Endocrine Flashcards

Question

What are the major clinical and biochemical features of Cushing's syndrome? (signs and symptoms)

Answer 1

Symptoms: * Central weight gain * Change in appearance * Depression * Insomnia * Poor libido * Thin skin/easy bruising * Excess hair growth/acne * Diabetes symptoms Signs: * Moon face * Frontal balding * Striae * Hypertension * Pathological fractures * 'Buffalo hump' (dorsal fat pad on back of neck) * Proximal myopathy

Answer 2

* Primary adrenal insufficiency * Destruction of the entire adrenal cortex leading to glucocorticoid (cortisol), mineralocorticoid (aldosterone), and sex-steroid deficiencies * This differs from hypothalamic-pituitary (HPA) disease as HPA disease generally spares mineralocorticoid production, which is stimulated by ATII (sex steroids are also largely independent of pituitary stimulation) **Causes:** * Autoimmune: 80% in the UK * TB: most common cause worldwide * Overwhelming sepsis * Metastatic cancer: lung/breast * Lymphoma * Adrena haemorrhage * Waterhouse-Friderichsen syndrome

Answer 3

Symptoms: (often vague and non-specific) * Weight loss * Malaise * Weakness * Myalgia (muscle pain) Signs: * Pigmentation, especially of new cars and palmar creases * Postural hypotension * Signs of dehydration * Loss of body hair (paticularly axillary/pubic)

Answer 4

* Adrenal adenoma leading to primary hyperaldosteronism (excess production of aldosteronism from adrenal glands) * (Conn's syndrome is responsible for primary hyperaldosteronism in 60% of cases) * Hyperaldosteronism leads to sodium and water retention

Answer 5

**Presentation:** * Mostly asymptomatic * Hypertension * resistant to treatment * may causes headaches * Features of hypokalaemia * May cause cramps, weakness, tetany * May be polyuria **Biochemical features:** * Hypokalaemia, with urinary potassium loss * Elevated plasma aldosterone:renin ratio * Plasma aldosterone levels will not be suppressed by fludrocortisone administration

Answer 6

A neuroendocrine tumor of the medulla of the adrenal glands (originating in the chromaffin cells), or extra-adrenal chromaffin tissue that failed to involute after birth,that secretes high amounts of catecholamines, mostly norepinephrine, plus epinephrine to a lesser extent

Answer 7

* There are 4 parathyroid glands, lying posteriorly to the thyroid * The chief cells are responsible for secreting parathyroid hormone (PTH) * PTH is secreted when plasma calcium levels are low * PTH can also be secreted in response to low vitamin D, or high phosphate levels * PTH works to increase plasma calcium reabsorption from bone by: * Directly stimulating calcium resabsorption from bone * Directly increasing renal tubular calcium reabsorption * Indirectly stimulating increased GI calcium absorption * By increasing vitamin D activation in the kidney * PTH has a secondary effect of increasing renal phosphate excretion

Answer 8

Vitamin D acts to sustain plasma calcium and phosphate levels by increasing their inflow from the GI tract * It i also required for normal bone formation * Endogenously it is synthesized in the skin, forming D₃, cholecalciferol * Exogenously it is ingested as D_2, ergocalciferol (common in fish, liver and dairy products) * 'Active' vitamin D is then formed by a second hydroxylation in the kidney, to produce to 1,25-(OH)₂-D_2/3

Answer 9

Most commonly occur in people with inadequate sunlight exposure, malabsorptive conditions and liver/kidney disease

Answer 10

* Calcitonin is secreted by parafollicular/'C' cells of the thyroid gland in response to increased plasma calcium levels * It acts to decrease plasma calcium levels, by antagonism of the effect of PTH on the bone

Answer 11

* Removal of thyroid, and complete calcitonin deficiency does not lead to overt hypercalcemia * Extreme hypersecretion of calcitonin by tumours rarely produces hypocalcaemia * It is likely that PTH/Vitamin D levels are adjusted in response to calcitonin changes

Answer 12

* Intestinal uptake of calcium depends on the amount of ionized calcium in the lumen, and the presence of activated vitamin D * 90% of renal excretion of calcium is related to sodium reabsorption in the proximal tubule, with 10% regulated by PTH in the distal tubule

