Summary Book Endocrine Flashcards
Examination steps for hyperthyroidism
Thyroid followed by cardio, then upper limb reflex and confirm proximal myopathy
What are increased beat adrenergic effects
hyperreflexia, bounding pulse, tremor, sweaty palm, tachycardia, atrial fibrillation, flow murmur, high output heart failure
Graves eye signs
proptosis, exophthalmos, ophthalmoplegia
Diffuse goitre with bruit
graves or if hypothyroid then iron deficiency or chronic autoimmune
Nodular goitre ddx
MNG, nodule, cancer
Tender goitre
thyroiditis
Retrosternal goitre examination findings
pembertons sign and dullness to percussion
Cause of hoarseness
Recurrent laryngeal nerve palsy
Signs of hyperthyroidism
If graves = proptosis, exophthalmos, ophthalmoplegia. Goitre. Increased cardiac rate wit possible associated failure. Proximal myopathy, hyperreflexia, tremor, sweaty, hypopigmentation of skin, nail changes (thyroid acropachy = clubbing, swelling, periosteal reaction), accelerated bone remodelling with risk of osteoporosis, pretibial myxoedema
Autoimmune conditions associated with hyperthyroidism
diabetes mellitus, vitiligo, coeliac disease
Aetiology for hyperthyroidism
Autoimmune = graves and Hashimoto. Drug induced = amiodarone (type 1 increases synthesis due to iodine load, type 2 due to thyroid toxicity). Multinodular goitre, toxic nodule, thyroiditis (infectious, ischaemic, lymphocytic), hCG mediated, TSH dependant (TSHoma), iodine induced, paraneoplastic, iatrogenic (thyroxine therapy), factitious
Investigations for hyperthyroidism
Thyroid function tests (TSH secreted by anterior pituitary), T3/4, thyroid antibodies, TSH receptor (graves = activating, Hashimoto = inhibiting), thyroid peroxidase (hashimoto thyroiditis - most common), thyroglobulin. Can also consider ultrasound, radioactive iodine uptake and biopsy.
Management of graves disease.
Symptom control - beta blocker. Reduced thyroid hormone synthesis - thioamides (carbimazole or propylthiouracil), radioactive iodine ablation, thyroidectomy. Adjunctive therapies - corticosteroids (inhibit peripheral conversion and secretion). Management of orbitopathy - smoking cessation, if severe radioactive iodine is contraindicated, corticosteroids, Teprotumumab, Tocilizumab, Rituximab.
Examination for hypothyroidism
Thyroid plus hand, then upper limb reflex
Signs of decreased beta adrenergic effects
slowed mentation, hyporeflexia, bradycardia, pericardial effusion, obesity
Signs of hypothyroidism
goitre, hyporeflexia, slowed mentation, bilateral ptosis, loss of distal eyebrows, tongue swelling, macroglossia, bradycardia, pericardial effusion, proximal myopathy, carpel tunnel syndrome, dry skin and hair thinning, weight gain, ascites, other autoimmune conditions
Aetiology of hypothyroidism
Autoimmune - hashimoto. Thyroid organ failure - atrophy, infiltration, ischaemic, fibrosis, post infectious, amiodarone. Thyroiditis. Iatrogenic - radioactive iodine, thyroidectomy. TSH dependent - pituitary or hypothalamic. Thyroid hormone resistance.
TFT finding differences between primary, secondary and tertiary hypothyroidism
Primary = TSH >10, low T3/4. Secondary = low TSH, low T3/4. Tertiary = low TSH, low T34, low thyroid releasing hormone.
Goals and strategy for management of hypothyroidism
Goals = symptom management, normalise TSH, avoid iatrogenic hyperthyroidism. To normalise TSH titrate levothyroxine (T4).
When should levothyroxine be increased or decreased?
Increase in pregnancy. Decrease in weight loss, aging and androgen therapy.
