ABNORMALITIES OF

PITUITARY
DR CHANDRIMA PATTADAR
A. CONGENITAL VS ACQUIRED HYPOPITUITARISM
1. SOME CONGENITAL PROBLEMS
2. ADULT GH DEFICIENCY
3. SECONDARY ACTH DEFICIENCY
4. GONADOTROPIN DEFICIENCY

B.PITUITARY TUMOR
5. PITUITARY ADENOMA-
6. PROLACTINOMA
7. ACROMEGALY
8. NONFUNCTIONAL PITUITARY ADENOMA
HYPOPTUITARISM
 HYPOPTUITARISM

CONGENITAL ACQUIRED
• PITUITARY DYSPLASIA- 1.aplasia 2. • In newborn -birth trauma like cranial
Hypoplasia 3. ectopic pituitary gland hemorrhage, asphyxia, and breech delivery
• Traumatic -Surgical resection ,Radiation damage ,
• Congenital central nervous system mass, Head injuries
encephalocele
• Neoplastic
• Primary empty sella
• Infiltrative/inflammatory
• Congenital hypothalamic disorders (septo-optic
• Infections
dysplasia, Prader-Willi syndrome, Bardet-Biedl
syndrome, Kallmann syndrome) • Vascular
 Tissue-Specific Factor Mutations

Familial and sporadic PROP1 mutations

AUTOSOMAL DOMINANT PIT1
• GH, TSH, PROLACTIN
DEFICIENCY
• The pituitary may appear hypoplastic
on magnetic resonance imaging (MRI)
• GH, PRL, TSH, and GONADOTROPIN deficiency
• Due to gonadotropin deficiency, these
individuals do not enter puberty spontaneously
• small minority later develop adrenocorticotropic
hormone (ACTH) deficiency
• In some cases, the pituitary gland appears enlarged
on MRI
 Mutation in the HESX1 gene

SEPTO-OPTIC DYSPLASIA
Hypothalamic dysfunction and hypopituitarism ABSENT SEPTUM PELLUSIDUM

 Affected children may have following features:

• cleft palate
• syndactyly
• ear deformities
• hypertelorism,
• optic nerve hypoplasia
• micropenis
• anosmia.
 Kallmann syndrome
• Kallmann syndrome results from defective hypothalamic gonadotropin-releasing hormone (GnRH) synthesis and is
associated with anosmia or hyposmia due to olfactory bulb agenesis or hypoplasia

• Color blindness, optic atrophy, nerve deafness, cleft palate, renal abnormalities, cryptorchidism, and neurologic
abnormalities such as mirror movements.
• The initial genetic cause was identified in the X-linked KAL gene, mutations of which impair embryonic migration of
GnRH neurons from the hypothalamic olfactory placode to the hypothalamus.

• low luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and low concentrations of sex steroids
(testosterone or estradiol)
• GnRH deficiency prevents progression through puberty.
• Males =delayed puberty and pronounced hypogonadal features, including micropenis, probably the result of low
testosterone levels during infancy.
• Females = primary amenorrhea and failure of secondary sexual development

 Repetitive GnRH administration restores normal pituitary gonadotropin responses, pointing to a hypothalamic
defect in these patients.

 Long-term treatment of males with human chorionic gonadotropin (hCG) or testosterone restores pubertal
development and secondary sex characteristics; women can be treated with cyclic estrogen and progestin.

 , Fertility may be restored by the administration of gonadotropins or by using a portable infusion pump to deliver
subcutaneous, pulsatile GnRH
 Hypothalamic Infiltration Disorders
sarcoidosis, histiocytosis X, amyloidosis, and hemochromatosis— frequently involve both hypothalamic and pituitary
neuronal and neurochemical tracts
 Empty Sella Syndrome
• An empty sella may develop as a consequence of a primary congenital weakness
of the diaphragm in those patients in whom no secondary cause is evident, 50%
of patients have associated benign intracranial hypertension.
• A secondary empty sella may develop subsequent to infarction of a pituitary
adenoma or surgical or radiation-induced damage to the sellar diaphragm.

