Endocrine Flashcards

Question

What are the signs of Carcinoid Syndrome on physical examination?

Answer 1

``` Facial flushing Telangiectasia Wheeze Right-sided heart murmurs: -Tricuspid stenosis, regurgitation or pulmonary stenosis Nodular hepatomegaly in cases of metastatic disease Carcinoid crisis: -Profound flushing -Bronchospasm -Tachycardia -Fluctuating blood pressure ```

Answer 2

24-h urine collection: -5-HIAA levels (a metabolite of serotonin, false positive with high intake of certain fruit/drugs e.g. bananas and avocados, caffeine, paracetamol) Bloods: -Plasma chromogranin A and B, fasting gut hormones: elevated -Metabolic profile: elevated creatinine if dehydrated from diarrhoea -LFTs: changes depending on location of tumour/presence of metastases CT or MRI scan: To localise the primary tumour and detect live metastases (routine every 4-6 months) Endoscopy/bronchoscopy: localise tumour Radioisotope scan: -Radiolabelled somatostatin analogue (e.g. indium-111 octreotide) helps localize tumour

Answer 3

The clinical manifestation of pathological hypercortisolism (chronic inappropriate elevation of free circulating cortisol) from any cause

Answer 4

Exogenous corticosteroid exposure is the most common cause Endogenous: ACTH-dependent (80%): -Excess ACTH secreted from a pituitary adenoma: Cushing's disease (80%). -ACTH secreted from an ectopic source, e.g. small-cell lung carcinomas, pulmonary carcinoid tumours (20%) ACTH-independent (20%): - Excess cortisol secreted from a benign adrenal adenoma (60%) - RARE: 1% of Cushing's syndrome cases are caused by adrenal carcinoma - BUT of this 1%, adrenal overproduction of cortisol is seen in 30% to 40% of adrenal carcinomas

Answer 5

Cushing's syndrome is relatively uncommon in the general population Exogenous Cushing's syndrome is the most common cause Endogenous Cushing's syndrome is more common in females (x4) Peak incidence is 20–40 years, although it can occur at any age

Answer 6

Increasing weight and fatigue Muscle weakness Myalgia Thin skin Easy bruising Poor wound healing Fractures (resulting from osteoporosis) Hirsutism Acne Frontal balding Oligo- or amenorrhoea Depression or psychosis

Answer 7

Specific features: - Facial plethora: increased perfusion, redness, one of the earliest features of Cushing's syndrome - Proximal muscle weakness - Bruises Other signs: - Facial fullness - Interscapular fat pad - Thin skin - Central obesity - Pink/purple striae on abdomen, breast, thighs - Kyphosis (due to vertebral fracture) - Poorly healing wounds - Hirsutism, acne, frontal balding. - Hypertension - Ankle oedema (salt and water retention as a result of mineralocorticoid effect of excess cortisol) - Pigmentation in ACTH-dependent cases

Answer 8

Initial high-sensitivity tests: - Urinary free cortisol (two or three 24 h urine collections) -Late-night salivary cortisol - Overnight dexamethasone suppression test - Low dose dexamethasone suppression test, involves giving 0.5mg dexamethasone orally every 6h for 48h * In Cushings syndrome, serum cortisol measured 48 h after the first dose of dexamethasone fails to suppress below 50 nmol/L (morning cortisol) Tests to determine the underlying cause: -ACTH-independent (adrenal adenoma/carcinoma): low Plasma ACTH, CT or MRI of adrenals -ACTH-dependent (pituitary adenoma): High Plasma ACTH, Pituitary MRI. High-dose dexamethasone suppression test (DOES NOT SUPPRESS) ?Inferior petrosal sinus sampling: Central: peripheral ratio of venous ACTH > 2:1 (or >3:1 after CRH administration) in Cushings disease ACTH-dependent (ectopic): - If lung cancer is suspected: CXR, sputum cytology, bronchoscopy, CT scan - Radiolabelled octreotide scans to detect carcinoid tumours as they express somatostatin receptors. Others: - Urine pregnancy test - Serum glucose: elevated, Cushing's syndrome commonly leads to diabetes and glucose intolerance - Non-specific changes include hypokalaemia (particularly in ectopic Cushings)

Answer 9

In iatrogenic cases, discontinue administration, lower steroid dose or use an alternative steroid-sparing agent if possible Medical: - Pre-operative or if unfit for surgery - Inhibition of cortisol synthesis with metyrapone (competitive inhibitor of 11β-hydroxylation in the adrenal cortex inhibiting cortisol production) or ketoconazole (potent inhibitor of cortisol and aldosterone synthesis) - Treat osteoporosis and provide physiotherapy for muscle weakness Surgical: -Pituitary adenomas(Cushing's disease): Trans-sphenoidal adenoma resection (hydrocortisone replaced until pituitary function recovers) -Adrenal adenoma/carcinoma: Surgical removal of tumour (plus adjuvant therapy with mitotane for adrenal carcinoma) Ectopic ACTH production: Treatment is directed at the tumour. *In refractory cases of Cushings disease, bilateral adrenalectomy may be performed

Answer 10

Diabetes Osteoporosis Hypertension Pre-disposition to infections Adrenal insufficiency secondary to adrenal suppression Complications of surgery: -CSF leakage, meningitis, sphenoid sinusitis, hypopituitarism Complications of radiotherapy: Hypopituitarism, radionecrosis, small increased risk of second intracranial tumours and stroke Bilateral adrenalectomy may rarely be complicated by development of Nelsons syndrome (locally aggressive pituitary tumour causing skin pigmentation due to excessive ACTH secretion)

Answer 11

In the untreated, 5-year survival rate is 50%, mortality is mainly from cardiovascular disease Depression usually persists for many years following successful treatment

Answer 12

A disorder of inadequate secretion of or insensitivity to vasopressin (ADH) leading to hypotonic polyuria (production of large quantities of dilute urine)

Answer 13

DI may be central in origin, resulting from an absolute or relative deficiency of vasopressin (ADH); or it may be nephrogenic in origin, resulting from a renal insensitivity or resistance of the collecting duct to vasopressin Both mechanisms result in the failure of activation of Water channels (aquaporins) and the luminal membrane of the collecting duct remains impermeable to water This results in large volume hypotonic urine and polydipsia

Answer 14

``` Idiopathic *Tumours (e.g. pituitary tumours) Infilitrative (e.g. sarcoidosis) Infection (e.g. meningitis) Vascular (e.g. aneurysms, Sheehan syndrome) Trauma (e.g. head injury, neurosurgery) ```

