Endocrine Diagnosis And Management Flashcards
diabetes mellitus
Chronic hyperglycemia resulting from relative insulin deficiency, resistance or both
Secondary DM:
Pancreatic e.g. total pancreatectomy, chronic pancreatitis
Endocrine diseases e.g. acromegaly, cushing syndrome
Drug induced: thiazide diuretics, corticosteroids
Primary DM:
Type 1: congenital insulin deficiency
Type 2: acquired insulin resistance/deficiency
comparison of DM type 1 and 2
type 1:
younger (<30 years)
usually lean
cause is hereditary in 90% cases
caused by autoimmune disease where islet cell Abs attack and destroy beta cells leaving pts unable to produce any insulin
are insulin dependent (clinically INSULIN DEFICIENT)
often associated with other autoimmune diseases
may develop ketoacidosis
always need insulin as treatment
type 2: usually older onsey >30 years often overweight more common in african/asian mostly acquired from lifestyle no immune disturbance partial insulin deficiency mostly INSULIN RESISTANCE may develop hyperosmolar state sometimes need insulin in treatment
type 1 DM
Prone to ketoacidosis and weight loss
Termed ‘insulin dependent’ as need insulin injections and can still respond to insulin - just don’t produce enough/any
Autoimmune disease no capacity to produce insulin
Destroys beta cells of islets of langerhans
Aitiology:
Typical onset 10-14 years old
type 1 DM signs and symptoms
polydipsia (thirst) - Polyuria Lethargy Weight loss/ thin Young Mood swings Hyperglycaemia (random glucose >11 mmol/L)
type 1 DM investigations
diagnosis is a MEDICAL EMERGENCY: first diagnosis must be referred to medics! pass patient over with SBAR technique give all relevant BG and ketone results etc.
Plasma glucose criteria
Urine dipstick for glucose in urine, ketone and protein (impact on kidneys)
Pear drop smelling breath
Bloods: ketone, BG,
Evidence of peripheral vascular disease in retina, kidneys or feet
Peripheral neuropathy
HbA1c (potentially normal, don’t use for diagnosis, also too slow a process for diagnosis but can use for monitoring)
Random BG >11.1 or fasting >7mmol/L
TFTs - often hypothyroid also
type 1 DM treatment
Insulin
Long acting: once daily
Mixed insulin: twice daily
Basal bolus: multiple times daily
Follow-ups: Screen for neuropathy Vascular screening Urine checks for proteinuria BP check <130/80 Total cholesterol <3 All pt. Should be on statin unless contraindicated All should be on ACEi unless contraindicated **advise against pregnancy while on drug** Routine monitoring HbA1c Ask about hypoglycemia episodes Ask about retinal screening Depression screening Erectile dysfunction DMI annually Smoking cessation annually
DVLA and insulin use: Must have eaten within 2hrs driving Must carry metre 2x severe hypo episodes indicates loss of liscence Check injection sites
DKA
Body normally metabolises carbohydrates
Ketoacidosis is alternative pathway used in starvation states when there’s no carbohydrates available
Produces acetone as by-product (fruity breath)
In acute DKA there is still excessive glucose in blood but lack of insulin it can’t be metabolised
Pushes body into starvation state and ketoacidosis pathway is pursued
Caused by:
Absolute insulin deficiency (type 1 DM)
Complete insulin insensitivity (type 2 DM)
Characterised by:
hyperglycemia: BG >11mmol/L or known DM pt.
Ketonaemia: >3mmol/L ketones or significant ketonuria (>2+ standard urine stick)
Acidosis: venous bicarb <15mmol/L venous pH <7.3
Triggers: infection, surgery, MI, pancreatitis, chemotherapy, antipsychotics, incorrect insulin dose/non-compliance etc.
DKA signs and symptoms
Gradual drowsiness leading to unconsciousness Vomiting Dehydration Excessive thirst Increased urination Sudden weight loss Leg cramps Fruity smelling breath High BG >14mmol/L Ketones in urine or blood Tachycardia Hypotension Reduced skin turgor Dry mouth Reduced urine output Altered consciousness Kussmaul breathing Abdominal pain
DKA management
pts presenting with vomiting should always be admitted regardless of BG or ketones*
ABCDE approach (geeky meds ABCDE is fab)
2 large bore cannula for IV fluids (rehydrate with saline
Add 50 units soluble insulin to 50mL saline infuse continuously at 0.1unit/kg/h
Continue pts regular insulin at usual dose and times (or consider adding insulin if newly diagnosed DM)
Aim for fall in blood ketones of 0.5mmol/L/h or rise in venous bicarb of 3mmol/L/h with fall in glucose of same.
If not achieving this increase insulin infusion until targets reached
Check BG and ketones hourly
Check VBG at 2, 4, 8, 12, 24hrs or more frequent PRN
Assess for potassium deficit
Consider catheter if no urine output to measure UO
Consider NG tube if vomiting or drowsy
Start all pts on LMWH
Ketones <6mmol/L, pH >7.3, bicarb >15 (venous) target to stop fixed rate insulin. Avoid hypoglycemia.
Assess and treat underlying causes for DKA
Once stable, put pt on 4xdaily insulin regimen
Continue to monitor vital signs, potassium and BG every 8 hours
DKA investigations and diagnosis
gold standard: ketone metre (all diabetics must have access to)
BG
Urine sample (U+Es; ketones, glucose, infections, potassium levels)
Bloods (FBC, CRP, potassium levels)
ECG: arrhythmias
CXR
ABG (pH etc. for acidosis)
Diagnostic criteria:
Acidaemia
Hyperglycaemia or known case of DM
Ketonaemia or significant ketonuria
type 2 DM
Non-insulin dependent
Caused by low insulin secretion +/- high insulin resistance
Associated with obesity, lack of exercise, calorie and alcohol excess
Typically progresses from preliminary phase of impaired glucose tolerance (IGT) or imparied glucose fasting (IGF)
Persistent hyperglycemia (HbA1c >48mmol/mol or random plasma glucose >11mmol/L); does not exclude diagnosis if tests show lower values
In symptomatic person; never base diagnosis on single HbA1c or fasting glucose test
Peak incidence in ages 40-49
insulin counter regulatory hormones
Counter-Regulatory hormones (stress hormones) oppose insulin:
- Glucagon
- Adrenaline (epinephrine)
- Cortisol
- Growth hormone
T2DM risk factors
Obesity
Inactivity
Family history (type 1 & 2)
Gestational diabetes or baby weighing >10lb
Ethnicity: Chinese, African Caribbean, Indian, Pakistani, Bangladeshi - Metabolic syndrome
T2DM presentations
Asymptomatic Thirst (polydipsia) Polyuria Pruritus (itch) Fatigue/lethargy Recurrent infections (thrush) Hyperglycemia (BG >11mmol/L) Visual problems Candida infection; white patches
T2DM investigations
GOLD STANDARD: HbA1c (>48 is diabetic; 42-48 on verge; <42 normal)
*Imitations of HbA1c
- not accurate where gammopathy present
- People carrying sickle cell trait- results should be interpreted with caution
- Pregnancy
- Can use fructosamine test as alternative (NOT PREGNANT WOMEN)
= if HbA1c of 48, may want to try diet, if inital HbA1c is 100, diet alone is unliekly
2x fasting BG roughly >7mmol/L (normal 4-6)
Random glucose >11.1
GTT initial result 7+ PLUS 2 hour result >11.1
pre diabetic values of glucose/ impaired glucose tolerance values
*Pre-diabetes/ Suspicious* Impaired fasting glucose Fasting glucose of 6.1-6.9 mmol/L Impaired glucose tolerance fasting glucose <7.0 PLUS 2-hour venous plasma glucose 7.8-11.0 (after ingestion of 75g oral glucose load) - 45-50% will progress to type 2 diabetes within their lifetime
T2DM complications
Vasculopathy/angiopathy
Cataracts
Palsies (6th and 3rd CN palsy)
Infection
Macro-vasculopathy: PAD, stroke, MI, renovascular disease, limb ischaemia
Micro-basculopathy: Nephropathy, retinopathy, neuropathy etc.
Reduced life expectancy (70% CV problems, CKD 10%, infections 6% most cause of premature deaths in treated pts.)
Complications directly related to degree and duration of condition!
Can be reduced/improved with control of condition
T2DM management overview
initial measurements
lifestyle advice
drugs - first line metformin (BMI>35) or gliclizade (normal BMI)
insulin is needed (sometimes first line)
bariatric surgery if recommended
all pts should be on statins unless contraindicated
all should be on ACEi unless contraindicated (should not try for pregnancy on this drug!!)
routine HbA1c monitoring!
regular screening for complications/diabetic foot checks/urine checks/blood checks etc.
T2DM initial measurements
Waist circumference BMI Smoking status Depression screen (if possible) ED screen BP Urine sample for ACR Bloods: HbA1c, renal function, lipid profile, liver function
T2DM lifestyle management
Weight loss: if pts can lose up to 15kg diabetes can be ‘reversed’ if still in early stages (20% T2DM is not weight related so this may not always be the case)
Smoking cessation
NHS 10 minute workout scheme for chronic conditions to build up exercise slowly
Management of hyperlipidemia if present
Exercise regimen
BP control (drugs/lifestyle)
Improve diet/reduce alcohol; low fat dairy products: fruit, veg, whole grains and pulses: oily fish
Orlistat if BMI >28 BAD SIDE EFFECTS
T2DM drug intervention
Metformin (first line all BMI)
Monitor LFTs before starting
500mg starting increase in 500mg increments per week to 3g
Don’t leave on a low dose!
Stop drug if creatine >150 and/or eGFR <45
If LFT is bad or complex CVD present use metformin with caution/seek advice
Can be used in pts who aren’t overweight
Causes mild to severe GI upset
Usually settles within 3 months
If not switch to MR
GI symptoms reduced if taken with food
Helps regulate liver a bit more, and prevent it letting go of all glucose
Gliclizade (2nd line):
monitor renal function and LFT
Duration of action 12-18 hr, should be given OD or BD
Direct effect on blood glucose
HYPO high risk
Can cause weight gain
Caution in elderly, moderate BG results are better than #NOF
Some type 2 diabetes pt will need insulin within 10 years
Some type 2 may want to start insulin first line
Initiation is usually long acting (Humulin I) at night starting dose 10 units and increased in 2-4
Unit intervals according to fasting blood glucose readings
Insulin regimens:
- long acting (once daily)
- Mixed insulin (twice daily)
- Basal bolus (multiple times daily)
T2DM less used drugs
Alpha-glucodisae inhibitors (acarbose)- not regularly used. Slows down digestion of carbs in SI, helpful post prandial hyperglycemia
Glitazones - improve insulin sensitivity and decrease triglyceride levels. Only one available (pioglitazone). Linked to bladder cancer and not recommended for use in anyone high risk for bladder cancer
DPP4 inhibitors/ Gliptins - sitagliptin/ vildagliptin/ saxagliptin. Last line oral diabetic meds. Modest results- mop up drug. Max dose 100mg OD. In Severe renal failure can use 25mg; Moderate renal failure 50mg. Help stimulate insulin production
GLP-1 analogues - require extra training to initiate. Range from once weekly (bydureon), once daily (victoza), twice daily regime (exenatide). Only available as injection. Mimics incretin which stimulate insulin production. Slows gastric emptying. Patient will lose weight. Nausea likely and vomiting very common
SGLT2 - Forxiga. Urinate glucose. High risk for GU infections such as UTI and thrush. Should not be given to patients with hx of urosepsis. Not licensed to treat type 1 or DKA
T2DM bariatric surgery
Can reverse/ help control type 2 diabetes
- Nesidioblastosis issue
- Similar to hyperinsulinemia hypoglycaemia in neonates
- Reduce antihyperglycemic agents which can cause hypos such as gliclazide
T2DM follow ups
- screen for neuropathy
- Carry out vascular screen
- Look for risk areas in feet
- Check urine for proteinuria
- Ensure BP <130/80
- Total cholesterol <3.0
- All patients should be on statin unless contraindicated - All patients should be on ACEi unless contraindicated. NOTE: SHOULDN’T GET PREGNANT ON THIS DRUG - routine monitoring of HbA1c with individual targets
- Ask about hypos
- Ask about retinal screening
- Depression screening
- Erectile dysfunction
- DMI annually
- Smoking cessation as and when needed until stable then annually to check on how they’re doing
retinopathy overview
Divided into two forms
Nonproliferative
Proliferative (abnormal new blood vessels (neuvascularisation)
Proliferative retinopathy leads to retinal detachment due to neuovascularisation producing fragile vessels, leading to haemorrhage etc.
Most pts are asymptomatic until too late (often untreatable) stage
Diabetes is most common cause of blindness in people over 65
DM infection risk
Poorly controlled diabetes impairs polymorphonuclear leukocyte functions
Increases infection risk
Particularly UTI and skin (cellulitis, boils, abscesses)
TB and candidiasis also more common in DM
Infections can lead to loss of glycaemic control (common cause of DKA)
In infections DT1 may need to increase insulin dosage
Same with DT2
diabetic foot/charcot
Condition causing weakness in bones of the foot; occurs in pts with significant nerve damage (peripheral neuropathy)
ischaemia causing tissue necrosis
Neuropathy: high foot arc, pressure sore and infection leads to diabetic foot
As pt walks small bones of foot fracture and become deformed
Presents with inflammation, erythema, warmth, neuropathy, bounding pedal pulses and possible deformities.
Treatment is offloading weight from feet and surgical opinion in severe cases
assessing diabetic foot risk
12-17 years annual assessment should include diabetic foot assessment. If problem suspected then refer to appropriate specialist
When diagnosed: should be assessed at least annually or if anymore problems arise or any hospital admission or any change is status while in hospital.