• MRI- pituitary tissue compressed against the sellar floor, with lateral stalk
deviation

• Although an empty sella is usually an incidental finding, if more than 90% of

pituitary tissue is compressed or atrophied, pituitary failure usually occurs.

• About 10% of patients may develop small GH-secreting or PRL-secreting

adenomas within the narrow rim of compressed pituitary tissue.
 Pituitary Apoplexy
• Risk factors: Preexisting adenoma; postpartum (Sheehan’s syndrome); association with diabetes,
hypertension, sickle cell anemia, or acute shock.

Acute intrapituitary hemorrhagic vascular events

Damage to the pituitary and surrounding sellar structure

Severe hypoglycemia, hypotension and shock,

central nervous system(CNS) hemorrhage, and death.

• Acute symptoms -severe headache with signs of meningeal irritation, bilateral visual changes,
ophthalmoplegia, and, in severe cases, cardiovascular collapse and loss of consciousness.
• (CT) or MRI may reveal signs of intratumoral or sellar hemorrhage, with pituitary stalk deviation and
compression of pituitary tissue.
• Treatment –
 Patients with no evident visual loss or impaired consciousness can be observed and managed conservatively
with high-dose glucocorticoids

 Those with significant or progressive visual loss, cranial nerve palsy, or loss of consciousness rNequire
urgent surgical decompression

Intrasellar mass is heterogenous. There is

blooming due to blood products on gradient echo
image corresponding to hemorrhage
 Immunotherapy
• Pituitary cells express cytotoxic T lymphocyte antigen-4 (CTLA-4).

• cancer immunotherapy with CTLA-4 blockers (e.g., ipilimumab) may develop hypophysitis with
associated thyroid adrenal and gonadal failure

• Treatment :
Pituitary hormone replacement, with or without high-dose glucocorticoids, may be safely tolerated with
continued immunotherapy.
 ADULT GH DEFICIENCY
• This disorder usually is caused by acquired hypothalamic or pituitary somatotrope damage.
• The sequential order of hormone loss is usually GH → FSH/LH → TSH → ACTH

• CLINICAL FEATURES:
 Impaired quality of life

• Impaired
Decreased quality of life
energy and drive  Body composition changes
Decreased energy and drive
• Poor concentration Increased body fat mass
Poor concentration
Central fat deposition
Low
• Lowself-esteem
self-esteem Increased waist-to-hip ratio
Social isolation
• Social isolation Decreased lean body mass
  Cardiovascular risk factors
• Impaired cardiac structure and
 Reduced exercise capacity
function
• Reduced maximum O2 uptake
• Abnormal lipid profile
• Impaired cardiac function
• Decreased fibrinolytic activity
• Reduced muscle mass
• Atherosclerosis
• Omental obesity
 INVESTIGATION
Testing should be restricted to patients with the following predisposing factors: (1) pituitary surgery, (2)
pituitary or hypothalamic tumor or granulomas, (3) history of cranial irradiation, (4) radiologic evidence of a
pituitary lesion, and (5) childhood requirement for GH replacement therapy.

The most validated test to distinguish pituitary-sufficient patients from those with AGHD is insulin-induced
(0.05–0.1 U/kg) hypoglycemia.
After glucose reduction to ~40 mg/dL, most individuals experience neuroglycopenic symptoms , and peak GH
release occurs at 60 min and remains elevated for up to 2 h. About 90% of healthy adults exhibit GH responses
>5 μg/L;

AGHD is defined by a peak GH response to hypoglycemia of <3 μg/L.

Although insulin-induced hypoglycemia is safe when performed under appropriate supervision, it is

contraindicated in patients with diabetes, ischemic heart disease, cerebrovascular disease, or epilepsy and in
elderly patients.
• Alternative stimulatory tests include intravenous arginine (30 g), GHRH (1 μg/kg), GHRP-6 (90 μg), and
glucagon (1 mg). Combinations of these tests may evoke GH secretion in subjects who are not responsive to
a single test.

