Endocrine Pathology Flashcards

Question

MYXEDEMA Clinical features Most common cause

Answer 1

**Hypothyroidism in older children or adults** Clinical features are based on decreased basal metabolic rate and decreased sympathetic nervous system activity. 1. **Myxedema** - accumulation of glycosaminoglycans in the skin and soft tissue; results in a**_ $ deepening of voice and large tongue_** 2. **Weight gain** despite normal appetite 3. **Slowing of mental activity** 4. **Muscle weakness** 5. **Cold intolerance** with decreased sweating 6. **Bradycardia** with decreased cardiac output, leading to shortness of breath and fatigue 7. **Oligomenorrhea** 8. **Hypercholesterolemia** 9. **Constipation** Most common causes are **iodine deficiency** and **Hashimoto thyroiditis**; other causes include drugs (e.g., lithium) and surgical removal or radioablation of the thyroid.

Answer 2

**Autoimmune destruction of the thyroid gland; associated with _HLA-DR5_ - Most common cause of hypothyroidism in regions where iodine levels are adequate** Clinical features 1. Initially may present as hyperthyroidism (due to follicle damage) 2. Progresses to hypothyroidism decreased T4, and increased TSH 3. **Antithyroglobulin and antimicrosomal antibodies** are often present (sign of thyroid damage). **_$ Chronic inflammation with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles) is seen on histology _** **_$ Increased risk for B-cell (marginal zone) lymphoma; presents as an enlarging thyroid gland late in disease course_**

Answer 3

**Granulomatous thyroiditis** that follows a **viral infection** * Presents as a $**_tender thyroid_** with **transient hyperthyroidism** * Self-limited; **does not progress to hypothyroidism**

Answer 4

**Chronic inflammation with extensive fibrosis of the thyroid gland** **_$ Presents as hypothyroidism with a ' hard as wood,' nontender thyroid gland_** **_$ Fibrosis may extend to involve local structures (e.g., airway) _** **_$ Clinically mimics anaplastic carcinoma (patients usually in 70s), but patients are younger (40s), and malignant cells are absent. Classically a young female_**

Answer 5

REIDEL FIBROSING THYROIDITIS ## Footnote B. Presents as hypothyroidism with a ' hard as wood,' nontender thyroid gland C. Fibrosis may extend to involve local structures (e.g., airway). l. Clinically mimics anaplastic carcinoma, but patients are younger (40s), and malignant cells are absent

Answer 6

**_B-cell (marginal zone) lymphoma_** **- **presents as an enlarging thyroid gland late in disease course

Answer 7

Usually presents as a **distinct, solitary nodule** - Thyroid nodules are more likely to be benign than malignant. I-131 radioactive uptake studies are useful to further characterize nodules. 1. **Increased uptake ('hot' nodule) is seen in Graves disease or nodular goiter.** 2. **Decreased uptake ('cold' nodule) is seen in adenoma and carcinoma; often warrants biopsy** **_$Biopsy is performed by fine needle aspiration (FNA)_**

Answer 8

**_Benign_ proliferation** of follicles surrounded by a **_fibrous capsule_** **- Usually nonfunctional; less commonly, may secrete thyroid hormone**

Answer 9

**#1 PAPILLARY CARCINOMA (70-85%)** #2 FOLLICULAR CARCINOMA (10%) #3 MEDULLARY CARCINOMA (5%) #4 ANAPLASTIC CARCINOMA "Paul Fifer Meets Ana"

Answer 10

**Most common type of thyroid carcinoma (80% of cases)** **_$Exposure to ionizing radiation in childhood is a major risk factor._** * **_$Most common mutation in the BRAF gene (serine/threonine kinase)_** * **_$Commonly associated with rearrangements in RET oncogene or NTRK1_** Comprised of **papillae l**ined by cells with **_clear, 'Orphan Annie eye' nuclei and nuclear grooves papillae_** are often associated with **_psammoma bodies _**(concentric layers of calcification) Often spreads to **cervical (neck) lymph nodes**, but prognosis is excellent (10-year survival\> 95%)