Answer 15

``` Idiopathic *Drugs (e.g. lithium) Post-obstructive uropathy Pyelonephritis Pregnancy Osmotic diuresis (e.g. diabetes mellitus) ```

Answer 16

DI is uncommon | No differences in prevalence between sexes or among ethnic groups but median age of onset is 24 years

Answer 17

Polyuria Nocturia Polydipsia (excessive thirst) Enuresis (involuntary urination) and sleep disturbances in children

Answer 18

Cranial diabetes insipidus has few signs if patients drink adequate fluids Urine output is often >3 L/24 h If fluid intake < fluid output, signs of dehydration may be present (e.g. tachycardia, reduced tissue turgor, postural hypotension, dry mucous membranes) Signs of the cause (e.g. visual field defect bitemporal hemianopia from pituitary tumour)

Answer 19

Blood: -U&Es: HIGH Plasma osmolality LOW Urine osmolality Water deprivation test: -Water is restricted for 8 h Plasma and urine osmolality are measured every hour over the 8 h Weigh the patient (hourly) to monitor the level of dehydration; stop the test if the fall in body weight is >3% Desmopressin (2 mg IM) is given after 8 h and urine osmolality is measured

Answer 20

Normal: -Water restriction causes a rise in plasma osmolality and increase in ADH secretion This leads to increased water reabsorption in the collecting ducts Urine is concentrated: (Urine osmolality > 600 mosmol/kg) Diabetes Insipidus: - Lack of ADH activity means that urine is unable to be concentrated by the collecting ducts - (Urine osmolality < 400 mosmol/kg) - Cranial: Urine osmolality rises by >50%, following administration of desmopressin (due to deficiency in vasopressin) - Nephrogenic: Urine osmolality rises by <45%, following administration of desmopressin (resistance to vasopressin)

Answer 21

Treat the identified cause if possible Cranial diabetes insipidus: -Desmopressin (DDAVP), a vasopressin analogue, can be given 10 mg/day, intranasally (parenteral DDAVP is 5 to 20 times more potent) Nephrogenic diabetes insipidus: -Sodium and/or protein restriction may help polyuria -Thiazide diuretics

Answer 22

Hypernatraemic dehydration: -Mild to moderate hypernatraemia may present with irritability, restlessness, lethargy, muscle twitching, spasticity, or hyper-reflexia -Severe hypernatraemia may present with delirium, seizures, or coma Excess desmopressin therapy may cause hyponatraemia.

Answer 23

Variable depending on cause While DI is often a lifelong condition cranial DI may be transient following head trauma Cure of cranial or nephrogenic diabetes insipidus may be possible on removal of cause, e.g. tumour resection, drug discontinuation

Answer 24

A common chronic syndrome of impaired carbohydrate, protein, and fat metabolism owing to insufficient secretion of insulin and/or target-tissue insulin resistance

Answer 25

A metabolic disorder characterised by hyperglycaemia due to absolute insulin deficiency The condition develops due to destruction of pancreatic beta cells, mostly by immune-mediated mechanisms

Answer 26

Caused by destruction of the pancreatic insulin-producing b-cells, resulting in absolute insulin deficiency The b -cell destruction is caused by an autoimmune process in 90% of patients Likely to occur in genetically susceptible patients and is probably triggered by environmental agents

Answer 27

Type 1 diabetes accounts for about 5% to 10% of all patients with diabetes It is the most commonly diagnosed diabetes of youth (under 20 years of age) and is one of the most common chronic diseases in childhood HLA DR3 and 4 carry a significant link

Answer 28

*Often of juvenile onset (<30 years) Polyuria/nocturia Polydipsia (thirst) Non-specific symptoms: tiredness, weight loss Symptoms of complications e.g. Diabetic ketoacidosis: -Nausea and vomiting -Abdominal pain -Drowsiness, confusion, coma -Kussmaul breathing (deep and rapid) -Ketotic breath -Signs of dehydration (e.g. dry mucous membranes, reduced tissue turgor) Signs of complications e.g. diabetic retinopathy, neuropathy

Answer 29

*Blood glucose: -Fasting blood glucose >7mmol/L -Random blood glucose >11 mmol/L *Two positive results are needed before diagnosis Others: HbA1C: Estimates overall blood glucose levels in past 2–3 months -FBC, U&Es: Monitor for nephropathy and hyperkalaemia caused by ACE inhibitors -Lipid profile -Urine albumin creatinine ratio (to detect microalbuminuria- nephropathy) -Urine: Glycosuria, elevated ketones, MSU (microscopy, culture) -CXR: To exclude any infection. -ECG: To look for acute ischaemic changes Patients presenting with suspected DKA: -Bloods: FBC (raised WCC even without infection), U&Es (raised urea and creatinine from dehydration), LFT, CRP, glucose, amylase, blood cultures, ABG (metabolic acidosis with high anion gap), blood/urinary ketones

Answer 30

In the short term, insulin is life-saving because it prevents diabetic ketoacidosis The long-term goal of insulin treatment is the prevention of chronic complications by maintaining blood glucose levels as close to normal as possible Monitoring: control of symptoms (e.g. thirst, tiredness), regular finger prick tests by the patient, monitoring HbA1c levels (target <7%) every 3–6 months Good glycaemic control in type 1 diabetes requires attention to diet, exercise, and insulin therapy-all three components should be co-ordinated for ideal control with Diabetes nurse specialists and dietitians *Self-monitoring of blood glucose (SMBG) is a core component of good glycaemic control Insulin: SC insulin: Short- acting insulin (e.g. Lispro, aspart, glulisine) three times daily before each meal and one long-acting insulin (isophane, glargine, detemir) injection once daily Injection sites should be rotated Insulin pumps may give slightly better glycaemic control

Answer 31

If reduced consciousness: -50 ml of 50% glucose IV or 1 mg glucagon IM If conscious and cooperative: -50 g oral glucose (e.g. in the form of Lucozade! , milk, sugar or 3 dextrose tablets) -Followed with a starchy snack Should not drive for 45 min *Screening and management cardiovascular risk factors

Answer 32

Diabetic ketoacidosis, may be precipitated by infection or errors in management Microvascular: Retinopathy, nephropathy, neuropathy Macrovascular: Peripheral vascular disease, ischaemic heart disease, stroke/TIA. Susceptible to infections (especially on feet) Complications of insulin treatment: Weight gain, fat hypertrophy at insulin injection sites

Answer 33

* Caused my missing a meal or overdosage of insulin Meuroglycopenic and adrenergic signs: - Personality change - Fits, confusion, coma - Pallor - Sweating - Tremor, tachycardia, palpitations - Dizziness - Hunger - Focal neurological symptoms * Hypoglycaemic symptoms may be masked by autonomic neuropathy, b-blockers and brain adapting to recurrent episodes

Answer 34

Depends on early diagnosis, good glycaemic control and compliance with screening and treatment Vascular disease and renal failure are major causes of increased morbidity and mortality

Answer 35

A progressive disorder defined by increased peripheral resistance to insulin action, impaired insulin secretion and increased hepatic glucose output

Answer 36

Often presents on a background genetic predisposition (HLA DR3/4) and is characterised by insulin resistance and relative insulin deficiency Insulin resistance is aggravated by ageing, physical inactivity, and overweight (BMI 25-29.9 kg/m²) or obesity (BMI >30 kg/m²)

Answer 37

Prevalence in the UK: 5–10% People of Asian, African and Hispanic descent are at greater risk The incidence has increased in parallel with increased prevalence of obesity ad being overweight worldwide

Answer 38

``` Obesity/overweight Older age Gestational diabetes (50% of women will go on to develop DM within 10 years of delivery) *Significant genetic link (HLA DR3/4) Physical inactivity Polycystic ovary syndrome Hypertension Dyslipidaemia Cardiovascular disease ```

Answer 39

May be incidental finding due to being asymptomatic Polyuria Polydypsia Tiredness Patients may present with hyperosmolar hyperglycaemic state (also known as hyperosmolar non-ketotic state) Infections (infected foot ulcers, candidiasis, balanitis or pruritus vulvae) Assess for other cardiovascular risk factors: e.g. hypertension, hyperlipidaemia and smoking

Answer 40

BMI: weight(kg)/ height(m)2), waist circumference Hypertension Look for signs of complications (retinopathy, nephropathy, neuropathy) Diabetic foot: -Both ischaemic and neuropathic signs -Dry skin, reduced subcutaneous tissue, corns and calluses, ulceration, gangrene -Signs of peripheral neuropathy: foot pulses are diminished in ischaemic foot -Skin changes (rare)

Answer 41

Diabetes mellitus 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 􏰂7.0 mmol/L (after an overnight fast of at least 8 h). -Two-hour plasma glucose 􏰂11.1 mmol/L after a 75 g oral glucose tolerance test Monitor: -HbA1C: 48 mmol/mol (6.5%) or greater -U&Es, lipid profile, estimated glomerular filtration rate (GFR) using the MDRD calculator -Spot urine albumin: Creatinine ratio (to detect microalbuminuria)

Answer 42

Mature onset diabetes of the young: a rare cause of type 2 diabetes due to mutations transmitted in an autosomal dominant manner

Answer 43

FIRST: lifestyle modifications (diet and exercise) and Metformin If HbA1C ≥ 7% after 3 months: 2. Lifestyle + metformin + sulphonylurea* If HbA1C ≥ 7% after 3 months: 3. Lifestyle + metformin + basal insulin If HbA1C≥7% after 3 months and fasting blood glucose >7mmol/L: 4. Add premeal rapid-acting insulin

Answer 44

``` Metformin: -Biguanide, Insulin sensitiser -Inhibits hepatic gluconeogenesis, hence GI side effects Sulphonylureas: -e.g. gliclazide -block ATP-sensitive K+ channels in b cells, stimulating insulin release Acarbose: -Alpha glucosidase inhibitor -Prolongs absorption of oligosaccharides -Allows insulin secretion to cope Thiazolidinediones: -e.g. Pioglitazone -Insulin sensitizer, mainly peripheral Glucagon-like peptide-1 (GLP-1): -Secreted in response to nutrients in gut -Stimulates insulin, suppresses glucagon -Increases satiety -Restores B cell glucose sensitivity Gliptins: -Given alongside GLP-1 to increase half life ```

Answer 45

This is due to insulin deficiency, as diabetic ketoacidosis, but patients are usually old and may be presenting for the first time History is longer (e.g. 1 week) There is marked dehydration, high Na + , high glucose (>35 mmol/ L), high osmolality (>340 mosmol/kg), no acidosis

Answer 46

Neuropathy: -Distal symmetrical sensory neuropathy -Painful neuropathy -Carpal tunnel syndrome -Diabetic amyotrophy (asymmetrical wasting of proximal muscle) -Mononeuritis (e.g. III nerve palsy with preservation of pupillary response, VI nerve) -Autonomic neuropathy (e.g. postural hypotension), gastroparesis (abdominal pain, nausea, vomiting), impotence, urinary retention Nephropathy: -Microalbuminuria, proteinuria and, eventually, renal failure -Prone to UTIs and renal papillary necrosis Retinopathy: -Background: Dot and blot haemorrhages, hard exudates -Pre-proliferative: Cotton wool spots, venous beading -Proliferative: New vessels on the disc and elsewhere -Maculopathy: Macular oedema, exudates within 1 disc diameter of the centre of fovea, haemorrhage -Also prone to glaucoma, cataracts, transient visual loss

Answer 47

Ischaemic heart disease Stroke Peripheral vascular disease

Answer 48

``` Diabetes increases the likelihood of major cardiovascular events and death, but the increased risk is variable across patients depending on: -age at diabetes onset -duration of diabetes -glucose control -blood pressure control -lipid control -tobacco control -renal function* -microvascular complication status Mortality can be attenuated by cardiovascular risk factor control ```

