endocrine ii parathyroid glands

Upload: hoatbui

Post on 02-Jun-2018

214 views

Category:

Documents


0 download

TRANSCRIPT

  • 8/10/2019 Endocrine II Parathyroid Glands

    1/12

  • 8/10/2019 Endocrine II Parathyroid Glands

    2/12

    Hypercalcemia

    Incidental hypercalcemia (came for something else but incidentally found)

    o Primary hyperthyroidism

    o Serum PTH levels high for serum Ca+ levels

    Clinically apparent hypercalcemia

    o

    Malignancy Solid cancers secrete PTH related protein (PTHrp)

    Solid tumors (lung, breast, head and neck and renal cancers)

    and hematologic malignancies mostly multiple myeloma

    Nonparathyroid causes

    PTH too low to undetectable in hypercalcemia

    Parathyroid Diseases

    Hyperparathyroidism

    o Primary

    o Secondary

    o

    Tertiary Hypoparathyroidism

    Tumors

    o Attn. bc high PTH rather than mass effects.

    Primary hyperparathyroidism

    PTH overproduction

    Autonomous, spontaneous

    Imp. b/c incidental hypercalcemia

    Higher in women; usually age 50+

    Causes

    o

    Adenoma (85%) *o Hyperplasia (15%)

    o Carcinoma (~1%)

    1) Adenoma

    95% sporadic

    o Monoclonal

    o Associated w/ Cyclin D1 and MEN1 mutations

    5-10% are familial:

    o MEN 1 and MEN 2A syndromes

    Adenoma- morphologic changes

    o Solid, circumscribed, encapsulated, tan brown nodule

    o Rim of compressed, non-neoplastic parathyroid tissue separated by

    fibrous capsule present

    o Composed mostly chief cells w/ few oxyphil cells

    o Adipose tissue is low

  • 8/10/2019 Endocrine II Parathyroid Glands

    3/12

    2) Hyperplasia

    Sporadic /Component of MEN syndrome

    All 4 glands or asymmetric involvement with sparing of 1 or 2 glands

    Fat is low

    Hyperplasia=more than 1 gland

    Adenoma= one gland

    3) Parathyroid carcinomas

    May involve one gland

    Big gray-white irregular masses

    Cytologic similarity to adenomas

    Invasion of surrounding tissues and metastasis are only reliable criteria for

    malignancy

    Local recurrence in 1/3rdcases

    Distant dissemination in 1/3rdcases

    Morphologic changes in other organs

    Skeletal changes***

    o High Osteoclastic- high bone resorption

    o High Osteoblastic- high new bony trabeculae

    o resultant bone

    thin trabeculae

    severe cases:

    cystformation

    marrow withhemorrhage

    fibrosis(osteitis fibrosa cystica)

    o

    usually form masses (brown tumors) composed of:

    giant cells

    hemorrhagic debris

    Morphologic changes in other organs

    o Urinary tract

    Urinary tract stones

    Nephrocalcinosis

    calcification of renal interstitium and tubules

    o

    Metastatic calcification Stomachs, lungs, myocardium and blood vessels

  • 8/10/2019 Endocrine II Parathyroid Glands

    4/12

    Secondary Hyperparathyroidism

    Chronic decreased calcium lead to compensatory hyperplasia of the

    parathyroid (parathyroid working hard to increase Ca+)

    o Chronic renal failure common*

    o Other causes:

    inadequate dietary intake of calcium steatorrhea xcess fat in feces

    vitamin D deficiency

    Treatment

    o dietary vitamin D supplementation

    o phosphate binders

    Tertiary Hyperparathyroidism

    autonomous + excessive w/ resultant hypercalcemia

    o produces PTH w/o stimulation

    Treatment

    o

    Parathyroidectomy

    Hypoparathyroidism

    Causes:

    o Congenital absence

    o Surgery/radiation

    o Automimmune

    o Familial

    Severe, chronic hypocalcemia (all due to decrease PTH)

    o Muscle:

    Tetany neuromuscular irritability (circumoral numbness or

    paresthesias of the distal extremities and carpopedal spasm)

    o CNS

    anxiety and depression

    confusional states, hallucinations,+ frank psychosis.

    calcifications of the basal ganglia

    parkinsonian-like movement disorders

    increased intracranial pressure w/ resultant papilledema.

    o Long QT interval in EKG ** BOARDS

    o Mouth

    dental hypoplasia, failure of eruption, defective enamel, rootformation

    Pseudohypoparathyroidism

    normal or elevated PTH levels

    hypoparathyroidism b/c end-organ no respond (resistance to PTH action)

  • 8/10/2019 Endocrine II Parathyroid Glands

    5/12

    Thyroid

    store thyroid hormones- composed of 65% iodine.

