Chapter 24- The Endocrine System Flashcards
What are the two classes of hormones and how do they differ?
- Peptide/amino acid derived- bind cell surface receptors
2. Steroid- bind intracellular receptors
What gland primarily controls the pituitary?
The hypothalamus
What are the two lobes of the pituitary and how do they differ?
- Anterior/adenohypophysis- secretes hormones
2. Posterior/neurohypophysis- extension of the hypothalamus, stores oxytocin and ADH
What are the five basic cell types in the anterior pituitary and what do they secrete?
- Somatotrophs- GH
- Lactotrophs- Prl
- Corticotrophs- ACTH, MSH, endorphins, lipotropin, proopiomelanocortin
- Thyrotrophs- TSH
- Gonadotrophs- FSH, LH
What can cause hyperpituitarism?
Anterior adenomas
Hyperplasia
Malignancy
Hormone secretion by non-pituitary tumours
Hypothalamic disorders
What can cause hypopituitarism?
Ischemic injury
Surgery
Radiation
Inflammation
Nonfunctional compressive tumours
Hypothalamic disorders
What is pituitary apoplexy?
Acute hemorrhage into an adenoma
What is the most common cause of hyperpituitarism?
Adenomas
Nonfunctional pituitary adenomas affect the pituitary in what way?
Hypopituitarism (loss of normal tissue)
What is the most common form of pituitary adenoma?
Lactotroph
What is Sheehan syndrome?
The pituitary doubles in size during pregnancy but blood supply does not change
What disorders affect the secretion of ADH and how do they exert their effects?
Posterior pituitary syndrome- ADH deficiency (kidney can’t resorb water), DI
SIADH- excess ADH secretion causes hyponatremia
What are the most common causes of hypothalamic suprasellar tumours?
Gliomas and craniopharyngiomas
What are the morphologies of craniopharyngiomas?
Mix of squamous cells and stroma
Adamantinomatous- often calcify, kids
Papillary- often calcify, adults
What hormones does the thyroid produce and what are their functions?
T3/T4- regulate metabolic rate, influence growth and maturation
Calcitonin- lowers blood calcium (inhibits osteoclasts)
T3/T4 is regulated by what pituitary hormone?
TSH
What epithelium lines the thyroid follicles?
Cuboidal/low columnar
How is T3/T4 secreted?
TRH is released from the hypothalamus when levels are low
Stimulates TSH release from the pituitary
Stimulates thyroid growth and hormone synthesis
Thyroglobulin is concerted to T3/T4
T3/T4 binds receptors forming TRE and upregulating the transcription of certain genes
What is the feedback mechanism for T3/T4?
Reduced levels stimulate TRH release
Increased levels suppress TRH secretion
Negative feedback
What is thyrotoxicosis?
Increased circulating T3/T4
Hypermetabolic state
What is thyroid storm?
Abrupt onset of severe hyperthyroidism
Acute elevation of circulating catecholamines
What are the most common causes of primary hypothyroidism worldwide and in iodine sufficient areas?
Worldwide- iodine deficiency
Sufficient areas- Hashimoto’s
What are the forms of hypothyroidism in children and adults?
Children- cretinism, impaired development (skeletal system, CNS)
Adults- myxedema, fatigue, reduced mental activity and sympathetic activity, CHF
What are the two forms of cretinism?
Endemic (iodine deficiency, goiter)
Sporadic (hormone synthesis defects)
What are the different causes of thyroiditis and what are their characteristics?
- Hashimoto’s/autoimmune- diffusely enlarged, intact capsule, Hurthle cells (eosinophilic cytoplasm)
- Granulomatous/De Quervain- viral infection causes self limited immune response, symmetric or irregular enlargement, firm, yellow-white involved areas
- Subacute lymphocytic/painless- autoimmune in middle aged women, goiterous enlargement, mild hyperthyroidism (overtime can become hypo)
What is the most common cause of thyroid pain?
Granulomatous thyroiditis
What is the most common cause of endogenous hyperthyroidism?
Graves’ disease
What triad of findings is associated with Graves’ disease?
- Hyperthyroidism with diffuse gland enlargement
- Exophthalmos
- Pretibial myxedema
What causes Graves’ disease?
Auto antibodies against thyroid proteins
Binding and stimulation of the TSH receptor
What is the morphology of Graves’ disease?
Symmetrically enlarged
Red/meaty
What causes goiter formation?
Impaired synthesis of thyroid hormone leads to increased TSH and thyroid enlargement
What are the different types of goiters and their characteristics?
- Diffuse nontoxic/simple- no nodularity
- Multinodular- recurrent episodes of hyperplasia and involution produce irregular enlargement, fibrosis with colloid-like areas, follicles can rupture
What are the malignant risk factors associated with thyroid neoplasms?
Single nodule
Younger patient
Male
Head and neck radiation
Nodules that take up radioactive iodine
What are the two types of thyroid neoplasms?
- Adenomas
2. Carcinomas
What are the characteristics of thyroid adenomas?