Answer 11

**Malignant proliferation** of **follicles** surrounded by a **_fibrous capsule with invasion through the capsule _** Second most common thyroid cancer (10%) 40% have RAS mutations 1. Invasion through the capsule helps distinguish follicular carcinoma from follicular adenoma. * *_$2. Entire capsule must be examined microscopically._** * *_3. $ FNA only examines cells and not the capsule; hence, a distinction between follicular adenoma and follicular carcinoma cannot be made by FNA._** $ Metastasis generally occurs **_hematogenously_** Good prognosis

Answer 12

**Malignant proliferation of _parafollicular C cells_; comprises 5% of thyroid carcinomas - Calcitonin often deposits within the tumor as amyloid** $ Biopsy reveals sheets of **_malignant cells in an amyloid stroma _** Familial cases are often due to **multiple endocrine neoplasia (MEN) 2A and 2B**, which are associated with mutations in the **RET oncogene**. _**1. MEN 2 results in medullary carcinoma, pheochromocytoma, and parathyroid adenomas (2A) or ganglioneuromas of the oral mucosa (2B).**_ $2. **_Detection of the RET mutation warrants prophylactic thyroidectomy._**

Answer 13

MEN 2 results in * _medullary carcinoma,_ * pheochromocytoma, and * **parathyroid adenomas (2A) or ganglioneuromas of the oral mucosa (2B)**

Answer 14

**Undifferentiated malignant tumor** of the **thyroid** usually seen in **_elderly_** * **_Often invades local structures_**, leading to dysphagia or respiratory compromise * Poor prognosis

Answer 15

A. **Chief cells** regulate serum free (ionized) calcium via parathyroid hormone (PTH) secretion, which: 1. Increases bone osteoclast activity (by **_activating osteblasts first)_**, releasing calcium and phosphate 2. Increases small bowel absorption of calcium and phosphate (ind irectly by activating vitamin D) 3. Increases renal calcium reabsorption (distal tubule) and decreases phosphate reabsorption (proximal tubule) B. Increased serum ionized calcium levels provide negative feedback to decrease PTH secretion.

Answer 16

Most common cause is **_parathyroid adenoma_** (\>80% of cases); sporadic parathyroid hyperplasia and parathyroid carcinoma are less common causes.

Answer 17

**Parathyroid adenoma** is a benign neoplasm (most common cause of primary hyperparathyroidism), usually involving one gland. 1. Most often results in **asymptomatic hypercalcemia;** however, may present with consequences of increased PTH and hypercalcemia such as i. **Nephrolithiasis** (calcium oxalate stones) ii. **Nephrocalcinosis**- metastatic calcification of renal tubules (Fig. 15.9), potentially leading to renal insufficiency and polyuria iii. **CNS disturbances** (e.g., depression and seizures) iv. **Constipation**, peptic ulcer disease, and $ **_acute pancreatitis_** v. **Osteitis fibrosa cystica** - resorption of bone leading to fibrosis and cystic spaces (Fig. 15.10)

Answer 18

Laboratory findings include * Increased serum PTH, * Increased serum calcium, * Decreased serum phosphate, * **_$ Increased urinary cAMP,_** * **_$ Increased serum alkaline phosphatase - sign of osteoblast activity, PTH receptors on osteoblasts_**

Answer 19

**_$ Increased urinary cAMP - PTH receptor on tubular cells stimulates a G-stimulatory protein that activates Adenylate Cyclase converting ATP to cAMP that is released into the urine_** $ Increased serum alkaline phosphatase - sign of osteoblast activity, PTH receptors on osteoblasts

Answer 20

Excess production of PTH due to a disease process extrinsic to the parathyroid gland - Most common cause is chronic renal failure.

Answer 21

**Low PTH - Causes include autoimmune damage to the parathyroids, surgical excision, and DiGeorge syndrome** Presents with symptoms related to **low serum calcium** 1. **Numbness and tingling** (particularly circumoral) 2. **Muscle spasms** (tetany)-may be elicited with filling of a blood pressure cuff (Trousseau sign) or tapping on the facial nerve (Chvostek sign) Labs reveal decreased PTH levels and Decreased serum calcium.

