Flashcards in Endocrine Pathology Deck (74):
What is the location of the pituitary gland?
Situated in the Sella Turcica beneath the hypothalamus
What is the relevant anatomy of the pituitary gland?
- Consists of two parts; Anterior and Posterior
- 75% of the gland formed by anterior lobe formed by outpouching of the oral cavity ( Rathke’s pouch) ( Adenohypophysis )
- 25% posterior lobe formed by down growth of the hypothalamus ( Neurohypophysis )
What are the causes of anterior pituitary hypofunction?
- Tumours - Non-secretory adenoma, metastatic carcinoma
- Inflammation – granulomatous, autoimmune, other infections
What are the features of primary pituitary tumours?
- Vast majority are adenomas and benign
- May be derived from any hormone producing cell
- If functional clinical effect secondary to hormone being produced
- Local effects due to pressure on optic chiasma or adjacent pituiary
Name the types of anterior pituitary adenoma?
- Prolactinoma – Commonest, galactorrhoea and menstrual disturbance
- Growth hormone secreting – Gigantism in children, acromegaly in adults
- ACTH secreting – Cushing’s syndrome
Describe the structure of the thyroid gland.
Bilobed organ joined by an isthmus encased in thin fibrous capsule located at the level of 5th, 6th and 7th vertebra in the anterior neck in close proximity to the trachea.
What is the average weight of the thyroid?
Average weight 18g for adult males, 15g for adult females.
Describe the relationship between the thyroid, the thyroid cartilage and the laryngeal nerve?
Abuts the thyroid cartilage of the larynx, recurrent laryngeal nerve located in the tracheo-oesophageal groove close to posterior aspects of lateral lobes.
Describe the development of the thyroid gland?
- Main part migrates from foregut to anterior neck ( remnant is foramen caecum at junction ant 2/3 and post 1/3 of tongue )
- Ultimobranchial body forms in branchial arches and fuses with main bit laterally
What is thyroid ectopy?
- Thyroid tissue in an abnormal place
- From Foramen cecum to suprasternal notch.
- >75% of patients with lingual thyroid have no other thyroid tissue. 70% hypothyroid; 10% with cretinism.
- Other sites: Sella turcica, larynx, trachea, aortic arch, esophagus, heart, pericardium, liver, GB, pancreas, vagina.
What is a thyroglossal duct cyst?
- Persistent track representing the embryological migratory path of thyroid anlage in the anterior neck.
- Approximately 7% of adults.
- 75% in anterior midline of neck at or immediately below hyoid bone.
- Most common in children and young adults.
- Asymptomatic midline neck mass.
What is the treatment for thyroglossal duct cyst
4-6% recurrence rate with Sistrunk procedure.
What is acute thyroiditis?
- Acute inflammation of the thyroid parenchyma associated with local or systemic viral, bacterial or fungal infection.
What is the usual cause of acute thyroiditis?
- Most cases due to generalised sepsis.
What are the symptoms of acute thyroiditis?
Fever, chills, malaise, pain, swelling of anterior neck.
What is palpation thyroiditis?
- Microscopic granulomatous foci centred on thyroid follicles.
- Secondary to rupture of thyroid follicles due to palpation or surgery.
- Patients almost always have a thyroid nodule.
What is riedel thyroiditis?
Rare fibrosing form of chronic thyroiditis.
Fibrosing disorder may also affect retroperitoneum, lung, mediastinum, biliary tree, pancreas, kidney, subcutis.
What are the symptoms of riedel thyroiditis?
- Present with firm goitre.
- Symptoms include dysphagia, hoarseness, stridor.
- May be mistaken for malignant neoplasm.
- Benign self-limited disease.
What is chronic lymphocytic thyroiditis?
- Present with firm goitre.
Symptoms include dysphagia, hoarseness, stridor.
May be mistaken for malignant neoplasm.
Benign self-limited disease.
What is the peak age for Hashimoto's?
What are the features of Hashimoto's?
- Diffusely enlarged non-tender gland.
Serum thyroid antibodies elevated.
- Lymphocytic infiltration of thyroid parenchyma, often with germinal centre formation.
What are the symptoms and risks associated with Hashimoto's?
- Many patients become hypothyroid.
80-fold increased risk of thyroid lymphoma.
- Increased risk of papillary carcinoma of the thyroid.
What is diffuse hyperplasia of the thyroid?
An autoimmune process results in clinical hypothyroidism and diffuse hyperplasia of the follicular epithelium.
aka Grave's disease
What is the epidemiology of Grave's disease?
- Incidence 1% world wide.
- Responsible for 80% of cases of hyperthyroidism.
- Females much more common than men.
- Peak in third and fourth decades.
What are the physical findings in Grave's disease?
