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Anterior-Pituitary-function-and-diseases.ppt
1. Anterior Pituitary
function and diseases
Dr.Abdel-Ellah Al-shudifat
Consultant Internist
Associate professor,
Hashemite University
2. Anatomy
๏ The pituitary gland lies at the base of the
skull, in a portion of the sphenoid bone
called sella turcica
๏ The size of the pituitary is about15x10x6
mm.
3. Blood supply and histology
๏ The anterior pituitary is the most richly
vascularised of all mamalian tissues
๏ It receive 0.8mg/min from a portal
circulation connecting hypothalamus and
ant. Pituitary
๏ Arterial supply from the int. carotid via
superior,middle and the inferior
hypophyseal arteries
๏ Venous drainage venous channels to the
cavernous sinus post. Into sup and inferior
petrosal sinuses
6. Histology
๏ somatotrophs: secrete Growth hormone,
acidophilic Somatotrophs on hematoxylin-
Eosin staining, constitute 50% of
adenohypophysis cells
๏ Lactotrophs:acidophylic, constitue 10-25%
of ant.pituitary cells.these cells proliferate
during pregnancy and increase in size due
to high estrogen level
7. Histology
๏ Thyrotrophs:
๏ TSH producing cells,constitute less than 10% of
adenohypophysis cells, basophilic,hypertrophy
markedly in pregnancy
๏ Corticotroph:
๏ ACTH and related peptide are secreted by
basophilic cells that embryologically of
intermediate lobe origin, constitute 15-20% of
adenohypophysis cells
8. Histology
๏ Gonadotrophs:
LH and Follicle stim hormone(FSH) originate
from basophilic staining cells,const.10-15% of
ant.pituitary cells,hypertrophy in cases of
primary gonadal failure (e.g Klienfilter synd)
๏ Other cell types
Called nun cells and may give rise to
nonfunctioning adenoma
9. Hypothalamic hormones
๏ Secreted by the hypothamus into the
hypophyseal portal vessels:
1. GHRH-GH releasing hormone
2. CRH-corticotropin releasing hormone
3. GnRH: gonadotropin releasing hormone
4. TRH
5. Somatostatin
6. Dopamine-the primary prolactin inhibiting
hormone
10. Posterior pituitary hormones:
Arginine vasopressin(ADH) :
syntehesized in the large cell bodies in the
supraoptic nuclei, control water balance and
is a potent vasoconstrictor,regulates Blood
pressure.
๏ Oxytocin: cause contraction of the smooth
muscles,esp in the myoepithelial cells in the
ducts of mammary glands-express milk
11. Anterior pituitary Hormones
๏ 6 Hormones:
1. ACTH &related peptides:
A 39 aa molecule produced inside the
corticotrophs .
Stimulates the secretion of glucocorticoids from
the adrenal cortex
12. Anterior pituitary hormones
๏ Function of ACTH:
๏ Stimulates the secretion of
glucocorticoids,mineralocorticoids and
androgenic steroids from the adrenal cortex
๏ Binds to receptors on the adrenal cortex and
induces steroidogenesis using c-AMP
๏ The hyperpigmentation is due to ACTH binding
to the MSH receptors(observed in Addisonโs
disease and Nelsonโs disease)
13. ACTH
๏ Secretion:
๏ Basal morning conc ranges 9-52 pg/ml
๏ Mediated through neural stimuli(stress,
physical emotional or chemicall) mainly by
CRH,which is secreted in a pulstile
manner.
๏ Diurnal rhythm,highest concentration in
early morning hours,and declines as day
progress .
14. ACTH
๏ Negative feedback by cortisol and
synthetic steroids (e.g dexamethasone,
prednisolone and methylprednisolone)
occurs at both the hypothalamic and
pituitary levels.
๏ Use clinically in dexamethasone
suppression test in the diagnosis of
Cushings disease
15. Growth Hormone
๏ GH or somatotropin is 191 a.a polypeptide
hormone synthesized and secreted by the
somatotrophs
๏ Function: promotes linear growth through
Insulin like growth factor 1(IGF1)
๏ Effects โprotein sparing by increasing utilization
of fat as energy source.