Answer 22

**_$ Pseudohypoparathyroidism is due to end-organ resistance to PTH due to a defect in the G stimulatory protein that the PTH receptor uses._** $ 1. Labs reveal **hypocalcemia with _Increased PTH levels_.** $ 2. **Autosomal dominant** form is **associated with short stature and short 4th and 5th digits.**

Answer 23

Pseudohypoparathyroidism is due to end-organ resistance to PTH. Labs will show elevated PTH and low serum calcium.

Answer 24

Insulin is secreted by beta cells, which lie in the **_center of the islets_**

Answer 25

**Characterized by inflamma tion of islets** HLA-DR3 and HLA-DR4 Autoantibodies against insulin are often present (sign of damage) and may be seen years before clinical disease develops. Type IV hypersensitivity

Answer 26

Obesity leads to decreased numbers of insulin receptors. Strong genetic predisposition exists. **Insulin levels are increased early in disease, but later, insulin deficiency develops due to beta cell exhaustion; histology reveals amyloid deposition in the islets**

Answer 27

1. Glucose freely enters into Schwann cells (which myelinate peripheral nerves),** pericytes** of retinal blood vessels, and the lens. 2. **Aldose reductase** converts glucose to sorbitol, resulting in osmotic damage. 3. Leads to **peripheral neuropathy, impotence, blindness, and cataracts**; diabetes is the leading cause of blindness in the developed world.

Answer 28

**Tumors of islet cells; account for \< 5% of pancreatic neoplasms - Often a component of MEN I along with parathyroid hyperplasia and pituitary adenomas + pancreatic endocrine tumor** * **Insulinomas** present as episodic hypoglycemia with mental status changes that are relieved by administration of glucose - $ **_Diagnosed by decreased serum glucose levels (usually\< 50 mg/dL), increased insulin, and increased C-peptide_** * **Gastrinomas** present as treatment-resistant peptic ulcers (Zollinger-Ellison syndrome); ulcers may be multiple and can extend into the jejunum. * **Somatostatinomas** present as achlorhydria (due to inhibition of gastrin) and cholelithiasis with steatorrhea (due to inhibition of cholecystokinin). * **VIPomas** secrete excessive vasoactive intestinal peptide leading to **watery diarrhea, hypokalemia, and achlorhydria.**

Answer 29

**Excess cortisol** Clinical features 1. **Muscle weaknes**s with thin extremities-Cortisol breaks down muscle for gluconeogenesis. 2. **Moon facies, buffalo hump, and truncal obesity**-High insulin (due to high glucose) increases storage of fat. 3. **Abdominal striae**-due to impaired synthesis of collagen with thinning of skin 4. **Hypertension** 5. Osteoporosis 6. **Immune suppression** Diagnosis is made by increased 24-hour urine cortisol levels. 4. **_Exogenous corticosteroids_**- leads to bilateral adrenal atrophy; steroids suppress ACTH secretion (negative feedback). 2. **_Primary adrenal adenoma_**, hyperplasia, or carcinoma- leads to atrophy of the uninvolved adrenal gland 3. **_ACTH-secreting pituitary adenoma_**-leads to bilateral adrenal hyperplasia 4. **_Para neoplastic ACTH_** secretion (e.g., small cell carcinoma of the lung)-leads to bilateral adrenal hyperplasia

Answer 30

1. Cortisol induces the synthesis of lipocortin which inhibits phospholipase A2 preventing production of arachadonic product pathway 2. Inhibits IL-2 3. Inhibits the release of histamine and serotonin from mast cells and platelets

Answer 31

High-dose dexamethasone (cortisol analog) suppresses ACTH production by a** pituitary adenoma** (cortisol levels decrease), but fails to suppress ectopic ACTH production by a **small cell lung carcinoma** (cortisol levels remain high).

Answer 32

**Excess aldosterone** Presents as **hypertension with hypernatremia, hypokalemia, and metabolic alkalosis** 1. Aldosterone **increases sodium absorption** and **secretion of potassium** and **hydrogen ions (distal tubules and collecting duct).** 2. Increased absorption of sodium expands plasma volume leading to hypertension.

