Endocrinology Flashcards
Define acromegaly.
Constellation of signs and symptoms caused by hypersecretion of GH in adults.
What does excess GH causes in children pre-puberty?
o Gigantism
What are the presenting symptoms of acromegaly?
o Very gradual progression of symptoms over many years
o Rings and shoes becoming tight
o Increased sweating
o Headaches
o Carpal tunnel syndrome
o Hypopituitary symptoms = Hypogonadism, Hypothyroidism, Hypoadrenalism
o Visual disturbances (due to compression of optic chiasm by tumour)
o Hyperprolactinaemia = Irregular periods, Decreased libido, Impotence
What are the signs of acromegaly on examination?
o Hands - large spade-like hands with thick greasy skin, carpel tunnel syndrome signs and premature osteoarthritis
o Face - prominent eyebrow ridge, prominent cheeks, broad nose bridge, prominent nasolabial folds, thick lips, increased gap between teeth, large tongue, prognathism, husky resonant voice (due to thickening of vocal cords)
o Visual Field Loss - bitemporal superior quadrantopia progressing to bitemporal hemianopia
o Neck - multinodular goitre
o Feet - enlarged
What are the appropriate investigations for acromegaly?
o Serum IGF-1 - useful screening test (GH stimulates IGF-1 secretion)
o Oral Glucose Tolerance Test (OGTT) - positive result = failure of suppression of GH after 75 g oral glucose load
o Pituitary Function Tests - 9am cortisol, free T4 and TSH, LH and FSH, testosterone, prolactin
o MRI of Brain - visualise the pituitary adenoma
What is the treatment of acromegaly?
o Surgical = trans-sphenoidal hypophysectomy
o Radiotherapy = adjunctive to surgery
o Medical = if surgery is contraindicated or refused
- Subcutaneous Somatostatin Analogues - octreotide, lanreotide -> side-effects = abdominal pain, steatorrhoea, glucose intolerance, gallstones
- Oral Dopamine Agonists - bromocriptine, cabergoline -> side-effects = nausea, vomiting, constipation, postural hypotension, psychosis (RARE)
- GH Antagonist (pegvisomant)
- Monitoring GH and IGF1 levels
What are the possible complications of acromegaly?
o CVS = cardiomegaly, hypertension
o Respiratory = obstructive sleep apnoea
o GI = colonic polyps
o Reproductive = hyperprolactinaemia (in 30% of cases)
o Metabolic = hypercalcaemia, hyperphosphataemia, renal stones, DM, hypertriglyceridaemia
o Psychological = depression, psychosis (from dopamine agonists)
What are the possible complications of acromegaly surgery treatment?
Nasoseptal perforation
Hypopituitarism
Adenoma recurrence
CSF leak
Infection
Define carcinoid syndrome.
Constellation of symptoms caused by systemic release of humoral factors from carcinoid tumours.
What are the presenting symptoms of carcinoid syndrome?
o Main symptom = Paroxysmal Flushing
o Diarrhoea
o Crampy abdominal pain
o Wheeze
o Sweating
o Palpitations
What are the signs of carcinoid syndrome on examination?
Facial flushing
Telangiectasia
Wheeze
Right-sided murmurs (tricuspid stenosis/regurgitation or pulmonary stenosis)
Nodular hepatomegaly in cases of metastatic disease
What are the signs of carcinoid crisis on examination?
Profound flushing
Bronchospasm
Tachycardia
Fluctuating blood pressure
What are the appropriate investigations for carcinoid syndrome?
o 24 hours urine collection - check 5-HIAA levels (metabolite of serotonin)
o Blood - plasma chromogranin A and B, fasting gut hormones
o CT or MRI Scan - localise the tumour
o Radioisotope Scan - radiolabelled somatostatin analogue helps localise the tumour
o Investigations for MEN-1
What is MEN-1?
o Multiple Endocrine Neoplasia Type 1 (MEN1)
- a hereditary condition associated with tumors of the endocrine (hormone producing) glands
Define Cushing’s syndrome.
Syndrome associated with chronic inappropriate elevation of free circulating cortisol.
What are the types of Cushing’s syndrome?
o ACTH Dependent (80%)
- excess ACTH from a pituitary adenoma (Cushing’s disease)
- ectopic ACTH (e.g. lung cancer, pulmonary carcinoid tumours)
o ACTH Independent (20%)
- benign adrenal adenoma
- adrenal carcinoma
What are the presenting symptoms of Cushing’s syndrome?
Increasing weight
Fatigue
Muscle weakness
Myalgia
Thin skin
Easy bruising
Poor wound healing
Fractures
Hirsuitism
Acne
Frontal balding
Oligomenorrhoea/amenorrhoea
Depression or psychosis
What are the signs of Cushing’s syndrome on examination?
Moon face
Facial plethora
Interscapular fat pad
Proximal muscle weakness
Thin skin
Bruises
Central obesity
Pink/purple striae on abdomen/breast/thighs
Kyphosis (due to vertebral fracture)
Poorly healing wounds
Hirsuitism, acne, frontal balding
Hypertension
Ankle oedema (due to salt and water retention from the mineralocorticoid effect of cortisol)
Pigmentation in ACTH dependent cases
What are the appropriate investigations for diagnosing Cushing’s disease?
o Must be performed on patients with a high pre-test probability
o Bloods - U&Es (hypokalaemia due to mineralocorticoid effect), glucose
o Initial High-Sensitivity Tests - urinary free cortisol, late-night salivary cortisol, overnight dexamethasone suppression test, low dose dexamethasone suppression test (LDDST) = Give 0.5 mg dexamethasone orally ever 6 hrs for 48 hrs
What are the appropriate investigations for identifying underlying causes of Cushing’s disease?
o ACTH-independent (adrenal adenoma/carcinoma) = low plasma ACTH, CT or MRI of adrenals
o ACTH-dependent (pituitary adenoma) = high plasma ACTH, pituitary MRI, high-dose dexamethasone suppression test, inferior petrosal sinus sampling (SUPERIOR to high-dose dexamethasone suppression test)
o ACTH-dependent (ectopic) = if lung cancer suspected: CXR, sputum cytology, bronchoscopy, CT san
What is the treatment for Cushing’s syndrome?