Answer 49

An acute metabolic complication of diabetes that is potentially fatal and requires prompt medical attention for successful treatment It is characterised by absolute insulin deficiency and is the most common acute hyperglycaemic complication of type 1 diabetes mellitus

Answer 50

Reduced Insulin and increased counter-regulatory hormones result in increased hepatic gluconeogenesis and reduced peripheral glucose utilization. Renal reabsorptive capacity of glucose is exceeded causing glycosuria, osmotic diuresis and dehydration. Increased lipolysis leads to ketogenesis and metabolic acidosis The two most common precipitating events are: - Infection - Discontinuation of, or inadequate, insulin therapy Underlying medical conditions, such as myocardial infarction or pancreatitis, that provoke the release of counter-regulatory hormones are also likely to result in DKA in patients with diabetes

Answer 51

The incidence of hospital admissions for DKA among adults with Type 1 AND type 2 diabetes mellitus has increased

Answer 52

``` PMH of DM Nausea and vomiting Abdominal pain Dehydrated Hyperventilation Acetone smell on breath Confusion ```

Answer 53

``` Signs of dehydration: -Dry mucous membranes -Decreased skin turgor or skin wrinkling -Slow capillary refill -Tachycardia with a weak pulse -Hypotension Polyuria Polydipsia Kussmaul breathing (deep and rapid) Ketotic breath Coma ```

Answer 54

Venous blood gas: -Metabolic acidosis (pH can determine the severity of DKA) -pH ≥7.0 indicates mild or moderate DKA -pH <7.0 indicates severe DKA (critical care) -Hyperkalaemia is common -Plasma osmolality is high (>320 mmol/kg) in DKA and is an indication of dehydration Blood ketones: ketonaemia (ketones ≥3.0 mmol/L) Blood glucose: hyperglycaemia (blood glucose >11.1 mmol/L) U&Es: Hyponatraemia and Hyperkalaemia are common in DKA, but hypokalaemia is an indicator of severe FBC: Leukocytosis is common in DKA and correlates with blood ketone levels Urinalysis: ketones, leukocytes ECG: look for cardiac precipitates for DKA such as MI (and check cardiac enzymes) Pregnancy test Amylase and lipase: for pancreatitis Creatinine kinase: elevated with rhabdomyolysis (breakdown of damaged skeletal muscle) CXR: if low oxygen sats Blood cultures: if infection suspected

Answer 55

URGENT: Start intravenous fluids as soon as DKA is confirmed (fluid bolus of 500 mL of normal saline), repeat if SBP remains low (<90mmHg) Start a fixed-rate intravenous insulin infusion Ensure continuous cardiac monitoring Identify and treat any precipitating acute illness e.g. MI, sepsis, pancreatitis

Answer 56

Cerebral oedema/brain injury *most common cause of mortality in DKA* Arterial or venous thromboembolic events: Standard prophylactic low-dose heparin SE of high insulin dose therapy: hypokalaemia, hypoglycaemia Pulmonary oedema/ARDS: rare but significant complications of treatment for DKA (fluid overload)

Answer 57

Improved understanding of the pathophysiology of DKA, together with close monitoring and correction of electrolytes, has resulted in a significant reduction in the overall mortality rate from this life-threatening condition Death is rarely caused by the metabolic complications of hyperglycaemia or ketoacidosis but rather relates to the underlying illness *The prognosis is substantially worsened at the extremes of age and in the presence of coma and hypotension

Answer 58

Dyslipidaemia is classified as serum Total cholesterol, LDL-C, triglycerides, apolipoprotein B, or lipoprotein(a) concentrations above the 90th percentile for the general population

Answer 59

Primary causes: due to single or multiple gene mutations, resulting in a disturbance of low-density lipoprotein (LDL) and triglyceride production or clearance - most commonly seen in children and young adults Secondary causes: caused by lifestyle factors or disorders that interfere with blood lipid levels over time such as obesity, chronic renal insufficiency, abdominal obesity, diabetes mellitus and hypothyroidism

Answer 60

Common, particularly in developing countries Strong correlation between body mass index and coronary heart disease Primary causes are common in children and young adults whereas secondary is seen more in adults

Answer 61

Excess body weight PMH Diabetes Mellitus Type 2 or cardiovascular disease Consumption of saturated fats FH of early onset of coronary heart disease or Dyslipidaemia

Answer 62

Xanthelasmas: Yellow plaques that occur most commonly near the inner canthus of the eyelid Tendinous xanthomas: Slowly enlarging subcutaneous nodules (on tendons or ligaments)

Answer 63

Lipid profile: -total cholesterol (TC) >5.18 mmol/L (>200 mg/dL) -LDL-cholesterol >2.59 mmol/L (>100 mg/dL) -triglycerides >1.7 mmol/L (>150 mg/dL) Fasting (12h) triglycerides: ≥2.3 mmol/L (200 mg/dL) Thyroid stimulating hormone: elevated in primary hypothyroidism Lipoprotein (a): values >50 mg/dL or >125 nmol/L are considered high

Answer 64

Combination of lifestyle changes to diet and exercise, medications, and dietary supplements Lifestyle changes: dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise Drug therapy: Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a key enzyme in cholesterol synthesis, which leads to up-regulation of LDL receptors and increased LDL clearance

Answer 65

``` Atherosclerosis: Ischaemic heart disease Peripheral vascular disease Acute coronary syndrome Stroke Erectile dysfunction (endothelial dysfunction) ```

Answer 66

The rate of adverse outcomes has been significantly reduced with the use of statins Useful in the rid reduction of coronary heart disease

Answer 67

Having a fasting plasma triglyceride level of ≥2.3 mmol/L (≥200 mg/dL)

Answer 68

Eruptive xanthomas: Small yellowish papules, frequently surrounded by an erythematous base, that appear predominantly on the buttocks, elbows, and other pressure-sensitive areas

Answer 69

An autoimmune thyroid condition associated with hyperthyroidism caused by TSH (thyroid-stimulating hormone) receptor antibodies

Answer 70

Graves' disease is an autoimmune condition | The aetiology of thyroid hormone overproduction is stimulation of the thyroid by TSH receptor antibodies

Answer 71

Graves' disease is the most common form of hyperthyroidism in most areas of the world (other cause is toxic multinodular goitre)

Answer 72

``` Features of hyperthyroidism: -Heat intolerance -Palpitations -Sweating -Weight loss -Tremor Neck lump ```

Answer 73

*Diffuse goitre (smooth) Tremor Exophthalmos - bulging of the eye anteriorly The presence of upper eyelid retraction with thyroid dysfunction, exophthalmos/optic neuropathy, and/or extraocular muscle involvement is diagnostic of Graves' orbitopathy (25% of patients) Menstrual disturbances e.g. oligomenorrhoea

Answer 74

Thyroid function tests: -Suppressed/low TSH -Serum free/total T3 or T4: elevated Calculation of T3/T4 ratio: high compared to in thyroiditis Radioactive iodine uptake test: elevated Thyroid isotope scan: diffuse uptake (rather than patchy in multi nodular goitre) TSH receptor antibodies: POSITIVE Colour-flow Doppler Ultrasound: may help to distinguish Graves' from painless thyroiditis; highly vascular; diffuse; enlarged thyroid Others: -CT/MRI of orbit: may show muscle thickening -Skin biopsy: may confirm thyroid dermopathy

Answer 75

Primary: Increased secretion of parathyroid hormone (PTH) unrelated to the plasma calcium concentration Secondary: Increased secretion of PTH secondary to hypocalcaemia Tertiary: Autonomous PTH secretion following chronic secondary hyperparathyroidism

Answer 76

Primary: -Parathyroid gland adenoma(s) (80%)or hyperplasia (18% hyperplasia/multiple adenomas) -Rarely, parathyroid carcinoma (2%) -May be associated with multiple endocrine neoplasia (MEN) Secondary: -Chronic renal failure -Vitamin D deficiency

Answer 77

Primary: relatively common disorder, annual incidence is five in 100,000 Twice as common in females Peak incidence 40–60 years *Vitamin D deficiency is the most common cause of elevated serum parathyroid hormone levels

Answer 78

Primary: Many patients have mild hypercalcaemia and are asymptomatic Secondary: May present with symptoms and signs of hypocalcaemia and/ or the underlying cause (chronic renal failure, vitamin D deficiency)

Answer 79

``` Polyuria Polydipsia Renal calculi Bone pain Abdominal pain Nausea Constipation Psychological depression Lethargy ```

Answer 80

*Serum calcium: High in primary and tertiary Low/normal in secondary *Serum phosphate: Low in primary and tertiary High in secondary PTH levels: -High -Patients with parathyroid carcinomas are more likely to have a marked hypercalcaemia with very high serum PTH levels 25-hydroxyvitamin D level: may be low Serum alkaline phosphatase: may be raised due to bone disease 24h Urine Calcium: high or normal in PHPT; low in familial hypocalciuric hypercalcaemia Dual energy x-ray absorpitometry (DXA): Once diagnosis of PHPT is confirmed, a DXA scan should be completed to assess progression of disease in 3 sites: lumbar spine, hip, and forearm Ultrasonography/CT neck: for planning of surgery

Answer 81

Primary: Parathyroid surgery is the definitive treatment It is indicated for all symptomatic patients, and is recommended for many asymptomatic patients Secondary: treat the underlying renal failure. Calcium and vitamin D supplements Acute hypercalcaemia: -IV fluids (often 4–6 in the first 24 h) Conservative management: -Avoid factors that can exacerbate hypercalcaemia including thiazide diuretics -Maintain adequate hydration (at least 6–8 glasses of water per day), moderate calcium and vitamin D intake.

Answer 82

