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EndoDIABETES INSIPIDUS..............................................................................................................................................PITUITARYHYPOPITUITARISM - PITUITARY FAILURE PITUITARY.....................................................................................

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ENDOCRINE

CONDITIONS Endo

PITUITARY......................................................................................................................................................... 2 HYPOPITUITARISM - PITUITARY FAILURE............................................................................................................2 DIABETES INSIPIDUS..............................................................................................................................................3 PITUITARY TUMOURS.............................................................................................................................................5 ACROMEGALY..........................................................................................................................................................6 PROLACTINOMA......................................................................................................................................................7 SIADH (syndrome of inappropriate antidiuretic hormone secretion).........................................................................8 FEMALE HYPOGONADISM...................................................................................................................................10 MALE HYPOGONADISM........................................................................................................................................11 ADRENALS..................................................................................................................................................... 12 ADRENAL INSUFFICIENCY...................................................................................................................................12 ADDISONIAN CRISIS / ADRENAL SUPPRESSION..............................................................................................14 CUSHING SYNDROME..........................................................................................................................................15 PRIMARY HYPERALDOSTERONISM....................................................................................................................17 PHAEOCHROMOCYTOMA....................................................................................................................................18 DIABETES....................................................................................................................................................... 19 DIABETES MELLITUS TYPE 1...............................................................................................................................19 DIABETES MELLITUS TYPE 2...............................................................................................................................21 OTHER TYPES OF DIABETES..............................................................................................................................27 DYSLIPIDAEMIA.....................................................................................................................................................28 STATINS..................................................................................................................................................................29 OBESITY.................................................................................................................................................................29 DIABETIC EMERGENCY................................................................................................................................ 31 HYPOGLYCAEMIA..................................................................................................................................................31 HYPERGLYCAEMIA...............................................................................................................................................32 KETOACIDOSIS (DKA)...........................................................................................................................................32 HYPEROSMOLAR HYPERGLYCAEMIC STATE....................................................................................................34 THYROID......................................................................................................................................................... 36 HYPERTHYROIDISM..............................................................................................................................................36 THYROTOXIC CRISIS............................................................................................................................................37 GRAVE’S DISEASE................................................................................................................................................38 THYROIDITIS..........................................................................................................................................................40 HYPOTHYROIDISM................................................................................................................................................42 MYXOEDEMA COMA..............................................................................................................................................43 THYROID NODULES  NODULAR HYPERPLASIA............................................................................................44 THYROID CANCER................................................................................................................................................45 DISORDERS RELATED TO CALCIUM........................................................................................................... 47 HYPERCALCEMIA..................................................................................................................................................47 HYPOCALCEMIA....................................................................................................................................................48 HYPERPARATHYROIDISM....................................................................................................................................49 HYPOPARATHYROIDISM......................................................................................................................................51 OSTEOMALACIA....................................................................................................................................................52 OSTEOPOROSIS....................................................................................................................................................53 PAGET’S DISEASE OF BONE................................................................................................................................56 BISPHOSPHONATES.............................................................................................................................................57 MULTIPLE ENDOCRINE NEOPLASIA............................................................................................................ 58 CARCINOID SYNDROME.......................................................................................................................................60

