Anterior Pituitary Flashcards
Which artery supplies the anterior pituitary to carry hormones from the hypothalamus to the anterior pituitary
Superior hypophyseal artery
What artery supplies the posterior pituitary gland after hypothalamic hormones travel through direct neural extension?
Inferior hypophyseal artery
Which hormone released from the hypothalamus increases prolactin release from the anterior pituitary gland? Which hormones inhibit prolactin release from the anterior pituitary gland?
Prolactin-releasing peptide
Prolactin-inhibiting factor (may be dopamine)
Which hormone is released from the hypothalamus to stimulate the anterior pituitary gland to release growth hormone?
Growth hormone releasing hormone
What are the 5 types of endocrine cells in the anterior pituitary that are defined by the hormones they secrete?
Somatotrophs: GH
Lactotrophs: LH
Gonadotrophs: LH and FSH
Corticotroph: ACTH
Thyrotroph: TSH
Underproduction of hormones released by the pituitary gland to cause symptoms based on which hormones are under secreted
Hypopituitarism
What are inherited disorders that cause hypopituitarism?
Pituitary dysplasia/aplasia
Congenital CNS mass
Congenital hypothalamic disorders
What are traumatic conditions that can cause hypopituitarism?
Surgical resection, radiation, head injury
What are tumors that can cause hypopituitarism?
Pituitary adenoma, pituitary metastasis
What are inflammatory causes of hypopituitarism?
Hemochromatosis, sarcoidosis
What are vascular causes of hypopituitarism?
Arteritis, sickle cells disease
What are infection causes of hypopituitarism?
Fungal, parasite, TB
What are congenital causes of hypopituitarism?
Prader Willi syndrome
Kallmann syndrome
What are acquired conditions that cause hypopituitarism?
Radiation, TBI, chemotherapy, ischemic stroke
What are functional causes of hypopituitarism?
Opioid use, normal aging, malnutrition, CKD
Loss of this pituitary hormone will cause growth disorders in children and abnormal body composition in adults
GH deficiency
Loss of this pituitary hormone will cause menstrual disorders and infertility in women and decreased sexual function, infertility, and loss of secondary sex characteristics in men
Gonadotropin deficiency
Loss of this pituitary hormone will cause hypothyroidism in children and adults
TSH deficiency
Loss of this pituitary hormone will cause hypocortisolism
ACTH deficiency
Loss of this hormone will cause failure of lactation
Prolactin deficiency
Name the correct anterior pituitary hormone that is triggered by the following hypothalamic releasing hormones:
1) CRH
2) TRH
3) GnRH
4) GHRH
5) Dopamine (inhibits)
1) ACTH
2) TSH
3) LH and FSH
4) GH
5) Prolactin
Prolactin is synthesized in ____. What condition causes significant Lactotrope cell hyperplasia?
Lactotrophs; pregnancy and first few months of lactation
What are normal serum PRL levels in women and men in absence of pregnancy?
Women: 10-25 ug/L; men: 10-20 ug/L
How is prolactin kept from being active without pregnancy?
In an inhibited state most of the time and inhibited by dopamine type 2 receptors. PRL increases dopamine to inhibit itself
What are conditions where serum PRL levels would rise mildly and transiently?
-Exercise, meals, sexual intercourse
-Breast exam, chest wall injury
-Minor surgical procedures, general anesthesia
-Stress of any kind
Pulsatile with highest secretion during non-REM sleep with peak between 4-6 AM (circulating half life of 50 mins)
How does PRL change during pregnancy?
-Increase tenfold during pregnancy in response to elevated estrogen and progesterone
-decline rapidly within 2 weeks of parturition if breast-feeding not initiated
How does breast feeding impact prolactin?
Suckling stimulates reflex increases in PRL levels that last about 30-45 min due to decrease in dopamine released by hypothalamus
Suckling also stimulates the posterior pituitary to release oxytocin
Oxytocin stimulates milk release and prolactin stimulates milk production
Magnitude of PRL increase is proportional to degree of preexisting lactotroph hyperplasia due to estrogen
What are the functions of prolactin?
Induce and maintain lactation, decrease reproductive function, and suppress sex drive
Inhibits reproductive function by suppressing hypothalamic GnRH and pituitary gonadotropin secretion and impairing gonadal steroidogenesis in women and men
—>@ovary leads to hypoestrogenism and anovulation
—>shortened or inadequate literal phase of menstrual cycle
—>in men, low testosterone levels and decreased spermatogenesis—> decreased libido and fertility
What is the etiology of hyperprolactinemia?
