Endocrine Disorders Etiology of Endocrine Disorders • Hyposecretion or hypersecretion can occur in the: – Hypothalamus/pituitary – Hormone-producing gland – Target tissue • Etiology can be: – Congenital – Infectious – Autoimmune – Neoplastic – Idiopathic – Iatrogenic
Elevated or Depressed Hormone Levels• Failure of feedback systems• Dysfunction of an endocrine gland• Secretory cells are unable to produce, obtain, or convert hormone precursors• The endocrine gland synthesizes or releases excessive amounts of hormone or not enough hormone• Increased hormone degradation or inactivation• Ectopic hormone release• Target cell failure
Endocrine Disorders: Classification • Endocrine disorders involving control by anterior pituitary gland are classified as: – Primary: intrinsic malfunction of the hormone-producing target gland – Secondary: malfunction of the hypothalamus/pituitary cells that control the hormone-producing target gland
Alterations of theHypothalamic-Pituitary System
Diseases of the Anterior Pituitary• Hypersecretion of growth hormone (GH) – Acromegaly • Hypersecretion of GH during adulthood • (cause: GH-secreting pituitary adenoma) – Gigantism • Hypersecretion of GH in children & adolescents
Diseases of the Anterior Pituitary Giantism: Hypersecretion of growth hormone (GH)(excess somatotropin [GH] BEFORE epiphyseal closure)
Diseases of the Anterior Pituitary • Acromgaly: Hypersecretion of growth hormone (GH)(excess somatotropin [GH] AFTER epiphysealclosure)
Hypothyroidism • CONGENITAL HYPOTHYROIDISM (cretinism) is typically due to thyroid dysgenesis • Majority are PRIMARY, due to intrinsic dysfunction of the thyroid gland • PRIMARILY LYMPHOCYTIC THYROIDITIS (Hashimoto or autoimmune thyroiditis) Acquired • Irradiation of the thyroid gland • Surgical removal of thyroid tissue • Iodine deficiency
Cretinism Congential hypothyroidism: can be endemic (iodine deficiency), genetic, or sporadicDelayed bone maturation, puberty, mentalretardation, abdominal protrusion with umbilical hernia
A 3-month-old male was diagnosed withcongenital hypothyroidism. If left untreated, thechild would have:A. mental retardation and stunted growth.B. increased risk of childhood thyroid cancer.C. hyperactivity and attention deficit disorder.D. liver, kidney, and pancreas failure.
ETIOLOGY AND PATHOGENESIS:Hypothyroidism: Primary Hypothyroidism • Iodine is essential for T3 and T4 synthesis • Deficiency in iodine leads to lack of T3/T4 but does not affect thyroglobulin levels • Insufficient hormone available to inhibit secretion of TSH • Increased TSH causes thyroid cells to secrete large amounts of thyroglobulin, which leads to a goiter
Many vegetables are goiterogens
ETIOLOGY AND PATHOGENESIS:Hypothyroidism: Secondary hypothyroidism is caused by defects in TSH production and can result from: • Severe head trauma • Cranial neoplasms • Brain infections • Cranial irradiation • Neurosurgical procedures
Hashimoto’s thyroiditis• Chronic lymphocytic thyroiditis• Infiltration by lymphocytes• Destruction of thyroid by antibodies• Goiter formation is common• Can occur with other autoimmune diseases: Type 1 DM, vitiligo
CLINICAL FEATURES of Hashimoto’s Thyroiditis• Onset of disease – 30-60 years of age• 5 times more common in females than males• Patients have T4 and TSH• Patients have enlarged thyroid (goiter)• Symptoms include: – Dry skin, tiredness, weight gain, puffy face, intolerance to cold, mild depression• Treatment – thyroid hormone replacement
Hypothyroidism: characteristic sign of long-standing disease
Myxedema• Severe or prolonged thyroid deficiency• Accumulation of glycosaminoglycans in interstitial spaces Myxedema (coma) • Sluggishness • Cool skin, ↑cholest erol
DIAGNOSIS: Hypothyroidism • Primary hypothyroidism will manifest as elevated TSH • Low levels of T3 and T4 may not occur until later in the disease course • Hypothalamic-pituitary dysfunction results in low levels of TSH and T4
TREATMENT: Hypothyroidism: • Treatment goal is return of euthyroid state • Oral levothyroxine is used to replace or supplement hormone production • Resolution of symptoms occurs over weeks • Intravenous levothyroxine used for myxedema coma
Hyperthyroidism • Primary—autonomous • Secondary—mediated through stimulation of TSH receptors by substances such as TSH • Autoimmune—related to TSH receptor antibodies
ETIOLOGY AND PATHOGENESIS: Hyperthyroidism What causes Hyperthyroidism? • Pituitary adenoma • Thyroid carcinoma • Autoantibodies that bind and stimulate TSH receptors on the thyroid gland leading to a diffuse toxic goiter (Graves disease) • Ingestion of thyroid hormone preparations or excessive iodides
CLINICAL MANIFESTATIONS: Hyperthyroidism • Changes in behavior, insomnia, restlessness, tremor, irritability, p alpitations, heat intolerance, diaphoresis, inability to concentrate that interferes with work performance • Increased basal metabolic rate leads to weight loss, although appetite and dietary intake increase • Amenorrhea/scant menses
Graves Disease: autoimmune most common form of hyerpthyroidismEdema of orbit, exopthalmos, extrocular muscle weakness
Clinical Features of Graves’ Disease• Onset of disease – 20-50 years of age• 10 times more common in females than males• Patients have goiter with thyroid gland 2-3 times normal size• Symptoms include: – Nervousness, fatigue, weight loss; 50% have thyroid- associated ophthalmopathy with eyelid retraction and periorbital edema• Treatment – anti-thyroid drugs, surgery, and radioactive iodine ablation
Graves’ Disease: Diagnosis• Diagnosis often made on clinical symptoms alone• Elevated T3 and T4; low TSH – Why?
