thyroid & parathyroid patho Flashcards
symptoms of hyperthyroid
- weight LOSS
- INCREASED appetite
- HEAT intolerant
- DIARRHOEA
- IRRITABLE
symptoms of hypothyroid
- weight GAIN
- POOR appetite
- COLD intolerant
- CONSTIPATION
- mental SLOWness
signs of hyperthyroid
- thin
- staring gaze, lid lag
- warm, sweaty
- tachycardia
- pretibial myxoedema (graves), proximal myopathy
normal weight of the thymus?
20-25g
location of the thymus?
lower part of the anterior neck
if the mass presses on the trachea, it will lead to ___ symptoms
difficulty breathing, stridor
if the mass presses on the oesophagus, it will lead to ___ symptoms
difficulty swallowing
if the mass presses on the Recurrent Laryngeal Nerve, it will lead to ___ symptoms
hoarseness
signs of hypothyroidism
- mildly obese
- peaches and cream skin
- dry, cool
- bradycardia
- proximal myopathy
Hashimoto’s is a ________ disease
When T4 is ____, if TSH is high, it is ___________
When T4 is ____, if TSH is low, it is ___________
Hashimoto’s is a hypothyroidism disease
When T4 is low, if TSH is high, it is primary hypothyroidism
When T4 is low, if TSH is low, it is secondary hypothyroidism
Graves is a _______ disease
When T4 is ____, if TSH is low, it is __________
Graves is a hyperthyroidism disease
When T4 is high, if TSH is low, it is primary hyperthyroidism
What are some diseases that can result in DIFFUSED goitre?
Graves disease
Hashimoto thyroiditis
DeQuervain thyroiditis
Simple goitre
What are some diseases that can result in LOCALISED nodule goitre?
Nodular goitre
Neoplasms
Pathogenesis of simple diffused goitre (non-toxic)
Impaired synthesis of thyroid hormones
-> compensatory increase in TSH
-> hypertrophy and hyperplasia of follicular cells
-> enlargement of thyroid gland (simple goitre)
Morphology of simple diffused goitre
- Hyperplastic stage
- diffuse mild enlargement
- micro: crowded columnar cells, pseudopapillae - Colloid involution
- abundant colloid
- micro: flattened cuboidal epithelium
Pathogenesis of localised nodular goitre
Impaired synthesis of thyroid hormones
-> compensatory increase in TSH
-> hypertrophy and hyperplasia of follicular cells
-> enlargement of thyroid gland (simple goitre)
-> recurrent hyperplasia and involution
-> nodular enlargement
Features of localised nodular goitre
- evolution from simple goitre
- extreme, irregular enlargement
- cystic change
- commonest cause of goitre
- mass effects (compression on trachea, RLN, oesophagus)
What is the most common cause of goitre?
Localised Nodular goitre
Pathogenesis of Hashimoto thyroiditis
Breakdown of self-tolerance to thyroid antigens
-> destruction of thyroid parenchyma
-> progressive thyroid failure
#1 cause of hypothyroidism
Gross morphology of thyroid gland in Hashimoto disease
Pale, enlarged gland
Pale yellow firm cut surface
Hashimoto thyroiditis can lead to higher risk of ___________
B cell lymphoma of thyroid eg MALT lymphoma
Clinical triad of Graves disease
- Hyperthyroidism
- Infiltrative ophthalmopathy
- Infiltrative dermopathy (pretibial myxoedema)
Pathogenesis of Graves disease
Thyroid stimulating immunoglobulin
-> binds to TSH receptor
-> mimics TSH
-> increased released of thyroid hormones
-> increased growth of thyroid gland
TSH-binding inhibitor immunoglobulins
there will be ______ radioiodine uptake (imaging test) in graves disease
increased
(hyperfunctioning thyroid will take up radioiodine)
Gross morphology of thyroid gland in graves disease
- symmetrical diffuse enlargement
- soft, reddish meaty cut suface
What are some thyroid neoplasms that are of non-follicular cell origin?