o If iatrogenic = discontinue steroids, use lower dose or use a steroid-sparing agent
o Medical = inhibit cortisol synthesis with metyrapone or ketoconazole, treat osteoporosis, physiotherapy for muscle weakness
o Surgical = pituitary adenomas - trans-sphenoidal adenoma resection or for adrenal adenoma/carcinoma - surgical removal of tumour
o Radiotherapy = performed in those who are not cured and have persistent high cortisol after trans-sphenoidal resection of the tumour
What are the possible complications of Cushing’s syndrome?
o Of the disease = Diabetes, Osteoporosis, Hypertension, Pre-disposition to infections, Long-term depression even years following treatment starting
o Surgery treatment = CSF leakage, Meningitis, Sphenoid sinusitis, Hypopituitarism
Medicinal treatment = Hypopituitarism, Radionecrosis, Increased risk of second intracranial tumours and stroke
Define diabetes insipidus.
A disorder of inadequate secretion or of insensitivity to vasopressin (ADH) leading to hypotonic polyuria.
o Central DI = failure of ADH secretion by the posterior pituitary
o Nephrogenic DI = insensitivity of the collecting duct to ADH
What are the causes of central diabetes insipidus?
Idiopathic
Tumours (e.g. pituitary tumour)
Infiltrative (e.g. sarcoidosis)
Infection (e.g. meningitis)
Vascular (e.g. aneurysms, Sheehan syndrome)
Trauma (e.g. head injury, neurosurgery)
What are the causes of nephrogenic diabetes insipidus?
Idiopathic
Drugs (e.g. lithium)
Post-obstructive uropathy
Pyelonephritis
Pregnancy
Osmotic diuresis (e.g. diabetes mellitus)
What are the presenting symptoms of diabetes insipidus?
o Polyuria
o Nocturia
o Polydipsia
o In children =enuresis (bed-wetting), sleep disturbance
o Other symptoms depend on aetiology
What are the signs of diabetes insipidus on examination?
o Central DI has few signs if the patient drinks sufficiently to maintain adequate fluid levels
o Urine output > 3 L/day
o If fluid intake < fluid output, signs of dehydration will be present (e.g. tachycardia, reduced tissue turgor, postural hypotension, dry mucous membranes)
o Signs related to the cause (e.g. visual defect due to pituitary tumour)
What are the appropriate investigations for diabetes insipidus?
o Water Deprivation Test - water is restricted for 8 hrs and plasma and urine osmolality are measured every hour for 8 hrs, desmopressin is given after 8 hrs and urine osmolality is measured (stop the test if the fall in body weight is > 3%)
o Bloods - U&Es and Ca2+
What is the treatment of diabetes insipidus?
o Treat the cause
o Cranial DI - give Desmopressin (vasopressin analogue) or if mild chlorpropamide or carbamazepine can be used to potentiate the residual effects of any residual vasopressin
o Nephrogenic DI - Sodium and/or protein restriction helps with polyuria and thiazide diuretics
What are the possible complicatios of diabetes insipidus?
Hypernatraemic dehydration
Excess desmopressin –> hyponatraemia
Define diabetes mellitus type 1.
Metabolic hyperglycaemic condition caused by absolute insufficiency of pancreatic insulin production.
What auto-antigens are associated with T1DM?
Glutamic acid decarboxylase (GAD)
Insulin
Insulinoma-associated protein 2
Cation efflux zinc transporter
What are the presenting sign and symptoms of T1DM?
Juvenile onset (< 30 yrs)
Polyuria/nocturia
Polydipsia
Tiredness
Weight loss
What are the appropriate investigations for T1DM?
o Blood Glucose - fasting blood glucose > 7 mmol/L or random blood glucose > 11.1 mmol/L, FBC (MCV, reticulocytes), U&Es, lipid profile
o HbA1c
o Urine albumin creatinine ratio - used to detect microalbuminuria
o Urine - glycosuria, ketonuria, MSU
What is management for T1DM?
o Advice and patient education
o Short-acting insulin (three times daily before meals) - lispro, aspart, glulisine
o Long-acting insulin (once daily) - isophane, glargine, detemir
o DAFNE courses (dose adjustment for normal eating)
o Monitoring - regular capillary blood glucose tests, HbA1c every 3-6 months
o Screening and management of complications
What is the treatment of hypoglycaemia?
If reduced consciousness: 50 ml of 50% glucose IV OR 1 mg glucagon IM
If consciousness and cooperative: 50 g oral glucose + starchy snack
What are the possible complications of T1DM?
o DKA - can be precipitated by infection, errors in management of diabetes, newly diagnosed diabetes, idiopathic
o Microvascular complications - retinopathy, nephropathy, neuropathy
o Macrovascular complications - peripheral vascular disease, ischaemic heart disease, stroke/TIA
o Increased risk of infection
o Treatment Complications = Weight gain, Fat hypertrophy at insulin injection sites, Hypoglycaemia
What are the possible complications of T1DM treatment?
Weight gain
Fat hypertrophy at insulin injection sites
Hypoglycaemia
What are the symptoms of hypoglycaemic attacks?
Personality changes
Fits
Confusion
Coma
Pallor
Sweating
Tremor
Tachycardia
Palpitations
Dizziness
Hunger
Focal neurological symptoms
Define diabetes mellitus type 2.
Characterised by increased peripheral resistance to insulin action, impaired insulin secretion and increased hepatic glucose output.
What are the presenting symptoms of T2DM?