Examination for cushings syndrome
Skin with blood pressure and proximal myopathy
Pathophysiology of cushings syndrome
high cortisol
Signs of cushings syndrome
cognitive dysfunction / psychosis, increased facial width, dorsal fat pad, skin pigmentation, hypertension, decreased limb fat, thin skin / bruising, osteoporosis, insulin resistance, increased abdominal fat, abdominal striae, hypogonadism, hypercoagulable state and increased infection risk
Organ and ddx of primary cushings syndrome
Adrenal. DDX: adenoma, carcinoma, bilateral macronodular adrenal hyperplasia, primary pigmented nodular adrenocortical disease.
Organ and ddx of secondary cushings syndrome
Anterior Pituitary = Cushings Disease. DDX: ACTH -secreting pituitary adenoma.
Organ and ddx of tertiary cushings
Hypothalamic. DDX: CRH secreting lesion.
Most common and oncological causes of cushings
Most common is endogenous with steroid use. Paraneoplastic causes of cushings are SCLC, pancreatic and thyroid.
Investigations for suspected cushings
- Exclude steroids. 2. Demonstrate hypercortisolism with either 24hr urinary cortisol, midnight salivary cortisol or low dose dexamethasone suppression test. 3. Also serum ACTH (<1.1 = ACTH independence, >4.4 ACTH/CRH dependence). 4. If low ACTH can use high dose dexamethasone suppression test = if cortisol <5 microg/dL then pituitary cause, if no suppression then ectopic. 5. CRH stimulation test -> ACTH response = pituitary, no response = ectopic.
Tests for suspected primary cushings
CT of adrenals +/- MRI, and petrosal sinus sampling of microadenoma
How to screen for complications of cushings syndrome
HbA1c, fasting blood sugar, urinalysis, ECG, ECHO, sleep study, colorectal cancer screening, DEXA, vit D, dyslipidaemia
Management of primary cushings
laparoscopic adrenalectomy
Management of secondary cushings
Transsphenoidal pituitary resection, stereotactic radiotherapy for persistent or recurrent disease, bilateral adrenalectomy (require lifelong supplementation, may cause nelsons syndrome - enlarged pituitary gland / abnormal hormones / invasive adenomas)
Medical therapy to lower cortisol
Adrenal enzyme inhibitor (ketoconazole), adrenolytic agent, dopamine agonist (cabergoline), somatostatin analogue (pasirotide), glucocorticoid antagonists (mifepristone)
Pathophysiology of addisons
low cortisol
3 key findings of addisons
- hyperpigmentation. 2. postural BP. 3. electrolyte derangement (low sodium / BLS, high K)
Causes of addisons
autoimmune adrenal disease (80%), TB, histoplasmosis, amyloid/sarcoid, bilateral adrenal haemorrhage
Diagnosis of addisons
short synacthen test - no increase in plasma cortisol level with ACTH
Management of addisons crisis
glucocorticoid stress dosing
Examination of acromegaly
hands + cardio + visual fields + thyroid palpate + abdo palpate
Signs of acromegaly
enlarged head circumference, hypopituitarism, bilateral hemianopia, macroglossia, obstructed sleep apnea, prominent jaw, gaps between teeth, thyroid nodules, left ventricular hypertrophy, cardiomyopathy, aortic or mitral regurgitation, hypertension, osteoarthrtis, carpel tunnel syndrome, spade like hands, diabetes mellitus, organomegaly, BPH, colonic polyposis, hypogonadism, osteoporosis, peripheral neuropathy
Pathophysiology of acromegaly
excessive secretion of growth hormone and thus insulin life growth factor 1.
Causes of acromegaly
> 95% are due to somatotroph pituitary adenoma
Mortality of acromegaly
> 60% cardiovascular and 25% cancer
Diagnosis of acromegaly
serum IGF-1 (high sensitivity), glucose suppression test (growth hormone >1mg/ml 2 post 75g oral glucose), MRI of pituitary
Investigations of acromegaly
Reduced cortisol / TSH / T4 / FSH / LH / testosterone. elevated prolactin 25%. Also HbA1c, blood glucose, urinalysis, ECG, ECHO, sleep study, colorectal cancer screening, DEXA, vit D, calcium, dyslipidaemia.
