Week 2 - ENDOCRINE Flashcards
Pituitary, Thyroiditis
From what does the anterior and posterior pituitary develop from?
Anterior:
-rathke’s pouch (epithelium of nasal cavity)
Posterior:
-diencephalon (neural crest)
What are the 3 types of cells present in the anterior pituitary?
- basophilic (blue cells)
- acidophilic (red cells)
- chromophobes (clear cells)
What structures are present in the posterior pituitary?
- astrocytes
- axons
What is the commonest pituitary disorder (hyperpituitarism)?
prolactinoma --> lactotroph -adenoma galactorrhoea -amenorrhoea (females) -sexual dysfunction/infertility
*no. 2 = somatotroph (GH) –> gigantism/acromegaly
What are the 6 cells/adenomas in pituitary, there respective hormones, and associated Sx.?
- lactotroph –> prolactin –> glactorrhoea, amenorrhoea, infertility
- somatotroph –> GH –> gigantism (kids), acromegaly (adults)
- mammosomatotroph –> GH + PRL –> combined PRL + GH Sx.
- corticotroph –> ACTH –> cushing’s, nelson’s syndrome
- thyrotroph –> TSH –> secondary hypothyroidism
- gonadotroph –> FSH/LH –> hypogonadism + hypopituitarism
What is the commonest cause of hypopituitarism?
- injury
- trauma
- tumour
- infarction
Why will women typically have increased hormone-related features and men have increased tumour-related features in prolactinomas? and what are these features?
- microadenomas increased in females (90%) - <10mm
- macroadenomas increased in males (10%) - >10mm
- micro = functional/macro = non-functional
- F –> hormone –> amenorrhoea, galactorrhoea, infertility
- M –> tumour –> headache, visual loss, hypogonadism, infetility
What is the microscopy of pituitary adenomas?
-uniform ONE type of cells –> compared to normal when there are 3 types of cells (acidophilic, basophilic, chromophobes)
How does GH cause clinical features in somatotroph adenoma?
GH induces insulin-like growth factor 1 (somatomedin C) –> clinical features
What are the clinical features of acromegaly?
- long arms/legs
- prominent lower jaw
- large hands/feet
- DM, CCF, arthritis, HTN
- increased head circumference
- prominent supraorbital ridges
- organomegaly/cardiomegaly
True or False?
Physiologically, during pregnancy there is hypertrophy of anterior pituitary
True
What is Sheehan’s syndrome, its Sx and Tx.?
Post-partum anterior pituitary necrosis
-shock/bleeding –> necrosis of hypophyseal portal system –> hypopituitarism
Sx: - inability to breastfeed, severe fatigue/depression, lack of menstrual bleeding, loss of pubic/axillary hair, decreased BP
Tx: replace ant. pituitary hormones
What % of anterior pituitary loss leads to hypopituitarism?
75% (with or wihtout post. pituitary loss)
What are the clinical features of hypopituitarism?
*BASED ON HORMONE INVOLVED
GH: - pituitary dwarfism (proportional) FSH/LH: - infertility, impotence TSH: - hypothyroidism MSH: - pallor (melanocytes) ACTH: - hypo-adrenalism
Post. pituitary: - diabetes insipidus (decr. ADH)
When do we suspect hypothalamic disorder in hypopituitarism?
When there is COMBINED anterior and posterior features (i.e. including D. insipidus)
What are the 2 main posterior pituitary disorders?
- SIADH:
- increased ADH (decreased urine output)
- water intoxication
- hyponatremia
- high urine osmolality - Diabetes Insipidus:
- decreased ADH (increased urine output)
- dehydration
- hypernatremia
- high serum osmolality
What are C cells?
- calcitonin producing cells found in between thyroid gland follicles
- calcitonin = bone forming (opposite to PTH)
What are the normal morphological features of the thyroid?
- cuboidal cells
- plenty of colloid (location of thyroglobulin protein)
- few vacuoles –> reflect levels of activity
What do presence of vacuoles on microscopy of thyroid reflect?
ACTIVITY
- increased vacuoles = hyperthyroid
- no vacuoles = hypothyroid
What is microscopic features of hyper and hypothyroidism?
HYPER:
- reabsorption of colloid
- markedly increased vacuolisation –> therefore increased T3/T4 release
HYPO:
- no vacuoles (no activity)
- colloid becomes solid with no vacuolisation
- epithelial cell degeneration
What is the pathogenesis of exopthalmos in hyperthyroidism?