- Pretibial myxoedema
- hair loss
- wide-eyed stare or proptosis
- hyperactive reflexes.
- Thyroid diffusely enlarged.
What are the blood findings in Grave's?
- T3 and T4 elevated.
- TSH markedly suppressed.
- Thyroid autoantibodies, especially thyroid stimulating immunoglobulin.
What is multinodular goitre?
- Enlargement of thyroid with varying degrees of nodularity.
- 1 or more thyroid nodules discovered by patient or health care provider.
- Most patients are euthyroid.
- Dominant nodule may be mistaken clinically for thyroid carcinoma.
- Tracheal compression or dysphagia may develop with large nodules.
What is follicular adenoma?
- Benign encapsulated tumour with evidence of follicular cell differentiation.
- Painless neck mass, often present for years.
- Solitary nodule involving only one lobe.
- Usually cold nodule on radioactive iodine imaging.
What is the epidemiology of follicular adenoma?
- Females more than males.
- Wide age range, usually fifth to sixth decade.
What is the epidemiology of papillary carcinoma?
- Commonest type of thyroid carcinoma >70%
- Female predominance 2.5:1
- Wide age range mean 43years
What are the causes of papillary carcinoma?
- Familial, autosomal dominant non-medullary thyroid carcinoma
- Cowden’s syndrome
- Therapeutic irradiation
- Radiation exposure
What are genetics behind papillary carcinoma?
- Activation of RET or NTRK1
- Variety of chromosomal translocations or inversions
- Fusion of RET tyrosine kinase regions with constitutively expressed thyroid proteins eg PTC1 in inv(10)(q11;q21). PTC2 t(10;17(q11.2;q21)
- BRAF V600E mutation
- RAS mutations
What is the macroscopic appearance of papillary carcinoma?
- Ill defined, infiltrative
- Some encapsulated
- May be cystic
What are the various types of follicular neoplasm?
- Follicular adenoma
- Minimally invasive follicular carcinoma
- Widely invasive follicular carcinoma
- Hurthle cell neoplasms
What percentage of all thyroid cancers are follicular carcinomas?
What percentage of thyroid cancers present with a solitary nodule?
What percentage of thyroid cancers present with distant metastasis?
What percentage of widely invasive tumours metastasise?
What are the features of minimally invasive follicular carcinoma?
Completely encapsulated. Invasion only detectable histologically
What are the features of widely invasive follicular carcinoma?
Macroscopic evidence of invasion. Widespread invasion histologically. Minimally invasive but tumour invades > 4 capsular blood vessels
What the epidemiology of Hurthle cell carcinoma?
- 3% of all differentiated thyroid carcinomas
- Median age 53 ( range 24-85 years)
- Sex ratio of F:M; 7:3
What is the clinical behaviour of Hurthle cell carcinoma?
- Unlike Follicular Carcinoma there is a significant incidence of cervical lymph node metastases
- Common haematogenous sites – Bone, Liver and Lung
What are the features of insular carcinoma?
- Elderly patients mean age 58years
- Often locally advanced
- Lymph node and distant metastases at presentation in up to 50%
- At least 60% of patients will die of disease
What are the features of anaplastic carcinoma?
- Older Patients. Mean age 65years
- Rapidly enlarging thyroid mass
- May be preceeded by a history of longstanding goitre
Median survival in months
What are the features of medullary carcinoma?
- Malignant tumour showing differentiation to parafollicular C cells
- 70-80% are sporadic
- 20-30% Autosomal dominant inherited
- MEN 2a & 2b
- Familial MTC
- Mutations in the RET gene
What are the clinical features of MEN2A medullary carcinoma?
- Parathyroid hyperplasia
What are the clinical features of MEN2B medullary carcinoma?
- Thickened corneal nerves
- Mucosal neuromas
- GI ganglioneuromatosis
What is primary thyroid lymphoma?
- Primary lymphoma arising within the thyroid gland, often associated with lymphocytic thyroiditis. May be of extranodal marginal zone type or diffuse large B-cell.
- Mass in thyroid, often associated with rapid enlargement, pain, dysphagia.
- May have associated cervical lymphadenopathy.
What is the epidemiology of primary thyroid lymphoma?
- About 2% of thyroid neoplasms.
- Mean age in seventh decade.
What is the prognosis of primary thyroid lymphoma?
Which cancers commonly metastesise to the thyroid gland?
- Renal cell carcinoma – differential diagnosis with primary clear cell thyroid tumours
- Small cell lung cancer
- Neuroendocrine carcinoma ( usually lung) – Differential diagnosis with medullary carcinoma
- Breast cancer
What is primary hyperparathyroidism?
Excessive secretion of parathyroid hormone from one or more glands (PHPT)
What is secondary hyperparathyroidism?
