Disorders of Endocrine Function

Chapter 40

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

Endocrine Disorders

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 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

Endocrine Disorders: Classification

Alterations of the Hypothalamic-Pituitary System

Endocrine Disorders

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 PituitaryGiantism:

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 epiphyseal closure)

Thyroid Gland Disorders

• Hypothyoidism– Congenital – Acquired

• Hyperthyroidism

Thyroid Hormone Disorders

• 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)

• Irradiation of the thyroid gland

• Surgical removal of thyroid tissue

• Iodine deficiency

HypothyroidismAcquired

CretinismCongential hypothyroidism: can be endemic (iodine

deficiency), genetic, or sporadic

Delayed bone maturation, puberty, mental retardation, abdominal protrusion with umbilical hernia

A 3-month-old male was diagnosed with congenital hypothyroidism. If left untreated, the child 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.

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

ETIOLOGY AND PATHOGENESIS: Hypothyroidism:

GOITER

Many vegetables are goiterogens

Secondary hypothyroidism is caused by defects in TSH

production and can result from:• Severe head trauma

• Cranial neoplasms

• Brain infections

• Cranial irradiation

• Neurosurgical procedures

ETIOLOGY AND PATHOGENESIS: Hypothyroidism:

Clinical ManifestationsInfants

• Dull appearance, thick,

protuberant tongue, and thick

lips result in feeding difficulties

• Prolonged neonatal jaundice

• Poor muscle tone

• Bradycardia, mottled extremities

• Umbilical hernia

• Hoarse cry

Children/Adults

• Decreased basal metabolic rate

• Weakness, lethargy, cold intolerance,

decreased appetite

• Bradycardia, narrowed pulse pressure,

and mild/moderate weight gain

• Elevated serum cholesterol and

triglycerides

• Enlarged thyroid, dry skin, constipation

• Depression, difficulties with

concentration/memory

• Menstrual irregularity

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,

↑cholesterol

• 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

DIAGNOSIS: 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

TREATMENT: Hypothyroidism:

• Primary—autonomous

• Secondary—mediated through stimulation of TSH

receptors by substances such as TSH

• Autoimmune—related to TSH receptor antibodies

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

ETIOLOGY AND PATHOGENESIS: Hyperthyroidism

• Changes in behavior, insomnia, restlessness, tremor, irritability, palpitations, 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

CLINICAL MANIFESTATIONS: Hyperthyroidism

Graves Disease: autoimmunemost common form of hyerpthyroidism

Edema of orbit, exopthalmos, extrocular muscle weakness

Antibodies mimic TSH by binding to and activating TSH receptors

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

HYPER HYPO

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-stimulating antibodies.B. ectopic secretion of thyroid-stimulating hormone (TSH).C. low circulating levels of thyroid hormones.D. stimulation of thyroid-binding globulin.

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

CLINICAL MANIFESTATIONS: 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

DIAGNOSIS: 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

TREATMENT: Hyperthyroidism

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

Adrenal Gland Disorders

1- Adrenal cortex:• Constitutes 90% of gland volume• Secrete steroid hormones (adrenocortical hormones):

- Mineralocorticoids (aldosterone) SALT- Glucocorticoids (cortisol) SUGAR- Adrenal androgens SEX

2- Adrenal medulla:• Secrete catecholamines:- Norepinephrine (NE, nonadrenaline)- Epinephrine (E, adrenaline)- Dopamine

Main hormones

Adrenal Gland

• Hypoadrenalism1- Primary adrenal insufficiency (Addison’s disease)2- Secondary adrenal insufficiency: CRH, ACTH, result from: - pituitary or hypothalamic disease. - long-term suppression of hypothalamic-pituitary-adrenal axis by

glucocorticoids adrenal atrophy.

• Hyperadrenalism1- Cushing’s syndrome: cortisol production2- Primary hyperaldosteronism (Conn’s syndrome): aldosterone

production 3- Congenital adrenal hyperplasia: caused by enzymatic

abnormalities in steroid synthesis.

Disorders of the Adrenal Cortex

Adrenocortical Insufficiency

Unable to produce adequate levels of cortisol

• Disorders of the adrenal cortex– Adrenocortical hypofunction

• PRIMARY: Addison disease– Destruction of the adrenal gland through:

• Idiopathic or autoimmune mechanisms• Tuberculosis, • Trauma or hemorrhage,• Fungal disease• Neoplasia

Adrenocortical Insufficiency

ENTIRE CORTEX

• Insufficient Adrenal hormones: chronic fatigue, muscle weakness, loss of appetite, weight loss, low BP, dehydration, cardiac arrythmias, bronzed appearance

Addison’s Disease: Clinical Manifestations

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.