๏ Decrease carbohydrate metabolism in excess,
and impairs glucose uptake by cells(insulin
resistance)
16. Growth Hormone
๏ Measurement:
๏ Has short half life time of 15-20 min
๏ The early morning concentration of GH in
adults is 2 ng/ml, no sex difference
๏ IGF1 concentration are measured by radio
immune assay- more accurate of the
biologic activity of GH than GH
measurement
20. Characterestics of common pit tumors
Tumor Usual size Clinical
presentation
Prolactinoma Most<10 mm
Some>1 0 mm-
macroprolactinoma
Galactorrhea
Amenorrhea
Headache,visual
field defects,
hypopituitarism
Acromegaly Few mms-several
CM
Change in
apparance,V.F
defects
Cushing`s
disease
Mostly few mms Central obesity
Cushingoid
21. Tumor or
condition
Usual size Most common
presenting
symptoms/signs
Nelson`s
syndrome
Often>10 mm Post
adrenalectomy
hyperpigmentation
Non-functioning
pit
tumors
Often large>10 mm Visual field defect
Hypopituitarism
Incidental finding
craniopharyngio
ma
Large and cystic
Calcification +
Headache
Visual field defect
Growth failure
22. Pituitary tumors cause symptoms
by pressure or infiltration
๏ the visual pathways, with field defects and visual
loss, the cavernous sinus, with III, IV and VI
cranial nerve lesions
๏ bony structures and the meninges surrounding
the fossa, causing headache
๏ hypothalamic centres: altered appetite, obesity,
thirst, somnolence/wakefulness or precocious
puberty
๏ the ventricles, causing interruption of
cerebrospinal fluid (CSF) flow leading to
hydrocephalus
๏ the sphenoid sinus with invasion causing CSF
rhinorrhoea
23. Is there hormonal secretion?
๏ There are 3 major conditions usually caused by
secretion from pituitary adenomas which will show
positive immunostaining for the relevant hormone:
๏ prolactin excess (prolactinoma ) - histologically,
prolactinomas are 'chromophobe' adenomas (a
description of their appearance on classical
histological staining)
๏ GH excess, leading to acromegaly or gigantism -
somatotroph adenomas, usually 'acidophil', and
sometimes due to specific G-protein mutations .
๏ Cushing's disease and Nelson's syndrome (excess
ACTH secretion) - corticotroph adenomas, usually
'basophil'
24. Is the tumor functionally active?
๏ Some pituitary tumours cause no clinically
apparent hormone excess and are referred
to as 'non-functioning' tumours, which are
common and usually 'chromophobe'
adenomas.
๏ Laboratory studies such as
immunocytochemistry show that these
tumours may often produce LH and FSH or
the ฮฑ-subunit of LH, FSH and TSH ,and
occasionally ACTH
25. Is there hormonal deficiency?
๏ Clinical examination may give clues; thus,
short stature in a child with a pituitary
tumour is likely to be due to GH deficiency.
A slow, lethargic adult with pale skin is
likely to be deficient in TSH and/or ACTH.
