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Endocrinology Shanice Richardson www.peermedics.com Contents Hyperthyroidism + thyrotoxicosis crisis Hypothyroidism + myxoedema crisis Cushing’s Syndrome Addison’s Disease Hyperaldosteronism Multiple Endocrine Neoplasia (MEN) Parathyroid pathology (Hypercalcemia) Phaeochromocytoma Thyroid – HPT axis Hyperthyroidism Most common cause is Grave’s disease. Others = Toxic multinodular goitre & Amiodarone Characterised by Low TSH, High T4 Symptoms • Weight loss • Restlessness • Heat intolerance • Palpitations • Increased sweating • Pretibial myoxedema • Diarrhoea • Oligomenorrhea • Anxiety • Tremor • Exopthalmus Investigations • TFTs! – TSH + T4 • TSH receptor antibodies (90-100% present in Grave’s Disease) • ECG Treatment • Propanalol = Can be used to relieve symptoms • Carbimazole = anti thyroid function, reducing thyroid hormone production. AGRANULOCYTOSIS - Watch out for sore throat • Radioiodine = destroys thyroid stunts child growth and unborn fetus • Surgery = thyroidectomy followed by levothyroxine Thyrotoxic Storm Life threatening condition Precipitated by infection, amiodarone, thyroxine, non compliance with carbimazole, surgery, DKA, MI, trauma • • • • • Symptoms Hyperthermia >41oC Tachy/AF >140bpm NVD, Abdo pain Agitation/psych osis Seizure/Coma Investigations • BM • ABG • TFT • CRP • Cultures • Infection screen • Chest Xray • ECG Treatment • Immediate IV access and fluids • IV propanolol C/I in asthmatics – esmolol • Antithyroid drugs e.g. carbimazole/PTU for 4 hours, followed by Lugol’s solution (iodine) • Steroids to prevent peripheral conversion of T4 to T3 • Treat underlyingcause e.g. antibiotics Hypothyroidism Primary Iodine deficiency, Druginduced Hashimoto’s thyroiditis (goitre) Subacute thyroiditis (de Quervains) – painful goitre and raised ESR Secondary Not enough TSH hypopituitarism Symptoms • Big neck (goitre) • Reflexes reduced/slow • Ataxia • Dry, thin hair and skin • Yawning/drowsy/coma • Cold hands and reduced temperature • Ascites +/- non pitting oedema (lids, han • Round puffy face, obese • Depression • Immobile +/- ileus • CCF Investigations • TFTs! Primary = high TSH, low T4 Secondary (rare) = low/normal TSH, low T4 • Anti-TPO antibodies – positive in 90% of those with Hashimoto’s thyroiditis Treatment Levothyroxine (T4) , review at 12 weeks Myxoedema Crisis • Ultimate hypothyroid state before death • Precipitated by: Infection, Trauma/Surgery, MI, Stroke, non compliance to levothyroxine Signs and symptoms • Looks hypothroid • Hypothermia <35.5oc • Bradycardia • Low blood pressure • Respiratory depression • Confusion/Psychosis • Seizure/Coma • Intestinal obstruction • Hypoglycaemia Investigations • BM • ABG • TFT • CRP • Cultures • Infection screen • Chest Xray • ECG Treatment • ITU for ventilation • Fluids, oxygen • Correct hypoglycemia • IV T3 slowly • IV hydrocortisone • Antibiotics to treat infective cause • ACTIVE WARMING Cushing’s Syndrome Chronic glucocorticoid excess from the adrenal glands, resulting in hypercortisolism Causes • ACTH dependent = Cushing’s disease (pituitary tumour secreting ACTH producing adrenal hyperplasia) • ACTH independent = Steroids, adrenal adenoma Signs and symptoms Buffalo neck hump Moon face – facial plethora Central obesity - “lemon on a stick” Purple striae Acne Hirsutrism Cellulitis Thin skin Bitemporal hemianopia Osteoporosis Tiredness Depression Diabetes Hyperpigmentation (Ahmed Al-Naher) Investigations • Dexamethasone suppression test • 24hr urinary free cortisol • MRI pituitary Treatment • If iatrogenic, remove steroids • Medications = ketoconazole/metyrapone acts as a cortisol inhibitor • Surgery - leading cause is cushing’s disease, removal of pituitary adenoma Addison’s disease Adrenal insufficiency, caused by autoimmunity in 80% of cases. Global glucocorticoid and mineralocorticoid insufficiency. (reduction in cortisol and aldo Signs and symptoms • Hyperpigmentation • Tiredness • Tearful, weakness • Anorexia • Faints • Depression • N+V • Abdominal pain • Postural hypotension • Hypoglycaemia Investigations FBC/U&E – low Na+ and high K+ due to lack of mineralcorticoid (aldosterone) Glucose – reduced due to a lack of cortisol Short synacthen (ACTH) test - Adrenal insufficiency is generally excluded if: The 30 minute increment in serum cortisol is >200 nmol/L The maximum serum cortisol level is >550 nmol/L Treatment • Replace glucocorticoids with hydrocortisone 15-25mg daily Must warn patients of abruptly stopping steroids. Steroid intake should be increased before strenuous activity/exercise • Replace mineralocorticoids with fludrocortisone daily Hyperaldosteronism Excess production of aldosterone independent of the RAAS system. Commonly caused by Conn’s syndrome or bilateral idiopathic