Endocrine Pathology Flashcards
The pituitary gland is made up of what 2 lobes, what are the relative proportions of each?
Anterior lobe = 75%
Posterior love = 25%
Give the 5 causes of pituitary gland hypofunction?
1) Tumours - non secretory adenoma, metastatic carcinoma
2) Trauma
3) Infarction
4) Inflammation - granulomatous, autoimmune, other infections
5) Iatrogenic
The vast majority of primary pituitary tumours are of what type?
Benign adenomas (can be derived from any hormone producing cell)
What are the 2 main effects of pituitary tumours?
1) If functional the clinical effect secondary to the hormone being produced
2) Local effects due to pressure on optic chiasm or adjacent pituitary
Give the 3 commonest types of pituitary adenoma and what each causes?
1) Prolactinoma - commonest, galactorrhea and menstrual disturbance
2) Growth hormone secreting - gigantism in children and acromegaly in adults
3) ACTH secreting - Cushing’s disease
The thyroid gland is made up of 2 parts, how does each part get to its position embryologically?
1) Main part migrates from foregut to anterior neck
2) Ultimobranchial body forms in brachial arches and fuses with main bit laterally
Does ectopic thyroid just exist in the head and neck region?
No can exist in the larynx, trachea, heart, pericardium, liver, gall bladder and as far as vagina
What is the most common ectopic thyroid?
Lingual thyroid: at the base of the tongue
What percentage of patients with lingual thyroid have no other thyroid tissue?
> 75%
What is cretinism?
Cretinism is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones
What percentage of patients with lingual thyroid are hypothyroid and what percentage have cretinism?
70% hypothyroid
10% cretinism
What is a thyroglossal duct cyst?
A persistent track representing the embryological migratory path of thyroid anlage in the anterior neck
Where do 75% of thyroglossal duct cysts occur?
In the anterior midline of the neck or immediately below the hyoid bone
Do symptoms occur with a thyroglossal duct cyst?
No - its an asymptomatic midline neck mass
In which group is a thyroglossal duct cyst most common?
Children and young adults
What procedure can be used to remove a thyroglossal duct cyst?
Sistrunk procedure
What is acute thyroiditis?
Acute inflammation of the thyroid parenchyma associated with local viral, bacterial or fungal infection
What are most cases of acute thyroiditis due to?
Generalised sepsis
What are the 5 symptoms of acute thyroiditis?
1) Fever
2) Chills
3) Malaise
4) Pain
5) Swelling of anterior neck
What is the prognosis of acute thyroiditis?
Related to the underlying condition
What is palpation thyroiditis and what is it often associated with?
Microscopic granulomatous foci centered on thyroid follicles, secondary to rupture of follicles due to palpation or surgery
Patients almost always have a thyroid nodule
What is Riedel thyroiditis?
Rare, fibrosing form of chronic thyroiditis which may alos affect lots of other structures
How does Riedel thyroiditis present, what are the 3 main symptoms?
Presents with a firm goitre
Symptoms = dysphagia, hoarseness and stridor
(May be mistaken for malignant neoplasm)
Does Riedel’s thyroiditis require treatment?
No - it is a benign self-limiting disease
What is Chronic lymphocytic thyroiditis also known as?
Hashimoto’s thyroiditis
What is Hashimoto’s thyroiditis?
Autoimmune chronic inflammatory disorder with diffuse enlargement and raised serum thyroid antibodies, get lymphocytic infiltration of the thyroid parenchyma, often with germinal center formation
Hashimotos thyroiditis occurs most commonly in which group?
Females at age of 59
Is Hashimoto’s thyroiditis associated with hypo or hyper thyroidism?
Hypothyroidism
Hashimoto’s thyroiditis increases the risk of what 2 conditions?
80 fold increased risk of thyroid lymphoma
Increased risk of papillary carcinoma of the thyroid
What is diffuse hyperplasia of the thyroid also known as?
Grave’s disease
What is the most common cause of hyperthyroidism?
Grave’s disease (80% of cases)
What are the thyroid hormone levels in Graves disease?
T3 and T4 elevated, TSH markedly suppressed
What are the 5 physical findings in Grave’s disease?
1) Pretibial myxoedema
2) Hair loss
3) Wide eyed stare or proptosis
4) Tachycardia
5) Hyperreactive reflexes
What is a multinodular goitre?
Enlargement of the thyroid with varying degrees of nodularity -1 or more thyroid nodules
Do patients with a multinodular goitre tend to get changes to their thyroid levels?
No - most are euthyroid
What 2 symptoms may develop with large nodules in a multinodular goitre?
Tracheal compression
Dysphagia
What is a follicular adenoma of the thyroid?
