Endo E2 -review

What are pituitary adenomas?

common benign tumors of the pituitary gland

*up to 10% of people will have one by time of their death

Some pituitary adenomas secrete 1+ hormones in excess, how are these secretory adenomas usually found?

discovered d/t hormonal imbalances affecting bodily functions

What are ssx of pituitary adenomas?

HA, N/V, alt consciousness, seizures, bilateral hemianopsia

*depends on the type of tumor

How does hyperprolactenima present in men?

ED, dec libido, gynecomastia, hypogonadism, infertility

How does hyperprolactenima present in women?

oligomenorrhea, amenorrhea, galactorrhea, CMP

What ssx of hyperprolactenima present in both men and women?

osteoporosis/osteopenia, HA, bilateral hemainopsia, wt gain

What are pathologic causes of hyperprolactinemia?

cirrhosis, renal failure, hypothyroidism, MS, spinal cord lesion, SLE, chronic chest wall stimulation (post mastectomy, herpes zoster, chest acupuncture, nipple rings)

What are pharmacologic causes of hyperprolactinemia?

amphetamines, cimetidine, ranitidine (Zantac), estrogens, opioids, nicotine, verapamil, cocaine

What is the tx for hyperprolactinemia?

d/c any causative meds, endo/neuro referral

dopaminergics: Bromocriptine, Cabergoline

Where is GH produced?

somatotroph cells of ant. pituitary gland

What affects the production of GH?

stimulated by GHRH; inhibited by somatostatin

(both produced via hypothalamus)

What is the key pathologic factor in gigantism and acromegaly?

IGF-1

What lab is consistently elevated in pts w/ acromegaly & is used to monitor tx success?

serum levels of IGF-1

What is gigantism?

abn high linear growth d/t excessive action of IGF-1 while the epiphyseal growth plates are open during childhood

What is acromegaly?

abn high linear growth d/t IGF-1 excess when it occurs after the growth plate cartilage fuses in adulthood

What are ssx of acromegaly and gigantism?

tall stature, enlarged hands/feet, hyperhidrosis, HA, CTS, paresthesia, impotence, HTN, OSA, skull enlarges, hat size inc, tooth spacing widens, macroglossia, deep course voice, goiter, temporal hemianopsia, dilated left ventricle

What causes Cushing’s syndrome?

prolonged exposure to elevated levels of either endogenous or exogenous glucocorticoids

What is the MCC of Cushing syndrome?

use of exogenous glucocorticoids

What are the 3 causes of Cushing syndrome?

exogenous steroid administration, endogenous glucocorticoid overproduction (adenoma/lesions), ectopic ACTH

What causes ectopic ACTH secretion leading to Cushing’s?

secreted by oat cell or small-cell lung tumors OR by carcinoid tumors

What are ssx of Cushing’s?

buffalo hump, moon facies, central obesity, purple striae, thin skin, muscle weakness, menstrual irregularities, pscyh changes, HTN, hirsutism

What lab should be done in Cushings if pt presents w/ amenorrhea?

hCG (r/o pregnancy)

What lab findings indicate Cushing’s?

inc ACTH & cortisol, hyperglycemia, glycosuria, hypokalemia

When does a urinary free cortisol (UFC) r/o the diagnosis of endogenous Cushing syndrome?

3 UFC levels in the normal range

*often used as an initial screening tool

How is an overnight dexamethasone suppression test conducted?

1 mg of DEXA administered at 11 pm w/ subsequent measurement of cortisol level at 8 am

In healthy individuals, what should serum cortisol levels be?

< 1.8 mcg/dL

*this excludes Cushing’s

What is the result of a low dose dexamethasone test in a normal pt?

suppression of pituitary production of cortisol

What is the result of a low dose dexamethasone test in pts w/ a pituitary adenoma?

no suppression of cortisol

What is the result of a high dose dexamethasone test in pts w/ a pituitary adenoma?

suppression of cortisol (some cells are still responsive)

What is the result of a low or high dose dexamethasone test in pts w/ ectopic source of cortisol?

no suppression of cortisol

What is the tx for Cushing disease?

refer to endo/neuro surg, surgical excision if pituitary adenoma, possible bilateral adrenalectomy, gradual withdrawal from steroids if using them; may need K supplements, tx osteoporosis if present

What is ADH?

hormone secreted from post. pituitary and acts on the kidney to increase water reabsorption from the renal tubules

What does an inc in ADH cause?

inc BV → inc BP (SIADH)

What does a dec in ADH cause?

inc water elimination → inc urinary output (DI)

What causes DI?

