Endocrinology Study Materials

Endocrinology • • • • • • Pituitary o Pituitary disease Adrenal gland o Adrenal disease GI tract o Diabetes o Diabetes – metabolic complications o Diabetes – vascular complications Thyroid gland o Hyperthyroidism o Hypothyroidism o Thyroid cancer Hypercalcaemia / Parathyroid disease Hypocalcaemia Endocrine 1 2 4 6 8 11 13 17 20 24 27 29 30 31 33 Pituitary • Appreciate the embryological development of the pituitary gland Ectoderm grows upwards (from the primative mouth). From rathke’s pouch à anterior lobe Neuroectoderm grows downward (from the diencephalon in the 3rd ventricle). From infundibulum à posterior lobe Superior hypophyseal arteries Portal vessels Inferior hypophyseal artery Posterior Pituitary • Anterior Pituitary List the structures anatomically related to the pituitary, highlighting those likely to be affected by an enlarging tumour Growth of the pituitary most commonly causes impingement of the optic chiasm à bitemporal hemianopia • Outline the regulation of the posterior pituitary hormones, vasopressin (ADH) and oxytocin and summarize their actions. Posterior pituitary is controlled directly from neurones. Supraoptic nucleus à Vasopressin (ADH). Released in response to osmotic and haemodynamic stimuli (decreased blood volume à increased conc à ADH release). Targets distal convoluted tubule Paraventricular nucleus à Oxytocin. Released in lactating female in response to suckling during pregnancy & during birth à smooth muscle contraction Endocrine 2 • Outline control of the secretion of the anterior pituitary hormones and respective hypothalamic releasing hormones Anterior pituitary is controlled from nuclei in the hypothalamus. Hypothalamic neurones release pituitary stimulating hormones into the infundibular capillary plexus à portal vessels à adenohypophysis GHRH à GH (Somatotrophs) é by stress / starvation ê by metabolism & somatostatin TRH à Prolactin (Mamotrophs) é by suckling, ê by anxiety and DA CRH (and ADH) à ACTH (Corticotrophs) – regulated by stress, anxiety & illness, é by cytokines TRH à TSH (Thyrotrophs) - é by cold / stress, ê by metabolism GnRH à LH & FSH (Gonadotrophs) – GnRH is inhibited by LH, FSH & Oestrogen Endocrine 3 Pituitary Disease • Classify pituitary adenomas according to size and function and outline other causes of hypothalamic-pituitary disturbance such as craniopharyngioma, sarcoidosis, and parapituitary growths. Prolactinoma – 50% Micro (< 10mm) à Female – amenorrhoea, galactorrhoea Male – impotence, galactorrhoea, visual problems Macro (> 10mm) à as above but with space occupying signs (headache, visual disturbance) Rx – dopamine agonists (suppress PRL secretion) GH secreting – 20% à acromegaly / gigantism Enlarging jaw (à dental problems), hands and feet enlarging and becoming “dough like” (rings no longer fit), headache & sweating, nerve entrapment (carpal tunnel), arthritis, hypertension, diabetes, increased CVS disease Ix – require an oral glucose tolerance test as secretion is pulsatile & MRI of pituitary GTT – normal / impaired GTT with serial measures (every 30 mins) of GH. GH should be inhibited by the glucose --> almost undetectable (<2) Rx – surgery, radiotherapy, Somatostatin (cardioprotective and reduces GH secretion). Dopamine also inhibits GH release Non secreting – 20% à pressure effects and can à Hypopituitarism Often > 10 mm – visual field problems & hypopituitarism ACTH secreting – 5% à increased cortisol à cushings disease Sx - Moon face, central obesity, striae, bruising, peripheral myopathy, osteroporosis, hypertension, diabetes / glucose intolerance Ix – dexamethasone suppression test required as pulsatile release (or 24 hrs urine cortisol collection) Rx – surgery Other causes include Craniopharyngioma Large, benign cystic tumour Sx - headaches, visual field problems, growth failure, obesity, loss of thirst sensation & disturbance of temperature regulation Rx – requires craniotomy bec cant be reached transphenoidal. Usually require follow up radiotherapy. Often still recur Sarcoidosis – multisystem granulomatous disorder Parapituitary growths • Describe the local symptoms that result from a large pituitary adenoma. Headache Bi-temporal hemianopia Ocular nerve palsies CSF rhinorrhoea Nausea & vomiting Light headed on standing • Describe the laboratory assessment of pituitary function. ACTH deficiency à fatigue, hypotension, hypoglycaemia (presents same as addisons) Short ACTH (synacthen) stimulation test – IM injection of ACTH à check plasma cortisol at 0 and 30 minutes. Look for normal level at baseline or at 30 minutes Endocrine 4 Insulin tolerance test (if ACTH test inconclusive) LH/FSH deficiency à loss of 2o sexual characteristics Male – measure random testosterone, LH & FSH Pre-menopausal women – ask if menses are regular Post menopausal women – random LH & FSH (> 30mU/l = normal) TSH deficiency à weight gain, fatigue, dry skin, constipation Random serum thyroxine – TSH can still be detected in 2o hypothyroid due to inactive isomers GH deficiency à growth failure, weakness, loss of stamina Only do if considering replacement Measure immediately after exercise (or consider other stimulatory tests) Cranial Diabetes Insipidus Only investigate if Sx which may be masked by ACTH / TSH deficiency Exclude other causes Water deprivation test Hormone excesses Measure prolactin Investigate for acromegaly & Cushings if Sx • Outline the radiological techniques used to investigate pituitary disease. Image the pituitary by CT / MRI If calcified can be seen on lateral skull XR • Outline the treatment of a prolactinoma, including the use of dopamine agonists as first line therapy. 1st line – dopamine agonists. Often à shrinkage of tumour 2nd line – surgery with radiotherapy • Outline the treatment options for pituitary disorders Non functioning adenoma Trans sphenoidal / transfrontal surery with 2nd line radiotherapy Acromegaly 1st line surgery 2nd line radiotherapy with somatostatin analogues (octreotide, bromocryptine), dopamine agonists and GH receptor antagonists Cushings Disease 1st line surgery 2nd line radiotherapy & metyrapone • Syndrome of Inappropriate Antidiuresis (SiADH) Excess of ADH à increases permeability of distal tubule to water à free water retention, volume expansion and dilutional hyponatraemia. Increased blood flow à suppression of RAA system à urinary Na+ loss à further hyponatraemia Causes Bronchial CA, cerebral tumour/infection/CVA/trauma, PE, pneumonia, trauma, TB, opiates, oral hypoglycaemics, oxytocin, hypothyroidism, acute porphyria Rx – fluid restriction – wont be thirsty until the osmolarity normalises. Demeclocycline will stop the distal