Extracellular secreting molecules can be classified into:

Autocrine, paracrine, or endocrine

Hormones that interact with cell-surface receptors...

-Are amino acids

-Can not cross the phospholipid bilayer

-Require "secondary messengers" to stimulate target cells

-Are G-proteins

-Examples: GH, glucagon, epi

Hormones that interact with intracellular receptors...

-Libid soluabel steroids

-make direct contact to nucleus (no secondary messenger needed)

-Examples: estrogen, progesterone, glucocorticoids

Thyroxin

Amino acid base hormone that is unusually and can cross the cell membrane and interacts with nucleus

Calssification: Intracellular

PITUITARY GLAND

-Located in the base of the brain, in the sella turcica close proximity to the optic chiasm

-Hypothalamus and Pituitary regulates most endocrine glands

-Made up of Anterior and Posterior Lobes

Anterior pituitary hormones

Growth hormone (GH)

Luteinizing hormone (LH)

Follicle-stimulatinghormone (FSH) Prolactin (PRL)

Thyroid-stimulatinghormone (TSH)
Adrenocorticotropic hormone (ACTH)

 

Posterior Pituitary Hormones

Anti-diuretichormone (ADH)

Oxytocin

Releasing hormones and inhibiting hormones come from where?

hypothalamus

Hyperpituitarism

-Increase in pituitary hormone

-generally caused from an adenoma

-other causes hyperplasia, CA of anterior pituitary

Local mass effects

Radiographic abnormalities of the sella turcica

Visual field abnormalities
Elevated intracranial pressure

Seizures

Hypopituitarism

-Decreased secretion of pituitary hormone

-Can reult from disease of the hypothalamus or pituitary

-no S/S till 70-90% is destroyed

-Most cases come from direct involvement of the anterior pituitary (ischemia, surgery, radiation, nonfuncation adenomas)

Additional causes: Tumor in the sella, Pituitary surgery or radiation, pituitary apoplexy, pituitary infarction, hypothalamic disorders (DI), genetic defects

Pituitary infarction and Sheehan Syndrom

-Ischemic necrosis of the anterior pituitary

-Sheehan Syndrom: postpartum necrosis of anterior pituitary

-Pituitary increases in size during pregancy without an increase in blood supply. -At risk for decreased blood supply, with

-Further reduction of blood supply bc of shock, or hemmorhage, infarction can occure to anterior lobe

-Additional causes of Pituitary Infarction: DIC, Sickle cell anemia, increased ICP, Shock

-Whatever the cause a nubbin of fibrous tissue will attach to the wall of the empty sella post necrosis.

Pituitary apoplexy

-Sudden hemmorrhage into the pituitary gland

-Generally caused from pituitary adenoma with rapid enlargement

-May cause cardiac collapse, loss of condciousness and even sudden death

-NEURO SURGICAL EMERGENCY

-may present with no vision in 1 eye

Empty sella syndrome

-The empty sella syndrome refers to the presence of an enlarged, empty sella turcica that is not filled with pituitary tissue

-Any condition that destroys part or all of the pituitary gland, such as surgery or radiation, can result in an empty sella

-Example: Pituitary adenoma, enlarges the sella, but then it is either surgically removed or undergoes spontaneous necrosis, leading to loss of pituitary tissue

Clinical Manifestation of

Hypopituitarism

-Generally occures gradually

-May occure as life threatening event (pituitary apoplexy)