    Two lobes connected by isthmus

    Have follicles of diff. sizes

    Colloid- pink homogenous material

    Thyroid hormones

    Thyroid follicularepithelial cells convert thyroglobulinto #T4/T3

    Blood

    o T3/T4 binds reversibly with thyroglobulin + thransthyretenin**

    Periphery

    o T4 deiodinated to T3**

    T3 binds to thyroid hormone nuclear receptors w/ 10 fold greater affinity

    Function:

    o increase protein synthesis

    o catabolism of carbohydrates and fats (basal metabolic rate)

    o

    brain development in fetus Types of thyroid hormone:

    o C cells (parafollicular cells)

    secrete Calcitonin

    lowers calcium via:

    bone absorption of Ca+

    inhibit bone resorption by osteoclasts

    o Goitrogens

    inhibit function of thyroid gland

    suppress T4/T3 synthesis

    ex. propylthiouracil

    large doses iodine and vegetables (cabbage, turnips and

    cassava)

    Diseases of Thyroid

    Hyperthyroidism

    Hypothyroidism

    Mass lesions of the thyroid

    Hyperthyroidism

    Hypermetabolic state by increase free T3 and T4 in blood

    Primaryo Diffuse hyperplasia (Graves disease) -85% cases***

    o Toxic multinodular goiter*

    TOXIC MEANS START PRODUCING EXCESS OF T4/T3

    o Toxic adenoma

    o Iodine induced hyperthyroidism

    o Neonatal thyrotoxicosis.

  • 8/10/2019 Endocrine II Parathyroid Glands

    6/12

    Secondary

    o TSH secreting pituitary adenoma

    Hyperthyroidism- clinical course

    Cardiac manifestationsearly, distinct feature

    o

    increase in cardiac output, tachycardia, palpitations, arrhythmias.o Untreated may die

    Neuromuscular system

    o tremor, hyperactivity, emotional lability, anxiety, inability to

    concentrate, and insomnia.

    o proximal muscle weakness and decreased muscle mass (thyroid

    myopathy)

    Increased BMR

    o Heat intolerance + sweating

    o Weight loss even w/ increased appetite

    Ocular changes

    o

    wide, staring gaze + lid lag Gastrointestinal system

    o hypermotility, malabsorption, and diarrhea

    Skeletal system

    o Osteoporosis

    o increased risk of fractures

    Thyroid storm

    o Severe onset of hyperthyroidism

    o from acute increase in catecholamine

    via infection, surgery, cessation of antithyroid

    medication, stress

    o

    common in Graves** Apathetic hyperthyroidism

    o thyrotoxicosis in elderly; features are blunted

    o unexplained weight loss/ worsening cardiovascular disease

    Hyperthyroidism- diagnosis

    o Clinical as discussed

    o Laboratory findings

    Low TSH- most useful single screening test

    Elevated free T4/ freeT3

    Radioactive iodine uptake test

  • 8/10/2019 Endocrine II Parathyroid Glands

    7/12

    Graves disease women 10x

    common cause- endogenoushyperthyroidism

    triad of clinical findings****

    1) hyperthyroidism

    diffuse

    hyperfunctional enlargement of the thyroid2) infiltrative ophthalmopathyw/ resultant exophthalmos