Milder deficiencies may not be obvious,
and require specific testing
26. Tests for hypothalamic-pituitary
function
Axis Pit
Hormone
End
organ/funct
ion
Common
Dynamic
test
Other
tests
H-Pituit
ovarian
LH Estradiol Ovarian
US
FSH Progestero
ne,Day 21
LHRH
test
H-Pituit
Testicu
lar
LH Testostoste
rone
Sperm
count
FSH LHRH
29. Replacement therapy in
hypopituitarism
Axis Usual replacement therapy
Adrenal Hydrocortisone 15-40 mg/d
No need for mineralocorticoids
Thyroid Thyroxine 100-150 mcg/d
Gonadal /Male Testosterone-IM ,oral, or transdermal
Gonadal /female Cyclical estrogen/progesterone oral
or patch
Fertility HCG plus FSH
GNRH pulsatile to produce testicular
development and spermatogenesis
30. Replacement therapy in
hypopituitarism
Axis Usual replacement
Growth Recombinant human GH used
routinely to achieve normal growth
In children (and adults with GH def)
Thirst Desmopressin 10-20 mcg nasal
spray2-3/day, or 100-200 mcg oral
Prolactin
inhibition
Dopamine agonists (cabergoline
500 mcg/ twice per wk
32. Acromegaly
Definition:
๏ Uncommon disease of GH oversecretion,
annual incidence 3-4/million
๏ Hypersecretion of GH
๏ Normally GH secreted in a pulsatile fashion,
stimulatory effect by GHRH, and inhibited by
somatostatin
๏ Over 95% are due to somatotroph adenoma
๏ Could be a part of MEN1(multiple endocrine
Neoplasia)
33. Clinical presentation
๏ Mean age at Dx 4o years
๏ Prevalence in Male=female
๏ The classic image:
๏ฑ Frontal bossing
๏ฑ Coarse facial features
๏ฑ Thick lips, protruding jaw,widely spaced
teeth
๏ฑ Large hands and feet
34. Clinical presentation
๏ Most patients do not complain to physician of
somatic growth as these are subtle and gradual
๏ 40% are detected accidentally by a dentist or
orthopedic surgeon
๏ The most common presenting complaints in
women is menstrual disorder
๏ Acromegaly is a chronic disease, slowly
progressive that may go undetected for about 10
years
35. Medical complications
๏ Local Tumor growth:
1) Hadache
2) Visual field defect
3) Cranial nerve palsies
๏ Metabolic consequences
1) HTN
2) heart failure
3) sleep apnea
4) arthropathy
5) diabetes
๏ Increase incidence of neoplasia , esp. colon
๏ Greater risk of premature death due to
cardiovascular disease,followed by malignancy
36. Diagnosis
๏ Most clinicians rely on measurement of
IGF-1,the IGF-1 value is fairly stable .
๏ IGF1 levels followed by growth hormone
levels before and after glucose tolerance
test
๏ GH measurement is not reliable as it is
pulsatile,also may be high in uncontrolled
DM, liver disease and malnutrition
๏ Radiological: MRI pituitary with
Gadalinium contrast to show the tumor
37. Treatment
Surgery:
๏ Trans-sphenoidal surgery is the treatment
of choice in most patients
๏ The efficacy of surgery is a function of size
and location of the tumor, and skill and
experience of the neurosurgeon
๏ Following transphenoidal surgery GH and
IGF-a normalize in about 80% of patients
with micradenoma vs 50-60% for
macroadenoma
38. Treatment of acromegaly
๏ Radiotherapy
๏ Medical therapy
1) Somatostatin analogs:Octreotide LAR
and lanreotide autogel, can be given
monthly by IM or SC injection, decrease
GH secretion in up to 90% of patients
2) Dopamine agonists:Bromocriptine and
cabergoline
3) GH receptor antagonist(pegvisomant)
39. Hypopituitarism
๏ Hypopituitarism refers to decreased
secretion of pituitary hormones, which can
result from diseases of the pituitary gland or
from diseases of the hypothalamus.
41. ๏ Hypothalamic diseases
๏ Mass lesions - benign
(craniopharyngiomas) and malignant
tumors (metastatic from lung, breast,
etc.)
๏ Radiation - for CNS and
nasopharyngeal malignancies
๏ Infiltrative lesions - sarcoidosis,
Langerhans cell histiocytosis
๏ Trauma - fracture of skull base
๏ Infections - tuberculous meningitis
42. Clinical manifestations of
hypopituitarism
๏ The presentation of hypopituitarism can be
considered as the presentation of deficiency
of each anterior pituitary hormone
๏ Damage to the anterior pituitary can occur
suddenly or slowly, can be mild or severe, and
can affect the secretion of one, several, or all
of its hormones.
๏ As a result, the clinical presentation of
anterior pituitary hormone deficiencies varies.
43. ๏ As a general rule, the secretion of
gonadotropins and growth hormone is
more likely to be affected than ACTH
and thyroid-stimulating hormone (TSH).
๏ Many exceptions occur, however, so
that one may see a patient who has
only isolated ACTH deficiency.
๏ Patients in whom the hypopituitarism is
due to a sellar mass may also have
symptoms related to the mass, such as
headache, visual loss, or diplopia
44. HORMONE DEFICIENCIES
๏ ACTH โ The presentation of ACTH deficiency
(secondary adrenal insufficiency) is almost
exclusively that of the resulting cortisol deficiency.