-Progressive deficiency follows sequence 1)GH 2)LH 3)FSH 4)TSH 5)ACTH

-GH: pituitary dwarfism in children

-Gonadotropin deficiency in women-amenorrhea and infertility

-Gonadotropin deficiency in men- impotency and loss of pubic and axillary hair

-Prolactin deficiency- Failure of postpartum lactation

-TSH-hypothyroidism

-ACTH- hypoadrenealism

Treatment for hypopituitarism

replacement therapy

Growth Hormone
Disorders

-Growth hormone (somatotropin) is a polypeptide hormone produced by somatotropes
- Effects of GH are mediated via IGFs (somatomedins) esp. IGF-1
-Secretion of GH by anterior pituitary is controlled by hypothalamic GHRH which increases GH release & somatostatin which inhibits GH release
-Secretion of GH peak levels are 1-4h after onset of sleep
-Secretion of GH is stimulated by hypoglycemia, fasting, starvation, increased levels of amino acids (esp. arginine, stress)
-Secretion of GH is inhibited by increased blood glucose levels, FFA levels, cortisol

GH Deficiency in Children

-Cogential Gh deficiency: may be due to lack of hypothalamic GHRH or genetic defect of IGF production

-Aquired GH deficiency: developes later, causes pituiary tumor

-s/s dcreased growth rate during first year, short stature, obesity, delayed skeletal maturity, normal intelligence

DX: Non endocrine causes excluded, GH and IGF-1 levels determined. Xrays for bone age, CT, MRI

Treatment: GH replacing theray

GH Deficiency in Adults

-May present in childhood

-Developes during adulthood results from a pituitary afenoma or its treatment

-High levels of artherosclerosis

-Associated with metabolic syndrom

DX: GH response to provocative tests, insulin-induced hypoglycemia is the gold standard test for GH reserve

-Treatment with rhGH only if poor GH response with 2 stimuli, hypopituitarism

Growth Hormone Excess

in children and adults

Children

-somatotrophic adenoma before the epipheses have closed may result in gigantism --> replated to elevated levels of GH and IGF-1

Adults:

-Increased levels of GH after epiphyses closure result in acromegaly

-40-45 y/o

Causes:

-Somatotrophic adenoma- 95%

-GHRH producing hypothalamic tumor- 5%

-Ectopic GHRH producing non endocrine tumors (small cell CA, lung)

Clinical manifestation of Acromegaly

-goiter

-cardiomegaly

-barrel chest

-adnormal glucose tolorance r/t insulin resistance

-increased hanf size

-arthritis

-peripheral neuropathy

-thickened skin

Growth Hormone Excess in Adult

DX and treatment

Dx:
-Elevated levels of GH not suppressed by an oral glucose load

-Increased IGF-1 levels

-MRI & CT scan to detect pituitary adenoma

Treatment:

-Surgical removal of adenoma, radiation therapy

-Medical:

1)Somatostatin analogs

2) Bromocriptine (dopamine agonist)

3) GH receptor antagonists

Diabetes Insipidus

-ADH deficiency causing excessive uriniation (polyuris) due to inability of kidneys to reabsorbe water

-Causes Head trauma, tumors, inflammatory disorders, and surgical procedures of the hypothalamus and pituitary

-urine has low specifia of gravity

-thirst and polydipsia

-Serum osmolality is increased

-can cause life threatening dehydration

Posterior Pituitary disorders

SIADH and DI

Anterior Pituitary disorders

Sheehan syndrom, pityitary ischemia

Pituitary apoplexy

Empty Slla syndrome

hyper and hypo growth hormone production

SIADH

-ADH excess --> causes resorption of excessive amounts of water by kidneys

-Causes secreation of ectopic ADH by neoplasms (small call CA of lung)and injury to the hypothalamus or poterior pituitary

-s/s: hyponatremia, cerebral edema, neurologic dysfunction

Thyroid Function...

