Summary MSN 629 Exam II (Endocrine and Cardiovascular) Complete Solution Guide_ Updated 2025.

1 Exam II (Endocrine, Cardiovascular) Hormone Response  Released in response to an alteration in the cellular environment, or in response to maintaining certain level of substance or other hormones.  Regulated by chemical, hormonal, or neural factors.  Uses a feedback loop (mostly negative). o Allows for narrow range of parameter, allowing for an internal adjustment.  Positive feedback loop increases the synthesis and secretion of a hormone.  Negative feedback loop decreases the synthesis and secretion of a hormone. Water Soluble vs Lipid Soluble Hormones  Water: Brief response, binds to surface receptor. o Epinephrine, Norepinephrine, Growth Hormone, Insulin, Glucagon, PTH, Prolactin, FSH, LH, TSH, ACTH, ADH, Calcitonin, Endorphins, MSH, Oxytocin, Somatostatin o Must bind to receptor, then signaled to activate enzyme to carry out action within cell.  Lipid: rapid and long-lasting response, steroid crosses plasma membrane and creates instant process. Detach from carrier in blood to cross membrane. o Estrogens, Steroids, Thyroxine, Corticoids, Leukotrienes, Prostaglandins Endocrine System Overview  Various glands throughout the body.  Synthesize messengers called hormones.  Works in conjunction with the nervous and immune system to respond to changes in the internal and external environment.  Five general functions: o Differentiation of the reproductive and CNS o Stimulation of sequential growth and development o Coordination of male and female reproduction o Homeostasis maintenance o Respond to emergencies in a corrective and adaptive way. Hormones General characteristics:  Specific rates and rhythms of secretions o Diurnal (twice a day), pulsatile (within a range), cyclic, and patterns that depend on levels of circulating substances.  Operate within a feedback system (mostly negative)  Affect only target cells with specific receptors for the hormone.  Steroid hormones (lipid soluble) are excreted by the kidneys or metabolized by the liver, inactivating them, and rendering them water soluble for excretion by kidneys. Hormone Transportation and Action  An equilibrium between the concentrations of free hormones (not bound to a carrier protein) and bound hormones, a significant change in the concentration of carrier proteins can affect the concentration of free hormones in the plasma. o Malnutrition and liver disease decrease albumin, causing a decrease in the lipid-soluble hormones thyroxine, cortisol, and aldosterone.  Up-regulation: when a low concentration of hormones occurs, the cell increases the number of receptors to catch the hormone.  Down-regulation: when a high concentration for hormones occurs, the cell decreases the number of receptors on the cell to “inhibit catching”.  Direct effects: directly cause an action to the cell.  Permissive effects: enable 2nd hormone to complete the job.2 Exam II (Endocrine, Cardiovascular) Hormone Receptors  Water soluble: the hormone is the first messenger. Initiates a signal that generates a small molecule in the cell, called the second messenger. o High molecular weight o Cannot diffuse across the plasma membrane.  Second messenger conveys the signal from the receptor to the cytoplasm and mediates the effect of the hormone on the target cell. o Cyclic adenosine monophosphate (cAMP), cycle guanosine monophosphate (cGMP), calcium, inositol triphosphate (IP3), tyrosine kinase.  Located in the plasma membrane or in the intracellular compartment of the target cell.  Lipid-soluble hormones: o Easily diffuse cross the plasma membrane and bind to cytosolic or nuclear receptors. o Steroid hormones Hypothalamic-Pituitary  Forms the structural and functional basis for central integration of the neurologic and endocrine systems, creating the neuroendocrine system.  Hypothalamus is located at the base of the brain. Connected to the pituitary gland by the pituitary stalk.  Connected to the anterior pituitary through hypophysial portal blood vessels and to the posterior pituitary via never tract called the hypothalamohypophysial tract.  Contains neurosecretory cells that synthesize and secrete the hypothalamic-releasing hormones that regulate the release of hormones from the anterior pituitary.  