In its most severe form, cortisol deficiency leads to
death due to vascular collapse because cortisol is
necessary for maintenance of peripheral vascular
tone.
๏ A less severe form of the same phenomenon is
postural hypotension and tachycardia.
๏ Mild, chronic deficiency may result in lassitude,
fatigue, anorexia, weight loss, decreased libido,
hypoglycemia, and eosinophilia.
45. ๏ There are two important clinical distinctions between
ACTH deficiency and primary adrenal insufficiency
with a secondary increase in ACTH release :
1) ACTH deficiency does not cause salt wasting,
volume contraction, and hyperkalemia because it
does not result in clinically important deficiency of
aldosterone.
2) ACTH deficiency does not result in
hyperpigmentation.
๏ Both forms of adrenal insufficiency can cause
hyponatremia. This abnormality is due to
inappropriate secretion of antidiuretic hormone
(vasopressin) that is caused by cortisol (not
aldosterone) deficiency .
46. ๏ TSH โ Common symptoms include
fatigue, cold intolerance, decreased
appetite, constipation, facial puffiness,
dry skin, bradycardia, delayed
relaxation phase of the deep tendon
reflexes, and anemia.
๏ The degree of symptoms and abnormal
physical findings usually parallels the
degree of thyroxine deficiency, but as
the case with ACTH deficiency, some
patients with marked TSH deficiency
have few or no symptoms.
47. ๏ Growth hormone โ Growth hormone
deficiency in children typically presents as
short stature .
๏ Likely clinical manifestations of growth
hormone deficiency in adults are changes in
body composition (increased fat mass with a
decrease in lean body mass) and decreased
bone mineral density in men. Also possible,
but not yet confirmed, are decreased bone
mineral density in women, dyslipidemia,
cardiovascular disease, impaired
psychological function, and an increase in
mortality.
48. ๏ Prolactin
๏ The only known clinical manifestation
of prolactin deficiency is the inability to
lactate after delivery. Isolated prolactin
deficiency is rare; most patients with
acquired prolactin deficiency have
evidence of other pituitary hormone
deficiencies .
49. ๏ Gonadotropins โ Deficient secretion of the FSH and
LH results in hypogonadotropic hypogonadism
(secondary hypogonadism) in both women and men.
๏ In women, hypogonadism means ovarian
hypofunction, which results in decreased estradiol
secretion.
๏ The clinical consequences of estradiol deficiency in
women with secondary hypogonadism are similar to
those seen in women with primary hypogonadism .
๏ Findings in premenopausal women include irregular
periods or amenorrhea, anovulatory infertility,
vaginal atrophy, and hot flashes. No physical
findings of hypogonadism are detectable initially,
but after several years, breast tissue decreases and
bone mineral density declines.
50. ๏ In men, hypogonadism means
testicular hypofunction, which results
in infertility and decreased testosterone
secretion.
๏ The latter causes decreased energy
and libido, and hot flashes if
sufficiently severe, within weeks to
months, but does not cause decreased
muscle mass (and perhaps strength)
for several years.
๏ Testosterone deficiency also causes
decreased bone mineral density .
51. Diagnosis of hypopituitarism
๏ CORTICOTROPIN
๏ For normal health, the basal secretion of
corticotropin (ACTH) must be sufficient to
maintain the serum cortisol concentration
within the normal range. For survival, it
must increase to raise serum cortisol
concentrations in times of physical stress.
52. ๏ Basal ACTH secretion
๏ To test basal ACTH secretion, serum cortisol should be measured
at 8 to 9 AM, and the results should be interpreted as follows:
๏ A serum cortisol value of โค3 mcg/dL (83 nmol/L; normal range 5 to
25 mcg/dL [138 to 690 nmol/L]), confirmed by a second
determination, is strong evidence of cortisol deficiency, which in a
patient with a disorder known to cause hypopituitarism is usually
the result of that disorder.
๏ Such a finding in the absence of any known cause of
hypopituitarism mandates measurement of serum ACTH.
๏ A serum ACTH value not higher than normal is inappropriately low
and establishes the diagnosis of secondary adrenal deficiency (ie,
pituitary or hypothalamic disease).
๏ A value higher than normal documents primary adrenal
insufficiency (ie, adrenal disease).