Management of acromegaly.
- surgical resection - 1st line trans-sphenoid pituitary surgery. 2. Somatostatin analogue (octreotide) - inhibits GH release. 3. Dopamine agonist (cabergoline) for hyperprolactinemia. 4. Growth hormone receptor antagonist (pegvisomant). 5. stereotactic radiotherapy - 40% risk of hypopituitarism. 6. cardiovascular risk reduction
Examination for systemic lupus erythematous
hands and cardio
Presentation for SLE
malaise, weight loss, nausea/vomiting, fever, sicca - dry eyes/mouth
Signs of SLE
delirium, dementia, seizures, psychosis, anaemia, malar butterfly rash (spares nasolabial folds), diffuse photosensitive erythema, discoid rash, alopecia, oral and nasal ulcers, pleurisy, pleural effusions, tenosynovitis, myositis, myalgia, arthralgia, jaccoud’s arthropathy (symmetric, polyarticular, migratory, non-erosive arthritis with correctable deformities), proteinuria, cellular casts, membranous nephropathy, pericarditis, myocarditis, endocarditis, mitral and aortic valve involvement (usually regurg), pulmonary arterial hypertension, accelerated atherosclerosis, haemolytic anaemia, leukopenia, lymphopenia, thrombocytopenia, antiphospholipid antibodies (lupus anticoagulant)
Risk factors of SLE
procainamide, hydralazine, isoniazid, methyldopa
Autoantibodies for SLE
ANA sensitive 99.95%, dsDNA specific, anti-RO (sjogrens + neonatal lupus), anti-U1 RNP (myositis overlap), ESR, CRP, compliment
Investigations for SLE
autoantibodies, Xray (symmetric nonerosive deforming polyarthropathy), renal (uec, urinalysis, proteinuria, casts, sediment +/- biopsy), haem (FBC, low complement correlates with activity, anaemia, low platelets), endocrine (osteoporosis screen), cardiovascular (antiphospholipid antibodies, TTE ?pHTN, exclude coronary artery disease), MRI CNS involvement
Non-pharmacological management of SLE
smoking cessation, immunisation, exercise
Pharmacological management of SLE
NSAID - arthralgia. Hydroxychloroquine - skin / joints. Glucocorticoids - flares, also CNS / cardiac / pleural / blood involvement. Maintenance therapy - steroid sparing agent (Azathioprine (after TPMT test) or Methotrexate (with folic acid). Severe disease requires high dose steroids plus immunosuppression with mycophenolate, cyclophosphamide, rituximab, azathioprine, methotrexate. Also management of lupus nephritis, raynuads, antiphospholipid syndrome and osteoporosis.
Management of lupus nephritis
Mycophenolate, steroid, anti-proteinuric (ACEi/ARB), renal biopsy,
Management of raynauds
calcium channel blocker (nifedipine as dihydropyridines)
Management of antiphospholipid syndrome
warfarin
Management of OP
vit D, calcium, bisphosphonates
Examination of scleroderma
Hands plus cardio
What does CREST stand for
calcinosis, Raynaud’s, oesophageal dysfunction, sclerodactyly, telangiectasia
Signs of limited scleroderma
CREST. bird like facies and restricted oral aperture, telangiectasia of fingers / lips / GIT. Oesophagitis, dysphagia, primary biliary cholangitis, pulmonary arterial hypertension, raynauds, digital ischaemic ulceration, calcinosis, contractions, sclerodactyly (thickening of skin on fingers), functional limitations. Skin thickening is limited to fingers, hands, forearms and lower legs.