Answer 13

In a patient with hypercalcaemia, 97% of cases are due to primary hyperparathyroidism or malignacy (PTH high in hyperparathyroidism, low in malignancy) _Causes_: * Excessive PTH secretion * Primary hyperparathyroidism * Tertiary hyperparathyroidism * Ectopic PTH secretion (very rare) * Malignancy * Myeloma * Metastatic deposits in bone * Paraneoplastic * PTHrp secretion: e.g. SCC (of lung or other tissues) * Production of osteoclastic factors * Excess Vitamin D * Exogenous excess * Granulomatous disease: TB/sarcoid * Lymphoma * Excess calcium intake * 'Milk-alkali' syndrome (antacids + large amounts of calcium lead to excessive absorption * Other endocrine disease * Thyrotoxicosis * Addison's * Renal disease * Severe AKI * Drugs * Thiazide diuretics * Lithium * Hereditary * Familial hypocalciuric hypercalcaemia

Answer 14

* Peripheral irritability: * Tetany/cramps * Carpo-pedal spasm * Wrist flexion and fingers drawn together * Happens especially after occulusion of brachial artery, e.g. with a blood pressure cuff: Trosseau's sign * Tapping over the facial nerve causes twitches: Chvostek's sign * Central irritability * Seizures * Depression/anxiety * Perioral paraesthesia * Cataracts

Answer 15

_With low PTH (hypoparathyroidism)_ * Idiopathic/primary hypoparathyroidism (autoimmune) * Post thyroid/parathyroid surgery * Post neck irradiation * Infiltration: sarcoid/malignancy * Congential absence of the gland: Digeorge syndrome * Severe hypomagnesia: impairs PTH secretion _With high PTH_ * Vitamin D deficiency * Acute pancreatitis * Alkalosis * Acute hyperphosphataemia * renal failure * rhabdomyolysis * tumour lysis * Drugs: bisphosphonates, calcitonin

Answer 16

1. Diabetes mellitus - a metabolic disorder of multiple causes characterized by chronic hyperglycaemia resulting from defects in insulin secretion, insulin action or both 2. Impaired glucose tolerance (IGT) is a pre-diabetic state of hyperglycemia that is associated with insulin resistance and increased risk of cardiovascular pathology. 3. Impaired Fasting Glycaemia is a type of prediabetes, in which the blood sugar level during fasting is consistently higher than what are considered normal levels; however, the level is not high enough to be diagnosed as diabetes mellitus. This pre-diabetic state is associated with insulin resistance and increased risk of cardiovascular pathology, although of lesser risk than impaired glucose tolerance (IGT). Patients identified to have IFG should undergo the 2hr glucose test to rule out IGT.

Answer 17

Normal * Fasting: \<6.1 * 2hr after 75g glucose: \<7.8 Impaired fasting glycaemia * Fasting: \>6.1 * 2hr after 75g glucose: n/a Impaired glucose tolerance * Fasting: 6.1-7.0 * 2hr after 75g glucose: 7.8-11.1 Diabetes Mellitus * Fasting: \>7.0 * 2hr after 75g glucose: 11.1

Answer 18

**Type I DM:** * Autoimmune disease, with autoantibodies targeted against the insulin-secreting ß cells of the Islets of Langerhans in the pancreas, leading to cell death and inadequate insulin secretion * It is hypothesised that viral infection **Type II DM:** * Unlike type I diabetes, blood insulin levels are initially normal, or even increased in the early stages to compensate for insensitivity of the bodily tissues to the insulin * The 'insulin resistance' is associated with aging, genetic factors, obesity, high fat diets and a sedentary lifestyle * Eventually the ß cells decompensate, and can no longer produce excess insulin, leading to hyperglycaemia **Gestational Diabetes Mellitus** * may occur during pregnancy. It results in a similar hyperglycaemia, of variable severity, recognised first during pregnancy. Impaired glucose control may antedate pregnancy. * Capillary glucose levels for impaired glucose tolerance are used for diagnosis with clinical symptoms. **Maturity Onset Diabetes of the Young (MODY)** * may represent 5-10% of diabetic patients. * This form of diabetes is clinically similar to T2DM but presents in young patients

Answer 19

* Pancreatic disease: * CF, chronic pancreatitis, pancreatic carcinoma * Endocrine disease: * Cushing's disease, acromegaly, thyrotoxicosis, PCC, glucagonoma * Drug induced: * Thiazide diuretics, corticosteroids, antipsychotics, antiretrovirals * Congential disease: * Insulin receptor abnormalities, myotonic dystrophy, Friedreich's ataxia

