Download EN-2-10-99

Endocrine
(2-10-99)
pituitary: “master gland of the body”
called this because it was believed to control all the other glands
Disorders of the Pituitary:
difficult to spot primary disorders because you often spot the secondary ones first
Hormones:
ACTH
GH
PRL
TSH
FSH
LH
Corticotropin
Growth Hormone
Prolactin
Thyrotropin
Follicle Stimulating Hormone
Luteinizing Hormone
ACTH: bound by cell surface receptors, which activate cAMP
in the adrenals, ACTH stimulates steroidogenesis (of cortisol)
has extra adrenal actions
stimulates lipolysis in fat cells
stimulates amino acid and glucose uptake in muscle
stimulates secretion of GH
stimulates insulin secretion
but - the above are not significant at normal levels
ACTH hypersecretion:
one result could be hypoglycemia
increased cortisol (Cushing’s)
if pituitary problem  hyperpigmentation (Cushing’s Disease)
Cushing’s Disease – wake up with headaches due to hypoglycemia
secretion of ACTH is stimulated by CRF (Corticotropin Releasing Factor)
ACTH levels are normally highest in the AM (5-9 AM), lowest in the PM
so – a value is ‘OK’ or ‘not OK’ depending on the time of day it is
if levels are constant, it’s not normal (loss of the circadian rhythm)
lots of things occur in pulses (Circadian rhythms, etc.)
WBCs fighting the flu virus
typically released in the PM (afternoon/early evening)
30-40X increase
phagocytize the viruses and release lysozymes
their contents give you nausea and make you feel bad
get over it after 3-5 days
dual regulation of ACTH
“long loop” cortisol inhibition of ACTH at the pituitary and CRF at the
hypothalamus
“short loop” ACTH inhibition of CRF at the hypothalamus
GH: very popular today
may be replacing steroids among athletes as a performance enhancer
its anti-aging effects are being researched
its secretion is stimulated by GHRF
its secretion is inhibited by somatostatin
Actions:
stimulation of cellular differentiation/growth
(both skeletal and soft tissue)
promotes islet Beta cell hyperplasia
increases lipolysis
increases oxidative fatty acid metabolism
Note: Release is not the same as activity!
Factors Influencing GH Secretion:
augmented by:
stress (traumatic, surgical, infection)  increased concentration
alpha adrenergic agonists
beta adrenergic antagonists
** hypoglycemia (fasting)
decreased fatty acid levels
uremia
hepatic cirrhosis
estrogens, glucagon, vasopressin
inhibited by:
emotional deprivation
alpha adrenergic blockers (antagonists)
beta adrenergic agonists
hyperglycemia (ex – insulin-dependent DM)
twin studies: you have a 50% chance of getting DM if your twin has it
the diabetic twin is smaller than the non-diabetic twin
(they think hyperglycemia is the culprit)
increased fatty acid levels
obesity
somatostatin, high doses of cortisol
There is an inverse relationship between blood glucose and GH concentration.
You can use hyperglycemia to check GH control
If you make them hyperglycemic, but the GH does not decrease  BAD sign
Prolactin: inhibited by estrogen during pregnancy
once the placenta is delivered, the estrogen decreases, so the lactogenic action
of prolactin is expressed
TSH:
synthesis is stimulated by TRH
inhibited by somatostatin and T3 (feedback inhibition)
(T3 usually stimulates the other stuff)
stimulates the thyroid gland
FSH:
controlled by gonadotropin releasing hormone (GRH)
stimulates gametogenesis (both sexes)
males: Sertoli cells
females: ??
LH: controlled by GRH
males: Leydig cells
females: ??
Mechanisms of Pituitary-Hypothalamus Dysfunction:
1)
2)
3) helps you explain to the Pt why the condition is present
a biggie in terms of secondary disorders
the pituitary suffers from primary disorders like hyperchromatosis (??)
Developmental: often associated with cleft palate or other midline deformities
the pituitary often fails to grow in these cases
Infectious Agents: viral encephalitis  hypothalamus  pituitary
acquired “idiopathic” diabetes insipidus
may be due to a viral infection
pyrogenic abscess  bacteremia
 severe headaches and loss of vision
(signs of systemic infection)
TB, syphilis (rare today)
devastating when they do occur
Granulomas and Infiltrative: ( cells accumulate a foreign substance)
noninfectious granulomas
sarcoidosis
hemochromatosis
myxedema
often see hypopituitarism with these
Autoimmune Disorders:
lymphocytic hypophysitis
 hypopituitarism
Ischemia: relatively common in the 1950s
due to severe postpartum hemorrhagic or infectious shock
Sheehan’s Syndrome:
tissue anoxia following postpartum hemorrhage
(6-8 weeks later, 3-4 months later)
the Pt developed symptoms resembling a loss of pituitary function
due to a 40-60% increase in the size of the pituitary gland during pregnancy
(due to lactotropic cell hyperplasia)
but – in a bony structure (unyielding)
hemorrhage  vasospasm
cellular edema  increased tissue pressure
 decreased circulation in the area
(circulation was not re-established)
 pituitary necrosis
Today: We can rapidly replenish the blood supply following a hemorrhage
so that people don’t get Sheehan’s Syndrome.
Most Common Cause of Pituitary Dysfunction: Tumor
Tumors are the most common cause of hypopituitarism.
Tumors are also the most common cause of hyperpituitarism.
Hypopituitarism:
If acute and complete, this can be life threatening.
In its mild form, it can remain undetected for years.
We see more cases of it now, possibly due to better detection.
It has a wide range of symptoms, with many different presentations.
(unlike hyperthyroid, which has one presentation)
Disease states are influenced by:
The Pt’s age
The rapidity of onset of the disorder
The extent of impaired hormone secretion
The pathologic process involved in the cause
How the Pt’s age affects a GH deficiency (Two 40-year-old Pts)
#1: Age of onset = 30
fewer clinical consequences
(actually, we don’t know the Pt has it)
#2: Age of onset = 9
Pt is much shorter
GH deficiency in adults – unknown
‘normal’ is unknown/undefined (just declines in adults)
Rapidity of Onset:
Ex: 30 lb. Weight gain
#1: Over a 10-year period (SLOW)
probably won’t notice the cause
#2:
Over a 10-day period
a definite clinical difference
TSH deficiency:
30 days vs. 3 years
3 years: The Pt may have adapted to it and not notice the subtle clinical
findings
There may or may not be a drop in thyroid hormone
(it depends on the amount of the deficiency)
Extent of Impaired Hormone Secretion:
3% TSH excess vs. 30% TSH excess
It’s easier for the body to compensate/adapt for a 3% excess
(Innate can handle it)
If the 3% excess is caused by a tumor, you get down-regulation of the
thyroid receptors
Pathologic Process:
Speed of progression
Extra endocrine manifestations
ACTH Deficiency vs. Prolactin Deficiency
Hypopituitarism:
Many clinical pictures with diverse symptoms.
Range from unrecognized to death (panhypopituitarism)
Often associated with nuisance Pts.
Tired, don’t feel good, …
Often describes geriatric Pts, but would b abnormal in a younger Pt.
2nd Quiz in 2 weeks.
Lab Dx Midterm on March 1.