Deck 3 Flashcards
Anterior pituitary secretes
GH (GHRH) - Measure by IGF-1. Growth, glucose, FFA
TSH (TRH) - >basal met rate
ACTH (CRH)
FSH (follicular growth/spermatogenesis - GnRH)
LH (testosterone/progesterone - GnRH)
Prolactin (dopamine inhibits)
Posterior pituitary scretes
Vasopressin (ADP - released if ECF hyperosmolarity. Acts on CD and arteriolar smooth muscle)
Oxytocin
Macroadenoma
Pituitary adenoma >10mm.
Causes local effects (headache, bitemooral heminaopia, diplopia, disconnection prolactinaemia, pituitary apoplexy, hydrocephlus (3rd ventricle compression), sphenoid sinus invasion (CSF rhinorrhoea), hypothalamous compression (altered appetite, thirst, sleep cycle)
Can also cause systemic effects (hyperprolactinaemia (galactorrhoea, amenorrhoea, hypogonadism), acromegaly, Cushings.
Can also hypopituitarism (ACTH loss gives addisons symptoms, gonadotrophin loss causes lethargy, libido loss, hair loss, ED, infertility, amenorrhoea. GH loss gives lethargy. TSH loss gives hypothyroid symptoms. Vasopressin loss gives diabetes insipidus)
Microadenoma
Unlikely to cause local effects, often secreting hormones (or rarely causing hypopituitarism)
Pituitary tumour
May be associated with MEN1 (tumours of PT gland, endocrine GI tumours)
Classed by size, function and histology
Chromophobes (70%) secrete prolactin or non-functional. 30% have local pressure effects
Acidophils (15%) secrete GH or prolactin. 10% local pressure
Basophils (15%) tend to secrete ACTH - rarely cause local pressure issue
Hyperprolactinaemia
Galactorrhoea, oligo/amenorrhoea, decreased libido, subfertility, arrested puberty.
Long term, can give osteoporosis.
Distinguish from drug induced, idiopathic or stress. Diagnose by MRI and raised serum prolactin
Acromegaly
Almost always pit tumour in adults, but can be rare paraneoplastic tumour secretion.
Diagnose by raised IGF-1 (gives 24h GH correlation) and OGTT (>2mcg/mL GH at 2h)
Growth symptoms, headaches, diabetes, interdental separation, large tongue, HTN, excessive sweating, tiredness
Cushings (exogenous)
Exogenous is more common.
Can also be Adrenal adenoma (5-10%, carney complex (syndrome with cardiac myxoma) and micronodular adrenal dysplasia (very rare)
Endogenous cushings
80% are cushing’s disease (pituitary tumour) 5-10% are ectopic ACTH (small cell lung cancer is most common)
Pseudocushing’s
Mimic’s cushings. Often due to alcohol excess or severe depression. Causes FP dex suppression test and raised 24h urine cortisol. Distinguish with insulin stress test
Note that alcohol excess can give cushingoid appearnace
Cushing’s S+S
Central weight gain, depression, insomnia, poor libido, thin skin/easy bruising, hirsutism, acne, diabetes symptoms, moon face, frontal balding, striae, HTN, pathological fractures, dorsal fat pad, proximal myopathy.
Predisposes to CVD, diabetes and osteoporosis
Cushing diagnosis
Overnight dex suppresion test (1mg at midnight)
48h dex suppresion test
24h urinary cortisol
Midnight cortisol
Plasma ACTH (if N/D, adrenal cause liekly and CT needed)
In high ACTH, try high dose dexa suppression (will reduce if pituitary, but not in ectopic secretion).
Note that if ACTH or CRH is high then Cushing’s disease, otherwise syndrome
Adrenal gland
Cortex has: Zona glomerulosa (aldosterone) Zona Fasicula (cortisol and some sex hormones) Zona reticularis (testosterone and some cortisol)
Medulla secretes catecholamines (Adrenaline is alpha (vasoconstriction) and beta (tachycardia, insulin resistance and skeletal muscle vasodilation) agonist. NA is alpha)
Conns
More common in young females
Primary is adrenal hyperplasia or adrenal adenoma
Secondary is RAAS overactivation in renal artery stenosis or JGA tumour
HTN, muscle weakness/cramps, paraesthesia, polyuria, headaches.
