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