Discrete solitary masses from follicular epithelium, well, demarcated solitary, encapsulated lesions
Are toxic adenomas functional or nonfunctional?
Functional (TSH receptor GOF mutation)
What are the four types of thyroid carcinomas and their characteristics?
- Papillary- many variations, branching papillae with fibrovascular stalk, psammoma bodies, RET/PTC and BRAF mutations
- Follicular- disorganized, tiny follicles histologically, can mimic adenomas, RAS, PI3K/AKT, PTEN mutations
- Anaplastic- aggressive elderly variant, can arise from a better differentiated tumour, TP53, bets catenin mutations
- Medullary- neuroendocrine (from C-cells), firm, pale and infiltrative, RET, MEN mutations
What are the occurrences of each type of thyroid carcinomas?
Papillary >85%
Follicular 5-15%
Anaplastic <5%
Medullary 5%
What are the two forms of medullary thyroid tumours and what are their characteristics?
Sporadic- solitary
MEN associated- multiple lesions
What is a useful biomaterial for medullary thyroid carcinoma?
Carcinoembryonic Ag
What areas show higher incidences of follicular thyroid carcinoma?
Iodine deficient areas
What causes thyroglossal duct cysts?
Developmental remnants of thyroid migrating from the tongue foramen cecum
How are thyroglossal ducts cysts differential from branchial cleft cysts?
Thyroglossal- midline masses anterior to trachea
Branchial- lateral masses
How does the location affect thyroglossal duct cysts?
High in neck- lined by stratifies squamous
Inferior- lined by thyroid acinar epithelium
What cell types makes up the parathyroid glands?
Chief and oxyphil
What is the function of the parathyroid glands?
Secretes PTH
Regulates calcium homeostasis (increases blood calcium)
What are the clinical symptoms of hyperparathyroidism?
Painful bones
Renal stones
Abdominal groans
Psychic moans
What are the types of hyperparathyroidism and how are they different?
Primary- autonomous increase (adenoma or hyperplasia)
Secondary- compensatory hypersecretion due to hypocalcemia (renal failure)
Tertiary- persistent hypersecretion even after the cause of hypocalcemia is corrected
What is a brown tumour and what type of hyperparathyroidism are they associated with?
Osteolytic lesions
Secondary
What is normally the cause of hypoparathyroidism?
Surgery
What are the less common causes of hypoparathyroidism?
Autoimmune (APSI)
Autosomal dominant (CASR gene)
Familial isolated
Congenital absence
Why are the clinical symptoms of hypoparathyroidism?
Tetany
Mental status change
Intracranial manifestations
Ocular disease (calcification)
Cardiovascular manifestations
Dental abnormalities
What are the different types of cells found in the islets of Langerhans and what do they produce?
Beta- insulin
Alpha- glucagon
Delta- somatostatin
PP- pancreatic polypeptide
DI- elaborated VIP glycogenolysis
Enterochromaffin- serotonin
DM is a group of metabolic disorders sharing what common feature?
Hyperglycemia
A random glucose score of what amount indicates DM?
> 200mg/dL
What are the differences between type I and II DM?
I- autoimmune beta cell destruction, younger onset
II- peripheral resistance to insulin and inadequate secretory response by beta cells (hypersecretion then cell failure), associated with obesity
How can viral infections lead to DMI?
Bystander damage- beta cell injury releases Ags (targeted by immune system)
Molecular mimicry- virus produces protein that mimics beta cell Ags
Virus lies dormant in beta cells, later infection with related virus leads to immune response
What are the characteristics of monogenetic forms of DM?
Due to primary defect in beats cell function or insulin receptor signalling
Early onset
What is the largest subgroup of monogenetic DM?
Maturity onset diabetes (MODY)
What is the most important stimulation for insulin synthesis and release?
Glucose
What is the action of insulin?
Increases glucose transport into cells (promotes storage)
What glucose transporters are present in the pancreas?
GLUT2
What are the complications associated with DM?
Macrovascular disease
Microvascular disease
Diabetic nephropathy
Diabetic ketoacidosis is associated with what type of DM?
I
What is the most common pancreatic neoplasm?
Insulinomas
What percentage of insulinomas are benign?
90%
What are the morphological characteristics of insulinomas?
Solitary, <2cm, well encapsulated
What percentage of “other” pancreatic endocrine neoplasms are malignant?
60-90%
What is the triad associated with Zollinger-Ellison syndrome?
- PUD
- Gastric hypersecretion
- Pancreatic islet lesions
What are the two areas of the adrenal glands?
Cortex (external)
Medulla (internal)
What are the zones in the adrenal cortex and what hormones do they secretes?
- Glomerulosa- mineralcorticoids (aldosterone)
- Fasiculata- glucocorticoids (cortisol)
- Reticularis- sex steroids (estrogen, androgens)
What is the difference between Cushing syndrome and disease?