• A significant proportion (~25%) of truly GH-deficient adults have low-normal IGF-I levels. Thus, as in the
evaluation of GH deficiency in children, valid age- and sex-matched IGF-I measurements provide a useful
index of therapeutic responses but are not sufficiently sensitive for diagnostic purposes
 CONTRAINDICATION OF
THERAPY:
 active neoplasm,
 intracranial hypertension
 uncontrolled diabetes
 retinopathy
• About 30% of patients exhibit reversible dose-related fluid retention, joint pain, and carpal tunnel syndrome,
and up to 40% exhibit myalgias and paresthesia.

• Patients receiving insulin require careful monitoring for dosing adjustments, as GH is a potent
counterregulatory hormone for insulin action. Patients with type 2 diabetes mellitus may initially develop
further insulin resistance.

• However, glycemic control usually improves with the sustained loss of abdominal fat associated with long-
term GH replacement.

• Headache, increased intracranial pressure, hypertension, and tinnitus occur rarely.

• Pituitary tumor regrowth and progression of skin lesions or other tumors have not been encountered in long-
term surveillance programs with appropriate replacement doses.
 ACTH DEFICIENCY
 Pituitary ACTH deficiency =>Secondary adrenal insufficiency

• Causes:
1.glucocorticoid withdrawal after treatment-associated suppression of the hypothalamic-pituitary-adrenal
(HPA) axis
2.surgical resection of an ACTH-secreting pituitary adenoma that has suppressed the HPA axis
3.mass effects of other pituitary adenomas or sellar lesions may lead to ACTH deficiency, usually in
combination with other pituitary hormone deficiencies
4.Rarely, TPIT or POMC mutations
 Clinical features :
• fatigue,
• weakness
• anorexia, nausea, vomiting
• occasionally hypoglycemia.

ACTH
 Insulin tolerance-dose : 0.1–0.15 U/kg IV Response: Peak cortisol response >18 μg/dL, or
increase by 7 μg/dL
 Metyrapone dose Oral administration of 30 mg/kg at 11 pm
Response
Peak 11-deoxycorticosterone; ≥7 μg/dL
Peak cortisol ≤7 μg/dL
Peak ACTH >75 pg/mL
 CRH stimulation dose100 μg IV, Response Peak ACTH ≥ twofold to fourfold
Peak cortisol ≥20 μg/dL or ↑ ≥7 μg/dL
 ACTH stimulation, dose:250 μg IV or IM or 1 μg IV, Response Peak cortisol ≥20 μg/dL Rare
 TREATMENT

• The total daily dose of hydrocortisone replacement preferably should generally not exceed 20 mg daily,
divided into two or three doses.

• Prednisone (5 mg each morning 8AM) is longer acting and has fewer mineralocorticoid effects than
hydrocortisone.

• Cortisone acetate (15–25 mg/d in divided doses)

• Doses should be increased severalfold during periods of acute illness or stress

 GONADOTROPIN DEFICIENCY
• Hypogonadism is the most common presenting feature of adult hypopituitarism even when other
pituitary hormones are also deficient.

• Acquired forms of GnRH deficiency : anorexia nervosa, stress, starvation, and extreme exercise but
also may be idiopathic.

• Hypothalamic defects associated with GnRH deficiency include Kallmann syndrome and
mutations in more than a dozen genes that regulate GnRH neuron migration, development, and
function . Mutations in GPR54, DAX1, kisspeptin, the GnRH receptor, and the LHβ or FSHβ
subunit genes also cause pituitary gonadotropin deficiency.
 CLINICAL PRESENTATION:
 In premenopausal women, hypogonadotropic hypogonadism presents as
diminished ovarian function leading to oligomenorrhea or amenorrhea, infertility,
decreased vaginal secretions, decreased libido, and breast atrophy.

 In hypogonadal adult men, secondary testicular failure is associated with

decreased libido and potency, infertility, decreased muscle mass with weakness,
reduced beard and body hair growth, soft testes, and characteristic fine facial
wrinkles.