Synthesize ADH and oxytocin, which are released from the posterior pituitary. Hormones of Anterior Pituitary F Adrenocorticotropic Hormone (ACTH) F Melanocyte-stimulating Hormone (MSH) F Somatotropic Hormones o Growth & Prolactin F Glycoprotein Hormones o Follicle-stimulating hormone, luteinizing hormone, thyroidstimulating hormone Pituitary Gland o Located in the sella turcic (saddle-shaped depression of the sphenoid bone at the base of the skull). o Anterior Pituitary (adenohypophysis) is composed of three regions. o Pars Distalis: major component, source of anterior pituitary hormones. o Pars tuberalis: thin layer of cells on the anterior and lateral portions of the stalk o Pars intermedia: lies between the two, secretes melanocyte-stimulating hormone in the fetus. o Two main cell types: chromophobes (nonsecretory) and chromophils (secretory) o Regulated by hypothalamic releasing factors, feedback signals, and direct effects of other neurotransmitters. o Secretes tropic hormones that affect physiologic function of specific target organs. Second Messenger Associated Hormones Cyclic AMP ACTH, LH, hCG, FSH, TSH, ADH, TRH, PTH, Glucagon Cyclic GMP Atrial natriuretic peptide Calcium and IP3 Angiotensin II, Gonadotropin releasing hormone, ADH, LHRH Tyrosine Kinases Insulin, growth hormone, leptin, prolactin3 Exam II (Endocrine, Cardiovascular) Pineal Gland  Located near center of the brain (epithalamus).  Secretes melatonin which regulates circadian rhythms and reproductive systems. Oxytocin  Responsible for contraction of the uterus and milk ejection in lactating women.  Secreted in response to suckling and mechanical distention of the female reproductive tract.  Binds to receptors on myoepithelial cells in the mammary tissues and causes contraction of those cells.  Acts on the uterus near the end of labor to enhance the effectiveness of contraction, promote delivery of the placenta, and stimulate postpartum uterine contractions, thereby preventing excessive bleeding. Antidiuretic Hormone  Major homeostatic function of the posterior pituitary is the control of plasma osmolality regulated with ADH.  ADH increases permeability of the distal renal tubules leading to increased water reabsorption into the blood, concentrating the urine and reducing serum osmolality.  Osmoreceptors of the hypothalamus.  No direct effect on electrolyte levels, but causes a dilutional effect from water resorption.  Also stimulated by decreased intravascular volume.  Stress, trauma, pain, exercise, nausea, nicotine, exposure to heat, and drugs such as morphine increase ADH secretion.  Decreases with decreased plasma osmolality, increased intravascular volume, hypertension, alcohol ingestion, and an increase in estrogen, progesterone, or angiotensin II levels. Posterior Pituitary  Neurohypophysis derived from the hypothalamus and is comprised of three parts. o Median eminence: composed largely of the nerve ending of axons from the ventral hypothalamus. Contains at least 10 biologically active hypothalamic releasing hormones, as well as neurotransmitters dopamine, norepinephrine, serotonin, acetylcholine, and histamine. o Pituitary Stalk: contains the axons of neurons that originate in the supraoptic and paraventricular nuclei of the hypothalamus and connects the pituitary gland to the brain. o Pars Nervosa: axons originating in the hypothalamus terminate here which secretes the hormones of the posterior pituitary.  Secretes two polypeptide hormones. Antidiuretic Hormone (vasopressin) and oxytocin. Thryoid Gland  Two lobes of the thyroid gland lie on either side of the trachea, inferior to the thyroid cartilage and joined by a small band of tissues (isthmus)  Pyramidal lobe is superior to the isthmus  Normal gland is not visible but can be palpated.  Consists of follicles surrounding a viscous substance called colloid.  Follicular cells synthesize and secrete thyroid hormones.  Parafollicular cells (C Cells) secrete calcitonin [used to treat bone disorders]  Thyrotropin-releasing hormone and thyroid-stimulating hormone  Neurotransmitters (acetylcholine, catecholamines) may directly affect secretory activity.  Thyroid hormone is regulated through a negative-feedback loop w/ hypothalamus, anterior pituitary, and thyroid gland.  Initiated with TRH, TRH then released into hypothalamic-pituitary portal system where makes its way to anterior pituitary to release TSH4 Exam II (Endocrine, Cardiovascular) Parathyroid Gland & Hormone  Two pairs of small parathyroid are present behind the upper and lower poles of the thyroid gland.  Produce parathyroid hormone which is the single most important factor in the regulation of serum calcium concentration.  