May be an incidental finding
Polyuria
Polydipsia
Tiredness
Patients may present with hyperosmolar hyperglycaemic state (HHS)
Infections (e.g. infected foot ulcers, candidiasis, balanitis)
Assess cardiovascular risk factors: hypertension, hyperlipidaemia and smoking
What are the signs of T2DM on examination?
o High BMI
o Waist circumference
o Blood pressure
o Diabetic foot (ischaemic and neuropathic signs)
o Reduced subcutaneous tissue
o Gangrene
o Charcot’s arthropathy
o Weak foot pulses
o Skin changes = dry skin, ulceration, necrobiosis lipoidica diabeticorum, granuloma annulare, diabetic dermopathy
What are the appropriate investigations for T2DM?
o T2DM is diagnosed if one or more of the following are present = symptoms of diabetes and a random plasma glucose > 11.1 mmol/L, fasting plasma glucose > 7 mmol/L, two-hour plasma glucose > 11.1 mmol/L after 75 g oral glucose tolerance test
o Monitor = HbA1c, U&Es, lipid profile, eGFR
o Urine albumin = creatinine ration (look out for microalbuminuria)
What is the treatment of T2DM?
o At diagnosis: lifestyle + metformin
o If HbA1c > 7% after 3 months: lifestyle + metformin + sulphonylurea
o If HbA1c > 7% after 3 months: lifestyle + metformin + basal insulin
o If HbA1c > 7% after 3 months and fasting blood glucose > 7 mmol/L: add premeal rapid-acting insulin
o Close monitorment during pregnancy
What are the possible complications of T2DM?
o Hyperosmolar hyperglycaemic state = due to insulin deficiency
o Neuropathy = distal symmetrical sensory neuropathy, painful neuropathy, carpel tunnel syndrome, diabetic amyotrophy, mononeuritis, autonomic neuropathy, gastroparesis, impotence, urinary retention
o Nephropathy
o Retinopathy = background, pre-proliferative, proliferative, maculopathy, prone to glaucoma, cataracts and transient visual loss
o Macrovascular complications = IHD, stroke, peripheral vascular disease
Define Graves’ disease.
Caused by the presence of TSH-receptor stimulating antibodies that lead to hyperthyroidism due to loss of negative feedback.
- most common cause of hyperthyroidism.
What are the risk factors for hyperthyroidism?
Family history
High iodine intake
Smoking
Trauma to the thyroid gland
Toxic multinodular goitre
HAART
Childbirth
What are the presenting symptoms of Graves’ disease?
Weight loss despite increased appetite
Irritability
Weakness
Diarrhoea
Sweating
Tremor
Anxiety
Heat intolerance
Loss of libido
Oligomenorrhoea/amenorrhoea
What are the signs of Graves’ disease on examination?
Palmar erythema
Sweaty and warm palms
Fine tremor
Tachycardia (may be AF)
Hair thinning
Urticaria/pruritus
Brisk reflexes
Goitre
Proximal myopathy
Lid lag
Gynaecomastia
What are the appropriate investigations for Graves’ disease?
o TFTs = low TSH + high T3/T4
o Autoantibodies = anti-TPO antibodies (found in 75% of Graves), anti-thyroglobulin antibodies, TSH-receptor antibodies (very sensitive and specific for Graves)
o Imaging - thyroid ultrasound, thyroid uptake scan
o Inflammatory Markers = CRP/ESR will be raised in subacute thyroiditis
Define primary hyperparathyroidism.
Increased secretion of PTH unrelated to the plasma calcium concentration.
Define secondary hyperparathyroidism.
Increased secretion of PTH secondary to hypocalcaemia.
Define tertiary hyperparathyroidism.
Autonomous PTH secretion following chronic secondary hyperparathyroidism.
What are the causes of primary hyperparathyroidism?
Parathyroid adenoma
Parathyroid hyperplasia
Parathyroid carcinoma
MEN syndrome
What are the causes of secondary hyperparathyroidism?
Chronic renal failure
Vitamin D deficiency
What are the presenting signs and symptoms of hyperparathyroidism?
o Primary - many patients have mild hypercalcaemia and may be asymptomatic
- symptoms/signs of hyperclacaemia - polyuria, polydipsia, renal calculi, bone pain, abdominal pain, nausea, constipation, psychological depression, lethargy
o Secondary - may present with signs/symptoms of hypocalcaemia or of the underlying cause (e.g. renal failure, vitamin D deficiency)
What are the appropriate investigations for hyperparathyroidism?
o Bloods = U&Es, serum calcium (high in primary and tertiary, low/normal in secondary), serum phosphate (low in primary and tertiary, high in secondary), albumin, ALP, vitamin D, PTH
o Renal ultrasound - can visualise renal calculi
What is the treatment for hyperparathyroidism?
o Acute hypercalcaemia = IV fluids, avoid factors that exacerbate hypercalcaemia (e.g. thiazide diuretics), maintain adequate hydration, moderate calcium and vitamin D intake
o Surgical management = subtotal parathyroidectomy, total parathyroidectomy
o Secondary hyperparathyroidism management = treat underlying cause (e.g. renal failure), calcium and vitamin D supplements may be needed
What are the possible complications of primary hyperparathyroidism?
Increased bone resorption
Increased tubular calcium reabsorption
Increased 1a-hydroxylation of vitamin D
All of these lead to hypercalcaemia
What are the possible complications of secondary hyperparathyroidism?
Increased stimulation of osteoclasts and increased bone turnover
This leads to osteitis fibrosa cystica
What are the possible complications of hyperparathyroidism surgical treatment?
Hypocalcaemia
Recurrent laryngeal nerve palsy
Define female hypogonadism.
Characterised by impairment of ovarian function.
What are the types of female hypogonadism?
o Primary hypogonadism
- gonadal dysgenesis (due to chromosomal abnormalities e.g. Turner’s syndrome)
- gonadal damage (e.g. autoimmune, chemotherapy, radiotherapy)
o Secondary hypogonadism
- functional (e.g. stress, weight loss, excessive exercise, eating disorders)
- pituitary/hypothalamic tumours and Infiltrative Lesions (e.g. pituitary adenomas, haemochromatosis)
- hyperprolactinaemia (e.g. due to prolactinoma)
- congenital GnRH deficiency: Kallmann’s syndrome, idiopathic
What are the presenting symptoms of female hypogonadism?
o Symptoms of oestrogen deficiency = night sweats, hot flushing, vaginal dryness, dyspareunia, decreased libido, infertility
o Symptoms of the underlying cause
What are the signs of female pre-pubertal hypogonadism on examination?
o Delayed puberty = primary amenorrhoea, absent breast development, no secondary sexual characteristics
o Eunuchoid = long legs, arm span greater than height
What are the signs of female post-pubertal hypogonadism on examination?
