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Flashcards in Endocrine System Deck (61):
1

Pituitary

Small, bean shaped structure within the sella turcica and connected to the hypothalamus by stalk of axons
Hypothalamus and pituitary play central role in regulating other endocrine organs

2

Hyperpituitarism

Excessive secretion of trophic hormones
Usually caused by adenoma of anterior pituitary

3

Pituitary adenoma

Usually composed of a single cell type that produces a single hormone
Well circumscribed, soft
Can be:
-Functional or silent
-Most occur in isolation
-3% are asciated with MEN-1
-Microadenoma (<1 cm)/macroadenoma (> 1 cm)

4

What are the best known molecular abnormalities in pituitary adenomas?

GNAS1 gene
Encodes Gs alpha
Result in constitutive activation, unchecked cell growth

5

Prolactinoma

Most common pituitary adenoma
Amenorrhea, galactorrhea, loss of libido, infertility

6

Growth hormone-producing adenoma

Second most common pituitary adenoma
GH stimulates hepatic secretion of IGF I
Before epiphyses close: gigantism
After epiphyses close: acromegaly

7

Corticotroph cell adenoma

ACTH- producing adenoma
Cushing disease and hyperpigmentation

8

Hypopituitarism

Deficiency of anterior pituitary hormone(s)
Panhypopituitarism is rare

9

Hypopituitarism in growth hormone

Pituitary dwarfism

10

Pituitary adenomas that extend beyond sella turcica into base of brain

Seizures
Obstructive hydrocephalus
Cranial nerve palsy

11

Radiographic abnormalities of the sella turcica

Bitemporal hemianopsia- lateral visual field defect caused by compression of fibers of optic chiasm
Elevated ICP, leading to HA, N/V

12

ADH deficiency

Diabetes insipidus

13

Oxytocin

Abnl production not associated with significant clinical sx

14

ADH excess

SIADH

15

Diabetes insipidus

Polyuria caused by ADH deficiency and inability of kidney to properly reabsorb water from urine
Excretion of large volumes of dilute urine
Polydipsia

16

Central diabetes insipidus

Caused by damage to hypothalamus (or pituitary) from head injury, tumors, infections, surgery

17

Nephrogenic diabetes insipidus

Caused by renal tubule unresponsiveness to ADH from certain drugs, hypercalcemia, kidney disease

18

SIADH

Excessive fluid accumulation caused by inappropriately elevated levels of ADH
MCC: ectopic ADH secretion by small-cell lung cancer

19

Pathophysiology of SIADH

Excessive ADH enhances the reabsorption of water by kidney tubules and the concentration of urine
Excess free water absorption causes hyponatremia, which may lead to cerebral edema and changes in mental status

20

Hyperthryroidism (thyrotoxicosis)

Elevated circulating levels of free T3 and T4

21

Graves disease

Autoantibodies to TSH receptor
20-40 yoa
Females > males
Genetic susceptibility
-HLA-B8, HLA-DR3

22

Characteristics of Graves disease

Exopthalmos
Thyrotoxicosis (diffusely enlarged and hyperfunctional thyroid)
Thyroid dermatopathy

23

Characteristics of hyperthyroidism

Weight loss in spite of increased appetite
Cardiac: palpitations, tachycardia
Neuromuscular: tremor, irritability
Eye: staring gaze and lid lag
Skin: warm, flushed, sweating, heat intolerant
GI: diarrhea
Skeletal: osteoporosis
Thyroid storm: abrupt onset of severe hyperthyroidism, often in Graves pts

24

Causes of hypothyroidism

Congenital hypothyroidism
Iodine deficiency
Hashimoto thyroiditis
Postablative (surgery, radiation)
Drugs (lithium, iodides, others)

25

Cretinism

Hypothyroidism developing in infancy or early childhood

26

Congenital hypothyroidism

Genetic mutations result in absent or small thyroid gland or gland of nl size with low or absent hormone levels

27

Iodine deficiency

Less frequent now that foods are supplemented with iodine

28

Clinical features of cretinism

Impaired development of skeletal and nervous systems
Short stature
Severe mental retardation
Course facial features
Protruding tongue
Umbilical hernia

29

Myxedema

Hypothyroidism developing in older children and adults
Often obese
Myxedema in skin and tissues results in broad, coarse facial features, enlargement of tongue, and deepening of voice
Cardiac: bradycardia
Neuromuscular: muscle weakness, apathy, mental sluggishness
Skin: dry, cool, pale, cold intolerant
GI: constipation

30

Hashimoto thyroiditis

Autoimmune destruction of thyroid gland
MCC of hypothyroidism in areas where iodine is sufficient
Most prevalent: 45-65 yoa
Females > males
Risk of developing B-cell non-Hodgkin lymphomas
Hypothyroidism

31

Pathogenesis of Hashimoto thyroiditis

Genetic: HLA-DR3 and HLA-DR5
Environmental- virus or bacteria

32

de Quervain thyroiditis

Probably viral etiology
Women > men
Usually btwn 30-50 yoa
Most have recent URI prior
Painful thyroid, esp. when swallowing, fever
Irregularly enlarged
Self-limited (6-8 wks)

33

Thyroiditis

Inflammation of thyroid gland

34

Subacute lymphocytic thyroiditis

Silent, painless, or postpartum thyroiditis- often occurs following pregnancy
Painless
Lymphocytic inflammation of thyroid
Most likely autoimmune in etiology
Thyroid nl on gross inspection
Rarely progresses to hypothyroidism

