Ch 22 Alterations of hormonal regulation

SECONDARY ALTERATIONS OF THYROID FUNCTION

-conditions that cause alterations in pituitary or hypothalamic functioning -alters TSH or thyrotropin-releasing hormone (TRH) production

TREATMENT OF SIADH secretion

-correction of underlying causal problems -fluid restriction (betw. 800-1000 mL/day) -resistant or chronic SIADH: Demeclocycline

What are RECEPTOR-ASSOCIATED DISORDERS?

-decrease in # of receptors -impaired receptor function -presence of antibodies against specific receptors -antibodies that mimic hormone action -unusual expression of receptor function

WHAT IS HYPOTHYROIDISM

-deficient production of thyroid hormone by the thyroid gland

What is DIABETES MELLITUS -affects what? -characterized by what?

-dysfunction of endocrine pancreas -affects metabolism of fat, protein, and carbohydrates -characterized by hyperglycemia, resulting from defects in insulin secretion, insulin action/both.

PRIMARY ALTERATIONS OF THYROID FUNCTION

-dysfunction or disease of the thyroid gland -alters thyroid hormone (TH) production

Diabetic nephropathy

-end-stage kidney disease -glomerular enlargement, glomerular basement membrane thickening

AUTOIMMUNE TYPE of TYPE 1 DIABETES

-environmental and genetic factors are thought to trigger cell-mediated destruction of pancreatic beta cells (type 1A) -autoantibody, T-cell, and macrophage destruction of pancreatic beta cells occur with a loss of insulin production and a relative excess of glucagon.

PRIMARY HYPERPARATHYROIDISM

-excess secretion of PTH from one or more parathyroid glands and hypercalcemia -80-85% caused by parathyroid adenomas

HYPERALDOSTERONISM

-excessive aldosterone secretion by adrenal cortex

TARGET CELL DYSFUNCTION

-failure of target cell to respond to its hormone (hormone insensitivity) -receptor-associated disorders

Signs of Type 2 DM

-fatigue -pruritus -recurrent infections -visual changes -symptoms of neuropathy (paresthesia or weakness)

GENETIC SUSCEPTIBILITY (Type 1)

-first degree relative (parent or sibling) with Type 1 -strongest association with major histocompatibility complex (MHC)

GESTATIONAL DM

-glucose intolerance with the onset or first recognition occurring during pregnancy -contributing factors: insulin resistance and inadequate insulin secretion -if this develops, the risk for type 2 diabetes increases

Diagnosis of DM

-glycosylated hemoglobin (HgA1C) levels -->permanent attachment of glucose to hemoglobin molecules; reflects average glucose exposure over life of a RBC (approx 120 days)

ACROMEGALY -what is it? -who does it affect? -mortality

-hypersecretion of GH during adulthood -slowly progressive pituitary adenoma -->mortality: cardiac hypertrophy; hypertension; atherosclerosis; type 2 diabetes mellitus (leading to coronary artery disease)

CLINICAL MANIFESTATIONS of PHEOCHROMOCYTOMAS

-hypertension -diaphoresis -tachycardia -palpitations -severe headache

CLINICAL MANIFESTATIONS OF HYPERALDOSTERONISM

-hypertension -hypokalemia, renal potassium wasting -neuromuscular manifestations

GRAVES DISEASE

-hyperthyroid condition -autoimmune disease (develops autoantibodies)

CLINICAL MANIFESTATIONS of hypoparathyroidism

-hypocalcemia -lowering the threshold for nerve and muscle excitation -muscle spasms; hyperreflexia -tonic-clonic convulsions -laryngeal spasms, death from asphyxiation -Chvostek and Trousseau signs -phosphate retention

CLINICAL MANIFESTATIONS of Addison disease

-hypocortisolism -hypoaldosteronism -weakness, hyperpigmentation (bronze skin), vitiligo

ACUTE COMPLICATIONS of DM

-hypoglycemia -diabetic -hyperosmolar hyperglycemic nonketotic syndrome (HHNKS) -Somogyi effect -Dawn phenomenon

SOMOGYI Effect -what is it? -most common in...