-produces thyroxine or T3 and T4

-there is more t4

-T3 is the active form

-T4 is converted to T3

-Thyroid hormones are bound to TBG, TBA, and TBPA

-TBG decreases in conditions with decreased serum protein

     and this influences binding of hormones

-Free unbound hormones helps regulates pituitary feedback

      mechanism

Actions of Thyroid hormones

-Metabolic rate

-Cardiovascular function

-GI function

-Neuromuscular effects

Hypothyroidsim

Causes structural or functions interferance with tht eproduction of adequate levels of thyroid hormones

-Cogential hypothyroidism: infants: Rare inborn errors in metabolism that interfere with synthesis of thyroid homones or deficient TSH screation

-Past occures in mountainous areas wher dietary iodine deficiency is endemis

Transient congenital hypothyroidism

iodine excess, antithyroid drugs cross the placenta

Cretinism

-comes from untreated congenital hypothyroidism

-s/s mental retardation, impaired growth, short stature, coarse facial features and protruding tongue

-Neonatal screening for T4 and TSH now done

-T4 supplements withinn 6 weeks- can have normal intelligence

Primary hypothyroidism

Hashimoto thyroiditid

Thyroidectomy

Radiation

Antithyroid drugs

Goitrogenic agents-lithium carbonate

Large amounts of iodine

Iodine deficiency-now rare

Secondary hypothyroidism

TSH deficiency

Tertiary hypothyroidism

TRH deficiency

Hashimoto thyroiditis

-most common cause of hypothyroidism in areas where iodine levels are sufficient

-autoimmune destruction of thyroid

-45-65 y/o and more common in women

-Genetic predisposition

-Presents with goiter and hypothyroidism in some vases my present by transient thyrotoxicosis

myxedema

-applied to hypothyrodism developing in older children or adults

-non pitting edema (typically pre-tibial) a broadening and coarsening of facial features, enlargement of the tongue and hoarse husky voice

Clinical manifestation of hypothyroidism

-older children show s/s in between cretin and those of adult hypothyroidism

-adult: initally generalized fatigue, apathy, mental sluggishness, slowed speech, intolorance to cold, weight gain, decreased CO and exercise capacity

Hypothyroidism DX and treatment

-Serum TSH level is the most sensitive screening

-TSH increased in primary hypothyroidism

-TSH not increased with secondary or thrtiary

-T4 levels are decreased in all

-Treatment: replacement therapy

Myxedematous Coma

-Life threatening uncommon condition

-seen in elderly hypothyroid women in winter months

-body may be stressed or over whelmed and go into a coma

-Causes: cold exposure, indection, sedatives and analgesics

-s/s hypothermia, cardiac collapse, hypoventilation, decreased BG,hyponatremia, decrease in mental status and coma may present

-Treatment: IV T4, management of cardio respiatory status and hypoglycemia, supportive treatment

Diffuse and Multinodular Goiters

-Goiter: enlarged thyroid r/t impaired synthesis of thyroid hormone

-Diffused nontoxic (simple) goiter: caused by dietary iodine deficiency- occurs as endemic and sporadic goiters--> lack of iodine causes increase TSH and increase in function of mass of the thyroid- euthyroid

-Multinodular goiter: long standing simple goiters conver into multinodular goiters: may develope hyperthyrodism (toxic multinodular goiter)

-Diffused toxic goiter (Graves disease)

Thyrotoxicosis and hyperthyroidism

elevated levels of T3 and T4 caused by hyperthyroidism

secondary cause can be caused by a TSH-secreating pituitary hormone

Most common causes of thyrotoxicosis

1)Graes disease

2) Multinodular goiter

3)Functional afnoma of the thyroid

Clinical manifestation of hyperthyroidism

-Heat intolorance

-sweating

-warm flushed skin

-weight loss despite increases appetite

-increased CO

-increased HR

-Palpitations

-Arrhythmias

-Particularly atrial fibrillation in elderly

-Tremors

-Hyperactivity

-anxiety and insomnia

-lid lag

-Thyroid ophthalmopathy associated with proptosis is seen only in graves disease

Hyperthyroidism DX

-Serum TSH is most usful screening decreased levels will be seen

-Increased T4

-Pituitary (Secondary) associated hyperthyroidism--> TSH levels raised--> TRH stimulation test- normal rise in TSH after adminsteration of TRH excludes sedondary hyperthyrodism

