Endocrinology Flashcards
What are some common causes of primary hypothyroidism and what would TFTs typically show.
TFTs show high TSH and low T4.
Common causes are:
- Autoimmune (Hashimoto’s, atrophic)
- Iodine defiency
- thyroiditis (Riedel’s, Postpartum, de Quervains (Subacute). Note the last two initially present with a hyperthyroid state followed by a prolonged hypothyroid state)
- Iatrogenic (cytotoxics, thyroidectomy, radioiodine, Lithium, Amiodarone)
What are some common causes of secondary hypothyroidism and what would TFTs typically show.
TFTs show low TSH and low T4
Pituitary insuffiency most likely cause and so MRI of gland neccesary
What is sick euthyroid syndrome and what would TFTs typically show.
TFTs show slightly low TSH and low T4.
Associated with systemic illness during which TFTs become deranged. Test should be repeated after recovery. T3 may be particularly low.
Describe Graves’ disease, its features, investigations, and management.
Most common cause of hyperthyroidism (66%), Typical patient female (9:1) 40-60yrs. Caused by Thyrotropin-activating IgG autoantibodies.
Features:
Hyperthyroidism: tremor, agitation, diarrhoea, insomnia, weight loss, tachycardia, sweating, feeling hot, itching, muscle weakness, irritability/anxiety
Thyroid eye disease: double vision, exophthalmos, blurred vision, loss of colour vision
Graves specific: pretibial myxoedema, thyroid acropachy, thyroid bruit, smooth goitre.
Investigations: TFTs show low TSH, increased T3 and T4. Increased uptake of radioactive iodine. Anti-TSH-receptor.
Management:
- Stopping smoking is most important modifiable risk factor in thyroid eye disease.
- radioiodine can cause an increase in eye symptoms, though concurrent prednisolone may reduce impact.
What is subacute deQuervain’s thyroiditis?
Self-limiting post viral hyperthyroidism followed with longer hypothyroid phase, with painful goitre, febrile, and typically increased ESR. low isotope uptake on scan. Managed with NSAIDs.
Describe insulinoma its tests and treatment
This often benign (90-95%) pancreatic islet cell tumour is sporadic or seen with MEN-1. It presents as fasting hypoglycaemia, with whipple’s triad:
- Symptoms associated with fasting or exercise
- Recorded hypoglycaemia with symptoms
- Symptoms relieved with glucose
Tests: Screening test - hypoglycaemia and increased plasma insulin during a long fast. Suppressive test - give IV insulin and measure C peptide, normally exogenous insulin supresses c-peptide production but this does not occur in insulinoma. CT/MRI imaging
Treatment: excision
Diazoxide (a K channel activator, leading to hyperpolarisation of cell membrane, a decrease in calcium influx and inhibition of insulin release)
Describe Diabetic Ketoacidosis, it’s presentation, investigation, and management
A medical emergency. Ketoacidosis is an alternative metabolic pathway that occurs in starvation states, an breaks down protein giving acetone as a by product. In diabetic Ketoacidosis there is excessive glucose but because of lack of insulin this cannot be taken up into cells pushing the body into a starvation state where Ketoacidosis occurs.
Presentation: Gradual drowsiness, vomiting and dehydration in a type 1 diabetic. May also be history of polyuria, polydipsia, lethargy, anorexia. Signs of dehydration and ketotic breath occur later deep and rapid (Kussmaul) breathing.
Investigations:
- Urinalysis (glucose, ketones)
- BM (hyperglycaemia greater than 11mmol/L)
- Blood Gas (Acidaemia pH less than 7.3) (Severity on pH e.g. Mild = less than 7.3, moderate less than 7.2, severe less than 7.1) (Bicarb less than 18mmol/L)
- Bloods, U+Es, Glucose, HbA1c, Cultures (if pyrexial), FBC. Ketones (over 3mmol/L)
- ECG (looking for peaked t-waves hyperkalaemia)
Management:
- DR ABCDE Assessment
- Be wary of sudden fluid changes as risk of cerebral oedema.
- Fluid status examination + fluids replacement
- 1L NS over 1hr then Fixed rate IV insulin e.g. 0.1 unit/kg, then 1L over 2,2,4,4,6 HRs +/- potassium (over 5.5 nil, 3.5-5.5 20mmol, less than 3.5 40mmol), unless able to orally rehydrate and SC insulin.
- Monitor bloods stop insulin when ketones less than 1mmol/L if glucose falls to less than 14mmol/L give dextrose alongside fluids.
Describe Hyperosmolar Hyperglycaemic State (HHS),its symptoms, and management.
Typically those with type 2 diabetes are at risk of this. Presents with profound hypovolaemia, hyperglycaemia over 35mmol/L, and increased plasma osmolality over 340mosmol/L. There may or may not be metabolic acidosis but it is less profound than in DKA due to there being no switch to amino-acid metabolism. Occlusive events are a danger due to increased viscosity (Focal CNS signs, Chorea, DIC, leg ischaemia, rhabdomyolysis)
Symptoms: Generalised weakness, leg cramps, visual disturbance, nausea and vomiting, delirium, seizures.
Management:
- Risk of DVT so give LMWH prohylaxis.
- Rehydrate slowly only use insulin if blood glucose not falling by 5mmol/L/Hr with rehydration or ketonaemia is present.
- Look for a cause such as MI, drugs, bowel infarct, Stoke, Hyperthermia, AKI, Cushings, GI bleeds.
Describe Cushing’s syndrome, it’s causes, symptoms, investigations, and management.
Syndrome due to chronic glucocorticoid excess.
ACTH dependent causes:
- Cushing’s disease (pituitary adenoma)
- ectopic ACTH production especially small cell lung cancer and carcinoid tumours, often atypical presentation with pigmentation, hypokalaemic metabolic alkalosis, weight loss, hyperglycaemia.
- rarely ectopic CRF production some thyroid and prostate cancers
ACTH independent causes:
- adrenal neoplasi, may also cause pain and virilisation in females
- adrenal modular hyperplasia
- iatrogenic steroid therapy (most common)
- rarely carney complex, McCune-Albright syndrome
Symptoms: increased weight, mood change (depression, irritability), proximal weakness, gonadal dysfunction, acne, Achilles’ tendon rupture, Central obesity, plethoric, moon face, buffalo neck hump, supraclavicular fat distribution, skin and muscle atrophy, bruises, abdominal striae, osteoporosis, Hypertension, hyperglycaemia.
Investigations: Midnight cortisol, Dexamethasone suppression test, 24hr Urinary Cortisol, U+E (Hypokalaemia in ectopic ACTH), (Metabolic acidosis), MRI pituitary, CT chest + Abdomen
Management:
- Treat cause, ketoconazole and nicotine can be used to lower cortisol by inhibiting synthesis and secretion in the adrenal gland.
- surgical/radiotherapy for tumour causes.
Describe primary adrenocortical insufficiency (addisons disease), it’s symptoms, tests and treatment
It is rare but can be fatal. Destruction of adrenal cortex leads to glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency. 80% are due to autoimmunity in UK, TB is commonest world wide cause, may be neoplasm
Symptoms: lean, tanned, tired, tearful +/- weakness, anorexia, dizzy, faints, flu-like myalgia. Nausea vomiting, abdominal pain, diarrhoea constipation, pigmented Palmer creases and buccal mucosa as ACTH cross reacts with melanin receptors. Postural hypertension vitiligo.
Tests: hyponatreaemia, hyperkalaemia due to decreased mineralocorticoid. Hypoglycaemia due to decreased cortisol, also uraemia, hypercalcaemia, eosinophilia, anaemia. ACTH stimulation test, 21-hydroxylase adrenal autoantibodies
Treatment:
- replace steroids hydrocortisone 20mg/d in divided dose 10, 5, 5 with fludrocortisone 50mcg/d
- double hydrocortisone for sick day rules.