Benign encapsulated tumour with evidence of follicular differentiation, a solitary nodule only involving one lobe
How does follicular adenoma present, which sex is it most common in?
Painless neck mass, often present for years
Females more than males
Give the 4 most common malignant tumours of the thyroid?
1) Differentiated thyroid carcinoma
2) Medullar carcinoma
3) Anaplastic carcinoma
4) Malignant lymphoma
What is the commonest type of thyroid carcinoma, which sex it most common in?
Papillary carcinoma, most common in females
What are the 5 main risk factors for developing a papillary carcinoma?
1) Familial, autosomal dominant non medullary thyroid carcinoma
2) FAB
3) Cowden’s syndrome
4) Therapeutic irradiation
5) Radiation exposure
In addition to the variety of chromosomal translocations in papillary carcinoma, what are the 4 most common molecular abnormalities?
1) Activation of RET or NTRK1
2) Fusion of RET tyrosine kinase regions with constitutively expressed thyroid proteins
3) BRAF V600E mutation
4) RAS mutations
What is the macroscopic appearance of a papillary carcinoma of the thyroid?
Ill defined, infiltrative, some encapsulated, may be cystic, granular
Follicular neoplasms can also occur in the thyroid, give the 4 common follicular neoplasms?
1) Follicular adenoma
2) Minimally invasive follicular carcinoma
3) Widely invasive follicular carcinoma
4) Hurthle cell neoplasms
Follicular carcinoma accounts for what percentage of all thyroid cancers?
10-20%
How does follicular carcinoma present?
90% present with a solitary nodule in the thyroid
10% present with distant metastasis
Hurthle cell carcinoma accounts for what percentage of all differentiated thyroid carcinomas?
3%
How does Hurthle cell carcinoma behave differently clinically to follicular carcinoma?
Unlike follicular carcinoma there is a significant incidence of cervical lymph node metastases
What are the commonest haematogenous sights of spread of Hurthle cell carcinoma?
Bone, liver and lung
Insular carcinoma occurs in what groups of patients and has what prognosis?
Occurs in elderly patients, poor prognosis as often locally advanced, lymph node and distant metastases present in up to 50% - atleast 60% of patients will die of the disease
How does an anaplastic carcinoma of the thyroid present?
Rapidly enlarged thyroid mass which may be preceeded by a history of long standing goitre
What is the prognosis of anaplastic carcinoma of the thyroid gland?
Usually inoperable with a median survival in months
What is a medullary carcinoma of the thyroid?
Malignant tumour showing differentiation to parafollicular C cells
Is medullary carcinoma of the thyroid inherited?
70-80% are sporadic but 20-30% are autosomal dominant inherited
Which 3 common mutations are found in medullary carcinoma?
1) Men 2a & 2b
2) Familial MTC
3) Mutations in the RET gene
What is a primary thyroid lymphoma and what is it often associated with?
Primary lymphoma arising within the thyroid gland, often associated with lymphocytic thyroiditis.
What are the 2 types of primary thyroid lymphoma?
1) Extranodal marginal zone type
2) Diffuse large B cell
Primary thyroid lymphoma accounts for what percentage of thyroid neoplasms?
2%
What is the mean age of incidence of primary thyroid lymphoma?
Seventh decade
How does a primary thyroid lymphoma present? 5
1) Mass in thyroid
2) Often associated with rapid enlargement
3) Pain
4) Dysphagia
5) May have associated cervical lymphadenopathy
What is the overall percentage survival of primary thyroid lymphoma?
60%
What are the 5 common metastatic tumours of the thyroid?
1) Renal cell carcinoma
2) Melanoma
3) Small cell lung cancer
4) Neuroendocrine tumours (usually lung)
5) Breast cancer
What is the difference between primary and secondary hyperparathyroidism?
Primary - excessive section of PTH from one or more glands
Secondary - hyperplasia of the gland with elevated PTH in response to hypocalcaemia
What is tertiary hyperparathyroidism?
Adenoma in association with long standing secondary hyperparathyroidism
Which group is primary hyperparathyroidism most common in?
White women
Primary hyperparathyroidism is associated with what 3 risk factors (including on mutation)?
1) Aging, tumourogenesis in general
2) Association with ionizing radiation
3) MEN 2a
Is primary HPT symptomatic?
Over 50% asymptomatic or oligosymptomatic (having few or minor symptoms)
In symptomatic PHPT what are the 8 symptoms?
1) Arterial hypertension
2) Psychiatric problems
3) Hypercalcemia
4) Decreased renal function
5) Osteoporosis
6) HPT bone disease
7) Hypercalcaemia symptoms
8) Urolithiasis (bladder stones)
What are the 3 causes of PHPT?