- autoimmune-mediated inflammatory process of the orbital tissues, predominantly affecting the fat and extraocular muscles
- deposition of glycosaminoglycans (GAG) and water infulx increases the orbital contents
What are the clinical features of hyperthyroidism?
- anxiety
- exopthalmos
- hypermetabolism (wt. loss, diarrhoea, osteoporosis, myopathy)
- goitre
- hair loss
- CVS –> tachycardia, palpitations, AF
- menorrhagia
- warm, moist palms; fine tremor
- pretibial myxoedema
What are the commonest causes of hyperthyroidism?
- primary, autoimmune (GRAVES)
2. iodine excess; toxic change in a tumour
What is thyroid storm?
acute, sudden severe complication of hyperthyroidism
- fever
- tachycardia
- AF
- arrhythmias
What are the clinical features of hypothyroidism?
- hypometabolism –> wt. gain, apathy/depression, constipation, weakness
- non-pitting oedema –> pretibial myxoedema
- dry hair, loss of outer 1/3 of eyebrows
- CVS –> bradycardia, IHD, ECG changes
- decreased sweating
- goitre/deafness ?
- dry, cold skin –> cold insensitivity
- myxoedemic face
- hoarseness (gruff voice)
What is the commonest cause of hypothyroidism?
- primary, autoimmune (destructive) thyroiditis (HASHIMOTO’S)
- iodine deficiency
- common in Himalayan/mountainous regions (decreased iodine in water)
What is cretinism and its features?
Hypothyroidism in infancy/childhood
- mental retardation (severe)
- protruding tongue
- short stature (dwarf)
- umbilical hernia
What are the characteristic features of hashimotos thyroiditis?
- thick, firm subcutaneous tissue
- non-pitting oedema (increased pretibial)
- dermatitis
What is the pathogenesis of Hashimoto’s thyroiditis?
Genetic: -HLA DR3/5, CTLA4, PTPN22
Environmental: -viral?
Autoimmunity: -TSI, anti-thyroglobulin and anti-thyroid peroxidase antibodies
-T cell mediated cytotoxicity
-thyrocyte injury (via activated macrophages)
-Ab-dependent cell-mediated cytotoxicity
What are the gross and microscopic features of Hashimoto’s thyroiditis?
Gross:
- less vascular
- pale
- grey
- lymph node-like
- firm
Micro:
- atrophy of thyroid follicles
- plenty of lymphocytes
- lymphoid follicles
What is the triad of clinical features seen in Graves disease and the causative antibody?
- HYPERTHYROIDISM; vascular enlarged thyroid
- infiltrative ophthalmopathy - EXOPTHALMOS
- dermatopathy, PRETIBIAL MYXOEDEMA
*TSH receptor stimulating Ig (TSI/LATS)
What are the gross and microscopic features of Graves disease?
Gross:
- increased vascularity (bruit on auscultation)
- soft, smooth, red
- hyperaemic
- enlarged gland
Micro:
- cells become prominent and columnar (cluster rather than single line of cuboidal cells)
- marked vacuolisation within colloid
- large follicles with papillary epithelial hyperplasia
- pale, scanty, vacuolated colloid (increased activity)
What is subacute granulomatous thyroiditis?
- subacute, PAINFUL, fever, fatigue
- viral/post-viral
- De Quervain thyroiditis
- hyperthyroidism - but decr. iodine uptake (release)
- heals with normal thyroid function
- granulomas on microscopy
What is subacute lymphocytic thyroiditis?
- subacute, SILENT/PAINLESS
- females, middle age, increased risk post-partum
- initial thyrotoxicosis –> euthyroid in months
- minority progress to hypothyroidism
What will the TSH, free T3 and free T4 levels be like in Graves and Hashimotos?
Graves:
TSH - low
T3 - high/normal
T4 - high
Hashimoto’s
TSH - high
T3 - low/normal
T4 - low
True or False?
TSH is most sensitive test and earliest subclinical abnormality
True
-do serum TSH levels over T3/T4 if thyroid abnormality is suspected
Clinically, what is the most common thyroid tumour?
Multinodular Goitre (MNG) -hormone induced hyperplasia in response to decreased hormone
What is the pathogenesis of multinodular goitre and why is there no change in thyroid function?
