Endocrine Disorders Flashcards
What is the anatomy of the pituitary?
o Anterior pituitary = epithelial cells
§ Blood supply from portal system
o Posterior pituitary = nerve cells
§ Nerves from supraoptic and paraventricular nuclei
§ Release ADH and oxytocin
What is the anterior pituitary made of?
o Composed of epithelial cells from the developing oral cavity
o Secrete hormones that are under the influence of control factors released by the hypothalamus
What are the symptoms of pituitary disease?
o Hyperpituitarism
§ Excess secretion of trophic hormones
§ Usually due to a functional adenoma
o Hypopituitarism
§ Deficiency of hormones
o Local mass effect
What are the adenoma growths?
o 30% prolactinoma, 15% ACTH-oma, 15% GH-oma
o 20% non-functioning adenoma
How do we classify tumours?
Classified on basis of the hormones produced
o Detected by immunohistochemistry
o Prolactinoma most frequent
o N.B. “null cell” produces no hormones
What is the epidemiology of tumours?
o Pituitary adenomas = ~10% overt intracranial tumours
o Discovered incidentally in up to 25% of autopsies
o Age: 30-50 years
o Defined as a ‘microadenoma’ if <1 cm
What are the clinical effects of the functioning pituitary adenomas?
o Prolactinomas
§ Amenorrhoea, galactorrhoea, loss of libido, infertility
§ Usually diagnosed quicker in females of reproductive age
o Growth Hormone Adenomas
§ Prepubertal children -> gigantism
§ Adult -> acromegaly
§ Diabetes, muscle weakness, hypertension, congestive cardiac failure
o Corticotroph Cell Adenomas
§ Cushing’s disease
What is hypopituitarism caused by?
Most cases are caused by:
o Non-secreting pituitary adenoma
o Ischaemic necrosis -> MOST COMMONLY post-partum (Sheehan syndrome)
§ This is because the pituitary enlarges during pregnancy and is more susceptible to ischaemia
§ If you get a post-partum haemorrhage (Sheehan syndrome) you may develop ischaemia
§ Other causes… DIC, sickle cell anaemia, elevated ICP, shock
o Iatrogenic: ablation of pituitary by surgery or irradiation
What are the clinical features of hypopituitarism?
o Children – growth failure (pituitary dwarfism)
o Gonadotrophin deficiency
§ Amenorrhoea and infertility in women
§ Decreased libido and impotence in men
o TSH and ACTH deficiency – secondary hypothyroidism and secondary hypoadrenalism
o Prolactin deficiency – failure of post-partum lactation
What are the posterior pituitary syndromes?
Posterior pituitary syndromes = 2 peptides released by the posterior pituitary:
o ADH -> deficiency, insensitivity, excess -> DI or SIADH
o Oxytocin
What is the Local Mass Effect of Pituitary Tumours?
· Compression of optic chiasm gives rise to bitemporal hemianopia
· As the tumour gets larger, you may get features of raised ICP (e.g. headaches)
o In severe cases, you may get obstructive hydrocephalus
What is the thyroid gland?
· The follicles have a small amount of stromal tissue in between them
· Follicles lined by epithelial cells and have lots of colloid in the middle
· Parafollicular cells are found in between the follicles
What is the physiology of thyroid?
o In response to TSH, follicular epithelial cells pinocytose the colloid and convert thyroglobulin into T4 and T3
o T4 and T3 are released into the circulation and they increase basal metabolic rate
o Parafollicular cells (C cells) produce calcitonin which promotes the absorption of calcium by the skeletal system
What is a non toxic goitre?
enlargement without overproduction of thyroid hormones
§ Common if there is impaired synthesis of thyroid hormones (most often due to iodine deficiency)
· There are certain parts of the world where iodine intake is low (developing countries)
§ May be seen during puberty in girls
§ Ingestion of some substances that interfere with thyroid hormone synthesis can cause it (e.g. brassicas)
§ May be due to hereditary enzyme deficiency
What is a multinodular goitre?
§ With time, simple thyroid enlargement may be transformed to multinodular pattern
§ May become massive and cause mechanical effects such as dysphagia and airway obstruction
§ A hyperfunctioning nodule may develop -> hyperthyroidism
What are the causes of thyrotoxicosis?
o Primary Causes
§ Graves’ disease Hyperfunctioning multinodular goitre
§ Hyperfunctioning adenoma Thyroiditis
o Secondary Causes
§ TSH secreting pituitary adenomas (RARE)
o Causes that are NOT associated with the thyroid gland
§ Struma ovarii (ovarian teratoma with ectopic thyroid)
§ Factitious thyrotoxicosis (exogenous thyroid intake)
What is Graves’?
