nodules are neoplastic.

▪ Follicular adenomas are the most common benign neoplasms, while papillary carcinoma
is the most common malignancy.

▪ Multiple genetic pathways are involved in thyroid carcinogenesis. Some of the genetic
abnormalities that are fairly unique to thyroid cancers include PAX8/PPARG fusion genes
or mutations that activate RAS or PI-3K (in follicular carcinomas), chromosomal
rearrangements involving the RET oncogene or mutations in BRAF (in papillary
carcinomas), and mutations of RET (in medullary carcinomas).

▪ Follicular adenomas and carcinomas both are composed of well-differentiated follicular

epithelial cells; the latter are distinguished by evidence of capsular and/or vascular
invasion.

▪ Papillary carcinomas are recognized based on nuclear features (ground-glass nuclei,

pseudoinclusions) even in the absence of papillae. Psammoma bodies are a characteristic
feature of papillary cancers; these neoplasms often metastasize by way of lymphatics, but
the prognosis is excellent.

▪ Anaplastic carcinomas are thought to arise by dedifferentiation of more differentiated

neoplasms. They are highly aggressive, uniformly lethal cancers.

▪ Medullary cancers are neoplasms arising from the parafollicular C cells and can occur in
either sporadic (70%) or familial (30%) settings. Multicentricity and C cell hyperplasia are
features of familial cases. Amyloid deposits are a characteristic histologic finding.

Congenital Anomalies
Thyroglossal duct cyst is the most common clinically significant congenital anomaly of the thyroid. A
sinus tract may persist as a vestige of the tubular development of the thyroid gland. Parts of this tube
may be obliterated, leaving small segments to form cysts. These occur at any age and might not become
evident until adult life. Mucinous, clear secretions may collect within the cysts to form either spherical
masses or fusiform swellings, rarely over 2 to 3 cm in diameter, that present in the midline of the neck
anterior to the trachea. Segments of the duct and cysts that occur high in the neck are lined by stratified
squamous epithelium resembling the covering of the posterior portion of the tongue in the region of the
foramen cecum. Anomalies that occur in the lower neck more proximal to the thyroid gland are lined by
epithelium resembling the thyroidal acinar epithelium. Characteristically, subjacent to the lining
epithelium, there is an intense lymphocytic infiltrate. Superimposed infection may convert these
lesions into abscess cavities, and rarely, they give rise to cancers.

Parathyroid Glands
The four parathyroid glands are composed of two cell types: chief cells and oxyphil cells. Chief cells
predominate; they are polygonal, 12 to 20 µm in diameter, and have central, round, uniform nuclei and
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 light to dark pink cytoplasm. Sometimes these cells take on a water-clear appearance due to the
presence of large amounts of cytoplasmic glycogen. In addition, they have secretory granules
containing parathyroid hormone (PTH) . Oxyphil cells and transitional oxyphils are found throughout
the normal parathyroid, either singly or in small clusters. They are slightly larger than the chief cells,
have acidophilic cytoplasm, and are tightly packed with mitochondria. Glycogen granules are also
present in these cells, but secretory granules are sparse or absent. In early infancy and childhood, the
parathyroid glands are composed almost entirely of solid sheets of chief cells. The amount of stromal
fat increases up to age 25, reaching a maximum of approximately 30% of the gland, and then plateaus.

The function of the parathyroid glands is to regulate calcium homeostasis. The activity of
the parathyroid glands is controlled by the level of free (ionized) calcium in the bloodstream. Normally,
decreased levels of free calcium stimulate the synthesis and secretion of PTH. The metabolic functions
of PTH that regulate serum calcium levels are several. Specifically, PTH:

• Increases the renal tubular reabsorption of calcium, thereby conserving free calcium

• Increases the conversion of vitamin D to its active dihydroxy form in the kidneys

• Increases urinary phosphate excretion, thereby lowering serum phosphate levels

• Augments gastrointestinal calcium absorption

The net result of these activities is to elevate the level of free calcium, which, in turn, inhibits further
PTH secretion in a classic feedback loop. Similar to the other endocrine organs, abnormalities of the
parathyroid glands include both hyperfunction and hypofunction. Tumors of the parathyroid glands, in
contrast to thyroid tumors, usually come to attention because of excessive secretion of PTH rather than
mass effects.

Hyperparathyroidism
Hyperparathyroidism is caused by elevated parathyroid hormone and is classified into primary,
secondary, and least commonly, tertiary types.