Signs of diffuse scleroderma
Oesophagitis, dysphagia, gastroparesis, GAVE, 30% have ILD (bibasal predominance), renal failure / renal crisis, bird like facies with restricted oral aperture, hypertension, pulmonary hypertension, restrictive cardiomyopathy, pericarditis, reynauds, digital ischaemic ulceration, calcinosis, contractions, sclerodactyly. Skin thickening extends to upper arms, thighs, back, abdomen, trunk and face. Peripheral deforming small joint polyarthritis and tenosynovitis with DIPs affected.
Risk factor of scleroderma
family history
Autoantibodies for scleroderma
Centromere - CREST and limited. Scl70/topoisomerase - diffuse and severe lung disease. RNA polymerase 1 and 3 - renal and skin disease. U1 - RNA - overlap with mixed connective tissue disease.
Investigations for scleroderma
autoantibodies, raised ESR / IgG, anaemia, malabsorption of vitamins ADEK, renal function (crisis occurs early in disease and more common with doses of prednisolone above 15g/day, CXR (reduced lung volumes, reticular interstitial opacities), HRCT (ILD particularly NSIP), respiratory function tests (restrictive picture with reduced TLC / RV / DLCO), ECHO (?pHTN, ?RV failure, restrictive biventricular failure), 6MWT+ABG on room air, endoscope (oesophagitis).
Management of Scleroderma
General (skin care, cold avoidance, smoking cessation, avoidance of alcohol). Reynauds (dihydropyridine calcium channel blocker, iloprost). Oesophagitis (PPI). Skin (methotrexate or mycophenolate if within 3 years of onset, cyclophosphamide if severe). Arthritis (low dose steroid, hydroxychloroquine). ILD (cyclophosphamide or mycophenolate). Pulmonary Hypertension(endothelin antagonist, PDE5 inhibitor, prostacyclin, riocigent). Renal (ACEi also hypertension). Influenzae and pneumococcal vaccinations. Haemopoietic stem cell transplantation.
Examination of Dermatomyositis
hands and lung/heart
Pathophysiology of dermatomyositis and polymyositis
Polymyositis and dermatomyositis are idiopathic inflammatory myopathies with proximal muscle weakness and muscle inflammation. DM has characteristic skin findings. Both carry a risk of solid organ malignancies (cervix, ovarian, lung, bladder, pancreas, stomach).
Signs of dermatomyositis
Shawl sign, photodistribution erythema, heliotropic reaction (swollen / purple eyelids), oesophageal dysfunction, symmetrical muscle weakness / wasting / tenderness, ILD, cardiac conduction issues, grottans papules, raynauds, small joint symmetrical polyarthritis, scaly rough dry skin, muscle weakness of neck / girdle.
Investigations of dermatomyositis
Myositis specific auto-antibodies - anti-Jo1. Muscle inflammation markers - CK, LDH, troponin, AST, ALT. Skin biopsy - interface dermatitis. Xray - dystrophic calcification of affected muscles (also consider MRI). Muscle biopsy - both polymyositis and dermatomyositis demonstrate muscle fibre necrosis, degeneration, regeneration and cellular infiltrates. PM = CD8 predominant. DM = CD4 predominant.
Management of dermatomyositis
Non pharmacological (exercise, aspiration precautions, sun protection). Pharmacological (corticosteroids for induction, azathioprine (post TPMT testing), IVIG for severe disease, hydroxychloroquine for skin disease). Malignancy screening. Management of chronic steroid complications.
Key findings for polymyositis
Symmetrical proximal weakness (painless) with raised CK/anti Jo. Muscle only.
Key findings for induction body myositis
Distal hand involvement, wasting, dysphagia, antibody negative, foot drop - ankle / quadriceps / hand / forearm involvement.
5 types of HLA-B27 Seronegative Spondyloarthopathies
- Ankylosing Spondylitis. 2. Reactive Arthritis. 3. Psoriatic Arthritis. 4. IBD-associated Arthritis. 5. Juvenile Idiopathic Arthritis
Signs of Ankylosing Spondylitis
Anterior uveitis, neck instability, aortic regurgitation, apical lung fibrosis, amyloidosis, autoimmune bowel disease, enthesis Achilles tendon, veritable joint fusion, reduced spinal mobility, modified Schober’s test (>5cm), occiput to wall distance increased, dactylitis (sausage fingers, swelling, PIP), asymmetrical peripheral oligoarthropathies, fixed flexion of hips, decreased chest expansion.
