Endocrine Part I Flashcards
What are factors released the pitutiary gland that stimualts the production of hrmones from endocrine glands?
Trophic factors
What are the general classification of ALL endocrine disorders?
Hypo/hyperfunctioning of the endocrine organ
Mass lesions/neoplasms
Autoimmune disorders
Infections —> these are rare
WHat is ADH for?
Water retention, Na excretion
What are the 4 clinical manifestations of pituitary diseases?
Hyperpituitarism
Hypopituitarism
Local mas effects
Decreaesd & Increased secretion of AHD
What are the 2 types of neoplasms of hyperitutarism? What is their difference?
Pituitary adenoma - functioning/non-functioning
Pitutiary carcinoma - hyperfuncitoning pituitary (PRL & ACTH)
What is the diff between functioning and non-functioning pituitary adenomas?
Functioning - hormone excess & clinical manifestations
Nonfunctioning - w/o clinical sx of hormone excess
What are the genetic alteration in pituitary hormones? There are 7 genes
GNAS - GH adenomas
PKAR1A - GH adenomas & PRL adenomas
CYclin D1 = Aggresive adenomas
HRAS = Pituitary adenomas
MEN1 = GH adenomas, PRL adenomas, ACTH adenomas
CDKN1B = ACTH adenomas
AIP = GH adenomas
RB (retinoblatoma) = Aggressive adenomas
What genetic alterations is one of the most common alterations seen in pituitary adenomas?
G-protein mutations
WHat is the gross morphology of pituitary adenomas?
Typical: soft & well-circumscribed
Smaller = confined to the sella turcica
Larger = extend superiorly thorugh the diaphram of sella into the suprasellar region
Invasive/Aggressive = could infiltrate the neighboring tissues
What is the histology of pituitary adenomas?
Only one typical cell
Uniform polygonal cells arranged in sheets or cords
Soft gelatinuous consistency
What is the key characterisitc of pituitary adenomas?
cellular monomorphism + absence of reticular network
What is the most common type of hyperfunctioning adenoma?
Lactotroph adenomas
What are the histological features of lactotroph adenoma?
Sparsely granulated
Has chromophobe cells
What are the diff pituitary adenomas?
Lactotoroph adenoma
Somatotroph adenomas
Corticotroph adenoma
GOnadotroph adenomas
Thyrotoph adenoma
Non-funcitoning adenoma
What is the clinical cours eof lactotoroph adenoma?
GAL = common in girls sooo…..
Galactorrhea
Amenorrhea
Loss of libido & sexual function
How do u differentiate physiologic hyperprolactinemia from Lactotroph hyperplasia?
If physiologic HYPERprolactinemia —> seen often in pregnancy & breastfeeding women
Lactototrph hyperplasia => Pathologic
What is the 2nd most common funcitoning adenoma and presents w/ GIGANTISM in children & ACROMEGALY in adults?
Somatotroph adenomas
-> remember sa GH to
What is the morphology of Somatotroph adenomas?
Monomorphic => Densely granulated
Sparsely granulated => Chromophobe cells
Bihormonal => Mammosomatotrophs (PRL & GH)
WHat are the causes of HYPOpitutarism?
Tumors & other masses
Traumatic brain injury & subarachnoid hemorrhage
Pituitary surgery or radiation
Pitutiary apoplexy
Ischemic necrosis or Sheehan’s syndrome
Rathke’s cleft cyst
Empty sella syndrome
Hypothalamic lesions
Inflammatory disorders & infections
Genetic Defects
What are the 2 types of Empty sella syndrome?
Primary empty sella => defect in the dipahragm sella allows the arachnoid mater & CSF to HERNIATE into the sella —> women w/ hx of multiple pregnancies
SEcondary empty sella => mass enlarges the sella —> loss of pitutiary function
What are the manfiestations of hypopituitarism?
Gonadotropin loss —> amenorrhea, inferitlity in women, loss of libido in men
TSH & ACTH def -> simialr to hypothyroidism
PRL deficiency
MSH deficiency
What are the different local mass effects in the pituitary gland?
Visual field abnormlaities
Elevated ICP —> headache, nausesa, vomiting
Obstructive hydrocephalus & seizures
Pituitary apoplexy —> acute hemorrhages into an adenoma —> rapid enlargement of lesion
What are the diff posterior pitutary syndromes?