``` Symptomatic patients Or asymptomatic patients with: Age <50 years Bone mineral density: T-score <2.5 Calculi (renal stones) Creatinine clearance reduced by 30% Difficult to do follow up periodically Elevated serum calcium >0.25 mmol/L above upper limit of normal or 24-h urinary calcium >10 mmol ```

Answer 83

Primary: Increased PTH results in increased bone resorption and increased renal tubular calcium reabsorption, 1a- hydroxylation of vitamin D and intestinal calcium absorption, leading to hypercalcaemia Secondary: Increased stimulation of osteoclasts and bone turnover leading to osteitis fibrosa cystica Complications of surgery: Hypocalcaemia, recurrent laryngeal nerve palsy (<1%)

Answer 84

Primary: Surgery is curative for benign disease in most cases Secondary or tertiary: prognosis for chronic kidney disease- progressive and will eventually lead to end-stage renal disease (ESRD) and the need for renal replacement therapy (i.e., dialysis, transplant)

Answer 85

Characterized by impairment of ovarian function

Answer 86

Primary hypogonadism (hypergonadotrophic): - Gonadal dysgensis: Chromosomal abnormalities (e.g. Turners syndrome), FMR1 gene pre-mutation carriers - Gonadal damage: Autoimmune, iatrogenic (chemotherapy, radiation, surgery) Secondary hypogonadism (hypogonadotrophic): - Functional: Stress, weight loss, excessive exercise, eating disorders (anorexia nervosa, bulimia) - Pituitary/hypothalamic tumours and infiltrative lesions: Pituitary adenomas, craniopharyngiomas, haemochromatosis - Hyperprolactinaemia: Prolactinomas or tumours causing pituitary stalk compression - Congenital GnRH deficiency: Kallmanns syndrome, idiopathic

Answer 87

Secondary hypogonadism is a more common cause of anovulation and amenorrhoea than primary hypogonadism Turners syndrome occurs in up to 1.5% of conceptions,

Answer 88

Symptoms of oestrogen deficiency: -Night sweats -Hot flush -Vaginal dryness and dyspareunia (painful intercourse) -Reduced libido -Infertility Symptoms of the underlying cause e.g. prolactinomas

Answer 89

``` Pre-pubertal hypogonadism: -Delayed puberty (primary amenorrhoea, absent breast development, no secondary sexual characteristics) Eunuchoid proportions (e.g. long legs, increased arm span for height) ``` Post-pubertal hypogonadism: -Regression of secondary sexual characteristics (loss of secondary sexual hair, breast atrophy) -Perioral and periorbital fine facial wrinkles -Signs of the underlying cause/associated conditions: ~Hypothalamic/pituitary disease: Visual field defects (bitemporal hemianopia) ~Kallmanns syndrome: Anosmia ~Turners syndrome: Short stature, low posterior hairline, high arched palate, widely spaced nipples, wide carrying angle, short fourth and fifth metacarpals, congenital lymphoedema -Patients with autoimmune primary ovarian failure: Signs of other autoimmune diseases e.g. hyperpigmentation in Addisons disease or vitiligo

Answer 90

Serum oestradiol: LOW Serum FSH and LH: -HIGH in primary hypogonadism (due to -ve feedback inhibition by ovarian oestradiol and inhibin). -LOW or inappropriately normal FSH/LH in secondary hypogonadism Investigating aetiology: Primary: -Genetic testing/ Karyotype Secondary: - Pituitary function tests (9 a.m. cortisol, TFTs, prolactin) - Visual field testing - Hypothalamic-pituitary MRI - Smell tests for anosmia - Serum transferrin saturation if hereditary haemochromatosis is suspected

Answer 91

A syndrome of reduced testosterone production, sperm production or both

Answer 92

Primary (hypergonadotrophic) hypogonadism: - Gonadal dysgensis: Klinefelters syndrome (XXY), undescended testes (cryptorchidism) - Gonadal damage: Infection (e.g. mumps), torsion, trauma, autoimmune, iatrogenic (chemotherapy, surgery, radiation) - Rare causes: Defects in enzymes involved in testosterone synthesis, myotonic dystrophy Secondary (hypogonadotrophic) hypogonadism: - Pituitary/hypothalamic lesions - GnRH deficiency: Kallmanns syndrome (associated with anosmia) - Idiopathic Hyperprolactinaemia - Systemic/chronic diseases - Rare causes: Genetic mutations *Secondary hypogonadism may be seen in a number of rare syndromes: -Prader–Willi syndrome: Loss of a critical region on chromosome 15 causing obesity and short stature, small hands, almond-shaped eyes, learning difficulty/postnatal hypotonia

Answer 93

The prevalence of hypogonadism increases with age Primary hypogonadism accounts for 30–40% of cases of male infertility; secondary hypogonadism accounts for 1–2% Most common cause of primary hypogonadism is Klinefelters syndrome

Answer 94

Delayed puberty (if the onset is before puberty) Reduced libido, impotence, infertility Symptoms of the underlying cause: -e.g. Klinefelters syndrome: intellectual dysfunction and behavioural abnormalities which cause difficulty in social interactions

Answer 95

Measure testicular volume: normal adult testicular volume is 15–25 ml Prepubertal hypogonadism: - Signs of delayed puberty (high-pitched voice, lack of pubic/axillary/facial hair, small or undescended testes, small phallus), gynaecomastia, eunuchoid proportions: arm span>height, lower segment > upper segment (due to delayed fusion of the epiphyses and continued growth of long bones) - Features of the underlying cause e.g. cryptorchidism, anosmia in Kallmanns syndrome Postpubertal hypogonadism: - Lack of Pubic/axillary/facial hair - Soft and small testes - Gynaecomastia - Fine perioral wrinkles - Features of the underlying cause e.g. visual field defects due to a pituitary tumour, signs of systemic/chronic illness

Answer 96

Serum total testosterone: -Check between 6 a.m. and 8 a.m. ideally -less than 10.4 nanomol/L (<300 nanograms/dL) is generally accepted as indicating hypogonadism Results: -Primary: LOW Testosterone, HIGH LH and FSH (due to -ve negative feedback) -Secondary: LOW Testosterone, LOW or inappropriately normal LH and FSH levels Primary: Karyotype Secondary: Pituitary function tests (9 a.m. cortisol, TFTs, prolactin), MRI of the hypothalamic- pituitary area, visual field testing, smell tests for anosmia. Iron studies (ferritin and transferrin saturation) if hereditary haemochromatosis is suspected

Answer 97

Deficiency of one or more of the hormones secreted by the anterior pituitary Panhypopituitarism is deficiency of all pituitary hormones

Answer 98

GH FSH/LH Prolactin ACTH TSH

Answer 99

Vasopressin | Oxytocin

Answer 100

Pituitary masses: Most commonly adenomas. Other parapituitary tumours or cysts Pituitary trauma: Radiation, surgery or skull base fracture Hypothalamus (functional): Anorexia, starvation, over-exercise Infiltration: Tuberculosis, sarcoidosis, haemochromatosis Vascular: Pituitary apoplexy (bleeding into or impaired blood supply of the pituitary gland), Sheehans syndrome Infection: Meningitis, encephalitis, syphilis (rare), fungal abscess Genetic mutations: Pit-1 and Prop-1 genes

Answer 101

Hypopituitarism is relatively rare | Annual incidence of pituitary adenomas is 􏰀1 in 100,000

Answer 102

Symptoms or signs depending on aetiology (e.g. bitemporal hemianopia caused by a pituitary mass) Symptoms and signs according to type of hormone deficiency *Pituitary apoplexy: Life-threatening hypopituitarism with headache, visual loss and cranial nerve palsies

Answer 103

Children: | -Short stature (

Answer 104

``` Delayed puberty Females: -Loss of secondary sexual hair -Breast atrophy -Menstrual irregularities -Dyspareunia -Reduced libido -Infertility Males: -Loss of secondary sexual hair -Gynaecomastia -Small or soft testes -Reduced libido -Impotence ```

Answer 105

Chronic presentation: Non-specific vague symptoms such as dizziness, anorexia, weight loss, diarrhoea, vomiting, abdominal pain, lethargy, weakness, depression Acute presentation: (Addisonian crisis) Acute adrenal insufficiency with major haemody- namic collapse often precipitated by stress (e.g. infection or surgery) Hypotensive shock, tachycardia, pale, cold, clammy, oliguria

Answer 106

Hypothyroidism: - Cold intolerance - Weight gain

Answer 107

Pituitary infarction, haemorrhage and necrosis following post-partum haemorrhage

Answer 108

Pituitary function tests: - Basal tests: 9 a.m. cortisol, LH, FSH, testosterone, oestradiol, IGF-1, prolactin, free T4 and TSH - Dynamic tests (rarely performed) Short Synacthen test: Serum cortisol <550 nmol/L at 30 min indicates adrenal failure (primary) MRI or CT of brain: pituitary masses, vascular lesions Visual field testing