• Primary hyperparathyroidism : an autonomous overproduction of parathyroid hormone

(PTH), usually resulting from an adenoma or hyperplasia of parathyroid tissue

• Secondary hyperparathyroidism : compensatory hypersecretion of PTH in response to

prolonged hypocalcemia, most commonly from chronic renal failure

• Tertiary hyperparathyroidism : persistent hypersecretion of PTH even after the cause of

prolonged hypocalcemia is corrected, for example after renal transplant

Primary Hyperparathyroidism
Primary hyperparathyroidism is one of the most common endocrine disorders, and it is
an important cause of hypercalcemia. The frequency of the various parathyroid lesions
underlying the hyperfunction is as follows:

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 • Adenoma: 85% to 95%

• Primary hyperplasia (diffuse or nodular): 5% to 10%

• Parathyroid carcinoma: ~1%

Primary hyperparathyroidism is usually a disease of adults and is more common in women than in men
by a ratio of nearly 4 : 1. The annual incidence is now estimated to be about 25 cases per 100,000 in the
United States and Europe; as many as 80% of patients with this condition are identified in the
outpatient setting, when hypercalcemia is discovered incidentally on a serum electrolyte panel. Most
cases occur in the 50s or later in life.

The most common cause of primary hyperparathyroidism is a solitary parathyroid

adenoma arising sporadically ( Fig. 24-24 (f0125) ). Most, if not all, sporadic parathyroid adenomas
are monoclonal, consistent with their being neoplasms. As with nodules in goitrous thyroids, sporadic
parathyroid “hyperplasia” is also monoclonal in many instances, particularly when associated with a
persistent stimulus for parathyroid growth (refractory secondary or tertiary parathyroidism; see later),
suggesting that these lesions lie in the gray zone between reactive hyperplasias and neoplasia. There are
two molecular defects that have an established role in the development of sporadic adenomas:

• Cyclin D1 gene inversions leading to overexpression of cyclin D1, a major regulator of the cell
cycle. A pericentromeric inversion on chromosome 11 results in relocation of the cyclin D1 gene
(normally on 11q), so that it is positioned adjacent to the 5′-flanking region of the PTH gene (on
11p). As a consequence of these changes, a regulatory element from the PTH gene 5′-flanking
sequence directs overexpression of cyclin D1 protein, causing the cells to proliferate. Between 10%
and 20% of adenomas have this clonal rearrangement. In addition, cyclin D1 is overexpressed in
approximately 40% of parathyroid adenomas, suggesting that mechanisms other than cyclin D1
gene inversion can lead to its overexpression.

• MEN1 mutations: Approximately 20% to 30% of sporadic parathyroid tumors have mutations in
both copies of the MEN1 gene, a tumor suppressor gene on chromosome 11q13. Germline
mutations of MEN1 are also found in patients with familial parathyroid adenomas (see later). The
spectrum of MEN1 mutations in sporadic tumors is virtually identical to that in familial
parathyroid adenomas.

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 Figure 24-24
Parathyroid adenoma imaging. Technetium- 99 m-sestamibi radionuclide scan demonstrates an area of increased
uptake corresponding to the left inferior parathyroid gland (arrow) , which contained a parathyroid adenoma.
Preoperative scintigraphy is useful in localizing and distinguishing adenomas from parathyroid hyperplasia, where
more than one gland would demonstrate increased uptake.

Familial syndromes are a distant second to sporadic adenomas as causes of primary

hyperparathyroidism. The genetic syndromes associated with familial parathyroid adenomas include
Multiple Endocrine Neoplasia, types 1 and 2, caused by germline mutations of MEN1 and RET ,
respectively (both are discussed in further detail later), and familial hypocalciuric hypercalcemia, a rare
autosomal-dominant disorder caused by loss-of-function mutations in the parathyroid calcium-sensing
receptor gene ( CASR ), which results in decreased sensitivity to extracellular calcium.