- warn against abruptly stopping due to risk of addisonian crisis
Describe secondary adrenal insufficiency
The commonest cause is iatrogenic due to long term steroid therapy leading to suppression of the pituitary adrenal axis. This only becomes apparent on withdrawal of steroids. Other causes are rare and include hypothalamic pituitary disease leading to decreased ACTH production. Mineralocorticoid production remains intact and there is no hyperpigmentation
Describe male hypogonadism it’s features and causes
Hypogonadism is the failure of testes to produce testosterone, sperm or both.
Features: small testes, decreased libido, erectile dysfunction, loss of pubic hair, decreased muscle
Bulk, increased fat, gynaecomastia, osteoporosis, mood disturbance.
Primary hypogonadism causes:
•testicular failure from trauma, torsion, radiotherapy
•post-orchitis e.g mumps
•renal failure, liver failure or alcohol excess
•chromosomal abnormalities e.g. Klinefelters syndrome
Causes of secondary hypogonadism:
•hypopituitarism
•prolactinoma
•kallman’s syndrome (isolated GnRH deficiency often with anosmia and colour blindness
•systemic illness
•Laurence-moon-biedl and prader-willi syndromes
Describe Hyperprolactinaemia, its causes, symptoms and management
Prolactin is secreted by the anterior pituitary and release is inhibited by dopamine produced in the hypothalamus.
Causes:
- excess production from the pituitary e.g. prolactinoma
- disinhibition, by compression of the pituitary stalk e.g. pituitary adenoma, or hypothalmic disease
- Drugs e.g. Dopamin receptor antagonists, e.g. Domperidone, neuroleptics. Also anti-depressants, verapamil, methlydopa, optiates, protease inhibitors, fibrates, H2 antagonists, Omeprazole.
Symptoms:
- females = amenorrhoea, oligomemorrhea, infertilty, galactorrhoea, also decreased libido, increased weight and dry vagina.
- males = erectile dysfunction, decreased facial hair, galactorrhoea.
- Low FSH and LH
Management:
- depending on cause, Dopamine agonist e.g. Carbegoline
- if adenoma transphenoidal surgery can be used second line
Describe the menstrual cycle
Pulsatile production of GnRH by the hypothalamus stimulates the pituitary to produce the gonadotrophins LH and FSH. These stimulate the ovary to produce oestrogen and progesterone.
In the first 4 days of the menstrual cycle FSH levels are high, stimulating the development of a primary follicle in the ovary. The follicle produces oestrogen, which stimulates the development of a glandular ‘proliferative’ endometrium and of cervical mucus which is receptive to sperm.
Around the 14th day oestrogen levels becomes high enough to stimulate a surge of LH. This stimulates ovulation. Having released the ovum, the primary follicle forms a corpus luteum and starts to produce progesterone. under this influence the endometrial lining is prepared for implantation and enters the secretory phase.
If the ovum is not fertilised the corpus luteum breaks down and hormone levels fall. This causes spiral arteries in the in the uterine endothelial lining to constict and the lining sloughs hence mensturation.
Normal menstruation lasts 2-7 days and normal blood loss is 20-80ml.
Describe Diabetes insipidus, its symptoms, causes and tests.
This is the passage of large volumes of dilute urine due to impaired water resorption by the kidneys because of reduced ADH secretion from the posterior pituitary (cranial DI) or impaired response to ADH (nephrogenic DI)
Symptoms: polyuria, polydipsia, dehydration, irritability, confusion.
Causes of cranial DI:
- Idiopathic
- congenital defects in ADH gene
- tumour (may present with DI + hypopituitarism)
- Trauma
- Infiltration e.g. sarcoidosis
- vascular e.g. haemoorhage
- infection e.g. menigoencephalitis
Causes of nephrogenic DI:
- inherited
- metabolic e.g. hypokalaemia, hypercalcaemia
- drugs e.g. lithium, demeclocycline
- chronic renal diseas
- post-obstructive uropathy
Tests: serum and urine osmalalities and water deprivation test. Patients are deprived of water for 4+ hours urine osmalality and output is measured which should remain low. They are then given desmopressin and lack of sufficient response leads to diagnosis of nephrogenic diabetes insipidus
Management:
- Cranial: desmopressin
- Nephrogenic: stop any drug causes, High dose DDAVP may be used in mild to moderate cases.
Describe acromegaly its symptoms, complications, investigations, and management.
Due to increased secretion of GH from a pituitary tumour (99%) or hyperplasia e.g. via ectopic GH-releasing hormone from a carcinoid tumour. GH stimulates bone and soft tissue growth through increased secretion of insulin-like growth factor-1 (IGF-1)
Symptoms: Headache, arthralgia, amenorrhoea, spade-like hands, coarsening of face, big supraorbital ridges, macroglossia, acanthosis nigricans, snoring/obstructive sleep apnoea, proximal myopathy, goitre, carpel tunnel signs, bitemporal hemianopia
Complications:
- impaired glucose tolerance and DM
- vascular e.g. hypertension, left ventricular hypertrophy, increased risk of IHD and stroke
- increased colon cancer risk
Investigations:
-hyperglycaemia, hypercalcaemia, hyperphosphataemia, raised IGF-1, oral glucose tolerance test (GH should be suppressed by glucose, if GH is above 3mIU/L acromegaly is confirmed. MRI pituitary to assess cause. Echo
Management:
- for pituitary tumour transphenoidal surgery
- if surgery fails, somatostatin analogues e.g. Octreotide may be used.
- GH antagonist (pegvisomant) can be used in cases resistant or intolerant to somatostatin analogues.
- radiotherapy is also an option
Describe the WHO criteria for diagnosis of Diabetes Mellitus
- Symptoms of hyperglycaemia (e.g. polyuria, polydypsia, unexplained weight loss, visual blurring, genital thrush, lethargy) and raised venous glucose detected once either fasting >7mmol/L or random >11.1mmol/L
- Raised venous glucose on 2 separate occasions
- HbA1C >48mmol/L (6.5%) but below doesnt exclude DM
Describe metabolic syndrome (syndrome X)
A syndrome that can lead to increased risk of MI and insulin resistance, defined as central obesity (waist circumference greater than 102cm or 40” plus 2 of:
- BP>130/85
- triglycerides >1.7mmol/L
- HDL less than 1.03(male) or 1.29 (female)mmol/L
- fasting glucose greater than 5.6mmol/L or DM
Describe Hypoglycaemia its symptoms and causes, and management
This is the commonest endocrine emergency it is defined as a plasma glucose less than 4mmol/L
Symptoms: Sweating, anxiety, hunger, tremor, palpitations, dizziness, confusion, drowsiness, visual trouble seizures and coma.
Causes: the chief cause is insulin or sulfonylurea treatment in a known diabetic after increased activity, missed meal or overdose. if non-diabetic you must EXPLAIN.
- EXogenous drugs e.g. insulin or oral hypoglycaemics (Do Sulfonylurea screen as bloods mimic insulinoma)
- Pituitary insufficiency
- Liver failure
- Addisons disease
- Islet cell tumour (insulinoma)
- Non-pancreatic neoplasm
Management:
Step 1: Orientated and able to swallow try 15-20g quick acting carbohydrate e.g.
-150-200mL orange juice
-2 tubes Glucogel
-4-5 Glucotabs
-3-4 Jelly babies
Step 2: Repeat CBG after 15mins and repeat step 1 up to 3 times
Step 3: Consider 1mg IM Glucagon
Step 4: IV 10% glucose infusion at 100ml/Hr
Step 5: After treatment give long acting carbohydrate e.g. Two biscuits, slice of toast, glass of milk, normal meal if due
If Patient is unconscious IM glucagon or IV Glucose 80ml of 20% Glucose over
Describe Diabetic Neuropathy, its symptoms, and management.