Hypernatraemia, hypokalaemia, alkalaemia (met alkalosis), acidic urine, raised aldosterone:renin ratio
Addison’s definition and causes
Primary andrenocortisol insufficiency
80% in UK are autoimmune, TB is most common cause worldwide
Can also be adrenal met (lymphoma).
Secondary adrenocortisol insufficiency
Not addisons.
Occurs in steroids withdrawal or pituitary apoplexy with reduced ACTH release)
Note will not see hyperpigmentation in this case
Addison’s signs and symptoms
Fatigue, muscle weakness, anorexia, weight loss, diarrhoea, N&V, hyperpigmentation, depression/irritability, myalgia, arthalgia, postural hypotension, faints, loss of body hair.
Crisis is abdo pain, vomiting, shock and coma.
Addison’s biochemistry
Hyperkalaemia (cardiac arrythmia risk), hyponatraemia, high ACTH, low cortisol, 21 hydroxylase adrenal autoantibodies, CXR for TB, adrenal CT
Addison’s management
fludrocortisone for aldosterone, hydroxycortisol.
21 alpha hydroxylase deficiency
congenital adrenal hyperplasia. Enzyme needed for cortisol and aldosterone, but not sex hormones so see hypergonadism and raised 17 alpha hydroxyprogesterone levels
phaeochromocytoma
Chromaffin tumour.
Secretes catocholaemines. Can be in medulla or ectopid (e.g. abdominal).
10% malignant, 10% extra adrenal, 10% bilateral, 10% familial (MEN2a/2b, neurofibromatosis, von Hippel Lindau syndrome)
Causes headache, diaphoresis, tachycardia, episodic severe HTN, orthostatic HTN, heat intolerance.
Gives arrythmias/MI, tremor
Horner’s syndrome, tremor, CNS haemorrhage
Diarrhoea, vomiting, abdominal pain
Hyperglycaemia
Sweating, flushing, heat intolerance
Pallor
Symptoms can be worsened by stress, exercise, drugs (beta blockers without alpha blockade causes massive HTN)
See raised metadrenaline in plasma and urine, raised WCC
Surigcally managed
DM definition
Metabolic disorder with hyperglycaemia in the absence of treatment
Insulin inhibitors
alpha adrenergics, beta blockers and adrenaline
T1DM
Autoimmune
Associated with PA, addison’s, autoimmune thyroid diseases
Typical features are 2-6 week polyuria, polydipsia and weight loss
T2DM
metabolic state
Pancreatic insulin insufficiency and insulin resistance.
Strong hereditary factor.
Associated with hyperlipidaemia, obesity, sleep apnoea, and CVD
Longer onset, polydipisa/polyuria/weight loss may be present, but more commonly see fatigue, visual blurring, pruritis vulvae/balanitis.
mAY FIRST PRESENT WITH COMPLICATIONS
mody
Autosomal dominant diabetes
Defective beta cells
May or may not need insulin
Mimics T2DM, usually <25years
Other diabetes mellitus conditions
Type A insulin resistance
Rabson Menderhall syndrome
Down syndrome
Leprechainism/donohue syndrome
Secondary diabetes causes
Pancreatic disease, endocrinopathies (Acromegaly, Cushing's, phaeochromocytoma) Drug induced (steroids, thiazide, beta blockers) Infections (congenital rubella, CMV, mumps), Gestational
Glucose homeostasis
Insulin allows glucose uptake and promotes glycolysis (glucose to ATP) and reduces gluconeogenesis.
Acts on GLUT
Glucagon promotes gluconeogenesis and glucose release
GLUT2
beta cell sensing
GLUT4
skeletal muscle/adipose tissue uptake
DKA
Dehydration, elevated FFA with acidosis.
