Endocrine Pathology March 27, 2007

New assignment:
Define cortisol and name 5 effects cortisol has on the body. Due next week. Point form is
fine.

• Hormonal system responsible for homeostasis

• Very complex system
• Cancer in endocrine organ can act as SOL which can cause it to under-secrete d/t
pressure on the gland
• Or growth can over-secrete hormone

Review of Endocrine System:

• Metabolism
• Reproduction
• Circadian Rhythms
• Regulation of BP
• Electrolyte balance
• Blood sugar levels

Hormones: float around in blood and bind to receptor on cells. Cell responds according
to signal from receptor.

Feedback: mainly negative feedback. Oxytocin is only hormone with positive feedback
mechanism.

Diseases:
Overproduction of TH: increases activity of thyroid.

Pituitary Gland
• Sits at base of brain in the sella turcica (bony fossa)
• Anterior and posterior different communications with hypothalamus
• Anterior- venous connection. Receives messages hormonally from hypothalamus.
Receives blood from hypothalamus. Gland structure
• Posterior- neural connection. Has an external blood supply other than the
hypothalamus. Neuronal structure
• Anterior: FSH, LH, ACTH, TSH, GH, Prolactin, MSH (melanocyte stimulating
hormone)
• Posterior: vasopressin (ADH), oxytocin
• Lots of different cell type in anterior pituitary
• Hormones secreted by hypothalamus: Somatostatin (inhibits GH release), Dopamine
(inhibits prolactin). All other hormones released by hypothalamus are excitatory.
• Abhorrent = out of whack
• Adenoma = glandular tissue, nonmalignant, solitary, well defined, harmful b/c space
 occupying. Can be functional- hypersecrete a hormone.

Anterior Pituitary Adenoma

• m/c pathology of pituitary
• pituitary adenoma can impinge on optic chiasm- affects peripheral vision
• can secrete different hormones, depends which cells type is forming adenoma
• Nonfunctional adenoma→ (doesn’t secrete hormones) normally larger when
discovered b/c no symptoms to give us an idea that there is an adenoma there.
• Nonfunctional adenoma can put pressure on gland and cause undersecretion
• Often found at autopsy
• GH: affects all cells
• Gigantism: before adolescents, typically d/t tumour, proportional growth b/c
epiphyseal plates haven’t closed yet.
• Acromegaly: after adolescents, plates in long bones have fused. Increase in size of
head, thickening of structures: face, vertebrae, heart, other soft tissue
• Both conditions: often have undersecretion of other hormones: like low FSH/LH.
Lack of development of sexual characteristics
• DM common with these conditions b/c growth hormone inhibits insulin
• Pituitary Dwarfism: decreased proportional growth. D/t decreased GH
• if this is d/t Panhypopituitarism all other hormones will be low

• Prolactin: stimulates milk production and breast tissue.

• Excess: galactorrhea often w/amenorrhea (amenorrhea comes first)
• Deficiency: difficulty producing milk in response to childbirth
• If a disease originates in thyroid gland (primary thyroid problem) . If there is a
problem in the thyroid and problem is in pituitary (secondary thyroid problem) and if
problem in hypothalamus (tertiary problem in thyroid)

Panhypopituitarism

Causes:

1. Nonsecretory adenoma- takes up space and puts pressure on glands so can’t secrete
properly.

2. Ischemic necrosis- Death of gland so can’t produce hormones. Common in Sheehan’s

3.Iatrogenic-Medically induced, perhaps d/t radiation

4.Hypothalamus not functioning properly

5.Congential

• This would be secondary hypothyroidism b/c problem at level of anterior pituitary

Posterior Pituitary

• ADH- Acts on collecting tubules of Kidney. Monitors osmolarity of blood. Retains

sodium and water. Decrease urination. Increases BP

• Deficient in ADH: Excessive loss of water. Large quantities of dilute urine. Diabetes
Insipidus. Kidney problems can cause similar symptoms (i.e nephrogenic- Kidnery
tubules can’t respond to ADH)

• Syndrome of inappropriate ADH secretion: Lung cancers can cause this

• ADH in excess: scanty dark urine, edema, retaining way too much water,
hyponatremia, increased osmotic pressure, water moves in cells. Most dangerous in
brain- neurological symptoms. Can cause herniation in brain.

Thyroid Gland

• T3 (triidothyronine) & T4 (thyroxine) secreted from follicular cells

• T4 is secreted in greater quantity

• T3 active form

• T4 converted to T3 in periphery

• T3 carried with receptor into nucleus of cells

• T3 & T4 increase metabolism, increase heart rate, increase sympathetic nervous

system

• Hyperthyroidism: Hot, sweaty, increased heart rate, diarrhea, anxiety, eyelids wide
open.

• Thyroid hormone very connected to adrenal gland.

• Calcitonin: lays calcium in bones, decreases concentration of calcium in blood.

Goiter:

• Enlargement of thyroid

• Normally d/t iodine deficiency

• Thyroid telling brain to increase TSH to stimulate thyroid gland

• Hypertrophy/ hyperplasia of gland

• Endemic- can affect entire populations. Mountainous areas, away from water.
Himalayas. Solution: iodine in salt.

• Sporadic goiter: problems with absorption, changes in life cycles ex. teen years
need more. Congenital enzymatic defects, can’t incorporate iodine for production
of thyroxine.

• Brasica family (broccoli, cauliflower) can interfere w/thyroid hormone formation

• Toxic Goiter: excessive secretion of thyroid hormone

• Nontoxic Goiter: don’t have enough secretion of thyroid hormone. This is

what most goiters are. Activating TSH receptor like in Graves.