 Osteoporosis occurs in both untreated hypogonadal women and men

 DIAGNOSIS :
 NORMAL RESPONSE : Intravenous GnRH (100 μg) stimulates gonadotropes to secrete LH
(which peaks within 30 min) and FSH (which plateaus during the ensuing 60 min). Normal
responses vary according to menstrual cycle age, age, and sex of the patient. Generally, LH
levels increase about threefold, whereas FSH responses are less pronounced.

 In the setting of gonadotropin deficiency, a normal gonadotropin response to GnRH indicates

intact pituitary gonadotrope function and suggests a hypothalamic abnormality. An absent
response, however, does not reliably distinguish pituitary from hypothalamic causes of
hypogonadism.
 For this reason, GnRH testing usually adds little to the information gained from baseline
evaluation of the hypothalamic-pituitary-gonadotrope axis except in cases of isolated GnRH
deficiency (e.g., Kallmann syndrome)

 MRI examination of the sellar region and assessment of other pituitary functions usually are
indicated in patients with documented central hypogonadism.
 TREATMENT :
 Males :Testosterone may be administered by intramuscular injections(200mg) every 1–4
weeks or by using skin patches or testosterone gels(5-10gm/d)
 Gonadotropin injections (hCG or human menopausal gonadotropin [hMG]) over 12–
18 months are used to restore fertility.
 Pulsatile GnRH therapy (25–150 ng/kg every 2 h), administered by a subcutaneous
infusion pump, is also effective for treatment of hypothalamic hypogonadism when fertility
is desired.

 Premenopausal women:
 Gonadotropin therapy is used for ovulation induction. Follicular growth and maturation are
initiated using hMG or recombinant FSH; hCG or human luteinizing hormone (hLH) is
subsequently injected to induce ovulation. As in men, pulsatile GnRH therapy can be used
to treat hypothalamic causes of gonadotropin deficiency.
PITUITARY ADENOMA
• Pituitary adenomas are the most common cause of pituitary hormone hypersecretion and hyposecretion
syndromes in adults.
• They account for ~15% of all intracranial neoplasms. These is benign lesion.
• Morphologically, these tumors may arise from a single polysecreting cell type or include cells with mixed
function within the same tumor..
• Hormone production does not always correlate with tumor size. Small hormone-secreting adenomas
may cause significant clinical perturbations, whereas larger adenomas that produce less hormone may be
clinically silent and remain undiagnosed (if no central compressive effects occur).
• About one-third of all adenomas are clinically nonfunctioning and produce no distinct clinical
hypersecretory syndrome
 NOTE:
• Several physiologic states are associated with pituitary enlargement. Lactotroph hyperplasia occurs
during pregnancy, and thyrotroph, gonadotroph, or rarely corticotroph hyperplasias occur in the presence
of long-standing primary thyroid, gonadal, or adrenal failure, respectively.
Pituitary enlargement may also occur as a result of ectopic GH-releasing hormone (GHRH) or
corticotrophin-releasing hormone (CRH) secretion, from pulmonary and pancreatic neuroendocrine tumors
or hypothalamic
gangliocytomas, with resultant hyperplasia of somatotroph or corticotroph cells.
• The presenting clinical features of functional pituitary adenomas (e.g., acromegaly, prolactinomas, or
Cushing syndrome) should guide the laboratory studies.

• When a pituitary adenoma is suspected based on MRI, initial hormonal evaluation usually includes (1)
basal prolactin (PRL); (2) insulin-like growth factor (IGF)-I; (3) 24-h urinary free cortisol (UFC) and/or
overnight oral dexamethasone (1 mg) suppression test; (4) α subunit, follicle-stimulating hormone (FSH),
and luteinizing hormone (LH); and (5) thyroid function tests.