Medullary carcinoma
Lymphoma
BENIGN thyroid neoplasms of follicular cell origin:
Follicular adenoma
Oncocytic adenoma
LOW grade MALIGNANT thyroid neoplasms of follicular cell origin:
Papillary thyroid carcinoma
Follicular carcinoma
HIGH grade MALIGNANT thyroid neoplasms of follicular cell origin:
Poorly differentiated thyroid carcinoma
Differentiated high grade thyroid carcinoma
UNDIFFERENTIATED MALIGNANT thyroid neoplasms of follicular cell origin:
Anaplastic thyroid carcinoma
Morphology of adenoma
- rounded, encapsulated
- well demarcated
- no capsular/vascular invasion
Key features of follicular adenoma
- Completely intact fibrous capsule with no capsular or vascular invasion
- Nuclei small and round
- No vascular or capsular invasion
- Microfollicular mixed with macrofollicular
What is follicular carcinoma?
Follicular adenoma + capsular and/or vascular INVASION = follicular carcinoma
What are the variants of papillary thyroid carcinoma?
- classic PTC
- follicular variant PTC
4 Key nuclear features of Papillary Thyroid Carcinoma
- finely dispersed chromatin - ground glass nuclei
- nuclear grooves (coffee beans)
- pseudoinclusions
- oval nuclei
Features of classic PTC
4 key features of PTC + well formed papillae with fibrovascular cores
Features of follicular variant PTC
4 key features of PTC + follicular architecture (no papillae)
What is a possible differential diagnosis of follicular variant PTC?
follicular carcinoma (will not exhibit the 4 key features of PTC)
Features of anaplastic carcinoma
- cells highly pleomorphic (variation in sizes)
- giant tumour cells
- spindle cells
- small anaplastic cells - pale chromatin
- prominent nucleoli
Features of medullary carcinoma
Cells
- epithelioid or spindled
- salt and pepper chromatin
Calcium metabolism mainly occurs at ____
bones (25 mol)
What are the hormones involved in calcium regulation?
parathyroid hormone
vitamin D
calcitonin
adrenal hormones
thyroid hormones
osteoclast activating factor
prostaglandins
PTH secretion is controlled by
- Ionised calcium concentration
- 1,25 dihydroxyvitamin D
- Magnesium as a co-factor
Actions of PTH
DIRECT:
Bone - stimulates bone resorption
Kidney
- increase distal nephron calcium reabsorption
- phosphate excretion
INDIRECT:
Kidney - promotes formation of vitamin D
-> vit D promotes reabsorption of calcium from the gut
-> vit D stimulates bone resorption
causes of hypercalcaemia
1) hyperparathyroidism
- primary
- tertiary
*secondary hyperparathyroidism is physiological
2) malignancy
- bone metastasis -> seeds into the bone and causes bone resorption
- multiple myeloma -> secretes osteoclast activating factor and causes bone resorption
- cancer cells secrete parathyroid hormone related peptide
-> behaves similar to PTH
-> causes humoral hypercalcaemia of malignancy (HHM)
3) Vitamin D Excess
- sarcoidosis
- vit D intoxication
4) milk alkali syndrome
5) immobilisation
6) familial hypocalciuric hypercalcaemia
7) endocrine disorders
- thyrotoxicosis
- Addisons disease
8) drugs
- thiazide diuretics
lab investigations:
Increase plasma calcium, decrease plasma phosphate
primary hyperparathyroidism
malignancy (HHM)
lab investigations:
Increase plasma calcium, increase plasma phosphate
malignancy
hypervitaminosis D
lab investigations:
decrease plasma calcium, increase plasma phosphate
hypoparathyroidism
renal failure (untreated)
lab investigations:
decrease plasma calcium, decrease plasma phosphate
vitamin D deficiency
hyperparathyroidism vs malignancy
hyperparathyroidism:
hypercalcaemia <3.5mmol/L
months/years
slow rate of increase of calcium
renal stones common
increase in plasma PTH
malignancy:
hypercalcaemia >3.5mmol/L
weeks/months
rapid rate of increase of calcium
renal stones uncommon
low plasma PTH
causes of hypocalcaemia
1) hypothyroidism
2) vitamin D deficiency
- malabsorption
- inadequate diet
- poor exposure to sunlight
3) renal disease
- can lead to vit D deficiency because the 1-alpha hydroxylase enzyme found in the kidney
4) pseudohypoparathyroidism
adrenal cortex secretes:
aldosterone, cortisol, sex hormones
adrenal medulla secretes:
epinephrine, norepinephrine
what condition will lead to Cushing’s disease?
