Hormones of pituitary gland and its disorders

Hormones of pituitary gland and
its disorders
Dr Joyce MWATONOKA
Mmed PCH
2/18/2019 Dr Joyce Mwatonoka

Outline
• Introduction
• Hormones of the anterior and posterior pituitary gland
• Disorders of pituitary gland;
-Galactorrhea
-Gigantism and Acromegaly
-SIADH
-Generalized Hypopituitarism
-Central Diabetes Inspidus (CDI)
-Kallmann syndrome
-Isolated thyroid-stimulating hormone deficiency
-ACTH deficiency
-Prolactin deficiency
-Isolated gonadotropin deficiency

Introduction
• The pituitary gland is only about 1/3 of an
inch in diameter (that’s about as large as a
pea) and located at the base of the brain
• It is located near the hypothalamus connected
by the pituitary stalk (the infundibulum)

Cont…
• The hormones of the pituitary gland help
regulate the functions of other endocrine
glands (master gland)
• The pituitary gland has two parts; the anterior
lobe and posterior lobe
• The hypothalamus sends signals to the
pituitary to release or inhibit pituitary
hormone production

Hormones of the anterior and
posterior pituitary gland
Anterior
• Adrenocorticotropic
hormone (ACTH)
• Growth hormone (GH)
• Thyroid stimulating
hormone (TSH)
• Prolactin
• Gonadotrophins
Posterior
• Anti-diuretic hormone
(ADH)/vasopressin
• Oxytocin

Cont…
• Between the anterior and the posterior
pituitary lies the intermediate pituitary gland
• Cells here produce: melanocyte-stimulating
hormone (MSH), which acts on cells in the
skin to stimulate the production of melanin

Cont…

ADH ( Arginine Vasopressin)
• AVP has hydro-osmotic effect promoting
water reabsorption from the tubular fluid in
the collecting duct, however it does not exert
a significant effect on the rate of
Na+ reabsorption
• A second action of AVP is to cause arteriolar
vasoconstriction and a rise in arterial blood
pressure, the pressor effect

Cont..
• Synthesized by neurons in the supraoptic and
paraventricular nuclei of the hypothalamus as a
precursor protein, the vasopressin-neurophysin
2–copeptin preprotein (pre-pro-vasopressin),
which travels along the supraopticohypophyseal
tract into the posterior pituitary
• There, the preprotein is cleaved to AVP,
neurophysin 2 (its carrier protein) and co-peptin
and stored in secretory granules with
neurophysin, in the terminal of secretory neurons
that rest against blood vessels

Cont…
• The major stimuli for AVP secretion are
hyperosmolality and effective circulating
volume depletion, which are sensed by
osmoreceptors in the hypothalamus and
baroreceptors in the carotid sinus, aortic arch,
and left atrium
• AVP is rapidly metabolised in the liver, half life
15-20min

AVP Receptors
I. V1a; vascular smooth muscles, stimulates
vasoconstriction. Also found in hepatocytes,
myocytes, platelets, brain, and testis
II. V1b (aka V3); anterior pituitary, where they
stimulate ACTH secretion
III. V2; distal nephron; insertion of the water
channel aquaporin-2 in the luminal
membrane of the collecting duct, thus
making it more permeable to water

Oxytocin
• A peptide hormone and neuropeptide
• Released into the bloodstream as a hormone
in response to stretching of the cervix and
uterus during labor and with stimulation of
the nipples from breastfeeding
• This helps with birth, bonding with the baby,
and milk production
• Produced by paraventricular nucleus, to some
extent supraoptic nucleus in hypothalamus

Cont…
• Oxytocin peptide is synthesized as an inactive
precursor protein which also includes the
oxytocin carrier protein neurophysin I
• Which is progressively hydrolyzed into smaller
fragments (one of which is neurophysin I) via a
series of enzymes. The last hydrolysis that
releases the active oxytocin nonapeptide is
catalyzed by peptidylglycine alpha-amidating
monooxygenase (PAM)
• PAM activity is dependent upon vitamin C, which
is a necessary cofactor

Thyroid stimulating hormone (TSH)
• A glycoprotein hormone produced by
thyrotrope cells in the anterior pituitary gland
• It controls production of the thyroid
hormones, thyroxine and then
triiodothyronine, by the thyroid gland, by
binding to receptors located on cells in the
thyroid gland
• Thyroid hormones stimulate metabolism
• Stimulant TRH, inhibitor Somatostatin

Cont…
• TSH consists of two subunits;
I. The alpha subunit (i.e. chorionic gonadotropin
alpha) is nearly identical to that of hCG, LH,
and FSH. The α subunit is thought to be the
effector region responsible for stimulation of
adenylate cyclase (involved the generation
of cAMP)
II. The beta subunit (TSHB) is unique to TSH, and
therefore determines its receptor specificity

