Endocrine Flashcards
MCC of hyperpituitarism
Associated with distinct endocrine signs and symptoms
FUNCTIONING ANTERIOR PITUITARY ADENOMA
1 cm - limit size to determine micro/macroadenoma
Prolactin cell adenoma - MC
Somatotroph adenoma - 2nd MC
2nc MC pituitary adenoma
present with mass effects - visual disturbance
NON-FUNCTIONING ADENOMA
Microscopic findings in pituitary adenoma
Uniform (monomorphic)
Sparse reticulin network
Few mitosis
Sine qua non of Pituitary Carcinomas
atypical adenoma + metastases (CSF/systemic)
METASTASES (craniospinal/systemic)
Occurs at ~75% parenchymal loss
CAUSES:
tumors/mass lesions
PITUITARY APOPLEXY
SHEEHAN SYNDROME
Empty sella syndrome
HYPOPITUITARISM
GH and gonadotropin (FSH and LH) lost FIRST –> TSH and ACTH –> prolactin (lost LAST)
ADH DEFICIENCY
CAUSES:
CNS disorders
Central Diabetes Insipidus
serum osmolality - N - H
urine osmolality - L
serum ADH - L
Unresponsiveness of renal tubules to ADH
CAUSES:
drugs
renal disorders
Nephrogenic Diabetes Insipidus
serum osmolality - N - H
urine osmolality - L
serum ADH - H
ADH EXCESS
CAUSES:
SCLC
CNS disorders
SIADH
serum osmolality - L
urine osmolality - N - H
serum ADH - H
slow-growing tumors account for 1% to 5% of intracranial tumors
suprasellar, with or without intrasellar extension
bimodal age distribution - one peak in childhood (5 to 15
years) and a second peak in adults 65 years of age or older
ADULTS - headaches and visual disturbances
CHILDREN - growth retardation due to pituitary hypofunction and GH deficiency
CRANIOPHARYNGIOMA
from vestigial remnant of RATHKE’S POUCH
Adamantinomatous - compact, lamellar
*WET KERATIN
*DYSTROPHIC CALCIFICATION
Papillary
*papillae
MCC of primary hyperthyroidism
Autoantibodies against TSH receptor
GRAVES DISEASE
symmetrically enlarged thyroid
MICROSCOPIC:
diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells
pseudopapillary structures
pale, scalloped colloid
MCC of congenital hypothyroidism
IODINE DEFICIENCY
MCC of hypothyroidism in iodine-sufficient areas
AUTOIMMUNE
i.e. Hashimoto
MCC of hypothyroidism in iodine-sufficient areas
autoimmune disease that results in destruction of the thyroid gland and gradual and progressive thyroid failure
T cell mediated injury
Autoantibodies against THYRPGLOBULIN and TPO
COMPLICATIONS:
development of neoplasms (marginal zone B cell lymphoma, papillary thyroid ca)
HASHIMOTO THYROIDITIS
PAINLESS thyroid enlargement
diffusely enlarged thyroid
HURTHLE cell changes
GERMINAL CENTERS
(+) FIBROSIS
Autoantibodies against TPO
Family history of autoimmunity
(+) URTI
SUBACUTE LYMPHOCYTIC
thyroid grossly normal
PAINLESS thyroid enlargement
(-) fibrosis
(-) Hurthle cells
Antigen-mediated immune damage to follicular cells
(+) URTI prior to thyroiditis
believed to be triggered by a viral infection
majority of patients have a history of an URTI just before the onset of thyroiditis
Granulomatous thyroiditis (also called De Quervain thyroiditis)
unilateral or bilaterally enlarged and firm thyroid
PAINFUL thyroid enlargement
multinucleate giant cells enclose pools of colloid
TRIAD of GRAVES DISEASE
Hyperthyroidism
Exophthalmos - fibrosis (orbit and EOM)
Dermopathy - pretibial myxedema (dermal thickening)
Thyroid enlargement caused by IMPAIRED THYROID HORMONE synthesis
MASS EFFECT
LOW incidence of malignancy
GOITER
iodine deficiency –> compensatory increase in TSH –> trophic effect of TSH on thyroid –> enlargement of the thyroid gland