Regression of secondary sexual characteristics (e.g. loss of secondary sexual hair, breast atrophy)
Perioral and periorbital fine facial wrinkles
Signs of underlying cause
What are the signs of female hypothalamic/pituitary hypogonadism on examination?
Visual field defects
What are the signs of female Kallmann’s syndrome hypogonadism on examination?
o Amnosia
What are the signs of female Turner’s syndrome hypogonadism on examination?
Short statue
Low posterior hair line
High arched palate
Widely spaced nipples
Wide carrying angle
Short fourth and fifth metacarpals
Congenital lymphoedema
What are the signs of female autoimmune primary ovarian failure hypogonadism on examination?
Other autoimmune disease - e.g. vitiligo
What are the appropriate investigations for female hypogonadism?
o Low serum oestradiol
o Serum FSH/LH = high in primary but low in secondary
o Primary Hypogonadism Investigations = karyotype, pelvic imaging for structural,
o Screen for FMR1 gene in patients with unexplained pre-mature ovarian failure
o Secondary Hypogonadism Investigations = pituitary function tests (e.g. 9 am cortisol, TFTs, prolactin), visual field testing, hypothalamic-pituitary MRI, smell tests for anosmia, serum transferrin saturation (check for haemochromatosis)
o Investigating associated conditions
- Turner’s Syndrome - periodic echocardiography, renal US
- Autoimmune Oophoritis - check autoimmune adrenal insufficiency
Define male hypogonadism.
A syndrome of decreased testosterone production, sperm production or both.
What are the types of male hypogonadism?
o Primary Hypogonadism
- gonadal dysgenesis (e.g. Klinefelter’s syndrome, undescended testicles)
- gonadal damage (e.g. infection, torsion, trauma, autoimmune, iatrogenic)
- rare causes (e.g. defects in enzymes involved in testosterone synthesis)
o Secondary Hypogonadism
- pituitary/hypothalamic lesions
- GnRH deficiency (Kallmann’s syndrome)
- hyperprolactinaemia
- systemic/chronic diseases
- rare causes: genetic mutations
- Prader-Willi syndrome (short, small hands, almond-shaped eyes, learning difficulty, postnatal hypotonia)
- Laurence-Moon-Biedl syndrome (obesity, polydactyly, retinitis pigmentosa, learning difficulty)
What are the presenting symptoms of male hypogonadism?
o Delayed puberty
o Decreased libido
o Impotence
o Infertility
o Symptoms of underlying cause (e.g. Klinefelters –> intellectual dysfunction, behavioural abnormalities)
What are the signs of male pre-pubertal hypogonadism on examination?
- high pitched voice
- decreased pubic/axillary/facial hair
- small or undescended testicles
- small penis
What are the signs of male post-pubertal hypogonadism on examination?
- Decreased pubic/axillary/facial hair
- Soft and small eyes
- Gynaecomastia
- Fine perioral wrinkles
- Features of underlying cause (e.g. visual defects if pituitary cause)
What are the signs of general male hypogonadism on examination?
- Decreased testicular volume using Prader’s orchidometer (normal adult volume = 15-25 mL)
- Gynaecomastia
- Eunuchoid proportions (arm span > height)
- Features of underlying cause (e.g. undescended testicle, anosmia in Kallmann’s syndrome)
What are the signs of Klinefelter’s syndrome on examination?
- XXY
What are the appropriate investigations for male hypogonadism?
o Serum total testosterone
o Sex hormone binding globulin (SHBG)
o Albumin
o LH and FSH
o Primary Hypogonadism = low testosterone and high LH and FSH
- check for Klinefelter’s using katyotyping
o Secondary Hypogonadism = low testosterone and inappropriately normal/low LH and FSH
- check pituitary function via pituitary function tests, MRI of the pituitary area and visual field testing
- check for Kallmann’s = smell testing (for anosmia)
- check iron testing (for hereditary haemochromatosis)
o Assess bone age (risk of fracture)
Define panhypopituitarism.
Deficiency of ALL pituitary hormones.
What are the risk factors for hypopituitarism?
o Pituitary Masses - adenomas, craniopharyngioma, meningioma, glioma, metastases, cysts
o Pituitary Trauma - radiation, surgery, base of skull fractures
o Hypothalamic Dysfunction - due to anorexia, starvation, over-exercise
o Infiltrative Diseases - sarcoidosis, haemochromatosis, Langerhans’ cell histiocytosis
o Vascular - pituitary apoplexy, Sheehan’s syndrome
o Infection - meningitis, encephalitis
o Genetic Mutations - Pit-1 and Prop-1 genes
What are the signs and symptoms of panhypopituitarism?
o Symptoms of lacking all the pituitary hormones
o GH - children = short stature - adults = low mood, fatigue, reduced muscle strength, reduced libido
o LH or FSH - delayed puberty, loss of secondary sexual hair, breast atrophy, decreased libido and impotence
o ACTH - adrenal insufficiency
o TSH - hypothyroidism
o Prolactin - not usually clinically significant
o Pituitary Apoplexy - headaches, visual loss, cranial nerve palsies
What are the appropriate investigations for panhypothyroidism?
o Pituitary Function Tests
- Basal Tests = 9 am cortisol, LH and FSH levels, testosterone levels, oestrogen levels, IGF-1 levels, prolactin levels, free T4 and TSH levels
- Dynamic Tests = insulin-induced hypoglycaemic (should cause a rise in GH and cortisol)
- Short synacthen test (for adrenal insufficiency)
o Others = MRI/CT of brain or visual field testing
What is the management of panhypopituitarism?
o Hormone Replacement = hydrocortisone, levothyroxine, sex hormones etc
o Complications of Panhypothyroidism = Addisonian crisis, hypoglycaemia, myxoedema coma, infertility, osteroporosis, dwarfism (children)
o Complications of a pituitary mass = optic chiasm compression, hydrocephalus, temporal lobe epilepsy
Define hypothyroidsm.