Most common pituitary hormone hypersecretion syndrome in men and women
PRL-secreting adenomas are most common cause of PRL >200 ug/L (more common in women, may be familial MEN type 1 or 4)
Microprolactinoma (less pronounced elevation) due to drugs (lots of psych drugs), pituitary stalk compression, hypothyroidism, or renal failure
Pregnancy
Renal failure
Oral contraceptives
Liver failure
Adenoma
Chest wall disease
Thyroidal disease (hypothyroidism)
Infiltration disease of the pituitary
Nursing/nipple stimulation
Stalk effect
How does hyperprolactinemia present in women?
Amenorrhea, galactorrhea, and infertility
May also complain of decreased libido, weight gain, mild hirsutism
-vaginal dryness/atrophy, irritability, anxiety and depression (estrogen deficiency)
-long term: osteopenia, reduced muscle mass
How does hyperprolactinemia present in men?
Hypogonadotropic hypogonadism
-decreased libido
-impotence/erectile dysfunction
-infertility
-gynecomastia
-galactorrhea (less often than women)
If long-standing, osteopenia, reduced muscle mass, decreased facial hair growth
What should you ask about when evaluating hyperprolactinemia causes?
Pregnancy? Medications? Renal failure? Thyroid disease? Headache or vision changes? (Rule out tumor @ optic chiasm)
What physical examinations should you do for hyperprolactinemia?
Test for chiasmal syndrome, signs of hypothyroidism, or hypogonadism
What lab tests can be ordered for hyperprolactinemia?
Serum prolactin concentration: basal, fasting morning PRL (may increase during sleep, strenuous exercise, occasionally emotional or physical stress, breast stimulation, high-protein meals)—> high value should be repeated and confirmed
TSH/T4: to exclude hypothyroidism
serum HCG: in every woman
CMP: to rule out kidney disease
Serum total and free testosterone, LH, FSH: evaluate for hypogonadism in men
Serum estradiol, LH, FSH in women who have amenorrhea for hypogonadism
If no other cause is determined and PRL elevated or if PRL >200, what can be done to assess for hyperprolactinemia cause? What are concerning findings?
MRI: sella turcica lesion- secretion of other pituitary hormones should be evaluated
If normal, idiopathic hyperprolactinemia diagnosis
Can be due to micro adenomas not seen on imaging
How is hyperprolactinemia treated?
Specific management of cause
Normalize PRL levels with estrogen, estrogen/progesterone, or testosterone replacement if microprolactinomas (<1 cm)
Dopamine agonists regardless of underlying cause
What are the dopamine agonists and their MOA?
Cabergoline and bromocriptine: suppress PRL secretion and synthesis and lactotrope cell proliferation
This is a long-acting dopamine agonist and suppresses PRL for >14 days after one oral dose with less adverse effects and drug intolerance
Cabergoline
This is a dopamine agonist that is short acting and preferred when pregnancy is desired. When should it be administered?
Bromocriptine; low dose at bedtime with a snack and gradually increasing dose
What are side effects of dopamine agonists?
Constipation, nausea, vomiting
Postural hypotension, nasal stuffiness/congestion, dry mouth, insomnia, vertigo
Should be dosed at bedtime and continued use/dose reduction usually resolves
Rare: leukopenia, thrombocytopenia, pleural fibrosis, cardiac arrhythmias, hepatitis
Patients with Parkinson’s with >3 mg Cabergoline at risk for cardiac valve insufficiency (recommend echo prior to starting therapy)
What is the efficacy dopamine agonists?
Very effective with prolactinomas (90% see reduction of PRL to less than 10% of pre-treatment and 80% achieve normal PRL levels)
PRLoma shrinks quickly but max benefit may take up to a year
Long-term therapy required unless surgery
How do you manage women who desire fertility and dopamine agonists?
Safe with pregnancy
Micro adenoma- may safely hold, conceive, and safely breastfeed
Macro adenoma- may grow during pregnancy, so if stopped must carefully monitor serum PRL and visual-field testing
Low prolactin levels due to damaged lactotroph cells in anterior pituitary
Hypoprolactinemia
What is the clinical manifestation of prolactin deficiency?
Inability to lactate after delivery (but often not an isolated deficiency and have other pituitary hormone deficiencies)
What are causes of hypoprolactinemia?
