Endocrinology Flashcards
What is type 1 diabetes?
Autoimmune destruction of pancreatic beta-cells causes reduced insulin production, resulting in hyperglycaemia
List aetiology/risk factors for type 1 diabetes
Autoimmunity
Genetics (HLA DR3/4)
Latent autoimmune diabetes of adulthood
List clinical features of type 1 diabetes
Polyuria Polydipsia Weight loss Fatigue Malaise Blurred vision (retinopathy)
What investigations would you do for type 1 diabetes?
Bloods: FBC, U+E, LFT’s, eGFR
Antibodies: anti- islet cell, GAD
Screening for retinopathy/nephropathy/neuropathy
What are the parameters for impaired glucose tolerance testing in diabetes?
Fasting: less than 7 mmol/l
2h oral glucose level: greater than 7.8, less than 11.1 mmol/l
What are the parameters for impaired fasting glucose testing in diabetes?
Fasting: greater than 6.1, less than 7 mmol/l
What are the WHO diagnostic criteria for diabetes?
Fasting glucose greater than 7 mmol/l
Random glucose greater than 11.1 mmol/l
HbA1C greater than 48
Either symptomatic + 1 positive lab test or asymptomatic + 2 positive lab tests
List two rapid-acting insulins
Humalog
Novorapid
List two short-acting insulins
Actrapid
Humulin S
List two intermediate-acting insulins
Insulatard
Humulin I
List two long-acting insulins
Lantus
Levemir
Novomix 30 insulin has how much short and how much long -acting insulin?
30% short-acting
70% long-acting
List the main insulin regimens that patients may be on
Once-daily: long-acting before bed
Twice-daily: short-acting pre-breakfast and pre-dinner
Basal-bolus: long-acting before bed, short-acting before meal
What is type 2 diabetes?
Relative insulin deficiency caused by insulin resistance/reduced sensitivity, resulting in hyperglycaemia
List aetiology/risk factors for type 2 diabetes
Asians Obesity Low level of exercise Cardiovascular disease Monogenic twins
List clinical features of type 2 diabetes
Polyuria Polydipsia Obesity Fatigue Malaise Blurred vision Recurrent infections
List the main drug classes (and examples) used in type 2 diabetes
Biguanides (metformin) Sulfonylureas (gliclazide, glibenclamide) TZD's (pioglitazone) DPP-IV inhibitors (sitagliptin) GLP-1 analogue (exenatide) Alpha-glucosidase inhibitors (acarbose)
What does metformin do? List side effects
Reduces hepatic gluconeogenesis, increases insulin sensitivity
No weight gain or hypo risk
SE: lactic acidosis, GI upset, avoid if eGFR less than 35
What does gliclazide do? List side effects
Increases insulin secretion from pancreatic B-cell
SE: weight gain, hypoglycaemia
What does pioglitazone do? List side effects
Enhances PPAR-alpha to increase insulin gene transcription, also reduces hepatic gluconeogenesis
SE: fluid overload, weight gain, osteoporosis
What does sitagliptin do?
Increases incretin effect of GLP-1 and GDP (delays gastric emptying, reduces appetite)
What are the components of metabolic syndrome?
Central obesity
Hypertension
Hyperglycaemia
Dyslipidaemia
Outline management of metabolic syndrome
Exercise (Tai Chi)
Weight reduction, orlistat
Statin, anti-hypertensive, metformin +/- pioglitazone
What is the pathophysiology of diabetic ketoacidosis?
Reduced insulin results in reduced cellular uptake of glucose, causing less pyruvate and more acetyl-coA
Acetyl-coA is converted to ketone bodies and acetate
List aetiology/risk factors for diabetic ketoacidosis
Non-compliance Missed dose, missed meal Infection (esp UTI) MI Steroid use Pancreatitis Surgery Alcohol-induced
List clinical features of diabetic ketoacidosis
Drowsiness Vomiting Dehydration Polyuria, polydipsia Ketotic "pear-drop" breath Kussmaul (deep) breathing
What investigations would you do for diabetic ketoacidosis?