-hypoglycemia with rebound hyperglycemia -counterregulatory hormones cause gluconeogenesis -most common in person with type 1 diabetes mellitus and in children

CLINICAL MANIFESTATIONS OF SIADH

-hyponatremia: sodium (<135mEq/L) -hypoosmalility: <280 mOsm/kg -urine hyperosmolality (higher than serum osmolality) -hypervolemia -weight gain -serum sodium levels <110-115 mEq/L: Can cause severe and irreversible neurologic damage

CATEGORIES at risk for diabetes

-impaired glucose tolerance (IGT): From diminished insulin secretion -impaired fasting glucose (IFG): From enhanced hepatic glucose output

SECONDARY HYPERPARATHYROIDISM

-increase in PTH, secondary to chronic disease -->chronic renal failure -->dietary deficiency of vitamin D, calcium HYPERCALCEMIA DOES NOT OCCUR

CLINICAL MANIFESTATIONS of THYROTOXICOSIS

-increased metabolic rate with heat intolerance -increased tissue sensitivity to stimulation by the sympathetic nervous system -enlargement of thyroid gland (goiter)

DIABETES INSIPIDUS

-insufficiency of ADH -polyuria and polydipsia -partial or total inability to concentrate the urine

MECHANISMS OF TYPE 2 DM

-insulin resistance and decreased insulin secretion by beta cells -leptin resistance (alteration in the production of adipokines by adipose tissue) -elevated serum free fatty acids and intracellular lipid deposits -release of inflammatory cytokines from adipose tissue

HYPERTHYROIDSIM: THYROTOXICOSIS

-is a condition that results from any cause of increased level of thyroid hormone -excess amounts of thyroid hormone are secreted from the thyroid gland

Diabetic retinopathy -develops more rapidly in...

-leading cause of blindness worldwide -develops more rapidly in type 2

HYPERSECRETION OF ESTROGENS -how does it affect men? women?

-leads to feminization and development of female sex characteristics -most evident in men and results in gynecomastia (breast enlargement), testicular atrophy, decreased libido -leads to early development of secondary sex characteristics in female children

HYPERSECRETION OF ANDROGENS -effect on women

-leads to virilization and development of male sex characteristics -changes are more easily observed in women (hirsutism, clitoral enlargement, deepening of the voice, amenorrhea, acne, breast atrophy) -promote sexual development and bone aging in children

SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE (SIADH) secretion -what is it? -what the most common cause? -what is a common manifestation?

-levels of ADH are abnormally high -ectopic secretion of ADH is most common cause -common manifestation: water retention (Action of ADH on renal collecting ducts increases their permeability to water, thus increasing water reabsorption by the kidneys.

CLINICAL MANIFESTATIONS of Type 1 DM

-long preclinical period with gradual beta cell destruction, leading to insulin deficiency and hyperglycemia develops

HYPOTHYROIDISM SYMPTOMS (from picture on slide)

-loss of hair -coarse, brittle hair -periorbital edema -puffy face -normal, enlarged or small thyroid -heart failure (bradycardia) -constipation -cold intolerance -muscle weakness -decreased bone mineral density (osteoporosis) -edema of extremities

CLINICAL MANIFESTATIONS OF HYPOTHYROIDISM

-low BMR, cold intolerance -lethargy, tiredness -slightly lowered basal body temp. -diastolic hypertension -myxedema -myxedema coma

CUSHING DISEASE

-overproduction of pituitary ACTH by a pituitary adenoma -lose diurnal and circadian patterns of ACTH and cortisol secretion -lack of ability to increase ACTH and cortisol in response to stressors

CLINICAL MANIFESTATIONS of DKA

-polyuria and dehydration -Kussmaul respirations -sweet or "fruit" breath odor

CLINICAL MANIFESTATIONS of diabetes insipidus

-polyuria, nocturia (peeing at night), continual thirst -low urine-specific gravity -low urine osmolality -hypernatremia

ADDISON DISEASE -what is it?