A complication of diabetes, including peripheral neuropathy, autonomic neuropathy, gastroparesis.
Symptoms: numbness/burning sensation in extremities in glove and stocking distribution. May also affect Autonomic nervous system with loss of bladder control. Gastroparesis presents with erratic blood glucose control, bloating and vomting.
Management:
- amitryptilline, Duloxetine, gabapentin, or pregabalin.
- pain management clinics for resistant problems
- metoclopramide, domperidone or erythromycin may be used in gastroparesis (pro kinetic agents)
Describe Hirsutism, it’s causes, and a management.
Implies hair growth in women in the male pattern. May be associated with virilism (onset of amenorrhoea, clitoromegaly, deep voice) and Gynaecomastia.
Causes: Familial, idiopathic or hyperandrogenism from ovary (PCOS, Ovarian Cancer) or Adrenal gland (late-onset congenital adrenal hyperplasia, Cushing’s syndrome, adrenal carcinoma) or iatrogenic e.g. Steroids.
Management:
- Oestrogens may help, considered COCP
- Clomifene is used for infertility.
What are the types of hermaphroditism and some causes?
True Hermaphroditism describes an individual born with ovarian and testicular tissue, these may be as separate or more commonly an ovotestis.
Pseudo hermaphroditism describes an indictable with primary characteristics of one sex but develops secondary characteristics of another e.g. Ambiguous genitalia (cliteromegaly). Causes include congenital adrenal hyperplasia, androgen insensitivity, 5alpha-reductive deficiency
Describe Subclinical Hypothyrodisim and its management
TSH raised but T3,T4 normal.
No obvious symptoms. Small risk of progressing to overt hypothyroidism risk further increased by presence of thyroid autoantibodies.
Management:
- Treat if TSH over 10, or antibody positive.
- (Consider lower threshold if pregnancy or with CVD)
Describe normal calcium homeostasis.
Parathyroid hormone increases calcium levels and decreases phosphate levels by action on osteoblasts which acts in increase calcium in extra cellar fluid and also produce a protein that activates osteoclast bone resorption. It also acts to increase renal tubular reabsoprtion of calcium and increases synthesis of active vitamin d in the kidney which increases bowel absorption of calcium
Active vitamin D acts to increase plasma calcium and phosphate by increases renal tubular reabsorption and gut absorption of calcium and increases osteoclast ice activity.
Calcitonin is secreted by C cells of thyroid and acts to inhibit intestinal calcium absorption and inhibitors osteoclasts activity and rental tubular absorption of calcium.
Describe Primary Hyperparathyroidism, its hormone profile, symptoms, and management,
Most cases due to solitary adenoma, typical presentation is elderly lady with unquenchable thirst and inappropriately raised or normal parathyroid hormone.
Hormone profile: PTH elevated, Calcium Elevated, Phosphate low,
Symptoms: Asymptomatic, recurrent abdominal pain (pancreatitis, renal colic), changes to emotional or cognitive state, polydipsia, Polyuria, hypertension.
Management: Total parathyroidectomy.
Describe Primary Hypoparathyroidism, its hormone profile, symptoms, and management.
Hormone profile: Decreased PTH, Low calcium, high phosphate.
Symptoms: Tetany (muscles twitching, cramping, spasm), perioral paraesthesia, trousseau’s sign (carpal spasm when inflating blood pressure cuff), chvosteks sign (tapping over parotid causes facial muscles to twitch), depression, cataracts, prolonged QT.
Management: Alfacalcidol
Describe Secondary Hyperparathyroidism, its hormone profile, symptoms, and management.
Parathyroid gland hyperplasia occurs as result of low calcium almost always in a setting of chronic renal failure.
Hormone profile: Elevated PTH, Low/normal calcium, phosphate elevated, vitamin D levels low.
Symptoms: Asymptomatic, bone disease, and soft tissue calcifications.
Management:
-Vit D and Calcium replacement
Which Diabetic medications requiring glucose fingerprick monitoring?
Those causing hypoglycaemia e.g. Sulphonylureas, insulin, glitazones.
Describe Maturity Onset Diabetes of the Young (MODY) and the different types.
Autosomal dominant non-ketotic diabetes, in childhood or young adults. The defect is one of pancreatic beta cell dysfunction leading to impaired insulin secretion. It is caused by a single gene defect. There are different types depending on the gene defect. Sulphonylureas shown to be most effective.
Types:
- MODY2 (GCK subtype) is caused by mutation in the glucokinase gene on chromosome 7. Usually there is mild asymptomatic stable hyperglycaemia from birth. Microvascular disease is rare and drugs are rarely needed.
- MODY3 (HNF1A subtype) is the most common type. It is caused by a defect on chromosome 12 leading to progressive decrease in insulin production. It features severe hyperglycaemia after puberty which often leads to a diagnosis of type 1 DM. Diabetic retinopathy and nephropathy often occur.
- MODY5 (HNF1B subtype) is associated with pancreatic atrophy, renal abnormalities and genital tract malformations.
- MODY1,4,6 also exist but are very rare.
What are the different causes of diabetes?
- Type 1 DM
- Type 2 DM
- Pancreatic insufficiency e.g. Pancreatitis, surgery, trauma, haemochromatosis, CF, pancreatic cancer
- Cushings disease
- acromegaly
- phaeochromocytoma
- hyperthyroidism
- pregnancy
- Congenital lipodystrophy
- Glycogen storage diseases.
Describe Primary Hyperaldosteronism (Conn’s), it causes, symptoms, investigations, and management.
Excess production of aldosterone, independent of the renin-angiotensin system, causing hypernatraemia and water retention and decreased renin release.
Causes: Bilateral idiopathic adrenal hyperplasia is the cause sin up to 70%, with adrenal adenoma accounting for up to 30%. Rare causes include Adrenal carcinoma and glucocorticoid-remediable aldosteronism (ACTH regularlroty element of the 11-Betahydroxylase gene fuses to aldosterone synthase gene leading to aldosterone production under control of ACTH)
Symptoms: Consider if the following features, hypertension, hypokalaemia, alkalosis is someone not on diuretics. May also get weakness, cramps, paraesthesia, polyuria, polydipsia.
Investigations: U+E (Hypokalaemia, hypernatraemia), renin (reduced), aldosterone (raised), genetic testing for GRA if family history. Adrenal CT + Adrenal vein sampling, 18-Hydroxycorticosterone testing. Saline suppression test (2L Saline infused over 4 hrs testing of aldosterone and renin, levels stay the same in conn’s)
Treatment:
- Conn’s = laparoscopic Adrenalectomy, Spironolactone 4wks pre-op
- Hyperplasia treated medically, spironolactone, amiloride, eplerenone (selective aldosterone antagonist, which doesn’t cause gyneacomastia)
- GRA Dexamethasone 1mg/24hr PO for 4wks
- Adrenal carcinoma = surgery + post-op adrenolytic therapy with mitotane (poor prognosis)
What are the main types of antibodies in type 1 diabetes?
Islet cell autoantibodies, insulin autoantibodies and glutamic acid decarboxylase (GAD) antibodies
What is a typical formula used when perscribing insulin
1/2 BW (ideal body weight if obese) units of insulin 50/50 long/short acting
When converting a patient from insulin to a sliding scale/ fixed rate insulin what should you do with their normal insulin?
Never stop the basal insulin and when converting back from VRII only stop 30 minutes after subcutaneous insulin has been given ideally at meal time after short acting insulin or mixed insulin has been given.
What is pancreatogenic Diabetes?