tubule responding to ADH (causes nephrogenic DI in excess dose) Endocrine 5 Adrenal gland • Appreciate the different embryological origin of the adrenal cortex and medulla. Each gland is composed of two separate endocrine organs with different embryological origins, types of secretion and functions. The outer cortex Developed from coelomic mesothelium Producing steroid hormones Controlled by the adenohypophysis The inner medulla Derived from neural crest (neuroectoderm) Consisting of cells secreting catecholamines (chromaffin cells) Under nervous control. • List the histological features of the adrenal cortex and medulla. Cortex has 3 zones - ALL stimulated by ACTH Zona glomerulosa (below capsule) Columnar / ovoid cells in whorls / U shapes Produces mineralocorticoids (aldosterone) Zone fasiculata Irregular outlined cells with foamy cytoplasm Produces glucocorticoids (cortiosol) and gonadocorticoids Zona Reticularis (next to medulla) Anastomosing cords and sinusoids Produces glucocorticoids (cortisol) and gonadocorticoids (androgens) Medulla Contains pale staining cells with a rich blood supply. Controlled by preganglionic sympathetic nerve fibres à release of catecholamines Produces adrenaline, noradrenaline and opioid peptides • Describe the structural/functional regions of the adrenal gland and outline quantitative aspects of normal hormone production of the main adrenocorticosteroids in humans. Arterial supply is from A branch of the renal artery Inferior phrenic branch A branch from the aorta Venous drainage All to the adrenal vein à IVC / Renal vein Endocrine 6 • Describe the regulation of cortisol secretion via ACTH, CRH and vasopressin (ADH) steroid feedback and effects of psychological, physical stress and circadian control. Stress + CRH + hypothalamus NA, A, DA, GABA - + AVP hypothalamus + - ACTH pituitary + NA, A Adrenal medulla + - CORTISOL Adrenal cortex • Review the pharmacological, immunosuppressive and anti-inflammatory actions, permissive and synergistic effects of cortisol. Actions of cortisol Essential to cope with severe stress – increases energy substrate in the blood Anabolic effects in liver, catabolic in adipose & muscle Synergistic with Adrenalin in smooth muscle Antagonises ADH action Inhibits ACTH secretion (-ve feedback) Supresses the inflammatory response & immune system (by inhbiting arachadonic acid production Endocrine 7 Adrenal Disease • Discuss the possible clinical presentation of a phaeochromocytoma and list the syndromes of which it is a component. Phaeochromocytoma = rare tumour of chromaffin cells à secretion of catecholamines 10% are malignant 10% are extra adrenal 10% are familial Presentation Hypertension – usually paroxysmal with postural drop Paroxysms of pallor, palpitations, sweating, headache, anxiety (fear of death), abdominal pain with vomiting, constipation, weight loss or glucose intolerance Syndromes Can be a part of Neurofibromatosis, Von Hippel-lindau or MEN type 2 Investigations Measure of serum adrenaline / noradrenaline / dopamine (may be –ve as paroxysmal) Increased levels often occur in response to stress (surgery / illness) Suppression of sympathetic control (clonidine) will not suppress catecholamine release from tumour Imaging with abdo CT / MRI Management A-blockers to suppress effects for 6 weeks à surgery • List the major clinical and biochemical features of Cushing's disease, Addison's disease Conn's syndrome and congenital adrenal hyperplasia. Cushings – overactive adrenal à excess cortisol Causes 80% pituitary adenoma (increased ACTH) = cushings disease 10% adrenal neoplasm = cushings syndrome 10% ectopic ACTH production (e.g. small cell Ca in lung) NB: can be iatrogenic cortisol administration Features - Moon face, truncal obesity, glucose intolerance à hyperglycaemia (NB can develop DM due to weight increase), Hypogonadism, hirsuitism, osteoporosis, muscle weakness, bruising / striae, oedema, buffalo hump, acne, skeletal pains, mental changes, poor healing, peptic ulcers, psychosis, hypertension. Dx – ACTH measurement, 24hrs urine cortisol collection, dexamethasone suppression test. Blood glucose to check for DM Ix cause – prolonged dexamethasone, CRH test, CT/MRI Prognosis – 50% untreated die in 5 yrs (vascular disease, heart problems, increased BP. Rx – surgery (transphenoidal / transoral to remove tumour), radiotherapy, medical (suppress cortisol production with metyrapone / ketoconazole) Addisons disease – inability to make cortisol and aldosterone No cortisol = cant respond to stress No aldosterone = Na+ not reabsorbed in distal tubule à high K+ & high H+ (metabolic acidosis), Low Na+, fluid loss in urine Causes 1o causes – 95% autoimmune, TB, infections, infiltrations 2o to pituitary failure, lack of ACTH Sx – weight loss, postural hypotension (low Na+, low BP), increased pigmentation, loss of body hair, vomiting Endocrine 8 Addisonian crisis – circulatory shock, severe hypotension, hyponatraemia, hyperkalaemia, muscle cramps, nausea, vomiting, diarrhoea, unexplained fever. Ix – low serum Na+, high K+, high urine Na+, normocytic, normochromic anaemia, ST changes on ECG, hyperkalaemia ECG changes, possible TB on CXR, adrenal calcification on AXR Special Ix – ACTH test of feedback loops, adrenal Ab, aldosterone & renin levels SHORT SYNACTHEN TEST – simple test can be done on the ward. Check cortisol level, inject synacthen (ATCH analogue) then measure cortisol 30 mins later. +ve if 30 minute cortisol < 550nmol/l Rx – hydrocortisone = cortisol. Fludrocortisone (1o adrenal failure), normal BP, retain Na+, glucocorticoid in stress. Increased doses required during times of stress. Advise medic alert bracelet Conns syndrome – primary hyperaldosteronism Due to adrenal adenoma Sx - Hypertension & hypokalaemia, high normal Na+, metabolic alkalosis Aldosterone increases Na+ reabsorption in the distal tubule (Na+/K+ transport channel) à Na+ reabsorption at cost of K+ loss. Some K+ reabsorbed at cost of H+ (K+/H+ transport). Loss of H+ à high bicarb = Metabolic alkalosis. Water follows Na+ by diffusion à fluid retention à hypertension (see renal notes for more info) Ix – high aldosterone, low renin, CT/MRI Rx – spironolactone, surgery for adenoma Congenital adrenal hyperplasia 21-OH deficiency à insufficiency of hormones distal to block & increased ACTH à increase in production of hormones before the block à hyperplasia Impaired production of aldosterone & cortisol Increased production of adrenal androgens Sx - ambiguous genitalia at birth, failure to thrive, salt wasting, virilisation & developmental problems, hirsuitism Ix – high levels of 17OH-progesterone Rx – aim to replace deficiencies & suppress ACTH à suppress excess androgens. Needs close monitoring to ensure appropriate levels produced • Outline the common methods for imaging the adrenal glands including ultrasound, CT, and isotope scanning. US – show increased adrenal size CT – show mass in 3D context Isotope scans – use marked cholesterol compounds taken up for hormone production • Describe the importance of steroid cover in patients with inadequate endogenous steroid reserve, either as a result of pituitary or adrenal failure or due to long-term treatment with pharmacological doses of steroid. Increased steroid levels are required to cope with stress If levels are reduced (or suppressed due to iatrogenic use) then the body will be unable to respond to the stress à adrenal crisis Avoid this by giving steroid cover before (and during) surgery • Describe the underlying principles and interpret the results of a Synacthen test and a dexamethasone suppression test Synacthen test (addisons) Tests ability of body to produce cortisol (normally and in response to ACTH) Synacthen is synthetic ACTH Endocrine 9 Give by IM injection at any time of day Test blood at 0 and 30 minutes for plasma cortisol If Addisons is considered also test for ATCH levels a 0 minutes Normal test – cortisol > 550 nmol/l at baseline or 30 minutes Dexamethasone suppression test (cushings) High dose of glucocorticoid (dexamethasone) should suppress ACTH production à suppression of cortisol secretion After administration monitor ACTH and cortisol levels. Can be done as short test (overnight) or long test (4 days) If ACTH normal / low but cortisol remains high = adrenal problem If ACTH levels remain high (> 50) = due to high ACTH production (cushings disease / ectopic production) If some response to high dose (on 4 day test) then most likely a pituitary adenoma rather than ectopic as still some feedback mechanism Endocrine 10 GI tract & pancreas • Identify and describe the microanatomy of the pancreatic islet, including cellular interactions, vascular organisation and autonomic innervation. Islets of langerhans only makeup 1-2% of pancreas volume Exocrine tissue is dark pink/purple on H&E stain. Cells arranged in acinus with centroacinar cells Endocrine tissue is paler pink with a very dense capillary network A-Cells à Glucagon B-Cells à Insulin D-Cells à Somatostatin PP-Cells à pancreatic polypeptide • Briefly describe the steps involved in the biosynthesis of insulin. RER Insulin Synthesized in b-cells Pre-pro insulin is synthesised by the RER Transferred and processed through cell Pro insulin à insulin by cleaving of C peptide (C-peptide has no biological activity) NB: exogenous insulin doesn’t contain C peptide so check C-peptide levels if ? insulin OD Micro-vesicles Golgi (membranebound proteases) Secretory granules Hyperproinsulinaemia Occurs with high glucose when the body increases insulin release greater than processing ability Endocrine 11 Plasma membrane • Outline the control of insulin and glucagon secretion – including effects of nutrients, antonomic innervation and intrapancreatic paracrine effects. Insulin Release Nutrient stimulus – blood glucose > 5mmol/l Due to ATP à closes K+ channels à Ca2+ entry à vesicle release Potentiators – gut hormones enhance nutrient stimulated release Neural control Sympathetic à decrease release Parasympathetic à increase release Action Promotes uptake and utilisation of glucose in skeletal muscle & adipose tissue Promotes storage Glucagon Release Low blood glucose <3.5mmol/l Neural control Amino acids in gut Inhibited by high blood glucose, insulin & Somatostatin Action Hepatic glycogenolysis & gluconeogenesis Lipolysis à raise glucose Endocrine 12 Diabetes Mellitus • Describe the diagnostic criteria for diabetes mellitus. Fasting plasma glucose > 7.0 mmol / l (with no calorific intake for 8 hours) Random plasma glucose > 11.1 mmol / l One value required if the patient is symptomatic 2 independent values required if asymptomatic Glucose tolerance test is used only for borderline cases or gestational diabetes Fast for 8 hrs before test (water only) Give 75g of glucose (usually as lucosade) then… Blood samples at 0 minutes and 120 minutes Diabetes – as above Impaired fasting glucose - fasting = 6-7mmol / l Impaired glucose tolerance – 120 minute = 7.8-11 mmol / l • Classify the major types of diabetes mellitus. Type 1 = Insulin deficiency Slowly progressive T-cell mediated autoimmune destruction of the B-cells Hyperglycaemia only occurs when 70-90% of B cells destroyed 1/3 of cases are familial, also some environmental influence Young at presentation, usually lean May develop ketoacidosis ALWAYS need insulin (fatal without treatment) Glucose raises, the BP, then lipids à More prone to microvascular disease Type 2 = insulin resistance No immune disturbance. Due to a resistance to insulin à increased production à cells give in = impaired B-cell function Assoc with FH, obesity, increased BP & hyperlipidaemia Patients are usually > 30 & often overweight May develop HONK Require insulin eventually when the B-cells fail Lipids raise, then BP, then glucose à more prone to Macrovascular disease • Outline the secondary causes of diabetes including pancreatic disease, endocrine disease, drug related and genetic syndromes. Pancreatic disease – CF, Chronic pancreatitis, Pancreatectomy, Haemochromatosis, Cancer Endocrine – Cushings, acromegaly, tyrotoxicosis, Phaeochromocytoma, glucagonoma Drug induced – thiazide diuretics, corticosteroid therapy, atypical antipsychotics, antiretroviral protease inhibitors Others – lipodystrophy, acanthosis nigricans, freidreichs ataxia, dystrophia myotonica • Compare and contrast the typical presentations of Type I and Type II diabetes Type I Both types Type II Weight loss (due to fluid depletion & increased muscle & fat breakdown) Nausea & vomiting Ketoacidosis Thirst Polyuria Fatigue & malaise Blurred vision Increased infections Complications (25%) due to delayed presentation Altered mental state Endocrine 13 • Understand the principles of the dietary treatment of type 1 and type 2 diabetes Aims of good dietary treatment Good glycaemic control Avoiding hypoglycaemia (spread CHO throughout the day) Maintain appropriate weight Avoid complications and diets that aggrovate them (e.g. high protein in nephropathy) Low in sugar (but not sugar free) High in starchy CHO (esp with low glycaemic index) Low in fat (esp saturated fats) High in fibre 50-55% calories 30-35% calories NB: slowly absorbed CHO prevent rapid peaks in circulating glucose = low glycaemic index Alcohol can be taken in moderation but can à hypoglycaemia as suppresses gluconeogenesis. Also beware