Prolactin
• A peptide hormone, encoded by the PRL gene
• In mammals, prolactin is associated with milk
production
• Prolactin also acts in a cytokine-like manner and
as an important regulator of the immune system
• The hormone acts in endocrine, autocrine and
paracrine manner through the prolactin
receptor and a large number of cytokine
receptors

Cont...
• Stimulants; nipple stimulation, estrogen,
Thyrotropin-releasing hormone (TRH)
• Inhibitor; dopamine

Growth hormone
• It is a polypeptide that is synthesized, stored
and secreted by somatotropic cells in the
anterior pituitary gland
• It is a major participant in control of several
complex physiologic processes,
including growth and metabolism
• GH stimulates liver to synthesize and secrete
Insulin-like Growth factor 1 (IGF-1)

Cont…
• Insulin-like growth factor (IGF), is any of the
several peptide hormones that function
primarily to stimulate growth but that also
possess some ability to decrease
blood glucose level
• The name IGF reflects the fact that these
substances have insulin-like actions in some
tissues, though they are far less potent than
insulin in decreasing blood glucose conc.

Cont…
• IGF-1 binds to at least two cell
surface receptor tyrosine kinases: the IGF-1
receptor (IGF1R), and the insulin receptor
• IGF-1 activates the insulin receptor at
approximately 0.1 times the potency of insulin
• Stimulant of IGF; GH – stimulated by GHRH
• Inhibitors; somatostatin (SS), undernutrition,
growth hormone insensitivity, lack of growth
hormone receptors

Cont…
• There are two IGFs: IGF-1 and IGF-2
• IGF-1, which in turn stimulates both
hypertrophy (increase in cell size) and
hyperplasia (increase in cell number) of most
tissues, including bone
• IGF-2 is less dependent on the secretion of GH
than is the production of IGF-1, and IGF-2 is
much less important in stimulating linear
growth

Adrenocorticotropic hormone (ACTH)
• It stimulates the adrenal cortex to secret
glucocorticoids such as cortisol, and has little
control over secretion of aldosterone, the
other major steroid hormone from the
adrenal cortex
• Stimulant; corticotropin-releasing hormone,
whose stimulant; many types of stress

Cont…
• Within the pituitary gland, ACTH is produced
in a process that also generates several other
hormones. A large precursor protein named
pro-opiomelanocortin (POMC) is synthesized
and proteolytically chopped into several
fragments;
a) ACTH

Cont…
b) Lipotropin: Originally described as having weak
lipolytic effects, its major importance is as the
precursor to beta-endorphin
c) Beta-endorphin and Met-enkephalin: Opioid
peptides with pain-alleviation and euphoric
effects
d) Melanocyte-stimulating hormone (α-MSH): acts
onmelanocortin 4 receptor (MC4R) in the
hypothalamic paraventricular nucleus to
stimulate satiety

Gonadotrophins
• LH and FSH are known collectively as
gonadotrophins
• LH is also referred to as interstitial cell
stimulating hormone (ICSH) in males
• Controls reproductive functioning and sexual
characteristics
• Stimulates the ovaries to produce oestrogen
and progesterone and the testes to produce
testosterone and sperm

Specific pituitary disorders include
• Pituitary lesions
• Generalized hypopituitarism
• Selective disorders of pituitary hormone
deficiencies (including central diabetes
insipidus)
• Pituitary hormone excesses,
including gigantism, acromegaly, galactorrhea,
syndrome of inappropriate ADH secretion,
and Cushing disease

Galactorrhea
• Galactorrhea is lactation in men or in women
who are not breastfeeding
• It is generally due to a prolactin-secreting
pituitary adenoma
• Nonfunctioning pituitary mass lesions also can
increase prolactin levels by compressing the
pituitary stalk and thus reducing the action
of dopamine, a prolactin inhibitor

Cont…
• Hyperprolactinemia and galactorrhea also may be
caused by certain drugs, some antipsychotics eg;
phenothiazines, certain antihypertensives
(especially alpha-methyldopa), and opioids
• Primary hypothyroidism can cause
hyperprolactinemia and galactorrhea, because
increased levels of TRH increase secretion of TSH
as well as prolactin
• It is unclear why hyperprolactinemia is associated
with hypogonadotropism and hypogonadism

Signs and Symptoms
• Milk release that is inappropriate, persistent, or
worrisome to the patient
• Amenorrhea or oligomenorrhea, anovulation
• Symptoms and signs of estrogen deficiency eg;
loss of libido/androgen excess
• Men with prolactin-secreting pituitary tumors
typically have headaches or visual difficulties
• About two thirds of affected men have loss of
libido and erectile dysfunction

