Rydstedt Flashcards
Describe the regulation of prolactin
hypothalamus causes tonic inhibition of prolactin secretion via dopamine; neurons travel down the pituitary stalk which then releases dopamine into the portal system that supplies the lactotrophs causing a decrease secretion of prolactin.
Pathological chronic levels of prolactin inhibit GnRH release (more on frequency of pulses than amplitude of pulses) leading to oligomenorrhea or amenorrhea in women impotence in men
stimulated by releasing factor VIP
Describe the regulation of growth hormone
Somatotrophs = 50% of the cells in the pituitary and are under control of GHRH and Somatropin Release-Inhibiting Factor (SRIF)
GH levels are high are birth then decrease and donot rise again until early puberty; at puberty thre are bursts of GH secretion interrupted by minimal secretion during the night. Later, GH levels stay elevated through the day;
GH binds to its receptor in the liver and causes an increased synthesis and release of IGF-1 which mediates 95% of its effect in the body. In this way, GH ALMOST ACTS like a pro-hormone although GH itself does exhibit a minor effect on anti-insulin metabolism;
Both IGF-1 and GH are partially regulated by negative feedback and sensitivity of this feedback is dependent on puberty status.
IGF -1 production is also dependent on nutrition. Malnourished children often have high circulating levels of GH as a result of gluconeogenesis, but IGF-1 production by the liver is low because the liver fails to respond to the elevated GH, leading to growth failure. A growth spurt ensues if the child is supplied nutrients.
Also, children who do not receive emotional contact often fail to grow because when an infant is help close to mother/father chest, GH secretion is increased which helps explain why neglected children fail to grow appropriately.
High IGF and high GH decrease hypothalamus secretion of GHRH
Thus growth hormone is under control of nutritional and metabolic factors
What is congenital hypopituitarism-hormone deficiency? what is it caused by? what does it cause?
mutation in PROP-1 causes a decrease in PIT-1 transcriptional factor which leads to a lack of differentiation of pituitary hormones and thus a deficiency in PRL, GH, TSH
clinically presents = droopy face, asleep (due to decreased TSH), jaundice
What is Laron’s dwarf? what is it caused by? what does it cause?
presentation = short stature, obese, impaired intellect, acromicria, small genitalia;
patients can produce GH, but not IGF-1, because they have a receptor mutation involving the extracellular domain of the GH receptor in the liver
HIGH GH LEVELS WITH LOW IGF-1
low incidence of diabetes mellitus and cancer (due to low IGF-1)
treatment = IGF-1
What is androgen insufficiency syndrome (testicular feminization) ? what is it caused by? what does it cause?
X-linked recessive mutation, with a maternal carrier.
genotype = 46 XY
phenotype = XX
female habitus with “inguinal masses” (undescended testicles)
The genetic males that have circulating Testosterone in circulation, but are unable to respond to it. At puberty the genetic male develops breasts due to unopposed increased estrogen and testosterone, but they do not menstruate. do not develop osteoporosis since testosterone aromatized to estrogen in the periphery can stimulate bone formation
Describe pituitary adenomas. how do they present clinically? what limitations does radiology have? What would a hormone assay show? which hormones would you look at and when?
tumor mass in pituitary;
Clinical presentation:
present as headaches (due to tumor pushing down on dura), bilateral temporal hemianopsia or decreased visual acuity (running ton walls, sideswiping cars) if the tumor is growing anteriorly and superiorly
Radiology shows you that the mass is there but can’t distinguish functional from the non-functional adenomas; need an endocrine hormone assessment.
AM blood sample:
cortisol (tells you if cortisol is low; cushings needs a suppression test also)
testosterone and estradiol levels in relation to LH/FSH.
GH levels are not measured since the hormone is released in bursts, but IGF-1 has a longer half life so its levels integrate GH levels are useful
hormone levels allow classification of the adenoma (what is considered excess secretion)
How does a prolactinoma present in males vs females?
prolactinoma = most common pituitary adenoma
Males:
macroadenoma because impotence is often attributed to other factors and possibly the tumors are more aggressive (mass effect) the prolactin levels are > 500 ng/mL
Females:
microadenoma leading to irregular menses (oligomenorrhea) or amenorrhea, or galactorrhea; prolactin levels are 100-500ng/mL
What is a gonatotroph adenoma? how does it present? lab results? treatment?
= non-functional adenoma
present with headache and visual field or incidental finding on MRI; mass effect
Lab results;
normal FSH and LH levels, but elevated alpha subunit of FSH and LH; normally the tumor does not secrete FSH or LH, but if it does they are not biologically active
Treatment = surgical removal
What is a somatotroph adenoma? how does it present?
= excess growth hormone;
if it occurs pre-puberty: the epiphyseal plates are not fused, leads to giantism
if it occurs post-puberty: epiphyseal plates close; known as acromegaly
elevated GH leads to increased blood glucose as a result of reduced liver uptake of glucose and increased gluconeogenesis in the liver;
decreased insulin sensitivity (diabetogenic)
increased muscle mass through protein anabolism with increased amino acid uptake
increased myocyte hypertrophy (large cells but sarcomeres do not overlap properly so not an increase in strength; shake the person’s hand and its like dull weight)
decreased adipose tissues as a result of TAG breakdown/oxidation (lipolysis)
Physical characteristics: prominent jaw (prognathism), macroglossia, large gaps between the teeth, acral growth and soft tissue growth (hands = doughy) , enlarged feet and hands; hyperhidrosis (sweaty palms and soles) and increased growth of all internal organs except brain
Diagnosis = measuring IGF-1 levels for age of teh patient; prognosis is poor without treatment due to effects of GH on cardiocytes
what is a corticotrophic adenoma? how does it present? what is the effect of its excess hormone?
= adenoma in the pituitary gland that produces large amounts of ACTH which in turn elevates cortisol = cushings DISEASE;
symptoms = rapid weight gain (esp in trunk and face with sparing of the limbs.. central obesity).
stimulation of lipolysis and redistribution of lipid stores
increased straie due to decreased collagen and CT in the skin so the capillaries and hemorrhages are more visible and there is easy brusiability due to dermal atrophy;
acne develops due to testosterone binding to the hair follicle and causing an increase in sebaceaus gland secretion and bacterial overgrowth; androgens transform the villus hair into a terminal hair
hypertension, diabetes
increased epinephrine’s vasoconstrictive effect
increased androgens
What is pituitary apoplexy? what are some of the signs/symptoms?
occurs when the pituitary outgrows its blood supply. The patient complains of severe headache and may show visual disturbances due to hemorrhage and edema placing pressure on the optic chiasm. The necrosis causes hormone deficiency; most worrisome is cortisol deficiency which causes hypotension and eventually death.
If the patient has an altered mentation suggesting temporal lobe herniation, immediate surgery for decompression is indicated.
The more common cause of apoplexy is growth of adenoma and sometimes pregnancy (SHEEHAN SYNDROME); the pituitary during pregnancy increases in size by 200-300% (increase in lactotrophs) and if the mother experiences decreased blood pressure during delivery this can lead to apoplexy and failure to lactate after delivery. During pregnancy ned more blood, but if it doesn’t get to the pituitary then results in pituitary apoplexy that presents hypotension (due to low cortisol); treat with cortisol
GH are 50% of the cells in the pituitary (somatotrophs) but they are in the periphery so they are perfused by blood last, so most pituiatry apoplexy’s present GH deficiency
