Download ENDOCRINOLOGY Pituitary Diseases (secondary) Pituitary Tumor

ENDOCRINOLOGY
Pituitary Diseases (secondary)
1.
Pituitary Tumor sx: bitemporal heminopsia, change in hormones
a. Functional tumor- produces hormones
b. Non-functional tumor- don’t produce hormones
c. TYPES of Pituitary Tumors:
i. Prolactin (mc) associated w/ hypogonadism + infertility (sx: amenorrhea + galactorrhea)
ii. GH  causes acromegaly (in adults)
iii. ACTH  Cushing’s disease
d. DX of choice- MRI
Panhypopituitarism: (decrease in all hormones)
Gradual onset: loose LH/FSH first  then GH  then TSH/ACTH last
Risks: MEN, trauma, post-partum hemorrhade, SHOCK, congential deficiences
Etiologies: hypothalamic tumor, truam (basal skull fx), surgical resection, autoimmune, vascular thrombosis, tumor
MC tumor that causes hypopituitarism in children: craniopharyngioma (Rathke’s Pouch squished pit gland in sella)
Secondary decrease in FSH/LH: secondary amenorrhea, infertility, decreased libido, testicular atrophy, decreased spermatogeneis
(failure of secondary sex characteristics), cryptorchidism, delayed puberty, loss of axillary/pubic hair
Kallman’s Syndrome (mcc of isolated congenital gonadotopin deficiency)  defective GnRH
X-linked recessive (sx: HYPOSMIA- can’t smell), unilateral renal agenesis
2ndary adrenal deficiency (decrease in ACTH)- no cortisol
Sx: weakness, fatigue, hypoglycemia, hypotension, “intolerance to stress + infection” NO Hyperpigmentation
2ndary Thyroid deficiency (low TSH)- can cause “cretinism” in children
Short stature, delayed mental development, infertile
2ndary decrease in GH (in adults-central obesity, weakness, HTN, small heart)
In children- normal mental development, hypoglycemia + growth retardation + short stature
Sheehan’s Syndrome: pituitary necrosis due to hypovolemic shock post-partum
** post-partum mom who has no lactation, looses pubic/axillary hiar, looses menses, hypothyroid, w/ LOW BP
Pituitary Apoplexy: hemorrhagic infarction of pit gland **sx: severe HA, stiff neck, Blood in CSF, visual changes, “sudden loss of
all hormones”
Tx: neurosurgery + hormone replacement
Diagnosis of Panhypopituitarism:
stimulation test- stimulate gland to increase hormones when you suspect it’s low
suppression test- suppress hormone when you expect hyper-function of gland
1.
2.
Measure TSH
a. low TSH = 2ndary hypothyroidism
b. High TSH = primary hypothyroidism
Measure ACTH/cortisol- stress stimulation test
a. Cosyntropin test- give synthetic ACTH  should normally increase cortisol (however, in primary adrenal diseaseADDISON’S disease- you get low cortisol response to ACTH)
Metyrapone test- clinician decreases level of cortisol  normally this should increace ACTH (however, in panhypo-pituitarism there is no increase)
3. GH- hard to dx b/c GH is pusitile
a. Insulin Tolerance Test- give IV insulin  measure: GH, cortisol, glucose (normally glucose decreases, GH
increases, cortisol increases) ** this test is contraindicated in elderly, Pt with cardio or cerebral disease- seizures
4. LH/FSH (Give synthetic GnRH and LH/FSH should increase)
General Dx: MRI + visual field exam
b.
Generally: TRH,GnRH, Insulin are given together  measure: glucose, cortisol, TSH, prolactin, LH/FSH, ACTH
Normally:
Empty Sella Syndrome: normal hormone production, but CSF replaces pit gland
1. primary cause- genetic defect (mc in women w
2. secondary- caused by surgery
HyperProlactinemia
mcc- functional pit tumor (microadenoma)
note: estrogens usually inhibit secretion of milk + Prolactin Inhibiting Factor (dopamine)
risks: meds (Da-blockers: phenothiazine), renal disease (decrease prolactin clearance), MEN syndromes
sx: “hypogonadotropic hypogonadism”, change in visual field
in women sx: change in menses, secondary galactorrhea + amenorrhea
in men sx: impotence, infertility, low libido, gynecomastia
Dx: MRI, high prolactin, low FSH/LH
Tx: BROMOCRIPTINE
Exessive GH (mcc- pit adenoma):
Gigantism- in children
Acromegaly- in adults
Sx: tall stature
Sx: enlargement of head, hands, feet
Sleep apnea (snoring)
Hoarse voice, soft doughy handshake
Diaphoresis, Dm, HTN, bitemporal hemianopsia, macroglossia, protrusion of jaw, acne
Skull Xray- enlarged sinuses, Hand xray- “tufting of terminal phalanges”
Tx: transphenoidal resection + octreotide (somatostatin- GH antagonist)
Diabetes Insipidus
Sx: thirst, polyuria (urine is very very very pale- looks like water), dehydration, HA, bed wetting
1.