Diagnosis
• Prolactin levels, typically > 5 times normal
-prolactin levels correlate with the size of a
pituitary tumor and can be used for follow up
• Thyroxine (T4) and TSH levels
• Serum gonadotropin and estradiol levels (can
be low or in the normal range in women with
hyperprolactinemia)
• CT or MRI

Treatment
• Depends on sex, cause, symptoms, and other
factors
• Dopamine agonist such as bromocriptine
(1.25 to 5 mg po bid), or cabergoline (0.25 to
1.0 mg po once/wk or twice/wk)
• Surgical ablation
• Radiation therapy (side effect –
hypopituitarism)

Gigantism and Acromegaly
• Gigantism and acromegaly are syndromes of
excessive secretion of growth hormone
(hypersomatotropism) that are nearly always
due to a pituitary adenoma
• Before closure of the epiphyses, the result is
gigantism. Later, the result is acromegaly,
which causes distinctive facial and other
features

Gigantism
• This rare condition occurs if GH hypersecretion
begins in childhood, before closure of the
epiphyses
• Skeletal growth velocity and ultimate stature are
increased, but little bony deformity occurs
• However, soft-tissue swelling occurs, and the
peripheral nerves are enlarged
• Delayed puberty or hypogonadotropic
hypogonadism is also frequently present,
resulting in a eunuchoid habitus

Acromegaly
• In acromegaly, GH hypersecretion usually starts
between the 20s and 40s
• When GH hypersecretion begins after epiphyseal
closure, the earliest clinical manifestations are
coarsening of the facial features and soft-tissue
swelling of the hands and feet
• Appearance changes, and larger rings, gloves, and
shoes are needed
• Photographs of the patient are important in
delineating the course of the disease

Diagnosis
• CT or MRI
• Insulin-like growth factor 1 (IGF-1) levels,
elevated 3-fold to 10-fold. Preferred because
IGF-1 levels do not fluctuate like GH levels do,
they are the simplest way to assess GH
hypersecretion
• GH levels
• Screening for complications, including
diabetes, heart disease, and GI cancer

Management
• Surgery or radiation therapy; Trans-sphenoidal
resection is preferred
• Pharmacologic suppression of GH secretion or
activity; if surgery and radiation therapy are
contraindicated/if they have not been
curative. Eg; octreotide

Syndrome of inappropriate
antidiuretic hormone secretion
(SIADH)
• Is defined by the hyponatremia and hypo-
osmolality resulting from inappropriate,
continued secretion or action of vasopressin
despite normal or increased plasma volume,
which results in impaired water excretion
• The key to understanding the pathophysiology,
signs, symptoms, and treatment of SIADH is the
awareness that the hyponatremia results from an
excess of water rather than a deficiency of
sodium

Aetiology of SIADH
• CNS diseases that directly stimulate the
hypothalamus; infection, stroke
• Various cancers that secret ectopic ADH;
common in small cell lung cancer
• Some drugs; some antidepressants, opiates,
anticonvulsants eg; carbamazepine
• Inherited mutations
• Miscellaneous

Cont…
• Prominent physical findings may be seen only
in severe or rapid-onset hyponatremia and
can include the following:
• Confusion, disorientation, delirium
• Generalized muscle weakness, myoclonus,
tremor, hyporeflexia, ataxia, dysarthria,
Cheyne-Stokes respiration, pathologic reflexes
• Generalized seizures, coma

Diagnosis
• Hyponatremia with corresponding hypo-
osmolality
• Continued renal excretion of sodium
• Elevated urine osmolality
• Absence of clinical evidence of volume
depletion
• Absence of other causes of hyponatremia
• Correction of hyponatremia by fluid restriction

Management
• 3% hypertonic saline (513 mEq/L)
• Loop diuretics with saline
• Vasopressin-2 receptor antagonists
(aquaretics, such as conivaptan or tolvaptan) if
unavailable, loop diuretics eg; furosemide
• Water restriction

Generalized Hypopituitarism
• Refers to endocrine deficiency syndromes due
to partial or complete loss of anterior lobe
pituitary function
• Various clinical features occur depending on
the specific hormones that are deficient
• Function of all target glands decreases when
all hormones are deficient
(panhypopituitarism)

Cont…
• Most commonly, GH is lost first, then
gonadotropins, and finally TSH and ACTH
• Vasopressin deficiency is rare in primary pituitary
disorders but is common with lesions of the
pituitary stalk and hypothalamus
• Treatment;
-Hormone replacement, eg; IGF-1
analogue, mecasermin, in growth failure
-Treatment of cause (eg, tumor)

Central Diabetes Inspidus (CDI)
• DI results from a deficiency of
vasopressin (ADH) due to a hypothalamic-
pituitary disorder (central DI), or from
resistance of the kidneys
to vasopressin (nephrogenic DI [NDI])
• CDI may be
I. Complete (absence of vasopressin)
II. Partial (insufficient amounts of vasopressin)

Etiology
a) Primary CDI
• Due to genetic abnormalities of the vasopressin gene
on chromosome 20 responsible for ADH formation, but
many cases are idiopathic
b) Secondary CDI (acquired)
• Caused by various lesions, including hypophysectomy,
cranial injuries (basal skull fractures), tumors (primary
or metastatic), lymphocytic hypophysitis, granulomas
(sarcoidosis or TB), vascular lesions (aneurysm,
thrombosis), and infections (encephalitis, meningitis).

