THYROID DISORDERS

The thyroid gland secretes thyroxine (T4) and smaller amts of tri-iodothyronine (T3) T3 is three to eight more times potent than T4 both modulate energy use, heat production and facilitate growth thyroid hormones exert metabolic effects in several body tissues increasing O2 consumption and heat production which increases metabolic rate

The thyroid gland

secretes thyroxine (T4) and smaller amts of tri-iodothyronine (T3)

T3 is three to eight more times potent than T4

both modulate energy use, heat production and facilitate growth

thyroid hormones exert metabolic effects in several body tissues increasing O2 consumption and heat production which increases metabolic rate

Thyroid hormones affect several organ systems which are lacking in hypothyroidism and exaggerate in hyperthyroidism Thyroid evaluation can be evaluated for functional status euthyroid, hypothyroid or Hyperthyroid etiology of dysfunction, or structural abnormalities causing dysfunction

Thyroid hormones affect several organ systems which are lacking in hypothyroidism and exaggerate in hyperthyroidism

Thyroid evaluation

can be evaluated for functional status

euthyroid,

hypothyroid or

Hyperthyroid

etiology of dysfunction, or structural abnormalities causing dysfunction

Tests of Serum Thyroid Hormone levels Total T4 and T3 measures total amt of hormone bound to thyroid binding proteins (TBG) and in the free state by radio-immunoassay Total T4 and Total T3 are elevated in hyperthyroidism and low in hypothyroidism increase in TBG from pregnancy or estrogen tx increases Total T4 and T3 in absence of hyperthyroidism cirrhosis and nephrotic syndrome can lower TBG and thus lower Total T4 and T3

Tests of Serum Thyroid Hormone levels

Total T4 and T3

measures total amt of hormone bound to thyroid binding proteins (TBG) and in the free state by radio-immunoassay

Total T4 and Total T3 are elevated in hyperthyroidism and low in hypothyroidism

increase in TBG from pregnancy or estrogen tx increases Total T4 and T3 in absence of hyperthyroidism

cirrhosis and nephrotic syndrome can lower TBG and thus lower Total T4 and T3

Apathetic hyperthyroidism pt’s present w/flat affect, emotional lability, weight loss, muscle weakness, atrial fibrillation resistant to tx or congestive ht failure Separation of nail beds (onycholysis) often occurs in Graves disease

Apathetic hyperthyroidism

pt’s present w/flat affect, emotional lability, weight loss, muscle weakness, atrial fibrillation resistant to tx or congestive ht failure

Separation of nail beds (onycholysis) often occurs in Graves disease

Lab findings elevated free T4 and a suppressed TSH confirm Dx for thyrotoxicosis increased uptake of 123I differentiates Graves disease from early sub-acute or Hashimoto’s thyroiditis 123I is low in sub-acute or Hashimoto’s thyroiditis MRI or ulta-sound can show orbital muscle enlargement w/o signs of opthalmopathy

Lab findings

elevated free T4 and a suppressed TSH confirm Dx for thyrotoxicosis

increased uptake of 123I differentiates Graves disease from early sub-acute or Hashimoto’s thyroiditis

123I is low in sub-acute or Hashimoto’s thyroiditis

MRI or ulta-sound can show orbital muscle enlargement w/o signs of opthalmopathy

Onset may be insidious Atrial fib is rare in young patient but occur in over 50% of males patient over 60 y/o Results from IgG antibodies against the TSH – receptor These antibodies are termed thyroid – stimulating antibodies (TSAb) May be responsible for thyroid enlargement in this disease

Onset may be insidious

Atrial fib is rare in young patient but occur in over 50% of males patient over 60 y/o

Results from IgG antibodies against the TSH – receptor

These antibodies are termed thyroid – stimulating antibodies (TSAb)

May be responsible for thyroid enlargement in this disease

The cardinal signs of Graves’ disease are: Diffuse goiter Vascular bruit can be heard over these goiters Pretibial myxoedema Tachycardia with a bounding pulse Exophthalmos Lid lag (usually on downward eye movement) Lid retraction Peri-orbital puffiness Increased lacrimation Conjunctival edema and ulceration

The cardinal signs of Graves’ disease are:

Diffuse goiter

Vascular bruit can be heard over these goiters

Pretibial myxoedema

Tachycardia with a bounding pulse

Exophthalmos

Lid lag (usually on downward eye movement)

Lid retraction

Peri-orbital puffiness

Increased lacrimation

Conjunctival edema and ulceration

In the elderly a ‘masked’ hyperthyroidism may be found. If presentation of a 60 y/o with atrial fib, heart failure and weight loss THINK HYPERTHYROIDISM!!! Diagnosis is made clinically with confirmation by labs: T3 and T4 and undetectable TSH levels if a single nodule is suspected a thyroid scan may provide useful information

In the elderly a ‘masked’ hyperthyroidism may be found. If presentation of a 60 y/o with atrial fib, heart failure and weight loss

THINK HYPERTHYROIDISM!!!

Diagnosis is made clinically with confirmation by labs:

T3 and T4 and undetectable TSH levels

if a single nodule is suspected a thyroid scan may provide useful information

Graves disease tx: Anti-thyroid drugs: thiocarbamide drugs, propylthiouracil, methimazole, and carbimazole block thyroid hormone synthesis propythiouracil partially inhibits peripheral conversion of T4 to T3 tx must be given until ds undergoes spontaneous remission (12 to 18 months) only 20-30% remain in remission pts who relapse must undergo surgery or radioactive iodine tx

Graves disease tx:

Anti-thyroid drugs: thiocarbamide drugs, propylthiouracil, methimazole, and carbimazole block thyroid hormone synthesis

propythiouracil partially inhibits peripheral conversion of T4 to T3

tx must be given until ds undergoes spontaneous remission (12 to 18 months)

only 20-30% remain in remission

pts who relapse must undergo surgery or radioactive iodine tx

Pts must be instructed to d/c med if sore throat or fever develops -> agranulocytosis beta blockers can be given at onset to alleviate cardiac abnormalities Radioactive iodine 131I in terms of cost, ease, efficacy and short-term side-effects, radioactive iodine has benefits that exceed anti-thyroid drugs or surgery pts w/severe thyrotoxicosis, or very large thyroids should tx’ed first w/anti-thyroid drugs to become euthyroid

Pts must be instructed to d/c med if sore throat or fever develops -> agranulocytosis

beta blockers can be given at onset to alleviate cardiac abnormalities

Radioactive iodine 131I

in terms of cost, ease, efficacy and short-term side-effects, radioactive iodine has benefits that exceed anti-thyroid drugs or surgery

pts w/severe thyrotoxicosis, or very large thyroids should tx’ed first w/anti-thyroid drugs to become euthyroid

Pt’s become euthyroid w/radioactive iodine in 3wks to 6 months 10-20% become hypothyroid in first yr 50-80% who receive radioactive tx eventually become hypothyroid Surgery: subtotal thyroidectomy is tx of choice in pt’s as a treatment for thyroid cancer when an enlarged thyroid (goiter) or multiple nodules cause cosmetic, breathing or swallowing problems in a pregnant woman, when her hyperthyroidism is not controllable by antithyroid drugs, and requires immediate treatment

Pt’s become euthyroid w/radioactive iodine in 3wks to 6 months

10-20% become hypothyroid in first yr

50-80% who receive radioactive tx eventually become hypothyroid

Surgery: subtotal thyroidectomy is tx of choice in

pt’s as a treatment for thyroid cancer

when an enlarged thyroid (goiter) or multiple nodules cause cosmetic, breathing or swallowing problems

in a pregnant woman, when her hyperthyroidism is not controllable by antithyroid drugs, and requires immediate treatment

when other forms of treatment for hyperthyroidism -- i.e,. antithyroid drugs or radioactive iodine have not been effective. (This is applicable in the U.S. Outside the U.S., surgery is sometimes performed as a hyperthyroidism treatment before or instead of radioactive iodine.) in children, if the practitioner or parent wishes to avoid radioactive iodine when the patient refuses antithyroid medications or radioactive iodine when a patient wants to try to get pregnant quickly after treatment

when other forms of treatment for hyperthyroidism -- i.e,. antithyroid drugs or radioactive iodine have not been effective. (This is applicable in the U.S. Outside the U.S., surgery is sometimes performed as a hyperthyroidism treatment before or instead of radioactive iodine.)

