Histo: Endocrine disease Flashcards
What types of cell are the anterior and posterior pituitary made up of?
Anterior = epithelial cells (derived from developing oral cavity)
Posterior = nerve cells
What is the blood supply to the anterior pituitary?
Pituitary portal system
Where do the nerves that make up the posterior pituitary originate?
Paraventricular nucleus
Supraoptic nucleus
What are the 3 symptoms catergories of pituitary disease?
- Hyperpituitarism symptoms - due to excess hormone secretion
- Hypopituitarism symptoms - due to deficiency of hormone secretion
- Mass effect symptoms
What is the most common cause of hyperpituitarism?
Functional adenoma
- Orignally classified by morphology of predominant cell type (e.g. acidophil, basophil, chromophobe)
- Now classified by hormone produced
What is the most common type of pituitary adenoma?
Prolactinoma
What is a microadenoma?
A pituitary adenoma with a diameter < 1 cm
Outline the clinical features of prolactinoma.
- Amenorrhoea
- Galactorrhoea
- Loss of libido
- Infertility
What are the clinical manifestations of growth hormone adenomas?
- Gigantism (prepubertal children)
- Acromegaly (adults)
- Diabetes
- Muscle weakness
- Hypertension
- Heart failure
What disease is caused by corticotroph cell adenomas?
Cushing’s disease
List some causes of hypopituitarism.
- Non-secretory pituitary adenoma
- Ischaemic necrosis
- Iatrogenic (surgery, radiotherapy)
What is the most common cause of ischaemic necrosis of the pituitary gland?
Sheehan’s syndrome - the pituitary enlarges during pregnancy and is more susceptible to ischaemia. A post-partum haemorrhage may induce ischaemia.
Other causes: DIC, sickle cell anaemia, shock
List some clinical features of hypopituitarism.
- Growth failure in children (pituitary dwarfism)
- Gonadotrophin deficiency - amenorrhoea and infertility (women); impotence and loss of libido (men)
- Hypothyroidism and hypoadrenalism
- Prolactin deficiency - failure of post-partum lactation
Which hormones are produced by the posterior pituitary?
ADH and oxytocin
Which conditions involve ADH?
Diabetes insipidus
SIADH
List some consequences of the local mass effect of pituitary tumours.
- Bitemporal hemianopia (optic chiasm)
- Headaches (raised ICP)
- Obstructive hydrocephalus
Describe the histological appearance of the thyroid gland.
- Arranged into follicles with a small amount of stromal tissue between them
- They are lined by epithelial cells and have a large amount of colloid in the middle
- Parafollicular cells are found between the follicles
Describe the physiological response of the thyroid gland to TSH.
- Stimulating of TSH receptors leads to pinocytosis of the colloid by the thyroid follicular cells and promotes the conversion of thyroglobulin into T3 and T4
- Release of thyroid hormones into the circulation results in a rise in basal metabolic rate
Which hormone do parafollicular cells produce?
Calcitonin - this promotes the absorption of calcium by the skeletal system
What is a non-toxic goitre?
Enlargement of the thyroid gland without overproduction of thyroid hormones
What is the most common cause of non-toxic goitre?
Iodine deficiency - leads to impaired thyroid hormone synthesis
Other causes involves hereditary enzyme defects
List some primary and secondary causes of thyrotoxicosis.
Primary
- Graves’ disease
- Toxic multinodular goitre/adenoma
- Thyroiditis
Secondary
- TSH-secreting pituitary adenoma (rare)
List some causes of thyrotoxicosis that are not associated with the thyroid gland.
- Struma ovarii - ovarian teratoma with ectopic thyroid hormone production
- Factitious thyrotoxicosis - exogenous thyroid hormone intake
What is the most common cause of endogenous hyperthyroidism?
Grave’s disease
Which antibodies are often seen in Graves’ disease?
- TSH receptor
- Thyroglobulin (TG)
- Thyroid peroxidase (TPO)
Describe the effect of TSH receptor-stimulating antibodies.
They stimulate thyroid hormone release and increase proliferation of the thyroid epithelium.
What is the triad of Grave’s?
