Endocrine Flashcards
Hyperthyroidism
Hypothalamus secretes TRH - Anterior parathyroid secretes TSH - thyroid gland - T3 (more active) and T4
Thyrotoxicosis: clinical effect of excess thyroid hormone
Causes: Grave's Toxic multinodular goitre Toxic adenoma Subacute de Quervain's thyroiditis (painful goitre, post-viral, reduced uptake on iodine-131) Drugs: amirodarone
Sx: heat intolerance, weight loss, diarrhoea, amenorrhea, anxiety
Signs: tremor, palpitations, brisk reflexes, palmar erythema
Ix: Low TSH, high T3/4 (primary) High TSH, low T3/T4 (secondary) Subclinical: Low TSH, normal T3/4 US goitre FNA goitre Radioisotope scan
Grave’s disease:
Autoimmine disease in which IgG antibodies stimulate TSH receptor on thyroid gland, release thyroid hormones
Can become hypo-, eurothyroid
Sx: thyrotoxicosis (heat intolerance, weight loss, diarrhoea, tremor, palpitations), eye disease, goitre (smooth, diffuse)
Eye disease:
Sx: grittiness, eye discomfort, photophobia
Signs: proptosis, opthalmoplegia, periorbital oedema, lid retraction (risk fx: smoking)
Worsened with radio-iodine
Tx: methylprednisolone
Ix: Anti-thyroglobulin, Anti-TSH antibodies
Toxic multinodular goitre (nodules secrete thyroid hormones)
Elderly
Cardiac symptoms - palpitations, tremor
Tx: radio-iodine, subtotal thyroidectomy indicated if compressive e.g. dysphagia
Toxic adenoma
Single nodule
“Hot” on isotope, whilst gland is suppressed
Complications: AF, heart failure, thyroid storm
Tx:
B-blockers - symptoms
Carbimazole (inhibits prodcution thyroxine) - titrate, block and replace (carbimazole + levothyroxine)
SE: agranulocytosis
Radioiodine. SE: hypothyroidism. Contra:pregnancy, lactation
Thyroidectomy. Complications: damage to recurrent laryngeal nerve - voice hoarseness, hypoparathyroidism, hypothyroidism, thyrotoxic storm
Thyroid storm
Severe hyperthyroidism
Sx: Increased HR, agitation, confusion, coma
Triggers: recent thyroid surgery, infection, MI
Ix: TSH, T3/4
Tx: IV fluids (if dehydrated), NG tube (if vomiting)
IV Propranolol
High dose-digoxin
Carbimazole (PO or NG)
IV hydrocortisone (stop conversion T4 to T3)
Hypothyroidism
Causes:
Hashimoto’s thyroditis
Iodine deficiency
Amiodarone (iodine excess so T4 inhibited), lithium
Atrophic thyroiditis (hypo+no goitre. end stage Hashimoto’s)
Pituitary problems - Sheehan’s (postpartum pituitary necrosis)
Sx: Cold intolerance, weight gain, constipation, menorrahgia, depression
Signs: bradycardia, slow reflexes, hair loss (outer 1/3 eyebrow), dry skin, goitre
Assoc with TMD1, Addison’s, vitiligo
Ix: Primary: TSH high, T3/4 low Secondaary: TSH low, T3/4 high Sick euthyroid: TSH low, T3/4 low FBC (normo/macrocytic anaemia) Antithyroglobulin, Anti-TPO (Hashimoto's) US goitre FNA goitre Isotope scan
Tx:
Levothyroxine
Hashimoto’s
Autoimmune disease where thyroid infiltrated by plasma cells, lymphocytes leading to development goitre, and thyroid dysfunction
60-70 yrs
Sick euthyroid
Abnormal thyroid function due to systemic disease
Causing dysregulation of thyroid hormone feedback control
TSH low, T3/4 low
TSH normal, T3/4 low
Myxoedema coma
Severe hypothyroidism before death
Sx: hypothermia, hyporeflexia, decreased glucose
Signs: goitre, hypotension, HF
Ix:
T3/T4, TSH, UEs (low Na+)
ABG
Tx:
ICU
IV Liothyronine (T3) or levothyroxine
IV hydrocoritsone
Thyroid cancer
Papillary (most common)
Follicular
Medullary
Anaplastic - rare, aggressive
Papillary
Multiple lesions in gland
Not encapsulated
Spread via lymphatics
Follicular
Focal
Encapsulated
Spread via blood to bones, lungs
Medullary
Parafollicular (C) cells
Secrete calcitonin (reduces Ca+ levels. Opp of PTH)
Assoc. MEN2
Risk fx: female, MEN2 (medullary) radiation exposure
Sx: palpable lump
red flag: rapid growth, pain, hoarse voice, lymphadenoapthy
DDx: toxic mulitnodular goitre, thyroglossal cyst
Ix:
TFTs
Radionucleotide imaging - if “hot” then mostly likely not malignant