in children, if the practitioner or parent wishes to avoid radioactive iodine

when the patient refuses antithyroid medications or radioactive iodine

when a patient wants to try to get pregnant quickly after treatment

Toxic adenoma solitary toxic nodules occur more frequently in older pt’s usually benign S&S are those of thyrotoxicosis TSH is suppressed w/ high levels of T3 w/a moderate elevation of T4 thyroid scan shows a “hot” nodule usually managed w/131I, may need unilateral thyroidectomy if nodule is large

Toxic adenoma

solitary toxic nodules occur more frequently in older pt’s

usually benign

S&S are those of thyrotoxicosis

TSH is suppressed w/ high levels of T3 w/a moderate elevation of T4

thyroid scan shows a “hot” nodule

usually managed w/131I, may need unilateral thyroidectomy if nodule is large

Toxic Multi-nodular Goiter occurs in older pts w/long standing multi-nodular goiter S&S usually are tachycardia, heart failure and arrthymias PE reveals a multi-nodular goiter TSH is suppressed, markedly elevated T3 and a moderately elevated T4 tx of choice is subtotal thyroidectomy heart disease may be contraindication to surgery toxic nodules tx’ed w/131I

Toxic Multi-nodular Goiter

occurs in older pts w/long standing multi-nodular goiter

S&S usually are tachycardia, heart failure and arrthymias

PE reveals a multi-nodular goiter

TSH is suppressed, markedly elevated T3 and a moderately elevated T4

tx of choice is subtotal thyroidectomy

heart disease may be contraindication to surgery

toxic nodules tx’ed w/131I

Thyroiditis can be classified as acute, sub-acute, or chronic may eventually result in hypothyroidism easily differentiated from other causes of hyperthyroidism by a suppressed 123I uptake Acute suppurative thyroiditis is a rare complication of septicemia S&S: high fever, redness over gland, tenderness may be confused w/sub-acute thyroiditis if blood cultures are neg, needle aspiration can identify organism; tx w/antibiotics or Incision &Drainage (I&D)

Thyroiditis

can be classified as acute, sub-acute, or chronic

may eventually result in hypothyroidism

easily differentiated from other causes of hyperthyroidism by a suppressed 123I uptake

Acute suppurative thyroiditis is a rare complication of septicemia

S&S: high fever, redness over gland, tenderness

may be confused w/sub-acute thyroiditis

if blood cultures are neg, needle aspiration can identify organism; tx w/antibiotics or Incision &Drainage (I&D)

Sub-acute thyroiditis (de Quervain’s thyroiditis or granulomatous thyroiditis) an acute inflammatory disorder probably due to viral infection resolves in a few months in 90% of pts S&S: hyperthyroidism, fever, anterior neck pain; classical feature is an exquisitely tender gland labs vary w/course of ds: initially T4 is elevated, TSH is suppressed, 123I uptake is very low may fluctuate from euthyroid to hypothyroid and back

Sub-acute thyroiditis (de Quervain’s thyroiditis or granulomatous thyroiditis)

an acute inflammatory disorder probably due to viral infection

resolves in a few months in 90% of pts

S&S: hyperthyroidism, fever, anterior neck pain; classical feature is an exquisitely tender gland

labs vary w/course of ds: initially T4 is elevated, TSH is suppressed, 123I uptake is very low

may fluctuate from euthyroid to hypothyroid and back

Increase in 123I on scan reflects recovery of gland tx is usually non-steroidal anti-inflammatory drugs (NSAID’s), short course of prednisone may be needed if fever and pain are severe; levothyroxine may be needed for clinical symptoms of hypothyroidism

Increase in 123I on scan reflects recovery of gland

tx is usually non-steroidal anti-inflammatory drugs (NSAID’s), short course of prednisone may be needed if fever and pain are severe; levothyroxine may be needed for clinical symptoms of hypothyroidism

Chronic Thyroiditis (Hashimoto’s thyroiditis, lymphocytic thyroiditis) results from destruction of normal thyroidal architecture by lymphocytic infiltration resulting in hypothyroidism and goiter Hashimoto’s thyroiditis is more common in women and most common cause of hypothyroidism and goiter in the US

Chronic Thyroiditis (Hashimoto’s thyroiditis, lymphocytic thyroiditis)

results from destruction of normal thyroidal architecture by lymphocytic infiltration resulting in hypothyroidism and goiter

Hashimoto’s thyroiditis is more common in women and most common cause of hypothyroidism and goiter in the US

Occasionally pts may have transient hyperthyroidism w/ low 123I uptake gland non-tender to palpation serum T4 and T3 are nl or low, when low TSH is elevated FNA reveals lymphocytes and Hurthle cells (enlarged basophilic follicular cells) hypothyroidism and goiter are indications for levothyroxine tx

Occasionally pts may have transient hyperthyroidism w/ low 123I uptake

gland non-tender to palpation

serum T4 and T3 are nl or low, when low TSH is elevated

FNA reveals lymphocytes and Hurthle cells (enlarged basophilic follicular cells)

hypothyroidism and goiter are indications for levothyroxine tx

Thyrotoxicosis Factitia presents w/ clinical features of thyrotoxicosis from ingestion of large amts of thyroxine often occurs in an attempt to lose weight TSH is suppressed, T4 and T3 levels are elevated 123I uptake is absent pts may require psychotherapy

Thyrotoxicosis Factitia

presents w/ clinical features of thyrotoxicosis from ingestion of large amts of thyroxine

often occurs in an attempt to lose weight

TSH is suppressed, T4 and T3 levels are elevated

123I uptake is absent

pts may require psychotherapy

Rare causes of thyrotoxicosis Struma ovarii: occurs when an ovarian teratoma contains thyroid tissue and secrets thyroid hormone dx confirmed by 123I uptake in pelvis on body scan Hydatidiform mole: due to proliferation and swelling of trophoblasts during pregnancy w/excess production of chorionic gonatrophin which has intrinsic TSH-like activity form sharing a common TSH alpha-subunit; tx surgery

Rare causes of thyrotoxicosis

Struma ovarii: occurs when an ovarian teratoma contains thyroid tissue and secrets thyroid hormone

dx confirmed by 123I uptake in pelvis on body scan

Hydatidiform mole: due to proliferation and swelling of trophoblasts during pregnancy w/excess production of chorionic gonatrophin which has intrinsic TSH-like activity form sharing a common TSH alpha-subunit; tx surgery

Hypothyroidism due to deficiency of thyroid hormone in infants and children hypothyroidism causes growth and development retardation; can result in mental and motor retardation congenital causes include: agenesis (complete absence of thyroid gland), hypoplastic thyroid, thyroid dyshormogenesis and central hypothyroidism

Hypothyroidism

due to deficiency of thyroid hormone

in infants and children hypothyroidism causes growth and development retardation; can result in mental and motor retardation

congenital causes include:

agenesis (complete absence of thyroid gland),

hypoplastic thyroid,

thyroid dyshormogenesis and

central hypothyroidism

Also known as Myxoedema results from the reduced secretion of T3 and T4 from the thyroid. Hashimoto’s accounts for over 90% of the cases Secondary hypothyroidism is much less common and is caused by pituitary disease [ absence of TSH leads to atrophy of thyroid gland]

Also known as Myxoedema results from the reduced secretion of T3 and T4 from the thyroid.

