Parathyroid Glands

4 glands in 2 pairs

Endocrine II

Location
upper poles of thyroid lobe, lower poles of thyroid lobe; also other locations
Microanatomy
Chief cells
o basic cell type
o has calcium sensing receptor
o Under control of Ca+ (anterior pituitary under control of
hypothalamus)
o contain granules that secrete parathyroid hormone (PTH)
Ca+ low, PTH is secreted

Oxyphil cells
o see at puberty
o in singles or small clusters
o lots of mitochondria
o no secretory granules

Parathyroid hormone receptors

o expressed on cell surface of target tissues
o acts via GTP binding alpha subunit

Histology
Chief cells=blue
Oxyphil cells=pink
Adipocytes= clear, egg like
Stromal fat increases (30%) at age 35 then plateau
Physiology
Parathyroid activity controlled by:
# free (ionized) calcium in blood
NOT BY trophic hormones secreted by hypothalamus + pituitary
High Ca+ inhibit PTH via feedback loop
Low Ca+ stimulate PTH
o Bone
Release Ca+
o Kidney
Return Ca+ via reabsorption
Secrete vitD3
o Intestine
Absorb more Ca+

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

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 1/3rd cases
Distant dissemination in 1/3rd cases
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:
cyst formation
marrow with hemorrhage
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

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, root
formation

Pseudohypoparathyroidism
normal or elevated PTH levels
hypoparathyroidism b/c end-organ no respond (resistance to PTH action)

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 follicular epithelial cells convert thyroglobulin to #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
Primary
o 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.

Secondary
o TSH secreting pituitary adenoma

Hyperthyroidism- clinical course

Cardiac manifestations early, 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

Graves disease women 10x

common cause- endogenous hyperthyroidism
triad of clinical findings****
1) hyperthyroidism
diffuse
hyperfunctional enlargement of the thyroid
2) infiltrative ophthalmopathy w/ 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 findings
o 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 iodinesufficient areas of the world
Hashimotos thyroiditis
o Laboratory findings- elevated TSH, low T4**

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 Constipation
o 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

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.

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 so goitrous 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 calcification
o Colloid rich follicles intermixed w/ areas of follicular hyperplasia (no
distinct capsule)

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, <5% of cases
o Medullary carcinoma (5% of cases)
Papillary carcinomas****KNOW ALL
RET/PTC rearrangements and BRAF point mutations
Follicular carcinomas
RAS and PIK3CA mutations and PAX8-PPARG fusion genes (t 2;3 q13;p25)
Anaplastic carcinomas
o Inactivation of p53 or activation of beta catenin
Medullary carcinomas
o RET mutations

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 inclusions
o 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 age
o Bilateral, multicentric
o C-cell hyperplasia
Activate point mutations in RET proto-oncogene