-sporadic (enzymes, drugs, food)
-endemic (iodeine deficiency)
*both result in decreased T3/T4 levels
THEREFORE –> increased TSH levels (proliferative hormone) –> gland HYPERPLASIA –> compensates for function –> EUTHYROID state
What are clinical presentations for multinodular goitre?
- mass effect (disfigurement)
- dysphagia
- SVC syndrome (if retrosternal expansion present)
What is Plummer’s syndrome?
toxic change in one of the nodules in multinodular goitre whereby it begins to produce increased T3/T4
What is the microscopy and characteristic feature on scan of multinodular goitre?
Micro:
- nodular hyperplasia (which compresses BVs)
- inflammation, haemorrhage, fibrosis, calcification
Scan:
-uneven iodine uptake
Prognosis –> small risk of follicular cancer
What are 3 key microscopic features of multinodular goitre?
- nodules of hyperplastic follicles
- colloid-rich follicles
- inflammation, haemorrhage, fibrosis, necrosis, calcification
Is multinodular goitre non-neoplastic or neoplastic?
non-neoplastic
What is the commonest cause of thyroid enlargement?
multinodular goitre
What is meant by thyroid adenomas being hot or cold?
When we do a radio-iodine scan:
- if activity shown –> HOT nodule (usually benign)
- if no activity shown –> COLD nodule (can also be malignant)
What is the commonest thyroid carcinoma? and what are the others?
Papillary carcinoma (85%) -young (males), solitary nodule, good prognosis
also: -follicular carcinoma, medullary carcinoma, anaplastic carcinoma
What is microscopy of papillary carcinoma?
papillary structures with fibrovascular cores
True or False?
commonest type of thyroid ca. in pts with endemic goitre is follicular carcinoma
True
Outline structure of adrenal gland
CORTEX: -glands
- Zona glomerulosa –> mineralocorticoids (aldost.)
- Zona fasciculata –> glucocorticoids (cortisone)
- Zona reticularis –> gonadocorticoids (andro/estro)
1–>3 (sup. –> deep) (GFR) - salty, sweet, sexy
MEDULLA: -neural
- catecholamines
- chromaffin cells + sympathetic nerve endings
What is cushings syndrome vs. cushings disease? and what is the difference between resultant adrenal gland structure?
Cushings Syndrome:
-exogenous cause of increased glucocorticoids (i.e. chronic steroid therapy)
Cushings Disease:
-endogenous cause of increased glucocorticoids (i.e. pituitary ACTH adenoma - 70%)
Exogenous (syndrome) –> adrenal gland atrophy
Endogenous (disease) –> adrenal gland hypertrophy
Besides pituitary ACTH adenoma (70%) what are the other causes of Cushings disease?
- ectopic ACTH –> SCLC paraneoplastic synd. (10%)
- adrenal adenoma (10%), ca. (5%)
What are the clinical features of Cushings disease?
- HTN
- central adiposity
- myopathy
- hyperglycemia (DM)
- osteoporosis
- moon face/buffalo hump
- hair thinning
- striae; easy bruising
- tendency to infections
- menstrual disturbance
- renal stones
- peptic ulcer
What are diagnostic tests for Cushings syndrome and disease?
- increased 24hr urine cortisol
- loss of diurnal variation
- SERUM ACTH* –> used to distinguish between exogenous (syndrome) and endogenous (disease)
- exogenous = low ACTH
- endogenous = high ACTH
What are the 2 most common causes of primary hyperaldosteronism?
- idiopathic (60%)
- nodular hyperplasia
- later age, moderate HTN - aldosterone adenoma (35%)
- Conn syndrome
- middle age, F:M (2:1), severe HTN
What are the effects of primary hyperaldosteronism and how is it diagnosed?
- suppression of RAAS mechanism
- increased Na+ retention –> common secondary HTN
- increased K+ loss
Dx: - hypokalemia, increased aldosterone
Why do you get adrenal hyperplasia in adrenogenital syndrome?
21-hydroxylase deficiency –> decreased mineralo/glucocorticoids –> decreased cortisol –> increased compensatory ACTH via negative feedback –> adrenal hyperplasia
What is the commonest adrenogenital syndrome?
21-hydroxylase deficiency
What are the clinical types of adrenogenital syndrome and what is the most common?
- simple virilizing –> increased testosterone *COMMON
- salt wasting synd. –> Na loss, K ret (decreased aldost.)
- late onset adult virilism –> partial deficiency
What are the causes of acute adrenocortical insufficiency?