Hyperplasia of glands with elevated PTH in response to hypocalcemia.
- Renal insufficiency, malabsorption, vitamin D deficiency
What is tertiary hyperparathyroidism?
Adenoma in association with longstanding secondary hyperparathyroidism.
What is the incidence of PHPT?
1. 25-28 cases per 100,000 population
2. White women over 60 – 190/100,000
What is the pathogenesis of PHPT?
1. Aging, tumorigenesis in general
2. Association with ionizing irradiation
3. MEN 2a
What conditions are associated with PHPT?
- Asymptomatic in 50%
- Arterial hypertension in 5-48%
- Psychiatric problems in 14-20%
- Hypercalcaemia in 20%
- Decreased renal function in 4-14%
- Osteoporosis in 12%
- Hyperparathyroid bone disease in 8%
- Hypercalcaemia in 8%
- Urolithiasis in 4-7%
What are the causes of PHPT?
1. Single adenoma in 85-90%
2. Diffuse chief or clear cell hyperplasia 10-15%
3. Carcinoma 1%
What is primary chief cell hyperplasia?
Non-neoplastic increase in parathyroid parenchymal cell mass within all parathyroid tissue without a known stimulus.
What are the signs/symptoms of primary chief cell hyperplasia?
- Abnormalities in calcium metabolism.
- Symptoms include fatigue, lethargy, anorexia, weakness, vomiting.
- Bones, stones and abdominal moans.
- Elevated calcium, decrease in organic phosphorous, increased parahormone levels.
What is a parathyroid adenoma?
- An encapsulated benign neoplasm of parathyroid cells.
- Association with MEN1 and MEN2 syndrome and hyperparathyroidism and jaw tumour syndrome
What symptoms are associated with parathyroid adenoma?
- Symptoms of hypercalcaemia
- Single enlarged parathyroid gland, remaining suppressed and small
What are the features of secondary and tertiary parathyroidism?
- Non-neoplastic increase in parathyroid parenchymal cell mass within all parathyroid tissue with a known stimulus.
- Common in patients with renal failure and on dialysis.
- Identical pathologic features to primary hyperplasia. May be associated with massive gland enlargement.
What is a parathyroid carcinoma?
- Malignant tumour derived from parathyroid parenchymal cells.
- Less than 5% of primary hyper-parathyroidism.
- Symptoms referable to excess calcium.
- Indolent with recurrencies common (about 50%).
50% 10-year survival.
- Treated with surgery.
What are the features of adrenal congenital hypoplasia?
- Reduced volume of adrenocortical tissue leading to adrenal cortical insufficiency.
- May be part of a familial hereditary condition.
- Mortality is high if untreated.
- Male predominance, often X-linked.
- Clinical features of hypoadrenalism.
- Used to be uniformly fatal; now managed with glucocorticoid and mineralocorticoid replacement yields good outcome.
What are the features of congenital adrenal hyperplasia?
- Inherited disorder caused by deficiency of enzymes required for synthesis of glucocorticoids and mineralocorticoids.
- 21 hydroxylase deficiency accounts for more than 90%.
- 11-beta-hydroxylase deficiency around 5%.
- Deficiencies of cortical and aldosterone secretion.
- Genital ambiguity in females. Normal in males.
- May be evidence of virilisation and hyperandrogenism.
- Advanced bone growth with premature epiphyseal maturation leading to short adult stature.
What is Addinson's disease?
- Primary adrenal cortical insufficiency caused by adrenal dysgenesis, adrenal destruction.
- Autoimmune form is most common. Tuberculosis more common in developing world.
- Triad of hyperpigmentation, postural hypotension and hyponatraemia.
- High mortality if not diagnosed
What is the treatment for Addinson's disease?
Long-term steroid replacement
What is an adrenal cortical nodule?
- Benign non-functional nodules of adrenal cortex.
- Between 1.5 and 3% of population. Higher in elderly, hypotensive and diabetic patients.
- No clinical symptoms. Incidental discovery on radiographic studies.
- No treatment required.
What is an adrenal cortical adenoma?
- Benign neoplastic proliferation of adrenal cortical tissue.
Incidence from 1-5% of population.
- Symptoms related to endocrine hyperfunction
- Unilateral solitary masses.
- Average size 2cm, weight less than 100g.
- Well-circumscribed yellow/brown nodules.
- Formed form lipid-filled adrenal cortical cells.
What is the cause of Conn's syndrome?
Aldosterone-producing adenomas of the adrenal gland
What is the cause of Cushing's disease?
Cortisol-producing adenomas of the adrenal gland
What are the features of adrenal cortical carcinoma?
- 3% of endocrine neoplasms. About 1 per million of population.
- Symptoms related to hormone excess.
- Abdominal mass.
- 5 year survival about 70%.