Pathology of the Endocrine System Flashcards
What is the endocrine system?
Integrated network of glands that secrete chemical messengers (hormones) directly into bloodstream
What do hormones act on?
-Target cells distant from site of synthesis. -They bind to receptors the change cell activity
What is the endocrine system responsible for?
-Regulation of metabolism, growth and development, tissue function
Maintenance of functional balance
How can normal endocrine glands be described?
Packets of cells with secretory granules that are vascular and ductless
How is balance within the endocrine system maintained?
By feedback inhibition
What are the components of the classic endocrine system?
- Pineal gland
- Hypothalamus
- Pituitary gland
- Thyroid gland
- Parathyroid gland
- Adrenal glands
- Pancreas
- Other (organs such as ovaries, testes and kidneys) (diffuse endocrine cells)
How are endocrine organs linked?
Feedback axes
What do endocrine disease processes lead to?
Changes in function and/or structure
What can dysregulated hormone release lead to?
- Hyperfunction
- Hypofunction
Hyperplasia
Increased number and secretory activity of cells
Atrophy
-Diminution of cells due to lack of stimulation
What can cause tissue damage?
- Inflammation
- Autoimmune disease
- Compression
- Trauma
- Infection
Give example of disease processes of endocrine organs.
- Hyperplasia
- Atrophy
- Tissue damage
- Neoplasia
- Congenital abnormality
Give 2 examples of neoplasia
- Adenoma
- Carcinoma
How can adenomas be classified?
- Functioning
- Non-functioning
How can carcinomas be classified?
- Primary
- Metastatic
How can cause of endocrine disease be determined?
- Morphologic findings
- Biochemical measurements of hormone levels, regulators and metabolites
What general considerations are there when it comes to endocrine disease?
- Disease in one endocrine gland may have multiorgan clinical effects
- Disease in one endocrine gland may lead to altered activity of another endocrine gland
- Feedback effects may cause changes in endocrine gland
- Endocrine organs have high reserve capacity
What is the main function of the thyroid gland?
Synthesis, storage and release of T4 and T3
What is the main function of T4 and T3?
Regulate basal metabolic rate
What is the main function of calcitonin?
Regulates calcium homeostasis
What are the main histological features of the thyroid gland?
- Follicles
- Colloid-contains thyroglobulin
- Epithelial cells – TG synthesis, iodination, resorption & release of T4 and T3
- C-cells – secrete calcitonin
How can hyperthyroidism manifest?
Thyroxicosis
How can hypothyroidism manifest?
- Myxoedema
- Cretinism
- Subclinical
How can thyroid enlargement manifest?
- Goitre
- Isolated nodule/mass
How can most thyroid diseases be classified?
Primary
Give examples of thyroid diseases.
- Thyroiditis (autoimmune/others)
- Gland destruction
- Multinodular goitre
- Tumours (benign/malignant)
What can cause hyperthyroidism?
- Diffuse toxic hyperplasia (Graves disease) – 70%
- Toxic multinodular goitre – 20%
- Toxic adenoma
What is the pathophysiology of Grave’s disease?
- Autoimmune production of anti- TSH receptor antibodies
- Stimulate activity, growth, inhibit TSH binding
- Ophthalmopathy immune mediated – ocular fibroblasts have TSH receptor
Who does Grave’s disease usually affect?
- F>M
- Peak 20-40 years
- Genetic predisposition
How does the thyroid present in Grave’s disease?
Diffuse hyperplasia and hyperfunction
What changes are there in the histology of Grave’s disease?
- Increased cell activity
- Increase in cell numbers
What can cause hypothyroidism?
- Hashimoto’s thyroiditis (auto-immune destruction)
- Iatrogenic (surgery drugs)
- Iodine deficiency
- Congenital hypothyroidism
Who does Hashimoto’s thyroiditis usually affect?
- F>M
- 45-65years
What is the pathophysiology behind Hashimoto’s thyroiditis?
-Autoimmune destruction of thyroid epithelial cells
-Cytotoxic T cells, cytokine and antibody mediated destruction
-Circulating autoantibodies to
thyroglobulin, thyroid peroxidase
How does the thyroid present in Hashimoto’s thyroiditis?
Diffuse enlargement with gradual failure
What changes are there in the histology of Hashimoto’s thyroiditis?
- Hurthle cell change
- Intense infiltrate of lymphocytes and plasma cells
How does iodine deficiency cause multinodular goitre?
- Iodine deficiency, goitrogens
- Impaired synthesis of T3 and T4
- Increase in TSH
- Hypertrophy and hyperplasia of epithelium
- Simple goitre leads to multinodular
What changes are there in the histology of multinodular goitre?
- Crowded follicles
- Distended colloid filled follicles
- Haemorrhage, fibrosis, cystic change
- Nodular appearance
What may a thyroid nodular be?