Also known as type 3c diabetes it is a form that relates to the exocrine and digestive function of pancreas. Insuffiency of both insulin and glucagon leads to a very difficult and lability blood glucose which is hard to control and treat
Describe Hyperthyroidism, its causes, features, and investigations, and management
Causes:
- Graves disease 60% thyrotropin receptor autoantibodies
- toxic multinodular goitre - elderly and iodine -deficient
- toxic adenoma
- ectopic thyroid tissue
- exogenous
- Subacute de Quervains thyroidits (self-liming frost viral with painful goitre and reduced isotope uptake)
Features: Diarrhoea, Weight Loss, Increased Appetitie, over-activity, sweats, heat intolerance, palpitations, tremors, irritability, labile emotions, oligomennorhoea,
Signs: warm moist skin, palmar erythema, fine tremor, lid lag, thin hair, goitre, thyroid nodules, bruit (graves)
Specific Graves signs:
- Eye disease: exophthalmos, opthalmoplegia
- pretibial myxoedema: oedematous swellings above lateral malleoli
- Thyroid acropachy: extreme manifestation with clubbing painful finger and toe swelling
Investigations: ESR, Ca, LFT, Thyroid autoantibodies, isotope scan if cause unclear.
Management:
- B-blockers and carbimazole (SE agranulocytosis)
- radioiodine
- thyroidectomy
What are the effects of exercise on blood glucose?
Aerobic exercise can cause blood glucose to drop rapidly while anaerobic exercise may cause it to rise.
Describe Hypomagnesaemia, its symptoms, causes, and management
Mostly asymptomatic until levels drop below 0.5mmol/L, also commonly associated with other metabolic abnormalities such as hypokalaemia, hypocalcaemia, and metabolic acidosis and exacerbates digoxin toxicity
Symptoms: asymptomatic, weakness and apathy, tremor, paraesthesia, tetany, fasiculations, seizures, confusion, arrhymias, prolonged QT, U waves, wide QRS, decreased PTH secretion and hypocalcaemia
Causes: Diuretics, total parenteral nutrition, diarrhoea, alcohol, hypokalaemia, hypocalcaemia, Malabsorption syndromes e.g. IBD, metabolic disorders e.g. Gitelman’s and Bartter’s
Management:
- serum Mg, protein loss may be cause, check glucose,
- ECG
- Mild to moderate (0.5-0.6) Magnesium Glycerophosphate (4mmol Mg) 2 tablets TDS OR Magnesium sulphate 4-8mmol IV infusion over 1 hr.
- less than 0.5 IV replacement 16mmol of magnesium sulphate in 100ml 0.9% NaCl over 1hrs. Repeat level after transfusion
What are the different parts of the adrenal gland?
The capsule the cortex and the medulla:
The cortex consists of:
Zona Glomerulosa aldosterone is produced
Zona Fasciculata Cortisol is produced
Zona Reticulata Sex hormones are produced
Medulla is where catecholamines are made e.g. Adrenaline
What is the difference in profile between Levermir and Lantus
Levemir has a flatter profile where as Lantus has a slight peak before plateauing.
Describe Pagets Disease, its features, and management
Also known as osteitis deformans, there is increased bone turnover associated with increased numbers of osteoblasts and osteoclasts with resultant remodelling, bone enlargement, deformity and weakness. Rarely occurs under 40yrs. Commonor in Anglo-saxons. Osteosarcoma is 30 times more common in these patients.
Features: Asymptomatic in 70%, deep, boring pain, bony Deformity and enlargement. Pathological fracture, osteoarthritis may develop, nerve compression from overgrowth. Radiographs show enlargement of bone with patchy coarsening of the trabeculae pattern. Calcium and phosphate often normal ALP is raised.
Management: Analagesia + Alendronate
Describe Acute Charcot, its features, investigations and management
Neuropathic joint caused by loss of sensation in the joint and foot so that it becomes damaged and disrupted. Most common cause is diabetic neuropathy.
Features: Acute redness, warmth, swelling of deformity most commonly pes planus in foot.
Investigations: X-ray may show considerable disruption but in early disease may not show any changes. MRI is needed to differentiate osteomyelitis.
Management:
- take weight off foot
- referral to diabetic foot clinic
- immobilise in cast for 3-6 months
What is the diagnostic criteria for diabetes?
Diabetes Criteria:
- fasting glucose greater than 7.0
- glucose over 11.1 after oral glucose tolerance test
- HbA1c greater than 6.5% (48mmol/mol)
Pre-Diabetes Criteria:
- fasting glucose between 6.0-6.9
- glucose between 7.8-11.1 after oral glucose tolerance test.
- HbA1c 41-47
Describe Hoffman’s syndrome and its features.
A specific form of hypothyroid myopathy
Features: painful proximal myopathy, muscular psuedohypertrophy (rigidity) +/- symptoms of hypothyroidism.
Describe hypothyroidism, its features, causes, and management
Features: tired, sleepy, cold-disliking, weight gain, constipation, menorrhagia, hoarse voice, decreased memory, dementia, myalgia cramps, weakness BRADYCARDIC Reflex relax slowly Ataxia (cerebellar) Dry/thin hair/skin Yawning/drowsy/coma Cold hands / hypothermia Ascites +/- non-pitting oedema +/- pericardial/Pleural effusions Round face/double chin/ obese Defeated demeanour Immobile +/- Ileus CCF, also neuropathy, myopathy, goitre
Causes:
Primary e.g. Primary atrophic hypothyroidism (more common in younger women), Hashimoto’s thyroiditis (more common in women aged 60-70yrs), drug-induced (antithyroid drugs, amiodarone, lithium iodine), post thyroidectomy/radioiodine, subacute thyroiditis (after hyperthyroid phase)
Secondary e.g. Hypopituitarism
Management:
- levothyroxine start with 25mcg in elderly or IHD, otherwise 50-100mcg
- following a change in thyroxine dose TFTs should be checked after 8-12 weeks.
- the therapeutic ‘goal’ is normalisation of TSH (0.5-2.5mU/L)
- Pregnant woman should have their dose increased by 25-50mcg
- note iron leads to reduced absorption of levethyroxine give at least 2 hours apart.
Describe Medullary Thyroid Carcinoma, its features, investigations
Malignancy of parafollicular C-cells of the thyroid that produce calcitonin (therefore hypocalcaemia)
Features: Solitary thyroid nodule in patient with flushing, sweating, weight loss, diarrhoea and altered voice. Hypocalcaemia (calcitonin lowers serum calcium partly by reducing gastrointestinal calcium absorption causing diarrhoea).
Investigations: Raised Calcitonin, Hypocalcaemia, Histoligically absence of thyroid follicles and stromal amyloid.
What are the types of amiodarone induced thyroid disorder?
Around 1 in 6 patients taking amiodarone develop thyroid dysfunction.
Amidarone-induced hypothyroidism:
Occurs in patients with a previously normal thyroid gland. This is due to the autoregulatory phenomenon where high levels of circulating iodine reduces thyroid hormone synthesis and is known as the Wolff-Chaikoff effect.
Amiodarone-induced Thyrotoxicosis: Two main types:
- Type 1 -Usually occurs in patients with either pre-existing Thyroid disorders or iodine deficiency. Patients with underlying thyroid disorder or iodine deficiency cannot auto regulate effectively and so there is increased sensitivity and increased production and hyperthyroidism. This is known as the Joe-Basedow phenomenon. There is a goitre and it is managed through carbimazole or potassium perchlorate
- Type 2 amiodarone-related destructive thyroiditis, goitre absent and managed by corticosteroids. Elevated IL 6.
What is Nelson’s syndrome?