- sudden withdrawal from long term steroid therapy
- crisis in a chronic insufficiency pt. (Addison’s)
- Waterhouse-Friderichsen Syndrome (acute haemorrhagic necrosis (apoplexy); secondary to DIC, meningoccal meningitis, new born, trauma)
What are the clinical features of acute adrenocortical insufficiency?
- shock, DIC, purpura, septicemia
- salt + water loss (decreased aldost.)
- hypoglycemia, fatigue
- hypovolemic shock
What is primary chronic adrenal insufficiency known as?
Addison’s Disease
- decreased serum cortisol
- increased ACTH
What are the clinical features of Addison’s Disease?
- anorexia, wt. loss
- vomiting
- weakness, lethargy
- hypotension (low Na, high K –> low aldost.)
- skin pigmentation in primary (increased MSH)
- GI disturbances
- chronic dehydration and sexual dysfunction
- changes in body hair distribution
True or False?
In Addison’s Disease, plasma Na is high and K is low
False
-other way around
What is the commonest etiology of Addison’s disease, and what are the others?
Commonest = autoimmune (70%) Also: -APS1, APS2 -infections (TB, fungal) -tumours
How is Addison’s disease diagnosed?
Serum ACTH
- high = primary
- low = secondary
What is a pheochromocytoma?
- benign tumour of adrenal medulla chromaffin cells
- young age –> fluctuating secondary HTN
- increased catecholamines –> HTN
- 25% familial (MEN2 syndrome, NF1, VH2)
- 10% extraadrenal, bilat. (MEN), malig, no HTN
What is the Dx. of pheochromocytoma?
increased urinary VMA ( vanillylmandelic acid)
-epinephrine metabolite
What does PTH do?
- releases Ca from bone
- reabsorbs Ca in kidneys
- absorbs Ca in small intestine (+phosphate)
***INCREASE SERUM CALCIUM
What is the main cause for hyperparathyroidism?
Primary: - ADENOMA (90%)
-F:M = 4:1
What are the Sx. of hyperparathyroidism?
- hypercalcemia
- renal calculus
- bone resorption –> osteoporosis
- depression
- seizures
- osteitis fibrosa cystica (brown tumour of bone) –> in severe form
What is secondary, tertiary and quaternary hyperparathyroidism?
#2: -Chronic Renal Failure --> Ca loss --> increase PTH #3: -#2 + hyperplasia, not responding to Ca levels #4: -#3 + adenoma
What does MEN1 consist of and what is the most common?
PPPP -Pituitary adenoma -Parathyroid adenoma --> MOST COMMON* -Pancreatic adenoma (-Peptic ulcers)
What does MEN2 consist of and what are the subclasses 2A + 2B?
PTAG
- Parathyroid adenomas –> MEN2A
- Thyroid medullary carcinoma –> MEN2
- Adrenals (pheochromocytoma) –> MEN2B
- GIT (neuromas + ganglioneuromas) –> MEN2B
What is APS1 and what does it consist of?
Autoimmune Polyendocrine Syndrome
*APECED:
Autoimmune Polyendocrinopathy, Candidiasis and Ectodermal Dystrophy
Sx: -alopecia, anemia, cataract, vitiligo, malabsorption, hypoparathyroidism
-childhood, Addisons, Pernicious anemia, hypoPTH, etc
-Ab against IL-17 (increased fungal inf.)
What does APS2 consist of?
Sx: -nausea, polyuria, wt. loss, hypotension, hypoparathyroidism, anorexia, myalgia
- early adult
- adrenal insufficiency (Addison’s) with autoimmune thyroiditis and T1DM
- NO infections (unlike in APS1)
What is the likely Dx. of 18yr old boy with sudden severe episodes of fluctuating episodes of hyper and hypotension?
Pheochromocytoma
What type of MEN does pheochromocytoma fit into?
MEN2(B)
-adrenal medullary adenoma
What is the commonest type of thyroid adenoma and its microscopy?
Follicular adenoma
-plenty of small follicles
What is Waterhouse-Friederechsen Syndrome?
- large blood clot replacing adrenal gland
- severe stress –> adrenal haemorrhage –> necrosis
- acute loss of adrenal function –> shock, haemorrhage, hypoglycemia, hypovolemia, DIC, etc.
N.B. severe stress: -meningococcal meningitis, speticemia, multi organ failure, DIC
What are 3 microscopic features of papillary carcinoma?
- irregular cells forming papillary structures
- dense fibrous stroma
- microcalcifications