MORPHOLOGY

The morphologic changes seen in primary hyperparathyroidism include those in the parathyroid
glands as well as those in other organs affected by elevated levels of PTH and calcium.
Parathyroid adenomas are almost always solitary and, similar to the normal parathyroid glands,
may lie in close proximity to the thyroid gland or in an ectopic site (e.g., the mediastinum). The
typical parathyroid adenoma averages 0.5 to 5 gm and consists of a well-circumscribed, soft, tan
to reddish-brown nodule invested by a delicate capsule. In contrast to primary hyperplasia, the
glands outside the adenoma are usually normal in size or somewhat shrunken because of
feedback inhibition by elevated levels of serum calcium. Microscopically, parathyroid adenomas
are mostly composed of uniform, polygonal chief cells with small, centrally placed nuclei ( Fig.
24-25 (f0130) ). At least a few nests of larger oxyphil cells are present as well; uncommonly,
adenomas are composed entirely of this cell type (oxyphil adenomas) . These may resemble
Hürthle cell tumors in the thyroid. A rim of compressed, nonneoplastic parathyroid tissue,
generally separated by a fibrous capsule, is often visible at the edge of the adenoma. Mitotic
figures are rare, but it is not uncommon to find bizarre and pleomorphic nuclei even within
adenomas (so-called endocrine atypia ); this is not a criterion for malignancy. In contrast to
the normal parathyroid parenchyma, adipose tissue is inconspicuous.

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 Figure 24-25
Parathyroid adenoma. A, Solitary chief cell parathyroid adenoma (low-power photomicrograph) revealing
clear delineation from the residual gland below. B, High-power detail of a chief cell parathyroid adenoma.
There is some slight variation in nuclear size but no anaplasia and some slight tendency to follicular
formation.

Primary hyperplasia may occur sporadically or as a component of MEN syndrome. Although

classically all four glands are involved, there is frequently asymmetry with apparent sparing of
one or two glands, making the distinction between hyperplasia and adenoma difficult. The
combined weight of all glands rarely exceeds 1 gm and is often less. Microscopically, the most
common pattern seen is that of chief cell hyperplasia, which may involve the glands in a diffuse or
multinodular pattern. Less commonly, the constituent cells contain abundant water-clear cells
(“water-clear cell hyperplasia”). In many instances there are islands of oxyphils, and poorly
developed, delicate fibrous strands may envelop the nodules. As in the case of adenomas, stromal
fat is inconspicuous within hyperplastic glands.

Parathyroid carcinomas may be circumscribed lesions that are difficult to distinguish from
adenomas, or they may be clearly invasive neoplasms. These tumors enlarge one parathyroid
gland and consist of gray-white, irregular masses that sometimes exceed 10 gm in weight. The
cells are usually uniform and resemble normal parathyroid cells, and are arrayed in nodular or
trabecular patterns. The mass is usually enclosed by a dense, fibrous capsule. Diagnosis of
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 carcinoma based on cytologic detail is unreliable, and invasion of surrounding
tissues and metastasis are the only reliable criteria. Local recurrence occurs in one third
of cases, and more distant dissemination occurs in another third.

Morphologic changes of hyperparathyroidism in the skeletal system ( Chapter 26 ) and the urinary
tract deserve special mention. Symptomatic, untreated primary hyperparathyroidism manifests
with three interrelated skeletal abnormalities: osteoporosis, brown tumors and osteitis fibrosa
cystica. The osteoporosis results in decreased bone mass, with preferential involvement of the
phalanges, vertebrae and proximal femur. For unknown reasons, the increased osteoclast activity
in hyperparathyroidism affects cortical bone (subperiosteal and endosteal surfaces) more severely
than medullary bone. In medullary bone, osteoclasts tunnel into and dissect centrally along the
length of the trabeculae, creating the appearance of railroad tracks and producing what is known
as dissecting osteitis ( Fig. 24-26 (f0135) ). The marrow spaces around the affected surfaces are
replaced by fibrovascular tissue. The correlative radiographic finding is a decrease in bone density
or osteoporosis.

Figure 24-26
Hyperparathyroidism with osteoclasts boring into the center of the trabeculum (dissecting osteitis).
(Photomicrograph reproduced from Horvai A: Bone and Soft Tissue Pathology: A Volume in the High Yield
Pathology Series, Elsevier, Philadelphia, 2012.)