Diabetes inspidus —> Central & Nephrogenic DI
SIADH
How do u diffenretiate Diabetes inspidus from SIADH?
Urinary output
= HIGH: Diabetes Inspidius
= LOW: SIADH
Levels of ADH
= HIGH: SIADH
= LOW: DI
Serum Na
= HIGH: DI
= LOW: SIADH
Hydration status
= HIGH (over hydrated): SIADH
= LOW: DI
Both will present with excessive thirst
What neoplasm may present as DI or SIADH? What are the common implicated tumors of this neoplasm?
Hypothalamic Suprasellar tumors
Implicated tumors:
- Gliomas
- Cranipharyngiomas
What are the different pathologies of the thyroid gland?
Hyperthyroidism
Hypothyroidism
Thyroiditis
Riedel’s thryoiditis
Graves’ disease
Goiters
Neoplams of the TG
How would u characterize thyrotoxicosis?
Elevated levels of free T3 & T4
Hypermetabolic state
What are the most common causes of thyrotoxicosis?
Diffuse hyperplasia of the thyroid assoc w/ Graves dis
Hyperfunctional multinodular goiter
Hyperfunctional thyroid adenoma
WHat are the clinical features of thyrotoxicosis?
INC in the basal metabolic rate
Cardiac manifestations
Overactivity of the sympathetic NS
Ocular changes
Thyroid storm
Apathetic hyperthyroidism
How do we diagnose px w/ THyrotoxicosis?
Low TSH, INC T3 & T4
What causes hypothyroidism?
structural or functional derangement that interferes with the production of thyroid hormone
WHat are the 3 causes of primary hypothyroidism?
Congenital hypothyroidism
Autoimmune hypothyroidism
Iatrogenic hypothyroidism
What are possible defective steps of congenital hypothyroidism? Other causes?
Iodide transport into thyrocytes
Organificaiton of iodine
Processing to form hormonally active T3&T4
Other causes:
- Complete absence of thyroid parenchyma (thyroid agenesis)
Whata causes secondary hypothyroidism?
Central hypothyroidism
Deficiencies of TSH
Deficiencies of TRH
What is cretinism? What are its clinical manfiestations?
hypothyroidism that developed during infancy/childhood
common in regions where dietary iodine deficiency is endemic
Severe intellectual disability, short stature, coarse facial features, protruding tongue, umbilical hernia
What type of hypothyroidism develops in older children/adult aka Gull’s disease? What are the clin manifestations of this dis?
Myxedema
Mimic depression
Listless, cold intolerant, frequently overweight, DEC sympathetic activity
What is the histologic feature of Myxedema?
Accumulation of Glycosaminoglycans, & hyaluronic acid
What are the 3 groups of thyroiditis?
Hashimoto’s thyroiditis
Granulomatous thyroiditis
Subacute lymphocytic thyroiditis
What type of thyroiditis is an autoimmune disorder that results in destruction of the TG & major cause of non-endemic goiter in the pediatric population?
Hashimoto’s thyroiditis
What causes Hashimoto’s thyroiditis?
Breakdown in self-tolerance to thyroid autoantigens
INC suscpetibility to CTLA4, PTPN22, & IL2RA
CD8 CTX Tcell med death
Cytokine-mediated cell death
What are the morphological features of Hashomoto’s thyrodiitis?
Gross:
- Thyroid is diffusely enlarge, capsule intact
Histology:
- Extensive inflammation of the parenchym
- Thyroid follicles are atrophic
- Hurthle cells w/ heterogenous lymphocytes
What cells are pathognomonic for Hashimotos thyroiditis?
Hurthle cells
What are the clinical features of Hashimotos thyroiditis?
painless enlargement of thyroid
INC T3, T4, uptake of radiactive iodine
DEC TSH
What is aka as De Quervain Thyroiditis & occurs less frequently as Hashimoto?
Granulomatous thyropiditis
What causes Granuloamtous thyroiditis? What is its morphology?
Viral infections (URTI)
Gross: unilateral or bilateral enlargement & firm TG
Histo
- patchy and depends on stage of disease
- multinucleated Giant cells enclose pools of coloid
What are the clinical features of Granulomatous thyroiditis?
most common cause of thyroid pain
self-limiting
INC T3, T4, DEC TSH
normal TG functions return after 6-8 wks of recoery
What is aka painless thyroiditis? What is the cause of this condition?
