Endocrine Pathology Flashcards
What is the anterior pituitary?
Epithelial cells derived from developing oral cavity.
Secrete trophic hormones under the control of factors released by the hypothalamus.
What are the hormones produced by the anterior pituitary?
FLAT PEG
- FSH
- LH
- ACTH
- Prolactin
- Estogen
- Growth Hormone
What are symptoms of pituitary disease?
Hyperpituitarism: Excess secretion of trophic hormones, usually due to functional adenoma.
Hypopituitarism: Deficiency of trophic hormones
Local mass effects
What is hyperpituitarism?
Usually due to functional adenoma.
Originally classified on the morphological character of the predominant cell type e.g acidophil, basophil or chromophobe adenomas.
Now classified on the basis of the hormones produced - detected by immunohistochemistry.
What is the most common cause of anterior pituitary tumour?
Prolactinoma
What is the epidemiology of pituitary adenomas?
10% of intracranial tumours that come to clinical attention
Discovered incidentally in up to 25% of autopsies
Adults. Peak 4th - 6th decade
Microadenomas if < 1cm
What are clinical features of a prolactinoma?
Amenorrhea, galactorrhea, loss of libido, infertility
Usually diagnosed earlier in females of reproductive age
What are clinical features of growth hormone adenomas?
Prepubertal children: Gigantism
Adults: Acromegaly
Diabetes mellitus, muscle weakness, hypertension, congestive cardiac failure
What are clinical features of corticotroph adenomas?
Cushing’s syndrome
What are the most common causes of hypopituitarism?
Nonsecretory pituitary adenomas
Ischaemic necrosis:
- Most commonly post-partum (Sheehan’s syndrome)
- DIC, sickle cell anaemia, elevated intracranial pressure, shock
blation of pituitary by surgery or irradiation
What are clinical features of hypopituitarism?
Children: Growth failure (pituitary dwarfism)
Gonadotrophin deficiency: Amenorrhea and infertility in women. Decreased libido and impotence in men.
TSH and ACTH deficiency: Hypothyroidism and hypoadrenalism
Prolactin deficiency: Failure of post-partum lactation
What are the hormones released by the posterior pituitary?
Posterior pituitary releases two peptides - antidiuretic hormone (ADH) and oxytocin. Clinically important posterior pituitary syndromes involve ADH:
- Diabetes insipidus
- Syndrome of inappropriately high ADH
What are signs and symtoms of a local mass?
Compression of optic chiasm leading to bitemporal hemianopia
Signs and symptoms of elevated intracranial pressure e.g. Obstructive hydrocephalus
What is this?
Thyroid
How does the thyroid function?
In response to TSH from anterior pituitary follicular epithelial cells pinocytose colloid and convert thyroglobulin into T4 and T3.
T4 and T3 released into circulation.
Effect is to increase the basal metabolic rate.
Thyroid also contains a population of parafollicular or ‘C’ cells that synthesize calcitonin - promotes absorption of calcium by the skeletal system.
What is a goitre?
Enlargement of the thyroid
What is a non-toxic goitre?
Goitre is enlargement of the thyroid. Common if there is impaired synthesis of thyroid hormone - most often due to iodine deficiency.
Endemic in areas where iodine in the soil and water is low (‘Derbyshire neck’). May be seen at puberty particularly in females.
May be due to ingestion of substances that interfere with thyroid hormone synthesis e.g. brassicas. May be due to hereditary enzyme defects.
What is a multinodular goitre?
With time simple thyroid enlargement may be transformed to a multinodular pattern.
May reach massive size.
May lead to mechanical effects including dysphagia and airways obstruction.
A hyperfunctioning nodule may develop leading to hyperthyroidism.
What is this?
Multinodular goitre
What is thyrotoxicosis?
Hypermetabolic state caused by elevated circulating levels of free T3 and T4
What are primary causes of thyrotoxicosis?
Grave’s disease
Hyperfunctioning multinodular goitre
Hyperfunctioning adenoma
Thyroiditis
What are secondary causes of thyrotoxicosis?
TSH secreting pituitary adenoma (rare)
What are causes of thyrotoxicosis not associated with thyroid disease?
Struma ovarii (ovarian teratoma with ectopic thyroid)
Factitious thyrotoxicosis (exogenous thyroid intake)
What is Grave’s Disease?
Most common cause of endogenous hyperthyroidism.
Triad of:
- Thyrotoxicosis
- Infiltrative ophtahalmopathy with exophthalmos in up to 40%
- Infiltrative dermopathy (pretibibial myxoedema) in a minority of cases
Primarily younger adults. F:M, 7:1
What is the pathogenesis of Grave’s Disease?
Autoimmune disorder.
Variety of antibodies including antibodies to TSH receptor and thyroglobulin.
