Exam 2 Path Flashcards
Pituitary adenoma:
Female vs male presentation of lactotroph adenoma
Females present at a young age with primary amenorrhea
Males present at an older age with mass effect
*PRL is a more common workup in young females vs males, therefore caught earlier
Pituitary adenoma type?
stromal hyalinization w/ psammoma bodies,
dense calcifications can become pituitary stones
Lactotroph adenoma
Pituitary adenoma:
Effect of a somatotroph adenoma in a younger child who is still growing
Gigantism (very tall)
*GH effect on bone prior to closure of epiphyseal plates
Pituitary adenoma:
Effect of a somatotroph adenoma in an adult who has finished growing
Acromegaly (thicc bones)
- GH effect on bone after closure of epiphyseal plates
- large face and hands, jaw, nose, lips, organs
Diagnostic test for pituitary somatotroph adenoma?
Measure serum IGF-1 (more stable and predictable)
Oral glucose tolerance test
*oral glucose would normally inhibit GH, if IGF-1 remains high after ogt then suggestive of somatotroph adenoma
Diagnostic test for corticotroph adenoma?
*in setting of high ACTH
Dexamethasone suppression test: pituitary corticotroph adenoma will be suppressed (decreased ACTH), ectopic ACTH will not be suppressed
*inferior petrosal sinus sampling would also show increased ACTH in setting of pituitary adenoma
Diagnosis?
Elevated ACTH and hyperpigmentation
Surgical hx = bilateral adrenalectomy
Nelson syndrome
removal of adrenals leads to increase in ACTH, which stilmulates MSH (melanocyte stimulating hormone), leads to hyperpigmentation
Paraneoplastic syndromes:
Ectopic ACTH releasing tumor type?
Small cell lung cancer
*causes cushing syndrome
- cushing and SIADH can be caused by small cell
- hypercalcemia of malignancy caused by squamous cell
Paraneoplastic syndromes:
Ectopic ADH releasing tumor type?
Small cell lung cancer
*causes SIADH
- cushing and SIADH can be caused by small cell
- hypercalcemia of malignancy caused by squamous cell
Paraneoplastic syndromes:
Ectopic PTHrP releasing tumor type?
Squamous cell lung carcinoma
- hypercalcemia of malignancy caused by squamous cell
- cushing and SIADH can be caused by small cell
Typical presentation of a gonadotroph pituitary adenoma?
Mass effect
*minimal secretion, “silent” or “null cell” adenoma
Diagnosis?
HA, N/V, papilledema,
Bilateral temporal hemianopsia
Under production of all pituitary hormones except prolactin
Pituitary lesion mass effect
*caused by neoplasm or hemorrhage
What transcription factor is elevated in most pituitary adenomas? (somato-, lacto-, thyro-)
PIT-1 transcription factor
*less clinically useful because it does not narrow it down very much
What transcription factor is elevated in corticotroph pituitary adenomas? (cushings disease)
TPIT transcription factor
*more useful because it is specific for corticotroph adenomas
What SOMATIC mutation is associated with somatotroph pituitary adenomas?
GNAS mutation
Somatic GNAS mutation pathophysiology in development of pituitary somatotroph adenoma?
- GNAS mutation = loss of function in Gs-a GTPase (part of GH receptor),
- Leads to increased GTP (cant break it down)
- Uninhibited cAMP driven somatotroph proliferation
What SOMATIC mutation is associated with corticotroph pituitary adenomas?
USP8 mutation
*leads to EGFR upregulation
What GERMLINE mutation is associated with somatotroph pituitary adenomas?
AIP (FIPA)
Other pituitary neoplasms:
Cystic mass lined with ciliated columnar epithelium
Can cause mass effect and/or rupture (pituitary inflammation and meningitis)
Rathke’s cleft cyst
Other pituitary neoplasms:
Cyst lined with squamous epithelium,
Calcified cyst
Wet keratin
Presents with growth retardation or hypopituitarism
Craniopharyngeoma
*kid form (adamantinomatous)
Other pituitary neoplasms:
Cyst lined with squamous epithelium,
Papillary structure
Presents with increased ICP or hypopituitarism
Craniopharyngeoma
*adult form (papillary)
Infarct and death of the pituitary due to disrption of the diaphragma sella,
CSF leak into the sella that compresses the pituitary
Primary empty sella syndrome
Expansion of the pituitary leading to infarction and death, leaving empty space in sella
Secondary empty sella syndrome
Diagnosis?
New mom presents with lactational dysfunction (hypopituitarism) and empty space in sella on imaging
Sheehan syndrome
*postpartum necrosis of anterior pituitary (secondary empty sella syndrome: pituitary expands in pregnancy leading to infarct and death of pit)
Diagnosis?
Polyuria and polydipsia
Hypernatremia (excess water loss)
DDAVP administration leads to water retention
Central DI
- if no response to DDAVP then it would be nephrogenic DI
- thirst is appropriate
Diagnosis?