-primary adrenal insufficiency, hypocortisolism -rare, autoimmune mechanisms -inadequate corticosteroid and mineralocorticoid synthesis; elevated ACTH

PATHOPHYSIOLOGY of SECONDARY HYPOCORTISOLISM

-prolonged administration of exogenous glucocorticoids (suppress ACTH secretion)

THYROID CARCINOMA -cause -manifestations -levels of thyroid hormones

Hypothyroidism -most common endocrine malignancy from ionizing radiation -changes in voice and swallowing and difficulty in breathing, related to a tumor growth impinging the trachea or esophagus -some may have normal T3 and T4 levels

HYPOGLYCEMIA -aka what -newborns vs children and adults -manifestations

Lowered plasma glucose level (aka insulin shock, insulin reaction) Newborns: <35 mg/dl Children and adults <45-60 Manifestations: -tachycardia, palpitations, diaphoresis, tremors, pallor, arousal anxiety

Maculopathy

progressive process that accompanies retinal capillary permeability, vessel occlusion, ischemia

HYPERSECRETION OF PROLACTIN is caused by... -in women vs in men

prolactinomas (most common hormonally active pituitary tumor) -in women: amenorrhea, galactorrhea, hirsutism, osteoporosis -in men: hypogonadism, erectile dysfunction

MYXEDEMA COMA

symptom of hypothyroidism -medical emergency -diminished level of consciousness -hypothermia without shivering -hypoventilation -hypotension -hypoglycemia -lactic acidosis -coma

MYXEDEMA

symptom of hypothyroidism -nonpitting, boggy edema (especially around the eyes, hands, feet) -thickening of tongue

PRIMARY (Conn disease) aldosteronism

single benign aldosterone-producing adrenal adenoma

HYPERPITUITARISM-what is it?

-commonly from benign, slow-growing pituitary adenoma

TYPE 2 MANIFESTATIONS -beta cell dysfunction

--Beta cell mass is decreased --inflammation and changes occur in adipokines=leptin resistance

TYPE 2 MANIFESTATIONS -glucagon

--Pancreatic alpha cells are less responsive to glucose inhibition; hyperglycemia--abnormally high levels of glucagon increase hepatic production of glucose

GIANTISM -what is it? -who does it affect?

-GH hypersecretion in children and adolescents.

DIABETES INSIPIDUS SYMPTOMS: -NEUROGENIC: -NEPRHOGENIC: -DIPSOGENIC:

-Neurogenic (insufficient amounts of ADH) -Nephrogenic (insensitivity of the renal collecting tubules to ADH) -Disogenic (excessive fluid intake, lowering plasma osmolarity to the point that it falls below the threshold for ADH secretion)

ECTOPIC HORMONE RELEASE

-Nonendocrine sites -autonomous production; no feedback mechanisms

HYPOPARATHYROIDISM (what is increased? decreased?)

-abnormally low PTH levels -->DEPRESSED serum CALCIUM level (calcitonIN puts calcium IN the bone; PTH takes it OUT of the bone into blood) -->increased serum phosphate level

HYPOPITUITARISM is characterized by...

-absence of selective pituitary hormones or the complete failure of all pituitary hormone functions -pituitary is vascular and therefore vulnerable to ischemia and infarction

DIABETIC KETOACIDOSIS (DKA) -what is it? -common in type 1 or 2? -precipitating factors? -what is increased?

-absolute or relative deficiency of insulin and increase in insulin counterregulatory hormones -most common in Type 1 -precipitating factors: illness, trauma, surgery, myocardial infarction -increased fat mobilization with release of fatty acids

PHEOCHROMOCYTOMAS -where are they located? -caused by... -secrete...

-adrenal medulla hyperfunction -caused by tumors derived from chromaffin cells of adrenal medulla -secrete catecholamines

RISK FACTORS for Type 2 DM?