Subacute lymphocytic thyroiditis
Circulating antithyroid peroxidase antibodies
What are the morphologic features of Subacute lymphocytic thyroiditis? Clinical features?
Gross: normal
Histo: Lymphocytic infltration with large germinal centers & patchy disruption & collapse of thyroid follicles
Clinical features:
- mild transient HYPERthyroidism, painless goiter
What is the difference betw Hashimotos thyroiditis & Subacute lymphocytic thyroiditis?
SCLT: Fibrosis & Hurthle cell metaplasia not prominent
What is a rare condition of the TG with chronic inflammation, fibrosis, obstructive symptoms with invasiono of surrounding structures?
Riedel’s thyroiditis
Aka Riedel struma, Chronic invasive fibrous thyroiditis, or Ligneus struma
What is the hallmark of RIedel’s thyrodiitis?
Replacement of thyroid tissue with dense fibrotic tisue
What is the diagnostic confirmation of the biopsy of Riedel’s thyroiditis?
Dense fibrous tissue with characteristic eosinophilic infiltrate
Whta are the clinical manifestation sof RIedel’s thyroiditis?
PE: hard & enlarged thyroid, (+) Chvostek or Trousseau sign
S/Sx:
Dyspnea, Dysphagia, Stridor, Venous sinus thrombosis, Exophthalmos
What are the diagnostic criteria of RIedel thyroiditis?
Extrathyroidal extension of inflammatory process
Occlusive phlebitis
Absence of granulomas, giant cells, lymphoid follicles, or Oncocytes
Absenceof thyroid malignancy
What are the 3 tx options for Riedel’s thyroiditis?
Glucocorticoid tx
Tamoxifen
Mycophenolate Mofetil
What is an autoimmune disorder with production of autoAbs against multiple thyroid proteins (TSH receptor) & is the most common cause of endogenous HYPERthyroidism?
Graves’ disease
GRAVEEEE yern
What triad of clinical findings are seen in Graves’ dis?
HYPERthyroidism
Opthalmopathy
Infiltrative dermopahty (pretibial myxedema)
WHat are the morphological features of Graves dis?
Symmetrical enlargement of thyroid gland
Gross: Beefy red parenchyma
Histo: Follicles are lined by tall, columnar epithelium, crowded, enlarged epithelial cells
What are the clinical features of Graves disease?
Diffuse enlargement of thryoid present in all cases
Ophthalmopathy —> exophthalmos
Infiltrativedermpathy —> scaly thickening & induration
INC free T4, T3, DEC TSH
What are the tx options for Graves disease?
B-blockers
Thionamides
Radioiodine ablation, thyroidectomy
Surgery
What condition has an enlargement of the TG caused by impaired synthesis of thyroid hormone due to deficiency of Iodine in the diet?
Goiter
What is the pathophysiology of Goiters?
DEC TH production —> compensatory INC in serum TSH —> Hypertrophy & Hyperplasia of Thyroid follicles —> Enlargement of TG
INC in functional mass —> Euthyroid metab state (overcomes hormone def)
Severe dis —> inadequate compensatory response —> Goitrous hypothyroidism
What are the 2 types of Goiter?
Diffuse non-toxic
Multinodular
What causes Diffuse nontoxic (simple goiter)/Colloid goiter?
Enlargement of TG w/o producing nodularity
Occurs in geographic areas where water, soil, and food contain low levels of Iodine
What are substances that interfere with thyroid hormone synthesis in Simple Goiter/Diffuse Nontoxic Goiter?
Thiocyanate that inhibits Iodide transport
What are the 2 phases in evolution of diffuse nontoxic goiter?
Hyperplatic phase
Colloid involution phase
What is the difference betw Hyperplastic phase & COlloid involution phase of Simple goiter?
Hyperplastic -> follicles are lined by crowded columnar cells (piles up)
Colloid involution-> happens when dietary Iodine INC or if demand for TH decreases
WHat are the clinical features of Simple Goiter/Diffuse nontoxic goiter?
Normal serum T3, T4
Elevated TSH
What type of Goiter reuslts from recurrent episodes of hyperplasia and involution that ocmbine to produce irregular enlargement of the TG/
Multinodular goiter
What is the morphology of Goiters?