benign adenoma of anterior pituitary
-> ant pit produces more ACTH -> produces more cortisol
possible causes of Cushing’s syndrome
- ectopic ACTH (benign or malignant) -> some tumour elsewhere releasing ACTH
- adrenal adenoma or carcinoma (benign or malignant)
- iatrogenic Cushing’s syndrome (exogenous glucocorticoids)
- Cushing’s disease
in overnight dexamethasone test, failure to suppress is
suggestive of Cushing’s syndrome
what are the causes of primary hyperaldosteronism?
- adrenal aldosterone producing adenoma
- idiopathic hyperaldosteronism with bilateral adrenal hyperplasia
consequences of primary hyperaldosteronism
- increase Na+ retention
- increase water retention
=> increase BP - increase ECF
=> decrease plasma renin - decrease K+
-> hypokalemia - decrease H+
=> metabolic alkalosis
phaechromocytoma is the tumour of the
adrenal medulla
-> leads to overproduction of catecholamines
symptoms and signs of pheochromocytoma
hypertension
sweating
tachycardia and palpitations
headache
diagnostic tests used to detect catecholamine-secreting tumours
serum:
- free unconjugated catecholamines
- metanephrines (24h)
urine:
- free unconjugated catecholamines
- metanephrines (24h)
- VMA (24h)
primary causes of chronic adrenal insufficiency (ENTIRE adrenal gland becomes non-functioning)
- idiopathic adrenal atrophy
- granulomatous diseases
- tuberculosis
- histoplasmosis
- sarcoidosis - neoplastic infiltration
- haemochromatosis
- amyloidosis
- post bilateral adrenalectomy
secondary causes of chronic adrenal insufficiency (ENTIRE adrenal gland becomes non-functioning)
- tumours
- pituitary
- craniopharyngioma
- tumour of the 3rd ventricle - pituitary infarction and haemorrhage
- postpartum necrosis
- haemorrhage in tumours - granulomatous disease
- sarcoidosis - post hypophysectomy
- prolonged-exogenous steroid administration
what are the 2 tests used for Addison’s disease (insufficient cortisol/aldosterone)?
Long and Short Synacthen Tests
What is the purpose of short synacthen test?
an increase in cortisol to >550 nmol/L would rule out Addison’s disease
What is the Wolff-Chaikoff effect?
- an autoregulatory phenomenon
- excess iodine is transported to thyroid gland
- inhibit thyroid peroxidase enzyme
- cause decrease synthesis of thyroid hormones
Is liothyronine or levothyroxine better for chronic replacement treatment?
levothyroxine, because the half life of liothyronine is short and high cost
Long term use of high dose L-T4 will cause:
increase bone resorption and decrease bone mineral density
Who are the special considerations of L-t4 replacement?
- Pregnant patients
- Elderly patients
- Patients with Ischemic heart disease
- Patients with subclinical hypothyroidism
causes of hyperthyroidism
- graves disease
- overactive thyroid gland
- increased consumption of iodine
- increased consumption of thyroid hormones
- inflammation of release of stored thyroid hormones
causes of hyperthyroidism
- graves disease
- overactive thyroid gland
- increased consumption of iodine
- increased consumption of thyroid hormones
- inflammation of release of stored thyroid hormones
what is the half-life of PTU and carbimazole?
PTU: 75 mins
carbimazole: 4-6h
Contraindication of using iodide for hyperthyroidism treatment
Pregnancy: avoid use in pregnant/breastfeeding women to avoid causing fetal goitre