The bone loss predisposes to microfractures and secondary hemorrhages that elicit an influx of
macrophages and an ingrowth of reparative fibrous tissue, creating a mass of reactive tissue,
known as a brown tumor ( Fig. 26-16 , Chapter 26 ). The brown color is the result of the
vascularity, hemorrhage, and hemosiderin deposition, and it is not uncommon for the lesions to
undergo cystic degeneration. The combination of increased osteoclast activity, peritrabecular
fibrosis, and cystic brown tumors is the hallmark of severe hyperparathyroidism and is known as
generalized osteitis fibrosa cystica (von Recklinghausen disease of bone ). Osteitis
fibrosa cystica is now rarely encountered because hyperparathyroidism is usually diagnosed on
routine blood tests and treated at an early, asymptomatic stage (see later).
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 PTH-induced hypercalcemia favors formation of urinary tract stones (nephrolithiasis) as well
as calcification of the renal interstitium and tubules (nephrocalcinosis). Metastatic calcification
secondary to hypercalcemia may also be seen in other sites, including the stomach, lungs,
myocardium, and blood vessels.

Clinical Course.
Primary hyperparathyroidism may be (1) asymptomatic and identified on routine blood chemistry
profile, or (2) associated with the classic clinical manifestations of primary hyperparathyroidism.

Asymptomatic Hyperparathyroidism.
Because serum calcium levels are routinely assessed, most patients with primary hyperparathyroidism
are diagnosed incidentally, on the basis of clinically silent hypercalcemia. In fact, primary
hyperparathyroidism is the most common cause of asymptomatic hypercalcemia. Hence, many of the
classic manifestations, particularly those referable to bone and renal disease, are now seen infrequently
in clinical practice. Among other causes of hypercalcemia ( Table 24-5 (t0030) ), malignancy stands out as
the most frequent cause of symptomatic hypercalcemia in adults, and must be excluded by appropriate
clinical and laboratory investigations. As discussed in Chapter 7 , hypercalcemia can occur both with
solid tumors, such as lung, breast, head and neck, and renal cancers, and with hematologic
malignancies, notably multiple myeloma. The most common mechanism (in ~80% of cases) through
which osteolytic tumors induce hypercalcemia is by secretion of PTH-related peptide (PTHrP), whose
functions are similar to PTH in inducing osteoclastic bone resorption and hypercalcemia; the
remaining 20% induce hypercalcemia through metastases to the bone and subsequent cytokine-
induced bone resorption. In individuals with primary hyperparathyroidism, serum PTH levels are
inappropriately elevated for the level of serum calcium, whereas PTH levels are low to undetectable in
hypercalcemia caused by of nonparathyroid diseases ( Table 24-5 (t0030) ). Radioimmunoassays specific
for PTH and PTHrP are available and can be useful in distinguishing primary hyperparathyroidism and
malignancy-associated hypercalcemia. Other laboratory alterations referable to PTH excess include
hypophosphatemia and increased urinary excretion of both calcium and phosphate. Secondary renal
disease may lead to phosphate retention with normalization of serum phosphate levels.

Table 24-5
Causes of Hypercalcemia

Raised [PTH] Decreased [PTH]

Hyperparathyroidism Hypercalcemia of malignancy *

Primary (adenoma > hyperplasia) *
Vitamin D toxicity
Secondary †
Immobilization
Tertiary †

Thiazide diuretics
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 Raised [PTH] Decreased [PTH]

Familial hypocalciuric hypercalcemia Granulomatous disease (sarcoidosis)

[PTH], Parathyroid hormone concentration.

* Primary hyperparathyroidism is the most common cause of hypercalcemia overall. Malignancy is the
most common cause of symptomatic hypercalcemia. Primary hyperparathyroidism and malignancy
account for nearly 90% of cases of hypercalcemia.

† Secondary and tertiary hyperparathyroidism are most commonly associated with progressive renal
failure.

Symptomatic Primary Hyperparathyroidism.

The signs and symptoms of hyperparathyroidism reflect the combined effects of increased PTH
secretion and hypercalcemia. Primary hyperparathyroidism is associated with “painful bones, renal
stones, abdominal groans, and psychic moans.” The constellation of symptoms includes:

• Bone disease and bone pain secondary to fractures of bones weakened by osteoporosis or
osteitis fibrosa cystica.

• Nephrolithiasis (renal stones) in 20% of newly diagnosed patients, with attendant pain and
obstructive uropathy. Chronic renal insufficiency and abnormalities in renal function lead to
polyuria and secondary polydipsia.

• Gastrointestinal disturbances, including constipation, nausea, peptic ulcers, pancreatitis, and

gallstones.

• Central nervous system alterations, including depression, lethargy, and eventually seizures.

• Neuromuscular abnormalities, including weakness and fatigue.