Answer 109

Hormone replacement: -Hydrocortisone: 20 mg in morning, 10 mg in evening (double oral dose for febrile illnesses, IM hydrocortisone at times of surgery) -*Should be provided with Medicalert bracelet and steroid card -Levothyroxine: 􏰀100 mg daily (always taken after hydrocortisone to avoid Addisonian crisis) -Sex hormones: Testosterone in males. Oestrogen and progestogerone in females -Growth hormone: SC 1.2 unit/day in adults, Children require specialist supervision *Posterior pituitary deficiency (damaged to pituitary stalk): Desmopressin (vasopressin analogue) 10–20 mg/day intranasally

Answer 110

Adrenal crisis Hypoglycaemia Myxoedema coma: severe hypothyroidism leading to decreased mental status, hypothermia, and slowing of function in multiple organs- it is a medical emergency with a high mortality rate Infertility Osteoporosis; dwarfism (children) Complications of the pituitary mass: -Optic chiasm compression -Hydrocephalus (third ventricular compression) -Temporal lobe epilepsy

Answer 111

Good with lifelong hormone replacement

Answer 112

The clinical syndrome resulting from insufficient secretion of thyroid hormones

Answer 113

Primary (reduced thyroid hormone production): Acquired: -Autoimmune (Hashimotos) thyroiditis (cellular and antibody-mediated) -Iatrogenic (post-surgery, radioiodine, medication for hyperthyroidism) -Severe iodine deficiency or iodine excess (Wolff–Chaikoff effect) -Thyroiditis Congenital: -Thyroid dysgenesis -Inherited defects in thyroid hormone biosynthesis Secondary (<5% of cases): Pituitary or hypothalamic disease (e.g. tumours) resulting in reduced TSH and reduced stimulation of thyroid hormone production

Answer 114

The frequency of hypothyroidism varies from 0.1 to 2% of adults Females to Men ratio is 6:1 Age of onset commonly >40 years, but can occur at any age Iodine deficiency is seen in mountainous areas (e.g. Alps, Himalayas)

Answer 115

``` Onset is usually insidious. Cold intolerance Lethargy Weight gain Constipation Dry skin Hair loss Hoarse voice Mental slowness Depression Dementia Cramps Ataxia Paraesthesia Menstrual disturbances (irregular cycles, menorrhagia) in females *Personal or family history of other autoimmune conditions e.g. Addisons disease, type 1 DM, pernicious anaemia and pre-mature ovarian failure ```

Answer 116

``` Severe hypothyroidism usually seen in the elderly): Hypothermia Hypoventilation Hyponatraemia Heart failure Confusion Coma ```

Answer 117

Hands: Bradycardia, cold hands Head/Neck/Skin: -Pale puffy face -Goitre -Oedema -Hair loss -Dry skin -Vitiligo Chest: Pericardial or pleural effusions Abdomen: Ascites Neurological: Slow relaxation of reflexes, signs of carpal tunnel syndrome

Answer 118

Thyroid function tests: LOW T4/T3 and HIGH TSH (due to reduced negative feedback) Secondary: LOW T3/T4 and LOW or inappropriately normal TSH ``` Others: FBC: Normocytic anaemia (non-specific) U&Es: May show low Na+ Cholesterol: May be high In suspected secondary cases: Pituitary function tests, pituitary MRI and visual field testing ```

Answer 119

Levothyroxine (25–200 mg/day) Rule out underlying adrenal insufficiency and treat before starting thyroid hormone replacement to avoid Addisonian crisis Adjust dosage depending on TFT and clinical picture (monitor at 6 weeks) In patients with ischaemic heart disease, start at low dose (25 mg/day) and gradually increase at 6 week intervals if ischaemic symptoms do not deteriorate

Answer 120

Oxygen Rewarming Rehydration IV T4/T3 IV hydrocortisone (in case hypothyroidism is secondary to hypopituitarism) Treat the underlying disorder e.g. infection

Answer 121

``` Myxoedema coma Mxoedema madness (psychosis with delusions and hallucinations or dementia) in severe hypothyroidism (may be seen in the elderly after starting levothyroxine treatment) ```

Answer 122

Lifelong levothyroxine replacement therapy required | Myxoedema coma has a mortality of up to 80%

Answer 123

Hereditary tumours of variable neoplastic patterns and characterised by the development of multiple endocrine tumours Can be: -Parathyroid adenomas -Pituitary adenomas (which may be non-secretory or secretory) -Enteropancreatic neuroendocrine tumours (which may affect the profiles of gastrin, insulin, glucagon, and/or vasoactive intestinal protein) -Facial lipomas -Medullary thyroid cancers -Phaeochromocytomas

Answer 124

MEN1 and MEN2 are caused by autosomal-dominant mutations that can be inherited or occur sporadically MEN1 (mutation in menin gene on chromosome 11): -Parathyroid adenoma or hyperplasia -Pancreatic endocrine tumours -Pituitary adenomas MEN type 2 (mutation in RET gene on chromosome 10): -Medullary thyroid carcinoma -Phaeochromocytoma

Answer 125

MEN syndromes are relatively rare | At least 90% of patients develop primary hyperparathyroidism (PHPT) by the age of 50 years with MEN1 syndromes

Answer 126

``` Young age Positive FH Clinical features of kidney stones Weight changes Hypertension Abdominal pain Altered bowel habit Palpitations Easy bruising/ slow wound healing Anxiety Confusion Dehydration Clinical features of Cushing's syndrome ```

Answer 127

``` Facial lesions (angiofibromas) Irregular menses/ infertility/ erectile dysfunction Visual changes Clinical features of acromegaly Clinical features of thyrotoxicosis Heat intolerance ```

Answer 128

Episodic triad of sweating, palpitations and headaches Palpable thyroid nodule (medullary thyroid cancer) Unexplained flushing GI bleeding Hepatomegaly: if there are liver metastases

Answer 129

MEN1: - Fasting serum gastrin: raised - Serum chromogranin A: raised - Serum prolactin: raised - Insulin-like Growth Factor 1 (IGF-1): raised - Serum T4 and TSH: low or elevated depending on the tumour and what it is secreting (T4 or TSH) - Chest CT/MRI: thymic or bronchopulmonary masses - Pituitary MRI: adenoma MEN2: - Serum calcitonin: raised (medullary thyroid cancer) - Plasma metanephrines: elevated levels suggest phaeochromocytoma - 24h urine metanephrines and catecholamines MEN1 and 2: - Serum PTH and calcium: suggest primary hyperparathyroidism due to parathyroid adenomas or hyperplasia - Overnight dexamethasone suppression test: Failure to suppress serum cortisol to <50 nanomol/L (<1.8 micrograms/dL) is suggestive of Cushing's syndrome - Abdominal CT/MRI: adrenal or pancreatic masses

Answer 130

Can be defined as a chronic adverse condition due to an excess amount of body fat

Answer 131

``` Caused by calorie intake, over time, is greater than the calorie expenditure Other factors: -Genetic predisposition -Behavioural dynamics (portion sizes) -Hormonal disturbances -Cultural influences (diet) ```

Answer 132

WHO: worldwide prevalence of obesity (BMI ≥30 kg/m²) in adults ranges widely from <10% in many African and Southeast Asian countries, to between 20% and 40% in Europe and the Americas, and >40% in some Pacific islands

Answer 133

``` Calculate BMI: (weight/height2) -Height -Weight Waist circumference Co-morbidities such as type 2 diabetes, cardiovascular disease, hypertension, hyperlipidaemia ```

Answer 134

*Clinical diagnosis ECG: Routine screen for signs of heart disease if suspected TFTs: Routine screen if hypothyroidism is suspected Abdominal ultrasound: Routine screen for fatty liver, steatohepatitis

Answer 135

A metabolic bone disease characterised by incomplete mineralisation of the underlying mature organic bone matrix (osteoid) following growth plate closure in adults

Answer 136

A disorder of defective mineralization of cartilage in the epiphyseal growth plates of children

Answer 137

Vitamin D deficiency is the primary cause of osteomalacia in the Western world, resulting from inadequate endogenous production of vitamin D3 in the skin, caused by: -Lack of sunlight exposure -Dietary deficiency -Malabsorption (small bowel disease e.g. coeliac disease/inflammatory bowel disease) Other causes of Vitamin D deficiency include: -Chronic kidney disease -Hypoparathyroidism

Answer 138

In US and Europe, more than 40% of the adult population older than age 50 years are vitamin D deficient, this being the most prominent cause of osteomalacia- the disease itself is relatively uncommon More common in females

Answer 139

``` Osteomalacia: -Bone pain (especially axial skeleton) -Weakness -Malaise Rickets: -Hypotonia -Growth retardation -Skeletal deformities ```

Answer 140

Osteomalacia: - Bone tenderness - Proximal muscle weakness - Waddling gait Signs of hypocalcaemia may be present: - Trousseaus sign: Inflation of the sphygmomanometer cuff to above the systolic pressure for >3 min causes tetanic spasm of wrist and fingers. - Chvosteks sign: Tapping over the facial nerve causes twitching of the ipsilateral facial muscles Rickets: - Bossing of frontal and parietal bones- unusually prominent forehead - Swelling of costochondral junctions (upper ribs) (rickety rosary) - Bow legs in early childhood, knock knees in later childhood - Short stature