- Hyperthyroidism
- Infiltrative ophthalmopathy - exopthalmos (40%)
- Infiltrative dermopathy - pretibial myoedema (minority)
Also associated with other autoimmune diseases e.g. SLE, T1DM, pernicious anaemia, Addison’s
List some primary and secondary causes of hypothyroidism.
Primary
- Post-ablative
- Autoimmune (Hashimoto’s)
- Iodine deficiency
- Congenital biosynthetic defect
Secondary
- Pituitary or hypothalamic failure (uncommon)
Describe the presentation of Hashimoto’s thyroiditis.
- Painless enlargement of the thyroid gland
- Symptoms of hypothyroidism.
Describe the histology of Hashimoto’s thyroiditis.
- There are lots of lymphoid cells with germinal centres
- The epithelial cells become large with lots of eosinophilic cytoplasm (Hurthle cells)
Types of thyroid neoplasms:
- Adenoma - benign tumours of follicular epithelium
- Carcinoma - uncommon (accounts for < 1% of solitary thyroid nodules)
List some features of a thyroid lump that would be suggestive of neoplasia.
- Solitary rather than multiple
- Solid rather than cystic
- Younger patients
- Male more than female
- Less likely to take up radioiodine (cold nodules)
How thyroid neoplasms diagnosed?
- Fine needle aspiration cytology
- Histology
List some features of adenomas of the thyroid gland.
- Usually solitary
- Well circumscribed
- Well-formed capsule
- Small proportion will be functional
List the four types of thyroid cancer in order of decreasing prevalence.
- Papillary (80%)
- Follicular (15%)
- Medullary (5%)
- Anaplastic (< 5%)
What are some risk factors for thyroid cancer?
- Genetic factors (e.g. MEN)
- Ionisation radiation (mainly papillary)
What is the histological features of papillary thyroid cancer?
Nuclear features
- Optically clear nuclei (Orphan Annie Eye)
- Intranuclear inclusions
There may also be psammoma bodies (round calcifications)
What are some clinical features of papillary thyroid cancer?
- Non-functional
- Presents with painless neck lump
- Can metastasize
- 90% 10 year survival
Where does papillary thyroid cancer tend to metastasise to?
Cervical lymph nodes
Where does follicular thyroid cancer tend to metastasise?
Lungs, bone and liver (via the bloodstream)
Which cells are medullary thyroid cancers derived from?
Parafollicular C cells
NOTE: 80% are sporadic (50-60 yrs), 20% are familial (MEN - younger patients)
What tends to happen to the calcitonin produced by tumour cells in medullary thyroid cancer?
- It is broken down and deposited as amyloid within the thyroid
What is the most aggressive thyroid cancer?
Anaplastic
- Occurs in elderly
- Metastases common
- Usually death in < 1 year
What are the parathyroid glands derived from?
Developing pharyngeal pouches
What controls PTH secretion?
Serum calcium concentration (sensed by CaSR)
List the actions of PTH.
- Activates osteoclasts
- Increased renal absorption of calcium
- Increases activation of vitamin D
- Increases urinary phosphate exretion
- Increases intestinal calcium absorption
What is hyperparathyroidism usually caused by?
- 80% solitay adenoma
- 20% due to hyperplasia of all four glands (sporadic or part of MEN1)
- < 1% carcinoma
Describe the histological appearance of a parathyroid adenoma.
Very cellular tissue with no fat (whereas the normal parathyroid gland is quite fatty)
What bone change is seen in hyperparathyroidism?
Osteitis fibrosa cystica - caused by bone resorption with thinning of the cortex
What are the effects of primary hyperparathyroidism?
- Bone - increased resorption (OFC)
- Kidneys - stones and obstructive nephropathy
- GI - constipation, pancreatitis, gallstones
- CNS - depression, lethary, seizures
- Muscular weakness
- Polyuria and polydipsia
“Painful bones, renal stones, abdominal groans, psychic moans”
What is the most common cause of secondary hyperparathyroidism?
Renal failure
- Parathyroid can be enlarged
- Leads bone disease as with primary disease
Can be caused by any condition with chronic calcium depression
List some causes of hypoparathyroidism.