§ MOST COMMON cause of endogenous hyperthyroidism; mostly in FEMALES (7x)
§ Triad presentation: Thyrotoxicosis Exophthalmos Pretibial myxoedema
§ Autoimmune disorder associated with a variety of antibodies to the TSH-R and thyroglobulin
· They stimulate thyroid hormone release and increases proliferation of the epithelium
§ Associated with other AI diseases (SLE, pernicious anaemia, T1DM and Addison’s disease)
§ NOTE: autoimmune diseases of the thyroid gland are a SPECTRUM (from Graves to Hashimoto’s)
· Antibodies against thyroid antigens are common to both conditions but they differ in functio
What are the causes of hypothyroidism?
o Primary Causes
§ Post-ablative (after surgery or radioiodine therapy) Autoimmune (Hashimoto’s)
§ Iodine deficiency Congenital biosynthetic defect
o Secondary Causes
§ Pituitary or hypothalamic failure (UNCOMMON)
o Hashimoto’s Thyroiditis (the opposite of AI disease from Graves’ disease)
§ Common; F>M; 45-65yo Anti-TG ABs
§ Painless enlargement Anti-TPO ABs
§ Histology à lot of lymphoid cells with germinal centres
· Hurthle cells = epithelial cells become large with lots of eosinophilic cytoplasm
· Lymphoid cells = chronic infection / A
What are the neoplasms of the thyroid gland?
· Adenomas – benign neoplasms of the follicular epithelium
· Carcinomas – uncommon and account for <1% of solitary thyroid nodules
What are the features suggestive of neoplasia?
o Solitary rather than multiple
Solid rather than cystic
o Younger patients
M>F
o Nodules NOT take up radioiodine (cold nodule)
What is required to give a definitive answer?
o FNA
o Histology
What are adenomas of the thyroid like?
o Usually solitary
Well circumscribed and compress the surrounding parenchyma
o Well-formed capsule
Small proportion will be functional and cause thyrotoxicosis
o Important to examine the capsule for invasion to exclude follicular carcinoma
What are the 4 types of thyroid cancer?
FOUR types – PFMA:
§ Papillary (80%) Psammoma bodies (calcifications), Orphan’s Annie Eyes (clear nuclei)
§ Follicular (15%)
§ Medullar (5%) Amyloid in thyroid (Congo red stain)
§ Anaplastic (< 5%)
What are the RFs for thyroid cancer?
§ Genetic factors (e.g. MEN)
§ Ionising radiation (mainly papillary carcinoma)
Describe papillary carcinoma?
§ Can occur at any age
§ May have papillary architecture (central connective tissue stalk with surrounding epithelium)
§ Diagnosis is based on nuclear features:
· Optically clear nuclei
· Intranuclear inclusions
· May have psammoma bodies (little foci of calcification)
§ Generally non-functional and present as a painless mass in the neck
§ May present with cervical lymph node metastasis
§ 10-year survival of 90%
What is follicular carcinoma?
§ Peak incidence in middle age
§ Follicular morphology
§ May be well demarcated or show invasion
§ Usually metastasise via the bloodstream to the lungs, bone and liver
What is medullary carcinoma?
§ Neuroendocrine neoplasm derived from parafollicular C-cells
§ 80% are sporadic (40-50-year-olds); 20% are familial (MEN - younger patients -> 2A, 2B)
§ Characteristic feature: calcitonin produced by the tumour cells is broken down and deposited as amyloid within the thyroid -> visualised using Congo Red and looking at it under polarised light
What is anaplastic carcinoma?
§ Occur in elderly patients
§ Very aggressive
§ Metastases are COMMON -> most patients die within 1 year due to local invasion
What is parathyroid tissue?
Derive from developing pharyngeal pouches -> 4 parathyroid glands [can be located in thymus or anterior mediastinum]
What is the physiology of parathyroid hormone?
Physiology = decreased calcium stimulates PTH release -> PTH actions:
o 1 alpha hydroxylase activation -> calcidol to calcitriol -> gut effects
o Osteoclast activation-> Ca2+ liberation
o Direct renal calcium resorption
o Direct renal phosphate excretion
What is normally hyperparathyroidism?
§ 80-90% are due to a solitary adenoma
§ 10-20% are due to hyperplasia of ALL four glands
· Sporadic OR a component of MEN T1, 2a
§ <1% are due to carcinoma
Clinical features of high PTH?
§ Hypercalcaemia
· Most common case of incidentally discovered hypercalcaemia
· PTH is high in comparison with the hypercalcaemia due to non-parathyroid disease
· Bone resorption with thinning of the cortex and cyst formation (osteitis fibrosa cystica)
o This can lead to fractures = BONES N.B. normal PTH with a high calcium
§ Renal stones and obstructive uropathy = STONES = hyperparathyroidism
§ GI disturbance (constipation, pancreatitis, gallstones) = GROANS
§ CNS alterations (depression, lethargy, seizures) = PSYCHIC MOANS
§ Neuromuscular abnormalities (weakness)
§ Polyuria and polydipsia
What is secondary hyperparathyroidism?