Rapid enlargement of a pituitary corticotroph adenoma (ACTH producing adenoma) that occurs after the removal of both adrenal glands an operation rarely used for severe Cushings Syndrome.
What picture would the U+Es show in Cushing’s Syndrome?
Hypokalaemic metabolic alkalosis
In a patient on monotherapy (metformin) for type 2 diabetes, at what threshold should you consider adding a second agent?
HbA1c over 58mmol/mol (7.5%)
Describe Lipohypertrophy
Accumulation of extra fat often at its of SC insulin. It may change the timing or completeness of insulin action. Will gradually disappear over months if injections in area are avoided.
Describe Milk-Alkali Syndrome and its features.
A triad of Hypercalcaemia, Metabolic Alkalosis, and AKI associated with the ingestion of large amounts of calcium and absorbable alkali. Most usually occurs in those taken supplements to prevent osteoporosis and peptic ulcer disease.
Features: Poor appetite, dizziness, headache, confusion, psychosis, dry mouth.
Management:
- stop supplements
- rehydration
Describe McArdle’s disease and its features.
Autosomal recessive type V glycogen storage disease caused by myophosphorylase defiency. This causes decreased muscle glycogenolysis.
Features:
- Muscle pain and stiffness following exercise
- muscle cramps
- myoglobinuria +/- rhabdomyolysis
- low lactate levels during exercise.
Describe Androgen Insensitivity Syndrome, its features, and management.
An X-linked recessive condition due to end-organ resistance testosterone causing genotypically male children to have a female phenotype. Complete androgen insensivity syndrome is the new term for testicular feminisation syndrome.
Features:
- ‘primary amennorhoea’
- Undescended testes causing groin swellings
- Breast development may occur as a result of conversion of testosterone to oestradiol
Management:
- Buccal smear or chromosomal analysis to reveal 46XY genotype
- Counselling - raise child as female
- Bilateral orchidectomy (increased risk of testicular cancer in undescended testes)
- Oestrogen therapy.
Describe Hypokalaemic Periodic Paralysis, its features, and management.
Rare autosomal dominant condition characterised by episodes of generalised flaccid weakness or paralysis associated with transient reductions in serum potassium levels The condition is due to a mutation on chromosome 17, with 90% penetrance in males and 50% in females. 1/3 of cases give no FHx and so may be spontaneous mutation. It is assoicated with muscle calcium channel CACLN1A3 mutations. (CACNA1, SCN4A)
Features:
- most commonly presents in second decade.
- Weakness may range from severe and generalised to limited to a particular muscle group or only transient weakness.
- Attacks usually begin in the opening when their has been strenuous exercise or a high carbohydrate meal the previous day
- weakness duration can vary but rarely over 72hrs
Management:
- Oral or IV potassium depending on if swallow is safe.
- Continuous ECG monitoring.
- Acetazolamide may be used at a dose of 125-1500mg/day as prophylaxis. Potassium-sparing diuretics may be used second-line.
- Attacks can be minimised by a very low-sodium diet and avoidance of high carbohydrate meals.
Describe Thyrotoxic Periodic Paralysis, its features and management.
A rare condition featuring attacks of muscle weakness in the presence of hyperthyroidism. Thought to be due to a genetic mutation in genes on chromosome 1 that code for ion channels. The channelopathy is thought to lead to shifts of potassium into cells, under conditions of high thyroxine. Predominantly affects males of Asian descent.
Features:
- Attacks often begins with muscle pain and stiffness followed by weakness or paralysis that tend to develop rapidly.
- Weankess is usually symmetrical with proximal muscles affected predominantly. Reflexes are usually diminished.
- Attacks may be precipitated by physical exertion, alcohol, of high salt/carbohydrate foods.
- May also be symptoms of thyroid overactivity e.g. Weight loss, tachycardia, tremor, diarrhoea.
Management:
-Treatment of hypokalaemia and correction of hyperthyroidism leads to complete resolution.
Describe Lesch-Nyhan syndrome and its features.
Aka Hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) deficiency. An X-linked recessive condition
Features: Gout, Renal Failure, Neurological deficits, learning difficulties, self-mutilation.
Describe the Renin-angiotensin system
A hormone system that is involved in the regulation of the plasma sodium concentration and arterial blood pressure.
When the plasma sodium concerntration is lower than normal or renal blood flow is reduced, the juxtaglomerular cells in the kidneys convert prorenin into renin, which is secreted directly into the circulation. Plasma renin converts plasma angiotensinogen into angiotensin I.
Angiotensin I is then converted to Angiotensin II by ACE found in the endothelial cells of the capillaries. Angiotensin II is a potent vaso-active peptide that causes arterioles to constrict increasing blood pressure. It also stimulates the secretion of Aldosterone from the adrenal cortex.
Aldosterone causes the Tubular epithelial cells of the kidneys to increase resorption of sodium whilst at the same time causing them to excrete potassium.
Describe secondary Hyperaldosteronism, its causes, and features
This is the result of excessive renin in the circulation, which stimulates normal adrenals to produce aldosterone. The excess renin is usually secondary to decreasing circulating volume reaching the glomerulus stimulating renin release.
Causes: diuretics, CCF, hepatic failure, nephrotic syndrome, renal artery stenosis, malignant Hypertension.
Features: hypernatraemia, hypokalaemia, Hypertension, increased renin (as opposed to low renin in primary Hyperaldosteronism)
Describe Metabolic Acidosis, its pathogenesis, assessment and some causes.
Metabolic acidosis can be produced by three major mechanisms:
- Increased Acid generation e.g. lactic acidosis, ketoacidosis, salicylate poisoning, Methanol, ethylene glycol.
- Loss of bicarbonate e.g. severe diarrhoea, Proximal Type 2 renal tubular acidosis
- Diminished Renal Acid excretion e.g. reduced GFR, distal Type 1 RTA and type 4 RTA.
Causes can be further differentiated by Anion Gap. Normal Anion gap (10-18mmol/L (HARDUP): -Hyperchloraemia -Acetazolamide, Addison's -RTA -Diarrhoea, ileostomies, fistulae -Ureterosigmoidostomy/Ileostomy -Post-treatment of DKA
Raised Anion Gap (MUDPILES)
- Methanol Poisoning
- Uraemia e.g. Renal failure
- DKA
- Paracetamol, theophylline, paraldehyde
- Iron, isoniazid, inborn errors of metabolism
- Lactic acidosis (Type A shock, hypoxia, burns or Type B metformin)
- Ethanol, Ethylene glycol
- Salicylates/ASA/aspirin
What are the causes of metabolic alkalosis?
Loss of hydrogen or gain of bicarbonate, usually due to GI or kidney pathology.
Causes:
- Vomiting/Aspiration
- Diuretics
- Liquorice, carbenoxolone
- Hypokalaemia
- Primary hyperaldosteronism (Conn’s)
- Cushing’s syndrome
- Bartter’s syndrome
- Congenital Adrenal Hyperplasia
Describe Autoimmune Polyendocrinopathy Syndrome (APS), its types and features.
Addison’s disease (autoimmune hypoadrenalism) is associated with other endocrine deficiencies in approximately 10% of patients. There are two distinct types of APS, with type 2 (sometimes referred to as Schmidt’s syndrome) being much more common.
APS Type 2 has a polygenic inheritance and is linked to HLA DR3/DR4. Patients have Addison’s disease plus either Type 1 Diabetes Mellitus or autoimmune thyroid disease. Vitiligo can also occur.
APS type 1 is occasionally referred to as Multiple Endocrine Deficiency Autoimmune Candidiasis (MEDAC). It is a very rare autosomal recessive disorder caused by mutation of AIRE1 gene on chromosome 21. Features of APS type 1 include Chronic Mucocutaneous candidiasis (typically first feature as young child), Addison’s disease, primary hypoparathyroidism. Vitiligo can also occur.