adrenal hyperplasia Role of aldosterone • Na+ and Cl- reabsorption • K+ excretion • H20 retention Condition will result in increased sodium and water retention aswell as decreased renin production. Signs and symptoms Polyuria Polydipsia Hypertension Signs of hypokalemia – weakness, tiredness, muscle cramps Alkalosis Investigations • U&Es, Renin and aldosterone levels – if on diuretics, anti-hypertensives, steroids, potassium or laxatives, withhold for 4 weeks before testing • High resolution CT abdomen • Adrenal vein sampling Treatments Conn’s : Laparascopic adrenalectomy Bilateral adrenocortical hyperplasia: aldosterone anatagonist e.g. spironalactone/amiloride/eplerone Parathyroid • Parathyroid hormone • Reduction in serum calcium/increased phosphate • Increases serum calcium, decreases phosphate via the bones, kidney and small intestine Hyperparathyroidism Primary 80% solitary adenoma, 20% hyperplasia of all 4 glands Associated with MEN Secondary Parathyroid hyperplasia and a result of low calcium, normally always caused by chronic renal failure Tertiary A result of ongoing secondary hyperparathyroidism, but the secondary cause has been resolved. Usually 4 gland hyperplasia Signs and Symptoms Depends if primary/secondary, and how long it has been going on for, but for exam purposes… “BONES, STONES, ABDOMINAL GROANS and PSYCHIC MOANS” Bone pain/Fracture Renal stones Peptic ulceration/constipation/pancreatitis Polydipsia/Polyuria Hypertension Depression Investigations Bloods – FBC, U&E high Ca2+ high PTH low phosphate (unless in renal failure) High ALP Imaging Osteopenia Erosion of terminal phalangeal tufts Sub periosteal resorption Renal osteodystrophy (secondary) Management Conservative: • Increase fluid intake to prevent stones • Avoid thiazides • Reduce calcium and vit D intake Surgery indications (primary): • Elevated serum calcium >1mg/dL above normal • Hypercalciuria >400mg/day • Creatinine clearance <30% compared with normal • Episode of life threatening hypercalcemia • Nephrolithiasis • Age <50 years • Neuromuscular symptoms • Reduction in BMD , T score lower than -2.5 Excision of adenoma or all 4 glands S/E: Hypoparathyroidism, recurrent laryngeal nerve damage Secondary Phosphate binders Vit D Multiple Endocrine Neoplasia Autosomal dominant inheritance, causing the formation of functioning hormoneproducing tumours in multiple organs 3P’s MEN1 gene Parathyroid (95%) Pituitary (70%) Pancreas (50%) insulinoma, gastrinoma Most common presentation is symptoms of: Hypercalcemia Acromegaly Cushings Prolactinoma Anaemia Weight loss Raised plasma glucose MEN type IIa RET oncogen e 2P’s, 1T Parathyroid (60%) Phaechromocytoma Medullary Thyroid Cancer (70%) Most common presentation is symptoms of: Thyroid mass Diarrhoea Agression Raised plasma calcitonin Hypercalcemia MEN type IIb RET oncogen e 1P, 1T Phaechromocytoma (50%) Medullary Thyroid Cancer (100%) MARFANOID NEUROMAS Most common presentation is symptoms of: Visible lumps Muslce hypotonia Chronic constipation Phaechromocytoma symptoms MEN management Most treatable form of pancreatic neoplasia and hypercalcemia Surgical exicision of tumours where possible, plus symptomatic relief Surveillance for development of additional tumours Family screening by serum calcium in MEN1, and genetic testing for RET mutations in MEN2 Phaeochromocytoma Catecholamine producing tumour of the adrenal cortex (adrenaline, noradrenaline,dopamine) Symptoms Severely hypertensive – episodic or sustained Headaches Palpitations Sweating Anxiety Investigations 24hr urine collection CT imaging? Management Surgery with alpha & beta blockade Quiz 1) Name 5 (or more) signs/symptoms of Cushing’s Syndrome 2) A 33 year old female is referred by her GP with thyrotoxicosis. Following a discussion of management options she elect to have radioiodine therapy. Which one of the following is the most likely adverse effect? 1) Hypothyroidism 2) Thyroid Malignancy 3) Agranulocytosis 4) Oesophagitis 3) A 36 year old woman presents feeling cold all the time. On examination a firm, non-tender goitre is noted. Blood test reveal: TSH 34.2 mU/l (0.5-5.5mu/l) Free T4 5.4 pmol/l (9-18pmol/l) What is the most likely diagnosis? 1) Primary atrophic hypothyroidism 2) Pituitary failure 3) De Quervain’s thyroiditis 4) Iodine deficiency 5) Hashimoto’s thyroiditis 4) A 20 year old woman presents to the ED feeling drowsy and with generalised abdominal pain. Her blood pressure is 94/30mmHg. U&Es show: 1) Gastroenteritis 2) Addisonian crisis 3) Intra-abdominal haemorrhage 4) Ecstasy abuse 5) T1DM Which one of the following is most likely to be seen in a patient with multiple endocrine neoplasia (MEN) type 1? 1) Phaeochromocytoma 2) Insulinoma 3) Marfanoid body habitus 4) Medullary thyroid carcinoma 5) RET gene