Hashimoto’s accounts for over 90% of the cases

Secondary hypothyroidism is much less common and is caused by pituitary disease [ absence of TSH leads to atrophy of thyroid gland]

Affects all the systems of the body, but the wide range of clinical features means that the diagnosis will be missed. Dominant features in children are: Reduction in growth velocity Arrest of pubertal development Clinical presentation in adults may vary greatly

Affects all the systems of the body, but the wide range of clinical features means that the diagnosis will be missed.

Dominant features in children are:

Reduction in growth velocity

Arrest of pubertal development

Clinical presentation in adults may vary greatly

Non – pitting edema [most marked on the skin of the eyelids and hands]  often associated with loss of eyebrow and scalp hair Dryness of the skin Reduced body hair Bradycardia Hypothermia Pericardial and pleural effusions [ can occur and is life threatening]

Non – pitting edema [most marked on the skin of the eyelids and hands]  often associated with loss of eyebrow and scalp hair

Dryness of the skin

Reduced body hair

Bradycardia

Hypothermia

Pericardial and pleural effusions [ can occur and is life threatening]

Diagnosis is based on Clinical suspicion Prolonged relaxation time of peripheral reflexes A low voltage EKG Biochemical estimation of T4 and TSH Thyroid Antibodies Assays Causes of hypothyroidism Autoimmune (most common Hashimotos) Drugs induced (Lithium carbonate- which like iodide inhibits the release of thyroid hormones  goiter and hypothyroidism

Diagnosis is based on

Clinical suspicion

Prolonged relaxation time of peripheral reflexes

A low voltage EKG

Biochemical estimation of T4 and TSH

Thyroid Antibodies Assays

Causes of hypothyroidism

Autoimmune (most common Hashimotos)

Drugs induced (Lithium carbonate- which like iodide inhibits the release of thyroid hormones  goiter and hypothyroidism

Adult hypothyroidism results in slowed metabolic processes which are reversible w/tx hypothyroidism is usually primary (thyroid failure), can be secondary (pituitary deficiency) or tertiary (hypothalamus deficiency), or from resistance at thyroid hormone receptor. In adults, auto-immune thyroiditis (Hashimoto’s thyroiditis) is the most common cause

Adult hypothyroidism results in slowed metabolic processes which are reversible w/tx

hypothyroidism is usually primary (thyroid failure), can be secondary (pituitary deficiency) or tertiary (hypothalamus deficiency), or from resistance at thyroid hormone receptor.

In adults, auto-immune thyroiditis (Hashimoto’s thyroiditis) is the most common cause

Iatrogenic causes include; 131I tx, thyroidectomy, and tx w/amiodarome or lithium, iodine excess or deficiency can cause hypothyroidism clinical presentations depends on age of onset infants w/congenital hypothyroidism (cretinism) may have feeding problems, open posterior fontanelle, hypotonia, and/or edematous hands and face short stature, mental retardation and delayed puberty can occur if not tx’ed early

Iatrogenic causes include; 131I tx, thyroidectomy, and tx w/amiodarome or lithium, iodine excess or deficiency can cause hypothyroidism

clinical presentations depends on age of onset

infants w/congenital hypothyroidism (cretinism) may have feeding problems, open posterior fontanelle, hypotonia, and/or edematous hands and face

short stature, mental retardation and delayed puberty can occur if not tx’ed early

In adults, hypothyroidism usually develops insidiously S&S: fatigue, lethargy, cold intolerance, weakness, menstrual abnormalities, cool dry skin, coarse hair or hair loss, wght gain, constipation, brittle nails, delayed tendon reflexes (severe hypothyroidism), myxedema (severe hypothyroidism), bradycardia severe untreated hypothyroidism can result in myxedema coma S&S: hypothermia, extreme weakness, stupor, hypoventilation, hypoglycemia and hyponatremia often precipitated by by exposure, infection, psychoacitve drugs

In adults, hypothyroidism usually develops insidiously

S&S: fatigue, lethargy, cold intolerance, weakness, menstrual abnormalities, cool dry skin, coarse hair or hair loss, wght gain, constipation, brittle nails, delayed tendon reflexes (severe hypothyroidism), myxedema (severe hypothyroidism), bradycardia

severe untreated hypothyroidism can result in myxedema coma

S&S: hypothermia, extreme weakness, stupor, hypoventilation, hypoglycemia and hyponatremia

often precipitated by by exposure, infection, psychoacitve drugs

Lab eval serum TSH is elevated, and low free T4 pts w/ mild hypothyroidism; TSH is elevated w/a low to nl T4 due to pituitary sensitivity to decreased levels of circulating T3 resulting in increased TSH output TSH levels >8 microU/ml should receive tx w/levothyroxine even w/ nl levels of T4

Lab eval

serum TSH is elevated, and low free T4

pts w/ mild hypothyroidism; TSH is elevated w/a low to nl T4 due to pituitary sensitivity to decreased levels of circulating T3 resulting in increased TSH output

TSH levels >8 microU/ml should receive tx w/levothyroxine even w/ nl levels of T4

Secondary hypothyroidism has a low or low nl morning serum TSH in the setting of hypothalamic or pituitary dysfunction often serum total and free T4 are at lower limit of nl secondary hypothyroidism may be due to biologically inactive, but immunulogically active TSH causing morning TSH levels to be only mildly subnormal or from nocturnal surge of TSH

Secondary hypothyroidism

has a low or low nl morning serum TSH in the setting of hypothalamic or pituitary dysfunction

often serum total and free T4 are at lower limit of nl

secondary hypothyroidism may be due to biologically inactive, but immunulogically active TSH causing morning TSH levels to be only mildly subnormal or from nocturnal surge of TSH

Central (Secondary) Hypothyroidism a diurnal test w/ a mid-night value of serum TSH level <1.5 times the afternoon value is indicative of central hypothyroidism Hypothyroidism is associated w/ other abnormal labs hypercholesterolemia, elevated creatinine phosphokinase w/ and increase in MB bands (fraction characteristic of cardiac muscle), anemia (normocytic, normochromic but may be macrocytic (vit B deficiency from pernicious anemia) or microcytic (nutritional deficiency or menstrual blood loss)

Central (Secondary) Hypothyroidism

a diurnal test w/ a mid-night value of serum TSH level <1.5 times the afternoon value is indicative of central hypothyroidism

Hypothyroidism is associated w/ other abnormal labs

hypercholesterolemia,

elevated creatinine phosphokinase w/ and increase in MB bands (fraction characteristic of cardiac muscle),

anemia (normocytic, normochromic but may be macrocytic (vit B deficiency from pernicious anemia) or microcytic (nutritional deficiency or menstrual blood loss)

Hypothyroidism Differential Dx initial S&S of hypothyroidism are subtle early dx depends S&S, early symptoms often overlooked are: menorrhagia, arthralgias and myalgias euthyroid sick syndrome: total and occasionally free T4 are low, TSH mildly elevated must not give these pts levothyroxine can be distinguished from hypothyroidism by absence of goiter, absence of antithyroid antibodies and elevated rT3 levels as well as S&S

Hypothyroidism Differential Dx

initial S&S of hypothyroidism are subtle

early dx depends S&S, early symptoms often overlooked are: menorrhagia, arthralgias and myalgias

euthyroid sick syndrome: total and occasionally free T4 are low, TSH mildly elevated

must not give these pts levothyroxine

can be distinguished from hypothyroidism by absence of goiter, absence of antithyroid antibodies and elevated rT3 levels as well as S&S

Hypothyroidism tx synthetic L-thyroxine Tri-iodothyronine should be avoided due to rapid absorption and disappearance from stream causing uneven blood levels therapeutic responses should be evaluated by S&S and TSH levels pt’s w/myxedema coma: IV L-thyroxine, IV hydrocortisone, IV fluids many pts recover in 2-3days w/full recovery