Sheehan’s syndrome: postpartum hypopituitarism caused by necrosis of the pituitary gland from severe hypotension or shock from hemorrhage during delivery
Medications: dopamine agonists, antiparkinsonian drugs
Tumors
What is the treatment of hypoprolactinemia?
Dopamine antagonists: oppose dopamine in those who want to breastfeed
Surgery
What does GHIH stand for?
GH?
IGF-1?
Somatostatin
Somatotropin
Somatomedin
What is the function of GH?
Induces protein synthesis
Impairs glucose tolerance by antagonizing insulin action
Stimulates lipolysis
Promotes lean muscle mass by amino acid uptake
Skeletal growth and formation of cartilage
Most abundant anterior pituitary hormone
Growth hormone
What causes growth hormone fluctuation?
GHRH—> GH synthesis and release
Somatostatin—> synthesized in hypothalamus and inhibits GH secretion
Pulsatile with highest levels at night
Decreases with age
Increased by sleep, stress, exercise, decreased blood glucose levels
Growth and differentiation factor synthesized by the liver as GH levels increase and decreased when GH levels decrease. Mediates effects of GH indirectly (bone growth, lean muscle mass)
Somatomedin C (insulin-like growth factor)
What are the physiologic factors that impact serum IGF-1 concentrations?
Aging: increases during puberty, peaks at 16 years, declines by 80% during aging process
Higher in women than men
Abnormalities of GH synthesis or action decrease IGF-1
A 9 y/o male presents with complaint of short stature relative to his peers. He is the shortest person in his class. Otherwise, he met all developmental milestones at appropriate times. Height is 3rd percentile
Initial screen with IGF-1 was low. Basal serum growth hormone was also low. IGF-BP3 was WNL. Testosterone is normal. Adrenal, thyroid, liver, and Hgb A1c were all normal. MRI is unremarkable. GH stimulation testing performed after a 12 hour fast revealed peak GH level of 1.4 NG/ml (lower limit of normal 10 NG/ml). What condition do you suspect?
GH deficiency
What are causes of growth hormone deficiency?
Acquired: trauma, infections, cranial irradiation, and systemic diseases
Congenital disruption of growth hormone axis:
Mutations of GH productions or secreting cells (can also involve other pituitary hormone deficiencies), recessive mutations —> severe dwarfism
GH insensitivity due to defects of GH receptor structure or signaling —> partial or complete insensitivity (homozygous or heterozygous)
What causes mortality of children with growth hormone deficiency? Adults?
Other pituitary hormone deficiencies
Cardiovascular causes from altered body composition and dyslipidemia (increased fat, cholesterol, health problems)
What are characteristics of isolated GH deficiency?
Short stature
Micro penis
Increased fat
High-pitched voice
Hypoglycemia
How is GH insensitivity diagnosed?
Based on normal or high GH levels, with decreased circulating growth hormone binding protein and low IGF-1
What is the single most important clinical manifestation of GHD? What should you focus history on?
Growth failure
Birth weight and height
Height of parents
Timing of puberty in parents
Previous growth points
General health of child
Nutritional history
What should physical exam evaluating growth hormone deficiency focus on?
Proper height and weight measurement, proportionality, pubertal status, evidence of genetic syndromes
Which children should be evaluated for growth hormone deficiency?
Marked short stature more than 2.5 SD below mean for age, sex, and ethnic background
Growth failure defined as height velocity less than 25th percentile with or without short stature
Less severe short stature (2 to 2.5 SD below mean) for age, sex, and ethnic background with growth failure in the absence of alternative explanation
Evidence suggesting hypothalamic-pituitary dysfunction with decelerating growth
What evidence would suggest a hypothalamic-pituitary dysfunction?
Hypoglycemia, microphallus, cryptorchidism, optic nerve hypoplasia, intracranial tumor, or history of cranial irradiation
How is growth hormone deficiency evaluated?
1) evaluation for other causes of growth failure: chronic systemic disease, hypothyroidism, Turner syndrome, skeletal disorders
2) GH stimulation test, IGF-1, IGFGP-3 (main carrier of IGF-I in body), bone age
Test that relies upon use of physiological or pharmacological stimuli (sleep, fasting and exercise or L-dopa, clonidine, propranolol, arginine, and insulin-induced hypoglycemia) to diagnose impaired GH secretion. How many tests need to be completed to confirm diagnosis? When is this test performed?