Decrease in serum calcium stimulates PTH secretions, which increases serum calcium and decreases serum phosphate.  PTH acts directly on the bone to release calcium by stimulating osteoclast activity.  Also acts on kidney to increase calcium reabsorption while phosphate reabsorption is decreased.  Vitamin D3 is activated by the kidney and works as a cofactor with PTH to promote calcium and phosphate absorption in the gut and enhance bone mineralization.  Phosphate and magnesium concentrations also affect PTH secretion. Thyroid Hormone  Synthesis of hormone:  Uniodinated thyroglobulin is produced by endoplasmic reticulum of thyroid follicular cells.  Tyrosine is incorporated into the thyroglobulin  Iodine is actively transferred from the blood into the colloid, iodide trap  Iodide is oxidized and attaches to tyrosine  Coupling of iodinated tyrosine forms TH.  T3 is formed as well as T4, T3 more potent, body will convert T4 to T3.  TH stored attached to thyroglobulin until released.  90% T4, 10% T3  Affects growth and maturation of tissues, cell metabolism, heat production, and oxygen consumption. Endocrine Pancreas  Pancreas is both an endocrine and exocrine gland.  Houses the islets of Langerhans which has four types of hormone secreting cells: o Alpha cells – glucagon o Beta cells – insulin and amylin o Delta cells – gastrin and somatostatin o F cells – pancreatic polypeptide  Insulin – beta cells of the pancreas o Regulated by chemical, hormonal, and neural control. o Increase in blood glucose levels is primary stimulus. o Amino acids and gastrointestinal hormones also stimulus. o Diminishes in response to low levels of blood glucose, high levels of insulin, and sympathetic stimulation of beta cells in the islets. o Insulin sensitivity is affected by age, weight, abdominal fat, and physical activity. o Implicated in hypertension, heart disease, and type 2 diabetes. o Effective measure to improve insulin sensitivity is weight loss and exercise. o Anabolic hormone that promotes glucose uptake in the liver, muscle, and adipose tissue. o Increases synthesis of proteins, carbs, lipids, and nucleic acids. o Facilitates the intracellular transport of potassium, phosphate, and magnesium.  Amylin – peptide hormone co-secreted with insulin by beta cells in response to nutrient stimuli. Regulates blood glucose by delaying gastric emptying and suppressing glucagon secretion after meals5 Exam II (Endocrine, Cardiovascular) Adrenal Glands  Paired, pyramid-shaped organs behind the peritoneum and close to the upper pole of each kidney. Surrounded by a capsule, embedded in fat, and well supplied with blood from the aorta and phrenic and renal arteries.  Two separate portions – an outer cortex and inner medulla. o Adrenal Cortex: 80% adrenal gland’s weight  Zona glomerulosa: aldosterone completed here  Zona fasciculata: largest, cortisol, thinnest, closest to medulla.  Zona reticularis: aldosterone started here, androgens made here. o Adrenal Medulla  Innervated by the sympathetic nervous system  Chromaffin cells – Epinephrine  Stimulated by ACTH from pituitary.  Glucocorticoids o Steroid hormones that metabolic, neurologic, anti-inflammatory, and growth-suppressing effects. o Affect carbohydrate metabolism. o Increase blood glucose concentration by promoting gluconeogenesis in the liver and by decreasing uptake of glucose into muscle cells, adipose cells, and lymphatic cells. o Adaptive immunity is affected by a glucocorticoid-mediate inhibitory effect on the proliferation of T lymphocytes, which decreases cellular immunity. o Affect innate immunity and inflammation through several pathways.  Decreased function of macrophages and natural killer cells, suppression of inflammatory cytokines, and decreased release of proteolytic enzymes. o Psychological and physiologic stress increases glucocorticoid production. o Leads to suppression of innate and adaptive immunity and implicates wound healing and increases susceptibility to infection. o Potentiate the effects of catecholamines, including sensitizing the arterioles to the vasoconstrictive effects of norepinephrine, thus increasing the blood pressure. o Inhibition of bone formation, inhibition of ADH secretion, and stimulation of gastric acid secretion.  Cortisol – potent naturally occurring glucocorticoid o Main secretory product of the adrenal cortex and is needed to maintain life and protect the body from stress. o Circulates in bound form attached to albumin but is primarily bound to the plasma protein transcortin. o Corticotropin-releasing hormone is produced by several nuclei in the hypothalamus and stored in the median eminence.  