Investigations for ankylosing spondylitis
Elevated inflammatory markers, negative autoantibodies, HLA-B27, sacral lumbar imaging (xray +/- MRI), CXR, renal function and ECHO before NSAIDs
Management of ankylosing spondylitis
Non-pharmacological (smoking cessation, exercise, education). Pharmacological (NSAID first line, methotrexate / sulfasalazine for peripheral arthritis, TNF-alpha inhibitors (infliximab) - second line for axial arthritis (remember to exclude HBV + TB), IL-17 inhibitor (secukinumab)).
Presentation of ankylosing spondylitis
lower back pain with morning stiffness and worse at night. +/- hip/shoulder pain and peripheral joint involvement
Risk factors for ankylosing spondylitis
family history
Diagnosis of ankylosing spondylitis
- age <45y. 2. >3months of back pain. 3. sacroiliitis (bilateral grade 2 or unilateral grade 3). 4. HLA B27 + two other features (head pain, uveitis, dactylitis, IBD, raised CRP, response to NSAID)
Describe the disease and demographics of mixed connective tissue disease
Overlap with SLE / SSc / PM and females 20 - 40 years old.
Signs of mixed connective tissue disease
pulmonary hypertension (main cause of death), ILD, oesophagitis, reynauds, hand and finger oedema, deforming polyarthritis of small joints (like RA)
Serum findings of mixed connective tissue disease
anti-U1 RNP, ANA + speckled, also monitor renal function
xray findings for mixed connective tissue disease
erosive deforming polyarthropathy
ECHO, cxr and HRCT findings for mixed connective tissue disease
ECHO: pulmonary hypertension. CXR + HRCT: basal predominant fibrosis and restrictive lung disease.
Management of mixed connective tissue disease
- Corticosteroids (good response for SLE, poor for SSc). 2. Cyclophosphamide or Rituximab for severe or refractory disease. 3. Pulmonary hypertension management (calcium channel blocker, prostacyclin analogue, endothelin-1 antagonist, PDE5 inhibitor, guanylate cyclase inhibitor). 4. Complications of chronic corticosteroids (diabetes, osteoporosis, hypertension, infections). 5. Management cardiovascular risk factors.
Complications of obesity
IHD, stroke, OA, diabetes, OSA, NAFLD, hypogonadism, social issues
Management of obesity
Exercise, diet, bariatric surgery (if BMI >40 or >35 with diabetes or hypertension), liraglutide (GLP-1 analogue) or orlistat (lipase inhibitor)
Risk factors and diagnosis of obesity
Diagnosis = increased waist circumference, triglycerides, blood pressure, fasting glucose and decreased HDL. Risk factors = family history, medications (anti-psychotics, TCA, steroids, insulin) lifestyle, eating, depression, cushings, thyroid disease
Management of hypercalcaemia
IVH, bisphosphonates, calcitonin, parathyroidectomies
Investigations for hypercalcaemia
calcium, vit D, PTH, PTH receptor protein, malignancy screen (CT CAP), 24 hour urine for Familial Hypocalciuric Hypercalcemia
Examination for hypercalcaemia
neck scar for parathyroid surgery, lymphadenopathy, organomegaly, bradycardia for hypercalcaemia, symptoms of thyrotoxicosis or addisons
Symptoms and risk factors for hypercalcaemia
Symptoms = fatigue, confusion, constipation, polyuria/polydipsia, muscle/bone aches. Risk factors = history of cancer (b symptoms), history of PTH or CKD (tertiary PTH) or MEN (parathyroid cancer), drug history (thiazide, lithium, vit D, calcium), family history of Familial Hypocalciuric Hypercalcemia.