• Immunohistochemical staining of pituitary tumor specimens obtained at transsphenoidal surgery confirms

clinical and laboratory studies and provides a histologic diagnosis when hormone studies are equivocal and
in cases of clinically nonfunctioning tumors.
 HYPERPROLACTINEMIA
• Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men and women.
• Prolactin secreting pituitary adenomas (prolactinomas) are the most common cause of PRL levels >200 μg/L.
Less pronounced PRL elevation can also be seen with microprolactinomas but is more commonly caused by
drugs, pituitary stalk compression, hypothyroidism, or renal failure

 PROLACTINOMA :
• Tumors arising from lactotrope cells account for about half of all functioning pituitary tumors, with a
population prevalence of ~10/100,000 in men and ~30/100,000 in women.
• Mixed tumors that secrete combinations of GH and PRL, ACTH and PRL, and rarely TSH and PRL are also
seen.
• Microadenomas are classified as <1 cm in diameter and usually do not invade
the parasellar region.
• Macroadenomas are >1 cm in diameter and may be locally invasive and
impinge on adjacent structures.
• The female-to-male ratio for microprolactinomas is 20:1, whereas the sex
ratio is near 1:1 for macroadenomas.
• Tumor size generally correlates directly with PRL concentrations; values >250
μg/L usually are associated with macroadenomas.
• Men tend to present with larger tumors than women, possibly because the
features of male hypogonadism are less readily evident.
• PRL levels remain stable in most patients, reflecting the slow growth of these
tumors.
• About 5% of microadenomas progress in the long term to macroadenomas.
 Lesions of the hypothalamic-pituitary region that disrupt hypothalamic dopamine synthesis, portal
vessel delivery, or lactotrope responses are associated with hyperprolactinemia.
Tumors -Craniopharyngioma ,Suprasellar pituitary mass ,Meningioma ,Dysgerminoma ,Metastases
,Plurihormonal adenomas (including GH and ACTH tumors) may hypersecrete PRL directly
 Empty sella
 Lymphocytic hypophysitis
 Adenoma with stalk
 Compression
 Granulomas
 Rathke cyst
Irradiation (elevated prolactin usually in the range of 30–100 μg/L.)
 Trauma -Pituitary stalk section ,Suprasellar surgery

 Pituitary hypersecretion
 Prolactinoma
 Acromegaly
 CLINICAL PRESENTATION IN WOMEN:

• Amenorrhea, galactorrhea, and infertility.

• If hyperprolactinemia develops before menarche, primary amenorrhea results.
• More commonly, hyperprolactinemia develops later in life and leads to oligomenorrhea
and ultimately to amenorrhea.
• If hyperprolactinemia is sustained, vertebral bone mineral density can be reduced
compared with age-matched controls, particularly when it is associated with pronounced
hypoestrogenemia.
• Galactorrhea is present in up to 80% of hyperprolactinemic women. Although usually
bilateral and spontaneous, it may be unilateral or expressed only manually.
• Patients also may complain of decreased libido, weight gain, and mild hirsutism .
 CLINICAL PRESENTATION IN MEN:

• Diminished libido, infertility, visual loss (from optic nerve compression) , headache are
the usual presenting symptoms.
• Gonadotropin suppression leads to reduced testosterone, impotence, and oligospermia.
• True galactorrhea is uncommon in men with hyperprolactinemia.
• If the disorder is long-standing, secondary effects of hypogonadism are evident,
including osteopenia, reduced muscle mass, and decreased beard growth
• DIAGNOSIS:
• The diagnosis of idiopathic hyperprolactinemia is made by exclusion of known causes of
hyperprolactinemia in the setting of a normal pituitary MRI.
• Some of these patients may harbor small microadenomas below visible MRI sensitivity (~2 mm)
• Basal, fasting morning PRL levels (normally <20 μg/L) should be measured to assess
hypersecretion.