Syndrome- hypercortisolism (exogenous or endogenous)
Disease- ACTH secreting pituitary adenoma causes hypercortisolism
What is the most common cause of endogenous hypercortisolism?
ACTH secreting pituitary adenomas
What are the most common causes of ACTH independent Cushing syndrome?
Adrenal adenoma and carcinoma
What is the morphology of Cushing disease?
Nodular cortical hyperplasia
What is crooke hyaline change?
The granular basophilic cytoplasm is ACTH producing cells becomes homogenous and pale due to increases in glucocorticoids
What are the four abnormalities seen with hypercortisolism and what are their most likely causes?
- Cortical atrophy- exogenous glucocorticoids or adenoma
- Diffuse hyperplasia- ACTH dependent Cushing syndrome or Cushing disease
- Macro/micronodular hyperplasia
- Adenoma or carcinoma
What pigment is seen in micronodular hyperplasia of the adrenals?
Lipofuschin
What are the clinical symptoms of Cushing disease?
Central obesity, moon face, buffalo hump fat
Muscle atrophy
Secondary diabetes
Poor wound healing
Osteoporosis
Mental disturbances
Hirsuitism
Menstrual abnormalities
What are the differences in primary (Conn syndrome) and secondary hyperaldosteronism?
Primary- autonomous overproduction of aldosterone (RAS and renin activity suppressed)
Secondary- aldosterone released through RAS activation
What are the clinical symptoms of hyperaldosteronism?
Hypertension
Hypokalemia
Hypernatremia
What are the different forms of Conn syndrome and their characteristics?
Bilateral idiopathic- bilateral nodular hyperplasia
Adrenocortical neoplasm- solitary adenoma
Rare hereditable form- remediable with glucocorticoids
What can cause secondary hyperaldosteronism?
CHF
Reduced renal perfusion
Pregnancy
What characterizes androgenital syndromes?
Disorders of sexual differentiation
What adrenal causes result in androgenital syndromes?
Androgen excess- andrenocortical neoplasms and congenital adrenal hyperplasia
What is the pathology of congenital adrenal hyperplasia?
Inherited metabolic disorders
Precursors to cortical steroids build up and are used in other pathways (androgen production)
Adrenal hyperplasia, increases ACTH, reduced cortisol
What is salt wasting syndrome?
Cortisol and mineralcorticoid production is blocked
What are the different forms of adrenocortical insufficiency and their causes?
Primary acute- sudden increase in glucocorticoid requirements in patients with chronic insufficiency
Primary chronic/Addison disease- destruction of ~90% of the cortex
Secondary- hypothalamic or pituitary disorder leads to reduced ACTH
How are primary chronic and secondary adrenocortical insufficiency distinguished?
Hyponatremia and hyperkalemia are not features of secondary
What is a common cause of primary acute adrenocortical insufficiency (what causes a rapid increase in glucocorticoid requirements)?
Massive adrenal hemorrhage
What familial cancer syndromes increase the risk of adrenocortical carcinoma?
Li Fraumeni syndrome (TP53 mutations)
Beckwith-Weidemann syndrome
What are the different types of adrenal cortical neoplasms and their characteristics?
- Adenomas- well circumscribed yellow-brown lesions
- Carcinomas- variegated tumours with hemorrhage and central necrosis
- Myelolipomas- benign lesions (fat and hematopoietic elements)
What is a feature of function adrenocortical adenomas?
Cortex is atrophic
What cells make up the adrenal medulla?
Neuroendocrine chromaffin cells
Sustenacular cells (supporting)
What hormones are produced by the adrenal medulla?
Epinephrine and norepinephrine
The primary pathological finding associated with pheochromocytoma is what?
Hypertension
What is the “rule of 10s” associated with pheochromocytomas?
10% extra adrenal
10% of sporadic cases are bilateral
10% are malignant
10% don’t cause hypertension
What is the morphology of pheochromocytomas?
Tan hemorrhagic cut surface
Can be necrotic with cystic changes
What are the characteristics of multiple endocrine neoplasia (MEN) syndromes?
Group of inherited diseases resulting in proliferative lesions of multiple endocrine organs (synchronously)
Young onset
MEN onset is preceded by what?
Asymptomatic stage of hyperplasia
What are the characteristics of MEN type I/Wermer syndrome?
Primary hyperparathyroidism
Aggressive and functional tumours of the pancreas
Prolactinomas (most common in pituitary)
Duodenum is the most common site of gastrinomas
What are the different forms of MEN type II and their characteristics?
2A/Sipple syndrome- medullary thyroid cancer, pheochromocytomas and parathyroid hyperplasia, RET protooncogene mutation
2B- medullary thyroid cancer and pheochromocytomas without parathyroid hyperplasia
Familial medullary thyroid cancer- variant with no other manifestations
What are the functions of pineocytes?
Photosensory and neuroendocrine
What hormone does the pineal gland secrete?
Melatonin
Tumours of the pineal gland resemble what form of malignancy?
Germinomas
What are the two forms of pinealomas?
Pineoblastomas
Pineocytomas