Answer 20

* Presents in childhood/aldolescence with a 2-6 week history of; * Polyuria: high sugar content in urine leading to osmotic diuresis * Polydipsia: due to resulting fluid loss * Weight loss: fluid depletion plus fat/muscle breakdown * Diabetic Ketoacidosis (DKA) is also a common first presentation

Answer 21

* The clinical onset may be over many months/years, with the classic triad of symptoms present, but less obvious than in type I DM * More common presenting features are: * Lack of energy * Visual blurring: glucose-induced refractive changes * Pruritis vulvae/balantitis: due to candida infection * In older patients, it may be the complications of diabetes that are the presenting feature: * Retinopathy: noted by the optician * Polyneuropathy: tingling and numbness in the feet * Erectile dysfunction * Arterial disease: MI/peripheral vascular disease * Type II DM is recognised as part of the metalbolic syndrome: * T2DM * Central obesity * Dyslipidaemia: low HDL cholesterol, hypertriglyceridaemia

Answer 22

* Ketoacidosis * younger patient * polyuria * polydipsia * weight loss * onset over weeks.

Answer 23

Diet: no different to that considered healthy for everyone: * High in low-GI carbohydrates * Limit foods high in sugar and saturated fats * Diabetic specific foods are not required * Can see nutritionist to help with meal plans * Allowed alchol but may exacerbate/prolong effect of hypoglycaemic drugs and may make the signs of hypo less clear Toms guide: Protein – 1g/kg Fat - \<35% total intake. Keep sat+trans fat\<10% of total intake. CHO – 40-60% of total intake. Choose low GI foods. Fruit, vegetables, some alcohol allowed. Salt \< 6g Recommend fibre. Salt \<6g a day (\<3g a day in hypertensive diabetic patients)

Answer 24

**Urine testing;** * Urine tests using dipsticks give patients who do not use blood testing some idea of how well controlled their glucose levels are. However, the relationship between urine glucose levels and blood glucose levels is not exact, for 3 main reasons: 1. changes in urine glucose lag behind blood changes 2. the mean renal threshold is 10mM, but the range is wide 3. urine tests can give no guidance concerning glucose levels below the renal threshold (hypos go unchecked) **Home blood glucose testing** * Home blood glucose testing is the best place for assessment of day-to-day control, and is an essential aid to that control. * Patients are able to control their insulin dose appropriately. * Patients should generate a profile, for example: 4 tests aday, 2 days a week; and share this with nurses to help enable the best system available for them to be used. **HbA1c:** * HbA1c is generated as a two step reaction eventually resulting in glucose attaching to the valine in the Beta chain of a Hb molecule. * The rate at which this occurs depends on glucose concentrations. Normal range is between 4-6.2% (\<48). This gives us an idea of control of blood glucose levels over the lifespan of Hb, about 6 weeks. * Should be checked 6 monthly * The figure will be misleading in anaemia, thalassaemia, haemoglobinopathy or pregnancy, in which case the shorter-term fructosamine test may be used.

Answer 25

**Diabetic Ketoacidosis** * metabolic emergency in which hyperglycaemia is associated with metabolic acidosis due to greatly raised ketone levels * It is associated with type I DM but can rarely occur in type 2 DM **Hyperosmolar Hyperglycaemic State** * Characteristic of type 2 DM, a severe hyperglycaemia causes a hyperosmolar state in absence of severe ketosis

Answer 26

* Absolute insulin deficiency leads to uncontrolled catabolism * In the absence of insulin, hepatic glucose production is increased, and peripheral uptake of glucose is reduced * Rising glucose levels leads to an osmotic diuresis, leading to severe dehyrdation * Rapid lipolysis occurs in glucose-starved tissues, leading to elevated free fatty acids, which are converted to fatty acetyl-CoA in liver cells * Fatty acetyl-CoA can be converted to ketone bodies in mitochondria to generate energy * Accumulation of ketone bodies causes a metabolic acidosis (can be detected on breath) * Respiratory compensation leads to hyperventilation * Acidosis causes vomiting, and further fluid/electrolyte loss * Renal perfusion falls, leading to impaired excretion of the raised H⁺ and ketones * There is increased excretion of sodium and potassium * Despite a significant total body deficit of K⁺, initial serum K⁺ is typically normal, or even elevated (pseudo-hyperkalaemia) * This is due to extracellular migration of K⁺ in response to acidosis & insulin deprivation * Serum K⁺ levels will then usually fall during treatment as the exogenous insulin drive K⁺ into cells * If serum K⁺is not monitored and replaced as needed, life-threatening hypokalaemia may develop