30% idiopathic

25% malignant/benign tumors of brain or pituitary

20% follow cranial surgery

16% d/t head trauma

What are the predominant sx of DI?

polyuria, polydipsia, nocturia (3-18L)

How might a pt w/ DI present?

predilection for drinking cold liquids (often water); neuro sx vary w/ pts access to water; pts w/ free access may have no sx at all

What test can be helpful in dx DI?

water deprivation test

What is the tx for central DI?

1st: Desmopressin Acetate/DDAVP

2nd: Vasopressin

What is SIADH?

hyponatremia & hypo-osmolality d/t inappropriate, continued secretion of the hormone despite normal or inc plasma volume, which results in impaired water excretion

What is the MCC of euvolemic hyponatremia in hospitalized pts?

SIADH

Which has fewer sx: slowly progressive hyponatremia or a rapid drop of serum Na to the same value?

slowly progressive hyponatremia

What are ssx of sever/rapid-onset SIADH?

confusion, disorientation, delirium, muscle weakness, myoclonus, tremor, asterixis, hyporeflexia, ataxia, dysarthria, Cheyne-Stokes respiration, seizures, coma

What does tx of SIADH and the rapidity of correction depend on?

degree of hyponatremia, sx, acute vs chronic, urine osmolality, Cr clearance

What is the tx for chronic asx SIADH?

fluid restriction, Vasopressin-2 receptor antagonist

*if unavailable options include: loop diuretics w/ inc salt intake, urea, mannitol, demeclocycline

When treating acute SIADH aggressive tx needs to be done carefully to avoid what complication?

central pontine myelinolysis

What SIADH pts require aggressive correction of hyponatremia?

severe sx (seizure, stupor, coma) regardless degree of hyponatremia

mod/severe hyponatremia w/ duration less than 48 hrs

What is the goal when correcting hyponatremia?

correct at a rate that does not cause neuro complications

At what rate should serum sodium be corrected?

raise by 0.5-1 mEq/hr and NOT more than 10-12 mEq w/in 1st 24 hr

*aim max serum Na of 125-130 mEq/L

What is the feared complication of excessive, overly rapid correction of hyponatremia?

central pontine myelinolysis

What complication may arise when plasma osmolality dec faster than 10 mOsm/kg/hr when correcting SIADH?

cerebral edema (can lead to cerebral herniation)

*noncardiogenic pulm edema may also develop

What are sx of Central PontineMyelinolysis?

disorders of UMN, spastic quadriparesis, pseudobulbar palsy, confusion, coma

Risk of Central Pontine Myelinolysis is inc in what pts?

pts w/ hepatic failure, potassium depletion, large burns, malnutrion

What is the tx for Central Pontine Myelinolysis?

none; once occurs as a complication, there is no proven tx

DI or SIADH:

excessive thirst, high urinary output, low ADH, HYPERnatremia, dehydrated, lose too much fluid

DI

DI or SIADH:

excessive thirst, low urinary output, high ADH, HYPOnatremia, over hydrated, retain too much fluid

SIADH

What is the tx for Sheehan syndrome?

hormone replacement w/ physiologic doses of glucocorticoids, levothyroxine, sex steroids

*inc glucocorticoid doses for stress

What is Sheehan syndrome?

infarction/necrosis of pituitary gland secondary to hemorrhage during childbirth; uncommon in US but common in developing countries

Who is at an inc risk of Sheehan syndrome?

pregnant women w/ T1DM & pre-exisitng vascular disease

What is the MC presentation of Sheehan syndrome?

breast involution and failure to lactate (d/t prolactin deficiency)

failure of menses to resume

What are uncommon but potentially lethal complications of Sheehan syndrome?

hypotension and acute adrenal crises

*uncommon except under stress

When do mental disturbances seen in pts w/ Sheehan syndrome resolve?

revert w/ appropriate hormone replacement

What is the role of PTH?

inc blood Ca levels via: inc release of Ca & phosphate from bone matrix, inc Ca reabsorption by the kidney, inc renal production of Vit D, which inc intestinal absorption of Ca