Stratify by risk: low risk (no RFs present but callus alone), mod (deformity, neuropathy or non-critical limb ischaemia), high risk (previous ulceration, previous amputation, renal replacement therapy, neuropathy and non-critical limb ischaemia together or neuropathy in combo with callus or deformity or non-critical limb ischaemia in combo with callus or deformity), active diabetic foot problem (ulceration, spreading infection, critical iscaemia or gangrene or suspicion of acute Charcot arthropathy or unexplained hot, red, swollen foot with or without pain.
diabetic foot management
Principles of foot care: well-fitting shoes, regular chiropody, avoid trauma, daily inspection of feet and seek advice if damaged, avoid heat sources like radiators and hot water (for everyone)
Low risk: annual foot checks
Moderate risk: refer within 6-8 wks to foot protection service, assess feet and provide skin and nail care, specialist footwear if needed, vascular status of lower limbs etc. every 3-6 months
High risk: refer within 2-4 wks to foot protection service, assess feet and provide skin and nail care, specialist footwear if needed, vascular status of lower limbs etc. every 1-2 months
hyperglycaemic hyperosmolar state (HHS)
Seen in unwell pts with DT2
Triggers include; MI, drugs, sepsis, bowel infarct
History of deterioration is longer than DKA roughly 1 week
Signs of marked dehydration, hypovolaemia, high osmolarity and glucose >30mmol/L
Small amount of insulin means they don’t switch to DKA, instead have high osmolarity >320mosmol/kg
HHS presentation
dehydration stupor or coma unconscious profound dehydration hypotension (later) tachycardia glucose >30mmol/L osmolarity >320
HHS treatment:
treat dehydration with fluids (2 large bore cannulae)
insulin therapy to correct hyperglycemia
electrolyte replacement
monitor throughout treatment for deterioration and improvements
Intensive monitoring (including calculating osmolarity regularly)
High dependency unit admission (CV catheter insertion)
Saline 0.9% IV fluids to replace Na, Cl and K loss and correct hypovolemia
Insulin started if significant ketonaemia is present but if not do not start insulin (CORRECT HYPOVOLAEMIA FIRST as insulin administration before correction can result in CV COLLAPSE)
Once BG has stopped falling as result of fluid resuscitation; then insulin may be started; aim for BG fall of 5mmol/L per hour
Monitor K+ and offer correction if needed
Anticoagulation for pts with increased thromboembolism risk
hypoglycemia
Most common endocrine emergency
Most common complication of insulin treatment
Triggers: high activity, missed meal, insulin overdose
Glucose <3mmol/L (normal fasting range 4-6; 2hrs post meal up to 7.8)
hypoglycemia causes
In seemingly unwell pts: Drugs: insulin, sulfonylureas, pentamidine, propranolol Non-pancreatic tumour eg sarcoma or hepatoma Addison’s disease Fulminant liver failure End stage kidney disease Excess alcohol Gastric surgery
Seemingly well pts: Factitious hypoglycemia (surreptitious self-administration of insulin often in non-DM Functional beta cell disorders Autoimmune hypoglycaemia Islet cell tumour (insulinoma)
hypoglycemia symptoms
Sympathetic overactivity: Sweating Hunger Anxiety Tremor Palpitations Pallor Dizziness Neuroglycopenia: Confusion Drowsiness Visual trouble Personality changes Seizures Hemiparesis Coma Brain damage Death
hypoglycemia investigations/diagnosis
Whipple's triad: diagnosis: Symptoms of hypoglycemia Low plasma glucose Glucose delivery resolves symptoms Investigations: In unwell pts: Plasma glucose Medication review Hepatic, renal and cardiac function tests Adrenocortical function Nonislet cell tumors Seemingly well pts: Observe during episode or after fast of up to 72 hours or after mixed meal Measure glucose Insulin C-peptide Pro-insulin Beta-hydroxy butyrate
insulinoma indications in hypoglycemia
Hyperglycaemia within 24 hrs fasting
Increased plasma insulin, C-peptide and proinsulin
Decreased plasma glucose <3mmol/L
These are rare and mostly benign
Needs CT scan imaging to isolate mass and begin treatment
hypoglycemia indications
Retinopathy Kidney complications Nerve problems Heart conditions Foot complications (peripheral neuropathy) Brain conditions; stroke, dementia MI, infections etc.
main endocrine glands
Pineal gland - melatonin
Pituitary
Hypothalamus - neural and hormonal functions
Thyroid and parathyroid glands
Thymus - thymosins and training T cells
Adrenal
Pancreas - both hormones and exocrine products
Ovary - both hormones and exocrine products
Testis - both hormones and exocrine products
Other organs with endocrine glands:
Heart
Kidneys
Stomach
Small intestine
hypothalamus
A line between the CNS and endocrine system
Regulates thirst, appetite, sleep cycles, menstrual cycle, stress/mood etc.
Hypothalamus releases factors which reach the anterior pituitary gland via the portal system (pituitary stalk)
These factors stimulate or inhibit hormone production from the anterior pituitary (queen of the endocrine system)
Vasopressin and oxytocin are produced in the hypothalamus and stored and released from the posterior pituitary
hormone regulation mechanisms
Negative feedback - response to hormone synthesis stops production
Counter-regulation - hormones working against the action of another hormone such as insulin raising BG levels and glucagon and adrenaline released in response to decrease BG levels
Positive feedback - rare; hormones secreted in response to hormone to increase it’s effect/action making it more potent e.g. oxytocin in labour is released to cause uterus contraction; more oxytocin is released in response and so on until delivery
biochemical hormone types
Tyrosine derived: T3 and 4 from thyroid. Can pass through cell membrane and cytoplasm and reach nucleus of cell (nucleic receptors). Affect cells all over the body, very widespread effects.
Steroid hormones: from adrenal or gonadal glands. Do not need receptor on cell surface membrane to enter as are lipophilic so can diffuse through. Bind to receptors in either the cytoplasm or nucleus of the target cell to form active receptor-hormone complex and produce response. Examples: oestrogen, progesterone, testosterone.
Peptide hormones: part of proteins; includes all other hormones other than the two types above. Hydrophilic and lipophobic; cannot freely cross plasma memb. Bind to receptors in cell surface to activate series of complex secondary messengers to initiate cell response. Examples: insulin, glucagon, leptin, ADH, oxytocin.
hypophysis
AKA The pituitary gland
Centre of the endocrine system, under control the hypothalamus, which in turn is under control of the upper CNS centres
Endocrine gland around the size of a pea weighing roughly 0.5G
Rests on the hypophyseal fossa of the sphenoid bone
Surrounded by small bony cavity (sella turcica) covered by dural fold (diaphragma sellae)
Below and behind the optic chiasma = pituitary mass = visual problem!
Located just behind upper sphenoid sinus (preferred surgical route of approach)
Helps to control blood pressure, energy management, gonadal organs, thyroid glands, metabolism and some aspects of pregnancy, birth and breastfeeding, water/salt concentration, temperature and pain relief!
The anterior pituitary (or adenohypophysis) is a lobe of the gland that regulates several physiological processes (including stress, growth, reproduction, and lactation). [LH,FSH, GH, TSH, ACTH, PRL]
The intermediate lobe synthesizes and secretes melanocyte-stimulating hormone [MSH].
The posterior pituitary (or neurohypophysis) is a lobe of the gland that is functionally connected to the hypothalamus by the median eminence via a small tube called the pituitary stalk (also called the infundibular stalk or the infundibulum). [ADH/Vasopressin, Oxytocin]
pituitary adenomas
Most common form of pituitary disease
Some are silent while others cause symptoms due to:
Inadequate hormone production (hypopituitarism)
Excess hormone secretion (hyperpituitarism)
Local effects of tumour (such as progressive visual impairment from mass pressing into sella turcica)
diabetes insipidus
Types: Reduced ADH secretion from post. Pituitary (cranial DI, CDI) Impaired response of kidney to ADH (nephrogenic DI, NDI) Causes: Improper hormone production Injury to hypothalamus Tumour or head surgery Kidney disorders Infections Genes
diabetes insipidus presentation
Results in Impaired water reabsorption by kidney
Causes passing of large volumes of water (>3L/day) of dilute urine
Also causes nocturia and compensatory polydipsia (excessive thirst/drinking)
This is due to lack of ADH causing dehydration and hyperatremia (hyperosmolar blood)
diabetes insipidus investigations/diagnosis
Clinical history of classic symptoms (polyuria, nocturia, polydipsia)
Tests for diabetes type 1 and 2 to rule these out
Water deprivation test: not drinking liquid for several hours and measure urine output (will continue to pee lots)
Blood test for ADH concentration, Ca and K concentration
Urine tests for same (very dilute low conc of substances)
Vasopressin test: injection of ADH to test reaction (decreased urine output = CDI, still continue to wee = NDI)
MRI scan: assess for CDI damage to hypothalamus or pituitary glands/abnormalities
diabetes insipidus risk factors and complications
Traumatic brain injury Atherosclerosis Pituitary abnormalities Autoimmune diseases Family history Genetic mutations
complications: dehydration and electrolyte imbalance
diabetes insipidus management
not always needed in mild cases
Increase water intake - mild CDI
Desmopressin (ADH analog) - mod/severe CDI
Low solute diet (mostly low sodium and low protein to help increase Na retention etc.) - mild NDI
Thiazide like diuretics - mod/severe NDI
NSAIDs - Mod/severe NDI
Classifications and management:
Mild CDI - 3-4 L urine over 24 hours; advise to drink 2.5L water everyday to compensate
Mod/Severe CDI - more than 4 L urine output over 24 hours; first line desmopressin
Mild NDI - reducing salt and protein in diet to increase kidney Na retention
Mod/Severe NDI - unlikely to respond to desmopressin due to kidney malfunction. Instead recommend thiazide diuretics to reduce kidney filter rate. NSAIDs like ibuprofen to further help reduce urine volume in combo with diuretics.
acromegaly
Pituitary gland releases GH under control of GHRH (stimulates) and somatostain (inhibits) from the hypothalamus
GH stimulates bone and soft tissue growth via increasing insulin -like growth factor-1 (IGF-1), made in the liver and other tissues
Excessive GH production in children (before long bone fusion of epiphyses) causes GIGANTISM
Excessive production in adults causes ACROMEGALY (acro-extremity; causes more effects in distal limbs)
Rare condition caused by benign pituitary GH producing adenoma in almost all cases
Gender doesn’t influence
Incidence highest in middle age
acromegaly presentation
Hand growth (spade like), jaw and feet Coarsening face (large hands and face, but not strong); wide nose, big tongue Wide spaced teeth
Puffy lips, eyelids Oily and large pores in skin Scalp folds Skin darkening Laryngeal dyspnoea (fixed cords) Obstructive sleep aponea Goitre (increase thyroid vascularity) Proximal weakness and arthropathy Carpal tunnel syndrome (50% cases) Cardiomegaly Hepatomegaly Nephromegaly Skin tags Splenomegaly
Signs of pituitary mass:
Hypopituitarism in other hormones
Reduced vision; hemianopia
Fits
acromegaly complications
in some cases; DM or CHF can be first signs of presentation so always check hormone levels when screening these pts.
Diabetes (impaired glucose tolerance; GH is stress hormone increase glucose secretion)
IHD ischaemic heart disease
HTN
Stroke (GH increases fibrinogen and decreases protein S; inhibits clot formation increasing IHD)
CHF (could be first presentation of acromegaly)
Increased risk of colon cancer
prolactin axis
Released from anterior pituitary
Suppressed by secretion of dopamine from hypothalamus
Has wide fluctuation level in blood
Many major tranquilisers, antipsychotics etc. are essentially anti-dopaminergic and so increase prolactin secretion
hyperprolactinaemia
Most common hormonal disturbance in pituitary
Cause:
Physiological: mild hyperprolactinemia is usually asymptomatic; occurs during pregnancy, breastfeeding, stress, post-orgasm
Pathological: prolactinoma, microprolactinoma - macroprolactinoma
Most common pituitary tumour and cause of severe hyperprolactinaemia
Also caused by drugs such as: metodopramide, phenothiazides, oestrogens, cimetidine
Other causes: primary hyperthyroidism (high TSH levels stimulate prolactin)
PCOS
Acromegaly (co-secretion of prolactin with GH by tumour)
hyperprolactinaemia presentation
Amenorrhea-galactorrhea syndrome
PRL increase causes galactorrhea (spontaneous milk flow not associated with childbirth or breast feeding)
Inhibits GnRH; decreasing LH/FSH and testosterone causing Oligo-/amenorrhoea (women), erectile dysfuntion (men), decreased libido, subfertility, osteoporosis (in both but specifically women)
Pituitary tumour: headache, visual field defects
hyperprolactinaemia management
Treat the underlying cause if feasible.
Asymptomatic patients with hyperprolactinaemia +/- a prolactinoma may not need treatment; 90-95% of of prolactinomas never increase in size. Indications for treatment are:
Adverse effects of tumour size.
Adverse effects of hyperprolactinaemia.
Treat with dopamine agonists: cabergoline, bromocriptine or quinagolide.
If DAs are ineffective:
Surgery - to reduce tumour size.
Radiotherapy - rarely used due to significant adverse effects and lack of effectiveness.
Women with hypogonadism and microprolactinomas who do not wish to become pregnant may be treated for their hypogonadism with oestrogen-containing contraception, as long as their prolactin levels (checked annually) do not increase substantially and there is no evidence of tumour enlargement.
hyperprolactinaemia during pregnancy
Small risk of tumour enlargement, particularly with macroadenomas (one third will enlarge). Refer urgently if there are headaches or visual disturbance.
Patients should be under an endocrinologist (ideally for pre-conception counselling too).
Depending on the individual situation, management may be:
Omitting DAs for the duration of pregnancy and during lactation.
If treatment is required, bromocriptine and cabergoline appear to be safe during pregnancy - bromocriptine is the most ‘tried and tested’ in this scenario.
drug induced hyperprolactinaemia management
This may be treated by withdrawing the drug (if feasible), with oestrogen/testosterone replacement, or with a cautious trial of a DA.
macroprolactinaemia treatment
This condition usually requires no treatment and does not generally cause infertility
hyperprolactinaemia complications
These will depend on the underlying cause, endocrine function and the tumour size (if due to a pituitary tumour). Possible complications are:
Complications of hypogonadism
Osteoporosis:
Bone loss occurs in about 25% of women with hyperprolactinaemia and doesn’t necessarily improve when prolactin levels return to normal
A small retrospective study of men with prolactinoma demonstrated significant bone loss whether treatment was with surgery or medical therapy. The authors suggest that a prolactinoma, even when adequately treated, increases the risk of osteoporosis in men by about 5 times
Reduced fertility.