53. ๏ A serum cortisol value of โฅ18 mcg/dL (497
nmol/L) indicates that basal ACTH secretion
is sufficient and also that it is probably
sufficient for times of physical stress.
๏ A serum cortisol value >3 mcg/dL (83 nmol/L)
but <18 mcg/dL (497 nmol/L) that is
persistent on repeat determination is an
indication to evaluate ACTH reserve.
๏ ACTH reserve โ ACTH reserve should be
measured in patients with intermediate
serum cortisol values. Several tests of ACTH
reserve are available; each has advantages
and disadvantages.
54.
55. ๏ Metyrapone test โ
๏ The rationale for the administration of
metyrapone is that it blocks 11-beta-hydroxylase
(CYP11B1), the enzyme that catalyzes the
conversion of 11-deoxycortisol to cortisol,
resulting in a reduction in cortisol secretion . The
ensuing fall in serum cortisol should, if the
hypothalamic-pituitary-adrenal axis is normal,
cause an increase in ACTH secretion and
therefore an increase in adrenal steroidogenesis
up to and including 11-deoxycortisol.
56. ๏ In normal subjects, administration of
750 mg of metyrapone orally every four
hours for 24 hours results in a decline
in 8 AM serum cortisol to less than 7
mcg/dL (172 nmol/L) and an elevation
in 8 AM serum 11-deoxycortisol to โฅ10
mcg/dL (289 nmol/L) at the end of the
24 hours . Patients taking phenytoin
metabolize metyrapone more rapidly
than normal; as a result, each
metyrapone dose should be 1500 mg.
57. ๏ After the 8 AM blood sample is taken at
the end of the 24 hours, 100 mg of
hydrocortisone should be administered
intravenously to reverse the cortisol
deficiency caused by the metyrapone.
๏ In patients who have decreased ACTH
reserve due to hypothalamic or
pituitary disease, the serum 11-
deoxycortisol concentration will be less
than 10 mcg/dL (289 nmol/L) at the end
of 24 hours .
58. ๏ Interpretation of the metyrapone test requires
adequate inhibition of cortisol production. If the
serum 11-deoxycortisol concentration at the
end of 24 hours is <10 mcg/dL (289 nmol/L) but
the serum cortisol concentration is โฅ7 mcg/dL
(193 nmol/L), the reason for the insufficient rise
in 11-deoxycortisol may be insufficient
inhibition by metyrapone. In this case, reasons
for insufficient inhibition should be sought,
such as failure to take all of the metyrapone,
rapid metabolism, and malabsorption. The test
should be then be repeated using a double
dose of metyrapone.
59. ๏ The advantages of the metyrapone test
are that it can be administered to adults
of any age and the results correlate
reasonably well with the serum cortisol
response to surgical stress. The principal
disadvantage is that the patient must be
observed in an inpatient setting so that
blood pressure and pulse can be
measured lying and standing before each
four-hourly dose for 24 hours.
60. ๏ If postural hypotension occurs, the test
should be terminated by administration
of 100 mg of hydrocortisone
intravenously.
๏ A shorter version of this test involves the
administration of a single 750 mg dose of
metyrapone at midnight and
measurements of serum 11-deoxycortisol
and cortisol at 8 AM . It may not,
however, separate normal from abnormal
as well as the longer test.
61. ๏ Insulin-induced hypoglycemia test โ
๏ The rationale for this test is that hypoglycemia
induced by insulin administration is a sufficient
stress to stimulate ACTH and therefore cortisol
secretion. The test is performed by
administering 0.1 unit of insulin per kg of body
weight and measuring serum glucose and
cortisol before and 15, 30, 60, 90, and 120
minutes after the injection .
๏ In normal subjects, serum cortisol increases to
โฅ18 mcg/dL (498 nmol/L) if the serum glucose
falls to <50 mg/dL (2.8 mmol/L).
62. ๏ The advantage of this test is that the results also
correlate relatively well with the serum cortisol
response to surgical stress. The disadvantages
are that hypoglycemia can be dangerous in
elderly patients and those with cardiovascular or
cerebrovascular disease or a seizure disorder,
and that constant monitoring is required during
the first hour after the administration of insulin.