• Assuming that physiologic and medication-induced causes of hyperprolactinemia are excluded

(Table 373-5), the diagnosis of prolactinoma is likely with a PRL level >200 μg/L. PRL levels
<100 μg/L may be caused by microadenomas, other sellar lesions that decrease dopamine
inhibition, or nonneoplastic causes of hyperprolactinemia.
• Both false-positive and false-negative results may be encountered. In patients with markedly
elevated PRL levels (>1000 μg/L), reported results may be falsely lowered because of assay
artifacts; sample dilution is required to measure these high values accurately.
• Falsely elevated values may be caused by aggregated forms of circulating PRL, which are usually
biologically inactive (macroprolactinemia).
• Hypothyroidism should be excluded by measuring TSH and T4 levels.
 CABERGOLINE :long-acting dopamine agonist with high D2 receptor affinity.
 The drug effectively suppresses PRL for >14 days after a single oral dose and induces prolactinoma
shrinkage in most patients.
 Cabergoline (0.5–1.0 mg twice weekly) achieves normoprolactinemia and resumption of normal
gonadal function in ~80% of patients with microadenomas; galactorrhea improves or resolves in 90%
of patients.
 Cabergoline normalizes PRL and shrinks ~70% of macroprolactinomas. Mass effect symptoms,
including headaches and visual disorders, usually improve dramatically within days after cabergoline
initiation; improvement of sexual function requires several weeks of treatment but may occur before
complete normalization of PRL levels.
 After initial control of PRL levels has been achieved, cabergoline should be reduced to the lowest
effective maintenance dose.
 In ~5% of treated patients harboring a microadenoma, hyperprolactinemiamay resolve and not recur
when dopamine agonists are discontinued after long-term treatment.
 Cabergoline also may be effective in patients resistant to bromocriptine.
 Adverse effects and drug intolerance are encountered less commonly than with bromocriptine.
 Bromocriptine :dopamine receptor agonist that suppresses PRL secretion. Because it is short-
acting, the drug is preferred when pregnancy is desired.
• In microadenomas, bromocriptine rapidly lowers serum PRL levels to normal in up to 70% of
patients, decreases tumor size, and restores gonadal function.
• In patients with macroadenomas, PRL levels are also normalized in 70% of patients, and tumor
mass shrinkage (≥50%) is achieved in most patients.
Therapy is initiated by administering a low bromocriptine dose (0.625–1.25 mg) at bedtime
with a snack, followed by gradually increasing the dose. Most patients are controlled with a
daily dose of <7.5 mg (2.5 mg tid).
• Initial PRL normalization is achieved in ~70% of microprolactinomas after surgical resection, but only
30% of macroadenomas can be resected successfully.
• Hyperprolactinemia recurs in up to 20% of patients within the first year after surgery; long-term
recurrence rates exceed 50% for macroadenomas

