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THE ENDOCRINE SYSTEM

Ghazi Zaatari, MD
In general, the paradigm of linking morphology to function is essential in understanding disease
and this is particularly true in understanding endocrine pathology. Most of the endocrine organs
are small in size and weight and are anatomically deeply located in not so easily accessible sites;
therefore, their expression of disease is often manifested by the hormone produced by these
specialized organs. In pathologic states, the levels of these hormones may be normal, increased
or decreased. In our discussions on pathology of these individual organs, several pathologic
states will be typically reviewed in association with their function. Hence, there is the
designation of hyperfunctional state when the level of hormone produced by a particular organ
is increased above normal reference range (e.g. hyperthyroidism, hyperadrenalism, etc..). In
contrast, there is the designation of hypofunctional state when the level of hormone falls below
normal reference range (e.g. hypopituitarism, hypoparathyroidism, etc..). Furthermore, not all
pathological conditions are necessarily reflected by abnormal level of the hormone and thus
retain normal serum levels, such as in euthyroidism. Over the coming five pathology lectures,
these general principles will applied to pathology of the pituitary gland, thyroid gland,
adrenal gland, parathyroid gland and the endocrine pancreas and its relationship to
diabetes mellitus.

ANATOMY, HISTOLOGY & EMBROLOGY OF THE PITUITARY GLAND


I.

Anatomy:
It is a small gland, measures 1 cm in diameter, and weighs 0.5 gm. It is located at the base of
the skull and resides in the sella turcica (Turkish saddle) in close proximity to the sphenoid
sinuses and connects with the hypothalamus via a stalk. It consists of 2 major parts:
1) adenohypophysis (anterior pituitary) - has 3 parts: pars distalis (largest), pars
intermedia, pars tuberalis. It constitutes 70-80% of the gland.
2) neurohypophysis (posterior pituitary).
The pituitary gland is partly covered by a diaphragm of the dura mater and its stalk is in close
proximity to the optic chiasm of the optic nerves. Embryologic derivation is from Rathke's
pouch and its fusion with the diencephalic brain tissue that leads to the development of the
two major parts of the pituitary gland. The anterior part is of ectodermal origin and has
epithelial differentiation while the posterior pituitary is of neural origin and has neural
differentiation. In between, some embryologic remnants may be entrapped and these may
lead to pathologic states as will be discussed later in rare pathological states.
In the adenohypophysis, 3 cell types have been classically identified using the hematoxylin
and eosin stain of the gland: a. acidophilic cells, b. basophidic cells, c. chomophobe cells.
With immunohistochemical stains for cytoplasmic peptides and ultrastructural studies, at
least 6 distinct types can be identified:

1.
2.
3.
4.
5.
6.

Somatotroph-growth hormone - GH cells - 50% of cells


Lactotroph - prolactin cell - 15-25%
Corticotroph or melanocorticotroph - ACTH & MSH cells - 15-20%
Thyrotroph-TSH cell- 5%
Gonadotroph-FSH & LH cell - 5-10%
Non-secretory undifferentiated - 15-20%

Corticotroph (ACTH producing) cells are concentrated in the median wedge of the gland, the
somatotrophs in the lateral wings while the lactrotrophs are in the posterolateral wings.
Thyrotrophs are scattered with some concentration in the anterior median wedge and
gonadotrophs are found throughout the parenchyma. The undifferentiated cells are hormonally
functional but not in concentrations high enough to give positive histochemical staining. Newer
techniques, such as in situ hybridization for mRNA and catalyzed signal amplified (CSA), have
led to better identification of the peptide hormones in these cells.
Molecular biology advances have identified three major pathways of embryogenesis and
cytodifferentiation of adenohypophyseal cells, nicely regulated by a complex pattern of
transcription factor expression.

These 3 major pathways of differentiation of adenophyseal cells are: 1) Corticotrophs


differentiate first and the expression of proopiomelanocortin (POMC) gene is regulated by the
Tpit transcription factor. 2) The second is determined by growth factor, Pit-1 growth
hormone factor-1, a member of a family of transcriptional factors that regulate mammalian
development. It regulates the functional differentiation toward GH, PRL and TSH. Some
anterior pituitary cells are capable of transdifferentiation i.e. cell of one cell line may transform
to another cell line; this is best illustrated by the identification of mammosomatotrophs. 3) The
third line of cytodifferentiation is that of gonadotrophs whose hormone production is dependent
on streoidogenic factor 1 and GATA-2 in the presence of estrogen receptor.

In understanding disease, we should keep in mind the importance of the hypothalamicpituitary axis and the role of folliculostellate cells of the anterior pituitary which have
important regulatory functions including hormone release from other anterior pituitary cells. The
folliculostellate cell is a specialized sustentacular-like cell that appears to have multiple functions
related to phagocytosis and secretion of growth factors. They are scattered within the anterior
lobe and comprise less than 5% of the cell population. They are readily identified by their
reactivity for S-100 protein and can also be identified by glial fibrillary acidic protein (GFAP)
and vimentin. They participate in regulating the activity of anterior pituitary endocrine cells
through the production of cytokines (such as interleukin-6, and leukemia inhibitory factor) and
growth factors (including basic fibroblast growth factor and vascular endothelial growth factor.
Additionally, ultrastructural and immunohistochemical studies on human adenomatous and
nonneoplastic pituitary folliculostellate cells suggest that they may represent an adult stem cell
progenitor population
The posterior pituitary consists of modified glial cells (termed pituicytes) and axonal processes
that extend from the hypothalamus through the pituitary stalk to the posterior lobe (axon
terminals). Two peptide hormones, oxytocin and antidiuretic hormone (ADH, also called
vasopressin), are secreted from the posterior pituitary. They are actually synthesized in the
hypothalamus and stored within the axon terminals residing in the posterior pituitary.

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