic patient who has lost weight and no signs of acromegaly. Oral glucose tolerance test positive
Oral glucose tolerance test: Failure of suppression of GH after 75 g oral glucose load (falsepositive results are seen in anorexia nervosa, Wilson’s disease, opiate addiction
What is the metabolic effect of acromegaly
XS GH production leads to increased endogenous glucode production and reduced muscle glucose uptake
Insulin production goes up and leads to insulin resistance
Impaired glucose tolerance and diabetes mellitus
Management of acromegaly
1st line:
-Transphenoidal surgery
Medical treatment:
- SC or monthly depot Somatostain analogue (octreotide)
- Dopamine agonist (GH secreting pituitary tunours frequently express D2 receptors)- cabergoline
Radiotherapy
What is the use of ocreotide for acromegaly if it’s not first line
Reduces GH secretion and tumour size
Pre-treatment before surgery may make resection easier
Use post-operatively if not cured or whilst waiting for radiotherapy to take effect (slow)
Side effects of ocreotide
GI side effects common eg nausea, diarrhoea, gallstones can occur
Complications of acromegaly
Obstructive sleep apnoea
HTN (direct effects of GH and IGF-1 as well as GH mediated renal sodium reabsorption)
Cardiomyopathy (HTN, DM, toxic effects of excess GH on myocardium)
Increased risk of cancer (colonic polyps)
Complications of transphenoidal surgery
Nasoseptal perforation, hypopituitarism, adenoma recurrence, CSF leak, infection (meninges, sphenoid sinus).
Rashes with hypothyroidism;
- Vitiligo
- Alopecia areata
- Myxoedema
- Erythema ab igne
Vitiligo appears as hypopigmented patches, sometimes with hyperpigmented borders
Alopecia areata is a condition that causes hair to fall out in small patches,
Erythema ab igne (EAI), also known as hot water bottle rash, is a skin condition caused by long-term exposure to heat (infrared radiation). Prolonged thermal radiation exposure to the skin can lead to the development of reticulated erythema, `hyperpigmentation, scaling and telangiectasias in the affected area.
What effect does hypothyroidism vs hyperthyroidism have on periods
Hypo- menorrhagia
Hyper- oligo/amenorrhoea
Describe the goitre in Hashimoto’s
Typically the goitre is firm, non-tender and moderate in size.
What antibody is commonest in pernicious anaemai
Anti-parietal cell
How to give thyroxine in hypothyroidism
Patients with symptomatic hypothyroidism require thyroxine replacement. This is usually given as 25, 50 or 100 micrograms tablets.
Typical doses of 100 to 150 micrograms are effective in most patients
wever, caution should be exercised in the elderly and those with known heart disease, as thyroxine treatment may induce an acute coronary syndrome, myocardial infarction or even death due to tachycardia and increased cardiac work.
It is therefore important to start replacement at a low dose then titrate up until the patient is euthyroid.
Define type II diabetes
Insensitivity to insulin by peripheral tissues, impaired insulin secretion and increased HGO
Causes of type II diabetes
Multifactorial.
Genetic factor
Obesity (adipokines contribute to peripheral insulin resistance)
What secondary diseases can lead to type II diabetes mellitus
Chronic pancreatitis
Hereditary haemochromatosis
Pancreatic cancer
Endocrinopathies: Cushing’s, acromegaly, phaeo, glucagonoma
Drugs: corticosteroids
How can obesity impact on type II diabetes
Plasma FFAs and adipokines contribute to peripheral insulin resistance
Chronic hyperglycaemia can have toxic effect on beta cells (glucotoxicity) as can free fatty acid levels (lioptoxicity)
Hx of type II diabetes
Can be incidental
Polyuria, polydypsia, tiredness.
Can present with hyperosmolar hyperglycaemic state
Infection (infected foot ulcers, candidiasis, balanitis, pruritis vulvae)
Examination for type II diabetes
Weight and height- calculate BMI
BP
Examination of diabetic foot?