Describe Hypophosphataemia, its causes, features, and management.
Mild to moderate hypophosphataemia is defined as 0.32-0.9mmol/L. Severe is less than 0.32mmol/L.
Causes: DKA, HHS, Malnourishment, alcoholism, respiratory alkalosis, antacids, chronic diarrhoea, hyperparathyroidism, vitamin D deficiency, renal wasting syndromes, and renal replacement therapy.
Features: Mostly asymptomatic, myopathy, rhabdomyolysis, cardiomyopathy, RBC/WBC/Platelet dysfunction, Parasethesia, delirium, seizures, Coma.
Management:
- Mild to moderate: Oral Phosphate Sandoz (16.1mmol phosphate) 2 tablets BD. Or if not tolerated Phosphate Polyfusor (50mmol/500ml) 9mmol (90ml) IV over 12 hours (7.5ml/Hr)
- Severe: Phosphate Sandoz 2 tablets TDS AND Phosphate polyfusor 9mmol (90mL) IV over 12hrs.
What are the features of Zinc defiency?
Features:
- Perioral dermatitis - red crusted lesions
- Acrodermatitis
- Alopecia
- Short stature
- Hypogonadism
- Hepatosplenomegaly
- geophagia (ingesting clay/soil)
- Cognitive impairment
Describe the 72 Hour fast for investigation of spontaneous hypoglycaemia.
Start fast - water only
2hourly BM + 6hrly venous samples for Glucose, Insulin, and c-peptide.
Twice daily ketones at 08:00 and 17:00
If glucose drops below 3, take urgent sample of blood glucose. If lab confirms less than 2.2 then stop fast and take post test c-peptide + Insulin + Ketones. If lab glucose greater than 2.2 continue fast with 1hrly or even 30mins BM testing.
Describe Osteopetrosis, its features and management.
Aka Marble bone disease, a rare disorder of defective osteoclast function resulting in failure of normal bone resorption resulting in dense, thick bones that are prone to fracture.
Features: Bone pain, multiple fractures, Neuropathy, Calcium, phosphate and ALP are normal.
Management:
-Stem cell transplant and interferon gamma have been used
Describe Riedel’s thyroiditis and its features.
A rare cause of hypothyroidism characterised by dense fibrous tissue replacing the normal thyroid parenchyma. On examination a hard, fixed painless goitre is noted. It is usually seen in middle-aged women and is associated with retro Peritoneal fibrosis.
Classify the causes of hypokalaemia with the association of hypertension.
Hypokalaemia with hypertension:
- Cushing’s syndrome
- Conn’s Syndrome
- Liddles Syndrome
- 11-beta hydroxylase deficeincy
- Carbenoxolone
- Liqourice excess
Hypokalaemia without hypertension:
- Diuretics
- GI loss (e.g. D+V)
- Renal tubular acidosis (type 1 + 2)
- Bartter’s syndrome
- Gitelman’s syndrome
What is the Insulin Stress test?
Used in investigations of hypopituitarism, IV insulin given, GH and cortisol levels are measured. With normal pituitary function GH and cortisol should rise.
Contraindications:
- Epilepsy
- IHD
- Adrenal insufficiency
Describe Hurler Syndrome and its types.
A lysosomal storage disease usually inherited in autosomal recessive fashion
Type 1 due to a defect in Alpha-1-iduronidase there is accumulation of glycosaminoglycans (Heparan and dermatan sulphate). Key features include gargoylism, hepatosplenomegaly, corneal clouding
Type 2 is due to a defect in iduronate sulfatase, there is accumulation of glycosaminoglycans (Heparan and dermatan sulphate). Key features include coarse facial features, behavioural problems/learning difficulties, short stature, no corneal clouding.
Describe Fabry Disease and its features.
X-Linked recessive deficiency of alpha-galactosidase A, leading to accumulation of ceramide trihexodase.
Features:
- Burning pain/ paraesthesia in childhood (Peripheral neuropathy)
- Angiokeratomas
- Lens opacties
- Proteinuria / Renal Failure
- Early cardiovascular disease
Describe Pendred’s Syndrome, its features, investigations and management.
An autosomal recessive disorder caused by a. defect in the organification of iodine, leading to dyshormonogenesis.
Features: Bilateral sensorineural deafness, mild hypothyroidism (Often clinically euthyroid), Goitre. Patients tend to present with progressive hearing loss and delay in academic progression. Often head trauma makes the deafness worse leading to patients having to avoid contact sports.
Investigations: Diagnosed via genetic testing (PDS gene on chromosome 7), audiometry and MRI imaging to look for characteristic one and a half turns in the cochlea compared to the normal two and half turns.
Management:
- Thyroid hormone replacement
- Cochlear implants.
Describe Abetalipoproteinaemia and its features.
A rare autosomal recessive disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food. It is caused by a. mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicron and VLDL respectively.
Features: Failure to thrive, steatorrhoea, frothy foul-smelling stool. Protuding abdomen, Developmental delay, Developmental coordination disorder, muscle weakness, scoliosis, Retinitis Pigementosa, Acanthocytosis, Hypocholesterolaemia.
Describe Alkaptonuria, its features, and management
AKA Ochronosis is a rare autosomal recessive disorder of phenylalanine and tyrosine metabolism caused by a lack of the enzyme Homogentisic dioxygenase (HGD) which results in a build up of toxic homogentisic acid. The kidneys filter the homogentisic acid (Hence black urine) but eventually it accumulates in cartilage and other tissues.
Features:
- often asymptomatic
- Pigmented sclera
- black urine when exposed to air
- Intervertebral disc calcification + back pain
- renal stones
Management:
- High-dose vitamin C
- Dietary restriction of phenylalanine and tyrosine.
Describe Hypernatraemia, its causes
Causes:
- Dehydration
- Osmotic Diuresis e.g. Hyperosmolar non-ketotic diabetic coma
- Diabetes insipidus
- Excess IV Saline.
- Primary hyperaldosteronism (Conn’s)
Features: Lethargy, Thirst, Weakness, Confusion, Seizures.
Management:
- Water orally or IV Glucose 5% slowly (1L/6h) if hypovolaemic can use 0.9% Saline as its hypotonic in a hypertonic patient and causes less marked fluid shifts.
- Aim for reduction in Na no more than 0.5mmol/hr
Describe Thyroid Eye disease, its features and management.
Thyroid eye disease affects between 25-50% of graves disease patients, it is thought to be caused by an autoimmune response against an auto antigen, possibly the TSH receptor leading to retro-orbital inflammation and glycosaminoglycan and collagen deposition in the muscles.
Features:
- Exopthalmos
- Conjunctival oedema
- optic disc swelling
- opthalmoplegia
- exposure keratopathy
- may worsen with radio iodine treatment.
Management:
- quit smoking
- Topical lubricants
- Steroids
- radiotherapy /surgery
- refer to ophthalmologist if unexplained deterioration in vision, sudden eye popping out (Globe subluxation), loss of colour vision, corneal opacity, disc swelling, or cornea visible when eyelids are closed. Due to fear of Dysthyroid Optic Neuropathy
Describe Pituitary Apoplexy and its features
Sudden enlargement of pituitary tumour secondary to haemorrhage or infarction
Features:
- Sudden onset headache similar to that seen in SAH
- Vomiting
- Neck stiffness
- Visual field defects classically bitemporal superior quadratic defect
- extraocular nerve palsies e.g.
- features of pituitary insufficiency e.g hypotension secondary to hypoadrenalism
Describe Pseudohypoparathyroidism, its features and investigations.
Caused by target cell insensitivity to PTH due to a. mutation in G-protein. In Type 1 there is complete receptor defect whereas in type 2 the cell receptor is intact. It is typically inherited in an autosomal dominant fashion.