-Measurement of radioactive iodine uptake by thyroid gland to determine the cause(Iodine uptake increased with a diffuse uptake of iodine in graves diseae)

Hyperthyroidism Treatment

-Eradication of thyroid with radio-active iodine

-Surgical removal

-Beta blockers

-Antithyroid drugs (propylthiouracil, metamizole)

Graves DIsease

Most common cause of hyperthyroidism

-20-40 y/o women

-genetic factors are important

-autoimmune disorder increased association with HLA-B8 and HLA-DR3

Ophthalmopathy of Graves disease

occurs in 1/3 of pts

-Caused by autoimmune mechanisms

-increased volume of the retro-orbital connective tissue

-exophthalmos

Thyroid storm

-life threating

-present in pt with graves disease

-starked by infection, surgery, or any stress to body

-s/s/ high fever, tachy, angina, agitiation,restlessness, delirius

-Medical emergency wit hight mortality rate

Functions of the Parathyroid

1)PTH activates osteocalasts keeping CA++ in bone

2)increase renal tubular reabsorption of CA++

3) Increases the conversion of VIt D to its active form

4)Increases urinary phosphate excretion

5)Increases GI CA++ absorption

6)increase in CA++ levels which inhibits PTH secreation in a feedback loop

Primary
Hyperparathyroidism

-Important cause of hypercalcemia

-Women in 50's

-Causes: Adenoma, primary hyperplasia, parathyroid CA

-S/s: no symptoms and identified with labs or will present with "painful bones, renal stones, abdominal groans, and psychic moans" 1) Bone pain secondary to fractures of osteoporotic bones 2) Renal stones in 20% 3) GIT-constipation, pancreatitis, and gallstones
4) CNS- depression, lethargy, seizures

SECONDARY
HYPERPARATHYROIDISM

-any condition associated with a chronically depressed serum calcium levels- which leads to compensatory overactivity of the parathyroid
glands

-Causes Chroinc renal failure, decreased intake of calcium, statorrhea vit D deficiency

less common

surgically induced (thyroidectomy)

-s/s hypocalcemia, tetany, chvostek sign, and trousseau sign anxiety, depression, confusion, frank psychosis

Adrenal Gland

made up of Medulla and cortex

-Cortex secretes 3 different steriods

1)Glucocorticoids

2)Mineralocorticodis

3) Adrenal sex hormones

Glucocorticoids

-regulated by HPA-axis

-ACTH and cortisol peak in morning

-stress response, maintains emotional stability

Addison Disease

Primary

Adrenalcortical Insufficiency

-Adrenalcortical Insufficiency

-adrenal cortical levels are decreased and ACTH levels are increased

-uncommon disorder resulting from progressive destruction of adrenal cortex

-causes autoimmune, TB, AIDS, lung CA

-no s/s till 90% destroyed

Clinical Manifestations of

Addisons Disease

-mineralcorticoids deficiency:urinary loss of Na, volume depletion and dehydration, hyperkalemia, decreased CO, orthostatic hypotension

-Glucocorticoid deficiency: hypoglycemia, poor stress tolorance

-Lack of androgens: loss of axillary and pubic hair

-Hyperpigmentation (found only in primary)

-Stresses trigger aute crises

Addisons treatment

Replacement therapy

Secondary adrenocortical insufficiency

-decreased stimulation of the adrenals due to a deficiency of ACTH

-NO HYPERPIGMENTATION

-Decreased coritisol and androgen output but normal aldosterone synthesis

-low ACTH

-causes: hyperpituitarism, surgery, infarction

Acute Adrenal Crises

-dehydration-> hypotention and vascular collapse

-stres induced

-rapid withdra of steriods

-Adrenal hemorrhage: in pts on anticoags, DIC, Bacterial infection, Waterhouse-Friderichsen Syndrome

-Treatment: IV Corticosteriods, IV fluids