that alcohol is high in calories • Classify the different types of oral hypoglycaemic drugs used in Type II diabetes and outline their indications and contraindications. Sulphonylureas (chlopropamide, glibenclamide, gliclazide, tolbutamide) Promote insulin secretion (but only when there is some remaining B-cell function) High glucose à ATP production à inactivate K-ATP à depolarisation à Ca2+ influx & insulin secretion Low glucose à decrease ATP à channels open à hyperpolarisation à decreases insulin secretion Sulphonylureas à channel inhibition à increase insulin secretion Can be used in patients who Metformin is contraindicated SE - Increase weight – NOT for use in the obese & can à increased insulin resistance. Some GI disturbance (nausea, vomiting, diarrhoea, constipation) NB: If used with B-Blockers à loss of hypoglycaemic awareness (esp in elderly). Particular problem with glibenclamide (long acting sulphonylureas) AVOID – in severe renal and hepatic impairment and breast-feeding. Not for use in the obese (as can increase weight) Meglitinide analogues Promote insulin secretion because also cause K-ATP closure but act at a different site to sulphonylureas Rapid onset so used at meal times Effects are enhanced by high glucose Can à obesity and do not improve plasma lipid profile Is a risk of hypoglycaemia Biguanides (e.g. metformin) Decrease gluconeogenesis & increases peripheral utilization of glucose but mechanism unclear Required endogenous insulin 1st choice in obese patients (doesn’t cause weight gain). Doesn’t cause hypoglycaemia SE – anorexia, epigastric discomfort, diarrhoea NB: NOT for use in renal / hepatic impairment (can à lactic acidosis) Thiazolidinediones (glitazones) Decrease insulin resistance by genetic effect Activate nuclear peroxisome proliferator activated receptors (PPARs) à Altered gene expression Endocrine 14 à Insulin like effects Effects - Decrease hepatic glucose output, increase peripheral uptake & increase fatty acid uptake into adipose cells NB: LFTs need monitoring SE – weight gain, salt & water retention Can be used alone but shouldn’t be used as 2nd line unless metformin & sulphonylurea not tollerated Intestinal enzyme inhibitors Inhibit CHO digestion SE – abdominal discomfort, flatulence, diarrhoea Lipase inhibitors (e.g. orlistat) Assists in weight loss SE - steatorrhoea Hyperglycaemia 3-month diet trial OK Continue Poor control Obese Non-Obese Renal Impairment Metformin Sulphonylurea Poor control 2 from: Metformin Sulphonylurea Glitazone • Outline the principles of insulin therapy. Types of insulin Soluble insulin Acts within 30-60 minutes (give 15-30 minutes before meal) Lasts 4-6 hours Used mainly during surgery or in emergencies Rapid Acting Insulin (human insulin analogue) Acts within 15 minutes Lasts 2-4 hours Used as a pre meal bolus to increase flexibility. Good if prone to low BP pre meals Prolonged acting Insulin Intermediate = 12-24 hrs Long = > 24 hrs Mixed with Protamine or Zinc to delay absorption Endocrine 15 Administration routes IV – used only in hospital Subcut – by syringe / pen. MUST rotate site to prevent lipohypertrophy à unpredictable absorption Insulin pumps – sub cut. Continuous infusions with increase at meals. Insulin regimes Twice daily 30 minutes before breakfast (2/3 of daily dose) before evening meal Mixture of short and long acting insulin Most common regime Basal-Bolus regime Single dose of long acting and then short acting before each meal. Allows increased flexibility of meals Single daily regimes Single daily dose of intermediate Used for Type II unable to use tablets NB: Insulin requirements increase with stress, infection, trauma, puberty and the lastter 2/3 of pregnancy NB: Requirements decrease in coeliac disease, renal / hepatic impairment & Addisons disease • Describe the methods of evaluating diabetic control including urine testing, selfmonitored blood glucose testing and measurement of HBA1c. Urine Stix – used for type II Not always accurate as relies on renal thresholds Home blood glucose Finger prick tests HbA1C Gives average reading based on the last 6 weeks control (target <7%) • Describe the essential components of the annual review in diabetes care including the need for biochemical assessment of renal function (serum creatinine, proteinuria and albumin-creatinine ratio) and lipids and clinical evaluation of the eyes and feet. HbA1C Weight, BP, Plasma lipids, check for proteinuria, check renal creatinine clearance Visual acuity & examine retina Check feet, pulses & neuropathy Review CVS risk factors Review monitoring & injection techniques Review eating habits Endocrine 16 Diabetes - Metabolic complications • Outline the process of diabetic ketoacidosis (DKA) including its metabolic pathways, common reasons for its development and its management. Diabetic Ketoacidosis Due to insulin deficiency Due to undiagnosed DM / Stress / Illness / Interrupted insulin therapy Pathology Ketoacidosis is uncontrolled catabolism assoc with insulin deficiency Increased gluconeogenesis High glucose à osmotic diuresis by kidneys à dehydration Peripheral lipolysis à increased free fatty acids à liver à acidic ketones à metabolic acidosis Worsened by stress hormones (catecholamines, glucagon and cortisol) Features Hyperglycaemia à Profound dehydration due to osmotic diuresis (sunken eyes, poor turgor, low BP) due to loss of sodium, potassium and water. Hyperketonia à characteristic smell with ketones in blood and urine Metabolic acidosis à Kussmaul’s respiration = respiratory compensation à Polyuria, thirst, weight loss, abdominal pains, leg cramps, blurred vision, vomiting, weakness, Can have altered conscious level NB: in total can lose upto 3 litres extracellular (replace with saline) and 3 litres intracellular (replace with dextrose) NB: Potassium may be normal or high at presentation due to proportion of water loss. As treatment à K+ into cells à significant drop so MONITOR closely Complications Cerebral oedema can be caused by rapid reduction of glucose on starting treatment, use of Hypotonic fluids or bicarbonate. Assoc with high mortality, treat with mannitol Acute respiratory distress syndrome Thromboembolism DIC Acute circulatory failure Investigation Blood glucose > 20 mmol/l (& Ketones in plasma) Glucose & ketones in urine ABG showing acidosis (with bicarb < 12 mmol/l) U&E increased due to dehydration. Hyperkalaemia (no insulin to force it into cells) NB: will drop rapidly with Rx Increased WCC Then investigate for cause – infection screen (FBC, blood & urine culture, CRP, CXR) Management Fluid & electrolytes to replace losses Rapid acting Insulin à sliding scale Restore acid-base