Answer 33

**Primary - #1 adrenal adenoma, LOW renin** **Secondary - Activation of RAAS and HIGH renin** **_Primary hyperaldosteronism_** is most commonly due to an **adrenal adenoma**; sporadic adrenal hyperplasia and adrenal carcinoma are less common causes. Characterized by **high aldosterone** and $**_low renin_** (high blood pressure downregulates renin via negative feedback) **_Secondary hyperaldosteronism_** is seen with activation of the renin-angiotensin system (e.g., renovascular hypertension or CHF). Characterized by **high aldosterone and $ _high renin_**

Answer 34

**Excess sex steroids** with **hyperplasia of both adrena**l glands -**_ Inherited 21-hydroxylase deficiency_** is the most common cause. Deficiency of cortisol leads to increased ACTH secretion (lack of negative feedback), which results in bilateral adrenal hyperplasia. Clinical features include 1. Salt wasting with hyponatremia, hyperkalemia, and hypovolemia due to lack of aldosterone. 2. Life-threatening hypotension due to lack of cortisol. 3. Clitoral enlargement (females) or precocious puberty (males) due to excess androgens

Answer 35

**Lack of adrenal hormones** **_Acute insufficiency_** may arise with **Waterhouse-Friderichsen syndrome** - Characterized by $**_hemorrhagic necrosis of the adrenal glands,_** classically due to DIC in young children with *N meningitidis* infection. Lack of cort isol exacerbates hypotension, often leading to death. **_Chronic insufficiency (Addison disease)_** is due to progressive destruction of the adrenal glands. 1. Common causes include **autoimmune destruction** (most common cause in the West), **TB** (most common cause in the developing world), and metastatic carcinoma (e.g., arising from lung, LUNG CANCER LOVES ADRENAL). 2. Clinical features include **_hypotension, hyponatremia, hypovolemia, hyperkalemia, weakness, hyperpigmentation (increased ACTH by-products stimulate melanocytic production of pigment), vomiting, and diarrhea._**

Answer 36

Composed of **_neural crest-derived chromaffin cells._** **Main physiologic source** of **_catecholamines (epinephrine and norepinephrine)_**

Answer 37

**Tumor of chromaffin cells** Clinical features are due to increased serum catecholamines - **Episodic hypertension, headache, palpitations, tachycardia, and sweating** Diagnosed by **increased serum metanephrines** and increased 24-hour **_urine metanephrines and vanillylmandelic acid_**

Answer 38

1. Hemangioblastoma of cerebellum 2. RCC 3. Pheochromocytoma

Answer 39

Often follows the 'rule of lOs:' 10% bilateral, 10% familial, 10% malignant, and 10% located outside of the adrenal medulla (e.g., bladder wall or organ of Zuckerkandl at the inferior mesenteric artery root) **_Associated with MEN 2A and 2B, von Hippel-Lindau disease, and neurofibromatosis type 1_**

Answer 40

**Albright's hereditary osteodystrophy ** * the result of **defective Gs protein** in kidney and bone, which causes end-organ **resistance to PTH** * **Hypocalcemia** and **hyperphosphatemia** occur (as in hypoparathyroidism), which are not correctable by administration of exogenous PTH * Circulating **PTH levels are elevated** (stimulated by hypocalcemia)

Answer 41

15.4 Classic Waterhouse-Friderichsen syndrome - sac of blood in adrenal

Answer 42

Amyloid in islets, type II DM - beta cell exhaustion

Answer 43

Pheochromocytoma - classic finding is brown tumor

Answer 44

Hyaline Arteriolosclerosis - Complications of diabetes, Non-enzymatic glycosylation of small vessels (arterioles)

Answer 45

Glomerulosclerosis - **Non Enzymatic glycosylation of renal arterioles** is MOA - small scarred kidneys with granular surface

Answer 46

* midline above quadrigemmal plate * Site for melatonin production * commonly undergoes dystrophic calcification * **majority are germ cell tumors** * paralysis of upward gaze ("setting sun" sign)

Answer 47

an ectodermal derivative derived from the oral cavity. It develops into the anterior lobe of the pituitary gland.

Answer 48

hemorrhage into preexisting adenoma

Answer 49

Empty sella syndrome:

Answer 50

Prolactinoma

Answer 51

adrenogenital syndrome

Answer 52

Addison's disease

Answer 53

Neuroblastoma

Endocrine Pathology Flashcards

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