Features:
- High PTH, Low Ca2+, High PO4-
- short fourth and fifth metacarpals
- short stature
- cognitive impairment
- obesity
- round face
Investifations:
- PTH (High, Ca2+ (Low), PO4- (High)
- Infusion of PTH followed by measurement of urinary phosphate and cAMP. This can help differentiate between type I (neither phosphate or cAMP levels rise) and II (cAMP rises but phosphate levels do not changed.
What is Pompe’s Disease?
type II glycogen storage disease. caused by deficiency in Lysosomal alpha-1,4-glucosidase. Leads to cardiac, hepatitis and muscle glycogen accumulation. Key features include cardiomegaly.
What is Von Gierke’s Disease?
Type I glycogen storage disease, caused by glucose-6-phosphatase. Leads to hepatic glycogen accumulation. Key features include hypoglycaemia, lactic acidosis, hepatomegaly.
Describe the management of Cushing’s syndrome.
Treatment of Cushing’s syndrome depends on the cause.
Pituitary Tumour (Cushing’s disease):
- first line = trans-sphenoidal removal of pituitary tumour (Hypophysectomy) (Ketoconazole can be used prior to treatment 600-800mg OD, it acts on several p450 enzymes decreasing production of cortisol helping to control blood sugar and BP prior to surgery
- second-line = repeat trans-sphenoidal surgery +/- pituitary Radiotherapy
- third line = bilateral adrenalectomy
2 major complications of bilateral adrenalectomy are:
- Hypoadrenal crisis - requires lifelong glucocorticoid and mineralocorticoid replacement
- Nelson’s syndrome - low/ no endogenous cortisol leads to massive ACTH production which causes rapid pituitary enlargement + Mass effects and skin hyperpigmentation
Adrenal Cushing’s:
- Adrenalectomy
- radiotherapy
- adrenolytic drugs e.g. mitotane if unfit for surgery
Ectopic Cushing’s:
-remove tumour if possible
Describe Vitamin D, its sources, and functions.
Vitamin D is a fat soluble vitamin that plays a key role in calcium and phosphate metabolism.
Sources:
- Vitamin D2 (Ergocalciferol) Plants
- Vitamin D3 ( Cholecalciferol) dairy products, can be synthesised by the skin from sunlight.
Functions:
- Increases plasma calcium and plasma phospahte
- increase renal tubular reabsorption and gut absorption of calcium (Main effect)
- Increases osteoclastic activity
- Increases renal phosphate reabsorption.
Consequences of vitamin D deficiency:
- Rickets seen in children
- Osteomalacia seen in adults.
Describe the main management of Type 2 Diabetes.
- Diet modification, low fat dairy products, oil fish, low GI Carbohydrates
- HbA1c target 48 with Lifestyle +/- Metformin
- HbA1c target 53 if hypoglycaemic agents.
- Metformin is first line
- If metformin not tolerated try gliptin, sulphonylurea or pioglitazone.
- If not controlled try dual therapy with above agents.
- If metformin tolerated and not controlled add gliptin, or sulfonylurea, or pioglitazone or SGLT-2 inhibitor.
- If still not controlled triple therapy e.g.
- Metformin + Gliptin + Sulfonylurea
- Metformin + Pioglitazone + Sulfonylurea
- Metformin + Sulfonylurea + SGLT-2 Inhibitor
- Metformin + Pioglitazone + SGLT-2 Inhibitor
- If not controlled and BMI above 35 try metformin + Sulfonylurea + GLP-1 Mimetic
- If not controlled switch to insulin
- NICE recommend starting with human NPH insulin (Isophane, intermediate acting) taken at bed-time or twice daily according to need. continue metformin,
Describe Cerebral salt-wasting syndrome, its features, and management
A rare condition featuring hyponatraemia, dehydration in response to trauma/injury or presence of tumours surrounding the brain. A diagnosis of exclusion difficult to distinguish from SIADH, main difference is fluid status is hypovolaemic vs euvolaemic in SIADH.
Features: Polyuria (over 3L/day), Hyponatraemia, polydipsia, dehydration. muscle cramps, dizziness, Hypotension, seizures.
Management:
- IV Fluids
- Fludrocortisone.
Describe Carney Complex and it’s features
An autosomal dominant condition caused by an inactivating mutation of protein Kinase A on chromosome 17. Diagnosis is made if there are two features out of the following or one plus an effected first degree relative.
Features:
- spotty skin pigmentation
- myxoma
- endocrine tumours (the commonest is primary pigmented nodular adrenocortical disease but it is also associated with Sertoli cell tumours, growth hormone or prolactin producing pituitary adenomas)
- psammomatous melanotic schwannoma
Describe Carney Complex and its features.
Autosomal dominant condition most commonly caused by mutations in the PRKAR1A gene on chromosome 17, which may function as a tumour suppressor gene. (Less commonly caused by genetic changes at chromosome 2). Two subsets LAMB syndrome and NAME syndrome.
Features:
- Spotty skin hyperpigmentation most commonly on the face, especially on the lips, eyelids, and oral mucosa.
- Cardiac myxomas
- Endocrine tumours may manifest as Cushing syndrome.
- LAMB syndrome: Lentigines, atrial myxomas, Blue Nevi.
- NAME syndrome: Nevi, Atrial Myxoma, Myxoid neurofibromas, ephelides.
Describe Post-Partum Thyroiditis, its features, and management
Characterised by hyperthyroidism + hypothyroidism sequentially. Affects 5% of women within a year of giving birth. Initially develops hyperthyroidism which either turns to normal or becomes hypothyroidism, of these women 1 in 5 require lifelong replacement.
Features: Painless smooth enlargement on thyroid gland, symptoms of hyperthyroidism, associated with positive anti-thyroid peroxidase enzymes
Management:
- Hyperthyroid phase usually conservative short cause of beta-blockers most resolve
- Hypothyroidism requires levothyroxine if TSH high.
Describe Prolactin, its main effects and interactions with the hypothalamic-pituiary system
Aka luteotropic hormone. its best known for its role in enabling females to produce milk. Secreted in the pituitary gland and regulated by the release of dopamine from hypothalamus causing inhibition of prolactin release.
Prolactin tends to suppress the secretion of GnRH leading to decreased secretion of FSH and LH from the anterior pituitary.
Describe Lipodystrophy syndrome and its features
Characterised by complete or partial loss of adipose tissue. May occur in conjunction with pathological acummulation of fat in other distinct areas. Can be inherited (very rare) or acquired. Strong associated with HIV infection and medications (PIs and NRTIs)
Features:
- Metabolic abnormalities e.g. Insulin resistance, DM, Hypertriglycerideamia, hepatic steatosis
- Peripheral lipoatrophy e.g. face and lower limbs. Central lipohypertrophy e.g. abdomen and neck
Describe Diabetic Amyotrophy and its features
Aka Proximal Diabetic Neuropathy. A peripheral nerve disorder that can affect the thighs, hips, buttocks or lower legs. The second most common type of diabetic neuropathy.
Features: Characterised by muscle wasting or weakness, pain or changes in sensations of the leg or buttocks.Symptoms often start on one side but can spread to both. Fasciculations may occur with severe wasting.
Describe Non-classical Congenital Adrenal Hyperplasia and its features
Due to 21-hydroxylase deficiency, it is a milder and later onset form of congenital adrenal hyperplasia.
Features: Androgen excess, hirsutism, forntal baldness, delayed menarche, menstrual irreglalties, infertility. (Men early beard growth and small testes).