Upon release CRH travels to portal vessel to stimulate ACTH o ACTH regulation:  Negative-feedback effects of high levels of cortisol, diurnal rhythms, with peak levels during sleep, and psychological and physiologic stress increasing ACTH secretion. o ACTH binds to specific plasma membrane on the receptors of cells.6 Exam II (Endocrine, Cardiovascular) Adrenal Glands  Mineralocorticoids: Aldosterone o Steroids directly affect ion transport by epithelial cells, causing sodium retention and potassium and hydrogen loss.  Aldosterone o Most potent naturally occurring mineralocorticoid and conserves sodium by increasing the activity of the sodium pump of epithelial cells. o Synthesis and secretion is regulated primarily by the renin-angiotensin system. o Renin-angiotensin system is activated by sodium and water depletion, increased potassium levels, and a diminished effective blood volume. o Angiotensin II is the primary stimulant of aldosterone synthesis and secretion; however, sodium and potassium levels also may directly affect aldosterone secretion. o Enhancement of cardiac muscle contraction, stimulation of ectopic ventricular activity through secondary cardiac pacemakers in the ventricles, stiffening of blood vessels with increased vascular resistance, and decrease in fibrinolysis.  Adrenal Estrogens and Androgens o Secretes minimal amounts of estrogen and androgens. ACTH appears to be a major regulator.  Adrenal Medulla o Chromaffin cells (pheochromocytes) of the adrenal medulla secrete and store the catecholamines epinephrine and norepinephrine. o Both synthesized from the amino acid phenylalanine. o 30% of epinephrine comes from the adrenal medulla o Functions as a sympathetic ganglion without postganglionic processes. o Physiologic stress to the body triggers the exocytosis of the storage granules from chromaffin cells, with release of epinephrine and norepinephrine into the bloodstream. Alterations of the Hypothalamic-Pituitary System  Common cause is interruption of the pituitary stalk.  Without hypothalamic hormones, the pituitary releases inadequate amounts of FSH, LH, ACTH, TSH, and growth hormone.  Interruption in the negative-feedback loop.  Prolactin predominantly inhibitory by dopamine. Syndrome of Inappropriate Antidiuretic Hormone Secretion F Characterized by high levels of ADH in the absence of normal physiologic stimuli for release. F SIADH is the ectopic production of ADH by tumors, such as cancers of the lung, stomach, pancreas, bladder, prostate, and endometrium; lymphomas; and sarcomas. F Pulmonary disorders associated with SIADH include pneumonia, asthma, cystic fibrosis, and respiratory failure requiring mechanical ventilation. F CNS disorders that may cause SIADH include encephalitis, meningitis, intracranial hemorrhage, tumors, and trauma. F Iatrogenic causes include surgery and medications (healthcare related causes) F N7 Exam II (Endocrine, Cardiovascular) Signs and Symptoms Diabetes Insipidus SIADH Urine Output High Low Urine Osmolality Low High Urine Specific Gravity Low High Serum Sodium High Low Serum Osmolality High Low Symptoms Polyuria, thirst, weight loss, high urine output, signs of dehydration Water retention, weight gain, low urine output, nausea, vomiting, mental changes. Diabetes Insipidus $ Characterized by insufficient ADH activity, leading to loss of too much free water in the urine. Two forms: o Neurogenic or Central DI: insufficient secretion, lesion of hypothalamus, pituitary stalk, or posterior pituitary interferes with ADH synthesis, transport, or release. Hereditary o Nephrogenic DI: inadequate response of the renal tubules to ADH. Acquired caused by disorder and drugs that damage renal tubules. Pyelonephritis, amyloidosis, destructive uropathies, polycystic kidney disease. Drugs such as lithium, colchicine, amphotericin B, loop diuretics, general anesthetics, and demeclocycline. o Gestational DI: vasopressin-degrading enzyme vasopressinase is increased. $ Patho o DI have a partial to total inability to concentrate urine. Causes excretion of large volumes of dilute urine, leading to increased plasma osmolality. Thirst mechanism is stimulated and induces polydipsia. Dehydration develops rapidly without ongoing fluid replacement. Hypernatremia and Hyperosmolality will occur. $ S/S o Polyuria, nocturia, continuous thirst, polydipsia. Neurogenic DI has abrupt onset, nephrogenic more gradual onset. $ Evaluation/Treatment: o Findings of a low urine osmolality with associated elevated serum sodium and osmolality. o Confirmed through water deprivation testing in which urine output is maintained despite dehydration. o Fluid replacement, synthetic vasopressin analog desmopressin (DDAVP), thiazide diuretics, chlorpropamide, carbamazepine, and clofibrate for ADH deficiency. Hypopituitarism8 Exam II (Endocrine, Cardiovascular) Hyperpituitarism: Primary Adenoma  Benign, slow-growing tumors that arise from cells of the anterior pituitary.  