Hypothyroidism tx

synthetic L-thyroxine

Tri-iodothyronine should be avoided due to rapid absorption and disappearance from stream causing uneven blood levels

therapeutic responses should be evaluated by S&S and TSH levels

pt’s w/myxedema coma: IV L-thyroxine, IV hydrocortisone, IV fluids

many pts recover in 2-3days w/full recovery

Goiter enlargement of thyroid gland pt’s may be euthyroid (simple goiter), hyperthyroid (toxic nodular goiter or Grave’s ds) or hypothyroid (non-toxic goiter or Hashimoto’s thyroiditis), may also be focal (adenoma or carcinoma) in non-toxic goiter; inadequate thyroid hormone synthesis leads to TSH stimulation resulting in an enlarged thyroid gland -> iodine deficiency was most common cause hormone replacement quickly shrinks the goiter

Goiter

enlargement of thyroid gland

pt’s may be euthyroid (simple goiter), hyperthyroid (toxic nodular goiter or Grave’s ds) or hypothyroid (non-toxic goiter or Hashimoto’s thyroiditis), may also be focal (adenoma or carcinoma)

in non-toxic goiter; inadequate thyroid hormone synthesis leads to TSH stimulation resulting in an enlarged thyroid gland -> iodine deficiency was most common cause

hormone replacement quickly shrinks the goiter

Dietary goitrogens can cause goiter iodine is most common; lithium, cabbage goiters may become very large causing respiratory distress, dysphagia, or hoarseness surgery indicated if obstructive symptoms are present Solitary Thyroid Nodules thyroid nodules are common; detected in about 4% of population and about 50% at autopsy Benign thyroid nodules are usually benign cyst, follicular adenomas, nodular thyroiditis, or colloid nodules

Dietary goitrogens can cause goiter

iodine is most common; lithium, cabbage

goiters may become very large causing respiratory distress, dysphagia, or hoarseness

surgery indicated if obstructive symptoms are present

Solitary Thyroid Nodules

thyroid nodules are common; detected in about 4% of population and about 50% at autopsy

Benign thyroid nodules are usually benign cyst, follicular adenomas, nodular thyroiditis, or colloid nodules

Although a majority are benign, some are malignant major etiologic factor for thyroid cancer is childhood or adolescent exposure to head and neck radiation pts w/hx of irradiation should have their thyroids palpated q 2yrs “ cold “lesions require FNA because benign nodules can be “cold” benign nodules should be tx’ed w/L-thyroxine w/ follow up in 6 months

Although a majority are benign, some are malignant

major etiologic factor for thyroid cancer is childhood or adolescent exposure to head and neck radiation

pts w/hx of irradiation should have their thyroids palpated q 2yrs

“ cold “lesions require FNA because benign nodules can be “cold”

benign nodules should be tx’ed w/L-thyroxine w/ follow up in 6 months

In general, the recommended dosage is: GOITER: ADULTS: 100-150 (200) mcg daily. CHILDREN UP TO AGE 14: 50-100 (150) mcg daily. PREVENTIVE TREATMENT FOR RELAPSE AFTER GOITER REMOVAL: 100 mcg daily. THYROID DEFICIENCY: ADULTS: Initial dose of 50 mcg daily (for approximately two weeks). The daily dose may be increased by 50 mcg by intervals of approximately 14-15 days until reaching the maintenance dose of 100-200 (300) mcg daily; 2-2.5 mcg/kilo of body weight daily on the average. SMALL CHILDREN: 0-6 months: 10 mcg/kilo of body weight/day; 6-12 months: 8 mcg/kg of body weight/day; 1-5 years: 6 mcg mcg/kg of body weight/day; 5-10 years: 4 mcg/kg of body weight/ day.

In general, the recommended dosage is:

GOITER: ADULTS: 100-150 (200) mcg daily. CHILDREN UP TO AGE 14: 50-100 (150) mcg daily.

PREVENTIVE TREATMENT FOR RELAPSE AFTER GOITER REMOVAL: 100 mcg daily.

THYROID DEFICIENCY:

ADULTS: Initial dose of 50 mcg daily (for approximately two weeks). The daily dose may be increased by 50 mcg by intervals of approximately 14-15 days until reaching the maintenance dose of 100-200 (300) mcg daily; 2-2.5 mcg/kilo of body weight daily on the average.

SMALL CHILDREN: 0-6 months: 10 mcg/kilo of body weight/day; 6-12 months: 8 mcg/kg of body weight/day; 1-5 years: 6 mcg mcg/kg of body weight/day; 5-10 years: 4 mcg/kg of body weight/ day.

Thyroid Carcinoma most common type is papillary carcinoma (60%), Follicular carcinoma (20%), anaplastic carcinoma (14%), medullary carcinoma (5%) and lymphoma (1%) papillary carcinoma is associated w/ lymph node spread and local invasion poor prognosis : thyroid capsule invasion, sz > 2.5 cm, age of onset >45 y/o, tall cell variant, and lymph node involvement

Thyroid Carcinoma

most common type is papillary carcinoma (60%), Follicular carcinoma (20%), anaplastic carcinoma (14%), medullary carcinoma (5%) and lymphoma (1%)

papillary carcinoma is associated w/ lymph node spread and local invasion

poor prognosis : thyroid capsule invasion, sz > 2.5 cm, age of onset >45 y/o, tall cell variant, and lymph node involvement

Follicular carcinoma is a bit more aggressive than papillary carcinoma Anaplastic carcinoma occurs in >50 y/o, very aggressive,causes pain, dysphagia, and hoarseness; pt’s die within 1st yr Medullary carcinoma is derived from calcitonin-producing follicular cells may be sporadic or familial measurement of serum calcitonin levels can confirm etiology

Follicular carcinoma is a bit more aggressive than papillary carcinoma

Anaplastic carcinoma occurs in >50 y/o, very aggressive,causes pain, dysphagia, and hoarseness; pt’s die within 1st yr

Medullary carcinoma is derived from calcitonin-producing follicular cells

may be sporadic or familial

measurement of serum calcitonin levels can confirm etiology

Thyroid Carcinoma tx lobectomy for papillary or follicular carcinomas <1.5 cm in sz pts require lifelong L-thyroxine tx and yearly thyroid exams anaplastic carcinoma requires an isthmusectomy to confirm dx and prevent tracheal compression

Thyroid Carcinoma tx

lobectomy for papillary or follicular carcinomas <1.5 cm in sz

pts require lifelong L-thyroxine tx and yearly thyroid exams

anaplastic carcinoma requires an isthmusectomy to confirm dx and prevent tracheal compression

Prognosis of well differentiated thyroid carcinoma is good age of onset most important indicator men >40 and women >50 y/o have higher recurrence rate of death 5 yr survival rate for invasive medullary carcinoma is 50% mean survival for anaplastic carcinoma is 6 months

Prognosis of well differentiated thyroid carcinoma is good

age of onset most important indicator

men >40 and women >50 y/o have higher recurrence rate of death

5 yr survival rate for invasive medullary carcinoma is 50%

mean survival for anaplastic carcinoma is 6 months

The Parathyroid Glands four are situated around thyroid occasionally one may be in thyroid or in mediastinum Parathyroid hormone (PTH) secretion is controlled by serum ionized calcium primarily serum level falls -> PTH secretion stimulated serum level rises above nl ->secretion suppressed main function -> defend against hypocalcemia

The Parathyroid Glands

four are situated around thyroid

occasionally one may be in thyroid or in mediastinum

Parathyroid hormone (PTH)

secretion is controlled by serum ionized calcium primarily

serum level falls -> PTH secretion stimulated

serum level rises above nl ->secretion suppressed

main function -> defend against hypocalcemia

PTH actions bone reabsorption stimulated by osteoclasts causes release of phosphate and calcium into extracellular fluid (ECF) stimulation of renal tubular reabsorption of calcium (and magnesium) inhibition of renal tubular reabsorption of bicarbonate and phosphate stimulation of synthesis of active form of vitamin D, calcitrol PTH indirectly enhances intestinal absorption of calcium

