Hyposecretion

Hypersecretion

Hyporesponsives

n  Primary:  direct malfunction of hormone producing gland

n  Secondary:  malfunciton of the hypothalamus/pituitary cells that control the hormone producing gland

n  Measurement of of pituitary and endocrine gland hormones allows differentiation between primary and secondary endocrine failure.

In primary you see a low levels of hormone but high levels of trophic pituitary hormone and in secondary there is a decrease in both types.

What do you know about hyposecretion?

Primary:  endocrine gland secretes an abnormally high amount of hormone (in this case the TSH will remain low)‏

Secondary:  caused by increased secretions caused by either a tropic hormone (ie TSH) or by hormone secretion from an ectopic source (as sometimes occurs in malignancies)‏

n  This is hormone resistance of the target organ and causes the same signs and symptoms as hyposecretion.

n  The usual cause is lack of or deficiency of receptors. 

n  In this case, plasma hormone levels may be high, even though showing signs of hyposecretion.

n  Caused by nonendocrine disease such as cronic renal failure,liver disease, or heart failure.  n  Dysfunction may arise if end organ fails to respond to hormones

n  Presence of normal hormone levels w/out norm  action indicates hormone resistance

n  May be genetic or acquired and may include defects at receptor sites, antibody reaction to hormone receptors, and defective post receptor hormone action.

n  May be an inborn error of metabolism.  Can include excessive production of hormone precursors due to an enzymatic block in the synthetic pathway, and enzyme deficiencies that impair hormone synthesis. n  Also nonendocrine tissue can produce hormones such as malignant tumors

n  Some disorders may be induced by medical treatments.  These iatrogenic disorders can be caused by chemotherapy, radiation therapy, or surgical removal of glands

n  Osmotic pressure of plasma (tracked by osmoreceptors in hypothalamus)‏

n  When body fluids become too concentrated ADH is released leading to incr reabsorption of water in the kidneys

n  In presence of ADH permeability of renal collecting ducts and tubules to water increases greatly and allows most H2O to be reabsorbed

n  ADH deficiency

n  Damage to ADH producing cells in hypothalamus can occur w/ closed head trauma, intracranial tumors, and neurosurgery.  Some pharmocologic agents can do this, too.

n  Damage to posterior pituitary.  Which may be temp or perm n  Large diuresis of very dilute urine resulting in large volume excretion of hypotonic water n  30% idiopathic, 20% caused by surgical removal of brain tumor, 16%  result from nonsurg brain trauma, and 25% are secondary to brain tumors, while 9% follow a hypophysectomy n  Because free water is lost it causes hyperosmolality  n  Central DI is caused when lack of ADH is produced while nephrogenic DI occurs in chronic renal disease and results from renal tubules being less responsive to ADH

n  Polyuria and polydipsia (hallmark signs n  Symptoms persist at night and interrupt norm sleep patterns n  Dry mucous membranes n  Poor skin turgor  n  Decr saliva and sweat

n  If thirst center damaged then DI become life threatening illness because incr losses by kidney does not trigger thirst center!

n  DI results in hypernatremia thus s/s similar to dehydration, also hypotonic polyuria, and hypertonicity

Daily replacement of ADH

Free access to fluids

Home testing of urine specific gravity

n  Syndrome of inappropriate ADH excretion

n  Ectopic production of ADH has been noted in association w/ several types of tumors (most common lung malignancy but non malig lung disorders also can synthesize ADH), drug induced ADH occurs w/ such meds as morphine and barbiturates.

n  Causes hyponatremia

n  Fluid restriction n  IV admin of saline combined w/ furosemide may cause loss of free water

n  Hyponatremia should be corrected slowly n  Can use meds to block ADH 

n  Lithium can be given because blocks affects of ADH in kidneys...low therapeutic level   n  Demetrocycline (antibiotic):  blocks affect of ADH in the kidney....super infections

n  Thyroid is in neck region and secretes thyroxine and triodothyronine    n  Secretion of TH regulated by hypothalamic-pituatary-thyroid feedback system

n  Effect of system to maintain appropriate concentration of free thyroid hormones   n  Amount of TH released controlled by TSH release   n  TSH regulated by thyrotropin releasing hormone from hypothalamus

n  Ths influences metabolic rate

       congenital or acquiredn  Most cases are primary due to direct dysfx of thyroid glandn  Congen hypo may result from:  thyroid dysgenesis (most common), blocking of TSH receptors and defective synthesis of THn  Most common cause of acq is lymphocytic thyroiditis, also caused by irradiation of T gland, iodine deficiency, food w/substances that interfere w/TH synthesis, also some drugs like lithiumn  2nd hypo is caused by defects in TSH production and occurs in those w/ severe head trauma, cranial neoplasms, brain infxn, cranial irradiation, an neurosurgery

Clinical mainifestations of

Hypothyroidism VS. Hyperthyroidism?

n  Goal is to return to euthyroid state

n  Given oral thyroid hormone (levothyroxine)‏

n  Must be not be given too quickly or pt may experience insomnia, anxiety, and mood lability

^{n    Thyroid follicular cell hyperfunction w/ synthesis of THn    Caused by stim of TSH receptors by substances like TSH or TSH receptor antibodiesn    Autonomous hyperfunction can be caused by adenomas and (rarely) thyroid carcinoman    Stim of TSH receptors by TRAb leads to diffuse toxic goiter (graves disease):  most common cause of hyperthyroidism.  Mediated through autoimmune process.  More common in womenn    Thyroid follicular destruction w/ realse of THn    Ingestion of excessive TH or iodide prepsn    Incr levels incr metabolic rate}

^{n    TH production decreased w/ class of antithyroid drugs called thionamides}

^{n    Radioactive iodine treatment to ablate the gland (but must watch for hypothyroidism)‏}

^{n    Surgical removal of T gland (rarely practiced) (can lead to hyperparathyroidism)‏}

^{Helps maintain homeostasis thru  regulation of ca+ concentrations in the bloodn    PTH acts on bones and renal tubules and incr serum levels of calciumn    In bone PTH incr osteoclastic activity resulting in release of calcium to ECFn    Incr reabsorption of ca+n    Stims activation of V-D which incr intestinal ca+ absorptionn    Serum ca+ provide feedcback to reg PTH:  decr in ca causes release of PTHn    Calcitonin (produced by thyroid parafollicular cells) also influences ca in bone cellsn    It incr bone formation by osteoblasts thus inhibiting breakdown by osteoclasts:  it tends to decr calcium blood levles and promote conservation of bone}

n  Genetics

n  Malignant tumors may release PTH

n  During pregnancy can lead to neonatal complications

n  In chronic renal failure:  secondary hyperparathyroidism may result from abnormal levels of phosphate and calcium

Clinical manifestations of hyperparathyroidism

 n  Related to level of hypercalcemia n  May present asymptomatic hypercalcemia but are prone to kidney stones and osteoporosis n  Other include:  polyuria n  Dehydration n  anorexia/nausea/vomitting/constipation n  Bradycardia n  Heart block n  Cardiac arrest

Treatment of Hyperparathyroidism

n  Surg removal of parathyroid is treatment of choice

n  Hydration (to prevent kidney stones)‏

n  Ambulation

n  Alendronate (may prevent bone loss)‏

Etiology of Hypoparathyroidism

Clinical manifestations of Hypoparathyroidism

n  Result of low serum calcium

Treatment of Hyperparathyroidism

Which hormones are adrencorticals?

nSteroids including: 

Etiology of Adrenocortical Insufficiency

^{n    Primary is Addison disease:  caused by disease of adrenal cortex}

^{n    Also from inadequate secretion of ACTH from anterior pituitary n    Also lack of CRH secretion from hypthalamus}

^{n    Syndrome:  congenital adrenal hyperplasia:  is a rare cause of adrenal insufficiency in peds:  due to enzymatic defects in biosynthesis of cortisol by the adrenal}

^{n    Severe and life threatening symptoms occur due to lack of circulating cortisol}

^{What is specfic cause of primary adrenal insuffcienc(addison disease)‏}

ease)

Specific cause of secondary adrenal insufficiency

 nUsually iatrogenic in origin because of large number of patients receiving corticosteroid therapy for chron illness

Clinical manifestations of adrenocortical insufficiency?

Treatment of Adrenocortical insufficiency

Replacing absent or deficient hormones

Etiology of hypercortisolism

Clinical manifestations of hypercortisolism

n  Round face w/ prom flushed cheecks n  Noticeable weight gain n  Incr total body fat especially in abdomen n  Cervical fat ad n  Capillary friability n  Thinning of skin w/ formation of purple striae & ecchymoses over abs, arms and thighsn  Hypertension may develop n  W/ chron cushing diseae:  Demineralization of bones/fracturesemotinal changes:  depression emotional liability, anxiety irritability, rarely euphoria n  Decr in short term mem, concentration, attention span n decr Muscle mass n  Muscle weakness

Treatment for Hypercortisolism

nTransphenoidoal hypophysectomy