Clinical syndrome resulting from insufficiency secretion of thyroid hormones.
What is the aetiology of hypothyroidism?
o PRIMARY HYPOTHYROIDISM
- Acquired = Hashimoto’s thyroiditis (autoimmune), iatrogenic (post-surgery, radioiodine, hyperthyroid medication), severe iodine deficiency, iodine excess (Wolff-Chaikoff effect), thyroiditis
- Congenital = thyroid dysgenesis, inherited defects in thyroid hormone biosynthesis
o SECONDARY HYPOTHYROIDISM (5% of cases)
- Pituitary and Hypothalamic Disease - resulting in reduced TSH and TRH hence, reduced stimulation of thyroid hormone production
What are the presenting symptoms of hypothyroidism?
INSIDIOUS onset
Cold intolerance
Lethargy
Weight gain with reduced appetite
Constipation
Dry skin
Hair loss
Hoarse voice
Mental slowness
Depression
Cramps
Ataxia
Paraesthesia
Menstrual disturbance (irregular cycles, menorrhagia)
History of surgery or radioiodine therapy for hyperthyroidism
Personal/family history of other autoimmune conditions (e.g. Addison’s, type 1 diabetes mellitus)
Myxoedema coma
What are the presenting symptoms of myxoedema coma?
Hypothermia
Hypoventilation
Hyponatraemia
Heart failure
Confusion
Coma
What are the signs of hypothyroidism on physical examination?
o Hands = bradycardia, cold hands/slowed cap refill/lack of perfusion
o Head/Neck/Skin = pale puffy face, goitre, oedema, hair loss, dry skin, vitiligo
o Chest = pericardial effusion, pleural effusion
o Abdomen = ascites
o Neurological = slow relaxation of reflexes, signs of carpal tunnel syndrome
What are the appropriate investigations for hypothyroidism?
TFTs
FBC - may show normocytic anaemia
U&Es - may show low sodium
Cholesterol - may be high
What is the management of hypothyroidism?
o Levothyroxine (25-200 mcg/day)
- Important to rule out underlying adrenal insufficiency before starting thyroid hormone replacement - thyroid hormone replacement in the context of adrenal insufficiency can precipitate an Addisonian crisis
- Adjust dose based on clinical picture and TFTs
What is the management of myxoedema coma?
Oxygen
Rewarming
Rehydration
IV T4/T3
IV hydrocortisone
Treat underlying cause (e.g. infection)
What are the possible complications of hypothyroidism?
- myoedema coma = 80% mortality
- myoedema madness -> psychosis with delusions and hallucinations or dementia
Define Multiple Endocrine Neoplasia.
An autosomal dominant condition characterised by a predilection to develop tumours of endocrine glands.
What are the types of MEN?
o MEN 1
- Pituitary adenomas
- Parathyroid tumours
- Pancreatic islet-cell tumours (and other endocrine tumours of the gastroenterohepatic tract e.g. gastrinomas)
- Fascial angiofibromas and collagenomas
o MEN 2a
- Parathyroid tumours
- Medullary thyroid cancer
- Phaeochromocytomas
o MEN 2b
- Same as MEN 2a
- Marfanoid appearance
- Neuromas of the GI tract
What are the presenting symptoms of MEN 1?
o Age of onset of tumours is usually teenage years - > however symptoms of the tumours may not become apparent for years - > diagnosis is commonly made in the 4th decade of life
o Symptoms and signs are dependent on the organs affects:
- Hyperparathyroidism –> symptoms of hypercalcaemia + nephrolithiasis
- Hypergastrinaemia –> Zollinger-Ellison syndrome
- Hyperinsulinaemia –> hypoglycaemia
- Hyperprolactinaemia –> amenorrhoea
- Hypersomatotrophinaemia –> acromegaly
o Pituitary tumours may cause visual defects
What are the presenting symptoms of MEN 2?
o Symptoms of medullary thyroid cancer, hyperparathyroidism or phaeochromocytoma
o Medullary thyroid cancer symptoms = hypertension, episodic sweating, diarrhoea, pruritic skin lesions, lump in the neck
o Hypercalcaemia symptoms = constipation, polyuria/polydipsia, depression, kidney stones, fatigue
What are the appropriate investigations for MEN 1?
Screening first and/or second degree relatives
Hormone hypersecretion blood tests
DNA testing
What are the appropriate investigations for MEN 2?
o Phaeochromocytoma test - 24 hr urine metanephrines -> can be followed by abdominal MRI
o Medullary thyroid cancer test - elevated calcitonin concentration or USS and FNA
o Parathyroid tumours - simultaneously elevated Ca2+ and PTH
Define obesity.
o A BMI > 30 kg/m2
o Alternative = Waist circumference
- Men = Low Risk = < 94 cm and Very High Risk = > 102 cm
- Women = Low Risk = < 80 cm and Very High Risk = > 88 cm
What are the presenting signs and symptoms of obesity?
- Patient notices that they are fat/have gained weight
- Symptoms of complications (e.g. T2DM, coronary heart disease, obstructive sleep apnoea)
What are the appropriate investigatiosn for obesity?
Measure serum lipids
Measure HbA1c
Hormone profile (check for hormonal cause of obesity)
TFTs - hypothyroidism can cause obesity
Other investigations depending on comorbidities
Define osteoporosis.