Answer 27

* Previously undiagnosed diabetes * Interruption of insulin therapy * The stress of intercurrent illness/surgery

Answer 28

* Severe hyperglycaemia causes a hyperosmolar state in the absence of severe ketosis * Typically occurs in the elderly, often with undiagnosed T2DM * Precipitating factors: * Consumption of glucose-rich fluids * Medications: thiazide diuretics, steroids, B-blockers * Intercurrent illness: infection/MI * These patients may be more severely dehyrdated than DKA patients, but there will be no raised ketones (can be lactic acidosis but is generally mild)

Answer 29

* Prostration (collapse - complete physical or mental exhaustion) * Kussmaul respiaration: air hunger * Nausea & vomiting * Abdominal pain * Confusion/stupor On examination there may be evidence of marked dehydration, with the smell of ketones of breath. There is often a history of marked polyuria (litres)

Answer 30

* Dehydration * Stupor/coma/seizures * Evidence of an underlying illness

Answer 31

Hypoglycaemia is defined as plasma glucose \<3mmol/L, but individual thresholds for symptoms are variable. Symptoms are autonomic or neuroglycopenic: **Autonomic:** * Sweating * Anxiety * Hunger * Tremor * Palpitations **Neuroglycopenic:** * Confusion * Drowsiness/coma * Seizures

Answer 32

In episodes of hypoglycaemia, the aplha cells of the pancreas will release glucagon, which works to: * Increase glycogenolysis * Increase gluconeogenesis * Inhibit glycogen synthesis The adrenaline response may be absent in patients with a long history of diabetes (associated with a loss of warning symptoms). Growth hormone and cortisol may be released over a longer period of time to give a small increase in blood glucose levels

Answer 33

In type I DM, the alpha cells (of pancreas) become insensitive to falls in glucose, thus becoming increasingly vulnerable to hypoglycaemia _Aetiology of hypoglycaemia:_ * Excess insulin * Inhibits hepatic gluconeogenesis and glycogenolysis * Either exogenous or insulinoma * Depletion of hepatic glycogen * Malnutrition, fasting, exercise or alcohol * Liver failure can also cause this Pituitary insufficiency, adrenal insufficiency and non-pancreatic neoplasms can also cause hypoglycaemia

Answer 34

* Prompt consume 10-20g of fast-acting form of carbohydrate, preferably in liquid form (lucozade) * Recheck blood glucose levels after 10-15 minutes * Hypoglycaemia should be reversed in about 10 minutes * Improvements in signs and symptoms may lag behind improvement in blood glucose * If inadequate response, repeat as above and recheck again * When symptoms improve, the patient should eat some long-acting carbohydrate

Answer 35

* Administer IM glucagon immediately * If \<8 years old: 500 micrograms * If \>8 years old: 1mg * If glucagon not available, the patient has consumed alcohol (glucagon not effective if alcholol drunk), or the person does not respond to glucagon within 10 minutes, call 999 for emergency hospital transfer - IV treatment * If the patient responds to glucagon, advise intake of long-acting carbohydrates when able * Vomiting is common during recovery, which can precipitate further episodes of hypoglycaemia * Within hospital, 100ml of 20% glucose can be used as an alternative to glucagon, and this can be repeated 3 times Following recovery, never omit insulin in patients with T1DM

Answer 36

Metabolic acidosis will show a low pH, negative base excess and compensatory low pCO2.

Answer 37

Microvascular disease, unlike macrovascular disease is specific to diabetes. * Small vessels of the retina, glomeruli and nere sheaths are particuarly affected * Symptoms manifest 10-20 years after diagnosis in young patients **Diabetic eye disease** - Most common cause of blindness in under 65s **Diabetic Retinopathy (DR) -** can be non-prolifertive (NPDR) or proliferative (PDR) **Diabetic malculopathy -** retinopathy that affects the macula **Cataract formation -** clouding of the lens in the eye which leads to a decrease in vision **Glaucoma -** optic nerve damaged