• Goiter should decrease in size when add iodine to diet

• Multinodular: d/t correction and then deficiency again and again. Thyroid
involutes and grows over and over. This cycle of involution and then growth
creates a multinodular thyroid, which increases risk for thyroid cancer.

• Goiter can act as SOL, impinge airway

• Can mask cancer

Thyrotoxicosis:

• Excess production of T3/T4

• Can be ectopic: exogenous d/t meds

• Up regulation of metabolic rate, upregulation of sympathetic nervous system

• Labs: T3/T4 elevated, TSH down (b/c of negative feedback) If problem at level of
thyroid

• Problem at pituitary: TSH normal or elevated, T3/T4 elevated

• Toxic adenoma: solitary discrete nonmalignant growth of thyroid gland producing

T3/T4

• Thyroiditis- self study. Compare to grave’s disease.

Graves Disease:

• Antibodies to receptor on thyroid gland (thyroid stimulating immunoglobulins

– TSI). Antibodies over-stimulate TSH receptor.
• Different than goiter b/c this is toxic enlargement. Goiter is nontoxic.

• Genetic predispostion telling CD4 helper t-cells to turn on B-Cells

• Antibodies also stimulate receptors behind the eyes and pretibial fibrolasts

• Fibroblasts turn into adipocytes

• Adipocytes secrete hydrophilic substances. Attract water---- leads to edema

• Also lymphoctyic infilitration

• Exophthalmos- eyes bulging. Risks can push on nerves, can’t close lids which can
lead to corneal irritation. Can cause fibrosis of muscles of eye.

• Non-pitting edema of shins.

Hypothyroidism:

• High TSH, decreased T3/T4 (if primary thyroid problem)

• Could be d/t iodine deficiency, enzymatic deficiency, thyroid cancer, can be

secondary.

• Problem at pituitary then would have low TSH, low T3/T4 (secondary thyroid
problem)

• Also have myxedema like in Graves

• Thickening of tissues: tongue, skin etc..

• Nonpitting edema

• enlargement of organs- ex. heart enlarges

• Cretinism- Hypothyroidism in fetus d/t mom’s hypothyroidism. Fetus thyroid

tissue not fxning yet. T3/T4 very important for brain development. Mental
retardation.

• Subclinical hypothyroidism: labs normal, but symptoms there: dry skin, hair,
cold, constipation, sluggish metabolism etc …

• Can treat this by managing stress better.

Hashimoto’s Thyroditis

• Lymphocytic infiltration
 • Autoimmune

• m/c type of hypothyroidism

• Anti- TSH receptor antibody, other Ab’s produced by B-cell used as marker not
part of pathology (antithyroglobulin &antithyroid peroxidase)

• Flow chart in text: helper T cells activates both plasma cells and cytotoxic t-cells

• Humoral and cell mediated response (Grave’s only humoral response)

Thyroid Cancer
• Always assume cancer with any nodules on the thyroid. Refer always for biopsy!
• Solitary- not normally multiple nodules
• If nodule in males more likely to be cancer. But cancer is most common in women.
• Cold- radioactive iodine not taken up by gland (nonfunctioning)

Thyorid Carcinoma
• Same distribution among males and females after and before childbearing years
• Hormonal influences
• Risks: multinodular- cells changing a lot so increased risk of mistakes being made.
• Papillary: good prognosis, doesn’t look cancerous, need to do biopsy to diagnose:
ground-glass appearance of nucleus
• Fill in chart on 4 types of cancer look in text
• Anaplastic- locally invasive- veins, arteries, esophagus, trachea

Parathyroid gland:
• Often parathyroid gland gets removed with thyroid gland
• Responds to calcium in blood, not pituitary

Primary Hyperparathyroidism
• Functioning adenoma- adenoma secrete PTH (m/c casue)
• Dx: Increased Calcium, increased PTH. Can lead to osteoporosis
• If you have an adenoma in one gland, then the other 3 glands atrophy.
• Kidney: KI stones
• Calcification of soft tissue
• Lethargy, weakness in muscles, constipation,
• Increased electrical differential b/w cell and extracellular environment, takes more
energy to create an action potential
• Calcification of blood vessels- atherosclerosis, high BP
• Text book diagram shows different manifestation: polyuria, gallstones…

Secondary Hyperparathyroidism
• Can be d/t Kidney problems
• Drop in calcium d/t to renal failure, increases PTH
• Similar bone changes
• Won’t have calcification of soft tissue b/c have low serum calcium levels
• Labs: high PTH, low serum calcium.

Hypoparathyroidism
• Low serum calcium
• Iatrogenic- removal of parathyroid gland
• Congenital- enzyme deficiency
• Idiopathic
• Familial
• Hypertonic muscles, tetany, diarrhea

Multiple Endocrine Neoplasia

• Cancer development in more than one endocrine organ.
• Consistent genetic predisposition
• Don’t need to memorize MEN organs affected
• Now cancer mutuation in MEN-1 & MEN-2
• Sporadic-happens in one location, when you are older (MEN is not sporadic)
• MEN is familial, occurs in many places, recurs.

Self Study for this week:

Sheehan’s syndrome
Empty sella turcica
Glioma
Cranipharyngioma
Subacute thyroiditis
Thyroiditis de quevains

Self study for next week:

Congenital adrenal hyperplasia
Waterhouse-Friderichsen syndrome
Neuroblastoma
Insulinoma
Gastrinoma