Pathophysiology
• The posterior lobe of the pituitary is the primary site
of vasopressin storage and release, but vasopressin is
synthesized within the hypothalamus
• Newly synthesized hormone can still be released into
the circulation as long as the hypothalamic nuclei and
part of the neurohypophyseal tract are intact
• Only about 10% of neurosecretory neurons must
remain intact to avoid CDI. The pathology of CDI thus
always involves the supraoptic and paraventricular
nuclei of the hypothalamus or a major portion of the
pituitary stalk

Cont…
Symptoms and Signs
• The only symptoms in
primary CDI are
polydipsia and polyuria
-Large volumes (3 to 30
L/day) of very dilute
urine (specific gravity
usually < 1.005 and
osmolality < 200
mOsm/L)
Diagnosis
• Water deprivation test
• Vasopressin levels

Management
• Treatment is with vasopressin synthetic
analogs desmopressin or lypressin
• Nonhormonal drugs
I. Diuretics, primarily thiazides
II. Vasopressin-releasing drugs
(eg, chlorpropamide, carbamazepine,
clofibrate)
III. Prostaglandin inhibitors

Kallmann syndrome
• Lack of gonadotropin-releasing hormone
(GnRH)
• A genetic defect, localized to the X
chromosome in the X-linked form of the
disorder and termed the KALIG-1 gene
(Kallmann syndrome interval gene 1)
• It is associated with midline facial defects,
including anosmia and cleft lip or palate, color
blindness, and delayed or absent puberty

Isolated thyroid-stimulating hormone
deficiency
• Is likely when clinical features of hypothyroidism
exist, serum TSH levels are low or not elevated,
and no other pituitary hormone deficiencies exist
• Serum TSH levels, as measured by immunoassay,
are not always lower than normal, suggesting
that the TSH secreted is biologically inactive
• Administration of recombinant human TSH
increases thyroid hormone levels

Clinical features of hypothyroidism
• Fatigue, loss of energy,
lethargy
• Weight gain
• Decreased appetite
• Cold intolerance
• Dry skin
• Hair loss
• Sleepiness
• Decreased perspiration
• Constipation
• Muscle pain, joint pain,
weakness in the
extremities
• Depression
• Emotional lability, mental
impairment
• Forgetfulness, impaired
memory, inability to
concentrate
• Menstrual disturbances,
impaired fertility

Isolated ACTH deficiency
• Is rare
• Weakness, hypoglycemia, weight loss, and
decreased axillary and pubic hair suggest the
diagnosis
• Blood and urinary steroid levels are low and rise
to normal after ACTH replacement
• Clinical and laboratory evidence of other
hormonal deficiencies is absent
• Treatment is with cortisol replacement, as
for Addison disease; mineralocorticoid
replacement is not required

Isolated prolactin deficiency
• Deficiency occurs secondary to anterior pituitary
dysfunction
• It has been noted rarely in women who fail to
lactate after delivery
• The most common associated condition is post-
partum pituitary necrosis (Sheehan syndrome)
• Basal prolactin levels are low and do not increase
in response to provocative stimuli, such as
thyroid-releasing hormone
• Administration of prolactin is not indicated

Isolated gonadotropin deficiency
• Occurs in both sexes and must be
distinguished from primary hypogonadism
• However, patients with primary
hypogonadism have elevated levels of LH and
FSH, whereas those with gonadotropin
deficiency, either secondary (pituitary) or
tertiary (hypothalamic), have low-normal, low,
or unmeasurable levels of LH and FSH

Cont…
• Most cases of hypogonadotropic
hypogonadism involve deficiencies of both LH
and FSH, in rare cases the secretion of only
one is impaired
• Isolated gonadotropin deficiency must also be
distinguished from
hypogonadotropic amenorrhea secondary to
exercise, diet, or mental stress

Clinical Features
WOMEN
• Amenorrhea
• Low serum
estrogen levels, and
infertility
• Eunuchoid habitus
generally present
MEN
• Low serum testosterone
levels
• Infertility
• Eunuchoid habitus

Thank you for your
attention!!!

Hormones of pituitary gland and its disorders

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