Multilobulated, asymmetrically enlarged glands
Pressure on midline structures (trachea & esophagus)
Brown, gelatinous colloid on cut surface
Hemorrhage, fibrosis, calcification, & cystic changes
Histo: Colloid-rich follicles lined by flattened inactive epithelium & areas of follicle hyperplasia w/ degenerative changes
What are the 2 types of neoplasms in the TG?
Adenoma
Thyroid carcinoma
What is a benign neoplasm of the TG w/ discrete solitary masses derived from follicular epithelium?
Follicular adenomas
What is the gross morphology of Follicular adenoma?
Intact, well-formed fibrous capsule encircling the tumors
Well-demarcated nodule, typically encapsulated
What is the diff betw Adenoma & Hyperplasia?
Both have INC in # of cells
Adenoma:
- there’s crowding but cells are cuboidal in shape, (+) - (+) Fibrous capsule
What cell is a histologic feature of Follicular adenoma?
Hurthle cell/Oxyphil adenoma
Also seen in Hashimoto’s thyroiditis
What is a malignant tumor of the thyroid gland? What are the diff subtypes under this?
Thyroid carcinoma
Subtypes:
Papillary TCA
Follicular TCA
Anaplastic TCA
Medullary TCA
What genetic alteration is seen in each subtype of THyroid carcinoma?
Papillary TCA = MAP kinase, RET/PTC translocation, BRAF point mutation
Follicular TCA = RAS point mutation, PTEN point mutation, PI3K point mutation, PAX8:PPARG translocation
ANaplastic TCA: RAS point mutation, PTEN point mutation & PI3K point mutation
Medullary TCA: MEN 2 with RET mutations
What is the most comomn type of cancer in the TG?
Papillary carcinoma
What is the distinguishing feature of follicular adneomas from follicular carcinomas?
Integrity of the capsule
What is the morphology of papillary carcinoma? Dx feature?
Gross: discernable papillary structures
Histo:
- Finger-like/Papillary-like projections
- Orphan Annie eyes (empty-appearing nuclei w/ optical clearing) - Dx feature
What are concentirc calcified structures seen in Papilary CA usuall seen at the core of the papilla, not a dx feature of papillary CA/
Psamomma bodies
What are the 4 cell variants of Papillary carcinoma of thyroid gland? What are its distinguishing features?
Follicular variant => Orphan ANnie nuclei
Tall-cell variant => Follicle is lined w/ tall columnar cells w/ intensely eosinophilic cytolasm
Diffuse-sclerosing variant => youger px, might have Psamomma bodies, prominent lymphocytic infiltration
Papillary microcarcinoma => contains Orphan annie nuclei, good prognosis, distant metastasis
In what pop is Follicular carcinoma more frequent? What are the morphologic features of Follicular carcnoma?
Areas w/ iodine deificiency
Gross: replacement of entire thyroid parenchyma, light in appearance but contains small foci of hemorrhage
Histo: Recognizable colloids
WHat are the clinical manifestations of Follicular carcinoma?
Solitary cold thyroid nodules
Tend to metastasize through the bloodstream to the lungs, bone, & liver
WHat are the 3 diff cell variants of FOllicular carcinoma?
Hurthle cell variant
Minimally invasive follicular CA => infiltation of thyroid parenchyma & capsule
Vascular invasion follicular CA => fibrous capsule, compressed normal thyroid parenchyma
What type of TG carcinoma is higliy aggresive, seen in older px, well-differentiated papillary or follicular carcinoma?
Anaplastic carcinoma
What are the morphological features of ANaplastic carcinoma?
Gross: bulky mass, grows rapidly beyond the thyroid capsule into adjunct structures of the neck
Histo: Large pleomorphc giant cells, osteoclat-like multinucleated giant cells, Spindle type, Mixed spindle & giant cell type
From what cells is Medullary carcinoma derived from? What hormones do it secrete?
Parafollicular C cells
Calcitonin, ACTH, VIP, Serotonin
WHat are the morphologic features of Medullary carcinoma?
Gross: Solid pattern of growth
Histo: remnants of thyroid follicle, abundant deposition of AMYLOID
What are the clincial manifestationsof Medullary carcinoma?