Compensatory hyperventilation
and vomiting
Renal perfusion falls, reduced acid and ketone secretion. Get gastric ileus.
Hyponatraemia, and hyperkalaemia (but may get pseudohyperkalaemia as it exhanges out of the cell)
Can be precipitated by MI or infection.
Acidosis, reduced bicarb <15), ketosis
Give fluids, ACTRAPID insulin.
If K <5.4 then 40mmol/L
If <3.4 then critical care.
Can give glucose (10% at 125mL/hour) once glucose <14
HONK/HSS
More insidious.
Can occur in glucose consumption, thiazide diuretics, steroids, beta blockers, infection/MI
Hypovolaemia, hyperglycaemia (>30), no significant ketonaemia, no significant acidosis, osmolarity >320 (2Na+glucose +urea)
May get hypernatraemia, may get mild lactic acidosis.
High thrombosis risk
Hypoglycaemia
<3mmol/L
Sweating, anxiety, hunger, trmor, palpitations, neuroglycopoenic (confusion, drowsiness, seizures)
Alpha pancreas cells can become insensitive. Can also be due to too much insulin, or depletion of hepatic glycogen (malnutrition, alcohol, liver failure).
Give 10-20g of fast acting carb if able to swallow, otherwise glucagon and 100mL 20% dlucose.
Diabetes complications
Macrovascular (Cardio/cerebrovascular disease, Peripheral arterial disease)
Microvascular:
Retinopathy, nephropathy, sensorimotor issues, peripheral neuropathy
Diabetic foot
Combination of micro and macro vascular problems, leading to peripheral neuropathy , ulcers, rocker bottom foot and infections
Diabetic neuropathy
Sensory neuropathy (loss of protection against minor injury) Autonomic neuropathy (lack of sweating - dry fissured skin allowing bacterial entry) Motor neuropathy - msall muscle wasting gives loss of arches and abnormal pressure areas
Tend to get stabbing pains in feet but still has warmth and colour (in contrast to PAD)
Impact of diabetes mentally etc
Diabulaemia (avoid insulin to avoid weight gain)
Lipohypertrophy (repeated finger prick and insulin injections)
DVLA notified if insulin or hypoglycaemia inducing meds, or have reduce hypo awareness
Must inform if 2 hypos in 12 months
Diabetic retinopathy
Can be NPDR - asymptomatic. Often see aneurysms, exudates, haemorrhages and cotton wool spots.
pDR is new vessel growth due to ischaemia, but new vessels are fragile and bleed (pre-retinal or vitreous haemorrhage). Can cause fibrosis or retinal detachment.
Diabetic maculopathy
Blurs vision.
Other diabetic eye problems
Cataracts and open angle glaucoma.
Diabetic nephropathy
microalbuminaemia - needs ACEi
Diabetic sensorimotor
May involve vagus, gastroparesis, ED, Horner’s urinary retention, postural hypotension
Normal blood sugar
Fasting 6.0 or less
Random (/OGTT) 7.7 or less
HbA1c is <42
Prediabetes
Hba1c 42-47
OGTT 7.8-11 (impaired tolerance)
Fasting glucose 6.1-.6.9 (impaired fasting)
Diabetes
Hba1c 48+ OGTT 11.1 Random 11.1 Fasting glucose 7.0 Need 1 result + symptoms, or 2 results asymptomatic
HbA1c aims (insulin and none)
38 initialy, 53 is on insulin or hypoglycaemia inducing medication
BP control in diabetes
<140/80, or <130/80 if kidney, eye or cerebrovascular involvement
Calcium balance
Hypercalcaemia more common than hypcalcaemia
Calcium is albumin bound, so corrected calcium accounts for albumin level
Acidosis increases free calcium by reducing binding.
Alkalosis increases binding
Calcium homeostasis
Hypocalcaemia stimulates PTH, causing bone reabsorption, phosphate excretion, renal hydroxylation of 25HCC (1:25 DHCC) to promote calcium reabsorption in small intestine.