The monitoring is necessary to detect
neuroglycopenic symptoms, which should be
treated with intravenous glucose.
63. ๏ Cosyntropin stimulation test โ
๏ The rationale for the administration of
cosyntropin (ACTH) is that the adrenal glands
atrophy when they have not been stimulated
for a prolonged period; as a result, they do not
secrete cortisol normally in response to a
bolus dose of ACTH. The test is usually
performed by administering 0.25 mg (25 units)
of cosyntropin (synthetic ACTH 1-24)
intramuscularly or intravenously and
measuring serum cortisol 60 minutes later. A
serum cortisol concentration of โฅ18 mcg/dL
(497 nmol/L) is considered a normal response.
64. ๏ In practice, this test is not often useful
because a patient who has such severe
ACTH deficiency that the adrenal glands
do not respond normally to cosyntropin
will also probably have an 8 to 9 AM basal
serum cortisol value that is โค3 mcg/dL (83
nmol/L) and therefore will not need a test
of ACTH reserve. On the other hand, a
patient who has partial ACTH deficiency
may respond normally to cosyntropin and
requires a test of ACTH reserve .
65. ๏ THYROTROPIN โ
๏ The adequacy of thyrotropin (TSH)
secretion in a patient with known
hypothalamic or pituitary disease can be
assessed simply by measuring serum
thyroxine (T4) or free T4 index.
๏ If the serum T4 concentration is normal,
TSH secretion is normal; if the serum T4
concentration is low, TSH secretion is
low.
66. ๏ In patients who have hypothyroidism due to
damage to the hypothalamus or pituitary, the
serum TSH concentration is usually not helpful
in making the diagnosis of hypothyroidism
because a low serum T4 concentration is
usually associated with a serum TSH
concentration within the normal range.
๏ Consequently, serum TSH alone should not be
used as a screening test for hypothyroidism in
patients who have pituitary or hypothalamic
disease.
67. ๏ GONADOTROPINS โ
๏ The approach to the diagnosis of
gonadotropin deficiency in a patient with
known hypothalamic or pituitary disease
varies with the gender of the patient.
68. ๏ In a man with hypopituitarism, luteinizing
hormone (LH) deficiency can best be detected
by measurement of the serum testosterone
concentration. If it is repeatedly low at 8 to 10
AM, LH secretion is subnormal and the patient
has secondary hypogonadism. When the
serum testosterone concentration is low, the
serum LH concentration is usually within the
normal range, but low compared with elevated
values in primary hypogonadism.
๏ If fertility is an issue, the sperm count should
be determined.
69. ๏ In a woman of premenopausal age who
has pituitary or hypothalamic disease
but normal menses, no tests of LH or
FSH (follicle-stimulating hormone)
secretion are needed because a normal
menstrual cycle is a more sensitive
indicator of intact pituitary-gonadal
function than any biochemical test.
๏ If the woman has oligomenorrhea or
amenorrhea, serum LH or FSH should
be measured to be sure it is not high
due to ovarian disease.
70. ๏ In addition, the following three tests should be
obtained:
๏ Measurement of serum estradiol.
๏ Administration of medroxyprogesterone, 10 mg
daily for 10 days, to determine if vaginal
bleeding occurs after the 10-day course and, if
so, if it is similar in amount and duration of flow
to the patient's menses when they were normal.
๏ Subnormal results for any two of these tests
indicate estradiol deficiency as a consequence
of gonadotropin deficiency, and warrant
consideration of estrogen treatment.
71. ๏ Normal results, in association with oligomenorrhea
or amenorrhea, could indicate sufficient
gonadotropin secretion to maintain normal basal
estradiol secretion but insufficient to cause
ovulation and normal progesterone secretion. This
situation should prompt consideration of intermittent
progestin treatment.
๏ The serum LH response to a single bolus dose of
gonadotropin-releasing hormone (GnRH) is not
helpful in distinguishing secondary hypogonadism
due to pituitary disease from that due to
hypothalamic disease because patients who have
hypogonadism due to pituitary disease may have
normal or subnormal serum LH responses to GnRH,
as may those who have hypothalamic disease.
