anterior pituitary Flashcards
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 pubery in the adolescent weight less affected than height, occasionally present (physical defects of the skull, midline craniofascial and cleft palate, and single central incisor
GH deficiency in children diagnosis, potential stimuli to provoke a GH and IGF1 response
Usually test IGF1 when curious because its very stable
Then if youre thinking GH deficiency
give clonidine, arginine, insulin (hypoglycemia), glucagon, GHRH (not available), Exercise, levodopa
to see if GH can be released
Arginine- clonidine stimulation test
Clinical suspicion of GH deficiency, patient is fasting and has IV inserted, Basal blood sample for GH measurement (then inject arginine 500mg/kg bw) IV, At 30, 60, 90 draw blood samples for GH (give oral clonidine 150 mcg)
Blood samples at 120 min, 150 and 180 mins
Peak serum GH Concentration (>10 ng/ml - GH deficiency unlikely), (<10 ng/ml– GH deficiency likely
GH deficincy 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 product, but all the same meds
- Dosing is based on mg/kg/week, need much smaller doses of GH than a child with idipathic short stature and the dose is .2-.3 (the receptors are fine)
- Check IGF1 levels to determine dose changes
headaches with nausea/vomiting, growth pains SE
Pearls of panhypopituitary associated Growth hormone deficiency
GH deficiency usually presents with hypoglycemia in the neonatal period or growth failure (deceleration) in childhood
There are many pharmacologic agents to stimulate growth hormone production for testing purposes. We uaually se Arginine and clonidine (and insulin and glucagon)
If children are treated for GH def, rhGH is given each night by subQ injection, and insulin- like growth factor IGF1 levels are checked to ensure proper dosing
SEs are rare and include slipped capital fermoral epiphysis, scoliosis, pseudotumor cerbri, obstructive sleep apnea
Hyper prolactinemia Diagnosis
Single measurement of increased serum prolactin, A serum prolactin >250 ng/ml
Prolactinoma (prolactin secreting pituitary tumor)
Some drugs, 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 non non prolactinsecreting tumor with infundibular stalk compression and inhibition of dopamine transport to the lactotroph
Tumor blocks dopamines inhibitory effects on lactotrophs
Causes of hyperprolactinemia
Physiolologic: Pregnancy, lactation, exercise, sleep, Stress
Meds: Antihypertensives (methyldopa- dopamine antagonis), Estrogens, D2 dopamine receptor antagonists such as metoclopramide, domperidone, Neuroleptis/antipsychotics such as phenothisazines, butyphenones, reperidone, also block dopamine receptors
Pathologic:
Prolactinomas- obviously
Things that decrease dopamine (Hypothalamic pituitary stalk damage)
Hypothalamic- pituitary stalk damage: infiltrative disorders (sarcoidosis), irradiation to brain, trauma with pituitary stalk section or pituitary surgery, tumors, pituitary prolactinomas (compression of infundibular stalk, lymphocytic hypophysitis)
Clinical presentation of hyper prolactinemia
Varies with age and gender of the patient
Young women: menstrual irregularities, galactorrhea–too much milk (occurs in 50-80% of affected) and infertility
Men- decreases 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 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 post menopaustl women at presentation
Macroprolactinomas: headaches, neurologic deficits due to cavernous sinus involvement and visions changes due to optic chiasm compresssion and cavernous involvemnt
Treatment of hyperprolactinemia
Dopamine agonists- suppress prolacting 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, lowger half life, higher affinity, greatery selectivity for the D2 receptors (four times more potentthan bromocriptine), SE: nausea, vomiting, orthostatic lightheadedness, dizziness and nasal congestion, cardiac valvulopathy in parkinsons pts
Bromocriptine: recommended in pts undergoing fertility induction undergoing fertility inudction that also have hyperprolactinemia, because of its greater track record, short half life, 2-8 hours, Normalize prolactin, decrease tumor size , and restore gonadal dunction in greater than 80% of patients with prolactinomas, intital treatment for macroprolactinomas
acromegaly
abnormal enlargement of extremities, gigantism in children due to excess GH Prior to pubernal closure of epiphyseal growth plates
Almost always caused by GH secreting pituitary tumor (30% plurihormonal GH and prolactin)
Clinical fetures of acromegaly
Headache, enlargement of lips/nose/tongue, cardiomyopathy, hypertension, enlargement of liver, enlargement of hands, arthropathy, carpal tunnel syndrome
Skull growth, prognathism, increasing sweating, thick skin, Diabetes type 2, Colon cancer, myopathy, enlargement of feet increased heal pad thickness
Acromegaly diagnosis
Measure using serum IGF1 (made in liver), diagnoses excess GH in 99% of patients, half life of 16 hrs so a single measurement is more constant and acccurate 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 (normally glucose suppresses GH to less than 1 ng/ml by 2 hours, GH levels may paradoxically increase, remain unchanged or decrease, but not below 1 ng/ml
Acromegaly treatmnet
Transsphenoidal surgery, usually performed first (as opposed to prolactinoma where drug therapy is first)
Radiation therapy
Drug therapy - go back to GH control system for physiological logic behind each drug
Somatostatin receptor ligand (SRLs)- octreotide, lanreotide, pasireotide
Cabergoline- is the most efficacious of the dopamine agonists 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), decreases IGF 1 (the mediator of somatic growth)
Causes of panhypopituitarism/ hypopituitarism
Mass lesions: such as pituitary tumors, craniophayngiomas, cysts (Rathke’s cleft cyst), other brain tumors, pitiotary carcinoms, metastatic tumor– Sheehans
Treatment of sellar/ para sellar and hypothalamic diseases
Infiltrative diseases, trauma, vascular, meds (opiates, glucocorticoids, thyroxine therapy suppressrs, sex steroids, hypophysitis)
Infections, genetic, devlopmental