Erectile dysfunction, and infertility.
Complications relating to tumour size:
Visual loss.
Headache.
Pituitary apoplexy:
This is the sudden onset of neurological symptoms (headache, visual symptoms, altered mental status, meningism) and hormonal dysfunction due to acute haemorrhage or infarction of a pituitary gland.
It is uncommon.
More likely in larger lesions.
May develop in patients with giant prolactinomas if their tumours do not reduce in size substantially with a chosen form of therapy.
CSF rhinorrhoea may occur with rapid size reductions in large prolactinomas that are highly sensitive to DA therapy.
Very rarely, prolactinomas may be malignant.
hyperprolactinaemia prognosis
This depends on the underlying cause.
In women microprolactinomas spontaneously resolve in around a third, especially after the menopause or pregnancy. Treatment should be discontinued intermittently to see if it is still needed. The treatment dose may be decreased slowly over time. It is reasonable to attempt DA withdrawal in all patients who have been treated for three years, if prolactin levels are normal and the tumour volume has markedly reduced
Five-year recurrence rates depend on the presence or absence of visible adenoma on MRI:
Macroprolactinoma:
Without visible remnant 33%.
With visible remnant 78%.
Microprolactinoma:
Without visible remnant 26%.
With visible remnant 42%.
Follow-up to detect recurrence of hyperprolactinaemia and tumour enlargement is essential.
thyroid histology
Follicles: small groupings of cells surrounding core of colloid cells (produce thyroid-precursor proteins called thyroglobulin)
Follicular cells: follicle core surrounded by single layer of follicular cells. When stimulated by TSH from hypophysis they metabolise thyroglobulin in the colloid to secrete T3 and 4
Parafollicular cells: scattered among follicular cells. Secrete calcitonin (called C cells). Has no important endocrine role in humans
T3/4
80-90% T4 secreted (inactive form of T3)
10-20% T3 (active hormone)
T3/4 is protein bound eg to thyroid binding globulin (TBG) is inactive
Free unbound is active hormone
Regulation of thyroid hormone usually based on T3
T3 is 5 times more active than T4
T4 transformed to T3 in peripheral tissues
Thyroid hormone abnormalities usually due to the gland itself
Rarely caused by hypothalamus or pituitary
Act on nearly every cell in body to regulate basal metabolic rate
Affect protein synthesis, long bone growth, neural maturation, increase sensitivity to catecholamines (adrenaline), essential in cell development and differentiation, heat generation
Hormone regulation:
Primarily regulated by TSH from anterior hypophysis (stimulated by TRH from hypothalamus)
TSH stimulates secretion
Negative feedback from high conc of hormone stops secretion of regulatory molecules
TRH and TSH production and release suppressed by high conc
TFTs
Serum hormone levels (TSH, T4, T3, fT4, fT3)
Iodine or technetium uptake scans
Ultrasound scans
Anti-thyroid antibodies
TRH test
Measure TSH
Total hormone = bound + free
Scan the gland to analyse the shape – is there a tumour or cyst
Fine needle aspiration - for solid nodules
Isotope scan for suspicious thyroid nodule: can detect HOT/COLD or neutral nodules based on uptake of isotope and comparing to remaining thyroid. Increased uptake is hot (metabolically active), decreased is cold (metabolically inactive) and the same is neutral. Few neutral and almost no hot nodules are malignant. 20% cold nodules are malignant.
THR test: administer THR and look for TSH response. Normal = goes up after 20 mins then returns to normal level. Secondary hypothyroidism or thyrotoxicosis indicated if lack of TSH response or TSH response is too high/no return to normal levels.
parathyroid glands
Four small endocrine glands behind each lobe of thyroid
yellow/brownish flat ovoid shaped resembles a lentil seed
6mm long, 3-4 mm wide
Share similar blood supply, venous and lymphatic drainage to thyroid glands
Produce parathyroid hormone PTH
Regulated by negative feedback from Ca levels
Act to increase Ca levels by:
- increasing osteoclast activity releasing Ca and PO4 from bones
- increase Ca and decrease PO4 reabsorption in kidney
- increase production of vit D active form from precursor vit D3
Overall increases Ca and decreases PO4
adrenal glands
Two small glands above the kidney
Each has a cortex and medulla
Cortex secretes steroid hormones, mineralocorticoids, glucocorticoids and androgens
Medulla secretes catecholamines: adrenaline a noradrenaline
Mineralocorticoids: aldosterone regulates BP, electrolytes balance
Glucocorticoids: cortisol and corticosterone regulate carbohydrates, lipids and proteins metabolism
Androgens: DHEA, no overall effect in males; converted to testosterone and DHT or to oestrogens in relevant gonads
side effects of cortisol therapy
Cushing’s syndrome Weight gain, moon face, increased appetite Skin atrophy, purple striae, acne Brittle vessels, easy-bruising Muscle wasting Gynecomastia Immunocompromised - increased infection chance Osteoporosis HTN DM Glaucoma, cataracts Rapid mood changes, irritable and anxious Depression Sleep disorders Growth retardation in children
cushings syndrome
Clinical presentations of chronic glucocorticoids excess
Loss of normal feedback in HPA axis ie is not suppressed by DEXA administration
Loss of circadian rhythm of cortisol secretion
Causes: generally divided into two groups: ACTH dependent causes (high ACTH) such as pituitary adenoma (cushings DI) most common cause 80%
ACTH independent causes : low ACTH chief cause of cushing syndrome in general is oral steroids (iatrogenic)
primary causes of elevated T3/4
Hyperthyroidism – hyperfunction of the thyroid gland, too much
Thyrotoxicosis – exposure to high levels of thyroid hormones, not because gland is hyperfunctioning e.g. took too much medication (thyroxine)
Graves’ Disease - autoimmune
Toxic nodules – overactive regions of thyroid gland
Toxic adenoma – hormone producing tumour
Thyroiditis – e.g. viral infection
Iodine containing drugs – amiodarone (drug for heart?)
Excessive T3 and T4 ingestion – replacement therapy, supplement
Treatment – suppress hormone production eg carbimazole, surgery/radiotherapy to remove hyperfunctioning nodules
Viral infections damage the gland, the gland releases too much hormone. Hypothyroidism can occur when the gland recovers before returning to normal
Drugs containing iodine can cause a predisposition to thyroid hyperfunction
Supplement demand of patients will change throughout their life so should be monitored and medication reviewed.
thyrotoxicosis/hyperthyroidsism
Excessive thyroid hormone, usually caused by thyroid hyperfunction Hyper acute F:M 4:1 ratio Thyrotoxicosis: excessive hormone Hyperthyroidism: excessive hormone due to thyroid hyperactivity Triggers in unprepared pt: recent thyroid surgery, radioiodine, infection, MI, trauma, stress Causes: Graves disease Toxic multinodular goitre TMG Toxic adenoma Ectopic thyroid tissue Exogenous iodine excess
thyrotoxicosis/hyperthyroidism signs and symptoms
Severe hyperthyroidism Agitation Confusion Coma Goitre Tachycardia Palpitations AF HF Acute abdomen syndrome Diarrhoea Weight loss Increased appetite Irritability Excessive sweating Heat intolerance Oligomenorrhea +/- infertility Fast and irregular pulse
thyrotoxicosis/hyperthyroidism complications
HF Angina AF Osteoporosis Ophthalmopathy Gynaecomastia Thyroid storm
thyrotoxicosis/hyperthyroidism investigations
Bloods: TSH, FT3/4, FBC, autoantibodies: low TSH with high T3/4. may show mild normocytic anaemia, mild neutropenia, increased autoantibodies
Isotope scan: if cause unclear or to detect nodular disease or subacute thyroiditis
Visual tests: if ophthalmopathy present test visual fields, acuity and eye movements
thyrotoxicosis/hyperthyroidism treatment
Drugs:
Beta blockers (propranolol 40mg/6h) rapid symptom control
Antithyroid meds: titration eg carbimazole 20-40mg/24h PO 4wks then reduce according to TFTs every 1-2mnths. Block replace eg carbimazole and levothyroxine simultaneously (less risk of iatrogenic hypothyroidism)
Radioiodine:
Most become hypothyroid post treatment
In active hyperthyroidism there is risk of thyroid storm
Pregnancy and lactation
Thyroidectomy:
Risk of damage to recurrent laryngeal nerve (hoarse voice) and hypoparathyroidism
Patients will become hypothyroid so will need a levothyroxine hormone replacement post. surgery
toxic multinoular goitre TMG overview
Gland with at least two autonomous nodules
Seen in elderly and in iodine deficient areas
Nodules secrete thyroid hormones
Develops from endemic goitre becomes multinodular goitre and some nodules become autonomous (hot nodules); pt becomes hyperthyroid - TMG
Surgery indicated for compressive symptoms from enlarged thyroid (dysphagia or dyspnoea)
toxic adenoma
Solitary nodule producing T3/4
Isotope scan shows hot nodule and rest of gland is suppressed
ectopic thyroid tissue
Metastatic follicular thyroid cancer
Struma Ovarii: ovarian teratoma with thyroid tissue
single toxic nodule
Autonomous and produce sufficient hormone to suppress TSH secretion and contralateral lobe of thyroid gland
Usually >3cm before symptoms arise
Linked to activating mutations in TSH receptor or signalling
iodine containing drugs which may cause thyrotoxicosis
Amiodarone is main cause
Type 1: caused by iodine in pts with underlying toxic multinodular goitre
Type 2: inflammatory effect due to toxic effect of iodine on thyroid follicular cells
thyroid storm
rare life threatening condition with rapid deterioration of thyrotoxicosis with hyperpyrexia, tachycardia and extreme restlessness.
Eventually delirium, coma and death.
Diagnosis if strong suspicious urgent treatment needed (don’t wait for tests).
thyroid storm symptoms
Florid hyperthyroidism (graves disease; goitre, exophalamos, infiltrative dermopathy. Thyroiditis. Multinodular goitre) Fever Marked weakness and muscle wasting Extreme restlessness Wide emotional swings Confusion Psychosis Coma: particularly elderly Nausea Vomiting Diahrrhoea Hepatomegaly with mild jaundice Tachycardia AF Cardio collapse and shock
thyroid storm investigations
TSH,
free T4/3
confirm technetium uptake (radioiodine scan if possible).
thyroid storm treatment
large doses of carbimazole (20mg 8hr orally) to block thyroid hormone synthesis.
Propranolol (80mg 12hr orally to block orme effects.
Lugol’s solution (K iodine 15mg 6 hr orally blocks release of hormone from gland acutely).
Hydrocortisone (100mg IV 6hrly inhibits peripheral conversion of T4 to T3)
graves disease
Prevalence 0.5% of population roughly ⅔ of hyperthyroidism cases
F:M ratio 9:1
Typical onset 40-60 years
Triggers: stress, infection, childbirth
Associated with other diseases such as T1DM, Addison’s etc.
Cause:
Circulating IgG autoantibodies binding and activating thyroid receptors causing smooth thyroid enlargement (goitre) and high thyroid hormone production/secretion (esp. T3)
Reacts with orbital autoantigens causing Graves eye signs
graves disease presentation
Diffuse goitre
Thyroid bruit due to hyperfunctioning and hyperperfusion of thyroid
Thyroid acropachy: clubbing, painful finger/toe swelling, periosteal reaction in limb bones
Ophthalmopathy: exophthalmos, ophthalmoplegia
Pretibial myxoedema: oedematous swelling above lateral malleoli
graves disease investigation
Autoantibodies
TSH and FT3/4
Clinical exam if goitre present
graves disease management
Initially either regimen of antithyroid medication (carbimazole +/- levothyroxine for 12-18 months then withdraw
50% relapse then need radioiodine or surgery
hypothyroidism/myxoedema
Clinical effect of lack of thyroid hormone
Common (4 in 1000/year)
Many times is insidious
If treated has good prognosis but very poor if untreated (heart disease, dementia)
Etiology:
Primary autoimmune hypothyroidism: primary atrophic and Hashimoto’s thyroiditis
Iodine deficiency
Post thyroidectomy of after radioiodine treatment
Drug induced anti-arrhythmics, amiodarone, lithium, iodine
Subacute thyroiditis
Seonary - due to hypopituitarism: lack of TSH (rare)
hypothyroidism symptoms
non specific especially in women in 40s: Fatigue Lethargic Low mood Avoids the cold Weight gain Constipation Menorrhagia Hoarse voice Reduced memory/cognition Dementia Myalgia Cramps Weakness Bradycardia Neuropathy Myopathy Goitre Ataxia (lack of balance) Dry thin skin/hair Ascites +/- pitting oedema Round puffy face CHF
hypothyroidism investigations
TFTs: high TSH, low T4
Cholesterol and triglyceride profile - high
FBC - larger RBC high MCV
Have low threshold for abnormality with suspicious or vague symptoms or in middle ages women
are they on any drugs like amiodarone or OTC supplements? (vit D)
hypothyroidism management
Levothyroxine 25-50mcg/24hr PO
Review at 12 wks
Aim to keep TSH >0.5mU/L
In elderly or IHD pts; levothyroxine, L-thyroxine (T4) has risk of angina or MI so start with lower dose/be cautious
normal TSH, FT3/4 levels in average adult and important factors relevant to results
TSH - 0.4-4mU/l
FT4 - 9-25pmol/l
FT3 - 3.5-7.8pmol/l
Ranges differ during pregnancy, children and infants, also vary from lab to lab so always look up guideline*
Key points of interpretation guidelines:
Acute illness ‘sick euthyroid’: Not recommended to perform TFTs in secondary care due to acute illness/treatments skewing results and interpretations leading to false diagnoses.
Ethnicity; black ppl have lower TSH levels
Age: mild TSH elevation 4-7mU/L may be normal with ageing
Pregnancy: physiological TSH suppression in first trimester
Medications: dopamine, high dose glucocorticoids, amphetamines, octreotide and bromocriptine suppress TSH levels
Medications: containing iodine like lithium, amiodarone produce low TSH and high T4 can produce hyperthyroidism!