balance within 24 hrs NB: monitor K+ & replace as required Catheterise if no urine within 3 hrs NG tube if ongoing Treat any cause found Endocrine 17 Check local protocol • Outline the process of hyperosmolar non-ketotic (HONK) including its metabolic pathways, common reasons for its development and its management. Severe hyperglycaemia (< 50 mmol/l) without ketosis or acidosis Characteristic of type II DM Precipitated by glucose rich foods, non compliance with meds or illness Usually in elderly patients with previously undiagnosed Type II DM 40% mortality Features Decreased insulin levels (but enough to prevent ketogenesis) Glucose production unrestrained Profound dehydration (due to osmotic diuresis) Decreased consciousness (due to high osmolarity) Management Similar to DKA but monitor closely. Less insulin needed Give Heparin (hyperosmolar state à risk of stroke, MI or thrombus) Osmolality Osmolality = 2 (Na+ + K+) + glucose + urea Normal = 280-300, depressed consciousness if < 340 • Describe the typical symptoms of hypoglycaemia and outline the difference between autonomic and neuroglycopaenic symptoms. Normal blood glucose = 4-7mmol / l Hypoglycaemia = Blood glucose < 3.5 mmol / l Usually due to excess treatment (insulin overdose, sulphonylurea) Autonomic Sx Sweating Trembling Pounding heart Hunger Anxiety Neuroglypaenic Sx Confusion Drowsiness Speech difficulty Inability to concentrate Incoordination Non specific symptoms Nausea Tiredness Headache Age specific Children - Naughty / irritable Adults – Irritable / anger / aggression Elderly – visual disturbance / ataxia NB: if long standing DM with neuropathy then sympathetic features may be absent NB: If patients are aware of the Sx they can take action. Some patients lose awareness (e.g. during sleep, on B-blockers etc) • Outline the major counter-regulatory hormone responses to hypoglycaemia Suppression of insulin release Release of glucagon (impaired within 5 yrs of type I) & adrenaline (impaired a few yrs later) Release of GH & cortisol • Describe why a patient may develop hypoglycaemia. Insulin related Endocrine 18 Increased insulin levels e.g. poor diabetic control, insulinoma, intentional OD Lipohypertrophy at injection site (à poor uptake) Glucose related Missed / delayed / inadequate meal Unusual / unexpected exercise Alcohol Gastroparesis (autonomic neuropathy) or malabsorption Fulminant hepatic failure (decreased glucose production) Others Other endocrine disorder – Hypopituitarism, ACTH deficiency, Addisons disease Drug induced (sulphonylureas, quinine, salicylates, propranalol, pentamidine) • Describe the treatment of hypoglycaemia. Acute management Oral sugar (dextrose tablets) / IV dextrose Glucagon Monitor until stable Prevention Advise regular meals & snacks Carry supply of fast acting carbohydrate (sweets / lucosase) Lower insulin levels prior to planned exercise Increase CHO prior to and during unplanned exercise Frequent BM checks Endocrine 19 Microvascular and Macrovascular Complications • Describe the appearances of background retinopathy, proliferative retinopathy and maculopathy and recognise these on examination using direct ophthalmoscopy and recognise the appearance of cataract. Background Retinopathy Normal vision Haemorrhages: dot(small), blot(large) from the venous end of retinal capillaries occur deep in the retina; flame shaped haemorrhages (located in nerve fibre layer) may occur Exudates: yellowish-white deposits with well defined edges; represent precipitation of leaked lipoproteins from diseased retinal vasculature Microaneursyms focal dilatations of retinal capillaries which may leak; usually temp to macula Pre-Proliferative Diabetic Retinopathy Normal vision unless mucula involved Occurs usually after >8-10 yrs dm May be mild, moderate or severe Ischaemia – over large areas Cotton wool spots (CWS): greyish white, poorly defined fluffy edged lesions in the nerve fibre layer; represent axoplasmic accumulations adjacent to retinal nerve fibre microinfarcts Venous changes – looping & dilation / beading (compensation for ischaemia) Arterial changes – arteriolar narrowing & AV nicking – due to atherosclerosis Severe NPDR - large number of dark haemorrhages, irregular calibre variation (beading) and dilatation of retinal veins, and intraretinal microvascular abnormalities. Most patients with severe NPDR will progress to PDR in 12 months Proliferative Diabetic Retinopathy Occurs in ~ 5% of DM (more common in type I) New vessels (NV) in response to significant retinal ischaemia The new vessels… Appear as small tufts of irregularly ramifying vasculature arising from veins Are initially flat but enlarge and move forward into the vitreous Are fragile and likely to bleed with slight traction resulting in pre-retinal and/or vitreous haemorrhage Late PDR changes Retinal fibrosis Traction retinal detachment Iris neovascularisation (rubeosis iridis) & neovascular glaucoma Diabetic Maculopathy Specific type of DR with macular involvement Endocrine 20 May occur with either NPDR or PDR but more common with type II Leads to visual loss if untreated 3 types which may occur in different combinations Focal: focal leakage from microaneurysms or dilated capillaries resulting in focal retinal thickening and surrounding exudates Diffuse: diffuse leak from dilated capillaries resulting in diffuse retinal oedema which may be associated with some retinal haemorrhages but usually no exudates Ischaemic: due to closure of the perifoveal capillary network; manifests as diffuse oedema plus associated dark haemorrhages. Fluorescein angiography is important in confirming ischaemia Cateracts - Symptoms and Signs Decreased acuity, both near and distant, glare in sunshine / lights (esp with posterior subcapsular), monocular diplopia, altered colour vision (white and yellow). NO pain. Decreased red reflex +/- central black shadows, white pupil only in advanced cases. • Outline the treatment of proliferative retinopathy (pan-retinal photocoagulation) and maculopathy (focal grid laser photocoagulation) including how treatment is given. Control of diabetes and other risk factors Reduces progression & severity of retinopathy PRP – PanRetinal Photocoagulation For proliferative DR, reduces vision loss due to bleed and detachment 1500 – 3000 tiny burns in peripheral retina, spares macula, reduced peripheral vision Macular Laser Focal laser – Destroy microanerysms, exudates will slowly resolve Grid Laser – For diffuse macular oedema, low powered laser stops worsening, no improvements, can cause scotoma Vitrectomy Removal of vitreous via trans-pars-plana incision (TPPV) Removes haemorrhage, stops detatchment Future: Anti-VEGFs etc • Outline the pathology & management of renal complications of diabetes mellitus. 