HISTO: Endocrine disease Flashcards
What cells does the anterior vs posterior pituitary consist of?
Anterior – epithelial cells, supplied by blood from pituitary portal system (hypothalamus –> pituitary)
Posterior – nerve cells, supplied by nerves from the supraoptic nucelus and paraventricular nucelus
What are anterior pituitary cells derived from? What do they secrete and under what control?
Epithelial cells derived from developing oral cavity
Secrete trophic hormones under the control of factors released by the hypothalamus
List the hormones produced by the anterior pituitary and their stimulus.
Define hyperpituitarism and name the most common cause.
Excess secretion of trophic hormones
Usually due to functional adenoma
How are pituitary adenomas classified?
Now classified on the basis of the hormones produced - detected by immunohistochemistry
What cell type is most common in pituitary adenomas?
Prolactin cells are found in ~20% of pituitary adenomas
Sometimes none of these cells are present and sometimes there is a mix of several different ones
What % of intracranial tumours do pituitary adenomas make up?
When do pituitary adenomas usually occur?
What is a microadenoma?
10% of intracranial tumours - discovered incidentally in of autopsies 25%
Peak in 4th - 6th decade
Microadenomas = < 1cm
What are the clinical features associated with different pituitary adenomas? (e.g. prolactinomas, GH adenomas, CRH adenomas)
Prolactinomas
- Amenorrhea, galactorrhea, loss of libido, infertility
- Usually diagnosed earlier in females of reproductive age
Growth hormone adenomas
- Prepubertal children - gigantism
- Adults - acromegaly
- Diabetes mellitus, muscle weakness, hypertension, congestive cardiac failure
Corticotroph cell adenomas = Cushing’s syndrome
Name 3 causes of hypopituitarism.
- Nonsecretory pituitary adenomas
- Ischaemic necrosis
- Ablation of pituitary by surgery or irradiation
What are some causes of ischaemic necrosis of the pituitary leading to hypopituitarism?
Most commonly post-partum (Sheehan’s syndrome) – pituitary enlarges during pregnancy and so is susceptible to ischaemia especially in PPH
DIC, sickle cell anaemia, elevated ICP, shock
What are the manifestations of anterior pituitary hypofunction in children vs adults?
Children: growth failure (pituitary dwarfism)
Adults:
- 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 hormones are produced by the posterior pituitary?
Posterior pituitary releases two peptides - antidiuretic hormone (ADH) and oxytocin
What is a common clinical defects of the posterior pituitary?
Clinically important posterior pituitary syndromes involve ADH
- diabetes insipidus
- Inappropriately high ADH
What are 3 complications of large pituitary tumours?
- Compression of optic chiasm - bitemporal hemianopia
- Elevated ICP and its symptoms
- Obstructive hydrocephalus
Describe the main functions of the thyroid.
BMR
- TSH from anterior pituitary
- –> follicular epithelial cells take up (pinocytose) colloid
- –> convert thyroglobulin into T4 and T3
- –> released into circulation
- –> Increased in BMR
Calcium regulation
- Thyroid also contains parafollicular/‘C’ cells that synthesize calcitonin
- Promotes absorption of calcium by the skeletal system
What is the difference between toxic and non-toxic goitre?
Non toxic = no production of hormones.
What is the most common cause of non-toxic goitre? What are some other causes?
- Iodine deficiency - endemic in areas where iodine in soil and water is low
- Puberty in females
- Ingestion of brassicas or other substances interfering with TH synthesis
- Hereditary enzyme defects
What are the complications of multinodular goitres (which can become large)?
- dysphagia and airways obstruction
- hyperthyroidism if hyperfunctioning nodule present
What is thyrotoxicosis?
Hypermetabolic state caused by elevated circulating levels of free T3 and T4
What are the causes of thyrotoxicosis? What is the most common cause?
Graves disease is the most common cause
Primary
- Grave’s disease
- Hyperfunctioning multinodular goitre
- Hyperfunctioning adenoma
- Thyroiditis
Secondary
- TSH secreting pituitary adenoma (rare, <1%)
What are some rare causes of thyrotoxicosis not associated with thyroid disease?
- Struma ovarii (ovarian teratoma with ectopic thyroid)
- Factitious thyrotoxicosis (exogenous thyroid intake)
What is the triad of Grave’s disease?
- Thyrotoxicosis
- Infiltrative ophthalmopathy with exophthalmos in up to 40%
- Infiltrative dermopathy (pretibibial myxoedema) in a minority of cases
Who is most affected by Grave’s disease?
Primarily younger adults. F:M, 7:1
What is the pathogenesis of Grave’s disease? What other conditions is it associated with?
Autoimmune - variety of antibodies including antibodies to TSHr and thyroglobulin (TG)
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
- Addison’s disease
What is the ‘opposite’ of Grave’s disease?