Glucose usually greater than 11
Bloods: FBC, U+E, osmolarity, ABG
CXR
Urinary ketones, culture
Outline management of diabetic ketoacidosis
NG tube if vomiting/unconscious
IV insulin 6u per hour, increase if poor response
IM insulin 20u if no infusion pump
Monitor U+E ever hour, aim for glucose to drop by 5mmol/l
IV fluids
What is hyperosmolar hyperglycaemic state (HHS)?
Hyperosmolar state caused by uncontrolled hyperglycaemia, usually in type 2 diabetics
List clinical features of HHS
Dehydration
Stupor, coma
Impaired consciousness
Outline management of HHS
9L saline over 48h (slower rate than DKA)
Replace K
May or may not need insulin
List aetiology/risk factors of hypoglycaemia
Insulin/sulfonylurea use Increased activity Missed meal Alcohol binge Drugs (aspirin, ACEi, B-blocker, quinine) Pituitary insufficiency Liver failure Addison's disease Islet cell tumour
List clinical features of hypoglycaemia
Sweaty Anxious Tremor Confusion, coma Dizziness Vision trouble Seizure
What investigations would you do for hypoglycaemia?
Blood glucose
Prolonged OGTT, fasting tests
Blood insulin/c-peptide/ketones if symptomatic
Outline management of hypoglycaemia
Oral sugar + long-acting starch
IV dextrose/IM glucagon
List aetiology/risk factors for hyperthyroidism
Autoimmunity (Grave's disease, associated conditions such as vitiligo, T1DM, Addison's) Toxic multinodular goitre (elderly, iodine-deficient) TSH-secreting tumour Acute thyroiditis (De Quervain's) Amiodarone, lithium Ectopic thyroid tissue Iodine excess Radiation exposure
List clinical features of hyperthyroidism
Irritability, anxiety Heat intolerance Sweating, warm skin Tremor Increased sympathetic drive Weight loss, diarrhoea Labile emotions Oligomenorrhoea Thin hair Goitre/nodule, bruit Eye disease Pretibial myxoedema in Grave's
List typical eye signs seen in Grave’s disease
Lid lag Lid retraction Exophthalmus Ophthalmoplegia Proptosis
What investigations would you do for hyperthyroidism?
TSH (low), T4 (high), T3 (high) Anti-TPO antibody Anti-TSH receptor antibody IgG Isotope scan for nodule/goitre shows smooth symmetrical butterfly-shape
Outline management of hyperthyroidism
Carbimazole, propylthiouracil in pregnancy
B-blocker for symptoms
Radioiodine
Thyroidectomy
What is thyroid storm?
Rapid deterioration of hyperthyroidism
List clinical features of thyroid storm
Hyperthyroid signs and symptoms Fever Confusion, coma Diarrhoea and vomiting Goitre AF/tachycardia Heart failure
Outline management of thyroid storm
Counteract peripheral effects and treat complications Propranolol, osmolol in asthmatic Carbimazole Steroid Digoxin if heart is fast
List aetiology/risk factors for hypothyroidism
Autoimmunity (Hashimoto's) Primary atrophy (diffuse lymphocytic infiltration) Thyroidectomy Radioiodine Postpartum Amiodarone, lithium, iodine Turner's, Down's syndrome
List clinical features of hypothyroidism
Tired, slow, sleepy Low mood Cold intolerance Bradycardia Sparse hair, dry skin, cold hands Constipation Menorrhagia Weakness Goitre Weight gain, puffy face Memory change/loss
What investigations would you do for hypothyroidism?
TSH (high), T4 (low), T3 (low)
Anti-TPO antibody
Anti-TBG antibody
FBC for anaemia
Outline management of hypothyroidism
Levothyroxine (T4)
Restore and monitor metabolic rate
What is myxoedema coma?