- Reduced bone density resulting bone fragility and increased fracture risk
- Clinically defined as > 2.5 standard deviations below peak bone mass achieved by healthy adults (i.e. T-score > 2.5)
What are the causes of osteoporosis?
o Primary = idiopathic (if < 50 yrs) or post-menopausal
o Secondary
- Malignancy = myeloma, metastatic carcinoma
- Endocrine = Cushing’s disease, thyrotoxicosis, primary hyperparathyroidism, hypogonadism
- Drugs = corticosteroids, heparin
- Rheumatological = rheumatoid arthritis, ankylosing spondylitis
- Gastrointestinal = malabsorption (e.g. coeliac disease, partial gastrectomy), liver disease, anorexia
What are the risk factors for osteopororsis?
Age
Family history
Low BMI
Low calcium intake
Smoking
Lack of physical exercise
Low exposure to sunlight
Alcohol abuse
Late menarche
Early menopause
Hypogonadism
What are the presenting symptoms of osteoporosis?
- Often asymptomatic until fractures occur
- Characteristic fractures = neck of femur (after minimal trauma), vertebral fractures, Colles’ fractures (falling on outstretched hand)
What are the signs of osteoporosis on examination?
o Often no signs until complications occur
- tenderness on percussion - over vertebral fractures
- thoracic kyphosis - multiple vertebral fractures
- severe pain when hip is flexed and externally rotated - NOF fracture
What are the appropriate investigations for osteoporosis?
o Bloods - calcium, phosphate, ALP = all are NORMAL in PRIMARY osteoporosis
o X-Ray
- diagnose fractures
- often normal because it takes > 30% loss of bone density before showing any changes in radiolucency or cortical thinning -> can show bioconcave vertebrae or crush fractures
o Isotope Bone Scans
o DEXA (Dual-Energy X-Ray Absorptiometry) Scan
- T-score = number of standards deviations the bone mineral density measurement is above or below the young normal mean bone mineral density - used for diagnosis
- Z-score = the number of standard deviations the measurement is above or below the age-matched mean bone mineral density. Z-score may be helpful in identifying patients who may need a work-up for secondary causes of osteoporosis
Define Paget’s Disease of Bone.
Characterised by excessive bone remodelling at one (monostotic) or more (polyostotic) sites resulting in bone that is structurally disorganised.
What are the presenting symptoms of Paget’s disease?
- may be asymptomatic
- Insidious onset of pain -> aggrevated by weight bearing and movement
- headaches
- deafness
- increasing skull size
What are the signs of Paget’s disease on examination?
- Bitemporal skull enlargement -> frontal bossing (prominent forehead)
- Spinal kyphosis
- Anterolateral bowing of femur, tibia or forearm
- Skin over affected bones in warm
- Sensorineural deafness - compression of the vestibulocochlear nerve
What are the appropriate investigations for Paget’s disease?
o Bloods = High ALP and normal Ca2+ and phosphate
o Bone Radiographs = enlarged, deformed bones with lytic and sclerotic appearance, lack of distinction between cortex and medulla and skull changes (osteoporosis circumscripta, enlargement of frontal and occipital areas, cotton wool appearance)
o Bone Scan - assesses extent of skeletal involvement
o Resorption Markers - monitors disease activity and check urinary hydroxyproline
Define Phaeochromocytoma.
Catecholamine-producing tumours that usually arise from chromaffin cells of the adrenal medulla.
- 10% of cases are extra-adrenal
- 10% are bilateral
- 10% are malignant
- Extra-adrenal phaeochromocytomas are referred to as paragangliomas
What are the risk factors for phaeochromocytoma?
o Sporadic cases are of unknown aetiology
o Familial in up to 30%
- Familial cases are seen in patients with MEN2a, von Hippel-Lindau syndrome, Neurofibromatosis type 1
What are the presenting symptoms of phaeochromocytoma?
o PAROXYSMAL episodes
- Headache (due to malignant hypertension)
- Sweating
- Cardiorespiratory Symptoms -> palpitations, chest pain, dyspnoea
- GI Symptoms -> epigastric pain, nausea, constipation
- Neuropsychiatric Symptoms -> weakness, tremor, anxiety
What are the signs of phaeochromocytoma on examination?
Paroxysmal episodes of:
Hypertension
Postural hypotension
Pallor
Tachycardia
Fever
Weight loss
What are the appropriate investigations for phaeochromocytoma?
- 24 hr urine collection - check for catecholamine levels (and check for fractionated metanephrine levels) - metanephrines are metabolites of adrenaline
- Plasma free metanephrines
- Tumour localisation (MRI or CT)
- I-MIBG scintigraphy (another way of visualising the tumour)
- Screen for associated conditions
- Genetic testing
Define Non-functioning Pituitary Tumours.
Benign tumours of the pituitary gland formed from pituitary cells that do not produce any active pituitary hormones.
What are are the presenting symptoms of non-functioning pituitary tumours?
- Symptoms develop very SLOWLY because there are no hormonal derangements
- Headaches
- Bitemporal hemianopia
- Panhypopituitarism - symptoms develop depending on which hormone is affected
What are the appropriate investigations for non-functioning pituitary tumours?
- MRI
- CT
- Bloods - check hormone levels
- Visual Field Testing
Define PCOS.
Characterised by oligomenorrhoea/amenorrhoea and hyperandrogenism (clinical or biochemical). Frequently associated with:
Obesity
Insulin resistance
Type 2 diabetes mellitus
Dyslipidaemia
What are the presenting symptoms of PCOS?
Menstrual irregularities
Dysfunctional uterine bleeding
Infertility
Symptoms of hyperandrogenism:
Hirsuitism
Male-pattern hair loss
Acne
What are the signs of PCOS on examination?
Hirsuitism
Male-pattern hair loss
Acne
Acanthosis nigricans (sign of severe insulin resistance) - velvety thickening and hyperpigmentation of the skin of the axillar or neck
What are the appropriate investigations for PCOS?
o Bloods = High LH, High LH : FSH ratio, High testosterone, androstenedione and DHEA-S and/or Low sex hormone binding globulin
o Transvaginal USS = look for ovarian follicles and an increase in ovarian volume
- Other things to test for = hyperprolactinaemia, hypo/hyperthyroidism, congenital adrenal hyperplasia (check 17-OH-progesterone levels), Cushing’s syndrome
- Look for impaired glucose tolerance/T2DM = fasting blood glucose, HbA1c
- Fasting lipid profile
Define Hyperaldosteronism.