Hashimoto’s disease manifested by hypothyroidism
What are the primary and secondary causes of hypothyroidism?
Primary
- Postablative (after surgery or radioiodine therapy)
- Autoimmune - Hashimoto’s thyroiditis
- Iodine deficiency
- Congenital biosynthetic defect
Secondary
- Pituitary or hypothalamic failure (uncommon)
How does Hashimoto’s present?
- Hypothyroidism
- Painless enlargement of the thyroid
- Females 15:1 ages 45-65 years
What is a histopathological feature of Hashimoto’s seen here?
Epithelial cells become enlarged with eosinophilic cytoplasm - Hürthle cells
There is also usually:
- Infiltration of lymphoid cells
- Presence of germinal centres within the thyroid showing that it is AI disease
What are the types of neoplasms of the thyroid split into?
- Adenomas –Benign neoplasms of follicular epithelium
- Carcinomas - Uncommon and account for less than 1% of solitary thyroid nodules
NB: neoplasms of the thyroid are uncommon in general
What characteristics suggest that a thyroid nodule may be neoplastic?
- Solitary rather than multiple
- Solid rather than cystic
- Younger patient
- Male
- Cold nodule (does not take up iodine)
What is the most important investigation for diagnosing a neoplastic thyroid nodule?
Ultimately it is the morphology that provides the answer
- Fine needle aspiration cytology
- Histology
What are the characteristics of thyroid adenomas?
- Solitary
- Well circumscribed + compresses the surrounding parenchyma
- Well formed capsule
- May rarely cause thyrotoxicosis
*Important to examine the capsule for invasion to exclude follicular carcinoma*
What are the types of thyroid carcinomas? Which is the most common?
- Papillary (75-85%)
- Follicular (10-20%)
- Medullary (5%)
- Anaplastic (<5%)
Usually occur in adults and make up <1% of cancer deaths.
What are the risk factors for thyroid carcinomas?
Genetic factors - inc. MEN
Ionizing radiation - papillary carcinomas
What type of thyroid tumour does ionizing radiation most commonly cause?
Primarily papillary carcinomas
What is diagnosis of papillary carcinomas based on?
They don’t all have papillary features (as the name may suggest) so diagnosis is based on NUCLEAR FEATURES:
- Optically clear nuclei
- Intranuclear inclusions
They may also contain psammoma bodies
When do papillary carcinomas occur in terms of age?
Any age
How do papillary carcinomas present?
- May present with metastases in cervical nodes
- Painless neck mass
- Nonfunctional
What is seen on this slide of papillary carcinoma?
- Psammoma body seen in the middle (focus of calcification)
- Nuclei look empty
What is the prognosis with papillary carcinomas?
- 10 year survival up to 90%
Where do follicular carcinomas metastasise to?
- Lung
- Bone – lung, breast and adrenal also characteristically metastasise to bone
- Liver
What are the features of follicular carcinomas? When do they occur?
- Follicular morphology
- May be well demarcated with minimal invasion or clearly infiltrative
Peak incidence in middle age
What are medullary carcinomas?
Neuroendocrine neoplasm derived from parafollicular C cells
What is the aetiology of most medullary carcinomas?
- 80% sporadic - adults 5-6th decade
- 20% familial - MEN - younger patients
What feature of medullary carcinomas is seen here?
Calcitonin that they produce is broken down and deposited in the tumour like amyloid
Congo red stain under polarised light allows its detection (as seen in green)
What is the causes of death in most anaplastic carcinomas of the thyroid?
Most cases death within one year due to local invasion
Features:
- Occur in elderly patients
- Very aggressive
- Metastases common
Where can the parathyroid glands be located?
Usually close to upper and lower poles of thyroid but may be in the thymus or anterior mediastinum
What are the functions of the parathyroid glands?
Paarthyroid activity is controlled by level of free calcium in blood whereby 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 the most common causes of hyperparathyroidism?
- 80-90% - solitary adenoma
- 10-20% hyperplasia of all 4 glands - sporadic or component of MEN type 1
- <1% carcinoma
What are the features seen in this parathyroid adenoma?
- Thin capsule
- Normal parathyroid at the bottom
- Normal parathyroid is about 50% fat whereas the adenoma has very little fat
What are the laboratory features of hyperparathyroidism?
- High serum ionised calcium
- PTH is high in parathyroid causes of hypercalcaemia
What are the clinical features of 1o 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 is the pathophysiology of secondary hyperparathyroidism?
Caused by any condition associated with chronic depression of serum calcium e.g. renal failure which is the most common cause
Parathyroid glands become enlarged - may be asymmetrical
Leads to bone changes as with primary disease
What are the causes of hypoparathyroidism?