Antibodies to TSH receptor most important in pathogenesis; may stimulate release of thyroid hormones and increased proliferation of epithelium.
Associated with other autoimmune diseases such as SLE, pernicious anaemia, type 1 diabetes and Addison’s disease.
What is the association between autoantibodies and thyroid disease?
Autoimmune disorders of the thyroid span a continuum with Grave’s disease at one end and Hashimoto’s disease manifested by hypothyroidism at the other.
Autoantibodies against thyroid antigens are common to both but their specificities differ leading to different functional consequences.
What are primary causes of hypothyroidism?
Postablative (after surgery or radioiodine therapy)
Autoimmune - Hashimoto’s thyroiditis
Iodine deficiency
Congenital biosynthetic defect
What are secondary causes of hypothyroidism?
Pituitary or hypothalamic failure (uncommon)
What is Hashimoto’s thyroiditis?
Other end of the spectrum of autoimmune thyroid disease from Grave’s disease.
Common cause of hypothyroidism.
Most common from 45 - 65 years.
F:M 15:1.
Presents with painless enlargement.
What is this?
Hashimoto’s thyroiditis
What are neoplasms of the thyroid?
Adenomas: Benign neoplasms of follicular epithelium.
Carcinomas: Uncommon and account for less than 1% of solitary thyroid nodules.
What are clues which can be used to identify thyroid nodules?
Solitary nodules more often neoplastic than multiple nodules.
Solid nodules more likely to be neoplastic than cystic nodules.
Nodules in younger patients more likely to be neoplastic than in older patients.
Nodules in males more likely to be neoplastic than those in females.
Nodules that do not take up radioactive iodine (cold nodules) more commonly neoplastic than ‘hot’ nodules.
What are techniques used to identify the nature of thyroid nodules?
Fine needle aspiration cytology
Histology
Whatr are thyroid adenomas?
Usually solitary.
Well circumscribed lesion that compresses the surrounding parenchyma.
Well formed capsule.
Small proportion cause thyrotoxicosis.
Important to examine the capsule for invasion to exclude follicular carcinoma.
What are carcinomas of the thyroid?
<1% of cancer deaths
Most cases in adults
- Papillary (75-85%)
- Follicular (10-20%)
- Medullary (5%)
- Anaplastic (<5%)
What is the pathogenesis of thyroid carcinomas?
Genetic factors - inc. MEN
Ionizing radiation –Primarily papillary carcinomas
What is papillary carcinoma?
May occur at any age
May have papillary architecture
BUT diagnosis is based on nuclear features:
- Optically clear nuclei
- Intranuclear inclusions
May be psammoma bodies
What is this?
Papillary carcinoma
What is this?
Papillary carcinoma
What are clinical features of papillary carcinoma?
Nonfunctional
Present as painless mass in neck
May present with metastasis in cervical lymph node
10 year survival up to 90%
What is a follicular carcinoma?
Peak incidence in middle age
Follicular morphology
May be well demarcated with minimal invasion or clearly infiltrative
Usually metastasise via bloodstream to lungs bone and liver
What is a medullary carcinoma?
Neuroendocrine neoplasm derived from parafollicular C cells
80% sporadic: Adults 5-6th decade
20% familial: MMEN - younger patients
What is this?
Medullary carcinoma
What is an anaplastic carcinoma?
Occur in elderly patients
Very aggressive
Metastases common
Most cases death within one year due to local invasion
What are the parathyroid glands?
Derive from developing pharyngeal pouches
Usually 4
Usually close to upper and lower poles of thyroid but may be in the thymus or anterior mediastinum
What is this?
Parathyroid gland
What is the function of the parathyroid glands?
Activity controlled by level of free calcium in blood.
Decreased calcium stimulates release of PTH.
PTH:
- Activates osteoclasts
- Increases renal tubular reabsorption of calcium
- Increases conversion of vitamin D to its active form
- Increases urinary phosphate excretion
- Increases intestinal calcium absorption
What are causes of hyperparathyroidism?
80-90% - solitary adenoma
10-20% hyperplasia of all 4 glands: Sporadic or component of MEN type 1.
<1% carcinoma
What is this?
Parathyroid adenoma
What is hyperparathyroidism?
Increased level of serum ionised calcium.
Most common cause of clinically silent hypercalcaemia.
PTH is high in comparison with hypercalcaemia due to non-parathyroid diseases.
What is primary hyperparathyroidism?
Bone resorption with thinning of cortex and cyst formation - osteitis fibrosa cystica - may lead to fractures.
Renal stones and obstructive uropathy.
GI disturbances - constipation, pancreatitis and gallstones.
CNS alterations - depression, lethargy and fits.
Neuromuscular abnormalities - weakness
Polyuria and polydipsia
What are symptoms of primary hyperparathyroidism?