Answer 141

Bloods: -Serum Calcium: normal/low -Serum 25-hydroxyvitamin D: LOW -Serum phosphate: low -PTH: High (in vitamin D deficiency, renal failure, and hypocalcaemia) -Serum alkaline phosphatase: high *24h Urine calcium: confirm diagnosis, low Radiographs (Bone x-rays): -Looser psudeofractures (Loosers zones) -Characteristic findings of long-standing secondary hyperparathyroidism; reversible with treatment of the underlying disorder Dual energy x-ray absorpitometry: DXA reveals a low bone mass in both osteoporosis and osteomalacia Bone biopsy with double tetracycline labelling: -Definitive diagnostic test available; however, due to the invasive nature, it is rarely performed -The distance between the bands of deposited tetracycline is reduced in osteomalacia

Answer 142

Vitamin D and calcium replacement: - Typically, vitamin D supplementation leads to dramatic improvements in muscle strength and a reduction of bone tenderness within weeks of initiation - Monitor 24 h urinary calcium, serum calcium, phosphate, Alk Phos, PTH and vitamin D - Vitamin D dose may need to be increased in patients with malabsorption Treat the underlying cause (e.g. advice on diet and sunlight exposure) X-linked hypophosphataemia: Oral phosphate and 1,25 (OH)2 vitamin D

Answer 143

Bone deformities Hypocalcaemia may cause epileptic seizures Cardiac arrhythmias Hypocalcaemic tetany: spasms of the hands and feet, cramps, spasm of the larynx and overactive neurological reflexes Depression

Answer 144

Symptoms and radiological appearances improve with vitamin D treatment Bone deformities in children tend to be permanent

Answer 145

A complex skeletal disease characterised by low/reduced bone density and micro-architectural defects in bone tissue, resulting in increased bone fragility and susceptibility to fracture

Answer 146

<2.5 standard deviations below peak bone mass achieved by healthy adults

Answer 147

Primary: Idiopathic (<50 years), post-menopausal Secondary: -Malignancy: Myeloma, metastatic carcinoma -Endocrine: Cushings disease, thyrotoxicosis, primary hyperparathyroidism, hypogonadism -Drugs: Corticosteroids, heparin -Rheumatological: Rheumatoid arthritis, ankylosing spondylitis -Gastrointestinal: Malabsorption syndromes (e.g. coeliac disease, partial gastrectomy), liver disease (primary biliary cirrhosis), anorexia

Answer 148

``` Age Family history Low BMI Low calcium intake Smoking Lack of physical exercise Low exposure to sunlight Alcohol abuse Late menarche Early menopause Hypogonadism ```

Answer 149

Most common chronic bone-remodelling disorder Predominantly affects white postmenopausal women (> 50), but men, premenopausal women, and children of any ethnicity can develop this condition More common in caucasians than in afro-carribeans *Causes >200 000 fractures annually in UK (especially hip fractures)

Answer 150

Often asymptomatic until characteristic fractures occur: - Femoral neck fractures (commonly after minimal trauma) - Vertebral factures (loss of height or stooped posture or acute back pain after lifting) - Colles fracture of the distal radius after fall onto outstretched hand

Answer 151

Often no signs until complications develop: - Tenderness on percussion (over vertebral fractures) - Thoracic kyphosis-roundback (if multiple vertebral fractures) - Severe pain with leg shortened and externally rotated (in a femoral neck fracture)

Answer 152

*Dual energy x-ray absorptiometry: DXA is considered the standard for measurement of bone density: -T-score of ≤-2.5 indicates osteoporosis -T-score ≤-2.5 with fragility fracture(s) indicates severe (or established) osteoporosis X-ray: Usually to diagnose fractures when symptomatic, often normal (>30% loss in density before showing radiolucency, abnormal trabeculae or cortical thinning evident), biconcave vertebrae, crush fractures Bloods: -Biochemical markers of bone resorption and bone formation: elevated urinary deoxypyridinoline and N-telopeptides (predictor of bone fracture risk) -Ca2+ , PO4 3-􏰆 and AlkPhos are normal in primary osteoporosis Others: Isotope bone scans: Can highlight stress or microfractures, but not commonly used Quantitative ultrasound: QUS may be as predictive of hip fracture Differentials: -AlkPhos: if elevated could indicate osteomalacia -Phosphate: low serum levels could indicate osteomalacia -Serum calcium: hypocalcaemia could indicate osteomalacia, hypercalcaemia could indicate hyperparathyroidism -25-hydroxyvitamin D: exclude Vit D deficiency -PTH levels; may be elevated or normal -TFTs: hyperthyroidism

Answer 153

The number of standard deviations the bone mineral density measurement is above or below the young normal mean bone mineral density. T-score is used to define osteoporosis The Z-score is 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

Answer 154

Characterized by excessive bone remodelling at one (monostotic) or more (polyostotic) sites resulting in bone that is structurally disorganised

Answer 155

Unknown *Genetic factors and viral infection (such as measles) may play a role 1. Excessive bone resorption by abnormally large osteoclasts is followed by increased bone formation by osteoblasts in a disorganised fashion 2. This results in an abnormal (mosaic) pattern of lamellar bone 3. The marrow spaces are filled by an excess of fibrous tissue with a marked increase in blood vessels

Answer 156

``` It is the second most common chronic bone-remodelling disorder after osteoporosis Common in older age 3% of all >50-year-olds 10% of all >80-year- olds Men and women are equally affected ```

Answer 157

``` May be asymptomatic May present with insidious onset pain Can be aggravated by weight bearing and movement (may be caused by Pagetic process, associated degenerative joint disease or stress fractures) Headaches Deafness Increasing skull size ```

Answer 158

Bitemporal skull enlargement with frontal bossing Spinal kyphosis Anterolateral bowing of femur, tibia or forearm Skin over involved bone may be warm (as a result of increased vascularity) Sensorineural deafness (compression of vestibulocochlear nerve)

Answer 159

*Plain X-rays: -Classical appearance: lytic changes -Enlarged, deformed bones with mixed lytic/sclerotic appearance -Lack of distinction between cortex and medulla -Skull: osteoporosis circumscripta, enlargement of frontal and occipital areas, associated with a cotton wool appearance Bone scan: -Non-specific -Areas of dense uptake in pagetoid bone (hot spots) Bloods: -Raised AlkPhos (85% to 100%) -Bone specific AlkPhos: more sensitive blood test for diagnosis (>40 international units/L) -Markers of bone resorption: pro collagen 1 N-terminal Peptide and C terminal pro-peptide of type 1 collagen: initially raised Others: -CT/MRI: evaluation of atypical patients -Bone biopsy: most sensitive and specific test for diagnosis however avoided in weight bearing long bones (femur) because of the risk of fracture in an already compromised bone: presence of osteoclasts with multiple nuclei; wide canaliculi with disorganised matrix in bone; a mosaic pattern of poorly organised lamellar bone

Answer 160

A catecholamine-producing tumour that usually arises from chromaffin cells of the adrenal medulla but are extra-adrenal in about 10% of cases 10% are bilateral and 10% are malignant

Answer 161

Most phaeochromocytomas are sporadic but may be familial in up to 30% of patients Familial cases may be seen in patients with: -multiple endocrine neoplasia type 2a (MEN2a) -von Hippel-Lindau (VHL) syndrome: hereditary condition associated with tumors arising in multiple organs -neurofibromatosis type 1 (NF1) -mutations in the genes encoding subunits of the mitochondrial enzyme succinate dehydrogenase: SDHB, SDHD, SDHC

Answer 162

Phaeochromocytoma is a rare condition | <0.2% of hypertensive patients

Answer 163

Paroxysmal episodes of headache, sweating: Cardio/respiratory: Palpitations, chest pain, dyspnoea GI: Epigastric pain, nausea, constipation Neuro/psychiatric: Weakness, tremor, anxiety

Answer 164

Hypertension (50–70%): -2/3 sustained -1/3paroxysmal Postural hypotension: Secondary to low plasma volume Others: Pallor, tachycardia, fever, weight loss

Answer 165

Headaches Diaphoresis (sweating) Palpitations in the setting of paroxysmal hypertension (episodic and volatile high blood pressure)

Answer 166

*24h urine collection for catecholamines, metanephrines and creatinine: Elevated- most appropriate in patients with a low pre-test probability for a phaeochromocytoma and ideally collected during or immediately after a hypertensive crisis *Plasma free metanephrines: In patients at high risk (sensitivity of 99%) Plasma catecholamines: may be elevated, but are released episodically, unlike plasma metanephrines, which are released continually Tumour localization: CT or MRI scan Screen for associated conditions: -MEN 2a: Serum calcium and calcitonin. -VHL: Ophthlamoscopy, MRI posterior fossa and renal USS. -NF 1: Clinical examination for neurofibromas, cafe-au-lait spots and axillary freckling Genetic testing (and counselling): identify potential hereditary tumour disorders (up to 40%)

Answer 167

When the bones are weak but are still strong enough that they wouldn't break easily during a fall Osteopenia is defined as a T-score between -􏰆1.0 and -􏰆2.5

Answer 168

Pituitary adenomas that do not cause a characteristic hormone hypersecretion syndrome

Answer 169

Pituitary adenomas are monoclonal in origin, suggesting intrinsic genetic alterations as initiating events, but the exact aetiology is unknown FH of multiple endocrine neoplasia type1 (MEN1) and Familial pituitary adenomas

Answer 170

Pituitary adenomas are the third most common intracranial neoplasms (behind meningiomas and astrocytomas), accounting for about 10% of all intracranial tumours in adults There is no known sex or racial difference in prevalence

Answer 171