Oestrogens: birth control pills cause high total T3/4
Biotin: OTC supplement causes abnormal result; check with pts and ensure they don’t take for at least few days before any TFTs
guide to starting hypothyroidism treatment
Must be symptomatic
TSH levels must be outside of normal range (for non-physiological states)
Start pts on levothyroxine (synthetic T4 hormone)
There is no evidence that T3 treatment is effective (leothyronine) any treatment with this needs specialist endocrinologist opinion to see if it gains benefit or not.
TSH >10 is over-hypothyroidism; indication to start treatment (NICE)
Starting dose 25-50mcg levothyroxine, increase if no effect
subclinical hypothyroidism
Subclinical hypothyroidism is an early, mild form of hypothyroidism, a condition in which the body doesn’t produce enough thyroid hormones. It’s called subclinical because only the serum level of thyroid-stimulating hormone from the front of the pituitary gland is a little bit above normal
Asymptomatic pts with raised TSH but still <10 with normal FT3/4 levels.
Treatment:
Monitor pt regularly, start with repeating tests within 3 months to see if anomaly or real change
Until then no further treatment needed as no symptoms and is subclinical
two repeated readings <10 can start treatment
Start on 6 month trial after discussing with endocrinologist
Always start on lowest dose; especially in elderly or those with cautions such as heart problems
Subclinical hypothyroidism is likely an incidental finding as doesn’t actually present with symptoms
Usually not a problem unless TSH keeps increasing with monitoring; there is under-lying problem, like above.
thyroiditis
Inflammatory condition - autoimmune, infectious and toxic resulting in apoptotic pathways and follicle cell death
Disruption of follicles results in thyroid hormone release and hyperthyroidism followed by mild hypothyroidism then recovery
Presents first as hyperthyroidism followed by hypothyroidism
Two conditions cause this presentation: Hashimoto’s and Postpartum thyroidosis
Other inflammatory diseases of thyroid: subacute thyroiditis, acute thyroiditis, silent thyroiditis, riedel’s thyroiditis, palpation thyroiditis (traumatic injury)
hasimoto’s condition/thyroiditis
hypothyroid condition
Affects around 1% population
More common in women (x6)
More common after age 60
Goitre and autoimmune destruction of gland
Autoimmune disorder where gland is infiltrated by lymphocyte B cels
Anti-microsomal and anti-thyroid peroxidase Abs found in 95% cases
Anti thyroglobulin Abs in 60% cases
hasimoto’s thyroiditis pathology
Gland can’t produce hormones anymore
No -ve feedback on TSH so rises significantly while T3/4 decrease
Initially presents with hyperthyroidism
Then a period of hypothyroidism
Patients diagnosed are hypothyroid or euthyroid
Rarely diagnosed in initial hyperthyroid period (hasi-toxicosis)
Also more common in pts with T1DM, pernicious anaemia, addison’s disease etc.
Hasimoto’s thyroiditis investigations
Immunoassay for anti thyroid peroxidase antibodies most sensitive test
Elevated TSH
Postpartum thyroiditis
In females following childbirth
Glands become inflamed
Initially presents with period of hyperthyroidism followed by hypothyroidism
Usually function returns to normal after period of time (several months)
Characterised by painless goitre
Antibodies against thyroid peroxidase found in testing
Usually doesn’t require treatment although thyroid hormone replacement may be needed during hypothyroid period for symptomatic relief
Subacute granulomatous thyroiditis (De Quervain thyroiditis)
URTI causes thyrotoxicosis followed by hypothyroidism
Uncommon
Affects all ages, sexes but is most common in 40-50’s
SYMPTOMS: URTI sudden and painful thyromegaly, neck pain, dysphagia, fever
Diagnosed by blood tests
Resolution is spontaneous with no treatment needed
5-10% develop permanent hypothyroidism and need thyroid hormone replacement
Goitre
Thyromegaly Etiology: Diffuse: Physiological e.g. pregnancy Graves’ disease Hashimoto's thyroiditis Subacute thyroiditis Nodular: Multinodular goitre (MNG) Adenoma Carcinoma *Around 10% nodules are malignant. Lymphadenopathy strongly suggests may be malignant
nodular thyroid and investigations
Cause: MNG, fibrotic goitre
Solitary thyroid nodule cause: cyst, adenoma, discrete nodule in MNG, malignant (10%)
Investigations:
TFTs: FT3/4, TSH
USS: solid/cystic
USS guided FNA - cytology benign or malignant (can’t differentiate between follicular adenoma and follicular carcinoma)
Autoantibodies if suspicious of hashimoto’s/graves
Radionuclide scans (cold hot nodules): 10% cold nodules malignant, 90% other. Hot nodule: toxic adenoma.
CXR large goitres located low in the neck; lung metastases in thyroid cancer
thyroid cancer and risk factors
Often asymptomatic thyroid nodule presentation
Uncommon
Red flags!! Progressive in size, hard and irregular nodule, presence of enlarged neck lymph nodes
Types:
Papillary 60% well differentiated good prognosis
Follicular 25% well diff. Good prognosis
Medullary 5%
Thyroid 5%
Anaplastic carcinoma: rare, undifferentiated, poorest prognosis
Risk factors:
Low dose neck radiation in childhood - papillary carcinoma
Positive family history of thyroid cancer
papillary carcinoma
In younger pts
Spread via lymph nodes into lungs - papilli grow slowly spreading towards nodes
Risk factor: neck RT in childhood, exposure to ionising radiation
Management is total thyroidectomy +/- node excision and radioiodine ablation with T4 suppression
Post op radioiodine ablation removes possible necrosis of remaining thyroid tissue/metastases
Post op levothyroxine needed to replace thyroid hormones and suppress TSH
follicular carcinoma
Well differentiated
AKA follicular adenocarcinomas
In middle aged pts
Spread via the blood to the bone and lungs; grows until it breaks through thyroid capsule into blood vessels
FNA can’t differentiate between follicular adenoma and carcinoma
Management: total thyroidectomy + radioiodine ablation and T4 suppression
medullary carcinoma
Origin in C cells of thyroid; do not concentrate iodine so radioiodine scan or ablation does not work !!
C cells more concentrated in upper 1/3rd of gland
May produce calcitonin which can be used as tumour marker in post op follow ups (should decrease post op).
May also release serotonin and vasoactive intestinal peptide increasing gastrointestinal mobility: ask about toilet habits changing?
Sporadic mutation in 80% cases but can be familial; associated as part of MEN multiple endocrine neoplasia syndrome 20% cases
For all cases need to screen for pheochromocytoma before operation; measure catecholamine metabolites in urine (if +ve in men screen for PCC 1st)
Management: thyroidectomy and node excision
lymphoma and angioplasty carcinoma
Lymphoma:
Treatment chemo/radiotherapy
Angioplasty carcinoma:
Aggressive, no response to treatment, poor prognosis but radiotherapy may help
Very rare, altered cells
Grows beyond fibrous capsule and invade nearby structures
Derived from existing papillary or follicular cancer
first signs of thyroid cancers
Solitary painless nodule
Hard and immovable nodules more likely tumors
Larynx : hoarse voice
Oesophagus : dysphagia
Usually no signs of hyper or hypothyroidism
In medullary - diarrhoea and skin flushing (serotonin)
thyroid cancer diagnosis and treatment overview
Thyroid ultrasound Calcitonin levels elevated - medullary carcinoma Radioiodine scan FNA: identify tumour type Treatment overview: Depends on type and how it spreads Partial or total thyroidectomy T4 suppression Radioiodine ablation
primary hyperparathyroidism causes and presentation
Causes: 80% solitary adenoma 20% hyperplasia of all glands Rarely parathyroid cancer Presentation: Asymptomatic often High Ca on routine tests picked up incidentally Tired Weak feeling Depressed Thirsty Dehydrated but polyuric renal stones Abdominal pain Pancreatitis Duodenal ulcers Bone pain, fracturing, osteropenia/osteoporosis High BP MEN-1 syndrome: adenoma/hyperplasia can present as part of multiple endocrine neoplasia type 1
primary hyperthyroidism investigations
Bloods: high Ca, high PTH, low PO4
High ALP (bone activity)
High 24hr urinary Ca
CXR: subperiosteal erosions, cysts, brown tumours of phalanges, acro-osteolysis, pepper-pot skull, osteritis fibrosa cystica (severe reabsorption - rare)
DEXA scan for bone densitometry: osteoporosis
Primary hyperthyroidism management
Mild: high fluid intake to prevent stone, avoid thiazides, avoid high Ca and Vit D intake
Follow ups every 6 months for bloods check
Severe: excision of adenoma or all four hyperplastic glands. If high serum or urinary Ca, bone disease, peptic ulcers, osteoporosis, renal calculi, low renal function, age >50
Pre-op USS and sestamibi (liquid radioactive material injected into body and absorbed by overactive parathyroid but not healthy parathyroid) may localse adenoma
Intra-op blood PTH sampling to confirm removal of correct parathyroid
Secondary hyperthyroidism and causes
Low Ca and high PTH
Causes:
Low vit D intake
Chronic renal failure
Secondary hyperthyroidism treatment
Correct cause Phosphate binders Vitamin D Cinacalet if PTH is very high. Is a calcimimetic - increases sensitivity of parathyroids to Ca causing increase in -ve feedback so reduced PTH secretion Parathyoidectomy
Tertiary hyperthyroidism overview
High Ca and very high PTH
Causes:
Chronic renal failure, prolonged secondary hyperparathyroidism or hyperplastic or adenomatous parathyroid
Glands act autonomously (no Ca -ve feedback) resulting in very high PTH and hypercalcemia
Treatment: endocrinologist and other expert referrals
MEN syndrome associations of type and complicatins
type 1: 3 P’s; pituitary adenoma, parathyroid hyperplasia, pancreatic tumors
type 2: PPM; parathyroid hyperplasia, medullary thyroid carcinoma, pheochromocytoma
type 3: MMMP; mucosal neuromas, marfanoid body habitus, medullary thyroid carcinoma, pheochromocytoma
primary hypoparathyroidism overview
PTH secretion is low due to gland failure
Caused by autoimmune diseases (DiGeorge syndrome) thymus aplasia and T cell immunity failure
Signs and symptoms: hypocalcaemia (cramps, corpopedal spasm, bronchospasm, dysphagia, laryngospasm with co-morbidities like addison’s, pernicious anaemia, alopecia etc.)
Investigations: PTH low, Ca low, PO4 high or neutral, ALP neutral
Management: Ca supplements, calcitriol, synthetic PTH
DiGeorge syndrome and symptoms
Deletion syndrome of small segment from C.22 Causes cardiac abnormality Abnormal faeces Thymic aplasia Cleft palate hypocalcaemia/hypoparathyroidism
secondary hypoparathyroidism causes and IX
Radiation
Surgery on thyroid or parathyroids
Hypomagnesaemia (Mg needed for PTH secretion)
Investigations:
Ca low
PTH low
PO4 high or neutral
pseudohypoparathyroidism overview
Failure of target cell response to PTH
Cause is genetic
Signs: short metacarpals (esp. 4+5th), round face, short stature, calcified basal ganglia
Investigations: Ca low, PTH high, ALP neutral or high
Management: Ca supplements, calcitriol, synthetic PTH
pseudopseudoparathyroidism
morphological features of pseudohypoparathyroidism but with normal biochemistry. Caused by genetics also.
subclinical hypothyroidism and hypothyroidism pregnancy advice
Subclinical hyperthyroidism needs referral if TSH is <0.1mU/L for at least 3 months and there is evidence of thyroid disease
*pre-pregnancy counselling needed for all women with overt or subclinical hyperthyroidism planning pregnancy.
Advised to seek medical advice if pregnancy suspected or confirmed
Arrange urgent specialist referral for all pregnant women with current or previous overt or subclinical hyperthyroid disease
Check TFTs postpartum depending on specialist advice
Hypoglycemia management
Mild:
Eating and drinking 15-20g fast acting carbohydrate such as glucose tablets, sweets, fizzy drinks or fruit juice
May also need 15-20g slower acting carbohydrate if not due next meal soon
Regularly test blood glucose
Moderate-severe:
If unconscious; glucagon injection/glucogel/dextrogel/rapilose gel, if they wake up within 10 minutes then encourage carbohydrate fluid or food to help correct hypoglycemia. If not; can repeat gel up to 3 times in total or if in hospital give IV glucose 10% as this is a medical emergency. Long acting carbohydrates given ASAP when conscious and BG >4mmol/L again.
If seizures: time duration and frequency: if very aggressive stop IV glucose 10% and treat with glucogel up to 3 times and go back to IV if no response
If not responding within 30-45 minutes of glucose gel; treat with IM glucagon or glucose 10% IV
In alcoholic patients, thiamine supplementation should be given with, or following, the administration of intravenous glucose to minimise the risk of Wernicke’s encephalopathy.
If Insulin injection is due do NOT omit giving this; consider reviewing regimen however
Hypoglycaemia caused by a sulfonylurea or long-acting insulin, may persist for up to 24–36 hours following the last dose, especially if there is concurrent renal impairment.
Blood-glucose monitoring should be continued for at least 24–48 hours.
