Discovery Curriculum:

nd
2 year Medical Students
Pathophysiology
Growth Hormone
Deficiency

Minilecture for Session

D2_1-2
January 30, 2015 Friday
AM
Maas and Auble

Hyperprolactinemia: Diagnosis

Single measurement of increased serum

prolactin
A serum prolactin concentration >250 ng/ml:
Prolactinoma (prolactin-secreting pituitary tumor).
Some drugs, including metoclopramide and
risperidone (dopamine antagonists), may
increase prolactin to >200 ng/ml.
Microprolactinomas can also have prolactin levels in
the 100-250 ng/ml range.

Hyperprolactinemia due to infundibular stalk

compression

Mild to moderate hyperprolactinemia

(25-100 ng/ml range)
Presence of a larger pituitary mass
More likely to be due to a
nonprolactin-secreting tumor with
infundibular stalk compression and
inhibition of dopamine transport to
the lactotroph.

Causes of hyperprolactinemia

Physiological causes:
Pregnancy
Lactation
Exercise
Sleep
Stress

Causes of hyperprolactinemia

Medications:
Antihypertensives such as methyldopa
Estrogens
D2 dopamine receptor antagonists such as
metoclopramide, domperidone
Neuroleptics/antipsychotics such as
phenothiazines, butyrophenones,risperidone
also block dopamine receptors

Causes of hyperprolactinemia
Pathological:
Hypothalamic-pituitary stalk damage

Infiltrative disorders (Sarcoidosis)

Irradiation to brain

Trauma with pituitary stalk section or

pituitary
surgery

Tumors
Pituitary

Prolactinomas

Macroadenoma (compression of
infundibular
stalk)

Lymphocytic hypophysitis (autoimmune)

Clinical Presentation of
Hyperprolactinemia
Varies with age and gender of the patient.
Young women - menstrual irregularities, galactorrhea
(occurs in 50-80% of affected women) and infertility.
Men - decrease in libido and erectile dysfunction as a
result of hypogonadism, but galactorrhea is less
common, occurring in approximately 20-30% of affected
men.
Hypogonadism: caused by the hyperprolactinemia
inhibiting the pituitary gonadotropins, FSH and LH.
Prolactinoma
Women: microadenomas due to the early presentation
and work up of the menstrual irregularities
Macroprolactinomas more frequent in men and
postmenopausal women at presentation.
Macroprolactinomas: headaches, neurologic deficits due
to cavernous sinus involvement and visions changes due
to optic chiasm compression and cavernous sinus
involvement.

Treatment of
Hyperprolactinemia
Dopamine agonist - suppress prolactin production via

activation of D2 receptors.
Cabergoline - preferred dopamine agonist
higher efficacy in normalizing prolactin levels and in
shrinking tumor size and fewer side effects.
longer half-life (65 hours), higher affinity, and greater
selectivity for the D2 receptor (approximately four times
more potent) than bromocriptine.
Side effects: nausea, vomiting, orthostatic lightheadedness,
dizziness and nasal congestion, but cabergoline has also
been reported to cause a cardiac valvulopathy in
Parkinsons patients treated with much higher doses of
cabergoline.
Bromocriptine: recommended in patients undergoing fertility
induction that also have hyperprolactinemia, because of its
greater track record. Bromocriptine has a relatively short
elimination half-life (between 2 and 8 hours) and requires
frequent dosing.
Normalize prolactin, decrease tumor size and restore gonadal
function in greater than 80% of patients with prolactinomas
Initial treatment for macroprolactinomas that have caused
compromise of vision, neurologic deficits and pituitary function.

Acromegaly

Clinical Features of
Acromegaly

Acromegaly: Diagnosis

Measurement of serum IGF-1

diagnose excess GH in 99% of patients.
Half life of 16 hours so a single measurement is
more constant and accurate than a single
measurement of GH due to its very short half life
and very pulsatile secretion.
Inaccuracies due to malnutrition, acute illness,
celiac disease, poorly controlled diabetes mellitus,
liver disease, and estrogen ingestion.
Oral glucose tolerance test (100 gram glucose
load)
Normally glucose suppresses GH levels to less
than 1 ng/ml by 2 hours
GH levels may paradoxically increase, remain
unchanged or decrease, but not <1 ng/ml.