US thyroid (microcalcifications, irregular margin)
FNA cytology
Tx: Hemi-thyroidectomy Total thyroidectomy Complications: Haematoma - cause airway obstruction Hypocalcaemia due to damage parathyroid glands (tetany) Vocal cord paralysis/hoarse voice
External beam radiotherpy
Parathyroid disease
PTH secreted in response to low Ca Bone: Increases osteoclast activity Kidneys: Increases absorption Ca, production Vit D, decreases phosphate absorption Gut: absorption Ca (helped via Vit D) - Increased Ca, decrease phosphate
Primary hyperparathyroidism
Pituitary adenoma, pituitary hyperplasia/cancer
Sx: moans, groans, stones, bones, increased BP, OP
Signs: pepper pot-skull
Ix:
High Ca, high or inappropriately normal PTH
Low phosphate
Increased ALP
Tx: IV fluids, avoid thizaides
Cincalcet (mimics Ca2+) (lead to decreased PTH)
Excision adenoma: if renal failure, bone disease
Complications: hypoparathyroidism, hoarse voice (recurrent laryngeal nerve damage)
Secondary hyperparathyroidism High PTH (appropriately high), Low Ca2+
Causes: Low Vit D, chronic renal failure
Tx: correct cause, Vit D, phosphate binders, cinalcalceet
Tertiary hyperparathyroidism
Very high PTH, high Ca2+
Due to prolonged 2ndary hypereparathyroidism, leading glands to act independently, no feedback control
Causes: chronic renal failure
Malignant hyperparathyroidism
PTHrp related hormone secreted produced - squamous cell lung ca., breast, renal Ca.
Mimics PTH leading to increase Ca (low actual PTH)
Hypoparathyroidism Primary: Low PTH due to gland failure Causes: Congenital (Di George), Thyroidectomy, parathyroidectomy, hypomagnesia (as Mg needed PTH secretion) Low Ca2+ and PTH, high phosphate Tx: calcium + calcitrol
Sx: confusion, tetany, seizures (hypocalcaemia)
Tx: calcium or calcitrol, correct Mg
Multiple endocrine neoplasia
Autosomal dom
MEN 1/2
Neurofibromatosis
Von Hippel Lindau
MEN1
Parathyroid adenoma
Pancreatic islet cell tumors
Pituitary adenoma
MEN2a:
Medullary thyroid
Phaeochromocytoma
TMD1
Chronic metabolic disorder characterised by hyperglycaemia due to no inuslin secretion due to autoimmune destruction of B cells in islet of Langerhans
Age <30
5% all diabetic cases
HLA DR3/4
Risk fx: Enterovirus, Coxsackie B virus, high socioeconomic status
Sx: acute onset, polyuria, polydipsia, weight loss, fatigue, blurred vision
Ix:
Random plasma glucose: >11.1
Fasting plasma glucose (fasting 8hrs) >6.9
OGTT (glucose measured 2hrs after 75g carbs): >11.1
HbA1C >48
Markers: IA2 (islet cell antibody), GAD (glutamic acid decarboxylase), no C-peptide
Management:
Basal-bolus regime:
Long-acting: Insulin Glargine (Lantus)
Short acting: given pre-meal. Humalog (Lispro)
Combination: Novomix 30: 30:70 (rapid: intermediate)
One unit every 15g carbs
Insulin pump, pancreatic transplant
TMD2
Chronic metabolic disorder, hyperglycaemia due to reduced insulin sensitivity and secretion
Assoc. with obesity, HTN, dyslipidaemia, family hx
90% diabetic cases
Sx: asymptomatic. gradual onset, fatigue
Signs: candidal, skin infections
Ix:
2 values: fasting plasma glucose (>6.9) + HbA1c (>48)
or
OGTT (> 11.1) or Random (11.1) + symptoms
C-peptide (only in TMD2)
Tx:
Life style modification
1st line: metformin
SE: diarrhoea, nausea, lactic acidosis, pulm fibrosis
Contra if eGFR <30, should be stopped before CT dye
2nd line
DPP4 antagonists: Sitagliptin
SE: GI upset, pancreatitis
Sulponyureas: Glicazide
SE: hypo, weight gain, increased CVD risk
Thiazolidinediones: Pioglitazone
SE: fractures, overload
SGLT2-inhibitors: Dapaglifozin, Emapgiflozin
SE: genital infections, decreased CVD risk
3rd line: Add another class or Insulin (isophane) - long-acting insulin If BMI >30: GLP-1 agonist: Exenatide SE: GI disturbance, weight loss
DKA
Excessive hyperglycaemia which does not enter cells due to lack of insulin, causes state of ketogenesis (as body think its starving). Leads to production of ketone acids.