Acromegaly investigations
random plasma GH is unreliable so cannot use to detect disease:
Oral glucose tolerance test (OGTT): high glucose fails to suppress GH levels
MRI: of pituitary fossa to look for adenoma
Visual fields and acuity
ECG; Echo: cardiomegaly
Biochem tests: assessing pituitary hormone secretion
Old photos if possible to compare progression of signs in person
Acromegaly treatment
Trans-sphenoidal surgery (first line) Somatostain analogues (SSA) such as octreotide or lanreotide and/or radiotherapy GH antagonist (Pegvisomant); for those resistant to SSA; suppresses IGF-1 production by liver reducing metabolic effects
Cushing’s syndrome vs disease
Syndrome: excess ACTH in the body
Disease: excess ACTH caused specifically by adneomas/cancers
Cushing’s and causes
Clinical presentations of chronic glucocorticoids excess
Loss of normal feedback in HPA axis ie is not suppressed by DEXA administration
Loss of circadian rhythm of cortisol secretion
Causes: generally divided into two groups:
ACTH dependent causes (high ACTH) such as pituitary microadenoma (cushings DI) most common cause 80%; ectopic ACTH such as SCLC or carcinoid secretion
ACTH independent causes : low ACTH chief cause of cushing syndrome in general is oral steroids (iatrogenic); adrenal adenoma or nodular hyperplasia causing high cortisol secretion
paraneoplastic Cushing’s is excess ACTH secretion from cancer; can be ectopic or not
Cushing’s presentation
Obesity, moon face, buffalo hump Easy bruising, atrophic skin, purple striae, hirsutism Poor wound healing Susceptibility to infections Proximal myopathy High BP DM Menstrual irregularity/gynecomastia in males Osteoporosis Subtle mood changes Growth retardation in children peptic ulcer disease in GI
Cushing’s complications
High chance of heart problems due to increase BP and increased fat storage
High chance of DM from increased BG and increased fat storage (affect beta cells)
Low immunity: prone to infection
ACTH dependent causes of Cushing’s
Bilateral adrenal hyperplasia from ACTH secreting pituitary microadenoma
Occurs equally in males and females peak incidence between 30-50years
Specific features of ectopic ACTH:
Pigmentation (ACTH stimulates melanocyte stimulating hormone MSH
Hypokalaemic metabolic alkalosis
Weight loss
Hyperglycemia (DM)
ACTH independent causes of Cushing’s
Iatrogenic: pharma steroids; most common cause of Cushing’s
Adrenal adenoma/cancer: tumor is autonomous so high dose DST fails to suppress cortisol production. Pts may also present with abdominal pain +/- virilisation in women
Adrenal nodular hyperplasia: autonomous so high dose DST fails to suppress cortisol also
Cushing’s investigations
Low dose dexamethasone suppression test (1mg): If cortisol levels/ACTH/CRH do not decrease = Cushing’s disease; if abnormal; perform next step to differentiate between underlying causes. Normal response is decrease in hormone secretion from all glands.
High dose dexamethasone suppression test (8mg): suppresses cortisol in cases of pituitary adenoma (still shows some negative feedback). In cases of ectopic ACTH (e.g. SCLC or adrenal adenomas) neither cortisol or ACTH will be suppressed as ACTH production is independent of the hypothalamus so no negative feedback is taking place
24 hr urinary free cortisol can be used as alternative to DST’s to diagnosis Cushing’s; but does not indicate underlying cause - high cortisol over 24 hrs = Cushing’s
Bloods: FBC: raised WCC and electrolytes (potassium may be low if aldosterone also secreted by adrenal adenoma); plasma ACTH (low=adrenal adenoma/cancer, need CT/MRI; high = non adrenal cause indicates DST or CRH test; IV CRH increases cortisol in pituitary adenoma but not in ectopic)
MRI: pituitary adenoma; detects only 70% microadenomas in Cushing’s
Chest CT: SCLC
Abdominal CT: adrenal tumours
Dexamethasone suppression test overview
Start low dose (1mg) test: results show low cortisol = normal axis function
high/normal range cortisol= Cushings syndrome
High DST (8mg): Low cortisol = Cushings disease from pituitary adenoma High/normal cortisol = check ACTH levels high ACTH levels = Ectopic ACTH secretion from SCLC Low ACTH levels = Adrenal Cushing's (adrenal adenoma)
Cushing’s management
If iatrogenic: taper medications if possible
Trans-sphenoidal removal of pituitary adenoma
Surgical removal of adrenal tumour
Surgical removal of tumour producing ectopic ACTH
If surgical removal of the cause is not possible: may remove both adrenal glands and give pt steroidal replacements for life +/- radiotherapy + mitotane (direct selective cytotoxic effect on adrenal cortex causing adrenal atrophy)
For ectopic ACTH (SCLC-carcinoid) that is inoperable or unlocatable; metyrapone, ketoconazole, fluconazole to decrease cortisol secretion
Addison’s and cause
Adrenal insufficiency syndrome
Primary: addison’s disease (rare; fatal) shows high pigmentation
Secondary: iatrogenic: abrupt cessation of long term steroid therapy (common; fatal) does NOT show high pigmentation
tertiary: caused from over secretion of CRH from hypothalamus (rare!) usually from long term steroid use axis suppression
Addisonian crisis: shock and death
Destruction of the adrenal cortex causing glucocorticoid and mineralocorticoid deficiency
Can be associated with other autoimmune diseases like Graves, pernicious anaemia, T1DM etc.
CAUSE:
Autoimmune disease in 80% cases UK
TB is most common cause in the world
Addison’s presentation
in both addison’s disease and steroid withdrawal: Lean, tanned (pigmentation in palmar creases and buccal mucosa), vitiligo Tired, anorexia, tearful +/- weakness Dizzy, faint, postural Hypotension Flu-like myalgias Depression, psychosis Nausea, vomiting Abdominal pain diarrhoea/constipation
pigmentation only in addison’s disease NOT steroid withdrawal
Difficult to diagnose symptoms are all over the place - think of Addisons always in unexplained abdominal pain or vomiting with any other findings!
Addisons management
Hydrocortisone (20mg on waking and 10mg evening to mimic normal diurnal rhythm) to correct glucocorticoid stress
Mineralocorticoids (fludrocortisone 50-200mcg daily) to correct postural hypotension, hyponatraemia and hyperkalaemia
Medic alert bracelet or necklace: carry steroid card: keep ampoule of hydrocortisone at home
During any stress (infection, trauma, surgery) increase normal doses to compensate for increase demand of hormones
Addisonian crisis and presentation
Acute presentation of severe Addisons, where the absence of steroid hormones leads to a life threatening presentation. Present with: Reduced consciousness/confusion Hypotension Oligura Profound weakness Hypoglycaemia, Hyponatraemia, Hyperkaemia Patients can be very unwell, similar to shock
Addisonian crisis history
can be the first presentation of Addison’s Disease or triggered by infection, trauma, MI, asthma, alcohol intake, pregnancy, exogenous steroid withdrawal or reduction or other acute illness in someone with established Addisons. Or just forgot to take tablets.
Most common cause is steroid withdrawal: always look for medic alert bracelet to indicate pt on steroids
Addisonian crisis management
Do not wait to perform investigations and establish a definitive diagnosis before treating someone with suspected Addisonian Crisis as this is life threatening and they need immediate treatment.
Take bloods for plasma cortisol and ACTH before treatment but dont wait for results!
Ask for FBC, urea, electrolytes, BG, serum Ca and blood cultures
Hydrocortisone 100mg IV
0.9% saline 1L over 30-60mins
50mL 50% dextrose for hypoglycaemia
Find cause/trigger eg infection
Hydrocortisone then given IM 6 hourly until BP stable and vomiting ceased
saline 2-4L IV in 12-24hrs; monitor JVP and CVP
Expect recovery of BP, BG and Na within 12-24hrs
When stable, convert to oral maintenance for life
Steroid therapy advice
Never stop therapies abruptly, always taper off to prevent inducing Addisons disease
Steroid card: all prescribing Drs/dentists/surgeons must be informed of steroid use
Whenever acutely unwell: go to GPs to increase steroid dose
Pt should be aware of the side effects of steroid therapy; Peptic ulcer disease, HTN, osteoporosis, Cushingoid syndrome
Receive regular check ups
Calculate plasma osmolarity
2(Na) + 2(K) + Glucose + urea (Can calculate +/- potassium also. not sure it matterrrrs
OPQRST approach to weight history taking
OPQRST:
Onset: “When did you first begin to gain weight?” “Have you struggled with your weight since childhood?” “What did you weigh in high school, college, early 20s, 30s, 40s?” “Did the weight gain begin when you started taking a certain medication?”
Precipitating factors: “What life events may have led to your weight gain—such as college, work stress, marriage, divorce, financial loss, a period of depression, onset of an illness?” “How much weight did you gain with pregnancy?” “How much weight did you gain when you stopped smoking?” “How much additional weight did you gain when you started insulin, steroid ?” “Do you recall specific challenges or barriers to maintaining weight loss that led to regaining weight?”
Quality of life: What do they struggle to do because of this? Does it impact their daily life at all? How do they feel and function; assess sleep (sleep apnea)
Remedy: What have you tried in the past? Diets; supplements; Exercise; medications; what worked/didn’t. What did you find difficult about each? What worked best?
Setting: What was going on in your life around this time? Stress factors; social support network
Temporal pattern: Any patterns of weight gain? Seasonal? Over time? Over short periods? Triggers; stresses; What is their lightest and heaviest weight?
BMI values for >18 and how to calculate
Weight (kg) / Height (m2)
Underweight - <18.5 Healthy weight - 18.5-24.9 Overweight - 25-29.9 Obese - 30-34.9 Severely obese - 35 - 39.9 Morbidly obese - 40+
Metabolic syndrome and diagnostic criteria
Combination of Obesity; diabetes and HTN:
to diagnose need 3 or more of the following:
Waist circumference of 94cm or more in European men, or 90cm or more in South Asian men
Waist circumference of 80cm or more in European and South Asian women
High triglyceride levels (fat in the blood) and low levels of HDL (the “good” cholesterol) in your blood, which can lead to atherosclerosis
High blood pressure that’s consistently 140/90mmHg or higher
Inability to control blood sugar levels (insulin resistance)
Potassium
From diet
K+ rich foods: white beans, potatoes, parsnips, spinach, bananas, oranges, pineapples, apricots, leafy greens, lean meats, avocados, yogurt, coconut, water, beans and nuts
Important for cell function, digestion, heart rhythm, pH, nerve impulses, maintaining water balance and muscle contractions
Mostly intracellular stored in large reservoirs for cells to gain quickly
Extra K+ not needed is removed from blood via the kidneys
Hyperkalaemia values
Mild: 5.5-5.9mmol/L
Moderate: 6-6.4mmol/L
Severe: 6.5+ mmol/L
Hyperkalaemia causes
➤PSEUDOHYPERKALEMIA: haemolysis, prolonged transit time to lab or poor storage conditions, difficult venepuncture, marked leukocytosis
➤RENAL IMPAIRMENT: AKI/ CKD
➤ACIDOSIS
➤ADDISON’S DISEASE
➤ENDOGENOUS CAUSES: Tumour lysis syndrome, trauma, burns, rhabdomyolysis
➤DRUGS:
Potassium sparing diuretics:
Aldosterone antagonists: spironolactone
ACE inhibitors and angiotensin II receptor blockers
Potassium containing laxatives e.g. macrogol, fybogel
Hyperkalaemia presentation
Muscle cramps, paralysis, weakness Numbness, tingling SoB Nausea, vomiting Chest pain Palpitations Hypo-or a reflexia Irritability ECG changes
Hyperkalaemia ECG changes
always take ECG for all severities!!
Peaked T waves (5.5+ mild/moderate hyperkalaemia)
Progressive paralysis of atria: P waves wide and flattens; PR prolonged; P waves eventually hidden (6.5+severe hyperkalaemia)
Conduction abnormalities and bradycardia: wide QRS bizarre morphology; conduction blocks; sinus bradycardia; slow AF; sine wave (7+ severe)
Cardiac arrest: asystoles; VF; Pulseless electrical activity (PEA) with bizarre wide complex rhythm (9+ life threatening)
Hyperkalaemia management overview
Five key steps:
Protect the heart: Calcium gluconate/Calcium chloride
Shift K+ into cells: Insulin and glucose infusion and nebulised salbutamol
Remove K+ from body: Calcium resonium/haemodialysis
Monitor K+ and glucose: Serum levels using VBG
Prevent recurrence: Regular BP; prescribing and risk factors assessments and moitoring
Hyperkalaemia heart protection (step 1)
calcium gluconate/ calcium chloride
Reduced cardiomyocyte excitability to reduce chance of cardiac arrhythmia including VF
10 ml 10% calcium chloride (6.8 mmol Ca2+) IV over 5 - 10 minutes OR
30 ml 10% calcium gluconate (6.8 mmol Ca2+) IV over 15 minutes
Dose can be repeated after 5 - 10 minutes if hyperkalaemic ECG changes persist and repeated later as required for recurrence of ECG changes.
Calcium salts are irritant to veins – monitor injection site closely. Use large peripheral vein if a central venous access device is unavailable
Hyperkalaemia shift K+ intracellularly (step 2)
insulin and glucose infusion AND nebulised salbutamol:
Facilitates glucose uptake into cell which also results in K+ doing the same
Give 10units soluble insulin (eg actrapid) in 50ml glucose 50% over 15 mins with regular capillary blood glucose checks
Effective within 15-30mins
Duration of action 4-6hrs
NEBULISED SALBUTAMOL: Increases shift of extracellular potassium into intracellular space
Nebulised salbutamol (10 - 20mg) should only be used as an adjuvant therapy in severe hyperkalemia (K+ ≥ 6.5 mmol/L). It should be used with caution in patients with cardiovascular disease. The effect of salbutamol is dose-dependent. A further dose may be given if necessary.
Effective within: 30 - 60 minutes; max. effect should be seen 90 minutes after dose.
Duration of action: 4 - 6 hours
Hyperkalaemia: remove K+ from body (step 3)
calcium resonium/hemodialysis:
Not recommended in emergency treatment of severe hyperkalaemia (onset action within 4hrs)
Should be considered in pts with mild-mod hyperkalaemia. Use restricted to max 2 days and stopped once K+ normalalised
Oral: 15 g every 6 - 8 hours in a suspension of water or syrup in the ratio of 3 - 4 ml/ g of resin. Rectal: Add 30 g to 150 ml water or 10% dextrose. Enema should be retained for at least 9 hours then colon irrigated to remove resin Co-prescribe lactulose with oral resin to avoid constipation and the formation of bezoars which could perforate the gut.
Haemodialysis may be required to remove potassium in resistant cases, particularly in patients with acute kidney injury (AKI) or pre-existing chronic kidney disease.
Hyperkalaemia: monitor K+ and glucose (step 4)
Measure serum K+ at least 1, 2, 4, 6 and 24 hrs after treatment
Look for rebound hyperkalaemia after initial response
VBG used for monitoring
BG should be monitored at 0, 15, 30, 60, 90, 120, 180, 240, 300 and 360 mins for minimum of 6hrs after administration to check for hypo/hyperglycemia etc.