10% of DM patients die of renal failure Pathology Thickening of BM & accumulation of deposits in mesangium = Glomerular damage Large vessel damage à HT Ascending infection à renal damage Dilation of the afferent arteriole (due to ischaemia) è increased glomerulofiltration pressure à damage à proteinuria & albuminuria Clinical features Endocrine 21 1st Sx = microalbuminuria ( > 2.5 mmol/l in men, > 3.5 mmol/l in women) Risk factors: duration of DM, poor glycaemic control, increased BP, dyslipidaemia, FH of renal disease à albuminuria à full DM nephropathy à end stage renal disease Management Aggressive BP & lipid control ACEi are good for reducing protein loss Good glycaemic control Dietary protein restriction Once at end stage consider dialysis or transplantation • Describe the features of diabetic sensorimotor neuropathy and outline the important risks (foot ulcers and Charcot deformity). Affects approx 30% of DM pateints Due to decreased blood supply & disruption of function by sugar deposition à delayed nerve conduction velocity Symetrical sensory polyneuropathy Loss of vibration, pain & temperature sensation à progressing to proprioception loss. Usually in a glove and stocking distribution Acute Painful neuropathy Burning pains in feet, shins and thighs, worse at night Rx – TCAs, gabapentin, Valproate, Carbemazepine, TENs Multiple mononeuritis Abrupt painful onset Often affects CN III & IV Diabetic Amyotrophy Painful asymmetric wasting of quads seen in older men Autonomic neuropathy Can à tachycardia, AF, gastroparesis, bladder problems and erectile dysfunction Charcot Deformity Motor supply affected à intraosseous wasting à high arch and clawing of the foot à abnormal pressure à calluses & injury Diabetic foot ulcers Develop due to combination of pressure effects reducing arterial flow and poor sensation (so feet are moved less à greater trauma to the same area of the foot each time) Once the skin is broken there is a higher infection risk à greater incidence of amputations Management Neuopathic pain – treat as for peripheral neuropathy (see neuro notes) Ulcers – regular foot care, prompt Rx of any sores, aggressive Abx if open wounds • Discuss the macrovascular complications of diabetes; compare and contrast the distribution and severity of macrovascular disease in patients with and without diabetes (see also the section on Vascular Medicine and Surgery). Endocrine 22 2 x risk of stroke 3-5 x risk of MI (70% of DM patients die of cardiovascular disease) 50 x risk of foot amputation due to gangrene NB: DM enhances the effects of other CVS risk factors Pathology Changes seem are similar to non-DM atherosclerosis but occur earlier, are more extensive and severe Hyperinsulinaemia à promotes atherogenic changes in lipids & coagulability and raises BP Main features are thickening of capillary BM and increased vascular permeability à HT, increased deposition of lipids Peripheral vascular disease à intermittent claudication, gangrene, amputation, foot ulcers (poor blood supply & neuropathy) Endocrine 23 Thyroid gland • Understand how the embryological origins of the thyroid and parathyroid glands explains the possible location of ectopic glandular tissue. Develops from an endodermal downgrowth of the floor of the pharynx between the anterior two thirds and posterior third of the tongue. Grows from FORAMEN CAECUM (between 1st and 2nd pharyngeal arches) to thyroid cartilage thus forming the THYROGLOSSAL DUCT In adult may à thyroglossal cysts (ectopic thyroid tissue) • Understand the blood supply and relations of the thyroid gland. 10% of people have a thyroid ima artery 10% of people have a pyramidal lobe • Appreciate the histological appearance of the thyroid and parathyroid glands. The thyroid tissue comprises of a large no of follicles, lined by cuboidal epithelium and containing a pink staining colloid. The cell boundaries are poorly defined. follicle Parafollicular cells produce calcitonin (regulates Ca2+ levels) Cuboidal cells Colloid Basal lamina Normal thyroid tissue will have variable amounts of colloid in the follicles Inactive thyroid has flattened cells with large amounts of colloid Hyperactive thyroid will have little coloid Parathyroid cells are derived from the 3rd & 4th pharyngeal arches. Chief cells are the main secretory cells. Endocrine 24 Parafollicular C cells à calcitonin Capillaries • Describe the hypothalamo-pituitary control of the thyroid gland. Cold, Trauma Stress Somatostatin - + TRH (hypothalamus) + TSH (ant pituitary) + - T4 has –ve feedback T3, T4 (thyroid gland) + Cell metabolism • Outline the steps involved in the biosynthesis and storage of thyroxine (T4) and triiodothyronine (T3) in the thyroid gland, and in their secretion. Precursors of Thyroid hormone are tyrosine & iodine Trapping – cells have uptake system to obtain I2 from blood & peripheral tissues. Increased by TSH release from pituitary Oxidation – thyroid peroxidase turns I- to I2 (making it able to react). Increased by TSH. Most anti-thyroid drugs target thyroid peroxidase Organification – I2 added to benzene ring. The complex forms on the outside of the cell membrane & synthesis continues in the colloid. Taken back into cells by pinocytosis Proteolysis – complex is broken down into active form Release – hormone is released into the blood. • Describe the factors involved in the peripheral conversion of T4 to T3 or reverse T3. Conversion – after eating / at times of stress deiodinase turns T4 to T3. Thyroxine = T4, t1/2 = 7 days (bound to globulins), 80% of output of the thyroid Tri-iodothyrodine = T3, t1/2 = 2 days, 20% of output, more potent than T4 Reverse T3 = isomer which is inactive (up to 45% of T4 is converted to reverse T3) • Describe briefly the effects of thyroid hormone on cellular metabolism and the consequences of excessive or deficient hormone action. Direct actions Increased BMR & O2 consumption Stimulates CHO & Fat metabolism (like insulin), increases glucose uptake, increases lipolysis, decrease protein levels Promotes early growth in children – esp CNS – low levels à cretinism Indirect actions Enhances adrenoceptors response Increase CVS activity Increase steroid metabolism Increase bone maturation • List the common causes of goitre and the appropriate investigations required Causes of Goitre Multinodular (occurs with ageing) – can cause compression Endocrine 25 Focal nodular – may be benign or malignant. MUST be investigated Symmetrical slightly nodular – hashimotos Symmetrical diffuse enlargement Hyperthyroid (graves etc) Physiological (pregnancy & puberty) Hypertrophy to compensate for Iodine deficiency (endemic) Investigation of goitre T4, T3, TSH Thyroid antibodies Ultrasound / isotope imaging Fine needle aspiration biopsy Endocrine 26 Hyperthyroidism Primary hyperthyroid = high T3 & T4 with normal/low TSH Secondary hyperthyroid = high T3 & T4 with high TSH • Describe the classical symptoms and examination findings of hyperthyroidism Weight loss Increased appetite Irritable / altered behaviour / restlessness Tremor Heat intolerance Malaise Muscle weakness Decreased libido Gynaecomastia Oligomenorrhoea Choreoathetosis Breathlessness Palpitations Vomiting Diarrhoea Eye complaints *** Goitre Onycholysis Tall stature (childhood hyperthyroid) Hyperkinesis Tremor Tachycardia / AF with HT V/D with warm peripheries Exopthalmus *** immune infiltration of periorbital fat Lid Lag Goitre Bruits Proximal weakness Irritability / Psychosis Cardiac Failure Onycholysis Palmar erythema Conjunctival oedema Opthalamoplegia Thyroid acropachy *** Pretibial Myxoedema *** *** = only in Graves Thyrotoxic crisis Rare but life threatening - 10% mortality Sx - Fever, agitation, confusion, tachycardia, AF & can à cardiac failure PPT - by infection, radioiodine Rx or few days post thyroidectomy Rx Rehydrate & broad spectrum Abx Propranolol to control Sx Sodium Iponate will restore T3 levels within 48-72 hrs (reduces T4àT3 and inhibits release) Carbimazole will prevent synthesis of new hormone to maintain levels • Classify the causes of hyperthyroidism and outline the pathological features of Graves' disease, a toxic adenoma and a toxic multinodular goitre. Graves – (75%) IgG binds to TSH receptor à high T3 & T4, low TSH 60% have thyroid peroxidase Ab (not pathogenic but a useful marker) F:M = 10:1 High levels of HLA B8 antigen & IgG Classical triad of hyperplastic goitre, infiltrative opthalmopathy and infiltrative dermopathy. Dermopathy only in 15% Toxic multinodular goitre (20%) Solitary toxic nodule (5%) De Quervains thyroiditis – Usually in young and middle age women. transient acute inflammation, fever, malaise, neck pain. ? due to viral illness. Rx aspirin. 2o – to TSH secreting pituitary tumour Investigations T3, T4, TSH levels Thyroid scintigraphy (radioisotope scan) shows pattern of production If Sx of graves – Thyroid antibodies Endocrine 27 Thyroid peroxidase (high, but also in autoimmune hypo & multinodular) Thyroglobulin (high, but also in autoimmune hypo & multinodular) TSH receptor (only significant raised in graves) • Discuss medical therapy for hyperthyroidism including the advantages, disadvantages and important side effects. Antithyroid drugs – carbimazole Blocks thyroid hormone biosynthesis – block iodination of thyroperoxidase Will also suppress the graves process Takes 10-20 days to act – due to long t1/2 of hormone Indications – 1st episode in under 40 yrs Contraindicated in breast feeding SE– hypersensitivity rash (2%), agranular cytosis (0.2%), > 50% will relapse on stopping drug B Blockers give symptomatic control while waiting for Rx to take effect If in AF Give warfarin & return T3 to normal 50% will spontaneously convert to sinus rhythm. The other 50% require DC cardioversion • Discuss the indications for surgical treatment and the risks of complications postoperatively. This should include a description of the management of respiratory obstruction due to haematoma. Indication - Relapse after medical therapy or poor drug compliance, Cancer, large goitre Contraindications – previous thyroid surgery, dependence on voice for career (singer) Complications – Hypothyroidism – ALL! Hypocalcaemia (parathyroids often removed) – 10%, usually transient Hypoparathyroidism – 1% Recurrent laryngeal nerve palsy – 1% Recurrent hypertyroidism – if ectopic tissue Respiratory haematoma – rare if surgery done to standard. Avoid my meticulous haemostasis during surgery. If occurs then --> surgery for drainage and haemostasis • Discuss the indications for radioactive iodine therapy and the risk of complications. Radioactive iodine I 131 destroys the gland by local radiation Takes several months to act Indications – patients over 40 yrs, recurrence following surgery, other serious comorbidity Contraindicated in pregnancy & breast feeding, active graves opthamopathy Complications – hypothyroidism (40% in 1st year, 80% in 15 years), can à exacerbation of opthalmopathy Precautions – Advise meticulous toilet hygiene for 2 weeks after taking as excreted in urine. Avoid close contact with all people for 1 week and contact with children, elderly or pregnant for 2-3 weeks until dose has reduced. Endocrine 28 Hypothyroidism • Describe the classical symptoms & examination findings of hypothyroidism. Mental slowness (in infants = cretinism) Dry thin hair (inc eyebrows) and skin Tiredness Weight gain à mild obesity Carpal tunnel syndrome Deafness Deepening of voice Anaemia Cold intolerance Constipation • Bradycardia with raised BP Goitre Large tongue Slow relaxing reflexes Ataxia Heart failure, Oedema (inc periorbital), pericardial effusion Myotonia & proximal myopathy Muscular hypertrophy Classify the causes of hypothyroidism and outline the pathological features of Hashimoto's thyroiditis. Atrophic (autoimmune) Autothyroid Ab à lymphoid infiltration à atrophy & fibrosis More common in women and with increasing age Assoc with other autoimmune conditions Hashimotos thyroiditis More common in middle age women (F:M = 9:1) Atrophic changes with regeneration à goitre Firm & rubbery thyroid due to lymphoid infiltration Autoimmune component (TPO (thyroglobulin) autoantibodies) 90% have thyroid peroxidase Ab (not pathogenic but a useful marker) à hypothyroid (can initially go hyperthyroid) Thyroxine may à shrinking of goitre Post partum thyroiditis Due to immune changes during pregnancy Self limiting Iodine deficiency In Alps, Himalayas, South America and central Africa “Derbyshire neck” à Cretinism in children Dyshormonogenesis Defect in synthesis of T3 & T4 (genetic) Iatrogenic Post thyroidectomy or Iodine ablation • Describe the morphology and pathological consequences of a nodular goitre. Can à tracheal compression & dyspnoea Risk of haemorrhage into cyst Risk of malignant change • Describe the treatment of hypothyroidism. Replace thyroxine aiming to restore normal TSH levels Endocrine 29 Thyroid Cancer • Classify thyroid cancer including papillary, follicular, medullary, and anaplastic types and thyroid lymphoma. Benign adenoma More common in females Slow increase in size Rarely produce hormones Papillary - 75-85% Most common – usually in 3rd – 5th decade. F:M = 3:1 Well differentiated, multifocal lesions Mets to nodes in the neck Slow