PTH actions

bone reabsorption stimulated by osteoclasts

causes release of phosphate and calcium into extracellular fluid (ECF)

stimulation of renal tubular reabsorption of calcium (and magnesium)

inhibition of renal tubular reabsorption of bicarbonate and phosphate

stimulation of synthesis of active form of vitamin D, calcitrol

PTH indirectly enhances intestinal absorption of calcium

Hypercalcemia common may be found in serious underlying ds or in asymptomatic patients on routine labs Primary Hyperparathyroidism mcc (metastatic calcinosis cutis) in adults malignancy mcc in hospitalized pt’s >90% of pts w/hypercalcemia have either Primary hyperparathyroidism or a malignancy

Hypercalcemia

common

may be found in serious underlying ds or in asymptomatic patients on routine labs

Primary Hyperparathyroidism mcc (metastatic calcinosis cutis) in adults

malignancy mcc in hospitalized pt’s

>90% of pts w/hypercalcemia have either Primary hyperparathyroidism or a malignancy

Primary Hyperparathyroidism S&S: CNS : lethargy progressing to coma; Neuromuscular: proximal muscle weakness, hyporeflexia GI: N/V, anorexia, constipation, peptic ulcer ds (PUD), pancreatitis Renal: polyuria, polydipsia, decreased urine concentration, impaired renal function, nephrocalcinosis, nephrolithiasis Cardiac: HTN, short QT interval, bradycardia, increased sensitivity to digitalis

Primary Hyperparathyroidism

S&S: CNS : lethargy progressing to coma; Neuromuscular: proximal muscle weakness, hyporeflexia GI: N/V, anorexia, constipation, peptic ulcer ds (PUD), pancreatitis Renal: polyuria, polydipsia, decreased urine concentration, impaired renal function, nephrocalcinosis, nephrolithiasis Cardiac: HTN, short QT interval, bradycardia, increased sensitivity to digitalis

Arthralgias, bone pain, bone cysts, gout , pseudogout due to effects of PTH on bones and joints Etiol: peak incidence 20-40’s more common in women 85% of cases present w/single parathyroid gland enlargement (Parathyroid adenoma) can appear as a familial disorder or in association w/ other disorders causing hypersecretion of PTH

Arthralgias, bone pain, bone cysts, gout , pseudogout

due to effects of PTH on bones and joints

Etiol: peak incidence 20-40’s

more common in women

85% of cases present w/single parathyroid gland enlargement (Parathyroid adenoma)

can appear as a familial disorder or in association w/ other disorders causing hypersecretion of PTH

Labs: serum calcium levels continuously elevated or intermittently serum phosphate usually low elevated urine calcium levels help distinguish pts with primary hyperparathyroidism from familial hypocalciuric hypercalcemia most pts w/primary hyperparathyroidism show no radiographic evidence of bone ds if found, most common finding is osteopenia

Labs:

serum calcium levels continuously elevated or intermittently

serum phosphate usually low

elevated urine calcium levels help distinguish pts with primary hyperparathyroidism from familial hypocalciuric hypercalcemia

most pts w/primary hyperparathyroidism show no radiographic evidence of bone ds

if found, most common finding is osteopenia

Primary Hyperparathyroidisn DX is based on finding hypercalcemia w/ an elevate or inappropriately nl PTH lvl 24hr urine should be done to R/O familial hypocalciuric hypercalcemia nodule in neck more likely be a thyroid nodule than a parathyroid adenoma Tx: surgical removal for symptomatic pts

Primary Hyperparathyroidisn

DX is based on finding hypercalcemia w/ an elevate or inappropriately nl PTH lvl

24hr urine should be done to R/O familial hypocalciuric hypercalcemia

nodule in neck more likely be a thyroid nodule than a parathyroid adenoma

Tx: surgical removal for symptomatic pts

Surgical tx for asymptomatic pts when: serum calcium lvl 1.0-1.6 mg/dl above upper limit hx of life threatening hypercalcemia kidney stone found of abdominal x-ray creatinine clearance reduced by 30% reduced bone density >2 standard deviations below age and sex controls Hypercalcemia of malignancy occurs in 20-30% of cancer pt’s during course of their injury

Surgical tx for asymptomatic pts when:

serum calcium lvl 1.0-1.6 mg/dl above upper limit

hx of life threatening hypercalcemia

kidney stone found of abdominal x-ray

creatinine clearance reduced by 30%

reduced bone density >2 standard deviations below age and sex controls

Hypercalcemia of malignancy

occurs in 20-30% of cancer pt’s during course of their injury

Hypercalcemia frequently seen in pts w/breast cancer, squamous carcinoma of hd, neck, lung, and kidney and hematologic malignancies , T-cell lymphomas pts w/malignancies, localized bone destruction often important cause of hypercalcemia hypercalcemia due to vitamin D intoxication can be due to excess ingestion of vit D or endogenous production

Hypercalcemia

frequently seen in pts w/breast cancer, squamous carcinoma of hd, neck, lung, and kidney and hematologic malignancies , T-cell lymphomas

pts w/malignancies, localized bone destruction often important cause of hypercalcemia

hypercalcemia due to vitamin D intoxication can be due to excess ingestion of vit D or endogenous production

Tx of Hypercalcemia aimed toward reversing underlying abnormality tx indicate if symptomatic or serum calcium levels > or equal to 13mg/dl hydration furosemide (or etharcrynic acid) loop diuretics facilitate sodium and calcium excretion glucocorticoids may lower serum lvls calcitonin inhibits osteoclastic bone reabsorption phosphate (caution w/severe hypercalcemia; may cause metastic calcification

Tx of Hypercalcemia

aimed toward reversing underlying abnormality

tx indicate if symptomatic or serum calcium levels > or equal to 13mg/dl

hydration

furosemide (or etharcrynic acid) loop diuretics facilitate sodium and calcium excretion

glucocorticoids may lower serum lvls

calcitonin inhibits osteoclastic bone reabsorption

phosphate (caution w/severe hypercalcemia; may cause metastic calcification

Biophosphates inhibit osteoclast mediated bone absorption gallium nitrate in selected pts w/malignancy dialysis Hypocalcemia an abnormal reduction in serum ionized calcium concentration causes: hypoparathyroidism, parathyroid hormone resistance, Vit D deficiency or resistance, chronic renal failure, hyperphosphatemia, prostate CA, acute pancreatitis, gram-neg sepsis, drugs

Biophosphates inhibit osteoclast mediated bone absorption

gallium nitrate in selected pts w/malignancy

dialysis

Hypocalcemia

an abnormal reduction in serum ionized calcium concentration

causes: hypoparathyroidism, parathyroid hormone resistance, Vit D deficiency or resistance, chronic renal failure, hyperphosphatemia, prostate CA, acute pancreatitis, gram-neg sepsis, drugs

Chronic renal failure is the mcc of hypocalcemia S&S: often asymptomatic most frequent symptoms are: neuromuscular irritability, paresthesias (hands, ft, circumoral, muscle cramps) in severe hypocalcemia bronchospasm, laryngeal stridor, diplopia, blepharospasm, and seizures QT prolongation, CHF, (+) chovtecks sign, (+) Troussseu sign

Chronic renal failure is the mcc of hypocalcemia

S&S: often asymptomatic

most frequent symptoms are: neuromuscular irritability, paresthesias (hands, ft, circumoral, muscle cramps)

in severe hypocalcemia

bronchospasm, laryngeal stridor, diplopia, blepharospasm, and seizures

QT prolongation, CHF, (+) chovtecks sign, (+) Troussseu sign

Lab findings hypocalcemia due to hypoparathyroidism characterized by hyperphosphatemia serum PTH is undetectable or inappropriately low for serum calcium level hypocalcemia caused by malabsorption or vit D deficiency serum inorganic phosphate lvs are low or nl, serum PTH increased TX: calcium or vit D, thiazide diuretic in absence of PTH