1) Single adenoma
2) Diffuse chief or clear cell hyperplasia
3) Carcinoma
What is primary chief cell hyperplasia of the PT gland?
Non-neoplastic increase in PT parenchymal cell mass within all parathyroid tissue without a known stimulus
What are the 5 symptoms of primary chief cell hyperplasia?
1) Fatigue
2) Lethargy
3) Anorexia
4) Weakness
5) Vomiting
(Bones, stones and abdominal moans)
How is primary chief cell hyperplasia treated?
With surgery
What is parathyroid adenoma?
An encapsulated benign neoplasm of parathyroid cells, have a single enlarged parathyroid gland, remaining glands are suppressed and small
What are the symptoms of parathyroid adenoma?
Symptoms of hypercalcaemia
What 3 conditions is parathyroid adenoma associated with?
MEN1 and MEN2 syndrome
Hyperparathyroidism
Jaw tumour syndrome
Do secondary and tertiary HPT have a known stimulus?
Yes - non neoplastic increase in parathyroid parenchymal cell mass within all parathyroid tissue with a known stimulus (hypocalcemia)
Secondary and tertiary PT are common in what patients?
Patients with renal failure and on dialysis
Parathryroid carcinoma accounts for what percentage of PHPT?
Less than 5%
The symptoms of parathyroid carcinoma are due to what?
Excess calcium
How is parathyroid carcinoma treated, what is the percentage 10 year survival?
Treated with surgery
50% 10 year survival
What is adrenal congenital hypoplasia?
Reduced volume of adrenocortical tissue leading to adrenal cortical insufficiency - rare
Why is adrenal congenital hypoplasia more common in males?
Often X linked
How is adrenal congenital hypoplasia now managed, how has the prognosis changed?
No managed with glucocorticoid and mineralocorticoid replacement which yields good outcome - mortality is high if left untreated
What is congenital adrenal hyperplasia?
Inherited disorder caused by deficiency of enzymes required for synthesis of glucocorticoids and mineralocorticoids - have deficiencies of cortical and aldosterone secretion
What 2 enzymes are often deficient in congenital adrenal hyperplasia?
1) 21 hydroxylase
2) 11-beta-hydroxylase
What are the clinical features of congenital adrenal hyperplasia?
1) Genital ambiguity in females - normal in males
2) May be evidence of virilisation and hyperandrogenism
3) Advanced bone growth with premature epiphyseal maturation leading to short adult stature
What is Addison’s disease?
Primary adrenal cortical insufficiency caused by adrenal dysgenesis, adrenal dysfunction
What is the most common form of Addison’s disease?
Autoimmune disease
What cause of Addison’s disease is becoming more common in the developing world?
TB
Addison’s disease is a triad of what 3 symptoms?
1) Hyperpigmentation
2) Postural hypotension
3) Hyponatraemia
What is the treatment of Addison’s disease?
Long term steroid replacement
What is an adrenal cortical nodule, does it have any symptoms?
Benign, non-functional nodule of adrenal cortex
No clinical symptoms - usually and incidental discovery
Do adrenal cortical nodules require treatment?
No
Adrenal cortical nodules are higher in what 3 groups of patients?
1) Elderly
2) Hypotensive
3) Diabetic patients
What is an adrenal cortical adenoma?
Benign neoplastic proliferation of adrenal cortical tissue
What are the symptoms of adrenal cortical adenoma?
Related to endocrine hyperfunction
hypertension, Cushing’s syndrome and virilisation
What is virilisation?
The development of male characteristics due to excess androgens
Aldosterone producing adrenal cortical adenomas cause what syndrome?
Conn’s syndrome
How does an adrenal cortical adenoma appear macroscopically?
Unilateral solitary mass of well circumscribed yellow/brown nodules, formed from lipid filled adrenal cortical cells
Adrenal cortical carcinoma accounts for what percentage of endocrine neoplasms?
3%
What are the symptoms of adrenal cortical carcinoma?
Symptoms related to hormone excess plus abdominal mass
What is the percentage 5 year survival of adrenal cortical carcinoma?
70%
What is phaeochromocytoma?
Catecholamine-secreting tumour arising from the adrenal medulla
Most phaeochromocytomas are sporadic, but what are the 2 familial syndromes involved?
MEN2a von
MEN2b von
What is the prognosis of phaeochromocytoma?
Excellent prognosis when benign and managed surgically
Malignant tumour may pursue and aggressive course
What 3 chemicals would be elevated in the urine in phaeochromocytoma?
1) Catecholamines
2) Noradrenaline
3) Adrenaline