Comparison of Graves’ disease and Hashimoto’s thyroiditis HYPOHYPER
A 35-year-old female with Graves disease is admitted to a medical-surgical unit. Lab tests would most likely reveal:A. high levels of circulating thyroid-stimulatingantibodies.B. ectopic secretion of thyroid-stimulatinghormone (TSH).C. low circulating levels of thyroid hormones.D. stimulation of thyroid-binding globulin.
CLINICAL MANIFESTATIONS: Hyperthyroidism Thyroid storm—form of life-threatening thyrotoxicosis that occurs when excessive amounts of thyroid hormones are acutely released into circulation • Manifestations – Elevated temperatures, tachycardia, arrhythmias – Extreme restlessness, agitation, and psychosis – Vomiting, nausea, diarrhea, and jaundice
DIAGNOSIS: Hyperthyroidism: DIAGNOSIS Primary hyperthyroidism will manifest as: • Undetectable TSH levels • Elevated serum T4 and T3 TREATMENTS: • Symptomatic relief: Beta blockers • Reduce circulating hormones: methimazole, propylthioricil • More permanent treatment: surgical removal of thyroid, radioactive iodine
TREATMENT: Hyperthyroidism Treatment of thyroid storm • Aggressive management to achieve metabolic balance • Antithyroid drugs are given followed by iodine administration • Beta-blockers to alleviate symptoms • Antipyretic therapy • Fluid replacement • Glucocorticoids
Alterations of Thyroid Function: Table 40.2 Hypothyroidism Hyperthyroidism Basal metabolic rate Sympathetic ANS Weight Temp tolerance GI function Cardio/Respiratory function Reproductive Muscle tone Appearance General behavior
o By the time of the missile crisis, Kennedy was taking antispasmodics to control colitis; antibiotics for a urinary tract infection; and increased amounts of hydrocortisone and testosterone, along with salt tablets, to control his adrenal insufficiency and boost his energy.
Adrenocortical Insufficiency • SECONDARY: Hypothalamic-Pituitary Dysfunction – usually iatrogenic, related to corticosteroid therapy, which suppresses ACTH, CRH – May also occur due to damage of the anterior pituitary or hypothalamus by tumors, infection, radiation, postpartum necrosis, trauma, or surgery
Adrenocortical Insufficiency Addisonian crisis/acute adrenal insufficiency • Life-threatening condition caused by inadequate levels of glucocorticoids and mineralocorticoids in circulation • May occur with acute withdrawal of corticosteroids or due to periods of stress or trauma
Adrenocortical Insufficiency Clinical manifestations • Early signs include: – anorexia, – weight loss – weakness – malaise – apathy – electrolyte disturbances – hyperpigmentation of skin • Diminished vascular tone, reduced cardiac output, inadequate circulating blood volume; can lead to cardiovascular collapse
Adrenocortical Insufficiency Diagnosis • Patient history and physical exam, decreased plasma cortisol levels • ACTH provocation test may be administered • Abdominal CT/MRI may be performed to evaluate the size of the adrenal glands Treatment • Replacing the absent or deficient hormones in a manner that mimics natural production • 2/3 of the daily dosage is given in the morning and 1/3 in the evening • Treatment of adrenal crisis – Intravenous glucocorticoids
Alterations of Adrenal FunctionDisorders of the adrenalcortex: HYPERCORTISOLISM – Cushing disease • Excessive ANTERIOR PITUITARY secretion of ACTH – Cushing syndrome • Excessive level of cortisol, regardless of cause
Hypercortisolism: Etiology and Pathogenesis • PRIMARY adrenocortical hyperfunction due to disease of the adrenal cortex (adrenal adenoma) • SECONDARY disease caused by hyperfunction of the anterior pituitary ACTH-secreting cells • TERTIARY disease caused by hypothalamic dysfunction or injury • EXOGENOUS STEROID use is the most common cause of Cushing syndrome in the United States
Causes of ACTHCushing’s Syndrome Most common cause
Cushing’s Syndrome Redistribution of adipose: Truncal obesity, moon face, buffalo hump Protein wasting: limb muscles Loss of collagen: thin skin, striae, bruising
Cushing Syndrome: Clinical Manifestations STRIAE BUFFALO HUMP MOON FACE
