Endocrine Disorders

Effects of Corticosteroid Therapy

1. Antiinflammatory. Decrease circulating lymphocytes, monocytes, and eosinophils. 2. Immunosuppression: atrophy of lymphoid tissue, suppress cell-mediated immune responses and decrease production of antibodies. 3. Maintenance of normal BP: potentiate vasoconstrictor effect of norepinephrine and act on renal tubules to increase sodium reabsorption and enhance potassium and hydrogen excretion. Retention of sodium increases blood volume. Mineralocorticoids: direct effect on sodium reabsorption in distal tubule of kidney and result increase sodium and water retention 4. Carbohydrate and protein metabolism. Antagonize effects of insulin and can induce glucose intolerance, increases hepatic glycogenolysis and insulin resistance. Breakdown of protein for gluconeogenesis, lead to muscle wasting.

Syndrome of inappropriate antidiuretic hormone (SIADH) Etiology and Pathophysiology

ADH released despite normal or low plasma osmolarity. Abnormal production of sustained secretion of ADH. Characterized by fluid retention, serum hypposmolality, dilutional hyponatremia, hypochloremia, concentrated urine in presence of normal or increased intravascular volume, normal renal function. Various causes, most in older adults: most common cause malignancy. Self-limiting when caused by head trauma or drugs, but chronic w/ tumors or metabolic diseases.

Disorders of Posterior pituitary

ADH, oxytocin: produced in hypothalamus and transported and stored in posterior pituitary. ADH: regulation of water balance and osmolarity. ADH secretion: overproduction is SIADH, underproduction: DI

Hypothyroidism Clinical Manifestations

All have certain features in common, regardless of cause. Has systemic effects characterized by insidious and nonspecific showing of body processes. Onset of symptoms may occur over months to years, severity depends on degree of deficiency, pronounced long term effects in neurologic, cardiovascular, GI, reproductive, hematologic. Fatigue, lethargic. Personality, mental changes (impaired memory, slowed speech, decreased initiative, somnolence, depressed). Sleeps long, stages of sleep altered. Decreased cardiac contractility, decreased CO, low exercise tolerance, SOB, hemodynamic compromise (preexisting cardio), anemia common. Low hematocrit. Cobalamin, iron, folate deficiencies. Serum cholesterol, triglyceride levels can result in coronary atherosclerosis (angina), GI motility decreased, achlorhydria (absence or decrease of hydrochloric acid) is common. Constipation, cold intolerance, hair loss, dry and coarse hair, brittle nails, hoarseness, muscle weakness, swelling, weight gain. Myxedema: accumulation of hydrophilic mucinous edema causes puffiness, periorbital edema masklike effect. Menorrhagia.

Goiter

An enlarged thyroid gland. Thyroid cells stimulated to grow, may result in overactive thyroid (hyperthyroidism) or underactive one (hypothyroidism). Excess: toxic tumor. Common in Grave's disease. Nontoxic goiter: normal levels of thyroid disorders. Most common cause of goiter: lack of iodine in the diet. More often caused in US: over or underproduction of thyroid hormones or to nodules that develop in gland itself. TSH and T4 measured to determine whether goiter is associated with hyperthyroidism, hypo, or normal thyroid function.

Diabetes Insipidus (DI) Etiology and Pathophysiology

Associated with deficiency of production of or secretion of ADH or decreased renal response to ADH. Results in fluid and electrolyte imbalances caused by increase urinary output and increase plasma osmolality. May be transient or chronic. Neurogenic (central) DI: lesion of hypothalamus, infundibular stem, posterior pituitary interferes with ADH synthesis, transport, or release. Most common. Nephrogenic: adequate ADH, decreased response in kidney. Lithium most common drug-induced cause. Hypokalemia and hypercalcemia also. Primary (psychogenic): less common, associated with excessive water intake. Structural lesion in thirst center, may be caused by psychiatric problems.