- Surgical ablation
- Congenital absence
- Autoimmune
List some clinical features of hypoparathyroidism.
- Neuromuscular irritability - paresthesia, muscle spasm, tetany
- Cardiac arrhythmias
- Seizures
- Cataracts
CATs go numb
Which cell types constitute the cortex and medulla of the adrenal gland?
Cortex = epithelial
Medulla = neural
What are the layers of the adrenal cortex and which hormones do they produce?
GFR - AGS
* Glomerulosa - aldosterone
* Fasciculata - glucocorticoids
* Reticularis - sex steroids
Which conditions causes adrenal hyperfunction?
- Cushing’s syndrome - excess glucocorticoids
- Hyperaldosteronism (Conn’s)
- Virilising syndrome - excess androgens
What is the most common cause of Cushing’s syndrome?
Iatrogenic - administration of exogenous corticosteroids (leads to adrenal atrophy)
What happens to the adrenal glands in Cushing’s disease?
Undergo nodular hyperplasia of the cortex
List 4 endogenous causes of Cushing’s syndrome.
- Cushing’s disease - ACTH producing pituitary adenoma (> 50%)
- Adrenal adenoma/carcinoma
- Adrenal hyperplasia
- Ecotopic ACTH production - small cell lung cancer
What are the clinical features of Cushing’s syndrome?
- Hypertension
- Weight gain
- Truncal obesity
- Moon face
- Buffalo hump
- Cutaneous striae
What are the causes of hyperaldosteronism?
- 35% adenoma (Conn’s syndrome)
- 60% bilateral adrenal hyperplasia
List the two main clinical features of hyperaldosteronism.
- Hypertension
- Hypokalaemia
What causes virilising syndromes?
- Neoplasms (more commonly carcinoma than adenoma)
- Congenital adrenal hyperplasia
Describe the pathophysiology of congenital adrenal hyperplasia.
- Autosomal recessive
- Hereditary defect in an enzyme involved in cortisol synthesis leads to cortisol deficiency
- This leads to increased ACTH release from the pituitary gland
- ACTH stimulates adrenal hyperplasia and androgen synthesis
What is the most common cause of CAH?
21-hydroxylase deficiency
List three causes of acute primary adrenal failure.
- Sudden withdrawal of corticosteroid treatment
- Haemorrhage (neonates)
- DIC associated with sepsis (Waterhouse-Friderichson syndrome)
List some causes of chronic primary adrenal failure. (UK)
- Autoimmune (90%)
- TB
- HIV
- Metastatic tumour (lung and breast)
- Amyloid, fungal infection, haemochromatosis, sarcoid (very rare)
What are some secondary causes of adrenal insufficiency?
- Non-functional pituitary adenoma
- Pituitary/hypothalamic lesions including infarction
What are the two types of adrenocortical neoplasm?
- Adenomas - mostly functional, may be associated with Cushing’s syndrome or Conn’s syndrome
- Carcinomas - rare, more commonly associated with virilisng syndromes than adenomas
What are the two types of tumours of the adrenal medulla?
- Phaeochromocytoma
- Neuroblastoma
What is the rule of 10s regarding phaeochromocytomas?
- 10% associated with a familial syndrome (MEN)
- 10% bilateral
- 10% malignant
- 10% oustide the adrenal gland (paraganglioma)
Secrete catecholamine and causes a surgically correctable form of hypertension
Define multiple endocrine neoplasia and its inheritance.
A group of autosomal dominant conditions resulting in proliferative lesions (hyperplasia, adenoma, carcinoma) of multiple endocrine organs
Outline the characteristics of tumours in MEN.
- Tend to occur at a younger age
- Tend to arise in multiple endocrine organs or may be multifocal within one organ
- Often preceded by hyperplasia
- Usually more aggressive than sporadic tumours
What are the different types of MEN and the tumours associated with them?
3Ps - Pituitary, Parathyroid, Pancreatic
2Ps + M - Parathyroid, Phaeochromocytoma + Medullary Thyroid Carcinoma (MEN2a/b -> Medullary)
1P + 2Ms- Phaeochromocytoma + Medullary Thyroid Carcinoma (MEN2a/b -> Medullary) + Marfanoid