Hyperkalaemia preventing recurrence (step 5)
Regular blood monitoring for pts with CKD
Careful drug prescribing
Assess risk factors e.g. current medications and make new follow up plan for pt treatment
Hypokalaemia and values
Risk of re-entrant arrhythmias
Often associated with hypomagnesia; increases risk of malignant ventricular arrhythmias
Should always check Mg with K+ in any arrhythmia pt
Top up Mg to >1mmol/L and K+ to 4-4.5mmol/L to stabilise myocardium and protect against arrhythmias
Mild: 3.1-3.5mmol/L
Moderate: 2.6-3mmol/L
Severe: <2.5mmol/L
Hypokalaemia causes
Drugs: diuretics (particularly loop, thiazides and thiazide like such as indapamine and metolazone), mineralcorticoids (esp. fludrocortisone), B adrenergic mimetics, insulin, Drugs primarily causing hypomagnesaemia, including aminoglycosides, cisplatin, amphotercin B, Abusive use of laxatives
Nutritional status (anorexia nervosa, chronic alcoholism, vomiting/diarrhoea)
DKA
Urinary loss (Conn’s Syndrome, heart/liver failure, Cushing’s Syndrome)
Ectopic ACTH production
Hypokalaemia presentation
Weakness Fatigue Muscle cramps Constipation Palpitations ECG changes: K+ <2.7mmol/L: increased P wave amp and width; PR prolongation; T wave flattening/inversion; ST depression; prominent U waves in precordial leads; long QT interval (due to fusion of T and U waves)
Hypokalaemia management
always look at local guidelines:
Mild: give one or the other:
Sando-K dispersible tablets (contain 12mmols K+); 2 tablets OD.
Kay-Cee-L liquid (1mmol/ml K+) 20ml OD.
Moderate:
ORAL: SandoK: 2-3 tablets 3xdailys
Kay-Cee-L syrup 20ml 3xdaily
IV: 20-40mmol K+ replacement over 6-8hrs
Severe:
20-40mmol K+ IV max rate 20mmol/hr
Cardiac monitoring
Solutions with more than 30mmol K+ given via large vein
Infusion site should be checked every 4hrs for thrombophlebitis
Recheck K+ at regular intervals to prevent hyperkalaemia
Sodium
Mostly located in blood and fluid around cells
Helps maintain fluid balance
Plays key role in normal nerve and muscle function
Obtained via diet and lost primarily in sweat and urine
Healthy kidneys maintain Na level via excretion
Hypernatraemia causes
dehydration/fluid loss
Decreased thirst: with age thirst sensitivity decreases so aren’t as hydrated as needed
Changes to kidney: aging kidney may be less able to reabsorb water and electrolytes from urine resulting in greater water excretion
Less fluid in the body: in elderly the body contains less fluid. Only 45% body weight is fluid compared to 60% in younger people. This means a smaller fluid change in elderly can have more serious consequences than younger
Inability to obtain water: some elderly physical problems prevent them getting something to drink when thirsty such as dementia pts who depend on other people to give them water and remind them to drink etc.
Drugs: high BP drugs, DM or heart disorder drugs can increase excretion and magnify ill effects of fluid loss
Hypernatraemia investigations
➤ Serum Na >146mmol/L can be caused by reduced water intake (dehydration), or where water losses are greater than sodium losses (e.g. watery diarrhoea).
➤ There are no specific clinical features of hypernatraemia. It is usually diagnosed incidentally on serum testing. Also check other biochemical indices such as renal failure, hyperglycaemia and hypercalcaemia.
➤ Identify underlying cause of hypernatraemia. Consider measuring urine osmolality.
➤ Urine osmolality < plasma osmolality – look for diabetes insipidus
➤ Urine osmolality > plasma osmolality – look for osmotic diuresis / heatstroke, etc.
➤ If patient is also hypovolaemic, then monitor urinary output and renal function.
Hypernatraemia management
Replace missing water with oral water
Address underlying cause where possible e.g. gastro fluid loss, control pyrexia, correct hypergycemia, withhold lactulose and diuretics which may be sufficient to reverse hypernatraemia.
Where active correction is needed; fluids administered orally or enterally with IV as last resort
Regular monitoring of serum Na and water then adjusting hypotonic infusion accordingly
Hyponatraemia values
Mild: 130-134mmol/L
Moderate: 125-129
Severe: <125mmol/L
Hyponatraemia causes
Pulmonary cancers (SCLC; mesothelioma)
Gastrointestinal cancer (duodenum, pancreas and colon)
Other cancers (brain tumours; carcinoid tumours; ewing sarcoma; leukaemia; thyroma etc.)
Drugs (adenine arabinoside; cyclophosphamide; ifosfamide; methotrexate; antidepressants; antipsychotics; NSAIDs; anti-epileptics)
Iarogenic volume depleted +/- NBM with inappropriate hypotonic fluid
Hypovolaemic (hypotension, tachycardia, dry mucus membrane: GI loss; renal Na loss; hypoadrenalism; loop diuretics +/- ACEi; thiazide diuretics (elderly may be esp sensitive); cerebral salt wasting (e.g. after subarachnoid) hypothyroidism
Hypervolaemia - CCF, advanced liver disease, renal failure
Euvolaemia (SIADH)
Hyponatraemia presentation
Weakness, fatigue, anorexia, lethargy Nausea, vomiting Muscle cramps Headache Worsening mental status Irritability, agitation, confusion, disorientation Hallucinations Poor balance Seizures Coma
Hyponatraemia investigations
➤ Urea and electrolytes
➤ Serum osmolality: Readily differentiates between true hyponatraemia and pseudohyponatraemia (secondary to hyperlipidaemia or hyperproteinaemia) or may be hypertonic hyponatraemia associated with elevated glucose, mannitol, glycine (posturologic or postgynaecologic procedure), sucrose.
➤ Urine osmolality: Helps differentiate between impaired free-water excretion and primary polydipsia. In SIADH, >100mOsm/kg (submaximally dilute) indicates impaired ability of the kidneys to dilute the urine.
➤ Urine sodium In SIADH the urine sodium >20–40mEq/L. With hypovolaemia <25mEq/L
➤ TSH, serum cortisol - if hypothyroidism or hypoadrenalism is suspected
➤ LFTs and Lipids - high levels of hyperproteinaemia and hyperlipidaemia can cause pseudohyponatraemia
➤ CXR - ?underlying pulmonary cause of SIADH
➤ CT Head - cerebral oedema, R/O other causes of neurological status of pt
Hyponatraemia complications
Developing within 48hrs has high risk of permanent neurological sequelae as result of cerebral oedema unless plasma Na corrected
Pts with chronic hyponat. At risk of cerebral osmotic demyelination if correction is excessive or too rapid
Hyponatraemia ACUTE management
Acute hyponatremia: moderate symptoms:
Aim to raise Na by 1mmol/L each hr until symptoms resolve or serum Na >130mmol/L
DO NOT raise by more than 12mmol/L in first 12hrs
Consider giving furosemide to enhance free water loss
If pt has severe neurological symptoms; consider hypertonic (3%) NaCl as IV infusion at 1-2mL/kg/hr
Close monitoring esp for IV infusion preferably in HDU
Hyponatraemia CHRONIC management
Chronic hyponatraemia:
Water restriction to 1L/day if volume repleted
Investigate underlying cause
Demeclocycline may be useful for patients with SIADH secondary to malignancy. This drug takes 1–2 weeks to have an effect
Vasopressin-2 receptor antagonists – Tolvaptan (titrate starting at 15mg OD to 60mg OD, PO) Can also be used after Demeclocycline, if no improvement.
Pts to be treated with fluid restriction often require education regarding free water content of foods and explanation of need to limit intake of liquids to predetermined level
SIADH
The syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH) is defined by the hyponatraemia and hypo-osmolality resulting from inappropriate, continued secretion or action of the hormone despite normal or increased plasma volume, which results in impaired water excretion
SIADH causes
Primary brain injury (e.g. meningitis. subarachnoid haemorrhage)
Malignancy (e.g. small-cell lung cancer)
Drugs (e.g. carbamazepine, SSRIs, amitriptyline)
Infectious (e.g. atypical pneumonia, cerebral abscess)
Hypothyroidism
SIADH symptoms
vary depending on severity and rate of development: mild cases may cause significant symptoms if it develops acutely (fast) whereas chronic cases may be completely asymptomatic. This is thought to be from cerebral adaptation (compensatory process) where metabolism adapts to consistently lowered Na levels
Mild hyponatraemia: nausea, vomiting, headache, anorexia and lethargy.
Moderate hyponatraemia: muscle cramps, weakness, confusion and ataxia.
Severe hyponatraemia: drowsiness, seizures and coma.
SIADH investigations
Fluid status
Bloods: serum Na low; reduced plasma osmolarity; TFTs (potential hypothyroidism); serum cortisol to rule out Addison’s
U+Es: osmolarity; Na
CXR/chest CT to rule out SCLC etc.
SIADH diagnosis
Hyponatraemia with corresponding hypo-osmolality (plasma osmolality <280mosmol/kg
• Urine less than maximally dilute (greater than 100mOsm/kg, generally greater than 400–500mOsm/kg with normal renal function)
• Continued renal excretion of sodium (>40mmol/l)
• Absence of clinical evidence of volume depletion
• Absence of other causes of hyponatraemia
• Correction of hyponatraemia by fluid restriction
Magnesium
Carries electric charge when dissolved in body fluids
Majority is bound to proteins stored in bones so does not carry charge
Bone contains around 50% body’s Mg; blood contains very little
Mg needed for bone and teeth formation; nerve and muscle function; enzyme function; also related to metabolism of Ca2+ and K+
Level in blood depends largely on how Mg is obtained from foods and excreted in urine and stool and less to do with total body stores
Hypomagnesia
Under-diagnosed problem particularly as Mg is not routine biochem testing
Common in oncology pts receiving treatment as can be caused by no. of chemotherapies
Can also be caused by malabsorption, malnutrition, chronic alcoholism, uncontrolled DM, acute renal failure, diarrhea or fistulae and secondary to other electrolyte abnormalities (hyper/hypocalcaemia, hypokalaemia/TPN)
Often accompanied by low Ca and K levels so must check these along with renal function
If cause unclear order 24hr urinary Mg test
Hypomagnesia grading
grade 1: Lower limit normal - 0.5mmol/L grade 2: 0.5-0.4 grade 3: 0.4-0.3 grade 4: <0.3 grade 5: Death
Hypomagnesia presentation
CV: ventricular arrhythmias; SVTs: HTN: Digoxin toxicity
ECG changes: ST depression; altered T waves; reduced voltage; Prolonged PR interval and wide QRS complexes
Neuromuscular: Tetany; muscle cramps; convulsion; muscle fasciculation; carpopedal spasm; peripheral paraesthesia; weakness
Neurological: Confusion; psychosis; depression; agitation; ataxia; spasticity; Tremor; Delirium
Other: Nausea; vomiting; diarrhoea
Hypomagneisa management
(per stage):
Grade 1: No replacement needed; pts usually asymptomatic
Grade 2: 5g (20mmol) Mg sulfate (MgSO4) in 500ml normal saline over 6-8hrs. Oral Mg supplements may be tried (not well tolerated usually causes diarrhoea) Mg glycerophosphate 4-8mmol up to qds.
Grade 3 OR 4: risk of cardiac arrhythmias so also consider cardiac monitoring in severe cases.
5g (20mmol) MgSO4 in 1L normal saline over 8–10 hours.
Repeat daily for up to 3–5 days until serum magnesium normal.
If renal impairment: reduce dose to 2.5g (10mmol) MgSO4 over 24 hours. If hypocalcaemic, correct magnesium level until calcium in normal range.
If hypokalaemic, Replace 40mmol potassium chloride (KCl) and 1.25mg (5mmol) MgSO4 in 500ml normal saline over 6 hours and repeat for up to 24 hours, checking potassium and Mg levels regularly.
Hypomagnesia emergency management
Severe hypomagnesaemia with cardiac arrhythmias e.g. VT :
- 2g MgSO4 IV over 15 minutes (max rate 0.6mmol/minute).
- Followed by infusion of 5g (20mmol) MgSO4 in 1 normal saline for 3–5 days (see above).
- Rapid IV Mg therapy can cause hypocalcaemia, hypotension: this should only be undertaken in an emergency, with adequate acute medical support.
- Patients must be on a cardiac monitor and have regular assessment of all electrolytes.
Calcium
99% Ca stored in bones but cells (esp. muscle) and blood also contain Ca
Essential for bone and teeth formation; muscle contraction; normal enzyme; blood clotting and heart rhythm function
Body precisely controls Ca in cells and blood
Moves Ca out of bones into blood as needed to maintain steady Ca levels
If not enough dietary Ca consumed then too much Ca is mobilised frombones wekneing them which can result in osteoporosis
Need to consume around 1,000-1,500 milligrams Ca per day to prevent this weakening
Regulated by PTH and calcitonin mainly
Hypercalcaemia and values
Hypercalcaemia can be a presenting feature of serious disease, including malignancy; even when calcium is not raised to acutely dangerous levels, it is important to define the cause.
Mild: 2.65-3 (non-emergency)
Mod: 3-3.5 (possible emergency)
Severe: >3.5mmol/L (med emergency)
Hypercalcaemia causes
More than 90% cases are due to: ➤Primary hyperparathyroidism ➤Renal disease – tertiary hyperparathyroidism, treatment with vitamin D analogues. ➤Malignancy Less common causes of hypercalcaemia ➤Sarcoidosis ➤Vitamin D toxicity Other causes, including drugs e.g. lithium, thiazide
Hypercalcaemia management
➤Ensure dehydration is corrected with IV sodium chloride 0.9%
➤Withhold or discontinue all medications that may promote hypercalcaemia E.g. thiazides, vitamin D compounds, lithium
➤Do not give infusion fluids containing calcium (such as Hartman’s)
➤First-line treatment is with disodium pamidronate; see BNF/ guidelines
➤In all cases, infusion rate must not exceed 1 mg/minute and concentration must not exceed 30 mg/125 mls.
➤The maximum treatment course in all patients is 90 mg. Higher doses do not improve clinical response.
➤A significant decrease in serum calcium is generally observed 24 to 48 hours after administration of pamidronate disodium, and normalisation is usually achieved within 3 to 7 days.
➤If normocalcaemia is not achieved within this time, a further dose may be given. The duration of the response may vary from patient to patient, and treatment can be repeated whenever hypercalcaemia recurs.