growing and excellent prognosis (even if mets) 90% @ 20 yrs Follicular – 10-20% 5th & 6th decade. F:M = 3:1 Mets to bone via blood Good prognosis – 30% @ 5 yrs Medullary – 5% 5th or 6th decade Tumour of parafollicular cells Neuroendocrine cells à increased calcitonin Usually in middle age and elderly Slow growing Met to local LNs Good prognosis Anaplastic - Rare Elderly only Small undifferentiated cells Rapid growing with extensive invasion around trachea Causes effects by compression of trachea & invasion of Jugular veins Poor prognosis – usually fatal within 1 yr Lymphoma - <5% of thyroid cancers 3f : 1m 80% of patients have autoimmune disease Tissue diagnosis Refer to oncologist • Outline the clinical presentation, diagnosis and principles of treatment of thyroid cancer. Presentations Lump in neck Dysphagia / uncomfortable swallowing Pain with local infiltration Hoarse voice – recurrent laryngeal nerve affected Palpable cervical nodes Diagnosis Check thyroid hormone levels US / MRI FNAC – Gives cytology NOT histology If in doubt then biopsy and remove Management With differentiated carcinomas – total thyroidectomy fb large dose of radioiodine to ablate any remaining tissue. à Rx with thyroxine to suppress TSH Checking endogenous T3 levels will indicate if any 2o deposits have survived If any nodes involved – removal of node chain Radio and chemotherapy can help with poorly differentiated tumours Endocrine 30 Hypercalcaemia/Parathyroid Disease • Discuss the normal control of serum calcium and outline the actions of PTH, vitamin D and calcitonin. Vitamin D – required for Ca absorption in gut PTH Increases osteoclastic activity (reabsorb bone) Increases Ca2+ absorption in gut Increases Vit D production Increases Renal Ca2+ reabsorption à increased plasma Ca2+ & increased PO4 excretion Calcitonin Inhibits osteoclasts Increases renal Ca excretion 99% of body calcium is stored in the bone Plasma calcium is carried in several forms 40-50% ionised 40-50% protein bound (to albumin) 5-10% complexed Albumin levels will affect total Ca2+ levels Adjusted Ca2+ on blood results accounts for bound Ca2+) Renal handling of Ca2+ 98% of filtered Ca2+ is reabsorbed in the tubules 90% - proximal tubule linked to Na+ reabsorption (so if dehydrated à retain Na+ & Ca2+) 10% - distal tubule regulated by PTH • List the causes of a raised serum calcium concentration including hyperparathyroidism and malignancy. Primary hyperparathyroidism (high PTH & Ca2+) or tertiary hyperparathyroidism Slow rise in Ca2+, stays below 3mmol/L. PTH high / N, steroids have no effect Malignant disease Rapid rise in Ca2+ to > 3.0mmol/L. PTH low / undetectable, suppressed by steroids 3 mechanisms Granuloma type cells produce active Vit D à absorption from gut Some tumours produce PTHrh (related hormone). Causes high Ca2+ with low PTH (ask for specific PTHrh) Lytic bone lesions Excess Vit D Excess Ca2+ intake from diet Sarcoidosis – sarcoid cells produce vit D (so avoid sun exposure) Other endocrine diseases – thyrotoxicosis, Addisons Drugs – thiazides, Vit D analogues, Lithium, Vit A Renal failure (unable to filter) • Describe the signs & symptoms of hypercalcaemia “Stones, bones, groans and psychic moans” Anorexia, nausea, vomiting, constipation Depression, fatigue, psychosis Polyuria, polydipsia, thirst (à dehydration) Proximal muscle weakness, tiredness, lethargy • Describe the classification, and pathology of parathyroid disorders. Endocrine 31 Primary Hyperparathyroidism Increased PTH and increased Ca2+ Presents with bones, moans and groans F> M, mostly in patients > 50yrs Adenoma – 75-80% Benign solitary – increased mass of chief cells in one gland (and others atrophy) Present with Sx of hypercalcaemia (general tiredness, malaise, dehydration, depression, renal calculi, polyuria, nocturia, haematuria, pain in bones, bone cysts, abdominal pain, peptic ulcers, chondrocalcinosis, corneal calcificiation Diffuse hyperplasia 10-15% Parathyroid carcinoma 5% Secondary hyperparathyroidism Increased PTH with normal or low Ca2+ Usually 2o to low serum Ca (e.g. in renal failure, low diet intake, vit D deficiency) Diffuse hyperplasia of parathyroid glands à increased resorption à normal Ca levels Tertiary hyperparathyroidism Increased PTH, increased Ca2+, Low PO4 and elevated Alk Phos Follows a long period of secondary hyperparathyroidism • Describe the investigation and early clinical management of a patient presenting with acute hypercalcaemia. Rehydration with normal saline Bisphosphonates à fall in Ca2+ May require: forced diuresis, glucocorticoids, calcitonin or haemodialysis if very severe Assess and treat cause Endocrine 32 Hypocalcaemia • List the causes of acute & chronic hypocalcaemia Acute Surgical removal (of thyroid à permanent damage of parathyroids in 1%, temporary low Ca in 10%) Parathyroid surgery (well duh!) Autoimmune parathyroid disease Rhabdomyolysis Acute pancreatitis (usually clinically obvious with increased PTH & Amylase) Alkalosis (resp or metabolic à decreased ionised Ca with normal / raised PTH) Chronic Hypoalbuminaemia (low Ca but PO4 and PTH normal) Vitamin D deficiency (will have increased PTH) Malabsorption (will have raised PTH) Hypoparathyroidism (high serum phosphate and low PTH) Pseudohypoparathyroidism (high serum phosphate and PTH – tissue becomes resistant to PTH à increased levels. Features include short stature, obesity and subcutaneous calcification) Chronic renal failure (due to impaired vit D, should have raised creatinine) Hypomagnesaemia (PTH usually normal or low, Rx low MG & Ca should correct) Bisphosphonates – prevent release from bone NB: Pseudopseudohypoparathyroidism is the Sx of Pseudohypoparathyroidism but with normal PTH and Ca • Describe the symptoms and signs of hypocalcaemia including tetany and seizures. Tetany Usually occurs if total serum Ca < 2.0 mmol/l à Increased excitability of nerves Children – carpopedal spasm, stridor (glottis spasm) and convulsions Adults – tingling in hands and feet (spams, stridor & convulsions are rare). Tappind over branches of facial nerve à twitching of facial muscles Other features Papilloedema Prolonged QT interval (may à ventricular arrhythmias) Hypocalcaemia & hyperphosphataemia à calcification of basal ganglia à grand mal epilepsy, psychosis & cateracts Hypocalcaemia with low vit D à rickets / osteomalacia • Outline the investigation and treatment of a patient presenting with hypocalcaemia. Investigation Check Ca2+ levels, PTH and Vit D Management Treat alkalosis by rebreathing air (paper bag / give 5% CO, 95% O2) Slow IV injection of Calcium Gluconate Long term can give oral Ca2+ & Vit D supplements Endocrine 33