Cushing Syndrome: Clinical Manifestations Clinical manifestations: • Round face with flushed cheeks, “moon face” • Weight gain with excess total body fat, particularly in the abdomen • Cervical fat pad, capillary friability, thin skin with formation of purple striae and ecchymosis over the abdomen, arms and thighs • Decreased muscle mass, muscle weakness • Glucose intolerance, hyperglycemia • Hypertension • Demineralization of bone (osteoporosis) • Increased androgen production causing excessive hair production, acne, menstrual irregularities • Emotional changes
Characteristic physical features of individualswith Cushing syndrome include:A. weight loss and muscle wasting.B. truncal obesity and thin skin.C. pallor and swollen tongue.D. depigmented skin and eyelid lag.
Cushing Syndrome: Treatment Treatment is based on etiology • Exogenous dose reduction • Pituitary adenomas are treated surgically with transsphenoidal hypophysectomy, laser ablation, or radiation • Adrenal tumor is treated with unilateral adrenalectomy • Chemotherapeutic agents block cortisol production
Hyperaldosteronism: • Primary (Conn syndrome)—usually due to aldosterone-secreting tumors • Secondary—typically associated with poor kidney perfusion that stimulates the renin-angiotensin- aldosterone cascade (heart failure, reduced kidney perfusion, liver cirrhosis)
Hyperaldosteronism: • Aldosterone facilitates salt and water retention by the kidney with resultant potassium excretion • Typically low potassium level • Treatment includes spironolactone to increase sodium excretion and potassium retention • Sodium restriction and potassium replacement may also be necessary
Adrenal Medulla Disorders
PheochromocytomaEtiology and PathogenesisAdrenal medulla hyperfunction • Caused by tumors derived from the chromaffin cells of the adrenal medulla – Pheochromocytomas • Secrete catecholamines on a continuous or episodic basis
Pheochromocytoma: Clinical Manifestations
Pheochromocytoma: Diagnosis and Treatment • Diagnosed with abdominal CT/MRI • Treatment includes sympathetic blocking medications to manage blood pressure and surgical removal of the tumor • If surgery is contraindicated, medication to block catecholamine production is possible but surgery is the only curative therapy
Parathyroid Gland Disorders
Parathyroid Gland What does PTH do? • Increases serum calcium & decrease serum phosphate 1. Increase bone reabsorption of calcium 2. Increase kidney reabsorption of calcium 3. Decrease kidney reabsorption of phosphate 4. Increase Vitamin D production in kidneyParathyroid glandslocated at the upperand lower poles ofthe thyroid
Regulation of Calcium level
Regulation of Calcium level osteoblasts osteoclasts
Regulation of Blood CalciumPTH Calcitonin• Serum calcium levels provide the • Calcitonin produced by thyroid feedback to regulate parathyroid parafollicular cells also hormone (PTH) secretion influences the processing of• Decrease in calcium causes PTH calcium by bone cells release • Calcitonin controls calcium• Elevated calcium levels lead to suppression of PTH secretion content of blood by increasing bone formation by osteoblasts• PTH acts on bones, intestine, and and inhibiting bone renal tubules to increase calcium levels breakdown by osteoclasts• In bone, PTH increases osteoclastic • Calcitonin decreases blood activity calcium levels and promotes• PTH increases renal calcium conservation of hard bone reabsorption matrix
Parathyroid Disorders Hyperparathyroidism: PTH, Ca+2, Phosphorous (1) Primary hyperparathyroidism: • PTH, Ca+2, Phosphorous • Causes demineralization, extensive resorption • Hypercalcemia mostly affect the nervous system and kidney (2) Secondary hyperparathyroidism: secondary to conditions that cause chronic hypercalcemia of nonparathyroid cause: major causes: • Vitamin D-metabolite deficiencies • High phosphorus load
Hyperparathyroidism Clinical manifestations • Kidney stones • Bone demineralization (osteoporosis) • Polyuria and dehydration • Anorexia, nausea, vomiting, constipation • Bradycardia, heart block, and cardiac arrest
Hyperparathyroidism Treatment • Surgical removal of parathyroid gland • Medical management includes hydration and ambulation to maintain bone density • For hypercalcemic crisis, rapid volume expansion with 0.9% NS to treat dehydration and improve glomerular filtration rate; diuretics to increase calcium excretion by the kidneys
A problem associated with chronichyperparathyroidism is:A. seizure disorder.B. vitamin D malabsorption.C. hyponatremia.D. osteoporosis and pathologic fractures.