Answer 38

It can be non-proliferative (NPDR) or proliferative (PDR) **Non-proliferative diabetic retinopathy (NPDR)** * Usually asymptomatic, and always occurs at some severity after 8-10y of DM * Features on fundoscopy; * Micro-aneurysms * Exudates: due to leaky vasculature * Haemorrhages: dot, blot, flame shaped * Cotton wool spots (\>5 indicates 'pre-proliferative' retinopathy) * Can progress into proliferative diabetic retinopathy **Proliferative diabetic retinopathy (PDR) -more common in T2DM** * Characterised by the development of new vessels on the optic disc or retina as a response to significant retinal ischaemia (ischaemia leads to vascular endothelial growth factor (VEFG) production) * The vessels are fragile, and likely to bleed with the traction that occurs when they are growing forward to give a pre-retinal or vitreous haemorrhage * If untreated, the blood vessels will cause fibrosis and a tractional retinal detachment, again leading to loss of acuity * They can also cause acute angle closure glaucoma due to iris neovascularisation, known as rubeosis iridis

Answer 39

* More common in type II diabetes * Maculopathy is damage to the macula, the part of the eye which provides us with our central vision. A common from of damage is from diabetic macular oedema (DMO) in which fluid builds up on the macula. * Typically presents with as blurring of vision * 3 subtypes: focal, diffuse and ischemic

Answer 40

A cataract is a clouding of the lens in the eye which leads to a decrease in vision * Symptoms are trouble with bright light/headlights and reading vision * Increased rates of age-related cataracts in diabetics * Postior sub-capsular cataracts are the most common

Answer 41

* Symmetrical polyneuropathy * Acute painful neuropathy * Mononeuropathy * Diabetic amyotrophy * Autonomic neuropathy

Answer 42

* 'Glove and stocking' sensory loss, with vibration, deep pain and temperature lost first * Patients complain of losing their balance when eye are closed, e.g. when washing their face, due to proprioception (walking on cotton walk feeling is common) * Interosseous wasting of the small muscle of the feet results in a charactistic foot shape, and abnormal pressure areas lead to ulcers * Unrecognised trauma with poor wound healing may also lead to ulcers * Neuropathic arthropathy can also develop -Charcot's foot - progressive degeneration of a weight bearing joint, a process marked by bony destruction, bone resorption, and eventual deformity

Answer 43

* Painful burning pains in the feet, shins and anterior thighs * Associated with poor glycaemic control * Typically worse at night (pressure from bedclothes may be intolerable) * Usually remits after 3-12 months of good glycaemic control * More chronic forms may be resistant to all forms of therapy

Answer 44

* Type of damage to nerves outside the brain and spinal cord Commonest types of mononeuropathy that may occur in diabetes: * Cranial nerve lesions can occur in patients with diabetes * Mainly CNs III, IV and VI; ocular palsies * Isolated peripheral nerve lesions can also occur * Any nerve compression syndrome is more common in diabetes, e.g. carpal tunnel syndrome * Foot drop may occur due to lesions of the sciatic nerve * When more than one nerve is affected, this is known as mononeuritis complex

Answer 45

* Amyotrophy is progressive wasting of muscle tissues * It is rare, usually developing in middle aged men * In diabetes, it presents as painful wasting of quadriceps * Course is variable, often with gradual but incomplete improvement

Answer 46

* Autonomic neuropathy is a group of symptoms that occur when there is damage to the nerves that manage every day body functions * Sympathetic dysfunction leads to postural hypotension, ejaculatory failure, reduced sweating and Horner's syndrome * Parasympathic dysfunction leads to erectile dysfunction, constipation, urinary retention and a Holmes-Adie pupil (large and irregular pupil)

Answer 47

* Usually manifests 15-25 years after diagnosis * CKD is leading cause of premature death in young diabetics (neuropathy will affect 30%) * Most important intervention is adequate blood pressure control

Answer 48

* Diabetes is a risk factor in the development of atherosclerosis * Increased risk: * 2x increased risk of stroke * 4x increased risk of MI * 50x increased risk of amputation for gangrene

Answer 49

* 10-15% of diabetic patients develop foot ulcers at some point in their lives. * Foot problems are responsible for 50% of diabetes-related hospital admissions. * Ischaemia, infection and neuropathy combine to produce tissue necrosis. * Medical supervision and patient education hope to reduce the number of amputations required. * Patients may lose some proprioceptive function and fall more easily.

Endocrine Flashcards

(73 cards)