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Endocrine Part I Flashcards

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1
Q

What are factors released the pitutiary gland that stimualts the production of hrmones from endocrine glands?

A

Trophic factors

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2
Q

What are the general classification of ALL endocrine disorders?

A

Hypo/hyperfunctioning of the endocrine organ
Mass lesions/neoplasms
Autoimmune disorders
Infections —> these are rare

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3
Q

WHat is ADH for?

A

Water retention, Na excretion

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4
Q

What are the 4 clinical manifestations of pituitary diseases?

A

Hyperpituitarism
Hypopituitarism
Local mas effects
Decreaesd & Increased secretion of AHD

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5
Q

What are the 2 types of neoplasms of hyperitutarism? What is their difference?

A

Pituitary adenoma - functioning/non-functioning
Pitutiary carcinoma - hyperfuncitoning pituitary (PRL & ACTH)

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6
Q

What is the diff between functioning and non-functioning pituitary adenomas?

A

Functioning - hormone excess & clinical manifestations
Nonfunctioning - w/o clinical sx of hormone excess

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7
Q

What are the genetic alteration in pituitary hormones? There are 7 genes

A

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

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8
Q

What genetic alterations is one of the most common alterations seen in pituitary adenomas?

A

G-protein mutations

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9
Q

WHat is the gross morphology of pituitary adenomas?

A

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

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10
Q

What is the histology of pituitary adenomas?

A

Only one typical cell
Uniform polygonal cells arranged in sheets or cords
Soft gelatinuous consistency

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11
Q

What is the key characterisitc of pituitary adenomas?

A

cellular monomorphism + absence of reticular network

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12
Q

What is the most common type of hyperfunctioning adenoma?

A

Lactotroph adenomas

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13
Q

What are the histological features of lactotroph adenoma?

A

Sparsely granulated
Has chromophobe cells

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14
Q

What are the diff pituitary adenomas?

A

Lactotoroph adenoma
Somatotroph adenomas
Corticotroph adenoma
GOnadotroph adenomas
Thyrotoph adenoma
Non-funcitoning adenoma

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15
Q

What is the clinical cours eof lactotoroph adenoma?

A

GAL = common in girls sooo…..

Galactorrhea
Amenorrhea
Loss of libido & sexual function

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16
Q

How do u differentiate physiologic hyperprolactinemia from Lactotroph hyperplasia?

A

If physiologic HYPERprolactinemia —> seen often in pregnancy & breastfeeding women

Lactototrph hyperplasia => Pathologic

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17
Q

What is the 2nd most common funcitoning adenoma and presents w/ GIGANTISM in children & ACROMEGALY in adults?

A

Somatotroph adenomas

-> remember sa GH to

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18
Q

What is the morphology of Somatotroph adenomas?

A

Monomorphic => Densely granulated
Sparsely granulated => Chromophobe cells
Bihormonal => Mammosomatotrophs (PRL & GH)

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19
Q

WHat are the causes of HYPOpitutarism?

A

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

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20
Q

What are the 2 types of Empty sella syndrome?

A

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

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21
Q

What are the manfiestations of hypopituitarism?

A

Gonadotropin loss —> amenorrhea, inferitlity in women, loss of libido in men

TSH & ACTH def -> simialr to hypothyroidism
PRL deficiency
MSH deficiency

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22
Q

What are the different local mass effects in the pituitary gland?

A

Visual field abnormlaities

Elevated ICP —> headache, nausesa, vomiting
Obstructive hydrocephalus & seizures

Pituitary apoplexy —> acute hemorrhages into an adenoma —> rapid enlargement of lesion

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23
Q

What are the diff posterior pitutary syndromes?

A

Diabetes inspidus —> Central & Nephrogenic DI
SIADH

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24
Q

How do u diffenretiate Diabetes inspidus from SIADH?