Hyperparathyroidism Clinical Manifestations and Complications

Asymptomatic to overt symptoms. Major manifestations: muscle weakness, loss of appetite, constipation, fatigue, emotional disorders, and shortened attention span. Signs: loss of calcium from bones (osteoporosis), fractures, kidney stones (nephrolithiasis). Neuromuscular abnormalities: muscle weakness, proximal muscles of lower extremities. Serious complications: renal failure, pancreatitis, cardiac changes, long bone, rib, vertebral fxs.

Clinical Presentation of Cushing

CLINICAL PRESENTATION: 1) centripetal (truncal) obesity or generalized obesity 2) moon facies (fullness of face) with facial plethora 3) purplish red striae (usually depressed below skin surface) on abdomen, breast, buttocks 4) hirsutism in women 5) menstrual disorders in women 6) hypertension 7) unexplained hypokalemia

Hyperparathyroidism Etiology and Pathophysiology

Condition involving increased secretion of parathyroid hormone (PTH). PTH: helps regulate serum calcium and phosphate levels by stimulating bone resorption of calcium, renal tubular reabsorption of Ca++, activation of vitamin D. Increased serum calcium levels. Primary: increased secretion of PTH leading to disorders of calcium, phosphate, bone metabolism. Most common cause: benign tumor (adenoma) in parathyroid gland. Head and neck radiation: may be at increased risk for adenoma. Secondary: compensatory response to conditions that cause hypocalcemia (stimulus of PTH secretion). Diseases: vitamin D deficiencies, malabsorption, chronic kidney disease, hyperphosphatemia. Tertiary: hyperplasia of parathyroid glands and loss of negative feedback from circulating calcium levels. Autonomous secretion of PTH, even with normal levels (kidney disease after on dialysis). Hypercalcemia and hypophosphatemia. Hypercalciuria.

Adrenocortical Insufficiency Diagnostic studies

Cortisol levels are subnormal or fail to rise over basal levels with aCTH stimulation test. Indicates primary adrenal disease. Positive response to ACTH stimulation: functioning adrenal gland and point to pituitary disease. Hyperkalemia, hypochloremia, hyponatremia, hypoglycemia, anemia, increased BUN. Low free cortisol in urine and low aldosterone in urine. ECG: low voltage and peaked T waves (hyperkalemia). CT and MRI: localize tumors or identify adrenal calcifications

Corticosteroid Therapy

Cortisol, related glucocorticoids, used to relieve the s/s associated with many diseases. Long term administration: therapeutic doses leads to serious complications and side effects. Not recommended for minor conditions. Risk of death or permanent loss of function, or short term therapy likely to produce remission or recovery.

Adrenocortical Insufficiency Clinical Manifestations

Does not become apparent until 90% adrenal cortex is destroyed. Insidious onset: progressive weakness, fatigue, weight loss, and anorexia. Skin hyperpigmentation, primarily in sun exposed area, pressure points, over joints, in creases (especially palmar). Orthostatic hypotension, hyponatremia, salt craving, hyperkalemia, nausea and vomiting, and diarrhea. Irritability and depression with primary. Secondary: a lot of symptoms similar to Addison's, not hyperpigmented

Acromegaly Clinical Manifestations

Enlargement of hands and feet. Changes in physical appearance occur, with thickening and enlargement of bony and soft tissues on the face and head. Enlargement of tongue (speech difficulties), hypertrophy of vocal cords (voice deepens). Sleep apnea (upper airway narrowing- increased amounts of pharyngeal soft tissues). Skin: thick, leathery, oily. Peripheral neuropathy and proximal muscle weakness, menstrual disturbances. Can exert pressure on surrounding structures in brain (visual disturbances headache). Hyperglycemia. Manifestations of diabetes may occur (antagonizes insulin). Untreated: cardiac and respiratory diseases, DM, colorectal CA, atherosclerosis, cardiomegaly, LV hypertrophy, angina pectoris, HTN

Excess of Tropic Hormones

Excess of tropic hormones, overproduction of single anterior pituitary hormone usually produce syndrome related to hormone excess from target organ. Prolactinomas: prolactin-secreting adenomas most frequently occurring pituitary hormone. Women s/s with this tumor: galactorrhea, ovulatory dysfunction, menstrual dysfunction, decreased libido, hirsutism. Men: impotence, decreased libido/sperm density, headaches, visual problems. Drug therapy first line tx.