§ Caused by any condition (usually low vitamin D) -> causes chronically low calcium
§ Vitamin D deficiency is the MOST COMMON cause (i.e. renal failure -> low vitamin D)
§ The parathyroid glands become enlarged (may be asymmetrical)
§ Leads to bone changes (as in primary disease)
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What is hypoparathyroidism?
o Causes:
§ Surgical ablation
§ Congenital absence (DiGeorge syndrome)
§ Autoimmune
o Clinical features:
§ Neuromuscular irritability (tingling, muscle spasms, tetany)
§ Cardiac arrhythmias
§ Fits
§ Cataracts
o Mnemonic: CATS go numb (convulsions, arrhythmia, tetany, spasms, numbness)
What is MEN?
a group of inherited conditions resulting in proliferative lesions (hyperplasia, adenomas and carcinomas) of multiple endocrine organs
· Tumours occur at a younger age than sporadic tumours
· Arise in more than one endocrine organ or may be multifocal within one endocrine organ
· Tumours are often preceded by hyperplasia
· Tumours are usually more aggressive than sporadic tumours and harder to treat
What tumour exists of the adrenal medulla?
o Secretes catecholamines in response to signals from the CNS
o Diseases:
§ Phaeochromocytoma = secretes catecholamines à 2nd HTN; rule of 10s
· 10% associated with syndromes (MEN, vHL, Sturge-Weber)
· 10% bilateral
· 10% malignant occur outside the adrenal glands (paragangliomas)
§ Neuroblastoma
What is the anatomy of the adrenal medulla?
Anatomy – GFR-Medulla:
o Glomerulosa -> aldosterone [OUTER]
o Fasciculata -> glucocorticoids
o Reticularis -> androgens and glucocorticoids
§ Cortex = epithelial cells
o Medulla -> noradrenaline/adrenaline [INNER]
§ Medulla = neural cells
What are the facets of adrenal hyperfunction?
o Cushing’s syndrome – excess glucocorticoids
o Hyperaldosteronism
o Virilising syndromes – excess androgens
What are the features of cushing’s syndrome?
§ HTN Weight gain Truncal obesity “Moon face”
§ “Buffalo hump” Cutaneous striae
What are the causes of Cushings syndrome?
§ Administration of glucocorticoids (adrenal glands are atrophic) = highest exogenous cause
· Other exogenous cases due to ectopic ACTH (i.e. SCLC)
· Adrenals show bilateral hyperplasia
§ Primary hypothalamic or pituitary disease with inc. ACTH (Cushing’s disease) = highest endogenous cause
· 30% of cases of endogenous Cushing’s syndrome are primary adrenal disorders
· Most will be due to a solitary neoplasm (either adenoma or carcinoma)
· It can sometimes be due to bilateral hyperplasia
o Most of these are associated with an ACTH-producing pituitary adenoma
o It can sometimes be caused by hyperplasia of the ACTH-secreting cells rather than a discrete adenoma
§ In these cases, the adrenal glands show nodular hyperplasia of the cortex
What is hyperaldosteronism?
o 35% due to an adenoma (Conn’s syndrome)
o 60% bilateral adrenal hyperplasia
o Clinical features:
§ Hypertension – accounts for very small percentage of causes
§ Hypokalaemia
What is virilising syndromes?
o May be associated with neoplasms (more commonly carcinoma than adenoma)
o Congenital Adrenal Hyperplasia – most common = 21-OH deficiency
§ Autosomal recessive
§ Caused by hereditary defects in enzymes involved in cortisol biosynthesis
§ Reduced cortisol production -> increased ACTH, adrenal stimulation and increased androgen synthesis
§ More commonly presents in childhood (more obvious in females)
What are the types of adrenal insufficiency?
o Primary
o Secondary to reduced ACTH
§ Non-functional pituitary adenoma
§ Another lesion of pituitary or hypothalamus (inc. infarction)
What is primary adrenal insufficiency?
o ACUTE
§ Sudden withdrawal of corticosteroid therapy
§ Haemorrhage (neonates)
§ Sepsis with DIC -> haemorrhage into adrenals (Waterhouse-Friderichson syndrome)
o CHRONIC (Addison’s Disease)
§ Autoimmune (90%), TB, HIV
§ Metastatic tumour (in particular, lung and breast)
§ RARE: amyloidosis, fungal infections, haemochromatosis, sarcoidosis
What is adrenocorticol neoplasms?
o Adenomas
§ Mostly non-functional
§ May be associated with Cushing’s syndrome or Conn’s syndrome
o Carcinomas
§ RARE; usually LARGE
§ Most commonly associated with virilising syndromes than adenomas