• Cardiac manifestations, including aortic or mitral valve calcifications (or both).

The abnormalities most directly related to hyperparathyroidism are nephrolithiasis and bone disease,
whereas those attributable to hypercalcemia include fatigue, weakness, pancreatitis, metastatic
calcifications, and constipation.

Secondary Hyperparathyroidism
Secondary hyperparathyroidism is caused by any condition that gives rise to chronic
hypocalcemia, which in turn leads to compensatory overactivity of the parathyroid
glands. Renal failure is by far the most common cause of secondary hyperparathyroidism , although
several other diseases, including inadequate dietary intake of calcium, steatorrhea, and vitamin D
deficiency, may also cause this disorder. The mechanisms by which chronic renal failure induces
secondary hyperparathyroidism are complex and not fully understood. Chronic renal insufficiency is
associated with decreased phosphate excretion, which in turn results in hyperphosphatemia. The
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 elevated serum phosphate levels directly depress serum calcium levels and thereby stimulate
parathyroid gland activity. In addition, loss of renal substance reduces the availability of
α-1-hydroxylase necessary for the synthesis of the active form of vitamin D, which in turn reduces
intestinal absorption of calcium ( Chapter 9 ). Because vitamin D has suppressive effects on parathyroid
growth and PTH secretion, its relative deficiency compounds the hyperparathyroidism in renal failure.

MORPHOLOGY

The parathyroid glands in secondary hyperparathyroidism are hyperplastic. As in

primary hyperparathyroidism, the degree of glandular enlargement is not necessarily symmetric.
Microscopically, the hyperplastic glands contain an increased number of chief cells, or cells with
more abundant, clear cytoplasm (so-called water-clear cells) in a diffuse or multinodular
distribution. Fat cells are decreased in number. Metastatic calcification may be seen in many
tissues, including lungs, heart, stomach, and blood vessels.

Clinical Course.
The clinical features of secondary hyperparathyroidism are usually dominated by the inciting chronic
renal failure. Secondary hyperparathyroidism per se is usually not as severe or as prolonged as primary
hyperparathyroidism, hence the skeletal abnormalities (referred to as renal osteodystrophy) tend to be
milder. Control of the hyperparathyroidism allows the bony changes to regress significantly or
disappear completely. The vascular calcification associated with secondary hyperparathyroidism may
occasionally result in significant ischemic damage to skin and other organs, a process sometimes
referred to as calciphylaxis . Patients with secondary hyperparathyroidism often respond to dietary
vitamin D supplementation, as well as phosphate binders, which decrease the prevailing
hyperphosphatemia.

In a minority of patients, parathyroid activity may become autonomous and excessive, with resultant
hypercalcemia, a process that is sometimes termed tertiary hyperparathyroidism . Parathyroidectomy
may be necessary to control the hyperparathyroidism in such patients.

KEY CONCEPTS

Hyperparathyroidism

▪ Primary hyperparathyroidism is the most common cause of asymptomatic hypercalcemia.

▪ In a majority of cases, primary hyperparathyroidism is caused by a sporadic parathyroid

adenoma and, less commonly, by parathyroid hyperplasia.

▪ Parathyroid adenomas are solitary, while hyperplasia typically is a multiglandular process.

▪ Skeletal manifestations of hyperparathyroidism include bone resorption, osteitis fibrosa

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 cystica, and brown tumors. Renal changes include nephrolithiasis (stones) and
nephrocalcinosis.

▪ The clinical manifestations of hyperparathyroidism can be summarized as “painful bones,

renal stones, abdominal groans, and psychic moans.”

▪ Secondary hyperparathyroidism most often is caused by renal failure, which lowers serum
calcium levels, resulting in reactive hyperplasia of parathyroid glands.

▪ Malignancies are the most important cause of symptomatic hypercalcemia, which results
from osteolytic metastases or release of PTH-related protein from nonparathyroid tumors.

Hypoparathyroidism
Hypoparathyroidism is far less common than is hyperparathyroidism. Acquired hypoparathyroidism is
almost always an inadvertent consequence of surgery; in addition, there are several genetic causes of
hypoparathyroidism.

• Surgically induced hypoparathyroidism occurs with inadvertent removal of all the parathyroid
glands during thyroidectomy, excision of the parathyroid glands in the mistaken belief that they
are lymph nodes during radical neck dissection for some form of malignant disease, or removal of
too large a proportion of parathyroid tissue in the treatment of primary hyperparathyroidism.