Alterations of Parathyroid Function:HYPOPARATHYROIDISM– Abnormally low PTH levels– Usually caused by parathyroid damage in thyroid surgery
Parathyroid DisordersHypoparathyroidism: PTH, Ca+2, Phosphorous(1) Primary hypoparathyroidism: a) Idiopathic hypoparathyroidism * hormone-deficient hypoparathyroidism * PTH b) Pseudohypoparathyroidism * hormone-sufficient, receptor-deficient hypoparathyroidism * PTH(2) Secondary hypoparathyroidism: result from other disorders.
HYPOPARATHYROIDISM Etiology • Parathyroid or thyroid surgery or surgery in the area of these glands; may be temporary or permanent • Permanent hypothyroidism can develop after thyroidectomy due to damage to parathyroid gland blood supply, postsurgical swelling, or fibrosis • Congenital lack of parathyroid tissue and idiopathic hypoparathyroidism are causes of hypoparathyroidism in children and infants • Autoimmune processes may target and damage the parathyroid glands
What happens to serum calcium? Causes lowered threshold for nerve and muscle excitationClinical manifestations• Circumoral numbness, paresthesias of the distal extremities, muscle cramps, fatigue, hyperirritability, anxiety, depression, ECG changes, increases in intracranial pressure• Severe symptoms include carpopedal spasm, laryngospasm, and seizures
Hypoparathyroidism Treatment • Acute hypocalcemic crisis (tetany, laryngospasm, and convulsions)—parenteral calcium administration and calcitriol, an activated form of vitamin D • Long-term treatment: oral calcium supplement with vitamin D
Antidiuretic Hormone (ADH) Disorders
Antidiuretic Hormone • ADH (vasopressin) secreted by the posterior pituitary gland in response to changes in blood osmolality • ADH acts directly on the renal collecting ducts and distal tubules, increasing membrane permeability to and reabsorption of water The single most important effect of antidiuretic hormone is to conserve body water by reducing the loss of water in urine
DIABETES INSIPIDUS: Antidiuretic HormoneDisorders: • Etiology and pathogenesis – Disorder of INSUFFICIENT ADH activity resulting in excessive loss of water in urine – DAMAGE to ADH-producing cells in the hypothalamus can result from: • Traumatic brain injury • Intracranial tumors • Neurosurgical procedures – Some pharmacologic agents can lead to abnormalities in ADH secretion
DIABETES INSIPIDUS: Antidiuretic HormoneDisorders • Central diabetes insipidus is due to the inability to produce and release ADH from the pituitary gland • Nephrogenic diabetes insipidus results from the INABILITY of the kidneys to respond to ADH due to chronic renal disease, serum electrolyte abnormalities, or drugs
SIADH: Antidiuretic Hormone Disorders Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Etiology • EXCESSIVE ADH from ectopic production due to several types of tumors, notably primary lung malignancies • Pulmonary tuberculosis • Drug-induced ADH secretion can occur
SIADH: Antidiuretic Hormone DisordersREMEMBERWhat does Aldosterone do?
Clinical ManifestationsDiabetes Insipidus SIADH• Polyuria, polydipsia • Hyponatremia• Low urine specific gravity • High urine osmolality• Hypernatremia due to water • Low serum osmolality • Cell swelling deficit • Weakness, muscle• Dry mucous membranes, poor cramps, postural BP skin turgor, decreased saliva changes, poor skin and sweat production turgor, fatigue, anorexia, lethargy• Disorientation, lethargy, seizur • Confusion, seizures, coma es
TreatmentDiabetes Insipidus SIADH• Daily replacement of ADH • Free water restriction with desmopressin (DDAVP) • If severe symptoms, IV• Free access to fluids administration of saline with diuretics is used• Home testing of urine • Hyponatremia should be specific gravity corrected slowly to avoid rapid changes in brain cell volume
The most common cause of elevated levels of antidiuretic hormone (ADH) secretion is:A. autoimmune disease.B. cancer.C. pregnancy.D. heart failure.
A 54-year-old patient with pulmonary tuberculosis (lung infection) is evaluated for syndrome of inappropriate ADH secretion (SIADH). Which of the following electrolyte imbalances would be expected in this patient?A. HyponatremiaB. HyperkalemiaC. HypernatremiaD. Hypokalemia