Hypercalcaemia feeds back to Pt gland, renal 1 alpha hydroylase, C cells of thyroid (calcitonin) -> stimulates osteoblast, reduces osteoclast, decreases renal calcium absorption
Calcitonin
Transient effects. Excess or deficiency have no significant effects
Calcium required for
Nerve/muscle activation, clotting, complement, bone
PTH
From parathyroid gland
Has calcium and vitamin D receptor. Secretes in response to hypocalcaemia, hyperphosphatemia and low vitamin D
Ergocalciferol
D2 in plants and fungi. Vegan.
Cholecalciferol
D3. From cholesterol. Converted to cholecaciferol by UV
Active vitamin D
Cholecalciferol hydroxylased in liver (25HCC) - caldidiol then 1 alpha hydroxylase in kidney converts to 1:25 DHCC.
This is calcitriol
Hypercalcaemia S+S
Mild is asymptomatic.
Bones (pain, fracture, limb weakness), stones (renal stones, polyuria, AKI/CKD), abdominal moan (pain, vomiting, constipation, pancreatitis, GI ulcer) and psychiatric groans (depression, confusion, tiredness, hypotonicity)
Can see chondrocalcinosis (calcium on hyaline cartilage and corneas)
“brown tumour” - > vascular lytic bone lesion in hyperparathyroidism (brown colour from haemosiderin).
ECG can give short QT (can lead to CA)
Hypercalcaemia causes
PTH excess (often primary if benign adenoma, or diffuse hyperplasia of all 4 glands)
Malignancy (second most common cause)
Vitamin D excess (iatrogenic, supplements, granulomatous disease (sarcoidosis/TB) or lymphoma
Excessive calcium intake
Drug induce (lithium, thiazides)
MEN1 or 2b
Tertiary hyperparathyroidism (seen in CKD/vit deficiency - get phosphate and calcium rise)
Malignant causes of hypercalcaemia
(second most common cause, seee low PTH). Common tumours are myeloma, mets from breast/prostate, lytic bone lesions from tumour osteoclastic factor, ectopic production (lung SCC, oesophagus, head/neck, renal cell, ovarian and bladder cancers)
Hypocalcaemia S+S
Can be false due to low albumin and non correct lab value
Often asymptomatic, but abrupt change can produce symptoms
Neuromuscular (tetany, cramps, Chvostek sign, tingling)
Bradycardia, arrythmias, prolonged QT, hypotension
CNS disturbance (confusion, seizures, irritation)
Carpo-pedal spasm (Trosseau’s sign - wrist flex and finger tips tog. esp with brachial artery occlusion)
Hypocalcaemia causes
Autoimmune
Increased phosphate (CKD, phosphate therapy, rhabydomyolysis, tumour lysis)
Hypoparathyroidism (removal of gland, congenital gland defect (e.g. Digeorge), severe hypomagnesaemia
Vitamin D deficiency
Gut problem
Osteomalacia/rickets
Drug induced (calcium chelators, citrate in blood transfusion, bisphosphonates, phenytoin, ketoconazole)
Acute pancreatitis
Acute rhabdomyolysis
Tumour lysis (post chemo)
Investigating hypocalcaemia
Rule out low albumin Measure vitamin D (if deficient then will have raised PTH) Measure PTH (low in surgical removal autoimmune damage or tumour infiltration). Consider calcium comsumption (including precipitation into tissues in pancreatitis, bone consumption during malignancy)
Technetium 99 isotope is taken up by parathyroid gland and show adenoma
Management of hypercalcaemia
Surgery in primary
If levels are very high, surgical admission, IV fluid, bisphosphonates. Cinacalet is calcium mimick that can help to induce negative feedback.