72. ๏ GROWTH HORMONE
๏ The availability of growth hormone for
treatment of abnormal body composition
in adults who have growth hormone
deficiency increases the interest in testing
growth hormone secretion in patients who
have hypothalamic or pituitary disease.
๏ Measurement of basal serum growth
hormone concentration does not
distinguish reliably between normal and
subnormal growth hormone secretion in
adults.
73. ๏ Three other criteria, however, are useful:
๏ Deficiencies of multiple other pituitary
hormones โ The likelihood that the growth
hormone response to all provocative stimuli will
be subnormal in patients who have organic
pituitary disease, eg, a macroadenoma, and
deficiencies of ACTH, TSH, and gonadotropins
is about 95 percent .
๏ Serum IGF-1 โ A serum IGF-1 concentration
lower than the age-specific lower limit of normal
in a patient who has organic pituitary disease
confirms the diagnosis of growth hormone
deficiency .
74. ๏ Provocative tests of growth hormone
secretion โ Either insulin-induced
hypoglycemia or the combination of
arginine and growth hormone-releasing
hormone (GHRH) is a potent stimulus of
growth hormone release. Subnormal
increases in the serum growth hormone
concentration (<5.1 ng/mL for the former
and <4.1 ng/mL for the latter) in a patient
who has organic pituitary disease
confirms the diagnosis of growth
hormone deficiency .
75. ๏ PROLACTIN โ The main physiologic role of prolactin
is for lactation. Women who have severe
hypopituitarism due to hypothalamic or pituitary
disease may, in the postpartum period, have a serum
prolactin concentration that is inappropriately low and
not be able to nurse.
๏ Routine testing for prolactin deficiency is not
currently performed, as it is difficult to distinguish low
from normal serum prolactin concentrations, and
there is no standardized test of prolactin reserve.
76. Treatment of hypopituitarism
๏ Treatment of patients with hypopituitarism is the sum
of the treatments of each of the individual pituitary
hormonal deficiencies detected when a patient with a
pituitary or hypothalamic disease is tested.
๏ treatment consists of the administration of
hydrocortisone or other glucocorticoid in an amount
and timing to mimic the normal pattern of cortisol
secretion. Most authorities recommend replacement
with hydrocortisone because that is the hormone the
adrenal glands make normally, but others prefer
prednisone or dexamethasone for their longer
durations of action.
๏
77. ๏ Most authorities recommend hydrocortisone
doses of 15 to 25 mg/day , because those
doses are similar to daily production rates .
๏ Although dividing the total daily dose into two
or even three doses (with the largest dose on
arising in the morning) makes sense
physiologically.
๏ An inadequate dose may result in persistence
(or recurrence) of the symptoms of cortisol
deficiency, while an excessive dose can lead to
symptoms of cortisol excess and to bone loss.
Small deviations from the optimal dose are
usually not detected clinically.
78. ๏ Unmasking diabetes insipidus
๏ โ An unusual side effect of glucocorticoid
replacement is the unmasking of underlying
central diabetes insipidus, leading to marked
polyuria .
๏ Correction of cortisol deficiency can
increase the blood pressure and renal blood
flow and, in patients with partial diabetes
insipidus, reduce the secretion of
vasopressin. All of these effects increase
urine output.
79. ๏ Need for mineralocorticoid coverage โ Unlike the
situation in primary adrenal insufficiency,
mineralocorticoid replacement is rarely necessary in
hypopituitarism. Angiotensin II and potassium, not
ACTH, are the major regulators of aldosterone
secretion.
๏ Adrenal androgen replacement โ In women with
secondary adrenal insufficiency, exogenous
dehydroepiandrosterone (DHEA) replacement appears
to have a modest beneficial effect on psychological
well-being. However, the available data are from
women with panhypopituitarism, who have combined
adrenal and ovarian androgen deficiency. No data are
available in women with isolated ACTH deficiency, a
very rare disorder.
80. ๏ TSH DEFICIENCY โ
๏ TSH deficiency results in thyroxine (T4) deficiency and is treated
with Levothyroxine. The factors that influence dosing are similar to
those of primary hypothyroidism. However, treatment of secondary
hypothyroidism differs in two ways:
๏ T4 should not be administered until adrenal function, including
ACTH reserve, has been evaluated and either found to be normal or
treated. In a patient with coexisting hypothyroidism and
hypoadrenalism, treatment of the hypothyroidism alone may
increase the clearance of the little cortisol that is produced, thereby
increasing the severity of the cortisol deficiency.