- Surgical ablation (most common) – usually surgeons aim to remove 3 and a half of the glands to treat hyperparathyroidism due to hyperplasia. In adenoma you just remove the adenoma.
- Congenital absence
- Autoimmune
What are the clinical manifestations of hypoparathyroidism?
- Neuromuscular irritability - tingling, muscle spasms, tetany
- Cardiac arrhythmias
- Fits
- Cataracts
What types of cells does the adrenal cortex vs medulla consist of?
Cortex = epithelial
Medulla = neural cells
What are the layers of the adrenal gland? What does each layer produce?
- Zona glomerulosa – secretes aldosterone
- Zona fasciculata – secretes glucocorticoids
- Zona reticularis – secretes androgens and glucocorticoids
- Medulla – noradrenaline and adrenaline
What are the main three clinical manifestations of arenocortical hyperfunction?
- Cushing’s syndrome – excess glucocorticoids
- Hyperaldosteronism
- Virilising syndromes – excess androgens
What are the clinical features 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?
Administration of exogenous glucocorticoids - adrenal glands become atrophic
What are the endogenous causes of Cushing’s syndrome?
(1) >50% caused by Cushing’s disease (high ACTH)
- Pituitary adenoma - producing ACTH
- Pituitary hyperplasia -of ACTH secreting cells
- Adrenal glands show nodular cortical hyperplasia
(2) 30% are primary adrenal disease due to:
-
Solitary neoplasm:
- Adenoma
- Carcinoma
- Bilateral hyperplasia (uncommon)
What are the exogenous causes of Cushing’s syndrome?
Secretion of ectopic ACTH by non-endocrine tumours - most commonly small cell carcinoma of the lung
Adrenals show bilateral hyperplasia
What is a serious consequence of stopping steroids suddenly?
Addisonian crisis.
What is the most common cause of primary hyperaldosteronism?
Conn’s syndrome in 35% = aldosterone secreting adenoma
60 % have bilateral adrenal hyperplasia
What are the clinical manifestations of primary hyperaldosteronism?
HTN and hypokalaemia
NB accounts for <1% of causes of hypertension but important to recognise as surgically correctable
What are adrenogenital syndromes? What is a common cause?
Syndromes due to excess androgens
Causes:
- Commonly from neoplasms (usually carcinomas rather than adenomas)
- May be caused by congenital adrenal hyperplasias
What is the cause of congenital adrenal hyperplasia? What is the pathophysiology?
AR inheritance
Enzymes of cortisol biosynthesis are defective
Decreased cortisol –> high ACTH –> adrenal stimulation –> increased androgen synthesis
Usually presents in childhood
What are the primary causes of adrenal insufficiency?
Acute
- Sudden withdrawal of corticosteroid therapy
- Haemorrhage (neonates)
- Sepsis with DIC (Waterhouse-Friderichson syndrome)
Chronic (Addison’s disease)
- Autoimmune (75-90%)
- TB
- HIV
- Metastatic tumour (lung and breast particularly)
- Rarely amyloid, fungal infections, haemochromatosis, sarcoidosis
What are the secondary causes of adrenal insufficiency?
Secondary to reduced ACTH
- Non-functional pituitary adenomas
- Other lesions of pituitary or hypothalamus including infarction
What are the main features of adrenocortical neoplasms?
Adenomas - most non-functional but may be associated with Cushing’s syndrome or Conn’s syndrome
Carcinomas – rare, usually large and more commonly associated with virilizing syndrome than adenoma
What stimulates release of catecholamines from the adrenal medulla?
sympathetic nervous system
What 2 neoplasms may occur in the adrenal medulla?
- Phaeochromocytoma
- Neuroblastoma
What is the rule of 10s in phaeochromocytomas?
- 10% familial - arise in association with a familial syndrome inc. MEN 2A and 2B, von Hippel-Lindau disease and Sturge-Weber syndrome
- 10% bilateral
- 10% malignant
- 10% outisde - arise outside the adrenal (paragangliomas)
What is the name given to phaeochromocytomas that occur outside of the adrenals?
Paragangliomas – usually occur along sympathetic chain along the sides of the spine or in the neck
Define MEN syndrome.
Group of inherited diseases resulting in proliferative lesions (hyperplasias, adenomas and carcinomas) of multiple endocrine organs
What is the pattern of tumours occurring in MEN syndromes?
- Younger age
- Multiple endocrine organs affected
- Often multifocal
- Preceded by hyperplasia
- Aggressive and harder to treat
What is the most common form of thyroid cancer?
Papillary carcinoma
What type of thyroid carcinoma arises from the parafollicular or C cells of the thyroid?
Medullary carcinoma of the thyroid
What syndrome is caused by adrenal adenoma that secretes aldosterone?
Conn’s syndrome