Low urine output (concentrated)
Thirsty
Hyopnatremia
Lung tumor
SIADH
*inappropriate thirst
Gross findings for cushing syndrome due to priamry adrenal disease
Unilateral well-circumscribed adrenal cortical adenoma
*low ACTH due to primary adrenal dz
Gross findings for cushing syndrome due to secondary hyperadrenalism
Bilateral cortical hypertrophy of adrenal glands
- high ACTH causes hyperplasia of adrenals
- due to neoplastic release of ACTH
What is Conn syndrome?
HTN, hypokalemia, hypomagnesemia
Primary hyperaldosteronism
*idiopathic > adenoma
Diagnosis of hyperaldosteronism (primary vs secondary)?
HTN, hypokalemia
assess plasma renin activity (PRA)
- high PRA = secondary hyperaldosteronism
- low PRA = primary hyperaldosteronism
Adrenocortical CARCINOMA is more likely to secrete what hormone type?
androgens (virilizing)
Adrenogenital syndromes due to 21 hydroxylase def:
Complete lack of 21-hydroxylase
Virilization seen at birth
Hyponatremia, Hyperkalemia, Hypotension
Classic “salt wasting”adrenogenitalism
Adrenogenital syndromes due to 21 hydroxylase def:
Partial lack of 21-hydroxylase
Virilization
Some mineralcorticoid release (no salt wasting)
Simple virilizing syndrome
Adrenogenital syndromes due to 21 hydroxylase def:
Partial lack of 21-hydroxylase
Precocious puberty w/ acne and hirsutism
Nonclassic/ Late onset virilism
Treatment for adrenogenital syndromes due to 21-hydroxylase def.?
Glucocorticoids
Diagnosis?
Hypotension, abdominal pain
F, N/V
Hyperkalemia, Hyponatremia, Hypoglycemia
Acute adrenal insufficiency
*caused by rapid withdrawal of steroids, adrenal hemorrhage, stress, infection, trauma, burns, etc.
Diagnosis?
Chronic malaise and fatigue
Anorexia, weight loss, arthralgias
Skin hyperpigmentation
Primary chronic adrenocortical insufficency (Addison dz)
*primary adrenal dz so there will be elevated ACTH to try and compensate, leads to hyperpigmentation due to MSH stimulation (like in Nelson synd)
Diagnosis?
Adrenalitis (adrenal insufficiency) Parathyroiditis Hypogonadism Pernicious anemia Mucocutaneous candidiasis Ectodermal dystrophy (teeth and nail probs)
Autoimmune polyendocrine syndrome type 1
*APECED
Diagnosis?
Adrenalitis (adrenal insufficiency)
Thyroiditis
T1DM
Autoimmune polyendocrine syndrome type 2
Diagnosis?
HTN, HA, palpitations, diaphoresis
Urine and plasma metanephrines elevated
Pheochromocytoma (or paraganglioma)
MEN 1 tumors
*Pituitary adenoma
*Pancreatic endocrine tumor
Parathyroid adenoma
*=specific to this MEN syndrome
MEN 2A tumors
- Parathyroid adenoma
- *Pheochromocytoma
- *Medullary thyroid carcinoma
- =shared with MEN1
- *=shared with MEN2B
MEN 2B tumors
Pheochromocytoma
Medullary thyroid carcinoma
*Mucosal neuromas
- Marfanoid body habitus
- =specific to this MEN syndrome
What tumor is seen in both MEN1 and MEN2A?
Parathyroid adenoma
What tumors are seen in both MEN2A and MEN2B?
Pheochromocytoma
Medullary thyroid carcinoma
Pancreatic neuroendocrine tumors:
Pt presents with hypoglycemia and pancreatic mass
Labs show elevated insulin and C-peptide
Amyloid on histo
Insulinoma (B-cell tumor)
Pancreatic neuroendocrine tumors:
Pt presents with epigastric pain and pancreatic mass
Gastric/duodenal ulcers unresponsive to tx
Gastrinoma (G-cell tumor)
*Zollinger ellison synd
Pancreatic neuroendocrine tumors:
Pt presents with RUQ pain, steatorrhea and pancreatic mass
Labs show hyperglycemia
Somatostatinoma (delta-cell tumor)
*somatostatin shuts up the other hormones (decreased CCK leads to decreased gallbladder motility, decreased insulin leads to hyperglycemia)
Pancreatic neuroendocrine tumors:
Pt presents with hyperglycemia, LE dermatitis and pancreatic mass
May also have depression, DVT
Glucagonoma (a-cell tumor)
Pancreatic neuroendocrine tumors:
Pt presents with watery diarrhea and pancreatic mass
Labs show hypokalemia and achlorhydria (low HCl in gastric secretions)
VIPoma (D1 cell tumor)
WDHA syndrome
Diagnosis?