Lab findings

hypocalcemia due to hypoparathyroidism characterized by hyperphosphatemia

serum PTH is undetectable or inappropriately low for serum calcium level

hypocalcemia caused by malabsorption or vit D deficiency

serum inorganic phosphate lvs are low or nl, serum PTH increased

TX: calcium or vit D, thiazide diuretic in absence of PTH

Adrenal Gland lie at superior pole of each kidney composed of two distinct regions: cortex medulla Adrenal cortex three anatomical zones outer: zona glumerulosa  aldosterone intermediate: zona fascicualata  cortisol inner: zona reticularis  adreanal androgens

Adrenal Gland

lie at superior pole of each kidney

composed of two distinct regions:

cortex

medulla

Adrenal cortex

three anatomical zones

outer: zona glumerulosa  aldosterone

intermediate: zona fascicualata  cortisol

inner: zona reticularis  adreanal androgens

Adrenal medulla functionally related to sympathetic nervous system  catecholemines (norepinephrine and epinephrine) Synthesis of all steroids  cholesterol Glucocorticoids affect metabolism, CV function, behavior and inflammatory/immune response

Adrenal medulla

functionally related to sympathetic nervous system  catecholemines (norepinephrine and epinephrine)

Synthesis of all steroids  cholesterol

Glucocorticoids affect metabolism, CV function, behavior and inflammatory/immune response

Cortisol natural human glucocorticoid secreted by adrenal glands in response to ultradian, circadian, and stress-induced hormonal stimulation by adrenocorticotropin hormone (ACTH: corticotropin) plasma levels; highest in morning secretion of ACTH  pituitary; regulated by corticotropin-releasing hormone (CRH) and vasopressin

Cortisol

natural human glucocorticoid

secreted by adrenal glands in response to ultradian, circadian, and stress-induced hormonal stimulation by adrenocorticotropin hormone (ACTH: corticotropin)

plasma levels; highest in morning

secretion of ACTH  pituitary; regulated by corticotropin-releasing hormone (CRH) and vasopressin

Glucocorticoids exert negative feedback on CRH and ACTH secretion Hypothalamic-pituitary-adrenal (HPA) axis interacts w/ and influences function of reproductive, growth, and thyroid axes Renin-angiotensin system  aldosterone angiotensin II predominant regulator of aldosterone

Glucocorticoids exert negative feedback on CRH and ACTH secretion

Hypothalamic-pituitary-adrenal (HPA) axis interacts w/ and influences function of reproductive, growth, and thyroid axes

Renin-angiotensin system  aldosterone

angiotensin II predominant regulator of aldosterone

Adrenal androgens dehydroepiandosterone (DHEA) dehydroepiandosterone sulfate (DHEAS) androstenedione all synthesized in zona reticularis under influence of ACTH no intrinsic androgenic activity contribute to androgenicity by peripheral conversion to testosterone and dihydrotestosterone

Adrenal androgens

dehydroepiandosterone (DHEA)

dehydroepiandosterone sulfate (DHEAS)

androstenedione

all synthesized in zona reticularis under influence of ACTH

no intrinsic androgenic activity

contribute to androgenicity by peripheral conversion to testosterone and dihydrotestosterone

Adrenal insufficiency primary: resulting from destruction or dysfunction of adrenal cortex secondary: ACTH hyposecretion Addison’s Disease autoimmune destruction of adrenal glands mcc of primary adrenal insufficiency glucocorticoid and mineralcorticoids diminished if untreated; fatal approx 70% of pts have antiadrenal antibodies

Adrenal insufficiency

primary: resulting from destruction or dysfunction of adrenal cortex

secondary: ACTH hyposecretion

Addison’s Disease

autoimmune destruction of adrenal glands

mcc of primary adrenal insufficiency

glucocorticoid and mineralcorticoids diminished

if untreated; fatal

approx 70% of pts have antiadrenal antibodies

Tuberculosis was formerly mcc of adrenal insufficiency; now account for <20% calcified glands  50% of cases of tuberculous adrenal insufficiency Congenital causes : congenital adrenal hyperplasia, adrenal unresponsiveness to ACTH, congenital adrenal hypoplasia, and two demyelinating lipid metabolism disorders

Tuberculosis was formerly mcc of adrenal insufficiency; now account for <20%

calcified glands  50% of cases of tuberculous adrenal insufficiency

Congenital causes : congenital adrenal hyperplasia, adrenal unresponsiveness to ACTH, congenital adrenal hypoplasia, and two demyelinating lipid metabolism disorders

Adrenal insufficiency commonly presents as: weight loss, increasing fatigue, vomiting, nausea, diarrhea and salt craving muscle and jt pain , abdominal pain, postural dizziness increased pigmentation (extensor surfaces, creases of palms, and buccal mucosa) lab: hyponatremia and hyperkalemia, metabolic acidosis, azotemia, hypercalcemia, lymphocytosis, eosinophilia

Adrenal insufficiency

commonly presents as: weight loss, increasing fatigue, vomiting, nausea, diarrhea and salt craving

muscle and jt pain , abdominal pain, postural dizziness

increased pigmentation (extensor surfaces, creases of palms, and buccal mucosa)

lab: hyponatremia and hyperkalemia, metabolic acidosis, azotemia, hypercalcemia, lymphocytosis, eosinophilia

Acute adrenal insufficiency medical emergency plasma cortisol level >18 micrograms/dl r/o’s dx of adrenal crisis <18 micrograms/dl consistent w/ adrenal insufficiency Once dx of adrenal insufficiency is made need to distinguish between primary or secondary Secondary adrenal insufficiency results from inadequate stimulation of adrenal cortex by ACTH can be from lesions anywhere in HPA axis or prolonged suppression of HPA axis by exogenous glucocorticoids

Acute adrenal insufficiency

medical emergency

plasma cortisol level >18 micrograms/dl r/o’s dx of adrenal crisis

<18 micrograms/dl consistent w/ adrenal insufficiency

Once dx of adrenal insufficiency is made

need to distinguish between primary or secondary

Secondary adrenal insufficiency

results from inadequate stimulation of adrenal cortex by ACTH

can be from lesions anywhere in HPA axis or prolonged suppression of HPA axis by exogenous glucocorticoids

Secondary adrenal insufficiency same manifestations as primary; except no hyperpigmentation, no salt craving, no abnormalities of hyperkalemia or metabolic acidosis hyponatremia often due to inapproprite ADH secretion which accompanies glucocorticoid insufficiency pt’s w/ secondary adrenal insufficiency due to a pituitary lesion usually have same labs and symptoms of : hypothroidism, hypogonadism, or growth hormone deficiency

Secondary adrenal insufficiency

same manifestations as primary; except

no hyperpigmentation, no salt craving, no abnormalities of hyperkalemia or metabolic acidosis

hyponatremia often due to inapproprite ADH secretion which accompanies glucocorticoid insufficiency

pt’s w/ secondary adrenal insufficiency due to a pituitary lesion usually have same labs and symptoms of : hypothroidism, hypogonadism, or growth hormone deficiency

Labs Primary adrenal insufficiency: morning plasma ACTH >50 pico-grams/dl; standing plasma renin >3 nano-grams/ml/hr Secondadry adrenal insufficiency: morning plasma ACTH < 20 pico-grams/dl; standing plasma renin <3 nano-grams/ml/hr Secondary adrenal insufficiency occurs commonly after d/c of long term glucocorticoid therapy

Labs

Primary adrenal insufficiency: morning plasma ACTH >50 pico-grams/dl; standing plasma renin >3 nano-grams/ml/hr