PITUITARY HYPOPITUITARISM - PITUITARY FAILURE Define

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CONDITIONS

Deficiency in one or more of the hormones secreted by the anterior pituitary  GH, TSH, ACTH, LH, FSH, prolactin (posterior pituitary  ADH and oxytocin) Panhypopituitarism is deficiency of all pituitary hormones  progressive loss of all pituitary function, in the order of LH/FSH, GH, TSH, ACTH, prolactin Aetiology/risk factors  Pituitary Masses o Most commonly adenomas (including non-secretory) o Others include craniopharyngioma, meningioma, glioma, metastases o Cysts  Pituitary Trauma  radiation, surgery, base of skull fractures  Hypothalamic Dysfunction  due to anorexia, starvation, over-exercise  Infiltrative Diseases  TB, sarcoidosis, haemochromatosis, Langerhans' cell histiocytosis  Infection  meningitis, encephalitis  Genetic Mutations  Pit-1 and Prop-1 genes  Vascular  Pituitary apoplexy, Sheehan’s syndrome o Pituitary apoplexy  intra-pituitary haemorrhage or infraction in the presence of a pituitary adenoma. It results in ischaemia of the pituitary and life-threatening hypopituitarism. o Sheehan’s syndrome  pituitary infarction, haemorrhage and necrosis following post-partum  Simmonds disease  acquired Panhypopituitarism  infiltrative processes, adenomas, iatrogenic Epidemiology Pituitary adenoma annual incidence  1/100,000 Symptoms and signs  Depend on aetiology + type of hormone deficiency: o Hypogonadism (LH or FSH)  Females  delayed puberty, loss of secondary sexual hair, breast atrophy, amenorrhoea, dyspareunia, low libido, infertility, hot flushes  Males  erectile dysfunction, soft small testicles, gynaecomastia, infertility, decreased libido, delayed puberty, loss of secondary sexual hair o GH  low mood, fatigue, low exercise capacity/muscle strength, central adiposity, reduced muscle mass, osteopenia o Hypothyroidism (TSH)  weight gain, fatigue, constipation, cold intolerance, dry skin, hair loss, low mood o Adrenal insufficiency (ACTH)  anorexia, nausea, vomiting, weakness o Prolactin (uncommon)  absence of lactation, often following Sheehan’s syndrome  Simmond’s disease  insidious onset agalactorrhea, amenorrhoea and hypopituitarism  Pituitary apoplexy  sudden onset, life-threatening panhypopituitarism with headache, vomiting + visual disturbance (bitemporal superior quadrantanopia) + hormone dysfunction Investigation  Pituitary function tests  low T3, T4, + TSH, LH, FSH, testosterone (men), oestradiol (women), prolactin + 8am cortisol + ACTH o Can also do ATCH stimulation test and insulin tolerance test  inadequate cortisol response  MRI/CT brain  identify cause  Bloods  low IGF-1 Management 1. Treat correctable underlying cause

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2. Hormone replacement o ACTH deficiency  Hydrocortisone (need to double this if unwell) o TSH deficiency  levothyroxine o Females with GnRH deficiency  Oestrogen and/or progesterone  fertility not desired  Gonadotrophins  fertility desired o Males with GnRH deficiency  Testosterone  fertility not desired  Gonadotrophins  fertility desired o GH deficiency  recombinant human growth hormone (somatotropin) o ADH deficiency  desmopressin  (if posterior pituitary deficiency; causing central DI) Complications  Infertility  Dwarfism (children)  Myxoedema coma + Addisonian crisis  Corticosteroid over replacement  hypertension, diabetes, Cushing syndrome, peptic ulcers  Thyroxine over replacement  Osteoporosis, arrhythmias  GH over replacement  peripheral oedema, hypertension, paraesthesia, hyperlipidaemia, glucose intolerance DIABETES INSIPIDUS Define A disorder of inadequate secretion or of insensitivity to vasopressin (ADH) leading to hypotonic polyuria (lots of dilute urine) Aetiology/risk factors  Cranial/central DI  caused by failure of ADH secretion by the posterior pituitary o Idiopathic o Tumours  pituitary tumour, craniopharyngioma o Infiltrative  sarcoidosis o Infection  meningitis o Vascular  aneurysms, Sheehan syndrome o Trauma  head injury, neurosurgery o Inherited causes  recessive/dominant causes  Nephrogenic DI  caused by insensitivity of the collecting duct to ADH. This leads to aquaporins failing to be activated, so the luminal membrane of the collecting duct remains impermeable to water, leading to a large volume of hypotonic urine and polydipsia. o Idiopathic o Genetic  X linked recessive AVPV2 mutation o Polycystic kidney disease + sickle cell + renal sarcoidosis or amyloidosis o Drugs  lithium o Poorly controlled DM o Chronic hypercalcaemia or hypokalaemia or protein malnutrition  Psychogenic polydipsia (also called primary polydipsia)  excessive fluid intake