“Painful bones, renal stones, abdominal groans, psychic moans”
Less common now as hypercalcaemia more frequently picked up on routine blood tests.
What is secondary hyperparathyroidism?
Caused by any condition associated with chronic depression of serum calcium.
Renal failure is by far the most common cause.
Parathyroid glands are enlarged - may be asymmetrical.
Leads to bone changes as with primary disease.
What are causes of secondary hyperparathyroidism?
Surgical ablation
Congenital absence
Autoimmune
What are the clinical manifestations of hyperparathyroidism?
Neuromuscular irritability - tingling, muscle spasms, tetany
Cardiac arrhythmias
Fits
Cataracts
What are the layers of the adrenal glands?
Zona glomerulosa: Secretes aldosterone
Zona fasciculata: Secretes glucocorticoids
Zona reticularis: Secretes androgens and glucocorticoids
Medulla: Noradrenaline and adrenaline
What is adrenocortical hyperfunction?
Cushing’s syndrome – excess glucocorticoids
Hyperaldosteronism
Virilising syndromes – excess androgens
What are signs and symptoms of Cushing’s Syndrome?
Hypertension and weight gain
Truncal obesity
‘Moon’ facies
‘Buffalo hump’
Cutaneous striae
What is the most common cause of Cushing’s Syndrome?
Most cases caused by administration of exogenous glucocorticoids – Adrenal glands are atrophic.
What is endogenous Cushing’s Syndrome?
>50% due to primary hypothalamic-pituitary disease with increased ACTH – Cushing’s disease.
Most associated with ACTH-producing adenoma in the pituitary.
Some have hyperplasia of ACTH secreting cells in pituitary.
Adrenal glands show nodular cortical hyperplasia.
What are endogenous causes of Cushing’s Syndrome?
30% of cases – primary adrenal
Most cases are due to a solitary neoplasm
- Adenoma
- Carcinoma
Less commonly due to bilateral hyperplasia
What are exogenous causes of Cushing’s Syndrome?
Remaining cases due to secretion of ectopic ACTH by non-endocrine tumours.
Most commonly small cell carcinoma of the lung.
Adrenals show bilateral hyperplasia.
What is primary hyperaldosteronism?
35 % aldosterone secreting adenoma – Conn’s syndrome.
60 % bilateral adrenal hyperplasia.
Clinical manifestations are hypertension and hypokalaemia.
Accounts for <1% of causes of hypertension but important to recognise as surgically correctable.
What are adrenogenital syndromes?
Excess of androgens. May be associated with neoplasms – more commonly carcinoma than adenoma.
What is congenital adrenal hyperplasia?
Group of autosomal recessive disorders.
Hereditary defects in enzymes involved in cortisol biosynthesis.
Decreased cortisol results in increased ACTH, adrenal stimulation and increased androgen synthesis.
May present in childhood or less commonly in adults.
What are causes of primary adrenal insufficiency?
Primary
Secondary to reduced ACTH:
- Non-functional pituitary adenomas
- Other lesions of pituitary or hypothalamus including infarction
What are acute causes of primary adrenal insufficiency?
Sudden withdrawal of corticosteroid therapy
Haemorrhage (neonates)
Sepsis with DIC (Waterhouse-Friderichson syndrome)
What are chronic cuases of primary adrenal sufficiency (Addison’s Disease)?
Autoimmune (75-90%)
TB
HIV
Metastatic tumour (lung and breast particularly)
Rarely amyloid, fungal infections, haemochromatosis, sarcoidosis
What are adrenocortical neoplasms?
Adenomas:
- Most non-functional
- May be associated with Cushing’s syndrome or Conn’s syndrome
Carcinomas:
- Rare
- Usually large
- More commonly associated with virilizing syndrome than adenoma
What are neoplasms of the adrenal medulla?
Secretes catecholamines in response to signals from the sympathetic nervous system. Most important diseases are neoplasms:
- Phaeochromocytoma
- Neuroblastoma
What are phaeochromocytomas?
Secrete catecholamines and give rise to a surgically correctable form of hypertension.
Rule of 10s:
- 10% arise in association with a familial syndrome inc. MEN 2A and 2B, von Hippel-Lindau disease and Sturge-Weber syndrome.
- 10% are bilateral.
- 10% are malignant.
- In addition 10% of catecholamine-secreting tumours arise outside the adrenal (paragangliomas).
What is multiple endocrine neoplasia (MEN) syndrome?
Group of inherited diseases resulting in proliferative lesions (hyperplasias, adenomas and carcinomas) of multiple endocrine organs.
What are MEN tumours?
Occur at a younger age than sporadic tumours
Arise in multiple endocrine organs
Often multifocal in one organ
Often preceded by hyperplasia
Usually more aggressive than sporadic tumours