Severe hypothyroid state
List clinical features of myxoedema coma
Hypothyroidism signs and symptoms Often over 65yo Hypothermia Hyper-reflexia Coma, seizures Goitre Hypotension Cyanosis
Outline management of myxoedema coma
Liothyronine (T3) intravenously
Hydrocortisone
IV fluids
Treat complications and heart failure
List aetiology/risk factors for goitre
Pregnancy Puberty Autoimmunity Thyroiditis Iodine deficiency Radiation exposure Malignancy, cysts Tuberculosis
What are the typical types of goitre?
Smooth non-toxic
Toxic (Grave’s, De Quervain’s)
Multinodular non-toxic
Toxic multinodular
List clinical features of thyroid cancer
Palpable nodule in neck, goitre Dysphagia Hoarseness Weight loss Signs of hyper/hypo thyroidism
What investigations would you do for thyroid cancer?
USS-guided FNA
LN biopsy
Iodine scan
What are the different subtypes of thyroid cancer?
Papillary
Follicular
Medullary
Anaplastic
What is the most common subtype of thyroid cancer and how does it spread?
Papillary
Lymphatic spread to nodes, lung
How does follicular thyroid cancer spread?
Haematogenous spread to bone, lung
Which thyroid cancer may be part of MEN2 syndrome? From which cells does it arise and what does it produce?
Medullary
Derived from para-follicular C cells
Produces calcitonin
Which thyroid cancer has the poorest prognosis?
Anaplastic
List causes/pathophysiology of primary, secondary and tertiary hyperparathyroidism
Primary: adenoma, gland hyperplasia, cancer
Secondary: low vit D, chronic renal failure
Tertiary: prolonged secondary causes autonomous gland hyperplasia, causing unchecked PTH release
Which lung cancer may produce PTH?
Squamous cell lung cancer
List clinical features of hyperparathyroidism
Weakness Fatigue Low mood Thirst, dehydration Polyuria Renal stones Abdo pain Pancreatitis Ulcers Osteopenia/porosis, fractures
Describe PTH and Ca levels in primary, secondary and tertiary hyperparathyroidism
Primary: increased PTH, increased Ca
Secondary: increased PTH, decreased Ca
Tertiary: very increased PTH, increased Ca
Which scan would be used to detect PTH-related adenoma?
Sestamibi scan
List causes/pathophysiology of primary, secondary, pseudo and pseudopseudo hypoparathyroidism
Primary: gland failure, autoimmunity, DiGeorge syndrome
Secondary: radiation, surgery, hypomagnesium
Pseudo: end-organ resistance to PTH due to GNAS1 mutation
Pseudopseudo: pseudo with normal biochemistry
List clinical features of hypoparathyroidism
Cramps Numbness Parasthesiae Spasms Trousseau sign Rovstek sign
Outline management of hypoparathyroidism
Ca supplements
Calcitriol
Synthetic PTH
What are multiple endocrine neoplasia syndromes?
Inherited autosomal dominant disorders involving functioning hormone-producing tumours in multiple organs
MEN1 syndrome involves altered tumour-suppressor/ret proco-oncogene gene (delete as appropriate)
MEN1 syndrome involves altered tumour-suppressor gene
MEN2 syndrome involves altered tumour-suppressor/ret proco-oncogene gene (delete as appropriate)
MEN1 syndrome involves altered ret proco-oncogene
Which tumours typically occur as part of MEN1 syndrome?
Parathyroid hyperplasia/adenoma (95%) Pancreatic tumours (gastrinoma, insulinoma, glucagonoma) Pituitary adenoma Adrenal tumour Carcinoid tumour
Which tumours typically occur as part of MEN2 syndrome?
Thyroid (medullary) carcinoma
Adrenal (phaeochromocytoma)
Parathyroid adenoma
Mucosal neuroma
What is Von-Hippel Lindau syndrome?
Germ-line mutation of tumour suppressor on c3p
Which tumours typically occur as part of Von-Hippel Lindau syndrome?
Bilateral renal cell cancer
Retinal and cerebellar hemangioblastoma
Phaeochromocytoma
What is Addison’s disease?