Central Di- due to hypothalamis/pit damage (es: adenoma, mets, trauma, infection)
a. Hyperuricemia (Gout)  is indication of Central Di
b. TX: SQ desmopressin
2. Nephrogenic Di- defect in kidney tubules  unresponsive to vasopressin admin
a. Causes: hypercalcemia, hypokalemia, pyelonephritis (electrolyte problem)
b. Tx: HTCZ + amiloride
3. Drug- Induced (lithium, Amphotericin)
4. Pyschogenic Di (drink excessive H2O)
Dx: MRI, measure urine osmolality w/ 6 hr fluid restriction
Plasma ADH- low in central Di, high in nephrogenic Di
Vasopressin Challege- central Di will respond- low urine output; Nephrogenic will NOT respond
SIADHmcc- CVA (Cx: Cerebral edema- low Na in CSF)
dx: hyponatremia < 125, concentrate urine, high ADH
Tx: water restriction, furosemide, hypertonic saline
Thyroid dysfunction: “iodide is transported into thyroid via follicular basal membrane”
Iodide  iodine (at follicular lumen)
TSH  T4/T3 release  binds to TBG
**somatostain inhibits TRH
**dopamine inhibits TSH
**T4 is main thyroid hormone + is converted to T3 at periperhal tissues
T4/T3 play a negative feedback to TRH/TSH
Hypothyroidism:
Causes: MCC- Hashimoto’s thyroiditis (autoimmune rxn ; other : Iatrogenic (thyroidectomy, radiation)
MCC worldwide- Goiter (iodine deficiency)
Sx: low metabolism, loss of 1/3 of lateral eyebrow, coarse hair/ weight gain, macrogloassia, bradycardia, cool skin, hair loss
Thyroid panel
tx: levothyroxine
dx:
Myxedema Coma (severe hypothyroidism  AMS, hypothermia, cardio collapse)
Sx: hypotension, bradycardia, hypoglycemia, hypothermia
Hyperthryoidism
MCC- Grave’s disease (autoimmne rxn- mc in females 20-30’s) Sx: Goiter, exophthalmos
Other causes: subactue thyroiditis in pregnancy
Sx: anxiety, emotional lability, sweating, weight loss, palps, hot, high appetite, lid lag, tachycardia, increased DTRs, pretibial
myxedema, mosit skin
Tx of choice: radio-iodine ablation or B-blocker (propanolol)
Tx in pregnancy: PTU
Cx: Thyroid Storm- severe hyperthyroidism- fever, coma, delirium, tachycardia, hyperpyrexia, AMS
ADRENAL Hormones:
1.
Aldosterone (mineralcorticoid)- secreted by outer layer of cortex
a. Retains NA, wastes K  increased H2O absorption in kidneys
b. JG cells secrete rennin  angiotensin 
c.
2. Cortisol- counteracts insulin
a. “diurnal” b/c highest in morning and lowest at night
b. Causes hyperglycem
c.
 HTN
d.
e.
3. Androgens- inner layer of cortex, mc steroid-DHEAS
a. DHEAS- not the main androgen supply in your body)
b. DHEAS- causes 2ndary sex characterisitics, “anabolic effects”
4. Catecholamines (NOR/EPI) 
ADRENAL Diseases:
1.
2.
3.
4.
5.
6.