Cause unknown, some genetic. Larger adenomas are associated with morbidity and morality attributable to alterations in hormone secretion or invasion of surrounding structures.  Patho: o local expansion causes impingement on optic chiasma and cause various visual disturbances. Invasion of cavernous sinuses may occur, resulting in cranial nerve function impairment. o Extension to hypothalamus disturbs control of wakefulness, thirst, appetite, and temperature. o Hypersecretion from the adenoma itself and hyposecretion from surrounding pituitary  S/S: o Physical and laboratory evaluations needed. MRI. Medications to suppress tumor growth, transsphenoidal tumor resection, radiation, chemotherapy. Hypersecretion of Growth Hormone: Acromegaly  Results form continuous exposure to high levels of GH and insulin-like growth factor 1.  Almost always caused by a GH secreting pituitary adenoma.  Diagnosed in the 40-59 year old age group.  Slowly progressive disease, with decreased life expectancy.  Deaths caused by heart disease secondary to hypertension and coronary artery disease, stroke, DM, or malignancy.  Patho: o Epiphyseal plates have not closed, effect of increase GH termed giantism. o Skeletal growth is excessive. o In adults, closure has occurs, and increased amounts of GH cause connective tissue proliferation and increase cytoplasmic matrix, as well as bony proliferation o Significant effects on glucose, lipid, and protein metabolism. o Hyperglycemia – increased hepatic glucose production, hyperinsulinism, insulin resistance. o CV: hypertension, cardiomegaly, left ventricular heart failure. o Renal: increase phosphate reabsorption, leading to mild hyperphosphatemia. o Prolactin  S/S: o Enlarged tongue, interstitial edema, enlarged and overactive sebaceous and sweat glands, coarse skin and body hair. Enlargement of the bones of the face, hands, and feet. o Ribs to elongate at the bone-cartilage junction, leading to a barrel-chest, increased proliferation of cartilage in joints which cause backache and arthralgias. o Weakness, muscular atrophy, footdrop  Evaluation and Treatment: o Diagnosis by MRI, elevated levels of GH. o Transsphenoidal surgical removal9 Exam II (Endocrine, Cardiovascular) Prolactinoma $ Pituitary tumors that secrete prolactin, most common hormonally active pituitary tumors. $ Renal failure, polycystic ovarian disease, primary hypothyroidism, breast stimulation, or even stress of venipuncture, can increase prolactin levels. $ Prolactin is under tonic inhibitory hypothalamic control through the secretion of dopamine. Thus meds that block the effect of dopamine can increase prolactin levels. These include antipsychotics, metoclopramide, TCAs, and methyldopa. $ Estrogens can increase prolactin concentration. $ Any process that interferes with dopamine delivery from the hypothalamus to the lactotrophs also result in hyperprolactinemia. $ Because TRH stimulates prolactin, prolactin may be elevated in individuals with hypothyroidism. $ Patho: o Sustained increases in the levels of serum prolactin. Suppress LH and FSH, resulting in estrogen and progesterone deficiency in women, and low testosterone levels in men. o Hypopituitarism may occur because of the compression of surrounding hormone-secreting cells. $ S/S: o Galactorrhea (nonpuerperal milk production) and menstrual disturbances, including amenorrhea. Estrogen deficiency may cause hirsutism, and fractures may occur because of osteopenia or osteoporosis. In men causes gynecomastia, hypogonadism, and erectile dysfunction. $ Evaluation & Treatment: o Careful history to exclude medications, hypothyroidism screening. MRI of pituitary. Dopaminergic agonists (cabergoline) Alterations in Thyroid Function  Primary thyroid disorders result in either increased or decreased thyroid hormone levels. Also cause secondary feedback effects on pituitary TSH.  