Primary adrenal insufficiency
Destruction of adrenal cortex results in reduced aldosterone, cortisol and androgen release
List aetiology/risk factors for Addison’s disease
Autoimmunity Tuberculosis Adrenal mets (lung, breast, kidney) Lymphoma Opportunistic infections in HIV Adrenal haemorrhage, adrenalectomy
List clinical features of Addison’s disease
Pigmented skin/palmar creases Amenorrhoea Tiredness Weakness Dizziness Weight loss Abdo pain Vomiting Postural hypotension
What would you find on investigations for Addison’s disease?
Bloods: hyponatraemia, hypokalaemia Low glucose Raised 9am ACTH Short synACTHen test fails to increase cortisol Plasma renin + aldosterone
Outline management of Addison’s disease
Hydrocortisone
Fludricortisone if reduced aldosterone
Double dose in illness/injury
List aetiology/risk factors for secondary adrenal insufficiency
Long-term steroid use
HP axis disease (reduced ACTH production)
Skin pigmentation occurs in secondary adrenal insufficiency. True/False?
False
No ACTH produced so would not cross-react
What are the 2 main causes of hyperaldosteronism?
Conn’s syndrome (adenoma)
Bilateral adrenal hyperplasia
List clinical features of hyperaldosteronism
Asymptomatic
Hypertension
Hypokalaemia (weakness, tetany, cramps, numbness)
What would you find on investigations for hyperaldosteronism?
Aldosterone : renin ratio (raised aldosterone, reduced renin)
Saline suppression test if APR increased (would fail to suppress aldosterone)
CT/MRI adrenals
Adrenal vein sampling
Outline management of hyperaldosteronism
Adrenalectomy if unilateral adenoma
Spironolactone/amiloride if bilateral adrenal hyperplasia
What is phaeochromocytoma?
Rare catecholamine-producing tumour arising from chromaffin cells in adrenal medulla (sympathetic ganglion cells)
List aetiology/risk factors for phaeochromocytoma
10% malignant 10% bilateral 10% extra-adrenal 10% familial MEN2 Neurofibromatosis Von-Hippel Lindau syndrome
List clinical features of phaeochromocytoma
Episodic headache
Sweating
Tachycardia
Hypertension
What investigations would you do for phaeochromocytoma?
Urinary catecholamines
Clonidine suppression test if borderline
Abdo CT/MRI, PET scan
MIBG scan
Outline management of phaeochromocytoma
Alpha-blocker (phenoxybenzamine) then beta-blocker (propranolol)
Surgical excision
What is Cushing’s syndrome?
Chronic glucocorticoid (cortisol) excess
List ACTH-dependent causes of Cushing’s syndrome
Cushing’s disease (bilateral adrenal hyperplasia, ACTH-producing pituitary adenoma)
Ectopic ACTH production (small cell lung cancer)
Ectopic CRF (thyroid, medullary, prostate cancers)
List ACTH-independent causes of Cushing’s syndrome
Adrenal adenoma
Steroid use
Adrenal nodular hyperplasia
List clinical features of Cushing’s syndrome
Weight gain Mood change Proximal weakness Gonadal dysfunction Central obesity Moon-face Achilles tendon rupture Buffalo neck lump Abdominal striae
What would you find on investigations for Cushing’s syndrome?
Dexametasone suppression test in ACTH-dependent causes fails to suppress cortisol
Outline management of Cushing’s syndrome
Trans-sphenoidal excision of adenoma
Adrenalectomy
Ectopic ACTH (metyrapone)
List hypothalamic causes of hypopituitarism
Kallman's syndrome Tumour Inflammation Infection (meningitis, TB) Ischaemia
List pituitary causes of hypopituitarism
Trauma Surgery Irradiation Inflammation Autoimmunity Ischaemia (apoplexy, DIC, Sheehan syndrome)
List clinical features of hypopituitarism (split up into hormone deficient features)
GH: central obesity, dry wrinkly skin, reduced strength and balance
FSH/LH: oligo/amenorrhoea, reduced fertility, low libido, hypogonadism (reduced pubic hair, small testes, low volume ejaculate)
TSH: hypothyroidism features
ACTH: adrenal insufficiency features
Alabaster skin in panhypopituitarism
What investigations would you do for hypopituitarism?