๏ Measurement of serum TSH cannot be used as a guide to the
adequacy of Levothyroxine replacement therapy. We suggest
starting with a weight-based T4 dose of 1.6 mcg/kg. The dose should
be adjusted according to the serum T4 or free T4 values, aiming to
maintain them in the middle of the normal range.
81. ๏ GROWTH HORMONE DEFICIENCY โ The availability of several
recombinant human growth hormone preparations
(Humatropeยฎ, Nutropinยฎ, Serostimยฎ, and Genotropinยฎ) for
treating adults with growth hormone deficiency allows clinicians
to prescribe this treatment.
๏ Many patients who develop GH deficiency in adulthood have
unfavorable serum lipid profiles, increased body fat, decreased
muscle mass, decreased bone mineral density, and a diminished
sense of well-being. There is substantial evidence that growth
hormone treatment in these patients increases muscle mass and
reduces body fat. The evidence for improvement in bone mineral
density is good for men but not for women. The evidence
concerning improvements in the sense of well-being, muscle
strength, and serum lipids is conflicting. Thus, we do not
recommend recombinant human growth hormone as routine
treatment for all patients with adult-onset growth hormone
deficiency.
๏ PROLACTIN DEFICIENCY โ The only known presentation of
prolactin deficiency is the inability to lactate after delivery, for
which there is currently no available treatment.
82. ๏ LH AND FSH DEFICIENCY โ Treatment of LH and FSH
deficiency depends upon gender and whether or not
fertility is desired.
๏ Men โ Testosterone replacement is indicated in men
who have secondary hypogonadism and who are not
interested in fertility. The choice of treatment does not
differ from that in men with primary hypogonadism, but
serum LH measurements cannot be used to monitor the
adequacy of therapy. This can be achieved by
measurements of serum testosterone.
๏ Men with secondary hypogonadism who wish to become
fertile can be treated with gonadotropins if they have
pituitary disease or with either gonadotropins or
gonadotropin-releasing hormone (GnRH) if they have
hypothalamic disease.
83. ๏ Women โ Women with hypogonadism due to
pituitary disease, who are not interested in
fertility, should be treated with estrogen-
progestin replacement therapy. The goal of
treatment is not the same as in
postmenopausal women, in whom the goal is
to give estrogen and progestin only if
necessary to relieve hot flushes. Instead, the
goal of treatment of women of premenopausal
age is similar to that of replacement of
thyroxine and cortisol, ie, to replace the
missing hormones as physiologically as
possible.
84. ๏ Toward this end, we suggest treatment with
estradiol transdermally, so estradiol is
absorbed into the systemic circulation.
Women with an intact uterus must also take a
progestin to avoid the risk of endometrial
hyperplasia or carcinoma. We also recommend
that estradiol be administered cyclically with
progesterone or a progestin. Some clinicians
suggest a traditional regimen of estradiol on
days 1 through 25 of each month and
progesterone on days 16 through 25 of each
month.
85. ๏ The goals are to achieve both a normal late-
follicular serum estradiol concentration and
menses the patient considers normal. Another
regimen is to give transdermal estradiol
continuously throughout the month, with
progestin added days 1 to 10 of the calendar
month. This regimen is similar to that used for
treatment of premature ovarian failure. For
women who develop cyclic mood changes
(premenstrual syndrome) on either of these
regimens, a continuous daily regimen of both
estrogen and a lower dose of progestin is
usually better tolerated.
86. ๏ Women with secondary hypogonadism
who wish to become fertile should be
offered ovulation induction. Women
with GnRH deficiency are candidates
for either gonadotropin therapy or
pulsatile GnRH, while those with
gonadotropin deficiency due to
pituitary disease are candidates only
for gonadotropin therapy.
87. ๏ Androgen replacement โ Serum
androgen concentrations in women
with hypopituitarism, particularly those
with both gonadotropin and ACTH
deficiency, are significantly lower than
those in normal control women . The
role of exogenous testosterone therapy
in these women is unclear, but is not
recommended.