Ischaemic (reduced pulses, dry skin, ulceration, gangrene)
Neuropathic (Charcot’s foot, reduced sensation)
Describe the following skin changes in diabetes:
Necrobiosis lipoidica diabeticorum
Granuloma annulare
- Well-demarcated plaques on the shins or arms with shiny atrophic surface and red–brown edges
- Fesh-coloured papules coalescing in rings on the back of hands and fingers
- Diabetic dermopathy (depressed pigmented scars on shins)
How is diabetes diagnosed (type II)
Symptoms of diabetes + random plasma glucose >11.1
Fasting plasma glucose >7 (overnight fast 8hr)
Two-hour plasma glucose >11.1 after 75g OGTT.
Outline overall treatment for diabetes
- Conservative. Advice and information
- Glycaemic control
- BP control
- Control of complications `
Outline advice and information for management of type II diabetes
Information: Diabetic nurses, leaflets, websites, etc. explaining diabetes control, complications. Nutrition: Optimizing meal plans, diet (complex carbohydrates as opposed to simple sugars, reduced fat intake).
Foot care: Regular inspection, appropriate footwear, role of chiropodist.
Organizations: Local and national support groups.
Recognition and treatment of hypoglycaemia.
Monitoring capillary blood glucose and charting it. Monitoring for ketones during intercurrent illness.
Pregnancy: Strict glycaemic control and planning of conception.
Treatment: Action, duration and administration technique for insulin, change the site of injection (to avoid lipohypertrophy), explain the need to plan exercise
How is glycaemic control achieved in type II diabetes
At diagnosis:
Lifestyle advice + metformin
If HbA1c >7% after 3 months
1st intensification:
Lifestyle advice + metformin + gliptin (DPP4 inhibitor) /pioglitazone/sulphonylurea/SGLT-2i
If HbA1c >7% after 3 months
2nd intensification Triple therapy: Metformin + gliptin + sulphonylurea OR Starting insulin based treatment
If HbA1c >7% after 3 months
3rd intensification:
Metformin, a sulfonylurea, and a glucagon-like peptide-1(GLP-1) mimetic
Contraindications for metformin?
People at risk of lactic acidosis, which is people with:
- DKA
- eGFR<30mL/min (for standard release metformin) or <45 (for modified-release metformin)
- Acute or chronic disease which may cause tissue hypoxia, such as cardiac or respiratory failure, recent myocardial infarction, or shock.
- Hepatic insufficiency, acute alcohol intoxication, or alcohol addiction.
- DISCONTINUE 48hrs BEFORE ELECTIVE SURGERY UNDER GENERAL, SPINAL OR PERIDURAL ANAESTHESIA and restart no earlier than 48hrs post-surgery
Side effecfts of metformin
GI effects (nausea, vomiting, diarrhoea, abdo pain)
Lactic acidos`is
Vit b12 deficiency
What should you prescribe first if metformin is contraindicated
A gliptin (dipeptidyl peptidase-4 inhibitor).
Pioglitazone.
A sulfonylurea.
A Sodium-glucose cotransporter 2 inhibitors (SGLT-2i).
What treatment should be given for someone with T2DM who has symptomatic hyperglycaemia
If an adult with type 2 diabetes is symptomatically hyperglycaemic, consider insulin therapy or a sulfonylurea. Review treatment when blood glucose control has been achieved.
How is retinopathy screened for in type II diabetes
Regular digital retinal photography, ophthalmology referral and laser photocoagulation if necessary.
How is nephropathy screened for in diabetes
Send first-pass early morning for ACR
Measure creatinine for eGFR
Manage with BP control, ACEi/ARBs
When should you diagnose CKD?
Diagnose CKD if the person’s eGFR is persistently less than 60 mL/min/1.73 m2, and/or ACR is persistently greater than 3 mg/mmol.