Acromegaly - Treatment
Transsphenoidal surgery
Radiation therapy
Drug therapy

Somatostatin receptor ligands (SRLs):

octreotide and lanreotide
Cabergoline is the most efficacious of the
dopamine agonist in acromegaly but it is very
limited and is effective in less than 10% of
patients.
Pegvisomant
GH receptor antagonist
Blocks the peripheral action of GH (liver GH
receptor)

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Causes of Panhypopituitarism/Hypopituitarism
Mass lesions, such as pituitary tumors, craniopharyngiomas, cysts
(Rathkes cleft cyst), other brain tumors (meningiomas), pituitary
carcinomas, metastatic tumors (breast, lung, colon)
Treatment of sellar, parasellar and hypothalamic disease,
such as pituitary/hypothalamic surgery, radiotherapy, radiosurgery
(gamma knife)
Infiltrative disease, such as autoimmune (lymphocytic
hypophysitis), hemochromatosis, sarcoidosis
Traumatic, such as head injury, perinatal trauma
Vascular, such as Sheehans syndrome, pituitary tumor apoplexy
Medications, such as opiates, pharmacologic glucocorticoid
therapy, suppressive thyroxine therapy,sex steroid treatment
Infectious
Genetic, including combined pituitary hormone deficiencies and
isolated pituitary hormone deficiencies
Developmental, such as ectopic pituitary, pituitary hypoplasia or
aplasia, midline cerebral and cranial malformations

Panhypopituitarism: Clinical findings

ACTH deficiency or secondary

adrenal insufficiency
TSH deficiency or secondary
hypothyroidism
GH deficiency in adult
Prolactin deficiency
Gonadotropin deficiency or
hypogonadotropic hypogonadism

Panhypopituitarism: Pituitary
Hormone Diagnostic Testing

Prolactin Basal prolactin level

TSH

Basal TSH and free T4: low free T4 with low or inappropriately
normal TSH

ACTH

cortisol 8AM fasting: insufficient if cortisol <3 mcg/dl

ACTH stimulation test: serum cortisol insufficiency if response
<18 mcg/dl
Insulin tolerance test with serum measurement of cortisol at 0,
30, and 60 mins: insufficiency if serum cortisol response is <18
mcg/dl

FSH/LH

Males: 8AM fasting serum total testosterone, FSH, LH:

insufficiency if testosterone is below reference range with low or
inappropriately not increased LH and FSH.
Females: Basal serum estradiol, FSH, LH: insufficiency if estradiol
is low with low or inappropriately not increased FSH and LH.

GH

Basal IGF-1: low IGF-1 for age and gender-adjusted normal range
Insulin tolerance test
GHRH-arginine stimulation test
Glucagon stimulation test

Panhypopituitarism: Hormone Replacement

Thyroid: Levothyroxine (T4), adjust dose
according to free T4 and not TSH
Adrenal: hydrocortisone 10 mg QAM and 5 mg
QPM or prednisone 5-7.5 mg QD, no
mineralocorticoid is needed with secondary
adrenal insufficiency.
Gonadotropins:
Female is replaced with estrogen and
progesterone (if uterus present), such as OCP,
patch. Fertility will require fertility drugs,
gonadotropins, for ovulation.
Male is replaced with testosterone, such as
injections, gel, patch forms. Fertility will require
HCG injections IM 3 times per week.
Growth hormone is given as a daily
subcutaneous injection.

Growth Hormone Deficiency in

Children Clinical Findings

Clinical Signs of Growth Hormone Deficiency

In the neonate:
Jaundice
Hypoglycemia
Microphallus
Traumatic delivery (contributing factor)

In the child:
Propensity for hypoglycemia
Increased fat
High-pitched voice
Microphallus
Absent or delayed puberty in the adolescent
Weight less affected than height
Occasionally present:
Physical defects of the skull
Midline craniofacial abnormalities (including cleft lip and cleft palate,
and single central incisor)

GH deficiency in Children Diagnosis

Stimulus
Exercise
Levodopa
Clonidine
Arginine HCl
Insulin
Glucagon
GHRH

GH deficiency in children: Drug therapy (GH therapy)

Recombinant human growth hormone

(rGH), given as a subcutaneous injection.
Given each evening to mimic the normal
diurnal pattern of growth hormone release.
Many pharmaceutical products, but they
are essentially the same medication.
Dosing is based on mg/kg/week and the
etiology.
True growth hormone deficiency need
much smaller doses of GH than a child
with idiopathic short stature (ISS), and
the dose is around 0.2-0.3 mg/kg/week.
Check IGF-I (insulin-like growth factor 1)
levels to determine dose changes.

Pharmacology summary
Growth hormone (hGH) is used therapeutically in
children with short stature with growth hormone
deficiency and short stature despite adequate GH
production with other conditions including Turner's
syndrome, Noonan's syndrome etc.
Bromocriptine, a dopamine agonist, is used for the
treatment of hyperprolactinemia, prolactin-secreting
adenomas, acromegaly and Parkinson's disease.
Cabergoline is also a dopamine agonist used to treat
hyperprolactinemic disorders.
Octreotide and lanreotideare somatostatin analogs
used to treat acromegaly.
Pegvisomant is a GH receptor antagonist used for the
treatment of acromegaly.

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