Secondadry adrenal insufficiency: morning plasma ACTH < 20 pico-grams/dl; standing plasma renin <3 nano-grams/ml/hr

Secondary adrenal insufficiency

occurs commonly after d/c of long term glucocorticoid therapy

Addisons Ds requires life-long replacement of glucocorticoids and mineralocorticoids initial regimen of 15-20 mg of hydrocortisone in a.m and 5 mg around 4 p.m mimics physiologic dose mineralocorticoid tx varies greatly synthetic mineralocorticoid fludrocortisone (florinef) 100 micrograms/dl adjusted to keep standing plasma level above 3 nano-grams/ml/hr standing plasma rnin level >3 nano-grams w/ pt on correct glucocorticoid dose suggests undertreatment w/ florinef

Addisons Ds

requires life-long replacement of glucocorticoids and mineralocorticoids

initial regimen of 15-20 mg of hydrocortisone in a.m and 5 mg around 4 p.m mimics physiologic dose

mineralocorticoid tx varies greatly

synthetic mineralocorticoid fludrocortisone (florinef) 100 micrograms/dl adjusted to keep standing plasma level above 3 nano-grams/ml/hr

standing plasma rnin level >3 nano-grams w/ pt on correct glucocorticoid dose suggests undertreatment w/ florinef

Under stress of a minor illness (nausea , vomiting, or fever >100.5F) hydocortisone dose should be doubled for a short time period under major stress (surgery or major trauma) 150 mg -300mg of IV hydorcortisone given in 3 divided doses; then rapidly tapering during recovery pts should wear a medical alert bracelet and instructed in the use of IM hydorcortisone in emergencies

Under stress of a minor illness (nausea , vomiting, or fever >100.5F) hydocortisone dose should be doubled for a short time period

under major stress (surgery or major trauma) 150 mg -300mg of IV hydorcortisone given in 3 divided doses; then rapidly tapering during recovery

pts should wear a medical alert bracelet and instructed in the use of IM hydorcortisone in emergencies

Hyporeninemic hypoaldosteronism decreased renin secretion by kidney hyperkalemia and hyperchloremic metabolic acidosis occurs plasma sodium concentration usually normal plasma renin and aldosterone are low and unresponsive to stimuli Diabetes melitus (DM) and chronic tubulointerstitial ds of kidney are the most common underlying conditions

Hyporeninemic hypoaldosteronism

decreased renin secretion by kidney

hyperkalemia and hyperchloremic metabolic acidosis occurs

plasma sodium concentration usually normal

plasma renin and aldosterone are low and unresponsive to stimuli

Diabetes melitus (DM) and chronic tubulointerstitial ds of kidney are the most common underlying conditions

Hypersecretion of glucocorticoid hormone, cortisol, causes Cushing syndrome Cushing syndrome a metabolic disorder affecting carbohydrate, protein and lipid metabolism increased production of cortisol seen in physiologic states: stress, last trimester of pregnancy; chronic strenuous exercise

Hypersecretion of glucocorticoid hormone, cortisol, causes Cushing syndrome

Cushing syndrome

a metabolic disorder affecting carbohydrate, protein and lipid metabolism

increased production of cortisol seen in physiologic states: stress, last trimester of pregnancy; chronic strenuous exercise

Pathologic states: exogenous or endogenous Cushing syndrome, several psychiatric states (depression, alcoholism, anorexia nervosa, panic disorder, and alcohol or narcotic withdrawal) Cushing syndrome may be due to exogenous ACTH or glucorticoid tx or endogenous hypersecretion endogenous Cushing syndrome is either ACTH dependant or ACTH independant

Pathologic states: exogenous or endogenous Cushing syndrome, several psychiatric states (depression, alcoholism, anorexia nervosa, panic disorder, and alcohol or narcotic withdrawal)

Cushing syndrome may be due to exogenous ACTH or glucorticoid tx or endogenous hypersecretion

endogenous Cushing syndrome is either ACTH dependant or ACTH independant

ACTH dependant  85% of cases (pituitary causes of ACTH (Cushing Ds), ectopic sources of ACTH and ectopic sources of CRH Pituitary Cushing Ds  80% of ACTH dependant Cushing syndrome Ectopic ACTH  sm cell lung ca remaining pts have pancreatic, adrenal, or thyroid secreting tumors of ACTH ACTH independent cases  15% of Cushing syndrome ( adrenal adenomas, adrenal carcinoma, micronodular adrenal ds & autonomous macronodular adrenal ds

ACTH dependant  85% of cases (pituitary causes of ACTH (Cushing Ds), ectopic sources of ACTH and ectopic sources of CRH

Pituitary Cushing Ds  80% of ACTH dependant Cushing syndrome

Ectopic ACTH  sm cell lung ca

remaining pts have pancreatic, adrenal, or thyroid secreting tumors of ACTH

ACTH independent cases  15% of Cushing syndrome ( adrenal adenomas, adrenal carcinoma, micronodular adrenal ds & autonomous macronodular adrenal ds

Cushing Ds seen in 20-30 y/o Ectopic Cushing syndrome bimodal age increased incidence in children and young adults <20 y/o and in 50-60’s usually insidious; mena duration for dx 3-5 yrs clinical manifestations: centripetal obesity, wasting of arms and legs, rounding of face (moon facies), facial plethora, supraclavicular and temporal filling

Cushing Ds

seen in 20-30 y/o

Ectopic Cushing syndrome

bimodal age increased incidence in children and young adults <20 y/o and in 50-60’s

usually insidious; mena duration for dx 3-5 yrs

clinical manifestations: centripetal obesity, wasting of arms and legs, rounding of face (moon facies), facial plethora, supraclavicular and temporal filling

Proximal muscle weakness menstrual irregularities in females; decreased libido in males and impotence adult onset acne or hirsutism in females violacious ( purple or dark red) skin striae thinning of back of hands very specific sign in young adults growth arrest in pediatrics pts, pubertal arrest, virilization and menstrual irregularities frequently seen

Proximal muscle weakness

menstrual irregularities in females; decreased libido in males and impotence

adult onset acne or hirsutism in females

violacious ( purple or dark red) skin striae

thinning of back of hands very specific sign in young adults

growth arrest in pediatrics pts, pubertal arrest, virilization and menstrual irregularities frequently seen

Labs elevated plasma alkaline phosphatase, granulocytosis, thrombocytosis, hypercholesterolemia, hypertriglyceremia and glucose intolerance/DM central hypothyroidism occurs in about 70% Dx approach initially 90% have a urinary free cortisol (UFC) 24 hr urine collection >90 micrograms/dl lvl >300 micrograms/dl very specific

Labs

elevated plasma alkaline phosphatase, granulocytosis, thrombocytosis, hypercholesterolemia, hypertriglyceremia and glucose intolerance/DM

central hypothyroidism occurs in about 70%

Dx approach

initially 90% have a urinary free cortisol (UFC) 24 hr urine collection >90 micrograms/dl

lvl >300 micrograms/dl very specific

Pseudo-Cushing states from psychiatric disorders or alcoholism frequently have levels between 90-300 micrograms/dl ectopic ACTH syndrome and cortisol secreting adenomas or carcinomas frequently have UFC lvls >1000 micrograms/dl cortisol normally secreted in a diurnal fashion: highest plasma concentration in a.m, lowest around midnight Cushing syndrome similar to normals, afternoon and evening lvls higher, p.m lvls > 50% of a.m  Cushing syndrome

Pseudo-Cushing states from psychiatric disorders or alcoholism frequently have levels between 90-300 micrograms/dl

ectopic ACTH syndrome and cortisol secreting adenomas or carcinomas frequently have UFC lvls >1000 micrograms/dl

cortisol normally secreted in a diurnal fashion: highest plasma concentration in a.m, lowest around midnight