How is neuropathy screened for and managed
Regular examination and inspection of the feet for ulcers, 10g monofilament testing, joint vibration
Treat with:
foot hygiene, amitriptyline, duloxetine, gabapentin or capsaicin cream for painful neuropathy.
How to treat infected diabetic foot ulcer
Clean and dress regularly,
Swab for culture and sensitivity,
IV antibiotics (e.g. flucloxacillin, co-amoxiclav, cephalosporin and metronidazole).
Look for osteomyelitis on X-ray.
Surgical debridement or amputation if necessary.
What is the cause of hyperosmolar hyperglycaemiac state
Similar to DKA in that it commonly arises from infections and is characterised by hyperglycaemia and hyperosmolarity
There is more insulin secretion with hyperosmolar hyperglycaemiac state though which is enough to suppress lipolysis and ketogenesis, but not enough to regulate hepatic glucose production/promote glucose utilisation
What are the main metabolic disturbances in HHS?
Osmotic diuresis leads to hypernatraemia
Hypernatraemia and hyperglycaemia (potentially coupled with inadequate water intake) cause volume contraction
The hypovlaemia leads to a decline in GFR
The counter-regulatory hormones (in particular adrenaline) increase, which induce insulin resistance, decrease insulin production and increase lipolysis, ketogenesis and volume depletion, contributing to hyperglycaemic crises
Investigation for hyperosmotic hyperglycaemici state
Plasma glucose >33.3
Urinary ketones are negative or low (to distinguish DKA)
Management of hyperosmolar hyperglycaemic state
ALL PATIENTS:
1st line: IV fluids (0.9% Na solution, or 0.45% if serum Na+ >170mMol/L)
+
Vasopressor (IF hypotension persists after forced hydration. Start noradrenaline/dopamine).
IF baseline K+ <3.3mmol/L, then give potassium chloride therapy until you reach 3.3mmol/L. At this point, start IV insulin therapy
IF baseline K+ 3.3-5.3 mmol then give IV insulin therapy and potassium chloride therapy
IF K+ >5.3 then given IV insulin therapy
When HHS has resolved and patient can tolerate oral intake, switch to SUBCUTANEOUS INSULIN THERAPY
T/F ACEi are first line antihypertensives in those with diabetic nephropathy
T
An ACE Inhibitor is the first line antihypertensive in patients with diabetic nephropathy. Also patients should have all cardiovascular risk factors managed aggressively and maintain good glycaemic control.
Which fluids should be used in DKA
Fluid resuscitation is extremely important and usually normal saline is used. Once glucose level falls below 15mmol/L (but not initially), 5% dextrose can be used.
How should insulin be given in DKA vs HHS
DKA:
Initially 4-8U of soluble insulin is given if glucose is >20mmol/L. An insulin sliding scale via and intravenous infusion should be prepared as soon as possible.
HHS:
1-3U
Management of diabetic autonomic neuropathy
Fludrocortisone may be helpful.
Which type of diabetes is amytrophy more common in, and what is it
Uncommon peripheral diabetic neuropathic complaint.
It presents with severe muscle weakness and pain with proximal thigh muscle atrophy.
The weak knee flexion and quadriceps wasting is typical of diabetic amyotrophy
What is riedel’s thyroiditis
“Woody” swelling.
Autoimmune condition, causes hypothyroidism in 25-50% of those affected
Painless lump that can also cause local compressive symptoms like tracheal/oesophageal compression
No lymph/cancer slymtpoms
Which condition is Riedel’s associated with
sclerosing cholangitis and peculiarly responds to Tamoxifen, there can also be use for steroids.
What can riedel’s be treated with
peculiarly responds to Tamoxifen, there can also be use for steroids.
What medications can be used in grave’s during surgery
If they have grave’s and can’t get it settled with carbimazole, you can do surgery.
KI is used pre-surgery to saturate the thyroid and reduce vascularity