GH stimulation test
2 different tests
After overnight fast
What imaging can be done for growth hormone deficiency evaluation in children?
MRI, if not available, CT of the brain with contrast for pituitary tumor screening
If no other causes are found, what can be done?
Referral for genetic testing
How is growth hormone deficiency in children treated?
Replacement therapy with recombinant GH (somatotropin: genotropin, humatrope, norditropin, nutropin, omnitrope, saison, tevtropin)to restore growth velocity
If pituitary insufficiency, correction of other hormone deficits
If GH insensitivity and growth retardation due to mutations of GH receptor, treatment with IGF-1 (growth hormone levels will remain normal or elevated even though not functioning)
What is the pattern of acquired pituitary hormone deficiency in adults due to hypothalamic or pituitary somatotrope damage?
Loss of adequate GH reserve foreshadows subsequent hormone deficits
GH —> FSH/LH —> TSH —> ACTH hormone loss
What is the clinical presentation of acquired growth hormone deficiency?
Changes in body composition: reduced lean body mass, increased fat mass, increased waist-hip ratio
Changes in lipid metabolism: hyperlipidemia, LV dysfunction, hypertension
Cardiovascular dysfunction
Reduced bone mineral content and increased fractures
Depression, social isolation, fatigue
How is AGHD diagnosed?
Rare: (same testing as children)
GH stimulation test
IGF-I
IGFBP-3
MRI if suspecting pituitary tumor
What are risk factors for AGHD that warrant testing?
Pituitary surgery
Pituitary or hypothalamic tumor or granulomas
History of cranial irradiation
Radiologic evidence of a pituitary lesion
Childhood requirement for GH replacement therapy
Unexplained low age- and sex-matched IGF-I levels
How is AGHD treated?
Recombinant human growth hormone (rhGH, somatotropin): starting dose of .1-.3 mg/d and titrated to maintain IGF-I levels
What are contraindications to therapy with recombinant human growth hormone injections?
Presence of an active neoplasm, intracranial hypertension, uncontrolled diabetes, retinopathy
What is the mechanism of action of recombinant human growth hormone rhGH?
Purified polypeptide hormones of recombinant DNA origin that assists growth of linear bone, skeletal muscle, and organs by stimulating chondrocyte proliferation, lipolysis, protein synthesis, and hepatic glucose output, hepatic and renal metabolism
What are indications for recombinant human growth hormone rhGH?
Children-growth failure, short stature; adults-GH deficiency, hypopituitarism
What should you monitor with recombinant human growth hormone rhGH treatment?
Fundoscopic exam at initiation of therapy and periodically during treatment for intracranial hypertension
Adults: IGF-1 every 1-2 months during titration, then semiannually at maintenance
Children: monitor growth curve and physical exam with skeletal assessment with every visit
What are some side effects of recombinant human growth hormone rhGH treatment?
Dose-related fluid retention, joint pain, and CTS (30% of patients)
Myalgias, paresthesias (40%)
Hyperglycemia and DM can develop (monitor patients requiring insulins, GH is a potent counterregulatory hormone)
HA, increased ICP (usually in first 8-12 weeks of treatment), HTN, tinnitus, slipped capital femoral epiphysis
_____ secrete GH from the anterior pituitary
_____ is the hormone that inhibits GH secretion from anterior pituitary
_____ is another name for IGF-1
_____ is a treatment for GH deficiency
(Somatotrophs, somatotropin, somatostatin, somatomedin)
Somatotrophs, somatostatin, somatomedin, somatotropin
Hormonal disorder in adults that causes excess growth hormone leading to continued growth of extremities—> large face, hands, and feet
Acromegaly/gigantism
What are causes of acromegaly/gigantism?
GH hypersecretion due to somatotrope adenoma and rarely extrapituitary lesions
Ectopic GH secretion by tumors of pancreatic, ovarian, lung, or hematopoietic origin
Rarely, excess GHRH production (due to chronic stimulation of somatotropes): MCC chest or abdominal carcinoid tumor
What is the clinical presentation of acromegaly/gigantism?