If FHx then test for MEN syndromes
If due to hypomagnesaemia, then need to correct this first
Iodine uptake
Via Na/I symport for use in T3 and T4
Hypothyroidism causes
PRimary (most common in UK)
Can be congenital (Agenesis), hormone synthesis defect (antithyroid drugs (amiodarone, lithium, iodine excess, iodine deficiency, thyroid deficiency, other drugs)
Autoimmune
Infective
Can also be post surgery/irradiation/tumour infiltration
Can be secondary (hypopituitarism, peripheral resistance to thyroid hormone)
Autoimmune hypothyroidism
Atrophic autoimmune thyroiditis, Hashimotos, post partum thyrotoxicosis
Hypothyroid symptoms
Children have FLT, poor academic performance and delayed puberty.
Young women may havegynae issues( dysmenorrhoea, oligmenorrhoea, menorrhagia, infertility).
Older adults have cognitive decline and depression
Generally bradycardia, constipation, puffy eyes, arthralgia, myalgia, carpal tunnel, proximal myopathy, slow relaxing reflex, depression, coma, poor memory, psychosis, ataxia, dry skin, thin hair/eyebrows, hypothermia, mild obesity, cold peripheries, anaemia, myxoaedema, deep voice, goitre, peaches and cream complexion, anorexia, libido loss, malaise
Atrophic autoimmune thyroiditis
Most common autoimmune hypothyroid.
Has antithyroid antivodies. Lymphoid infiltration, atrophy and fibrosis. Can be intermittent. No goitre.
Hashimotos thyoid
Atrophic changes with regeneration. Goitre forms. Common from middle age (esp women.) Thyroid is firm/rubbery. TPO antibodies present.
Can start as thyrotoxicosis. Associated with autoimmunes like PA
Post partum thyrotoxicosis
Transient lymphocytic thyroiditis. Can cause hyperthyroidism too. Screen in post partum depression
Pendred syndrome
Dyshormonogenesis (defective hormone synthesis and sensorineural hearing loss)
Hypothyroidism O/I
Anaemia? (macrocytic in PA, microcytic in menorrhagia)
high TSH, low T4 in primary (low TSH in pituitary/hypothalamus disease or sick thyroid syndrome). TPO antibodies in Hashimotos.
Hypercholesterolaemia in hepatic hypothyroidism.
CK raised due to muscle wasting
Hyperthyroidism causes
Autoimmune, acute thyroiditis, gestational, exogenous iodine (e.g. amiodarone has iodine), thyrotoxicosis factitia (T4 consumption).
Rare causes are TSH secreting pituitary tumour, metastatic thyroid carcinoma, HCG producing tumour, hyperfunctioning ovarian teratoma.
Graves disease
Most common hyperthyroidism.
Can present with goitre.
Serum IgG antibodies on TSH receptor (TSH-rAB).
FHx component. Often relapses and patients become hypothyroid eventually
Solitary toxic nodule/adenoma
5% of hyperthyroidism. Firm, painless nodule in neck.
Hot nodules have hormones. Generally benign.
Controlled with antithyroid drugs, but often wont remiss
Toxic multinodular goitre
More common in women. Control with drugs
De Quervain’s
Transient hyperthyroidism. Associated with viral inflammation. Causes fever, malaise, pain in neck, tachycardia. Can progress to hypothyroidism.
Tx with aspirin and steroids in severe case
Hyperthyroidism S+S
AF, tachycardia, HF, lid lag, exopthalmos (Grave’s only), palmar erythema, myxoedema, vomiting/diarrhoea, warm peripheries, heat intolerance, tremor, thyroid bruit, weight loss.
Rarely, clubbing, new bone formation
Long term: osteoporosis, proximal myopathy, cardiomyopathy, increased clot risk
In children, see growth spurt and behavioural issues
TPOab
Associated with Hashimotos and hypothyroidism. Can also be found in Grave’s and normal people
TgAB
Thyroglobulin antibodies - associated with Hashimotos
TSHrAB
Graves disease
Scalloping on thyroid histology
Colloid reabsorption - seen in Grave’s disease
Thyroid disorder management
If hypothyroid then T4 (levothyroxine).