35

Goiter

Enlargement of the thyroid gland
Caused by:
-Mainly dietary iodine deficiency (endemic goiter)
-Other mainly unknown causes (sporadic goiter)
-Risk increased in females, >40, with FHx
Euthyroid metabolism in most pts

36

Pathophysiology of goiter

Impairment in production of T4, T3 leads to compensatory increase in TSH, which causes hypertrophy and hyperplasia of thyroid gland

37

Benign- adenomas of thyroid

Common
Presents as nodule of varying size
Most are small with limited clinical significance
Not premalignant

38

Malignant- carcinomas of thyroid

Rare
Occurs in several histological forms, with papillary carcinomas accounting for 80%
Multiple genetic pathways involved
Microscopic examination of bx material

39

Parathyroid glands

Activity of parathyroids controlled by the level of free (ionized) calcium in bloodstream
Composed mainly of chief cells
Chief cells contain secretory granules of parathyroid hormone (PTH)

40

Hyperparathyroidism

95% sporadic, 5% MEN-1 and MEN-2A

41

Primary hyperparathyroidism

MCC of clinically silent hypercalcemia
-Adenoma: solitary gland, most common
-Hyperplasia: multiglandular, second most common
-Carcinoma: solitary gland

42

Secondary hyperparathyroidism

Hyperplasia; compensatory response to hypocalcemia caused by kidney disease

43

Hypoparathyroidism

Underproduction of PTH
Rare

44

Sx of primary hyperparathyroidism

"Painful bones, renal stones, abdominal groans, psychic moans"
Osteoporosis, osteitis, fibrosa cystica, "brown tumor"
Renal stones
GI: constipation, peptic ulcer, pancreatitis, gallstones
CNS: Lethargy, depression
Muscle weakness and hypotonia

45

Major causes of hypoparathyroidism

Most commonly from inadvertent surgical ablation
Congenital absence
Autoimmune

46

Types of Islets of Langerhans

Endocrine pancreas
Beta cells (70%)- insulin
Alpha cells (20%)- glucagon
Delta cells (10%)- somatostatin
Pancreatic polypeptide (PP) cells (1%)- vasoactive intestinal peptide

47

Diabetes mellitus

A group of metabolic disorders sharing the common underlying feature of hyperglycemia
Defects in insulin secretion and/or action
Blood vessels: heart attack, stroke, kidney failure, lower extremity amputations
Eyes: blindness
Nerves: peripheral sensory and autonomic neuropathy

48

Insulin-dependent DM (type I)

Absolute deficiency of insulin secretion
Autoimmune destruction of beta cells
Starts in childhood
Depend on exogenous insulin for survival

49

Non-insulin dependent DM (type II)

Relative deficiency of insulin secretion
Peripheral resistance to insulin action
Inadequate compensatory response of insulin secretion by beta cells

50

Non-insulin dependent DM (type II)

Relative deficiency of insulin secretion
Peripheral resistance to insulin action
Inadequate compensatory response of insulin secretion by beta cells

51

Principles of insulin-dependent DM

Polygenic disease
Environmental trigger
Susceptibility allele
Protective allele

52

Major phenotypic features of insulin-dependent DM

Age at onset: childhood through adulthood
Polyuria, polydipsia, polyphagia
Hyperglycemia
Ketosis
Wasting
Multifactorial inheritance

53

Pathogenesis of Type I DM

Results from a genetic susceptibility and subsequent environmental insult
90% occurs in pts without a FHx of diabetes
However, there is familial clustering

54

10% of pheochromocytomas- characteristics

Familial syndrome
Extra-adrenal
Bilateral
Malignant

55

Familial syndromes with pheochromocytoma

MEN-2A, MEN-2B
von Hippel-Lindau disease (renal cell carcinoma, cerebellar hemangioblastoma)
NF1 (neurofibromas, cafe-au-lait spots, schwannoma, meningioma, glioma)
Sturge-Weber syndrome (cavernous hemangioma of 5th nerve distribution)

56

Neuroblastoma

Malignant tumor that develops from neural-crest derived cells in adrenal medulla or retroperitoneal sympathetic ganglia
Most common extra-cranial solid tumor of childhood
Usually dxed before age 5
Usually already metastasized at time of diagnosis
-Lymph nodes, liver, bones

57

Multiple endocrine neoplasia syndromes

Hyperplasia/adenoma/carcinoma of multiple endocrine organs
Autosomal dominant
Two forms
-MEN type 1: mutations in MEN1 gene
-MEN type 2: mutations in RET gene
More aggressive, recur more frequently than sporadic tumors
Younger age than sporadic tumors

58

MEN-1

Due to inactivation of MEN1 gene on chr 11q13
MEN1 is a tumor suppressor gene
Parathyroid (95%): parathyroid hyperplasia leads to primary hyperparathyroidism
Pancreas (40%): functional endocrine tumors
-Insulinomas lead to hypoglycemia
-Gastrinomas lead to Zollinger-Ellison syndrome
Pituitary (30%): prolactinoma

59

MEN-2

Mutations in RET protooncogene (chr 10q11.2)
Both forms with medullary thyroid carcinoma

60

MEN-2A

Most type 2
Thyroid: medullary thyroid carcinoma
-Develops in virtually all cases
-In the first 2 decades, multifocal
Adrenal medulla: Pheochromocytoma
Parathyroid: hyperplasia leads to primary hyperparathyroidism

61

MEN-2B

Rare
Medullary thyroid carcinoma
Pheochromocytoma
Do NOT develop parathyroid hyperplasia
Develop extraendocrine manifestations
-Ganglioneuromas on mucosal surfaces (lips, tongue, GI tract)
-Marfanoid habitus
Family members with germ-line RET mutations: prophylactic thyroidectomy