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o Seen in children and schizophrenics Epidemiology Epidemiology depends on aetiology, but mean age of onset is in 20s Symptoms and signs  Polyuria + nocturia of dilute urine  Polydipsia  In children  Enuresis (bed-wetting), sleep disturbance  Hypernatremia  irritability, restlessness, lethargy, spasticity, and hyper-reflexia, muscle twitching, seizures, coma  Dehydration  tachycardia, reduced tissue turgor, postural hypotension, dry mucous membranes  Signs of the cause Investigation  Blood + urine analysis  High plasma osmolality (>300mOsm/kg) but low urine osmolality ( 600 Osmol/kg) o DI  lack of ADH means urine cannot be concentrated so urine osmolality remains low (< 400 Osmol/kg)  Cranial  after desmopressin, urine osmolality rises >50% (800 after desmopressin)  Nephrogenic  after desmopressin, urine osmolality remains low (can’t respond to desmopressin) (rises by 400-600 Osmol/kg Management Cranial 1. Parenteral or oral desmopressin (DDAVP - vasopressin analogue) Nephrogenic 1. Maintenance of adequate fluid intake (drink lots)  Sodium restriction +/- pharmacotherapy  hydrochlorothiazide  Treat underlying cause Complications  Hypernatremia  high sodium  Thrombosis  Bladder and renal dysfunction  Desmopressin over replacement  water intoxication + hyponatremia Prognosis  Depends on cause  Cranial DI may be transient following head trauma  It may be cured by removing the cause (e.g. drug discontinuation, tumour resection) PITUITARY TUMOURS

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Define Benign tumours (adenomas) of the pituitary gland formed from pituitary cells that can produce active pituitary hormones or be non-secreting Aetiology/risk factors  Pituitary tumours are monoclonal in origin  arise from the proliferation of single, mutated pituitary cells, where somatic cell mutations stimulate cellular growth rate  There are 3 types: o Chromophobes  70%  Some are non-secretory and some cause hypopituitarism  50% produce prolactin, a few produce ACTH or GH  Local pressure effects in 30% o Acidophil  15%  Secrete GH or prolactin  Local pressure effects in 10% o Basophil  15%  Secrete ACTH  Local pressure effects rare  Tumours are either: o Microadenoma 1cm  aggressive  A non-functioning adenoma may crush the stalk leading to increase prolactin levels  by lowering dopamine inhibition as there is reduced blood flow o The increased prolactin will be relatively small  but will be massively raised in prolactinoma  No specific cause; can occur as a part of MEN 1 syndrome  Most common (in order)  prolactinomas, non-secreting, adenomas, GH secreting, then ACTH Epidemiology Common cause of intracranial neoplasms. Adenomas are much more common than carcinomas. Symptoms and signs Local effects  due to expanding pituitary mass:  Headaches  usually retro-orbital or bitemporal. Worse on waking o Sudden catastrophic headaches may be due to pituitary apoplexy o Very large tumours may cause obstruction of CSF, resulting in hydrocephalus and expansion of lateral ventricles  Visual field defects  bitemporal hemianopia  tumour compressing the optic chiasm o Upper quadrant defect > lower quadrant defect = inferior chiasmal compression = pituitary tumour o lower quadrant defect > upper quadrant defect = superior chiasmal compression = craniopharyngioma  Cranial nerve palsies  diplopia + facial numbness  Extensive extension into hypothalamus may cause disorders of appetite, thirst, temp regulation or consciousness Hypopituitarism  see above Feature of hormone excess, due to secretion by tumour  see below Investigation  MRI/CT with enhancement  see tumour

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Pituitary function tests  T3, T4, + TSH, LH, FSH, testosterone (men), oestradiol (women), prolactin + 8am cortisol + ACTH o Will be high if tumour secretes it o Low if tumour pressure is suppressing release  Alpha subunit of human pituitary glycoprotein hormones  elevated in non-functioning adenoma Management Micro-adenoma 1. Observation Macro-adenoma 1. Tran-sphenoidal surgery + hormone replacement 2. Radiotherapy + dopamine agonist or somatostatin analogues Pituitary apoplexy Without mass effects or neurological deficit 1. Glucocorticoids + Observation 2. Tran-sphenoidal surgery + hormone replacement With mass effects and/or neurological deficit 1. Parenteral glucocorticoids + analgesia and IV fluid hydration  Tran-sphenoidal surgery + hormone replacement Complication Meningitis, DI, neurological deficits, hypopituitarism, hydrocephalus 