    3)

    localized, infiltrative dermopathy

    Thyroid-stimulating immunoglobulin

    o IgG antibody binds to TSH receptor + mimics the action of TSH

    relatively specific for Graves disease

    o increased risk for other autoimmune diseases

    o ex. systemic lupus erythematosus

    o type 1 diabetes and others

    Laboratory findingso elevated free T4/ T3 levels*

    o depressed TSH levels*

    o diffuse and increased uptake of radioactive iodine

    Histology

    o Symmetrical diffuse hyperplasia of thyroid gland

    o Soft, meaty cut surface

    o Untreated cases

    tall follicular epithelial cells

    o form papillae that encroach on colloid

    o

    pale colloid with scalloped margins

    Hypothyroidism10x women

    Structural/ functional derangement

    o interferes w/ thyroid production

    Common disorder

    hypothalamic-pituitary-thyroid axis defect

    Primary (more common)

    o Congenital

    o Acquired

    Surgical/radiation induced ablation drugs

    o Autoimmune- most common cause of hypothyroidism in iodine-

    sufficient areas of the world

    Hashimotos thyroiditis

    o Laboratory findings- elevated TSH, low T4**

  • 8/10/2019 Endocrine II Parathyroid Glands

    8/12

    Secondary

    o Pituitary failure/ Hypothalamic failure

    o Laboratory findings- low TSH, low T4***

    Hypothyroidism clinical course

    Cretenism***o Develops in infancy/young

    o Clinical

    o short stature

    o severe mental retardation

    o coarse facial features

    Myxedema***

    o Older child or adult, insidious onset

    o Patients are listless

    o frequently overweight.

    o

    Constipationo decreased sweating

    o cold intolerant

    o Cool + pale skin b/c decrease blood flow.

    o Reduced cardiac output result in shortness of breath+decreased

    exercise capacity

    o increase in total cholesterol, low-density lipoprotein (LDL) levels

    o Accumulation of matrix substances in skin, subcutaneous tissue, and a

    number of visceral sites resulting in non-pitting edema, a broadening

    and coarsening of facial features

    Causes of Hypothyroidism Thyroiditis***

    o Inflammation of thyroid gland

    o Cause of primary hypothyroidism

    o Significant types

    Hashimotos thyroiditis

    Subacute (granulomatous) thyroditis

    Subacute lymphocytis (painless) thyroiditis

    Infectious

    1) Hashimoto thyroiditis

    common hypothyroidism in poor gradual thyroid failure b/c autoimmune destruction of the thyroid gland

    most prevalent between 45 and 65 years of age

    female predominance of 10 : 1 to 20 : 1

    Elevated serum levels of antibodies to thyroglobulin, thyroid peroxidase and

    TSH receptors

  • 8/10/2019 Endocrine II Parathyroid Glands

    9/12

    Hashimoto Morphology

    diffusely enlarged with intact capsule

    pale yellow-tan, firm , nodular cut surface

    mononuclear inflammatory infiltrate with well formed germinal centers,

    atrophic follicles, Hurthle cell change and fibrosis

    1) Hashimoto thyroiditis- clinical course

    painless enlargement of the thyroid

    increased risk of

    o other autoimmune diseases, both endocrine (type 1 diabetes,

    autoimmune adrenalitis) and nonendocrine (systemic lupus

    erythematosus, myasthenia gravis, and Sjgren syndrome

    o B-cell non-Hodgkin lymphomas**

    especially marginal zone lymphomas of mucosa-associated

    lymphoid tissues (MALT lymphomas).

    o papillary carcinomas**

    2) Subacute(granulomatous thyroiditis/ De Quervain thyroiditis)

    common cause of thyroid pain.

    triggered by a viral infection

    o ex. coxsackievirus, mumps, measles, adenovirus

    transient

    o diminish 2 to 6 weeks followed by recovery

    3) Riedel thyroiditis

    unknown etiology

    extensive fibrosis

    o

    involve thyroid + contiguous neck structures.

    stimulates thyroid carcinoma.

    may be associated with idiopathic fibrosis in other sites in the body, such as

    the retroperitoneum

    4) Subacute lymphocytic (painless) thyroiditis

    middle-aged women

    mild painless symmetric enlargement of thyroid with or without transient

    overt hyperthyroidism

    Postpartum thyroiditis

    occurs during the postpartum period in up to 5% of women

    circulating anti-thyroid peroxidase antibodies or a family

    history of other autoimmune disorders.

    80% are euthyroid by 1 year and rest may eventually

    progress to overt hypothyroidism over a 10-year period.

