Endocrine... Challenging & Important

Endocrine

Multiple Endocrine Neoplasia I
- parathyroid- primary hyperparathyroidism
- pituitary- adenomas

Multiple Endocrine Neoplasia II
- parathyroid hyperplasia
- medullary carcinoma of thyroid
- pheochromocytoma- adrenal medulla tumor

Pituitary
Anterior lobe- hormone producing (all the troph cells)
- corticotrophs- ACTH, MSH

Posterior lobe- hormone storage
- supraoptic nucleus- ADH

- paraventricular nucleus- oxytocin (stimulates uterine smooth muscle, lactation)




Anterior Lobe Hyperpituitiarism
Major Cause
- Pituitary Adenoma-
o Benign, uniform cells, stain uniformly
o pituitary apoplexy
o can eventually lead to hypopituitarism if destroy enough of the gland
o MEN I
o Common Types
Prolactinomas- most common
• Treated surgically, and w/ bromocriptime-
• See calcium deposits mico w/ uniform staining
Growth Hormone Adenoma (of somatotrophs)
• GSP oncogene
• Prolactin can be present sometimes
• GH can cause hyperglycemia
o (side note- both GH and cortisol cause hyperglycemia)
• kids- giantism
• adults- acromegaly
Corticotroph adenoma
• ACTH- cushing DISEASE
o Remember: cushing disease involves pituitary, cushing syndrome involves ACTH hypersecretion outside of pituitary
• Nelson syndrome- cushing symptoms, remove adrenal gland, persistant signs of hyperpigmentation- due to MSH of corticotroph adenoma

Anterior Lobe Hypopituitarism
- pallor

- Causes
o Tumors
pituitary carcinoma
• non functional, only diagnosed when metastasize
rathke's cleft cyst
• benign, ciliated cuboidal epithelium, remove surgically
suprasellar tumors- can grow and squish the pituitary
• gliomas
• germinomas: germ cell tumor, midline, look like gonads histologically, Japanese men, AFP elevated
• craniopharyngiomas: benign aggressive remnants of rathke's pouch
o kids: endocrine prob, adults:visual prob (optic chiasm)
o adamantinomatous: wet karatin, calcifications, cholesterol rich fluid in cyst
o papillary: no cystic, keratin, or calcification
o remove surgically
o ischemic necrosis
Sheehan syndrome: ant gland hyp during pregnancy, hypoperfusion postpartum, post gland more resistant
Other causes…results in ischemic necrosis
o empty sella syndrome
o Apoplexy- hemorrhage
o Hypothalamic disease- sarcoidiosis, TB
o Congenital Hypopituitarism- Pit-1 mutation


Posterior lobe syndromes
- ADH
o diabetes insipidus: impaired ADH, excessive urination
o syndrome of inappropriate ADH secretion- excessive ADH, hyponatremia (because resorption of escessive amounts of free water), increased in total body water, but blood volume stays the same
- oxytocin- no clinical symptoms

Adrenal

Cortex: zones GFR, products-sweeter as you go deeper
- glom- mineralocorticoids- aldosterone- controlled by angiotensin

- fasc- glucocorticoids- cortisol

- retulari- estrogen/androgen
o G/R- controlled by ACTH
o So remember, ACTH hypersecretion will only affect cortisol, estrogen

Diseases of Cortex
- Hypocorticism
o Acute
Waterhouse-Friderichsen syndrome
• Usually~ neisseria meningitis (meningococcus)- will see bacterial CSF
• Hypotension
o Red infarct of adrenal gland
• Schwartzman syndrome- breakdown of platelets, accumulation of fibrin- leads to DIC---
o diffuse petechial hemorrhages
o fibrin clumps in glomerulus of kidney
o chronic
Addison's disease
• Hypoglycemia, hyponatremia
• Focal hyperpigmentation- b/c high ACTH due to loss of cortisol neg feedback and ACTH stimulates corticotrophs to produce MSH- melanocytes
• Mostly idiopathic ATROPHY (lymphocytes), OR caused by TB-adrenal granulomas
• Feared complication: Adrenal Apoplexy- adrenal "collapse"---treat w/steroids

- Hypercorticism
o Cushing Syndrome: elevated cortisol
Hypernatremia, hypophos, increased gluconeogenesis---leading to diabetes, lymphopenia/eosinopenia- cortisol depresses lymphocyte generation
Trunkal obesity, buffalo hump, round face
Causes
• Iatrogenic-corticosteroid therapy
• Pituitary--cushing's Disease
• Adrenal cortical adenoma/carcinoma/hyperplasia
• Ectopic ACTH- lung, etc

Congenital Adrenal Hyperplasia
o 21 hydroxylase deficiency- shunts pathway to testosterone
o clitoral/penile enlargement
o hyperplasia in ZONA RETICULARIS (b/c excessive testosterone prod)
o treat- give cortisol

- Conn's syndrome (hypermineraloadrenocorticism)
o Increase in aldosterone (mineralcorticoid) W/O increase in cortisol (glucocort)
o Hypertrophy in zona glomerulosa
o Clinical: severe HTN, loss of renal K+, sodium retention
o Causes
Cortical adenoma: which is a treatable form of HTN
Nodular cortical hyperplasia/adrenocortical carcinoma