ACROMEGALY Define Constellation of signs and symptoms caused by hypersecretion of GH in adults (after puberty). Excess GH before puberty results in gigantism Aetiology/risk factors  Most cases are caused by a GH-secreting pituitary adenoma o Prolactin is co-secreted in 30% of causes  mixed tumour  Causes hyperprolactinaemia  galactorrhoea, irregular periods, decreased libido, impotence  Rarely caused by excess GHRH caused by somatotroph hyperplasia from hypothalamic ganglioneuroma, bronchial carcinoid or pancreatic tumours  Excess GH stimulates growth of bone and soft tissue through IGF-1 Epidemiology RARE (5/1,000,000), Age affected  40-50 yrs Symptoms and signs  Enlargement of: o Soft tissue  nose, ears, lips, vocal cords, hands + feet o Hands and feet  rings and shoes may not fit  Large spade-like doughy hands o Hepatomegaly, splenomegaly, cardiomegaly, colonic polyps  Hypopituitarism  due to compression of normal pituitary tissue o Symptoms of  hypogonadism, hypothyroidism, hypoadrenalism (see above)  Visual disturbances  bitemporal hemianopia, caused by optic chiasm compression  Impaired glucose tolerance, as GH opposes insulin  diabetes

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 HTN  probably due to chronic GH/IGF-1 excess  Headaches, lethargy  Joint pain + premature osteoarthritis  Carpel tunnel syndrome  Cartilage enlargement, paraesthesia  Increased sweating, thick greasy skin  Husky resonant voice  due to thickening of vocal cords  Hearing loss  Obstructive sleep apnoea  Acanthosis nigricans Face  Prominent eyebrow ridge  Supraorbital enlargement  Prominent cheeks + broad nose bridge  Prognathism  jaw protrudes out  Dental malocclusion  Large tongue (macroglossia)  causing snoring Investigation  Plasma GH measurement during + after an oral glucose tolerance test (OGTT) o Normal  glucose causes GH levels to drop o Acromegaly  GH levels remain high  Pituitary MRI or CT  to image tumour and see effect on optic chiasm  Serum IGF-1  high  GH stimulates IGF-1 secretion (but varies with age and increased during pregnancy and puberty)  Pituitary function tests  9am cortisol, free T4 and TSH, LH, FSH, testosterone (men)  to test for hypopituitarism Management 1. Trans-sphenoidal hypophysectomy for resect-able pituitary tumours (+ radiotherapy if needed) 2. Subcutaneous Somatostatin Analogues (SSA)  octreotide, lanreotide o Side-effects  abdominal pain, steatorrhoea, glucose intolerance, gallstones  Oral Dopamine Agonists if GH and prolactin secreting  bromocriptine, cabergoline o Side-effects  nausea, vomiting, constipation, postural hypotension, psychosis (RARE) 3. GH receptor Antagonist  pegvisomant 4. Radiotherapy Complications  CVS  Cardiomegaly, Hypertension, atheromatous disease  Respiratory  Obstructive sleep apnoea  GI  Colonic cancer  Metabolic  Hypercalcaemia, Hyperphosphataemia, Renal stones, DM, Hypertriglyceridaemia  Psychological  Depression, Psychosis (from dopamine agonists)  Complications of Surgery  Nasoseptal perforation, Hypopituitarism, Adenoma recurrence, CSF leak, Infection Prognosis GOOD with early diagnosis and treatment but physical changes are irreversible PROLACTINOMA

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Define A benign lactotroph adenoma that secretes prolactin. Aetiology/risk factors  Most prolactinomas occur sporadically  Some patients may have multiple endocrine neoplasia syndrome type 1 ( MEN-1) or familial isolated pituitary adenoma (FIPA).  Premenopausal women present earlier due to menstrual irregularity and hence usually have m...