Hyperaldosteronism

Excessive aldosterone secretion. Main effects of aldosterone are sodium retention, and potassium and hydrogen ion excretion. Hallmark: HTN with hypokalemic alkalosis. Primary hyperaldosteronism (PA): small, solitary adrenocortical adenoma. 30-50 yo. Secondary: nonadrenal cause of elevated aldosterone levels such as renal artery stenosis, renin-secreting tumors, chronic kidney disease. Elevated aldosterone: sodium retention and elimination of potassium. Leads to hypernatremia, hypertension, headache. Edema not common. Potassium wasting: hypokalemia: generalized muscle weakness, fatigue, cardiac dysrhythmias, glucose intolerance, metabolic alkalosis may lead to tetany. PA: elevated plasma aldosterone levels, elevated sodium levels, decreased serum K+ levels, decreased plasma renin activity. CT/MRI: adenomas.

Hyperthyroidism Etiology and Pathophysiology

Grave's Disease: autoimmune disease of unknown etiology marked by diffuse thyroid enlargement and excessive thyroid secretion. Insufficient iodine supply, infection, and stressful life events may interact with genetic factors to cause Grave's. 75% of hyperthyroidism. Antibodies to TSH receptor. Stimulate gland to release T3, T4 or both: clinical manifestations associated with thyrotoxicosis. May destruct thyroid tissue causing hypothyroidism. Toxic Nodular Goiters: thyroid-secreting nodules that function independent of TSH stimulation. Multiple: multinodular goiter or single: solitary autonomous nodule.

Complications with Corticosteroid Therapy

HTN. Reactivation of latent tuberculosis, reduces resistance to other infections and CAs. Inhibit antibody response to vaccines. Side effects: hypokalemia, PUD risk, skeletal muscle atrophy and weakness, mood and behavior changes may be observed, glucose intolerance predisposes to DM, fat from extremities redistributed to trunk and face, hypocalcemia related to anti-vitamin D effect may occur, healing delayed, increased wound dehiscence, susceptibility to infection increased, suppression of ACTH synthesis, corticosteroid deficiency likely if hormones withdrawn abruptly, increased BP (predisposed to HF), protein depletion decreases bone formation, density and strength, predisposition to pathologic pathologic fxs

Hyperthyroidism

Hyperactivity of thyroid gland with sustained increase in synthesis and release of thyroid hormones. Thyrotoxicosis: physiologic effects or clinical syndrome of hypermetabolism that results from excess of T3, T4 or both. Hyperthyroidism, thyrotoxicosis occur together in Grave's. Women more than men, 20-40 most frequent. Most common form is Grave's disease. Other causes: toxic nodular goiter, thyroiditis, excess iodine intake, pituitary tumors, thyroid cancer

Hypopituitarism

Hypofunction in pituitary gland. Decrease in one or more pituitary hormones. Anterior: ACTH, GH, TSH, FSH, LH, prolactin. Posterior: ADH, oxytocin. Selective hypopituitarism: only one hormone deficiency. Total failure of pituitary gland: deficiency of all, panhypopituitarism. Most common hormone deficiencies: GH, LH, FSH

Adrenocortical Insufficiency Etiology and Pathophysiology (Addison's)

Hypofunction of adrenal cortex. Primary: Addison's disease or secondary: lack of pituitary ACTH secretion. All 3 classes of adrenal corticosteroids reduced. Secondary: corticosteroids and androgens deficient but mineralocorticoids rarely are. ACTH deficiency: pituitary disease or suppression of hypothalamic-pituitary axis as result of exogenous corticosteroids. Most common: autoimmune response. Addison's: considered component of polyendocrine deficiency syndrome. Tuberculosis causes Addison's worldwide. Infarction, fungal infections, AIDS, metastatic cancer. Iatrogenic: adrenal hemorrhage (anticoagulant therapy, antineoplastic chemo, Nizoral therapy for AIDS, bilateral adrenalectomy). Younger than 60.