➤Clinical experience to date suggests that pamidronate disodium may become less effective as the number of treatments increases.
Hypercalcaemia monitoring
Renal function: check serum creatine before each dose of pamidronate (Bisphosphonates have been associated with renal toxicity manifested as deterioration of renal function and potential renal failure. Renal deterioration, progression to renal failure and dialysis have been reported in patients after the initial dose or a single dose)
Serum calcium, phosphate and magnesium as hypocalcaemia, hypophosphataemia and hypomagnesaemia can occur.
Monitor blood pressure
Hypocalcaemia overview
➤ Mild hypocalcaemia is usually asymptomatic.
➤ Symptoms of hypocalcaemia generally correlate with the rate and magnitude
of calcium depletion. It has been suggested that patients are less likely to be
symptomatic if the serum calcium concentration has declined slowly.
➤ Treatment regimen MUST NOT rely on serum calcium level alone.
Hypocalcaemia causes
➤Septic shock ➤Rhabdomyolysis ➤Hypomagnesaemia ➤Pseudohypoparathyroidism ➤Malignant disease ➤Calcium malabsorption ➤Severe acute pancreatitis ➤Chronic renal insufficiency ➤Hypoparathyroidism ➤Post parathyroidectomy ➤Inadequate dietary calcium intake ➤Vitamin D deficiency ➤Massive blood transfusion ➤Drug-induced: including some anticonvulsants, bisphosphonates, calcitonin, phosphate, colchicine overdose, foscarnet, citrated blood transfusions, radio contrast dye, ketoconazole and some antineoplastic agents
Hypocalcaemia management
ORAL: asymptomatic; mild cases usually oral Ca supplement given at dose of 10-50mmol daily adjusted to pt needs. IV replacement not thought to be any added benefit in mild cases
Prescribe 2.2 to 4.5 mmol calcium gluconate as a slow intravenous injection over 5 to 10 minutes with ECG monitoring throughout the injection -THEN 22.5 mmol calcium (as gluconate) in 1 litre sodium chloride 0.9% administered at a rate of 50ml/hour
10ml/kg of the above described preparation is estimated to increase serum calcium concentrations by 0.3 - 0.5 mmol/L
always need ECG monitoring
Hypocalcaemia monitoring and points to consider
Monitoring:
U+Es
PTH and vit D before treatment
Mg: if hypocalaemia secondary to hypoMg; correction of Mg may lead to spontaneous normalisation of Ca after lag of 2 days
ECG monitoring
Infusion site monitored regularly to ensure extravasation has not occurred
Points to think about:
There is a risk of cardiac arrhythmias if the calcium is administered too quickly.
Some prefer calcium chloride to calcium gluconate for parenteral
Administration, because retention of calcium from the chloride salt is thought to be greater than from the gluconate salt, and results in a more predictable increase in extracellular ionised calcium concentration.
Calcium chloride is considered to be the most irritant of the calcium salts.
Available preparations: - calcium gluconate 10% in 10ml injection (equivalent to 2.25mmol Ca2+)
Fluids
Recommended intake for adults is 1.5-2.5L
Indications for fluids: patients whose needs cannot be met by oral or enteral routes. Where possible oral fluid intake should be maximised and IV fluid only used to supplement the deficit.
5 Rs for giving fluids
Resuscitation Routine maintenance Replacement Redistribution Reassessment
Fluid types
Bloods
Crystalloids: solutions of small molecules in water (e.g. sodium chloride, Hartmann’s, dextrose)
Colloids: solutions of larger organic molecules (e.g. albumin, Gelofusine)
Colloids are used less often than crystalloid solutions as they carry a risk of anaphylaxis and research has shown that crystalloids are superior in initial fluid resuscitation
K+ cannot exceed around 10-20ml fast delivery must be set via pump to accurately measure delivery rate to avoid harmful arrhythmias/effects on heart
Fluid resuscitation steps
Administer initial 500ml fluid bolus of crystalloid solution (eg saline or hartmans) over <15mins
Reassess pt status using ABCDE
Give further 250-500ml bolus if needed the reassess again
Can repeat process if ongoing clinical evidence suggests need to do so until up to 2000ml given total
Seek expert help if fluids still needed
Pts with comorbidities such as heart or renal failure should be much more cautions about giving fluids
If pt if normovolaemic but has signs of shock seek expert help immediately
Fluid maintenance calculation
25-30 ml/kg/day of water and
approximately 1 mmol/kg/day of potassium, sodium and chloride and
approximately 50-100 g/day of glucose to limit starvation ketosis (however note this will not address the patient’s nutritional needs)
Weight-based potassium prescriptions should be rounded to the nearest common fluids available. Potassium should NOT be manually added to fluids as this is dangerous.
Obese, elderly, HF, renal impaired, malnourished pts: adjust prescription to ideal body weight (lower range for volume per kg) as pts rarely need more than 3 L fluid per day
Patients with existing fluid or electrolyte abnormalities require a more tailored approach to fluid prescribing (see basic examples below):
Dehydration – will require more fluid than routine maintenance
Fluid overload – will require less fluid than routine maintenance
Hyperkalaemia – will require less potassium
Hypokalaemia – will require more potassium
Estimate any fluid or electrolyte deficits/excesses:
Add or subtract these estimates from the standard routine maintenance fluid regime discussed in the last section to provide a more tailored fluid prescription.
Hypocalcaemia signs and symptoms
confusion or memory loss.
numbness and tingling in the hands, feet, and face.
depression.
hallucinations.
weak and brittle nails.
easy fracturing of the bones.
Chvostek sign: contraction of facial muscles in response to facial nerve stimulation via tapping lightly anterior to the ear on zygomatic arch; indicates nerve hyperexcitability
Trousseau sign: caropopedal spasm caused by inflating BP cuff to level above systolic pressure for 3 mins. Hand curls inwards towards the body.
Carpopedal spasm: frequent and involuntary muscle contractions in hands and feet. Can cause a lot of pain
Seizures
Tetany: spasms in hands and feet; cramps; overactive neurological reflexes. Generally specific to low blood Ca
Fluid overload causes
HF
AKI
Higher risk in elderly and those with cardiac/renal impairment, sepsis, major injury/surgery
Increased ADH secretion
Excretion of excess Na and water is more difficult for injured or surgical pts (physiological response i injury and surgery affect renal function and therefore fluid balance
Congenital adrenal insufficiency
Primary adrenal insufficiency due to:
CAH—certain types, most commonly 21-hydroxylase deficiency, are associated with MC deficiency.
Congenital lipoid adrenal hyperplasia (CLAH) caused by mutations in the genes encoding steroidogenic acute regulatory protein (StAR), responsible for rapid import of cholesterol into the mitochondrion, and the side chain cleavage protein (CYP11A1), responsible for the conversion of cholesterol to pregnenolone, i.e. the first step of steroidogenesis.
Adrenal hypoplasia congenita (AHC) caused by mutations in the genes encoding the transcription factors SF-1 (NR5A1) and DAX-1 (NR0B1) that play a crucial role in adrenal development.
Adrenoleukodystrophy affecting 1/20,000 ♂; very long chain fatty acids (VLCFA) cannot be oxidized in peroxisomes and accumulate in tissues and the circulation. CNS symptoms may be absent initially, in particular, in the milder form adrenomyeloneuropathy, but progressive demyelination can lead to hypertonic tetraparesis, dementia, epilepsy, coma, or death (in particular, in the early childhood onset variant adrenoleukodystrophy).
Rare inherited disorders of aldosterone biosynthesis.
Pseudohypoaldosteronism—inherited resistance to the action of aldosterone. Autosomal dominant and recessive forms are described. Usually presents in infancy. Treated with sodium chloride.
Acquired adrenal insufficiency
All forms of non-congenital primary adrenal insufficiency the RAA system remains intact as the adrenal glands are anatomically intact
Drugs—heparin (heparin for >5 days may cause severe hyperkalaemia due to a toxic effect on the zona glomerulosa); ciclosporin.
Hyporeninaemic hypoaldosteronism—interference with the renin-angiotensin system leads to mineralocorticoid deficiency and hyperkalaemic acidosis (type IV renal tubular acidosis), e.g. diabetic nephropathy. Treatment is fludrocortisone and potassium restriction. ACEI may produce a similar biochemical picture, but here the PRA will be elevated, as there is no angiotensin II feedback on renin.
Fluid overload
Hypervolemia
Too much fluid in the blood; excess fluid (mostly Na and water) builds in the body resulting in weight gain
Leading cause if from CHF
Or caused by acute kidney injury
Can be iatrogenic from fluid administration
Fluid overload presentation
Limb swelling (peripheral oedema)
Ascites (fluid in abdomen)
Extreme generalised oedema/skin swelling (anasarca)
Pleural effusion
Fluid overload diagnosis and investigations
Diagnosed via exclusion of other conditions such as: Lung conditions; blood clots; infections; asthma Heart problems; pericarditis Venous circulation or lymphatic circulation problems Hypoproteinaemia Liver disease Thyroid disease Investigations: ECG CXR Bloods: infection; BNP (CHF) Urine output and drink intake
Fluid overload management
Diuretics (loop and thiazide)
Mineralocorticoids/aldosterone receptor antagonists MRAs (spironolactone and eplerenone
Dialysis may be needed for future
Prognosis depends on the underlying condition and how progressed this condition was before fluid overload occurred
Pheochromocytoma PCC
Tumour develops in chromaffin cells in centre of adrenal gland
These cells are responsible for release of adrenaline and noradrenaline so help control HR, BP and blood sugar
Extra-adrenal tumours (paragangliomas) are more rare and often found by aortic bifurcation
PCC causes
10% rule 10% >> extra-adrenal 10% >> bilateral 10% >> malignant 10% >> in children 10% >> familial 10% >> is part of MEN-2 10% >> makes Stroke 10% >> is discovered incidentally 10% >> is not associated with HTN
PCC presentation and triggers
Presentation: Classic triad: headache, sweating, tachycardia BP can be abnormally high or low Malignant HTN Multisystemic signs
Triggers: Straining Exercise Stress Abdominal pressure Surgery Beta blockers Tricyclics IV contrast agents
PCC history
Often vague
Cardiovascular: Tachycardia Palpitations Dyspnea Syncope Angina
CNS: Headache Visual disorders Dizziness Tremor Numbness
Psychological:
Anxiety
Confusion
Episodic psychosis
Gut:
D+V
Abdominal pain over tumor sites
Other: sweats/flushes Heat intolerance Pallor Backache
PCC investigations and treatment
Investigations:
24 hr urine samples for metanephrines/metadrenaline
Abdominal CT/MRI
MIBG scan
Treatment:
Surgery
primary Hyperaldosteronism overview
excess aldosterone production independent of RAA system causing increase Na and water retention and decreased renin release from kidneys. Consider if HTN, hypokalaemia, alkalosis in pt not on diuretics. Na tends to be raised mildly or normal
secondary hyperaldosteronism overview
Secondary: due to high renin from decreased renal perfusion eg renal artery stenosis, accelerated HTN, diuretics, CHF or hepatic failure
Bartter’s syndrome overview
major cause of congenital (autosomal recessive) salt wasting. Na and Cl leak out of loop of henle via channel transporter mutations. Presents in childhood as failure to thrive, polyuria, polydipsia, volume depletion from Na loss, increased renin and aldosterone production leading to hypokalaemia and metabolic acidosis. Treated by replacing K+, NSAIDs to inhibit prostaglandins and ACEi
Gynaecomastia
Present in at least ⅓ rd of men in course of their lifetime
60-90% neonates
50-60% adolescents
70% men aged 50-69
Breast cancer only detected in 1% of cases of male breast enlargement
Pathophysiology:
Oestrogen stimulates breast tissue growth while androgens inhibit growth
The ratio of androgens to oestrogens determines overall growth
Oestrogen levels can be enhanced by testosterone reduction of production/action
Once this ratio falls, breast tissue growth is stimulated, leading to proliferation of breast ducts and fibroblastic stroma. If this stimulus continues then ducts and fibroblastic stroma replaced by fibrosis and gynaecomastia becomes well established and irreversible
PSEUDOGYNAECOMASTIA: build up of adipose tissue not breast tissue
Gynaecomastia causes
Conditions lowered testosterone: such as congenital absence of testes causing severe gynaecomastia. Androgen resistance. Klinefleter’s syndrome (XXY) associated with 80% cases (show increased risk of breast cancer), viral orchitis, trauma, castration or renal disease and dialysis
Conditions increasing oestrogen: testicular tumours (secreting oestradiol); hermaphroditism; neoplasms producing hCG increasing oestradiol secretion; adrenal tumours; liver disease or cirrhosis (increased aromatisation); malnourishment and re-feeding syndrome; hyperthyroidism; obesity; extreme stress; aromatase excess syndrome
Conditions affectsing sex hormone binding globulin (SHBG); liver disease and cirrhosis cause rise in SHBG
Conditions causing androgen resistance
Conditions causing increased conversion of testosterone to oestrogen (aromatase is one of the P450 enzymes involved in aromatisation of androgens to oestrogens. Found in many tissues such as adipose; enhanced adipose tissue in obesity increases this enzyme level and hence oestrogen production leading to gynaecomastia
NEWBORNS: result of maternal oestrogens and will resolve after few weeks
ADOLESCENCE: common around age 14; may be unilateral and tender. Resolves spontaneously within 1-2 years; may be due to relatively delayed testosterone surge with relation to oestrogen at puberty or temporary increase in aromatase activity
INCREASING AGE: associated with low testosterone levels
Medication accounts for up to 25% all cases in adult males: herbal remedies and cosmetics containing oestrogen; DIGOXIN (enhanced if liver derangement also exists); GnRH agonists; testosterone inhibitors; excessive testosterone replacement therapy; antiretrovirals; CCB; ACEi etc.