Characterised by autonomous aldosterone overproduction from the adrenal gland with subsequent suppression of plasma renin activity.
What are the risk factors for primary hyperaldosteronism?
- Adrenal adenoma (Conn’s syndrome) - responsible for 70% of cases
- Adrenal cortex hyperplasia (30% of cases)
- RARE = glucocorticoid-suppressible hyperaldosteronism or aldosterone producing adrenal carcinoma
What are the presenting symptoms of primary hyperaldosteronism?
- Usually asymptomatic > tends to be an incidental finding on routine blood tests
- Symptoms of Hypokalaemia = Muscle Weakness, Polyuria and Polydipsia (Nephrogenic DI), Paraesthesia, Tetany
What are the signs of primary hyperaldosteronism on examination?
Hypertension
Complications of hypertension (e.g. hypertensive retinopathy)
What are the appropriate investigations for primary hyperaldosteronism?
o Screening Tests = Low Serum K+, High Urine K+, High plasma aldosterone concentration, High aldosterone: renin activity ratio
o Confirmatory Tests
- Salt Loading = failure of aldosterone suppression following salt load confirms primary hyperaldosteronism
- Postural Test = measure plasma aldosterone, renin activity and cortisol when the patient is lying down at 8am and then again after 4 hrs of the patient being upright -> aldosterone-producing adenoma - aldosterone secretion decreases between 8 am and noon but bilateral adrenal hyperplasia - adrenals respond to standing posture and increase renin production leading to increased aldosterone secretion
- CT/MRI
- Bilateral adrenal vein catheterisation
- Radio-labelled cholesterol scanning
What is the managment plan for primary hyperaldosteronism - bilateral adrenal hyperplasia?
Spironolactone - Eplerenone can be used if the spironolactone side-effects are intolerable
Amiloride (potassium-sparing diuretic)
Monitor serum K+, creatinine and BP
ACE inhibitors and CCBs may also be added
What is the managment plan for primary hyperaldosteronism - aldosterone producing adenomas?
Adrenalectomy
What is the managment plan for primary hyperaldosteronism - adrenal carcinoma?
Surgery
Post-operative mitotane (anti-neoplastic)
What are the complications of primary hyperaldosteronism?
Complications of hypertension
Define Prolactinoma.
A pituitary adenoma that overproduces prolactin.
What are the presenting symptoms of prolactinoma in women?
Amenorrhoea/oligomenorrhoea
Galactorrhoea
Infertility
Hirsuitism
Reduced libido
- Symptoms due to size of the tumour = headache, bitemporal hemianopia, cranial nerve palsies, signs and symptoms of hypopituitarism
What are the presenting symptoms of prolactinoma in men?
Symptoms are subtle and develop slowly
Reduced libido
Reduced beard growth
Erectile dysfunction
- Symptoms due to size of the tumour = headache, bitemporal hemianopia, cranial nerve palsies, signs and symptoms of hypopituitarism
What are the appropriate investigations for prolactinoma?
Serum prolactin level (extremely high levels (> 5000 mU/L) suggests true prolactinoma)
Exclude pregnancy
TFTs - hypothyroidism –> high TRH –> stimulates prolactin release
MRI
Assessment of pituitary function
What is the management plan for prolactinoma?
o Dopamine Agonists (e.g. cabergoline and bromocriptine)
- usually need to be continued on a long-term basis
o If dopamine agonists are ineffective = Surgery or Radiotherapy
What are the possible complcations of prolactinoma?
o Complications of Hypogonadism = osteoporosis, reduced fertility, erectile dysfunction
o Complications of Tumour Size = bitemporal hemianopia, pituitary apoplexy, CSF rhinorrhoea
Define SIADH.
Characterised by continued secretion of ADH, despite the absence of normal stimuli for secretion (i.e. increased serum osmolality or decreased blood volume).
What are the risk factors for SIADH?
o Brain = haemorrhage/thrombosis, meningitis, abscess, trauma, tumour, Guillain-Barre syndrome
o Lung = pneumonia, TB, abscess, aspergillosis, small cell carcinoma
o Tumours = small cell lung caner, lymphoma, leukaemia, pancreatic cancer, prostate cancer, mesothelioma, sarcoma, thymoma
o Drugs = vincristine, opiates, carbamazepine, chlorpropamide
o Metabolic = porphyria, alcohol withdrawal
What are the presenting symptoms of SIADH?
May be ASYMPTOMATIC
Headache
Nausea/vomiting
Muscle cramp/weakness
Irritability
Confusion
Drowsiness
Convulsions
Coma
Symptoms of underlying cause
What are the signs of SIADH on examination
o Mild = Mild hyponatraemia = No signs
o Severe = Severe hyponatraemia = Reduced reflexes, extensor plantar reflexes
- signs of underlying causes
- Na+ < 110 mmol/L is associated with a high morbidity and mortality
What are the appropriate investigations for SIADH?
o SIADH Diagnosis = Low plasma osmolality, Low serum Na+ concentration, High urine osmolality and High urine Na+ along with the absence of hypovolaemia, oedema, renal failure, adrenal insufficiency and hypothyroidism
o Investigations for identifying the cause (e.g. CXR, CT, MRI)
- Must check = Creatinine, hypothyroidism/T4, short synacthen test (adrenal insufficicency) and glucose, serum protein, lipids for pseudohyponatraemia
What is the management of SIADH?
Treat underlying cause
Fluid restriction
Vasopressin receptor antagonists (e.g. tolvaptan)
In SEVERE cases - slow IV hypertonic saline and furosemide with close monitoring
What are the possible complications of SIADH?
Convulsions
Coma
Death
Central pontine myelinolysis - occurs with rapid correction of hyponatraemia - characterised by: Quadriparesis, Respiratory arrest and Fits and 50% mortality
What are the types of thyroid cancer?