- Dominant nodule in multinodular goitre
- Cyst
- Follicular adenoma
- Cracinoma
Give examples of different types of thyroid carcinomas.
-Differentiated thyroid carcinoma
-Papillary carcinoma (75-85%)
-Follicular
carcinoma (10-20%)
-Anaplastic carcinoma (5%)
-Medullary carcinoma (5%) (lymphoma)
How should thyroid nodules be investigated?
- TFTs
- Ultrasound
- FNA and cytlogy
Describe the features of follicular adenomas.
- Most non-functioning
- Circumscribed, encapsulated tumour
- Histology often small microfollicles
What are the featires of follicular carcinomas?
- Rare, usually solitary
- Malignant cells breach capsule
- Metastases – blood, bones
- RAS mutation of translocation
Who do papillary carcinomas usually affect?
- <50years
- ~2000/year
What can cause papillary carcinomas?
- BRAF mutation or RET/PTC gene rearrangement
- Exposure to ionising radiation
How do papillary carcinomas spread?
Lymphatics
What is the prognosis of papillary carcinomas?
Excellent prognosis - 95% survival (esp <45yrs 99% at 1yr)
What is the histology of papillary carcinomas?
- Papillary projections
- Empty nuclei
- Psammoma bodies
- May be cystic
What is a thyroid medullary carcinomas?
Malignant tumour of the C cells
What is produced by a thyroid medullary carcinoma?
Calcitonin (+/- other polypeptides)
What can cause thyroid medullary carcinomas?
- 70% sporadic
- 30% MEN2A, 2B, familial FMTC, mutations in RET proto-oncogene
What can be seen on histology of thyroid medullary carcinomas?
- Tumour cells
- Amyloid
How many parathyroid glands do you have?
4
How much do the parathyroid glands weigh?
120mg
How does primary hyperparathyroidism usually present?
Often asymptomatic hypercalcaemia
What can cause primary hyperparathyroidism?
- Sporadic or familial (MEN-1)
- Adenoma (85-95%
- Hyperplasia (5-10%)
- Carcinoma (rare)
What causes secondary hyperparathyroidism?
Physiological response to decrease Ca renal failure
What is the role of the hypothalamus?
- Maintain homeostasis
- Govern emotional behaviour
How is the nervous system linked to the endocrine system?
Via the pituitary gland
What is the pituitary?
Small gland located in the sella turcica
How is the pituitary connected to the hypothalamus?
By the pituitary stalk
What does the pituitary play a critical role in?
Regulating other endocrine glands
What does the anterior pituitary secrete?
- ACTH
- TSH
- GH
- Prolactin
- FSH/LH
How is the anterior pituitary controlled?
Controlled by release factors from hypothalamus
Where does the anterior pituitary receive its blood supply from?
Hypothalamus
What is the posterior pituitary?
Down growth of hypothalamus
What does the posterior pituitary secrete?
- ADH
- Oxytocin
Describe the histology of the anterior pituitary.
3 major cell types
- Pink acidophils which secrete GH and PRL
- Dark purple basophils which secrete ACTH, TSH, FSH and LH
- Pale chromophobes
What is the most common cause of pituitary hyperfunction?
Pituitary adenoma
Who is usually affected by pituitary adenomas?
-Adults aged 35-60 years
What can cause pituitary adenomas?
- Most sporadic
- 5% inherited e.g. MEN1
How do pituitary adenomas appear macroscopically?
- Soft, well-circumscribed lesion
- Small microadenomas may be incidental eg at post mortem
What is the histological appearance of pituitary adenomas?
- Cells of same appearance as normal gland
- Classified by hormone(s) produced by the neoplastic cells - detected by immunohistochemical stains
If functioning, what is the effect of a pituitary adenoma on the pituitary?
Hormone excess
What can a prolactinoma cause?
- Galactorrhoea
- Menstrual disorders
What does a GH secreting tumour lead to?
- Acromegaly
- Gigantism
What does a ACTH secreting tumour lead to?
-Cushing’s disease
If a pituitary tumour is large and produces mass pressure effect what can happen?
- Radiographic abnormalities
- Visual field abnormalities
- Elevated intracranial pressure
- Compression damage (hypopituitarism)
What can cause pituitary hypofunction?
- Compression by tumours such as craniopharnygiomas or metastatic lesions
- Trauma
- Infections such as TB or sarcoidosis
- Post partum ischaemic necrosis (Sheehan’s syndrome)
How much must be loss to result in pituitary hypofunction?
75%
What type of hormones does the adrenal cortex secrete?
Steroid hormones
What does the zona glomerulosa secrete?
-Mineralocorticoids such as aldosterone
What does the zona fasciculate secrete?
Glucocorticoids such as cortisol
What does the zona reticularis secrete?
Sex steroids such as oestrogen and androgens
What doe the neuroendocrine (chromaffin) cells of the adrenal medulla secrete?
Adrenaline/noradrenaline
What does adrenal hyperfunction lead to?