Basal tests (hormone levels)
Dynamic tests (stress tests)
Insulin stress test for GH/ACTH (would induce hypoglycaemia to raise GH and cortisol normally)
Prolonged glucagon test if insulin test contraindicated
Water deprivation test for ADH (would induce ADH release normally)
SynACTHen test for ACTH (would induce cortisol release normally)
List the common pituitary adenomas
Usually benign adenomas Prolactinoma GH-secreting PRL + GH -secreting ACTH-secreting LH/FSH/TSH - secreting
List clinical features of pituitary tumours
Headaches Bitemporal hemianopia Altered appetite Precocious puberty CN III, IV, VI palsy CSF rhinorrhoea Effect of hormone release
Outline management of pituitary tumours
Hormone replacement
Trans-sphenoidal surgery for macroadenomas
Radiotherapy if resistant/recurrent
Dopamine agonist for prolactinoma (cabergoline)
Where do craniopharyngiomas develop?
Arise from Rathke’s pouch, located between pituitary and floor of 3rd ventricle
How does hyperprolactinaemia typically arise?
Loss of tonic inhibition of prolactin release by dopamine
List aetiology/risk factors for hyperprolactinaemia
Prolactinoma Disinhibition by compression of pituitary stalk Dopamine antagonists (metoclopramide) Oestrogen therapy (OCP) Antipsychotics Alpha-methyldopa Pregnancy Breastfeeding Stress
List clinical features of hyperprolactinaemia
Oligo/amenorrhoea Infertility Galactorrhoea Weight loss Dry vagina Sexual dysfunction Reduced pubic/facial hair Osteoporosis
Outline management of hyperprolactinaemia
Dopamine agonist (cabergoline) Trans-sphenoidal surgery for adenoma
List clinical features of acromegaly
Thickened skin and soft tissues Change in appearance Headache, vision disturbance Big hands/feet Coarse face, wide nose, big supraorbital ridge, big tongue Weight gain Amenorrhoea Impotence, low libido Acanthosis nigricans Goitre Proximal weakness Carpal tunnel syndrome
What investigations would you do for acromegaly?
Glucose tolerance test (normally would suppress GH) IGF-1 levels MRI pituitary Visual fields Lipids, glucose
Outline management of acromegaly
Trans-sphenoidal surgery for adenoma Somatostatin analogue (octreotide) Dopamine agonist (cabergoline) GH antagonist (pegvisomant)
What is diabetes insipidus?
Deficiency (cranial) or insensitivity (nephrogenic) to ADH
List aetiology/risk factors for cranial diabetes insipidus
Idiopathic Congenital defect Tumour, craniopharyngioma, mets Trauma Hypophysectomy Histiocytosis Sarcoidosis Haemorrhae Encephalitis
List aetiology/risk factors for nephrogenic diabetes insipidus
Inherited
Metabolic (hypokalaemia hypercalcaemia)
Chronic kidney disease
Drugs (lithoum, demeclocycline)
List clinical features of diabetes insipidus
Polyuria Polydipsia Dehydration Nocturia "tasteless" urine
What would you find on investigations for diabetes insipidus?
Increased plasma osmolality
Decreased urine osmolality
Dilute urine
Water deprivation test would fail to concentrate urine
Outline management of diabetes insipidus
Desmopressin for cranial DI
Thiazide for nephrogenic DI
What is SIADH?
Inappropriately high ADH levels
List aetiology/risk factors for SIADH
Malignancy (SCLC, pancreas, prostate, thymus, lymphoma) Pneumonia, TB Meningitis Vasculitis Hypothyroidism Alcohol withdrawal Drugs (opiates, SSRI, psychotropics) Trauma
List clinical features of SIADH
Confusion Irritability Fits Coma Nausea
What would you find on investigations for SIADH?
Hyponatraemia (urine hypernatraemia)
Decreased plasma osmolality
Outline management of SIADH
Treat cause Fluid restrict Salt +/- loop diuretic if severe Demeclocycline (ADH inhibitor) Vaptans may be trialled