• 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

Adrenocortical Insufficiency

Alterations of Adrenal Function

Disorders of the adrenal cortex: HYPERCORTISOLISM

– Cushing disease• Excessive ANTERIOR

PITUITARY secretion of ACTH

– Cushing syndrome• Excessive level of

cortisol, regardless of cause

• 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

Hypercortisolism: Etiology and Pathogenesis

Causes of

Cushing’s SyndromeACTH

Most common cause

Cushing’s Syndrome

Redistribution of adipose:Truncal obesity, moon face, buffalo humpProtein wasting: limb musclesLoss of collagen: thin skin, striae, bruising

Cushing Syndrome: Clinical Manifestations

BUFFALO HUMP

STRIAE

MOON FACE

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

Cushing Syndrome: Clinical Manifestations

Characteristic physical features of individuals with 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.

Cushingism - Diagnosis

ACTH measurement Primary = low ACTHSecondary = high ACTH

Urinary free cortisol levels

Dexamethasone suppression test

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

Cushing Syndrome: Treatment

• 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

Hyperaldosteronism:

Adrenal Medulla Disorders

PheochromocytomaEtiology and Pathogenesis

Adrenal 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

• 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

Pheochromocytoma: Diagnosis and Treatment

Parathyroid Gland Disorders

What does PTH do?• Increases serum calcium & decrease serum phosphate1. Increase bone reabsorption of calcium2. Increase kidney reabsorption of calcium3. Decrease kidney reabsorption of phosphate4. Increase Vitamin D production in kidney

Parathyroid Gland

Parathyroid glands located at the upper and lower poles of the thyroid

Parathyroid Gland

Regulation of Calcium level

Regulation of Calcium level

osteoclasts

osteoblasts

Regulation of Blood Calcium

PTH• Serum calcium levels provide the

feedback to regulate parathyroid hormone (PTH) secretion

• Decrease in calcium causes PTH release

• Elevated calcium levels lead to suppression of PTH secretion

• PTH acts on bones, intestine, and renal tubules to increase calcium levels

• In bone, PTH increases osteoclastic activity

• PTH increases renal calcium reabsorption

Calcitonin • Calcitonin produced by thyroid

parafollicular cells also influences the processing of calcium by bone cells

• Calcitonin controls calcium content of blood by increasing bone formation by osteoblasts and inhibiting bone breakdown by osteoclasts

• Calcitonin decreases blood calcium levels and promotes conservation of hard bone matrix

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

Parathyroid Disorders

Stones, Bones, Groans, Moans

• Kidney stones• Bone-related

complications• Abdominal groans• Psychic moans

Etiology: Genetic origin, Parathyroid adenoma, Hyperplasia of

parathyroid glands

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

Hyperparathyroidism

A problem associated with chronic hyperparathyroidism 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

Hypoparathyroidism: 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.

Parathyroid Disorders

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

HYPOPARATHYROIDISM

What happens to serum calcium?Causes lowered threshold for nerve and muscle excitation

Clinical 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

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

Hypoparathyroidism

Antidiuretic Hormone

(ADH) Disorders

• 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

Antidiuretic Hormone

The single most important effect of antidiuretic hormone is to conserve body water by reducing the loss of water in urine

• 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 Hormone Disorders:

• 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

DIABETES INSIPIDUS: 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 Disorders

SIADH: Antidiuretic Hormone Disorders

REMEMBERWhat does Aldosterone do?

Clinical Manifestations

Diabetes Insipidus

• Polyuria, polydipsia

• Low urine specific gravity

• Hypernatremia due to water

deficit

• Dry mucous membranes, poor

skin turgor, decreased saliva

and sweat production

• Disorientation, lethargy,

seizures

SIADH

• Hyponatremia

• High urine osmolality

• Low serum osmolality

• Cell swelling

• Weakness, muscle cramps,

postural BP changes, poor skin

turgor, fatigue, anorexia, lethargy

• Confusion, seizures, coma

Treatment

Diabetes Insipidus

• Daily replacement of ADH

with desmopressin (DDAVP)

• Free access to fluids

• Home testing of urine

specific gravity

SIADH

• Free water restriction

• If severe symptoms, IV

administration of saline with

diuretics is used

• Hyponatremia should be

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