Central (secondary) thyroid disorders are related to disorders of pituitary gland TSH production. When in excess, the TH level is elevated secondary to primary elevation of TSH.  Majority are idiopathic and caused by autoimmune mechanisms that affect gland.  Most common autoimmune hypothyroid is Hashimoto thyroiditis, and the most common autoimmune hyperthyroid is Grave’s disease. Thyrotoxicosis/Hyperthyroidism  Thyrotoxicosis is a condition that results from any cause of increased TH levels and can result from dysfunction of the pituitary, the thyroid gland, ectopic thyroid tissue, or the ingestion of excessive amounts of TH medication.  Hyperthyroidism is a form of thyrotoxicosis in which excess amounts of TH are secreted from the10 Exam II (Endocrine, Cardiovascular) Hyperthyroid Conditions  Graves Disease is the underlying cause of 50-80% of cases of hyperthyroidism. Genetic factors interacting with environmental triggers play an important role in pathogenesis. Autoimmune disease and results from a form of type II hypersensitivity. TSI situation of TSH receptors in the gland results in hyperplasia of the gland (goiter) and increased synthesis of TH, especially T3.  Autoimmunity also contributes to major distinguishing clinical manifestation of Graves disease (ophthalmopathy and dermopathy). Periorbital edema, w/ bug eyes, pretibial myxedema.  Irritation, pain, lacrimation, photophobia, blurred vision, decreased visual acuity, papilledema.  Hyperthyroidism from Nodular Thyroid Disease o Enlarges in response to increased demand for TH. o Toxic multinodular goiter occurs when there are several hyperfunctioning nodules leading to hyperthyroidism. Unlike Graves, there is absence of an autoimmune stimulus. o Hyperthyroidism S/S o Treatment includes radioactive iodine, surgery, and antithyroid meds.  Thyrotoxic Crisis o Rare but dangerous worsening of the thyrotoxic state in which TH levels rise dramatically and death can occur within 48 hours without treatment. o Graves disease with physiologic stress, such as infection, pulmonary or cardiovascular disorders, trauma, seizures, surgery, obstetric complication, or dialysis. o S/S: hyperthermia, tachycardia, heart failure, agitation or delirium, N/V/D. o Treatment includes drugs that block TH synthesis (propylthiouracil or methimazole) Hypothyroidism F Results from deficient production of TH by thyroid. Most common. F Subclinical hypothyroidism is a mild thyroid failure estimated to occur in 4-8% of US adults. F Primary hypothyroidism, loss of function leads to decreased TH and increased TSH and TRH. F Autoimmune thyroiditis (Hashimoto disease), iatrogenic loss of thyroid tissue after surgical or radioactive treatment for hyperthyroidism or after head and neck radiation therapy, medications, and endemic iodine deficiency. F Central hypothyroidism is caused by the pituitary’s failure to synthesize adequate amounts of TSH and lack of TRH. F TBI, subarachnoid hemorrhage, pituitary infarction. F S/S: o Lower energy metabolism and heat production. Low basal metabolic rate, cold intolerance, lethargy. Excessive TSH production, goiter. o Myxedema Coma  Medical emergency diminished level of consciousness associated with severe hypothyroidism.11 Exam II (Endocrine, Cardiovascular) Hypothyroid Conditions  Hashimoto Disease o Most common cause of primary hypothyroidism is autoimmune thyroiditis which results in gradual, inflammatory destruction of the thyroid tissue. Linked with several genetic risk factors and is often associated with other autoimmune conditions.  Uncommon Types o Subacute thyroiditis is a rare nonbacterial inflammation of the thyroid preceded by a viral infection. Fever, tenderness, enlargement and transient hypothyroidism before recovery. o Postpartum thyroiditis generally occurs up to 6 months after birthing with a course similarly to that seen in subacute thyroiditis. o Iatrogenic hypothyroidism results from ablation of the thyroid gland during treatment.  