IDIOPATHIC
Gynaecomastia symptoms
Commonly asymptomatic
Breast enlargement
Tenderness of breast
Sexual dysfunction
Lack of testosterone: Hairless; shiny skin; testicular size; masses; tenor of voice
Signs of cushing’s or hyperthyroidism
Check medical history for drugs or abuse of drugs such as anabolic steroids, alcohol, heroin and marijuana
Past medical history and family history
Gynaecomastia investigations
Clinical exam to determine if breast tissue is enlarged: pinch breast tissue between finger and thumb: true breast tissue proliferation felt as distinct ‘disc’ of tissue under skin; if not is probably psuedogynaecomastia
Ultrasound or mammography to confirm if unsure
Assess size and asymmetry
LFTs; renal function tests; TFTs; hormone profile (oestradiol, testosterone, prolactin, beta-hCG, alpha fetoprotein AFP, LH) high LG and low testosterone indicated testicular failure, low LH and testosterone = increased oestrogens, high LH and testosterone = androgen resistance or neoplasms secreting GnRH
Chromosomal karyotyping: XXY syndromes
Ultrasounds
Mammography
CXR suspected lung lesions
Needle core biopsy for definitive diagnosis
Gynaecomastia red flags for breast cancer/general breast lumps
Unilateral enlargement hard/ irregular breast tissue Rapid enlargement Recent onset Fixed mass Nipple or skin abnormalities Painful >5cm large Axillary lymphadenopathy
Gynaecomastia management and prognosis
Management:
Refer if any red flag symptoms are present
Treat underlying cause if found; medication alterations etc.
Reassurance and pt. Education
Tamoxifen for pain relief and side effects (anti-oestrogen)
Prophylactic breast irradiation in cases of prostatic carcinoma as gynaecomastia is common reason for poor treatment adherence
Prognosis:
Mostly benign
Complete resolution can occur if underlying cause identified and treated before fibrosis occurs
Galactorrhea
More common in women than men at reproductive age
Can occur in nulliparous, menopausal woman and men
Can be physiological in women but only pathological in men
Cause:
Most commonly from hyperprolactinaemia
Galactorrhoea causes
Physiological:
pregnancy and post-lactation: women may lactate from second trimester and continue until up to two years after stopping breastfeeding;
fluctuating hormonal levels during menopause may cause this;
neonatal (exposure to maternal hormones in-utero can produce gynaecomastia and galactorrhea in newborn; will resolve spontaneously);
nipple stimulation or suckling
Pathological:
Idiopathic hyperprolactinaemia
Prolactinomas
Addison’s disease
Acromegaly
Cushing’s
Metastatic tumours
TB and other infections
Sarcoidosis
Histiocytosis
Drugs increasing PRL: antipsychotics; antidepressants; antihypertensives; contraceptives (combined pill and depot contraceptives); elicit drugs (cannabis, opiates and amfetamines); DIGOXIN
Chronic kidney disease; liver failure; hypothyroidism; epileptic seizures
Breast surgery; burns; herpes zoster; spinal cord injury; trauma
Galactorrhea history taking
Lactation: ask about duration, nature, colour, amount of fluid
Unilateral or bilateral discharge (uni suggests local pathology and needs breast clinic referral)
Spontaneous or expressed?
Check medications; prescribed; OTC; elicit?
Acne; menstrual irregularity; reduced libido; erectile dysfunction; infertility?
Thyroid and endocrine symptoms
Headaches; visual symptoms and cranial nerve symptoms (pituitary symptoms)
Galactorrhea investigations
Clinical exam: thyroid exam, neurological exam; abdo exam for pregnancy; breast examination (discharge; previous breast surgery; palpate lumps and nodes)
Bloods: PRL levels, TFTs, renal and LFTs; pregnancy test if needed
Visual field tests
MRI
Galactorrhea management
Exclude serious pathologies
Identify cause and treat if possible
Complications depend on underlying cause
Lactose intolerance
Result of enzyme lactase deficiency
Lactose allergy is Ig-E mediated reaction
Lactose is found exclusively in milk and it’s absorption is dependent on enzyme lactase
Essential enzyme in babies but level of enzyme tends to decrease after age 2 although symptoms of intolerance rarely occur before age 6
It’s argued that the enzyme only persists to adulthood because of our habit of drinking other species milk
Symptoms arise from reduced absorption of lactose which is broken down by intestinal bacteria leading to gas and short chain fatty acids
Lactose intolerance types
Primary: autosomal recessive condition develops with age aka lactase nonpersistence
Secondary: follows damage to intestinal mucosa eg bacterial or viral gastroenteritis. Resolves when the disease process is over. More common in children esp. In developing countries
Congenital: extremely rare autosomal recessive disorder associated with minimal or complete absence of lactase activity
Developmental: occurs in premature babies and improves as intestines mature
Lactose intolerance presentation
Bloating Flatulence Abdominal discomfort Loose watery stool; diarrhoea Perianal itching (acidic stool)] Occur 1-several hrs post eating
Lactose intolerance investigations
Clinical features: cut out then re-introduce lactose and observe reactions
Strict 2 week no lactose diet if symptoms resolve but recur on re-introduction then diagnosis made
Lactose intolerance test
Breath hydrogen test
Genetics test
Intestinal mucosal biopsy
Lactose intolerance differentials
IBS Milk protein allergy Infantile colic Diverticular disease Ulcerative colitis Coeliac disease CF
Lactose intolerance management
Avoid milk and dairy products
Ca supplements PRN
Primary: can often tolerate certain dairy’s
Secondary may need fluid resuscitation, should avoid antibiotics
Developmental: tube feeding containing reduced lactose milk or breast milk (lactase enzymes present)
Congenital: diet full of essential nutrients excluding lactose; lactose free formula milk (NOT BREAST); wean on lactose free foods
Hyperlipidaemia
Cholesterol carried in blood via lipoproteins
LDL = bad cholesterol increase fatty deposits in arteries leading to athlerosclerotic plaque formation
HDL = good cholesterol increase removal of these deposits and reduce atherosclerosis formation
Total cholesterol normal value 5mmol/L or less
LDL <3mmol/L
HDL >1.2mmol/L
Total cholesterol/HDL ratio 4.5 or less
Severe hypertriglyceridemia TGs = >10mmol/L
Hyperlipidaemia causes
Hypothyroidism Obstructive jaundice Cushing’s syndrome Anorexia nervosa Nephrotic syndrome CKD Familial dyslipidaemias Familial hypercholesterolaemia Apoprotein disorders Pregnancy Obesity Alcohol abuse Medications: thiazides, steroids, cyclosporin (after organ transplants), antiviral therapy, beta blockers, combined oral contraceptive pill etc.
Hyperlipidaemia risk factors
Family history Smoking Lack of physical activity Obesity Poor diet high in LDLs; excessive salt Excess alcohol HTN High triglycerides Diabetes Kidney function diseases Male Early menopause Increasing age Ethnicity: indian, pakistan, bangladesh or Sri lanka
Hyperlipidaemia presentations
Usually discovered during routine bloods screening when assessing QRISK
Fasting blood test (12hrs)
Premature arcus senilis (white/grey ring in front of eyes)
Tendon xanthomata (hard nodules on tendons of knuckles and achilles
Xanthelasma (fatty deposits in eye)
Hyperlipidaemia investigations
Total lipid profile, TGs, LDL, HDL, total lipid/HDL ratio
Fasting blood glucose
Familial history: DNA testing
TFTs; renal function tests; LFTs; pregnancy tests to exclude secondary causes
QRISK
Hyperlipidaemia management and referral guidelines
Lifestyle advice and changes: smoking cessation, healthy diet, increased exercise
Medications: statins
Referrals:
If need confirmation of familial diagnosis (DNA testing)
Diagnosed with familial hypercholesterolaemia with LDL-C conc >13mmol/L or possible signs of CHD (urgent referral unless life threatening in which case refer as emergency)
If signs of failure of therapy
Severe cases Tchol >10 or TGs >10mmol/L
Metabolic acidosis
Arterial pH <7.35 with plasma bicarbonate <22
Respiratory compensation normally takes effect immediately unless there is a respiratory pathology
Calculate expected pCO2 compensation: pCO2 = (1.5 x [HCO3-])+8+/-2
Metabolic acidosis causes
Lactic acidosis (HF, drugs, toxins, inborn errors of metabolism
DKA
Starvation
Excessive alcohol
Substance poisoning
Impaired acid excretion: renal failure; hyperaldosteronism; impaired H+ excretion
Excessive renal bicarb loss: carbonic anhydrase inhibitors
Excessive loss of GI bicarb: diarrhoea; faitulae of pancreas, biliary tree or intestine; urinary-GI diversion surgery; cholestyramine
Metabolic acidosis presentation
Nausea Vomiting Anorexia Increased respiratory rate; tachyponea Dyspnoea Varying non-specific symptoms: lethargy Hypotension Signs of underlying cause
Metabolic acidosis investigations
ABGs U+Es: anion gap; ketones LFTs ECG CXR for infection/cardiac failure Specific Ix for specific cause eg toxicity tests
Metabolic acidosis management
Transfer to HDU for monitoring
ECG, O2 sats, BP and HR
Intubation or ventilation PRN
Large bore IV access for rehydration
Treat underlying cause (drug toxicity etc)
Only use bicarb infusion in cases of drug poisoning (can be fatal!)
Respiratory acidosis
Lungs cannot remove enough CO2 from the body
pH <7.35
Typically caused by underlying disease or condition (COPD, asthma, pneumonia, sleep apnea, obesity, scoliosis)
Acute and chronic forms
Acute: occurs quickly and is medical emergency; can be life threatening if untreated
Chronic: develops over time. Does not cause symptoms and body adapts to acidity (metabolic compensation from kidneys producing more bicarb to maintain blood pH) can be exacerbated to cause acute acidosis
Resp. acidosis symptoms
Headache Anxiety Blurred vision Restlessness Confusion Fatigue Lethargy Delirium or confusion SoB Coma Sleep disturbances Personality changes Memory loss
Resp. acidosis diagnosis and management
ABGs Electrolytes Lung FTs: underlying conditions CXR Management: Acute and chronic both mainly require treatment of underlying conditions causing this
Metabolic alkalosis
pH >7.45
Caused by increased bicarb ions or too few H+ ions
Two kinds: chloride responsive alkalosis (loss of H+ ions usually vomiting or dehydration) and chloride resistant (too many bicarb ions or when H+ shift into cells from blood)
Respiratory acidosis takes effect quickly to partially or fully compensate while kidneys try to correct metabolic alkalosis
Metabolic alkalosis causes
Loss of stomach acids: vomiting, suction
Excess antacids: if weak or failing kidneys
Diuretics: increase H+ excretion
Hypokalaemia
Reduced blood volume; liver cirrhosis or weakened heart
Genetic causes: Bartter’s syndrome
Metabolic alkalosis symptoms
Vomiting Peripheral oedema Fatigue Diarrhea Agitation Disorientation or confusion Seizures Coma
Metabolic alkalosis diagnosis
ABGs Medical history (of vomiting etc.) U+Es Vitals: sats; HR; BP Can also present with hypochloremia which can cause pt to go into shock; however is also treated with saline IV**
Metabolic alkalosis management
Chloride responsive: adjust diet to increase salt (NaCl) to increase blood acidity
IV saline NaCl solution
Chlorine resistant: depleted K+ levels; take potassium chloride pills 2-4xdaily to increase K+
K+ given by IV PRN
Respiratory alkalosis and causes
Too little CO2 within the lung Occurs with hyperventilation (blowing off CO2) pH >7.45 Causes: Heart attack Anxiety Pain Drug use Fever COPD Infection PE Pregnancy
Respiratory symptoms
Dizzy Bloating Numbness and muscle spasms in hands and feet Chest discomfort Dry mouth Tingling arms Heart palpitations SoB Confusion
Resp. alkalosis diagnosis
ABGs
Medical history
Clinical presentation
Resp. alkalosis management
Depends on underlying cause: find and treat
Panic and anxiety related causes: breathing into paper bag increases inhalation of CO2 and should correct CO2 levels. Can also breathe in via pursed lips to restrict oxygen intake
TFTs results and diagnosis
thyrotoxicosis - TSH low; high T3/4
Primary hypothyroidism: High TSH with low T3/4
Secondary hypothyroidism: Low TSH with low T3/4
Subclinical hypothyroidism: TSH slightly raised but below 10; normal T3/4
Hyperthyroidism: low TSH high T3/4
T3 toxicosis: Low TSH; normal T4 and high T3
Hypercalaemia presentation
bones, stones, groans and moans High serum Ca Bone pain Kidney stones more likely Abdominal pain Psychiatric symptoms: mood changes etc.
Target HbA1c for type 2 diabetics
measure 3-6 monthly:
- adults using diet and lifestyle or on ONE drug (not associated with hypoglycaemia eg metformin) target 48mmol
adults on drug associated with hypoglycaemia (gliclazide) target is 53mmol
do not use aggressive techniques in elderly or frail
BP guide 130/80
cholesterol - total <3 (QRISK >10% start atorvastatin 20mg)
how to prescribe metformin
Start with standard release, can switch to modified release if patient has side effects can use modified release
Review renal profile; eGFR must be >30 use with caution if around this level
Start with 500mg WITH BREAKFAST and increase on weekly basis by 500mg until max dose 2g reached or max tolerated dose
Make sure patient takes food with it to minimise side effects
Pros:
- effective
- cheap
- does not cause hypo
Cons:
- large tablets difficult to swallow
- common to cause GI upset - wind, blasting, diarrhoea (severe and sudden very often)
DPP4 (glisten) vs sulphonurea
DPP4:
- no hypo
- modest effects on hba1c
- not as much long term data
- well tolerated
- stigagliptin 100mg OD
SU:
- hypo risk
- effective
- causes weight gain
- can induce beta cell failure at faster rate
- used for many years
- initially 40mg OD increased to max 160mg
- educate pt on home testing
Important patient education for diabetics with hypo risk drugs
When educating patients on hypoglycaemia as side effects of drugs - warn to always TEST BG before assuming hypo as might just be them adjusting to normal BG levels as a result of medications instead!! Warn it may take some time for them to adjust, to new levels of BG but not necessarily a hypo attack
type 1 diabetes pathology
Failure of pancreatic Islet of Langerhans cells to produce enough insulin
Either produce too little or none at all
Leads to failure of glucose uptake into cells (mostly into storage of the liver - glycogen)
Increased blood glucose levels leads to long term complications with eyes, kidneys, neuropathy, risk of stroke and MI etc.
Short term complication is patient is likely to enter starvation state due to lack of cellular energy, can enter DKA and deteriorate rapidly