Phases of Goiter
HYPERPLASTIC
*diffuse, symmetrical enlargement
*columnar
COLLOID
*brown, glassy, translucent
*flattened and cuboidal
*abundant
TYPES OF GOITERS
Diffuse Nontoxic (Simple)
*areas of iodine insufficiency and intake of goitrogens (cassava - thiocynate)
Multinodular
*irregular enlargement of thyroid
*repeated hyperplastic and colloid phases –> nodularity
*unencapsulated nodular architecture
Toxic Multinodular (PLUMMER SYNDROME)
*autonomous nodule in a long standing multinodular goiter
*(+) hyperthyroidism
*(-) ophthalmopathy, (-) dermopathy
Clinical Factors Favoring Malignancy in Solitary Thyroid Nodule
Solitary nodule
Young, Male
History of radiation therapy
NON-FUNCTIONAL - COLD nodules
Shares morphological features with ADENOMATOUS NODULE and FOLLICULAR CARCINOMAS
FOLLICULAR ADENOMA
encapsulated lesions
uniform-appearing follicles
little pleomorphism
rare mitosis
HALLMARKS of thyroid adenoma
intact, well formed capsule encircling the tumor
MC thyroid cancer
account for the majority of thyroid carcinomas associated with previous exposure to IONIZING RADIATION
PAPILLARY CA
(RET/PTC, BRAF)
papillary fronds with fibrovascular cores
ORPHAN ANNIE NUCLEI
PSAMMOMA BODIES - calcifications
LYMPHATIC METASTASIS
2nc MC thyroid cancer
FOLLICULAR CA
(RAS, PAX 8, PPAR y)
invading thyroid capsule and vasculature
oncoytic type of Hurthle cells
2nc MC thyroid cancer
FOLLICULAR CA
(RAS, PAX 8, PPAR y)
invading thyroid capsule and vasculature
oncoytic type of Hurthle cells
HEMATOGENOUS METASTASIS
represent aggressive neoplasms of the thyroid
follicular epithelium
less than 5% of thyroid tumors, but with a high mortality rate
RAPID ENLARGEMENT
LARGE MASS
ANAPLASTIC CA
pleomorphic GIANT CELLS
SARCOMATOUS appearance - spindle shaped cells
(+) CYTOKERATIN
(+) PAX - 8
Neuroendocrine neoplasms derived from the parafollicular cells (C cells)
(+) calcitonin
MEDULLARY
RET
small, polygonal to spindle shaped cells
acellular AMYLOID deposits
FAVORABLE prognosis
papillary thyroid ca
minimally invasive follicular ca
UNFAVORABLE prognosis
widely invasive follicular ca
medullary thyroid ca
anaplastic thyroid ca
Most helpful thyroid differentiation marker in anaplastic ca
PAX-8
Used to diagnose parathyroid gland pathologies
TECHNETIUM 99 radionuclide scan
SCINTIGRAPHY
SESTAMIBI SCANS
Clinical manifestations of symptomatic primary hyperparathyroidism
STONES, THRONES, BONES, GROANS, PSYCHIATRIC OVERTONES
kidney stones
polyuria and polydipsia
bone pain
weakness, constipation, abdominal/flank pain
confusion, hallucinations, irritability
Hallmark of Severe Hyperparathyroidism
increased osteoclast activity
peritrabecular fibrosis
cystic brown tumor
HALLMARK of HYPOCALCEMIA
TETANY
ABSOLUTE insulin deficiency
B cell destruction
TYPE IV
HLA - CHROMOSOME 6
antibodies against islet cells (anti-insulin, anti-GAD, anti-ICA2)
TYPE I DM
RELATIVE insulin deficiency
insulin resistance
B cell dysfunction
genetic, environmental, proinflammatory
TYPE II DM
Acute Complications of DM
hypoglycemia
DKA
HHS
Macrovascular diseases in DM
Coronary Heart Disease - MI - MCC of death
Peripheral Arterial Disease
Cerebrovascular Disease
Microvascular diseases in DM
Retinopathy
Nephropathy
Neuropathy
diffuse BM thickening and leaky capillaries
NODULAR GLOMERULOSCLEROSIS - KIMMELSTIEL WILSON LESION
pyelonephritis, necrotizing papillitis
NERVES - glove and stocking pattern - MC
Insulin deficiency sufficient to develop KETOACIDOSIS