Congenital Hypothyroidism o Infants occurs when thyroid tissue is absent or with hereditary defects in TH synthesis. High birthweight, hypothermia, delay in passing meconium, and neonatal jaundice. o Cord blood to obtain T4 and TSH levels. o Difficulty eating, hoarse cry, protruding tongue caused by myxedema, hypotonic muscles with constipation, abdominal protrusion, umbilical hernia; subnormal temperature, lethargy, excessive sleeping, slow pulse, cold, mottled skin. Thyroid Carcinoma F Most common endocrine malignancy F Exposure to ionizing radiation, during childhood, most consistent cause. F Small thyroid nodule or metastatic tumor in the lungs, brain, or bone., F Changes in voice, swallowing and difficulty breathing are related to tumor growth. F Ultrasound and fine-needle aspiration. F Most have normal T3 and T4 levels. F Partial or total thyroidectomy, TSH suppression therapy, radioactive iodine therapy, postoperative radiation, chemotherapy. Hyperparathyroidism F Greater than normal PTH with associated hypercalcemia. F Primary hyperparathyroidism inappropriate excess of PTH by one more parathyroid glands. o Parathyroid adenomas o Parathyroid hyperplasia o Parathyroid carcinoma o PTH secretion is increased and is not under the usual feedback control. Calcium level in blood12 Exam II (Endocrine, Cardiovascular) Hypoparathyroidism F Abnormally low levels of PTH, most commonly caused by damage to parathyroid glands during thyroid surgery. F Hypomagnesemia another cause of low PTH levels. F Genetic syndromes, DiGeorge syndrome. F Patho: o Absence of PTH impairs resorption of calcium from bone and renal tubules, leading to hypocalcemia. Also stimulated increase renal absorption of phosphate, leading to hyperphosphatemia. Hyperphosphatemia lowers calcium concentration by inhibiting the activation of Vitamin D. o Hypomagnesemia inhibits PTH secretion. May be related to chronic alcoholism, malnutrition, malabsorption, increased renal clearance, prolonged magnesium-deficient parenteral nutritional therapy. F S/S: o Hypocalcemia, muscle spasms, tetany, dry skin, loss of body and scalp hair. Horizontal ridges on ails, cataracts, basal ganglia calcification, and bone deformities. F Evaluation and Treatment: o Measurement of the serum magnesium level and urinary calcium can help in diagnosis. Treatment to alleviate hypocalcemia. Diabetes Mellitus F Hyperglycemia resulting from defects in insulin secretion, insulin action, or both. F Type 1: autoimmune beta-cell destruction, leading to insulin dependency F Type II: progressive loss of beta-cell insulin secretion, insulin resistance F Gestational Diabetes: second or third trimester F Other type for specific causes F HgA1C: 120 day look of average glucose. Type I  Most common pediatric chronic disease  Patho: o Idiopathic and autoimmune. Idiopathic is far less common, has a strong genetic component, occurs in Asian or African descent. o Autoimmune is slow, progressive disease that destroys beta cells of the pancreas. o Environmental factors. o Cellular immunity and humoral immunity are stimulated, resulting in beta-cell destruction and apoptosis. I13 Exam II (Endocrine, Cardiovascular) Type II Diabetes F Non-insulin-dependent DM, prevalence higher among American Indians and Alaska Natives F Obesity link F Family history, age, obesity, hypertension, poor diet, and physical activity are risk factors. F Patho: o Suboptimal response of insulin-sensitive tissues. o Obesity most important contributors because:  Adipokines: increase serum levels of leptin, decrease insulin sensitivity  Free fatty acids: decreased tissue responses to insulin  Inflammation: inflammatory cytokines released form adipocytes induce insulin resistance  Mitochondrial dysfunction: decreased insulin-induced activity leading to resistance  Hyperinsulinemia: decreased insulin receptor density  Elevated glucagon stimulates glycogenolysis and gluconeogenesis.  Ghrelin (regulates food intake, energy balance, and hormonal secretion) once decreased assists with insulin resistance and increasing fasting insulin levels.  Incretins are peptides released form GI to secrete insulin.  Hormones tire out from overwork or make perfect conditions for increased glucose levels and insulin resistance. F S/S: o Polyuria, polydipsia, fatigue, pruritis, infections, vision changes, neuropathy, overweight F Evaluation and Treatment o Restoration or near-euglycemia. Prevent metabolic disorders. Diet and exercise. Hypoglycemia F Insulin shock or insulin reaction. F Type I more than Type II F Pallor, tremor, anxiety, tachycardia, palpitation, diaphoresis, HA, dizziness, irritability, fatigue, poor judgment, confusion, visual disturbances, hunger, seizures, and coma. F Diabetic Ketoacidosis o Deficiency of insulin and increase in the levels of insulin counterregulatory hormones. o Type I o Hypoglycemia, acidosis, ketonuria. o Accumulation of ketone bodies causes