Hyperaldosteronism (mcc= CONN’S disease)
a. Conn’s: unilateral tumor of adrenal gland
b. Other causes: bilateral cortical hyperplasia; rennin producing tumor
i. Primary hyperaldosteronism- hypokalemia + HTN
ii. Seoncdary hyperaldosteronism- renal artery stenosis 

ldosterone
c. SX: hypokalemia, HTn, 2ndary nephrogenic Di, metabolic alkalosis (hypokalemia)
d. DX: 24 hr urinei. Aldosterone suppression test: give high Na infusion, normally this decreases aldosteron (but won’t if pt has
dz)
ii. Note: ANP (alpha-naturetic peptide) naturally opposes aldosterone by decreasing Na+
e. TX: Conn’s disease- adrenalectomy (but correct hypokalemis 1st with spironlactone)
i. If bilateral hyperplasis- tx is life long spironlactone
Hypercortisolism (Cushing’s)
a. Mcc- Cushing’s syndrome ( prolonged use of steroids)
b. Cushing’s disease ( pit. Adenoma secretion of ACTH)
c. Sx: increase in glucose- weight gain, facial plethora (moon face), easy bruising, supraclavicular fat pad, purple
striae, HTN, Dm, hirsuitism + amenorrhea, protein catabolism
d. Pt is pre-disposed to cataracts + glaucoma
e. DX:
i.
ii. MRI
iii.
iv.
ACTH in adrenal tumor
f. TX:
i. Cushing’s syndrome- taper steroids
ii. Cushing’s disease- transsphenoidal microsurgery w/ steroid replacement
1º (primary) adrenal insufficiency- Addison’s disease
a. definciency of cortisol + aldosterone + androgens
b. SX: Bronzing- change in skin pigmentation b/c
c.
d. DX: Cosyntropin stimulation test 
e. TX: IV hydrocortisone, aldosterone, D5W ( BV)
Addisonian Crisis- life threatening emergency
a. Sx: fever, shock, AMS, N/V/D, abdominal pain, dehydration
b. Causes: rapid steroid withdrawal after adrenalectomy; stress (pregnancy, trauma)
c.
d. TX: IV hydrocortisone w/ saline (IV fluids)
2º (secondary) adrenal insufficiency- pit. Problem (not enough ACTH)
a. MCC- long steroid use  body therefore won’t produce it’s own endogenous steroids (HPA suppression)
b.
c. Sx: salt craving, N/V/D, weight loss, dehydration
d. Dx: normal cosyntropin test (b/c ACTH problem not adrenal problem)
e. TX: IV hydrocortisone, aldosterone, D5W ( BV)
Congenital Adrenal Hyperplasia (genetic-recessive)
a. 21-hydroxylase enzyme deficiency- which is needed for cortisol + aldosterone production
Sx: low aldosterone, low cortisol, high ACTH-causing hyperplasia and high androgens (b/c it’s a precursor molecule
to the other hormones)
c. Sx in females: Virilization (female infants with ambiguous genitalis or clideromegaly)
d. Sx in males: 1st sx is “salt wasting” = hyponatremia, hyperkalemia, hypoglycemia
e. DX: high levels of 17 hydroxy-progesterone
f. TX: cortisol + mineralcorticoids
MEN Syndromes= Multiple Endocrine Neoplasia:
b.
MEN I – 3ps- PARATHYROID (hyper-parathryoidism)
Pancreatic islet cell tumor (Zolliner-Ellison) + Pit. tumor
MEN II-A (PAT): Parathroid (hyper-parathyroidism), Adrenal-Pheochromocytoma ; Thyroid- Medullary Cancer
MEN II-B (MAT): Mucosal- GI ganglioneuromas ; Adrenal-Pheochromocytoma ; Thyroid- Medullary Cancer
The Parathyroid :
Normally increases Calcium levels in blood by :
1. Osteoclastic activity in bone
2.
3. inhibits net reabsorption of PO4 + bicarb at renal tubules
4.
1,25 dihydroxycholecalciferol (Vit D analog)  Vit D 
Note : serum calcium levels are largely bound to albumin
Hyperparathyroidism (1st sx :
Ca levels
Ca)
Primary gland hyperplaisa :
PTH =
Ca
** mcc in young outpt- adenoma
**mcc in elderly inpt- Cancer
Secondary hyperparathyroidism : chronic renal dz or Vit D deficiency (causes
PTH =
Ca)
Sx : Stones, Bones, Groins, Psych overtones, 2ndary nephrogenic Di (polydipsia/polyuria), HTN, shortened QT interval
(hypercalcemia), Nephrolithiasis, depression/anxiety
Cx : Calciphylaxis, band keratopathy (Ca deposits in cornea)
DX :
serum Ca, urine Ca, urine cAMP,
PTH,
serum PO4, metabolic acidosis
Tx : surgery, Lasix (do NOT give HCTZ)
Hypoparathyroidism
mcc- neck surgery, thyroidectomy, neck radiation
1.
