endocrine ii parathyroid glands
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