Clinical syndromes which depend in which adrenal hormones are stimulated
What 3 syndromes are associated with adrenal cortical hyperfunction?
- Hypercortisolism(CUSHING’S SYNDROME)
- Hyperaldosteronism (Conn’s syndrome)
- Adrenoginital syndormes
What is hypercortisolism called?
Cushing’s syndrome
What is exogenous Cushing’s syndrome due to?
Iatrogenic steroids
What can endogenous Cushing’s syndrome be classified as?
- ACTH dependent
- ACTH independent
Give examples of ACTH dependent causes of Cushing’s syndrome.
- Pituitary adenoma Cushings disease – 70%
- Ectopic ACTH
What can cause ACTH independent Cushing’s syndrome?
Functioning adrenal adenoma 10%
What is hyperaldosteronism called?
Conn’s syndrome
What can cause Conn’s syndrome?
- Bilateral idiopathic hyperplasia
- Functioning adrenal adenoma
What is secondary hyperaldosteronism due to?
Physiological due to decreased renal perfusion and increased renin-angiotension
What can cause adrenogenital syndromes?
- Functioning adrenal tumour
- Pituitary tumour Cushings disease
- Congenital adrenal hyperplasia (steroid enzyme deficiency)
What can cause acute adrenal insufficiency destruction of glands?
Meningococcal septicaemia (Waterhouse friderichsen)
What is primary chronic adrenal insufficiency destruction of glands caused by?
Addison’s disease
What can cause Addison’s disease?
- Autoimmune :(autoimmune polyendocrine syndromes – spare medulla)
- Infections: (TB, fungus HIV-related infections)
- Replacement: (metastatic carcinoma amyloidosis)
- Atrophy: (prolonged steroid therapy)
- Congenital hypoplasia
What is secondary adrenal insufficiency destruction of glands caused by?
Pituitary failure
What can functioning adrenocortical adenomas lead to?
- Hyperadrenal syndromes
- Atrophy of adjacent cortex
How are non-functioning adrenocortical adenomas often diagnosed?
Often incidental i.e. on imaging/autopsy
How do adrenocortical adenomas appear?
- Yellow-brown circumscribed
- Most 2-3cm <30g
How do adrenocortical adenomas appear histologically?
- Cells similar to those of normal cortex
- Nuclei small
- Some pleomorphism (“endocrine atypia”).
- Cytoplasm eosinophilic to vacuolated, depends on lipid
- Mitoses inconspicuous
What carcinomas can affect the adrenal cortex?
- Primary adrenocortical carcinoma
- Metastatic carcinoma
How do primary adrenocortical carcinomas appear?
- More likely functional- virilising
- Most large >20cm, haemorrhage and necrosis, cystic
How do primary adrenocortical carcinomas metastasise?
- By lymphatics and blood
- Invades adrenal vein
Who do primary adrenocortical carcinomas usually affect?
Rare but can affect any age
Where are metastatic adrenocortical carcinomas usually found?
- Lung
- Breast
What tumour affects the adrenal medulla?
Pheochromocytoma
Why do pheochromocytomas cause hypertension?
Adrenal medulla corticoids cells secrete catecholamines which raises BP
What can cause pheochromocytomas?
- Sporadic
- Up to 25% inherited e.g. MEN2
How do pheochromocytomas usually appear?
-Usually benign behaviour, can be bilateral
What is the histological appearance of a pheochromocytoma?
- Nests “Zellballen” of polygonal cells in vascular network
- Granular cytoplasm containing catecholamines
Why are pheochromocytomas referred to as the 10% tumour?
- 10% bilateral
- 10% non-functioning
- 10% malignant
- 10% extra adrenal
What is multiple endocrine neoplasia?
- Inherited disorders with underlying genetic mutation
- Hyperplasia/ neoplasms of endocrine organs (younger age, multifocal)
- Several distinct syndromes
What syndrome is MEN1 associated with?
Wermer syndrome
What causes Wermer syndrome?
MEN 1 tumour suppressor gene mutation -defect in menin protein involved in regulating cell growth
How does Wermer syndrome manifest?
- Parathyroid hyperplasia and adenomas
- Pancreatic and duodenal endocrine tumours (hypoglycaemia and ulcers)
- Pituitary adenoma (prolactinoma)
What is the genetic association with MEN2?
RET proto-oncogene mutations
What tumours is MEN2 associated with?
- Medullary carcinoma of thyroid
- Pheochromocytoma
What syndrome is MEN2A associated with?
Sipple syndrome and parathyroid hyperplasia
What causes MEN2A?
Extracellular domain auto dimerisation of RET receptor
How does MEN2B manifest itself?
- Neuromas of skin &mucous membrane
- Skeletal abnormalities
Who does MEN2B affect?
Younger patients, agresisive
What does MEN2B cause?
Autoactivation of tyrosine kinase pathway