``` Symptoms are long standing and slow progressing Headaches Decreased visual acuity- bitemporal hemianopia Adrenal insufficiency: -Nausea and vomiting -Weakness -Anorexia Hypogonadism: -Gynaecomastia -Erectile dysfunction -Amenorrhoea -Infertility -Breast atrophy -Loss of libido -Hot flushes -Diaphoresis (sweating) Hypothyroidism: -Weight gain -Cold intolerance -Fatigue -Constipation -Dry skin -Hair loss -Low mood GH deficiency: -Similar to above plus increased central adiposity and reduced muscle mass ```

Answer 172

*Prolactin levels: exclude prolactinomas *Pituitary MRI with gadolinium enhancement: -preferred over CT -delineates the characteristics of the tumour including any invasion of cavernous sinuses and sphenoid sinus, in addition to chiasmal compression Bloods to demonstrate hormone deficiency: Insulin-like Growth Factor 1, LH and FSH, TSH, Cortisol, Testosterone, ACTH stimulation test, T4/T3, FBC (anaemia)- all either low or normal (or high if the it is a screwing tumour-unlikely)

Answer 173

A syndrome characterised by: -oligomenorrhoea/amenorrhoea -hyper-androgenism (clinical symptoms or biochemical) Usually associated with: obesity, insulin resistance and an increased risk of developing type 2 diabetes

Answer 174

Environmental factors: related to diet and development of obesity Genetic determinants: genes regulating gonadotrophin, insulin and androgen synthesis, secretion and action, weight and energy regulation

Answer 175

FHx of PCOS Premature adrenarche Weaker risk factors: obesity, low birth weight

Answer 176

PCOS is the most common cause of infertility in women Affects 6–8% of women Symptoms generally start at the age of puberty

Answer 177

``` Menstruation: Irregularities (oligomenorrhoea or amenorrhoea) Dysfunctional uterine bleeding Infertility Hyperandrogenism: Hirsutism (male pattern hair growth) Male-pattern hair loss Acne ```

Answer 178

``` Hirsutism, male pattern hair loss and acne Acanthosis nigricans (sign of severe insulin resistance-HYPERINSULINAEMIA): velvety thickening and hyperpigmentation of the skin of axillae or neck, more commonly seen in obese women ```

Answer 179

-Blood tests: Raised LH levels Raised LH: FSH ratio (>3) Raised Testosterone, androstenedione and DHEA-S Reduced sex hormone binding globulin (SHBG) -Exclude other endocrine causes: Serum prolactin (hyperprolactinaemia) Thyroid function tests (hypo/hyperthyroidism) 17OH-progesterone (congenital adrenal hyperplasia), Cushing's syndrome Impaired glucose tolerance test/DM type 2: (fasting glucose, HbA1c) -Transvaginal USS: Twelve or more follicles in each ovary, measuring 2–9 mm and/or raised ovarian volume >10 mL (CYSTS)

Answer 180

Fasting glucose > 7mmol/L | 2 hour glucose tolerance > 11mmol/L

Answer 181

Characterized by autonomous aldosterone overproduction from the adrenal gland with subsequent suppression of plasma renin activity Also known as Conn's syndrome

Answer 182

Excess aldosterone may be secondary to an adrenal adenoma (Conns syndrome; 70%) or hyperplasia of the adrenal cortex (30%)

Answer 183

Excess aldosterone results in: 1. Increased Na+ and water retention causing hypertension 2. Increased renal K+ loss and hypokalaemia 3. Suppression of renin because of NaCl retention

Answer 184

The prevalence in hypertensive patients is 1–2% Aldosterone producing adenoma (Conns) occurs more commonly in women and in younger patients (<50 years) Bilateral adrenal hyperplasia occurs more commonly in men and usually presents at an older age

Answer 185

Usually asymptomatic and picked up on routine blood tests Symptoms of hypokalaemia: -Muscle weakness -Polyuria and polydipsia (nephrogenic diabetes insipidus secondary to hypokalaemia) -Paraesthesia -Tetany

Answer 186

Hypertension | Complications of hypertension (e.g. retinopathy)

Answer 187

1st line: - Plasma potassium: normal or low (20%), (<4mmol/L) - Serum sodium: usually normal (due to parallel increase in the water content of the blood) - Aldosterone/renin ratio: HIGH: Hypokalaemia should be corrected prior to the test and after stopping anti-hypertensives (6 weeks for spironolactone and 2 weeks for most other anti-hypertensives) Others for confirmation: *-Fludrocortisone suppression test: most reliable means of definitively confirming or excluding PA, failure to suppress plasma aldosterone -Salt loading/saline infusion testing: Failure of aldosterone suppression following a sodium load (oral or IV 0.9% sodium chloride) confirms primary hyperaldosteronism -Adrenal CT/MRI: detection of adrenal mass lesion, can miss smaller aldosterone-producing adenomas -Bilateral adrenal vein catheterization: Allows distinction between Conns syndrome and bilateral adrenal hyperplasia by measuring adrenal vein aldosterone levels (adrenal venous sampling) -Radio-labelled cholesterol scanning: Unilateral uptake in adrenal adenomas; bilateral uptake in bilateral adrenal hyperplasia -Posture stimulation testing: Plasma aldosterone, renin activity and cortisol are measured with patient recumbent at 8 a.m. The tests are repeated after 4 h of being upright (at 12 noon) In adenomas which are mostly ACTH-sensitive, aldosterone secretion decreases from 8 a.m. until 12 noon In bilateral adrenal hyperplasia, adrenals respond to standing posture by increasing renin and thus increasing aldosterone secretion *This test has a 20% false negative rate

Answer 188

Bilateral adrenal hyperplasia: - Spironolactone (an aldosterone receptor antagonist) - Change to eplerenone if side effects are intolerable (gynaecomastia, impotence, menstrual irregularities, muscle cramps and gastrointestinal upset) - Amiloride (a potassium-sparing diuretic) is alternative - Monitor serum potassium and creatinine, and BP - ACE inhibitors and calcium channel blockers may need to be added - It can take 4–8 weeks for the hypertension to respond to the treatments Aldosterone producing adenomas: -Uilateral adrenalectomy : Laparoscopic surgery is associated with reduced post-operative morbidity, hospital stay and expense compared with open

Answer 189

Complications of hypertension: - Heart failure - Coronary artery disease and MI - Cerebrovascular accident - Peripheral vascular disease - Thomboembolism - Retinopathy - Renal failure

Answer 190

Surgery may either cure hypertension (in about 50-60%) or make it more amenable to anti-hypertensive therapy in those who are not cured (usually the elderly or those with long-standing hypertension)

Answer 191

Benign lactotroph adenomas expressing and secreting prolactin

Answer 192

Human pituitary adenomas, including prolactinomas, are monoclonal in origin The majority of prolactinomas occur sporadically A small percentage of patients may have multiple endocrine neoplasia syndrome type 1 (MEN-1) or familial isolated pituitary adenoma (FIPA)

Answer 193

Prolactinomas are the most common type of pituitary adenoma, constituting about 40% of these tumours Prolactin-secreting adenomas are more frequent in women, mainly during the child-bearing years, with a peak incidence between 20-30s Women and men of 10:1 Over 50s, frequency of prolactinomas is similar in men and women

Answer 194

``` Can be asymptomatic (12%) Amenorrhoea or oligomenorrhoea Infertility Loss of libido Decrease in visual acuity ```

Answer 195

Galactorrhea Visual deterioration Osteoporosis: fractures

Answer 196

Serum prolactin: elevated (over 150-200 ng/ml) Pituitary MRI gadolinium-enhanced: characteristic features of pituitary adenoma, may be compressing the optic chiasm Computerised visual field examination: may reveal unilateral or bitemporal hemianopia

Answer 197

Dopamine agonists: *primary treatment * -Inhibit prolactin secretion and synthesis -Cabergoline is the recommended first-line -Bromocriptine can also be given -Starts at low doses to avoid adverse effects, including low mood and irritability, with a gradual dose increase -If pregnancy occurs, medication must be stopped OR Trans-sphenoidal surgery for large and invasive macroprolactinomas

Answer 198

Visual field impairment Cabergoline associated (at high doses) valvular disease Pituitary apoplexy: due to acute haemorrhage into or ischaemic infarction of a large pituitary prolactinoma From Trans-sphenoidal surgery: anterior pituitary failure/ diabetes insipidus

Answer 199

This benign disease follows a progressive improving course while medically treated: continuous treatment with relatively large doses of dopamine agonists will result in prolactin normalisation, tumour shrinkage or disappearance, and rapid visual improvement

Answer 200

Characterised by continued secretion of ADH, despite the absence of normal stimuli for secretion (i.e. increased serum osmolality or low blood volume)

Answer 201

Brain: Haemorrhage/thrombosis, meningitis, abscess, trauma, tumour, Guillain–Barre syndrome Lung: Pneumonia, TB, abscess, aspergillosis, small cell carcinoma Tumours: Small cell lung cancer, lymphoma, leukaemia, pancreas, prostate, mesothelioma sarcoma, thymoma. It may be caused by ectopic ADH secretion Drugs: Vincristine (chemotherapy), opiates, carbamazepine, chlorpropamide Metabolic: Alcohol withdrawal, Porphyria

Answer 202

Hyponatraemia is the most common electrolyte imbalance seen in hospitals <50% of all severe hyponatraemia are due to SIADH

Answer 203