Diseases of Medulla
- Neuroblastoma: adrenal MEDULLA tumor
o Kids,
o abdominal mass, hemorrhagic tendencies, increase in urine VMA
o tumor secretes epi/norepi, histo forms rosettes
o Better prog in kids 1 year- because will progress to ganglioneuroma- benign form

- Pheochromocytoma: neoplasm of chromaffin cells
o 30-50 y/o
o secrete epi/nor epi
o MEN II- medullary cancers of thyroid and adrenal glands
o UNILATERAL, benign, will show HTN and increase in VMA

Thyroid

- Thyroid hormone
o Uncouples oxidative phosp: decrease ATP, greater heat release
o Increase
Cardiac output and SYSTOLIC blood pressure (will cause a widened pulse pressure)
GI motility
O2 consumption----atrophy, spastic muscle
Hyperthyroidism
- Grave's disease
o Ab to TSH receptor-autoimmune
o Diffuse goiter, hyperthyroidism, exopthalmos (not due to inc. TSH, doesn't recede when treat Grave's disease)
o More females
o Clin: increase in systolic blood pressure, heat intolerance, diffuse non-nodal thyroid enlargement, red color
o Maj complications
Exopthalmos
High output heart failure
Thyroid storm- collapse, heart failure shock

Hypothyroidism
- Cretinism- kids: tongue, short, mental retardation

- Myxedema- adults: periorbital edema, NON-PITTING EDEMA, infiltration of glycosaminoglycans into subcutaneous tissue


Thyroiditis- inflammation of thyroid
- Hashimotos
o females
o Autoimmune: Ab to thyroblobulin in colloid (anti microsomal Ab in follicle cells)
o Thyroid enlargement due to Lymphycyte infiltration
o hypothyroid

- subacute (granulomatous, deQuervains)
o formation of granulomas in thyroid
o usually ~ post febrile/viral illness- usu. self-limiting

- Riedel's struma (chronic, woody)
o Heavy fibrous infiltration of thyroid, must distinguish from cancer

Thyroid Tumors
- Benign colloid goiter
o Euthyroid fxn
o Non-uniform nodular enlargement w/ non functional enlarged follicles of colloid

- Benign Adenoma of Thyroid
o Mass w/capsule…capsule keeps it benign
o Microscopic- follicular adenoma

- Thyroid carcinoma
o Papillary- most common, best prog
NO CAPSULE, papillary formation, diffuse

o follicular carcinoma-
probably a follicular adenoma that invaded a capsule..remnants of capsule present with evidence of invasion (capsules and blood vessels)
bad prognosis---metastasizes to bone marrow

- Giant Spindle Cell carcinoma of thyroid
o BAD prog- 6 mo to live
o Rapidly growing- can compress trachea
o Contains BOTH Spindle cells and malignant giant cells

Parathyroid
- chief cells- secrete PTH

- waterclear cells (vasserhelle cells)- chief cell at different stage of secretion

- oxyphil cells- red granules, cytoplasm full of mitochondria

- parathyroid hormone: stim by low calcium
o increase Ca2+
indirect osteoclast resorption (via RANK-L)
stimulates 1 hydroxylation of 1, 25 Vit D in KIDNEY

o decrease phos via decreasing renal tubular resorption of phosp
urine PO4 up, serum PO4 down

o increase in alkalinephosphatase- b/c stim osteoclasts

- calcitonin- from parafolicular cells of thyroid, stim by high calcium
o direct inhibition of bone resorption

Diseases
Hypercalcitonin
- Medullary Carcinoma of thyroid
o tumor secreting calcitonin
o low calcium, high phosphate

Hyperparathyroidism
- symptoms
o resorption of distal phalanges
o high Ca2+, high alk phos
o osteitis fibrosa cystica- bone loss with Ca2+/phos release, anchovy paste
o metastatic calcification of kidney- via calcium phos

- Primary hyperparathyroidism: arising in parathyroid gland---high Ca2+, low phos in serum
o PT adenoma- benign, main cause, uniform chief cells
o PT hyperplasia- clear cell hyperplasia
o PT carcinoma- rare

- Secondary Hyperparathyroidism
o Chronic Renal Disease- big sign…high PTH, low Ca2+, high phos in serum
o Defective Vit D formation-impairs Ca2+ absorption
o Low serum Ca2+- chronic PTH secretion- diffuse hyperplasia of PT glands
o High serum phosp- b/c kidney can't effectively excrete phosphate even when PTH stimulates it to


NON-PTH Hypercalcemia
- coma is main cause of death
- high calcium, NORMAL PHOSPHATE (b/c not PTH induced)
- usu due to variety of tumors (lung, breast)
- malignant cells secrete PTH-Related Peptide

Hypoparathyrodism
- symptoms-
o hypocalcemia: tetani, hyperreflexia
o hyperphosphatemia
- causes:
o accidental removal of PT gland during surgery, Di George, autoimmune,
o pseudohypoparathyroidism
end organ resistance
hereditary- short stature, short neck, rounded face, short fingers
hyperplastic parathyroids (b/c PTH keeps trying to secrete/cause changes)