Sx: polyuria, polydipsia (due to glucose excreted into urine - osmotic diuresis - dehydration), abdo pain, vomiting
Signs: Ketotic breathe, Kassmual’s breathing
Triggers: Missed dose insulin, non-compliance, infection, MI
Diagnosis: Hyperglycaemia, acidosis, ketones
Ix: Plasma glucose, VBG, blood ketones
ECG, CXR, catheter, cultures, UEs (acid gap)
Severe if anion gap >16, K+ (low), GCS <12, O2 <92%: ITU/HDU
Complications: cerebral oedema, hypokalaemia
Tx: IV fluids IV insulin Dextrose + K+ (if 3.5-5.5) IV glucose
Hyperglycaemic hyperosmolar state
Profound hyperglycaemia (>33), hyperosmolality (>320) and dehydration, no ketoacidosis
Triggers: infection (pneumonia, UTI), MI, non-adherence to meds, drugs e.g. steroids, B-blockers
Sx: polyuria, polydipisa, weakness
Signs: hypotension, shock
Ix: plasma glucose, blood ketones, UEs, K+ (high)
Tx: IV fluids
K+
IV insulin when K+ >3.3
Vasopressors if still hypotensive e.g. NA or dopamine
Complications diabetes
Macrovascular:
Coronary a. disease
Peripheral ischaemia - ulcers, diabetic foot
Stroke
Microvascular:
Retinopathy
Non-proliferative (early)
Proliferative (late): neovascularisation which can haemorrhage leading to vision loss
Signs: microaneurysms, cotton wool spots (cluster haemorrhages), lipid exudates (yellow dots)
Peripheral neuropathy
Sx: asymptomatic, pain (peripheral), loss of sensation, reduced reflexes
Clinical diagnosis
Sx: BM control, duloxetine or gabapentin
Nephropathy
Albuminuria + reduced GFR + long-standing diabetes
Sx: odema (nephrotic syndrome), signs of retinopathy, peripheral neuropathy
Ix: urinalysis (protein), urinary albumin:creatinine ratio
Cushing’s
Cushing’s disease: pituitary adenoma leading to increase cortisol production
Cushing’s syndrome: sx and signs of increased cortisol
Causes:
ACTH dependent: pituitary adenoma, ectopic ACTH (SCLC)
ACTH independent: iatrogenic (steroid use), adrenal adenoma, adrenal carcinoma
Sx: weight gain, central obesity, moon face, hyperglycaemia
Signs: striae, buffalo hump (fat pad on back), OP
Ix:
Late night salivary cortisol (11-12pm)
1g overnight Dexamethasone suppression test (11pm-8am): if cortisol >50 then Cushing’s
High dose dexamethasone suppression test:
Pituitary adenoma: ACTH + cortisol suppressed
Adrenal adenoma: ACTH suppressed but not cortisol (as adenoma still secreting cortisol)
Ectopic ACTH: Neither suppressed
FBC, UEs(Low K+ if aldosterone also secreted by adrenal adenoma) MRI head (pituitary) CT chest (SCLC) Abdo CT (adrenals)
Tx:
Transphenoidal pituitary adenotectomy
Adrenalectomy
Medical: Ketoconazole
Adrenal insufficiency
Adrenal glands doesn’t secrete cortisol or aldosterone
Primary:
Addison’s: Adrenal glands damaged doesn’t secrete cortisol or aldosterone
Causes: Autoimmune, TB (most common worldwide)
Secondary: Not enough ACTH
After pituitary surgery, Sheehan’s syndrome
No hyperpigmentation, as decreased ACTH
Tertiary: Not enough CRH
Iatrogenic: withdrawal of steroid after chronic steroid use, >3wks (hypothalamus can’t make enough CRH fast enough)
Sx: fatigue, weight loss, abdo pain, mood disturbance, N+V