<7.25
(+) KETONES
usually VISCERAL (nausea, vomiting, abdominal pain)
DKA
Insulin deficiency insufficient to develop KETOACIDOSIS
> 7.30
usually NEUROLOGIC (altered mental status)
HHS
MC Pancreatic Neuroendocrine Tumor
INSULINOMA
Hyperinsulinism
WHIPPLE TRIAD
hypoglycemia (<50 mg/dl)
neuroglycopenic symptoms
relief upon parenteral glucose administration
INSULINOMA
pancreas
BENIGN
(+) amyloid deposition
Hypergastrinemia
pancreatic islet tumor
hypersecretion of gastric acid
severe peptic ulceration
GASTRINOMA (Zollinger Ellison Syndrome)
gastrinoma (Passaro) triangle
usually MALIGNANT
Ovoid, spherical, laminated nodules of matrix observed in diffuse and nodular diabetic glomerulosclerosis
KIMMELSTIEL-WILSON DISEASE
Hallmark of macrovascular disease in DM
ACCELERATED ATHEROSCLEROSIS
MI - MCC of death in diabetes
Abdominal striae, obesity, dorsocervical fullness (buffalo hump), moon facies
LAB FEATURES: increased 24 hr urine free cortisol
ACTH-independent - increased cortisol –> decreased ACTH
ACTH dependent - increased ACTH –> increased cortisol
pituitary (Cushing disease) or ectopic (SCLC) - increased ACTH
CUSHING SYNDROME
Exogenous steroids - MCC overall
ACTH secreting pituitary adenoma (Cushing disease) - MC endogenous cause
Crisis in patients with CHRONIC adrenocortical insufficiency
Rapid withdrawal of steroids in patients maintained on steroids
MASSIVE ADRENAL HEMORRHAGE - Waterhouse Friedrichsen syndrome
Primary Acute Adrenocortical Insufficiency
MCC of primary hyperaldosteronism (CONN DISEASE)
INCREASED ALDOSTERONE
PRIMARY - increased aldosterone – decreased renin
SECONDARY - increased aldosterone and renin
Bilateral idiopathic hyperaldosteronism
Primary Chronic Hypoaldosteronism (ADDISON DISEASE)
(-) mineralocorticoid
(-) glucocorticoid
(+) HYPERPIGMENTATION - secondary to collateral increase in MSH that accompanies the increase in ACTH to low adrenal cortisol output
NO response to ACTH stimulation test
Bilateral adrenal hemorrhage as a complication of DISSEMINATED bacterial infection
N. meningitidis
WATERHOUSE-FRIEDRICHSEN SYNDROME
Eosinophilic, laminated cytoplasmic inclusions in aldosterone secreting adenomas
SPIRONOLACTONE BODIES
Morphology of Addison Disease
irregular shrunken glands with LYMPHOID INFILTRATES
Chronic adrenal insufficiency (Addison Disease) in the developed world
secondary to autoimmune adrenalitis
Other important causes of chronic hypoadrenalism
Tuberculosis and infections due to opportunistic pathogens
associated with the human immunodeficiency virus and tumors metastatic to the adrenals
TRIAD
diaphoresis
headaches
palpitations
from CHROMAFFIN cells of MEDULLA
releases catecholamines
INCREASED urinary excretion of free catecholamines and metabolites (VANILLYLMANDELIC ACID (VMA) and METANEPHRINES)
PHEOCHROMOCYTOMA
Rule of 10’s
10% - extra-adrenal
10% - bilateral
10% - biologically malignant
10% - NOT associated with HPN
25% - have germline mutations
Histologic findings in Pheochromocytoma
ZELLBALLEN - clusters of polygonal or spindle shaped chromaffin or chief cells surrounded by sustentacular cells (like paraganglioma)
METASTASIS - only reliable criterion for malignancy
lymph nodes
liver
lungs
bone
MEN 1 (WERMER SYNDROME)
3PS
pituitary - prolactinoma - MC
parathyroid
pancreas
MEN 2 (SIPPLE SYNDROME)
2A
pheochromocytoma
parathyroid hyperplasia
medullary thyroid ca
2B
pheochromocytoma
medullary thyroid ca
neuromas
ganglioneuromas
marfanoid habitus