• Radiotherapy for prolactinomas is reserved for patients with aggressive tumors that do not respond to
maximally tolerated dopamine agonists and/or surgery.
• PREGNANCY :
• About 5% of microadenomas significantly increase in size, but 15–30% of
macroadenomas grow during pregnancy. Bromocriptine has been used for >30
years to restore fertility in women with hyperprolactinemia, without evidence of
teratogenic effects.
• For women taking bromocriptine who desire pregnancy, mechanical
contraception should be used through three regular menstrual cycles to allow
for conception timing.
• When pregnancy is confirmed, bromocriptine should be discontinued and PRL
levels followed serially, especially if headaches or visual symptoms occur.
• For women harboring macroadenomas, regular visual field testing is
recommended, and the drug should be reinstituted if tumor growth is apparent.
ACROMEGALY
 MORTALOTY
Cardiovascular disease is the leading cause of
death followed by respiratory disease (18%) and
cerebrovascular disease (14%). Diabetes mellitus,
occurring in 20% of patients, is associated with 2.5
times the predicted mortality rate, and hypertension
is present in about half of all patients.
The most significant mortality determinants are GH
levels greater than 2.5 μg/L,elevated IGF1 levels, the
presence of coexisting hypertension and cardiac
disease, older age, a history of pituitary irradiation,
and overreplaced ACTH-dependent adrenal
insufficiency.
Overtreatment of adrenal insufficiency with doses of
hydrocortisone more than 25 mg daily also is
predictive of mortality.
 Laboratory Investigation :
 Age-matched serum IGF-I levels are elevated in acromegaly. Consequently, an IGF-I level
provides useful laboratory screening measure when clinical features raise the possibility of
acromegaly.
 Owing to the pulsatility of GH secretion, measurement of a single random GH level is not
useful for the diagnosis or exclusion of acromegaly and does not correlate with disease severity.
 The diagnosis of acromegaly is confirmed by demonstrating the failure of GH suppression
to <0.4 μg/L within 1–2 h of an oral glucose load (75 g). When newer ultrasensitive GH
assays are used, normal nadir GH levels are even lower (<0.05 μg/L).
 About 20% of patients exhibit a paradoxical GH rise after glucose.
 PRL should be measured, as it is elevated in ~25% of patients with acromegaly.
 Thyroid function, gonadotropins, and sex steroids may be attenuated because of tumor mass
effects.
 Because most patients will undergo surgery with glucocorticoid coverage, tests of ACTH
reserve in asymptomatic patients are more efficiently deferred until after surgery.
 SOMATOSTATIN ANALOGUES:
 Exert therapeutic effects through SSTR2 and SSTR5 receptors, both of which are expressed by GH-secreting
tumors.
 Octreotide acetate is an eight-amino-acid synthetic somatostatin analogue. In contrast to native somatostatin,
the analogue is relatively resistant to plasma degradation. It has a 2-h serum half-life and possesses 40-fold
greater potency than native somatostatin to suppress GH.
 Octreotide is administered by subcutaneous injection, beginning with 50 μg tid; the dose can be increased
gradually up to 1500 μg/d. Octreotide suppresses integrated GH levels and normalizes IGF-I levels in ~60%
of treated patients.
 GH suppression occurs for as long as 6 weeks after a 30-mg intramuscular injection; long-term monthly
treatment sustains GH and IGF-I suppression and also reduces pituitary tumor size in ~50% of patients.
 Lanreotide Autogel, a slow-release depot somatostatin preparation, that suppresses GH and IGF-I
hypersecretion after a 60-mg subcutaneous injection. Long-term (every 4–6 weeks) administration controls
GH hypersecretion in about two-thirds of treated patients and improves patient compliance because of the
long interval required between drug injections. Rapid relief of headache and soft tissue swelling occurs in
~75% of patients within days to weeks of somatostatin analogue initiation. Most patients report symptomatic
improvement, including amelioration of headache, perspiration, obstructive apnea, and cardiac failure. For
those resistant to octreotide, pasireotide, with preferential SST5 binding, has been shown to exhibit efficacy.
 GH RECEPTOR ANTAGONIST

• Pegvisomant antagonizes endogenous GH action by blocking peripheral GH binding to its receptor.

• Daily subcutaneous injection (10–20 mg) and normalizes IGF-I in ~70% of patients. GH levels,
however, remain elevated as the drug does not target the pituitary adenoma.
• Side effects include reversible liver enzyme elevation, lipodystrophy, and injection site pain. Tumor size
should be monitored by MRI.

• Combined treatment with monthly somatostatin analogues and weekly or biweekly pegvisomant injections
has been used effectively in resistant patients

 DOPAMINE AGONISTS
Bromocriptine and cabergoline may modestly suppress GH secretion in some patients. Very high doses of
bromocriptine (≥20 mg/d) or cabergoline (0.5 mg/d) are usually required to achieve modest GH therapeutic
efficacy.
■■NONFUNCTIONING AND GONADOTROPINPRODUCING PITUITARY
ADENOMAS
 Secrete little or no pituitary hormones as well as tumors that produce too little hormone to
result in recognizable clinical features.

 They are the most common type of pituitary adenoma and are usually macroadenomas at the
time of diagnosis because clinical features are not apparent until tumor mass effects occur.

 Based on immunohistochemistry, most clinically nonfunctioning adenomas can be shown to

originate from gonadotrope cells. These tumors typically produce small amounts of intact
gonadotropins (usually FSH) as well as uncombined α, LH β, and FSH β subunits. Tumor
secretion may lead to elevated α and FSH β subunits and, rarely, to increased LH β subunit
levels. Some adenomas express α subunits without FSH or LH. TRH administration often
induces an atypical increase of tumor-derived gonadotropins or subunits.
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