A

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

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25
What neoplasm may present as DI or SIADH? What are the common implicated tumors of this neoplasm?
Hypothalamic Suprasellar tumors Implicated tumors: - Gliomas - Cranipharyngiomas
26
What are the different pathologies of the thyroid gland?
Hyperthyroidism Hypothyroidism Thyroiditis Riedel’s thryoiditis Graves’ disease Goiters Neoplams of the TG
27
How would u characterize thyrotoxicosis?
Elevated levels of free T3 & T4 Hypermetabolic state
28
What are the most common causes of thyrotoxicosis?
Diffuse hyperplasia of the thyroid assoc w/ Graves dis Hyperfunctional multinodular goiter Hyperfunctional thyroid adenoma
29
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
30
How do we diagnose px w/ THyrotoxicosis?
Low TSH, INC T3 & T4
31
What causes hypothyroidism?
structural or functional derangement that interferes with the production of thyroid hormone
32
WHat are the 3 causes of primary hypothyroidism?
Congenital hypothyroidism Autoimmune hypothyroidism Iatrogenic hypothyroidism
33
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)
34
Whata causes secondary hypothyroidism?
Central hypothyroidism Deficiencies of TSH Deficiencies of TRH
35
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
36
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
37
What is the histologic feature of Myxedema?
Accumulation of Glycosaminoglycans, & hyaluronic acid
38
What are the 3 groups of thyroiditis?
Hashimoto's thyroiditis Granulomatous thyroiditis Subacute lymphocytic thyroiditis
39
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
40
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
41
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
42
What cells are pathognomonic for Hashimotos thyroiditis?
Hurthle cells
43
What are the clinical features of Hashimotos thyroiditis?
painless enlargement of thyroid INC T3, T4, uptake of radiactive iodine DEC TSH
44
What is aka as De Quervain Thyroiditis & occurs less frequently as Hashimoto?
Granulomatous thyropiditis
45
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
46
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
47
What is aka painless thyroiditis? What is the cause of this condition?
Subacute lymphocytic thyroiditis Circulating antithyroid peroxidase antibodies
48
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
49
What is the difference betw Hashimotos thyroiditis & Subacute lymphocytic thyroiditis?
SCLT: Fibrosis & Hurthle cell metaplasia not prominent
50
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
51
What is the hallmark of RIedel’s thyrodiitis?
Replacement of thyroid tissue with dense fibrotic tisue
52
What is the diagnostic confirmation of the biopsy of Riedel’s thyroiditis?
Dense fibrous tissue with characteristic eosinophilic infiltrate
53
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
54
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
55
What are the 3 tx options for Riedel’s thyroiditis?
Glucocorticoid tx Tamoxifen Mycophenolate Mofetil
56
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
57
What triad of clinical findings are seen in Graves’ dis?
HYPERthyroidism Opthalmopathy Infiltrative dermopahty (pretibial myxedema)
58
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
59
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
60
What are the tx options for Graves disease?
B-blockers Thionamides Radioiodine ablation, thyroidectomy Surgery
61
What condition has an enlargement of the TG caused by impaired synthesis of thyroid hormone due to deficiency of Iodine in the diet?
Goiter
62
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
63
What are the 2 types of Goiter?
Diffuse non-toxic Multinodular
64
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
65
What are substances that interfere with thyroid hormone synthesis in Simple Goiter/Diffuse Nontoxic Goiter?
Thiocyanate that inhibits Iodide transport
66
What are the 2 phases in evolution of diffuse nontoxic goiter?
Hyperplatic phase Colloid involution phase
67
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
68
WHat are the clinical features of Simple Goiter/Diffuse nontoxic goiter?
Normal serum T3, T4 Elevated TSH
69
What type of Goiter reuslts from recurrent episodes of hyperplasia and involution that ocmbine to produce irregular enlargement of the TG/
Multinodular goiter
70
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
71
What are the 2 types of neoplasms in the TG?
Adenoma Thyroid carcinoma
72
What is a benign neoplasm of the TG w/ discrete solitary masses derived from follicular epithelium?
Follicular adenomas
73
What is the gross morphology of Follicular adenoma?
Intact, well-formed fibrous capsule encircling the tumors Well-demarcated nodule, typically encapsulated
74
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
75
What cell is a histologic feature of Follicular adenoma?
Hurthle cell/Oxyphil adenoma Also seen in Hashimoto’s thyroiditis
76
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
77
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
78
What is the most comomn type of cancer in the TG?
Papillary carcinoma
79
What is the distinguishing feature of follicular adneomas from follicular carcinomas?
Integrity of the capsule
80
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
81
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
82
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
83
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
84
WHat are the clinical manifestations of Follicular carcinoma?
Solitary cold thyroid nodules Tend to metastasize through the bloodstream to the lungs, bone, & liver
85
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
86
What type of TG carcinoma is higliy aggresive, seen in older px, well-differentiated papillary or follicular carcinoma?
Anaplastic carcinoma
87
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
88
From what cells is Medullary carcinoma derived from? What hormones do it secrete?
Parafollicular C cells Calcitonin, ACTH, VIP, Serotonin
89
WHat are the morphologic features of Medullary carcinoma?
Gross: Solid pattern of growth Histo: remnants of thyroid follicle, abundant deposition of AMYLOID
90
What are the clincial manifestationsof Medullary carcinoma?
ACTH: cushing-like syndrome Serotonin: CArcinoid tumor VIP: GI manifesations Mass in neck -> Dysphagia/Hoarseness
91
What are the 3 types of hyperparathyroidism?
Primary, secondary, & tertiary hyperparathyroidism
92
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
93
What is the most important cause of hypercalcemia?
Primary hyperthyroidism Usual cause of hyperfunctioning parathyroid
94
What are the diff causes of primary hyperparathyroidism?
Parathyroid adenoma Primary Hyperplasia Parathyroid carcinoma
95
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
96
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
97
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
98
What are the morphological features of Parathyroid carcinoma?
PTG enlarged, gray-white irregular mass Histo Dx: Invasion of surrounding tissues & metastasis
99
What are the diff bone changes in HYPERparathyroidism?
Osteoporosis Brown tumor Osteitis fibrosa cystica
100
What type of bone change in hyperparathyroidism results in DEC bone mass, INC osteoclast activity which produces dissecting Osteitis?
Osteoporosis
101
What causes brown tumor?
Bone loss predisposes to microfactures & secondary hemorrhages Vascularity, hemorrhage, hemosiderin deposition Not really a tumpr
102
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
103
What are the clinical features of hyperparathyroidism?
Nephrolithiasis => Metastatic calcification
104
What causes secondary hyperparathyroidism?
Compensatory state due to prolonged hypocalcemia Renal failure Other causes: Inadquate Ca intake, VIt D def, Steatorrhea
105
What is the most common cause of 2ndary hyperparathyroidism
Renal failure
106
What are the clinical manifestations of 2ndary hyperparathyroidism?
Skeletal abnormalities (milder compaired to primary) Cacliphylaxis - vascular calcification
107
What condition is caused by end organ resistance to the action of PTH & presents with hypocalcemia, hyperphosphatemia, INC PTH?
Pseudohypoparathyroidism
108
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
109
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
110
What conditions are assoc w/ AI hypoparathyroidism?
Chronic mucocutaneous candidiasis ff by hyperparathyroidism & primary adrenal insufficiency
111
What happens in autosomal dominant hypoparathyroidism?
SUppress parathyroid hormone ==> HYPOCALCEMIA, HYPERcalcemia
112
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
113
What are the classifc findigns on PE of HYPOparathyroidism?
Chvostek sign => tapping along facial nerve Trousseau sign => carpal spasms

Pathology (8 decks)

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