Signs: postural hypotension, hyperpigmentation skin (buccal mucosa/palmar creases), vitiligo
Ix:
SynACTHtest (give synthetic ACTH, no increase in cortisol)
Low Na, high K+
Renin:aldosterone (renin high, aldosterone low)
Low glucose
Tx: Hydrocortisone (glucocorticoids), fludrocortisone (mineralcorticoids)
Steroid bracelet/ID
Double steroid dose on sick days, increase before exercise
Addison's crisis: Sx: hypotension, reduced conciousness, increased HR Triggers: infection, surgery, missed dose Tx: IV hydrocortisone stat IV fluids monitor UES monitor glucose (IV glucose) Fludrocortisone (if adrenals affected)
Primary hyperaldosteronism
Commonest cause of curable HTN
Causes: Adrenal hyperplasia (most common), Conn’s syndrome (due to adrenal adenoma)
Sx: HTN, muscle weakness, palpitations (due to low K+)
High Na+, Low K+
Metabolic alkalosis (due to loss of K+ and H+)
Ix:
plasma renin:aldosterone ratio (aldosterone high, renin low)
CT abdo
Tx: adrenal adenoma (adrenalectomy) adrenal hyperplasia (spironolactone)
Secondary hyperaldosteronism:
Due to high renin leading high aldosterone
Causes: renal stenosis
High renin AND high aldosterone
Hypopituitarism
Deficiency of one or more ant. pituitary hormones (In order of affected: GH, FSH, LH, TSH, ACTH, prolactin)
Panhypopituitarism: loss of all.
Posterior: ADH, oxytocin)
Causes:
Hypothalamus: Kallman’s syndrome
Pituitary adenoma (can cause increase hormone secretion, or destroy tissue leading to loss of hormones)
Rathke’s cyst
Pituitary hypoplexy (haemorrhage of pre-existing adenoma)
Haemachromatosis
Post-radiation - pituitary
Sx: Loss of: GH (central obesity, asthersclerosis) FSH, LH (amenorrhoea, reduced libido, OP) TSH (sx of hypothyroidism) ACTH (sx of Addison's) Prolactin (absent lactation)
Ix:
LH, FSH, testosterone/oestradiol, morning cortisol, TSH, insulin like growth factor (to measure GH)
MRI head (pituitary lesion)
Tx: IV Hydrocortisone Testosterone, oestradiol patches, OCP Somatotrophin (GH) Levothyroxine
Pituitary hypoplexy:
Sudden onset headache, opthalmoplegia (CN palsies - III, IV, VI), first ACTH deficiency leading to decreased cortisol and addison’s crisis.
Can cause hypopiuitary coma.
Tx: IV hydrocortisone. Emergency surgery
Hypopiuitary coma
Sx: hypothermia, refractory hypotension, headache +/- sepsis WITHOUT fever
Signs: short stature, loss of axillary/pubic hair
Causes: Sheehan’s syndrome, pituitary apoplexy
Acromegaly
Increased secretion of GH, usually due to pituitary tumour or carcinoid
Assoc. with MEN1
GH stimulates growth via insulin like growth factor
Sx:
Parasthesia of extremities, amenorrhoea, headache
Signs: Growth of hands, jaw, feet, macroglossia, acanthosis nigricans, goitre
Complications:
Diabetes, HTN, ventricular dilatation (can cause CHF)
Increased colon Ca risk
Ix:
Serum Insulin-like growth factor
Normally GH inhibited by glucose
So OGTT + GH (if lack of suppression with 75g glucose, then acromegaly)
Tx: Trasnphenoidal surgery Complications: haemorrhage, meningitis If surgery fails: Octreotide (somatostatin analogue)