Compare MEN 1, MEN 2A and MEN 2B
MEN1 = pituitary adenoma, parathyroid hyperplasia, pancreatic tumour. MEN2A = parathyroid hyperplasia, medullary thyroid carcinoma, pheochromocytoma. MEN2B = mucosal neuromas, marfanoid body habitus, medullary thyroid carcinoma, pheochromocytoma.
Describe pathophysiology of renal osteodystrophy
Due to increase in phosphate levels due to decreased excretion. Increased parathyroid hormone and FGF-23 - which increases with phosphate excretion. Parathyroid hormone also increases calcium resorption - therefore bones become weaker. FGF-23 also lowers vit D activation, reducing calcium plasma levels.
Management of osteoporosis
calcium, vit D, bisphosphonate, denosumab (MAB for RANK-L), teripantide (fracture after 1 year of antiresorptive). Also reduce falls risk - rationalise meds, foot wear, eye wear, walking aides, allied health.
Indications for bisphosphonates
over 70 years old with T <2.5, primary prevention with osteopenia and three months of steroids, minimal trauma fracture
Investigations for osteoporosis
BMD with DEXA scan, calcium, vit D, PTH, ALP, TFT, investigate myeloproliferative disorder or metastatic cancer in minimal trauma fracture, bone biopsy in osteomalacia
Indications for DEXA scan
minimal trauma fracture, primary hyperparathyroidism, all women over 65 and men over 70, cushings disease, prolonged steroid use, CKD (renal osteodystrophy)
Risk factors for osteoporosis
post menopause, elderly, low body weight, inactivity, drugs, alcohol. Hyperthyroidism, steroids, hyperparathyroidism, CKD, gastrectomy, hypogonadism, chronic inflammation. Medications = steroids, PPI, anti-convulsant, CNI, SSRI, alcohol.
Diagnosis of diabetes
fasting glucose >7 on 2 occasions, HbA1c >6.5%, OGTT >11
Presentation of diabetes
polyuria, polydipsia, weight loss, infections
Secondary causes of diabetes
steroids, calcineurin inhibitors, cushings, acromegaly, pancreatic disease
Risk factors for diabetes
obesity, sedentary lifestyle, EtOH, family history, over 45years old, indigenous, gestational diabetes, PCOS. CV risks = hypertension, hyperlipidaemia, smoking, family history.
Investigations for diabetes
fasting BSL, HbA1c, insulin, GAD antibodies, c-peptide. T1DM antibodies = glutamine acid decarboxylase, insulin autoantibody, insulinoma associated protein 2, zinc transporter 8.
Monitoring for diabetes
Frequency? Hypoglycaemia awareness, check pre-drive (if asymptomatic, nil hypos in 6 months, then every 2nd trip), sick day management, insulin to carb ratio (T1DM).
Allied health required for diabetes
GP, podiatrist, ophthalmologist, dietitian
Pharmacological management of diabetes
1st line metformin. 2nd line sulfonylurea (beware of hypo). DPP4 inhibitor (sitagliptin). GLP-1 agonist (Lineglutide) use if CCF and obese (causes weight loss. SGLT2 (empagliflozin) - CCH/IHD.
Complications of diabetes
Episodes of DKA and hypoglycaemia. Microvascular - retinopathy, neuropathy (peripheral, autonomic, sexual), nephropathy (PCR). Macrovascular - cardiac, stroke, peripheral vascular disease (foot ulcer, sexual). Autonomic - orthostatic hypotension, gastroparesis, erectile dysfunction.
Autoimmune conditions associated with T1DM
vitiligo, thyroid disease, coeliac, pernicious anaemia, Addison’s, autoimmune polyglandular syndrome
Acute management of adrenal crisis
Steroids (hydrocortisone), fluids (normal saline), electrolyte replacement
Confirmation of adrenal crisis
Synacthen test
Long term management of adrenal crisis, primary verse secondary
Primary- hydrocortisone and fludrocortisone
Secondary- hydrocortisone (stress dose when sick)