Slow-moving often not diagnosed for 10 years or more
Acral bony overgrowth—> frontal bossing, increased hand and foot size, mandibular enlargement with prognathism, and widened space between the lower incisor teeth
Pituitary gigantism in children if hypersecretion before long bone closure
Soft tissue swelling—> heel pad thickness, increased shoe or glove size, ring tightening, coarse facial features, large fleshy nose
Hyperhidrosis, hollow-sounding voice, oily skin, arthroplasty, kyphosis, carpal tunnel syndrome, muscle weakness and fatigue, acanthosis nigiricans, skin tags
Generalized visceromegaly —> cardiomegaly, macroglossia, thyroid gland enlargement
What are complications of acromegaly/gigantism?
Cardiovascular system: cardiomyopathy with arrhythmias, left ventricular hypertrophy, decreased diastolic function, and hypertension if untreated
Upper airway obstruction with sleep apnea in 60%
Increased risk of colon polyps and mortality from malignancy
What is the prognosis of acromegaly/gigantism?
Mortality increased due to cardiovascular and cerebrovascular disorders and respiratory disease
Unless, GH levels controlled average survival of 10 years
How is acromegaly/gigantism diagnosed?
Age and sex-matched serum IGF-I levels
Confirmed with demonstration of failure of GH suppression to <.4 ug/L within 1-2 h of oral glucose load. High glucose stimulates somatostatin release
Thyroid function, gonadotropins, and sex steroids may be increased due to tumor mass effects
What is treatment of acromegaly/gigantism?
Goal: control GH and IGF-I hypersecretion, ablate or arrest tumor growth, restore mortality rates to normal, and preserve pituitary function
Surgery: transsphenoidal surgical resection preferred primary treatment
Radiation: external radiation therapy or high-energy stereotactic techniques as adjuvant therapy
Somatostatin analogues
Dopamine agonists
What is MOA and what are side effects of somatostatin analogues?
MOA: decrease GH secretion
Nausea, abdominal discomfort, fat malabsorption, diarrhea, flatulence that remits within 2 weeks
Octreotide suppresses post prandial gallbladder contractility and delays gallbladder emptying, 30% develop echogenic sludge or asymptomatic cholesterol gallstones
What treatment may induce additive biochemical control for acromegaly/gigantism?
Octreotide and Cabergoline
Most common presenting feature of adult hypopituitarism?
Hypogonadism (can be indication of hypothalamic or pituitary lesions that impair GnRH production or delivery through pituitary stalk)
What is the presentation of hypogonadism?
Women- Oligomenorrhea, amenorrhea, infertility, decreased vaginal secretions, decreased libido, osteoporosis
Men- testicular failure associated with decreased libido, impotency, infertility, decreased muscle mass, reduced beard and body hair growth
What lab values should be obtained with potential hypogonadism?
Low or inappropriately normal serum gonadotropin levels in the setting of low sex hormone concentrations
IV GnRH should stimulate secretion of LH/FSH. If normal response, hypothalamic abnormality with intact pituitary
MRI and assessment of other pituitary hormones indicated
How is hypogonadism evaluated in males specifically? Females?
Males: morning serum testosterone and free testosterone; low if <240 NG/dl; free testosterone low if <35 pg/ml
Verified with repeat testosterone, along with serum LH and PRL levels
Females: hCH, serum PRL, FSH and LH, TSH
What is treatment of hypogonadism in males?
Testosterone replacement to maintain normal growth and development of external genitalia, secondary sex characteristics, maintenance of muscle function and bone mass. Admin IM q 1-4 weeks or via patch or gel
Infertility due to oligospermia: hCG 3 times weekly or leuprolide (GnRH) if intact pituitary
Clomiphene—> stimulate pituitary gonadotropins if intact to increase testosterone/sperm production
What is treatment for hypogonadism in females?
Cyclical replacement of estrogen and progesterone to maintain secondary sexual characteristics and prevent osteoporosis
Gonadotropin therapy for ovulation induction
Follicular growth and maturation using human menopausal gonadotropin or recombinant FSH; LH to induce ovulation
Pulsatile GnRH to treat hypothalamic causes of infertility
____ is synthesized in the hypothalamus and stimulates the release of ACTH by the anterior pituitary
CRH
ACTH stimulates the adrenal cortex to secrete ____. Secretion is Pulsatile and peaks at ____ and is increased by _____
Cortisol; 6 AM; physical and psychological stress, exercise, acute illness, and insulin-induced hypoglycemia
Name the target organ/organs of the following hormones released by anterior pituitary:
1) ACTH
2) TSH
3) LH/FSH
4) Prolactin
5) GH
1) Adrenal gland
2) Thyroid gland
3) Gonads
4) Breasts
5) bone/liver