``` Mild hyponatraemia (Na+ : 125–135 mmol/L) may be asymptomatic Headache Nausea/vomiting Muscle cramp/weakness Irritability Confusion Drowsiness Convulsions Coma Symptoms of the underlying cause ```

Answer 204

Mild hyponatraemia: No signs Severe hyponatraemia: Reduced reflexes, extensor plantar reflexes (Babinski reflex) Signs of the underlying cause *The hyponatraemia in SIADH is dilutional from increased body water (reabsorption) and not decreased total body Na+ -Absence of hypo or hypervolaemia

Answer 205

Bloods: -Serum sodium: low, <135 mmol/L -Serum osmolality:low, <280 mmol/kg (hypotonic) Urine: -Urine osmolality: elevated, >100 mmol/kg H2O -Urine sodium: elevated, >40 mmol/L *The presence of the above and absence of hypovolaemia/hypotension, oedema, renal failure, adrenal insufficiency and hypothyroidism are required for a diagnosis of SIADH Excluding differentials: TSH (hypothyroidism), creatinine (renal failure), serum protein and lipids (exclude pseudohyponatraemia seen with increased protein or lipids), short ACTH stimulation test (to exclude adrenal insufficiency) Identifying the cause: CXR, CT chest/abdomen/pelvis, MRI/CT head

Answer 206

Salt administration and/or water restriction: -Water restriction (0.5–1 L/day). If ineffective, give demeclocycline (reduce responsiveness of the collecting tubule cells to ADH) -Vasopressin (V2) receptor antagonists e.g. tolvaptan are likely to be useful in moderate chronic hyponatraemia if water restriction is insufficient -In severe cases (seizures and reduced consciousness), give slow IV hypertonic 3% saline (and furosemide) with close monitoring. The change in [Na+] must not exceed 10 mmol/L in the first 24 h and 18 mmol/L in the first 48 h *Rapid correction can result in central pontine myelinolysis (rapid rise in sodium concentration is accompanied by the movement of small molecules and pulls water from brain cells)

Answer 207

Convulsions, coma, death | Central pontine myelinolysis: occurs with rapid correction of hyponatraemia (quadreparesis, respiratory arrest, fits)

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If the underlying cause is found and treated successfully, SIADH typically resolves High morbidity and mortality with [Na+] <110 mmol/L Up to 50% mortality with central pontine myelinolysis

Answer 209

The most common endocrinological malignancy and 4 types account for more than 98% of thyroid malignancies: - Papillary - Follicular - Anaplastic - Medullary

Answer 210

Genetic alterations are thought to underlie thyroid cancers (Family history is a strong RF) - Papillary: BRAF mutations - Follicular: PPAR gamma gene - Medullary: mutations in a tyrosine kinase receptor gene

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The most common endocrinological malignancy, the rates of new thyroid cancer cases have been rising over the past few decades More common in women than in men Most likely to be diagnosed between the ages of 45 to 54 years

Answer 212

Neck lump Hoarseness Dyspnoea Dysphagia

Answer 213

Palpable thyroid nodule (most common in early adulthood) Tracheal deviation: enlarged goitre Cervical lymphadenopathy suggestive of neck metastasis

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Initial screening test: TSH, often normal Ultrasound neck: micro-calcifications, a more-tall-than-wide shape, hypervascularity, marked hypoechogenicity, or irregular margins Fine needle biopsy: cytology of malignant features (variations in appearance), anapaestic (poorly differentiated) Laryngoscopy: paralysed vocal cord is highly suggestive of malignancy Others: -Free T3/T4: normal -Iodine thyroid scan/uptake: ordered for patients with overt or subclinical hyperthyroidism (Hot nodules: hyperfunctioning -almost always benign, cold nodule: hypofunctioning- most are benign but malignant nodules are also cold) -CT neck: lymphadenopathy -Serum calcitonin (parafollicular cells, opposes the action of parathyroid hormone): Normal is <10 nanograms/L, high in medullary cancer

Answer 215

Solid or fluid-filled lumps that form within the thyroid | Most thyroid nodules aren't serious and don't cause symptoms

Answer 216

- Overgrowth of normal thyroid tissue: thyroid adenoma, Some lead to hyperthyroidism - Thyroid cyst: fluid-filled cavities in the thyroid most commonly result from degenerating thyroid adenomas. Often, solid components are mixed with fluid in thyroid cysts - Chronic inflammation of the thyroid. Hashimoto's disease, a thyroid disorder, can cause thyroid inflammation and result in enlarged nodules, often associated with hypothyroidism - Multinodular goitre: multiple distinct nodules, cause is not well known - Thyroid cancer: small risk that a thyroid nodule is cancerous- if a nodule is large and hard or causes pain or discomfort - Iodine deficiency: can cause thyroid nodules

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Common and are usually benign

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Most thyroid nodules don't cause signs or symptoms Neck lump Cause dyspnoea or dysphagia Can cause hypo or hyperthyroidism (features of these)

Answer 219

Bloods: Thyroid function test, FBC | Colour Doppler Ultrasound of the neck

Answer 220

An autoimmune-mediated lymphocytic inflammation of the thyroid gland resulting in a destructive thyroiditis with release of thyroid hormone and transient thyrotoxicosis (hyperthyroidism) This is frequently followed by a hypothyroid phase and full recovery

Answer 221

Painless (lymphocytic) thyroiditis is part of the spectrum of autoimmune thyroid disease and considered by many to be a variant presentation of Hashimoto's thyroiditis It has been associated with HLA-DR3 and DR5

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The condition is twice as likely to occur in women and can occur in all age groups, although the mean age of onset is in the 30s Postnatal thyroiditis occurs after 7% of pregnancies Also seen in patients treated with cytokines or biological agents

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``` Postnatal period Receiving immune-modulatory therapy Lithium therapy PMH of Type 1 DM and other autoimmune conditions Weaker RF: -Female sex -FH ```

Answer 224

Features of hyperthyroidism: - Heat intolerance - Nervousness - Palpitations - Weight loss - Excessive fatigue

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Small non-tender goitre Features of hyperthyroidism (tachycardia) and then features of hypothyroidism (cold intolerance, poor concentration, weight gain)

Answer 226

Thyroid function tests: - TSH: low TSH suggests thyrotoxicosis; elevated in hypothyroid phase - Serum free T4 and T3: elevated in the thyrotoxic phase; low in the hypothyroid phase - Thyroid Peroxidase antibodies: confirm autoimmune aetiology: frequently positive - TSH-r antibodies: *distinguish between Graves' 4,6 or 24 hour radioiodine uptake: very low, usually <1% (Uptake elevated or within the normal range in Graves' disease and toxic multinodular goitre) Total T3/T4 ratio: when radioiodine uptake is contraindicated: distinguish thyroiditis from Graves' disease and toxic nodular goitre: LOW Others: - Thyroid biopsy: rarely necessary, lymphocytic infiltrate - techniteum 99pertechnetate: uptake scan - serum thyroglobulin: elevated - Colour flow doppler ultrasound: reduced flow (widely available but uncommonly used)

Answer 227

Thyrotoxic phase: - Treatment may not be necessary for asymptomatic patients - In symptomatic thyrotoxicosis: beta-blockers will ameliorate the tachycardia and tremulousness (or calcium-channel blocker) - If not responding to treatment: systemic corticosteroids Hypothyroid phase: - Again may not be needed - In moderate to severe: levothyroxine is given to normalise serum TSH concentrations - In permanent hypothyroidism: levothyroxine should be continued indefinitely Recurrent thyroiditis: Up to 11% of patients with sporadic painless thyroiditis will have recurrent thyroiditis -Although it is rarely done, such patients may elect to have their thyroid gland ablated with radioiodine or surgically removed between episodes when they are euthyroid

Answer 228

Arrhythmias: AF Exacerbation of co-morbidities particularly ismchaemic heart disease and congestive heart failure (lower risk) More likely to develop permanent hypothyroidism Can also develop Graves' disease, recurrent hyperthyroidism

Answer 229

Most patients recover normal thyroid function: - 6% remain permanently hypothyroid - 1/3 have persistent goitre or thyroid peroxidase (TPO) antibodies - Recurrent episodes are common postnatally (69%) but may also occur in up to 11% of patients with sporadic disease

Endocrine Flashcards

(253 cards)