2.
3.
4.
FunctionalDiGeorge’s Syndrome- hypoparathyroidism, thymic dysplasia, severe immunodeficency
Hungry Bone Syndrome- after surgical removal of parathyroid adenoma  Ca is reabs back into bones
Pseudohypoparathyroidism ( Ca) due to renal resistance to PTH
a. Sx
b. Also associated with short stature, obesity, short 4th metacarpal, mental retardation
General Sx : Prolonged QT interval, V.Fib, heart block, Ricket’s, DTRs, tetany
+ Chvostek’s sign- facial nerve spasm
+ Trouseeau’s sign- carpal spasm
Parkinson-like sx : b/c Ca deposits in Basal Ganglia (impaired memory, confusion, dementia)
DX :
Ca,
Mg,
PTH (if primary dz or Vit. D decif.),
PTH (if renal failure),
PO4,
urine cAMP
Tx : Emergency tx for tetany- IV Ca gluconate
Long term tx- oral Ca, Mg, Vit D plus hydration to avoid kidney stones
Pheochromocytoma
Paroxysmal HTN, high secretion of catecholamines
MC extra-adrenal site- organ of Zuckerland (aortic bifurcation)
Sx : sudden HTN, dyspnea, palps, tachycardia, hyperglycemia, tremor, weight loss
Note- when catecholamine surge stops  hypotension is cx (OH)
DX : 24 hr catecholamine (metanephrine-best indicator)
TX : alpha-1 blockers and B-blockers then surgery (acute HTN crisis- IV nitroprusside)
Dm-1 (insulin deficency of B cells )
mcc- autoimmune rapid destruction of Beta cells (can occur at any age, but mc in kids)
incidence in Scandinavians/Northern Europeans/US
Other causes : idiopathic or immune rxn from virus (mumps, coxsackie, enviromental)
**pt with pre-existing autoimmune disease is at increased risk for other autoimmune diseases : Graves, MG
Genetic pre-disposition : DR3 or DR4 subtypes
Sx : polydypsia, polyuria, nocturia, thirst, loss of pericytes in eyes  hazy macula, weight loss, hypotension (dehydration), neuro sx :
peripheral neuropathy, ketoacidosis, AMS, Kussmaul’s respiration (rapid deep breathing)
Diagnosis of Diabetes (1/2)
1.
Screening- Fasting plasma glucose
a. Recommended for >45 y/o w/ BMI > 25 (or family hx)
b. > 100 mg/dl = PRE Dm
c. > 126 mg/dl x 2 tests = Dm2
2. Random Glucose  shows if you need OGTT (not a dx test)
3. Oral Glucose Tolerance Test (gold standard)
a. 2hr plasma glucose test after fasting glucose (should be <140)
i. Dm2 > 200
4. Hba 1C  glucose over 3 months (should be < 6.5%)
5. UA- ketonuria, microalbuminuria
Treatment: maintain glucose (metformin), Bp (130/80), lipids (LDL <100, TG < 150), Fiber > 35 g/day
Diabeteic Cx:
Macrovascular Cx : coronary and cerebral artery disease
Microvascular Cx : retinopathy, nephropathy, neuropathy
Somogyi effect- rebound hyperglycemia b/c of nocturnal hypoglycemia
Dawn effect-
 hyperglycemia in morning
** Dm is the leading cause of renal failure/dialysis + blindness in US
DKA
Hyperglycemia  Kussmaul’s respirations, dehydration, hypotension, polyuria/polydipsia
TX: aggressive fluid replacement and add D5W when blood glucose is <250
+ Continuous insulin drip; supplemental potassium
Dm-2
**associated with obesity, dyslipidemia, HTN, B-blockers, HCTZ, steroids  all can increase insulin resistance
Sx: polydipsia, polururia, nocturia, weight gain, central obesity, acanthosis nicgricans, xanthomas, ulcerations
Dm-2 Cx:
1. Peripheral Neuropaht (stocking + glove)  charcot’s jts
2. mononeurpahty
3. Autonomic neuropathy  OH
4. PVD, athersclerosis, retinopathy, nephropathy  renal fialrue
5. HHTN (hyperosmolar hyperglycemic nonketotic coma) dx: AMS