• Autoimmune hypoparathyroidism is often associated with chronic mucocutaneous candidiasis

and primary adrenal insufficiency; this syndrome is known as autoimmune polyendocrine
syndrome type 1 (APS1) and is caused by mutations in the autoimmune regulator (AIRE) gene.
The syndrome typically presents in childhood with the onset of candidiasis, followed several years
later by hypoparathyroidism and then adrenal insufficiency during adolescence. APS1 is discussed
further under “Adrenal Glands.”

• Autosomal-dominant hypoparathyroidism is caused by gain-of-function mutations in the

calcium-sensing receptor ( CASR ) gene. Inappropriate CASR activity due to heightened calcium
sensing suppresses PTH, resulting in hypocalcemia and hypercalciuria . Recall that loss-of-
function CASR mutations are a rare cause of familial parathyroid adenomas.

• Familial isolated hypoparathyroidism (FIH) is a rare condition with either autosomal

dominant or autosomal recessive patterns of inheritance. Autosomal-dominant FIH is caused by a
mutation in the gene encoding PTH precursor peptide, which impairs its processing to the mature
hormone. Autosomal-recessive FIH is caused by loss-of-function mutations in the transcription
factor gene glial cells missing-2 ( GCM2 ), which is essential for development of the parathyroid.

• Congenital absence of parathyroid glands can occur in conjunction with other malformations,
such as thymic aplasia and cardiovascular defects, or as a component of the 22q11 deletion
syndrome. As discussed in Chapter 6 , when thymic defects are present, the condition is called
DiGeorge syndrome.
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 Clinical Features.
The major clinical manifestations of hypoparathyroidism are related to the severity and chronicity of
the hypocalcemia.

• The hallmark of hypocalcemia is tetany , which is characterized by neuromuscular irritability ,

resulting from decreased serum calcium levels. The symptoms range from circumoral numbness
or paresthesias (tingling) of the distal extremities and carpopedal spasm, to life-threatening
laryngospasm and generalized seizures. The classic findings on physical examination are
Chvostek sign and Trousseau sign . Chvostek sign is elicited in subclinical disease by tapping
along the course of the facial nerve, which induces contractions of the muscles of the eye, mouth,
or nose. Trousseau sign refers to carpal spasms produced by occlusion of the circulation to the
forearm and hand with a blood pressure cuff for several minutes.

• Mental status changes include emotional instability, anxiety and depression, confusional states,
hallucinations, and frank psychosis.

• Intracranial manifestations include calcifications of the basal ganglia, parkinsonian-like

movement disorders, and increased intracranial pressure with resultant papilledema. The
paradoxical association of hypocalcemia with calcifications may be because of an increase in
phosphate levels, resulting in tissue deposits with calcium that exists in local extracellular milieu.

• Ocular disease takes the form of calcification of the lens and cataract formation.

• Cardiovascular manifestations include a conduction defect that produces a characteristic

prolongation of the QT interval in the electrocardiogram.

• Dental abnormalities occur when hypocalcemia is present during early development. These
findings are highly characteristic of hypoparathyroidism and include dental hypoplasia, failure of
eruption, defective enamel and root formation, and abraded carious teeth.

Pseudohypoparathyroidism
In this condition, hypoparathyroidism occurs because of end-organ resistance to the actions of PTH.
Indeed, serum PTH levels are normal or elevated. In one form of pseudohypoparathyroidism, there is
end-organ resistance to TSH and FSH/LH as well as PTH. All of these hormones signal via G-protein–
coupled receptors, and the disorder results from genetic defects in components of this pathway that are
shared across endocrine tissues. PTH resistance is the most obvious clinical manifestation. It presents
as hypocalcemia, hyperphosphatemia, and elevated circulating PTH. TSH resistance is generally mild,
while LH/FSH resistance manifests as hypergonadotropic hypogonadism in females.

The Endocrine Pancreas

The endocrine pancreas consists of about 1 million clusters of cells, the islets of Langerhans , which
contain four major and two minor cell types. The four main types are β, α, δ, and PP (pancreatic
polypeptide) cells. They can be differentiated by the ultrastructural characteristics of their granules,
and by their hormone content ( Fig. 24-27 (f0145) ). The β cells produce insulin , which regulates glucose
69