Endocrine Bullets

Alteration in Endocrine FunctionEndocrine disorders

1. Hyperfunction -increased secretion/ concentration of its hormone (s) in the blood.

2. Hypofunction - decreased secretion /concentration of its hormone(s) in the blood.

3. Eufunction -normal secretion/concentration of its hormone

Causes:

1. Acquired causes

A. Tumors of endocrine glands.

B. Inammatory lesions of endocrine glands.

Autoimmune/ viral /bacterial infection.

C. Disorders of nutrition. Synthesis

ALTERATION IN HYPOTHALAMIC PITUITARY FUNCTIONSEmpty sella syndrome

- pituitary gland shrinks or becomes flattened.

When the pituitary gland shrinks or becomes flattened, it cannot be seen onMRIscans, giving the appearance of an "empty sella." This is referred to as empty sella syndrome.

The pituitary makes several hormones that control the other glands in the body, including the:

Adrenal glands

Ovaries

Testicles

Thyroid

Primary empty sella syndrome occurs when a hole in the membrane covering the pituitary gland allows fluid in, which presses on the pituitary.

Secondary empty sella syndrome occurs when the sella is empty because the pituitary gland has been damaged by:

A tumor

Radiation therapy

Surgery

Pituitary adenoma

These benign tumors do not spread outside the skull. They usually remain confined to the sella turcica (the tiny space in the skull that the pituitary gland sits in). Sometimes they grow into the walls of the sella turcica and surrounding blood vessels, nerves, and coverings of the brain. They do not grow very large, but they can have a big impact on a persons health.

There is very little room for tumors to grow in this part of the skull. Therefore, if the tumor becomes larger than about a centimeter (about half an inch) across, it can compress and cause damage to nearby parts of the brain and the nerves that arise from it.

The problems pituitary adenomas can cause include:

Vision loss or double vision:The nerves that connect the brain to the eyes (the optic nerves) and to the muscles that move the eyes pass near the pituitary gland. An enlarged pituitary can press on these nerves and affect vision.

Overproduction of hormones:Many pituitary adenomas make too much of a particular hormone, which can cause serious symptoms

Hormone deficiency:Sometimes the pituitary adenoma can crowd out the healthy pituitary tissue that remains. Damage to this tissue can lead to a shortage of the other pituitary hormones.

Microadenoma versus macroadenomaPituitary adenomas can be divided into 2 categories based on size:

Microadenomasare tumors that are smaller than 1 centimeter (cm) across. Because these tumors are small, they rarely damage the rest of the pituitary or nearby tissues. But they can cause symptoms if they release too much of a certain hormone into the bloodstream. Many people may actually have small adenomas that are never detected because they never grow large enough or secrete enough hormones to cause a problem.

Macroadenomasare tumors 1 cm across or larger. Macroadenomas can affect a persons health in 2 ways. First, they can cause symptoms if they make too much of a certain hormone. Second, they may cause symptoms by pressing on normal pituitary tissue or nearby nerves, such as the optic nerves.

Functional vs non-functional adenomaFunctional adenomas: Prolactin-producing adenomas (prolactinomas), which account for about 4 out of 10 pituitary tumors

Growth hormone-secreting adenomas, which make up about 2 in 10 pituitary tumors

Corticotropin (ACTH)-secreting adenomas (about 7%)

Gonadotropin (LH and FSH)-secreting adenomas (less than 1%)

Thyrotropin (TSH)-secreting adenomas (less than 1%)

Some adenomas secrete more than one type of hormone.

Non-functional adenomas: do not make any hormone They account for about 3 in 10 of all pituitary tumors that are found. They are usually detected as macroadenomas, causing symptoms because of their size as they press on surrounding structures.

Causes

Unknown, genetic changes, inherited.Exposure to cancer causing substances like radiation.

Risk Factors A family or personal history ofmultiple endocrine neoplasia, Other disorders :acromegaly (giantism)

Symptoms

General symptoms due to size may include:

Headache

Blurred vision or tunnel vision

Prolactin Secreting Adenoma symptoms (40% of all cases)

Milk production from nonlactating females

Loss of or irregular periods

Loss of sex drive

Vaginal dryness

Low bone density or osteoporosis

Symptoms from Thyrotropin-secreting Adenoma

Enlarged thyroid (eg goiter)

Symptoms of hyperthyroidism

Tremors

Heart palpitations

Anxiety

Weight loss

Insomnia

Corticotropin-secreting Adenoma Symptoms:

Menstrual disturbance

High blood pressure

High fasting glucose

Skin changes (increased facial hair, acne, bruising, bluish stretch marks

Buffalo hump (increased fatty tissue in back)

Obesity especially around the wrist

Round face

Growth Hormone-secreting Adenoma

Acromegaly (adult)

Gigantism (child)

High blood pressure

High fasting blood sugar

Facial features coarse

Oily skin

Excess sweating

Associated Conditions Pituitary Adenomas

Diabetes mellitus Kidney stones Cardiovascular disease

High blood pressure Osteoporosis Thyroid disease

http://www.med.nyu.edu/content?ChunkIID=96789Diabetes Insipidus (DI) D/O of water metabolism caused by deficiency of ADH, also called vasopressin, Antidiuretic hormone (ADH) prevents water loss in the body by increasing the re-uptake of water in the kidneys and reducing blood flow to sweat glands.

Pathophysiology and Etiology

Primary: idiopathic.

Secondary: head trauma, neurosurgery, tumors (intracranial or metastatic), vascular disease (aneurysms, infarct), infection (meningitis, encephalitis).

Nephrogenic DI: long-standing renal disease, hypokalemia, some medications.

Deficiency of ADH results in decreased renal water reabsorption; it may be partial or complete.

Normally, ADH is synthesized in hypothalamus and stored in posterior pituitary gland---release to circulation---increase water permeability of kidney to water reabsorptionDecreased ADH release from pituitary

Decreased renal tubular permeability to water

Decreased water reabsorption

Decreased urine osmolality(inappropriate urine dilution) and specific gravity

Marked polyuria (5 to 20 L/d of dilute urine (water, SG of 1.000 to 1.005, & urine osmolality of 50 to 200 mOsm/kg.) Nocturia, fatigue, dehydration, wt loss, poor skin turgor, dry m.m., constipation, muscle weakness, dizziness, tachycardia, hypotension

Polydipsia ( drinks 4 to 40 L /d; craving for cold water.

High serum osmolality (above 295 mOsm) and high serum sodium level (greater than 145 mEq/L).

SIADH

The syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Potentially life threatening condition that disturbs fluid and electrolyte balance

Causes

Neoplastic diseases( pancreatic, thymoma), CNS (brain tumor, GBS)and pulmonary( pneumonia, tb) disorders, Drugs that increase ADH production(antidepressants, NSAID)Understanding SIADH

Excessive ADH secretion

Increased renal tubule permeability

Increased water retention and expanded extracellular fluid volume

Reduced plasma osmolality Intracellular fluid shift\Cerebral edema

Diminished aldosterone secretion (regulate Na and water)Dilutional hyponatremia

Decreased Na resorption

Increased sodium secretion Hyponatremia

Elevated glomerular filtration rate

Increased sodium secretion

Hyponatremia and electrolyte imbalance

S/sx

Thirst, anorexia, fatigue, lethargy, vomiting, intestinal cramping, weight gain, edema, water retention, and decreased urine output, neurologic changes( restlessness, confusion, headache, irritability, decreasing reflexes, and seizures) decreased deep tendon reflexesALTERATION IN THYROID FUNCTIONGOITER

- enlargement of the thyroid gland and is not cancerous.

-The thyroid is a gland, shaped like a butterfly, located at the base of the neck

-can have normal levels of thyroid hormone (euthyroidism), excessive levels (hyperthyroidism) or levels that are too low (hypothyroidism).

CAUSES

-lack of iodine

-imbalance in thyroid hormone

-nodules that develop in the gland

-common: females than males, all ages

Types:1. Diffuse small goiter- feels smooth.

2. Nodular goiter- feels lumpy

S/SX

. swelling of the thyroid gland. Generally, painless. Hoarseness (voice)

Coughing more frequently than usual

A feeling of tightness in the throat

Swallowing difficulties (less common)

Breathing difficulties (less common)

HYPOTHYROIDISM

-in adeq. amounts of thyroid hormone

The thyroid gland affects:

1. metabolic rate of all tissues,

2. speed of chemical reactions,

3. volume of oxygen consumed,

4. amount of heat produced.

Two hormones:

1. Levothyroxine (T4); maintains body's metabolism in a steady state; T4 serves as a precursor of T3.

2.Triiodothyronine (T3) has a more rapid metabolic action and utilization than T4 does.


1. Primary hypothyroidism (common)

Autoimmune disease (Hashimoto's thyroiditis).

Use of radioactive iodine.

Destruction, suppression, or removal of all or some of the thyroid tissue by thyroidectomy.

Dietary iodide deficiency.

Subacute thyroiditis.

Lithium therapy.

Overtreatment with antithyroid drugs.

2. Secondary hypothyroidism is caused by inadequate secretion of TSH caused by disease of the pituitary gland (ie, tumor, necrosis).

Inadequate secretion of thyroid hormone leads to a general slowing of all physical and mental processes.

General depression of most cellular enzyme systems and oxidative processes occurs.

The metabolic activity of all cells of the body decreases, reducing oxygen consumption, decreasing oxidation of nutrients for energy, and producing less body heat.

Clinical Manifestations

Fatigue and lethargy.

Weight gain.

Complaints of cold hands and feet.

Temperature and pulse become subnormal; patient cannot tolerate cold and desires increased room temperature.

Reduced attention span; impaired short-term memory.

Severe constipation; decreased peristalsis.

Generalized appearance of thick, puffy skin; subcutaneous swelling in hands, feet, and eyelids.

Hair thins; loss of the lateral one-third of eyebrow.

Menorrhagia or amenorrhea; may have difficulty conceiving or may experience spontaneous abortion; decreased libido.

Neurologic signs include polyneuropathy (pins-and-needles sensation, numbness, burning pain, and loss of vibration sense and position sense), cerebellar ataxia(loss of coordination), muscle aches or weakness, clumsiness, prolonged deep tendon reflexes .

Hyperlipoproteinemia and hypercholesterolemia.

Enlarged heart on chest X-ray.

Increased susceptibility to all hypnotic and sedative drugs and anesthetic agents.

Diagnostic Evaluation

Low T3 and T4 levels.

Elevation of serum cholesterol.

Electrocardiogram (ECG) sinus bradycardia, low voltage of QRS complexes, and flat or inverted T waves.

HASHIMOTOS THYROIDITIS

Hashimoto's thyroiditis is a chronic progressive disease of the thyroid gland caused by infiltration of lymphocytes; it results in progressive destruction of the parenchyma and hypothyroidism if untreated.


Cause is unknown; autoimmune disease, genetically transmitted

women in their 40s or 50s.


Marked by a slowly developing, firm enlargement of the thyroid gland.

Usually no gross nodules.

Basal metabolic rate is usually low.

Periods of hyperthyroidism caused by large amounts of T3 and T4 being released into bloodstream.

Diagnostic Evaluation``

T3 and T4 may be normal but usually become subnormal as the disease progresses.

Antithyroglobulin antibodies and antimicrosomal antibodies are present.

Normal or high concentration of thyroglobulin-binding protein.

HYPERTHYROIDISM

This hypermetabolic condition is characterized by excessive amounts of thyroid hormone in the bloodstream.


More common in women than in men

Graves' disease (most prevalent) diffuse hyperfunction of the thyroid gland with autoimmune etiology and associated with ophthalmopathy;.

TSI, an immunoglobulin found in the blood of patients with Graves' disease, is capable of reacting with the receptor for TSH on the thyroid plasma membrane and of stimulating thyroid hormone production and secretion.

May appear after an emotional shock, an infection, or emotional stress.

Toxic nodular goiter (single or multiple)more common in older women with preexisting goiter; will continue to be overactive unless eradicated or kept under suppressive therapy.

Hyperthyroidism is characterized by hypertrophy and hyperplasia of the thyroid gland, which is accompanied by increased vascularity and blood flow and enlargement of the gland.

Most of the clinical manifestations result from increased metabolic rate, excessive heat production, increased neuromuscular and cardiovascular activity, and hyperactivity of the sympathetic nervous system.

Hyperthyroidism ranges from a mild increase in metabolic rate to the severe hyperactivity known as thyrotoxicosis, thyroid storm, or thyroid crisis.

Hyperthyroidism can also be the result of ingestion of excessive amounts of thyroid hormone medication (factitious hyperthyroidism).


Nervousness, emotional lability, irritability, apprehension.

Difficulty in sitting quietly.

Rapid pulse at rest and on exertion (ranges between 90 and 160); palpitations.

Heat intolerance; profuse perspiration; flushed skin (eg, hands may be warm, soft, moist).

Fine tremor of hands; change in bowel habitsconstipation or diarrhea.

Increased appetite and progressive weight loss; frequent stools.

Muscle fatigability and weakness; amenorrhea.

Atrial fibrillation possible (cardiac decompensation common in older patients).

Bulging eyes (exophthalmos) seen only in Graves' disease.

Thyroid gland may be palpable and a bruit may be auscultated over gland.

Course may be mild, characterized by remissions and exacerbations.

It may progress to emaciation, extreme nervousness, delirium, disorientation, thyroid storm or crisis, and death.

Thyroid storm or crisis, an extreme form of hyperthyroidism, is characterized by hyperpyrexia, diarrhea, dehydration, tachycardia, arrhythmias, extreme irritation, delirium, coma, shock, and death if not adequately treated.

Thyroid storm may be precipitated by stress (surgery, infection) or inadequate preparation for surgery in a patient with known hyperthyroidism.


Elevated T3 and T4.

Elevated serum T3 resin uptake.

131I uptake scan may be elevated or below normal depending on the underlying cause of the hyperthyroidism.

GRAVES DISEASE

Graves disease, named after Robert J. Graves, MD,[1]circa 1830s, is an autoimmune disease characterized byhyperthyroidismdue to circulating autoantibodies. Thyroid-stimulating immunoglobulins (TSIs) bind to and activate thyrotropin receptors, causing the thyroid gland to grow and the thyroid follicles to increase synthesis of thyroid hormone.

Pathophysiology

Graves disease

B and T lymphocyte-mediated autoimmunity

directed thyroid antigens: thyroglobulin, thyroid peroxidase, sodium-iodide symporter, and the thyrotropin receptor(primary autoantigen of Graves disease).

The thyroid gland is under continuous stimulation by circulating autoantibodies against the thyrotropin receptor,

pituitary thyrotropin secretion is suppressed because of the increased production of thyroid hormones.

These thyroid-stimulating antibodies cause release of thyroid hormone and thyroglobulin and they also stimulate iodine uptake, protein synthesis, and thyroid gland growth.

ALTERATION IN PARATHYROID FUNCTION

DISORDERS OF THE PARATHYROID GLANDS

The parathyroid glands are small, bean-sized structures embedded in the posterior section of the thyroid gland. Functions include the production, storage, and release of parathyroid hormone (PTH) in response to the serum level of ionized calcium. PTH increases serum calcium by decreasing elimination of calcium ions in the urine by the kidney, increasing absorption of calcium ions from the gut, and increasing bone contribution of calcium ions to the plasma.

HYPERPARATHYROIDISM

Hyperparathyroidism is hypersecretion of PTH.


women older than age 50.

Primary hyperparathyroidism.

Single parathyroid adenoma (common )

Parathyroid hyperplasia accounts for approximately 20% of cases.

Parathyroid carcinoma accounts for less than 1% of cases.

Secondary hyperparathyroidism.

Primarily the result of renal failure.

Excess secretion of PTH results in increased serum calcium levels


Decalcification of bones (Ca removal).

Skeletal pain, backache, pain on weight-bearing, pathologic fractures, deformities, formation of bony cysts.

Formation of bone tumors overgrowth of osteoclasts(break).

Formation of calcium-containing kidney stones.

Depression of neuromuscular function.

The patient may trip, drop objects, show general fatigue, lose memory for recent events, experience emotional instability, have changes in level of consciousness, with stupor and coma.

Cardiac arrhythmias, hypertension, cardiac standstill.


Persistently elevated serum calcium (11 mg/100 mL); test is performed on at least two occasions to determine consistency of results.

PTH levels are increased.

Serum calcium and alkaline phosphatase levels are elevated and serum phosphorus levels are decreased.

Skeletal changes are revealed by X-ray.

Early diagnosis typically is difficult. (Complications may occur before this condition is diagnosed.)

computed tomography (CT) will disclose parathyroid tumors more readily than X-ray.

HYPOPARATHYROIDISM

Hypoparathyroidism results from a deficiency of PTH and is characterized by hypocalcemia and neuromuscular hyperexcitability.


The most common cause is accidental removal or destruction of parathyroid tissue or its blood supply during thyroidectomy or radical neck dissection for malignancy.

Decrease in gland function (idiopathic hypoparathyroidism); may be autoimmune or familial in origin.

Malignancy or metastasis from a cancer to the parathyroid glands.

Resistance to PTH action.

With inadequate PTH secretion, there is decreased resorption of calcium from the renal tubules, decreased absorption of calcium in the GI tract, and decreased resorption of calcium from bone.

Blood calcium falls to a low level, causing symptoms of muscular hyperirritability, uncontrolled spasms, and hypo-calcemic tetany.

In response to decreased serum calcium levels and lack of PTH, the serum phosphate level rises and phosphate excretion by the kidneys decreases.


Tetany general muscular hypertonia; attempts at voluntary movement result in tremors and spasmodic or uncoordinated movements; fingers assume classic tetanic position.

Chvostek's sign a spasm of facial muscles that occurs when muscles or branches of facial nerve are tapped.

Trousseau's sign carpopedal spasm within 3 minutes after a BP cuff is inflated 20 mm Hg above the patient's systolic pressure.

Laryngeal spasm.

Severe anxiety and apprehension.

Renal colic is usually present if the patient has history of stones; preexisting stones loosen and migrate into the ureter.


Phosphorus level in blood is elevated.

Decrease in serum calcium level to a low level (7.5 mg/100 mL or less).

PTH levels are low in most cases; may be normal or elevated in pseudohypoparathyroidism.ALTERATIONS IN ADRENAL GLAND FUNCTIONThe adrenal medulla two hormones:

Epinephrine (adrenalin) increase contractility and excitability of heart muscle, --- increased cardiac output; --- blood flow to muscles, brain, and viscera;

enhances blood sugar by stimulating conversion of glycogen to glucose in liver;

inhibits smooth muscle contraction.

Norepinephrine (noradrenaline) increase peripheral vascular resistance ---increases in diastolic and systolic BP.

The adrenal cortex secretes adrenocortical hormones synthesized from cholesterol.

Glucocorticoids (cortisone and hydrocortisone) enhance protein catabolism and inhibit protein synthesis;

antagonize action of insulin and increase blood sugar;

increase synthesis of glucose by liver;

influence defense mechanism of body and its reaction to stress;

influence emotional reaction.

Mineralocorticoids (aldosterone and desoxycorticosterone)

regulate reabsorption of sodium; regulate excretion of potassium by renal tubules.

Adrenosterones (adrenal androgens) exert minimal effect on sex characteristics and function.

CUSHING'S SYNDROME

-plasma cortisol levels are elevated, causing signs and symptoms of hypercortisolism.

-excessive anterior pituitary hormone corticotropin

Cortisol(stress hormone)


10 times more frequently in women than in men.

Cushing's syndrome are the result of excess hormones (glucocorticoids, mineralocorticoids, and adrenal androgens).

Prolonged exposure to pharmacologic doses of exogenous glucocorticoids

Secretory adrenocortical tumors stimulating adrenal cortex to increase corticotrophin production

---excessive levels of glucocorticoids

---adrenal hyperplasia, suppression of pituitary corticotropin, and reduced hypothalamic secretion of corticotropin releasing hormone


Excessive Glucocorticoids

Endocrine and metabolic changes

Cortisol induced insulin resistance and increased glucogeneogenesis- DM, Decreased glucose tolerance, fasting hyperglycemia, glucosuria

Musculoskeletal changes

Hypokalemia- muscle weakness

Increased catabolism- loss of muscle mass

Decreased bone mineral ionization, osteopenia, osteoporosis characteristic kyphosis, backache, skeletal growth retardation- pathologic fractures

Skin Changes

Decreased collagen and weakened tissues

Fragile and thin skin, striae and ecchymosis, acne.

Heavy trunk; thin extremities.

Buffalo hump (fat pad) in neck and supraclavicular area.

Rounded face (moon face); plethoric, oily.

GI changes

Increased gastric secretion and pepsin production- peptic ulcer, abdominal pain, increased appetite, weight gain

Cardiovascular changes

Sodium and secondary fluid retention- hypertension, heart failure, left ventricular hypertrophy

Protein loss- capillary weakness, bleeding, ecchymosis

Other changes

Altered neurotransmission-Mental disturbances mood changes, irritability, psychosis,

Decreased lymphocyte production and suppressed antibody formation- increased susceptibility to infection

Increased susceptibility to infections.

Excessive Androgen production

Women experience virilism (masculinization).

Hirsutism excessive growth of hair on the face and midline of trunk.

Breasts atrophy, amenorrhea, oligomenorrhea

Clitoris enlargement.

Voice masculine.

Loss of libido.

If exposed in utero possible hermaphrodite.

Males loss of libido.

Excessive Mineralocorticoids

Hypertension.

Hypernatremia, hypokalemia.

Weight gain.

Expanded blood volume.

Edema.


Excessive plasma cortisol levels.

An increase in blood glucose levels and glucose intolerance.

Decreased serum potassium level.

Reduced eosinophils.

Elevation of plasma ACTH in patients with pituitary tumors.

Low plasma ACTH levels with adrenal tumor.

X-rays of the skull detect erosion of the sella turcica by a pituitary tumor.

CT scan and ultrasonography detect location of tumor.

A profound decline in blood levels of potassium (hypokalemia) and hydrogen ions (alkalosis) results in muscle weakness and inability of kidneys to acidify or concentrate urine, leading to excess volume of urine (polyuria).

A decline in hydrogen ions (alkalosis) results in tetany, paresthesia.

An elevation in blood sodium (hypernatremia) results in excessive thirst (polydipsia) and arterial hypertension.

ADRENOCORTICAL INSUFFICIENCY (ADDISONS DISEASE)

Adrenocortical insufficiency occurs with

-inadequate secretion of the hormones of the adrenal cortex, primarily the glucocorticoids, mineralocorticoids and androgens.

-impaired pituitary secretion of corticotrophin, decreased glucocorticoid secretion although aldosterone secretion is unaffected

Adrenal crisis (Addisonian crisis) adrenal hypofunction and involves critical deficiency of mineralocorticoids and glucocorticoids occurs after acute stress, sepsis, trauma, surgery or omission of steroid therapy (life threatening)


Primary adrenocortical insufficiency (Addison's dis-ease) destruction and subsequent hypofunction of the adrenal cortex, usually caused by autoimmune process.

Secondary adrenocortical insufficiency ACTH deficiency from pituitary disease or suppression of hypothalamic-pituitary axis by corticosteroid treatment for nonendocrine disorders causes atrophy of adrenal cortex.

Adrenal gland hypofunction

Absent or low cortisol levels

Liverdec. hepatic glucose outputhypoglycemia

Stomachreduced levels of digestive enzymesvomiting, cramps, and diarrhea

Cortisol deficiency produces abnormal fat, protein, and carbohydrate metabolism;

Absent or very low aldosterone levels

Kidneys -- sodium and water loss with potassium retention-hypovolemia---shock

Heart--- arrhythmias and decreased cardiac output---hypotension---shock


Hyponatremia and hyperkalemia.

Water loss, dehydration, and hypovolemia.

Muscular weakness, fatigue, weight loss.

GI problems anorexia, nausea, vomiting, diarrhea, constipation, abdominal pain.

Hypotension, hypoglycemia, low basal metabolic rate, increased insulin sensitivity.

Mental changes depression, irritability, anxiety, apprehension caused by hypoglycemia and hypovolemia.

Normal responses to stress lacking.

Hyperpigmentation.

Adrenal Crisis

Primary adrenal hypofunction

Mineralocorticoid or glucocorticoid deficiency

Weakness, fatigue, weight loss, nausea, vomiting, anorexia, decrease tolerance to stress, cardiovascular abn (orthostatic hypotension, decreased cardiac size and output, weak, irregular pulse) craving for salty food lead to sodium retention

Decreased cortisol levels and simultaneous secretion of excessive corticotrophin and melanocyte stimulating hormone

Bronze skin coloring (hand and finger, elbows and knees) darkening of scars. Absence of pigmentation(vitiligo)

Decreased glucogenesis

Fasting hypoglycemia

Secondary adrenal crisis

Low corticotropin and melanocyte stimulating hormone

Same with primary hypofunction but without hyperpigmentation


Blood chemistry decreased glucose, decreased sodium, increased potassium.

Increased lymphocytes on complete blood count.

Low fasting plasma cortisol levels; low aldosterone levels.

PHEOCHROMOCYTOMA

Pheochromocytoma is a catecholamine-secreting neoplasm associated with hyperfunction of the adrenal medulla.


Pheochromocytoma can occur at any age, but is most common between the ages of 30 and 60; it is uncommon in people older than age 65.

Most pheochromocytoma tumors are benign; 10% are malignant with metastasis.

Tumors located in the adrenal medulla produce both increased epinephrine and norepinephrine; those located outside the adrenal gland tend to produce epinephrine only.

May occur as component of multiple endocrine neoplasia II, an autosomal-dominant syndrome characterized by pheochromocytoma, thyroid cancer, hyperparathyroidism, and Cushing's syndrome with excess ACTH.


Variation in signs and symptoms depends on the predominance of norepinephrine or epinephrine secretion and on whether secretion is continuous or intermittent.

Excess secretion of norepinephrine and epinephrine produces hypertension, hypermetabolism, and hyperglycemia.

Hypertension may be paroxysmal (intermittent) or persistent (chronic).

Chronic form mimics essential hypertension; however, antihypertensives are not effective.

Headaches and vision disturbances are common.

The hypermetabolic and hyperglycemic effects produce excessive perspiration, tremor, pallor or face flushing, nervousness, elevated blood glucose levels, polyuria, nausea, vomiting, diarrhea, abdominal pain, and paresthesia.

Emotional changes, including psychotic behavior, may occur.

Symptoms may be triggered by allergic reactions, physical exertion, emotional upset, or may occur without identifiable stimulus.


Epinephrine and norepinephrine in urine and blood are elevated while patient is symptomatic.

CT scan and magnetic resonance imaging (MRI) of the adrenal glands or of the entire abdomen are done to identify tumor.

Clonidine suppression test is used to distinguish essential hypertension from pheochromocytoma.

Diabetes Mellitus

INSULIN SECRETION AND FUNCTION

Insulin is a hormone secreted by the beta cells of the islet of Langerhans in the pancreas.

Increased secretion or a bolus of insulin, released after a meal, helps maintain euglycemia.

blood glucose levels are maintained at a normal range of 60 to 110 mg/dL.

Insulin is essential for the utilization of glucose for cellular metabolism as well as for the proper metabolism of protein and fat.

Carbohydrate metabolism insulin affects the conversion of glucose into glycogen for storage in the liver and skeletal muscles, and allows for the immediate release and utilization of glucose by the cells.

Protein metabolism amino acid conversion occurs in the presence of insulin to replace muscle tissue or to provide needed glucose (gluconeogenesis).

Fat metabolism storage of fat in adipose tissue and conversion of fatty acids from excess glucose occurs only in the presence of insulin.

Glucose can be used in the endothelial and nerve cells without the aid of insulin.

Without insulin, plasma glucose concentration rises and glycosuria results.

CLASSIFICATION OF DIABETES

Type 1 Diabetes Mellitus

known as insulin dependent diabetes mellitus and juvenile diabetes mellitus.

Little or no endogenous insulin, requiring injections of insulin to control diabetes and prevent ketoacidosis.

Five to 10% of all diabetic patients have type 1.

Etiology: autoimmunity, viral, and certain histocompatibility antigens as well as a genetic component.

Usual presentation is rapid with classic symptoms of polydipsia, polyphagia, polyuria, and weight loss.

Most commonly seen in patients under age 30 but can be seen in older adults.


known as noninsulin dependent diabetes mellitus or adult onset diabetes mellitus.

Caused by a combination of insulin resistance and relative insulin deficiency some individuals have predominantly insulin resistance, whereas others have predominantly deficient insulin secretion, with little insulin resistance.

Approximately 90% of diabetic patients have type 2.

Etiology: strong hereditary component, commonly associated with obesity.

Usual presentation is slow and typically insidious with symptoms of fatigue, weight gain, poor wound healing, and recurrent infection.

Found primarily in adults over age 30; however, may be seen in younger adults and adolescents who are overweight.

Patients with this type of diabetes, but who eventually may be treated with insulin, are still referred to as having type 2 diabetes.

Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance occurring during pregnancy.

Occurs in approximately 4% of pregnancies and usually disappears after delivery.

Women with GDM are at higher risk for diabetes at a later date.

GDM is associated with increased risk of fetal morbidity.

Screening for GDM for all pregnant women other than those at lowest risk (under age 25, of normal body weight, have no family history of diabetes, are not a member of an ethnic group with high prevalence of diabetes) should occur between the 24th and 28th weeks of gestation.

DIABETES MELLITUS

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and results from defective insulin production, secretion, or utilization.



Hyperglycemia

Weight loss, - prevention of normal metabolism of carbo, protein, fats

Polyuria, polydipsia - high serum osmolality caused by high serum glucose level

Polyphagia - to depleted cellular storage of carbohydrates, fats and protein due to lack of insulin

Blurred vision- glucose induced swelling

Numbness and tingling- neural tissue damaged

Fatigue, headache, lethargy, reduced energy level- low intercellular glucose level

Muscle cramps, irritability, emotional lability- electrolyte imbalance

Abdominal discomfort and pain, nausea, diarrhea, constipation- dehydration, electrolyte imbalance

Altered Tissue Response

Poor wound healing

Recurrent infections, particularly of the skin

skin itching. Vaginal pruritus


FBS of greater than or equal to 126 mg/dL

Random blood glucose of greater than or equal to 200 mg/dL with classic symptoms (polyuria, polydipsia, polyphagia, weight loss)

Capillary blood glucose values obtained by finger stick samples tend to be higher than values in venous samples.

Pancreatitis

Signs and symptoms

Abdominal pain (cardinal symptom): Characteristically dull, boring, and steady; usually sudden in onset and gradually becoming more severe until reaching a constant ache; most often located in the upper abdomen and may radiate directly through to the back

Nausea and vomiting, sometimes with anorexia

Diarrhea

Patients may have a history of the following:

Recent operative or other invasive procedures

Family history of hypertriglyceridemia

Previous biliary colic and binge alcohol consumption (major causes of acute pancreatitis)

Clinical manifestations:

Fever (76%) and tachycardia (65%); hypotension

Abdominal tenderness, muscular guarding (68%), and distention (65%); diminished or absent bowel sounds

Jaundice (28%)

Dyspnea (10%); tachypnea; basilar rales, especially in the left lung

In severe cases, hemodynamic instability (10%) and hematemesis or melena (5%); pale, diaphoretic, and listless appearance

Occasionally, extremity muscular spasm secondary to hypocalcemia

Uncommon physical findings are associated with severe necrotizing pancreatitis:

Cullen sign (bluish discoloration around the umbilicus resulting from hemoperitoneum)

Grey-Turner sign (reddish-brown discoloration along the flanks resulting from retroperitoneal blood dissecting along tissue planes); more commonly, patients may have a ruddy erythema in the flanks secondary to extravasated pancreatic exudate

Erythematous skin nodules, usually no larger than 1 cm and typically located on extensor skin surfaces; polyarthritis

Pathophysiology

Normal pancreatic function

The pancreas is a gland located in the upper posterior abdomen. It is responsible for insulin production (endocrine pancreas) and the manufacture and secretion of digestive enzymes (exocrine pancreas) leading to carbohydrate, fat, and protein metabolism. Approximately 80% of the gross weight of the pancreas supports exocrine function, and the remaining 20% is involved with endocrine function.

Digestive enzymes are produced within the pancreatic acinar cells, packaged into storage vesicles called zymogens, and then released via the pancreatic ductal cells into the pancreatic duct, where they are secreted into the small intestine to begin the metabolic process.

Premature activation of pancreatic enzymes within the pancreas leads to organ injury and pancreatitis

Zymogen granules have an acidic pH and a low calcium concentration, which are factors that guard against premature activation until after secretion has occurred and extracellular factors have triggered the activation cascade. Under various conditions, disruption of these protective mechanisms may occur, resulting in intracellular enzyme activation and pancreatic autodigestion leading to acute pancreatitis.

Pathogenesis of acute pancreatitis

Predisposing factors

Extracellular: neural and vascular response(alcohol use, gallstones, and certain drugs)

Intracellular: intracellular digestive enzyme activation, increased calcium signaling, and heat shock protein activation

---injury to the acinar cell --- impairs the secretion of zymogen granules

Lysosomal and zymogen granule compartments fuse, enabling activation of trypsinogen to trypsin

Intracellular trypsin triggers the entire zymogen activation cascade

Secretory vesicles are extruded across the basolateral membrane into the interstitium, where molecular fragments act as chemoattractants for inflammatory cells

Activated neutrophils then exacerbate the problem by releasing superoxide (the respiratory burst) or proteolytic enzymes. Finally, macrophages release cytokines that further mediate local inflammatory responses.

These mediators of inflammation cause an increased pancreatic vascular permeability, leading to hemorrhage, edema, and eventually pancreatic necrosis. As the mediators are excreted into the circulation, systemic complications can arise, such as bacteremia due to gut flora translocation, acute respiratory distress syndrome (ARDS), pleural effusions, gastrointestinal (GI) hemorrhage, and renal failure.

The systemic inflammatory response syndrome (SIRS) can also develop, leading to the development of systemic shock. Eventually, the mediators of inflammation can become so overwhelming to the body that hemodynamic instability and death ensue.

Diagnosis

Serum amylase and lipase

Liver-associated enzymes

Blood urea nitrogen (BUN), creatine, and electrolytes

Blood glucose

Serum cholesterol and triglyceride

Diabetes Mellitus

INSULIN SECRETION AND FUNCTION

Insulin is a hormone secreted by the beta cells of the islet of Langerhans in the pancreas.

Increased secretion or a bolus of insulin, released after a meal, helps maintain euglycemia.

blood glucose levels are maintained at a normal range of 60 to 110 mg/dL.

Insulin is essential for the utilization of glucose for cellular metabolism as well as for the proper metabolism of protein and fat.

Carbohydrate metabolism insulin affects the conversion of glucose into glycogen

Protein metabolism amino acid conversion occurs in the presence of insulin to replace muscle tissue or to provide needed glucose (gluconeogenesis).

Fat metabolism storage of fat in adipose tissue and conversion of fatty acids from excess glucose occurs only in the presence of insulin.

CLASSIFICATION OF DIABETES


insulin dependent diabetes mellitus and juvenile diabetes mellitus.

Etiology: autoimmunity, viral, and certain histocompatibility antigens as well as a genetic component.

polydipsia, polyphagia, polyuria, and weight loss.

under age 30 but can be seen in older adults.


noninsulin dependent diabetes mellitus or adult onset diabetes mellitus.

Caused by insulin resistance and relative insulin deficiency

90% of diabetic patients have type 2.

Etiology: strong hereditary, associated with obesity.

slow and typically insidious with symptoms of fatigue, weight gain, poor wound healing, and recurrent infection.

adults over age 30; however, may be seen in younger adults and adolescents who are overweight.

Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance occurring during pregnancy.

Occurs in approximately 4% of pregnancies and usually disappears after delivery.

GDM is associated with increased risk of fetal morbidity.

Screening for GDM should occur between the 24th and 28th weeks of gestation.

DIABETES MELLITUS

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and results from defective insulin production, secretion, or utilization.



Hyperglycemia

Weight loss, - prevention of normal metabolism of carbo, protein, fats

Polyuria, polydipsia - high serum osmolality caused by high serum glucose level

Polyphagia - to depleted cellular storage of carbohydrates, fats and protein due to lack of insulin

Blurred vision- glucose induced swelling

Numbness and tingling- neural tissue damaged

Fatigue, headache, lethargy, reduced energy level- low intercellular glucose level

Muscle cramps, irritability, emotional lability- electrolyte imbalance

Abdominal discomfort and pain, nausea, diarrhea, constipation- dehydration, electrolyte imbalance

Altered Tissue Response

Poor wound healing

Recurrent infections, particularly of the skin

skin itching. Vaginal pruritus


FBS of greater than or equal to 126 mg/dL

Random blood glucose of greater than or equal to 200 mg/dL with classic symptoms (polyuria, polydipsia, polyphagia, weight loss)

Capillary blood glucose values obtained by finger stick samples tend to be higher than values in venous samples.

ALTERATION IN PANCREATIC FUNCTIONPancreatitis

Inflammation of the pancreas (acute and chronic)

Good prognosis when associated with biliary tract disease; poor when associated with alcoholism

Mortality is high 60%

Causes

Acute pancreatitis

Cholelithiasis, alcohol abuse, abnormal organ structure, metabolic or endocrine disorder, pancreatic cyst or tumors, penetrating peptic ulcer, blunt trauma or surgical trauma, drugs(glucocorticoids), kidney failure

Chronic pancreatitis

Alcohol abuse, Malnutrition, Heredity (rare)

Pathophysiology

Normal pancreatic function

The pancreas is responsible for insulin production (endocrine pancreas) and the manufacture and secretion of digestive enzymes (exocrine pancreas) leading to carbohydrate, fat, and protein metabolism.

Digestive enzymes are produced within the pancreatic acinar cells, packaged into storage vesicles called zymogens, and then released via the pancreatic ductal cells into the pancreatic duct, where they are secreted into the small intestine to begin the metabolic process.

Premature activation of pancreatic enzymes within the pancreas leads to organ injury and pancreatitis

Zymogen granules have an acidic pH and a low calcium concentration, which are factors that guard against premature activation disruption of these protective mechanisms may occur, resulting in intracellular enzyme activation and pancreatic autodigestion leading to acute pancreatitis.

Pathogenesis of acute pancreatitis

Predisposing factors

Extracellular: neural and vascular response(alcohol use, gallstones, and certain drugs)

Intracellular: intracellular digestive enzyme activation, increased calcium signaling, and heat shock protein activation

---injury to the acinar cell --- impairs the secretion of zymogen granules

Lysosomal and zymogen granule compartments fuse, enabling activation of trypsinogen to trypsin

Intracellular trypsin triggers the entire zymogen activation cascade

Secretory vesicles are extruded across the basolateral membrane into the interstitium, where molecular fragments act as chemoattractants for inflammatory cells

Activated neutrophils release proteolytic enzymes. Macrophages release cytokines that further mediate local inflammatory responses.

These mediators of inflammation cause an increased pancreatic vascular permeability,

leading to hemorrhage, edema, and eventually pancreatic necrosis.

As the mediators are excreted into the circulation, systemic complications can arise, such as bacteremia due acute respiratory distress syndrome (ARDS), pleural effusions, gastrointestinal (GI) hemorrhage, and renal failure.

The systemic inflammatory response syndrome (SIRS) can also develop, leading to the development of systemic shock. Eventually, the mediators of inflammation can become so overwhelming to the body that hemodynamic instability and death ensue.

ChangeSign and symptoms

InflammationLow grade fever

Mid epigastric abdominal pain (cardinal symptom)- dull, boring, and steady; usually sudden in onset and gradually becoming more severe until reaching a constant ache; most often located in the upper abdomen and may radiate directly through to the back

Muscle guarding

Hypermotility or paralytic ileus secondary to pancreatitis or peritonitisDiarrhea

Nausea and persistent vomiting,anorexia and abdominal distention, diminished or absent bowel sounds

Heart failureCrackles at lung bases

Circulating pancreatic enzymesLeft pleural effusion, basilar rales, dyspnea, tachypnea

Dehydration and possible hypovolemiaTachycardia, hypotension, hemodynamic instability, pale, diaphoretic, listless

MalabsorptionExtreme malaise, jaundice, muscular spasm(hypocalcemia)

Uncommon physical findings are associated with severe necrotizing pancreatitis:

Cullen sign (bluish discoloration around the umbilicus resulting from hemoperitoneum)

Grey-Turner sign (reddish-brown discoloration along the flanks resulting from retroperitoneal blood dissecting along tissue planes); more commonly, patients may have a ruddy erythema in the flanks secondary to extravasated pancreatic exudate

Erythematous skin nodules, usually no larger than 1 cm and typically located on extensor skin surfaces; polyarthritis

Diagnosis

Serum amylase and lipase

Liver-associated enzymes

Blood urea nitrogen (BUN), creatine, and electrolytes

Blood glucose

Serum cholesterol and triglyceride

Documents

Endocrine Bullets