ACTH: cushing-like syndrome
Serotonin: CArcinoid tumor
VIP: GI manifesations
Mass in neck -> Dysphagia/Hoarseness
What are the 3 types of hyperparathyroidism?
Primary, secondary, & tertiary hyperparathyroidism
What are the causes of hyperthyroidism?
Primary => secretion of excess PTH by chief cells in adenoma, DEC TSH, INC T4, T3
Secondary => renal disease results i impaired PO4 excretion, PTG enlarged, INC TSH, T4, T3
Tertiary => INC TSH, INC T4, T3
What is the most important cause of hypercalcemia?
Primary hyperthyroidism
Usual cause of hyperfunctioning parathyroid
What are the diff causes of primary hyperparathyroidism?
Parathyroid adenoma
Primary Hyperplasia
Parathyroid carcinoma
What is the most common cause of primary HYPERPARAthyroidism? What are the molecular defects of this dis?
Prathyroid adenoma
Molecular defects:
Cyclin D1 gene inversions
MEN1 mutations
What are the morphological features of Parathyroid adenomas?
Gross: Often solitary, mostly composed of Chief cells, well-circumscribed, soft, tan to reddish brown
Histo: Chief cells:, inconspicuou adipose tissue
What is primary hyperplasia and what are its morphological features (histo)?
4 glands are involved
Histo:
Chief cell hyperplaia
Water-clear cell hyperplasia => abundant glycogen
What are the morphological features of Parathyroid carcinoma?
PTG enlarged, gray-white irregular mass
Histo Dx: Invasion of surrounding tissues & metastasis
What are the diff bone changes in HYPERparathyroidism?
Osteoporosis
Brown tumor
Osteitis fibrosa cystica
What type of bone change in hyperparathyroidism results in DEC bone mass, INC osteoclast activity which produces dissecting Osteitis?
Osteoporosis
What causes brown tumor?
Bone loss predisposes to microfactures & secondary hemorrhages
Vascularity, hemorrhage, hemosiderin deposition
Not really a tumpr
What is a hallmark of severe hyperparathyroidism?
Osteitis fibrosa cystica
Aka Von Recklinghausen’s disease of the bone
Combination of INC osteoclast activity, peritrabecular fibrosisis, Cystic brown tumors
What are the clinical features of hyperparathyroidism?
Nephrolithiasis => Metastatic calcification
What causes secondary hyperparathyroidism?
Compensatory state due to prolonged hypocalcemia
Renal failure
Other causes: Inadquate Ca intake, VIt D def, Steatorrhea
What is the most common cause of 2ndary hyperparathyroidism
Renal failure
What are the clinical manifestations of 2ndary hyperparathyroidism?
Skeletal abnormalities (milder compaired to primary)
Cacliphylaxis - vascular calcification
What condition is caused by end organ resistance to the action of PTH & presents with hypocalcemia, hyperphosphatemia, INC PTH?
Pseudohypoparathyroidism
What are the diff causes of HYPOparathyroidism?
Surgically induced (thyroidectomy) -> most common
AI hypoparathyroidism
Autosomal dominant hypoparathyroidism
Familial isolated hypoparathyroidism
Congenital absence of PTG -> Digeorge syndrome
What causes AI hypoparathyroidism, Autosomal dominant Hypoparathyroidsim & familial isolated hypoparathyroidism?
AI hypoparathyroidism => Autoimmune polyendocrine system syndrome (APS-1 => Autoimmune regulator gene
Autosomal dominant hypoparathyroidism => Ca snesing receptor gene
Familial isolated hypoparathyroidism => PTH precursor peptide
What conditions are assoc w/ AI hypoparathyroidism?
Chronic mucocutaneous candidiasis ff by hyperparathyroidism & primary adrenal insufficiency
What happens in autosomal dominant hypoparathyroidism?
SUppress parathyroid hormone ==> HYPOCALCEMIA, HYPERcalcemia
What are the clinical manifestaions of HYPOCalcemia? What is the hallmark of hypocalcemia?
CATS love milk ==> Ca in milk ==> Hypocalcemia
Convulsions
Arrhythmias
Tetany => hallmark of hypocalcemia
Spasms & Stridor
What are the classifc findigns on PE of HYPOparathyroidism?
Chvostek sign => tapping along facial nerve
Trousseau sign => carpal spasms