How can PTH dec serum phosphate levels?

causes phosphaturia

What is primary hyperparathyroidism?

unregulated overproduction of PTH resulting in abn Ca homeostasis

What is secondary hyperparathyroidism?

overproduction of parathyroid hormone secondary to chronic abn stimulus for its production

What are the MCCs of secondary hyperparathyroidism?

chronic renal failure & Vit D deficiency

What does endogenous PTH do?

inc Ca absorption from the GI tract

Hyperparathyroidism causes chronic excessive resorption of Ca from bone caused by excessive PTH, what can this result in?

osteopenia

Hyperparathyroidism chronically increases excretion of Ca in the urine, what can this result in?

renal stones

What are sx of hyperparathyroidism d/t?

hypercalcemia

What are sx of hyperparathyroidism?

muscle weakness, fatigue, volume depletion, N/V, severe -coma/death, psych, bone pain, HTN, vit D deficiency

Hyperparathyroidism inc Ca which may increases odds of what?

PUD d/t inc gastric acid secretion

What EKG changes may be seen in hyperparathyroidism?

shortened QT interval, prolonged PR interval

What labs support a dx of hyperparathyroidism?

inc serum Ca on 2 occasions

low serum phosphate, high urine phosphate

vit D deficiency

inc serum PTH

What labs are diagnostic of primary hyperparathyroidism?

elevated PTH w/ elevated serum Ca

Saying for hyperparathyroid sx:

“bones, stones, abd groans, psychic moans, w/ fatigue overtones”

bone pain, renal calculi, mental changes, fatigue

What is the tx for hyperparathyroidism?

IV bisphosphonates (alendronate) for BMD

Calcimimetics (cincacalcet hydrochloride (Sensipar)) to dec PTH secretion)

What is hypoparathyroidism?

PTH deficiency; absence of adequate PTH results in hypocalcemia

What causes primary hypoparathyroidism?

iatrogenic causes or one of many rare disease

What are ssx of hypoparathyroidism?

paresthesia, hyperirritability, fatigue, mood swings, seizures, hoarseness, wheezing, dyspnea, muscle cramps

What are PE signs of hypoparathyroidism?

muscles cramps; severe → tetany; life-threatening laryngospasm or bronchospasm

*d/t hypocalcemia

What is Chvostek sign (seen in hypoparathyroidism)?

facial twitching is induced by gently tapping the ipsilateral facial nerve as it courses just ant. to the ear

What is Trousseau sign (seen in hypoparathyroidism)?

carpal spasm induced by inflating a BP cuff around the arm to 20 mmHg above obliteration of the radial pulse for 3-5 min

What labs support dx of hypoparathyroidism?

low serum Ca & mag

low PTH

high phosphate

low urine Ca

What imaging is supportive of hypoparathyroidism?

XR: inc bone density, cutaneous calcifications

CT skull: calcification of basal ganglia

What EKG changes may be seen in hypoparathyroidism?

prolonged QT interval and T wave abnormalities

What are the mainstays of tx in hypoparathyroidism?

Ca and Vit D

What puts pts at a high risk of developing permanent primary hypoparathyroidism?

undergoing parathyroidectomy for parathyroid hyperplasia

What is the tx for acute tetany?

airway management

IV Ca gluconate

Mag sulfate

How might hyperthyroidism present in the elderly?

Afib -irregularly irregular heart rhythm

What labs indicate hyperthyroidism?

TSH suppressed

T4, FT4, T3, FT3 elevated

What are ssx of hyperthyroidism?

sweating, wt loss, goiter, exophthalmos, lid lag, hyperreflexia, tachycardia, tremors, loose stools, anxiety, heat intolerance

What abs indicate Grave’s dz?

TSH-R Ab (TR-Ab) inc

*abs to TSH receptors

What abs indicate Hashimoto’s dz?

thyroperoxidase or thyroglobulin antibodies (TPO) inc

What drugs may alter labs showing hyperthyroidism?

estrogens, heparin, amiodarone, phenytoin, rifampin, salicylates

What is the hyperthyroidism DOC in pregnancy?

Propylthiouracil (PTU)

What is the DOC for hyperthyroidism -except for the first trimester of pregnancy?

Methimazole

What is the MCC of hyperthyroidism?

Grave’s dz

Who is more likely to have Grave’s?

F>M, age 20-40 yo