Cushing syndrome similar to normals, afternoon and evening lvls higher, p.m lvls > 50% of a.m  Cushing syndrome

Imaging may be helpful in eval for etiol of hypercortisolism MRI of pituitary CT and MRI of adrenal gland; CT and MRI of chest and abdomen useful for ectopic ACTH secreting tumors if suspected Tx surgery of all Cushing syndrome tumors pituitary Cushing ds tx by transphenoidal surgery (TSS)

Imaging may be helpful in eval for etiol of hypercortisolism

MRI of pituitary

CT and MRI of adrenal gland; CT and MRI of chest and abdomen useful for ectopic ACTH secreting tumors if suspected

Tx

surgery of all Cushing syndrome tumors

pituitary Cushing ds tx by transphenoidal surgery (TSS)

pts who fail initial pituitary surgery or have recurrent Cushing ds can be tx’ed w/ pituitary radioation almost all pts w/develop panhypopituitarism; so thyroid, gonadal, and even steroid tx may be needed pt’s w/Cushing Ds who remain hypercortisolemic after surgery and radiation should undergo B/L adrenalectomy

pts who fail initial pituitary surgery or have recurrent Cushing ds can be tx’ed w/ pituitary radioation

almost all pts w/develop panhypopituitarism; so thyroid, gonadal, and even steroid tx may be needed

pt’s w/Cushing Ds who remain hypercortisolemic after surgery and radiation should undergo B/L adrenalectomy

Primary Mineralcorticoid Excess manifested by salt retention, HTN, and metabolic alkalosis Primary adosteronism can be due to aldosterone-producing adenoma (75%). B/L adrenal hyperplasia (22%) adrenal carcinoma (1%) Secondary aldosteronism results from overactivation of the renin-angiotensin system

Primary Mineralcorticoid Excess

manifested by salt retention, HTN, and metabolic alkalosis

Primary adosteronism can be due to aldosterone-producing adenoma (75%). B/L adrenal hyperplasia (22%) adrenal carcinoma (1%)

Secondary aldosteronism results from overactivation of the renin-angiotensin system

Primary aldosteronism usually recognized during eval of HTN or hypokalemia curable cause of HTN less than 2% of pts w/HTN have primary aldosteronism Clinical manifestation HTN, hypokalemia, and metabolic acidosis most presenting symptoms are relate to hypokalemia mild hypokalemic pts have fatigue, muscle weakness, nocturia, lassitude and HA’,

Primary aldosteronism usually recognized during eval of HTN or hypokalemia

curable cause of HTN

less than 2% of pts w/HTN have primary aldosteronism

Clinical manifestation

HTN, hypokalemia, and metabolic acidosis

most presenting symptoms are relate to hypokalemia

mild hypokalemic pts have fatigue, muscle weakness, nocturia, lassitude and HA’,

Severe hypokalemic pt’s have polydypsia, polyuria, paresthesias, paralysis and tetany can occur positve Trousseu or Chovstek sign may occur from metabolic alkalosis BP can range from borderline to severely hypertensive lvls; rarely malignant HTN DX hypokalemia in presence of HTN elevated urinary aldosterone lvl >15 microgram/dl and a suppressed plasma renin lvl <2 nano-grams/ml/hr suggest hyperaldosteronism

Severe hypokalemic pt’s have polydypsia, polyuria, paresthesias, paralysis and tetany can occur

positve Trousseu or Chovstek sign may occur from metabolic alkalosis

BP can range from borderline to severely hypertensive lvls; rarely malignant HTN

DX

hypokalemia in presence of HTN

elevated urinary aldosterone lvl >15 microgram/dl and a suppressed plasma renin lvl <2 nano-grams/ml/hr suggest hyperaldosteronism

Basal plasma aldosterone lvl <8 nano-gram/dl is found in nl individuals lvls 8-20 nan-grams/dl usually found in pt’s w/ B/L adrenal hyperplasia tx’ed w/spironolactone lvls > 20 nano-grams/dl suggest adrenal adenoma

Basal plasma aldosterone lvl <8 nano-gram/dl is found in nl individuals

lvls 8-20 nan-grams/dl usually found in pt’s w/ B/L adrenal hyperplasia

tx’ed w/spironolactone

lvls > 20 nano-grams/dl suggest adrenal adenoma

Adrenal Medulla Hyperfunction adrenal medulla synthesizes the catecholamines: norepinephrine, epinephrine and dopamine from amino acid tyrosine norepinephrine-the major catecholemine produce by adrenal medulla predominantly has alpha-agonist actions  vasoconstriction epinephrine acts primarily on beta receptors  inotropic and chronotropic effects on ht  vasodilation,  ’s plasma glucose in response to hypoglycemia

Adrenal Medulla Hyperfunction

adrenal medulla synthesizes the catecholamines: norepinephrine, epinephrine and dopamine from amino acid tyrosine

norepinephrine-the major catecholemine produce by adrenal medulla predominantly has alpha-agonist actions  vasoconstriction

epinephrine acts primarily on beta receptors  inotropic and chronotropic effects on ht  vasodilation,  ’s plasma glucose in response to hypoglycemia

Norepinephrine synthesized in CNS and in sympathetic postganglionic neurons epinephrine synthesized almost entirely in adrenal medulla Hypersecretion of catecholemines produces the clinical syndrome of Pheochromcytoma can occur in any sympathetic ganglion >90% arise in adrenal medulla

Norepinephrine synthesized in CNS and in sympathetic postganglionic neurons

epinephrine synthesized almost entirely in adrenal medulla

Hypersecretion of catecholemines produces the clinical syndrome of Pheochromcytoma

can occur in any sympathetic ganglion

>90% arise in adrenal medulla

Pheochromocytoma occurs as part of multiple endocrine neoplasia (MEN) type 2A or 2B syndromes former (Sipple’s syndrome) marked by medullary carcinoma or thyroid, hyperparathyroidism, and pheochromocytoma latter characterized by medullary carcinoma of thyroid, mucosal neuromas, intestinal ganglioneuromas, marfanoid habitus and pheochromocytoma

Pheochromocytoma occurs as part of multiple endocrine neoplasia (MEN) type 2A or 2B syndromes

former (Sipple’s syndrome) marked by medullary carcinoma or thyroid, hyperparathyroidism, and pheochromocytoma

latter characterized by medullary carcinoma of thyroid, mucosal neuromas, intestinal ganglioneuromas, marfanoid habitus and pheochromocytoma

Clinical manifestation HTN most common finding may be associated w/common triad: HA, palpitations, and sweating other symptoms : flushing, anxiety, nausea, fatigue,, weight loss, abd and chest pain may be precipitated by emotional stress, exercise, anesthesia, abd pressure, or intake of tyramine containin foods wide fluctuations in BP may occur HTN if pheochromocytoma usually does not respond to tx for HTN

Clinical manifestation

HTN most common finding

may be associated w/common triad: HA, palpitations, and sweating

other symptoms : flushing, anxiety, nausea, fatigue,, weight loss, abd and chest pain

may be precipitated by emotional stress, exercise, anesthesia, abd pressure, or intake of tyramine containin foods

wide fluctuations in BP may occur

HTN if pheochromocytoma usually does not respond to tx for HTN

DX elevated urinary excretion of catecholamines or their metabolites metenephrines, and vanillylmandelic acid (VMA) lvls checked during periods of HTN measurement of plasma catecholemines may also be useful plasma norepinephrine lvls >1500 pico-grams/ml or an epinephrine lvl >500 pico-grams/ml Tx: surgical excision

DX

elevated urinary excretion of catecholamines or their metabolites

metenephrines, and vanillylmandelic acid (VMA)

lvls checked during periods of HTN

measurement of plasma catecholemines may also be useful

plasma norepinephrine lvls >1500 pico-grams/ml or an epinephrine lvl >500 pico-grams/ml

Tx: surgical excision