Diagnostic Studies DI

Identification of cause. Primary: overhydration, hypervolemia, rather than dehydration and hypovolemia. Water restriction test for central DI. Obtain baseline weight, pulse, urine and plasma osmolalities, urine specific gravity, BP. Withhold fluids 8-16 hrs before test. Observe for craving to drink. Assess BP, weight, urine osmolality hourly. Continues until osmolality stabilizes, or body weight declines by 3%, or orthostatic hypotension. Central DI: urine osmolality after vasopressin exceeds 9%. Nephrogenic DI: no response.

Hypoparathyroidism

Inadequate circulating PTH, uncommon. Hypocalcemia resulting from lack of PTH to maintain serum calcium levels. PTH resistance at cellular level: pseudohypoparathyroidism, caused by genetic defect resulting in hypocalcemia in spite of normal or high PTH levels (associated often with hypothyroidism and hypogonadism). Most common: iatrogenic. Accidental removal of parathyroid glands or damage to vascular supply of glands during neck surgery. Idiopathic: absence, fatty replacement, atrophy of glands rare (antiparathyroid antibodies). Severe hypomagnesemia. Clinical features due to hypocalcemia. Sudden decreases: tetany, tingling of lips and extremities stiffness. Tonic spasms of smooth and skeletal muscles can cause dysphagia, constricted feeling in throat, and laryngospasms that compromise breathing. Decreased serum calcium/PTH levels, increased serum phosphate levels. Other causes: chronic kidney disease, vitamin d deficiency, hypomagnesemia

Hypopituitarism Clinical Manifestations/Diagnostics

Manifestations related to hyposecretion of target glands and/or growing pituitary tumor. Common symptoms of tumor: headaches, visual changes, anosmia (loss of smell), seizures GH deficiency: subtle nonspecific clinical findings: truncal obesity, decreased muscle mass causing reduced strength, decreased energy, reduced exercise capability. Flat affect, depressed. FSH and LH deficiencies: women: menstrual irregularities, diminished libido, changes in secondary sex characteristics. Men: experience testicular atrophy, diminished spermatogenesis, loss of libido, impotence, and decreased facial hair and muscle mass. Deficiency of ACTH and cortisol: nonspecific clinical picture. Weakness, fatigue, headache, dry and pale skin, and diminished axillary and pubic hair. Postural hypotension, fasting hypoglycemia, diminished tolerance to stress, poor resistance to infection Thyroid hormone: cold intolerance, constipation, fatigue, lethargy, weight gain. MRI, CT (tumor), direct measurement of pituitary hormones

Diagnostic Studies Hypothyroidism

Most common: TSH and free T4. Serum TSH: helps determine cause. High: defect in thyroid. Low: defect in pituitary or hypothalamus. Increase in TSH after TRH injection: hypothalmic dysfunction, no change pituitary. Thyroid peroxidase antibodies: autoimmune problem. Elevated cholesterol and triglycerides, anemia, and increased creatine kinase.

Hypothyroidism Complications

Notable impairment of consciousness or coma. Myxedema coma: medical emergency. Subnormal temp, hypotension, hypoventilation, IV thyroid hormone replacement

Acromegaly Etiology and Pathophysiology

OVERPRODUCTION of growth hormone. Causes: benign pituitary tumor (adenoma), leading to overgrowth of bones and soft tissues. Acromegaly in adults (after epiphyseal closure). Children: gigantism.