Gestational Diabetes- diabetes begins with the onset of pregnancy
**insulin resistance
Cx: birth defects, fatal macrosomnia, erb’s palsy, birth trauma, resp. distress
Metabolic Syndrome (syndrome x)
**can lead to MI, CAD, CVA, TIA
Insulin resistance plus 3 of the following: Obesity, Dyslipidemia, HTN, athersclerosis, Endothelial dysfunction, Prothrombotic state, Acanthosis Nigracans, Hyperuricemia, Dm-2
Vipoma- VIP(casoactive intestinal peptide)
**Associated with MEN-1
**VIP secretes octreotide
Hx: chronic watery diarrhea with weight loss, colickly abdominal pain, FLUSHING and dehydration
Electorlytes: HYPOkalemia (metabolic acidosis), Hypercalcemia, hyperglycemia
Insulinoma tumor of islet cells
**mc neuroendocrine tumor of pancreas islet cells; Produces excess insulin
**associated with MEN-1
Sx: hypoglycemia, blurry vision, palpitations, confusion, diaphoresis
WHIPPLE’S TRIAD: 1.episodic hypoglycemia 2. temporary CNS dysfunction 3.dramatic reversal of CNS dysfunction w/ admin
of glucose
DX: Measure c-peptide (C-peptide with be high in insulinoma, low in exogenous insulin intake)
Tx: HCTZ, diazoxide, octreotide, surgical resection, doxorubicin, 5FU
Diabetic Foot- leading cause of Dm hospitalizations
Allodynia- burning pain at night b/c of loss of sensory nerve function
Dm neuropathy- symmetric peripheral-chronic neuropathy
1. Sensory- “stocking + glove”, loss of vibration is 1st, then temp, touch, position
2. Motor- Characot osteoarthropathy- Charcot Jts (new bone growth  jt subluxation at MCP)
3. Autonomic nerve dysfunction= PVD/venous statis  ulcers
**nueropahtic ulcers  no pain, on heel/pad of foot
**Arterial insufficnecy ulcers  painful, found on top of distal phalanges
Cx: gangrene (bacterial infection/ischemia)
Gonadal Dysfunction
Monosomy- missing a set of chromosomes
Polysomy- increase in more then 2 chromones
Aneuploidy- change in chromosome # during meiosis
Non-dysjunction- failure of autosomes to separate
Klinefelter syndrome (XXY)- “small firm testes”, infertility, gynecomastic, high voice, TALL stature
a. TX: androgen supplements
2. Turner’s syndrome (X)- “bilateral streak gonads”, amenorrhea, webbing of neck, no breasting, lymphedema
3. Mised Gonadal Dysgenesis (mosaicism- one person with 2 different karotypes)
a. MIXED 46xy, 45x  have ambigious genitalia
Phenotype Disorders
1.
1.
Female pseudohermaphroditism (46xx)
a. Normal ovarian tissue, but ambigious genitalis because of adrenal hyperplasia  androgen excess causes
masculization/fused labia
2. Male pseudohermaphroditism (46 xy)
a. Defect in androgen synthesis  feminization of external genitalia (small blind penis), gynceomastia
3. True hermaphrodite (have both 46xy + 46xx)
a. Gonadal asymmetry- testes + ovaries
Hypogonadotrophic Hypogonadism
**absence of FSH/LH  lack of puberty;
TX: give testosterone or estrogen + GnRH injections
Primary hypogonadism- testicular agenesis (absens of tests) or absence of ovaries
General Endorcinology Factoids
**FSH- causes follicle (egg/sperm) to grow and mature
**LH- stimulated Leydig cells to make testosterone, and stimulates ovaries to form corpus leuteum, estrogen, and progesterone
**Lipid soluable hormones- steroids + thyroid hormone (need carriers)
RESORPTION- bone breakdown
Alpha cells in pancreas- secrete glucagon
Delta cells- secrete somatostatin
Calcintonin- in thyroid tells Ca to back into bone
ADHAldosterone-
 increases water reabsorption