Young child with impaired development, low growth, coarse facial features, umbilical hernia
Hint of living in iodine deficient area
Congenital hypothyroidism (cretinism)
Diagnosis?
Young adult with mental and physical slowing, weight gain, cold intolerance, low CO and high cholesterol
Myxedema (hypothyroidism of the adult)
Thyroiditis types:
Diffuse painless thyroid enlargement
TPO and Tg auto-ab
Histo: lymphocytes w/ germinal centers, atrophic follicles with eosinophilic change (Hurthle cell metaplasia)
Hashimoto thyroiditis
- T-cell mediated (breakdown of self tolerance)
- hyper then hypothyroid
Thyroiditis types:
TRANSIENT thyroid irregularities (i.e. postpartum)
Painless enlargement
Subacute lymphocytic thyroiditis
*hypo or hyperthyroid
Thyroiditis types:
PAINFUL thyroid enlargement
Histo: granulomas
?preceded by viral infection
Granulomatous thyroiditis
*hypo or hyperthyroid
Thyroiditis types:
Fibrosis of thyroid tissue into nearby tissues
IgG4 related dz
Histo: fibrosis, lymphocytes, PLASMA CELLS
Riedel thyroiditis
*euthyroid
Thyroid tumors:
Benign
Clonal proliferation of follicular cells w/ “thyroid autonomy”
Capsule intact, no nuclear features
Follicular adenoma
Thyroid tumors:
Malignant
Histo: follicular architecture, enlarged nuclei with clear appearance (orphan annie eye)
RAS mutations
Papillary thyroid carcinoma: follicular variant
*nuclear features (orphan annie eye) determine papillary carcinoma!!!
Thyroid tumors:
Malignant
Histo: papillary architecture w/ columnar-looking cells, enlarged nuclei with clear appearance (orphan annie eye)
RET or BRAF mutations
Older patients, more aggressive
Papillary thyroid carcinoma: tall cell variant
*nuclear features (orphan annie eye) determine papillary carcinoma!!!
Thyroid tumors:
Malignant
Histo: papillary architecture w/ connective tissue, enlarged nuclei with clear appearance (orphan annie eye)
RET or BRAF mutations
Younger patients, metz more common
Papillary thyroid carcinoma: diffuse sclerosing variant
*nuclear features (orphan annie eye) determine papillary carcinoma!!!
Thyroid tumors:
Malignant, common in areas w/ iodine deficient goiter
Histo: follicular architecture, capsule invasion, angioinvasion
RAS, PAX8/PPARG mutations
Follicular thyroid carcinoma
Thyroid tumors:
Malignant, very deadly, elderly
Histo: high grade anaplastic features
p53 mutation
Anaplastic thyroid carcinoma
Thyroid tumors:
Malignant
Histo: c-cell hyperplasia, blue cells with dispersed chromatin, amyloid
RET mutation
Medullary thyroid carcinoma
- most are sporadic (worse prognosis)
- familial = best prognosis
- also think of MEN 2A & B (prophylactic thyroidectomy)
Diagnosis?
Elevated PTH, Elevated Ca
Typically asymptomatic
Short QT
Primary hyperparathyroidism (hypercalcemia)
*adenoma, hyperplasia, carcinoma
Diagnosis?
Elevated PTH, Low Ca
Stupor, numbness, cramps/spasms, Trosseau/Chovstek signs
Long QT
Secondary hyperparathyroidism (hypocalcemia)
*tissues dont respond to PTH => hypersecretion of PTH and hyperplasia of parathyroids
Diagnosis?
Low PTH, Elevated Ca
Painful bones, renal stones, abdominal groans, psychiatric moans
Short QT
Hypercalcemia of malignancy (symptomatic hypercalcemia)
*will have elevated PTHrP or Vit D mediatied or local osteolytic (breast ca, multiple myeloma)
Diagnosis?
Low PTH, Low Ca
Primary hypoparathyroidism
*can be caused by neck surgery, autoimmune dz, DiGeorge synd (3rd & 4th pharyngeal arch underdev, CaSR activating mutation, familial mutation in PTH synth)
Effect of an activating mutation in CaSR:
PTH
Ca
Urine Ca
PTH: Low
Ca: Low
Urine Ca: High (renal excretion)
*AD mutation
Effect of an inactivating mutation in CaSR:
PTH
Ca
Urine Ca
PTH: High
Ca: High
Urine Ca: Low (renal retention)
Diagnosis?
nl or high PTH, Low Ca
Pseudohypoparathyroidism
- tissues unresponsive to PTH
- can lead to Albright osteodystrophy
Diagnosis?
Child with short stature and obesity Short fingers and toes GNAS mutation (PTH receptor pathway)
Albright hereditary osteodystrophy
*results in pseudohypoparathyroidism (unresponsive to PTH)