Describe the schilling test
A test used to distinguish the causes of vitamin b12 deficiency there are 4 stages:
Stage 1: Vitamin B12 IM is given with radioisotope labelled Vitamin B12. The IM injection saturates the liver so that the radio labelled B12 is absorbed then exerted in the urine, 24hr urine collection is done and the level of b12 should be at least 10% of adminsistered, less means there is an issue with impaired absorption of lack of intrinsic factor
Stage 2: the test is repeated but with intrinsic factor, if the percentage collected increases the diagnosis is pernicious anaemia
Stage 3: The test is repeated but with antibiotics if it increases this the cause is bacterial overgrowth
Stage 4: The test is repeated but this time with pancreatic enzymes if the percentage increases the cause is pancreatitis
What are the causes of hypercalcaemia?
CHIMPANZEES
C = Calcium Supplementation H = Hyperparathyroidism I = Iatrogenic (Drugs such as thiazides)or Immobility after surgery M = Milk-alkali syndrome P = Paget’s disease of the bone A = Acromegaly and Addison’s disease N = Neoplasia Z = Zollinger-Ellison syndrome (MEN type 1) E = Excessive vitamin D E = Excessive Vitamin A S = Sarcoidosis
Describe Gaucher’s disease, and its features
A autosomal recessive lysosomal storage disorder in which glucocerebroside (aka glucosylcercamide) accumulates in cells (particularly macrophages) and certain organs due to a deficiency of the enzyme Glucocerebrosidase caused by a mutation on chromosome 1.
Features: Bruising, fatigue, anaemia, thrombocytopaenia, hepatosplenomegaly. Acid phosphatase and ACE are raised.
Describe Cystinuria, its features, and management.
An inherited Autosomal Recessive disease that is characterised by high concentration of the amino acid cysteine in the urine leading to the formation of cystine stones in the kidneys, ureter and bladder. It is a type of aminoaciduria. A disease involving the defective transepithelial transport of cystine and Dibasic amino acids in the kidney and intestine.
Features: A cause of persistent kidney stones. Crystals are usually hexagonal, translucent, hits, when removed the stones may be pink but later turn green from exposure to air. Usually asymptomatic but when a stone forms N&V, Renal colic, haematuria. Stones are not visible on X-RAY
Management:
- May be identified by positive nitroprusside cyanide test. ( Mixed with urine it breaks di-sulfide bonds freeing cysteine from cystine and homocysteine from homocystine. This is then mixed with a reagent reacts with the free sulfhydryl groups turning the mixture red/purple).
- Hydration
- Alakaziation of urine with citrate supplementation or acetazolamide.
- Chelation therapy with d-penicillamine
- ESWL for stones or surgery.
What are the types of Aminoaciduria?
Alkaptonuria Canavan disease Cystinosis Cystinuria Fructose intolerance Galactosaemia Harnup disease Homocystinuria.
Describe Wilson’s disease, its features, investigations, and management
An autosomal recessive condition caused by a mutation in the ATP7B gene which leads to decreased linking of copper to caeruloplasmin for release into the blood stream, and decreased biliary excretion of copper. This lead to copper accumulation in tissues mostly liver and brain.
Features: Liver failure, Renal failure (RTA type 2), Neurological symptoms (Parkinsonism, Cerebellar syndrome, seziures), Eyes (Kayser-Fleischer rings), Heart (Cardiomyopathy), Hypoparathyroidism, Hypogonadism.
Investigations:
- low serum caeruloplasmin
- Deranged LFTs
- low serum copper
- Raised urine copper
Management:
- Penicillamine
- Tridentine hydrochloride may be used second line if not tolerant penicillamine
- liver transplantation
Describe subclinical hyperthyroidism and its management
TSH low, Normal T4,T3
Treat if persistent especially if TSH fully suppressed to reduce AF, CVD and Fracture risk
Usually caused by nodular goitre and requires radioiodine
What is Primary Hyperoxaluria?
Autosomal recessive condition leading to increased excretion of oxalate, with oxalate stones being common.
Describe Tertiary Hyperparathyroidism, its features and management.
Usually occurs after prolonged Secondary Hyperparathyroidism, the glands become autonomous producing excessive PTH even after the cause of hypocalcaemia has been corrected resulting in hypercalcaemia. Long-standing kidney disease is the most common cause and it can persist after renal transplant.
Features: Hypercalcaemia. Pain, Confusion, Stones. Vomiting.
Raised PTH, Raised Calcium Raised Phosphate
Management:
- cinacalcet can be used
- Total or subtotal parathryoidectomy is recommended treatment
Describe Kallman syndrome, its features, and management.
A genetic disorder that causes GnRH deficiency.
Symptoms: Anosmia, Poorly defined secondary sexual characteristics. Hypogonadism. Infertility. Primary amenorrhoea, undescended testes. Micropenis.
Management:
-Pulsatile GnRH therapy.
What is the somogyi effect?
Rebound hyperglycaemia.
It is a response to low blood sugar, occasional seen in diabetics wit Nocturnal hypoglycaemic episode with morning Hyperglycaemic readings.
Describe Thyroxine Binding Globulin Deficiency, its features and management.
TBG deficiency is a non-harmful condition that is either acquired or inherited. 0.3% of thyroid hormones circulate unbound which are metabolically active. The rest is bound to TBG, Transthyretin and Albumin.
Features: A deficiency in TBG is suspected when abnormally low serum total thyroid hormone concentrations are encountered in a clinically euthyroid subject in the presence of a normal TSH. Bloods will show Normal TSH and Free T4 but low Total T3 and T4.
Management:
-No specific thyrodin management needed.
Describe Hypocalcaemia, its features, Causes, investigations and management
Defined as less than. 2.2mmol/L symptoms don’t usually occur until less than 1.9mmol/L. Less than 1.9mmol/L is a medical emergency and requires urgent replacement.
Features: Perioral and digital paraesthesia, Positive Trousseau’s and Chvostek’s sign. Tetany and carpopedal spasm. Laryngospasm, Prolong qt and arrhytmias Seizures.
Causes:
Severe Vitamin d defiency. Hypoparathyroidism, Magnesium deficiency (PPI-associated) Cytotoxic drug induced, Pancreatitis, Rhabdomyolysis, Large volume blood transfusions
Investigations: Calcium, Phosphate, PTH, U+Es, Vitamin D Magnesium.
Management:
- if mild replace PO e.g. ADCAL 3 tabs BD. If remains low after 3 days tart alfacalcidol 0.25mcg daily. Replace Mg and Vitamin D as appropriate.
- If Post thyroidectomy repeat in 24hrs.
- If severe give 20ml of 10% Calcium Gluconate in 100ml of 5% Dextrose over 10minutes with ECG monitoring. Followed up with 100ml 10% Calcium Gluconate in 1L NaCL or 5% Dextrose at 50-100ml/hr.
What monitoring is needed in Vitamin D replacement?
Check calcium after 1 month of vitamin D replacement to monitor for Hypercalcaemia secondary to unmasked Primary Hyperparathyroidism
Describe X Linked Dominant Hypophosphataemia, its features, and management
X Linked Dominant form of Rickets (Osteomalacia) that cannot be cured by Vitamin D Replacement. Associated with mutation in the PHEX gene Xp.22
Features: Short Stature, Bow-leggedness (Genu Varum). Joint Pain, Hearing Impairment. Dental abscesses.
Management:
- Oral phosphate, calcitriol
- Burosumab
Describe Osteogenesis Imperfecta and its features
Also known as brittle bone disease. A Group of genetic disorders that mainly affect bones. Due to a lack of Type I Collagen. More than 90% of cases are due to mutations in the COL1A1 or COL1A2 genes often inherited in an autosomal dominant manner or via a new mutation.
Features: Prone to fractures, Blue sclera, hearing loss, Dental issues. Cervical artery dissection and aortic dissection