-age -obesity -hypertension -physical inactivity -family history -metabolic syndrome

CONGENITAL ADRENAL HYPERPLASIA

-autosomal recessive disorder (enzyme for cortisol biosynthesis is deficient) -cortisol production is low -ACTH is increased -causes adrenal hyperplasia (overproduction of either mineralocorticoids or androgens)

THYROTOXIC CRISIS (THYROID STORM) -what is it? when does it occur? -results from? -clinical manifestations

-rare but life threatening within 48 hours if not treated -results from excessive stress (increased action of T4 and T3) Clinical manifestations: -hyperthermia, tachycardia, high-output heart failure; agitation or delirium; nausea, vomiting, or diarrhea

CLINICAL MANIFESTATIONS of hyperthyroidism resulting from nodular thyroid disease vs hyperthyroidism

-same as hyperthyroidism but occur slowly -exophthalmos and pretibial myxedema DO NOT OCCUR in nodular thyroid disease

Diabetic neuropathies

-sensory deficits generally precede motor involvement -distal portions of the neurons are initially and eventually more severely affected

CLINICAL MANIFESTATIONS of SECONDARY HYPOCORTISOLISM

-similar to Addisons -BUT HYPERPIGMENTATION DOESN'T OCCUR

Microvascular disease

-thickening of capillary basement membrane endothelial cell hyperplasia -thrombosis -hypoxia and ischemia

HYPERTHYROIDISM

-thin hair -exophthalmos -normal or enlarged thyroid (diffuse/"warm on palpation"; nodular; solitary "toxic" nodule) -heart failure (tachycardia) -weight loss -diarrhea -warm skin, sweaty palms -hyperreflexia -pretibial myxedema

CONGENITAL HYPOTHYROIDISM -what happens if it is not treated? -treatment?

-thyroid hormone deficiency present at birth -if not treated, cretinism develops -neonatal screening to reduce incidents -administration of T4

SECONDARY (secondary aldosteronism)

-typically caused by a reduced blood flow to the kidneys leading to excess aldosterone production. -from an extraadrenal stimulus, most often angiotensin II, through a renin-dependent mechanism

ENVIRONMENTAL FACTORS (Type 1)

-viral infection -helicobacter pylori -exposure to cow's milk proteins -relative lack of vitamin D (also implicated)

FEATURES OF ACROMEGALY

1) Connective tissue proliferation -->enlarged tongue, intestinal edema, increase in size and function of sebaceous and sweat glands, coarse skin and body hair 2) Bony proliferation -->large joint arthropathy, kyphosis, enlargement of facial bones and hands and feet, protrusion of the lower jaw and forehead, need for increasingly larger sized shoes, hats, rings and gloves 3) Symptoms of diabetes (polyuria and polydipsia) 4) CNS symptoms -->Headache, seizure activity, visual disturbances, papilledema

What is happening when there is TOO MUCH OR TOO LITTLE HORMONE?

1) Failure of feedback systems -->may fail to function properly -->may respond to inappropriate signals 2) Dysfunction of an endocrine gland -->inability to produce or obtain an adequate quantity of required hormone precursors -->inability to covert precursors to active hormone -->excessive or inadequate hormone production

CHRONIC COMPLICATIONS OF DM

1) Microvascular disease -->diabetic retinopathy -->diabetic nephropathy -->diabetic neuropathies 2) Macrovascular disease -->coronary artery disease -->stroke -->peripheral arterial disease 3) Infection

INTRACELLULAR DISORDERS (target cell dysfunction)

1) inadequate synthesis of second messenger -->cAMP 2) Failure of target cell to produce anticipated hormonal response -->faulty response to hormone-receptor binding

TYPE 2 MANIFESTATIONS -insulin resistance -glucagon

1) insulin resistance --response of insulin-sensitive tissues (especially liver, muscle, and adipose tissue) to insulin is suboptimal. --obesity makes one prone to insulin resistance

CLINICAL MANIFESTATIONS of Cushing disease and cushing syndrome

1) weight gain of adipose tissue in the trunk, facial, cervical areas -->described as "truncal [central] obesity, "moon face," and "buffalo hump" 2) Sodium and H20 retention, glucose intolerance, protein wasting 3) Renal stones 4) Purple striae 5) Bronze and brownish hyperpigmentation of the skin

What is PANHYPOPITUITARISM?

