Pathology of Pituitary and Adrenal Glands Flashcards
What are some features of the anterior pituitary?
Also called the adenohypophysis, derived from Rathke’s pouch, secretes trophic (TSH, ACTH, FSH, LH) and non-trophic (GH, PRL) hormones
What are some features of the posterior pituitary?
Also called the neurohypophysis, extension of neural tissue consisting of modified glial cells and axonal processes, secretes ADH and oxytocin
What is the appearance of the anterior pituitary histologically?
Islands, cords of cells
Acidophils = somatotrophs (GH, 50%), mammotrophs (PRL, 20%)
Basophils = corticotrophs (ACTH, 20%), thyrotrophs (TSH, 5%0, gonadotrophs (FSH/LH, 5%)
What is the histological appearance of the posterior pituitary?
Contains non-myelinated axons of neurosecretory neurons
What are some pathologies that affect the anterior pituitary?
Hyperfunction = adenoma, carcinoma Hypofunction = surgery/radiation, sudden haemorrhage into gland, ischaemic necrosis (Sheehan syndrome), tumours extending into sella, inflammatory conditions
What are some pathologies that can affect the posterior pituitary?
Diabetes insipidus = lack of ADH
Syndrome of inappropriate ADH secretion (SIADH) = ectopic ADH secretion by tumours, primary disorder of pituitary
What are some features of pituitary adenomas?
Derived from anterior pituitary cells, relatively common (10% of intra-cranial tumours), sporadic or associated with MEN1 (Wermer syndrome)
How are pituitary adenomas classified?
Cell type/hormone produced = prolatin (20-30%), ACTH (10-15%), FSH/LH (10-15%), GH (5%)
How many hormones can pituitary adenomas secrete?
Can secrete more than one = can also be hypo/non-functional (25-30%), hormone production may be at sub-clinical level
What are some complications of large adenomas?
Visual field defects, pressure atrophy of surrounding normal tissue, infarction can lead to panhypopituitarism
What are some examples of functional pituitary adenomas?
Prolactinoma, growth-hormone secreting, ACTH-secreting, carcinoma
What are some features of prolactinomas?
Most common functional tumour (30%), may cause infertility, lack of libido or amenorrhoea (25%)
What are some features of growth-hormone secreting adenomas?
Second most common functional tumour, GH causes increase in Insulin-like growth factor (IGF), stimulates growth of bone, cartilage and connective tissue (gigantism, acromegaly)
What are some features of ACTH-secreting adenomas?
Usually micro-adenomas, may cause Cushing’s disease or bilateral; adrenocortical hyperplasia
What are some features of pituitary carcinomas?
Rare (<1% of pituitary tumours), usually produce prolactin or ADH, metastasise late after multiple recurrences
How does pituitary hypofunction usually occur?
Usually panhypopituitarism = rarely affects individual hormones
What are the features of pituitary hypofunction?
Depends on the cause:
Granulomatous inflammation = sarcoidosis
Infarction = Sheehan’s syndrome
Primary or metastatic tumours
What are craniopharyngiomas?
Derived from remnants of Rathke’s pouch = 1-5% of intra-cranial tumours
What are some features of craniopharyngiomas?
Slow growing, often cystic, may calcify, some arise in sella but most are suprasellar
How do craniopharyngiomas present?
Headaches and visual disturbances, children may have growth retardation, bimodal incidence = age 5-25, 60-70s
What is the prognosis of craniopharyngiomas?
Excellent, especially if <5cm
SSC may develop after radiation (rarely)
What are some posterior pituitary syndromes?
Diabetes insipidus
SIADH secretion = ectopic production of ADH (paraneoplastic syndrome)
What are the types of diabetes insipidus?
Central = ADH deficiency, caused by trauma (including surgery), tumours and inflammatory disorders of hypothalamus and pituitary Nephrogenic = renal resistance to ADH effects
What is the anatomy of the adrenal gland?
Bilateral glands of 4-5g each, sit superior and medial to upper pole of kidneys, composed of outer cortex and inner medulla
What pathology can affect the adrenal gland?
Hypo/hyperfunction = both cortex and medulla
ACTH secretion from functional adenoma, shock/DIC, any condition that damages adrenal tissue
How is the adrenal cortex organised?
Into three zones = zona glomerulosa (mineralocorticoids, aldosterone), zona fasciculata (glucocorticoids, cortisol), zone reticularis (sex steroids, glucocorticoids)
What pathologies can affect the adrenal cortex?
Hyperfunction = hyperplasia, adenoma, carcinoma Hypofunction = acute (Waterhouse-Friderichsen), chronic (Addison's)
What causes congenital adrenocortical hyperplasia?
Group of autosomal recessive disorders = deficiency of enzyme required for steroid biosynthesis
What does congenital adrenocortical hyperplasia cause?
Altered biosynthesis leads to increased androgen = masculination, precocious puberty
What does the reduced cortisol caused by congenital adrenocortical hyperplasia cause?
Stimulate ACTH and causes cortical hyperplasia (10-15 times normal weight)
What are causes of acquired adrenocortical hyperplasia?
Endogenous ACTH production = pituitary adenoma (Cushing’s disease), ectopic ACTH (paraneoplastic)
Bilateral adrenal enlargement (up to 30g)
Diffuse (ACTH driven) or nodular (non-ACTH dependent)
What are some features of adrenocortical tumours?
Mainly adults (Li-Fraumeni syndrome in young), more common in men, present with incidental finding, hormonal effects or mass lesion
What can carcinomas with necrosis cause?
A fever
How do adrenocortical adenomas appear?
Well circumscribed, encapsulated lesions, usually small (2-3cm), yellow/yellow-brown cut surface (lipid), small nuclei
What are some features of adrenocortical adenomas?
Composed of cells resembling adrenocortical cells, usually non-functional, mitoses are rare
What are some features of adrenocortical carcinomas?
Rare, more likely to be functional, virilising tumours usually malignant, can closely resemble adenoma
How can adrenocortical carcinomas spread?
Local invasion to retroperitoneum or kidney, metastases usually vascular to liver, lung and bone, may spread to peritoneum, plura or regional lymph nodes
What is the prognosis of adrenocortical carcinomas?
% years survival = 20-35%
50% dead in two years
What features of a tumour are suggestive of an adrenocortical carcinoma?
Large size (>50g, >20cm), haemorrhage and necrosis, frequent and atypical mitoses, lack of clear cells, capsular or vascular invasion
What are the causes of primary hyperaldosteronism?
Conn’s syndrome, 60% associated with diffuse/nodular hyperplasia of both adrenal glands, 35% adenomas, rarely carcinoma
What are some features of adenomas associated with primary hyperaldosteronism?
Solitary, small, bright yellow and buried within the gland, don’t suppress ACTH so adjacent and contralateral tissue is not atrophic
What are some features of causes of primary aldosteronism that are glucocorticoid remediable?
Uncommon genetic disorder with production of hybrid steroids, cortisol and aldosterone, under influence of ACTH
What are some examples of adrenocortical hyperfunction?
Primary hyperaldosteronism ad hypercortisolism
What are some causes of hypercortisolism?
Cushing’s syndrome or disease, exogenous (iatrogenic i.e steroids), endogenous
What are some endogenous causes of hypercortisolism?
ACTH dependent = ACTH secreting pituitary adenoma (70%), ectopic ACTH (10%)
ACTH independent = adrenal adenoma (10%) or carcinoma (5%), non-lesional adrenal gland atrophies
What does ACTH-dependent endogenous hypercortisolism cause?
Gives rise to adrenal hyperplasia
What are secondary causes of adrenocortical hypofunction?
Failure to stimulate adrenal cortex (hypopituitarism), suppression of adrenal cortex (steroids)
What are some acute causes of primary adrenocortical hypofunction?
Rapid withdrawl of steroids, crisis in patient’s with chronic adrenocortical insufficiency, massive adrenal haemorrhage
In what cases would massive adrenal haemorrhage cause acute primary adrenocortical hypofunction?
Newborn, anticoagulation therapy, DIC, septicaemic infection
What are some causes of chronic primary adrenocortical hypofunction?
Addison’s, autoimmune adrenalitis, infection (TB, histoplasma, HIV), metastatic malignancy (lung, breast)
Unusual causes = amyloid, sarcoidosis, haemochromatosis
When do signs and symptoms of chronic primary adrenocortical hypofunction present?
Once >90% of the gland has been destroyed
How does Addison’s disease present?
Insidious onset = manifests once significant decrease in glucocorticoid and mineralocorticoid levels
What are the symptoms of Addison’s disease?
Weakness, fatigue, anorexia, nausea, vomiting, weight loss, diarrhoea, pigmentation (raised POMC)
What do the decreased mineralocorticoid levels in Addison’s disease cause?
K+ retention, Na+ loss, hyperkalaemia, hyponatraemia, volume depletion, hypotension
What does the decreased glucocorticoids in Addison’s disease cause?
Hypoglycaemia
What occurs in Addison’s disease crisis?
Triggered by stress (infection, surgery, trauma) = vomiting, abdominal pain, hypotension, shock, death
What is the anatomy of the adrenal medulla?
Central core of adrenal, innervated by pre-synaptic fibres from sympathetic nervous system, contains neuroendocrine (chromaffin) cells (secrete catecholamines)
What are some tumours of the adrenal medulla?
Phaeochromocytoma, neuroblastoma
What are some features of neurofibromas of the adrenal medulla?
Usually diagnosed at 18 months, 40% diagnosed in infancy, 40% arise in adrenal medulla, remainder mostly along sympathetic chain
What is the histological appearance of neurofibromas?
Composed of primitive appearing cells but can show maturation and differentiation towards the ganglion cells
What is associated with a poorer prognosis in neurofibromas?
Amplification of N-myc and expression of telomerase
What are phaeochromocytomas?
Neoplasm derived from chromaffin cells of adrenal medulla = secret catecholamines, rare cause of secondary hypertension
What are features of the hypertension associated with phaeochromocytomas?
Occur in 90%, paroxysmal episodes common, episodes triggered by stress, exercise, posture or palpation of tumour, associated with micturition when in bladder
What are complications of phaeochromocytomas?
Cardiac failure, infarction and arrhythmias
How are phaeochromocytomas diagnosed?
Detection of urinary excretion of catecholamines and metabolites
What is the “rule of 10” of phaeochromocytomas?
10% extra-adrenal (paragangliomas), 10% bilateral (up to 50% in familial), 10% malignant (more common in extra-adrenal), 10% not associated with hypertension
What are some features of familial phaeochromocytomas?
25% of cases, germline mutations, often bilateral, malignant if associated with germline mutations of B subunit of succinate dehydrogenase
What is the appearance of phaeochromocytomas?
Range from small to large (average 100g), may see adrenal remnants on surface, yellow, red/brown to haemorrhagic and necrotic
What effect does K2Cr2O7 have on phaeochromocytomas?
Turns the tumour dark brown
What do cells characteristically form in phaeochromocytomas?
Tumour cells form nests (zellballen)
How do phaeochromocytomas spread?
Propensity for skeletal metastasis = also regional lymph nodes, liver and lung
What does MEN2a (Sipple syndrome) cause?
Phaeochromocytomas (40-50%), medullary thyroid carcinoma (100%), parathyroid hyperplasia (10-20%)
What are the phaeochromocytomas that occur dues to Sipple syndrome like?
May be bilateral and extra-adrenal
What is the mutation that causes MEN2a?
Linked to germline gain of function mutation in RET oncogene on chromosome 10q11.2
What occurs in MEN2b?
Phaeochromocytoma, meduallry thyroid cancer, neuromas and gangliomas, marfanoid habitus
What mutation causes MEN2b?
Germline mutation in RET oncogene = almost always activating point mutation in the catalytic domain of the encoded enzyme