If Hyperthyroid, then carbimazole (caution over immune suppression and agranulocytis), radioiodine therapy (not in pregnancy/breastfeeding) or surgery (risk include recurrent laryngeal damage, trachea compression if bleeding and hypocalcaemia)
Goitres
If diffuse then ?Hastimotos/graves
If multinodular then can be eurthyroid or hyperthyroid
Solitary nodule can be malignancy, but cyst or benign tumour (or largest in multinodular)
Thyroid cancer types
Papillary (70%, 30s-50s)
Follicular (20%, 40s-60s)
Medullary (5% - often familial - MEN 2a/b) - poor prognosis. C cell
Anaplastic ( poor prognosis)
Lymphoma (2%, not true thyroid cancer. Can respond to radiotherapy, increased risk post hashimotos)
Papillary cancer histology
Psammoma bodies, little orphan annie eyes Has bony mets. Lymphatic spread. FNAC for investigation Thyroglobulin can be tumour marker
Medullary thyroid cancer
Often familial, aggressive, C cell cancer. MEN2a/2b in younger patients. Associated with phaeochromocytoma, PT tumour, pale brown birthmarks, megacolon and Marfans. May get diarrhoea and flushing.
Anaplastic thyroid cancer
Rare, aggressive, invasive. No thyroid synthesis. 60s-80s. Dull ache in neck is common. Skin can be blue/red from impaired venous drainage. May compress trachea, cause ear pain, hoarse voice, B symptoms and bone infiltration
Follicular thyroid cancer
second most common. 40-60s Blood spread. Associated with endemic goitre. Functional, so allows iodine uptake treatment. Angio invasion/capsular invsation. Unifocal Good prognosis if resectable
Diabetes insipidus
Central or nephrogenic (test with desmopressin -if urine osmolality low after fluid deprivation but high after desmopressin then neurogenic - if still low then nephrogenic.
If urine osmolality is high after fluid deprivation and high after desmopressin the primary polydipsia.
Tx in nephrogenic iis NSAIDs and thiazides to slow urine production rate and allow more reabsorption
Thyroid exam key
Thyroid matter will be in anterior triangle and will move on swallow. If not moving then lymph gland, carotid body tumour or abscess/cyst.
If it is in the posterior triangle then consider lymph gland, cystic hygroma, papillary carcinoma deposits.
Thyroglossal cyst will move side to side but not up and down unless tongue protruded (and hyoid moves).
Plummer’s disease
Solitary toxic nodule
Grave’s specific symptoms
Grave’s ophthalmopathy (oedema of eye muscle in extreme exophthalmos - normally SO/LR/IO and prevents eye looking out), goitre bruit, acropachy (swlling of fingers and toes)
Riedel’s
Rare condition, mimics anaplastic carcinoma - dense fibrous tissue replaces gland. Gives stony hard swelling (one lobe, then both)
Simple hyerplastic goitre
Excess TSH (due to low T3/T4 - often thyroid deficiency but also in pregnancy and puberty). Colloid goitre forms in late stage where TSH tapers off but acini are distended. Patient euthyroid on investigation. No lymph involvement, no eye involvement. Can be seen in excess cabbage intake
Multinodular goitre
Spontaneous or due to prolonged stimulation with disorganised response (hyper and hypoplasia)
Sudden enlargement, painless swelling, dyspnoea, dysphagia and engorged neck veins. If pain then consider haemorrhage into nodule. Can lead to Plummer’s syndrome but can also leave little functional gland left and hypothyroid.
Smooth on palpation, may only have one nodule palpable (dominant). Can be hard or soft, but wont transillunimate or fluctate, or have bruit
Solitary nodule
Often multinodular on investigation, but cancer until proven otherwise
Can be dominant multinodular, haemorrhage into nodule, cyst, adenoma, papillary/follicular carcinoma, unilateral hashimotos
Thyroid crisis/storm
Stress in untreated hyperthyroidism, gives hyperpyrexia, severe tachycardia, profuse sweating, confusion/psychosis. Use non selective beta blocker (e.g. propanalol)