  • 8/10/2019 Endocrine II Parathyroid Glands

    10/12

    Goiter

    Enlargement of the thyroid

    common manifestation of thyroid disease.

    size proportional to level/ duration of thyroid hormone deficiency

    Pathogenesis

    o

    impaired synthesis of thyroid hormone o compensatory rise in the serum TSH level

    o hypertrophy and hyperplasia of thyroid follicular cells

    to ensue a euthyroid metabolic state

    o compensatory responses are inadequate sogoitrous hypothyroidism

    results

    Diffuse non toxic (simple) goiter- colloid goiter

    Endemic goiter (when present in more than 10% of the population in a given

    region)

    o the soil, water, + food contain low levels of iodine.

    Esp dietary substances (referred to as goitrogens) Sporadic goiter - less frequent

    o Strike female preponderance

    o peak incidence at puberty or in young adult life.

    o ingestion of substances that interfere with thyroid hormone synthesis.

    o hereditary enzymatic defects

    o In many cases the cause is not apparent

    **MULTINODULAR GOITER extreme thyroid enlargements

    simple goiters convert to MNG b/c recurrent episodes of hyperplasia +

    involution.

    Clinical* cosmetic affects or mass effects like airway obstruction

    dysphagia

    superior vena cava syndrome.

    Euthyroid or have subclinical hyperthyroidism

    Morphology*

    o Asymmetrically enlarged glands

    o Cut surface has irregular nodules w/

    o Hemorrhage

    o fibrosis

    o cystic change

    o

    calcificationo Colloid rich follicles intermixed w/ areas of follicular hyperplasia (no

    distinct capsule)

  • 8/10/2019 Endocrine II Parathyroid Glands

    11/12

    Solitary nodule

    In US the incidence varies from 1% to 10%.

    More common in women

    Solitary Common causes

    o

    Majority non neoplastic

    Dominant nodule in MNG, simple cysts or foci of thyroiditis.o Neoplasms

    Benign out number malignant by a ratio of 10:1

    More likely to be neoplastic if

    1. Solitary

    2.

    younger patient

    3.

    male sex

    4. history of radiation

    5.

    Cold on radioactive studies

    FNAC is a critical part of evaluation

    Follicular Adenomas

    Discrete solitary

    Majority present as unilateral painless mass

    Majority are nonfunctional

    o Appear as cold nodules, 10% of which are histologically malignant.

    Encapsulated lesion

    compose of uniform-like follicles that contain colloid

    surgical removal necessary to evaluate integrity of the capsule which is critical in

    distinguishing it from follicular carcinoma

    Carcinomas of thyroid

    1.5% of all cancers

    Female predominance

    Risk factors

    o Ionizing radiation - PTC

    o Deficiency of iodine- FC

    o Genetic factors

    Major subtypes

    o Papillary carcinoma, >85%

    o

    Follicular carcinoma, 5-15% of cases

    o Anaplastic carcinoma,

  • 8/10/2019 Endocrine II Parathyroid Glands

    12/12

    Papillary carcinoma**

    Accounts for 85% of primary thyroid malignancies

    25-50 years

    Characterstic histologic features

    o Papillary features

    o

    Optically clear nuclei

    o

    Intranuclear cytoplasmic inclusionso Nuclear grooves

    o Psammoma bodies

    o Lymphatic invasion

    Excellent prognosis

    Follicular carcinoma

    5-15% of primary thyroid cancers

    common in women

    40-60 years

    areas w/ iodine deficiency

    Vascular spread- common

    Treatment

    thyroidectomy + then radioactive iodine

    Anaplastic (undifferentiated carcinoma)

    account for less than 5% of thyroid tumors.

    they are aggressive, with a mortality rate approaching 100%.

    older patients, mean age of 65 years.

    a quarter of patients have a past history of a well-differentiated thyroid carcinoma,

    and another quarter harbor a concurrent well-differentiated tumor in the resected

    specimen.

    the neoplastic cells express epithelial markers like cytokeratin, but are usually

    negative for markers of thyroid differentiation

    Medullary carcinoma ***

    neuroendocrine neoplasms derived from the parafollicular cells, or C cells * and

    therefore secrete calcitonin, ACTH, VIP

    account for approximately 5% of thyroid neoplasms.

    sporadic (70%)*

    o

    Adulthood

    o Solitary

    familial

    o MEN syndrome 2A or 2B or as familial tumors w/o associated MEN

    syndrome (familial medullary thyroid carcinoma, or FMTC).

    o

    Younger ageo Bilateral, multicentric

    o C-cell hyperplasia

    Activate point mutations in RET proto-oncogene