Papillary
Follicular
Medullary
Anaplastic
What are the risk factors for thyroid cancer?
Childhood exposure to radiation
Medullary thyroid cancers may be familial and are associated with MEN IIa or IIb
Lymphoma is associated with Hashimoto’s thyroiditis
What are the presenting symptoms of thyroid cancer?
Slow-growing neck lump
Discomfort swallowing
Hoarse voice
What are the signs of thyroid cancer on examination?
Palpable nodules or diffuse enlargement of thyroid gland
Cervical lymphadenopathy –> suspect malignancy
Patient is usually euthyroid (has normal thyroid function)
What are the appropriate investigations for thyroid cancer?
o Bloods = TFTs, Bone profile, Tumour Markers - Thyroglobulin = papillary and follicular while Calcitonin = medullary
o Fine-Needle Aspiration Cytology (FNA)
o Excision Lymph Node Biopsy
o Isotope Scan
o CT/MRI - for staging
Define thyroid nodules.
Abnormal growth of thyroid cells that forms a lump in the thyroid gland. The nodules are usually non-functioning and have little chance of becoming cancer.
- single isolated nodules are more likely to malignant
What are the presenting symptoms of thyroid nodules?
Usually asymptomatic and found on examination
Can cause pain and rarelt compress the trachea or cause dysphagia
What are the signs of thyroid nodules on examination?
Check to see if the nodule moves on swallowing
If regional lymphadenopathy is present consider malignancy
What are the appropriate investigations for thyroid nodules?
TFTs - most patients will be euthyroid
Ultrasound - useful for determining the character of the thyroid nodules
FNA - allows cytological analysis
Radionuclide Isotope Scanning - checks iodine uptake
CT/MRI - detect spread of thyroid cancer
Define thyroiditis.
Inflammation of the thyroid gland.
What are the causes of thyroiditis?
Hashimoto’s thyroiditis - an autoimmune condition - most common cause of hypothyroidism in the UK
de Quervain’s thyroiditis
Postpartum thyroiditis
Drug-induced thyroiditis
Acute or infectious thyroiditis
Riedel’s thyroiditis
What are the presenting symptoms of thyroiditis?
- Fatigue
- Constipation
- Dry skin
- Weight gain
- Cold intolerance
- Menstrual irregularities
- Depression
- Hair loss
- Symptoms caused by rapid enlargement of the thyroid gland = dyspnoea, dysphagia, tenderness
What are the appropriate investigations for thyroiditis?
- Based on clinical observations
- Histology: diffuse lymphocytic and plasma cell infiltration with formation of lymphoid follicles
- TSH - raised
- Antibodies = anti-TPO, anti-thyroglobulin
- Thyroid ultrasound
- Radionuclide isotope scanning
What is the management of thyroiditis?
- Pharmacological = thyroid hormone replacement - oral levothyroxine sodium
- Surgical = considered if there is a large goitre that is causing symptoms due to compression of surrounding structures or if there is a malignant nodule
What are the possible complications of thyroiditis?
Thyroid hormone over-replacement –> bone loss + tachycardia
Hyperlipidaemia
Hashimoto’s encephalopathy
Myxoedema coma
Define osteomalacia.
A disorder of mineralisation of bone matrix (osteoid).
Define Rickets.
A disorder of defective mineralisation of cartilage in the epiphyseal growth plates of children.
What are the risk factors for vitamin D deficiency?
Lack of exposure to sunlight
Dietary deficiency
Malabsorption
Decreased 25-hydroxylation of vitamin D (due to liver disease, anticonvulsants)
Decrease 1a-hydroxylation of vitamin D (due to chronic kidney disease, hypoparathyroidism)
Vitamin D resistance
What are the risk factors for osteomalacia?
- Vitamin D deficiency
- Renal Phosphate wasting
What are the presenting symptoms of osteomalacia/vitamin D deficiency?
Bone pain (mainly in the axial skeleton)
Weakness
Malaise
What are the presenting symptoms of Rickets?
Hypotonia
Growth retardation
Skeletal deformities
What are the signs of osteomalacia/vitamin D deficiency on examination?
Bone tenderness
Proximal muscle weakness
Waddling gait
Signs of hypocalcaemia:
Trousseau’s sign - inflation of a blood pressure cuff to above the systolic pressure for > 3 mins causes tetanic spasm of the wrist and fingers
Chvostek’s sign - tapping over the facial nerve causes twitching of the ipsilateral facial muscles
What are the signs of Rickets on examination?
Bossing of frontal and parietal bones
Swelling of costochondral junctions (rickety rosary)
Bow legs in early childhood
‘Knock knees’ in later childhood
Short stature
What are the appropriate investigations for osteomalacia/vitamin D deficiency?
o Bloods = Low or normal Ca2+, Low phosphate, High ALP, Low 25-hydroxy vitamin D, High PTH (secondary hyperparathyroidism), Check U&Es, Check ABGs (for renal tubular acidosis), Increased phosphate excreting (in renal phosphate wasting)
o Radiographs = may appear normal but may show osteopaenia - Looser’s zones = wide, transverse lucencies traversing part way through a bone, usually at right angles to the involved cortex and are associated most frequently with osteomalacia and rickets (AKA pseudofractures)
o Bone biopsy after double tetracycline labelling = after two course of tetracycline (separated by a few days), the distance between the bands of deposited tetracycline is reduced in osteomalacia -> not usually necessary for the diagnosis of osteomalacia
What is the management plan for osteomalacia/vitamin D deficiency?
Vitamin D and calcium replacement
Monitor 24 hr urinary calcium, serum calcium, phosphate, ALP, PTH, vitamin D
Treat the underlying cause
What are the possible complications of osteomalacia/vitamin D deficiency?
Bone deformities
Depression
Hypocalcaemia symptoms = CATS go NUMB
Convulsions
Arrhythmias
Tetany
Epileptic Seizures
NUMBness/paraesthesia