ALL hormones are affected -ACTH deficiency (cortisol deficiency) -TSH deficiency (altered metabolism) -FSH and LH deficiency (lack of secondary sex characteristics) -GH deficiency (lack of growth in children)

Glucagon excess may also be as important as insulin insufficiency of diabetes. Glucagon: A. Stimulates lipolysis. B. Stops the release of amylin. C. Increases somatostatin production. D. Decreases ghrelin levels.

ANS: A Lipolysis has a ketogenic effect caused by the metabolism of free fatty acids in the liver, and is stimulated by glucagon.

Obesity is present in 60% to 80% of patients with type 2 diabetes and is a major contributor to insulin resistance by many mechanisms including: A. Decreased release of inflammatory cytokines B. Minimization of free fatty acids C. Maintenance of oxidative phosphorylation in cellular mitochondria D. Increased insulin-receptor density

ANS: C Alterations in oxidative phosphorylation in cellular mitochondria have been documented resulting in reduced insulin-stimulated mitochondrial activity and insulin resistance

SECONDARY HYPOTHYROIDISM

Conditions that cause either pituitary or hypothalamic failure with deficiency or TRH and TSH

IODINE DEFICIENCY VS AUTOIMMUNE THYROIDITIS

PRIMARY HYPOTHYROIDISM 1) iodine deficiency (endemic goiter): most common worldwide 2) Autoimmune thyroiditis (Hashimoto disease): most common hypothyroidism in U.S.

CUSHING SYNDROME

Chronic excessive cortisol level, regardless of cause

HYPERPITUITARISM-Clinical manifestations

Insidious symptoms -headaches and fatigue -visual changes -hypersecretion of pituitary from tumor -hyposecretion of neighboring anterior pituitary hormones

TREATMENT for -neurogenic -nephrogenic -dipsogenic

Neurogenic: administration of synthetic vasopressin analog desmopressin acetate (DDAVP) Nephrogenic: Treatment of any reversible underlying disorders Dipsogenic: effective management of water ingestion

Pseudohypoparathyroidism vs familial hypocalciuric hypercalcemia Clinical manifestations

Pseudo=inherited VS Familial=benign autosomal dominant condition Clinical manifestations: most asymptomatic

Which is MORE COMMON: Type 1 or 2?

Type 2

METABOLIC SYNDROME is found in which type of diabetes?

Type 2 -central obesity -dyslipidemia -prehypertension -elevated fasting blood glucose level

HYPEROSMOLAR HYPERGLYCEMIC NONKETOTIC SYNDROME is usually associated with Type 1 or 2? -what is more marked in this than in DKA?

Type 2 -life-threatening emergency -precipitated by infections, meds -fluid deficiency, elevated glucose levels (more marked than in DKA)

Levels of AMYLIN in type 1 and 2

decreased in type 1 and 2

GHRELIN levels in type 2

decreased in type 2

Tertiary hyperparathyroidism

excessive secretion of PTH and hypercalcemia from long-standing secondary hyperparathyroidism

Macular edema

fluid accumulation and retinal thickening

MAIN DIFFERENCE BETWEEN primary and secondary hyperparathyroidism

hypercalcemia does not occur in secondary

SOLITARY TOXIC ADENOMA

hyperthyroidism resulting from nodular thyroid disease -only one nodule becomes hyperfunctioning

TOXIC MULTINODULAR GOITER

hyperthyroidism resulting from nodular thyroid disease -severe hyperfunctioning nodules secrete thyroid hormone

CLINICAL MANIFESTATIONS OF GRAVES DISEASE

ophthalmopathy 1) exophthalmos: increased secretion of hyaluronic acid, orbital fat accumulation, inflammation, and edema of the orbital contents -->diplopia: double vision 2)Pretibial myxedema (Graves dermopathy): leg swelling

WHAT IS TYPE 1 Diabetes

pancreatic atrophy and immunologically mediated destruction of beta cells -->lymphocyte and macrophage infiltrate islets (results in insulinitis and islet beta cell death) -results in relative excess of glucagon (contributing to hyperglycemia)

DIABETES INSIPIDUS IS CHARACTERIZED BY

the inability of the kidney to increase permeability to water -->excretion of large volumes of dilute urine -->increase in plasma osmolality -->urine output: 8-12 L/day (normal is 1-2)