Hyperparathyroidism Diagnostic Studies

PTH levels elevated, serum calcium levels exceed 10 mg/dL, serum phosphorus less than 3 mg/dL, elevations in urine calcium, serum chloride, uric acid, creatinine, amylase (if pancreatitis), alkaline phosphatase (presence of bone disease). Bone loss on dual-energy x-ray absorptiometry (DEXA) scan should be tested hypercalcemia, MRI, CT, ultrasound to localize adenoma

Cushing Diagnostic Studies

Plasma cortisol (primary glucocorticoid) levels may be elevated with loss of diurnal variation. 24 hour urine collection for free cortisol done. Normal cortisol (80-120 mcg) in 24 hours indicate disease. If borderline: low-dose dexamethasone suppression test done. False positives: pts with depression and on certain meds (Dilantin and rifampin). Urine levels of 17-ketosteroids may be elevated. CT and MRI of pituitary adrenal glands. Plasma ACTH: low, normal, or elevated. High or normal: cushing, low: adrenal or medication etiology.

Clinical Manifestations of DI

Polydipsia and polyuria. PRIMARY CHARACTERISTIC: excretion of large quantity of urine with low specific gravity (less than 1.005), urine osmolality of less than 100 mmol/kg. Serum osmolality elevated (greater than 295 mOsm/kg) as result of hypernatremia due to pure water loss in kidneys. Compensate by drinking great amounts of water so serum osmolality is normal or moderately elevated. Fatigue from nocturia, weakness. Central: acute, excessive fluid loss. After intracranial surgery: three phases: abrupt onset of polyuria, volume normalizes, central DI permanent. Cranial surgery DI more permanent than head injury. Onset and fluid losses of nephrogenic less than central. Severe fluid volume deficit. Weight loss, constipation, poor skin turgor, hypotension, tachy, shock. CNS manifestations: irritability to dullness to coma (increasing serum osmolality and hypernatremia). polyuria: severe dehydration, hypovolemic shock.

Hyperthyroidism Diagnostic Studies

Primary findings: decreased TSH, elevated T4 (free serum T4). RAIU test: differentiate Grave's from other forms. Grave's: diffuse, homogenous uptake 35-90%, thyroiditis: less than 2%. Nodular goiter: uptake in normal range. Thyroid antibodies, opthalmologic examination, ECG.

Clinical Manifestations/Diagnosis of SIADH

Reabsorption of water into circulation from kidneys. EC fluid volume expands, plasma osmolality declines, GFR increases, and sodium levels decline (dilutional hyponatremia). Hyponatremia: muscle cramping, pain, weakness. Thirst, dyspnea on exertion, fatigue. Low urinary output, increased body weight. Manifestations more severe as sodium falls further: vomiting, abdominal cramps, muscle twitching, seizures. Plasma osmolality, sodium continue to fall: cerebral edema (lethargy, anorexia, confusion, headache, seizures, coma). Diagnosis: measure of urine and serum osmolality. Sodium less than 134, serum osmolality less than 280 mOsm/kg, urine specific gravity greater than 1.005. Serum osmolality much lower than urine osmolality

Hyperthyroidism Clinical Manifestations

Related to effect of excess thyroid hormone, directly increases metabolism. Increases tissue sensitivity to stimulation of SNS. Goiter with bruit, ophthalmopathy (abnormal eye appearance or function), Grave's: exophthalmos which is protrusion of eyeballs from orbits, due to impaired venous drainage from orbit, causes edema. Increased pressure forces eyeballs outward. Multisystem responses. Common in younger adult (Grave's): nervousness, irritability, weight loss, heat intolerance, warm, moist skin, tachycardia and palpitations w/o HF. Older adult: Grave's or toxic nodular goiter. Anorexia, weight loss, apathy, lassitude, depression, confusion, exophthalmos less common, angina, dysrhythmia (esp A fib), HF

Cushing Syndrome Clinical Manifestations

Related to excess levels of corticosteroids. Pronounced changes in physical appearance. Weight gain most common, results in accumulation of adipose tissue in trunk, face, cervical spine area. Transient weight gain from sodium and water retention may be present because of mineralocorticoid effects of cortisol. Hyperglycemia because of glucose intolerance and increased gluconeogenesis by liver. Protein wasting: caused by catabolic effects of cortisol on peripheral tissue. Muscle weakness. Osteoporosis (pathologic fxs), bone and back pain, loss of collagen: skin weaker and thinner, wound healing delayed, mood disturbances, insomnia, irrationality, psychosis. Mineralocorticoid excess may cause hypertension (secondary to fluid retention), adrenal androgen: severe acne, virilization in women, feminization in men. Menstrual disorders and hirsutism in women and gynecomastia and impotence in men (adrenal carcinomas).

Hypothyroidism Etiology and Pathophysiology

Results from insufficient circulating thyroid hormone. Primary: destruction of thyroid tissue or defective hormone synthesis. Secondary: related to pituitary disease with decreased TSH secretion or hypothalamic dysfunction with decreased thyrotropin-releasing (TRH). Transient related to thyroiditis or discontinuance of thyroid hormone therapy. US: primary is atrophy of thyroid gland. End result of Hashimoto's thyroiditis and Grave's disease (autoimmune diseases), tx of hyperthyroidism specifically surgical removal of thyroid gland or RAI therapy. Drugs: amiodarone, lithium.

Adrenocortical Insufficiency complications

Risk for adrenal insufficiency (addisonian crisis), life-threatening emergency cause by insufficient adrenocortical hormones or sudden sharp decrease in hormones. Triggered by stress (physical or psychological), sudden withdrawal of corticosteroid hormone replacement therapy, after adrenal surgery, following sudden pituitary gland destruction. Severe manifestations of glucocorticoid and mineralocorticoid deficiencies are exhibited: hypotension, tachy, dehydration, hyponatremia, hyperkalemia, hypoglycemia, fever, weakness, confusion. Hypotension may lead to shock.

Cushing Syndrome Etiology and Pathophysiology

Spectrum of clinical abnormalities caused by excess of corticosteroids, particularly glucocorticoids. Causes: prolonged administration of high doses of corticosteroids, ACTH-secreting pituitary tumor, cortisol-secreting neoplasm within adrenal cortex that can be either carcinoma or adenoma, excess secretion of ACTH from carcinoma of lung or other malignant growth outside pituitary or adrenal glands. Most common: iatrogenic administration of exogenous corticosteroids like prednisone. Endogenous: mostly due to ACTH-secreting pituitary tumor.

Complications of Hyperthyroidism

Thyrotoxic crisis aka thyroid storm: acute, rare condition in which all hyperthyroid manifestations are heightened. Life-threatening emergency, but rarely causes death with tx. Thought to be result of stressors (infection, trauma, surgery) in pt with preexisting hyperthyroidism. Heart, nerve tissues become more sensitive to sympathetic nervous system activation. Tachycardia, HF, shock, hyperthermia, restlessness, agitation, seizures, abdominal pain, nausea, vomiting, diarrhea, delirium, coma. Tx: reduce circulating thyroid hormone levels, clinical manifestations of disorder by appropriate drug therapy.

Pheochromocytoma

Tumor of the adrenal medulla produces excessive catecholamines (epinephrine, norepinephrine). Severe hypertension. May lead to hypertensive encephalopathy, DM, cardiomyopathy, death. Severe pounding headache, tachy with palpitations, profuse sweating, unexplained abdominal or chest pain. Provoked by many meds: antihypertensives, opioids, radiologic contrast media, TCAs. Diagnosis often missed. Uncommon cause of HTN, consider in pts who do not respond to typical HTN txs. Measurement of urinary fractionated metanephrines (catecholamine metabolites), fractionated catecholamines and creatinine, usually as 24 hour urine collection (simple most reliable test). Values elevated. Serum catecholamines may be elevated during an attack. CT/MRI for tumor localization

Hypopituitarism Etiology and Pathophysiology

Usual cause is pituitary tumor. Autoimmune disorders, infections, pituitary infarction (Sheehan syndrome), or destruction of pituitary gland (trauma, radiation, surgical procedures). Sheehan syndrome: postpartum condition of pituitary necrosis and hypopituitarism that occurs after circulatory collapse from uterine hemorrhaging. Anterior pituitary hormone deficiencies: end-organ failure.