drop in pH, metabolic acidosis, and transient14 Exam II (Endocrine, Cardiovascular) Complications of DM F Microvascular: capillaries o Retinopathy, Nephropathy, Neuropathy, Skin and foot lesions F Macrovascular: arterioles o Stoke, CVD, CVA, PVD F Retinopathy: ischemia, inflammation, swelling, scarring, Cushing Syndrome/Disease F Syndrome refers to chronic exposures to excess cortisol F Disease refers to excess endogenous secretion of ACTH F Cushing-like syndrome may develop as a side effect of long-term pharmacologic administration of glucocorticoids. F Patho: o Excess ACTH stimulates excess of cortisol, loss of feedback control of ACTH secretion. o Secretion of both cortisol and adrenal androgens is increased, and cortisol-releasing hormone is inhibited. o ACTH independent secreting tumors of the adrenal cortex, secrete cortisol. o Elevated cortisol levels suppress CRH and ACTH levels. F S/S: o Weight gain, adipose tissue in the trunk, facial, and cervical areas. o Moon face, buffalo hump o Glucose intolerance. o Protein wasting with cortisol effects of peripheral tissue. Weakness, pathologic fracture, vertebral compression fractures, bone and back pain, kyphosis, and reduced height. o Thin, weak skin. Purple striae on trunk. o Hypertension, hypokalemia. o Irritability, disturbed sleep, difficulty concentrating, memory loss F Evaluation and Treatment o Labs: hyperglycemia, glycosuria, hypokalemia, and metabolic alkalosis. o ACTH levels, dexamethasone suppression testing. o Hypercorticoadrenalism includes surgery, medication, radiation. Congenital Adrenal Hyperplasia F Inherited deficiency of an enzyme that is critical in cortisol biosynthesis. F Concentration of ACTH increases and causes adrenal hyperplasia, which overproduces mineralocorticoids or androgens, or both. F Female are virilized F Treatment with corticoids.15 Exam II (Endocrine, Cardiovascular) Hyperaldosteronism F Excessive secretion of aldosterone. Primary and Secondary causes. F Primary: excssive secretion from abnormality on adrenal cortex. Usually adenoma. F Secondary: results from an extra-adrenal stimulus of aldosterone secretion; most often angiotensin II in response to decreased circulating blood volume. Bartter syndrome F Patho: o Increased renal sodium and water reabsorption w/ hypervolemia o Renal excretion of hydrogen and potassium o Renin secretion stimulated by pressure-initiated cellular changes, increase in angiotensin II and aldosterone F S/S: o Hypertension, hypokalemia, hypervolemia. Edema often absent. F Evaluation and Treatment: o BP, Serum and urinary electrolytes, Plasma aldosterone-to-renin ratio, Imaging o Managing hypetension, hypervolemia, hypokalemia. Often with aldosterone receptor antagonists such as spironolactone, or ACE inhibitors. Hypersecretion of Adrenal Androgens and Estrogens F Caused by adrenal tumors, Cushing syndrome, or defects in steroid synthesis. F Hypersecretion of estrogens cause feminization, androgens cause virilization. Addison Disease F Primary adrenal insufficiency F Chronic infections that affect the adrenal gland (Tuberculosis), account for the majority. F Patho: o Inadequate corticosteroid or mineralocorticoid synthesis and elevated levels of serum ACTH. o Idiopathic Addison disease causes adrenal atrophy and hypofunction and is an organ-specific autoimmune disease resulting from autoantibodies and autoreactive T cells that attack the adrenal cortical cells. o Especially Hashimoto thyroiditis, pernicious anemia, and idiopathic hypoparathyroidism F S/S o Hypercortisolism and hypoaldosteronism. Weakness, easy to fatigue. Skin changes including hyperpigmentation and vitiligo. Anorexia, N/V/D. Vascular collapse and shock. Adrenal crisis or Addisonian crisis. F Evaluation and Treatment o Serum and urine levels of cortisol are depressed, ACTH levels increased. BUN increased. Glucose low. Hyperkalemia. o Lifetime glucocorticoid and mineralocorticoid replacement therapy, with dietary changes. o 150 mEq/ of sodium per day; sodium intake should be increased if experience excessive sweating or diarrhea. With acute stressors, additional cortisol may be administered. F Secondary hypercortisolism o Prolonged administration of exogenous glucocorticoids; suppress ACTH secretion and cause internal adrenal atrophy. Pheochromocytomas (Chromaffin Cell) F Sympathetic paragangliomas of the adrenal medulla. F Patho: o Cause excessive production of norepinephrine, large tumors produce Epi and Norepi. F S/S: